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Health outcomes of non-nutritive sweeteners: analysis of the research landscape.

Lohner S, Toews I, Meerpohl JJ.

Nutr J. 2017 Sep 8;16(1):55. doi: 10.1186/s12937-017-0278-x. Review.

PMID: 28886707 Free PMC Article

Abstract

BACKGROUND:

Food products containing non-nutritive sweeteners (NNSs) instead of sugar have become increasingly popular in the last decades. Their appeal is obviously related to their calorie-free sweet taste. However, with the dramatic increase in their consumption, it is reasonable and timely to evaluate their potential health benefits and, more importantly, potential adverse effects. The main aim of this scoping review was to map the evidence about health outcomes possibly associated with regular NNS consumption by examining the extent, range, and nature of research activity in this area.

METHODS:

We systematically searched Ovid MEDLINE, EMBASE and the Cochrane CENTRAL databases for studies on NNSs (artificial sweeteners or natural, non-caloric sweeteners, either used individually or in combination) using text terms with appropriate truncation and relevant indexing terms. All human studies investigating any health outcomes of a NNS intervention or exposure were eligible for inclusion. No studies were excluded based on language, study design or methodological quality. Data for each health outcome were summarized in tabular form and were discussed narratively.

RESULTS:

Finally, we included 372 studies in our scoping review, comprising 15 systematic reviews, 155 randomized controlled trials (RCTs), 23 non-randomized controlled trials, 57 cohort studies, 52 case-control studies, 28 cross sectional studies and 42 case series/case reports. In healthy subjects, appetite and short term food intake, risk of cancer, risk of diabetes, risk of dental caries, weight gain and risk of obesity are the most investigated health outcomes. Overall there is no conclusive evidence for beneficial and harmful effects on those outcomes. Numerous health outcomes including headaches, depression, behavioral and cognitive effects, neurological effects, risk of preterm delivery, cardiovascular effects or risk of chronic kidney disease were investigated in fewer studies and further research is needed. In subjects with diabetes and hypertension, the evidence regarding health outcomes of NNS use is also inconsistent.

CONCLUSIONS:

This scoping review identifies the needs for future research to address the numerous evidence gaps related to health effects of NNSs use.It also specifies the research questions and areas where a systematic review with meta-analyses is required for the proper evaluation of health outcomes associated to regular NNSs consumption.

KEYWORDS:

Artificial sweetener; Aspartame; Cancer; Dental caries; Diabetes; Non-nutritive sweetener; Obesity; Overweight; Saccharin; Scoping review; Stevia; Weight gain

 

Plant-Based Nutrition: An Essential Component of Cardiovascular Disease Prevention and Management.

Patel H, Chandra S, Alexander S, Soble J, Williams KA Sr.

Curr Cardiol Rep. 2017 Sep 8;19(10):104. doi: 10.1007/s11886-017-0909-z. Review.

PMID: 28887684

http://sci-hub.cc/10.1007/s11886-017-0909-z

Abstract

PURPOSE OF REVIEW:

This review aims to summarize and discuss the role of plant-based nutrition as an adjunct to the management of cardiovascular disease (CVD). Discussion of nutrition and the benefits of a plant-based diet should be highlighted during healthcare provider visits as an essential part of the overall CVD prevention and management care plan.

RECENT FINDINGS:

Evidence from prospective cohort studies indicates that a high consumption of predominantly plant-based foods, such as fruit and vegetables, nuts, and whole grains, is associated with a significantly lower risk of CVD. The protective effects of these foods are likely mediated through their multiple beneficial nutrients, including mono- and polyunsaturated fatty acids, omega-3 fatty acids, antioxidant vitamins, minerals, phytochemicals, fiber, and plant protein. In addition, minimizing intake of animal proteins has been shown to decrease the prevalence of CVD risk factors. Substantial evidence indicates that plant-based diets can play an important role in preventing and treating CVD and its risk factors. Such diets deserve more emphasis in dietary recommendations.

KEYWORDS:

Cardiovascular disease; Cardiovascular disease prevention; Mediterranean diet; Plant-based nutrition; Vegan; Vegetarian

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Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians.

Haddad EH, Berk LS, Kettering JD, Hubbard RW, Peters WR.

Am J Clin Nutr. 1999 Sep;70(3 Suppl):586S-593S.

PMID: 10479236 Free Article

http://ajcn.nutrition.org/content/70/3/586s.long

http://ajcn.nutrition.org/content/70/3/586s.full.pdf+html

Abstract

Dietary and nutritional status of individuals habitually consuming a vegan diet was evaluated by biochemical, hematologic, and immunologic measures in comparison with a nonvegetarian group. On the basis of 4-d dietary records, the intake of female and male vegans tended to be lower in fat, saturated fat, monounsaturated fat, and cholesterol and higher in dietary fiber than that of vegetarians. With computed food and supplement intakes, vegan diets provided significantly higher amounts of ascorbate, folate, magnesium, copper, and manganese in both female and male participants. The body mass index (BMI; in kg/m(2)) of the vegans was significantly lower than that of the nonvegetarians and 9 of the 25 vegans had a BMI <19. Serum ferritin concentrations were significantly lower in vegan men but iron and zinc status did not differ between the sexes. Mean serum vitamin B-12 and methylmalonic acid concentrations did not differ; however, 10 of the 25 vegans showed a vitamin B-12 deficit manifested by macrocytosis, circulating vitamin B-12 concentrations <150 pmol/L, or serum methylmalonic acid >376 nmol/L. Vegans had significantly lower leukocyte, lymphocyte, and platelet counts and lower concentrations of complement factor 3 and blood urea nitrogen but higher serum albumin concentrations. Vegans did not differ from nonvegetarians in functional immunocompetence assessed as mitogen stimulation or natural killer cell cytotoxic activity.

 

Associations of 100% fruit juice versus whole fruit with hypertension and diabetes risk in postmenopausal women: Results from the Women's Health Initiative.

Auerbach BJ, Littman AJ, Tinker L, Larson J, Krieger J, Young B, Neuhouser M.

Prev Med. 2017 Sep 6. pii: S0091-7435(17)30315-8. doi: 10.1016/j.ypmed.2017.08.031. [Epub ahead of print]

PMID: 28888824

Abstract

The objective of this study was to determine whether consumption of 100% fruit juice as compared to whole fruit is associated with increased risk of hypertension or diabetes. We analyzed postmenopausal women in the United States enrolled in the Women's Health Initiative between 1993 and 1998. Whole fruit and 100% fruit juice intake were assessed by baseline food frequency questionnaire. Standardized questionnaires assessed outcomes every 6-12months during a mean 7.8years of follow-up. Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for incident hypertension (n=36,314 incident cases/80,539 total participants) and diabetes (n=11,488 incident cases/114,219 total participants). In multivariable analyses there was no significant association comparing the highest to lowest quintiles of 100% fruit juice consumption (8oz/day compared to none) and incident hypertension (HR 1.00, 95% CI 0.97-1.03) or diabetes (HR 0.96, 95% CI 0.90-1.03). There was also no significant association between whole fruit consumption (2.4servings/day compared to 0.3servings/day) and incident hypertension (HR 1.02, 95% CI 0.98-1.05) or diabetes (HR 1.03, 95% CI 0.96-1.10). Consuming moderate amounts of 100% fruit juice or whole fruit was not significantly associated with risk of hypertension or diabetes among postmenopausal US women.

KEYWORDS:

Diabetes; Fruit; Fruit juices; Hypertension

 

The association of weight loss with one-year mortality in hospital patients, stratified by BMI and FFMI subgroups.

de van der Schueren MAE, de Smoker M, Leistra E, Kruizenga HM.

Clin Nutr. 2017 Aug 31. pii: S0261-5614(17)30307-2. doi: 10.1016/j.clnu.2017.08.024. [Epub ahead of print]

PMID: 28890273

Abstract

BACKGROUND:

The European Society for Clinical Nutrition and Metabolism (ESPEN) has recently published consensus-based criteria for the diagnosis of malnutrition; in subjects identified at nutritional risk the diagnosis is confirmed by either BMI <18.5 kg/m2 or weight loss in combination with low BMI or low FFMI. Concerns have been raised whether this definition correctly classifies malnutrition in patients with normal weight or overweight and concomitant weight loss. Therefore, the aim of this research is to assess the association between weight loss and one-year mortality in hospitalized patients, stratified by BMI and FFMI subgroups.

METHODS:

This prospective study included 769 patients admitted to the VU University Medical Center. Critical weight loss (CWL) was defined as >5% weight loss in the previous month or >10% weight loss in the previous six months. The association between CWL and one-year mortality was analyzed with a priori stratification by BMI cut-off values (</≥20.0 kg/m2 for patients <70 years and </≥22.0 kg/m2 for patients ≥70 years) and FFMI cut-off values (derived from BIA measurements, </≥15 kg/m2 for females and </≥17 kg/m2 for males). Mortality risks were calculated (HR, 95% CI).

RESULTS:

CWL occurred in 35% of patients and was associated with an increased one-year mortality rate vs. no-CWL (25% vs. 15%, p = 0.001), HR for mortality risk 1.76 (1.26-2.45)). CWL + low FFMI was associated with higher mortality risk (HR 1.95 (1.20-3.17), whereas CWL + normal FFMI was not (HR 1.37 (0.85-2.21)). Among patients with normal/high BMI, those with CWL had a significantly higher mortality risk compared to those without critical weight loss, however additionally adding FFMI to that model showed that a low FFMI was crucial in the observed association with mortality (CWL + normal BMI + low FFMI, HR 2.69 (1.29-5.65); CWL + normal BMI + normal FFMI, HR 1.38 (0.84-2.27)).

CONCLUSION:

- Patients with critical weight loss have a higher one-year mortality compared to patients with no critical weight loss. FFMI seems to play a crucial role in this association, as normal weight patients with normal FFMI had lower mortality rates than their counterparts with low FFMI.

KEYWORDS:

Body mass index; ESPEN diagnostic criteria for malnutrition; Fat free mass index; Malnutrition; Mortality; Weight loss

 

Beneficial Effects of Common Bean on Adiposity and Lipid Metabolism.

Thompson HJ, McGinley JN, Neil ES, Brick MA.

Nutrients. 2017 Sep 9;9(9). pii: E998. doi: 10.3390/nu9090998.

PMID: 28891931 Free Article

http://www.mdpi.com/2072-6643/9/9/998/htm

Abstract

In developed countries which are at the epicenter of the obesity pandemic, pulse crop consumption is well below recommended levels. In a recent systematic review and meta-analysis of 21 randomized controlled clinical trials, pulse consumption was associated with improved weight control and reduced adiposity, although the underlying mechanisms were a matter of speculation. Common bean (Phaseolus vulgaris L.) is the most widely consumed pulse crop and was the focus of this investigation. Using outbred genetic models of dietary induced obesity resistance and of dietary induced obesity sensitivity in the rat, the impact of bean consumption was investigated on the efficiency with which consumed food was converted to body mass (food efficiency ratio), body fat accumulation, adipocyte morphometrics, and patterns of protein expression associated with lipid metabolism. Cooked whole bean as well as a commercially prepared cooked bean powders were evaluated. While bean consumption did not affect food efficiency ratio, bean reduced visceral adiposity and adipocyte size in both obesity sensitive and resistant rats. In liver, bean consumption increased carnitine palmitoyl transferase 1, which is the rate limiting step in long chain fatty acid oxidation and also resulted in lower levels of circulating triglycerides. Collectively, our results are consistent with the clinical finding that pulse consumption is anti-obesogenic and indicate that one mechanism by which cooked bean exerts its bioactivity is oxidation of long chain fatty acids.

KEYWORDS:

adiposity; bean; fatty acid oxidation; pulse crops

 

Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration.

Merle BMJ, Silver RE, Rosner B, Seddon JM.

Invest Ophthalmol Vis Sci. 2017 Sep 1;58(11):4569-4578. doi: 10.1167/iovs.17-21673.

PMID: 28892825

http://iovs.arvojournals.org/article.aspx?articleid=2653920

 

Complex interactions of circadian rhythms, eating behaviors, and the gastrointestinal microbiota and their potential impact on health

Jennifer L. Kaczmarek; Sharon V. Thompson; Hannah D. Holscher

 

Association between plant-based diets and plasma lipids: a systematic review and meta-analysis

Yoko Yokoyama; Susan M. Levin ; Neal D. Barnard

 

4,500 deaths a year from high Europe diesel emissions, researchers find

Risk is greatest in areas with high concentrations of diesel cars, such as northern Italy.

The Associated Press Posted: Sep 18, 2017

http://www.cbc.ca/news/health/diesel-deaths-1.4294574

 

Higher Protein Intake Does Not Improve Lean Mass Gain When Compared with RDA Recommendation in Postmenopausal Women Following Resistance Exercise Protocol: A Randomized Clinical Trial.

Rossato LT, Nahas PC, de Branco FMS, Martins FM, Souza AP, Carneiro MAS, Orsatti FL, de Oliveira EP.

Nutrients. 2017 Sep 12;9(9). pii: E1007. doi: 10.3390/nu9091007.

PMID: 28895933 Free Article

Abstract

The aim of this study was to evaluate the effect of a higher protein intake on lean body mass (LBM) gain in postmenopausal women practicing resistance exercise and compare it to the Recommended Dietary Allowance (RDA) recommendation. Twenty-three postmenopausal women (63.2 ± 7.8 years) were randomized into two groups. The group with higher protein intake (n = 11) (HP) received a dietary plan with ~1.2 g·kg-1·day-1 of protein, while the normal protein (NP) group (n = 12) was instructed to ingest ~0.8 g·kg-1·day-1 of protein (RDA recommendation). Both groups performed the same resistance training protocol, 3 times a week, with progression of the number of sets (from 1 to 6 sets) and 8-12 repetitions. The intervention occurred over 10 weeks. Body composition evaluation was performed by dual-energy X-ray absorptiometry. The diet was evaluated by nine 24-h food recall summaries over the course of the study. During the intervention period, the HP group presented a higher protein (1.18 ± 0.3 vs. 0.87 ± 0.2 g·kg-1·day-1, p = 0.008) and leucine (6.0 ± 1.4 vs. 4.3 ± 0.9 g/day, p < 0.001) intake than the NP group, respectively. At the end of the intervention, there were increases in LBM both in HP (37.1 ± 6.2 to 38.4 ± 6.5 kg, p = 0.004) and in NP (37.6 ± 6.2 to 38.8 ± 6.4 kg, p < 0.001), with no differences between the groups (p = 0.572). In conclusion, increased protein intake did not promote higher LBM gain when compared to RDA recommendation in postmenopausal women performing resistance exercise during 10 weeks.

KEYWORDS:

RDA recommendations; body composition; leucine intake; postmenopausal women; protein

 

Young adulthood and adulthood adiposity in relation to incidence of pancreatic cancer: a prospective study of 0.5 million Chinese adults and a meta-analysis.

Pang Y, Holmes MV, Kartsonaki C, Guo Y, Yang L, Bian Z, Chen Y, Bragg F, Iona A, Millwood IY, Chen J, Li L, Chen Z.

J Epidemiol Community Health. 2017 Sep 12. pii: jech-2017-208895. doi: 10.1136/jech-2017-208895. [Epub ahead of print]

PMID: 28900029 Free Article

Abstract

BACKGROUND:

Adult adiposity is positively associated with pancreatic cancer in Western populations. Little is known, however, about the association in China where many have lower body mass index (BMI) or about the relevance of young adulthood adiposity for pancreatic cancer in both Western and East Asian populations.

METHODS:

The China Kadoorie Biobank (CKB) recruited 512 891 adults aged 30-79 years during 2004-2008, recording 595 incident cases of pancreatic cancer during 8-year follow-up. Cox regression yielded adjusted HRs for pancreatic cancer associated with self-reported young adulthood (mean ~25 years) BMI and with measured adulthood (mean ~52 years) BMI and other adiposity measures (eg, waist circumference (WC)). These were further meta-analysed with published prospective studies.

RESULTS:

Overall, the mean BMI (SD) was 21.9 (2.6) at age 25 years and 23.7 (3.3) kg/m2 at age 52 years. Young adulthood BMI was strongly positively associated with pancreatic cancer in CKB (adjusted HR=1.36, 95% CI 1.16 to 1.61, per 5 kg/m2 higher BMI) and in meta-analysis of CKB and four other studies (1.18, 1.12 to 1.24). In CKB, there was also a positive association of pancreatic cancer with adulthood BMI (1.11, 0.97 to 1.27, per 5 kg/m2), similar in magnitude to that in meta-analyses of East Asian studies using measured BMI (n=2; 1.08, 0.99 to 1.19) and of Western studies (n=25; 1.10, 1.06 to 1.12). Likewise, meta-analysis of four studies, including CKB, showed a positive association of adulthood WC with pancreatic cancer (1.10, 1.06 to 1.14, per 10 cm).

CONCLUSIONS:

In both East Asian and Western populations, adiposity was positively associated with risk of pancreatic cancer, with a somewhat stronger association for young than late-life adiposity.

KEYWORDS:

Chinese; adiposity; adulthood; meta-analysis; pancreatic cancer; young adulthood

 

Role of Microalbuminuria in Predicting Cardiovascular Mortality in Individuals With Subclinical Hypothyroidism.

Tuliani TA, Shenoy M, Belgrave K, Deshmukh A, Pant S, Hilliard A, Afonso L.

Am J Med Sci. 2017 Sep;354(3):285-290. doi: 10.1016/j.amjms.2017.04.022. Epub 2017 May 13.

PMID: 28918836

http://sci-hub.cc/10.1016/j.amjms.2017.04.022

Abstract

PURPOSE:

Studies suggest that subclinical hypothyroidism (SCH) is related to cardiovascular mortality (CVM). We explored the role of microalbuminuria (MIA) as a predictor of long-term CVM in population with and without SCH with normal kidney function.

MATERIALS AND METHODS:

We examined the National Health and Nutrition Education Survey - III database (n = 6,812). Individuals younger than 40 years, thyroid-stimulating hormone levels ≥20 and ≤0.35mIU/L, estimated glomerular filtration rate <60mL/minute/1.73m2 and urine albumin-to-creatinine ratio of >250mg/g in men and >355mg/g in women were excluded. SCH was defined as thyroid-stimulating hormone levels between 5 and 19.99mIU/L and serum T4 levels between 5 and 12µg/dL. MIA was defined as urine albumin-to-creatinine ratio of 17-250mg/g in men and 25-355mg/g in women. Patients were categorized into the following 4 groups: (1) no SCH or MIA, (2) MIA, but no SCH, (3) SCH, but no MIA and (4) both SCH and MIA.

RESULTS:

Prevalence of MIA in the subclinical hypothyroid cohort was 21% compared to 16.4% in those without SCH (P = 0.03). SCH was a significant independent predictor of MIA (n = 6,812), after adjusting for traditional risk factors (unadjusted odds ratio = 1.75; 95% CI: 1.24-2.48; P = 0.002 and adjusted odds ratio = 1.83; 95% CI: 1.2-2.79; P = 0.006). MIA was a significant independent predictor of long-term all-cause (adjusted hazard ratio = 1.7, 95% CI: 1.24-2.33) and CVM (adjusted hazard ratio = 1.72, 95% CI: 1.07-2.76) in subclinical hypothyroid individuals.

CONCLUSIONS:

In a cohort of subclinical hypothyroid individuals, the presence of MIA predicts increased risk of CVM as compared to nonmicroalbuminurics with SCH. Further randomized trials are needed to assess the benefits of treating microalbuminuric subclinical hypothyroid individuals and impact on CVM.

KEYWORDS:

Biomarker; Microalbuminuria; Risk stratification

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Intermittent energy restriction improves weight loss efficiency in obese men: the MATADOR study.

Byrne NM, Sainsbury A, King NA, Hills AP, Wood RE.

Int J Obes (Lond). 2017 Aug 17. doi: 10.1038/ijo.2017.206. [Epub ahead of print]

PMID: 28925405

Abstract

BACKGROUND/OBJECTIVES:

The MATADOR (Minimising Adaptive Thermogenesis And Deactivating Obesity Rebound) study examined whether intermittent energy restriction (ER) improved weight loss efficiency compared with continuous ER and, if so, whether intermittent ER attenuated compensatory responses associated with ER.

SUBJECTS/METHODS:

Fifty-one men with obesity were randomised to 16 weeks of either: (1) continuous (CON), or (2) intermittent (INT) ER completed as 8 × 2-week blocks of ER alternating with 7 × 2-week blocks of energy balance (30 weeks total). Forty-seven participants completed a 4-week baseline phase and commenced the intervention (CON: N=23, 39.4±6.8 years, 111.1±9.1 kg, 34.3±3.0 kg m-2; INT: N=24, 39.8±9.5 years, 110.2±13.8 kg, 34.1±4.0 kg m-2). During ER, energy intake was equivalent to 67% of weight maintenance requirements in both groups. Body weight, fat mass (FM), fat-free mass (FFM) and resting energy expenditure (REE) were measured throughout the study.

RESULTS:

For the N=19 CON and N=17 INT who completed the intervention per protocol, weight loss was greater for INT (14.1±5.6 vs 9.1±2.9 kg; P<0.001). INT had greater FM loss (12.3±4.8 vs 8.0±4.2 kg; P<0.01), but FFM loss was similar (INT: 1.8±1.6 vs CON: 1.2±2.5 kg; P=0.4). Mean weight change during the 7 × 2-week INT energy balance blocks was minimal (0.0±0.3 kg). While reduction in absolute REE did not differ between groups (INT: -502±481 vs CON: -624±557 kJ d-1; P=0.5), after adjusting for changes in body composition, it was significantly lower in INT (INT: -360±502 vs CON: -749±498 kJ d-1; P<0.05).

CONCLUSIONS:

Greater weight and fat loss was achieved with intermittent ER. Interrupting ER with energy balance 'rest periods' may reduce compensatory metabolic responses and, in turn, improve weight loss efficiency.

 

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Dietary patterns and depressive symptoms in a UK cohort of men and women: a longitudinal study.

Northstone K, Joinson C, Emmett P.

Public Health Nutr. 2017 Sep 18:1-7. doi: 10.1017/S1368980017002324. [Epub ahead of print]

PMID: 28918774

Abstract

OBJECTIVE:

There is evidence to suggest that individual components of dietary intake are associated with depressive symptoms. Studying the whole diet, through dietary patterns, has become popular as a way of overcoming intercorrelations between individual dietary components; however, there are conflicting results regarding associations between dietary patterns and depressive symptoms. We examined the associations between dietary patterns extracted using principal component analysis and depressive symptoms, taking account of potential temporal relationships.

DESIGN:

Depressive symptoms in parents were assessed using the Edinburgh Postnatal Depression Scale (EPDS) when the study child was 3 and 5 years of age. Scores >12 were considered indicative of the presence of clinical depressive symptoms. Diet was assessed via FFQ when the study child was 4 years of age.

SETTING:

Longitudinal population-based birth cohort.

SUBJECTS:

Mothers and fathers taking part in the Avon Longitudinal Study of Parents and Children when their study child was 3-5 years old.

RESULTS:

Unadjusted results suggested that increased scores on the 'processed' and 'vegetarian' patterns in women and the 'semi-vegetarian' pattern in men were associated with having EPDS scores ≥13. However, after adjustment for confounders all results were attenuated. This was the case for all those with available data and when considering a sub-sample who were 'disease free' at baseline.

CONCLUSIONS:

We found no association between dietary patterns and depressive symptoms after taking account of potential confounding factors and the potential temporal relationship between them. This suggests that previous studies reporting positive associations may have suffered from reverse causality and/or residual confounding.

KEYWORDS:

ALSPAC; Depression; Dietary patterns; Edinburgh Postnatal Depression Scale; Principal components analysis

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J Affect Disord. 2017 Jul 28;225:13-17. doi: 10.1016/j.jad.2017.07.051. [Epub ahead of print]

Vegetarian diets and depressive symptoms among men.

Hibbeln JR, Northstone K, Evans J, Golding J.

Abstract

BACKGROUND:

Vegetarian diets are associate with cardiovascular and other health benefits, but little is known about mental health benefits or risks.

AIMS:

To determine whether self-identification of vegetarian dietary habits is associated with significant depressive symptoms in men.

METHOD:

Self-report data from 9668 adult male partners of pregnant women in the Avon Longitudinal Study of Parents and Children (ALSPAC) included identification as vegetarian or vegan, dietary frequency data and the Edinburgh Post Natal Depression Scale (EPDS). Continuous and binary outcomes were assessed using multiple linear and logistic regression taking account of potential confounding variables including: age, marital status, employment status, housing tenure, number of children in the household, religion, family history of depression previous childhood psychiatric contact, cigarette and alcohol consumption.

RESULTS:

Vegetarians [n = 350 (3.6% of sample)], had higher depression scores on average than non-vegetarians (mean difference 0.96 points [95%CI + 0.53, + 1.40]) and a greater risk for EPDS scores above 10 (adjusted OR = 1.67 [95% CI: 1.14,2.44]) than non-vegetarians after adjustment for potential confounding factors.

CONCLUSIONS:

Vegetarian men have more depressive symptoms after adjustment for socio-demographic factors. Nutritional deficiencies (e.g. in cobalamin or iron) are a possible explanation for these findings, however reverse causation cannot be ruled out.

KEYWORDS:

Cobalamin; Depression; Fathers; Nutritional psychiatry; Vegetarian

 

The effects of phenylalanine on exercise-induced fat oxidation: a preliminary, double-blind, placebo-controlled, crossover trial.

Ueda K, Sanbongi C, Yamaguchi M, Ikegami S, Hamaoka T, Fujita S.

J Int Soc Sports Nutr. 2017 Sep 12;14:34. doi: 10.1186/s12970-017-0191-x. eCollection 2017.

PMID: 28919843

Abstract

BACKGROUND:

When combined with exercise, dietary amino acid (AA) supplementation is an effective method for accelerating fat mobilization. However, the effects of single AAs combined with exercise on fat oxidation remains unclear. We hypothesized that consumption of a specific amino acid, L- phenylalanine, may result in the secretion of glucagon, and when combined with exercise may promote fat oxidation.

METHODS:

Six healthy, active male volunteers were randomized in a crossover study to ingest either phenylalanine (3 g/dose) or placebo. Thirty minutes after ingestion each subject performed workload trials on a cycle ergometer for 1 h at 50% of maximal oxygen consumption.

RESULTS:

Oral intake of phenylalanine caused a significant increase in the concentrations of plasma glycerol and glucagon during exercise. The respiratory exchange ratio was also decreased significantly following ingestion of phenylalanine.

CONCLUSION:

These results suggested that pre-exercise supplementation of phenylalanine may stimulate whole body fat oxidation. No serious or study-related adverse events were observed.

KEYWORDS:

Amino acid; Hormones; Metabolism; Pre-exercise nutrition

 

Low-fat Dietary Pattern and Pancreatic Cancer Risk in the Women's Health Initiative Dietary Modification Randomized Controlled Trial.

Jiao L, Chen L, White DL, Tinker L, Chlebowski RT, Van Horn LV, Richardson P, Lane D, Sangi-Haghpeykar H, El-Serag HB.

J Natl Cancer Inst. 2018 Jan 1;110(1). doi: 10.1093/jnci/djx117.

PMID: 28922784

Abstract

BACKGROUND:

Observational studies suggest that diet may influence pancreatic cancer risk. We investigated the effect of a low-fat dietary intervention on pancreatic cancer incidence.

METHODS:

The Women's Health Initiative Dietary Modification (WHI-DM) trial is a randomized controlled trial conducted in 48 835 postmenopausal women age 50 to 79 years in the United States between 1993 and 1998. Women were randomly assigned to the intervention group (n = 19 541), with the goal of reducing total fat intake and increasing intake of vegetables, fruits, and grains, or to the usual diet comparison group (n = 29 294). The intervention concluded in March 2005. We evaluated the effect of the intervention on pancreatic cancer incidence with the follow-up through 2014 using the log-rank test and multivariable Cox proportional hazards regression model. All statistical tests were two-sided.

RESULTS:

In intention-to-treat analyses including 46 200 women, 92 vs 165 pancreatic cancer cases were ascertained in the intervention vs the comparison group (P = .23). The multivariable hazard ratio (HR) of pancreatic cancer was 0.86 (95% confidence interval [CI] = 0.67 to 1.11). Risk was statistically significantly reduced among women with baseline body mass indexes (BMIs) of 25 kg/m2 or higher (HR = 0.71, 95% CI = 0.53 to 0.96), but not among women with BMIs of less than 25 kg/m2 (HR = 1.62, 95% CI = 0.97 to 2.71, Pinteraction = .01).

CONCLUSIONS:

A low-fat dietary intervention was associated with reduced pancreatic cancer incidence in women who were overweight or obese in the WHI-DM trial. Caution needs to be taken in interpreting the findings based on subgroup analyses.

 

Fructooligosaccharide (FOS) and Galactooligosaccharide (GOS) Increase Bifidobacterium but Reduce Butyrate Producing Bacteria with Adverse Glycemic Metabolism in healthy young population.

Liu F, Li P, Chen M, Luo Y, Prabhakar M, Zheng H, He Y, Qi Q, Long H, Zhang Y, Sheng H, Zhou H.

Sci Rep. 2017 Sep 18;7(1):11789. doi: 10.1038/s41598-017-10722-2.

PMID: 28924143

Abstract

The gut microbiota has been implicated in glucose intolerance and its progression towards type-2 diabetes mellitus (T2DM). Relevant randomized clinical trial with prebiotic intervention was inadequate. We sought to evaluate the impact of fructooligosaccharides (FOS) and galactooligosaccharides (GOS) on glycemia during oral glucose tolerance test (OGTT) and intestinal microbiota. A randomized double-blind cross-over study was performed with 35 adults treated with FOS and GOS for 14 days (16 g/day). Faeces sampling, OGTT and anthropometric parameters were performed. Short-term intake of high-dose prebiotics had adverse effect on glucose metabolism, as in FOS intervention demonstrated by OGTT (P < 0.001), and in GOS intervention demonstrated by fasting glucose (P < 0.05). A significant increase in the relative abundance of Bifidobacterium was observed both in FOS and GOS group, while the butyrate-producing bacteria like Phascolarctobacterium in FOS group and Ruminococcus in GOS group were decreased. A random forest model using the initial microbiota was developed to predict OGTT levels after prebiotic intervention with relative success (R = 0.726). Our study alerted even though FOS and GOS increased Bifidobacterium, they might have adverse effect on glucose metabolism by reducing butyrate-producing microbes. Individualized prebiotics intervention based on gut microbiome needs to be evaluated in future.

 

Longitudinal Association of Sleep Duration with Depressive Symptoms among Middle-aged and Older Chinese.

Li Y, Wu Y, Zhai L, Wang T, Sun Y, Zhang D.

Sci Rep. 2017 Sep 18;7(1):11794. doi: 10.1038/s41598-017-12182-0.

PMID: 28924238

Abstract

This study aimed to evaluate the associations of nighttime sleep duration and midday napping with risk of depressive symptoms incidence and persistence among middle-aged and older Chinese. Data from China Health and Retirement Longitudinal Study, CHARLS (2011-2013), were analyzed. Depressive symptoms were identified by the 10-item version of the Centre for Epidemiological Studies Depression scale (CESD-10). Multivariate binary logistic regression models were fitted. There were 7156 individuals with CESD-10 scores < 10 and 3896 individuals with CESD-10 scores ≥ 10 at baseline included in this study. After controlling for potential covariates, nighttime sleep duration <6 hours was associated with high risk of incident depressive symptoms (OR = 1.450, 95%CI: 1.193, 1.764 for middle aged population, and OR = 2.084, 95%CI:1.479, 2.936 for elderly) and persistent depressive symptoms (OR = 1.404, 95%CI: 1.161, 1.699 for middle aged population, and OR = 1.365, 95%CI: 0.979, 1.904 for elderly). For depressed individuals, longer midday napping (≥60 minutes) was associated with lower persistent depressive symptoms (OR = 0.842, 95%CI: 0.717, 0.989). Our study concluded that short nighttime sleep duration was an independent risk factor of depressive symptoms incidence and persistence. Depressed individuals with long midday napping were more likely to achieve reversion than those who have no siesta habit.

 

Postprandial Glucose Surges after Extremely Low Carbohydrate Diet in Healthy Adults.

Kanamori K, Ihana-Sugiyama N, Yamamoto-Honda R, Nakamura T, Sobe C, Kamiya S, Kishimoto M, Kajio H, Kawano K, Noda M.

Tohoku J Exp Med. 2017;243(1):35-39. doi: 10.1620/tjem.243.35.

PMID: 28924074

Abstract

Carbohydrate-restricted diets are prevalent not only in obese people but also in the general population to maintain appropriate body weight. Here, we report that extreme carbohydrate restriction for one day affects the subsequent blood glucose levels in healthy adults. Ten subjects (median age 30.5 years, BMI 21.1 kg/m2, and HbA1c 5.5%), wearing with a continuous glucose monitoring device, were given isoenergetic test meals for 4 consecutive days. On day 1, day 2 (D2), and day 4 (D4), they consumed normal-carbohydrate (63-66% carbohydrate) diet, while on day 3, they took low-carbohydrate/high-fat (5% carbohydrate) diet. The daily energy intake was 2,200 kcal for males and 1,700 kcal for females. On D2 and D4, we calculated the mean 24-hr blood glucose level (MEAN/24h) and its standard deviation (SD/24h), the area under the curve (AUC) for glucose over 140 mg/dL within 4 hours after each meal (AUC/4h/140), the mean amplitude of the glycemic excursions (MAGE), the incremental AUC of 24-hr blood glucose level above the mean plus one standard deviation (iAUC/MEAN+SD). Indexes for glucose fluctuation on D4 were significantly greater than those on D2 (SD/24h; p = 0.009, MAGE; p = 0.013, AUC/4h/140 after breakfast and dinner; p = 0.006 and 0.005, and iAUC/MEAN+SD; p = 0.007). The value of MEAN/24h and AUC/4h/140 after lunch on D4 were greater than those on D2, but those differences were not statistically significant. In conclusion, consumption of low-carbohydrate/high-fat diet appears to cause higher postprandial blood glucose on subsequent normal-carbohydrate diet particularly after breakfast and dinner in healthy adults.

KEYWORDS:

continuous glucose monitoring system; glucose fluctuations; insulin resistance; low carbohydrate diet; postprandial hyperglycemia

 

Red and processed meat intake and cancer risk: Results from the prospective NutriNet-Santé cohort study.

Diallo A, Deschasaux M, Latino-Martel P, Hercberg S, Galan P, Fassier P, Allès B, Guéraud F, Pierre FH, Touvier M.

Int J Cancer. 2017 Sep 15. doi: 10.1002/ijc.31046. [Epub ahead of print]

PMID: 28913916

http://sci-hub.cc/10.1002/ijc.31046

Abstract

The International Agency for Research on Cancer (WHO-IARC) classified red meat and processed meat as probably carcinogenic and carcinogenic for humans, respectively. These conclusions were mainly based on studies concerning colorectal cancer, but scientific evidence is still limited for other cancer locations. In this study, we investigated the prospective associations between red and processed meat intakes and overall, breast, and prostate cancer risk. This prospective study included 61,476 men and women of the French NutriNet-Santé cohort (2009-2015) aged ≥35y and who completed at least 3 24h dietary records during the first year of follow-up. The risk of developing cancer was compared across sex-specific quintiles of red and processed meat intakes by multivariable Cox models. 1,609 first primary incident cancer cases were diagnosed during follow-up, among which 544 breast cancers and 222 prostate cancers. Red meat intake was associated with increased risk of overall cancers (HRQ5vs.Q1 =1.31 (1.10-1.55), Ptrend =0.01) and breast cancer (HRQ5vs.Q1 =1.83 (1.33-2.51), Ptrend =0.002). The latter association was observed in both premenopausal (HRQ5vs.Q1 =2.04 (1.03-4.06)) and postmenopausal women (HRQ5vs.Q1 =1.79 (1.26-2.55)). No association was observed between red meat intake and prostate cancer risk. Processed meat intake was relatively low in this study (cut-offs for the 5th quintile=46g/d in men and 29g/d in women) and was not associated with overall, breast or prostate cancer risk. This large cohort study suggested that red meat may be involved carcinogenesis at several cancer locations (other than colon-rectum), in particular breast cancer. These results are consistent with mechanistic evidence from experimental studies.

KEYWORDS:

breast cancer; processed meat; prospective study; prostate cancer; red meat

 

Effects of Anthocyanins on Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Yang L, Ling W, Du Z, Chen Y, Li D, Deng S, Liu Z, Yang L.

Adv Nutr. 2017 Sep 15;8(5):684-693. doi: 10.3945/an.116.014852. Print 2017 Sep. Review.

PMID: 28916569

Abstract

Numerous clinical trials have examined the role of anthocyanins on cardiometabolic health, but their effects have not been quantitatively synthesized and systematically evaluated. The aim of our study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of anthocyanins on glycemic regulation and lipid profiles in both healthy populations and those with cardiometabolic diseases. The MEDLINE, EMBASE, Cochrane database, OVID EBM Reviews, and clinicaltrials.gov databases were searched until February 2017. RCTs with a duration of ≥2 wk that evaluated the effects of anthocyanins on glycemic control, insulin sensitivity, and lipids as either primary or secondary outcomes were included. The Cochrane Risk of Bias tool was used to assess the study quality. Standardized mean differences (SMDs) were determined by random-effects models. Meta-regression, sensitivity, and subgroup analyses were performed to explore the influence of covariates on the overall effects. Thirty-two RCTs (1491 participants) were eligible for meta-analysis. Anthocyanins significantly reduced fasting glucose (SMD: -0.31; 95% CI: -0.59, -0.04; I2 = 80.7%), 2-h postprandial glucose (SMD: -0.82; 95% CI: -1.49, -0.15; I2 = 77.7), glycated hemoglobin (SMD: -0.65; 95% CI: -1.00, -0.29; I2 = 72.7%), total cholesterol (SMD: -0.33; 95% CI: -0.62, -0.03; I2 = 86.9%), and LDL (SMD: -0.35; 95% CI: -0.66, -0.05; I2 = 85.2%). Sensitivity analyses showed that the overall effects remained similar by excluding the trials with a high or unclear risk of bias. The significant improvements in glycemic control and lipids support the benefits of anthocyanins in the prevention and management of cardiometabolic disease. Further well-designed RCTs are needed to evaluate the long-term effects of anthocyanins on metabolic profiles and to explore the optimal formula and dosage. The protocol for this review was registered at https://www.crd.york.ac.uk/PROSPERO/#index.phpas CRD42016033210.

KEYWORDS:

anthocyanins; cardiovascular disease; meta-analysis; randomized controlled trial; type 2 diabetes

 

https://en.wikipedia.org/wiki/Vaccenic_acid

Plasma trans-fatty acids levels and mortality: a cohort study based on 1999-2000 National Health and Nutrition Examination Survey (NHANES).

Li H, Zhang Q, Song J, Wang A, Zou Y, Ding L, Wen Y.

Lipids Health Dis. 2017 Sep 16;16(1):176. doi: 10.1186/s12944-017-0567-6.

PMID: 28915883

https://lipidworld.biomedcentral.com/articles/10.1186/s12944-017-0567-6

https://lipidworld.biomedcentral.com/track/pdf/10.1186/s12944-017-0567-6?site=lipidworld.biomedcentral.com

Abstract

BACKGROUND:

Trans-fatty acids (TFAs) occur in small amounts in nature but became widely produced by the food industry. The hazardous effects of different TFA subtypes to human health are controversial. We aimed to evaluate the association of plasma TFAs levels (elaidic acid, vaccenic acid, palmitelaidic acid, and linoelaidic acid) with mortality.

METHODS:

Utilizing 1999-2000 Nutrition Examination Survey (NHANES) and linked mortality data, we performed a cohort study with 1456 participants and used Cox proportional hazards models and penalized smoothing spline plots to elucidate the relationships between TFAs and all-cause, cardiovascular diseases (CVD) and cancer mortality.

RESULTS:

During 16,034 person-years of follow-up, a total of 221 deaths occurred. In the multivariate model, including mutual adjustment for the 4 TFA subtypes, elaidic acid associated with higher all-cause mortality (hazard ratio (HR) = 2.00, 95% confidence interval (CI) = 1.18 to 3.40, fourth quartiles versus second quartiles) and CVD mortality (HR = 1.64, 95% CI = 1.07 to 2.50, per 10 units increase). Higher palmitelaidic acid levels were associated with increased cancer mortality (HR = 2.91, 95% CI = 1.09 to 7.81, fourth quartiles versus second quartiles). A J-shaped pattern was observed in the regression curve of elaidic acid and all-cause mortality, as well palmitelaidic acid and cancer mortality.

CONCLUSIONS:

Plasma elaidic acid levels are associated with higher risk of all-cause and CVD mortality, and palmitelaidic acid levels are associated with higher cancer mortality in later life. Further studies are needed to investigate current inconsistent results in this field and the possible underlying mechanisms.

KEYWORDS:

Cancer; Cardiovascular diseases; Mortality; Trans-fatty acids

 

Adherence to a Mediterranean diet is associated with lower incidence of frailty: A longitudinal cohort study.

Veronese N, Stubbs B, Noale M, Solmi M, Rizzoli R, Vaona A, Demurtas J, Crepaldi G, Maggi S.

Clin Nutr. 2017 Sep 4. pii: S0261-5614(17)30311-4. doi: 10.1016/j.clnu.2017.08.028. [Epub ahead of print]

PMID: 28918168

Abstract

BACKGROUND & AIMS:

There is a paucity of data investigating the relationship between the Mediterranean diet and frailty, with no data among North American people. We aimed to investigate if adherence to a Mediterranean diet is associated with a lower incidence of frailty in a large cohort of North American people.

METHODS:

This study included subjects at higher risk or having knee osteoarthritis. Adherence to the Mediterranean diet was evaluated using a validated Mediterranean diet score (aMED) as proposed by Panagiotakos and classified into five categories. Frailty was defined using the Study of Osteoporotic Fracture (SOF) index as the presence of ≥2 out of: (i) weight loss ≥5% between baseline and the subsequent follow-up visit; (ii) inability to do five chair stands; (iii) low energy level.

RESULTS:

During the 8 years follow-up, of the 4421 participants initially included (mean age: 61.2 years, % of females = 58.0), the incidence of frailty was approximately half in those with a higher adherence to the Mediterranean diet (8 for 1000 person years) vs. those with a lower adherence (15 for 1000 persons-years). After adjusting for 10 potential confounders (age, sex, race, body mass index, education, smoking habits, yearly income, physical activity level, Charlson co-morbidity index and daily energy intake), participants with the highest aMED scores were found to have a significant reduction in incident frailty (hazard ratio = 0.71; 95% CIs: 0.50-0.99, p = 0.047) with respect to those in a lower category. Regarding individual components of the Mediterranean diet, low consumption of poultry was found to be associated with higher risk of frailty.

CONCLUSIONS:

A higher adherence to a Mediterranean diet was associated with a lower incidence of frailty over an 8-year follow-up period, even after adjusting for potential confounders.

KEYWORDS:

Frailty; Mediterranean diet; Older people; Osteoarthritis initiative

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The Scientist » News & Opinion » News Analysis

Publishers’ Legal Action Advances Against Sci-Hub

The pirate site plans to ignore the lawsuits from Elsevier and the American Chemical Society.

By Diana Kwon | September 19, 2017

http://www.the-scientist.com/?articles.view/articleNo/50361/title/Publishers--Legal-Action-Advances-Against-Sci-Hub/&utm_campaign=NEWSLETTER_TS_The-Scientist-Daily_2016&utm_source=hs_email&utm_medium=email&utm_content=56518498&_hsenc=p2ANqtz--CT9vtznynl9brYNrTrTbflM6GlK4hX_3S8tzBSX5BHWT4WrvE5AMscpIC8ROUXpdp3FVYnStA1053PSjFku1Mo1o1TA&_hsmi=56518498

 

The role of methionine on metabolism, oxidative stress, and diseases.

Martínez Y, Li X, Liu G, Bin P, Yan W, Más D, Valdivié M, Hu CA, Ren W, Yin Y.

Amino Acids. 2017 Sep 19. doi: 10.1007/s00726-017-2494-2. [Epub ahead of print] Review.

PMID: 28929442

http://sci-hub.cc/10.1007/s00726-017-2494-2

Abstract

Methionine is an aliphatic, sulfur-containing, essential amino acid, and a precursor of succinyl-CoA, homocysteine, cysteine, creatine, and carnitine. Recent research has demonstrated that methionine can regulate metabolic processes, the innate immune system, and digestive functioning in mammals. It also intervenes in lipid metabolism, activation of endogenous antioxidant enzymes such as methionine sulfoxide reductase A, and the biosynthesis of glutathione to counteract oxidative stress. In addition, methionine restriction prevents altered methionine/transmethylation metabolism, thereby decreasing DNA damage and carcinogenic processes and possibly preventing arterial, neuropsychiatric, and neurodegenerative diseases. This review focuses on the role of methionine in metabolism, oxidative stress, and related diseases.

KEYWORDS:

Cancer; Disease; Endogenous antioxidant enzyme; Mammalian; Methionine; ROS

 

Gender differences in longevity in free-living older adults who eat-with-others: a prospective study in Taiwan.

Huang YC, Cheng HL, Wahlqvist ML, Lo YC, Lee MS.

BMJ Open. 2017 Sep 18;7(9):e016575. doi: 10.1136/bmjopen-2017-016575.

PMID: 28928182

http://bmjopen.bmj.com/content/7/9/e016575

http://bmjopen.bmj.com/content/bmjopen/7/9/e016575.full.pdf

Abstract

OBJECTIVES:

Social activities such as 'eating-with-others' can positively affect the ageing process. We investigated the gender-specific association between eating arrangements and risk of all-cause mortality among free-living older adults.

SETTING:

A representative sample from the Elderly Nutrition and Health Survey in Taiwan during 1999-2000.

PARTICIPANTS:

Some 1894 participants (955 men and 939 women) who aged ≥65 and completed eating arrangement question as well as confirmed survivorship information.

PRIMARY AND SECONDARY OUTCOME MEASURES:

Eating arrangements, health condition and 24-hour dietary recall information were collected at baseline. We classified eating arrangements as the daily frequency of eating-with-others (0-3). Survivorship was determined by the National Death Registry until the end of 2008. Cox proportional-hazards regression was used to assess the association between eating-with-others and mortality risk.

RESULTS:

Overall, 63.1% of men and 56.4% of women ate with others three times a day. Both men and women who ate with others were more likely to have higher meat and vegetable intakes and greater dietary quality than those who ate alone. The HRs (95% CI) for all-cause mortality when eating-with-others two and three times per day were 0.42 (0.28 to 0.61), 0.67 (0.52 to 0.88) in men and 0.68 (0.42 to 1.11), 0.86 (0.64 to 1.16) in women, compared with those who ate alone. Multivariable HRs (95% CI) adjusted for sociodemographic, nutritional and 'activities of daily living' covariates were 0.43 (0.25 to 0.73), 0.63 (0.41 to 0.98) in men and 0.68 (0.35 to 1.30), 0.69 (0.39 to 1.21) in women. With further adjustment for financial status, HR was reduced by 54% in men who ate with others two times a day. Pathway analysis shows this to be dependent on improved dietary quality by eating-with-others.

CONCLUSIONS:

Eating-with-others is an independent survival factor in older men. Providing a social environment which encourages eating-with-others may benefit survival of older people, especially for men.

KEYWORDS:

diet; elderly; mortality; social activities

 

Leukocyte telomere length, T cell composition and DNA methylation age.

Chen BH, Carty CL, Kimura M, Kark JD, Chen W, Li S, Zhang T, Kooperberg C, Levy D, Assimes T, Absher D, Horvath S, Reiner AP, Aviv A.

Aging (Albany NY). 2017 Sep 20. doi: 10.18632/aging.101293. [Epub ahead of print]

PMID: 28930701

Abstract

Both leukocyte telomere length (LTL) and DNA methylation age are strongly associated with chronological age. One measure of DNA methylation age─ the extrinsic epigenetic age acceleration (EEAA)─ is highly predictive of all-cause mortality. We examined the relation between LTL and EEAA. LTL was measured by Southern blots and leukocyte DNA methylation was determined using Illumina Infinium HumanMethylation450 BeadChip in participants in the Women's Health Initiative (WHI; n=804), the Framingham Heart Study (FHS; n=909) and the Bogalusa Heart study (BHS; n=826). EEAA was computed using 71 DNA methylation sites, further weighted by proportions of naïve CD8+ T cells, memory CD8+ T cells, and plasmablasts. Shorter LTL was associated with increased EEAA in participants from the WHI (r=-0.16, p=3.1x10-6). This finding was replicated in the FHS (r=-0.09, p=6.5x10-3) and the BHS (r=-0.07, p=3.8x 10-2). LTL was also inversely related to proportions of memory CD8+ T cells (p=4.04x10-16) and positively related to proportions of naive CD8+ T cells (p=3.57x10-14). These findings suggest that for a given age, an individual whose blood contains comparatively more memory CD8+ T cells and less naive CD8+ T cells would display a relatively shorter LTL and an older DNA methylation age, which jointly explain the striking ability of EEAA to predict mortality.

KEYWORDS:

DNA methylation; T cells; aging; memory; naïve; telomeres

 

Testosterone Protects High Fat/Low Carbohydrate Diet Induced Non-Alcoholic Fatty Liver Disease in Castrated Male Rats Mainly via Modulating ER Stress.

Jia Y, Yee JK, Wang C, Nikolaenko L, Diaz-Arjonilla M, Cohen JN, French SW, Liu PY, Lue Y, Lee WP, Swerdloff RS.

Am J Physiol Endocrinol Metab. 2017 Sep 19:ajpendo.00124.2017. doi: 10.1152/ajpendo.00124.2017. [Epub ahead of print]

PMID: 28928235

http://sci-hub.cc/10.1152/ajpendo.00124.2017

Abstract

We previously showed that testosterone (T) deficiency enhanced high-fat diet (HFD) induced hepatic steatosis in rats that was independent of insulin resistance, and that T replacement reduced hepatic macrovesicular fat accumulation and inflammation. The present report explores the mechanism of T-protective effects on HFD-induced steatohepatitis. Adult male rats were randomized into four treatment groups for 15 weeks (intact rats on regular chow diet or HFD, and castrated rats on HFD with/without T replacement). Fatty acid β oxidation and de novo synthesis were not changed by castration and T replacement, but expressions of lipid export proteins ApoB100 and microsomal triglyceride transfer protein (MTP) were suppressed by HFD in both intact and castrated rats and restored by T replacement. Macrovesicular lipid droplet-related proteins perilipin 1 and fat-specific protein 27 were increased by HFD in castrated rats and suppressed by T replacement. Higher activation/expression of ER stress proteins [PERK, IRE-1α, JNK, NF-κB, and CHOP] were demonstrated in castrated rats fed HFD compared to intact animals, and T replacement suppressed these changes. We conclude that 1) HFD leads to ApoB100/MTP suppression reducing export of lipids; 2) Castration promotes progression to steatohepatitis through activation of the ER stress pathway and enhancement of macrovesicular droplet protein expression; 3) Testosterone suppresses ER stress, inhibits the formation of macrovesicular lipid droplets, promotes lipid export, and ameliorates steatohepatitis induced by HFD and castration.

KEYWORDS:

ER stress; Lipogenesis; hepatic steatosis; lipid droplet; testosterone deficiency

 

Capsaicin Supplementation Improved Risk Factors of Coronary Heart Disease in Individuals with Low HDL-C Levels.

Qin Y, Ran L, Wang J, Yu L, Lang HD, Wang XL, Mi MT, Zhu JD.

Nutrients. 2017 Sep 20;9(9). pii: E1037. doi: 10.3390/nu9091037.

PMID: 28930174

http://www.mdpi.com/2072-6643/9/9/1037/htm

Abstract

Low high-density lipoprotein cholesterol (HDL-C) is associated with an increased risk of coronary heart disease (CHD). This study aimed to evaluate the effects of capsaicin intervention on the serum lipid profile in adults with low HDL-C. In a randomized, double-blind, controlled clinical trial, 42 eligible subjects were randomly assigned to the capsaicin (n = 21, 4 mg of capsaicin daily) or to the control group (n = 21, 0.05 mg of capsaicin daily) and consumed two capsaicin or control capsules, which contained the powder of the skin of different peppers, twice daily for three months. Thirty-five subjects completed the trial (18 in the capsaicin group and 17 in the control group). The baseline characteristics were similar between the two groups. Compared with the control group, fasting serum HDL-C levels significantly increased to 1.00 ± 0.13 mmol/L from 0.92 ± 0.13 mmol/L in the capsaicin group (p = 0.030), while levels of triglycerides and C-reactive protein and phospholipid transfer protein activity moderately decreased (all p < 0.05). Other lipids, apolipoproteins, glucose, and other parameters did not significantly change. In conclusion, capsaicin improved risk factors of CHD in individuals with low HDL-C and may contribute to the prevention and treatment of CHD.

KEYWORDS:

anti-inflammatory; capsaicin; clinical trial; lipids; low high-density lipoprotein cholesterol; phospholipid transfer protein

 

Nutritional risk, hospitalization and mortality among community-dwelling Canadians aged 65 or older.

Ramage-Morin PL, Gilmour H, Rotermann M.

Health Rep. 2017 Sep 20;28(9):17-27.

PMID: 28930364

http://www.statcan.gc.ca/pub/82-003-x/2017009/article/54856-eng.htm

http://www.statcan.gc.ca/pub/82-003-x/2017009/article/54856-eng.pdf

Abstract

BACKGROUND:

Nutritional risk has been associated with various negative health outcomes among older people. Limited longitudinal research has examined the relationship between nutritional risk and hospitalization and death in community-dwelling older people.

DATA AND METHODS:

Data from the 2008/2009 Canadian Community Health Survey-Healthy Aging (CCHS-HA) linked to the Discharge Abstract Database and the Canadian Mortality Database were used to estimate the prevalence of nutritional risk among seniors and examine its relationship with acute care hospitalization and death during the 25- to 36-month period following the CCHS-HA interview. Multivariate Cox proportional hazards models were used to identify important covariates, while adjusting for demographic and socioeconomic characteristics, health status, and lifestyle factors.

RESULTS:

A third (34%; 979,000) of Canadians aged 65 or older living in 9 provinces (excluding Quebec) were at nutritional risk in 2008/2009. These seniors had a higher risk of an acute care hospitalization (hazard ratio (HR) 1.2; 95% CI: 1.1 to 1.4) or death (HR 1.6; 95% CI: 1.3 to 2.0) during the follow-up period, even when potential confounders were taken into account. Seniors at nutritional risk in 2008/2009 were more likely than those not at nutritional risk to die during follow-up (9% versus 5%) and averaged shorter survival times: 498 days (95% CI: 462 to 534) compared with 538 days (95% CI: 501 to 574).

INTERPRETATION:

Based on an analysis of data from a large population-based survey linked to routinely collected hospital and death data, nutritional risk is independently associated with acute care hospitalization and mortality. Results highlight the importance of monitoring seniors for nutritional risk.

KEYWORDS:

Data linkage; diet; eating; food intake; malnutrition; morbidity; nutrition assessment; seniors

 

Circulating MicroRNA Are Predictive of Aging and Acute Adaptive Response to Resistance Exercise in Men.

Margolis LM, Lessard SJ, Ezzyat Y, Fielding RA, Rivas DA.

J Gerontol A Biol Sci Med Sci. 2017 Oct 1;72(10):1319-1326. doi: 10.1093/gerona/glw243.

PMID: 27927764

Abstract

Circulating microRNA (c-miRNA) have the potential to function as novel noninvasive markers of the underlying physiological state of skeletal muscle. This investigation sought to determine the influence of aging on c-miRNA expression at rest and following resistance exercise in male volunteers (Young: n = 9; Older: n = 9). Primary findings were that fasting c-miRNA expression profiles were significantly predictive of aging, with miR-19b-3p, miR-206, and miR-486 distinguishing between age groups. Following resistance exercise, principal component analysis revealed a divergent response in expression of 10 c-miRNA, where expression profiles were upregulated in younger and downregulated in older participants. Using Ingenuity Pathway Analysis to test c-miRNA-to-mRNA interactions in skeletal muscle, it was found that response of c-miRNA to exercise was indicative of an anabolic response in younger but not older participants. These findings were corroborated with a positive association observed with the phosphorylation status of p-AktSer473 and p-S6K1Thr389 and expression of miR-19a-3p, miR-19b-3p, miR-20a-5p, miR-26b-5p, miR-143-3p, and miR-195-5p. These important findings provide compelling evidence that dysregulation of c-miRNA expression with aging may not only serve as a predictive marker, but also reflect underlying molecular mechanisms resulting in age-associated declines in skeletal muscle mass, increased fat mass, and "anabolic resistance."

KEYWORDS:

Anabolic resistance; miR-19b-3p; miR-206; miR-486

 

Replication of Genome-Wide Association Study Findings of Longevity in White, African American, and Hispanic Women: The Women's Health Initiative.

Shadyab AH, Kooperberg C, Reiner AP, Jain S, Manson JE, Hohensee C, Macera CA, Shaffer RA, Gallo LC, LaCroix AZ.

J Gerontol A Biol Sci Med Sci. 2017 Oct 1;72(10):1401-1406. doi: 10.1093/gerona/glw198.

PMID: 27707806

Abstract

BACKGROUND:

No study has evaluated whether genetic factors are associated with longevity in African Americans or Hispanics, and it is unclear whether genetic factors are associated with healthy aging.

METHODS:

In this prospective study, we determined whether 14 genetic variants previously associated with longevity in genome-wide association studies were associated with survival to ages 85 and 90 in 11,053 postmenopausal white, African American, and Hispanic women from the Women's Health Initiative. The associations of these variants with healthy aging, defined as survival to age 85 without chronic diseases or disability, were also determined.

RESULTS:

Among white women, three single nucleotide polymorphisms (SNPs) (rs2075650 [TOMM40], rs4420638 [APOC1], and rs429358 [APOE]) were significantly associated with survival to 90 years after correction for multiple testing (p < .001); rs4420638 and rs429358 were also significantly associated with healthy aging (p = .02). In African American women, no SNP was associated with longevity. In Hispanic women, 7 SNPs in linkage disequilibrium with a novel SNP, rs2149954, recently identified as being associated with increased longevity in a European population, were significantly associated with decreased survival to age 85 for carriers of the T versus C allele (p = .04). The association with decreased longevity was explained by higher risk of coronary heart disease in carriers of the T allele. There were no associations between FOXO3A SNPs and longevity in the analyses. In a meta-analysis, rs2075650 and rs429358 were significantly associated with longevity.

CONCLUSIONS:

Future studies are needed to identify novel loci associated with longevity in African American and Hispanic women to determine biologic pathways regulating life span in these groups.

 

Low Lean Mass With and Without Obesity, and Mortality: Results From the 1999-2004 National Health and Nutrition Examination Survey.

Batsis JA, Mackenzie TA, Emeny RT, Lopez-Jimenez F, Bartels SJ.

J Gerontol A Biol Sci Med Sci. 2017 Oct 1;72(10):1445-1451. doi: 10.1093/gerona/glx002.

PMID: 28207042

Abstract

BACKGROUND:

The Foundation for the NIH Sarcopenia Project validated cutpoints for appendicular lean mass. We ascertained the relationship between low lean mass (LLM), obesity, and mortality and identified predictors in this subgroup.

METHODS:

A total of 4,984 subjects aged 60 years and older were identified from the National Health and Nutrition Examination Survey 1999-2004 linked to the National Death Index. LLM was defined using reduced appendicular lean mass (men < 19.75 kg; females < 15.02 kg). Obesity was defined using dual-energy x-ray absorptiometry body fat (males ≥ 25%; females ≥ 35%). LLM with obesity was defined using criteria for both LLM and obesity. Proportional hazard models determined mortality risk for LLM and LLM with obesity, separately (referent = no LLM and no LLM with obesity, respectively).

RESULTS:

Mean age was 71.1 ± 0.19 years (56.5% female). Median follow-up was 102 months (interquartile range: 78, 124) with 1,901 deaths (35.0%). Prevalence of LLM with obesity was 33.5% in females and 12.6% in males. In those with LLM, overall mortality risk was 1.49 (1.27, 1.73) in males and 1.19 (1.02, 1.40) in females. Mortality risk in LLM with obesity was 1.31 (1.11, 1.55) and 0.99 (0.85, 1.16) in males and females, respectively. Age, diabetes, history of stroke, congestive heart failure, cancer, and kidney disease were predictive of death.

CONCLUSIONS:

Risk of death is higher in subjects with LLM than with LLM and obesity. Having advanced age, diabetes, stroke, heart failure, cancer, and renal disease predict a worse prognosis in both classifications.

KEYWORDS:

Epidemiology; Low lean mass; Survival

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Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia.

Wahl D, Coogan SC, Solon-Biet SM, de Cabo R, Haran JB, Raubenheimer D, Cogger VC, Mattson MP, Simpson SJ, Le Couteur DG.

Clin Interv Aging. 2017 Sep 8;12:1419-1428. doi: 10.2147/CIA.S145247. eCollection 2017. Review.

PMID: 28932108

https://www.dovepress.com/cognitive-and-behavioral-evaluation-of-nutritional-interventions-in-ro-peer-reviewed-fulltext-article-CIA

Abstract

Evaluation of behavior and cognition in rodent models underpins mechanistic and interventional studies of brain aging and neurodegenerative diseases, especially dementia. Commonly used tests include Morris water maze, Barnes maze, object recognition, fear conditioning, radial arm water maze, and Y maze. Each of these tests reflects some aspects of human memory including episodic memory, recognition memory, semantic memory, spatial memory, and emotional memory. Although most interventional studies in rodent models of dementia have focused on pharmacological agents, there are an increasing number of studies that have evaluated nutritional interventions including caloric restriction, intermittent fasting, and manipulation of macronutrients. Dietary interventions have been shown to influence various cognitive and behavioral tests in rodents indicating that nutrition can influence brain aging and possibly neurodegeneration.

KEYWORDS:

aging; calorie restriction; intermittent fasting; macronutrients; memory

 

Serum magnesium is associated with the risk of dementia.

Kieboom BCT, Licher S, Wolters FJ, Ikram MK, Hoorn EJ, Zietse R, Stricker BH, Ikram MA.

Neurology. 2017 Sep 20. pii: 10.1212/WNL.0000000000004517. doi: 10.1212/WNL.0000000000004517. [Epub ahead of print]

PMID: 28931641

Abstract

OBJECTIVE:

To determine if serum magnesium levels are associated with the risk of all-cause dementia and Alzheimer disease.

METHODS:

Within the prospective population-based Rotterdam Study, we measured serum magnesium levels in 9,569 participants, free from dementia at baseline (1997-2008). Participants were subsequently followed up for incident dementia, determined according to the DSM-III-R criteria, until January 1, 2015. We used Cox proportional hazard regression models to associate quintiles of serum magnesium with incident all-cause dementia. We used the third quintile as a reference group and adjusted for age, sex, Rotterdam Study cohort, educational level, cardiovascular risk factors, kidney function, comorbidities, other electrolytes, and diuretic use.

RESULTS:

Our study population had a mean age of 64.9 years and 56.6% were women. During a median follow-up of 7.8 years, 823 participants were diagnosed with all-cause dementia. Both low serum magnesium levels (≤0.79 mmol/L) and high serum magnesium levels (≥0.90 mmol/L) were associated with an increased risk of dementia (hazard ratio {HR} 1.32, 95% confidence interval [CI] 1.02-1.69, and HR 1.30, 95% CI 1.02-1.67, respectively).

CONCLUSIONS:

Both low and high serum magnesium levels are associated with an increased risk of all-cause dementia. Our results warrant replication in other population-based studies.

 

Serum phosphorus levels and risk of incident dementia.

Li T, Xie Y, Bowe B, Xian H, Al-Aly Z.

PLoS One. 2017 Feb 2;12(2):e0171377. doi: 10.1371/journal.pone.0171377. eCollection 2017.

PMID: 28152028 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289565/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289565/pdf/pone.0171377.pdf

Abstract

Higher serum phosphorous is associated with cerebral small vessel disease, an important driver of cognitive decline and dementia. Whether serum phosphorous, a potentially modifiable parameter, associates with risk of incident dementia is not known. We aimed to examine the association between serum phosphorous and risk of incident dementia and to determine if the association is modified by age. We used the United States Department of Veterans Affairs national databases to build a longitudinal observational cohort of US veterans without prior history of dementia and with at least one outpatient serum phosphorus between October 2008 and September 2010 and followed them until September 2014. Serum phosphorus was categorized into quintiles: ≤2.9, >2.9 to ≤3.2, >3.2 to ≤3.5, >3.5 to ≤3.9, >3.9 mg/dL. There were 744,235 participants in the overall cohort. Over a median follow-up of 5.07 years (Interquartile range [iQR]: 4.28, 5.63), adjusted Cox models show that compared to quintile 2, the risk of incident dementia was increased in quintile 4 (Hazard Ratio {HR} = 1.05; CI = 1.01-1.10) and quintile 5 (HR = 1.14; CI = 1.09-1.20). In cohort participants ≤60 years old, the risk of incident dementia was increased in quintile 4 (HR = 1.29; CI = 1.12-1.49) and 5 (HR = 1.45; CI = 1.26-1.68). In participants > 60 years old, the risk was not significant in quintile 4, and was attenuated in quintile 5 (HR = 1.10; CI = 1.05-1.16). Formal interaction analyses showed that the association between phosphorous and dementia was more pronounced in those younger than 60, and attenuated in those older than 60 (P for interaction was 0.004 and <0.0001 in quintiles 4 and 5; respectively). We conclude that higher serum phosphorous is associated with increased risk of incident dementia. This association is stronger in younger cohort participants. The identification of serum phosphorous as a risk factor for incident dementia has public health relevance and might inform the design and implementation of risk reduction strategies.

 

Effects of resveratrol supplementation on risk factors of non-communicable diseases: A meta-analysis of randomized controlled trials.

Guo XF, Li JM, Tang J, Li D.

Crit Rev Food Sci Nutr. 2017 Sep 21:1-15. doi: 10.1080/10408398.2017.1349076. [Epub ahead of print]

PMID: 28933578

Abstract

The results of randomized controlled trials (RCTs) investigating resveratrol supplementation on risk factors of non-communicable diseases (NCDs) have been inconsistent. The present meta-analysis aimed to quantitatively evaluate the effects of resveratrol intervention on risk factors of NCDs. PubMed and Scopus databases were searched up to June 2017. Weighted mean differences were calculated for net changes in risk factors of NCDs by using a random-effects model. Pre-specified subgroup and univariate meta-regression analyses were carried out to explore the sources of heterogeneity. Twenty-nine studies (30 treatment arms) with 1069 participants were identified. Resveratrol supplementation significantly reduced the concentrations of fasting glucose (-4.77 mg/dL; 95% CI: -9.33 to -0.21 mg/dL; P = 0.040), total cholesterol (TC) (-9.75 mg/dL; 95% CI: -17.04 to -2.46 mg/dL; P = 0.009), and C-reactive protein (CRP) (-0.81 mg/L; 95% CI: -1.42 to -0.21 mg/L; P = 0.009). Resveratrol intervention exerted significant reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in subjects with type 2 diabetes mellitus (T2DM). Subgroup analysis also showed that the trials with resveratrol intervention ≥3 months significantly reduced the low-density lipoprotein cholesterol (LDL-C), DBP, and glycated hemoglobin (HbA1c) values. The results did not support that resveratrol intervention had favorable effects in altering high-density lipoprotein cholesterol (HDL-C), triglyceride (TAG), and homeostasis model assessment of insulin resistance (HOMA-IR). The present study provides substantial evidence that resveratrol supplementation has favorable effects on several risk factors of NCDs.

KEYWORDS:

Resveratrol; meta-analysis; non-communicable diseases; randomized controlled trial; risk factors

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Change in weight and body mass index associated with all-cause mortality in Korea: A nationwide longitudinal study.

Kim YH, Kim SM, Han KD, Son JW, Lee SS, Oh SW, Lee WY, Yoo SJ; Taskforce Team of the Obesity Fact Sheet of the Korean Society for the Study of Obesity.

J Clin Endocrinol Metab. 2017 Aug 24. doi: 10.1210/jc.2017-00787. [Epub ahead of print]

PMID: 28938403

Abstract

BACKGROUND:

Many studies have reported conflicting evidence on the association between weight change and mortality.

OBJECTIVE:

We investigated the association between weight change and subsequent all-cause mortality, using a large-scale population-based cohort from the National Health Insurance System health checkup data between 2005 and 2015.

METHODS:

A total of 11,524,763 subjects aged over 20 years were included. Weight was measured every two years and weight change over 4 years was divided into eight categories, from weight loss ≥15% to weight gain ≥20%, for every 5% of weight change. The hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were analyzed using multivariable Cox's proportional hazard models compared to the stable weight group (weight change < 5kg) after adjusting for age, sex, smoking, drinking, exercise, diabetes mellitus, hypertension, dyslipidemia, cancer, and income.

RESULTS:

Weight loss was associated with increased mortality than weight gain; the group with weight loss ≥15% had the highest HR for all-cause mortality (HR; 95% CI=2·598; 2·537-2·659). The HR for all-cause mortality in the ≥20% weight gain group was 1·784 (95% CI=1·695-1·877). Across all body mass index (BMI) categories, weight loss ≥15% was associated with increased mortality rates and the highest mortality rates were found in the BMI ≥30 kg/m2 group (HR; 95% CI=3·469; 2·236-5·381).

CONCLUSIONS:

Weight change over 4 years showed a reverse J-shaped all-cause mortality curve, independent of BMI status. Weight loss was associated with a greater risk of increased mortality than weight gain.

 

SEX DIFFERENCES IN THE HORMONAL AND METABOLIC RESPONSE TO DIETARY PROTEIN DILUTION.

Larson KR, Russo KA, Fang Y, Mohajerani N, Goodson ML, Ryan KK.

Endocrinology. 2017 Aug 9. doi: 10.1210/en.2017-00331. [Epub ahead of print]

PMID: 28938440

Abstract

Consumption of a low-protein, high-carbohydrate diet induces a striking increase in circulating fibroblast growth factor-21 (FGF21), which is associated with improved cardiometabolic health and increased longevity. Increased lifespan during this dietary protein 'dilution' has been explained by resource-mediated trade-offs between reproduction and survival, such that fecundity is optimized at a greater relative intake of proteins:carbohydrates. The magnitude of this trade-off is thought to be sex-dependent. Here, we tested the hypothesis that metabolic responses to dietary protein dilution are likewise dependent on sex. We maintained age-matched adult male and female C57Bl/6J mice on isocaloric diets containing 22% fat and differing in the ratio of protein: carbohydrate. 'Normal protein' (NP) control diet contained 18% protein and 60% carbohydrate by kcal. 'Protein diluted' (PD) diet contained 4% protein and 74% carbohydrate. Consistent with previous reports, PD males gained less weight and less fat than NP controls and exhibited both improved glucose tolerance and decreased plasma lipids. In contrast, these metabolic benefits were absent among age-matched females maintained on the same diets. Likewise, whereas circulating FGF21 was increased up to 66-fold among PD male mice, this was substantially blunted among female counterparts. Sex differences in energy balance, glucose control, and plasma FGF21 were reversed upon ovariectomy. Collectively, our findings support that female mice are relatively less sensitive to the metabolic improvements observed following dietary protein dilution. This is accompanied by blunted circulating levels of FGF21, and requires an intact female reproductive system.

 

Preventive Effects of Cocoa and Cocoa Antioxidants in Colon Cancer.

Martín MA, Goya L, Ramos S.

Diseases. 2016 Jan 22;4(1). pii: E6. doi: 10.3390/diseases4010006. Review.

PMID: 28933386

http://www.mdpi.com/2079-9721/4/1/6/htm

Abstract

Colorectal cancer is one of the main causes of cancer-related mortality in the developed world. Carcinogenesis is a multistage process conventionally defined by the initiation, promotion and progression stages. Natural polyphenolic compounds can act as highly effective antioxidant and chemo-preventive agents able to interfere at the three stages of cancer. Cocoa has been demonstrated to counteract oxidative stress and to have a potential capacity to interact with multiple carcinogenic pathways involved in inflammation, proliferation and apoptosis of initiated and malignant cells. Therefore, restriction of oxidative stress and/or prevention or delayed progression of cancer stages by cocoa antioxidant compounds has gained interest as an effective approach in colorectal cancer prevention. In this review, we look over different in vitro and in vivo studies that have identified potential targets and mechanisms whereby cocoa and their flavonoids could interfere with colonic cancer. In addition, evidence from human studies is also illustrated.

KEYWORDS:

cocoa flavonoids; colon cancer; in vitro and in vivo studies; molecular mechanism

 

Physical activity helps people worldwide

Boosting physical activity a simple, low-cost global strategy to reduce deaths globally

CBC News Posted: Sep 21, 2017

http://www.cbc.ca/news/health/physical-activity-pure-1.4301443

>>>>>>>>>>>>>>>>>>>

The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low-income countries: the PURE study

Dr Scott A Lear, PhD'Correspondence information about the author Dr Scott A LearEmail the author Dr Scott A Lear, Weihong Hu, MSc, Sumathy Rangarajan, MSc, Danijela Gasevic, PhD, Darryl Leong, PhD, Romaina Iqbal, PhD, Amparo Casanova, PhD, Sumathi Swaminathan, PhD, R M Anjana, PhD, Rajesh Kumar, MD, Annika Rosengren, MD, Li Wei, PhD, Wang Yang, MSc, Wang Chuangshi, MM, Liu Huaxing, Sanjeev Nair, MD, Rafael Diaz, MD, Hany Swidon, MD, Rajeev Gupta, MD, Noushin Mohammadifard, PhD, Patricio Lopez-Jaramillo, MD, Aytekin Oguz, MD, Katarzyna Zatonska, PhD, Pamela Seron, PhD, Alvaro Avezum, MD, Paul Poirier, MD, Koon Teo, MB, Salim Yusuf, DPhil

Lancet Published: 21 September 2017

DOI: http://dx.doi.org/10.1016/S0140-6736(17)31634-3

Summary

Background

Physical activity has a protective effect against cardiovascular disease (CVD) in high-income countries, where physical activity is mainly recreational, but it is not known if this is also observed in lower-income countries, where physical activity is mainly non-recreational. We examined whether different amounts and types of physical activity are associated with lower mortality and CVD in countries at different economic levels.

Methods

In this prospective cohort study, we recruited participants from 17 countries (Canada, Sweden, United Arab Emirates, Argentina, Brazil, Chile, Poland, Turkey, Malaysia, South Africa, China, Colombia, Iran, Bangladesh, India, Pakistan, and Zimbabwe). Within each country, urban and rural areas in and around selected cities and towns were identified to reflect the geographical diversity. Within these communities, we invited individuals aged between 35 and 70 years who intended to live at their current address for at least another 4 years. Total physical activity was assessed using the International Physical Activity Questionnaire (IPQA). Participants with pre-existing CVD were excluded from the analyses. Mortality and CVD were recorded during a mean of 6·9 years of follow-up. Primary clinical outcomes during follow-up were mortality plus major CVD (CVD mortality, incident myocardial infarction, stroke, or heart failure), either as a composite or separately. The effects of physical activity on mortality and CVD were adjusted for sociodemographic factors and other risk factors taking into account household, community, and country clustering.

Findings

Between Jan 1, 2003, and Dec 31, 2010, 168 916 participants were enrolled, of whom 141 945 completed the IPAQ. Analyses were limited to the 130 843 participants without pre-existing CVD. Compared with low physical activity (<600 metabolic equivalents [MET] × minutes per week or <150 minutes per week of moderate intensity physical activity), moderate (600–3000 MET × minutes or 150–750 minutes per week) and high physical activity (>3000 MET × minutes or >750 minutes per week) were associated with graded reduction in mortality (hazard ratio 0·80, 95% CI 0·74–0·87 and 0·65, 0·60–0·71; p<0·0001 for trend), and major CVD (0·86, 0·78–0·93; p<0·001 for trend). Higher physical activity was associated with lower risk of CVD and mortality in high-income, middle-income, and low-income countries. The adjusted population attributable fraction for not meeting the physical activity guidelines was 8·0% for mortality and 4·6% for major CVD, and for not meeting high physical activity was 13·0% for mortality and 9·5% for major CVD. Both recreational and non-recreational physical activity were associated with benefits.

Interpretation

Higher recreational and non-recreational physical activity was associated with a lower risk of mortality and CVD events in individuals from low-income, middle-income, and high-income countries. Increasing physical activity is a simple, widely applicable, low cost global strategy that could reduce deaths and CVD in middle age.

Funding

Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Ontario SPOR Support Unit, Ontario Ministry of Health and Long-Term Care, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, GSK, Novartis, King Pharma ...

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Over-the-counter mouthwash use and risk of pre-diabetes/diabetes.

Joshipura KJ, Muñoz-Torres FJ, Morou-Bermudez E, Patel RP.

Nitric Oxide. 2017 Sep 19. pii: S1089-8603(17)30153-2. doi: 10.1016/j.niox.2017.09.004. [Epub ahead of print]

PMID: 28939409

Abstract

AIMS:

Over-the-counter mouthwash (most of which are antibacterial) comprises part of routine oral care for many; however, potential adverse effects of the long-term daily use have not been evaluated. Antibacterial mouthwash could destroy oral microbes critical for nitric oxide formation, and in turn predispose to metabolic disorders including diabetes. Our aim was to evaluate longitudinally the association between baseline over-the-counter mouthwash use and development of pre-diabetes/diabetes over a 3-year follow-up.

MATERIALS AND METHODS:

The San Juan Overweight Adults Longitudinal Study (SOALS) recruited 1206 overweight/obese individuals, aged 40-65, and free of diabetes and major cardiovascular diseases; 945 with complete follow-up data were included in the analyses. We used Cox Proportional Hazards adjusting for baseline age, sex, smoking, physical activity, waist circumference, alcohol consumption, and hypertension.

RESULTS:

Many participants (43%) used mouthwash at least once daily and 22% at least twice daily. Participants using mouthwash ≥ twice daily at baseline, had a significantly elevated risk of pre-diabetes/diabetes compared to less frequent (multivariate HR = 1.67, 95% CI: 1.24-2.26), or never users of mouthwash (multivariate HR = 1.65; 95% CI: 1.19-2.28). The effect estimates were similar after adding income, education, oral hygiene, oral conditions, sleep breathing disorders, diet (processed meat, fruit, and vegetable intake), medications, HOMA-IR, fasting glucose, 2hr post load glucose or CRP to the multivariate models. Both associations were significant among never-smokers and obese. Mouthwash use lower than twice daily showed no association, suggesting a threshold effect at twice or more daily.

CONCLUSIONS:

Frequent regular use of over-the-counter mouthwash was associated with increased risk of developing pre-diabetes/diabetes in this population.

KEYWORDS:

Antibacterial; Epidemiology; Human; Microbes; Mouthrinse; Mouthwash; Nitric oxide; Oral hygiene; Over-the-counter; Prediction and prevention of type 2 diabetes

 

Association between plant-based diets and plasma lipids: a systematic review and meta-analysis.

Yokoyama Y, Levin SM, Barnard ND.

Nutr Rev. 2017 Sep 1;75(9):683-698. doi: 10.1093/nutrit/nux030.

PMID: 28938794

Abstract

CONTEXT:

Although a recent meta-analysis of randomized controlled trials showed that adoption of a vegetarian diet reduces plasma lipids, the association between vegetarian diets and long-term effects on plasma lipids has not been subjected to meta-analysis.

OBJECTIVE:

The aim was to conduct a systematic review and meta-analysis of observational studies and clinical trials that have examined associations between plant-based diets and plasma lipids.

DATA SOURCES:

MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for articles published in English until June 2015.

STUDY SELECTION:

The literature was searched for controlled trials and observational studies that investigated the effects of at least 4 weeks of a vegetarian diet on plasma lipids.

DATA EXTRACTION:

Two reviewers independently extracted the study methodology and sample size, the baseline characteristics of the study population, and the concentrations and variance measures of plasma lipids. Mean differences in concentrations of plasma lipids between vegetarian and comparison diet groups were calculated. Data were pooled using a random-effects model.

RESULTS:

Of the 8385 studies identified, 30 observational studies and 19 clinical trials met the inclusion criteria (N = 1484; mean age, 48.6 years). Consumption of vegetarian diets was associated with lower mean concentrations of total cholesterol (-29.2 and -12.5 mg/dL, P < 0.001), low-density lipoprotein cholesterol (-22.9 and -12.2 mg/dL, P < 0.001), and high-density lipoprotein cholesterol (-3.6 and -3.4 mg/dL, P < 0.001), compared with consumption of omnivorous diets in observational studies and clinical trials, respectively. Triglyceride differences were -6.5 (P = 0.092) in observational studies and 5.8 mg/dL (P = 0.090) in intervention trials.

CONCLUSIONS:

Plant-based diets are associated with decreased total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, but not with decreased triglycerides.

KEYWORDS:

high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; meta-analysis; plant-based diets; plasma lipids; systematic review; total cholesterol

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925198/table/T2/

Meta-analysis of the association between the inflammatory potential of diet and colorectal cancer risk.

Fan Y, Jin X, Man C, Gao Z, Wang X.

Oncotarget. 2017 Jul 14;8(35):59592-59600. doi: 10.18632/oncotarget.19233. eCollection 2017 Aug 29.

PMID: 28938662

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=19233&path%5B%5D=61579

Abstract

OBJECTIVES:

The inflammatory potential of diet has been inconsistently linked to colorectal cancer (CRC) risk. This meta-analysis aimed to evaluate the association of the inflammatory potential of diet, as estimated by the dietary inflammatory index (DII) score, with CRC risk.

MATERIALS AND METHODS:

The PubMed and Embase databases were searched for relevant studies from inception to February 2017. All cohort and case-control studies investigating the association of the DII score with CRC risk were selected.

RESULTS:

Four prospective cohorts and four case-control studies, which enrolled a total of 880,380 participants, were included. The pooled adjusted risk ratio (RR) of CRC for the highest DII score versus the lowest category was 1.43 (95% confidence interval [CI]: 1.26-1.62). When stratified by study design, the RRs for the case-control and cohort studies were 1.27 (95% CI: 1.16-1.38) and 1.81 (95% CI: 1.48-2.22), respectively. Subgroup analysis showed that individuals with the highest category of DII score were independently associated with CRC risk in men (RR=1.51; 95% CI: 1.29-1.76), women (RR=1.25; 95% CI: 1.10-1.41), colon cancer (RR=1.39; 95% CI: 1.19-1.62), and rectal cancer (RR=1.32; 95% CI: 1.01-1.74). However, the pooled RR was 1.07 (95% CI: 0.87-1.31) for rectal cancer among the prospective cohort studies.

CONCLUSIONS:

As estimated by a high DII score, pro-inflammatory diet is independently associated with increased CRC risk. This finding confirms that low inflammatory potential diet may reduce CRC risk. However, the gender- and cancer site-specific associations of the DII score with CRC risk need to be further investigated.

KEYWORDS:

colorectal cancer; dietary inflammatory index; meta-analysis; systematic review

 

Physical activity and 22-year all-cause and coronary heart disease mortality.

Krause N, Arah OA, Kauhanen J.

Am J Ind Med. 2017 Sep 20. doi: 10.1002/ajim.22756. [Epub ahead of print]

PMID: 28940659

http://sci-hub.cc/http://onlinelibrary.wiley.com/doi/10.1002/ajim.22756/abstract;jsessionid=570CFABE2C81C7DBBC77BC9CBA3BF997.f02t03?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+7th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+08.00+EDT+%2F+13.00+BST+%2F+17%3A30+IST+%2F+20.00+SGT+and+Sunday+8th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+06.00+EDT+%2F+11.00+BST+%2F+15%3A30+IST+%2F+18.00+SGT+for+essential+maintenance.+Apologies+for+the+inconvenience+caused+.

Abstract

BACKGROUND:

This study explores the effects of occupational (OPA) and leisure time physical activity (LTPA) on mortality relative to cardiorespiratory fitness and pre-existing coronary heart disease (CHD).

METHODS:

Associations between OPA, measured as energy expenditure (kcal/day) and relative aerobic workload (%VO2 max), LTPA, and 22-year mortality among 1891 Finnish men were assessed by Cox regression models stratified by CHD and adjusted for 19 confounders.

RESULTS:

In fully adjusted models, each 10% of relative aerobic workload increased all-cause mortality by 13% and CHD mortality 28% (P < 0.01). Compared to healthy subjects, men with CHD experienced lower mortality risks due to OPA and higher risks due to LTPA. While LTPA had no effect among healthy men, in men with CHD each weekly hour of conditioning LTPA increased all-cause mortality risks by 10% and CHD mortality by14%.

CONCLUSION:

OPA was positively associated with both all-cause and CHD mortality. LTPA was not protective. Among men with CHD, LTPA increased mortality risks.

KEYWORDS:

cardiorespiratory fitness; energy expenditure; physical workload; prospective study; relative aerobic workload

 

Asthma status is associated with decreased risk of aggressive urothelial bladder cancer.

Rava M, Czachorowski MJ, Silverman D, Márquez M, Kishore S, Tardón A, Serra C, García-Closas M, Garcia-Closas R, Carrato A, Rothman N, Real FX, Kogevinas M, Malats N.

Int J Cancer. 2017 Sep 22. doi: 10.1002/ijc.31066. [Epub ahead of print]

PMID: 28940228

Abstract

Previous studies suggested an association between atopic conditions and specific cancers. The results on the association with urothelial bladder cancer (UBC) are scarce and inconsistent. To evaluate the association between asthma and risk of UBC, we considered 936 cases and 1022 controls from the Spanish Bladder Cancer/EPICURO Study (86% males, mean age 65.4 years), a multicenter and hospital based case-control study conducted during 1998-2001. Participants were asked whether they had asthma and detailed information about occupational exposures, smoking habits, dietary factors, medical conditions, and history of medication was collected through face-to-face questionnaires performed by trained interviewers. Since asthma and UBC might share risk factors, association between patients' characteristics and asthma was studied in UBC controls. Association between UBC and asthma was assessed using logistic regression unadjusted and adjusted for potential confounders. The complex interrelationships, direct, and mediating effect of asthma on UBC, were appraised using counterfactual mediation models. Asthma was associated with a reduced risk of UBC (odds ratio (OR)=0.54, 95% confidence interval (CI) 0.37, 0.79) after adjusting for a wide range of confounders. No mediating effect was identified. The reduced risk associated with asthma was restricted to patients with high-risk non-muscle invasive (OR=0.25, 95%CI 0.10, 0.62) and muscle invasive UBC (OR=0.32, 95%CI 0.15, 0.69). Our results support that asthma is associated with a decreased risk of UBC, especially among aggressive tumors. Further work on the relationship between asthma and other atopic conditions and cancer risk should shed light on the relationship between immune response mechanisms and bladder carcinogenesis.

KEYWORDS:

Asthma; Atopic diseases; Bladder cancer; Case-control study; Counterfactual mediation models; Risk

 

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

The Lancet

Published: September 20, 2017

Open Access

Emanuele Di Angelantonio, MD*, Prof Simon G Thompson, FMedSci*, Stephen Kaptoge, PhD*, Carmel Moore, PhD*, Matthew Walker, PhD, Prof Jane Armitage, FRCP, Prof Willem H Ouwehand, FMedSci, Prof David J Roberts, FRCPath†, Prof John Danesh, FMedSci†,'Correspondence information about the author Prof John DaneshEmail the author Prof John Danesh on behalf of the show INTERVAL Trial Group‡

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31928-1/fulltext

Summary

Background

Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries.

Methods

In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants.

Findings

45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups.

Interpretation

Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925198/table/T2/

The Relationship Between the Dietary Inflammatory Index and Incident Frailty: A Longitudinal Cohort Study.

Shivappa N, Stubbs B, Hébert JR, Cesari M, Schofield P, Soysal P, Maggi S, Veronese N.

J Am Med Dir Assoc. 2017 Sep 21. pii: S1525-8610(17)30459-0. doi: 10.1016/j.jamda.2017.08.006. [Epub ahead of print]

PMID: 28943182

Abstract

OBJECTIVE:

Inflammation is key risk factor for several conditions in the elderly. However, the relationship between inflammation and frailty is still unclear. We investigated whether higher dietary inflammatory index (DII) scores were associated with higher incidence of frailty in a cohort of North Americans.

DESIGN:

Longitudinal, with a follow-up of 8 years.

SETTING:

Osteoarthritis Initiative.

PARTICIPANTS:

A total of 4421 participants with, or at high risk of, knee osteoarthritis.

MEASUREMENTS:

DII scores were calculated using the validated Block Brief 2000 Food-Frequency Questionnaire and categorized into sex-specific quartiles. Frailty was defined as 2 out of 3 of the criteria of the Study of Osteoporotic Fracture study (ie, weight loss, inability to rise from a chair 5 times, and poor energy). The strength of the association between baseline DII score and incident frailty was assessed through a Cox's regression analysis, adjusted for potential baseline confounders, and reported as hazard ratios.

RESULTS:

A total of 4421 community-dwelling participants (2564 female participants; mean age: 61.3 years) without frailty at baseline were identified from the Osteoarthritis Initiative. During 8 years of follow-up, 356 individuals developed frailty (8.2%). Using Cox's regression analysis, adjusting for 11 potential confounders, participants with the highest DII score (quartile 4) had a significantly higher risk of experiencing frailty (hazard ratio 1.37; 95% confidence interval 1.01-1.89; P = .04) compared with participants with the lowest DII score (quartile 1). The association between DII score and frailty was significant only in men.

CONCLUSIONS:

Higher DII scores, indicating a more proinflammatory diet, are associated with higher incidence of frailty, particularly in men.

KEYWORDS:

Aged; dietary inflammatory index; frailty; inflammation

 

p53 inhibits the upregulation of sirtuin 1 expression induced by c-Myc.

Yuan F, Liu L, Lei Y, Tang P.

Oncol Lett. 2017 Oct;14(4):4396-4402. doi: 10.3892/ol.2017.6661. Epub 2017 Jul 24.

PMID: 28943955

Abstract

Sirtuin 1 (Sirt1), a conserved NAD+ dependent deacetylase, is a mediator of life span by calorie restriction. However, Sirt1 may paradoxically increase the risk of cancer. Accordingly, the expression level of Sirt1 is selectively elevated in numerous types of cancer cell; however, the mechanisms underlying the differential regulation remain largely unknown. The present study demonstrated that oncoprotein c-Myc was a direct regulator of Sirt1, which accounts for the upregulation of Sirt1 expression only in the cells without functional p53. In p53 deficient cells, the overexpression of c-Myc increased Sirt1 mRNA and protein expression levels as well as its promoter activity, whereas the inhibitor of c-Myc, 10058-F4, induced decreased Sirt1 basal mRNA and protein expression levels. Deletion/mutation mapping analyses revealed that c-Myc bound to the conserved E-box[-189 to -183 base pair (bp)] of the Sirt1 promoter. In addition, p53 and c-Myc shared at least response element and the presence of p53 may block the binding of c-Myc to the Sirt1 promoter, thus inhibit the c-Myc mediated upregulation of Sirt1 promoter activity. The present study indicated that the expression level of Sirt1 was tightly regulated by oncoprotein c-Myc and tumor suppressor p53, which aids an improved understanding of its expression regulation and tumor promoter role in certain conditions.

KEYWORDS:

c-Myc; p53; sirtuin 1; tumorigenesis

 

Progressive impairment of testicular endocrine function in ageing men: testosterone and dihydrotestosterone decrease, and luteinising hormone increases, in men transitioning from the 8th to 9th decades of life.

Yeap BB, Manning L, Chubb SAP, Handelsman DJ, Almeida OP, Hankey GJ, Flicker L.

Clin Endocrinol (Oxf). 2017 Sep 25. doi: 10.1111/cen.13484. [Epub ahead of print]

PMID: 28945276

http://sci-hub.cc/10.1111/cen.13484

Abstract

CONTEXT:

Sex hormone trajectories in ageing men and their health implications remain unclear. We examined longitudinal trajectories and associations of testosterone (T), dihydrotestosterone (DHT), estradiol (E2), luteinising hormone (LH) and sex hormone-binding globulin (SHBG) in oldest old men.

DESIGN:

Prospective cohort study.

PARTICIPANTS:

We studied 1,025 community-dwelling men median age 75.1 years at baseline with 8.6 years follow-up.

MEASUREMENTS:

Baseline and follow-up T, DHT and E2 were assayed using mass spectrometry. Physical performance was assessed at follow-up. Correlations and covariate-adjusted P-values were determined.

RESULTS:

Longitudinal change in T was -2.0%/year, DHT -7.2%/year, LH +7.5%/year, SHBG +5.6%/year while E2 remained stable. Annualised increases in LH correlated with decreases in T and DHT (r=-0.20, P<0.0001 and r=-0.12, P=0.0035 respectively). Higher baseline T correlated with better physical performance at follow-up (e.g. Step test r=0.07, P=0.03), as did higher baseline DHT (e.g. Time to Sit-Stand [TSS] r=-0.07, P=0.01). Larger annualised increases in LH predicted poorer physical performance at follow-up (e.g. TSS r=0.14, P=0.001). Higher T at follow-up was associated with better physical performance (e.g. TSS r=-0.07, P=0.04), as were higher DHT and lower LH. At baseline 24 men (2.4%) had abnormally high LH (>16 IU/L); at follow-up 175 (17.4%) had high LH of whom 70 had low T (<6.4 nmol/L).

CONCLUSIONS:

Annualised increases in LH are associated with declines in T and DHT, and predict poorer subsequent physical performance in oldest old men. Men transitioning from 8th to 9th decades exhibit biochemical evidence of progressively impaired testicular endocrine function, warranting further evaluation.

KEYWORDS:

Testosterone; ageing; dihydrotestosterone; estradiol; luteinising hormone; physical performance; sex hormone-binding globulin

 

More Evidence that Dementia Case Numbers Are Falling

18 Sep 2017

http://www.alzforum.org/news/research-news/more-evidence-dementia-case-numbers-are-falling

>>>>>>>>>>>>

JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1964. [Epub ahead of print]

Trends in Dementia Incidence in a Birth Cohort Analysis of the Einstein Aging Study.

Derby CA1,2, Katz MJ1, Lipton RB1,2, Hall CB1,2.

Author information

Abstract

IMPORTANCE:

Trends in dementia incidence rates have important implications for planning and prevention. To better understand incidence trends over time requires separation of age and cohort effects, and few prior studies have used this approach.

OBJECTIVES:

To examine trends in dementia incidence and concomitant trends in cardiovascular comorbidities among individuals aged 70 years or older who were enrolled in the Einstein Aging Study between 1993 and 2015.

DESIGN, SETTING, AND PARTICIPANTS:

In this birth cohort analysis of all-cause dementia incidence in persons enrolled in the Einstein Aging Study from October 20, 1993, through November 17, 2015, a systematically recruited, population-based sample of 1348 participants from Bronx County, New York, who were 70 years or older without dementia at enrollment and at least one annual follow-up was studied. Poisson regression was used to model dementia incidence as a function of age, sex, educational level, race, and birth cohort, with profile likelihood used to identify the timing of significant increases or decreases in incidence.

EXPOSURES:

Birth year and age.

MAIN OUTCOMES AND MEASURES:

Incident dementia defined by consensus case conference based on annual, standardized neuropsychological and neurologic examination findings, using criteria from the DSM-IV.

RESULTS:

Among 1348 individuals (mean [sD] baseline age, 78.5 [5.4] years; 830 [61.6%] female; 915 [67.9%] non-Hispanic white), 150 incident dementia cases developed during 5932 person-years (mean [sD] follow-up, 4.4 [3.4] years). Dementia incidence decreased in successive birth cohorts. Incidence per 100 person-years was 5.09 in birth cohorts before 1920, 3.11 in the 1920 through 1924 birth cohorts, 1.73 in the 1925 through 1929 birth cohorts, and 0.23 in cohorts born after 1929. Change point analyses identified a significant decrease in dementia incidence among those born after July 1929 (95% CI, June 1929 to January 1930). The relative rate for birth cohorts before July 1929 vs after was 0.13 (95% CI, 0.04-0.41). Prevalence of stroke and myocardial infarction decreased across successive birth cohorts, whereas diabetes prevalence increased. Adjustment for these cardiovascular comorbidities did not explain the decreased dementia incidence rates for more recent birth cohorts.

CONCLUSIONS AND RELEVANCE:

Analyses confirm decreasing dementia incidence in this population-based sample. Whether decreasing incidence will contribute to reduced burden of dementia given the aging of the population is not known.

PMID: 28873124

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Influence of dietary macronutrients on liver fat accumulation and metabolism.

Parry SA, Hodson L.

J Investig Med. 2017 Sep 24. pii: jim-2017-000524. doi: 10.1136/jim-2017-000524. [Epub ahead of print] Review.

PMID: 28947639

http://jim.bmj.com/content/early/2017/09/23/jim-2017-000524

http://jim.bmj.com/content/jim/early/2017/09/23/jim-2017-000524.full.pdf

Abstract

The liver is a principal metabolic organ within the human body and has a major role in regulating carbohydrate, fat, and protein metabolism. With increasing rates of obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD) is growing. It remains unclear why NAFLD, which is now defined as the hepatic manifestation of the metabolic syndrome, develops but lifestyle factors such as diet (ie, total calorie and specific nutrient intakes), appear to play a key role. Here we review the available observational and intervention studies that have investigated the influence of dietary macronutrients on liver fat content. Findings from observational studies are conflicting with some reporting that relative to healthy controls, patients with NAFLD consume diets higher in total fat/saturated fatty acids, whilst others find they consume diets higher in carbohydrates/sugars. From the limited number of intervention studies that have been undertaken, a consistent finding is a hypercaloric diet, regardless of whether the excess calories have been provided either as fat, sugar, or both, increases liver fat content. In contrast, a hypocaloric diet decreases liver fat content. Findings from both hyper- and hypo-caloric feeding studies provide some suggestion that macronutrient composition may also play a role in regulating liver fat content and this is supported by data from isocaloric feeding studies; fatty acid composition and/or carbohydrate content/type appear to influence whether there is accrual of liver fat or not. The mechanisms by which specific macronutrients, when consumed as part of an isocaloric diet, cause a change in liver fat remain to be fully elucidated.

KEYWORDS:

NAFLD; carbohydrate; diet; fat; human; liver; protein

 

Adherence to Mediterranean Diet and Risk of Cancer: An Updated Systematic Review and Meta-Analysis.

Schwingshackl L, Schwedhelm C, Galbete C, Hoffmann G.

Nutrients. 2017 Sep 26;9(10). pii: E1063. doi: 10.3390/nu9101063. Review.

PMID: 28954418

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123783/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123783/pdf/CAM4-4-1933.pdf

Abstract

The aim of the present systematic review and meta-analysis was to gain further insight into the effects of adherence to Mediterranean Diet (MedD) on risk of overall cancer mortality, risk of different types of cancer, and cancer mortality and recurrence risk in cancer survivors. Literature search was performed using the electronic databases PubMed, and Scopus until 25 August 2017. We included randomized trials (RCTs), cohort (for specific tumors only incidence cases were used) studies, and case-control studies. Study-specific risk ratios, hazard ratios, and odds ratios (RR/HR/OR) were pooled using a random effects model. Observational studies (cohort and case-control studies), and intervention trials were meta-analyzed separately. The updated review process showed 27 studies that were not included in the previous meta-analysis (total number of studies evaluated: 83 studies). An overall population of 2,130,753 subjects was included in the present update. The highest adherence score to a MedD was inversely associated with a lower risk of cancer mortality (RRcohort: 0.86, 95% CI 0.81 to 0.91, I² = 82%; n = 14 studies), colorectal cancer (RRobservational: 0.82, 95% CI 0.75 to 0.88, I² = 73%; n = 11 studies), breast cancer (RRRCT: 0.43, 95% CI 0.21 to 0.88, n = 1 study) (RRobservational: 0.92, 95% CI 0.87 to 0.96, I² = 22%, n = 16 studies), gastric cancer (RRobservational: 0.72, 95% CI 0.60 to 0.86, I² = 55%; n = 4 studies), liver cancer (RRobservational: 0.58, 95% CI 0.46 to 0.73, I² = 0%; n = 2 studies), head and neck cancer (RRobservational: 0.49, 95% CI 0.37 to 0.66, I² = 87%; n = 7 studies), and prostate cancer (RRobservational: 0.96, 95% CI 0.92 to 1.00, I² = 0%; n = 6 studies). Among cancer survivors, the association between the adherence to the highest MedD category and risk of cancer mortality, and cancer recurrence was not statistically significant. Pooled analyses of individual components of the MedD revealed that the protective effects appear to be most attributable to fruits, vegetables, and whole grains. The updated meta-analysis confirms an important inverse association between adherence to a MedD and cancer mortality and risk of several cancer types, especially colorectal cancer. These observed beneficial effects are mainly driven by higher intakes of fruits, vegetables, and whole grains. Moreover, we were able to report for the first time a small decrease in breast cancer risk (6%) by pooling seven cohort studies.

KEYWORDS:

Mediterranean Diet; cancer; meta-analysis; systematic review update

"The results of the largest MD trial, the PREDIMED study including 7447 subjects, showed that the highest category of nuts intake (>3 servings/week) was associated with a 40% risk reduction in cancer mortality when compared to the lowest category [63], whereas the differences observed between consumers of extra virgin olive oil did not attain statistical significance [64]."

 

Adherence to the dietary approaches to stop hypertension trial (DASH) diet is inversely associated with incidence of insulin resistance in adults: the Tehran lipid and glucose study.

Esfandiari S, Bahadoran Z, Mirmiran P, Tohidi M, Azizi F.

J Clin Biochem Nutr. 2017 Sep;61(2):123-129. doi: 10.3164/jcbn.16-95. Epub 2017 Aug 11.

PMID: 28955129

Abstract

Beneficial effects of Dietary Approaches to Stop Hypertension trial (DASH) diet on features of metabolic syndrome have been indicated in clinical studies. In this study, we aimed to assess possible association of DASH diet score and the risk of insulin resistance in an Iranian population. In this prospective cohort study, 927 adult men and women, were recruited. Fasting serum insulin and glucose were measured at baseline and again after 3 years. Usual dietary intakes were measured using a validated 168 item semi-quantitative food frequency questionnaire and DASH score was calculated. Multivariate logistic regression models were used to estimate the occurrence of the insulin resistance across tertiles of DASH diet. To investigate possible superiority of DASH score over other scoring system, we also assessed the association of healthy eating index and Mediterranean diet score with the risk of insulin resistance. Mean age of the participants was 40.34 ± 12.14 years old. The incidence rate of insulin resistance was 12.8%. Participants with higher DASH score had also higher intakes of potassium, calcium, magnesium, fiber, and lower intakes of cholesterol (p<0.05). After 3-years of follow-up, a significant negative association was observed between DASH score and the risk insulin resistance in the highest compared to the lowest tertile (OR = 0.39, 95% CI = 0.20-0.76, p for trend = 0.007). There was no significant association between healthy eating index and Mediterranean diet score with the incidence of insulin resistance. In conclusion, adherence to the DASH dietary pattern may be associated with a lower risk of insulin resistance and its related metabolic outcomes.

KEYWORDS:

dietary approaches to stop hypertension; insulin; insulin resistance

 

Lack of adverse health effects following 30-weeks of dietary exposure to acrylamide at low doses in male F344 rats.

Raju J, Kocmarek A, Roberts J, Taylor M, Patry D, Chomyshyn E, Caldwell D, Cooke G, Mehta R.

Toxicol Rep. 2016 Aug 31;3:673-678. doi: 10.1016/j.toxrep.2016.08.010. eCollection 2016.

PMID: 28959591

Abstract

Understanding the health hazards following exposure to food-borne acrylamide, especially at low levels typified by human diets, is an ongoing food safety issue. We recently published results from a study that aimed to understand the effects of acrylamide short-term exposure at doses known to cause tumors in rodents, demonstrating that a number of key toxicological end points were altered by acrylamide exposure. Additionally, we reported that at much lower doses for 30 weeks of exposure, dietary acrylamide was 'not a complete carcinogen' to the colon in an organ-specific rodent carcinogenesis study but acted as a co-carcinogen along with azoxymethane (AOM, a colon-specific carcinogen). Here, we present toxicological data from a sub-set of this long-term exposure study from animals that received saline (instead of AOM). Briefly, male F344 rats were randomized to receive acrylamide at 0.5, 1.0 and 2.0 mg/kg diet (∼0.02, 0.04, and 0.09 mg/kg BW/day, respectively) or no acrylamide (control), for 30 weeks; all rats were then euthanized and their tissues harvested and processed for toxicological evaluation. We report that at the doses tested, acrylamide did not cause any changes in general well-being, body weight or food intake. Similarly, acrylamide did not cause any biologically relevant change in parameters associated with immunophenotyping, serum biochemistry or hematology. Histopathology assessment of tissues showed no changes except in the testis, where non-specific mild lesions were observed in all the groups, inclusive of the controls. No neuropathological effects of acrylamide were observed in the brain and nerve tissues. Together, these results suggest that acrylamide administered to rats through the diet at low doses for 30 weeks did not cause any toxicologically relevant changes. Given that the doses of acrylamide in the current study are low and are comparable to human dietary exposure, this null-effect study provides data that contribute to the body of scientific evidence relevant to understanding the health effects of acrylamide.

KEYWORDS:

Acrylamide; Clinical biochemistry; Diet; F344 rats; Hematology; Pathology; Testosterone; Toxicity

 

How effective are weight-loss interventions for improving fertility in women and men who are overweight or obese? A systematic review and meta-analysis of the evidence.

Best D, Avenell A, Bhattacharya S.

Hum Reprod Update. 2017 Sep 13:1-25. doi: 10.1093/humupd/dmx027. [Epub ahead of print]

PMID: 28961722

Abstract

BACKGROUND:

The prevalence of obesity is increasing worldwide, with a corresponding increase in overweight and obese patients referred with infertility. This systematic review aimed to determine whether non-surgical weight reduction strategies result in an improvement in reproductive parameters affected by obesity, e.g. delayed time to pregnancy, oligozoospermia and azoospermia. No prior reviews have examined this within the general fertility population, or in both sexes.

OBJECTIVE AND RATIONALE:

Our objective was to answer the question: 'In overweight and obese women, men and couples seeking fertility treatment, what non-surgical weight-loss interventions have been used, and how effective are they at weight loss and improving reproductive outcomes?'

SEARCH METHODS:

An electronic search of MEDLINE, EMBASE and the Cochrane Library was performed for studies between January 1966 and March 2016. Text word and MESH search terms used related to infertility, weight and barriers to weight loss. Inclusion criteria were an intervention to change lifestyle evaluated in any study design in participants of either gender with an unfulfilled desire to conceive. Studies were excluded if they included participants not attempting pregnancy, with illnesses that might cause weight fluctuations, or studies evaluating bariatric surgery. Two reviewers performed data extraction and quality assessment using the Cochrane Risk of Bias Tool for randomized trials, and a ratified checklist (ReBIP) for non-randomized studies.

OUTCOMES:

A total of 40 studies were included, of which 14 were randomised control trials. Primary outcomes were pregnancy, live birth rate and weight change. In women, reduced calorie diets and exercise interventions were more likely than control interventions to result in pregnancy [risk ratio 1.59, 95% CI (1.01, 2.50)], and interventions resulted in weight loss and ovulation improvement, where reported. Miscarriage rates were not reduced by any intervention.

WIDER IMPLICATIONS:

Overweight and obese persons seeking fertility should be educated on the detrimental effects of fatness and the benefits of weight reduction, including improvement in pregnancy rates. A combination of a reduced calorie diet, by reducing fat and refined carbohydrate intake, and increased aerobic exercise should form the basis of programmes designed for such individuals. A lack of randomized studies in men and couples, and studies evaluating barriers to undertaking weight loss in infertile populations is evident, and future research should examine these issues further.

KEYWORDS:

diet; exercise; infertility; obesity; systematic review; weight loss

 

Prospective Study of Nut Consumption and Incidence of Metabolic Syndrome: Tehran Lipid and Glucose Study.

Hosseinpour-Niazi S, Hosseini S, Mirmiran P, Azizi F.

Nutrients. 2017 Sep 23;9(10). pii: E1056. doi: 10.3390/nu9101056.

PMID: 28946607 Free Article

http://www.mdpi.com/2072-6643/9/10/1056/htm

Abstract

This study aimed to assess the association of various types of nut per se, and total nut consumption with the incidence of metabolic syndrome (MetS). A 6.2 ± 0.7-year population-based prospective study was conducted among 1265 adults, aged 19-74 years, participants of the Tehran Lipid and Glucose Study. A 168-item semi-quantitative food frequency questionnaire was used to collect information on nut consumption. MetS was defined according to the Joint Interim Statement guidelines and 276 new cases of MetS were identified. Median ± interquartile range of nut consumption was 2.08 (0.88-5.68) servings/week. After adjusting for family history of diabetes, age, gender, smoking, physical activity, fasting serum glucose at baseline, serum high density lipoprotein cholesterol (HDL-C) at baseline, energy intake, fiber, macronutrients, cholesterol intake, fruit, vegetables, dairy products and body mass index (BMI), a statistically significant decrease was observed in MetS in the third (≥5 servings/week) tertile of nuts (odds ratio: 0.68, 95% CI: 0.44-0.91, p trend: 0.03) compared with the lowest (≤1 serving/week). Walnut consumption showed a significant, inverse association with MetS risk; associations for other nut varieties were not significant. For each additional serving/week of walnuts consumed, incidence of MetS decreased by 3% (ORs: 0.97 CI: 0.93-0.99), after adjusting for confounding factors. Total nut consumption, especially walnuts, reduces the risk of MetS.

KEYWORDS:

Tehran lipid and glucose study; metabolic syndrome; nuts; walnuts

 

Calcium and Cardiovascular Disease.

Reid IR, Birstow SM, Bolland MJ.

Endocrinol Metab (Seoul). 2017 Sep;32(3):339-349. doi: 10.3803/EnM.2017.32.3.339. Review.

PMID: 28956363 Free Article

https://e-enm.org/DOIx.php?id=10.3803/EnM.2017.32.3.339

https://e-enm.org/Synapse/Data/PDFData/2008ENM/enm-32-339.pdf

Abstract

Circulating calcium is a risk factor for vascular disease, a conclusion arising from prospective studies involving hundreds of thousands of participants and extending over periods of up to 30 years. These associations may be partially mediated by other cardiovascular risk factors such as circulating lipid levels, blood pressure, and body mass index, but there appears to be a residual independent effect of serum calcium. Polymorphisms of the calcium-sensing receptor associated with small elevations of serum calcium are also associated with cardiovascular disease, suggesting that calcium plays a causative role. Trials of calcium supplements in patients on dialysis and those with less severe renal failure demonstrate increased mortality and/or acceleration of vascular disease, and meta-analyses of trials in those without overt renal disease suggest a similar adverse effect. Interpretation of the latter trials is complicated by a significant interaction between baseline use of calcium supplements and the effect of randomisation to calcium in the largest trial. Restriction of analysis to those who are calcium-naive demonstrates a consistent adverse effect. Observational studies of dietary calcium do not demonstrate a consistent adverse effect on cardiovascular health, though very high or very low intakes may be deleterious. Thus, obtaining calcium from the diet rather than supplements is to be encouraged.

KEYWORDS:

Calcium; Calcium, dietary; Cardiovascular diseases; Myocardial infarction; Osteoporosis; Risk factors

 

Additional risk of diabetes exceeds the increased risk of cancer caused by radiation exposure after the Fukushima disaster.

Murakami M, Tsubokura M, Ono K, Nomura S, Oikawa T.

PLoS One. 2017 Sep 28;12(9):e0185259. doi: 10.1371/journal.pone.0185259. eCollection 2017.

PMID: 28957385

Abstract

The 2011 Fukushima disaster led to increases in multiple risks (e.g., lifestyle diseases and radiation exposure) and fear among the public. Here, we assessed the additional risks of cancer caused by radiation and diabetes related to the disaster and the cost-effectiveness of countermeasures against these conditions. Our study included residents of the cities of Minamisoma and Soma (10-40 km and 35-50 km north of the Fukushima Daiichi (N° 1) Nuclear Power Station, respectively). We used the loss of life expectancy (LLE) as an indicator to compare risks between radiation exposure and diabetes. We also estimated the cost-effectiveness of radiation-related countermeasures, including restricted food distribution, decontamination, and whole-body counter tests and interventions. Metformin therapy was selected as a representative management for diabetes. The diabetes-related LLEs among residents were 4.1 (95% confidence interval: 1.4-6.8) ×10-2 years for the whole population and 8.0 (2.7-13.2) ×10-2 years for 40s to 70s in a scenario that considered the additional incidence of diabetes during the first 10 years. The cancer-related LLEs caused by lifetime exposure to radiation were 0.69 (2.5-97.5 percentile: 0.61-0.79) ×10-2 years for the whole population and 0.24 (0.20-0.29) ×10-2 years for 40s to 70s. The diabetes-related LLEs among residents in the above-mentioned scenario were 5.9-fold and 33-fold higher than those attributed to average radiation among the whole population and among the 40s to 70s age groups, respectively. The costs per life-years saved of the radiation countermeasures (i.e., restricted food distribution, decontamination, and whole-body counter tests and interventions) were >1 to >4 orders of magnitude higher than those of general heath checkups and conventional management for diabetes. Our findings indicate that countermeasures to mitigate diabetes are warranted. Policy-makers' and individuals' understanding of multiple risks after any disaster will be essential to saving the lives of victims.

 

Isocaloric Dietary Changes and Non-Alcoholic Fatty Liver Disease in High Cardiometabolic Risk Individuals.

Della Pepa G, Vetrani C, Lombardi G, Bozzetto L, Annuzzi G, Rivellese AA.

Nutrients. 2017 Sep 26;9(10). pii: E1065. doi: 10.3390/nu9101065. Review.

PMID: 28954437

https://www.google.ca/search?q=Isocaloric+Dietary+Changes+and+Non-Alcoholic+Fatty+Liver+Disease+in+High+Cardiometabolic+Risk+Individuals&oq=Isocaloric+Dietary+Changes+and+Non-Alcoholic+Fatty+Liver+Disease+in+High+Cardiometabolic+Risk+Individuals&aqs=chrome..69i57j69i61l3.412j0j4&sourceid=chrome&ie=UTF-8PMID:28954437

Abstract

Non-alcoholic fatty liver disease (NAFLD) incorporates an extensive spectrum of histologic liver abnormalities, varying from simple triglyceride accumulation in hepatocytes non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), and it is the most frequent chronic liver disease in the industrialized world. Beyond liver related complications such as cirrhosis and hepatocellular carcinoma, NAFLD is also an emerging risk factor for type 2 diabetes and cardiovascular disease. Currently, lifestyle intervention including strategies to reduce body weight and to increase regular physical activity represents the mainstay of NAFLD management. Total caloric intake plays a very important role in both the development and the treatment of NAFLD; however, apart from the caloric restriction alone, modifying the quality of the diet and modulating either the macro- or micronutrient composition can also markedly affect the clinical evolution of NAFLD, offering a more realistic and feasible treatment alternative. The aim of the present review is to summarize currently available evidence from randomized controlled trials on the effects of different nutrients including carbohydrates, lipids, protein and other dietary components, in isocaloric conditions, on NAFLD in people at high cardiometabolic risk. We also describe the plausible mechanisms by which different dietary components could modulate liver fat content.

KEYWORDS:

NAFLD; NASH; carbohydrates; isocaloric dietary changes; monounsaturated fatty acids; polyphenols; polyunsaturated fatty acids; vitamins

 

Coffee didn't work to treat Parkinson's, but may play role in prevention

Researchers had hoped caffeine could be used to relieve symptoms of Parkinson's

CBC News Posted: Sep 29, 2017

http://www.cbc.ca/news/health/parkinson-caffeine-1.4311136

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Caffeine as symptomatic treatment for Parkinson disease (Café-PD): A randomized trial.

Postuma RB, Anang J, Pelletier A, Joseph L, Moscovich M, Grimes D, Furtado S, Munhoz RP, Appel-Cresswell S, Moro A, Borys A, Hobson D, Lang AE.

Neurology. 2017 Sep 27. pii: 10.1212/WNL.0000000000004568. doi: 10.1212/WNL.0000000000004568. [Epub ahead of print]

PMID: 28954882

Abstract

OBJECTIVE:

To assess effects of caffeine on Parkinson disease (PD).

METHODS:

In this multicenter parallel-group controlled trial, patients with PD with 1-8 years disease duration, Hoehn & Yahr stages I-III, on stable symptomatic therapy were randomized to caffeine 200 mg BID vs matching placebo capsules for 6-18 months. The primary research question was whether objective motor scores would differ at 6 months (Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale [MDS-UPDRS]-III, Class I evidence). Secondary outcomes included safety and tolerability, motor symptoms (MDS-UPDRS-II), motor fluctuations, sleep, nonmotor symptoms (MDS-UPDRS-I), cognition (Montreal Cognitive Assessment), and quality of life.

RESULTS:

Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement in motor parkinsonism (the primary outcome) with caffeine treatment compared to placebo (difference between groups -0.48 [95% confidence interval -3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1+4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo).

CONCLUSION:

Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects.

CLASSIFICATION OF EVIDENCE:

This study provides Class I evidence that for patients with PD, caffeine does not significantly improve motor manifestations.

 

[The below paper is pdf-availed.]

Association of Biotin Ingestion With Performance of Hormone and Nonhormone Assays in Healthy Adults

Danni Li, PhD; Angela Radulescu, MD; Rupendra T. Shrestha, MD; et al.

Abstract Full Text

JAMA. 2017;318(12):1150-1160. doi:10.1001/jama.2017.13705

This nonrandomized crossover trial evaluated associations between biotin supplement ingestion and the accuracy of common diagnostic assays that rely on biotinylation, such as tests of thyroid function, vitamin D, and prostate specific antigen.

Key Points

Question Does oral biotin supplementation interfere with hormone and nonhormone assays that use biotinylation in their design?

Findings In this nonrandomized crossover study of 6 healthy adults (2 women, 4 men), 10 mg/d of biotin ingested for 1 week was associated with potentially clinically important assay interferences in some but not all biotinylated hormone and nonhormone assays studied.

Meaning Oral biotin use may be associated with false hormone and nonhormone assay results.

Abstract

Importance Biotinylated antibodies and analogues, with their strong binding to streptavidin, are used in many clinical laboratory tests. Excess biotin in blood due to supplemental biotin ingestion may affect biotin-streptavidin binding, leading to potential clinical misinterpretation. However, the degree of interference remains undefined in healthy adults.

Objective To assess performance of specific biotinylated immunoassays after 7 days of ingesting 10 mg/d of biotin, a dose common in over-the-counter supplements for healthy adults.

Design, Setting, and Participants Nonrandomized crossover trial involving 6 healthy adults who were treated at an academic medical center research laboratory

Exposure Administration of 10 mg/d of biotin supplementation for 7 days.

Main Outcomes and Measures Analyte concentrations were compared with baseline (day 0) measures on the seventh day of biotin treatment and 7 days after treatment had stopped (day 14). The 11 analytes included 9 hormones (ie, thyroid-stimulating hormone, total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, parathyroid hormone, prolactin, N-terminal pro-brain natriuretic peptide, 25-hydroxyvitamin D) and 2 nonhormones (prostate-specific antigen and ferritin). A total of 37 immunoassays for the 11 analytes were evaluated on 4 diagnostic systems, including 23 assays that incorporated biotin and streptavidin components and 14 assays that did not include biotin and streptavidin components and served as negative controls.

Results Among the 2 women and 4 men (mean age, 38 years [range, 31-45 years]) who took 10 mg/d of biotin for 7 days, biotin ingestion–associated interference was found in 9 of the 23 (39%) biotinylated assays compared with none of the 14 nonbiotinylated assays (P = .007). Results from 5 of 8 biotinylated (63%) competitive immunoassays tested falsely high and results from 4 out of 15 (27%) biotinylated sandwich immunoassays tested falsely low.

Conclusions and Relevance In this preliminary study of 6 healthy adult participants and 11 hormone and nonhormone analytes measured by 37 immunoassays, ingesting 10 mg/d of biotin for 1 week was associated with potentially clinically important assay interference in some but not all biotinylated assays studied. These findings should be considered for patients taking biotin supplements before ordering blood tests or when interpreting results.

[Among the 23 biotinylated assays studied, biotin interference

was of greatest clinical significance in the OCD Vitros TSH

assay, where falsely decreased TSH concentrations (to

<0.15 mU/L) could have resulted in misdiagnosis of thyrotoxicosis

in otherwise euthyroid individuals. Likewise, falsely

decreased OCD Vitros NT-proBNP, to lower than assay detection

limits, could possibly result in failure to identify congestive

heart failure.18 Because healthy study participants had

normal baseline NT-proBNP, further study of patients with

high baseline NT-proBNP concentration would be required to

establish the effect of biotin interference on the diagnosis of

heart failure. The smaller changes observed in other assays,

namely OCD Vitros PTH; Roche cobas e602 TSH, total and

free T3, free T4, and 25-OHD; and Siemens Vista free T3,

although primarily producing false results within the reference

range among participants while taking biotin, could lead

to falsely normal or abnormal interpretation of the results for

individuals starting from baseline levels closer to the reference

range limits.19]

 

Low-Fat Dietary Pattern and Breast Cancer Mortality in the Women's Health Initiative Randomized Controlled Trial.

Chlebowski RT, Aragaki AK, Anderson GL, Thomson CA, Manson JE, Simon MS, Howard BV, Rohan TE, Snetselar L, Lane D, Barrington W, Vitolins MZ, Womack C, Qi L, Hou L, Thomas F, Prentice RL.

J Clin Oncol. 2017 Sep 1;35(25):2919-2926. doi: 10.1200/JCO.2016.72.0326. Epub 2017 Jun 27.

PMID: 28654363

Abstract

Purpose Earlier Women's Health Initiative Dietary Modification trial findings suggested that a low-fat eating pattern may reduce breast cancers with greater mortality. Therefore, as a primary outcome-related analysis from a randomized prevention trial, we examined the long-term influence of this intervention on deaths as a result of and after breast cancer during 8.5 years (median) of dietary intervention and cumulatively for all breast cancers diagnosed during 16.1 years (median) of follow-up. Patients and Methods The trial randomly assigned 48,835 postmenopausal women with normal mammograms and without prior breast cancer from 1993 to 1998 at 40 US clinical centers to a dietary intervention with goals of a reduction of fat intake to 20% of energy and an increased intake of fruits, vegetables, and grains (40%; n = 19,541) or to a usual diet comparison (60%; n = 29,294). Results In the dietary group, fat intake and body weight decreased (all P < .001). During the 8.5-year dietary intervention, with 1,764 incident breast cancers, fewer deaths occurred as a result of breast cancer in the dietary group, which was not statistically significant (27 deaths [0.016% per year] v 61 deaths [0.024% per year]; hazard ratio {HR}, 0.67; 95% CI, 0.43 to 1.06; P = .08). During the same period, deaths after breast cancer (n = 134) were significantly reduced (40 deaths [0.025% per year] v 94 deaths [0.038% per year]; HR, 0.65; 95% CI, 0.45 to 0.94; P = .02) by the dietary intervention. During the 16.1-year follow-up, with 3,030 incident breast cancers, deaths after breast cancer also were significantly reduced (234 deaths [0.085% per year] v 443 deaths [0.11% per year]; HR, 0.82; 95% CI, 0.70 to 0.96; P = .01) in the dietary group. Conclusion Compared with a usual diet comparison group, a low-fat dietary pattern led to a lower incidence of deaths after breast cancer.

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MicroRNAs mir-184 and let-7 alter Drosophila metabolism and longevity.

Gendron CM, Pletcher SD.

Aging Cell. 2017 Sep 29. doi: 10.1111/acel.12673. [Epub ahead of print]

PMID: 28963741

Abstract

MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression associated with many complex biological processes. By comparing miRNA expression between long-lived cohorts of Drosophila melanogaster that were fed a low-nutrient diet with normal-lived control animals fed a high-nutrient diet, we identified miR-184, let-7, miR-125, and miR-100 as candidate miRNAs involved in modulating aging. We found that ubiquitous, adult-specific overexpression of these individual miRNAs led to significant changes in fat metabolism and/or lifespan. Most impressively, adult-specific overexpression of let-7 in female nervous tissue increased median fly lifespan by ~22%. We provide evidence that this lifespan extension is not due to alterations in nutrient intake or to decreased insulin signaling.

KEYWORDS:

aging; diet restriction; let-7; miR-100; miR-125; miR-184

 

Selenocysteine modulates resistance to environmental stress and confers anti-aging effects in C. elegans.

Kim JS, Kim SH, Park SK.

Clinics (Sao Paulo). 2017 Aug;72(8):491-498. doi: 10.6061/clinics/2017(08)07.

PMID: 28954009 Free PMC Article

Abstract

OBJECTIVE::

The free radical theory of aging suggests that cellular oxidative damage caused by free radicals is a leading cause of aging. In the present study, we examined the effects of a well-known anti-oxidant amino acid derivative, selenocysteine, in response to environmental stress and aging using Caenorhabditis elegans as a model system.

METHOD::

The response to oxidative stress induced by H2O2 or ultraviolet irradiation was compared between the untreated control and selenocysteine-treated groups. The effect of selenocysteine on lifespan and fertility was then determined. To examine the effect of selenocysteine on muscle aging, we monitored the change in motility with aging in both the untreated control and selenocysteine-treated groups.

RESULTS::

Dietary supplementation with selenocysteine significantly increased resistance to oxidative stress. Survival after ultraviolet irradiation was also increased by supplementation with selenocysteine. Treatment with selenocysteine confers a longevity phenotype without an accompanying reduction in fertility, which is frequently observed in lifespan-extending interventions as a trade-off in C. elegans. In addition, the age-related decline in motility was significantly delayed by supplementation of selenocysteine.

CONCLUSION::

These findings suggest that dietary supplementation of selenocysteine can modulate response to stressors and lead to lifespan extension, thus supporting the free radical theory of aging.

 

 

Restless legs syndrome and cerebrovascular/cardiovascular events: Systematic review and meta-analysis.

Katsanos AH, Kosmidou M, Konitsiotis S, Tsivgoulis G, Fiolaki A, Kyritsis AP, Giannopoulos S.

Acta Neurol Scand. 2017 Sep 25. doi: 10.1111/ane.12848. [Epub ahead of print]

PMID: 28948600

Abstract

OBJECTIVE:

We performed a systematic review and meta-analysis to evaluate the proposed association of restless legs syndrome (RLS) with cerebrovascular/cardiovascular outcomes.

METHODS:

We calculated the corresponding odds ratios on the prevalence of cerebrovascular/cardiovascular risk factors and standardized mean differences on the reported mean age at baseline between RLS patients and controls. We also calculated the corresponding risk ratios and adjusted for potential confounders hazard ratios (HRsadjusted ) on the reported outcomes of interest between RLS patients and controls.

RESULTS:

We identified 8 eligible studies (644 506 patients, mean age: 60.2 years, 36.2% males; 3.3% with RLS). RLS patients were found to have significantly higher prevalence of hypertension (P = .002), diabetes (P = .003) and hyperlipidemia (P = .010) compared to controls. In the unadjusted analyses of prospective observational studies, RLS patients were found to have significantly higher risk for cerebrovascular ischaemia (P = .01) and all-cause mortality (P = .04) compared to controls during follow-up, while in the adjusted for potential confounders analyses RLS patients were only found to have a higher risk of all-cause mortality (HR adjusted=1.52, 95% CI: 1.17-1.97, P = .002).

CONCLUSIONS:

The present report does not provide evidence for an increased risk of cerebrovascular and cardiovascular events in RLS patients, which highlights the vast presence of confounding factors.

KEYWORDS:

cardiovascular; cerebrovascular; death; ischaemia; ischaemic stroke; myocardial infarction; restless legs syndrome

 

Serum 25-hydroxyvitamin D as a predictor of mortality and cardiovascular events: a 20 year study of a community-based cohort.

Zhu K, Knuiman M, Divitini M, Hung J, Lim EM, Cooke BR, Walsh JP.

Clin Endocrinol (Oxf). 2017 Sep 26. doi: 10.1111/cen.13485. [Epub ahead of print]

PMID: 28949411

http://sci-hub.cc/10.1111/cen.13485

Abstract

OBJECTIVE:

Prospective studies, mostly from Europe and North America, suggest that serum 25-hydroxyvitamin D (25(OH)D) is inversely associated with mortality and cardiovascular disease (CVD) risk. Data from other regions are limited, and threshold levels for adverse cardiovascular outcomes uncertain. We examined serum 25(OH)D as a predictor of total mortality and cardiovascular outcomes in an Australian cohort.

DESIGN:

A 20-year, community-based cohort study.

PATIENTS:

Participants in the 1994/1995 Busselton Health Survey (n=3946, baseline age 25-84 years).

MEASUREMENTS:

Baseline serum 25(OH)D and mortality and cardiovascular outcomes to 2014 obtained by record linkage.

RESULTS:

The mean serum 25(OH)D concentration was 60.6±18.0 nmol/L. During 20 years follow-up (excluding the first 2 years), 889 participants died (including 363 from CVD) and 944 experienced a CVD event (including 242 with heart failure). In the full cohort, controlling for Framingham risk score variables, higher baseline 25(OH)D was associated with significantly reduced all-cause mortality (adjusted HR 0.83 per SD increment of 25(OH)D, 95% CI 0.77-0.90), CVD death (HR 0.85, 95% CI 0.74-0.96) and heart failure (HR 0.81, 95% CI 0.69-0.94), but not CVD events (HR 0.99, 0.92-1.07). In restricted cubic spline regression models, serum 25(OH)D below 65 and 55 nmol/L was associated with higher total mortality and higher CVD mortality/heart failure, respectively. In participants without CVD at baseline (n=3220) results were similar, but hazard ratios were attenuated and associations with CVD mortality no longer significant.

CONCLUSIONS:

In an Australian community-based cohort, baseline vitamin D levels below 55-65 nmol/L are predictive of all-cause mortality, CVD death and heart failure. This article is protected by copyright. All rights reserved.

KEYWORDS:

Australia; cardiovascular disease; follow-up study; health survey; heart failure; mortality; vitamin D

 

Low serum insulin-like growth factor-I (IGF-I) level is associated with increased risk of vascular dementia.

Quinlan P, Horvath A, Nordlund A, Wallin A, Svensson J.

Psychoneuroendocrinology. 2017 Sep 21;86:169-175. doi: 10.1016/j.psyneuen.2017.09.018. [Epub ahead of print]

PMID: 28963885

Abstract

BACKGROUND:

Insulin-like growth factor-I (IGF-I) is important for the adult brain, but little is known of the role of IGF-I in Alzheimeŕs disease (AD) or vascular dementia (VaD).

METHODS:

A prospective study of 342 patients with subjective or objective mild cognitive impairment recruited at a single memory clinic. We determined whether serum IGF-I concentrations at baseline were associated with the risk of all-cause dementia, AD, or VaD. Patients developing mixed forms of AD and VaD were defined as suffering from VaD. The statistical analyses included Cox proportional hazards regression analysis.

RESULTS:

During the follow-up (mean 3.6 years), 95 (28%) of the patients developed all-cause dementia [AD, n=37 (11%) and VaD, n=42 (12%)]. Low as well as high serum IGF-I (quartile 1 or 4 vs. quartiles 2-3) did not associate with all-cause dementia [crude hazard ratio (HR) 1.30, 95% confidence interval (CI): 0.81-2.08 and crude HR 1.05, 95% CI: 0.63-1.75, respectively] or AD (crude HR 0.79, 95% CI: 0.35-1.79 and crude HR 0.94, 95% CI: 0.43-2.06, respectively]. In contrast, low serum IGF-I concentrations were associated with increased risk of VaD (quartile 1 vs. quartiles 2-3, crude HR 2.22, 95% CI: 1.13-4.36). The latter association remained significant also after adjustment for multiple covariates.

CONCLUSIONS:

In a memory clinic population, low serum IGF-I was a risk marker for subsequent VaD whereas low IGF-I did not associate with the risk of AD. High serum IGF-I was not related to the risk of conversion to dementia.

KEYWORDS:

Alzheimeŕs disease; IGF-I; Mild cognitive impairment; Serum; Vascular dementia

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Mediterranean diet, physical activity and their combined effect on all-cause mortality: The Seguimiento Universidad de Navarra (SUN) cohort.

Alvarez-Alvarez I, Zazpe I, de Rojas JP, Bes-Rastrollo M, Ruiz-Canela M, Fernandez-Montero A, Hidalgo-Santamaría M, Martínez-González MA.

Prev Med. 2017 Sep 27. pii: S0091-7435(17)30344-4. doi: 10.1016/j.ypmed.2017.09.021. [Epub ahead of print]

PMID: 28964855

Abstract

The health benefits of the Mediterranean diet (MedDiet) and of physical activity (PA) have been widely documented. However, no longitudinal studies have investigated their combined effect on mortality. We assessed the individual and combined effects of adherence to the MedDiet and PA on all-cause mortality. We used data from 19,467 participants from a prospective cohort of Spanish university graduates, the SUN cohort, followed-up between December 1999 and February 2016. Adherence to the MedDiet was assessed using four different dietary scores, categorizing the quantitative scores into tertiles of adherence. To assess multiple dimensions of PA, an 8-item score was built. Multivariable Cox regression models were used to study the individual and combined relationship of adherence to the MedDiet and PA with all-cause mortality. During a median follow-up of 10.3years, we registered 305 deaths. Compared with the lowest adherence to the MedDiet (<20 in the modified Mediterranean diet score), better adherence (23-30 points) was associated with lower mortality (multivariable-adjusted hazard ratio {HR}=0.66, 95% confidence interval [CI]: 0.46-0.96). Engaging in moderate or high levels of PA (versus lower levels) was associated with 44% and 52% relative reductions in mortality, respectively. High adherence to the MedDiet combined with engaging in higher amounts of PA showed a HR=0.36 (95% CI: 0.19-0.67). We documented that the combined effect of better adherence to the MedDiet and increased PA had multiplicative effects on mortality risk reduction.

KEYWORDS:

Exercise; Mediterranean diet; Mortality; Prospective studies

 

Endometriosis and the risk of skin cancer: a prospective cohort study.

Farland LV, Lorrain S, Missmer SA, Dartois L, Cervenka I, Savoye I, Mesrine S, Boutron-Ruault MC, Kvaskoff M.

Cancer Causes Control. 2017 Aug 10. doi: 10.1007/s10552-017-0939-2. [Epub ahead of print]

PMID: 28799019

Abstract

PURPOSE:

Endometriosis has been associated with an increased risk of skin melanoma. However, associations with other skin cancer types and how they compare with melanoma are unclear. Our objective was to prospectively investigate the relationships between endometriosis and risk of non-melanoma and melanoma skin cancers.

METHODS:

E3N is a prospective cohort of 98,995 French women aged 40-65 years in 1990. Data on surgically confirmed endometriosis and skin cancer diagnoses were collected every 2-3 years through self-report, with skin cancer cases confirmed through pathology reports. Hazard Ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox regression models.

RESULTS:

Between 1990 and 2008, 535 melanoma, 247 squamous-cell carcinoma (SCC), and 1,712 basal-cell carcinoma (BCC) cases were ascertained. Endometriosis was associated with an increased overall risk of skin cancer (HR 1.28, 95% CI 1.05-1.55). When considering skin cancer type, endometriosis was associated with melanoma risk (HR 1.64, 95% CI 1.15-2.35), but not with SCC (HR 1.21, 95% CI 0.62-2.36) or BCC (HR 1.16, 95% CI 0.91-1.48) (non-melanoma skin cancers combined: HR 1.17, 95% CI 0.93-1.46), although no heterogeneity was detected across skin cancer types (Phomogeneity = 0.13).

CONCLUSION:

These data support an association between a personal history of endometriosis and the risk of skin cancer and suggest that the association is strongest for melanoma.

KEYWORDS:

Cohort studies; Cutaneous melanoma; Endometriosis; Epidemiology; Skin cancer

 

Functional IGF1R variant predicts breast cancer risk in women with preeclampsia in California Teachers Study.

Powell MJ, Von Behren J, Neuhausen S, Reynolds P, Benz CC.

Cancer Causes Control. 2017 Aug 18. doi: 10.1007/s10552-017-0942-7. [Epub ahead of print]

PMID: 28822014

Abstract

PURPOSE:

Hypertension in pregnancy has been associated with decreased future risk of breast cancer in many but not all studies. In the Marin Women's Study, pregnancy-induced hypertension was shown to interact with the T allele of a functional IGF1R gene variant, rs2016347, to result in lower breast density, as well as decreased breast cancer risk. Our objective was to explore these findings in a larger sample of women from the California Teachers Study (CTS).

METHODS:

The CTS cohort consists of over 130,000 female educators. DNA was available from a nested case-control study, which included 2,030 non-Hispanic white women who developed breast cancer and 1,552 controls. The current study included all participants from the case-control group with a self-reported history of preeclampsia (80 cases/57 controls).

RESULTS:

Comparing TT to GG genotypes revealed adjusted odds ratios of 0.38 (CI 0.13, 1.14) for all invasive breast cancers, 0.26 (CI 0.07, 0.89) for hormone receptor-positive (HR+) breast cancers, 0.15 (CI 0.04, 0.56) for those with age at first birth (AFB) < 30, and 0.10 (CI 0.02, 0.49) for those with AFB < 30 and HR+ breast cancers. Trend analysis yielded p values of 0.09, 0.03, 0.005, and 0.004 respectively, suggesting a biological effect for each T allele.

CONCLUSION:

Study findings indicate that the T allele of IGF1R variant rs2016347 is associated with a significant reduction in breast cancer risk in women with a history of preeclampsia, most marked for HR+ breast cancer and in women with AFB < 30.

KEYWORDS:

Age at first birth; Breast cancer risk; Gestational hypertension; Insulin-like growth factor 1 receptor; Preeclampsia

 

The Scientist » June 2017 Issue » Features

Plastic Pollutants Pervade Water and Land

Contamination of marine and terrestrial ecosystems by microplastics is putting individual organisms at risk.

By Ee Ling Ng | June 1, 2017

http://www.the-scientist.com/?articles.view/articleNo/49476/title/Plastic-Pollutants-Pervade-Water-and-Land/

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d-Allulose, a stereoisomer of d-fructose, extends Caenorhabditis elegans lifespan through a dietary restriction mechanism: A new candidate dietary restriction mimetic.

Shintani T, Sakoguchi H, Yoshihara A, Izumori K, Sato M.

Biochem Biophys Res Commun. 2017 Sep 28. pii: S0006-291X(17)31928-9. doi: 10.1016/j.bbrc.2017.09.147. [Epub ahead of print]

PMID: 28965946

Abstract

Dietary restriction (DR) is an effective intervention known to increase lifespan in a wide variety of organisms. DR also delays the onset of aging-associated diseases. DR mimetics, compounds that can mimic the effects of DR, have been intensively explored. d-Allulose (d-Alu), the C3-epimer of d-fructose, is a rare sugar that has various health benefits, including anti-hyperglycemia and anti-obesity effects. Here, we report that d-Alu increased the lifespan of Caenorhabditis elegans both under monoxenic and axenic culture conditions. d-Alu did not further extend the lifespan of the long-lived DR model eat-2 mutant, strongly indicating that the effect is related to DR. However, d-Alu did not reduce the food intake of wild-type C. elegans. To explore the mechanisms of the d-Alu longevity effect, we examined the lifespan of d-Alu-treated mutants deficient for nutrient sensing pathway-related genes daf-16, sir-2.1, aak-2, and skn-1. As a result, d-Alu increased the lifespan of the daf-16, sir-2.1, and skn-1 mutants, but not the aak-2 mutant, indicating that the lifespan extension was dependent on the energy sensor, AMP-activated protein kinase (AMPK). d-Alu also enhanced the mRNA expression and enzyme activities of superoxide dismutase (SOD) and catalase. From these findings, we conclude that d-Alu extends lifespan by increasing oxidative stress resistance through a DR mechanism, making it a candidate DR mimetic.

KEYWORDS:

Caenorhabditis elegans; Dietary restriction; Dietary restriction mimetic; Lifespan; d-Allulose

 

The Scientist » The Nutshell

Water Level in a Cell Can Determine Its Fate

Adding or removing water changes how stem cells differentiate.

By Kerry Grens | September 27, 2017

http://www.the-scientist.com/?articles.view/articleNo/50503/title/Water-Level-in-a-Cell-Can-Determine-its-Fate/&utm_campaign=NEWSLETTER_TS_The-Scientist-Daily_2016&utm_source=hs_email&utm_medium=email&utm_content=56763381&_hsenc=p2ANqtz-9Cyq3J14K8c5D9QMJxGM8QdJKJL2PA3Of1zoZ3TmUJDzSaBqnUbp_r2_rosHEq8sCXodBPX6NXKOldyUZIrubhy7JBdw&_hsmi=56763381

Tags

water, stem cells, physical forces, mesenchymal stem cells, differentiation, developmental biology and Cell stiffness

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Cell volume change through water efflux impacts cell stiffness and stem cell fate

Ming Guo, Adrian F. Pegoraro, Angelo Mao, Enhua H. Zhou, Praveen R. Arany, Yulong Han, Dylan T. Burnette, Mikkel H. Jensen, Karen E. Kasza, Jeffrey R. Moore, Frederick C. Mackintosh, Jeffrey J. Fredberg, David J. Mooney, Jennifer Lippincott-Schwartz, and David A. Weitz

PNAS 2017 ; published ahead of print September 25, 2017, doi:10.1073/pnas.1705179114

Significance

Cell volume is thought to be a well-controlled cellular characteristic, increasing as a cell grows, while macromolecular density is maintained. We report that cell volume can also change in response to external physical cues, leading to water influx/efflux, which causes significant changes in subcellular macromolecular density. This is observed when cells spread out on a substrate: Cells reduce their volume and increase their molecular crowding due to an accompanying water efflux. Exploring this phenomenon further, we removed water from mesenchymal stem cells through osmotic pressure and found this was sufficient to alter their differentiation pathway. Based on these results, we suggest cells chart different differentiation and behavioral pathways by sensing/altering their cytoplasmic volume and density through changes in water influx/efflux.

Abstract

Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its volume decreases, while its stiffness concomitantly increases. We find that both cortical and cytoplasmic cell stiffness scale with volume for numerous perturbations, including varying substrate stiffness, cell spread area, and external osmotic pressure. The reduction of cell volume is a result of water efflux, which leads to a corresponding increase in intracellular molecular crowding. Furthermore, we find that changes in cell volume, and hence stiffness, alter stem-cell differentiation, regardless of the method by which these are induced. These observations reveal a surprising, previously unidentified relationship between cell stiffness and cell volume that strongly influences cell biology.

--------------

cell volume cell mechanics molecular crowding gene expression stem cell fate

 

Intermittent brain stimulation

Lisa D. Chong

http://science.sciencemag.org/content/357/6358/twil.full

Electrical stimulation of the brain to improve its function has been much debated. In an experimental test of working memory, Liu et al. showed that intermittent stimulation of the nucleus basalis in the forebrain of young adult Rhesus macaques improved their memory by up to five times. In contrast, continuous stimulation of the same region impaired memory. Improved memory depended on the neurotransmitter acetylcholine, given that the effect was blocked by antagonists of cholinergic receptors. The drug donepezil, which blocks cholinesterase's ability to degrade acetylcholine, restored memory performance in animals that received continual stimulation. Intermittent deep brain stimulation could boost the effects of acetylcholine on neurons and/or increase blood flow to the brain to improve memory.

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ntermittent Stimulation of the Nucleus Basalis of Meynert Improves Working Memory in Adult Monkeys.

Liu R, Crawford J, Callahan PM, Terry AV Jr, Constantinidis C, Blake DT.

Curr Biol. 2017 Sep 11;27(17):2640-2646.e4. doi: 10.1016/j.cub.2017.07.021. Epub 2017 Aug 17.

PMID: 28823679

Abstract

Acetylcholine in the neocortex is critical for executive function [1-3]. Degeneration of cholinergic neurons in aging and Alzheimer's dementia is commonly treated with cholinesterase inhibitors [4-7]; however, these are modestly effective and are associated with side effects that preclude effective dosing in many patients [8]. Electrical activation of the nucleus basalis (NB) of Meynert, the source of neocortical acetylcholine [9, 10], provides a potential method of improving cholinergic activation [11, 12]. Here we tested whether NB stimulation would improve performance of a working memory task in a nonhuman primate model. Unexpectedly, intermittent stimulation proved to be most beneficial (60 pulses per second, for 20 s every minute), whereas continuous stimulation often impaired performance. Pharmacological experiments confirmed that the effects depended on cholinergic activation. Donepezil, a cholinesterase inhibitor, restored performance in animals impaired by continuous stimulation but did not improve performance further during intermittent stimulation. Intermittent stimulation was rendered ineffective by either nicotinic or muscarinic receptor antagonists. In the months after stimulation began, performance also improved in sessions without stimulation. Our results reveal that intermittent NB stimulation can improve working memory, a finding that has implications for restoring cognitive function in aging and Alzheimer's dementia.

KEYWORDS:

Alzheimer’s; Nucleus Basalis of Meynert; deep brain stimulation; executive function; nonhuman primate; working memory

 

New insights into melanoma development.

Shay JW.

Science. 2017 Sep 29;357(6358):1358-1359. doi: 10.1126/science.aao6963. Epub 2017 Sep 28. No abstract available.

PMID: 28963245

http://sci-hub.cc/10.1126/science.aao6963

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Mutations in the promoter of the telomerase gene <i>TERT</i> contribute to tumorigenesis by a two-step mechanism.

Chiba K, Lorbeer FK, Shain AH, McSwiggen DT, Schruf E, Oh A, Ryu J, Darzacq X, Bastian BC, Hockemeyer D.

Science. 2017 Sep 29;357(6358):1416-1420. doi: 10.1126/science.aao0535. Epub 2017 Aug 17.

PMID: 28818973

http://sci-hub.cc/10.1126/science.aao0535

Abstract

TERT promoter mutations (TPMs) are the most common noncoding mutations in cancer. The timing and consequences of TPMs have not been fully established. Here, we show that TPMs acquired at the transition from benign nevus to malignant melanoma do not support telomere maintenance. In vitro experiments revealed that TPMs do not prevent telomere attrition, resulting in cells with critically short and unprotected telomeres. Immortalization by TPMs requires a gradual up-regulation of telomerase, coinciding with telomere fusions. These data suggest that TPMs contribute to tumorigenesis by promoting immortalization and genomic instability in two phases. In an initial phase, TPMs do not prevent bulk telomere shortening but extend cellular life span by healing the shortest telomeres. In the second phase, the critically short telomeres lead to genome instability and telomerase is further up-regulated to sustain cell proliferation.

 

Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial.

Langdahl BL, Libanati C, Crittenden DB, Bolognese MA, Brown JP, Daizadeh NS, Dokoupilova E, Engelke K, Finkelstein JS, Genant HK, Goemaere S, Hyldstrup L, Jodar-Gimeno E, Keaveny TM, Kendler D, Lakatos P, Maddox J, Malouf J, Massari FE, Molina JF, Ulla MR, Grauer A.

Lancet. 2017 Jul 26. pii: S0140-6736(17)31613-6. doi: 10.1016/S0140-6736(17)31613-6. [Epub ahead of print]

PMID: 28755782

Abstract

BACKGROUND:

Previous bisphosphonate treatment attenuates the bone-forming effect of teriparatide. We compared the effects of 12 months of romosozumab (AMG 785), a sclerostin monoclonal antibody, versus teriparatide on bone mineral density (BMD) in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy.

METHODS:

This randomised, phase 3, open-label, active-controlled study was done at 46 sites in North America, Latin America, and Europe. We enrolled women (aged ≥55 to ≤90 years) with postmenopausal osteoporosis who had taken an oral bisphosphonate for at least 3 years before screening and alendronate the year before screening; an areal BMD T score of -2·5 or lower at the total hip, femoral neck, or lumbar spine; and a history of fracture. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous romosozumab (210 mg once monthly) or subcutaneous teriparatide (20 μg once daily). The primary endpoint was percentage change from baseline in areal BMD by dual-energy x-ray absorptiometry at the total hip through month 12 (mean of months 6 and 12), which used a linear mixed effects model for repeated measures and represented the mean treatment effect at months 6 and 12. All randomised patients with a baseline measurement and at least one post-baseline measurement were included in the efficacy analysis. This trial is registered with ClinicalTrials.gov, number NCT01796301.

FINDINGS:

Between Jan 31, 2013, and April 29, 2014, 436 patients were randomly assigned to romosozumab (n=218) or teriparatide (n=218). 206 patients in the romosozumab group and 209 in the teriparatide group were included in the primary efficacy analysis. Through 12 months, the mean percentage change from baseline in total hip areal BMD was 2·6% (95% CI 2·2 to 3·0) in the romosozumab group and -0·6% (-1·0 to -0·2) in the teriparatide group; difference 3·2% (95% CI 2·7 to 3·8; p<0·0001). The frequency of adverse events was generally balanced between treatment groups. The most frequently reported adverse events were nasopharyngitis (28 [13%] of 218 in the romosozumab group vs 22 [10%] of 214 in the teriparatide group), hypercalcaemia (two [<1%] vs 22 [10%]), and arthralgia (22 [10%] vs 13 [6%]). Serious adverse events were reported in 17 (8%) patients on romosozumab and in 23 (11%) on teriparatide; none were judged treatment related. There were six (3%) patients in the romosozumab group compared with 12 (6%) in the teriparatide group with adverse events leading to investigational product withdrawal.

INTERPRETATION:

Transition to a bone-forming agent is common practice in patients treated with bisphosphonates, such as those who fracture while on therapy. In such patients, romosozumab led to gains in hip BMD that were not observed with teriparatide. These data could inform clinical decisions for patients at high risk of fracture.

FUNDING:

Amgen, Astellas, and UCB Pharma

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Bone-forming agents in non-responders to bisphosphonates.

Compston J.

Lancet. 2017 Jul 26. pii: S0140-6736(17)31824-X. doi: 10.1016/S0140-6736(17)31824-X. [Epub ahead of print] No abstract available.

PMID: 28755781

http://sci-hub.cc/10.1016/S0140-6736(17)31824-X

>>>>>>>>>>>>>>>>>>>>>>>>>>.

Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis.

Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A.

N Engl J Med. 2017 Sep 11. doi: 10.1056/NEJMoa1708322. [Epub ahead of print]

PMID: 28892457

Abstract

Background Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption. Methods We enrolled 4093 postmenopausal women with osteoporosis and a fragility fracture and randomly assigned them in a 1:1 ratio to receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) in a blinded fashion for 12 months, followed by open-label alendronate in both groups. The primary end points were the cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture (nonvertebral and symptomatic vertebral fracture) at the time of the primary analysis (after clinical fractures had been confirmed in ≥330 patients). Secondary end points included the incidences of nonvertebral and hip fracture at the time of the primary analysis. Serious cardiovascular adverse events, osteonecrosis of the jaw, and atypical femoral fractures were adjudicated. Results Over a period of 24 months, a 48% lower risk of new vertebral fractures was observed in the romosozumab-to-alendronate group (6.2% [127 of 2046 patients]) than in the alendronate-to-alendronate group (11.9% [243 of 2047 patients]) (P<0.001). Clinical fractures occurred in 198 of 2046 patients (9.7%) in the romosozumab-to-alendronate group versus 266 of 2047 patients (13.0%) in the alendronate-to-alendronate group, representing a 27% lower risk with romosozumab (P<0.001). The risk of nonvertebral fractures was lower by 19% in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group (178 of 2046 patients [8.7%] vs. 217 of 2047 patients [10.6%]; P=0.04), and the risk of hip fracture was lower by 38% (41 of 2046 patients [2.0%] vs. 66 of 2047 patients [3.2%]; P=0.02). Overall adverse events and serious adverse events were balanced between the two groups. During year 1, positively adjudicated serious cardiovascular adverse events were observed more often with romosozumab than with alendronate (50 of 2040 patients [2.5%] vs. 38 of 2014 patients [1.9%]). During the open-label alendronate period, adjudicated events of osteonecrosis of the jaw (1 event each in the romosozumab-to-alendronate and alendronate-to-alendronate groups) and atypical femoral fracture (2 events and 4 events, respectively) were observed. Conclusions In postmenopausal women with osteoporosis who were at high risk for fracture, romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone. (Funded by Amgen and others

 

Arsenic in seafood is associated with increased thyroid-stimulating hormone (TSH) in healthy volunteers - A randomized controlled trial.

Molin M, Ulven SM, Dahl L, Lundebye AK, Holck M, Alexander J, Meltzer HM, Ydersbond TA.

J Trace Elem Med Biol. 2017 Dec;44:1-7. doi: 10.1016/j.jtemb.2017.05.004. Epub 2017 May 13.

PMID: 28965562

http://sci-hub.cc/10.1016/j.jtemb.2017.05.004

Abstract

BACKGROUND:

Exposure to exogenous elements like arsenic (As) may influence thyroid enzymes, thyroid-stimulating hormone (TSH), and the two principal thyroid hormones, free thyroxine (FT4) and free triiodothyronine (FT3), but little is known about how this is related to organic arsenicals, the main form in seafood.

AIM:

To investigate whether a high intake of dietary arsenic from seafood can impact thyroid function and thyroid hormones by examining possible associations with changes in TSH, FT4, FT3 and the FT4:FT3-ratio in plasma.

METHODS:

Thirty-eight healthy subjects were randomized into four groups. During a 14-day semi-controlled dietary study, the subjects ingested daily portions of either 150g cod, salmon, blue mussels or potato (control). Plasma concentrations of total As, FT3, FT4, TSH and selenium (Se), and urinary concentrations of iodine were monitored.

RESULTS:

Plasma concentrations of TSH increased significantly in all seafood groups. The change in plasma As, with different coefficients for each seafood group, was the dominant factor in the optimal multiple regression model for change in TSH (R2=0.47). Plasma Se and iodine were negative and positive factors, respectively. There were also indications of changes in FT4, FT3 and the FT4:FT3 ratio consistent with a net inhibiting effect of As on FT4 to FT3 conversion.

CONCLUSION:

Ingestion of seafood rich in various organic As species was strongly associated with an increase of the TSH concentrations in plasma. Change in TSH was positively associated with total plasma As, but varied with the type of seafood ingested. These findings indicate that organic dietary As, apparently depending on chemical form, may influence thyroid hormones and function.

KEYWORDS:

Arsenic; Arsenic in seafood; Dietary intervention; Iodine; Randomized controlled trial; Thyroid-stimulating hormone

 

Comparison of Melatonin and Sertraline Therapies on Tinnitus: A Randomized Clinical Trial.

Abtahi SH, Hashemi SM, Mahmoodi M, Nilforoush MH.

Int J Prev Med. 2017 Aug 31;8:61. doi: 10.4103/ijpvm.IJPVM_229_17. eCollection 2017.

PMID: 28966750

Abstract

BACKGROUND:

Tinnitus is the perception of noise or ringing without external acoustic stimulants which affects almost 10% of general population. Many therapies have been recommended including diet modifications, herbal remedies, and chemical drugs. Most common utilized drugs for tinnitus are melatonin and antidepressants such as sertraline which have been proven in different studies. In this study, we aimed to compare the efficacy of melatonin and sertraline in treating tinnitus for the first time.

METHODS:

In this clinical trial, 70 patients with tinnitus according to inclusion and exclusion criteria were included and randomly divided into two groups: melatonin group, taking melatonin 3 mg once daily and sertraline group taking sertraline 50 mg once daily, all treating for 3 months. Before and after treatments, every patient received Tinnitus Handicap Inventory (THI) questionnaire and severity of tinnitus was assessed, and data analysis was performed.

RESULTS:

Before treatments, the mean of THI score for melatonin and sertraline groups were 45.02 ± 17.67 and 44.85 ± 20.57, respectively. There was no significant difference between both groups THI score (P = 0.23). After 3 months, the mean of THI scores for melatonin and sertraline groups were 30.29 ± 19.62 and 36.96 ± 25.03, respectively which the mean of THI scores in two groups was decreased significantly (P < 0.01, for-both). In addition, indicated the significant decline in THI score of melatonin group who were under treatments with melatonin 3 mg once daily (P = 0.02).

CONCLUSIONS:

Here in this clinical trial, we demonstrated that both melatonin and sertraline are efficient in treating tinnitus, but the usage of melatonin 3 mg once daily is more effective.

KEYWORDS:

Melatonin; sertraline; tinnitus

 

Fish intake is associated with lower cardiovascular risk in a Mediterranean population: Prospective results from the Moli-sani study.

Bonaccio M, Ruggiero E, Di Castelnuovo A, Costanzo S, Persichillo M, De Curtis A, Cerletti C, Donati MB, de Gaetano G, Iacoviello L; Moli-sani study Investigators.

Nutr Metab Cardiovasc Dis. 2017 Aug 23. pii: S0939-4753(17)30198-9. doi: 10.1016/j.numecd.2017.08.004. [Epub ahead of print]

PMID: 28967596

http://sci-hub.cc/10.1016/j.numecd.2017.08.004

Abstract

BACKGROUND AND AIMS:

Fish consumption reportedly reduces the risk of heart disease, but the evidence of cardiovascular advantages associated with fish intake within Mediterranean cohorts is limited. The aim of this study was to test the association between fish intake and risk of composite coronary heart disease (CHD) and stroke in a large population-based cohort adhering to Mediterranean Diet.

METHODS AND RESULTS:

Prospective analysis on 20,969 subjects free from cardiovascular disease at baseline, enrolled in the Moli-sani study (2005-2010). Food intake was recorded by the Italian version of the EPIC food frequency questionnaire. Hazard ratios were calculated by using multivariable Cox-proportional hazard models. During a median follow-up of 4.3 years, a total of 352 events occurred (n of CHD = 287 and n of stroke = 66). After adjustment for a large panel of covariates, fish intake ≥4 times per week was associated with 40% reduced risk of composite CHD and stroke (HR = 0.60; 95%CI 0.40-0.90), and with 40% lower risk of CHD (HR = 0.60; 95%CI 0.38-0.94) as compared with subjects in the lowest category of intake (<2 times/week). A similar trend of protection was found for stroke risk although results were not significant (HR = 0.62; 95%CI 0.26-1.51). When fish types were considered, protection against the composite outcome and CHD was confined to fatty fish intake.

CONCLUSIONS:

Fish intake was associated with reduced risk of composite fatal and non-fatal CHD and stroke in a general Mediterranean population. The favourable association was likely to be driven by fatty fish.

KEYWORDS:

Cardiovascular risk; Cerebrovascular events; Coronary heart disease; Fatty fish; Fish intake; Stroke

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Somatic growth, aging, and longevity.

Bartke A.

NPJ Aging Mech Dis. 2017 Sep 29;3:14. doi: 10.1038/s41514-017-0014-y. eCollection 2017. Review.

PMID: 28970944

http://sci-hub.cc/10.1038/s41514-017-0014-y

Abstract

Although larger species of animals typically live longer than smaller species, the relationship of body size to longevity within a species is generally opposite. The longevity advantage of smaller individuals can be considerable and is best documented in laboratory mice and in domestic dogs. Importantly, it appears to apply broadly, including humans. It is not known whether theses associations represent causal links between various developmental and physiological mechanisms affecting growth and/or aging. However, variations in growth hormone (GH) signaling are likely involved because GH is a key stimulator of somatic growth, and apparently also exerts various "pro-aging" effects. Mechanisms linking GH, somatic growth, adult body size, aging, and lifespan likely involve target of rapamycin (TOR), particularly one of its signaling complexes, mTORC1, as well as various adjustments in mitochondrial function, energy metabolism, thermogenesis, inflammation, and insulin signaling. Somatic growth, aging, and longevity are also influenced by a variety of hormonal and nutritional signals, and much work will be needed to answer the question of why smaller individuals may be likely to live longer.

 

Joint associations of sauna bathing and cardiorespiratory fitness on cardiovascular and all-cause mortality risk: a long-term prospective cohort study.

Kunutsor SK, Khan H, Laukkanen T, Laukkanen JA.

Ann Med. 2017 Oct 3:1-21. doi: 10.1080/07853890.2017.1387927. [Epub ahead of print]

PMID: 28972808

Abstract

PURPOSE:

We aimed to evaluate the joint impact of cardiorespiratory fitness (CRF) and frequency of sauna bathing (FSB) on the risk of cardiovascular and all-cause mortality.

DESIGN:

CRF measured by respiratory gas analyses and sauna exposure were assessed at baseline in a prospective study of 2,277 men. CRF was categorized as low and high (median cutoffs) and FSB as low and high (≤ 2 and 3-7 sessions/week respectively).

RESULTS:

During a median follow-up of 26.1 years, 520 cardiovascular and 1,124 all-cause deaths occurred. Comparing high vs low CRF, the multivariate-adjusted hazard ratios (HRs) 95% CIs for cardiovascular and all-cause mortality were 0.51 (0.41-0.63) and 0.65 (0.57-0.75) respectively. Comparing high vs low FSB, the corresponding HRs were 0.74 (0.59-0.94) and 0.84 (0.72-0.97) respectively. Compared to low CRF & low FSB, the HRs of CVD mortality for high CRF & high FSB; high CRF & low FSB; and low CRF & high FSB were 0.42 (0.28-0.62), 0.50 (0.39-0.63), and 0.72 (0.54-0.97) respectively. For all-cause mortality, the corresponding HRs were 0.60 (0.48-0.76), 0.63 (0.54-0.74), and 0.78 (0.64-0.96) respectively.

CONCLUSION:

A combination of high CRF and frequent sauna bathing confers stronger long-term protection on mortality outcomes compared with high CRF or high FSB alone.

KEYWORDS:

cardiorespiratory fitness; cardiovascular disease; mortality; sauna

 

Association of Nutrients with Biomarkers of Alzheimer's Disease.

Kalli EG.

Adv Exp Med Biol. 2017;987:257-268. doi: 10.1007/978-3-319-57379-3_23.

PMID: 28971464

Abstract

Prospective cohort studies, cross-sectional surveys, autopsy studies and intervention clinical trials that investigated the association between nutrients and Alzheimer's disease (AD) have been reviewed. To estimate the relationship between specific nutrient intake and the risk of AD, Cochrane Library, PubMed, EMBASE, and the Fisher Center for Alzheimer's Research Foundation were searched for this purpose. Most published observational studies found an inverse relationship between vitamins, n-3 fatty acids and AD. The majority of intervention studies support the beneficial effect of combined vitamins and n-3 fatty acids providing them in the early stages of the disease. Only vitamin E and Zn supplementation failed to show any significant difference on the study population. On the other hand, high dietary intake of saturated fat and brain metal accumulation were positively associated with the incidence of AD.

KEYWORDS:

Alzheimer’s disease; Cognitive impairment; Fatty acids; Metals; Minerals; Neurodegenerative disease; Nutrients; Polyphenols; Vitamins

 

Fruit form Influences Postprandial Glycemic Response in Elderly and Young Adults.

Tey SL, Lee DEM, Henry CJ.

J Nutr Health Aging. 2017;21(8):887-891. doi: 10.1007/s12603-017-0880-9.

PMID: 28972240

Abstract

OBJECTIVES:

This study compared the effects of consuming different forms (bite size, puree) and two fruit types (guava, papaya) on glycemic response (GR) in elderly and young adults.

DESIGN:

This study was conducted using a randomized, crossover design.

PARTICIPANTS:

Nineteen healthy participants (9 elderly, 10 young adults) were recruited from the general public in Singapore.

INTERVENTION:

Participants consumed glucose (reference food) on three occasions and test fruits (guava bites, guava puree, papaya bites, and papaya puree) on one occasion each.

MEASUREMENTS:

Blood glucose was analyzed prior to consuming the test food, at 15, 30, 45, 60, 90 and 120 minutes after food consumption.

RESULTS:

The incremental area under the blood glucose response curve (iAUC) over 120 minutes for all the treatments was significantly lower than glucose (all P < 0.001). All fruit forms and types studied were low glycemic index (GI) (guava bites: 29; papaya bites: 38; papaya puree: 42; guava puree: 47), albeit a significant difference in GI between the treatments was found (P = 0.003). Elderly exhibited significantly greater GR than young participants (P = 0.019).

CONCLUSION:

Although fruit form influences GR in the elderly and young adults, all fruit types and forms studied were found to be low GI. This study indicates that fruits are a valuable source of nutrient irrespective of the form of delivery in elderly and young adults. KEYWORDS:

Fruit; elderly; form; glycemic response; type

 

The relationship between drinking alcohol and esophageal, gastric or colorectal cancer: A nationwide population-based cohort study of South Korea.

Choi YJ, Lee DH, Han KD, Kim HS, Yoon H, Shin CM, Park YS, Kim N.

PLoS One. 2017 Oct 3;12(10):e0185778. doi: 10.1371/journal.pone.0185778. eCollection 2017.

PMID: 28973012

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185778

http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0185778&type=printable

Abstract

BACKGROUND:

Epidemiologic findings of low-volume alcohol consumption in relation to gastrointestinal cancers including gastric cancer are inconsistent.

METHODS:

The association between alcohol intake and esophageal, gastric and colorectal cancer risk was examined in a population-based prospective cohort of 23,323,730 adults in Korea who had undergone a biennial evaluation provided by the National Health Insurance Corporation between the years 2009 and 2012. After median 5.4 years of follow-up, 9,171 esophageal, 135,382 gastric and 154,970 colorectal cancer cases were identified. Cox regression models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI).

RESULTS:

Light drinking as well as moderate to heavy alcohol consumption significantly increased the risks of the three gastrointestinal cancers (HR 1.51; 95% CI, 1.43-1.60; HR 1.08; 95% CI, 1.06-1.09; HR 1.12; 95% CI, 1.11-1.14) compared with non-drinkers after adjusting for age, sex, smoking, exercise, income, body mass index, and diabetes. The synergistically increased cancer risk between excessive amount of alcohol consumption and currently smoking or underweight individuals was observed only in the esophageal cancers.

CONCLUSIONS:

Light drinking including even one alcoholic drink a day is associated with increased risks of esophageal, gastric and colorectal cancer.

 

Effect of Dietary Supplementation With Lutein, Zeaxanthin, and ω-3 on Macular Pigment: A Randomized Clinical Trial.

Korobelnik JF, Rougier MB, Delyfer MN, Bron A, Merle BMJ, Savel H, Chêne G, Delcourt C, Creuzot-Garcher C.

JAMA Ophthalmol. 2017 Sep 28. doi: 10.1001/jamaophthalmol.2017.3398. [Epub ahead of print]

PMID: 28973076

Abstract

IMPORTANCE:

Nutritional uptake of lutein, zeaxanthin, and ω-3 polyunsaturated fatty acids may increase macular pigment optical density (MPOD) and thereby protect against the development of age-related macular degeneration (AMD).

OBJECTIVES:

To estimate the efficiency of dietary supplementation containing lutein, zeaxanthin, ω-3 polyunsaturated fatty acids, and vitamins to increase the density of macular pigment in first-generation offspring of parents with neovascular AMD.

DESIGN, SETTING, AND PARTICIPANTS:

This study was a randomized clinical trial (Lutein Influence on Macula of Persons Issued From AMD Parents [LIMPIA]) with a 6-month treatment period, followed by a 6-month follow-up period. Analyses were based on the intent-to-treat principle. The setting was 2 university hospitals in France (at Bordeaux and Dijon) from January 2011 (first participant first visit) to February 2013 (last participant last visit). The analysis was conducted from January to November 2016. Participants were 120 individuals free of any retinal ocular disease. They were first-generation offspring of parents with neovascular AMD.

INTERVENTIONS:

Participants were randomized in a 1:1 ratio to receive either 2 daily dietary supplementation capsules or placebo for 6 months.

MAIN OUTCOMES AND MEASURES:

The primary assessment criterion was the evolution of MPOD after 6 months of supplementation (value of both eligible eyes) measured using the modified MPD-Visucam 200 (Carl Zeiss Meditec) and the modified Heidelberg Retina Angiograph (Heidelberg Engineering) (HRA) at 0.98° eccentricity. The statistical analysis was adjusted for hospital and for risk factors.

RESULTS:

Overall, 120 participants (60 in each group) were included, and 239 eyes were analyzed (119 in the lutein plus zeaxanthin [L + Z] group and 120 in the placebo group). Their mean (SD) age was 56.7 (6.6) years, and 71.7% (n = 86) were female. A statistically significant increase in plasma lutein and zeaxanthin was shown in the L + Z group after 3 months and 6 months of treatment compared with the placebo group. However, the difference between groups in the evolution of MPOD measured by HRA 0.98° eccentricity between 6 months and baseline was 0.036 (95% CI, -0.037 to 0.110) (P = .33).

CONCLUSIONS AND RELEVANCE:

Among first-generation offspring of parents with neovascular AMD in the LIMPIA trial, MPOD as measured with the modified HRA and the MPD-Visucam was not modified after 6 months of lutein and zeaxanthin dietary supplementation despite plasma levels showing continuous exposure to lutein and zeaxanthin. Further research is necessary to understand the mechanism of absorption and metabolism of these nutrients in the macula, the best way to measure MPOD, and the clinical benefit for the patients.

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The role of suppression of hepatic SCD1 expression in the metabolic effects of dietary methionine restriction.

Forney LA, Stone KP, Wanders D, Ntambi JM, Gettys TW.

Appl Physiol Nutr Metab. 2017 Oct 5. doi: 10.1139/apnm-2017-0404. [Epub ahead of print]

PMID: 28982014

Abstract

Dietary methionine restriction (MR) produces concurrent increases in energy intake and expenditure, but the proportionately larger increase in energy expenditure (EE) effectively limits weight gain and adipose tissue accretion over time. Increased hepatic FGF21 is essential to MR-dependent increases in EE, but it is unknown whether the downregulation of hepatic stearoyl-CoA desaturase-1 (SCD1) by MR could also be a contributing factor. Global deletion of SCD1 mimics cold exposure in mice housed at 23°C by compromising the insular properties of the skin. The resulting cold stress increases EE, limits fat deposition, reduces hepatic lipids, and increases insulin sensitivity by activating thermoregulatory thermogenesis. To examine the efficacy of MR in the absence of SCD1 and without cold stress, the biological efficacy of MR in Scd1-/- mice housed near thermoneutrality (28°C) was evaluated. Compared to wild type (WT) mice on the control diet, Scd1-/- mice were leaner, had higher EE, lower hepatic and serum triglycerides, and lower serum leptin and insulin. Although dietary MR increased adipose tissue UCP1 expression, hepatic Fgf21 mRNA, 24 h EE, and reduced serum triglycerides in Scd1-/- mice, it failed to reduce adiposity or produce any further reduction in hepatic triglycerides, serum insulin, or serum leptin. These findings indicate that even when thermal stress is minimized, global deletion of SCD1 mimics and effectively masks many of the metabolic responses to dietary MR. However, the retention of several key effects of dietary MR in this model indicates that SCD1 is not a mediator of the biological effects of the diet.

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Regulation of longevity and oxidative stress by nutritional interventions: role of methionine restriction.

Sanchez-Roman I, Barja G.

Exp Gerontol. 2013 Oct;48(10):1030-42. doi: 10.1016/j.exger.2013.02.021. Epub 2013 Feb 27. Review.

PMID: 23454735

Abstract

Comparative studies indicate that long-lived mammals have low rates of mitochondrial reactive oxygen species production (mtROSp) and oxidative damage in their mitochondrial DNA (mtDNA). Dietary restriction (DR), around 40%, extends the mean and maximum life span of a wide range of species and lowers mtROSp and oxidative damage to mtDNA, which supports the mitochondrial free radical theory of aging (MFRTA). Regarding the dietary factor responsible for the life extension effect of DR, neither carbohydrate nor lipid restriction seems to modify maximum longevity. However protein restriction (PR) and methionine restriction (at least 80% MetR) increase maximum lifespan in rats and mice. Interestingly, only 7weeks of 40% PR (at least in liver) or 40% MetR (in all the studied organs, heart, brain, liver or kidney) is enough to decrease mtROSp and oxidative damage to mtDNA in rats, whereas neither carbohydrate nor lipid restriction changes these parameters. In addition, old rats also conserve the capacity to respond to 7weeks of 40% MetR with these beneficial changes. Most importantly, 40% MetR, differing from what happens during both 40% DR and 80% MetR, does not decrease growth rate and body size of rats. All the available studies suggest that the decrease in methionine ingestion that occurs during DR is responsible for part of the aging-delaying effect of this intervention likely through the decrease of mtROSp and ensuing DNA damage that it exerts. We conclude that lowering mtROS generation is a conserved mechanism, shared by long-lived species and dietary, protein, and methionine restricted animals, that decreases damage to macromolecules situated near the complex I mtROS generator, especially mtDNA. This would decrease the accumulation rate of somatic mutations in mtDNA and maybe finally also in nuclear DNA.

KEYWORDS:

%FRL; 8-oxo-7,8-dihydro-2′deoxyguanosine; 8-oxodG; Aging; BER; Complex I; DNA damage; DR; Dietary restriction; IGF; IIS; MFRTA; MetR; Mitochondria; PR; Reactive oxygen species; S-adenosylhomocysteine; S-adenosylmethyonine; SAH; SAM; base excision repair; dietary restriction; insulin-like growth factor; insulin/insulin-like growth factor signaling; methionine restriction; mitochondrial DNA; mitochondrial ROS production; mitochondrial free radical theory of aging; mitochondrial oxygen consumption; mtDNA; mtROSp; mtVO(2); nDNA; nuclear DNA; percentage free radical leak; protein restriction

 

Magnesium Intake, Quality of Carbohydrates, and Risk of Type 2 Diabetes: Results From Three U.S. Cohorts.

Hruby A, Guasch-Ferré M, Bhupathiraju SN, Manson JE, Willett WC, McKeown NM, Hu FB.

Diabetes Care. 2017 Oct 4. pii: dc171143. doi: 10.2337/dc17-1143. [Epub ahead of print]

PMID: 28978672

http://sci-hub.cc/10.2337/dc17-1143

Abstract

OBJECTIVE:

Magnesium intake is inversely associated with risk of type 2 diabetes in many observational studies, but few have assessed this association in the context of the carbohydrate quality of the diet. We hypothesized that higher magnesium intake is associated with lower risk of type 2 diabetes, especially in the context of a poor-carbohydrate-quality diet characterized by low cereal fiber or high glycemic index (GI) or glycemic load (GL).

RESEARCH DESIGN AND METHODS:

In the Nurses' Health Study (NHS; 1984-2012, n = 69,176), NHS2 (1991-2013, n = 91,471), and the Health Professionals' Follow-Up Study (1986-2012, n = 42,096), dietary intake was assessed from food frequency questionnaires every 4 years. Type 2 diabetes was ascertained by biennial and supplementary questionnaires. We calculated multivariate hazard ratios (HRs) of magnesium intake and incident diabetes, adjusted for age, BMI, family history of diabetes, physical activity, smoking, hypertension, hypercholesterolemia, GL, energy intake, alcohol, cereal fiber, polyunsaturated fats, trans fatty acids, and processed meat, and we considered the joint associations of magnesium and carbohydrate quality on diabetes risk.

RESULTS:

We documented 17,130 incident cases of type 2 diabetes over 28 years of follow-up. In pooled analyses across the three cohorts, those with the highest magnesium intake had 15% lower risk of type 2 diabetes compared with those with the lowest intake (pooled multivariate HR in quintile 5 vs. 1: 0.85 [95% CI 0.80-0.91], P < 0.0001). Higher magnesium intake was more strongly associated with lower risk of type 2 diabetes among participants with high GI or low cereal fiber than among those with low GI or high cereal fiber (both P interaction <0.001).

CONCLUSIONS:

Higher magnesium intake is associated with lower risk of type 2 diabetes, especially in the context of lower-carbohydrate-quality diets.

 

Weight loss from 20 years of age is associated with cognitive impairment in middle-aged and elderly individuals.

Kitamura K, Watanabe Y, Nakamura K, Takahashi A, Takachi R, Oshiki R, Kobayashi R, Saito T, Tsugane S, Sasaki A.

PLoS One. 2017 Oct 5;12(10):e0185960. doi: 10.1371/journal.pone.0185960. eCollection 2017.

PMID: 28982190

Abstract

BACKGROUND:

Few empirical studies have been conducted to identify modifiable factors that may affect cognitive impairment in Japanese individuals. The present study aimed to clarify whether body mass and lifestyle are associated with cognitive impairment in Japanese middle-aged and elderly individuals.

METHODS:

Subjects were 1814 community-dwelling individuals aged 44-79 years, all of whom were participants of the Murakami Cohort Study baseline survey conducted in 2011-2013. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) in 2014-2016, and cognitive impairment, the outcome measure, was defined as an MMSE score <24. Predictor variables were body mass index (BMI), long-term weight changes from 20 years of age, and lifestyle factors, such as smoking, drinking, and physical activity levels, which were obtained from a self-administered questionnaire in the baseline survey. Covariates were sex, age, education level, and histories of stroke and diabetes. Multiple logistic regression analysis was used to calculate the adjusted odds ratios (ORs).

RESULTS:

The prevalence of overall cognitive impairment was 6.2%. The adjusted ORs of cognitive impairment in the lowest (<[-4]kg) (OR = 2.70, 95%CI, 1.18-6.20) and second ([-4]-[0]kg) (OR = 2.37, 95%CI, 1.04-5.37) quintiles for long-term weight change were significantly higher than the reference 4th quintile ([+4]-[+7]kg). The adjusted OR in the highest quintile (≥[+8]kg) was 2.24 (95%CI, 0.99-5.04). Current BMI was not associated with cognitive impairment.

CONCLUSIONS:

Long-term weight loss is associated with cognitive impairment in Japanese middle-aged and elderly individuals. Because the present study was retrospective in nature, prospective studies should also be conducted for further characterization of this association.

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A Walnut-Enriched Diet Reduces Lipids in Healthy Caucasian Subjects, Independent of Recommended Macronutrient Replacement and Time Point of Consumption: a Prospective, Randomized, Controlled Trial.

Bamberger C, Rossmeier A, Lechner K, Wu L, Waldmann E, Stark RG, Altenhofer J, Henze K, Parhofer KG.

Nutrients. 2017 Oct 6;9(10). pii: E1097. doi: 10.3390/nu9101097.

PMID: 28984822

http://www.mdpi.com/2072-6643/9/10/1097

Abstract

Studies indicate a positive association between walnut intake and improvements in plasma lipids. We evaluated the effect of an isocaloric replacement of macronutrients with walnuts and the time point of consumption on plasma lipids. We included 194 healthy subjects (134 females, age 63 ± 7 years, BMI 25.1 ± 4.0 kg/m²) in a randomized, controlled, prospective, cross-over study. Following a nut-free run-in period, subjects were randomized to two diet phases (8 weeks each). Ninety-six subjects first followed a walnut-enriched diet (43 g walnuts/day) and then switched to a nut-free diet. Ninety-eight subjects followed the diets in reverse order. Subjects were also randomized to either reduce carbohydrates (n = 62), fat (n = 65), or both (n = 67) during the walnut diet, and instructed to consume walnuts either as a meal or as a snack. The walnut diet resulted in a significant reduction in fasting cholesterol (walnut vs.

CONTROL: -8.5 ± 37.2 vs. -1.1 ± 35.4 mg/dL; p = 0.002), non-HDL cholesterol (-10.3 ± 35.5 vs. -1.4 ± 33.1 mg/dL; p ≤ 0.001), LDL-cholesterol (-7.4 ± 32.4 vs. -1.7 ± 29.7 mg/dL; p = 0.029), triglycerides (-5.0 ± 47.5 vs. 3.7 ± 48.5 mg/dL; p = 0.015) and apoB (-6.7 ± 22.4 vs. -0.5 ± 37.7; p ≤ 0.001), while HDL-cholesterol and lipoprotein (a) did not change significantly. Neither macronutrient replacement nor time point of consumption significantly affected the effect of walnuts on lipids. Thus, 43 g walnuts/d improved the lipid profile independent of the recommended macronutrient replacement and the time point of consumption.

KEYWORDS:

carbohydrate; cardiovascular disease; cholesterol; fat; lipids; macronutrient replacement; n-3-PUFA; nuts; walnuts

----------------

The research was supported by a grant from the California Walnut Commission (Folsom, CA) to K.G.P..

 

Differences in Parkinson's Disease Risk with Caffeine Intake and Postmenopausal Hormone Use.

Kim IY, O'Reilly ÉJ, Hughes KC, Gao X, Schwarzschild MA, Ascherio A.

J Parkinsons Dis. 2017 Oct 4. doi: 10.3233/JPD-171175. [Epub ahead of print]

PMID: 28984617

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554265/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554265/pdf/nihms378750.pdf

Abstract

BACKGROUND:

Caffeine intake has been associated with a lower risk of Parkinson's disease (PD). This association is robust in men, but inconsistent in women due to a possible interaction with post-menopausal hormone (PMH) use.

OBJECTIVE:

To (1) evaluate the association between caffeine intake and PD risk and (2) assess potential effect modification of the association by PMH use among women.

METHODS:

We examined associations between caffeine intake and incident PD risk in the Nurses' Health Study (NHS) (N = 121,701 women) and the Health Professionals Follow-up Study (HPFS) (N = 51,529 men). Dietary data on coffee and caffeine from other sources were collected every four years using a validated semi-quantitative food frequency questionnaire for both cohorts. Information on lifestyle and incident PD diagnosis was updated biennially and PD diagnoses were confirmed by medical record review. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models.

RESULTS:

We documented a total of 1,219 PD cases over the follow-up period. The multivariable-adjusted HR comparing the highest to lowest quintile of caffeine intake was 0.50 (95% CI: 0.37, 0.68; Ptrend<0.0001) in the HPFS. Among women, there was a suggestion of an interaction between coffee intake and PMH use (P = 0.08). In the pooled analyses combining men and women who have never used PMH, the risk of PD was lower as coffee intake increased (Ptrend<0.001).

CONCLUSIONS:

Our results support previous findings that increased caffeine intake may be associated with a decreased PD risk in men and women who have never used PMH.

KEYWORDS:

Health Professionals Follow-up Study; Nurses’ Health Study; Parkinson’s disease; caffeine; estrogens

 

Dietary intake of antioxidant vitamins and risk of stroke: the Japan Public Health Center-based Prospective Study.

Uesugi S, Ishihara J, Iso H, Sawada N, Takachi R, Inoue M, Tsugane S.

Eur J Clin Nutr. 2017 Oct;71(10):1179-1185. doi: 10.1038/ejcn.2017.71. Epub 2017 Jul 12.

PMID: 28699629

Abstract

BACKGROUND/OBJECTIVES:

Epidemiologic evidence on the relationship between antioxidant vitamin intake and stroke is limited. We aimed to investigate the association between dietary intake of antioxidant vitamins and the incidence of total stroke and ischemic stroke.

SUBJECTS/METHODS:

The subjects were 82 044 Japanese men and women aged 45-74 years under the Japan Public Health Center-based Prospective Cohort Study. Between 1995 and 1997, dietary assessment was done using a food frequency questionnaire. During 983 857 person-years of follow-up until the end of 2009 we documented 3541 incident total strokes and 2138 ischemic strokes.

RESULTS:

Dietary intakes of α-carotene, β-carotene, α-tocopherol and vitamin C were not inversely associated with the incidence of total stroke and ischemic stroke adjustment for cardiovascular risk factors and selected lifestyle variables. When stratified by current smoking status, the inverse association between dietary vitamin C intake and incidence of total stroke observed among non-smokers but not smokers, with respective multivariable hazard ratios for the highest versus lowest quintiles of vitamin C of 0.81 (95% confidence interval (CI), 0.68-0.96; P-trend=0.03) among non-smokers; and 1.03 (0.84-1.25; P-trend=0.55) among smokers. As for ischemic stroke, the corresponding multivariable hazard ratios were 0.76 (0.60-0.96; P-trend=0.02) among non-smokers; and 1.00 (0.78-1.28; P-trend=0.61) among smokers.

CONCLUSIONS:

Dietary vitamin C intake was inversely associated with the incidence of total stroke and ischemic stroke among non-smokers.

 

Soyfood and isoflavone intake and risk of type 2 diabetes in Vietnamese adults.

Nguyen CT, Pham NM, Do VV, Binns CW, Hoang VM, Dang DA, Lee AH.

Eur J Clin Nutr. 2017 Oct;71(10):1186-1192. doi: 10.1038/ejcn.2017.76. Epub 2017 May 10.

PMID: 28488690

Abstract

BACKGROUND/OBJECTIVES:

Animal studies have demonstrated that soy isoflavones exert antidiabetic effects. However, evidence regarding the association between soyfood intake, a unique source of isoflavones, and type 2 diabetes remains inconclusive. This study assessed the relationship between habitual intakes of soyfoods and major isoflavones and risk of type 2 diabetes in Vietnamese adults.

SUBJECTS/METHODS:

A hospital-based case-control study was conducted in Vietnam during 2013-2015. A total of 599 newly diagnosed diabetic cases (age 40-65 years) and 599 hospital-based controls, frequency matched by age and sex, were recruited in Hanoi, capital city of Vietnam. Information on frequency and quantity of soyfood and isoflavone intake, together with demographics, habitual diet and lifestyle characteristics, was obtained from direct interviews using a validated and reliable questionnaire. Unconditional logistic regression analyses were performed to examine the association between soy variables and type 2 diabetes risk.

RESULTS:

Higher intake of total soyfoods was significantly associated with a lower risk of type 2 diabetes; the adjusted odds ratio (OR) for the highest versus the lowest intake was 0.31 (95% confidence interval (CI): 0.21-0.46; P<0.001). An inverse dose-response relationship of similar magnitude was also observed for total isoflavone intake (OR: 0.35; 95% CI: 0.24 to 0.49; P<0.001). In addition, inverse associations of specific soyfoods (soy milk, tofu and mung bean sprout) and major isoflavones (daidzein, genistein and glycitein) with the type 2 diabetes risk were evident.

CONCLUSIONS:

Soyfood and isoflavone intake was associated with a lower type 2 diabetes risk in Vietnamese adults.

 

Different combinations of glucose tolerance and blood pressure status and incident cardiovascular disease and all-cause mortality events.

Hajebrahimi MA, Akbarpour S, Eslami A, Azizi F, Hadaegh F.

J Hum Hypertens. 2017 Nov;31(11):744-749. doi: 10.1038/jhh.2017.49. Epub 2017 Jul 27.

PMID: 28748918

http://sci-hub.cc/10.1038/jhh.2017.49

Abstract

The purpose of this study was to evaluate the effect of combinations of blood pressure and glucose tolerance status on cardiovascular and all-cause mortality. A total of 7619 participants aged ⩾30 years old were stratified to nine categories as follows: (1) normotension (NTN) and normal glucose tolerance (NGT) (reference group), (2) NTN and pre-diabetes mellitus (pre-DM), (3) NTN and DM, (4) pre-hypertension (pre-HTN) and NGT, (5) pre-HTN and pre-DM, (6) pre-HTN and DM, (7) HTN and NGT, (8) HTN and pre-DM and (9) HTN and DM. Cox proportional hazards were applied to calculate the multivariate hazard ratios (HRs) of different groups for outcomes. For all-cause mortality outcomes, prevalent cardiovascular disease (CVD) was also adjusted. In a median follow-up of 11.3 years, 696 CVD and 412 all-cause mortality events occurred. Among the population free from CVD at baseline (n=7249), presence of HTN was associated with increased risk of CVD, regardless of glucose tolerance status with HRs of 1.97 (95% confidence interval (CI), 1.49-2.61), 2.25 (1.68-3.02) and 3.16 (2.28-4.37) for phenotypes of HTN and NGT, HTN and pre-DM and HTN and DM for CVD, respectively; corresponding HRs for all-cause mortality were 1.65 (95% CI, 1.15-2.37), 1.69 (1.15-2.49) and 2.73 (1.80-4.14), respectively. Phenotypes of NTN and pre-DM (1.48; 1.03-2.14) and NTN and DM (2.04; 1.06-3.92) were also associated with CVD and all-cause mortality, respectively. HTN was significantly associated with CVD/mortality events, regardless of glucose tolerance status. Blood pressure <120/80 mm Hg among pre-diabetic/diabetic population, not on antihypertensive medications, was generally associated with worse outcomes.

 

[The below paper is not pdf-availed.]

Dietary Sodium Modifies Serum Uric Acid Concentrations in Humans.

Todd AS, Walker RJ, MacGinley RJ, Kelly J, Merriman TR, Major TJ, Johnson RJ.

Am J Hypertens. 2017 Sep 7. doi: 10.1093/ajh/hpx123. [Epub ahead of print]

PMID: 28985270

Abstract

BACKGROUND:

Subjects with hypertension are frequently obese or insulin resistant, both conditions in which hyperuricemia is common. Obese and insulin-resistant subjects are also known to have blood pressure that is more sensitive to changes in dietary sodium intake. Whether hyperuricemia is a resulting consequence, moderating or contributing factor to the development of hypertension has not been fully evaluated and very few studies have reported interactions between sodium intake and serum uric acid.

METHODS:

We performed further analysis of our randomized controlled clinical trials (Australian New Zealand Clinical Trials Registry #12609000161224 and #12609000292279) designed to assess the effects of modifying sodium intake on concentrations of serum markers, including uric acid. Uric acid and other variables (including blood pressure, renin, and aldosterone) were measured at baseline and 4 weeks following the commencement of low (60 mmol/day), moderate (150 mmol/day), and high (200-250 mmol/day) dietary sodium intake.

RESULTS:

The median aldosterone-to-renin ratio was 1.90 [pg/ml]/[pg/ml] (range 0.10-11.04). Serum uric acid fell significantly in both the moderate and high interventions compared to the low sodium intervention. This pattern of response occurred when all subjects were analyzed, and when normotensive or hypertensive subjects were analyzed alone.

CONCLUSIONS:

Although previously reported in hypertensive subjects, these data provide evidence in normotensive subjects of an interaction between dietary sodium intake and serum uric acid. As this interaction is present in the absence of hypertension, it is possible it could play a role in hypertension development, and will need to be considered in future trials of dietary sodium intake.

KEYWORDS:

blood pressure; hypertension; sodium; urate; uric acid

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Regional variation in health is predominantly driven by lifestyle rather than genetics.

Amador C, Xia C, Nagy R, Campbell A, Porteous D, Smith BH, Hastie N, Vitart V, Hayward C, Navarro P, Haley CS.

Nat Commun. 2017 Oct 6;8(1):801. doi: 10.1038/s41467-017-00497-5.

PMID: 28986520

https://www.nature.com/articles/s41467-017-00497-5

https://www.nature.com/articles/s41467-017-00497-5.pdf

Abstract

Regional differences in health-related phenotypes have been detected between and within countries. In Scotland, regions differ for a variety of health-related traits and display differences in mean lifespan of up to 7.5 years. Both genetics and lifestyle differences are potential causes of this variation. Using data on obesity-related traits of ~11,000 Scottish individuals with genome-wide genetic information and records of lifestyle and socioeconomic factors, we explored causes of regional variation by using models that incorporate genetic and environmental information jointly. We found that variation between individuals within regions showed substantial influence of both genetic variation and family environment. Regional variation for most obesity traits was associated with lifestyle and socioeconomic variables, such as smoking, diet and deprivation which are potentially modifiable. There was limited evidence that regional differences were of genetic origin. This has important implications for healthcare policies, suggesting that inequalities can be tackled with appropriate social and economic interventions.Health-related traits are known to vary geographically. Here, Amador and colleagues show that regional variation of obesity-related traits in a Scottish population is influenced more by lifestyle differences than it is by genetic differences.

 

Associations Between Diabetes and Both Cardiovascular Disease and All-Cause Mortality Are Modified by Grip Strength: Evidence From UK Biobank, a Prospective Population-Based Cohort Study.

Celis-Morales CA, Petermann F, Hui L, Lyall DM, Iliodromiti S, McLaren J, Anderson J, Welsh P, Mackay DF, Pell JP, Sattar N, Gill JMR, Gray SR.

Diabetes Care. 2017 Oct 6. pii: dc170921. doi: 10.2337/dc17-0921. [Epub ahead of print]

PMID: 28986505

http://sci-hub.cc/10.2337/dc17-0921

Abstract

OBJECTIVE:

Grip strength and diabetes are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to predispose to adverse health outcomes is unknown. This study determined the interactions between diabetes and grip strength and their association with health outcomes.

RESEARCH DESIGN AND METHODS:

We undertook a prospective, general population cohort study by using UK Biobank. Cox proportional hazards models were used to explore the associations between both grip strength and diabetes and the outcomes of all-cause mortality and CVD incidence/mortality as well as to test for interactions between diabetes and grip strength.

RESULTS:

347,130 UK Biobank participants with full data available (mean age 55.9 years, BMI 27.2 kg/m2, 54.2% women) were included in the analysis, of which 13,373 (4.0%) had diabetes. Over a median follow-up of 4.9 years (range 3.3-7.8 years), 6,209 died (594 as a result of CVD), and 4,301 developed CVD. Participants with diabetes were at higher risk of all-cause and CVD mortality and CVD incidence. Significant interactions (P < 0.05) existed whereby the risk of CVD mortality was higher in participants with diabetes with low (hazard ratio {HR} 4.05 [95% CI 2.72, 5.80]) versus high (HR 1.46 [0.87, 2.46]) grip strength. Similar results were observed for all-cause mortality and CVD incidence.

CONCLUSIONS:

Risk of adverse health outcomes among people with diabetes is lower in those with high grip strength. Low grip strength may be useful to identify a higher-risk subgroup of patients with diabetes. Intervention studies are required to determine whether resistance exercise can reduce risk.

 

Association between preconception maternal beverage intake and in vitro fertilization outcomes.

Machtinger R, Gaskins AJ, Mansur A, Adir M, Racowsky C, Baccarelli AA, Hauser R, Chavarro JE.

Fertil Steril. 2017 Oct 3. pii: S0015-0282(17)31911-8. doi: 10.1016/j.fertnstert.2017.09.007. [Epub ahead of print]

PMID: 28985907

Abstract

OBJECTIVE:

To study whether maternal intake of beverage type affects IVF outcomes.

DESIGN:

A prospective study.

SETTING:

Tertiary, university-affiliated center.

PATIENT(S):

Three hundred forty women undergoing IVF from 2014 through 2016 for infertility as well as for pregenetic diagnosis for autosomal recessive diseases were enrolled during ovarian stimulation and completed a questionnaire describing their usual beverage consumption.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

IVF outcomes were abstracted from medical records. Total caffeine intake was estimated by summing the caffeine content for specific beverages multiplied by frequency of intake. Associations between specific types of beverages and IVF outcomes were analyzed using Poisson and logistic regression models adjusting for possible confounders.

RESULT(S):

Higher intake of sugared soda was associated with lower total, mature, and fertilized oocytes and top-quality embryos after ovarian stimulation. Women who consumed sugared soda had, on average, 1.1 fewer oocytes retrieved, 1.2 fewer mature oocytes retrieved, 0.6 fewer fertilized oocytes, and 0.6 fewer top-quality embryos compared with women who did not consume sugared soda. Furthermore, compared with women who did not drink sugared soda, the adjusted difference in percent of cycles resulting in live birth for women consuming 0.1-1 cups/day and >1 cup/day were -12% and -16%, respectively. No associations were found between consumption of coffee, caffeine, or diet sodas and IVF outcome.

CONCLUSION(S):

Sugared beverages, independent of their caffeine content, may be a bigger threat to reproductive success than caffeine and caffeinated beverages without added sugar.

KEYWORDS:

IVF; caffeinated beverages; non-caffeinated beverages; sugared soda

 

Toenail selenium levels and prevalence of dyslipidaemia among Korean adults.

Jang J, Morris JS, Park K.

Br J Nutr. 2017 Sep;118(6):473-480. doi: 10.1017/S0007114517002343.

PMID: 28980892

https://sci-hub.cc/https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/toenail-selenium-levels-and-prevalence-of-dyslipidaemia-among-korean-adults/C2A69A8F3F8BAAA96135E73CF27189BB

Abstract

Multiple studies have elucidated the antioxidant properties of Se, which are now well known among the nutrition and biomedical science communities. Recently, considerable interest has been focused on the possible association between Se exposure and risk of metabolic disease, such as lipid dysregulation; however, there is limited epidemiological data on this topic. The present study aimed to investigate associations between toenail Se levels and dyslipidaemia or individual lipid levels, and to examine the effect of dietary supplement use on these associations. We analysed baseline data from a cohort in the Yeungnam area, including 232 men and 269 women. Information on demographic, dietary and lifestyle characteristics was obtained through a self-reported questionnaire. Se levels in toenail specimens were measured using neutron activation analysis. Fasting blood lipid levels were measured during medical examinations. After adjusting for multiple confounding variables, we observed no association between toenail Se levels and dyslipidaemia or individual lipid profiles. However, the association was modified by dietary supplement use. Among the supplement users, higher toenail Se levels were associated with a higher prevalence of lipid dysregulation, whereas non-users exhibited a lower prevalence of lipid dysregulation. Associations between toenail Se levels, lipid levels and dyslipidaemia may be influenced by taking dietary supplements. Future large-scale, prospective cohort studies should be conducted to further evaluate the association between Se levels in the body and metabolic health effects in light of increasing rates of dietary supplement use.

KEYWORDS:

SELEN Trace Element Study of Korean Adults in Yeungnam Area; TC total cholesterol; Asian adults; Dietary supplements; Dyslipidaemia; Epidemiological effect modifiers; Selenium; Toenail analysis

 

Dietary egg-white protein increases body protein mass and reduces body fat mass through an acceleration of hepatic β-oxidation in rats.

Matsuoka R, Shirouchi B, Umegatani M, Fukuda M, Muto A, Masuda Y, Kunou M, Sato M.

Br J Nutr. 2017 Sep;118(6):423-430. doi: 10.1017/S0007114517002306.

PMID: 28980893

http://sci-hub.cc/10.1017/S0007114517002306

Abstract

Egg-white protein (EWP) is known to reduce lymphatic TAG transport in rats. In this study, we investigated the effects of dietary EWP on body fat mass. Male rats, 4 weeks old, were fed diets containing either 20 % EWP or casein for 28 d. Carcass protein levels and gastrocnemius leg muscle weights in the EWP group were significantly higher than those in the casein group. In addition, carcass TAG levels and abdominal fat weights in the EWP group were significantly lower than those in the casein group; adipocyte size in abdominal fat in the EWP group was smaller than that in the casein group. To identify the involvement of dietary fat levels in the rats, one of two fat levels (5 or 10 %) was added to their diet along with the different protein sources (EWP and casein). Abdominal fat weight and serum and hepatic TAG levels were significantly lower in the EWP group than in the casein group. Moreover, significantly higher values of enzymatic activity related to β-oxidation in the liver were observed in the EWP group compared with the casein group. Finally, abdominal fat weight reduction in the EWP group with the 10 % fat diet was lower than that in the EWP group with the 5 % fat diet. In conclusion, our results indicate that, in addition to the inhibition of dietary TAG absorption reported previously, dietary EWP reduces body fat mass in rats through an increase of body protein mass and the acceleration of β-oxidation in the liver.

KEYWORDS:

β-Oxidation; EWP egg-white protein; Adipocyte size; Body composition; Egg-white protein; Rats

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Associations of Muscle Mass and Strength with All-Cause Mortality among US Older Adults.

Li R, Xia J, Zhang X, Gathirua-Mwangi WG, Guo J, Li Y, McKenzie S, Song Y.

Med Sci Sports Exerc. 2017 Oct 4. doi: 10.1249/MSS.0000000000001448. [Epub ahead of print]

PMID: 28991040

http://sci-hub.cc/10.1249/MSS.0000000000001448

Abstract

INTRODUCTION:

Recent studies suggested that muscle mass and muscle strength may independently or synergistically affect aging-related health outcomes in older adults; however, prospective data on mortality in the general population are sparse.

METHODS:

We aimed to prospectively examine individual and joint associations of low muscle mass and low muscle strength with all-cause mortality in a nationally representative sample. This study included 4,449 participants aged 50 years and older from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 with public-use 2011 linked mortality files. Weighted multivariable logistic regression models were adjusted for age, sex, race, BMI, smoking, alcohol use, education, leisure-time physical activity (LTPA), sedentary time, and comorbid diseases.

RESULTS:

Overall, the prevalence of low muscle mass was 23.1% defined by appendicular lean mass (ALM) and 17.0% defined by ALM/BMI, and the prevalence of low muscle strength was 19.4%. In the joint analyses, all-cause mortality was significantly higher among individuals with low muscle strength, whether they had low muscle mass (OR 2.03, 95% CI, 1.27-3.24 for ALM; OR 2.53, 95% CI, 1.64-3.88 for ALM/BMI) or not (OR 2.66, 95% CI 1.53-4.62 for ALM; OR 2.17, 95% CI 1.29-3.64 for ALM/BMI). In addition, the significant associations between low muscle strength and all-cause mortality persisted across different levels of metabolic syndrome (MetS), sedentary time, and LTPA.

CONCLUSIONS:

Low muscle strength was independently associated with elevated risk of all-cause mortality, regardless of muscle mass, MetS, sedentary time, or LTPA among US older adults, indicating the importance of muscle strength in predicting aging-related health outcomes in older adults.

 

 

A Systematic Review of Reminiscence Therapy for Older Adults in Taiwan.

Yen HY, Lin LJ.

J Nurs Res. 2017 Oct 10. doi: 10.1097/jnr.0000000000000233. [Epub ahead of print]

PMID: 29016468

Abstract

BACKGROUND:

Population aging is an increasing phenomenon in many countries around the world. It has been estimated that more than one quarter of all older adults experience a mental or neurological disorder or disease such as dementia, depression, anxiety, and substance abuse. Reminiscence is a popular treatment for enhancing well-being in older adults. Previous studies have shown that reminiscence therapy improves the cognitive functions, behaviors, and other psychosocial outcomes in older adult patients. The themes and materials that are used in reminiscence treatments for the older adults in Taiwan differ from those used in other countries because of Taiwan's unique historical background and culture.

PURPOSE:

The main purpose of the current study was to review systematically the application and outcomes of reminiscence therapy in Taiwan.

METHOD:

The terms "reminiscence," "dementia," "Alzheimer's disease," and "Taiwan" were used in an Integrated Resources Search that was conducted at National Taiwan Normal University. Sixteen articles were systematically reviewed using a synthesis of two matrices of experimental designs and intervention designs.

RESULT:

Reminiscence group sizes ranged between 7 and 12 participants, session frequencies were all once a week for periods lasting between 4 and 16 weeks, and session durations ranged from 30 minutes to 2 hours. The memories of the participants were stimulated using materials dating from their youth such as Taiwanese folk songs, toys, photos, radio programs, newspapers, and food and drinks. In terms of research methodology, most of the studies that were reviewed used quasi-experimental designs without random assignment or control group due to sample size. A minority of the reviewed studies applied the randomized controlled treatment method. Only a few of the studies evaluated indicators in pretest, posttest, and follow-up periods. The results of these studies identified several benefits of reminiscence therapy in Taiwanese older adults, including improvements in cognitive function, anxiety, depressive symptoms, self-esteem, life satisfaction, and personal interaction.

CONCLUSIONS:

Reminiscence is a good noninvasive treatment for the prevention and treatment of mental diseases in Taiwanese older adults. Furthermore, reminiscence promotes mental health in older adults. Finally, this study provides recommendations for further study and clinical application of reminiscence therapy in Taiwan.

 

Eating frequency predicts changes in regional body fat distribution in healthy adults.

Georgiopoulos G, Karatzi K, Yannakoulia M, Georgousopoulou E, Efthimiou E, Mareti A, Bakogianni I, Mitrakou A, Papamichael C, Stamatelopoulos K.

QJM. 2017 Jun 21. doi: 10.1093/qjmed/hcx120. [Epub ahead of print]

PMID: 29017004

Abstract

BACKGROUND:

Eating frequency (EF) has been associated with generalized obesity.

AIM:

We aimed to prospectively investigate potential associations of frequency of eating episodes with regional fat layers.

DESIGN:

EF was evaluated at baseline in 115 subjects free of clinically overt cardiovascular disease (54 ± 9.1 years, 70 women) in a prospective, observational study.

METHODS:

Metabolic parameters known to be associated with dietary factors and anthropometric markers including ultrasound assessment of subcutaneous (Smin) and pre-peritoneal (Pmax) fat and their ratio Smin/Pmax (AFI) were evaluated at baseline and at follow-up, 5 years later.

RESULTS:

EF at baseline positively correlated with Pmax, even after adjustment for potential confounders. EF above median was also an independent predictor for Pmax (beta coefficient = -0.192, P = 0.037) and AFI (beta coefficient = 0.199, P = 0.049) at follow up. Multivariable linear mixed models analysis demonstrated that subjects with increased EF presented a lower progression rate of Pmax (beta = -0.452, P = 0.006) and a higher progression rate of AFI (beta = 0.563, P = 0.003) over time, independently of age, sex, progression of BMI, energy intake, smoking and changes in parameters of glucose metabolism.

CONCLUSIONS:

High EF is associated with lower progression rate of pre-peritoneal fat accumulation. Future interventional studies should further investigate the clinical utility of these findings.

 

Effects of berberine, curcumin, resveratrol alone and in combination with chemotherapeutic drugs and signal transduction inhibitors on cancer cells-Power of nutraceuticals.

McCubrey JA, Abrams SL, Lertpiriyapong K, Cocco L, Ratti S, Martelli AM, Candido S, Libra M, Murata RM, Rosalen PL, Lombardi P, Montalto G, Cervello M, Gizak A, Rakus D, Steelman LS.

Adv Biol Regul. 2017 Oct 3. pii: S2212-4926(17)30166-5. doi: 10.1016/j.jbior.2017.09.012. [Epub ahead of print]

PMID: 28988970

http://sci-hub.cc/10.1016/j.jbior.2017.09.012

Abstract

Over the past fifty years, society has become aware of the importance of a healthy diet in terms of human fitness and longevity. More recently, the concept of the beneficial effects of certain components of our diet and other compounds, that are consumed often by different cultures in various parts of the world, has become apparent. These "healthy" components of our diet are often referred to as nutraceuticals and they can prevent/suppress: aging, bacterial, fungal and viral infections, diabetes, inflammation, metabolic disorders and cardiovascular diseases and have other health-enhancing effects. Moreover, they are now often being investigated because of their anti-cancer properties/potentials. Understanding the effects of various natural products on cancer cells may enhance their usage as anti-proliferative agents which may be beneficial for many health problems. In this manuscript, we discuss and demonstrate how certain nutraceuticals may enhance other anti-cancer drugs to suppress proliferation of cancer cells.

KEYWORDS:

Berberine; Curcumin; Metformin; Resveratrol

 

Sirt1 and Parp1 as epigenome safeguards and microRNAs as SASP-associated signals, in cellular senescence and aging.

Hekmatimoghaddam S, Dehghani-Firoozabadi A, Zare-Khormizi MR, Pourrajab F.

Ageing Res Rev. 2017 Oct 6. pii: S1568-1637(17)30085-5. doi: 10.1016/j.arr.2017.10.001. [Epub ahead of print] Review.

PMID: 28993289

Abstract

Cellular senescence (CS) is underlying mechanism of organism aging and is closely interconnected with age-related diseases (ARDs). Thus, any attempt that influences CS, may be undertaken to reverse or inhibit senescence, whereby could prolong healthy life span. Until now, two main proposes are epigenetic and genetic modifications of cell fate. The first one concerns rejuvenation through effective reprogramming in cells undergoing senescence, or derived from very old or progeroid patients, by which is effective in vitro in induced pluripotent stem cells (iPSCs). The second approach concerns modification of senescence signaling pathways like as IGF-induced agents. However, senescence research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of senescence is controlled, at least to some extent, by epigenetic pathways and biochemical processes conserved in evolution. In this review we try to concentrate in very specific pathway (DNA damage response (DDR) and epigenetic modifiers) and very specific determinants (senescence-associated secretory phenotype (SASP)-miRNAs) of human premature aging. A major challenge is to dissect the interconnectedness between the candidate elements and their relative contributions to aging, with the final goal of identifying new opportunities for design of novel anti-aging treatments or avoidance of age-associated manifestations while knowing that aging is unavoidable and we cannot expect its elimination, but prolonging healthy life span is a goal worth serious consideration.

KEYWORDS:

Cellular senescence; age-related diseases; epigenetic factors; miRNAs; stem cells

 

Sirtuins at the crossroads of stemness, aging, and cancer.

O'Callaghan C, Vassilopoulos A.

Aging Cell. 2017 Oct 10. doi: 10.1111/acel.12685. [Epub ahead of print] Review.

PMID: 28994177

Abstract

Sirtuins are stress-responsive proteins that direct various post-translational modifications (PTMs) and as a result, are considered to be master regulators of several cellular processes. They are known to both extend lifespan and regulate spontaneous tumor development. As both aging and cancer are associated with altered stem cell function, the possibility that the involvement of sirtuins in these events is mediated by their roles in stem cells is worthy of investigation. Research to date suggests that the individual sirtuin family members can differentially regulate embryonic, hematopoietic as well as other adult stem cells in a tissue- and cell type-specific context. Sirtuin-driven regulation of both cell differentiation and signaling pathways previously involved in stem cell maintenance has been described where downstream effectors involved determine the biological outcome. Similarly, diverse roles have been reported in cancer stem cells (CSCs), depending on the tissue of origin. This review highlights the current knowledge which places sirtuins at the intersection of stem cells, aging, and cancer. By outlining the plethora of stem cell-related roles for individual sirtuins in various contexts, our purpose was to provide an indication of their significance in relation to cancer and aging, as well as to generate a clearer picture of their therapeutic potential. Finally, we propose future directions which will contribute to the better understanding of sirtuins, thereby further unraveling the full repertoire of sirtuin functions in both normal stem cells and CSCs.

KEYWORDS:

EMT ; Sirtuins; aging; calorie restriction; cancer; stem cells

 

Adverse Effects of Nutraceuticals and Dietary Supplements.

Ronis MJJ, Pedersen KB, Watt J.

Annu Rev Pharmacol Toxicol. 2017 Oct 6. doi: 10.1146/annurev-pharmtox-010617-052844. [Epub ahead of print]

PMID: 28992429

https://sci-hub.cc/http://www.annualreviews.org/doi/10.1146/annurev-pharmtox-010617-052844

Abstract

Over 70% of Americans take some form of dietary supplement every day, and the supplement industry is currently big business, with a gross of over $28 billion. However, unlike either foods or drugs, supplements do not need to be registered or approved by the US Food and Drug Administration (FDA) prior to production or sales. Under the Dietary Supplement Health and Education Act of 1994, the FDA is restricted to adverse report monitoring postmarketing. Despite widespread consumption, there is limited evidence of health benefits related to nutraceutical or supplement use in well-nourished adults. In contrast, a small number of these products have the potential to produce significant toxicity. In addition, patients often do not disclose supplement use to their physicians. Therefore, the risk of adverse drug-supplement interactions is significant. An overview of the major supplement and nutraceutical classes is presented here, together with known toxic effects and the potential for drug interactions.

 

The therapeutic potential of resveratrol: a review of clinical trials.

Berman AY, Motechin RA, Wiesenfeld MY, Holz MK.

NPJ Precis Oncol. 2017;1. pii: 35. doi: 10.1038/s41698-017-0038-6. Epub 2017 Sep 25.

PMID: 28989978

https://www.nature.com/articles/s41698-017-0038-6

https://www.nature.com/articles/s41698-017-0038-6.pdf

Abstract

Resveratrol is a nutraceutical with several therapeutic effects. It has been shown to mimic effects of caloric restriction, exert anti-inflammatory and anti-oxidative effects, and affect the initiation and progression of many diseases through several mechanisms. While there is a wealth of in vitro and in vivo evidence that resveratrol could be a promising therapeutic agent, clinical trials must confirm its potential. In this work, we reviewed the current clinical data available regarding the pharmacological action of resveratrol. Most of the clinical trials of resveratrol have focused on cancer, neurological disorders, cardiovascular diseases, diabetes, non-alcoholic fatty liver disease (NAFLD), and obesity. We found that for neurological disorders, cardiovascular diseases, and diabetes, the current clinical trials show that resveratrol was well tolerated and beneficially influenced disease biomarkers. However resveratrol had ambiguous and sometimes even detrimental effects in certain types of cancers and in NAFLD. In most of the clinical trials, the major obstacle presented was resveratrol's poor bioavailability. Thus, this work provides useful considerations for the planning and design of future pre-clinical and clinical research on resveratrol.

 

Nutrient-extraction blender preparation reduces postprandial glucose responses from fruit juice consumption.

Redfern KM, Cammack VL, Sweet N, Preston LA; SoBHCS Student Team, Jarvis MA, Rees GA.

Nutr Diabetes. 2017 Oct 9;7(10):e288. doi: 10.1038/nutd.2017.36.

PMID: 28991222

http://www.nature.com/nutd/journal/v7/n10/full/nutd201736a.html?foxtrotcallback=true

https://www.nature.com/nutd/journal/v7/n10/pdf/nutd201736a.pdf

Abstract

Although whole-fruit consumption is regarded as protective against type 2 diabetes (T2DM), conventionally prepared fruit juice is associated with increased T2DM risk, and current public health advice recommends its restriction. 'Nutrient extractor' style blenders are increasing in popularity worldwide as an alternative means of juicing fruit, but little is known about their effect on postprandial glucose levels. The current study investigated the effect of nutrient extraction on postprandial blood glucose response and glycemic index (GI) compared with a glucose control for both mixed fruit and a high GI fruit (mango). Remarkably, consumption of nutrient-extracted mixed fruit resulted in a significant lowering of the GI (32.7±8.5) compared with whole mixed fruit (66.2±8.2, P<0.05). For the high GI mango, there were no differences between nutrient-extracted and whole fruit, indicating that even for a high GI fruit the effect of nutrient extraction does not increase GI compared with the whole fruit. These findings suggest that, in contrast to conventionally prepared fruit juice, fruit juice prepared by nutrient extraction in some cases elicits a more favorable postprandial glycemic response than whole fruit and even for high GI fruits do not worsen the response. The mechanism responsible for this effect is currently unclear. However, these results suggest that fruit homogenized by nutrient extraction should be considered as a potential dietetic strategy for glycemic control.

 

Fruit fly study IDs missing links in fat-signaling system

Hormone alerts brain to fat-storage status, but its packaging system goes awry in obesity

Oct. 9, 2017

| By Rachel Tompa / Fred Hutch News Service

Animated illustration of fruit flies flying over a bathroom scale

A new study — in fruit flies — identifies missing links that explain how fat cells signal nutritional status to the brain.

Illustration by Kim Carney / Fred Hutch News Service

http://www.fredhutch.org/en/news/center-news/2017/10/fruit-fly-fat-signaling-system.html

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A Mechanism Coupling Systemic Energy Sensing to Adipokine Secretion

Akhila Rajan, Benjamin E. Housden, Frederik Wirtz-Peitz, Laura Holderbaum, Norbert Perrimon

Developmental Cell DOI: http://dx.doi.org/10.1016/j.devcel.2017.09.007

http://www.cell.com/developmental-cell/fulltext/S1534-5807(17)30730-X

http://www.cell.com/developmental-cell/pdf/S1534-5807(17)30730-X.pdf

Summary

Adipocytes sense systemic nutrient status and systemically communicate this information by releasing adipokines. The mechanisms that couple nutritional state to adipokine release are unknown. Here, we investigated how Unpaired 2 (Upd2), a structural and functional ortholog of the primary human adipokine leptin, is released from Drosophila fat cells. We find that Golgi reassembly stacking protein (GRASP), an unconventional secretion pathway component, is required for Upd2 secretion. In nutrient-rich fat cells, GRASP clusters in close proximity to the apical side of lipid droplets (LDs). During nutrient deprivation, glucagon-mediated increase in calcium (Ca2+) levels, via calmodulin kinase II (CaMKII) phosphorylation, inhibits proximal GRASP localization to LDs. Using a heterologous cell system, we show that human leptin secretion is also regulated by Ca2+ and CaMKII. In summary, we describe a mechanism by which increased cytosolic Ca2+ negatively regulates adipokine secretion and have uncovered an evolutionarily conserved molecular link between intracellular Ca2+ levels and energy homeostasis.

 

Female sex, early-onset hypertension, and risk of dementia.

Gilsanz P, Mayeda ER, Glymour MM, Quesenberry CP, Mungas DM, DeCarli C, Dean A, Whitmer RA.

Neurology. 2017 Oct 4. pii: 10.1212/WNL.0000000000004602. doi: 10.1212/WNL.0000000000004602. [Epub ahead of print]

PMID: 28978656

http://sci-hub.cc/10.1212/WNL.0000000000004602

ABSTRACT

Objective: To evaluate the association of early-adulthood and mid-adulthood hypertension with dementia in men and women.

Methods: We evaluated 5,646 members of a diverse integrated health care delivery system who had clinical examinations and health survey data from 1964 to 1973 (mean age 32.7 years; early adulthood) and 1978–1985 (mean age 44.3 years; mid-adulthood) and were members as of January 1, 1996 (mean age 59.8 years). Hypertension categories based on measurements of blood pressure (BP) and change in hypertension categories between the 2 examinations (e.g., onset hypertension) were used to predict dementia incidence from January 1, 1996, to September 30, 2015. Cox proportional hazard models were adjusted for demographics, vascular comorbidities, and hypertension treatment; inverse probability weighting accounted for differential attrition between first BP measurement and start of follow-up.

Results: A total of 532 individuals (9.4%) were diagnosed with dementia. Early adulthood hypertension was not associated with dementia, though effect estimates were elevated among women. Mid-adulthood hypertension was associated with 65% (95% confidence interval [CI] 1.25–2.18) increased dementia risk among women but not men. Onset of hypertension in mid-adulthood predicted 73% higher dementia risk in women (95% CI 1.24–2.40) compared to stable normotensive. There was no evidence that hypertension or changes in hypertension increased dementia risk among men.

Conclusions: Though midlife hypertension was more common in men, it was only associated with dementia risk in women. Sex differences in the timing of dementia risk factors have important implications for brain health and hypertension management.

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Higher resting metabolic rate in long-lived breeding Ansell's mole-rats (Fukomys anselli).

Schielke CKM, Burda H, Henning Y, Okrouhlík J, Begall S.

Front Zool. 2017 Sep 22;14:45. doi: 10.1186/s12983-017-0229-6. eCollection 2017.

PMID: 29018488

https://frontiersinzoology.biomedcentral.com/articles/10.1186/s12983-017-0229-6

https://frontiersinzoology.biomedcentral.com/track/pdf/10.1186/s12983-017-0229-6?site=frontiersinzoology.biomedcentral.com

Abstract

BACKGROUND:

Reproduction is an energetically expensive process that supposedly impairs somatic integrity in the long term, because resources are limited and have to be allocated between reproduction and somatic maintenance, as predicted by the life history trade-off model. The consequence of reduced investment in somatic maintenance is a gradual deterioration of function, i.e. senescence. However, this classical trade-off model gets challenged by an increasing number of contradicting studies. Here we report about an animal model, which adds more complexity to the ongoing debate. Ansell's mole-rats are long-lived social subterranean rodents with only the founder pair reproducing, while most of their offspring remain in the parental burrow system and do not breed. Despite of a clear reproductive trade-off, breeders live up to twice as long as non-breeders, a unique feature amongst mammals.

METHODS:

We investigated mass-specific resting metabolic rates (msRMR) of breeders and non-breeders to gain information about the physiological basis underlying the reproduction-associated longevity in Ansell's mole-rats. We assessed the thermoneutral zone (TNZ) for breeders and non-breeders separately by means of indirect calorimetry. We applied generalized linear mixed-effects models for repeated measurements using the msRMR in the respective TNZs.

RESULTS:

TNZ differed between reproductive and non-reproductive Ansell's mole-rats. Contrary to classical aging models, the shorter-lived non-breeders had significantly lower msRMR within the thermoneutral zone compared to breeders.

CONCLUSION:

This is the first study reporting a positive correlation between msRMR and lifespan based on reproductive status. Our finding contradicts common aging theories, but supports recently introduced models which do not necessarily link reproductive trade-offs to lifespan reduction.

KEYWORDS:

Aging; Mole-rat; Oxidative stress; Reproduction; Resting metabolic rate

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Sexual activity and reproduction delay ageing in a mammal.

Dammann P, Burda H.

Curr Biol. 2006 Feb 21;16(4):R117-8. No abstract available.

PMID: 16488857 Free Article

http://www.cell.com/current-biology/fulltext/S0960-9822(06)01123-7?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0960982206011237%3Fshowall%3Dtrue

http://www.cell.com/current-biology/pdf/S0960-9822(06)01123-7.pdf

 

Association of walking pace and handgrip strength with all-cause, cardiovascular, and cancer mortality: a UK Biobank observational study.

Yates T, Zaccardi F, Dhalwani NN, Davies MJ, Bakrania K, Celis-Morales CA, Gill JMR, Franks PW, Khunti K.

Eur Heart J. 2017 Aug 21. doi: 10.1093/eurheartj/ehx449. [Epub ahead of print]

PMID: 29020281

https://academic.oup.com/eurheartj/article/doi/10.1093/eurheartj/ehx449/4090989/Association-of-walking-pace-and-handgrip-strength

https://watermark.silverchair.com/ehx449.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAfYwggHyBgkqhkiG9w0BBwagggHjMIIB3wIBADCCAdgGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM0JjrTywIpjLx--RwAgEQgIIBqU1M5QVgYfETD1GGsWyUIlHVWPk5um5lrFjqlOCFZmAo3LgdqEFH6YE-E1tydeXYis5jSVWEDXAHK-g_wnYE3VeqPiQ1C9HfTMEw2r9FLy-tkeh8niFVtBcTS38gP140rMuw4SW6Kjw_iVm5_McRzWeC-z8slxsQr-VOJd4shkfYtAE-Y7EjqtOvdLTwlXZCYQmH9WQhfEqNQS45gfbVg_z5oEOXRVJouiMHF4ow5KprG_6vn3b74kXPabRdtDaUZLQI35PmtJ9wYx2GUujXqZdcNiNbQl2efQ-XU7mFzNBPwdZo4wrm6A2acW8mBcrIguRyXJL1OrAkYho8uMX9K_hH9CyYV9fiOWKC1RnmI0lOo4DvCDZtxDnfp_0e1LzXVFenctPuISOst6r15ue_zB9HILpJ_mGeUYWuee8zEPUePB8AxdUq6xRW-DrLfp0NkyASjubJse0F7VWlxID4s0rMMW8Z_YR4WynnAhzKi0zDM5Mq2GRodhRTtfvascOg-9uEat_oYAgdk88wPFjITzyX7vXzulCDZ6Thsqd0BxcQoM9VJ0CADijh

Abstract

AIMS:

To quantify the association of self-reported walking pace and handgrip strength with all-cause, cardiovascular, and cancer mortality.

METHODS AND RESULTS:

A total of 230 670 women and 190 057 men free from prevalent cancer and cardiovascular disease were included from UK Biobank. Usual walking pace was self-defined as slow, steady/average or brisk. Handgrip strength was assessed by dynamometer. Cox-proportional hazard models were adjusted for social deprivation, ethnicity, employment, medications, alcohol use, diet, physical activity, and television viewing time. Interaction terms investigated whether age, body mass index (BMI), and smoking status modified associations. Over 6.3 years, there were 8598 deaths, 1654 from cardiovascular disease and 4850 from cancer. Associations of walking pace with mortality were modified by BMI. In women, the hazard ratio (HR) for all-cause mortality in slow compared with fast walkers were 2.16 [95% confidence interval (CI): 1.68-2.77] and 1.31 (1.08-1.60) in the bottom and top BMI tertiles, respectively; corresponding HRs for men were 2.01 (1.68-2.41) and 1.41 (1.20-1.66). Hazard ratios for cardiovascular mortality remained above 1.7 across all categories of BMI in men and women, with modest heterogeneity in men. Handgrip strength was associated with cardiovascular mortality in men only (HR tertile 1 vs. tertile 3 = 1.38; 1.18-1.62), without differences across BMI categories, while associations with all-cause mortality were only seen in men with low BMI. Associations for walking pace and handgrip strength with cancer mortality were less consistent.

CONCLUSION:

A simple self-reported measure of slow walking pace could aid risk stratification for all-cause and cardiovascular mortality within the general population.

KEYWORDS:

Cardiorespiratory fitness; Handgrip strength; Mortality; Walking pace

 

Polyunsaturated fatty acids: any role in rheumatoid arthritis?

Navarini L, Afeltra A, Gallo Afflitto G, Margiotta DPE.

Lipids Health Dis. 2017 Oct 10;16(1):197. doi: 10.1186/s12944-017-0586-3. Review.

PMID: 29017507

Abstract

BACKGROUND:

Polyunsaturated fatty acids (PUFAs) are members of the family of fatty acids and are included in the diet. Particularly, western diet is usually low in n-3 PUFAs and high in n-6 PUFAs. PUFAs play a central role in the homeostasis of immune system: n-6 PUFAs have predominantly pro-inflammatory features, while n-3 PUFAs seem to exert anti-inflammatory and pro-resolving properties. Rheumatoid arthritis (RA) is a chronic inflammatory arthritis in which many inflammatory pathways contribute to joint and systemic inflammation, disease activity, and structural damage. Research on PUFAs could represent an important opportunity to better understand the pathogenesis and to improve the management of RA patients.

METHODS:

We searched PubMed, Embase, EBSCO-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI and Wanfang to identify primary research reporting the role of n-3 PUFAs in rheumatoid arthritis both in humans and in animal models up to the end of March 2017.

RESULTS:

Data from animal models allows to hypothesize that n-3 PUFAs supplementation may represent an interesting perspective in future research as much in prevention as in treating RA. In humans, several case-control and prospective cohort studies suggest that a high content of n-3 PUFAs in the diet could have a protective role for incident RA in subjects at risk. Moreover, n-3 PUFAs supplementation has been assessed as a valuable therapeutic option also for patients with RA, particularly in order to improve the pain symptoms, the tender joint count, the duration of morning stiffness and the frequency of NSAIDs assumption.

CONCLUSIONS:

n-3 PUFAs supplementation could represent a promising therapeutic option to better control many features of RA. The impact of n-3 PUFAs on radiographic progression and synovial histopathology has not been yet evaluated, as well as their role in early arthritis and the combination with biologics.

 

Dietary Sodium to Potassium Ratio and Risk of Stroke in a Multiethnic Urban Population: The Northern Manhattan Study.

Willey J, Gardener H, Cespedes S, Cheung YK, Sacco RL, Elkind MSV.

Stroke. 2017 Oct 10. pii: STROKEAHA.117.017963. doi: 10.1161/STROKEAHA.117.017963. [Epub ahead of print]

PMID: 29018136

Abstract

BACKGROUND AND PURPOSE:

There is growing evidence that increased dietary sodium (Na) intake increases the risk of vascular diseases, including stroke, at least in part via an increase in blood pressure. Higher dietary potassium (K), seen with increased intake of fruits and vegetables, is associated with lower blood pressure. The goal of this study was to determine the association of a dietary Na:K with risk of stroke in a multiethnic urban population.

METHODS:

Stroke-free participants from the Northern Manhattan Study, a population-based cohort study of stroke incidence, were followed-up for incident stroke. Baseline food frequency questionnaires were analyzed for Na and K intake. We estimated the hazard ratios and 95% confidence intervals for the association of Na:K with incident total stroke using multivariable Cox proportional hazards models.

RESULTS:

Among 2570 participants with dietary data (mean age, 69±10 years; 64% women; 21% white; 55% Hispanic; 24% black), the mean Na:K ratio was 1.22±0.43. Over a mean follow-up of 12 years, there were 274 strokes. In adjusted models, a higher Na:K ratio was associated with increased risk for stroke (hazard ratio, 1.6; 95% confidence interval, 1.2-2.1) and specifically ischemic stroke (hazard ratio, 1.6; 95% confidence interval, 1.2-2.1).

CONCLUSIONS:

Na:K intake is an independent predictor of stroke risk. Further studies are required to understand the joint effect of Na and K intake on risk of cardiovascular disease.

KEYWORDS:

diet; epidemiology; potassium; sodium; stroke

 

Modeling Risk Factor Trajectories When Measurement Tools Change Sequentially During Follow-up in Cohort Studies: Application to Dietary Habits in Prodromal Dementia.

Wagner M, Dartigues JF, Samieri C, Proust-Lima C.

Am J Epidemiol. 2017 Aug 23. doi: 10.1093/aje/kwx293. [Epub ahead of print]

PMID: 29020158

Abstract

Modeling risk factor trajectories is critical to understand the natural history of diseases; yet, the measurement tools used to assess risk factors often evolve during follow-up in cohorts and such change prevents longitudinal analyses using standard models. The authors propose to address this issue with a Latent Process Model. Trajectories of average intakes of five food families (Fish, Meat, Fruits, Vegetables, Carbohydrate-rich foods) were described in prodromal dementia during the 10 years prior to diagnosis of cases and compared to those of controls, using a case-control sample nested within the Three-City Study, Bordeaux, France (1999-2012). Food intakes were measured by two to three different subquestionnaires across five repeated food frequency questionnaires. The sample comprised 205 incident cases and 410 controls matched for age, gender, education and number of repeated food frequency questionnaires. Intakes of fish, fruits and vegetables decreased at the approach of diagnosis among cases, suggesting reverse causation. This study demonstrates that Latent Process Model approach constitutes a powerful framework for modeling risk factor trajectories, even when measurement tools sequentially change over time. Coupled with a case-control approach to contrast trajectories in prodromal disease versus healthy status, it helps understand the dynamic, causal relationships between risk factors and diseases.

KEYWORDS:

dementia; epidemiologic methods; latent variable models; longitudinal studies; nonlinear dynamics; nutrition; risk reduction behavior

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Efficacy and safety of turmeric and curcumin in lowering blood lipid levels in patients with cardiovascular risk factors: a meta-analysis of randomized controlled trials.

Qin S, Huang L, Gong J, Shen S, Huang J, Ren H, Hu H.

Nutr J. 2017 Oct 11;16(1):68. doi: 10.1186/s12937-017-0293-y. Review.

PMID: 29020971

Abstract

BACKGROUND:

Dyslipidemia is an important and common cardiovascular risk factor in the general population. The lipid-lowering effects of turmeric and curcumin are unconfirmed. We performed a meta-analysis to assess the efficacy and safety of turmeric and curcumin in lowering blood lipids in patients at risk of cardiovascular disease (CVD).

METHODS:

A comprehensive literature search was conducted on PubMed, Embase, Ovid, Medline and Cochrane Library databases to identify randomized controlled trials (published as of November 2016) that assessed the effect of turmeric and curcumin on blood lipid levels including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was used to assess the effect.

RESULTS:

The analysis included 7 eligible studies (649 patients). Turmeric and curcumin significantly reduced serum LDL-C (SMD = -0.340, 95% confidence interval [CI]: -0.530 to -0.150, P < 0.0001) and TG (SMD = -0.214, 95% CI: -0.369 to -0.059, P = 0.007) levels as compared to those in the control group. These may be effective in lowering serum TC levels in patients with metabolic syndrome (MetS, SMD = -0.934, 95% CI: -1.289 to -0.579, P < 0.0001), and turmeric extract could possibly have a greater effect on reducing serum TC levels (SMD = -0.584, 95% CI: -0.980 to -0.188, P = 0.004); however, the efficacy is yet to be confirmed. Serum HDL-C levels were not obviously improved. Turmeric and curcumin appeared safe, and no serious adverse events were reported in any of the included studies.

CONCLUSIONS:

Turmeric and curcumin may protect patients at risk of CVD through improving serum lipid levels. Curcumin may be used as a well-tolerated dietary adjunct to conventional drugs. Further research is required to resolve uncertainties related to dosage form, dose and medication frequency of curcumin.

KEYWORDS:

Cardiovascular risk; Cholesterol; Curcumin; Meta-analysis; Triglycerides; Turmeric

 

[The below paper is not pdf-availed.]

Association between dietary fiber intake and bone loss in the Framingham Offspring Study.

Dai Z, Zhang Y, Lu N, Felson DT, Kiel DP, Sahni S.

J Bone Miner Res. 2017 Oct 12. doi: 10.1002/jbmr.3308. [Epub ahead of print]

PMID: 29024045

Abstract

Dietary fiber may increase calcium absorption, but its role in bone mineralization is unclear. Furthermore, the health effect of dietary fiber may be different between genders. We examined the association between dietary fiber (total fiber and fiber from cereal, fruits, vegetables, nuts and legumes) and bone loss at the femoral neck, trochanter and lumbar spine (L2-4) in older men and women. In the Framingham Offspring Study, at baseline (1996-2001), diet was assessed using the Willett food frequency questionnaire and bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Follow-up BMD was measured in 2001-2005 and 2005-2008 among 792 men (mean age, 58.1yr; BMI, 28.6kg/m2 ) and 1,065 women (57.3yr; 27.2kg/m2 ). We used sex-specific generalized estimating equations in multivariable regressions to estimate the difference (β) of annualized BMD change in percent (%ΔBMD) at each skeletal site per 5 g/d increase in dietary fiber. We further estimated the adjusted mean for bone loss (annualized %ΔBMD) among participants in each higher quartile (Q2, Q3 or Q4) compared with those in the lowest quartile (Q1) of fiber intake. Higher dietary total fiber (β = 0.06, p = 0.003) and fruit fiber (β = 0.10, p = 0.008) was protective against bone loss at the femoral neck in men but not in women. When examined in quartiles, men in Q2-Q4 of total fiber had significantly less bone loss at the femoral neck versus those in Q1 (all p < 0.04). For women, we did not observe associations with hip bone loss, although fiber from vegetables appeared to be protective against spine bone loss in women but not men. There were no associations with cereal fiber or nut and legume fiber and bone loss in men or women. Our findings suggest that higher dietary fiber may modestly reduce bone loss in men at the hip.

KEYWORDS:

Bone mineral density; Dietary fiber; Framingham Study; Sex-specific difference; bone loss

 

The Prognostic Impact of Mild Hypokalemia in Terms of Death and Stroke in the General Population - a Prospective Population Study.

Mattsson N, Nielsen OW, Johnson L, Prescott E, Schnohr P, Jensen GB, Køber L, Sajadieh A.

Am J Med. 2017 Oct 9. pii: S0002-9343(17)31012-4. doi: 10.1016/j.amjmed.2017.09.026. [Epub ahead of print]

PMID: 29024624

http://www.amjmed.com/article/S0002-9343(17)31012-4/fulltext

http://www.amjmed.com/article/S0002-9343(17)31012-4/pdf

Abstract

BACKGROUND:

Potassium supplementation reduces the risk of cardiovascular mortality and stroke in population studies; however, the prognostic impact of mild hypokalemia in the general population has not been thoroughly investigated. We aimed to investigate associations between mild hypokalemia and endpoints in the general population.

METHODS:

participants (48-76 year old) from the general population study "Copenhagen City Heart Study" (n=5916) were studied. Participants were divided into groups according to baseline-values of plasma-potassium (potassium); Hypokalemia (<3.7 mmol/L,n=758), normokalemia (3.7-4.5 mmol/L] n=4973, and high-potassium (>4.5 mmol/L,n=185). Hypokalemia was further divided in potassium<3.4 and 3.4-3.6 mmol/L. The primary endpoints were all-cause mortality and non-fatal validated ischemic stroke. Secondary endpoint was AMI. We adjusted for conventional risk factors, diuretics and atrial fibrillation (AF) at baseline.

RESULTS:

Mean potassium in the hypokalemic group was 3.5 mmol/L (range 2.6-3.6) and was associated (P<0.05) with increased systolic blood pressure, higher CHA2DS2-VASc-score, and increased use of diuretics as compared with normokalemia. Baseline AF was equally frequent across groups. Median follow-up-time was 11.9 years (Q1-Q3: 11.4-12.5 years). Hypokalemia was borderline associated with increased stroke-risk in a multivariable Cox model (including adjustment for competing risk) as compared with normokalemia (HR:1.40;95%CI:1.00-1.98). The subgroup with potassium<3.4 mmol/L had higher stroke- (HR:2.10;95%CI:1.19-3.73) and mortality-risk (HR:1.32;95%CI:1.01-1.74) as compared with normokalemia. Hypokalemia was not associated with AMI and no increased risk of mortality was seen with concomitant AMI and hypokalemia. No associations were seen with high-potassium.

CONCLUSIONS:

In a general population mild hypokalemia is associated with increased stroke-risk and to a lesser degree increased mortality-risk.

KEYWORDS:

Epidemiology; Hypokalemia; Longitudinal Population Based Cohorts; Mortality; Stroke

 

Cellular immune activation in Sardinian middle-aged, older adults and centenarians.

Sotgia S, Zinellu A, Mangoni AA, Serra R, Pintus G, Caruso C, Deiana L, Carru C.

Exp Gerontol. 2017 Oct 9. pii: S0531-5565(17)30429-1. doi: 10.1016/j.exger.2017.10.005. [Epub ahead of print]

PMID: 29024722

https://sci-hub.cc/http://linkinghub.elsevier.com/retrieve/pii/S0531556517304291

Abstract

In addition to viral infections, malignant disorders, autoimmune diseases, and allograft rejection episodes, neopterin increases in older people where it is found to be predictive of overall mortality. Thus, the serum concentrations of this biomarker of systemic immune and inflammation activation, were measured in a small cohort of Sardinian middle-aged, older adults and centenarians. There was a significant positive correlation between neopterin concentrations and age with the subjects in the 95-year-old group with the highest values. Notably, the group of centenarians had neopterin values comparable to those of 80- and 90-year-old groups, and significantly lower than that of 95-year-old group. This suggests a decreased monocyte/macrophage-mediated immune activation and an apparently preserved immune status in centenarians.

KEYWORDS:

Aging; Centenarians; Cytokines; Immunosenescence; Inflammaging; Longevity; Pteridines

 

Lower Performance in Orientation to Time and Place Associates with Greater Risk of Cardiovascular Events and Mortality in the Oldest Old: Leiden 85-Plus Study.

Rostamian S, van Buchem MA, Jukema JW, Gussekloo J, Poortvliet RKE, de Cren AJM, Sabayan B.

Front Aging Neurosci. 2017 Sep 27;9:307. doi: 10.3389/fnagi.2017.00307. eCollection 2017.

PMID: 29021754

https://www.frontiersin.org/articles/10.3389/fnagi.2017.00307/full

Abstract

Background: Impairment in orientation to time and place is commonly observed in community-dwelling older individuals. Nevertheless, the clinical significance of this has been not fully explored. In this study, we investigated the link between performance in orientation domains and future risk of cardiovascular events and mortality in a non-hospital setting of the oldest old adults. Methods: We included 528 subjects free of myocardial infarction (Group A), 477 individuals free of stroke/transient ischemic attack (Group B), and 432 subjects free of both myocardial infarction and stroke/transient ischemic attack (Group C) at baseline from the population-based Leiden 85-plus cohort study. Participants were asked to answer five questions related to orientation to time and five questions related to orientation to place. 5-year risks of first-time fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, as well as cardiovascular and non-cardiovascular mortality, were estimated using the multivariate Cox regression analysis. Results: In the multivariable analyses, adjusted for sociodemographic characteristics and cardiovascular risk factors, each point lower performance in "orientation to time" was significantly associated with higher risk of first-time myocardial infarction (hazard ratio {HR} 1.35, 95% confidence interval [CI] 1.09-1.67, P = 0.007), first-time stroke (HR 1.35, 95% CI 1.12-1.64, P = 0.002), cardiovascular mortality (HR 1.28, 95% CI 1.06-1.54, P = 0.009) and non-cardiovascular mortality (HR 1.37, 95% CI 1.20-1.56, P < 0.001). Similarly, each point lower performance in "orientation to place" was significantly associated with higher risk of first-time myocardial infarction (HR 1.67, 95% CI 1.25-2.22, P = 0.001), first-time stroke (HR 1.39, 95% CI 1.05-1.82, P = 0.016), cardiovascular mortality (HR 1.35, 95% CI 1.00-1.82, P = 0.054) and non-cardiovascular mortality (HR 1.45, 95% CI 1.20-1.77, P < 0.001). Conclusions: Lower performance in orientation to time and place in advanced age is independently related to higher risk of myocardial infarction, stroke and mortality. Impaired orientation might be an early sign of covert vascular injuries, putting subjects at greater risk of cardiovascular events and mortality.

KEYWORDS:

mortality; myocardial infarction; oldest old; orientation to place; orientation to time; stroke

 

The rise and fall and rise again of 23andMe

How Anne Wojcicki led her company from the brink of failure to scientific pre-eminence.

Erika Check Hayden

Nature 550, 174–177 (12 October 2017) doi:10.1038/550174a

http://www.nature.com/news/the-rise-and-fall-and-rise-again-of-23andme-1.22801?WT.ec_id=NATURE-20171012&spMailingID=55119582&spUserID=MjA1NzQwNzAwNwS2&spJobID=1261947732&spReportId=MTI2MTk0NzczMgS2

 

Fatty liver disease: turning the tide.

Drew L.

Nature. 2017 Oct 11;550(7675):S101. doi: 10.1038/550S101a. No abstract available.

PMID: 29019967

A progressive and potentially life-threatening condition previously associated with alcoholism is becoming more common — even in non-drinkers.

Subject terms: Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Obesity Diseases

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Fighting the fatty liver.

Drew L.

Nature. 2017 Oct 11;550(7675):S102-S103. doi: 10.1038/550S102a. No abstract available.

PMID: 29019968

Increased levels of obesity are driving an epidemic of non-alcoholic fatty liver disease. Understanding, diagnosing and treating this progressive condition are now priorities.

Subject terms: Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Obesity Diseases

 

Longitudinal Changes in Mean and Pulse Pressure, and All-Cause Mortality: Data From 71,629 Untreated Normotensive Individuals.

Protogerou AD, Vlachopoulos C, Thomas F, Zhang Y, Pannier B, Blacher J, Safar ME.

Am J Hypertens. 2017 Jun 26. doi: 10.1093/ajh/hpx110. [Epub ahead of print]

PMID: 28655182

Abstract

BACKGROUND:

Blood pressure (BP) includes a steady (mean arterial pressure, MAP) and a pulsatile component that independently predict mortality. The association between longitudinal changes in central © pulse pressure (PP), brachial (b) PP, MAP, and incident mortality has never been investigated in this context.

METHODS:

Brachial MAP and PP were measured at 2 routine checkups (1st visit 1992; mean interval, 5.8 ± 2.4 years) in 71,629 individuals, age 16-95 years, none on antihypertensive drugs. cPP was estimated with a validated algorithm. Each change (visit 2-1) in bPP, cPP, and MAP, expressed in mm Hg/year, was categorized as: increase, decrease, or no-change, with the latter representing the control-group. Follow-up data (6.9 ± 3.3 years) on all-cause mortality (2,033 deaths) were documented.

RESULTS:

All-cause mortality Cox regression models adjusted for confounders showed that compared to the subgroup with steady BP at both visits, the subgroup with: (i) increased bPP or cPP had an approximately 200% increase in relative risk (RR); (ii) decreased cPP and bPP had a 15% reduction in RR; (iii) increased MAP had a 68% increase in RR; (iv) decreased MAP had a 7% increase in RR of mortality. Interaction analysis stratified by gender showed that annual increases in PP, but not MAP, were greater in younger than older men and lower in younger than older women. Age cutoff value was 55 years.

CONCLUSIONS:

MAP and PP have distinct characteristics affecting all-cause mortality. PP integrates the effects of age and gender on all-cause mortality more notably than MAP, thus impacting significantly on cardiovascular risk.

KEYWORDS:

all-cause mortality; blood pressure; hypertension; mean arterial pressure; pulse pressure.

 

Sauna Bathing and Incident Hypertension: A Prospective Cohort Study.

Zaccardi F, Laukkanen T, Willeit P, Kunutsor SK, Kauhanen J, Laukkanen JA.

Am J Hypertens. 2017 Jun 13. doi: 10.1093/ajh/hpx102. [Epub ahead of print]

PMID: 28633297

Abstract

BACKGROUND:

Sauna bathing is associated with reduced cardiovascular risk, but the mechanisms underlying this beneficial effect are not entirely understood. We aimed to assess the relationship between sauna bathing and risk of incident hypertension.

METHODS:

Frequency of sauna bathing was ascertained using questionnaires in the Kuopio Ischemic Heart Disease Study, a prospective cohort study conducted in Eastern Finland that comprised a population-based sample of 1,621 men aged 42 to 60 years without hypertension at baseline. The incidence of hypertension was defined as a physician diagnosis of hypertension, systolic blood pressure (SBP) >140 mm Hg, diastolic blood pressure >90 mm Hg, or use of antihypertensive medication.

RESULTS:

During a median follow-up of 24.7 years, 251 incident cases (15.5%) were recorded. In Cox regression analysis adjusted for baseline age, smoking, body mass index, and SBP; compared to participants reporting 1 sauna session per week, the hazard ratio for incident hypertension in participants reporting 2 to 3 sessions and 4 to 7 sessions was 0.76 (95% confidence interval: 0.57-1.02) and 0.54 (0.32-0.91), respectively. The corresponding hazard ratios were similar after further adjustment for glucose, creatinine, alcohol consumption, heart rate, family history of hypertension, socioeconomic status, and cardiorespiratory fitness: 0.83 (95% confidence interval: 0.59-1.18) and 0.53 (0.28-0.98), respectively.

CONCLUSIONS:

Regular sauna bathing is associated with reduced risk of hypertension, which may be a mechanism underlying the decreased cardiovascular risk associated with sauna use. Further epidemiological and experimental studies could help elucidate the effects of sauna bathing on cardiovascular function.

KEYWORDS:

Sauna bathing.; blood pressure; cohort; hypertension; prevention

Edited by AlPater
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Four Genome-Wide Association Studies Identify New Extreme Longevity Variants.

Sebastiani P, Gurinovich A, Bae H, Andersen S, Malovini A, Atzmon G, Villa F, Kraja AT, Ben-Avraham D, Barzilai N, Puca A, Perls TT.

J Gerontol A Biol Sci Med Sci. 2017 Mar 15. doi: 10.1093/gerona/glx027. [Epub ahead of print]

PMID: 28329165

http://sci-hub.cc/10.1093/gerona/glx027

Abstract

The search for the genetic determinants of extreme human longevity has been challenged by the phenotype's rarity and its nonspecific definition by investigators. To address these issues, we established a consortium of four studies of extreme longevity that contributed 2,070 individuals who survived to the oldest one percentile of survival for the 1900 U.S. birth year cohort. We conducted various analyses to discover longevity-associated variants (LAV) and characterized those LAVs that differentiate survival to extreme age at death (eSAVs) from those LAVs that become more frequent in centenarians because of mortality selection (eg, survival to younger years). The analyses identified new rare variants in chromosomes 4 and 7 associated with extreme survival and with reduced risk for cardiovascular disease and Alzheimer's disease. The results confirm the importance of studying truly rare survival to discover those combinations of common and rare variants associated with extreme longevity and longer health span.

KEYWORDS:

Genetic profiles; Genetic variants; Healthy aging; Human longevity

 

Biological Aging and the Human Gut Microbiota.

Maffei VJ, Kim S, Blanchard E 4th, Luo M, Jazwinski SM, Taylor CM, Welsh DA.

J Gerontol A Biol Sci Med Sci. 2017 Apr 25. doi: 10.1093/gerona/glx042. [Epub ahead of print]

PMID: 28444190

http://sci-hub.cc/10.1093/gerona/glx042

Abstract

The human gastrointestinal microbiota plays a key homeostatic role in normal functioning of physiologic processes commonly undermined by aging. We used a previously validated 34-item frailty index (FI34) to identify changes in gut microbiota community structure associated with biological age of community-dwelling adults. Stool 16S rRNA cDNA libraries from 85 subjects ranging in age (43-79) and FI34 score (0-0.365) were deep sequenced, denoised, and clustered using DADA2. Subject biological age but not chronological age correlated with a decrease in stool microbial diversity. Specific microbial genera were differentially abundant in the lower, middle, and upper 33rd percentiles of biological age. Using Sparse Inverse Covariance Estimation for Ecological Association and Statistical Inference (SPIEC-EASI) and Weighted Gene Co-Expression Network Analysis (WGCNA), we identified modules of coabundant microbial genera that distinguished biological from chronological aging. A biological age-associated module composed of Eggerthella, Ruminococcus, and Coprobacillus genera was robust to correction for subject age, sex, body mass index, antibiotic usage, and other confounders. Subject FI34 score positively correlated with the abundance of this module, which exhibited a distinct inferred metagenome as predicted by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). We conclude that increasing biological age in community-dwelling adults is associated with gastrointestinal dysbiosis.

KEYWORDS:

Coabundance; Diversity; Dysbiosis; Frailty

 

Low Normalized Grip Strength is a Biomarker for Cardiometabolic Disease and Physical Disabilities Among U.S. and Chinese Adults.

Peterson MD, Duchowny K, Meng Q, Wang Y, Chen X, Zhao Y.

J Gerontol A Biol Sci Med Sci. 2017 Mar 10. doi: 10.1093/gerona/glx031. [Epub ahead of print]

PMID: 28329157

Abstract

BACKGROUND:

Evidence highlights the importance of muscular strength as a protective factor for health and function across aging populations. The purpose of this study was to examine the extent to which low normalized grip strength (NGS) serves as a biomarker for both cardiometabolic disease and physical disability in U.S. and Chinese adults.

METHODS:

Middle aged and older adults from the U.S. National Health and Nutrition Examination Survey 2011-2012 and 2013-2014 combined surveys (n = 4,544), and the 2011 wave of the China Health and Retirement Longitudinal Study (n = 6,030) were included. Strength was assessed using a handgrip dynamometer, and was normalized to body mass. Weighted logistic regression models were used to assess the association between NGS and diabetes, hyperglycemia, hypertriglyceridemia, low HDL-cholesterol, hypertension, and physical disability status, while controlling for age, sex, and sociodemographic characteristics.

RESULTS:

Every 0.05 lower NGS was independently associated with a 1.49 (95% confidence interval [CI]: 1.42-1.56) and 1.17 (95% CI: 1.11-1.23) odds for diabetes; a 1.46 (95% CI: 1.39-1.53) and 1.11 (95% CI: 1.07-1.15) odds of hyperglycemia; a 1.15 (95% CI: 1.07-1.25) and 1.11 (95% CI: 1.08-1.14) odds of hypertriglyceridemia; a 1.22 (95% CI: 1.17-1.27) and 1.15 (95% CI: 1.12-1.18) odds of low HDL-cholesterol; a 1.19 (95% CI: 1.14-1.24) and 1.10 (95% CI: 1.07-1.14) odds of hypertension; and a 1.36 (95% CI: 1.29-1.42) and 1.10 (95% CI: 1.05-1.15) odds for physical disability status in U.S. and Chinese adults, respectively.

CONCLUSIONS:

NGS was robustly associated with both cardiometabolic disease risk and physical disabilities in U.S. and Chinese aging adults.

KEYWORDS:

Aging; Diabetes; Disability; Epidemiology; Muscle weakness

 

Body Mass Index and Waist Circumference as Predictors of Disability in Nonagenarians: The Vitality 90+ Study.

Lisko I, Tiainen K, Raitanen J, Jylhävä J, Hurme M, Hervonen A, Jylhä M, Stenholm S.

J Gerontol A Biol Sci Med Sci. 2017 Mar 14. doi: 10.1093/gerona/glx032. [Epub ahead of print]

PMID: 28329171

Abstract

BACKGROUND:

Only scarce data exist on the association between obesity and disability in the oldest old. The purpose of this prospective study is to examine if body mass index and waist circumference (WC) are associated with incident mobility and activities of daily living (ADL) disability in nonagenarians.

METHODS:

We used longitudinal data from the Vitality 90+ Study, which is a population-based study conducted at the area of Tampere, Finland. Altogether 291 women and 134 men, aged 90-91 years, had measured data on body mass index and/or WC and did not have self-reported mobility or ADL disability at baseline. Incident mobility and ADL disability was followed-up on median 3.6 years (range 0.6-7.8 years). Mortality was also followed-up. Multinomial logistic regression models were used for the analyses, as death was treated as an alternative outcome. The follow-up time was taken into account in the analyses.

RESULTS:

Neither low or high body mass index, nor low or high WC, were associated with incident mobility disability. In women, the lowest WC tertile (<82 cm) was associated with an increased probability of incident ADL disability when compared to the middle WC tertile (odds ratio 3.98, 95% CI 1.35-11.77).

CONCLUSIONS:

Obesity is not associated with incident mobility or ADL disability in nonagenarians. Instead, low WC is associated with an increased risk of developing ADL disability in nonagenarian women.

KEYWORDS:

Disability; Mobility; Obesity; Obesity paradox; Oldest old; Physical function

 

Change in Bone Mineral Density During Weight Loss with Resistance Versus Aerobic Exercise Training in Older Adults.

Beavers KM, Beavers DP, Martin SB, Marsh AP, Lyles MF, Lenchik L, Shapses SA, Nicklas BJ.

J Gerontol A Biol Sci Med Sci. 2017 Apr 3. doi: 10.1093/gerona/glx048. [Epub ahead of print]

PMID: 28379325

Abstract

BACKGROUND:

To examine the effect of exercise modality during weight loss on hip and spine bone mineral density (BMD) in overweight and obese, older adults.

METHODS:

This analysis compared data from two 5-month, randomized controlled trials of caloric restriction (CR; inducing 5-10% weight loss) with either resistance training (RT) or aerobic training (AT) in overweight and obese, older adults. Participants in the RT + CR study underwent 3 days/week of 8 upper/lower body exercises (3 sets, 10 repetitions at 70% 1 RM) and participants in the AT+CR study underwent 4 days/week of treadmill walking (30 min at 65-70% heart rate reserve). BMD at the total hip, femoral neck, and lumbar spine was assessed via dual-energy X-ray absorptiometry at baseline and 5 months.

RESULTS:

A total of 123 adults (69.4 ± 3.5 years, 67% female, 81% Caucasian) participated in the RT+CR (n = 60) and AT+CR (n = 63) interventions. Average weight loss was 5.7% (95% CI: 4.6-6.7%) and 8.2% (95% CI: 7.2-9.3%) in RT+CR and AT+CR groups, respectively. After adjustment for age, gender, race, baseline BMI and BMD, and weight change, differential treatment effects were observed for total hip and femoral neck (both p < .05), but not lumbar spine. Total hip (1.83 [-3.90, 7.55] mg/cm2) and femoral neck (9.14 [-0.70, 18.98] mg/cm2) BMD was unchanged in RT+CR participants, and modestly decreased in AT+CR participants (total hip: -7.01 [-12.73, -1.29] mg/cm2; femoral neck: -5.36 [-14.92, 4.20] mg/cm2).

CONCLUSIONS:

Results suggest performing resistance, rather than aerobic, training during CR may attenuate loss of hip and femoral neck BMD in overweight and obese older adults. Findings warrant replication from a long-term, adequately powered, RCT.

KEYWORDS:

Bone aging; Caloric restriction; Exercise; Obesity

 

Living in a greener neighbourhood could lower risk of early death: study

Not just parks but also streetside trees and lawns could have health benefits, study suggests

By Emily Chung, CBC News Posted: Oct 12, 2017

http://www.cbc.ca/news/health/green-spaces-lower-mortality-1.3150812

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Urban greenness and mortality in Canada's largest cities: a national cohort study

Dr Dan L Crouse, PhD'Correspondence information about the author Dr Dan L CrouseEmail the author Dr Dan L Crouse, Lauren Pinault, PhD, Adele Balram, MPH, Perry Hystad, PhD, Paul A Peters, PhD, Hong Chen, PhD, Aaron van Donkelaar, PhD, Randall V Martin, PhD, Richard Ménard, PhD, Alain Robichaud, MSc, Paul J Villeneuve, PhD

Open Access

DOI: http://dx.doi.org/10.1016/S2542-5196(17)30118-3

http://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(17)30118-3/fulltext

Summary

Background

Findings from published studies suggest that exposure to and interactions with green spaces are associated with improved psychological wellbeing and have cognitive, physiological, and social benefits, but few studies have examined their potential effect on the risk of mortality. We therefore undertook a national study in Canada to examine associations between urban greenness and cause-specific mortality.

Methods

We used data from a large cohort study (the 2001 Canadian Census Health and Environment Cohort [2001 CanCHEC]), which consisted of approximately 1·3 million adult (aged ≥19 years), non-immigrant, urban Canadians in 30 cities who responded to the mandatory 2001 Statistics Canada long-form census. The cohort has been linked by Statistics Canada to the Canadian mortality database and to annual income tax filings through 2011. We measured greenness with images from the moderate-resolution imaging spectroradiometer from NASA's Aqua satellite. We assigned estimates of exposure to greenness derived from remotely sensed Normalized Difference Vegetation Index (NDVI) within both 250 m and 500 m of participants' residences for each year during 11 years of follow-up (between 2001 and 2011). We used Cox proportional hazards models to estimate associations between residential greenness (as a continuous variable) and mortality. We estimated hazard ratios (HRs) and corresponding 95% CIs per IQR (0·15) increase in NDVI adjusted for personal (eg, education and income) and contextual covariates, including exposures to fine particulate matter, ozone, and nitrogen dioxide. We also considered effect modification by selected personal covariates (age, sex, household income adequacy quintiles, highest level of education, and marital status).

Findings

Our cohort consisted of approximately 1 265 000 million individuals at baseline who contributed 11 523 770 person-years. We showed significant decreased risks of mortality in the range of 8–12% from all causes of death examined with increased greenness around participants' residence. In the fully adjusted analyses, the risk was significantly decreased for all causes of death (non-accidental HR 0·915, 95% CI 0·905–0·924; cardiovascular plus diabetes 0·911, 0·895–0·928; cardiovascular 0·911, 0·894–0·928; ischaemic heart disease 0·904, 0·882–0·927; cerebrovascular 0·942, 0·902–0·983; and respiratory 0·899, 0·869–0·930). Greenness associations were more protective among men than women (HR 0·880, 95% CI 0·868–0·893 vs 0·955, 0·941–0·969), and among individuals with higher incomes (highest quintile 0·812, 0·791–0·834 vs lowest quintile 0·991, 0·972–1·011) and more education (degree or more 0·816, 0·791–0·842 vs did not complete high school 0·964, 0·950–0·978).

Interpretation

Increased amounts of residential greenness were associated with reduced risks of dying from several common causes of death among urban Canadians. We identified evidence of inequalities, both in terms of exposures to greenness and mortality risks, by personal socioeconomic status among individuals living in generally similar environments, and with reasonably similar access to health care and other social services. The findings support the development of policies related to creating greener and healthier cities.

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Association between traditional cardiovascular risk factors and mortality in the oldest old: untangling the role of frailty.

Vaes B, Depoortere D, Van Pottelbergh G, Matheï C, Neto J, Degryse J.

BMC Geriatr. 2017 Oct 12;17(1):234. doi: 10.1186/s12877-017-0626-x.

PMID: 29025410

https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-017-0626-x

https://bmcgeriatr.biomedcentral.com/track/pdf/10.1186/s12877-017-0626-x?site=bmcgeriatr.biomedcentral.com

Abstract

BACKGROUND:

To date, there is no consensus regarding cardiovascular risk management in the very old. Studies have shown that the relationship between traditional cardiovascular risk factors and mortality is null or even inverted within this age group. This relationship could be modified by the presence of frailty. This study was performed to examine the effect of frailty on the association between cardiovascular risk factors and mortality in the oldest old.

METHODS:

The BELFRAIL study is a prospective, observational, population-based cohort study of 567 subjects aged 80 years and older. Data on cardiovascular risk factors were recorded. Frailty was assessed using three different models: the Groningen Frailty Indicator, Fried and Puts models. Participants were considered robust if they were 'not frail' according to all three models, and frail if they met the frailty criteria for one of the three models. The follow-up data on mortality and cause of death were registered.

RESULTS:

No cardiovascular risk factor was associated with mortality in subjects with and without cardiovascular disease. The presence of frailty was a strong risk factor for mortality [hr: 2.5, 95%CI: (1.9-3.2) for all-cause mortality; HR: 2.2, 95%CI: (1.4-3.4) for cardiovascular mortality]. In robust patients, a history of cardiovascular disease increased the risk for mortality [hr: 1.7, 95%CI: (1.1-2.5) for all-cause mortality; HR: 2.2, 95%CI: (1.2-3.9) for cardiovascular mortality]. In frail patients, there was no association between any of the traditional risk factors and mortality.

CONCLUSIONS:

Traditional cardiovascular risk factors were not associated with mortality in very old subjects. Frailty was shown to be a strong risk factor for mortality in this age group. However, frailty could not be used to identify additional subjects who might benefit more from cardiovascular risk management.

KEYWORDS:

Cardiovascular risk prediction; Cholesterol; Frailty; Hypertension; Mortality

 

Dietary carbohydrates, components of energy balance, and associated health outcomes.

Smith HA, Gonzalez JT, Thompson D, Betts JA.

Nutr Rev. 2017 Oct 1;75(10):783-797. doi: 10.1093/nutrit/nux045.

PMID: 29028272

Abstract

The role of dietary carbohydrates in the development of obesity and associated metabolic dysfunction has recently been questioned. Within the last decade, the Scientific Advisory Committee on Nutrition carried out a comprehensive evaluation of the role of dietary carbohydrates in human health. The current review aims to complement and extend this report by providing specific consideration of the effects of the component parts of energy balance, their interactions, and their culmination on energy storage and health. PubMed was searched for all published trials that had a minimum follow-up period of 3 months and were designed to manipulate dietary carbohydrate intake, irrespective of resultant differences in absolute carbohydrate dose (grams per day). Dietary carbohydrate manipulation has little effect on the individual components of energy balance that have been assessed. However, the role of dietary carbohydrates in influencing physical activity has yet to be assessed using gold-standard measurement tools. Moreover, adherence to a diet of modified carbohydrate content has not been found to result in a consistent pattern of changes in weight or indirect measures of metabolic health. However, certain markers of cardiovascular disease risk (ie, blood triglycerides and high-density lipoprotein cholesterol) may respond positively to a reduction in dietary carbohydrates.

KEYWORDS:

carbohydrate; cardiovascular disease; diet; energy balance; health; metabolism; obesity; type 2 diabetes

 

Antioxidant intake from diet and supplements and risk of digestive cancers in middle-aged adults: results from the prospective NutriNet-Santé cohort.

Egnell M, Fassier P, Lécuyer L, Gonzalez R, Zelek L, Vasson MP, Hercberg S, Latino-Martel P, Galan P, Druesne-Pecollo N, Deschasaux M, Touvier M.

Br J Nutr. 2017 Oct;118(7):541-549. doi: 10.1017/S0007114517002392. Epub 2017 Sep 20.

PMID: 28927476

http://sci-hub.cc/10.1017/S0007114517002392

Abstract

Experimental studies suggest beneficial effects of antioxidants in digestive cancer prevention. However, epidemiological results are contrasting and few studies quantitatively assessed supplemental intake. This study aimed at investigating the associations between antioxidant intakes (dietary, supplemental and total) and digestive cancer risk. This prospective study included 38 812 middle-aged subjects (≥45 years) from the NutriNet-Santé cohort (2009-2016). Dietary data were collected using repeated 24 h records. A specific questionnaire assessed dietary supplement use over a 12-month period. A composition database of about 8000 dietary supplements was developed. Associations between continuous and sex-specific quartiles of vitamins C and E, β-carotene and Se intakes and digestive cancer risk were characterised using multivariable Cox proportional hazard models. A total of 167 incident digestive cancers (120 colorectal, twenty-six pancreatic, nine oesophagus, seven stomach and five liver) were diagnosed during follow-up investigation. Dietary (hazard ratios (HR)Q4 v. Q1=0·56; 95 % CI 0·34, 0·91, P trend=0·01) and total (HRQ4 v. Q1=0·51; 95 % CI 0·30, 0·84, P trend=0·008) vitamin C intakes, dietary (HRQ4 v. Q1=0·56; 95 % CI 0·34, 0·92, P trend=0·005) and total (HRQ4 v. Q1=0·58; 95 % CI 0·36, 0·94, P trend=0·003) vitamin E intakes, and dietary (HRfor an increment of 10 µg/d=0·92; 95 % CI 0·85, 1·00, P=0·04) and total (HRfor an increment of 10 µg/d=0·92; 95 % CI 0·86, 0·99, P=0·03) Se intakes were associated with a decreased digestive cancer risk. Statistically significant interactions were observed between dietary and total Se intakes and alcohol consumption as well as between total vitamin E intake and smoking status. This prospective cohort study with quantitative assessment of supplemental intakes suggests a potential protective effect of several antioxidants (vitamins C and E and Se) on digestive cancer risk, and a modulation of some of these relationships by alcohol consumption and smoking status.

KEYWORDS:

HR hazard ratio; IPAQ International Physical Activity Questionnaire; Antioxidants; Diet; Dietary supplements; Digestive cancers; Prospective cohorts

 

Comprehensive maternal characteristics associated with birth weight: Bayesian modeling in a prospective cohort study from Iran.

Mansourian M, Mohammadi R, Marateb HR, Yazdani A, Goodarzi-Khoigani M, Molavi S.

J Res Med Sci. 2017 Sep 26;22:107. doi: 10.4103/jrms.JRMS_926_16. eCollection 2017.

PMID: 29026423

http://jrms.mui.ac.ir/files/journals/1/articles/10692/public/10692-39900-1-PB.pdf

Abstract

BACKGROUND:

In this study, we aimed to determine comprehensive maternal characteristics associated with birth weight using Bayesian modeling.

MATERIALS AND METHODS:

A total of 526 participants were included in this prospective study. Nutritional status, supplement consumption during the pregnancy, demographic and socioeconomic characteristics, anthropometric measures, physical activity, and pregnancy outcomes were considered as effective variables on the birth weight. Bayesian approach of complex statistical models using Markov chain Monte Carlo approach was used for modeling the data considering the real distribution of the response variable.

RESULTS:

There was strong positive correlation between infant birth weight and the maternal intake of Vitamin C, folic acid, Vitamin B3, Vitamin A, selenium, calcium, iron, phosphorus, potassium, magnesium as micronutrients, and fiber and protein as macronutrients based on the 95% high posterior density regions for parameters in the Bayesian model. None of the maternal characteristics had statistical association with birth weight.

CONCLUSION:

Higher maternal macro- and micro-nutrient intake during pregnancy was associated with a lower risk of delivering low birth weight infants. These findings support recommendations to expand intake of nutrients during pregnancy to high level.

KEYWORDS:

Bayesian modeling; bioinformatics; birth weight; maternal characteristics; nutritional risk factors

 

The association between omega-3 fatty acid biomarkers and inflammatory arthritis in an anti-citrullinated protein antibody positive population.

Gan RW, Bemis EA, Demoruelle MK, Striebich CC, Brake S, Feser ML, Moss L, Clare-Salzler M, Holers VM, Deane KD, Norris JM.

Rheumatology (Oxford). 2017 Oct 4. doi: 10.1093/rheumatology/kex360. [Epub ahead of print]

PMID: 29029330

Abstract

OBJECTIVES:

Higher circulating omega-3 fatty acids (n-3 FAs) are associated with a lower prevalence of anti-CCP antibodies and RF in subjects without RA. We examined whether, in anti-CCP+ subjects, n-3 FAs also play a role in development of inflammatory arthritis (IA).

METHODS:

At Colorado-based health fairs from 2008 to 2014, participants without a previous diagnosis of RA who were anti-CCP3+ (n = 47) were recruited into a follow-up study; symptom assessments and joint examinations were conducted every 6 months for the determination of IA. We measured n-3 FAs as a percentage of total lipids in red blood cell membranes (n-3 FA%) at each visit.

RESULTS:

We detected IA in 10 anti-CCP3+ subjects (21%) at the baseline visit. Increased total n-3 FA% in red blood cell membranes [odds ratio (OR) = 0.09, 95% CI: 0.01, 0.76], specifically docosapentaenoic acid (OR = 0.16, 95% CI: 0.03, 0.83) and docosahexaenoic acid (OR = 0.23, 95% CI: 0.06, 0.86), was associated with a lower odds of IA at the baseline visit, adjusting for n-3 FA supplement use, current smoking, RF+, elevated CRP+ and shared epitope. We followed 35 of the anti-CCP3+ subjects who were IA negative at baseline and detected 14 incident IA cases over an average of 2.56 years of follow-up. In a time-varying survival analysis, increasing docosapentaenoic acid significantly decreased risk of incident IA (hazard ratio = 0.52, 95% CI: 0.27, 0.98), adjusting for age at baseline, n-3 FA supplement use, RF+, CRP+ and shared epitope.

CONCLUSION:

n-3 FAs may potentially lower the risk of transition from anti-CCP positivity to IA, an observation that warrants further investigation.

KEYWORDS:

autoantigens and autoantibodies; autoinflammatory conditions; diet therapy; epidemiology; rheumatoid arthritis

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Association of red cell distribution width with all-cause and cardiovascular-specific mortality in African American and white adults: a prospective cohort study.

Tajuddin SM, Nalls MA, Zonderman AB, Evans MK.

J Transl Med. 2017 Oct 13;15(1):208. doi: 10.1186/s12967-017-1313-6.

PMID: 29029617

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1313-6

https://translational-medicine.biomedcentral.com/track/pdf/10.1186/s12967-017-1313-6?site=translational-medicine.biomedcentral.com

Abstract

BACKGROUND:

While the mortality rate is declining in the United States, the life expectancy gap among different population groups suggests a need to identify biomarkers to improve early identification of individuals at risk. Red cell distribution width (RDW), a measure of anisocytosis, is an emerging biomarker of chronic disease morbidity and mortality, particularly in the elderly. However, little is known about its association with mortality risk in younger adults. The objectives of this study were to investigate the association between RDW and overall and cause-specific mortality risk, and to identify novel determinants of RDW level.

METHODS:

We used prospectively collected data from the Healthy Aging in Neighborhoods of Diversity across the Life Span study conducted in Baltimore, Maryland. At baseline (2004-2009), the study recruited 3720 African American and white men and women aged 30-64 years. Participants provided peripheral venous blood for RDW measurement as part of complete blood count, and genotyping. Mortality status was ascertained using the National Death Index database through December 31, 2013. Multivariable adjusted Cox proportional hazards regression models were fitted to assess mortality risk, and multiple linear regression models to identify determinants of RDW level.

RESULTS:

Participants' mean age was 48.1 (9.2) years. Of 2726 participants included in the present analyses, 57% were African Americans, and 56% were women. After 18,424 person-years of follow-up time, there were 226 deaths, and the leading cause of death were cardiovascular diseases (31.9%). Participants in the highest quartile of RDW had a 1.73-fold increased all-cause mortality risk (highest quartile vs. lowest quartile, multivariable adjusted hazard ratio = 1.73, 95% confidence interval: 1.10-2.74, p-trend = 0.006). This effect was significantly modified by body mass index (p-interaction = 0.004). Similar risk was observed for cardiovascular disease-specific mortality. Independent of body mass index, waist-hip ratio and illicit drug use were significantly associated with RDW.

CONCLUSIONS:

Elevated RDW was associated with a substantial risk of all-cause and cardiovascular disease-specific mortalities that was modified by body mass index. Central obesity and illicit drug use influence RDW level. In vulnerable populations at-risk for health disparities, RDW could provide a useful and inexpensive biomarker of mortality.

KEYWORDS:

African Americans; Cardiovascular disease; Mortality biomarker; Premature mortality; Red cell distribution width; Survival analysis; Whites

 

Gut microbiota changes in the extreme decades of human life: a focus on centenarians.

Santoro A, Ostan R, Candela M, Biagi E, Brigidi P, Capri M, Franceschi C.

Cell Mol Life Sci. 2017 Oct 14. doi: 10.1007/s00018-017-2674-y. [Epub ahead of print] Review.

PMID: 29032502

Abstract

The gut microbiota (GM) is a complex, evolutionarily molded ecological system, which contributes to a variety of physiological functions. The GM is highly dynamic, being sensitive to environmental stimuli, and its composition changes over the host's entire lifespan. However, the basic question of how much these changes may be ascribed to variables such as population, diet, genetics and gender, and/or to the aging process per se is still largely unanswered. We argue that comparison among studies on centenarians-the best model of healthy aging and longevity-recruited from different geographical areas/populations (different genetics and dietary habits) can help to disentangle the contribution of aging and non-aging-related variables to GM remodeling with age. The current review focuses on the role of population, gender and host genetics as possible drivers of GM modification along the human aging process. The feedback impact of age-associated GM variation on the GM-brain axis and GM metabolomics is also discussed. We likewise address the role of GM in neurodegenerative diseases such as Parkinson's and Alzheimer's, and its possible therapeutic use, taking advantage of the fact that centenarians are characterized by an extreme (healthy) phenotype versus patients suffering from age-related pathologies. Finally, it is argued that longitudinal studies combining metagenomics sequencing and in-depth phylogenetic analysis with a comprehensive phenotypic characterization of centenarians and patients using up-to-date omics (metabolomics, transcriptomics and meta-transcriptomics) are urgently needed.

KEYWORDS:

Aging; Centenarians; Gut microbiota; Gut–brain axis; Host genome

 

A ketogenic diet supplemented with medium-chain triglycerides enhances the anti-tumor and anti-angiogenic efficacy of chemotherapy on neuroblastoma xenografts in a CD1-nu mouse model.

Aminzadeh-Gohari S, Feichtinger RG, Vidali S, Locker F, Rutherford T, O'Donnel M, Stöger-Kleiber A, Mayr JA, Sperl W, Kofler B.

Oncotarget. 2017 Aug 8;8(39):64728-64744. doi: 10.18632/oncotarget.20041. eCollection 2017 Sep 12.

PMID: 29029389

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=20041&path%5B%5D=63935

Abstract

Neuroblastoma (NB) is a pediatric malignancy characterized by a marked reduction in aerobic energy metabolism. Recent preclinical data indicate that targeting this metabolic phenotype by a ketogenic diet (KD), especially in combination with calorie restriction, slows tumor growth and enhances metronomic cyclophosphamide (CP) therapy of NB xenografts. Because calorie restriction would be contraindicated in most cancer patients, the aim of the present study was to optimize the KD such that the tumors are sensitized to CP without the need of calorie restriction. In a NB xenograft model, metronomic CP was combined with KDs of different triglyceride compositions and fed to CD1-nu mice ad libitum. Metronomic CP in combination with a KD containing 8-carbon medium-chain triglycerides exerted a robust anti-tumor effect, suppressing growth and causing a significant reduction of tumor blood-vessel density and intratumoral hemorrhage, accompanied by activation of AMP-activated protein kinase in NB cells. Furthermore, the KDs caused a significant reduction in the serum levels of essential amino acids, but increased those of serine, glutamine and glycine. Our data suggest that targeting energy metabolism by a modified KD may be considered as part of a multimodal treatment regimen to improve the efficacy of classic anti-NB therapy.

KEYWORDS:

Warburg effect; ketogenic diet; medium-chain triglycerides; neuroblastoma

 

Longitudinal associations between marine omega-3 supplement users and coronary heart disease in a UK population-based cohort.

Lentjes MAH, Keogh RH, Welch AA, Mulligan AA, Luben RN, Wareham NJ, Khaw KT.

BMJ Open. 2017 Oct 13;7(10):e017471. doi: 10.1136/bmjopen-2017-017471.

PMID: 29030414

Abstract

OBJECTIVES:

Assess the association between marine omega-3 polyunsaturated fatty acid (n-3 PUFA) intake from supplements, mainly cod liver oil, and coronary heart disease (CHD) mortality.

DESIGN:

Prospective cohort study, with three exposure measurements over 22 years.

SETTING:

Norfolk-based European Prospective Investigation into Cancer (EPIC-Norfolk, UK).

PARTICIPANTS:

22 035 men and women from the general population, 39-79 years at recruitment.

EXPOSURE:

Supplement use was assessed in three questionnaires (1993-1998; 2002-2004; 2004-2011). Participants were grouped into non-supplement users (NSU), n-3 PUFA supplement users (SU+n3) and non-n-3 PUFA supplement users (SU-n3). Cox regression adjusted for time-point specific variables: age, smoking, prevalent illnesses, body mass index, alcohol consumption, physical activity and season and baseline assessments of sex, social class, education and dietary intake (7-day diet diary).

PRIMARY AND SECONDARY OUTCOME MEASURES:

During a median of 19-year follow-up, 1562 CHD deaths were registered for 22 035 included participants.

RESULTS:

Baseline supplement use was not associated with CHD mortality, but baseline food and supplement intake of n-3 PUFA was inversely associated with CHD mortality after adjustment for fish consumption. Using time-varying covariate analysis, significant associations were observed for SU+n3 (HR: 0.74, 95% CI 0.66 to 0.84), but not for SU-n3 versus NSU. In further analyses, the association for SU+n3 persisted in those who did not take other supplements (HR: 0.83, 95% CI 0.71 to 0.97). Those who became SU+n3 over time or were consistent SU+n3 versus consistent NSU had a lower hazard of CHD mortality; no association with CHD was observed in those who stopped using n-3 PUFA-containing supplements.

CONCLUSIONS:

Recent use of n-3 PUFA supplements was associated with a lower hazard of CHD mortality in this general population with low fish consumption. Residual confounding cannot be excluded, but the findings observed may be explained by postulated biological mechanisms and the results were specific to SU+n3.

KEYWORDS:

cardiac epidemiology; epidemiology; nutrition & dietetics

 

 

Prospective study of plasma homocysteine, its dietary determinants, and risk of age-related macular degeneration in men.

Christen WG, Cook NR, Chiuve SE, Ridker PM, Gaziano JM.

Ophthalmic Epidemiol. 2017 Oct 16:1-10. doi: 10.1080/09286586.2017.1362009. [Epub ahead of print]

PMID: 29035128

Abstract

PURPOSE:

Cross-sectional and case-control studies generally support a direct association between elevated plasma homocysteine and age-related macular degeneration (AMD), but data from prospective studies are limited. We examined the prospective relation of plasma homocysteine level, its dietary determinants, and risk of AMD in a large cohort of apparently healthy male physicians.

METHODS:

During a mean follow-up of 11.2 years, we identified 146 incident cases of visually significant AMD (responsible for a reduction of visual acuity to 20/30 or worse), and 146 controls matched for age, smoking status, and time of blood draw. We measured concentration of homocysteine in blood samples collected at baseline using an enzymatic assay. and we assessed dietary intake of B vitamins and related compounds betaine and choline with a food frequency questionnaire administered at baseline.

RESULTS:

AMD was not associated with plasma level of homocysteine; the multivariable-adjusted odds ratio (OR) of AMD comparing the highest and lowest quartile of homocysteine was 1.09 (95% confidence interval [95% CI]: 0.52-2.31; p for trend = 0.99). However, AMD was inversely associated with quartile of intake of total folate (OR: 0.55; 95% CI: 0.24-1.23; p for trend = 0.08), vitamin B6 from food (OR: 0.39; 95% CI: 0.17-0.88; p for trend = 0.01), and betaine (OR: 0.53; 95% CI: 0.22-1.27; p for trend = 0.048).

CONCLUSIONS:

These prospective data from a cohort of apparently healthy men do not support a major role for homocysteine in AMD occurrence, but do suggest a possible beneficial role for higher intake of several nutrients involved in homocysteine metabolism.

KEYWORDS:

Homocysteine; age-related macular degeneration; case–control; diet

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Hypertension impairs neurovascular coupling and promotes microvascular injury: role in exacerbation of Alzheimer's disease.

Csiszar A, Tarantini S, Fülöp GA, Kiss T, Valcarcel-Ares MN, Galvan V, Ungvari Z, Yabluchanskiy A.

Geroscience. 2017 Aug 29. doi: 10.1007/s11357-017-9991-9. [Epub ahead of print]

PMID: 28853030

Abstract

Hypertension in the elderly substantially increases both the risk of vascular cognitive impairment (VCI) and Alzheimer's disease (AD); however, the underlying mechanisms are not completely understood. This review discusses the effects of hypertension on structural and functional integrity of cerebral microcirculation, including hypertension-induced alterations in neurovascular coupling responses, cellular and molecular mechanisms involved in microvascular damage (capillary rarefaction, blood-brain barrier disruption), and the genesis of cerebral microhemorrhages and their potential role in exacerbation of cognitive decline associated with AD. Understanding and targeting the hypertension-induced cerebromicrovascular alterations that are involved in the onset and progression of AD and contribute to cognitive impairment are expected to have a major role in preserving brain health in high-risk older individuals.

KEYWORDS:

Alzheimer’s disease; Angiotensin II; Endothelial dysfunction; Functional hyperemia; High blood pressure; Hypertension; Microcirculation; Neurovascular coupling; VCID

 

Androgen supplementation improves some but not all aspects of immune senescence in aged male macaques.

Rais M, Wilson RM, Urbanski HF, Messaoudi I.

Geroscience. 2017 Jun 14. doi: 10.1007/s11357-017-9979-5. [Epub ahead of print]

PMID: 28616771

Abstract

Aging leads to a progressive decline in immune function commonly referred to as immune senescence, which results in increased incidence and severity of infection. In addition, older males experience a significant disruption in their levels of circulating androgens, notably testosterone and dehydroepiandrosterone (DHEA), which has been linked to sarcopenia, osteoporosis, cardiovascular disease, and diabetes. Since sex steroid levels modulate immune function, it is possible that the age-related decline in androgen levels can also affect immune senescence. Therefore, in this study, we evaluated the pleiotropic effects of physiological androgen supplementation in aged male rhesus macaques (n = 7/group) on immune cell subset frequency and response to vaccination. As expected, frequency of naïve CD4 and CD8 T cells declined in aged non-treated macaques, while that of memory T cells increased. In contrast, frequency of naïve and memory T cells remained stable in androgen-supplemented males. In addition, levels of inflammatory cytokines increased less steeply in supplemented aged males compared to the aged controls. Despite these changes, androgen-supplemented animals only showed modest improvement in antibody responses following vaccination compared to age non-treated controls. These data indicate that short-term physiological androgen supplementation can improve some but not all aspects of immune senescence.

KEYWORDS:

Androgens; Andropause; Immune senescence; Inflammation; Rhesus macaques; T cells

 

Hypertension-induced synapse loss and impairment in synaptic plasticity in the mouse hippocampus mimics the aging phenotype: implications for the pathogenesis of vascular cognitive impairment.

Tucsek Z, Noa Valcarcel-Ares M, Tarantini S, Yabluchanskiy A, Fülöp G, Gautam T, Orock A, Csiszar A, Deak F, Ungvari Z.

Geroscience. 2017 Jun 29. doi: 10.1007/s11357-017-9981-y. [Epub ahead of print]

PMID: 28664509

http://sci-hub.cc/10.1007/s11357-017-9981-y

Abstract

Strong epidemiological and experimental evidence indicates that hypertension has detrimental effects on the cerebral microcirculation and thereby promotes accelerated brain aging. Hypertension is an independent risk factor for both vascular cognitive impairment (VCI) and Alzheimer's disease (AD). However, the pathophysiological link between hypertension-induced cerebromicrovascular injury (e.g., blood-brain barrier disruption, increased microvascular oxidative stress, and inflammation) and cognitive decline remains elusive. The present study was designed to characterize neuronal functional and morphological alterations induced by chronic hypertension and compare them to those induced by aging. To achieve that goal, we induced hypertension in young C57BL/6 mice by chronic (4 weeks) infusion of angiotensin II. We found that long-term potentiation (LTP) of performant path synapses following high-frequency stimulation of afferent fibers was decreased in hippocampal slices obtained from hypertensive mice, mimicking the aging phenotype. Hypertension and advanced age were associated with comparable decline in synaptic density in the stratum radiatum of the mouse hippocampus. Hypertension, similar to aging, was associated with changes in mRNA expression of several genes involved in regulation of neuronal function, including down-regulation of Bdnf, Homer1, and Dlg4, which may have a role in impaired synaptic plasticity. Collectively, hypertension impairs synaptic plasticity, reduces synaptic density, and promotes dysregulation of genes involved in synaptic function in the mouse hippocampus mimicking the aging phenotype. These hypertension-induced neuronal alterations may impair establishment of memories in the hippocampus and contribute to the pathogenesis and clinical manifestation of both vascular cognitive impairment (VCI) and Alzheimer's disease (AD).

KEYWORDS:

Blood pressure; Dementia; Hypertension; Inflammation; Microcirculation; Vascular aging

 

Rapamycin treatment attenuates age-associated periodontitis in mice.

An JY, Quarles EK, Mekvanich S, Kang A, Liu A, Santos D, Miller RA, Rabinovitch PS, Cox TC, Kaeberlein M.

Geroscience. 2017 Sep 9. doi: 10.1007/s11357-017-9994-6. [Epub ahead of print]

PMID: 28889220

http://sci-hub.cc/10.1007/s11357-017-9994-6

Abstract

Interventions that target biological mechanisms of aging have great potential to enhance quality of life by delaying morbidity and mortality. The FDA-approved drug rapamycin is a compelling candidate for such an intervention. In a previous study, it was reported that 3 months of rapamycin treatment is sufficient to increase life expectancy and remodel the gut microbiome in aged mice. Transient treatment with rapamycin or a rapamycin derivative has also been shown to delay immune stem cell senescence and rejuvenate immune function in aged mice and elderly people. Periodontal disease is an important age-related disease involving altered immune function, pathological changes to the oral microbiome, and systemic inflammation. Periodontal disease is defined clinically by loss of alveolar bone and by connective tissue degeneration. Here, we describe significant alveolar bone loss during aging in two different mouse strain backgrounds and report that rapamycin treatment is sufficient to reverse age-associated periodontal disease in mice. Partial restoration of youthful levels of alveolar bone is observed in 22-month-old rapamycin-treated mice as rapidly as 8 weeks after initiation of treatment. To the best of our knowledge, this represents the first intervention shown to substantially prevent or reverse age-associated alveolar bone loss. These findings suggest the possibility that inhibition of mTOR with rapamycin or other pharmacological agents may be useful to treat a clinically relevant condition for which there is currently no effective treatment.

KEYWORDS:

Aging; Dental health; Gum disease; Healthspan; Immune function; Inflammation; Mice; Microbiome; Oral health; Rapamycin; Teeth; mTOR

 

Mouse Study Shows Intermittent Fasting Limits Obesity and Improves Metabolism

Posted on October 17, 2017

MedicalResearch.com Interview with: Dr. Hoon-Ki Sung

https://medicalresearch.com/weight-research/mouse-study-shows-intermittent-fasting-limits-obesity-and-improves-metabolism/37513/

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Cell Research advance online publication 17 October 2017; doi: 10.1038/cr.2017.126

Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage

Kim, K-H. et al (2017).

http://www.nature.com/cr/journal/vaop/ncurrent/full/cr2017126a.html?foxtrotcallback=true

https://www.nature.com/cr/journal/vaop/ncurrent/pdf/cr2017126a.pdf

Abstract

Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.

Keywords: intermittent fasting; thermogenesis; vascular endothelial growth factor; adipose macrophage

Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage,

Cell Research DOI: doi:10.1038/cr.2017.126

 

The Scientist » The Nutshell

Compound Found in Red Wine Boosts Immune Cell Function

At low doses, resveratrol enhanced human T-cell activity in vitro, while at high doses it interfered with cell signaling.

By Catherine Offord | October 17, 2017

http://www.the-scientist.com/?articles.view/articleNo/50668/title/Compound-Found-in-Red-Wine-Boosts-Immune-Cell-Function/&utm_campaign=NEWSLETTER_TS_The-Scientist-Daily_2016&utm_source=hs_email&utm_medium=email&utm_content=57487231&_hsenc=p2ANqtz--pCX5HBLbzFQhvMgSdPIlCzeXBO7KNEmuLyYGbqih0JWq9Lbe4cflc7oLAvRYDjb7mKfDCaIRD-Nve8lLVfPK-XsENOw&_hsmi=57487231

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Resveratrol stimulates the metabolic reprogramming of human CD4+ T cells to enhance effector function

BY MARCO CRAVEIRO, GASPARD CRETENET, CÉDRIC MONGELLAZ, MARIA I. MATIAS, OLIVIER CARON, MARIA C. PEDROSO DE LIMA, VALÉRIE S. ZIMMERMANN, ERIC SOLARY, VALÉRIE DARDALHON, VJEKOSLAV DULIĆ, NAOMI TAYLOR

SCI. SIGNAL.17 OCT 2017 Vol. 10, Issue 501, eaal3024

DOI: 10.1126/scisignal.aal3024

http://sci-hub.cc/10.1126/scisignal.aal3024

Resveratrol alters human T cell responsiveness to antigens, coupling a replication stress response to metabolic reprogramming.

Editor's Summary

Resveratrol and lymphocyte responses

Resveratrol is a polyphenolic plant compound, which has attracted much interest as a pharmacological agent because of its potential therapeutic effects against cancer, aging, and inflammation. However, many studies have produced conflicting evidence of the effects of resveratrol in different contexts. Craveiro et al. found that high doses of resveratrol inhibited the responses of human CD4+ T cells to antigens. However, low doses of the drug reprogrammed the metabolism of the cells to make them more responsive to antigens and produce increased amounts of the inflammatory cytokine interferon-γ. These data suggest that the use of resveratrol to treat various pathologies should be carefully assessed, especially in an autoimmune setting.

Abstract

The polyphenol resveratrol activates the deacetylase Sirt1, resulting in various antioxidant, chemoprotectant, neuroprotective, cardioprotective, and anti-inflammatory properties. We found that at high concentrations of resveratrol, human CD4+ T cells showed defective antigen receptor signaling and arrest at the G1 stage of the cell cycle, whereas at low concentrations, cells were readily activated and exhibited enhanced Sirt1 deacetylase activity. Nevertheless, low-dose resveratrol rapidly stimulated genotoxic stress in the T cells, which resulted in engagement of a DNA damage response pathway that depended on the kinase ATR [ataxia telangiectasia–mutated (ATM) and Rad3-related], but not ATM, and subsequently in premitotic cell cycle arrest. The concomitant activation of p53 was coupled to the expression of gene products that regulate cell metabolism, leading to a metabolic reprogramming that was characterized by decreased glycolysis, increased glutamine consumption, and a shift to oxidative phosphorylation. These alterations in the bioenergetic homeostasis of CD4+ T cells resulted in enhanced effector function, with both naïve and memory CD4+ T cells secreting increased amounts of the inflammatory cytokine interferon-γ. Thus, our data highlight the wide range of metabolic adaptations that CD4+ T lymphocytes undergo in response to genomic stress.

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Cardiovascular and Metabolic Consequences of Testosterone Supplements in Young and Old Male Spontaneously Hypertensive Rats: Implications for Testosterone Supplements in Men.

Dalmasso C, Patil CN, Yanes Cardozo LL, Romero DG, Maranon RO.

J Am Heart Assoc. 2017 Oct 17;6(10). pii: e007074. doi: 10.1161/JAHA.117.007074.

PMID: 29042425

Abstract

BACKGROUND:

The safety of testosterone supplements in men remains unclear. In the present study, we tested the hypothesis that in young and old male spontaneously hypertensive rats (SHR), long-term testosterone supplements increase blood pressure and that the mechanism is mediated in part by activation of the renin-angiotensin system.

METHODS AND RESULTS:

In untreated males, serum testosterone exhibited a sustained decrease after 5 months of age, reaching a nadir by 18 to 22 months of age. The reductions in serum testosterone were accompanied by an increase in body weight until very old age (18 months). Testosterone supplements were given for 6 weeks to young (12 weeks-YMSHR) and old (21-22 months-OMSHR) male SHR that increased serum testosterone by 2-fold in young males and by 4-fold in old males. Testosterone supplements decreased body weight, fat mass, lean mass, and plasma leptin, and increased plasma estradiol in YMSHR but had no effect in OMSHR. Mean arterial pressure (MAP) was significantly higher in OMSHR than in YMSHR and testosterone supplements decreased MAP in OMSHR, but significantly increased MAP in YMSHR. Enalapril, the angiotensin-converting enzyme inhibitor, reduced MAP in both control and testosterone-supplemented YMSHR, but had a greater effect on MAP in testosterone-treated rats, suggesting the mechanism responsible for the increase in MAP in YMSHR is mediated at least in part by activation of the renin-angiotensin system.

CONCLUSIONS:

Taken together with previous studies, these data suggest that testosterone supplements may have differential effects on men depending on age, cardiovascular and metabolic status, and dose and whether given long-term or short-term.

KEYWORDS:

aging; hypertension; leptin; testosterone

 

Physical capability predicts mortality in late mid-life as well as in old age: Findings from a large British cohort study.

Keevil VL, Luben R, Hayat S, Sayer AA, Wareham NJ, Khaw KT.

Arch Gerontol Geriatr. 2017 Oct 4;74:77-82. doi: 10.1016/j.archger.2017.10.001. [Epub ahead of print]

PMID: 29040888

http://sci-hub.cc/10.1016/j.archger.2017.10.001

Abstract

INTRODUCTION:

Low physical capability predicts mortality, perhaps by association with co-morbidity. However, few studies include participants <70years old with lower co-morbidity burdens compared to older adults. We examined relationships between usual walking speed (UWS), timed chair stands speed, grip strength, standing balance and all-cause mortality in 8477 participants aged 48-92years enrolled in the European Prospective Investigation of Cancer-Norfolk study.

METHODS:

Participants (55.1% female) were followed up for 6.0 years (inter-quartile range 4.6, 7.5). Associations were examined using Cox proportional hazards regression by age-group (<70years versus ≥70years) and then in the whole cohort adjusted for age, sex, anthropometry, history of diabetes/stroke/myocardial infarction/cancer, smoking, alcohol intake, socioeconomic status, television viewing time and physical activity.

RESULTS:

Age and sex adjusted associations were similar in younger and older participants (Pinteraction all >0.05) and those with lower physical capability had higher mortality risk. For example, in those <70years old hazard ratios (95% confidence interval) for mortality in the third, second and lowest sex-specific quartiles of UWS compared to the highest were 1.21 (0.75, 1.96), 2.11 (1.35, 3.28) and 2.91 (1.84, 4.62) and in participants ≥70years old were 1.19 (0.73, 1.95), 2.09 (1.35, 3.24) and 2.64 (1.73, 4.02) respectively. In the whole cohort, strong associations between all physical capability tests and mortality persisted after multivariable adjustment and after excluding participants with co-morbidity.

CONCLUSIONS:

Physical capability was independently predictive of future mortality risk with similar associations in late mid-life, when co-morbidity burden is lower, as at older age.

KEYWORDS:

Epidemiology; Mid-late life; Mortality; Physical performance

 

Adiponectin circulating levels and 10-year (2002-2012) cardiovascular disease incidence: the ATTICA Study.

Kyrou I, Tsantarlioti O, Panagiotakos DB, Tsigos C, Georgousopoulou E, Chrysohoou C, Skoumas I, Tousoulis D, Stefanadis C, Pitsavos C; ATTICA study group.

Endocrine. 2017 Oct 16. doi: 10.1007/s12020-017-1434-y. [Epub ahead of print]

PMID: 29039145

Abstract

PURPOSE:

Adiponectin is an adipokine with anti-inflammatory and cardiovascular-protective properties. Existing epidemiological evidence is conflicting on the exact relationship between adiponectin and long-term cardiovascular disease (CVD) risk. Our aim was to prospectively assess whether circulating adiponectin is associated with long-term incident CVD.

METHODS:

A population-based, prospective study in adults (>18 years) without previous CVD history (ATTICA study). Circulating total adiponectin levels were measured at baseline (2001-2002) in a sub-sample (n = 531; women/men: 222/309; age: 40 ± 11 years) of the ATTICA cohort and complete 10-year follow-up data were available in 366 of these participants (women/men: 154/212; age: 40 ± 12 years).

RESULTS:

After adjusting for multiple factors, including age, sex, body mass index, waist circumference, smoking, physical activity, Mediterranean diet adherence, hypertension, diabetes, and hypercholesterolemia, our logistic regression analysis indicates that an increase in circulating total adiponectin levels by 1 unit was associated with 36% lower CVD risk (relative risk [RR]: 0.64, 95% confidence interval [CI] 0.42-0.96; p = 0.03). Further adjusting for interleukin-6 plasma levels had no significant impact (RR: 0.60, 95% CI 0.38-0.94; p = 0.03), while additional adjustment for circulating C-reactive protein (CRP) modestly attenuated this association (RR: 0.63, 95% CI 0.40-0.99; p = 0.046).

CONCLUSIONS:

In our study, elevated circulating total adiponectin levels were associated with lower 10-year CVD risk in adults without previous CVD, independently of other established CVD risk factors. This association appeared to be modestly attenuated by CRP, yet was not mediated by interleukin-6 which is the main endocrine/circulating pro-inflammatory cytokine.

KEYWORDS:

ATTICA study; Adiponectin; CVD risk; Cardiovascular disease

 

Food groups and risk of coronary heart disease, stroke and heart failure: A systematic review and dose-response meta-analysis of prospective studies.

Bechthold A, Boeing H, Schwedhelm C, Hoffmann G, Knüppel S, Iqbal K, Henauw S, Michels N, Devleesschauwer B, Schlesinger S, Schwingshackl L.

Crit Rev Food Sci Nutr. 2017 Oct 17:0. doi: 10.1080/10408398.2017.1392288. [Epub ahead of print]

PMID: 29039970

Abstract

BACKGROUND:

Despite growing evidence for food-based dietary patterns' potential to reduce cardiovascular disease risk, knowledge about the amounts of food associated with the greatest change in risk of specific cardiovascular outcomes and about the quality of meta-evidence is limited.Therefore, the aim of this meta-analysis was to synthesize the knowledge about the relation between intake of 12 major food groups (whole grains, refined grains, vegetables, fruit, nuts, legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened beverages [sSB]) and the risk of coronary heart disease (CHD), stroke and heart failure (HF).

METHODS:

We conducted a systematic search in PubMed and Embase up to March 2017 for prospective studies. Summary risk ratios (RRs) and 95% confidence intervals (95% CI) were estimated using a random effects model for highest versus lowest intake categories, as well as for linear and non-linear relationships.

RESULTS:

Overall, 123 reports were included in the meta-analyses. An inverse association was present for whole grains (RRCHD: 0.95 (95% CI: 0.92-0.98), RRHF: 0.96 (0.95-0.97)), vegetables and fruits (RRCHD: 0.97 (0.96-0.99), and 0.94 (0.90-0.97); RRstroke: 0.92 (0.86-0.98), and 0.90 (0.84-0.97)), nuts (RRCHD: 0.67 (0.43-1.05)), and fish consumption (RRCHD: 0.88 (0.79-0.99), RRstroke: 0.86 (0.75-0.99), and RRHF: 0.80 (0.67-0.95)), while a positive association was present for egg (RRHF: 1.16 (1.03-1.31)), red meat (RRCHD: 1.15 (1.08-1.23), RRstroke: 1.12 (1.06-1.17), RRHF: 1.08 (1.02-1.14)), processed meat (RRCHD: 1.27 (1.09-1.49), RRstroke: 1.17 (1.02-1.34), RRHF: 1.12 (1.05-1.19)), and SSB consumption (RRCHD: 1.17 (1.11-1.23), RRstroke: 1.07 (1.02-1.12), RRHF: 1.08 (1.05-1.12)) in the linear dose-response meta-analysis. There were clear indications for non-linear dose-response relationships between whole grains, fruit, nuts, dairy, and red meat and CHD.

CONCLUSION:

An optimal intake of whole grains, vegetables, fruit, nuts, legumes, dairy, fish, red and processed meat, eggs and SSB showed an important lower risk of CVD.

KEYWORDS:

cardiovascular; coronary heart disease; diet; dose-response; food; heart failure; meta-analysis; stroke

 

Dietary Animal-derived L-Arginine Intakes and Risk of Chronic Kidney Disease: a 6-year Follow-up of Tehran Lipid and Glucose Study.

Bahadoran Z, Mirmiran P, Golzarand M, Davudabadi-Farahani R, Azizi F.

Iran J Kidney Dis. 2017 Oct;11(5):352-359.

PMID: 29038390

http://www.ijkd.org/index.php/ijkd/article/view/3053/947

Abstract

INTRODUCTION:

There is inconsistent evidence regarding the potential role of L-arginine intake on kidney function. This study investigated the association of dietary L-arginine intake and the risk of chronic kidney disease (CKD) in adults.

MATERIALS AND METHODS:

We evaluated 1780 men and women participated in the Tehran Lipid and Glucose Study, followed for a median of 6.3 years. Dietary intakes of total L-arginine as well as animal- and plant-derived L-arginine were assessed using the validated semi-quantitative food frequency questionnaire, at baseline. Demographics, anthropometrics, and biochemical variables were evaluated at baseline and again after a 3-year and a 6-year follow-up. The incidence of CKD was assessed across tertiles of L-arginine and its categories using multivariable logistic regression models.

RESULTS:

The mean dietary intakes of total, plant-derived, and animal-derived L-arginine were 4.1 ± 1.5 g/d, 1.8 ± 0.9 g/d, and 2.1 ± 0.8 g/d, respectively. In the fully-adjusted logistic regression model, the highest compared to the lowest intakes of animal-derived L-arginine (2.57 g/d versus 1.05 g/d) increased the risk of CKD (relative risk, 1.54; 95% confidence interval, 1.06 to 2.14, P = .02 for trend). Animal-derived L-arginine was negatively associated with changes of estimated glomerular filtration rate and creatinine clearance rate during the follow-up. There was no significant association between total or plant-derived L-arginine intakes and the risk of CKD after 6.3 years of follow-up.

CONCLUSIONS:

Our findings suggested an adverse effect of higher intakes of L-arginine from animal sources that could be a dietary risk factor for development of kidney disease.

 

Association Between Sodium Excretion and Cardiovascular Disease and Mortality in the Elderly: A Cohort Study.

Lelli D, Antonelli-Incalzi R, Bandinelli S, Ferrucci L, Pedone C.

J Am Med Dir Assoc. 2017 Oct 14. pii: S1525-8610(17)30516-9. doi: 10.1016/j.jamda.2017.09.004. [Epub ahead of print]

PMID: 29042264

http://sci-hub.cc/10.1016/j.jamda.2017.09.004

Abstract

OBJECTIVE:

High dietary sodium intake is a risk factor for cardiovascular events and death. Recently, a J-shaped correlation between sodium intake and adverse outcomes has been shown. The evidence on the association between sodium intake and cardiovascular outcomes in the elderly is scant. The objective of this study was to evaluate the correlation between sodium intake and cardiovascular events and mortality in an elderly population, taking into account frailty status.

DESIGN:

Cohort study of community dwelling older people enrolled in the InCHIANTI (Invecchiare in Chianti - Aging in the Chianti) study from 1998 to 2000 and followed-up for 9 years.

SETTING:

Two communities in Tuscany, Italy.

PARTICIPANTS:

A total of 920 participants 65 years of age and older, with 24-hour urinary sodium excretion data.

MEASUREMENTS:

Nine-year mortality and incident cardiovascular events were analyzed using Cox and nonlinear log-binomial models, stratified by frailty status. Sensitivity analysis in participants without hypertension and cardiovascular diseases was performed.

RESULTS:

Mean age of the population was 74.5 years (standard deviation 6.99); 55.4% were women. There was a bi-modal association between sodium excretion and mortality, with risk increasing only below sodium excretion of 6.25 g/d [hazard ratio (HR) 1.29, 95% confidence interval (CI) 1.20-1.38], confirmed in the adjusted model (HR 1.12, 95% CI 1.04-1.22). These results were confirmed in participants without cardiovascular diseases. After stratification for frailty phenotype, the association was stronger in frail participants (adjusted HR 1.23, 95% CI 1.02-1.50 vs HR 1.11, 95% CI 1.01-1.22 in robust participants). There was no association between 24-hour sodium excretion and 9-year incidence of cardiovascular diseases (adjusted risk ratio 0.96, 95% CI 0.90-1.02).

CONCLUSIONS:

Reduced sodium excretion is associated with increased mortality in a sample of community-dwelling older people, especially among the frail participants. High levels of sodium excretion are not associated with adverse outcomes in this population; therefore, sodium restriction might not be beneficial in older people.

KEYWORDS:

Aged; cardiovascular diseases; dietary; frail elderly; mortality; sodium

 

Long-term exposure to residential railway and road traffic noise and risk for diabetes in a Danish cohort.

Roswall N, Raaschou-Nielsen O, Jensen SS, Tjønneland A, Sørensen M.

Environ Res. 2017 Oct 15;160:292-297. doi: 10.1016/j.envres.2017.10.008. [Epub ahead of print]

PMID: 29045908

Abstract

BACKGROUND:

Road traffic noise exposure has been found associated with diabetes incidence. Evidence for an association between railway noise exposure is less clear, as large studies with detailed railway noise modelling are lacking.

PURPOSE:

To investigate the association between residential railway noise and diabetes incidence, and to repeat previous analyses on road traffic noise and diabetes with longer follow-up time.

METHODS:

Among 50,534 middle-aged Danes enrolled into the Diet, Cancer and Health cohort from 1993 to 97, we identified 5062 cases of incident diabetes during a median follow-up of 15.5 years. Present and historical residential addresses from 1987 to 2012 were found in national registries, and railway and road traffic noise (Lden) were modelled for all addresses, using the Nordic prediction method. We used Cox proportional hazard models to investigate the association between residential traffic noise over 1 and 5 years before diagnosis, and diabetes incidence. Hazard ratios (HRs) were calculated as crude and adjusted for potential confounders.

RESULTS:

We found no association between railway noise exposure and diabetes incidence among the 9527 persons exposed, regardless of exposure time-window: HR 0.99 (0.94-1.04) per 10dB for 5-year exposure in fully adjusted models. There was no effect modification by sex, road traffic noise, and education. We confirmed the previously found association between road traffic noise exposure and diabetes including 6 additional years of follow-up: HR 1.08 (1.04-1.13) per 10dB for 5-year exposure in fully adjusted models.

CONCLUSION:

The study does not suggest an association between residential railway noise exposure and diabetes incidence, but supports the finding of a direct association with residential road traffic noise.

KEYWORDS:

Cohort study; Diabetes; Epidemiology; Railway noise; Road traffic noise

Edited by AlPater
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Living Too Long? Exploring Attitudes Toward Reaching 100 Years Old.

Ribeiro O, Canedo S, Cerqueira M, Nascimento A, Teixeira L.

Int J Aging Hum Dev. 2017 Jan 1:91415017720886. doi: 10.1177/0091415017720886. [Epub ahead of print]

PMID: 29048212

Abstract

Objective This study analyses the relationship between pro- and anti-longevity attitudes, attitudes toward centenarians, and the wish to reach 100 years of age in a sample of community dwelling older adults. Methods Participants ( N = 137) completed a questionnaire on attitudes toward life-extension and an aging semantic differential using centenarians as an attitudinal target. Sociodemographic information, perceived health status, and information on knowing a centenarian were also obtained. A cluster analysis was used to identify subgroups (leaning anti-longevity group vs. leaning prolongevity group), and their associations with personal attributes were tested using logistic regression models. Results Most respondents said they would wish to reach 100 years old (54.7%) and presented a leaning positive attitude toward centenarians (52.6%). Holding a negative attitude toward centenarians rather than any other attribute increases the odds of having more negative attitudes toward life extension. Conclusion Results stress the importance of social views on extreme longevity in shaping life extension attitudes.

KEYWORDS:

ageism; attitudes; centenarians; life extension; longevity

 

Nutrition, physical activity, and lifestyle factors in prostate cancer prevention.

Ballon-Landa E, Parsons JK.

Curr Opin Urol. 2017 Oct 18. doi: 10.1097/MOU.0000000000000460. [Epub ahead of print]

PMID: 29049045

Abstract

PURPOSE OF REVIEW:

To review current evidence for prostate cancer prevention with nutrition, physical activity, and lifestyle interventions and identify future research directions.

RECENT FINDINGS:

Multiple preclinical and observational studies have observed that diet, exercise, and lifestyle interventions may play a role in mitigating disease progression, mortality, and overall disease burden for high-grade and fatal prostate cancer. Increased vegetable and fruit intakes, decreased red meat and saturated fat intakes, and increased exercise are potentially associated with decreased risk of incident disease and increased progression-free, prostate cancer-specific, and overall survival. Randomized controlled trials (RCTs) have demonstrated that selenium and vitamin C supplements are ineffective in preventing incident prostate cancer and that vitamin E supplements potentially increase incident prostate cancer risk. A large RCT of a high vegetable diet intervention among prostate cancer patients on active surveillance, the Men's Eating and Living study, will soon complete analysis. An RCT for an exercise intervention among men with metastatic castrate-resistant prostate cancer is currently accruing.

SUMMARY:

Although preclinical and observational studies have identified potential benefits for high vegetable, low fat, low meat diets, and increased exercise, Level I evidence is limited. To inform clinical care, future research should focus on RCTs evaluating clinical effectiveness.

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Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE, Meyskens FL Jr, Baker LH.

JAMA. 2011 Oct 12;306(14):1549-56. doi: 10.1001/jama.2011.1437.

PMID: 21990298 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169010/pdf/nihms551257.pdf

 

[The below paper is not pdf-availed.]

Should Pre-hypertension Be Treated?

Kanegae H, Oikawa T, Kario K.

Curr Hypertens Rep. 2017 Oct 18;19(11):91. doi: 10.1007/s11906-017-0789-z. Review.

PMID: 29046988

Abstract

Hypertension is an important preventable risk factor for disease and death worldwide. In light of the world's population growth and aging, hypertension is a global public health issue. Many studies have shown associations between pre-hypertension and a higher risk of the future development of hypertension and cardiovascular disease in general populations. However, pre-hypertension per se is not a disease with an immediate high risk, and the clinical value of the identification of pre-hypertension is the potential detection of the early stage of the risk of hypertension and/or cardiovascular disease over an individual's lifespan. We recently assessed the impacts of age-related differences in risk factors on new-onset hypertension among normotensive individuals. As risk factors of the new onset of hypertension, the impact of diastolic blood pressure compared with systolic blood pressure (SBP), men compared with women, and higher body mass index were greater in the younger adults, whereas in the older adults, the impact of SBP and female sex were greater. Proteinuria was a risk factor for hypertension in both younger and older adults. Non-pharmacological approaches such as body weight reduction, low-salt diet, physical exercise, and good sleep hygiene should be first-line treatments for pre-hypertension. In addition, careful observation to detect the new onset of hypertension and the identification of the appropriate timing of pharmacologic treatment should be conducted, especially in adults with pre-hypertension and the risk factors mentioned above.

KEYWORDS:

Aging; Hypertension; Obesity; Pre-hypertension; Prevention of hypertension; Risk

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Association of low-density lipoprotein pattern with mortality after myocardial infarction: Insights from the TRIUMPH study.

Pokharel Y, Tang Y, Bhardwaj B, Patel KK, Qintar M, O'Keefe JH Jr, Kulkarni KR, Jones PH, Martin SS, Virani SS, Spertus JA.

J Clin Lipidol. 2017 Oct 3. pii: S1933-2874(17)30447-6. doi: 10.1016/j.jacl.2017.09.002. [Epub ahead of print]

PMID: 29050980

Abstract

BACKGROUND:

Studies of incident coronary heart disease risk within low-density lipoprotein (LDL) subclass (small, dense vs large, buoyant) have shown mixed results. No prospective cohort study has examined the association of small, dense, or large, buoyant LDL with mortality after myocardial infarction (MI).

OBJECTIVE:

The objective of the study was to examine association of LDL pattern after MI and death.

METHODS:

In 2476 patients hospitalized for MI, LDL pattern (A [large, buoyant], A/B [mixed], and B [small, dense]) was established by ultracentrifugation using Vertical Auto Profile. Using time-to-event analysis, we examined the association with 5-year mortality within LDL patterns, after adjusting for important patient and treatment characteristics. We additionally adjusted for LDL cholesterol (LDL-C) and triglyceride levels and used directly measured LDL-C and non-high-density lipoprotein cholesterol as exposures.

RESULTS:

Patterns A, A/B, and B were present in 39%, 28%, and 33% of patients, respectively, with incident rates (per 1000 patient-years) of 50, 34, and 24 for all-cause and 24, 19, and 10 for CV mortality. The hazard ratios (95% confidence interval) with LDL patterns A/B and B compared with pattern A were 0.77 (0.61, 0.99) and 0.67 (0.51, 0.88) for all-cause, 0.94 (0.67, 1.33) and 0.69 (0.46, 1.03) for cardiovascular, and 0.64 (0.45, 0.91) and 0.65 (0.45, 0.93) for noncardiovascular mortalities, respectively. Results were similar when further adjusted for LDL-C and triglycerides, or with LDL-C and non-high-density lipoprotein cholesterol as exposures.

CONCLUSION:

Compared with LDL pattern A, pattern B was significantly associated with reduced all-cause and non-CV mortalities with a trend for lower CV mortality after MI, independent of LDL-C and triglycerides.

KEYWORDS:

Density; Low-density lipoprotein pattern; Mortality; Myocardial infarction; Paradox; Size

 

Relationships of variations in the tongue microbiota and pneumonia mortality in nursing home residents.

Kageyama S, Takeshita T, Furuta M, Tomioka M, Asakawa M, Suma S, Takeuchi K, Shibata Y, Iwasa Y, Yamashita Y.

J Gerontol A Biol Sci Med Sci. 2017 Oct 19. doi: 10.1093/gerona/glx205. [Epub ahead of print]

PMID: 29053769

Abstract

BACKGROUND:

Aspiration of oral debris, containing dense oral bacteria, is a major cause of pneumonia in elderly adults. This study investigated the relationship between tongue microbiota composition and incidence of pneumonia-related deaths, in nursing home residents.

METHODS:

The subjects were assessed for health conditions, including their tongue microbiota, at baseline. We determined tongue microbiota profiles by 16S ribosomal RNA gene sequencing and clustering approach. All subjects (n = 173) were followed prospectively for a median of 19 months to assess the incidence of all-cause death, including pneumonia-related death. We evaluated risk estimates of microbiota effects on death using multivariate Cox proportional hazards regression analysis.

RESULTS:

Tongue microbiota were classified into two community types: type I was dominated by Prevotella and Veillonella species, while type II was dominated by Neisseria and Fusobacterium species. The subjects with type I microbiota exhibited a significantly greater risk of all-cause death (adjusted hazard ratio [aHR] = 3.79, 95% confidence interval [CI] = 1.38-10.39) and pneumonia-related death (aHR = 13.88, 95% CI = 1.64-117.21), than those with type II microbiota. There was no significant association between microbiota type and other-cause death.

CONCLUSIONS:

The tongue microbiota type was significantly associated with an increased mortality risk from pneumonia in nursing home residents.

KEYWORDS:

Aspiration pneumonia; Mortality risk; Oral cavity; Prospective cohort; Tongue microbiota

 

Does green tea consumption increase urinary oxalate excretion? Results of a prospective trial in healthy men.

Chen K, Chen D, Lan C, Liang X, Zeng T, Huang J, Duan X, Kong Z, Li S, Tiselius HG, Gurioli A, Lu X, Zeng G, Wu W.

Int Urol Nephrol. 2017 Oct 19. doi: 10.1007/s11255-017-1720-x. [Epub ahead of print]

PMID: 29052087

Abstract

OBJECTIVE:

To investigate the impact of green tea on urinary oxalate excretion in healthy male volunteers.

MATERIALS AND METHODS:

The oxalate concentrations after different brewing times (2-60 min) of different qualities (2-8 g) of green tea were measured in in vitro experiment. In in vivo experiment, the effects on urine composition were assessed in 12 healthy men with an age of 24-29 years. Each subject was requested to collect two 24-h urine samples under normal dietary conditions. Green tea prepared from tea bags containing 2 g of tea leafs was consumed by the subjects for 7 consecutive days, and 24-h urine samples were collected and analyzed on days 6 and 7. After 3-week washout interval, all subjects consumed green tea containing 4 g of leaf tea for another 7 consecutive days. Two 24-h urine samples were collected on the last 2 days. Urine volume, pH, calcium, magnesium, sodium, phosphate, potassium, chloride, citrate, oxalate, urate and creatinine were measured.

RESULTS:

In the in vitro experiments, oxalate in solution increased with brewing time (p < 0.05) and tea quality (p < 0.05). In the in vivo experiment, 24-h urinary oxalate increased significantly (0.24 ± 0.09 mmol to 0.32 ± 0.13 mmol, p = 0.045) when tea was prepared from 2-g bags of green leaf tea. Consumption of green tea containing 4 g of leaf tea resulted in 24-h urinary oxalate increase (0.25 ± 0.25 mmol to 0.34 ± 0.22 mmol, p = 0.041).

CONCLUSIONS:

In vitro studies showed that there was a gradual increase in solution concentrations of oxalate that was associated with increased brewing time and increased quality of green tea. Studies in normal men showed that green tea consumption was associated with increased urinary exertion of oxalate.

KEYWORDS:

24-h urine; Calcium oxalate; Green tea; Risk factors

 

Fish intake, genetic predisposition to alzheimer's disease and decline in global cognition and memory in five cohorts of older persons.

Samieri C, Morris MC, Bennett DA, Berr C, Amouyel P, Dartigues JF, Tzourio C, Chasman DI, Grodstein F.

Am J Epidemiol. 2017 Oct 19. doi: 10.1093/aje/kwx330. [Epub ahead of print]

PMID: 29053784

Abstract

Fish are a primary source of long-chain omega-3 fatty acids, which may help delay cognitive aging. We pooled participants from the French Three-City study and four US cohorts (Nurses' Health Study, Women's Health Study, Chicago Health and Aging Project and Rush Memory and Aging Project) with diet and cognitive data (n = 23,688 Caucasians aged ≥65 years, 88% female, baseline year range, 1992-1999, median follow-up range, 3.9-9.1 years) to investigate the relation of fish intake to cognitive decline and examine interactions with Alzheimer's disease-related genes. We estimated cohort-specific associations between fish and change in composite scores of global cognition and episodic memory using linear mixed models, and pooled results using inverse-variance weighted meta-analysis. In multivariate analyses, higher fish intake was associated with slower decline in both global cognition and memory (P-trend ≤ 0.031). Consuming ≥4 versus <1 fish serving/week was associated with 0.018 (95% CI: 0.004, 0.032) standard units lower rate of memory decline; an effect estimate equivalent to that found for 4 years of age. For global cognition, no comparisons of higher versus low fish intake reached statistical significance. In this meta-analysis, increasing fish intake was associated with decreasing memory decline. We found no evidence of effect modification by Alzheimer's disease genes.

KEYWORDS:

Alzheimer dementia; cognitive aging; gene-environment interaction; omega-3 fatty acids

 

Effect of Exceptional Parental Longevity and Lifestyle Factors on Prevalence of Cardiovascular Disease in Offspring.

Gubbi S, Schwartz E, Crandall J, Verghese J, Holtzer R, Atzmon G, Braunstein R, Barzilai N, Milman S.

Am J Cardiol. 2017 Sep 18. pii: S0002-9149(17)31460-1. doi: 10.1016/j.amjcard.2017.08.040. [Epub ahead of print]

PMID: 29050682

Abstract

Offspring of parents with exceptional longevity (OPEL) manifest lower prevalence of cardiovascular disease (CVD), but the role of lifestyle factors in this unique cohort is not known. Our study tested whether OPEL have lesser prevalence of CVD independent of lifestyle factors. Prevalence of CVD and CVD risk factors was assessed in a population of community-dwelling Ashkenazi Jewish adults aged 65 to 94 years. Participants included OPEL (n = 395), defined as having at least 1 parent living past the age of 95 years, and offspring of parents with usual survival (OPUS, n = 450), defined as having neither parent survive to 95 years. Medical and lifestyle information was obtained using standardized questionnaires. Socioeconomic status was defined based on validated classification scores. Dietary intake was evaluated with the Block Brief Food Frequency Questionnaire (2000) in a subgroup of the study population (n = 234). Our study found no significant differences in the prevalence of obesity, smoking, alcohol use, physical activity, social strata scores, and dietary intake between the 2 groups. After adjustment for age and gender, the OPEL demonstrated 29% lower odds of having hypertension (95% confidence interval [CI] 0.53 to 0.95), 65% lower odds of having had a stroke (95% CI 0.14 to 0.88), and 35% lower odds of having CVD (95% CI 0.43 to 0.98), compared with OPUS. In conclusion, exceptional parental longevity is associated with lower prevalence of CVD independent of lifestyle, socioeconomic status, and nutrition, thus highlighting the potential role of genetics in disease-free survival among individuals with exceptional parental longevity.

 

Pollution causing more deaths worldwide than war or smoking: Lancet

At least 9 million premature deaths were caused by diseases from toxic emissions

The Associated Press Posted: Oct 20, 2017

http://www.cbc.ca/news/health/pollution-worldwide-deaths-1.4363613

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The Lancet Commission on pollution and health

The Lancet Published: October 19, 2017

Executive Summary

For decades, pollution and its harmful effects on people’s health, the environment, and the planet have been neglected both by Governments and the international development agenda. Yet, pollution is the largest environmental cause of disease and death in the world today, responsible for an estimated 9 million premature deaths.

The Lancet Commission on pollution and health addresses the full health and economic costs of air, water, and soil pollution. Through analyses of existing and emerging data, the Commission reveals pollution’s severe and underreported contribution to the Global Burden of Disease. It uncovers the economic costs of pollution to low-income and middle-income countries. The Commission will inform key decision makers around the world about the burden that pollution places on health and economic development, and about available cost-effective pollution control solutions and strategies.

Philip J Landrigan, Richard Fuller, Nereus J R Acosta, Olusoji Adeyi, Robert Arnold, Niladri (Nil) Basu, Abdoulaye Bibi Baldé, Roberto Bertollini, Stephan Bose-O'Reilly, Jo Ivey Boufford, Patrick N Breysse, Thomas Chiles, Chulabhorn Mahidol, Awa M Coll-Seck, Maureen L Cropper, Julius Fobil, Valentin Fuster, Michael Greenstone, Andy Haines, David Hanrahan, David Hunter, Mukesh Khare, Alan Krupnick, Bruce Lanphear, Bindu Lohani, Keith Martin, Karen V Mathiasen, Maureen A McTeer, Christopher J L Murray, Johanita D Ndahimananjara, Frederica Perera, Janez Potočnik, Alexander S Preker, Jairam Ramesh, Johan Rockström, Carlos Salinas, Leona D Samson, Karti Sandilya, Peter D Sly, Kirk R Smith, Achim Steiner, Richard B Stewart, William A Suk, Onno C P van Schayck, Gautam N Yadama, Kandeh Yumkella, Ma Zhong

http://sci-hub.cc/10.1016/S0140-6736(17)32345-0

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Comments

Pollution, health, and the planet: time for decisive action

Pamela Das, Richard Horton

The Lancet Published: 19 October 2017 DOI: http://dx.doi.org/10.1016/S0140-6736(17)32588-6

http://sci-hub.cc/10.1016/S0140-6736(17)32588-6

Summary

For decades, pollution and its harmful effects on people's health, the environment, and the planet have been neglected both by governments and the international development community. Pollution is the largest environmental cause of disease and death in the world today, responsible for an estimated 9 million premature deaths in 2015.1 92% of all pollution-related mortality is seen in low-income and middle-income countries.1 A new Lancet Commission on pollution and health aims to confront and overturn this urgent predicament.

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Towards a healthier and safer environment

Maria Neira, Michaela Pfeiffer, Diarmid Campbell-Lendrum, Annette Prüss-Ustün

The Lancet

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Implications for the science of air pollution and health

H Ross Anderson

The Lancet Respiratory Medicine

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In control of ambient and household air pollution — how low should we go?

Stephen Gordon, Kevin Mortimer, Jonathan Grigg, John Balmes

The Lancet Respiratory Medicine

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Profile

Mathuros Ruchirawat: leading light in pollution control

Rachael Davies

The Lancet

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THE LANCET COMMISSIONS

Health and climate change: policy responses to protect public health

Nick Watts, W Neil Adger, Paolo Agnolucci, Jason Blackstock, Peter Byass, Wenjia Cai, Sarah Chaytor, Tim Colbourn, Mat Collins, Adam Cooper, Peter M Cox, Joanna Depledge, Paul Drummond, Paul Ekins, Victor Galaz, Delia Grace, Hilary Graham, Michael Grubb, Andy Haines, Ian Hamilton, Alasdair Hunter, Xujia Jiang, Moxuan Li, Ilan Kelman, Lu Liang, Melissa Lott, Robert Lowe, Yong Luo, Georgina Mace, Mark Maslin, Maria Nilsson, Tadj Oreszczyn, Steve Pye, Tara Quinn, My Svensdotter, Sergey Venevsky, Koko Warner, Bing Xu, Jun Yang, Yongyuan Yin, Chaoqing Yu, Qiang Zhang, Peng Gong, Hugh Montgomery, Anthony Costello

The Lancet, Vol. 386, No. 10006

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Levels of ambient air pollution according to mode of transport: a systematic review

Magda Cepeda, Josje Schoufour, Rosanne Freak-Poli, Chantal M Koolhaas, Klodian Dhana, Wichor M Bramer, Oscar H Franco

The Lancet Public Health, Vol. 2, No. 1

Open Access

http://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(16)30021-4/fulltext

Summary

Background

Controversy exists about the differences in air pollution exposure and inhalation dose between mode of transport. We aimed to review air pollution exposure and inhaled dose according to mode of transport and pollutant and their effect in terms of years of life expectancy (YLE).

Methods

In this systematic review, we searched ten online databases from inception to April 13, 2016, without language or temporal restrictions, for cohort, cross-sectional, and experimental studies that compared exposure to carbon monoxide, black carbon, nitrogen dioxide, and fine and coarse particles in active commuters (pedestrian or cyclist) and commuters using motorised transport (car, motorcycle, bus, or massive motorised transport [MMT—ie, train, subway, or metro]). We excluded studies that measured air pollution exposure exclusively with biomarkers or on the basis of simulated data, reviews, comments, consensuses, editorials, guidelines, in-vitro studies, meta-analyses, ecological studies, and protocols. We extracted average exposure and commuting time per mode of transport and pollutant to calculate inhaled doses. We calculated exposure and inhaled dose ratios using active commuters as the reference and summarised them with medians and IQRs. We also calculated differences in YLE due to fine particle inhaled dose and physical activity.

Findings

We identified 4037 studies, of which 39 were included in the systematic review. Overall, car commuters had higher exposure to all pollutants than did active commuters in 30 (71%) of 42 comparisons (median ratio 1·22 [iQR 0·90–1·76]), followed by those who commuted by bus in 57 (52%) of 109 (1·0 [0·79–1·41]), by motorcycle in 16 (50%) of 32 (0·99 [0·86–1·38]), by a car with controlled ventilation settings in 39 (45%) of 86 (0·95 [0·66–1·54]), and by MMT in 21 (38%) of 55 (0·67 [0·49–1·13]). Overall, active commuters had higher inhalation doses than did commuters using motorised transport (median ratio car with controlled ventilation settings 0·16 [0·10–0·28]; car 0·22 [0·15–0·30]; motorcycle 0·38 [0·26–0·78]; MMT 0·49 [0·34–0·81]; bus 0·72 [iQR 0·50–0·99]). Commuters using motorised transport lost up to 1 year in YLE more than did cyclists.

Interpretation

Proximity to traffic and high air interchange increased the exposure to air pollution of commuters using motorised transport. Larger inhalation rates and commuting time increased inhaled dose among active commuters. Benefits of active commuting from physical activity are larger than the risk from an increased inhaled dose of fine particles.

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COMMENT

Air pollution and health

Philip J Landrigan

The Lancet Public Health, Vol. 2, No. 1

Open Access

http://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(16)30023-8/fulltext

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