Al's papers' citations and possibly links and excerpts or my synopses

[AlPater]

Daily red wine vinegar ingestion for eight weeks improves glucose homeostasis and affects the metabolome but does not reduce adiposity in adults.
Jasbi P, Baker O, Shi X, Gonzalez LA, Wang S, Anderson S, Xi B, Gu H, Johnston CS.
Food Funct. 2019 Oct 24. doi: 10.1039/c9fo01082c. [Epub ahead of print]
PMID: 31647087
Abstract
Some studies have reported that vinegar ingestion at mealtime attenuates postprandial glycemia in healthy adults and individuals with type 2 diabetes. Emerging data suggest that chronic vinegar ingestion impacts fat metabolism and reduces adiposity, although no study has yet corroborated the events of vinegar supplementation metabolically through a metabolomics approach. To examine the impact of daily vinegar ingestion on glucose homeostasis, adiposity, and the metabolome, an 8-week, randomized controlled trial design was implemented utilizing two parallel treatment arms: daily red wine vinegar ingestion and a control treatment. Participants were 45 healthy adults at increased risk for metabolic complications as determined by high waist circumferences. Measurements and blood samples were collected pre- and post-intervention. Central adiposity and visceral fat were assessed by waist circumference and dual-energy X-ray absorptiometry, respectively. Plasma metabolites were analyzed using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS/MS. Analysis showed significant reductions in fasting glucose (p = 0.003) and insulin (p < 0.001). Insulin resistance was reduced 8.3% in the red wine vinegar group and increased 9.7% in the control group (p < 0.001). No significant between-group differences in body mass index, body weight, waist circumference, or visceral fat were observed. Significant differences were observed in amino valerate and indole-3-acetic acid (p < 0.05), with high magnitudes of fold change (>2) between groups. Metabolic pathway analysis revealed significant alterations in tryptophan metabolism. Although daily red wine vinegar ingestion for 8 weeks induced significant improvements in glucose homeostasis, our results indicate that daily red wine vinegar ingestion for 8 weeks is not associated with reductions in adiposity. This is the first study to investigate the effects of daily red wine vinegar supplementation using a metabolomics approach. Our results provide strong rationales for larger prospective studies to further clarify associations among obesity, chronic diseases, and functional foods such as vinegar using metabolomics.

The effect of Curcumin/Turmeric on blood pressure modulation: A systematic review and meta-analysis.
Hadi A, Pourmasoumi M, Ghaedi E, Sahebkar A.
Pharmacol Res. 2019 Oct 21:104505. doi: 10.1016/j.phrs.2019.104505. [Epub ahead of print] Review.
PMID: 31647981
Abstract
BACKGROUND AND AIM:
Hypertension is a chronic condition that can lead to several health problems, such as cardiovascular diseases, myocardial infarction, stroke, retinopathy and renal failure. In the present study, a systematic review and meta-analysis was undertaken with the main aim of estimating the quantitative effect of curcumin/turmeric supplementation on blood pressure (BP).
METHODS:
A systematic search was undertaken in Medline, Embase, Scopus, ISI Web of Science, Google Scholar and Cochrane library up to May 2019 to identify randomized clinical trials assessing the effect of curcumin/turmeric on systolic BP (SBP) and diastolic BP (DBP). A random-effects model was used to analyze the impact of combined trials. Cochrane Risk of Bias Tool was applied to assess potential risks of bias.
RESULTS:
A total of 11 studies comprising 734 participants were eligible and included in the meta-analysis to estimate pooled effect size. Results of the meta-analysis did not indicate any significant effect of curcumin/turmeric on SBP (-0.69 mmHg; 95% CI: -2.01, 0.64; I2 = 18%) and DBP (0.28 mmHg; 95% CI: -1.12, 1.68; I2 = 53%). However, subgroup analysis revealed a significant reduction only in SBP levels (-1.24 mmHg; 95% CI: -2.26, -0.22; I2 = 0%) but not DBP (0.29 mmHg; 95% CI: -0.65, 1.22; I2 = 1%) in studies with ≥12-week supplementation. No favorable effect of curcumin administration on SBP or DBP levels was found after stratification according to either participant's condition or type of intervention (turmeric, crude curcumin and high-absorption curcumin).
CONCLUSION:
The present meta-analysis suggests that consuming curcumin/turmeric may improve SBP when administered in long durations. However, more studies are needed to confirm these results.
KEYWORDS:
Blood pressure; Curcumin; Hypertension; Meta-analysis; Turmeric

Association of Dietary Fiber and Yogurt Consumption With Lung Cancer Risk: A Pooled Analysis.
Yang JJ, Yu D, Xiang YB, Blot W, White E, Robien K, Sinha R, Park Y, Takata Y, Lazovich D, Gao YT, Zhang X, Lan Q, Bueno-de-Mesquita B, Johansson I, Tumino R, Riboli E, Tjønneland A, Skeie G, Quirós JR, Johansson M, Smith-Warner SA, Zheng W, Shu XO.
JAMA Oncol. 2019 Oct 24. doi: 10.1001/jamaoncol.2019.4107. [Epub ahead of print]
PMID: 31647500
Abstract
IMPORTANCE:
Dietary fiber (the main source of prebiotics) and yogurt (a probiotic food) confer various health benefits via modulating the gut microbiota and metabolic pathways. However, their associations with lung cancer risk have not been well investigated.
OBJECTIVE:
To evaluate the individual and joint associations of dietary fiber and yogurt consumption with lung cancer risk and to assess the potential effect modification of the associations by lifestyle and other dietary factors.
DESIGN, SETTING, AND PARTICIPANTS:
This pooled analysis included 10 prospective cohorts involving 1 445 850 adults from studies that were conducted in the United States, Europe, and Asia. Data analyses were performed between November 2017 and February 2019. Using harmonized individual participant data, hazard ratios and 95% confidence intervals for lung cancer risk associated with dietary fiber and yogurt intakes were estimated for each cohort by Cox regression and pooled using random-effects meta-analysis. Participants who had a history of cancer at enrollment or developed any cancer, died, or were lost to follow-up within 2 years after enrollment were excluded.
EXPOSURES:
Dietary fiber intake and yogurt consumption measured by validated instruments.
MAIN OUTCOMES AND MEASURES:
Incident lung cancer, subclassified by histologic type (eg, adenocarcinoma, squamous cell carcinoma, and small cell carcinoma).
RESULTS:
The analytic sample included 627 988 men, with a mean (SD) age of 57.9 (9.0) years, and 817 862 women, with a mean (SD) age of 54.8 (9.7) years. During a median follow-up of 8.6 years, 18 822 incident lung cancer cases were documented. Both fiber and yogurt intakes were inversely associated with lung cancer risk after adjustment for status and pack-years of smoking and other lung cancer risk factors: hazard ratio, 0.83 (95% CI, 0.76-0.91) for the highest vs lowest quintile of fiber intake; and hazard ratio, 0.81 (95% CI, 0.76-0.87) for high vs no yogurt consumption. The fiber or yogurt associations with lung cancer were significant in never smokers and were consistently observed across sex, race/ethnicity, and tumor histologic type. When considered jointly, high yogurt consumption with the highest quintile of fiber intake showed more than 30% reduced risk of lung cancer than nonyogurt consumption with the lowest quintile of fiber intake (hazard ratio, 0.67 [95% CI, 0.61-0.73] in total study populations; hazard ratio 0.69 [95% CI, 0.54-0.89] in never smokers), suggesting potential synergism.
CONCLUSIONS AND RELEVANCE:
Dietary fiber and yogurt consumption was associated with reduced risk of lung cancer after adjusting for known risk factors and among never smokers. Our findings su

[AlPater]

Impact of follow-up time and analytical approaches to account for reverse causality on the association between physical activity and health outcomes in UK Biobank.
Strain T, Wijndaele K, Sharp SJ, Dempsey PC, Wareham N, Brage S.
Int J Epidemiol. 2019 Oct 25. pii: dyz212. doi: 10.1093/ije/dyz212. [Epub ahead of print]
PMID: 31651957
Abstract
BACKGROUND:
The advent of very large cohort studies (n > 500 000) has given rise to prospective analyses of health outcomes being undertaken after short (<4 years) follow-up periods. However, these studies are potentially at risk of reverse causality bias. We investigated differences in the associations between self-reported physical activity and all-cause and cardiovascular disease (CVD) mortality, and incident CVD, using different follow-up time cut-offs and methods to account for reverse causality bias.
METHODS:
Data were from n = 452 933 UK Biobank participants, aged 38-73 years at baseline. Median available follow-up time was 7 years (for all-cause and CVD mortality) and 6.1 years (for incident CVD). We additionally analysed associations at 1-, 2- and 4-year cut-offs after baseline. We fit up to four models: (1) adjusting for prevalent CVD and cancer, (2) excluding prevalent disease, (3) and (4) Model 2 excluding incident cases in the first 12 and 24 months, respectively.
RESULTS:
The strength of associations decreased as follow-up time cut-off increased. For all-cause mortality, Model 1 hazard ratios were 0.73 (0.69-0.78) after 1 year and 0.86 (0.84-0.87) after 7 years. Associations were weaker with increasing control for possible reverse causality. After 7-years follow-up, the hazard ratios were 0.86 (0.84-0.87) and 0.88 (0.86-0.90) for Models 1 and 4, respectively. Associations with CVD outcomes followed similar trends.
CONCLUSIONS:
As analyses with longer follow-up times and increased control for reverse causality showed weaker associations, there are implications for the decision about when to analyse a cohort study with ongoing data collection, the interpretation of study results and their contribution to meta-analyses.
KEYWORDS:
Exercise; bias; epidemiologic methods; follow-up studies; physical activity; prospective studies

Changes in nutrient and calorie intake, adipose mass, triglycerides and TNF-α concentrations after non-caloric sweetener intake: pilot study.
Sánchez-Delgado M, Estrada JA, Paredes-Cervantes V, Kaufer-Horwitz M, Contreras I.
Int J Vitam Nutr Res. 2019 Oct 28:1-12. doi: 10.1024/0300-9831/a000611. [Epub ahead of print]
PMID: 31656130
Abstract
Establishing the safety of non-caloric sweetener consumption in humans is a difficult task, since many contradictory results have been reported. The objective of this study was to compare the effect of frequent intake of sucrose, sucralose or steviol glycosides, on selected anthropometric, biochemical and immunological parameters in healthy, young adults. 38 individuals with normal body mass index were recruited and randomly divided into three experimental groups. After a washout week (where food with added sweeteners was restricted), each group was supplemented with sucrose (8 × 5 g packets/day), sucralose or steviol glycosides (4 × 1 g packets/day each) for 6 weeks. Selected variables were measured before and after treatment in each group and differences within and among groups were assessed. Our results showed that, compared to baseline, there was a modest but significant increase in weight (p = 0.0293) in the sucralose group, while the steviol glycosides group reduced their fat mass (p = 0.0390). No differences were observed in glycaemia; however, there was a significant increase in serum triglycerides (77.8-110.8 mg/dL) and cholesterol (162.0-172.3 mg/dL) in the sucrose group, whereas the steviol glycosides group presented lower triglycerides (104.7-92.8 mg/dL) and TNF-α concentrations (51.1-47.5 pg/mL). Comparison among groups showed differences in serum triglycerides (p = 0.0226), TNF-α (p = 0.0460) and IL-β (p = 0.0008). Our results suggest that, even in a short time span, frequent intake of steviol glycosides may have positive effects on metabolic parameters that may be relevant for human health.
KEYWORDS:
Non-caloric sweeteners; biochemical parameters; body mass index; cytokines; weight

Dietary tryptophan links encephalogenicity of autoreactive T cells with gut microbial ecology.
Sonner JK, Keil M, Falk-Paulsen M, Mishra N, Rehman A, Kramer M, Deumelandt K, Röwe J, Sanghvi K, Wolf L, von Landenberg A, Wolff H, Bharti R, Oezen I, Lanz TV, Wanke F, Tang Y, Brandao I, Mohapatra SR, Epping L, Grill A, Röth R, Niesler B, Meuth SG, Opitz CA, Okun JG, Reinhardt C, Kurschus FC, Wick W, Bode HB, Rosenstiel P, Platten M.
Nat Commun. 2019 Oct 25;10(1):4877. doi: 10.1038/s41467-019-12776-4.
PMID: 31653831
https://www.nature.com/articles/s41467-019-12776-4.pdf
Abstract
The interaction between the mammalian host and its resident gut microbiota is known to license adaptive immune responses. Nutritional constituents strongly influence composition and functional properties of the intestinal microbial communities. Here, we report that omission of a single essential amino acid - tryptophan - from the diet abrogates CNS autoimmunity in a mouse model of multiple sclerosis. Dietary tryptophan restriction results in impaired encephalitogenic T cell responses and is accompanied by a mild intestinal inflammatory response and a profound phenotypic shift of gut microbiota. Protective effects of dietary tryptophan restriction are abrogated in germ-free mice, but are independent of canonical host sensors of intracellular tryptophan metabolites. We conclude that dietary tryptophan restriction alters metabolic properties of gut microbiota, which in turn have an impact on encephalitogenic T cell responses. This link between gut microbiota, dietary tryptophan and adaptive immunity may help to develop therapeutic strategies for protection from autoimmune neuroinflammation.

Changes in waist circumference and risk of all-cause and CVD mortality: results from the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort study.
Mulligan AA, Lentjes MAH, Luben RN, Wareham NJ, Khaw KT.
BMC Cardiovasc Disord. 2019 Oct 28;19(1):238. doi: 10.1186/s12872-019-1223-z.
PMID: 31660867
https://bmccardiovascdisord.biomedcentral.com/track/pdf/10.1186/s12872-019-1223-z
Abstract
BACKGROUND:
Measures of abdominal adiposity are strongly associated with all-cause mortality and cardiovascular disease (CVD). However, data are limited and conflicting regarding the consequences of changes in body fat distribution. The main aims of this paper are to investigate the association between changes in waist circumference (WC) and all-cause and CVD mortality and to examine these changes in relation to concurrent changes in weight.
METHODS:
The European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study recruited 25,639 participants between 1993 and 1997, aged 39-79, a number of whom also attended a second examination (1998-2000), and were followed up to 2016 for mortality. Participants were eligible for inclusion if they had WC, weight and height measurements at both time-points; those with a self-reported history of CVD or cancer, body mass index < 18.5 kg/m2 or missing data on covariates were excluded, leaving 12,337 participants for analyses. The median (IQR) follow-up time was 16.4 (15.7, 17.2) years. Hazard Ratios (HRs) for all-cause (2866 deaths) and CVD mortality (822 deaths), by categories of WC change, were determined using Cox proportional hazards analyses.
RESULTS:
After multivariable adjustment, the HRs (95% CIs) for all-cause mortality for men and women with a WC gain (WCG) >  5 cm were 1.51 (1.29-1.75) and 1.25 (1.06-1.46) respectively. For CVD mortality in men and women with a WCG >  5 cm, the HRs were 1.84 (1.39-2.43) and 1.15 (0.85-1.55) respectively. In analyses of concurrent changes in WC and weight, the greatest risk (HRs) (95% CIs) in men occurred with weight loss and WCG: 1.80 (1.13-2.86) for all-cause and 2.22 (1.03-4.82) for CVD mortality. In women, the greatest risk for both all-cause (HR 1.50 (1.16-1.95)) and CVD mortality (HR 1.81 (1.15-2.85)) was observed in those with weight loss and maintenance of WC (WCM).
CONCLUSIONS:
Objectively measured WCG > 5 cm, was associated with subsequent higher total mortality risk and higher CVD mortality risk in men. Interventions focusing on preventing increase in central adiposity rather than lowering weight per se in later life may potentially have greater health benefits.
KEYWORDS:
All-cause mortality; CVD mortality; EPIC-Norfolk; Waist circumference change; Weight change

Effect of nutritional supplement based on melatonin on the intraocular pressure in normotensive subjects.
Carracedo-Rodríguez G, Martínez-Águila A, Rodriguez-Pomar C, Bodas-Romero J, Sanchez-Naves J, Pintor J.
Int Ophthalmol. 2019 Oct 24. doi: 10.1007/s10792-019-01199-1. [Epub ahead of print]
PMID: 31650354
Abstract
PURPOSE:
To evaluate the effect of a new nutritional supplement based on melatonin on the intraocular pressure (IOP) in normotensive subjects.
PATIENTS AND METHODS:
A short-term prospective study was designed. Sixty-seven normotensive subjects were recruited. Patients were divided into two groups. The daily group (DG) (n = 18) was instructed to take the supplement between 22:00 and 23:00 (before sleeping) for 3 consecutive days. IOP was measured from 10.00 to 11.00 am the day before treatment and during the 3 days of experiment. The acute group (AG) (n = 49) was instructed to take the supplement after the second measure (11.00) of the second day. IOP was measured 1 h and just before the intake of the supplement and 1 and 2 h after. All measurements in this group were taken 1 day before without any supplement (control) and the day of experiment.
RESULTS:
The DG group showed a significant decrease in IOP after supplement intake in all days of experiment, from 14.9 ± 3.4 mm Hg to 13.8 ± 2.9 mm Hg after 3 days of experiment (p value < 0.001). For AG, IOP did not change during the control day; however, a reduction of 1 mm Hg was found 2 and 3 h after supplement intake, from 15.7 ± 2.5 mm Hg to 14.7 ± 2.5 mm Hg and 15.1 ± 2.7 mm Hg, respectively, being statistically significant (p value < 0.001).
CONCLUSION:
The supplement based on melatonin was able to reduce the IOP in normotensive subjects after 2 h of intake. Moreover, the daily intake showed a reduction in IOP during the 3 days of experiment.
KEYWORDS:
Coadjuvant treatments; Intraocular pressure; Melatonin; Supplements

Helicobacter pylori Infection and the Development of Advanced Colorectal Neoplasia.
Ryoo SK, Kim TJ, Kim ER, Hong SN, Kim YH, Chang DK.
J Clin Gastroenterol. 2019 Oct 22. doi: 10.1097/MCG.0000000000001273. [Epub ahead of print]
PMID: 31651570
Abstract
BACKGROUND:
An association between Helicobacter pylori infection and colorectal neoplasia has been reported in cross-sectional studies.
GOALS:
We examined the association between H. pylori infection and the development of advanced colorectal neoplasia (AN) in a screening cohort.
STUDY:
We identified 3753 adults, who underwent screening and subsequent surveillance colonoscopies. The primary outcome was the development of metachronous AN, as confirmed by surveillance colonoscopy. H. pylori infection status was assessed by an H. pylori-specific immunoglobulin G antibody test. Sensitivity analysis was also performed by H. pylori infection status on the basis of histology.
RESULTS:
During a median follow-up of 41 months, the incidence of AN was 3.2% and 1.7% in participants with and without H. pylori infection, respectively. In multivariable analysis adjusted for age, body mass index, smoking status, alcohol intake, family history of colorectal cancer, and baseline adenoma characteristics, the hazard ratio [95% confidence interval (CI)] for metachronous AN was 1.74 (1.11-2.73) in participants with H. pylori seropositivity, compared with those without H. pylori seropositivity. The association was consistent with H. pylori infection status on the basis of histology (adjusted hazard ratio, 3.51; 95% CI, 1.64-7.51). In the subgroup analysis, the positive association was observed in both no-adenoma and adenoma removal subgroups.
CONCLUSIONS:
In a cohort study, H. pylori infection was associated with an increased risk of AN development. This association was consistent in both the serological and histologic assessment of H. pylori infection. Prospective studies are necessary to determine whether H. pylori eradication can reduce the risk of colorectal neoplasia.

Association of Metabolically Healthy Overweight Phenotype With Abnormalities of Glucose Levels and Blood Pressure Among Chinese Adults.
Xu R, Gao X, Wan Y, Fan Z.
JAMA Netw Open. 2019 Oct 2;2(10):e1914025. doi: 10.1001/jamanetworkopen.2019.14025.
PMID: 31651967
Abstract
IMPORTANCE:
Whether the metabolically healthy overweight (MHO) phenotype is resistant to metabolic abnormalities remains unknown.
OBJECTIVE:
To evaluate the association of MHO with glucose level abnormalities and high blood pressure (BP) in Chinese adults.
DESIGN, SETTING, AND PARTICIPANTS:
This prospective cohort study was conducted from January 1, 2013, to October 31, 2018, in the Health Management Center at Ren Ji Hospital, Shanghai, China, using data from 55 155 recruited Chinese adults. Body weight, fasting blood glucose (FBG) level, hemoglobin A1c (HbA1c) level, and BP were measured annually.
EXPOSURES:
Metabolically healthy overweight was defined as a body mass index (calculated as weight in kilograms divided by height in meters squared) of 24.0 in 2013 (baseline) and 2014, no history of metabolic diseases, and normal FBG level, HbA1c level, BP, lipid profile, serum uric acid level, and liver ultrasonographic findings at baseline; the remaining participants were defined as being metabolically healthy normal.
MAIN OUTCOMES AND MEASURES:
Glucose level abnormality was confirmed if the FBG level was 101 mg/dL or greater or the HbA1c level was 5.7%, and high BP was confirmed if the systolic BP was 130 mm Hg or higher or the diastolic BP was 80 mm Hg or higher at least twice during the subsequent 4 years of follow-up.
RESULTS:
A total of 3204 metabolically healthy Chinese adults (mean [SD] age, 39.8 [10.9] years; 1940 women [60.5%]) were included in the study. The prevalence of MHO was 7.0%. A total of 146 incident cases of glucose level abnormality and 220 cases of high BP during 4 years of follow-up were identified. Compared with the metabolically healthy normal group, the MHO group had a higher risk of glucose level abnormality (adjusted hazard ratio, 2.36; 95% CI, 1.52-3.64) and high BP (adjusted hazard ratio, 1.73; 95% CI, 1.18-2.53) after adjusting for several potential confounders.
CONCLUSIONS AND RELEVANCE:
Metabolically healthy overweight may be associated with a high future risk of glucose abnormality and high BP in Chinese adults. If the individuals are confirmed with MHO, early interventions, including diet and exercise, should be recommended to decrease the risk of developing abnormalities of glucose and BP.

Predicted Basal Metabolic Rate and Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (Epic).
Kliemann N, Murphy N, Viallon V, Freisling H, Tsilidis KK, Rinaldi S, Mancini FR, Fagherazzi G, Boutron-Ruault MC, Boeing H, Schulze MB, Masala G, Krogh V, Sacerdote C, Santucci de Magistris M, Bueno-de-Mesquita B, Weiderpass E, Kühn T, Kaaks R, Jakszyn P, Redondo-Sánchez D, Amiano P, Chirlaque MD, Barricarte Gurrea A, Ericson U, Drake I, Nøst TH, Aune D, May AM, Tjønneland A, Dahm CC, Overvad K, Tumino R, Ramón Quirós J, Trichopoulou A, Karakatsani A, La Vecchia C, Nilsson LM, Riboli E, Huybrechts I, Gunter MJ.
Int J Cancer. 2019 Oct 25. doi: 10.1002/ijc.32753. [Epub ahead of print]
PMID: 31652358
Abstract
Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of estimated BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition. Estimated BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (Hazard Ratio per 1-standard deviation change in BMR [HR1-sd ]: 2.46; 95%CI 1.20; 5.03), and distal colon cancer (HR1-sd : 1.33; 95%CI 1.001; 1.77) among men, and with proximal colon (HR1-sd : 1.16; 95%CI 1.01; 1.35), pancreatic (HR1-sd : 1.37; 95%CI 1.13; 1.66), thyroid (HR1-sd : 1.65; 95%CI 1.33; 2.05), postmenopausal breast (HR1-sd : 1.17; 95%CI 1.11; 1.22), and endometrial (HR1-sd : 1.20; 95%CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness.
KEYWORDS:
Basal metabolic rate; cancer; metabolic disorder; obesity

[AlPater]

The role of Ames dwarfism and calorie restriction on gut microbiota.
Wiesenborn DS, Gálvez EJC, Spinel L, Victoria B, Allen B, Schneider A, Gesing A, Al-Regaiey KA, Strowig T, Schäfer KH, Masternak MM.
J Gerontol A Biol Sci Med Sci. 2019 Oct 30. pii: glz236. doi: 10.1093/gerona/glz236. [Epub ahead of print]
PMID: 31665244
Abstract
The gut microbiome (GM) represents a large and very complex ecosystem of different microorganisms. There is an extensive interest in the potential role of the GM in different diseases including cancer, diabetes, cardiovascular diseases, and aging. The GM changes over the lifespan and is strongly associated with various age-related diseases. Ames dwarf (df/df) mice are characterized by an extended life- and healthspan, and although these mice are protected from many age-related diseases, their microbiome has not been studied. To determine the role of microbiota on longevity animal models, we investigated the changes in the GM of df/df and Normal control (N) mice, by comparing parents before mating and littermate mice at three distinct time points during early life. Furthermore, we studied the effects of a 6-month calorie restriction (CR), the most powerful intervention extending the lifespan. Our data revealed significant changes of the GM composition during early life development, and we detected differences in the abundance of some bacteria between df/df and N mice, already in early life. Overall, the variability of the microbiota by genotype, time-point and breeding pair showed significant differences. In addition, CR caused significant changes in microbiome according to gastrointestinal (GI) location (distal colon, ileum and cecum), genotype and diet. However, the overall impact of the genotype was more prominent than that of the CR. In conclusion, our findings suggest that the gut microbiota plays an important role during post-natal development in long-living df/df mice and CR dietary regimen can significantly modulate the GM.

[AlPater]

White cell counts in relation to mortality in a general population of cohort study in the Netherlands: a mediating effect or not?
Abete I, Lu Y, Lassale C, Verschuren M, van der Schouw Y, Bueno-de-Mesquita B.
BMJ Open. 2019 Oct 30;9(10):e030949. doi: 10.1136/bmjopen-2019-030949.
PMID: 31666267
https://bmjopen.bmj.com/content/bmjopen/9/10/e030949.full.pdf
Abstract
BACKGROUND:
White cell count (WCC) is a clinical marker of inflammation. Data are limited regarding the association of total and differential WCC with risk of mortality, and its role related with smoking and body mass index (BMI).
METHODS:
A total of 14 433 participants (4150 men; 10 283 women; average age 47.3±11.8 years) from the Dutch European Prospective Investigation into Cancer and Nutrition-Netherlands cohort were included. The associations between prediagnostic total WCC and its subtypes and risk of all-cause, cancer and cardiovascular disease (CVD) mortality were assessed. The role of WCC related with smoking and BMI on mortality was further explored. Multivariate Cox regression models were performed to estimate the HR and 95% CI.
RESULTS:
After an average follow-up of 15.8 years, a total of 936 death cases were identified (466 cancer; 179 CVD; 291 other causes). Statistically significant graded associations between total WCC, and counts of lymphocytes, monocytes, neutrophils and eosinophils and risk of total mortality were observed. These associations were more apparent in current smokers. Strong associations for all-cause mortality or cancer mortality were observed in subjects with BMI ≥25 kg/m2, ever smoking and elevated WCC (HR 3.92, 95% CI 2.76 to 5.57; HR 3.93, 95% CI 2.30 to 6.72). WCC partly mediated the associations between smoking or BMI and all-cause mortality.
CONCLUSIONS:
Prediagnostic WCC and its subtypes are associated with all-cause, cancer and CVD mortality risk. It may play a partially mediate role on the association between smoking or obesity and mortality.
KEYWORDS:
mediation; mortality; obesity; smoking; white cell count

Effects of Intake of Apples, Pears, or Their Products on Cardiometabolic Risk Factors and Clinical Outcomes: A Systematic Review and Meta-Analysis.
Gayer BA, Avendano EE, Edelson E, Nirmala N, Johnson EJ, Raman G.
Curr Dev Nutr. 2019 Oct 3;3(10):nzz109. doi: 10.1093/cdn/nzz109. eCollection 2019 Oct. Review.
PMID: 31667463
Abstract
Apples and pears contain nutrients that have been linked to cardiovascular health. We conducted a systematic review and meta-analysis to summarize related research. Medline, Cochrane Central, and Commonwealth Agricultural Bureau databases were searched for publications on apple or pear intake and cardiovascular disease (CVD)/ cardiometabolic disease (CMD). Studies in adults (healthy or at risk for CVD) that quantified apple or pear intake were included. Random-effects models meta-analysis was used when ≥3 studies reported the same outcome. In total, 22 studies were eligible including 7 randomized controlled trial, 1 nonrandomized trial, and 14 prospective observational studies. In RCTs, apple intake significantly decreased BMI, but made no difference in body weight, serum lipids, blood glucose, or blood pressure. In observational studies, apple or pear intake significantly decreased risk of cerebrovascular disease, cardiovascular death, type 2 diabetes mellitus, and all-cause mortality. No association was reported for cerebral infarction or intracerebral hemorrhage. In conclusion, apple or pear intake significantly decreased BMI and risk for CVD outcomes.
KEYWORDS:
BMI; apples; cardiovascular disease; cerebrovascular disease; pears; type-2 diabetes mellitus

Extension of Drosophila lifespan by Korean red ginseng through a mechanism dependent on dSir2 and insulin/IGF-1 signaling.
Lee SH, Lee HY, Yu M, Yeom E, Lee JH, Yoon A, Lee KS, Min KJ.
Aging (Albany NY). 2019 Oct 31;11. doi: 10.18632/aging.102387. [Epub ahead of print]
PMID: 31672931
Abstract
Many studies have indicated that Korean red ginseng (KRG) has anti-inflammatory and anti-oxidative effects, thereby inducing many health benefits in humans. Studies into the longevity effects of KRG are limited and have provided contradictory results, and the molecular mechanism of lifespan extension by KRG is not elucidated yet. Herein, the longevity effect of KRG was investigated in Drosophila melanogaster by feeding KRG extracts, and the molecular mechanism of lifespan extension was elucidated by using longevity-related mutant flies. KRG extended the lifespan of Drosophila when administrated at 10 and 25 μg/mL, and the longevity benefit of KRG was not due to reduced feeding, reproduction, and/or climbing ability in fruit flies, indicating that the longevity benefit of KRG is a direct effect of KRG, not of a secondary artifact. Diet supplementation with KRG increased the lifespan of flies on a full-fed diet but not of those on a restricted diet, and the longevity effect of KRG was diminished by the mutation of dSir2, a deacetylase known to mediate the benefits of dietary restriction. Similarly, the longevity effect of KRG was mediated by the reduction of insulin/IGF-1 signaling. In conclusion, KRG extends the lifespan of Drosophila through Sir2 and insulin/IGF-1 signaling and has potential as an anti-aging dietary-restriction mimetic and prolongevity supplement.
KEYWORDS:
Drosophila melanogaster; Sir2; insulin/IGF-1 signaling; korean red ginseng; lifespan

Estimating the effect of calorie menu labeling on calories purchased in a large restaurant franchise in the southern United States: quasi-experimental study.
Petimar J, Zhang F, Cleveland LP, Simon D, Gortmaker SL, Polacsek M, Bleich SN, Rimm EB, Roberto CA, Block JP.
BMJ. 2019 Oct 30;367:l5837. doi: 10.1136/bmj.l5837.
PMID: 31666218 Free Article
Abstract
OBJECTIVE:
To evaluate whether calorie labeling of menus in large restaurant chains was associated with a change in mean calories purchased per transaction.
DESIGN:
Quasi-experimental longitudinal study.
SETTING:
Large franchise of a national fast food company with three different restaurant chains located in the southern United States (Louisiana, Texas, and Mississippi) from April 2015 until April 2018.
PARTICIPANTS:
104 restaurants with calorie information added to in-store and drive-thru menus in April 2017 and with weekly aggregated sales data during the pre-labeling (April 2015 to April 2017) and post-labeling (April 2017 to April 2018) implementation period.
MAIN OUTCOME MEASURES:
Primary outcome was the overall level and trend changes in mean purchased calories per transaction after implementation of calorie labeling compared with the counterfactual (ie, assumption that the pre-intervention trend would have persisted had the intervention not occurred) using interrupted time series analyses with linear mixed models. Secondary outcomes were by item category (entrees, sides, and sugar sweetened beverages). Subgroup analyses estimated the effect of calorie labeling in stratums defined by the sociodemographic characteristics of restaurant census tracts (defined region for taking census).
RESULTS:
The analytic sample comprised 14 352 restaurant weeks. Over three years and among 104 restaurants, 49 062 440 transactions took place and 242 726 953 items were purchased. After labeling implementation, a level decrease was observed of 60 calories/transaction (95% confidence interval 48 to 72; about 4%), followed by an increasing trend of 0.71 calories/transaction/week (95% confidence interval 0.51 to 0.92) independent of the baseline trend over the year after implementation. These results were generally robust to different analytic assumptions in sensitivity analyses. The level decrease and post-implementation trend change were stronger for sides than for entrees or sugar sweetened beverages. The level decrease was similar between census tracts with higher and lower median income, but the post-implementation trend in calories per transaction was higher in low income (change in calories/transaction/week 0.94, 95% confidence interval 0.67 to 1.21) than in high income census tracts (0.50, 0.19 to 0.81).
CONCLUSIONS:
A small decrease in mean calories purchased per transaction was observed after implementation of calorie labeling in a large franchise of fast food restaurants. This reduction diminished over one year of follow-up.

High soy isoflavone or soy-based food intake during infancy and in adulthood is associated with an increased risk of uterine fibroids in premenopausal women: a meta-analysis.
Qin H, Lin Z, Vásquez E, Luan X, Guo F, Xu L.
Nutr Res. 2019 Jun 8. pii: S0271-5317(18)31433-7. doi: 10.1016/j.nutres.2019.06.002. [Epub ahead of print] Review.
PMID: 31668644
Abstract
Numerous studies have examined the association of soy isoflavones or soy-based food intake with the risk of uterine fibroids (UF), but the results are inconsistent. The purpose of this meta-analysis was to quantitatively assess whether high soy isoflavones intake is associated with an increased risk of UF. PUBMED and EMBASE databases were reviewed to screen for relevant published studies up to December 2018. Using key words of uterine fibroid and isoflavone, we identified 4 studies focusing on infancy intake and 7 studies evaluating intake during adulthood. The pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated using a random-effect model. In addition, subgroup analyses and 2-stage random-effect dose-response were also performed. When comparing high vs low intake of soy isoflavones, we found that there were positive associations of UF among patients being fed soy formula during infancy (OR, 1.19; 95% CI, 0.99-1.43; P = .06) and with high consumption of soy-based foods in adulthood (OR, 2.50; 95% CI, 1.09-5.74; P = .03), respectively. Additionally, dose-response analysis showed the pooled ORs (95% CIs) of UF risk for low, moderate, and high intake of soy isoflavones were 1.00 (0.87-1.14), 1.08 (0.94-1.24), and 1.23 (0.99-1.53) when compared to occasional intake, respectively. Our findings suggest that high soy isoflavones or soy-based food intake during infancy and in adulthood is associated with an increased risk of uterine fibroids in premenopausal women. There is a need for large-scale prospective cohort studies using more accurate measurements of soy isoflavones to further ascertain our study findings.
KEYWORDS:
Leiomyomas; Meta-analysis; Premenopausal women; Soy isoflavone; Uterine fibroid

[AlPater]

Current level of fish and omega-3 fatty acid intakes and risk of Type 2 diabetes in China.
Zhang Y, Zhuang P, Mao L, Chen X, Wang J, Cheng L, Ding G, Jiao J.
J Nutr Biochem. 2019 Oct 15;74:108249. doi: 10.1016/j.jnutbio.2019.108249. [Epub ahead of print]
PMID: 31683102
Abstract
Whether fish and marine omega-3 polyunsaturated fatty acid (PUFA) intakes are linked to type 2 diabetes (T2D) risk remains unclear in China. We aimed to assess the long-term associations in a nationwide cohort. Overall 15,100 Chinese adults, aged ≥20 years, were included from China Health and Nutrition Survey. The cumulative averages of fish and marine omega-3 PUFA intakes were evaluated based on 3-day 24-h records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of T2D risk. Overall 1017 T2D cases were documented over a median of 14 years of follow-up. Compared with non-fish consumers, low and moderate fish consumption were associated with higher T2D risk whereas high fish consumption was not associated. Multivariable-adjusted HRs (95% CIs) for low and moderate fish consumption were 1.43 (1.09, 1.86) and 1.42 (1.07, 1.85) respectively in men, and were 1.58 (1.22, 2.02) and 1.39 (1.08, 1.83) respectively in women. In meat substitution analyses, low and moderate fish consumption was related to 55% and 69% higher T2D risk for men, and was associated with 68% and 54% higher T2D risk for women, respectively. Fried but not non-fried fish intake was associated with higher T2D risk. Intake of marine omega-3 PUFAs was dose-dependently associated with higher T2D risk for both men and women (P-trend<0.001). Overall low and moderate intakes of fish, especially fried fish, and marine omega-3 PUFAs were associated with higher T2D risk. Current level of fish and marine omega-3 PUFA consumption is not protective against T2D incidence among Chinese people.
KEYWORDS:
China Health and Nutrition Survey; Fish consumption; Marine omega-3 polyunsaturated fatty acids; Nationwide cohort; Type 2 diabetes

Aspirin for primary prevention of cardiovascular disease: a meta-analysis with a particular focus on subgroups.
Gelbenegger G, Postula M, Pecen L, Halvorsen S, Lesiak M, Schoergenhofer C, Jilma B, Hengstenberg C, Siller-Matula JM.
BMC Med. 2019 Nov 4;17(1):198. doi: 10.1186/s12916-019-1428-0.
PMID: 31679516
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-019-1428-0
Abstract
Background
The role of aspirin in primary prevention of cardiovascular disease (CVD) remains unclear. We aimed to investigate the benefit-risk ratio of aspirin for primary prevention of CVD with a particular focus on subgroups.
Methods
Randomized controlled trials comparing the effects of aspirin for primary prevention of CVD versus control and including at least 1000 patients were eligible for this meta-analysis. The primary efficacy outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, major adverse cardiovascular events (MACE), myocardial infarction, ischemic stroke, and net clinical benefit. The primary safety outcome was major bleeding. Subgroup analyses involving sex, concomitant statin treatment, diabetes, and smoking were performed.
Results
Thirteen randomized controlled trials comprising 164,225 patients were included. The risk of all-cause and cardiovascular mortality was similar for aspirin and control groups (RR 0.98; 95% CI, 0.93–1.02; RR 0.99; 95% CI, 0.90–1.08; respectively). Aspirin reduced the relative risk (RRR) of major adverse cardiovascular events (MACE) by 9% (RR 0.91; 95% CI, 0.86–0.95), myocardial infarction by 14% (RR 0.86; 95% CI, 0.77–0.95), and ischemic stroke by 10% (RR 0.90; 95% CI, 0.82–0.99), but was associated with a 46% relative risk increase of major bleeding events (RR 1.46; 95% CI, 1.30–1.64) compared with controls. Aspirin use did not translate into a net clinical benefit adjusted for event-associated mortality risk (mean 0.034%; 95% CI, − 0.18 to 0.25%). There was an interaction for aspirin effect in three patient subgroups: (i) in patients under statin treatment, aspirin was associated with a 12% RRR of MACE (RR 0.88; 95% CI, 0.80–0.96), and this effect was lacking in the no-statin group; (ii) in non-smokers, aspirin was associated with a 10% RRR of MACE (RR 0.90; 95% CI, 0.82–0.99), and this effect was not present in smokers; and (iii) in males, aspirin use resulted in a 11% RRR of MACE (RR 0.89; 95% CI, 0.83–0.95), with a non-significant effect in females.
Conclusions
Aspirin use does not reduce all-cause or cardiovascular mortality and results in an insufficient benefit-risk ratio for CVD primary prevention. Non-smokers, patients treated with statins, and males had the greatest risk reduction of MACE across subgroups.

Glycaemic measures and risk of mortality in older Chinese: the Guangzhou Biobank Cohort Study.
Jiang CQ, Xu L, Lam TH, Jin YL, Sen Zhang W, Zhu F, Thomas GN, Cheng KK.
J Clin Endocrinol Metab. 2019 Nov 2. pii: dgz173. doi: 10.1210/clinem/dgz173. [Epub ahead of print]
PMID: 31679008
Abstract
CONTEXT:
China has the largest number of people with type 2 diabetes mellitus (T2DM) in the world. Data from previous studies suggested that up to one-fifth of individuals with diabetes would be missed without an oral glucose tolerance test (OGTT). To date there is little information on the mortality risk of these individuals.
OBJECTIVE:
We estimated the association of different indicators of hyperglycaemia with mortality in the general Chinese population.
DESIGN:
Prospective cohort study.
SETTING:
China.
PARTICIPANTS:
17,939 participants aged 50+ years.
EXPOSURES:
Previously diagnosed diabetes and newly detected diabetes defined by fasting glucose (≥7.0 mmol/L), 2h post-load glucose (≥11.1 mmol/L), or haemoglobin A1c (HbA1c, ≥6.5%).
MAIN OUTCOMES MEASURES:
Deaths from all-cause, cardiovascular disease and cancer were identified by record linkage with death registration.
RESULTS:
During 7.8 (standard deviation=1.5) years' follow-up, 1,439 deaths were recorded. Of 3,706 participants with T2DM, 2126 (57%) had known T2DM, 118 (3%) were identified by isolated elevated fasting glucose, 1022 (28%) had isolated elevated post-load glucose, and 440 (12%) had both elevated fasting and post-load glucose. Compared to normoglycaemia, the HR (95% CI) of all-cause mortality was 1.71 (1.46, 2.00), 0.96 (0.47, 1.93), 1.43 (1.15-1.78) and 1.82 (1.35-2.45) for the four groups above, respectively. T2DM defined by elevated HbA1c was not significantly associated with all-cause mortality (HR 1.17, 95% 0.81-1.69).
CONCLUSION:
Individuals with isolated higher 2h post-load glucose had a higher risk of mortality by 43% than those with normoglycaemia. Under-use of OGTT leads to substantial under-detection of individuals with a higher mortality risk and lost opportunities for early intervention.

Loneliness increases the risk of all-cause dementia and Alzheimer's disease.
Sundström A, Nordin Adolfsson A, Nordin M, Adolfsson R.
J Gerontol B Psychol Sci Soc Sci. 2019 Oct 24. pii: gbz139. doi: 10.1093/geronb/gbz139. [Epub ahead of print]
PMID: 31676909
https://watermark.silverchair.com/gbz139.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAApEwggKNBgkqhkiG9w0BBwagggJ-MIICegIBADCCAnMGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMP3mjfwfFVNf6x_u3AgEQgIICROXk5XWUxl1dkiEr2IwQLulkrJ6HkKywuleleRuXBeYzSXvYsexIhxZwnLQYuwKF6flM2UMCtrL10OmMWcxw0lIUF61QvG8tv1rANBiIhfVFHse-rfSKkns666LokqmEQluvc4EjvzCGU8_CioG26_LkUFIyhZt3Jv67rKWYUCDgT1JCROiqtGVtPiCjrmv6m6n2chVxtRb2MQhzyS6Gx8iWei9VzYBQKDABkZT66lelyNq3Z49SAuY2iUAIQFkHWz5KG6Jahdum3O59HN_349Xpg9FGaiATVOqAkYbu8VVKtbXcGhPsYKGWOsgY2Tb3NslFzlmwWhXuKhP-oOGklIEF6lnl6w52eODAyhD8pjo0hNhaZVzNbjy-FmP0K_gPil2UkuRkqMTdCFH9574H3KnVaLfnyz0hY4lZe5D2rArO2JdK0WLnMy-HxFD6OouIZ9km31IoyK3nJ6OF-nORUlQ9un_c4h2aIWZhFgxEEDwtYnpL3GMKA4YlKosxTU7PjwP8UopMsIVbcIZdaZpV6-_ZWIlp7pEcltU81BJLwtVdQSaL3KRfMqEuAaSMu-fnH6Tkv5uBf0xBKCHMqUGDZmVzI9_fvKYP1aH_zfPA2wlBAG30ZJAf6N1Ybq2XD4yk1Bu1a-BLsu74YNqdIhNwO7q6ixBf6_2InJsx1GR6-6H4i2vr76b8PcU06OVYEVGAqkibs40eRSDsFKMl6HjaY5TD1ArDtn9dUrqQ2goXq3DVThl7QF5XqDfVgm0xDwphVNCfNRM
Abstract
OBJECTIVES:
To examine the effect of perceived loneliness on the development of dementia (all-cause), Alzheimer´s disease (AD), and vascular dementia (VaD).
METHOD:
The study comprised 1,905 non-demented participants at baseline, drawn from the longitudinal Betula study in Sweden, with a follow-up time of up to 20 years (mean 11.1 years). Loneliness was measured with a single question: "Do you often feel lonely?".
RESULTS:
During follow-up, 428 developed dementia; 221 had AD, 157 had VaD, and 50 had dementia of other subtypes. The entire dementia group is denoted "all-cause dementia". Cox regression models, adjusted for age, gender, and a baseline report of perceived loneliness, showed increased risk of all-cause dementia (HR = 1.46, 95% CI 1.14-1.89), and AD (HR = 1.69, 95% CI 1.20-2.37), but not VaD (HR = 1.34, 95% CI 0.87-2.08). After adjusting for a range of potential confounders, and excluding participants with dementia onset within the first five years of baseline (to consider the possibility of reverse causality), the increased risk for the development of all-cause dementia and AD still remained significant (HR = 1.51, 95%, CI 1.01-2.25 for all-cause dementia, HR = 2.50, 95%, CI 1.44-4.36 for AD).
DISCUSSION:
The results suggest that perceived loneliness is an important risk factor for all-cause dementia and especially for AD, but not for VaD. These results underscore the importance of paying attention to subjective reports of loneliness among the elderly, and identifying potential intervention strategies that can reduce loneliness.
KEYWORDS:
Living alone; Longitudinal; Risk factors; Social isolation; Social relationship

Hydration status affects thirst and salt preference but not energy intake or postprandial ghrelin in healthy adults: A randomised control trial.
Carroll HA, Templeman I, Chen YC, Edinburgh R, Burch EK, Jewitt JT, Povey G, Robinson TD, Dooley WL, Buckley C, Rogers PJ, Gallo W, Melander O, Thompson D, James LJ, Johnson L, Betts JA.
Physiol Behav. 2019 Oct 29:112725. doi: 10.1016/j.physbeh.2019.112725. [Epub ahead of print]
PMID: 31676259
https://reader.elsevier.com/reader/sd/pii/S0031938419305542?token=4DE6A144FEFE30BC1FC7CCB01A4F7707505A02BE2154671C6EED3A265CF486A6A39ADB2AC92F2B724A1796075C9937BA
Abstract
BACKGROUND:
Few studies have investigated the effect of hydration status on appetite for food in healthy adults. Prior work suggests hydration status does not alter appetite or energy intake, with mixed findings regarding appetite hormone secretion. However, an extensive investigation into both the psychological and physiological appetitive responses to hydration status has never been conducted.
OBJECTIVE:
To investigate the effect of hydration status on multiple facets of appetite.
DESIGN:
After 3 days pre-trial standardization, a range of appetite tasks were conducted when hypohydrated (HYPO) and euhydrated (EUHY) in 16 healthy participants (8 men). Hydration status was manipulated via dehydration in a heat tent for 60 min and subsequent fluid restriction (HYPO) or replacement (EUHY). The next day, a food reward computer task was completed followed by an ad libitum pasta meal. Pre- and post-prandial visual analogue scales assessing hunger, fullness, and flavour desires (sweet, salty, savoury and fatty) were additionally completed. Blood samples were taken the previous day before the hydration interventions in a euhydrated state, and in the fasted and post-prandial state during HYPO and EUHY.
RESULTS:
HYPO induced -1.9 ± 1.2 % body mass change, compared to -0.2 ± 0.6 % , with accompanying changes in markers of hypohydration which were not seen during EUHY. A higher desire for foods was associated with a higher water content but the association was weaker in EUHY compared to HYPO, (β = -0.33 mm/g of food water content, p < 0.001) in the food reward task. Visual analogue scales showed similar hunger and fullness between interventions, but during HYPO there was consistently higher thirst (average range in difference 27-32 mm across all time points) and lower fasted desire for salt (-23, 95 % CI -10, -35 mm). Ad libitum energy intake (HYPO 1953 ± 742 kJ, EUHY 2027 ± 926 kJ; p = 0.542) and post-prandial ghrelin concentrations (HYPO 180 ± 65 pg∙mL-1, EUHY 188 ± 71 pg∙mL-1; p = 0.736) were similar by hydration status.
CONCLUSIONS:
An acute manipulation to hydration status altered desire for salt and foods of differing water contents, but did not influence energy intake at an ad libitum pasta meal. Further research should investigate whether these appetites would alter food choice.
KEYWORDS:
Appetite; Copeptin; Desire; Energy intake; Hydration; Water intake

Edited November 5, 2019 by AlPater

[AlPater]

Walking pace improves all-cause and cardiovascular mortality risk prediction: A UK Biobank prognostic study.
Argyridou S, Zaccardi F, Davies MJ, Khunti K, Yates T.
Eur J Prev Cardiol. 2019 Nov 7:2047487319887281. doi: 10.1177/2047487319887281. [Epub ahead of print]
PMID: 31698963
https://sci-hub.tw/10.1177/2047487319887281
Abstract
AIMS:
The purpose of this study was to quantify and rank the prognostic relevance of dietary, physical activity and physical function factors in predicting all-cause and cardiovascular mortality in comparison with the established risk factors included in the European Society of Cardiology Systematic COronary Risk Evaluation (SCORE).
METHODS:
We examined the predictive discrimination of lifestyle measures using C-index and R2 in sex-stratified analyses adjusted for: model 1, age; model 2, SCORE variables (age, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol).
RESULTS:
The sample comprised 298,829 adults (median age, 57 years; 53.5% women) from the UK Biobank free from cancer and cardiovascular disease at baseline. Over a median follow-up of 6.9 years, there were 2174 and 3522 all-cause and 286 and 796 cardiovascular deaths in women and men, respectively. When added to model 1, self-reported walking pace improved C-index in women and men by 0.013 (99% CI: 0.007-0.020) and 0.022 (0.017-0.028) respectively for all-cause mortality; and by 0.023 (0.005-0.042) and 0.034 (0.020-0.048) respectively for cardiovascular mortality. When added to model 2, corresponding values for women and men were: 0.008 (0.003-0.012) and 0.013 (0.009-0.017) for all-cause mortality; and 0.012 (-0.001-0.025) and 0.024 (0.013-0.035) for cardiovascular mortality. Other lifestyle factors did not consistently improve discrimination across models and outcomes. The pattern of results for R2 mirrored those for C-index.
CONCLUSION:
A simple self-reported measure of walking pace was the only lifestyle variable found to improve risk prediction for all-cause and cardiovascular mortality when added to established risk factors.
KEYWORDS:
Walking pace; cardiovascular risk; mortality; prognosis

The prediction of colorectal cancer using anthropometric measures: A Swedish population-based cohort study with 22 years of follow-up.
Andreasson A, Hagström H, Sköldberg F, Önnerhag K, Carlsson AC, Schmidt PT, Forsberg AM.
United European Gastroenterol J. 2019 Nov;7(9):1250-1260. doi: 10.1177/2050640619854278. Epub 2019 May 24.
PMID: 31700638
https://journals.sagepub.com/doi/pdf/10.1177/2050640619854278
Abstract
BACKGROUND:
Obesity is a risk factor for colorectal cancer (CRC).
OBJECTIVE:
The objective of this article is to investigate whether anthropometric measures reflecting visceral obesity are better predictors of CRC than body mass index (BMI).
METHODS:
Data were analysed from the Malmö Diet and Cancer study in Sweden, comprising 16,669 women and 10,805 men (median age 56.6 and 59.1 years) followed for a median 21.5 years. Diagnoses of CRC were identified using Swedish national registers. Cox regression was used to test the associations of BMI, waist circumference (WC), waist-hip ratio, waist-to-height ratio, waist-to-hip-to-height ratio, A Body Shape Index (ABSI) and percentage body fat with the development of CRC adjusted for age, alcohol consumption, smoking, education and physical activity in men and women.
RESULTS:
None of the measures were significantly associated with an increased risk for CRC in women. WC was the strongest predictor of colon cancer (CC) in men and the only measure that was independent of BMI. ABSI was the only measure significantly associated with the risk of rectal cancer in men.
CONCLUSIONS:
Visceral obesity, best expressed as WC, is a risk factor for CC in men but a poor predictive marker for CRC in women.
KEYWORDS:
A Body Shape Index; Anthropometric measures; body mass index; colon cancer; colorectal cancer; colorectal cancer risk; predictive value; rectal cancer; waist circumference; waist-to-height-ratio

The relationship between red cell distribution width and all-cause and cause-specific mortality in a general population.
Pan J, Borné Y, Engström G.
Sci Rep. 2019 Nov 7;9(1):16208. doi: 10.1038/s41598-019-52708-2.
PMID: 31700048
https://www.nature.com/articles/s41598-019-52708-2.pdf
Abstract
Red Cell Distribution Width (RDW) could be a risk factor for developing various chronic diseases, and seems to be a prognostic marker in patients with cardiovascular disease (CVD) or cancer. Our aim was to explore the association between RDW and all-cause and cause-specific mortality in a general population. RDW was measured in 27,063 participants (aged 45-73 years) from the population-based Malmö Diet and Cancer cohort. After a follow-up of 19.8 ± 5.5 years, Cox proportional hazards regression analysis was used to study the relationship between RDW and all-cause and cause-specific mortality, with adjustment for confounding factors. A total of 9388 individuals (4715 men and 4673 women) died during the follow up. High RDW was significantly associated with all-cause mortality (HR, 4th vs. 1st quartile: 1.34, 95%CI: 1.24-1.45), cancer mortality (HR: 1.27, 95%CI: 1.12-1.44), CVD mortality (HR: 1.39, 95%CI: 1.21-1.59), and respiratory disease mortality (HR: 1.47, 95%CI: 1.06-2.03). The C-statistic increased significantly from 0.732 to 0.737 when adding RDW to a model adjusted for age and sex. There was a significant interaction between RDW and BMI with respect to all-cause mortality. We concluded that RDW is associated with mortality and propose that high RDW is a significant, but non-specific marker of mortality risk in the general population.

High Betaine, a Trimethylamine N-Oxide Related Metabolite, Is Prospectively Associated with Low Future Risk of Type 2 Diabetes Mellitus in the PREVEND Study.
Garcia E, Osté MCJ, Bennett DW, Jeyarajah EJ, Shalaurova I, Gruppen EG, Hazen SL, Otvos JD, Bakker SJL, Dullaart RPF, Connelly MA.
J Clin Med. 2019 Nov 1;8(11). pii: E1813. doi: 10.3390/jcm8111813.
PMID: 31683780 Free Article
Abstract
BACKGROUND:
Gut microbiota-related metabolites, trimethylamine-N-oxide (TMAO), choline, and betaine, have been shown to be associated with cardiovascular disease (CVD) risk. Moreover, lower plasma betaine concentrations have been reported in subjects with type 2 diabetes mellitus (T2DM). However, few studies have explored the association of betaine with incident T2DM, especially in the general population. The goals of this study were to evaluate the performance of a newly developed betaine assay and to prospectively explore the potential clinical associations of betaine and future risk of T2DM in a large population-based cohort.
METHODS:
We developed a high-throughput, nuclear magnetic resonance (NMR) spectroscopy procedure for acquiring spectra that allow for the accurate quantification of plasma/serum betaine and TMAO. Assay performance for betaine quantification was assessed and Cox proportional hazards regression was employed to evaluate the association of betaine with incident T2DM in 4336 participants in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study.
RESULTS:
Betaine assay results were linear (y = 1.02X - 3.75) over a wide range of concentrations (26.0-1135 µM). The limit of blank (LOB), limit of detection (LOD) and limit of quantitation (LOQ) were 6.4, 8.9, and 13.2 µM, respectively. Coefficients of variation for intra- and inter-assay precision ranged from 1.5-4.3% and 2.5-5.5%, respectively. Deming regression analysis of results produced by NMR and liquid chromatography coupled to tandem mass spectrometry(LC-MS/MS) revealed an R2 value of 0.94 (Y = 1.08x - 1.89) and a small bias for higher values by NMR. The reference interval, in a cohort of apparently healthy adult participants (n = 501), was determined to be 23.8 to 74.7 µM (mean of 42.9 ± 12.6 µM). In the PREVEND study (n = 4336, excluding subjects with T2DM at baseline), higher betaine was associated with older age and lower body mass index, total cholesterol, triglycerides, and hsCRP. During a median follow-up of 7.3 (interquartile range (IQR), 5.9-7.7) years, 224 new T2DM cases were ascertained. Cox proportional hazards regression models revealed that the highest tertile of betaine was associated with a lower incidence of T2DM. Hazard ratio (HR) for the crude model was 0.61 (95% CI: 0.44-0.85, p = 0.004). The association remained significant even after adjusting for multiple clinical covariates and T2DM risk factors, including fasting glucose. HR for the fully-adjusted model was 0.50 (95% CI: 0.32-0.80, p = 0.003).
CONCLUSIONS:
The newly developed NMR-based betaine assay exhibits performance characteristics that are consistent with usage in the clinical laboratory. Betaine levels may be useful for assessing the risk of future T2DM.
KEYWORDS:
betaine; nuclear magnetic resonance spectroscopy; trimethylamine N-oxide related metabolites; type 2 diabetes mellitus

Vitamin D and Calcium Supplements: Helpful, Harmful, or Neutral for Cardiovascular Risk?
Heravi AS, Michos ED.
Methodist Debakey Cardiovasc J. 2019 Jul-Sep;15(3):207-213. doi: 10.14797/mdcj-15-3-207. Review.
PMID: 31687100 Free PMC Article
Abstract
Vitamin D has traditionally been known as the "bone vitamin". However, a large body of observational data has also linked low concentrations of serum 25-hydroxyvitamin D (25[OH]D), the primary storage form of vitamin D, to an increased risk of incident cardiovascular disease (CVD) and mortality, garnering public excitement about the purported nonskeletal benefits of vitamin D. Despite this, more recent meta-analyses and randomized clinical trials have failed to find a beneficial effect of vitamin D supplements on CVD and cancer outcomes. These findings, along with the lack of consensus on optimal serum 25(OH)D concentrations, have dampened some of the initial enthusiasm for vitamin D supplements. Residual confounding or reverse causation may explain some of the discrepancy between the observational and trial results. At this time, vitamin D supplements should not be prescribed for the primary purpose of CVD prevention. Adding to this complexity is the fact that many adults take vitamin D and calcium supplements together for bone health, and there is some concern (albeit inconclusive) related to calcium use and increased CVD risk. In this light, it may be best to achieve the recommended daily allowances of calcium intake through food and reserve calcium supplementation only for those at risk for calcium intake deficiency, with the smallest dosage needed after dietary modifications have been exhausted. In this review, we discuss vitamin D and calcium supplementation and how they may affect cardiovascular health.
KEYWORDS:
calcium; cardiovascular risk; supplements; vitamin D

Consumption of sugar-sweetened and artificially-sweetened soft drinks and risk of cancers not related to obesity.
Bassett JK, Milne RL, English DR, Giles GG, Hodge AM.
Int J Cancer. 2019 Nov 6. doi: 10.1002/ijc.32772. [Epub ahead of print]
PMID: 31693185
Abstract
Consumption of sugary drinks increases the risk of obesity. Previously we reported a positive association between sugar-sweetened soft drink consumption and obesity-related cancer but this association was not fully explained by obesity; in contrast, we found no association for consumption of artificially-sweetened soft drinks. Our aim was to determine whether the consumption of sugar-sweetened or artificially-sweetened soft drinks was associated with cancers other than those currently identified as being related to obesity. We used data from the Melbourne Collaborative Cohort Study. Participants completed a 121-item food-frequency questionnaire (FFQ) at baseline including separate questions about the number of times in the past year they had consumed sugar-sweetened and artificially-sweetened soft drinks. Cox regression models were fitted to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the risk of cancers not related to obesity. During 19 years of follow-up, there were 35,109 eligible participants who developed 4,789 cancers not related to obesity. There was no association between frequency of consuming sugar-sweetened soft drinks and the risk of these cancers, but an unexpected positive association was observed for consumption of artificially-sweetened soft drinks. Although, we did not find an association with sugar-sweetened soft drinks, we previously reported a positive association with obesity-related cancers, not fully explained by obesity. These findings leave unresolved the question of whether consumption of sugar-sweetened soft drinks influences cancer risk independently of their influence on body size. This article is protected by copyright. All rights reserved.
KEYWORDS:
Sugar-sweetened soft drinks; artificially-sweetened soft drinks; cancer; prospective study

Legume Consumption and Risk of Hypertension in a prospective cohort of Chinese Men and Women.
Guo F, Zhang Q, Yin Y, Liu Y, Jiang H, Yan N, Lin J, Liu XH, Ma L.
Br J Nutr. 2019 Nov 7:1-20. doi: 10.1017/S0007114519002812. [Epub ahead of print]
PMID: 31694733
Abstract
Prior data on long-term association between habitual legume consumption and hypertension risk remained sparse. We aimed to evaluate whether total legume and subtype intakes were prospectively related to lower hypertension incidence among 8,758 participants (aged ≥30 years) from the China Health and Nutrition Survey 2004-2011. Dietary intakes were assessed by interviews combining 3-day 24-h food recalls and household food inventory weighing method at each survey round (median dietary assessment times during follow-up was three). Incident hypertension was identified by self-reports or blood pressure measurements. Multivariable Cox regression model was applied to estimate hazard ratio (HR) for hypertension across increasing categories of cumulatively averaged legume intake. For 35,990 person-years (median 6.0 years per person), we documented 944 hypertension cases. After adjustment for covariates, higher consumption of total legumes was significantly associated with a lower hypertension risk, with HR comparing extreme categories being 0.56 (95% CI 0.43-0.71; P for trend <0.001). Then we found that intakes of dried legumes (HR 0.53; 95% CI 0.43-0.65; P for trend <0.001) and fresh legumes (HR 0.67; 95% CI 0.55-0.81; P for trend <0.001) were both related to reduced hypertension risks. However, further classification of dried legumes revealed that the inverse association with hypertension substantially held for higher soybean (HR 0.51; 95% CI 0.41-0.62; P for trend <0.001) but not non-soybean intakes. In stratified analyses, the association of interest remained similar within strata defined by gender, body mass index, physical activity, smoking and drinking status; however, significant heterogeneity of results was detected across age strata (P for interaction = 0.02). Total legume intake related to a more pronounced decrease in hypertension risk for the elderly (≥65 years [HR 0.47; 95% CI 0.30-0.73; P for trend <0.001]), in contrast to that for the non-elderly. Our findings suggest inverse associations of all kinds of legume but may not non-soybean intakes with risk of developing hypertension.
KEYWORDS:
Blood pressure; Chinese adults; Hypertension; Legume; Prospective study; Soybean

Insomnia symptoms and risk of cardiovascular diseases among 0.5 million adults: A 10-year cohort.
Zheng B, Yu C, Lv J, Guo Y, Bian Z, Zhou M, Yang L, Chen Y, Li X, Zou J, Ning F, Chen J, Chen Z, Li L; China Kadoorie Biobank Collaborative Group.
Neurology. 2019 Nov 6. pii: 10.1212/WNL.0000000000008581. doi: 10.1212/WNL.0000000000008581. [Epub ahead of print]
PMID: 31694922
Abstract
OBJECTIVE:
To examine the associations of individual insomnia symptoms with risks of incident cardio-cerebral vascular diseases (CVD) and possible moderating factors among Chinese adults.
METHODS:
The China Kadoorie Biobank is a prospective cohort study that recruited participants from 10 areas across China. Data from 487,200 adults 30 to 79 years of age who were free of stroke, coronary heart disease, and cancer at baseline were analyzed. Three insomnia symptoms were assessed with self-reported difficulties in initiating or maintaining sleep, early morning awakening, and daytime dysfunction for at least 3 d/wk at baseline. Incidences of CVD were followed up through disease registries and national health insurance databases until 2016.
RESULTS:
During a median of 9.6 years of follow-up, 130,032 cases of CVD were documented. Cox regressions showed that 3 insomnia symptoms were associated with increased risk of total CVD, with respective adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.09 (95% CI 1.07-1.11), 1.07 (95% CI 1.05-1.09), and 1.13 (95% CI 1.09-1.18). Participants with individual symptoms also had higher risks of ischemic heart disease (IHD; HR 1.13, 1.09, and 1.17) and ischemic stroke but not hemorrhagic stroke. Participants with all 3 symptoms were at an 18%, 22%, or 10% higher risk of CVD, IHD, or ischemic stroke compared to nonsymptomatic adults. Associations between 3 symptoms and CVD incidence were consistently stronger in younger adults or those without baseline hypertension (p for interaction <0.05).
CONCLUSIONS:
Individual and coexisting insomnia symptoms are independent risk factors for CVD incidence, especially among young adults or adults who have not developed hypertension.

The effect of the artificial sweeteners on glucose metabolism in healthy adults: a randomized double-blinded crossover clinical trial.
Ahmad SY, Friel JK, MacKay DS.
Appl Physiol Nutr Metab. 2019 Nov 7. doi: 10.1139/apnm-2019-0359. [Epub ahead of print]
PMID: 31697573
Abstract
BACKGROUND:
This study aims to determine the effect of pure forms of sucralose and aspartame, in doses reflective of common consumption, on glucose metabolism.
METHODS:
Healthy participants consumed pure forms of a non-nutritive sweetener (NNS) mixed with water that were standardized to doses of 14% (0.425 g) of the acceptable daily intake (ADI) for aspartame and 20% (0.136 g) of the ADI for sucralose every day for two weeks. Blood samples were collected and analysed for glucose, insulin, active glucagon-like peptide-1 (GLP-1), and leptin.
RESULTS:
Seventeen participants (10 females and 7 males; age 24 ± 6.8 years; BMI 22.9 ± 2.5 kg/m2) participated in the study. The total area under the curve (AUC) values of glucose, insulin, active GLP-1 and leptin were similar for the aspartame and sucralose treatment groups compared to the baseline values in healthy participants. There was no change in insulin sensitivity after NNS treatment compared to the baseline values.
CONCLUSIONS:
These findings suggest that daily repeated consumption of pure sucralose or aspartame for 2 weeks had no effect on glucose metabolism among normoglycaemic adults. However, these results need to be tested in studies with longer durations. Novelty: • Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on glucose metabolism. • Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on insulin sensitivity among healthy adults.

Relations of magnesium intake to cognitive impairment and dementia among participants in the Women's Health Initiative Memory Study: a prospective cohort study.
Lo K, Liu Q, Madsen T, Rapp S, Chen JC, Neuhouser M, Shadyab A, Pal L, Lin X, Shumaker S, Manson J, Feng YQ, Liu S.
BMJ Open. 2019 Nov 3;9(11):e030052. doi: 10.1136/bmjopen-2019-030052.
PMID: 31685499 Free Article
https://bmjopen.bmj.com/content/bmjopen/9/11/e030052.full.pdf
Abstract
OBJECTIVE:
To examine the associations of dietary and supplemental magnesium (Mg) as assessed by a semi-quantitative food frequency questionnaire with cognitive outcomes among ageing women.
DESIGN:
This work conducts a prospective cohort study of participants enrolled in the Women's Health Initiative Memory Study (WHIMS), which was subsequently extended and named WHIMS-Epidemiology of Cognitive Health.
SETTING:
Forty clinical centres in the USA.
PARTICIPANTS:
Postmenopausal women aged 65-79 years without dementia on enrolment.
MAIN OUTCOME MEASURES:
Physician-adjudicated mild cognitive impairment (MCI) and/or probable dementia (PD).
RESULTS:
Participants were excluded (n=1006) if they had extreme values of dietary energy intake, had missing or extreme body mass index values, with prevalent MCI/PD at baseline, received only one cognitive assessment or had been followed up for <1 year. During >20 years of follow-up, 765 (11.8%) out of 6473 participants developed MCI/PD. For MCI/PD and MCI, the risks tended to be lower among participants in quintiles Q2-Q5 of Mg consumption compared with those in the lowest quintile. Participants in Q3 had a significantly lower risk of MCI/PD (HR 0.69, 95% CI 0.53 to 0.91) and MCI (HR 0.63, 95% CI 0.45 to 0.87) after multivariate adjustments. No significant association was observed between total Mg intake and PD. The association between total Mg intake, MCI/PD and MCI was non-linear as suggested by the likelihood test.
CONCLUSIONS:
Total Mg intake between the estimated average requirement and the recommended dietary allowances may associate with a lower risk of MCI/PD and MCI.
KEYWORDS:
dementia; epidemiology; nutrition & dietetics

Impact of body mass index and metabolically unhealthy status on mortality in the Japanese general population: The JMS cohort study.
Izumida T, Nakamura Y, Ishikawa S.
PLoS One. 2019 Nov 7;14(11):e0224802. doi: 10.1371/journal.pone.0224802. eCollection 2019.
PMID: 31697720
Abstract
This study aimed to investigate the associations of body mass index (BMI) and metabolically unhealthy weight with all-cause mortality, cardiovascular disease (CVD) mortality, and cancer mortality as well as the effect of age on the associations. This prospective study enrolled Japanese individuals in the general population. Participants were divided into eight phenotypes according to the BMI classification and metabolic status. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox regression hazard model. In total, 10,824 individuals with a mean age of 55.3 years were evaluated. During a mean follow-up of 18.4 years (198,776 person-years), 2,274 participants died. Among the metabolically unhealthy, the association between BMI and mortality was J-shaped after adjustment for various confounders (multivariable HR [95% CI] for all-cause mortality: underweight, 2.0 [1.5-2.7]; obesity 2.8 [2.1-3.6]). The association remained the same in metabolically unhealthy participants aged <65 years and ≥65 years. The results were compatible in the analyses restricted to subjects who never smoked. Regardless of age, metabolically unhealthy underweight (MUHU) have approximately a 3-fold higher risk of CVD mortality, compared with metabolically healthy normal weight. Not only metabolically unhealthy obesity, but also MUHU was strongly associated with an increased risk of mortality. More attention should be given to the health issues of metabolically unhealthy participants without obesity, particularly those with MUHU.

Is running associated with a lower risk of all-cause, cardiovascular and cancer mortality, and is the more the better? A systematic review and meta-analysis.
Pedisic Z, Shrestha N, Kovalchik S, Stamatakis E, Liangruenrom N, Grgic J, Titze S, Biddle SJ, Bauman AE, Oja P.
Br J Sports Med. 2019 Nov 4. pii: bjsports-2018-100493. doi: 10.1136/bjsports-2018-100493. [Epub ahead of print] Review.
PMID: 31685526
Abstract
OBJECTIVE:
To investigate the association of running participation and the dose of running with the risk of all-cause, cardiovascular and cancer mortality.
DESIGN:
Systematic review and meta-analysis.
DATA SOURCES:
Journal articles, conference papers and doctoral theses indexed in Academic Search Ultimate, CINAHL, Health Source: Nursing/Academic Edition, MasterFILE Complete, Networked Digital Library of Theses and Dissertations, Open Access Theses and Dissertations, PsycINFO, PubMed/MEDLINE, Scopus, SPORTDiscus and Web of Science.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES:
Prospective cohort studies on the association between running or jogging participation and the risk of all-cause, cardiovascular and/or cancer mortality in a non-clinical population of adults were included.
RESULTS:
Fourteen studies from six prospective cohorts with a pooled sample of 232 149 participants were included. In total, 25 951 deaths were recorded during 5.5-35 year follow-ups. Our meta-analysis showed that running participation is associated with 27%, 30% and 23% lower risk of all-cause (pooled adjusted hazard ratio (HR)=0.73; 95% confidence interval (CI) 0.68 to 0.79), cardiovascular (HR=0.70; 95% CI 0.49 to 0.98) and cancer (HR=0.77; 95% CI 0.68 to 0.87) mortality, respectively, compared with no running. A meta-regression analysis showed no significant dose-response trends for weekly frequency, weekly duration, pace and the total volume of running.
CONCLUSION:
Increased rates of participation in running, regardless of its dose, would probably lead to substantial improvements in population health and longevity. Any amount of running, even just once a week, is better than no running, but higher doses of running may not necessarily be associated with greater mortality benefits.
KEYWORDS:
exercise; physical activity; running; sport; survival

A single combination gene therapy treats multiple age-related diseases.
Davidsohn N, Pezzone M, Vernet A, Graveline A, Oliver D, Slomovic S, Punthambaker S, Sun X, Liao R, Bonventre JV, Church GM.
Proc Natl Acad Sci U S A. 2019 Nov 4. pii: 201910073. doi: 10.1073/pnas.1910073116. [Epub ahead of print]
PMID: 31685628 Free Article
Abstract
Comorbidity is common as age increases, and currently prescribed treatments often ignore the interconnectedness of the involved age-related diseases. The presence of any one such disease usually increases the risk of having others, and new approaches will be more effective at increasing an individual's health span by taking this systems-level view into account. In this study, we developed gene therapies based on 3 longevity associated genes (fibroblast growth factor 21 [FGF21], αKlotho, soluble form of mouse transforming growth factor-β receptor 2 [sTGFβR2]) delivered using adeno-associated viruses and explored their ability to mitigate 4 age-related diseases: obesity, type II diabetes, heart failure, and renal failure. Individually and combinatorially, we applied these therapies to disease-specific mouse models and found that this set of diverse pathologies could be effectively treated and in some cases, even reversed with a single dose. We observed a 58% increase in heart function in ascending aortic constriction ensuing heart failure, a 38% reduction in α-smooth muscle actin (αSMA) expression, and a 75% reduction in renal medullary atrophy in mice subjected to unilateral ureteral obstruction and a complete reversal of obesity and diabetes phenotypes in mice fed a constant high-fat diet. Crucially, we discovered that a single formulation combining 2 separate therapies into 1 was able to treat all 4 diseases. These results emphasize the promise of gene therapy for treating diverse age-related ailments and demonstrate the potential of combination gene therapy that may improve health span and longevity by addressing multiple diseases at once.
KEYWORDS:
AAV; age-related diseases; combination therapy; gene therapy

Higher dietary diversity scores and protein-rich food consumption were associated with lower risk of all-cause mortality in the oldest old.
Lv Y, Kraus VB, Gao X, Yin Z, Zhou J, Mao C, Duan J, Zeng Y, Brasher MS, Shi W, Shi X.
Clin Nutr. 2019 Oct 25. pii: S0261-5614(19)33084-5. doi: 10.1016/j.clnu.2019.10.012. [Epub ahead of print]
PMID: 31685303
Abstract
BACKGROUND & AIMS:
Dietary diversity is widely advocated in national and international recommendations although whether the beneficial effects on survival or longevity still apply in the final phase of the lifespan remains understudied. We aimed to prospectively examine the association of dietary diversity, food items with all-cause mortality among the oldest old (80+) and determine whether dietary diversity recommendations were appropriate for this population.
METHODS:
The study included 28,790 participants aged 80+ (9957 octogenarians, 9925 nonagenarians, and 8908 centenarians). A baseline dietary diversity score (DDS) was constructed based on nine food items of a food frequency questionnaire. Cox models with penalized splines evaluated non-linear associations of DDS as continuous variable with mortality to identify cut-offs of DDS.
RESULTS:
We documented 23,503 deaths during 96,739 person-years of follow-up. Each one unit increase in DDS was associated with a 9% lower risk of mortality (adjusted hazard ratio (HR): 0.91; 95% confidential interval (CI): 0.90-0.92). Compared to participants whose DDS less than 2 scores, those with a DDS of 2, 3, 4, 5, and higher than 6 scores had a lower mortality risk, the HRs were 0.86 (0.82-0.89), 0.78 (0.75-0.81), 0.69 (0.66-0.72), 0.65 (0.62-0.68), and 0.56 (0.53-0.58) respectively, and a significant trend emerged (p < 0.001). Protein-rich food items were associated with prominent beneficial effects on mortality including meat (HR and 95% CI for high vs low frequency: 0.70 (0.68-0.72)), fish and sea food (HR, 0.74 (0.72-0.77)), egg (HR, 0.75 (0.73-0.77)), and bean (HR, 0.80 (0.78-0.82)).
CONCLUSIONS:
Even after the age of 80, the DDS tool may offer a simple and straightforward mean of identifying and screening individuals at high risk for mortality. Recommendation of dietary diversity, especially consumption of protein-rich food, may be advocated to reduce mortality risk and promote longevity in the oldest old.
KEYWORDS:
Cohort study; Dietary diversity; Elderly; Mortality; Oldest old; Protein-rich food

Monosodium Glutamate Supplementation Improves Bone Status in Mice Under Moderate Protein Restriction.
Blais A, Rochefort GY, Moreau M, Calvez J, Wu X, Matsumoto H, Blachier F.
JBMR Plus. 2019 Sep 16;3(10):e10224. doi: 10.1002/jbm4.10224. eCollection 2019 Oct.
PMID: 31687652
https://asbmr.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jbm4.10224
Abstract
Adequate protein intake during development is critical to ensure optimal bone gain and to attain a higher peak bone mass later. Using a mild protein restriction model in Balb/C mice consuming 6% of their total energy intake as soy protein (LP-SOY)-for which we observed a significantly lower femoral cortical thickness, bone volume, trabecular number, and thickness reduction-we evaluated the effects of monosodium glutamate (MSG) supplementation at different concentrations (0.5, 1, 5, 10, and 20 g/kg of diet) on bone characteristics in LP-SOY-fed mice. After 6 and 12 weeks, LP-SOY-fed mice had lower BMD and reduced body weight related to lower lean mass, which was associated with a reduced IGF-1 level. The negative effect of the LP-SOY diet on BMD correlated with impaired bone formation. MSG supplementation, at 5, 10, and 20 g/kg of diet, and PTH injection, used as a positive control, were able to improve BMD and to increase osteoblast activity markers (P1NP and osteocalcin), as well as glutamine plasma concentration. An analysis of bone microarchitecture found that cortical bone was less sensitive to protein restriction than trabecular bone, and that MSG ingestion was able to preserve bone quality through an increase of collagen synthesis, although it did not allow normal bone growth. Our study reinforces the view that glutamate can act as a functional amino acid for bone physiology and support clinical investigation of glutamate supplementation in adults characterized by poor bone status, notably as a result of insufficient protein intake. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
KEYWORDS:
BONE TURNOVER; BONE μCT; COLLAGEN SYNTHESIS; DIETARY PROTEIN RESTRICTION; MICE MODEL; MONOSODIUM GLUTAMATE

[AlPater]

Trajectories of physical activity from midlife to old age and associations with subsequent cardiovascular disease and all-cause mortality.
Aggio D, Papachristou E, Papacosta O, Lennon LT, Ash S, Whincup P, Wannamethee SG, Jefferis BJ.
J Epidemiol Community Health. 2019 Nov 8. pii: jech-2019-212706. doi: 10.1136/jech-2019-212706. [Epub ahead of print]
Abstract
INTRODUCTION:
It is well established that physical activity (PA) protects against mortality and morbidity, but how long-term patterns of PA are associated with mortality and cardiovascular disease (CVD) remains unclear.
METHODS:
3231 men recruited to the British Regional Heart Study, a prospective cohort study, reported usual PA levels at baseline in 1978-1980 (aged 40-59 years) and at 12-year, 16-year and 20-year follow ups. Twenty-year trajectories of PA, spanning from 1978/1980 to 2000, were identified using group-based trajectory modelling. Men were subsequently followed up until 30 June 2016 for mortality through National Health Service central registers and for non-fatal CVD events through primary and secondary care records. Data analyses were conducted in 2019.
RESULTS:
Three PA trajectories were identified: low/decreasing (22.7%), light/stable (51.0%) and moderate/increasing (26.3%). Over a median follow-up of 16.4 years, there were 1735 deaths. Compared with the low/decreasing group, membership of the light/stable (HR 0.83, 95% CI 0.74 to 0.94) and moderate/increasing (HR 0.76, 95% CI 0.66 to 0.88) groups was associated with a lower risk of all-cause mortality. Similar associations were observed for CVD mortality, major coronary heart disease and all CVD events. Associations were only partially explained by a range of confounders. Sensitivity analyses suggested that survival benefits were largely driven by most recent/current PA.
CONCLUSIONS:
A dose-response relationship was observed, with higher levels of PA from midlife to old age associated with additional benefits. However, even fairly modest and sustained PA was protective and may be more achievable for the most inactive.
KEYWORDS:
CHD/coronorary heart; ageing; cardiovascular disease; life course epidemiology; physical activity

Association between Nutrients and Visceral Fat in Healthy Japanese Adults: A 2-Year Longitudinal Study Brief Title: Micronutrients Associated with Visceral Fat Accumulation.
Ozato N, Saito S, Yamaguchi T, Katashima M, Tokuda I, Sawada K, Katsuragi Y, Imoto S, Ihara K, Nakaji S.
Nutrients. 2019 Nov 7;11(11). pii: E2698. doi: 10.3390/nu11112698.
PMID: 31703461
[pdf availed from Medline abstract page.]
Abstract
: High visceral fat area (VFA) is a stronger predictor of cardiovascular disease and overall mortality than body mass index or waist circumference. VFA may be decreased by proper dietary habits. Although previous epidemiologic studies demonstrated an association between nutritional components or foodstuffs and VFA, only the associations of a few nutrients, such as dietary fiber and calcium, are reported. We performed a comprehensive 2-year longitudinal study in more than 624 healthy people and analyzed 33 micronutrients to investigate nutrients that contribute to changes in visceral fat. Our analyses revealed that "macronutrients" and "micronutrients" were "mutual confounders". Therefore, when evaluating the association between VFA and micronutrients, associations were adjusted by macronutrients. The ingestion of 7 nutrients: soluble dietary fiber, manganese, potassium, magnesium, vitamin K, folic acid, and pantothenic acid, which are abundant components in vegetable diets, was significantly inversely correlated with a change in VFA. Additionally, a change in the ingestion of one nutrient, monounsaturated fat, was significantly positively correlated with a change in VFA. These associations were independent of body mass index and waist circumference. Thus, a predominantly vegetable diet may decrease VFA. In addition, adjusting the intake of macronutrients might help to clarify the association of micronutrients with VFA.
KEYWORDS:
BMI; macronutrients; micronutrients; obesity; vegetable; visceral fat

Association between separate items of the Mini Nutritional Assessment instrument and mortality among older adults: A prospective cohort study introducing a trimmed MNA version.
Söderström L, Rosenblad A.
Clin Nutr. 2019 Oct 22. pii: S0261-5614(19)33086-9. doi: 10.1016/j.clnu.2019.10.014. [Epub ahead of print]
PMID: 31703950
https://sci-hub.tw/10.1016/j.clnu.2019.10.014
Abstract
BACKGROUND & AIMS:
The predictive ability of the separate items of the full Mini Nutritional Assessment (MNA-F) instrument in relation to all-cause mortality (ACM) in older adults is unclear. The present study aimed to examine the magnitudes of the independent associations between separate MNA-F items and ACM among people aged ≥65 years old admitted to hospital. A secondary aim was to construct a trimmed MNA instrument (MNA-T) consisting of MNA-F items that contributed independently to predicting ACM, and compare its predictive ability with that of MNA-F and MNA short forms (MNA-SF).
METHODS:
This prospective cohort study included 1768 individuals aged ≥65 years old admitted to a Swedish hospital who answered MNA-F in 2008. They were followed-up for ACM after two years using national registers. Associations with ACM were calculated using Cox regression analysis. Predictive abilities for ACM were calculated using an R2-type measure.
RESULTS:
After a mean follow-up time of 1.7 years (3006 person-years), 455 (25.7%) participants had died. In adjusted analyses, nine MNA-F items contributed independently to predicting ACM (P < 0.20) and were included in MNA-T. Five items (food intake, independent living, > 3 prescription drugs, fluid intake, self-assessed health status) had significant contributions (P < 0.05). MNA-T had a better predictive ability for ACM than MNA-F and MNA-SF.
CONCLUSIONS:
MNA-F could possibly benefit from excluding less important and more time-consuming items when used for predicting the ultimate consequence of malnutrition, an early death. MNA-T should be a more reliable instrument to use for this purpose.
KEYWORDS:
All-cause mortality; Cox regression; Epidemiology; Malnutrition; Mini nutritional assessment; Predictive ability

A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study.
Papadimitriou N, Muller D, van den Brandt PA, Geybels M, Patel CJ, Gunter MJ, Lopez DS, Key TJ, Perez-Cornago A, Ferrari P, Vineis P, Weiderpass E, Boeing H, Agudo A, Sánchez MJ, Overvad K, Kühn T, Fortner RT, Palli D, Drake I, Bjartell A, Santiuste C, Bueno-de-Mesquita BH, Krogh V, Tjønneland A, Lauritzen DF, Gurrea AB, Quirós JR, Stattin P, Trichopoulou A, Martimianaki G, Karakatsani A, Thysell E, Johansson I, Ricceri F, Tumino R, Larrañaga N, Khaw KT, Riboli E, Tzoulaki I, Tsilidis KK.
Eur J Nutr. 2019 Nov 8. doi: 10.1007/s00394-019-02132-z. [Epub ahead of print]
PMID: 31705265
Abstract
PURPOSE:
The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive.
METHODS:
A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportional hazard regression models adjusted for total energy intake, smoking status, body mass index, physical activity, diabetes and education were used to estimate hazard ratios and 95% confidence intervals for standardized dietary intakes. As in genome-wide association studies, correction for multiple comparisons was applied using the false discovery rate (FDR < 5%) method and suggested results were replicated in an independent cohort, the Netherlands Cohort Study (NLCS).
RESULTS:
A total of 5916 and 3842 incident cases of prostate cancer were diagnosed during a mean follow-up of 14 and 20 years in EPIC and NLCS, respectively. None of the dietary factors was associated with the risk of total prostate cancer in EPIC (minimum FDR-corrected P, 0.37). Null associations were also observed by disease stage, grade and fatality, except for positive associations observed for intake of dry cakes/biscuits with low-grade and butter with aggressive prostate cancer, respectively, out of which the intake of dry cakes/biscuits was replicated in the NLCS.
CONCLUSIONS:
Our findings provide little support for an association for the majority of the 92 examined dietary factors and risk of prostate cancer. The association of dry cakes/biscuits with low-grade prostate cancer warrants further replication given the scarcity in the literature.
KEYWORDS:
Cohort study; Diet; Epidemiology; Nutrition; Prostate cancer

Modifiable risk and protective factors in disease development, progression and clinical subtypes of Parkinson's disease: What do prospective studies suggest?
Belvisi D, Pellicciari R, Fabbrini G, Tinazzi M, Berardelli A, Defazio G.
Neurobiol Dis. 2019 Nov 6:104671. doi: 10.1016/j.nbd.2019.104671. [Epub ahead of print] Review.
PMID: 31706021
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder whose pathogenesis depends on a combination of genetic and environmental factors. The aim of the present review was to provide an updated description of the findings emerging from prospective longitudinal cohort studies on the possible risk/protective factors underlying the development, progression and clinical subtypes of PD. We reviewed all the environmental, lifestyle, dietary, comorbid and pharmacological factors that have been investigated as possible modifiable protective/risk factors for PD by longitudinal studies. Only a few factors have the epidemiological evidence and the biological plausibility to be considered risk (pesticides, dairy products, β2-adrenoreceptor antagonists) or protective (smoking, caffeine and tea intake, physical activity, gout, vitamin E intake, non-steroidal anti-inflammatory drugs and β2-adrenoreceptor agonists) factors for PD. Caffeine intake and physical activity also seem to slow down the progression of the disease, thus representing good candidates for primary prevention and disease modifying strategies in PD. Possible modifiable risk factors of PD subtypes is almost unknown and this might depend on the uncertain biological and neuropathological reliability of clinical subtypes. The results of the present review suggest that only eleven risk/protective factors may be associated with the risk of PD. It may be possible to target some of these factors for preventive interventions aimed at reducing the risk of developing and the rate of progression of PD.
KEYWORDS:
Parkinson's disease; Progression; Protective factor; Risk factor; Subtype

Association between hand-grip strength and site-specific risks of major osteoporotic fracture: Results from the Japanese Population-based Osteoporosis Cohort Study.
Kamiya K, Kajita E, Tachiki T, Ikehara S, Kouda K, Sato Y, Tamaki J, Kagamimori S, Iki M.
Maturitas. 2019 Dec;130:13-20. doi: 10.1016/j.maturitas.2019.09.008. Epub 2019 Sep 23.
PMID: 31706431
Abstract
OBJECTIVES:
To investigate the association between hand-grip strength and site-specific risks of major osteoporotic fracture.
STUDY DESIGN:
Prospective cohort study.
MAIN OUTCOME:
Associations between low hand-grip strength and increased risk of fracture at the distal forearm, vertebrae, and hip.
MEASURES:
We enrolled 1342 postmenopausal women aged 50 years or more into baseline and follow-up surveys of the Japanese Population-based Osteoporosis Cohort Study in 1996, 1999, 2002, or 2006. Fracture events were ascertained by follow-up surveys until 2011 or 2012. The Cox proportional hazards model was used to estimate hazard ratios (HRs) of hand-grip strength on fracture event.
RESULTS:
During a median follow-up of 15.2 years, 162 women sustained at least one osteoporotic fracture and 135 of these women sustained at least one major osteoporotic fracture, the larger group including 65, 38, 35, and 8 women with fractures of the distal forearm, vertebrae, hip, and proximal humerus, respectively. In the crude models, the associations between low hand-grip strength and increased risk of fracture at the distal forearm, vertebrae, and hip were significant; the HRs (95% confidence interval) of the lowest tertile of hand-grip strength were 2.02 (1.10-3.71), 11.35 (4.07-31.63), and 4.72 (1.79-12.47), respectively. Age adjustment attenuated the significance of hip fracture risk, and adjusting for bone mineral density attenuated the significance of distal forearm fracture risk. After additional adjustment for body mass index, history of diabetes mellitus, and calcium intake, the HR for vertebral fracture risk was 4.55 (1.56-13.27). When limiting the follow-up period to 5 and 10 years, low hand-grip strength was associated with an increased risk of distal forearm fracture independently of the aforementioned covariates; the HRs were 4.22 (1.12-15.95) and 2.52 (1.03-6.17), respectively.
CONCLUSIONS:
Low hand-grip strength is specifically associated with the risk of distal forearm fractures within 10 years and clinical vertebral fractures within 15 years or more in Japanese postmenopausal women.
KEYWORDS:
Hand-grip strength; Osteoporotic fracture; Prospective cohort study

[AlPater]

Longitudinal associations between BMI change and the risks of colorectal cancer incidence, cancer-relate and all-cause mortality among 81,388 older adults : BMI change and the risks of colorectal cancer incidence and mortality.
Li JB, Luo S, Wong MCS, Li C, Feng LF, Peng JH, Li JH, Zhang X.
BMC Cancer. 2019 Nov 11;19(1):1082. doi: 10.1186/s12885-019-6299-4.
PMID: 31711465
https://bmccancer.biomedcentral.com/track/pdf/10.1186/s12885-019-6299-4
Abstract
BACKGROUND:
It remains controversial whether weight change could influence the risks of colorectal cancer (CRC) and mortality. This study aimed to quantify the associations between full-spectrum changes in body mass index (BMI) and the risks of colorectal cancer (CRC) incidence, cancer-related and all-cause mortality among midlife to elder population.
METHODS:
A total of 81,388 participants who were free of cancer and aged 55 to 74 years from the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening program were involved. The percentage change of BMI was calculated as (BMI in 2006 - BMI at baseline)/BMI at baseline, and was categorized into nine groups: decrease (≥ 15.0%, 10.0-14.9%, 5.0-9.9%, 2.5-4.9%), stable (decrease/increase < 2.5%), increase (2.5-4.9%, 5.0-9.9%, 10.0-14.9%, ≥ 15.0%). The associations between percentage change in BMI from study enrolment to follow-up (median: 9.1 years) and the risks of CRC and mortality were evaluated using Cox proportional hazard regression models.
RESULTS:
After 2006, there were 241 new CRC cases, 648 cancer-related deaths, and 2361 all-cause deaths identified. Overall, the associations between BMI change and CRC incidence and cancer-related mortality, respectively, were not statistically significant. Compared with participants whose BMI were stable, individuals who had a decrease in BMI were at increased risk of all-cause mortality, and the HRs were 1.21 (95% CI: 1.03-1.42), 1.65 (95% CI: 1.44-1.89), 1.84 (95% CI: 1.56-2.17), and 2.84 (95% CI: 2.42-3.35) for 2.5-4.9%, 5.0-9.9%, 10.0-14.9%, and ≥ 15.0% decrease in BMI, respectively. An L-shaped association between BMI change and all-cause mortality was observed. Every 5% decrease in BMI was associated with a 27% increase in the risk of all-cause mortality (HR = 1.27, 95% CI: 1.22-1.31, p < 0.001). The results from subgroups showed similar trends.
CONCLUSIONS:
A decrease in BMI more than 5% shows a significantly increased risk of all-cause mortality among older individuals; but no significant association between increase in BMI and all-cause mortality. These findings emphasize the importance of body weight management in older population, and more studies are warranted to evaluate the cause-and-effect relationship between changes in BMI and cancer incidence/mortality.
KEYWORDS:
BMI change; Colorectal cancer risk; Longitudinal association; Mortality; Older adults

Metabolically healthy obesity (MHO) in the Malmö diet cancer study - Epidemiology and prospective risks.
Korduner J, Bachus E, Jujic A, Magnusson M, Nilsson PM.
Obes Res Clin Pract. 2019 Nov 8. pii: S1871-403X(19)30493-4. doi: 10.1016/j.orcp.2019.10.002. [Epub ahead of print]
PMID: 31711772
Abstract
BACKGROUND/AIMS:
Metabolically healthy obesity (MHO) remains controversial, since the underlying mechanisms behind this phenotype remain unclear. We aimed to investigate the characteristics of MHO, as well as prospective risks.
METHOD:
A cross-sectional analysis was carried out in a subsample of 3812 obese subjects selected from the Malmo diet cancer study (n=28,403). Subjects with MHO (n=1182) were defined by having no records of hospitalization for somatic disorders prior to baseline examination. MHO subjects were further compared to subjects with metabolically unhealthy obesity, MUO (obese individuals with at least one recorded hospitalization: n=2630), and all non-obese cohort controls (NOC; n=24,591). Moreover, prospective risk analyses for incident cardiovascular (CV) morbidity and mortality were carried out.
RESULTS:
Compared to MUO individuals, MHO individuals reported a significantly lower proportion of sedentary life style (p=0.009), but also significantly lower HbA1c (p=0.012), fasting glucose (p=0.001) and triglyceride levels (p=0.011) than MUO. Cox-regression analysis (follow-up 20±6 years) showed both a significantly lower all-cause mortality risk for MHO individuals as compared to MUO (p=0.001), as well as lower incident CV morbidity risk (p=0.001). When comparing MHO individuals to NOC, there were no significant differences in neither mortality risk nor incident CV morbidity risk.
CONCLUSION:
Compared to MUO individuals, MHO individuals presented with a higher level of physical activity, a more favorable lipid- and glucose profile and a lower prospective risk of total mortality and CV morbidity during 20-years follow-up. Notably, no significant differences could be seen in mortality and CV morbidity risks when comparing MHO subjects to non-obese controls.
KEYWORDS:
Cardiovascular; Epidemiology; Metabolic syndrome; Morbidity; Mortality; Obesity

Midlife atherosclerosis and development of Alzheimer's or vascular dementia.
Gustavsson AM, van Westen D, Stomrud E, Engström G, Nägga K, Hansson O.
Ann Neurol. 2019 Nov 12. doi: 10.1002/ana.25645. [Epub ahead of print]
PMID: 31721283
Abstract
OBJECTIVE:
To investigate if midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies.
METHODS:
Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (n=6103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991-1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n=330), β-amyloid42 and tau were quantified in CSF and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on MRI (2009-2015).
RESULTS:
During 20 years of follow-up, 462 individuals developed dementia (mean age at baseline 57.5±5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all-cause dementia (adjusted HR 1.14 [95% CI 1.03-1.26]) and vascular dementia (adjusted HR 1.32 [1.10-1.57]), but not Alzheimer's dementia (AD) (adjusted HR 0.95 [0.77-1.17]). Carotid plaques were associated with vascular dementia when assessed as a three graded score (adjusted HR 1.90 [1.07-3.38]). In the cognitively unimpaired subcohort (53.8±4.6 years at baseline, 60% women) higher IMT in midlife was associated with development of small vessel disease (adjusted OR 1.47 [1.05-2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR 1.28 [0.87-1.90] and 1.35 [0.86-2.13]). Carotid plaques revealed no significant association with any of the underlying brain pathologies.
INTERPRETATION:
Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease, but not between atherosclerosis and subsequent AD or AD pathology. This article is protected by copyright. All rights reserved.
KEYWORDS:
dementia; intima media thickness; β-amyloid

Skeletal muscle mass in relation to 10 year cardiovascular disease incidence among middle aged and older adults: the ATTICA study.
Tyrovolas S, Panagiotakos D, Georgousopoulou E, Chrysohoou C, Tousoulis D, Haro JM, Pitsavos C.
J Epidemiol Community Health. 2019 Nov 11. pii: jech-2019-212268. doi: 10.1136/jech-2019-212268. [Epub ahead of print]
PMID: 31712252
Abstract
BACKGROUND:
Skeletal muscle mass (SMM) is inversely associated with cardiometabolic health and the ageing process. The aim of the present work was to evaluate the relation between SMM and 10 year cardiovascular disease (CVD) incidence, among CVD-free adults 45+ years old.
METHODS:
ATTICA is a prospective, population-based study that recruited 3042 adults without pre-existing CVD from the Greek general population (Caucasians; age ≥18 years; 1514 men). The 10 year study follow-up (2011-2012) captured the fatal/non-fatal CVD incidence in 2020 participants (50% men). The working sample consisted of 1019 participants, 45+ years old (men: n=534; women: n=485). A skeletal muscle mass index (SMI) was created to reflect SMM, using appendicular skeletal muscle mass (ASM) standardised by body mass index (BMI). ASM and SMI were calculated with specific indirect population formulas.
RESULTS:
The 10 year CVD incidence increased significantly across the baseline SMI tertiles (p<0.001). Baseline SMM showed a significant inverse association with the 10 year CVD incidence (HR 0.06, 95% CI 0.005 to 0.78), even after adjusting for various confounders. Additionally, participants in the highest SMM tertile had 81% (95% CI 0.04 to 0.85) lower risk for a CVD event as compared with those in the lowest SMM tertile.
CONCLUSIONS:
The presented findings support the importance of SMM evaluation in the prediction of long-term CVD risk among adults 45+ years old without pre-existing CVD. Preservation of SMM may contribute to CVD health.
KEYWORDS:
ageing; epidemiology of cardiovascular disease; physiology

Old dogs, new tricks: 10,000 pets needed for canine aging study
500 dogs will test a pill that could slow the aging process
The Associated Press · Posted: Nov 14, 2019
https://www.cbc.ca/news/health/dogs-aging-study-1.5359502

Associations of plasma high-sensitivity C-reactive protein concentrations with all-cause and cause-specific mortality among middle-aged and elderly individuals.
Li ZH, Zhong WF, Lv YB, Kraus VB, Gao X, Chen PL, Huang QM, Ni JD, Shi XM, Mao C, Wu XB.
Immun Ageing. 2019 Nov 5;16:28. doi: 10.1186/s12979-019-0168-5. eCollection 2019.
PMID: 31708993
Abstract
BACKGROUND:
The association of high-sensitivity C-reactive protein (hsCRP) with mortality is controversial. We aimed to investigate the associations of hsCRP concentrations with the risks of all-cause and cause-specific mortality and identify potential modifying factors affecting these associations among middle-aged and elderly individuals.
METHODS:
This community-based prospective cohort study included 14,220 participants aged 50+ years (mean age: 64.9 years) from the Health and Retirement Study. Cox proportional hazard models were employed to estimate the associations between the hsCRP concentrations and the risk of all-cause and cause-specific mortality with adjustment for sociodemographic and lifestyle factors, self-reported medical history, and other potential confounders.
RESULTS:
In total, 1730 all-cause deaths were recorded, including 725 cardiovascular- and 417 cancer-related deaths, after an 80,572 person-year follow-up (median: 6.4 years; range: 3.6-8.1 years). The comparisons of the groups with the highest (quartile 4) and lowest (quartile 1) hsCRP concentrations revealed that the adjusted hazard ratios and 95% confidence intervals were 1.50 (1.31-1.72) for all-cause mortality, 1.44 (1.13-1.82) for cardiovascular mortality, and 1.67 (1.23-2.26) for cancer mortality. The associations between high hsCRP concentrations and the risks of all-cause, cardiovascular, and cancer mortality were similar in the men and women (P for interaction > 0.05).
CONCLUSIONS:
Among middle-aged and older individuals, elevated hsCRP concentration could increase the risk of all-cause, cardiovascular, and cancer mortality in men and women.
KEYWORDS:
All-cause mortality; Cancer mortality; Cardiovascular mortality; High-sensitivity C-reactive protein

Cardiorespiratory fitness, muscular strength, and obesity in adolescence and later chronic disability due to cardiovascular disease: a cohort study of 1 million men.
Henriksson H, Henriksson P, Tynelius P, Ekstedt M, Berglind D, Labayen I, Ruiz JR, Lavie CJ, Ortega FB.
Eur Heart J. 2019 Nov 9. pii: ehz774. doi: 10.1093/eurheartj/ehz774. [Epub ahead of print]
PMID: 31710669
https://watermark.silverchair.com/ehz774.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAoMwggJ_BgkqhkiG9w0BBwagggJwMIICbAIBADCCAmUGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMMDqAfrecWfVEBHYVAgEQgIICNioI9TtQTXvCw7Ipv6bB-NRnQaXtykQu8tFlxSHKUBoNVbZ-DXgAMg7VyZpOzxMY_mllPb43QeyqIkcDepvM4euAu99ESMZwHvoeG0vkP4c-w_sAsiEmoD9xoHlgUnVFJly0KQrTThrBa65hjTuPS-qbp2Ph972jgTOjzdWnS4xGUtlw02zoqqNhPy0T-ZByt6H8Oz6BXlsWJ7RZ4NYrARo3uagu3FnXFWCStwPriYEwKg8ypYxz8iwhqzsAa5lksgPheeG7OGReCmlmsyQhiHEpJhozU2Tv0lmnZEpjLzMrYVQ5KNTCfQOzDnkTQt9jZoLy4sT1DqPoIXhgu7G8gVFnCuDom6g9DhZuXUnuGEdG5q0HyfYTVURI_6J3tn8jZxGl8EN6feq0Z47r8FJmI2zKQsJr1dzVJYgl72TkVTWip9J5Tl3W4eJ7O2-9BIm0_JA_-hD6WhsOXEahNg3IhKyGEyGh70XfjuAnjso6kokYNUTYA7tYzILn_5cc7wETvyAuxsHtCeTuOZHvh6FGBjSecaVV7XksS3sWuX8ot30TkGrV8OQ1Jl-JBT5gHYytw4P-_ZyX12GQHIHbfOIHmhLz1dDjQILYUlt9ppwfRTsCDi-TqkWGwcavS3ukaw3hnovno4mzDZRZlTr2vvYbONvI-gzEwsz2NKeXAZyOM0B0dlIBXtRUfS2JHlYmR1SFCNm9ytVO6kw9MQmIbMfiQcopfrRNTUb__nfng8eW_Ksty6WBd13P
Abstract
AIMS:
Cardiorespiratory fitness, muscular strength, and obesity in adulthood are risk factors for cardiovascular disease (CVD). However, little is known regarding the associations of these risk factors, already in adolescence, with later disability due to chronic CVD. Hence, we investigated associations of cardiorespiratory fitness, muscular strength, and body mass index (BMI) in adolescence with later chronic disability due to specific causes of CVD disability (i.e. cerebrovascular disease, ischaemic heart disease and heart failure).
METHODS AND RESULTS:
This population-based cohort study included 1 078 685 male adolescents (16-19 years) from the Swedish military conscription register from 1972 to 1994. Cardiorespiratory fitness (bicycle ergometer test), muscular strength (knee extension strength), and BMI were measured during the conscription examination. Information about disability pension due to CVD was retrieved from the Social Insurance Agency during a mean follow-up of 28.4 years. Cardiorespiratory fitness was strongly and inversely associated with later risk of chronic CVD disability for all investigated causes. The association was particularly strong for ischaemic heart diseases (hazard ratio 0.11, 95% confidence interval 0.05-0.29 for highest vs. lowest fitness-quintiles). Furthermore, overweight/obesity were associated with CVD disability for all investigated causes. Conversely, associations of muscular strength with CVD disability were generally weak.
CONCLUSIONS:
This study provides evidence for associations between low levels of cardiorespiratory fitness and obesity with later risk of chronic disability due to CVD. Preventive actions may begin at young ages and include promotion of cardiorespiratory fitness and healthy body weight.
KEYWORDS:
Cardiorespiratory fitness; Cardiovascular disease; Disability; Muscular strength; Obesity

10 Intermittent Fasting Side Effects That Might Mean It’s Not A Great Fit For You
It's trendy, but that doesn't mean IF comes without downsides.
BY SARAH BRADLEY
NOV 11, 2019
https://www.womenshealthmag.com/weight-loss/a29657614/intermittent-fasting-side-effects/

[AlPater]

Plant-Based Dietary Patterns, Plant Foods, and Age-Related Cognitive Decline.
Rajaram S, Jones J, Lee GJ.
Adv Nutr. 2019 Nov 1;10(Supplement_4):S422-S436. doi: 10.1093/advances/nmz081.
PMID: 3172850
https://academic.oup.com/advances/article-abstract/10/Supplement_4/S422/5624068?redirectedFrom=fulltext
Abstract
The aging population is expanding, as is the prevalence of age-related cognitive decline (ARCD). Of the several risk factors that predict the onset and progression of ARCD, 2 important modifiable risk factors are diet and physical activity. Dietary patterns that emphasize plant foods can exert neuroprotective effects. In this comprehensive review, we examine studies in humans of plant-based dietary patterns and polyphenol-rich plant foods and their role in either preventing ARCD and/or improving cognitive function. As yet, there is no direct evidence to support the benefits of a vegetarian diet in preventing cognitive decline. However, there is emerging evidence for brain-health-promoting effects of several plant foods rich in polyphenols, anti-inflammatory dietary patterns, and plant-based dietary patterns such as the Mediterranean diet that include a variety of fruits, vegetables, legumes, nuts, and whole grains. The bioactive compounds present in these dietary patterns include antioxidant vitamins, polyphenols, other phytochemicals, and unsaturated fatty acids. In animal models these nutrients and non-nutrients have been shown to enhance neurogenesis, synaptic plasticity, and neuronal survival by reducing oxidative stress and neuroinflammation. In this review, we summarize the mounting evidence in favor of plant-centered dietary patterns, inclusive of polyphenol-rich foods for cognitive well-being. Randomized clinical trials support the role of plant foods (citrus fruits, grapes, berries, cocoa, nuts, green tea, and coffee) in improving specific domains of cognition, most notably frontal executive function. We also identify knowledge gaps and recommend future studies to identify whether plant-exclusive diets have an added cognitive advantage compared with plant-centered diets with fish and/or small amounts of animal foods.
KEYWORDS:
berries; cognition; cognitive decline; elderly; nuts; plant-based dietary pattern; polyphenols; vegetarian diet; walnuts

Associations between Dietary Pulses Alone or with Other Legumes and Cardiometabolic Disease Outcomes: An Umbrella Review and Updated Systematic Review and Meta-analysis of Prospective Cohort Studies.
Viguiliouk E, Glenn AJ, Nishi SK, Chiavaroli L, Seider M, Khan T, Bonaccio M, Iacoviello L, Mejia SB, Jenkins DJA, Kendall CWC, Kahleová H, Rahelić D, Salas-Salvadó J, Sievenpiper JL.
Adv Nutr. 2019 Nov 1;10(Supplement_4):S308-S319. doi: 10.1093/advances/nmz113.
PMID: 31728500
Abstract
To update the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy, we conducted an umbrella review and updated systematic review and meta-analysis (SRMA) of prospective cohort studies of the association between dietary pulses with or without other legumes and cardiometabolic disease outcomes. We searched the PubMed, MEDLINE, EMBASE, and Cochrane databases through March 2019. We included the most recent SRMAs of prospective cohort studies and new prospective cohort studies published after the census dates of the included SRMAs assessing the relation between dietary pulses with or without other legumes and incidence and mortality of cardiovascular diseases (CVDs) [including coronary heart disease (CHD), myocardial infarction (MI), and stroke], diabetes, hypertension, and/or obesity. Two independent reviewers extracted data and assessed risk of bias. Risk estimates were pooled using the generic inverse variance method and expressed as risk ratios (RRs) with 95% CIs. The overall certainty of the evidence was assessed using the GRADE approach. Six SRMAs were identified and updated to include 28 unique prospective cohort studies with the following number of cases for each outcome: CVD incidence, 10,261; CVD mortality, 16,168; CHD incidence, 7786; CHD mortality, 3331; MI incidence, 2585; stroke incidence, 8570; stroke mortality, 2384; diabetes incidence, 10,457; hypertension incidence, 83,284; obesity incidence, 8125. Comparing the highest with the lowest level of intake, dietary pulses with or without other legumes were associated with significant decreases in CVD (RR: 0.92; 95% CI: 0.85, 0.99), CHD (RR: 0.90; 95% CI: 0.83, 0.99), hypertension (RR: 0.91; 95% CI: 0.86, 0.97), and obesity (RR: 0.87; 95% CI: 0.81, 0.94) incidence. There was no association with MI, stroke, and diabetes incidence or CVD, CHD, and stroke mortality. The overall certainty of the evidence was graded as "low" for CVD incidence and "very low" for all other outcomes. Current evidence shows that dietary pulses with or without other legumes are associated with reduced CVD incidence with low certainty and reduced CHD, hypertension, and obesity incidence with very low certainty. More research is needed to improve our estimates.
KEYWORDS:
GRADE; cardiovascular disease; diabetes; hypertension; legumes; meta-analysis; obesity; prospective cohort; pulses; systematic review

Animal and Plant Protein Sources and Cardiometabolic Health.
Mariotti F.
Adv Nutr. 2019 Nov 1;10(Supplement_4):S351-S366. doi: 10.1093/advances/nmy110.
PMID: 31728490
https://academic.oup.com/advances/article/10/Supplement_4/S351/5624056
Abstract
The sources or types of protein in the diet have long been overlooked regarding their link to cardiometabolic health. The picture is complicated by the fact that animal and plant proteins are consumed along with other nutrients and substances which make up the "protein package" so plant and animal protein come with clear nutrient clusters. This review aimed at deciphering the relation between plant and animal protein and cardiometabolic health by examining different nutritional levels (such as amino acids, protein type, protein foods, protein patterns, and associated overall dietary and nutrient patterns) and varying levels of scientific evidence [basic science, randomized controlled trials (RCTs), observational data]. Plant protein in Western countries is a robust marker of nutrient adequacy of the diet, whereas the contribution of animal protein is highly heterogeneous. Yet recent data from large cohorts have confirmed that total and animal proteins are associated with the risk of cardiovascular disease and diabetes, even when fully adjusting for lifestyle and dietary or nutritional factors. Here again, there is marked variability depending on the type of animal protein. Protein from processed red meat and total red meat on the one hand, and from legumes, nuts, and seeds on the other, are often reported at the extremes of the risk range. RCTs using purified proteins have contributed little to the topic to date, inasmuch as the findings cannot readily be extrapolated to current or near-future diets, but RCTs studying whole protein foods have shown a beneficial effect of pulses. Despite the fact that many of the benefits of plant protein reported in observational or interventional studies may stem from the protein package that they convey and the nutrients that they displace, there are also important indications that protein per se may affect cardiometabolic health via the many amino acids that are present in typically contrasting levels in plant compared with animal proteins.
KEYWORDS:
animal protein; cardiometabolic health; plant protein; cardiovascular risk; diabetes; protein sources; protein patterns; amino acids

Plant-Rich Dietary Patterns, Plant Foods and Nutrients, and Telomere Length.
Crous-Bou M, Molinuevo JL, Sala-Vila A.
Adv Nutr. 2019 Nov 1;10(Supplement_4):S296-S303. doi: 10.1093/advances/nmz026.
PMID: 31728493
Abstract
The world's population is aging as a consequence of an increased global life expectancy. Identifying simple strategies to promote healthy aging (i.e., absence of major chronic diseases, preserved physical and cognitive functions, intact mental health, and good quality of life) have emerged as a major public health concern. Identifying biomarkers to better characterize the aging process is a research priority. Telomeres are repetitive DNA sequences at chromosome ends that prevent the loss of genomic DNA, protecting its physical integrity. Telomere length (TL) is considered a biomarker of aging: shorter telomeres are associated with a decreased life expectancy and increased rates of age-related chronic diseases. Telomere attrition has been shown to be accelerated by oxidative stress and inflammation. Since edible plants contain plenty of compounds with antioxidant and anti-inflammatory properties, it is plausible that their sustained consumption might help counteract telomere attrition. In this narrative review, we update evidence on the association between plant-rich dietary patterns and plant-based foods and TL. First, we summarize findings from observational studies on the association between TL and 1) adherence to plant-rich dietary patterns (mainly, but not only, focused on the Mediterranean diet); 2) consumption of seeds (mostly focused on nuts, grains, and coffee); and 3) intake of carotenoids, one of the plant-derived bioactives most studied in health and disease. Second, we summarize the main randomized controlled trials evaluating the effect on TL of dietary interventions involving either plant-rich dietary patterns or plant foods. Even though evidence from trials is very limited, several observational studies have reinforced the suggestive benefits of adherence to the Mediterranean diet (a plant-rich dietary pattern), consumption of seeds (and its derivatives), and dietary intake of carotenoids on TL, which further supports the research benefits of plant-rich dietary patterns and plant foods to promote health and longevity.
KEYWORDS:
Mediterranean diet; aging; carotenoids; plant foods; seeds; telomeres

Subclinical hypothyroidism and cardiovascular risk factors.
Delitala AP, Scuteri A, Maioli M, Mangatia P, Vilardi L, Erre GL.
Minerva Med. 2019 Nov 11. doi: 10.23736/S0026-4806.19.06292-X. [Epub ahead of print]
PMID: 31726814
https://sci-hub.tw/10.1089/thy.2017.0414
Abstract
INTRODUCTION:
Thyroid hormones have multiple effects on lipid metabolism as well as on the cardiovascular system function. These negative cardiovascular effects have long been recognized in overt hypothyroidism but can be reversed by treatment with levothyroxine.
EVIDENCES ACQUISITION:
We performed on PubMed a literature search for the articles published until March 2019 by using the search terms 'subclinical hypothyroidism', 'cardiovascular disease', 'cholesterol', 'LDL', 'HDL', 'Triglycerides', 'coronary heart disease', 'heart failure', 'atherosclerosis', 'all-cause mortality', 'Levothyroxine'.
EVIDENCES SYNTHESIS:
Subclinical hypothyroidism, defined as an elevated thyrotropin (TSH) with a normal free thyroxine (FT4), is frequent in the general population and increase with age. Subclinical hypothyroidism has been linked to cardiovascular risk factors, dyslipidemia and increased atherosclerosis. Although some studies have demonstrated that lipids are elevated in subclinical hypothyroidism, other studies did not confirm these data. Clinical trials have also demonstrated there is no clear evidence that levothyroxine therapy in subjects with milder form (TSH< 10 mU/L) of subclinical hypothyroidism could improve lipid status and the other cardiovascular risk factors. Nevertheless, TSH level seems the best predictor of cardiovascular disease, in particular when its levels are above 10 mU/L.
CONCLUSIONS:
Prospective studies are necessary to clarify the cardiovascular risk in patients with mild subclinical hypothyroidism and to assess the importance of treating elderly people in order to improve or counteract the correlated risks. However, until clinical recommendations will be updated, the decision to treat or not treat patients with subclinical hypothyroidism will still base on clinical judgment, clinical practice guidelines, and expert opinion.

Methionine restriction delays aging-related urogenital diseases in male Fischer 344 rats.
Komninou D, Malloy VL, Zimmerman JA, Sinha R, Richie JP Jr.
Geroscience. 2019 Nov 14. doi: 10.1007/s11357-019-00129-4. [Epub ahead of print]
PMID: 31728897
Abstract
Dietary methionine restriction (MR) has been found to enhance longevity across many species. We hypothesized that MR might enhance longevity in part by delaying or inhibiting age-related disease processes. To this end, male Fischer 344 rats were fed control (CF, 0.86% methionine) or MR (0.17% methionine) diets throughout their life until sacrifice at approximately 30 months of age, and histopathology was performed to identify the incidence and progression of two important aging-related pathologies, namely, chronic progressive nephropathy (CPN) and testicular tumorigenesis. Although kidney pathology was observed in 87% CF rats and CPN in 62% of CF animals, no evidence of kidney disease was observed in MR rats. Consistent with the absence of renal pathology, urinary albumin levels were lower in the MR group compared to controls throughout the study, with over a six-fold difference between the groups at 30 months of age. Biomarkers associated with renal disease, namely, clusterin, cystatin C, and β-2 microglobulin, were reduced following 18 months of MR. A reduction in testicular tumor incidence from 88% in CF to 22% in MR rats was also observed. These results suggest that MR may lead to metabolic and cellular changes providing protection against age-related diseases.
KEYWORDS:
Aging; Metabolic changes; Methionine restriction; Nephropathy; Testicular cancer

[AlPater]

Dietary Protein Consumption and the Risk of Type 2 Diabetes: ADose-Response Meta-Analysis of Prospective Studies.
Fan M, Li Y, Wang C, Mao Z, Zhou W, Zhang L, Yang X, Cui S, Li L.
Nutrients. 2019 Nov 15;11(11). pii: E2783. doi: 10.3390/nu11112783. Review.
PMID: 31731672
Abstract
The relationship between dietary protein consumption and the risk of type 2 diabetes (T2D) has been inconsistent. The aim of this meta-analysis was to explore the relations between dietary protein consumption and the risk of T2D. We conducted systematic retrieval of prospective studies in PubMed, Embase, and Web of Science. Summary relative risks were compiled with a fixed effects model or a random effects model, and a restricted cubic spline regression model and generalized least squares analysis were used to evaluate the diet-T2D incidence relationship. T2D risk increased with increasing consumption of total protein and animal protein, red meat, processed meat, milk, and eggs, respectively, while plant protein and yogurt had an inverse relationship. A non-linear association with the risk for T2D was found for the consumption of plant protein, processed meat, milk, yogurt, and soy. This meta-analysis suggests that substitution of plant protein and yogurt for animal protein, especially red meat and processed meat, can reduce the risk for T2D.
KEYWORDS:
diet; dose-response; meta-analysis; protein; type 2 diabetes

Principal Results of the VITamin D and OmegA-3 TriaL (VITAL) and Updated Meta-analyses of Relevant Vitamin D Trials.
Manson JE, Bassuk SS, Buring JE; VITAL Research Group.
J Steroid Biochem Mol Biol. 2019 Nov 13:105522. doi: 10.1016/j.jsbmb.2019.105522. [Epub ahead of print] Review.
PMID: 31733345
Abstract
Whether supplemental vitamin D reduces risk of cancer or cardiovascular disease (CVD) is relatively unexplored in randomized trial settings. The VITamin D and OmegA-3 TriaL (VITAL) was a nationwide, randomized, placebo-controlled, 2 × 2 factorial trial of daily vitamin D3 (2000 IU) and marine omega-3 fatty acids (1 g) in the primary prevention of cancer and CVD among 25,871 U.S. men aged ≥50 and women aged ≥55, including 5,106 African Americans. Median treatment duration was 5.3 years. Vitamin D did not significantly reduce the primary endpoint of total invasive cancer incidence (hazard ratio {HR} = 0.96 [95% confidence interval 0.88-1.06]) but showed a promising signal for reduction in total cancer mortality (HR = 0.83 [0.67-1.02]), especially in analyses that accounted for latency by excluding the first year (HR = 0.79 [0.63-0.99]) or first 2 years (HR = 0.75 [0.59-0.96]) of follow-up. Vitamin D did not significantly reduce the co-primary endpoint of major CVD events (HR = 0.97 [0.85-1.12]), other cardiovascular endpoints, or all-cause mortality (HR = 0.99 [0.87-1.12]). Updated meta-analyses that include VITAL and other recent vitamin D trials indicate a significant reduction in cancer mortality but not in cancer incidence or CVD endpoints. Additional research is needed to determine which individuals may be most likely to derive a net benefit from vitamin D supplementation.
KEYWORDS:
cancer; cardiovascular disease; primary prevention; race and ethnicity; randomized controlled trial; vitamin D

A single dose of purple grape juice improves physical performance and antioxidant activity in runners: a randomized, crossover, double-blind, placebo study.
de Lima Tavares Toscano L, Silva AS, de França ACL, de Sousa BRV, de Almeida Filho EJB, da Silveira Costa M, Marques ATB, da Silva DF, de Farias Sena K, Cerqueira GS, da Conceição Rodrigues Gonçalves M.
Eur J Nutr. 2019 Nov 15. doi: 10.1007/s00394-019-02139-6. [Epub ahead of print]
PMID: 31732851
https://sci-hub.tw/https://link.springer.com/article/10.1007/s00394-019-02139-6
Abstract
PURPOSE:
To investigate the effects of a single dose of juice on physical performance, oxidative stress, inflammation and muscle damage in runners.
METHODS:
Fourteen recreational male runners (39 ± 9 years, VO2peak = 55.9 ± 6.5 ml/kg/min) performed two running tests to exhaustion at 80% of VO2max after ingesting grape juice or a placebo drink (10 ml/kg/day) randomly. Blood samples were taken before and 2 h after supplementation and immediately after running to analyze total antioxidant capacity (TAC), malondialdehyde (MDA), alpha-1 acid glycoprotein (A1GPA), high-sensitivity C-reactive protein (hs-CRP), creatine kinase (CK) and lactate dehydrogenase (LDH).
RESULTS:
The participants ran for an average of 59.2 ± 27.8 min until exhaustion in the placebo group and for 68.4 ± 29.7 min until exhaustion in the grape juice intake group, which was a significantly longer time (p = 0.008). This improvement in physical performance was accompanied by a 43.6% increase in TAC (p = 0.000) at the post-exercise timepoint compared to the level at baseline. MDA, A1GPA, hs-CRP, CK, and LDH did not exhibit changes. In contrast, no significant change in any variable was observed after consuming the placebo drink.
CONCLUSION:
The single-dose intake of purple grape juice demonstrated an ergogenic effect in recreational runners by increasing run time to exhaustion and increasing antioxidant activity.
KEYWORDS:
Athletic performance; Ergogenic substances; Oxidative stress; Polyphenols; Sports nutrition

Edited November 17, 2019 by AlPater

[AlPater]

Effect of flaxseed supplementation on markers of inflammation and endothelial function: A systematic review and meta-analysis.
Askarpour M, Karimi M, Hadi A, Ghaedi E, Symonds ME, Miraghajani M, Javadian P.
Cytokine. 2019 Nov 15;126:154922. doi: 10.1016/j.cyto.2019.154922. [Epub ahead of print] Review.
PMID: 31739218
Abstract
OBJECTIVES:
The rationale for the current study was to evaluate the efficacy of flaxseed supplementation on important adhesion molecules and inflammatory cytokines in adults.
METHODS:
We conducted searches of published literature in PubMed, Scopus, Web of Science, and Google Scholar databases from inception until May 2019. All randomized controlled trials (RCTs) which investigated the effects of flaxseed supplementation on the circulating concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), vascular cell adhesion protein 1 (VCAM-1), E-selectin, and intercellular adhesion molecule 1 (ICAM-1) were included in our analysis. Results were summarized using weighted mean differences (WMDs) by random-effects model.
RESULTS:
Forty eligible RCTs, including 2520 participants were identified. The results of the meta-analysis revealed flaxseed supplementation reduced the concentrations of CRP (WMD = -0.387 mg/L; 95% CI: -0.653, -0.121, p = 0.004), IL-6 (WMD = -0.154 pg/Ml; 95% CI: -0.299, -0.010, p = 0.036), and VCAM-1 (WMD = -22.809 ng/ml; 95% CI: -41.498, -4.120, p = 0.017) but had no significant effect on TNF-α (WMD = -0.077 pg/mL; 95% CI: -0.317, 0.163, p = 0.530), ICAM-1 (WMD = -8.610 ng/ml; 95% CI: -21.936, 4.716, p = 0.205), and E-selectin (WMD = -1.427 ng/ml; 95% CI: -4.074, 1.22, p = 0.291).
CONCLUSIONS:
These findings showed that flaxseed supplementation may improve some circulating concentrations of specific adhesion molecules and inflammatory cytokines. However, well-designed trials are needed to confirm the range of non-significant and/or equivocal findings.
KEYWORDS:
Endothelial function; Flaxseed; Inflammatory markers; Meta-analysis; Randomized controlled trials

Relationships between seafood consumption during pregnancy and childhood and neurocognitive development: Two systematic reviews.
Hibbeln CJR, Spiller P, Brenna JT, Golding J, Holub BJ, Harris WS, Kris-Etherton P, Lands B, Connor SL, Myers G, Strain JJ, Crawford MA, Carlson SE.
Prostaglandins Leukot Essent Fatty Acids. 2019 Oct 11;151:14-36. doi: 10.1016/j.plefa.2019.10.002. [Epub ahead of print] Review.
PMID: 31739098
Abstract
Abundant data are now available to evaluate relationships between seafood consumption in pregnancy and childhood and neurocognitive development. We conducted two systematic reviews utilizing methodologies detailed by the Dietary Guidelines for Americans Scientific Advisory Committee 2020-2025. After reviewing 44 publications on 102,944 mother-offspring pairs and 25,031 children, our technical expert committee developed two conclusion statements that included the following: "Moderate and consistent evidence indicates that consumption of a wide range of amounts and types of commercially available seafood during pregnancy is associated with improved neurocognitive development of offspring as compared to eating no seafood. Overall, benefits to neurocognitive development began at the lowest amounts of seafood consumed (∼4 oz/wk) and continued through the highest amounts, above 12 oz/wk, some range up to >100 oz/wk.", "This evidence does not meet the criteria for "strong evidence" only due to a paucity of randomized controlled trials that may not be ethical or feasible to conduct for pregnancy" and "Moderate and consistent evidence indicates that consumption of >4 oz/wk and likely >12 oz/wk of seafood during childhood has beneficial associations with neurocognitive outcomes." No net adverse neurocognitive outcomes were reported among offspring at the highest ranges of seafood intakes despite associated increases in mercury exposures. Data are insufficient for conclusive statements regarding lactation, optimal amounts, categories or specific species characterized by mercury content and neurocognitive development; although there is some evidence that dark/oily seafood may be more beneficial. Research was conducted in healthy women and children and is generalizable to US populations. Assessment of seafood as a whole food integrates inherently integrates any adverse effects from neurotoxicants, if any, and benefits to neurocognition from omega-3 fats, as well as other nutrients critical to optimal neurological development. Understanding of the effects of seafood consumption on neurocognition can have significant public health implications.

[AlPater]

Meta-analysis Comparing Combined Use of Eicosapentaenoic Acid and Statin to Statin Alone.
Doshi R, Kumar A, Thakkar S, Shariff M, Adalja D, Doshi A, Taha M, Gupta R, Desai R, Shah J, Gullapalli N.
Am J Cardiol. 2019 Oct 26. pii: S0002-9149(19)31155-5. doi: 10.1016/j.amjcard.2019.10.009. [Epub ahead of print]
PMID: 31740020
Abstract
Role of omega-3-Fatty acids, especially eicosapentaenoic acid (EPA), in reducing cardiovascular events is not clear. We conducted a meta-analysis including trial sequential analysis (TSA) of all available randomized controlled trials (RCTs) assessing the impact of EPA + statin on cardiovascular risk reduction. The aim is to appraise cardiovascular risk reduction with EPA and statin taken together. A comprehensive search of PubMed and EMBASE databases was conducted for all RCTs that compared EPA + Statin versus statin alone and included outcomes related to cardiovascular health. We calculated a comprehensive odds ratio (ORs) and 95% confidence intervals (CIs) using a random-effects model. We included 5 RCTs totaling 27,415 patients. Our results demonstrated that EPA + statin resulted in 18% reduction in the incidence of MACE (OR = 0.78; 95% CI: 0.65 to 0.93, I2 = 54%, p value <0.01) and 30% reduction in myocardial infarction (MI) (OR = 0.71; 95% CI: 0.61 to 0.82, I2 = 0% p value <0.01) as compared with statin alone. With respect to MACE, the number needed to treat was 49. The statistical significance for reduction in the incidence of MACE with EPA+ statin was further augmented with trial sequential analysis. However, combined therapy of EPA + statin demonstrated no significant association on incidence of stroke when compared with statin alone or all-cause mortality. In conclusion, this meta-analysis demonstrated that EPA significantly reduced the incidence of MACE when combined with statin therapy, which is mainly driven by a significant reduction in myocardial infarction.

[AlPater]

Calorie Restriction in Adulthood Reduces Hepatic Disorders Induced by Transient Postnatal Overfeeding in Mice.
Yzydorczyk C, Li N, Rigal E, Chehade H, Mosig D, Armengaud JB, Rolle T, Krishnasamy A, Orozco E, Siddeek B, Juvet C, Vergely C, Simeoni U.
Nutrients. 2019 Nov 16;11(11). pii: E2796. doi: 10.3390/nu11112796.
PMID: 31744052
Abstract
Impaired early nutrition influences the risk of developing metabolic disorders in later life. We observed that transient postnatal overfeeding (OF) in mice induces long-term hepatic alterations, characterized by microsteatosis, fibrosis associated with oxidative stress (OS), and stress-induced premature senescence (SIPS). In this study, we investigated whether such changes can be reversed by moderate calorie restriction (CR). C57BL/6 male mice pups were maintained during lactation in litters adjusted to nine pups in the normal feeding (NF) group and three pups in the transient postnatal OF group. At six months of age, adult mice from the NF and OF groups were randomly assigned to an ad libitum diet or CR (daily energy supply reduced by 20%) for one month. In each group, at the age of seven months, analysis of liver structure, liver markers of OS (superoxide anion, antioxidant defenses), and SIPS (lipofuscin, p53, p21, p16, pRb/Rb, Acp53, sirtuin-1) were performed. CR in the OF group reduced microsteatosis, decreased levels of superoxide anion, and increased protein expression of catalase and superoxide dismutase. Moreover, CR decreased lipofuscin staining, p21, p53, Acp53, and p16 but increased pRb/Rb and sirtuin-1 protein expression. CR did not affect the NF group. These results suggest that CR reduces hepatic disorders induced by OF.
KEYWORDS:
DOHaD; developmental programming; liver; oxidative stress; reversibility; stress-induced premature senescence

[AlPater]

Sub-Chronic Consumption of Dark Chocolate Enhances Cognitive Function and Releases Nerve Growth Factors: A Parallel-Group Randomized Trial.
Sumiyoshi E, Matsuzaki K, Sugimoto N, Tanabe Y, Hara T, Katakura M, Miyamoto M, Mishima S, Shido O.
Nutrients. 2019 Nov 16;11(11). pii: E2800. doi: 10.3390/nu11112800.
PMID: 31744119
Abstract
Previous research has shown that habitual chocolate intake is related to cognitive performance and that frequent chocolate consumption is significantly associated with improved memory. However, little is known about the effects of the subchronic consumption of dark chocolate (DC) on cognitive function and neurotrophins. Eighteen healthy young subjects (both sexes; 20-31 years old) were randomly divided into two groups: a DC intake group (n = 10) and a cacao-free white chocolate (WC) intake group (n = 8). The subjects then consumed chocolate daily for 30 days. Blood samples were taken to measure plasma levels of theobromine (a methylxanthine most often present in DC), nerve growth factor (NGF), and brain-derived neurotrophic factor, and to analyze hemodynamic parameters. Cognitive function was assessed using a modified Stroop color word test and digital cancellation test. Prefrontal cerebral blood flow was measured during the tests. DC consumption increased the NGF and theobromine levels in plasma, enhancing cognitive function performance in both tests. Interestingly, the DC-mediated enhancement of cognitive function was observed three weeks after the end of chocolate intake. WC consumption did not affect NGF and theobromine levels or cognitive performance. These results suggest that DC consumption has beneficial effects on human health by enhancing cognitive function.
KEYWORDS:
Stroop color word test; cognitive function; dark chocolate; digital cancellation test; nerve growth factor; subchronic effect; theobromine; young-adult

[AlPater]

Relationship of household salt intake level with long-term all-cause and cardiovascular disease mortality in Japan: NIPPON DATA80.
Shima A, Miyamatsu N, Miura K, Miyagawa N, Okuda N, Yoshita K, Kadota A, Suzuki H, Kondo K, Okamura T, Okayama A, Ueshima H; NIPPON DATA80 Research Group.
Hypertens Res. 2019 Nov 21. doi: 10.1038/s41440-019-0349-9. [Epub ahead of print]
PMID: 31748704
Abstract
In Asian countries, a major source of salt intake is from seasoning or table salt added at home. However, little is known about the adverse effects of salt intake evaluated according to household unit. We investigated the relationship between household salt intake level and mortality from all-cause and cardiovascular diseases (CVDs). Participants included 8702 individuals (56% women) who were living with someone else and who were aged 30-79 years and enrolled in the National Nutritional Survey of Japan in 1980 with a 24-year follow-up. Household nutrient intake was evaluated using a 3-day weighing record method in which all foods and beverages consumed by any of the household members were recorded. The household salt intake level was defined as the amount of salt consumed (g) per 1000 kcal of total energy intake in each household, and its average was 6.25 (2.02) g/1000 kcal. During the follow-up, there were 2360 deaths (787 CVD, 168 coronary heart disease [CHD], and 361 stroke). Cox proportional hazard ratios (HRs) for an increment of 2 g/1000 kcal in household salt intake were calculated and adjusting for sex, age, body mass index, smoking status, alcohol consumption status, self-reported work exertion level, household potassium intake, household saturated fatty acid intake, and household long-chain n-3 polyunsaturated fatty acid intake. The HRs (95% confidence intervals) were 1.07 (1.02, 1.12) for all-cause mortality, 1.11 (1.03, 1.19) for CVD, 1.25 (1.08, 1.44) for CHD, and 1.12 (1.00, 1.25) for stroke. The household salt intake level was significantly associated with long-term risk of all-cause, CVD, CHD, and stroke mortality in a representative Japanese population.
KEYWORDS:
Cardiovascular diseases; Cohort study; Household; Salt intake

[AlPater]

Exercise Mitigates the Loss of Muscle Mass by Attenuating the Activation of Autophagy during Severe Energy Deficit.
Martin-Rincon M, Pérez-López A, Morales-Alamo D, Perez-Suarez I, de Pablos-Velasco P, Perez-Valera M, Perez-Regalado S, Martinez-Canton M, Gelabert-Rebato M, Juan-Habib JW, Holmberg HC, Calbet JAL.
Nutrients. 2019 Nov 19;11(11). pii: E2824. doi: 10.3390/nu11112824.
PMID: 31752260
Abstract
The loss of skeletal muscle mass with energy deficit is thought to be due to protein breakdown by the autophagy-lysosome and the ubiquitin-proteasome systems. We studied the main signaling pathways through which exercise can attenuate the loss of muscle mass during severe energy deficit (5500 kcal/day). Overweight men followed four days of caloric restriction (3.2 kcal/kg body weight day) and prolonged exercise (45 min of one-arm cranking and 8 h walking/day), and three days of control diet and restricted exercise, with an intra-subject design including biopsies from muscles submitted to distinct exercise volumes. Gene expression and signaling data indicate that the main catabolic pathway activated during severe energy deficit in skeletal muscle is the autophagy-lysosome pathway, without apparent activation of the ubiquitin-proteasome pathway. Markers of autophagy induction and flux were reduced by exercise primarily in the muscle submitted to an exceptional exercise volume. Changes in signaling are associated with those in circulating cortisol, testosterone, cortisol/testosterone ratio, insulin, BCAA, and leucine. We conclude that exercise mitigates the loss of muscle mass by attenuating autophagy activation, blunting the phosphorylation of AMPK/ULK1/Beclin1, and leading to p62/SQSTM1 accumulation. This includes the possibility of inhibiting autophagy as a mechanism to counteract muscle loss in humans under severe energy deficit.
KEYWORDS:
autophagy-lysosome; caloric restriction; protein degradation; skeletal muscle; ubiquitin-proteasome
>>>>>>>>>>>>>>>>
Exercise Preserves Lean Mass and Performance during Severe Energy Deficit: The Role of Exercise Volume and Dietary Protein Content.
Calbet JAL, Ponce-González JG, Calle-Herrero J, Perez-Suarez I, Martin-Rincon M, Santana A, Morales-Alamo D, Holmberg HC.
Front Physiol. 2017 Jul 24;8:483. doi: 10.3389/fphys.2017.00483. eCollection 2017.
PMID: 28790922 Free PMC Article
Abstract
The loss of fat-free mass (FFM) caused by very-low-calorie diets (VLCD) can be attenuated by exercise. The aim of this study was to determine the role played by exercise and dietary protein content in preserving the lean mass and performance of exercised and non-exercised muscles, during a short period of extreme energy deficit (~23 MJ deficit/day). Fifteen overweight men underwent three consecutive experimental phases: baseline assessment (PRE), followed by 4 days of caloric restriction and exercise (CRE) and then 3 days on a control diet combined with reduced exercise (CD). During CRE, the participants ingested a VLCD and performed 45 min of one-arm cranking followed by 8 h walking each day. The VLCD consisted of 0.8 g/kg body weight/day of either whey protein (PRO, n = 😎 or sucrose (SU, n = 7). FFM was reduced after CRE (P < 0.001), with the legs and the exercised arm losing proportionally less FFM than the control arm [57% (P < 0.05) and 29% (P = 0.05), respectively]. Performance during leg pedaling, as reflected by the peak oxygen uptake and power output (Wpeak), was reduced after CRE by 15 and 12%, respectively (P < 0.05), and recovered only partially after CD. The deterioration of cycling performance was more pronounced in the whey protein than sucrose group (P < 0.05). Wpeak during arm cranking was unchanged in the control arm, but improved in the contralateral arm by arm cranking. There was a linear relationship between the reduction in whole-body FFM between PRE and CRE and the changes in the cortisol/free testosterone ratio (C/FT), serum isoleucine, leucine, tryptophan, valine, BCAA, and EAA (r = -0.54 to -0.71, respectively, P < 0.05). C/FT tended to be higher in the PRO than the SU group following CRE (P = 0.06). In conclusion, concomitant low-intensity exercise such as walking or arm cranking even during an extreme energy deficit results in remarkable preservation of lean mass. The intake of proteins alone may be associated with greater cortisol/free testosterone ratio and is not better than the ingestion of only carbohydrates for preserving FFM and muscle performance in interventions of short duration.
KEYWORDS:
VLCD; exercise; obesity; sucrose; very-low-calorie diet; whey protein

Rejuvenating subventricular zone neurogenesis in the aging brain.
Cutler RR, Kokovay E.
Curr Opin Pharmacol. 2019 Nov 19;50:1-8. doi: 10.1016/j.coph.2019.10.005. [Epub ahead of print] Review.
PMID: 31756641
https://www.sciencedirect.com/science/article/pii/S147148921930102X?via%3Dihub
Abstract
Neural stem cells exist in specialized regions of the brain and have the capacity to give rise to neurons and glia over the lifespan. The process of giving rise to new neurons, also known as neurogenesis, is thought to be important in cognition and certain types of brain repair. However, during aging, neural stem cell number and function is reduced resulting in fewer new neurons and declines in learning, memory and repair. Recently, research has approached this problem through the lens of rejuvenation that now has produced several strategies, from dietary to pharmacological interventions, to restore functional neurogenesis that resembles the youthful brain. Here, we outline aging in the subventricular zone neurogenic niche, review the multiple modalities of rejuvenation strategies, and propose next steps for future studies to approach translational outcomes.
"The dietary interventions caloric restriction (CR) (10–40% reduction in caloric intake) and the fasting mimicking diet (FMD) (50–90% reduction in caloric intake for 4 days twice a month) are perhaps the most robust, pleiotropic, and conserved methods of longevity extension [30] and rejuvenation [31] (reviewed in Ref. [32]). In a mouse model of caloric restriction starting at 14-weeks of age, the number of NB and new neurons in the OB were preserved in the aged (12-months to 18-months) and comparable to levels of ad libitum fed young (six-month) mice. This preservation of neurogenesis resulted in olfactory memory in aged mice that was similar to young (six-month) mice [33•]. Research should follow up this result by testing whether CR started at old ages, as has been tested in humans [34], produces the same magnitude of effect, as well as determining the optimal timing for this intervention. In addition, the FMD, a more compliant diet with similar effects as CR, should also be tested for increases of neurogenesis in the aging SVZ as it has already been shown to increase neurogenesis and function in the hippocampus in 23-month old mice [31]. The LMN diet, rich in methionine-rich proteins, vitamins, and fish, is neuroprotective during aging [35]. After 5 months of feeding 18-month old mice an LMN diet, it was found that SVZ proliferation was comparable to four-month old control mice [35]."

Alcohol consumption and subclinical atherosclerosis among South Asians: Findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study.
Chevli PA, Aladin AI, Kanaya AM, Kandula NR, Malaver D, Herrington DM.
Nutr Metab Cardiovasc Dis. 2019 Jul 31. pii: S0939-4753(19)30289-3. doi: 10.1016/j.numecd.2019.07.021. [Epub ahead of print]
PMID: 31753783
Abstract
BACKGROUND:
South Asians are the second fastest growing ethnic group in the United States, and they have a high risk for cardiovascular disease (CVD). Moderate alcohol consumption has been associated with lower CVD risk in some race/ethnic groups, but the association of alcohol consumption and atherosclerosis in South Asians has not been investigated.
METHODS AND RESULTS:
We used data from 906 South Asian participants who participated in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort (2010-2012). Alcohol consumption was ascertained via questionnaire, coronary artery calcium (CAC) was measured with computed tomography, and common carotid artery intima-media thickness (cIMT) was measured using B-mode ultrasonography. We used multivariable regression models to examine cross-sectional associations of alcohol consumption with the presence and amount of CAC and cIMT. Compared with never drinkers, participants consuming 4-7 drinks/week had a 63% decreased odds of any CAC after adjusting for potential confounders and mediators. Participants consuming 4-7 drinks/week had significantly lower odds of CAC score between 1 and 300 [OR (95% CI): 0.34 (0.16-0.72)]. A similar inverse association was seen for the odds of CAC>300 [OR (95% CI): 0.28 (0.07-0.97)]. Alcohol consumption of >7 drinks/week was associated with a 0.096 mm increase in common-cIMT.
CONCLUSION:
There was an inverse association between the amount of alcohol intake and CAC among South Asians while a positive association was found between alcohol consumption and common-cIMT. Long-term follow-up of the MASALA cohort will examine prospective associations of alcohol intake with the progression of subclinical atherosclerosis, incident CVD events, and mortality.
KEYWORDS:
Alcohol; Coronary artery calcium; South Asian; Subclinical atherosclerosis

Effects of cardamom supplementation on lipid profile: A systematic review and meta-analysis of randomized controlled clinical trials.
Shekarchizadeh-Esfahani P, Arab A, Ghaedi E, Hadi A, Jalili C.
Phytother Res. 2019 Nov 21. doi: 10.1002/ptr.6543. [Epub ahead of print] Review.
PMID: 31755188
Abstract
Cardiovascular disease is a highly prevalent issue worldwide and one of its main manifestations, dyslipidemia, needs more attention. Recent studies have suggested that cardamom has favorable effects beyond lipid lowering, but the result are contradictory. Our objective was to conduct a systematic review and meta-analysis on randomized controlled trials (RCTs) that assessed the effect of cardamom on lipids. The search included PubMed, Scopus, ISI Web of Science, Google Scholar, and the Cochrane library (up to March, 2019) to identify RCTs investigating the effects of cardamom supplementation on serum lipid parameters. Weighted mean differences (WMDs) were pooled using a random-effect model. Meta-analysis of data from five eligible RCTs showed that cardamom supplementation did not significantly change the concentrations of total cholesterol (WMD: -6.11 mg/dl, 95% CI [-13.06, 0.83], I2 = 0.0%), low-density lipoprotein cholesterol (WMD: -4.31 mg/dl, 95% CI [-9.75, 1.13], I2 = 0.0%), or high-density lipoprotein cholesterol (WMD: 1.75 mg/dl, 95% CI [-1.95 to 5.46], I2 = 71.4%). However, a significant reduction was observed in serum triglyceride (TG; WMD: -20.55 mg/dl, 95% CI [-32.48, -8.63], I2 = 0.0%) levels after cardamom supplementation. Cardamom might be able to change TG, but for confirming the results, more studies exclusively on dyslipidemia patients and considering the intake of lipid lowering agents as exclusion criteria are necessary.
KEYWORDS:
cardamom; lipids; meta-analysis; randomized controlled trials

Habitual Nut Exposure, Assessed by Dietary and Multiple Urinary Metabolomic Markers, and Cognitive Decline in Older Adults: The InCHIANTI Study.
Rabassa M, Zamora-Ros R, Palau-Rodriguez M, Tulipani S, Miñarro A, Bandinelli S, Ferrucci L, Cherubini A, Andres-Lacueva C.
Mol Nutr Food Res. 2019 Nov 22:e1900532. doi: 10.1002/mnfr.201900532. [Epub ahead of print]
PMID: 31755209
Abstract
SCOPE:
We prospectively evaluated the association between self-reported dietary intake and urinary metabolomic markers of habitual nut exposure with cognitive decline over a 3-year follow-up in an older Italian population.
METHODS AND RESULTS:
We selected 119 older participants, from the InCHIANTI cohort based on self referred nut intake: the non-nut consumer (n = 72) and the regular nut consumer (≥2.9 g/d, n = 47) groups. Nut exposure was measured at baseline either with the use of a validated food frequency questionnaire or with an HPLC-Q-ToF-MS metabolomic approach. Three years after, 28 from non-consumers group and 10 from consumers group experienced cognitive decline. Dietary nut exposure was characterized by urinary metabolites of polyphenols and fatty acids pathways. Nut consumption estimated either by the dietary marker or by the urinary marker model was in both cases associated with less cognitive decline (OR: 0.78, 95% CI: 0.61,0.99; P = 0.043 and OR: 0.995, 95% CI: 0.991,0.999; P = 0.016, respectively) with AUCs 73.2 (95% CI: 62.9,83.6) and 73.1 (62.5,83.7), respectively.
CONCLUSIONS:
A high intake of nuts may protect older adults from cognitive decline. The use of a panel of metabolites provides accurate and complementary information of the nut exposure and reinforces the results obtained using dietary information.
KEYWORDS:
InCHIANTI; cognition; diet; metabolomics; nuts

[AlPater]

Association of Magnesium Consumption with Type 2 Diabetes and Glucose Metabolism: a Systematic Literature Review and Pooled Study with Trial Sequential Analysis.
Zhao B, Deng H, Li B, Chen L, Zou F, Hu L, Wei Y, Zhang W.
Diabetes Metab Res Rev. 2019 Nov 22:e3243. doi: 10.1002/dmrr.3243. [Epub ahead of print] Review.
PMID: 31758631
https://sci-hub.tw/10.1002/dmrr.3243
bstract
Prevention of type 2 diabetes (T2D) with diet or diet supplementation is challenging. This article aims to draw conclusive associations between magnesium intake and T2D incidence and evaluate the effect of magnesium supplementation on glucose metabolism. Databases were searched for related articles from inception to May 15, 2019. Prospective cohort studies investigating the relevant relationship as well as randomized controlled trials (RCTs) assessing the effect of magnesium supplementation were eligible. We conducted trial sequential analysis (TSA) to prove the sufficiency of the current evidence. Twenty-six publications involving 35 cohorts were included in the analysis. Compared to the lowest magnesium intake, the highest level was associated with a 22% lower risk for T2D; the risk was reduced by 6% for each 100 mg increment in daily magnesium intake. Additional analysis of 26 RCTs (1168 participants) was performed, revealing that magnesium supplementation significantly reduced the fasting plasma glucose (FPG) level (SMD, -0.32 [95% CI, -0.59 to -0.05], 2-h oral glucose tolerance test (2-h OGTT) result (SMD, -0.30 [-0.58 to -0.02]), fasting insulin level (SMD, -0.17 [-0.30 to -0.04]), homeostatic model assessment-insulin resistance (HOMA-IR) score (SMD, -0.41 [-0.71 to -0.11]), triglyceride (TG) level, systolic blood pressure (SBP) and diastolic blood pressure (DBP). TSA showed an inverse association, with most benefits of magnesium supplementation on glucose metabolism being stable. In conclusion, magnesium intake has an inverse dose-response association with T2D incidence, and supplementation appears to be advisable in terms of glucose parameters in T2D/high-risk individuals.
KEYWORDS:
Magnesium; Magnesium supplementation; Meta-analysis; Prospective cohort studies; Trial sequential analysis; Type 2 diabetes

Physical activity without weight loss reduces the development of cardiovascular disease risk factors - a prospective cohort study of more than one hundred thousand adults.
Martinez-Gomez D, Lavie CJ, Hamer M, Cabanas-Sanchez V, Garcia-Esquinas E, Pareja-Galeano H, Struijk E, Sadarangani KP, Ortega FB, Rodríguez-Artalejo F.
Prog Cardiovasc Dis. 2019 Nov 20. pii: S0033-0620(19)30144-6. doi: 10.1016/j.pcad.2019.11.010. [Epub ahead of print] Review.
PMID: 31758975
https://sci-hub.tw/10.1016/j.pcad.2019.11.010
Abstract
PURPOSE:
Whether physical activity (PA) might have certain benefits for cardiovascular disease (CVD) primordial prevention even in the absence of clinically significant weight loss is of public health interest. In this study, we examined the independent and combined associations of simultaneous changes in PA and body weight with the subsequent development of major CVD risk factors in adults.
METHODS:
This prospective analysis included 116,134 healthy men and women, aged ≥18 years, with at least 3 medical examinations from the Taiwan MJ Cohort. Two-year changes in PA and body weight between the first and second examination were linked to subsequent development of hypertension, hypercholesterolemia, atherogenic dyslipidemia, metabolic syndrome, type 2 diabetes mellitus (T2DM), and chronic inflammation, which were assessed by physical examinations and laboratory tests.
RESULTS:
During an average follow-up of 5.7 ± 4.1 years after the second examination, 10,840 individuals developed hypertension, 10,888 hypercholesterolemia, 6078 atherogenic dyslipidemia, 13,223 metabolic syndrome, 4816 T2DM, and 2027 inflammation. Weight gain was associated with a subsequent higher risk of all CVD risk factors, with HR (95%CI) ranging from 1.11 (1.00-1.23) for inflammation to 1.74 (1.67-1.82) for metabolic syndrome, compared with participants who lost weight. A stable weight was also associated with a higher risk of all CVD risk factors except with inflammation. In combined analyses, participants who simultaneously gained weight and decreased PA levels had the highest risk compared with those who lost weight and increased PA. Increasing or maintaining PA reduced the increased subsequent risk of some CVD risk factors among participants who maintained a stable weight or gained weight. Among participants who lost weight, decreased PA was not associated with an increased risk.
CONCLUSIONS:
Although weight loss is crucial for the prevention of CVD risk factors, increasing or maintaining PA is also important to prevent them among adults who gain or maintain their weight.
KEYWORDS:
Cardiovascular disease risk factors; Obesity; Physical activity; Prevention; Prospective; Weight loss

[AlPater]

You're afraid of the wrong things: What evolution made you scared of versus what actually might kill you
An evolutionary biologist explains why we’re more afraid of snakes than climate change.
Clifton Mark · CBC Life · Posted: Apr 05, 2019
https://www.cbc.ca/life/culture/you-re-afraid-of-the-wrong-things-what-evolution-made-you-scared-of-versus-what-actually-might-kill-you-1.5086576

Effect of dietary intervention with a legume-based food product on malondialdehyde levels, HOMA index, and lipid profile.
Ruiz Esparza Cisneros J, Vasconcelos-Ulloa JJ, González-Mendoza D, Beltrán-González G, Díaz-Molina R.
Endocrinol Diabetes Nutr. 2019 Nov 20. pii: S2530-0164(19)30225-3. doi: 10.1016/j.endinu.2019.08.003. [Epub ahead of print] English, Spanish.
PMID: 31759909
Abstract
INTRODUCTION:
Prevalence of overweight and obesity, a condition that promotes development of chronic degenerative diseases, has increased in Mexico in recent years. Implementation of strategies to increase daily consumption of vegetables, legumes, whole grain cereals, and fruits by the population will result in an adequate intake of soluble fiber, antioxidants, protein of vegetable origin, and vitamins.
OBJECTIVE:
To assess the effect of a commercial food product prepared using 6 legumes on some anthropometric and biochemical parameters in apparently healthy subjects.
METHODS:
A randomized dietary intervention trial where subjects in the study group received for three months 15g of the product, administered daily in periods of five days with two days of rest. Before and after intervention, anthropometric and dietary assessments were performed, and serum glucose, lipid profile, insulin, ultrasensitive C-reactive protein, malondialdehyde (MDA) and insulin resistance (HOMA index) were measured. A Mann-Whitney U test was used and values of P<0.05 were considered statistically significant.
RESULTS:
Sixty university students were included in the study (53% males). At the end of the intervention, decreases were seen in serum glucose levels (P=0.001), MDA (P=0.001) and HOMA index (P=0.017), but there were no significant changes in all other parameters.
CONCLUSIONS:
Daily intake of 15g of the legume-based food product improved serum glucose and malondialdehyde levels in the study group, as well as insulin resistance; which could be attributed to the presence of polyphenols and isoflavones such as genistein in legumes.
KEYWORDS:
Insulin resistance; Legumes; Leguminosas; Lipid profile; Malondialdehyde; Malondialdehído; Perfil de lípidos; Resistencia a la insulina

[AlPater]

Decreased number of days of fever detection and duration of fever with continuous intake of a fermented milk drink: a randomized, double-blind, placebo-controlled study of elderly nursing home residents.
Kushiro A, Shimizu K, Takada T, Kusunoki I, Aiba N.
Biosci Microbiota Food Health. 2019;38(4):151-157. doi: 10.12938/bmfh.18-024. Epub 2019 Sep 6.
PMID: 31763118
https://www.jstage.jst.go.jp/article/bmfh/advpub/0/advpub_18-024/_pdf
Abstract
We conducted a randomized, double-blind, placebo-controlled parallel study to investigate the effects of a fermented milk on elderly nursing home residents. Eighty-eight participants each drank one bottle of fermented milk containing Lactobacillus casei strain Shirota, or a placebo, on a daily basis for 6 months in winter. Peripheral blood, saliva, fecal samples, and clinical data were analyzed to assess the milk's efficacy. Fermented milk consumption was associated with a significant decrease in the number of days on which fever was detected and the mean duration of fever compared with these values in the placebo group. No significant differences were observed in other biological parameters. Continuous intake of this fermented milk could be beneficial for the elderly in terms of suppressing the number of days of detection of fever and the duration of fever, which usually increase in winter.
KEYWORDS:
elderly; fermented milk drink; fever; probiotics

Metabolic Effects of Three Different Activity Bouts during Sitting in Inactive Adults.
Ma SX, Zhu Z, Zhang L, Liu XM, Lin YY, Cao ZB.
Med Sci Sports Exerc. 2019 Nov 15. doi: 10.1249/MSS.0000000000002212. [Epub ahead of print]
PMID: 31764465
Abstract
PURPOSE:
This study aimed to determine whether interrupting prolonged sitting with 3 different walking-bout schedules improves glycemic metabolism relative to continuous prolonged sitting in sedentary adults.
METHODS:
In a randomized, crossover trial, 16 inactive healthy adults (7 men, 24±3 years old) completed four 26-h laboratory sessions, including 22.5 h in an energy expenditure (EE)-testing calorimeter chamber. The four 9-h intervention periods were as follows: 9-h uninterrupted sitting (SIT); 30-min sitting/3-min brisk (60% VO2max) treadmill walk (WALK3); 45-min sitting/5-min (WALK5); or 60-min sitting/8-min (WALK8). Coprimary outcomes included the difference in the mean interstitial glucose concentration, total areas under the curve (tAUC), and incremental AUC (iAUC) for the entire 26 h and 9 h (intervention period) during three activity-bout conditions compared with SIT.
RESULTS:
Compared with SIT, the 26-h mean glucose concentration was attenuated in WALK8 (Δmean -0.22 mmol·L [95% CI -0.43--0.001], p= 0.048) without adjustment for EE and attenuated in WALK3 (Δ-0.47 mmol·L [-0.75--0.10]), WALK5 (Δ-0.47 mmol·L [-0.83--0.10]), and WALK8 (Δ-0.53 mmol·L [-0.92--0.13]) after adjustment for EE (all p < 0.01). The 26-h tAUC was reduced in WALK3 (Δ-11.18 mmol·L·h [-20.07--2.29]), WALK5 (2.12.67 mmol·L·h [-22.54--2.79]), and WALK8 (Δ-13.85 mmol·L·h [-24.60--3.10]) (all p < 0.01), as well as the iAUC (all p < 0.05), only after adjustment for EE. The 9-h mean glucose concentration, tAUC, and iAUC decreased in the three activity-break conditions regardless of EE adjustment (all p < 0.05).
CONCLUSIONS:
All three walking-bout conditions improved glycemic metabolism compared with SIT, independent of EE, in inactive, healthy adults.

[AlPater]

Impact of isocaloric exchanges of carbohydrate for fat on postprandial glucose, insulin, triglycerides, and free fatty acid responses-a systematic review and meta-analysis.
Kdekian A, Alssema M, Van Der Beek EM, Greyling A, Vermeer MA, Mela DJ, Trautwein EA.
Eur J Clin Nutr. 2019 Nov 25. doi: 10.1038/s41430-019-0534-6. [Epub ahead of print] Review.
PMID: 31767988
Abstract
Varying the macronutrient composition of meals alters acute postprandial responses, but the effect sizes for specific macronutrient exchanges have not been quantified by systematic reviews. Therefore the aim is to quantify the effect size of exchanging fat for carbohydrates in mixed meals on postprandial glucose (PPG), insulin (PPI), triglycerides (PPTG), and free fatty acids (PPFFA) responses by performing a systematic review and meta-analysis of randomized controlled trials. A systematic literature search was undertaken on randomized controlled trials comparing isocaloric high fat with high carbohydrate meals, with comparable protein contents and at least one postprandial glycemic- and one lipid outcome. The outcome data were extracted and expressed as mean postprandial levels over 2 h. Ten studies involving 14 comparisons met the eligibility criteria. Data were available for meta-analysis from 347 participants, consuming mixed meals containing 250-1003 kcal, and total fat contents of 33.3-75.6 percentage of energy (en%) (intervention) versus 0-31.7 en% (control). Each 10en% increase in fat, replacing carbohydrates produced a mean reduction in PPG of 0.32 mmol/l (95% CI -0.64 to -0.00, p = 0.047), a reduction in PPI of 18.2 pmol/l (95% CI -24.86 to -11.54), an increase in PPTG of 0.06 mmol/l (95% CI 0.02 to 0.09, p = 0.004), with no statistically significant effect on PPFFA. Modest exchange of carbohydrates for fats in mixed meals significantly reduces PPG and PPI and increases PPTG responses. The quantitative relationships derived here may be applied to predict responses, and to design and optimize meal macronutrient compositions in dietary intervention studies.

Intake or blood levels of n-3 polyunsaturated fatty acids and risk of colorectal cancer: A systematic review and meta-analysis of prospective studies.
Kim Y, Kim J.
Cancer Epidemiol Biomarkers Prev. 2019 Nov 25. pii: cebp.0931.2019. doi: 10.1158/1055-9965.EPI-19-0931. [Epub ahead of print]
PMID: 31767566
Abstract
BACKGROUND:
Previous results of the association between n-3 polyunsaturated fatty acids (PUFAs) and colorectal cancer were inconsistent. We conducted a systematic review and meta-analysis of prospective studies.
METHODS:
The PubMed and Embase databases were searched through July 10, 2019, followed by a manual search. A random-effects model was used.
RESULTS:
Twenty prospective studies including 18,102 cases and 1,360,046 participants were included. The pooled RR of colorectal cancer for the highest versus lowest category of n-3 PUFA intake was 0.97 (95% CI: 0.90-1.04). Regarding the type of n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes were inversely associated with 11% (RR=0.89; 95% CI: 0.80-0.99) and 12% (RR=0.88; 95% CI: 0.81-0.96) lower colorectal cancer risks, respectively, in the comparison of the highest versus lowest category. Increments of 0.1 g/day of EPA (RR=0.95; 95% CI: 0.92-0.98) and DHA (RR=0.97; 95% CI: 0.95-0.99) intakes were associated with a lower colorectal cancer risk. Regarding the blood levels of n-3 PUFAs, the pooled RR of colorectal cancer for the highest versus lowest category of blood levels of n-3 PUFAs was 0.79 (95% CI: 0.64-0.98). The risk of colorectal cancer decreased by 4% for every 1% increase in blood n-3 PUFA levels (RR=0.96; 95% CI: 0.92-1.00).
CONCLUSIONS:
High blood n-3 PUFA levels are inversely associated with colorectal cancer risk, and high n-3 PUFA intake is suggestively associated with lower colorectal cancer risk.
IMPACT:
Our findings suggest that high blood n-3 PUFA levels may be associated with reduced colorectal cancer risk, but further studies are needed.

[AlPater]

Acute caffeine intake increases muscle oxygen saturation during a maximal incremental exercise test.
Ruíz-Moreno C, Lara B, Brito de Souza D, Gutiérrez-Hellín J, Romero-Moraleda B, Cuéllar-Rayo Á, Del Coso J.
Br J Clin Pharmacol. 2019 Nov 29. doi: 10.1111/bcp.14189. [Epub ahead of print]
PMID: 31782534
Abstract
AIMS:
The main mechanism behind caffeine's ergogenicity lies in its tendency to bind to adenosine receptors although other mechanisms might be involved. The aim of this investigation was to analyze the effects of caffeine on muscle oxygen saturation during exercise of increasing intensity.
METHODS:
Thirteen healthy and active individuals volunteered to participate in a randomized, double blind, placebo-controlled crossover trial. During two different trials, participants either ingested a placebo (cellulose) or 3 mg/kg of caffeine. After waiting for 60 min to absorb the substances, participants underwent a maximal ramp cycle ergometer test (25 W/min). Near infrared spectrometers were positioned on each leg's vastus lateralis to monitor tissue O2 saturation. Blood lactate concentration was measured 1 min after the end of the exercise test.
RESULTS:
In comparison to the placebo, the ingestion of caffeine improved the maximal wattage (258±50 vs 271±54 W, respectively, P<0.001, effect size=0.27;0.14-0.35) and blood lactate concentration (11.9±3.8 vs 13.7±3.5 mmol/L, P=0.029, effect size=0.38;0.14-0.75) at the end of the test. Caffeine increased muscle oxygen saturation at several exercise workloads with a main effect found in respect to the placebo (F=6.28, P=0.029; effect sizes=from 0.30-to-0.54;0.01-0.78). Peak pulmonary ventilation (124±29 vs 129±23 L/min, P=0.035, effect size=0.25;0.07-0.40) and VO2 peak (3.18±0.70 vs 3.33±0.88 L/min, P=0.032, effect size=0.26;0.08-0.51) were also increased with caffeine.
CONCLUSION:
Acute ingestion of 3 mg/kg of caffeine improved peak aerobic performance and increased peak pulmonary ventilation. In addition, caffeine induced changes in muscle oxygen saturation during submaximal workloads, suggesting that this mechanism might also contribute to caffeine's ergogenic effect.
KEYWORDS:
VO2max; cycling; high intensity exercise; muscle oxygenation; near infrared spectroscopy

Long-Term Trajectories of Body Weight, Diet, and Physical Activity From Midlife Through Late-Life and Subsequent Cognitive Decline in Women.
Wagner M, Grodstein F, Proust-Lima C, Samieri C.
Am J Epidemiol. 2019 Nov 29. pii: kwz262. doi: 10.1093/aje/kwz262. [Epub ahead of print]
PMID: 31781745
Abstract
Healthy lifestyle are promising targets for prevention of cognitive aging, yet the optimal time-windows for interventions remain unclear. We selected a case-control sample nested within the Nurses' Health Study (starting year 1976, mean age=51 years-old), including 14,956 women aged ≥70 years and free of both stroke and cognitive impairment at enrollment in a cognitive sub-study (1995-2001). Cases (n=1,496) were women with the 10% worst slopes of cognitive decline and controls (n=7,478) those with slopes better than the median. We compared the trajectories of body mass index, the alternate Mediterranean diet (A-MeDi) score, and physical activity between groups, from midlife through 1 year preceding the cognitive sub-study. In midlife, cases had higher body mass index (mean difference [MD] versus controls=0.59 [95% confidence interval [CI]:0.39,0.80] kg/m2), lower physical activity (MD=-1.41 [95%CI:-2.07,-0.71] metabolic-equivalent hours/week) and worse A-MeDi scores (MD=-0.16 [95%CI:-0.26,-0.06] point). From mid- through later-life, compared to controls, cases had consistently lower A-MeDi scores, but a deceleration of weight gain and a faster decrease of physical activity. In conclusion, maintaining healthy lifestyle since midlife may help reduce cognitive decline in aging. At older ages, both deceleration of weight gain and decrease in physical activity may reflect early signs of cognitive impairment.
KEYWORDS:
Mediterranean diet; body mass index; cognitive decline; physical activity; prospective cohort study

Leading Determinants for Disease-Free Status in Community-Dwelling Middle-Aged Men and Women: A 9-Year Follow-Up Cohort Study.
Shang X, Wang W, Keel S, Wu J, He M, Zhang L.
Front Public Health. 2019 Nov 8;7:320. doi: 10.3389/fpubh.2019.00320. eCollection 2019.
PMID: 31781526
Abstract
Background: Identifying leading determinants for disease-free status may provide evidence for action priorities, which is imperative for public health with an expanding aged population worldwide. This study aimed to identify leading determinants, especially modifiable factors for disease-free status using machine learning methods. Methods: We included 52,036 participants aged 45-64 years from the 45 and Up Study who were free of 13 predefined chronic conditions at baseline (2006-2009). Disease-free status was defined as participants aging from 45-64 years at baseline to 55-75 years at the end of the follow-up (December 31, 2016) without developing any of the 13 chronic conditions. We used machine learning methods to evaluate the importance of 40 potential predictors and analyzed the association between the number of leading modifiable healthy factors and disease-free status. Results: Disease-free status was found in about half of both men and women during a mean 9-year follow-up. The five most common leading predictors were body mass index (6.4-9.5% of total variance), self-rated health (5.2-8.2%), self-rated quality of life (4.1-6.8%), red meat intake (4.5-6.5%), and chicken intake (4.5-5.9%) in both genders. Modifiable behavioral factors including body mass index, diets, smoking, alcohol consumption, and physical activity, contributed to 37.2-40.3% of total variance. Participants having six or more modifiable health factors were 1.63-8.76 times more likely to remain disease-free status and had 0.60-2.49 more disease-free years (out of 9-year follow-up) than those having two or fewer. Non-behavioral factors including low levels of education and income and high relative socioeconomic disadvantage, were leading risk factors for disease-free status. Conclusions: Body mass index, diets, smoking, alcohol consumption, and physical activity are key factors for disease-free status promotion. Individuals with low socioeconomic status are more in need of care.
KEYWORDS:
disease-free status; family history of chronic disease; healthy modifiable factors; leading predictors; psychological factors; socioeconomic status

Association of supplemental calcium and dairy milk intake with all-cause and cause-specific mortality in the UK Biobank: a prospective cohort study.
Stasinopoulos LC, Zhou A, Hyppönen E.
Br J Nutr. 2019 Nov 29:1-19. doi: 10.1017/S0007114519003076. [Epub ahead of print]
PMID: 31779733
https://www.cambridge.org/core/services/aop-cambridge-core/content/view/E33281873D8B17461CA9AF027F876A90/S0007114519003076a.pdf/div-class-title-association-of-supplemental-calcium-and-dairy-milk-intake-with-all-cause-and-cause-specific-mortality-in-the-uk-biobank-a-prospective-cohort-study-div.pdf
Abstract
Excessive calcium intakes have been proposed to associate with vascular calcification and a higher risk of prostate cancer. We investigated the associations of supplemental and dietary calcium intake with mortality using data from 497,828 UK Biobank participants. The average follow-up was 4.2 years and 14,255 participants died, 8,297 from cancer, 2,959 from cardiovascular diseases and 572 from respiratory disease. The use of calcium supplements and milk consumption were associated with differences in mortality in younger (≤65 years) but not in older participants (>65 years, Pinteraction≤0.04 for all comparisons). Among participants <65 years, there was an inverse association both between calcium supplementation (OR 0.91, 95% CI 0.83-0.99) and milk consumption (OR 0.93, 95% CI 0.86-1.00) with respect to all-cause mortality. In the same age group, milk drinkers had lower odds of cancer mortality (OR 0.89, 95% CI 0.80-0.98) but calcium supplement use was associated with increased odds of respiratory mortality (OR 1.69, 95% CI 1.16-2.74). All associations in participants aged ≥65 years were null after full adjustment. In sensitivity analyses stratifying by hormone replacement therapy, calcium supplement use associated with decreased odds of cancer mortality in users but increased risk in other women (OR 0.81, 95% CI 0.69-0.94 vs. OR 1.17, 95% CI 1.01-1.35, respectively). To conclude, we saw little evidence for harm with dietary or supplemental calcium. Further studies are required to confirm the proposed interaction with hormone replacement therapy and to exclude reverse causation as a determinant in the association between calcium supplements and increased risk of respiratory diseases.
KEYWORDS:
all-cause mortality; calcium supplements; cancer mortality; cardiovascular mortality; dairy milk; respiratory mortality.

Associations of dairy intake with risk of mortality in women and men: three prospective cohort studies.
Ding M, Li J, Qi L, Ellervik C, Zhang X, Manson JE, Stampfer M, Chavarro JE, Rexrode KM, Kraft P, Chasman D, Willett WC, Hu FB.
BMJ. 2019 Nov 27;367:l6204. doi: 10.1136/bmj.l6204.
PMID: 31776125
Abstract
OBJECTIVE:
To examine the association of consumption of dairy foods with risk of total and cause specific mortality in women and men.
DESIGN:
Three prospective cohort studies with repeated measures of diet and lifestyle factors.
SETTING:
Nurses' Health Study, Nurses' Health Study II, and the Health Professionals Follow-up Study, in the United States.
PARTICIPANTS:
168 153 women and 49 602 men without cardiovascular disease or cancer at baseline.
MAIN OUTCOME MEASURE:
Death confirmed by state vital records, the national death index, or reported by families and the postal system. During up to 32 years of follow-up, 51 438 deaths were documented, including 12 143 cardiovascular deaths and 15 120 cancer deaths. Multivariable analysis further adjusted for family history of cardiovascular disease and cancer, physical activity, overall dietary pattern (alternate healthy eating index 2010), total energy intake, smoking status, alcohol consumption, menopausal status (women only), and postmenopausal hormone use (women only).
RESULTS:
Compared to the lowest category of total dairy consumption (average 0.8 servings/day), the multivariate pooled hazard ratio for total mortality was 0.98 (95% confidence interval 0.96 to 1.01) for the second category of dairy consumption (average 1.5 servings/day), 1.00 (0.97 to 1.03) for the third (average 2.0 servings/day), 1.02 (0.99 to 1.05) for the fourth (average 2.8 servings/day), and 1.07 (1.04 to 1.10) for highest category (average 4.2 servings/day; P for trend <0.001). For the highest compared to the lowest category of total dairy consumption, the hazard ratio was 1.02 (0.95 to 1.08) for cardiovascular mortality and 1.05 (0.99 to 1.11) for cancer mortality. For subtypes of dairy products, whole milk intake was significantly associated with higher risks of total mortality (hazard ratio per 0.5 additional serving/day 1.11, 1.09 to 1.14), cardiovascular mortality (1.09, 1.03 to 1.15), and cancer mortality (1.11, 1.06 to 1.17). In food substitution analyses, consumption of nuts, legumes, or whole grains instead of dairy foods was associated with a lower mortality, whereas consumption of red and processed meat instead of dairy foods was associated with higher mortality.
CONCLUSION:
These data from large cohorts do not support an inverse association between high amount of total dairy consumption and risk of mortality. The health effects of dairy could depend on the comparison foods used to replace dairy. Slightly higher cancer mortality was non-significantly associated with dairy consumption, but warrants further investigation.

Modified alternate-day fasting vs. calorie restriction in the treatment of patients with metabolic syndrome: A randomized clinical trial.
Parvaresh A, Razavi R, Abbasi B, Yaghoobloo K, Hassanzadeh A, Mohammadifard N, Safavi SM, Hadi A, Clark CCT.
Complement Ther Med. 2019 Dec;47:102187. doi: 10.1016/j.ctim.2019.08.021. Epub 2019 Aug 28.
PMID: 31779987
Abstract
OBJECTIVE:
The aim of present study was to compare the effect of calorie restriction and modified alternate-day fasting diet on treatment of adults with metabolic syndrome.
DESIGN:
This randomized clinical trial was conducted on 70 participants diagnosed with metabolic syndrome.
SETTING:
Patients were randomly allocated into 2 groups to follow either calorie restriction or a modified alternate-day fasting diet for 8 weeks. Diets was prescribed by dietitians and specialized for each participant. Anthropometric parameters, blood pressure, fasting plasma glucose, fasting insulin, HOMA-IR and lipid profile were measured at baseline and after trial conclusion.
RESULTS:
69, out of 70, participants completed the study and were included in the final analysis. The results showed that, compared with calorie restriction, following the modified alternate-day fasting diet significantly reduced body weight (P = 0.003), waist circumference (P = 0.026), systolic blood pressure (P = 0.029) and fasting plasma glucose (P = 0.009). However, no significant difference was observed between the 2 groups in triglyceride (P = 0.614), total cholesterol (P = 0.759), LDL-C (P = 0.289), HDL-C (P = 0.909), diastolic blood pressure (P = 0.262), HOMA- IR (P = 0.425) and fasting insulin concentrations (P = 0.496). In addition, the participants did not report any complaint due to difficulties with diet adherence when following calorie restriction or modified alternate-day fasting diet.
CONCLUSIONS:
the present study suggests that modified alternate-day fasting diet may be a more effective option in managing body weight, waist circumference, systolic blood pressure, and fasting plasma glucose, compared with common calorie restriction. Further studies are needed to confirm the veracity of our results.
KEYWORDS:
Alternate-day fasting; Anthropometric; Energy restriction; Glycemic index; Metabolic syndrome x; Plasma lipids

Naive extrapolations, overhyped claims and empty promises in ageing research and interventions need avoidance.
Rattan SIS.
Biogerontology. 2019 Nov 27. doi: 10.1007/s10522-019-09851-0. [Epub ahead of print]
PMID: 31773357
https://sci-hub.tw/10.1007/s10522-019-09851-0
Abstract
Most proclamations about another wonder breakthrough and another imminent miracle treatment of ageing are usually overhyped claims and empty promises. It is not that the experimental science behind those claims is totally wrong or fake. But it is often a case of being ahistorical and ignoring the cumulated knowledge and understanding of the evolutionary and biological principles of ageing and longevity. Furthermore, remaining stuck to the body-as-a-machine viewpoint reduces ageing and its associated health challenges to a mere problem of engineering and design. However, highly dynamic nature of the living systems with properties of interaction, interdependence, tolerance, adaptation and constant remodelling requires wholistic and interactive modes of understanding and maintaining health. The physiological relevance and significance of progressively accumulating molecular damage remains to be fully understood. As for ageing interventions, the three pillars of health-food, physical activity, and social and mental engagement-which actually show health-promoting effect, cannot simply be reduced to a single or a limited number of molecular targets with hopes of creating an exercise pill, a fasting pill, a happiness pill and so on. If we want to increase the credibility and socio-political-economic support of ageing research and interventions, we need to resist the temptation to overhype the claims or to make far-fetched promises, which undermine the theoretical and practical significance of new discoveries in biogerontology.
KEYWORDS:
Ageing; Anti-ageing; Holistic; Homeodynamics; Homeostasis; Longevity; Stress

Life Expectancy and Mortality Rates in the United States, 1959-2017.
Woolf SH, Schoomaker H.
JAMA. 2019 Nov 26;322(20):1996-2016. doi: 10.1001/jama.2019.16932.
PMID: 31769830
Abstract
IMPORTANCE:
US life expectancy has not kept pace with that of other wealthy countries and is now decreasing.
OBJECTIVE:
To examine vital statistics and review the history of changes in US life expectancy and increasing mortality rates; and to identify potential contributing factors, drawing insights from current literature and an analysis of state-level trends.
EVIDENCE:
Life expectancy data for 1959-2016 and cause-specific mortality rates for 1999-2017 were obtained from the US Mortality Database and CDC WONDER, respectively. The analysis focused on midlife deaths (ages 25-64 years), stratified by sex, race/ethnicity, socioeconomic status, and geography (including the 50 states). Published research from January 1990 through August 2019 that examined relevant mortality trends and potential contributory factors was examined.
FINDINGS:
Between 1959 and 2016, US life expectancy increased from 69.9 years to 78.9 years but declined for 3 consecutive years after 2014. The recent decrease in US life expectancy culminated a period of increasing cause-specific mortality among adults aged 25 to 64 years that began in the 1990s, ultimately producing an increase in all-cause mortality that began in 2010. During 2010-2017, midlife all-cause mortality rates increased from 328.5 deaths/100 000 to 348.2 deaths/100 000. By 2014, midlife mortality was increasing across all racial groups, caused by drug overdoses, alcohol abuse, suicides, and a diverse list of organ system diseases. The largest relative increases in midlife mortality rates occurred in New England (New Hampshire, 23.3%; Maine, 20.7%; Vermont, 19.9%) and the Ohio Valley (West Virginia, 23.0%; Ohio, 21.6%; Indiana, 14.8%; Kentucky, 14.7%). The increase in midlife mortality during 2010-2017 was associated with an estimated 33 307 excess US deaths, 32.8% of which occurred in 4 Ohio Valley states.
CONCLUSIONS AND RELEVANCE:
US life expectancy increased for most of the past 60 years, but the rate of increase slowed over time and life expectancy decreased after 2014. A major contributor has been an increase in mortality from specific causes (eg, drug overdoses, suicides, organ system diseases) among young and middle-aged adults of all racial groups, with an onset as early as the 1990s and with the largest relative increases occurring in the Ohio Valley and New England. The implications for public health and the economy are substantial, making it vital to understand the underlying causes.

Pre- and post-diagnostic intake of whole grain and dairy products and breast cancer prognosis: the Danish Diet, Cancer and Health cohort.
Andersen JLM, Hansen L, Thomsen BLR, Christiansen LR, Dragsted LO, Olsen A.
Breast Cancer Res Treat. 2019 Nov 26. doi: 10.1007/s10549-019-05497-1. [Epub ahead of print]
PMID: 31773360
Abstract
PURPOSE:
Fiber rich foods and dairy products have been suggested to be associated with breast cancer prognosis, though existing research is limited and either report on pre- or post-diagnostic dietary intake in relation to breast cancer prognosis. We investigated the associations between intake of whole grain (WG) and dairy products assessed both pre- and post-diagnostically in relation to breast cancer prognosis.
METHODS:
A total of 1965 women from the Diet, Cancer and Health cohort who were diagnosed with breast cancer between baseline (1993-1997) and December 2013 were included and followed for a median of 7 years after diagnosis. During follow-up, 309 women experienced breast cancer recurrence and 460 women died, of whom 301 died from breast cancer. Dietary assessment by food frequency questionnaires was obtained up to three times, pre- and post-diagnostic, over a period of 18 years. Cox proportional hazard models were used to estimate hazard ratios.
RESULTS:
No associations were observed between pre- or post-diagnostic intake of total WG or total dairy products and breast cancer prognosis. A high pre-diagnostic intake of oatmeal/muesli was associated with lower all-cause mortality (HR 0.76, 95% CI 0.59-0.99), whereas high post-diagnostic intake of rye bread was associated with higher breast cancer-specific mortality (HR 1.29, 95% CI 1.02-1.63). A generally high intake of cheese was associated with a higher recurrence rate.
CONCLUSION:
Pre-diagnostic intake of oatmeal/muesli was associated with lower all-cause mortality, and post-diagnostic intake of rye bread was associated with higher breast cancer specific mortality.
KEYWORDS:
Breast cancer prognosis; Cohort study; Dairy products; Epidemiology; Whole grains

Mindfulness-Based Blood Pressure Reduction (MB-BP): Stage 1 single-arm clinical trial.
Loucks EB, Nardi WR, Gutman R, Kronish IM, Saadeh FB, Li Y, Wentz AE, Webb J, Vago DR, Harrison A, Britton WB.
PLoS One. 2019 Nov 27;14(11):e0223095. doi: 10.1371/journal.pone.0223095. eCollection 2019.
PMID: 31774807
Abstract
BACKGROUND AND OBJECTIVES:
Impacts of mindfulness-based programs on blood pressure remain equivocal, possibly because the programs are not adapted to engage with determinants of hypertension, or due to floor effects. Primary objectives were to create a customized Mindfulness-Based Blood Pressure Reduction (MB-BP) program, and to evaluate acceptability, feasibility, and effects on hypothesized proximal self-regulation mechanisms. Secondary outcomes included modifiable determinants of blood pressure (BP), and clinic-assessed systolic blood pressure (SBP).
METHODS:
This was a Stage 1 single-arm trial with one year follow-up. Focus groups and in-depth interviews were performed to evaluate acceptability and feasibility. Self-regulation outcomes, and determinants of BP, were assessed using validated questionnaires or objective assessments. The MB-BP curriculum was adapted from Mindfulness-Based Stress Reduction to direct participants' mindfulness skills towards modifiable determinants of blood pressure.
RESULTS:
Acceptability and feasibility findings showed that of 53 eligible participants, 48 enrolled (91%). Of these, 43 (90%) attended at least 7 of the 10 MB-BP classes; 43 were followed to one year (90%). Focus groups (n = 19) and semi-structured interviews (n = 10) showed all participants viewed the delivery modality favorably, and identified logistic considerations concerning program access as barriers. A priori selected primary self-regulation outcomes showed improvements at one-year follow-up vs. baseline, including attention control (Sustained Attention to Response Task correct no-go score, p<0.001), emotion regulation (Difficulties in Emotion Regulation Score, p = 0.02), and self-awareness (Multidimensional Assessment of Interoceptive Awareness, p<0.001). Several determinants of hypertension were improved in participants not adhering to American Heart Association guidelines at baseline, including physical activity (p = 0.02), Dietary Approaches to Stop Hypertension-consistent diet (p<0.001), and alcohol consumption (p<0.001). Findings demonstrated mean 6.1 mmHg reduction in SBP (p = 0.008) at one year follow-up; effects were most pronounced in Stage 2 uncontrolled hypertensives (SBP≥140 mmHg), showing 15.1 mmHg reduction (p<0.001).
CONCLUSION:
MB-BP has good acceptability and feasibility, and may engage with self-regulation and behavioral determinants of hypertension.

[AlPater]

Association Between Beverage Intake and Incidence of Gastroesophageal Reflux Symptoms: Beverages and GER symptoms.
Mehta RS, Song M, Staller K, Chan AT.
Clin Gastroenterol Hepatol. 2019 Nov 28. pii: S1542-3565(19)31380-1. doi: 10.1016/j.cgh.2019.11.040. [Epub ahead of print]
PMID: 31786327
Abstract
BACKGROUND & AIMS:
Patients are frequently advised to eliminate coffee, tea, and/or soda to reduce symptoms of gastroesophageal reflux (GER), such as heartburn or regurgitation. However, there are no data from prospective studies to support these recommendations.
METHODS:
We collected data from the prospective Nurses' Health Study II from 48,308 women, 42-62 years old, who were free of regular GER symptoms, without cancer, and not taking proton pump inhibitors or H2 receptor agonists. Multivariate Cox proportional hazards models were used to assess associations between beverage intake and risk for GER symptoms.
RESULTS:
During 262,641 person-years of follow up, we identified 7961 women who reported symptoms of GER once or more per week. After multivariable adjustment, hazard ratios (HRs) for women with the highest intake of each beverage (more than 6 servings/day) compared to women with the lowest intake (0 servings/day) were 1.34 for coffee (95% CI, 1.13-1.59; Ptrend<.0001), 1.26 for tea (95% CI, 1.03-1.55; Ptrend<.001), and 1.29 for soda (95% CI, 1.05-1.58; Ptrend<.0001). We obtained similar results when we stratified patients according to caffeine status. No association was observed between milk, water, or juice consumption and risk for GER symptoms. In a substitution analysis, replacement of 2 servings/day of coffee, tea, or soda with 2 servings of water was associated with reduced risk of GERD symptoms: coffee HR, 0.96 (95% CI, 0.92-1.00); tea HR, 0.96 (95% CI, 0.92-1.00); and soda HR, 0.92 (95% CI, 0.89- 0.96).
CONCLUSIONS:
In an analysis of data from the prospective Nurses' Health Study II, intake of coffee, tea, or soda was associated with an increased risk of GER symptoms. In contrast, consumption of water, juice, or milk were not associated with GER symptoms. Drinking water instead of coffee, tea, or soda reduced the risk of GER symptoms.
KEYWORDS:
GERD; NHS; PPI use; diet

[AlPater]

Stage 1 hypertension by the 2017 American College of Cardiology/American Heart Association hypertension guidelines and risk of cardiovascular disease events: systematic review, meta-analysis, and estimation of population etiologic fraction of prospective cohort studies.
Han M, Chen Q, Liu L, Li Q, Ren Y, Zhao Y, Liu D, Zhang D, Liu F, Chen X, Cheng C, Guo C, Zhou Q, Tian G, Qie R, Huang S, Wu X, Liu Y, Li H, Sun X, Lu J, Hu D, Zhang M.
J Hypertens. 2019 Nov 28. doi: 10.1097/HJH.0000000000002321. [Epub ahead of print]
PMID: 31790053
Abstract
BACKGROUND:
Epidemiological studies reported an inconsistent association between stage 1 hypertension (SBP 130-139 mmHg or DBP 80-89 mmHg) defined by the 2017 American College of Cardiology/American Heart Association hypertension guidelines and cardiovascular disease (CVD) events. In addition, the proportion of CVD events that could be prevented with effective control of stage 1 hypertension is unknown.
OBJECTIVES:
To assess the association between stage 1 hypertension and CVD events and estimate the population etiologic fraction.
METHODS:
PubMed, Embase, and Web of Science databases were searched from 1 January 2017 to 22 September 2019. Normal BP was considered SBP less than 120 mmHg and DBP less than 80 mmHg. Hazard ratios and 95% confidence intervals (95% CIs) were pooled by using a random-effects model.
RESULTS:
We included 11 articles (16 studies including 3 212 447 participants and 65 945 events) in the analysis. Risk of CVD events was increased with stage 1 hypertension versus normal BP (hazard ratio 1.38, 95% CI 1.28-1.49). On subgroup analyses, stage 1 hypertension was associated with coronary heart disease (CHD) (hazard ratio 1.30, 95% CI 1.20-1.41), stroke (1.39, 1.27-1.52), CVD morbidity (1.42, 1.32-1.53), and CVD mortality (1.34, 1.05-1.71). The population etiologic fraction for the association of CVD events, CHD, stroke, CVD morbidity, and CVD mortality with stage 1 hypertension was 12.90, 10.48, 12.71, 14.03, and 11.69%, respectively.
CONCLUSION:
Stage 1 hypertension is associated with CVD events, CVD morbidity, CVD mortality, CHD, and stroke. Effective control of stage 1 hypertension could prevent more than 10% of CVD events.

Dietary saturated fat intake and risk of stroke: Systematic review and dose-response meta-analysis of prospective cohort studies.
Kang ZQ, Yang Y, Xiao B.
Nutr Metab Cardiovasc Dis. 2019 Oct 1. pii: S0939-4753(19)30380-1. doi: 10.1016/j.numecd.2019.09.028. [Epub ahead of print]
PMID: 31791641
Abstract
BACKGROUND AND AIMS:
Because of the conflicting research results, the association between saturated fatty acid (SFA) consumption and the risk of stroke remains controversial. We conducted a meta-analysis to evaluate potential dose-response relation between SFA intake and stroke.
METHODS AND RESULTS:
PubMed, Embase, the Cochrane Library Central Register of Controlled Trials, and Web of Science were searched. Summary relative risks (RRs) of the highest vs. the lowest category of SFA intake and their 95% confidence intervals (CIs) were pooled by random-effects models. Linear or nonlinear dose-response trend estimations were evaluated with data from categories of SFA consumption in each study. Fourteen studies involving a total of 598,435 participants were eligible for high vs. low meta-analysis, and 12 studies involving a total of 462,268 participants were eligible for the dose-response relation assessment. Higher dietary SFA intake was associated with a decreased overall risk for stroke (RR, 0.87; 95% CI, 0.78-0.96; I2 = 37.8%). A linear relation between SFA and stroke was explored (P = 0.01), the pooled RR of stroke per 10 g/day increase in SFA intake was 0.94 (95% CI, 0.89-0.98; P = 0.01).
CONCLUSION:
This meta-analysis further demonstrated that a higher consumption of dietary SFA is associated with a lower risk of stroke, and every 10 g/day increase in SFA intake is associated with a 6% relative risk reduction in the rate of stroke. Further research is needed to explore the influence of specific SFA types and different macronutrient replacement models of SFA on the stroke risk.
KEYWORDS:
Dietary saturated fat intake; Dose–response relation; Meta-analysis; Stroke risk

[AlPater]

Relation of Total Sugars, Sucrose, Fructose, and Added Sugars With the Risk of Cardiovascular Disease: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies.
Khan TA, Tayyiba M, Agarwal A, Mejia SB, de Souza RJ, Wolever TMS, Leiter LA, Kendall CWC, Jenkins DJA, Sievenpiper JL.
Mayo Clin Proc. 2019 Dec;94(12):2399-2414. doi: 10.1016/j.mayocp.2019.05.034.
PMID: 31806098
https://www.mayoclinicproceedings.org/article/S0025-6196(19)30614-7/pdf
Abstract
OBJECTIVE:
To determine the association of total and added fructose-containing sugars on cardiovascular (CVD) incidence and mortality.
METHODS:
MEDLINE, EMBASE and Cochrane Library were searched from January 1, 1980, to July 31, 2018. Prospective cohort studies assessing the association of reported intakes of total, sucrose, fructose and added sugars with CVD incidence and mortality in individuals free from disease at baseline were included. Risk estimates were pooled using the inverse variance method, and dose-response analysis was modeled.
RESULTS:
Eligibility criteria were met by 24 prospective cohort comparisons (624,128 unique individuals; 11,856 CVD incidence cases and 12,224 CVD mortality cases). Total sugars, sucrose, and fructose were not associated with CVD incidence. Total sugars (risk ratio, 1.09 [95% confidence interval, 1.02 to 1.17]) and fructose (1.08 [1.01 to 1.15]) showed a harmful association for CVD mortality, there was no association for added sugars and a beneficial association for sucrose (0.94 [0.89 to 0.99]). Dose-response analyses showed a beneficial linear dose-response gradient for sucrose and nonlinear dose-response thresholds for harm for total sugars (133 grams, 26% energy), fructose (58 grams, 11% energy) and added sugars (65 grams, 13% energy) in relation to CVD mortality (P<.05). The certainty of the evidence using GRADE was very low for CVD incidence and low for CVD mortality for all sugar types.
CONCLUSION:
Current evidence supports a threshold of harm for intakes of total sugars, added sugars, and fructose at higher exposures and lack of harm for sucrose independent of food form for CVD mortality. Further research of different food sources of sugars is needed to define better the relationship between sugars and CVD.

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.
Brunner FJ, Waldeyer C, Ojeda F, Salomaa V, Kee F, Sans S, Thorand B, Giampaoli S, Brambilla P, Tunstall-Pedoe H, Moitry M, Iacoviello L, Veronesi G, Grassi G, Mathiesen EB, Söderberg S, Linneberg A, Brenner H, Amouyel P, Ferrières J, Tamosiunas A, Nikitin YP, Drygas W, Melander O, Jöckel KH, Leistner DM, Shaw JE, Panagiotakos DB, Simons LA, Kavousi M, Vasan RS, Dullaart RPF, Wannamethee SG, Risérus U, Shea S, de Lemos JA, Omland T, Kuulasmaa K, Landmesser U, Blankenberg S; Multinational Cardiovascular Risk Consortium.
Lancet. 2019 Dec 3. pii: S0140-6736(19)32519-X. doi: 10.1016/S0140-6736(19)32519-X. [Epub ahead of print]
PMID: 31810609
Abstract
BACKGROUND:
The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.
METHODS:
In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol.
FINDINGS:
Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced.
INTERPRETATION:
Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies.

Effects of cinnamon supplementation on body weight and composition in adults: A systematic review and meta-analysis of controlled clinical trials.
Yazdanpanah Z, Azadi-Yazdi M, Hooshmandi H, Ramezani-Jolfaie N, Salehi-Abargouei A.
Phytother Res. 2019 Dec 4. doi: 10.1002/ptr.6539. [Epub ahead of print] Review.
PMID: 31800140
Abstract
BACKGROUND:
This systematic review and meta-analysis aimed to investigate the effect of cinnamon on body weight, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and body fat mass including the maximum number of studies.
METHODS:
Medline, ISI Web of Science, Scopus, Google Scholar, and Cochrane library were searched with no limitation from inception up to August 2019 for relevant randomized controlled clinical trials (RCTs). The RCTs' risk of bias was assessed using the Cochrane collaboration's tool. Random-effects model was used for meta-analysis.
RESULTS:
Twenty-one RCTs with 1,480 participants were included. The meta-analysis showed that cinnamon supplementation significantly reduces BMI [weighted mean difference (WMD) = -0.40 kg/m2 , 95% confidence interval (CI): -0.57, -0.22 kg/m2 , p < .001, I2 = 78.9%], body weight (WMD = -0.92 kg; 95% CI: -1.51, -0.33 kg; p = .002; I2 = 84.2%), and WHR (WMD = -0.02, 95% CI: -0.038, -0.018; p < 0.001; I2 = 0%). Cinnamon supplementation did not significantly affect the WC (WMD = -1.76 cm, 95% CI: -3.57, -0.045 cm; p = .056; I2 = 90.8%) and body fat mass (WMD = -0.87%, 95% CI: -1.87, 0.025%; p = .057; I2 = 78.6%).
CONCLUSION:
Cinnamon supplementation significantly reduces body weight, BMI, and WHR. Future high-quality long-term RCTs are recommended to confirm these results.
KEYWORDS:
anthropometric indices; body composition; body weight; cinnamon; meta-analysis; systematic review

Effect of n-3 long-chain polyunsaturated fatty acids on mild cognitive impairment: a meta-analysis of randomized clinical trials.
Zhang X, Han H, Ge X, Liu L, Wang T, Yu H.
Eur J Clin Nutr. 2019 Dec 5. doi: 10.1038/s41430-019-0544-4. [Epub ahead of print] Review.
PMID: 31804628
Abstract
N-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have positive effect on cognitive function with mild cognitive impairment (MCI) is still controversial. The aim for this meta-analysis was to assess the scientific evidence published in the last 10 years on the effects of n-3 LC-PUFAs intake on MCI patients to explore whether n-3 LC-PUFAs have positive effective. A comprehensive literature search was developed using the Google Scholar, EMBASE, and PubMed database. The pooled effect for all studies was calculated using random-effects model. And the terms of weighted mean difference (WMD) with 95% confidence interval (CI) was pooled and indicated the effects. Heterogeneity was assessed by I2 statistics. A total of seven randomized clinical trials involving 213 cases of intervention and 221 cases of placebo were included in this analysis. Compared with placebo, n-3 LC-PUFAs supplements effectively improved cognition in elders with MCI (WMD = 0.85, 95% CI: 0.04-1.67, Z = 2.05, P = 0.04). Slight heterogeneity was detected across studies. Our results provided further evidence that n-3 LC-PUFAs may have beneficial effect in elderly with MCI.

The association of dietary macronutrients with anthropometric changes, using iso-energetic substitution models: Tehran lipid and glucose study.
Hosseini-Esfahani F, Koochakpoor G, Mirmiran P, Ebrahimof S, Azizi F.
Nutr Metab (Lond). 2019 Nov 27;16:83. doi: 10.1186/s12986-019-0411-2. eCollection 2019.
PMID: 31798665 Free Article
Abstract
BACKGROUND:
The consequences of optimal dietary macronutrient compositions especially quality of proteins on weight gain still remain controversial. The aim of the current study was to evaluate the iso-energetic substitution of dietary macronutrients in relation to anthropometric changes.
METHODS:
This prospective study was conducted on 2999 men and 4001 women aged 20-70 years who were followed for 3.6 years. A valid and reliable 168-item semi-quantitative food frequency questionnaire was used to assess usual dietary intakes. Weight (kg) and waist circumference (WC) (cm) changes were calculated by subtracting the weight and WC at baseline from their measurements at follow up. Participants were divided into two groups; those with no change or decrease in weight or WC and those with increase in weight or WC. Dietary macronutrients (percentage of energy) divided by 5 to calculate one unit.
RESULTS:
A one unit higher proportion of carbohydrates at the expense of all types of fatty acids was associated with weight loss in men (P < 0.05). A one unit higher proportion of plant proteins at the expense of animal protein (β = - 0.84), non-starch carbohydrates (β = - 0.86), saturated fat (β = - 0.76), mono-unsaturated fat (β = - 0.76) and poly-unsaturated fat (β = - 0.86) was associated with weight loss (P < 0.05). A one unit higher proportion of plant proteins at the expense of animal proteins (OR: 0.49), non-starch carbohydrates (OR: 0.49), saturated fat (OR: 0.49), mono-unsaturated fat (OR: 0.49), and poly-unsaturated fat (OR: 0.48) was associated with a lower risk of increase in WC (P < 0.05).
CONCLUSIONS:
A higher proportion of dietary plant protein in replacement of simple carbohydrates, fats and animal proteins was associated with a lower increase in weight or WC.
KEYWORDS:
Macronutrients composition; Obesity; Plant proteins; Replacement

Chronic inflammation in the etiology of disease across the life span.
Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW, Miller AH, Mantovani A, Weyand CM, Barzilai N, Goronzy JJ, Rando TA, Effros RB, Lucia A, Kleinstreuer N, Slavich GM.
Nat Med. 2019 Dec;25(12):1822-1832. doi: 10.1038/s41591-019-0675-0. Epub 2019 Dec 5. Review.
PMID: 31806905
https://sci-hub.tw/10.1038/s41591-019-0675-0
Abstract
Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.

The smell of longevity: a combination of Volatile Organic Compounds (VOCs) can discriminate centenarians and their offspring from age-matched subjects and young controls.
Conte M, Conte G, Martucci M, Monti D, Casarosa L, Serra A, Mele M, Franceschi C, Salvioli S.
Geroscience. 2019 Dec 5. doi: 10.1007/s11357-019-00143-6. [Epub ahead of print]
PMID: 31808027
Abstract
Aging is characterized by dynamic changes at metabolic level that lead to modifications in the composition of the metabolome. Since the identification of biomarkers that can discriminate people of different age and health status has recently attracted a great interest, we wondered whether age-specific changes in the metabolome could be identified and serve as new and informative biomarkers of aging and longevity. In the last few years, a specific branch of metabonomics devoted to the study of volatile organic compounds (VOCs) has been developed. To date, little is known about the profile of specific VOCs in healthy aging and longevity in humans; therefore, we investigated the profile of VOCs in both urine and feces samples from 73 volunteers of different age including centenarians that represent useful "super-controls" to identify potential biomarkers of successful aging and footprints of longevity. To this purpose, we performed a discriminant analysis by which we were able to identify specific profiles of urinary and fecal VOCs. Such profiles can discriminate different age groups, from young to centenarians, and, even more interesting, centenarians' offspring from age-matched controls. Moreover, we were able to identify VOCs that are specific for the couples "centenarians - offspring" or the trios "centenarians - offspring - spouse," suggesting the possible existence of a familiar component also for VOCs profile.
KEYWORDS:
Biomarkers; Centenarians; Human longevity; Volatile organic compounds

Intermittent fasting increases adult hippocampal neurogenesis.
Baik SH, Rajeev V, Fann DY, Jo DG, Arumugam TV.
Brain Behav. 2019 Dec 5:e01444. doi: 10.1002/brb3.1444. [Epub ahead of print]
PMID: 31804775
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/brb3.1444
Abstract
INTRODUCTION:
Intermittent fasting (IF) has been suggested to have neuroprotective effects through the activation of multiple signaling pathways. Rodents fasted intermittently exhibit enhanced hippocampal neurogenesis and long-term potentiation (LTP) at hippocampal synapses compared with sedentary animals fed an ad libitum (AL) diet. However, the underlying mechanisms have not been studied. In this study, we evaluated the mechanistic gap in understanding IF-induced neurogenesis.
METHODS:
We evaluated the impact of 3 months of IF (12, 16, and 24 hr of food deprivation on a daily basis) on hippocampal neurogenesis in C57BL/6NTac mice using immunoblot analysis.
RESULTS:
Three-month IF significantly increased activation of the Notch signaling pathway (Notch 1, NICD1, and HES5), neurotrophic factor BDNF, and downstream cellular transcription factor, cAMP response element-binding protein (p-CREB). The expression of postsynaptic marker, PSD95, and neuronal stem cell marker, Nestin, was also increased in the hippocampus in response to 3-month IF.
CONCLUSIONS:
These findings suggest that IF may increase hippocampal neurogenesis involving the Notch 1 pathway.
KEYWORDS:
Notch; brain-derived neurotrophic factor; hippocampus; intermittent fasting; neurogenesis

Carotenoid Intake and Circulating Carotenoids Are Inversely Associated with the Risk of Bladder Cancer: A Dose-Response Meta-analysis.
Wu S, Liu Y, Michalek JE, Mesa RA, Parma DL, Rodriguez R, Mansour AM, Svatek R, Tucker TC, Ramirez AG.
Adv Nutr. 2019 Dec 4. pii: nmz120. doi: 10.1093/advances/nmz120. [Epub ahead of print]
PMID: 31800007
Abstract
Some evidence indicates that carotenoids may reduce the risk of bladder cancer (BC), but the association is unclear. We conducted a systematic review and meta-analysis of case-control and cohort studies investigating the relation between carotenoid intake or circulating carotenoid concentrations and BC risk in men and women. All relevant epidemiologic studies were identified by a search of PubMed and Scopus databases, and the Cochrane Library from inception to April 2019 with no restrictions. A random-effects model was used to calculate pooled RRs and their 95% CIs across studies for high compared with low categories of intake or circulating concentrations. We also performed a dose-response meta-analysis using the Greenland and Longnecker method and random-effects models. A total of 22 studies involving 516,740 adults were included in the meta-analysis. The pooled RRs of BC for the highest compared with the lowest category of carotenoid intake and circulating carotenoid concentrations were 0.88 (95% CI: 0.76, 1.03) and 0.36 (95% CI: 0.12, 1.07), respectively. The pooled RR of BC for the highest compared with lowest circulating lutein and zeaxanthin concentrations was 0.53 (95% CI: 0.33, 0.84). Dose-response analysis showed that BC risk decreased by 42% for every 1 mg increase in daily dietary β-cryptoxanthin intake (RR: 0.58; 95% CI: 0.36, 0.94); by 76% for every 1 μmol/L increase in circulating concentration of α-carotene (RR: 0.24; 95% CI: 0.08, 0.67); by 27% for every 1 μmol/L increase in circulating concentration of β-carotene (RR: 0.73; 95% CI: 0.57, 0.94); and by 56% for every 1 μmol/L increase in circulating concentrations of lutein and zeaxanthin (RR: 0.44; 95% CI: 0.28, 0.67). Dietary β-cryptoxanthin intake and circulating concentrations of α-carotene, β-carotene, and lutein and zeaxanthin were inversely associated with BC risk.
KEYWORDS:
bladder cancer; blood; carotenoids; diet; lutein; lycopene; zeaxanthin; α-carotene; β-carotene; β-cryptoxanthin

Lifestyle Aspects As A Predictor Of Pain Among Oldest-Old Primary Care Patients - A Longitudinal Cohort Study.
Mallon T, Eisele M, König HH, Brettschneider C, Röhr S, Pabst A, Weyerer S, Werle J, Mösch E, Weeg D, Fuchs A, Pentzek M, Heser K, Wiese B, Kleineidam L, Wagner M, Riedel-Heller S, Maier W, Scherer M.
Clin Interv Aging. 2019 Nov 1;14:1881-1888. doi: 10.2147/CIA.S217431. eCollection 2019.
PMID: 31802858
Abstract
PURPOSE:
Dealing with the high prevalence of pain among the oldest-old (+75) is becoming a major health issue. Therefore, the aim of the study was to uncover health-related lifestyle behaviors (HLB) and age-related comorbidities which may predict, influence and prevent pain in old age.
PATIENTS AND METHODS:
In this longitudinal cohort study, data were obtained initially from 3.327 individuals aged 75+ from over 138 general practitioners (GP) during structured clinical interviews in 2003. Nine follow-ups (FU) were assessed until 2017. Available data from 736 individuals scoring in FU3 and FU7 were included in this analysis. Data were assembled in an ambulatory setting at participant's homes. Associations were tested using a linear regression model (model 1) and ordered logistic regression model (model 2).
RESULTS:
Statistical analyses revealed increased likelihood to experience pain for participants with comorbidities such as peripheral arterial disease (PAD) (coef. 13.51, P>t = 0.00) or chronic back pain (CBP) (coef. 6.64, P>t = 0.003) or higher body mass index (BMI) (coef. 0.57, P>t = 0.015) and, female gender (coef. 6.00, SE 3.0, t = 2.02, P>t = 0.044). Participants with medium education and former smokers showed significantly lower pain rating (coef. -5.05, P>t = 0.026; coef. -5.27, P>t = 0.026). Suffering from chronic back pain (OR = 2.03), osteoarthritis (OR = 1.49) or depressive symptoms (OR = 1.10) raised the odds to experience impairments in daily living due to pain. Physical activity showed no significant results.
CONCLUSION:
Chronic conditions such as PAD, or CBP, female gender and higher BMI may increase the risk of experiencing more pain while successful smoking cessation can lower pain ratings at old age. Early and consistent support through GPs should be given to older patients in order to prevent pain at old age.
KEYWORDS:
chronic conditions; health-related aspects; longitudinal cohort study; oldest-old; pain prevention

[AlPater]

Association of Aspirin Therapy with Risk of Hepatocellular Carcinoma: a systematic review and dose-response analysis of cohort studies with 2.5 million participants.
Wang S, Yu Y, Ryan PM, Dang M, Clark C, Kontogiannis V, Rahmani J, Varkaneh HK, Salehisahlabadi A, Day AS, Zhang Y.
Pharmacol Res. 2019 Dec 6:104585. doi: 10.1016/j.phrs.2019.104585. [Epub ahead of print] Review.
PMID: 31816436
https://sci-hub.tw/10.1016/j.phrs.2019.104585
Abstract
Although aspirin is commonly used for the prevention of cardiovascular disease, evidence from research has shown that these beneficial effects might extend to hepatocellular carcinoma (HCC). This dose-response analysis was performed to investigate the association between aspirin use and risk of HCC. A systematic search was conducted in MEDLINE/PubMed, SCOPUS, Cochrane, and Web of Science databases from inception up to 29th October 2019. DerSimonian and Laird Random-effects model was used to estimate pooled hazard ratios (HRs) from included studies. Overall, eight studies containing 2,604,319 participants evaluating the association between aspirin use and risk of HCC were uncovered and included in the present meta-analysis. Pooled results of included studies showed a significant reduction in risk of HCC in participants who used aspirin (HR 0.59, 95% CI 0.47-0.75, Pheterogeneity = 0.001, I2 = 90%). In total, 13636 cases of HCC detected during the follow-up period of these studies. Furthermore, linear dose-response model showed an significant inverse association between aspirin dose and risk of HCC (exp (b) = 0.994, p < 0.001), while non-linear dose-response analysis revealed an even more robust association (Coef1=-0.008, p1 = 0.04, Coef2 = 0.033, p2 = 0.13). This systematic review and dose-response analysis identified significant inverse relation between aspirin and risk of HCC using both linear and non-linear models.
KEYWORDS:
Aspirin; Hepatocellular Carcinoma; Liver Cancer

Quantitative Association Between Serum/Dietary Magnesium and Cardiovascular Disease/Coronary Heart Disease Risk: A Dose-Response Meta-analysis of Prospective Cohort Studies.
Zhao L, Hu M, Yang L, Xu H, Song W, Qian Y, Zhao M.
J Cardiovasc Pharmacol. 2019 Dec;74(6):516-527. doi: 10.1097/FJC.0000000000000739.
PMID: 31815866
Abstract
BACKGROUND:
The quantitative association between serum/dietary magnesium and cardiovascular disease (CVD) remains unclear. We conducted a dose-response meta-analysis to evaluate the quantitative association between serum/dietary magnesium and CVD, including coronary heart disease (CHD).
METHODS:
PubMed, China National Knowledge Infrastructure, and Web of Science were searched for publications. STATA 12.0 was used to analyze data. We used the random-effects model to reduce heterogeneity.
RESULTS:
Eighteen prospective cohort studies with 544,581 participants and 22,658 CVD cases were included. The follow-up duration was 1-28 years. The pooled relative risk (RR) of CVD for the relatively normal versus lowest serum and dietary magnesium level was 0.64 {[95% confidence interval (CI): 0.51-0.80] and 0.90 [95% CI: 0.84-0.96]}. The pooled RR of CHD for the relatively normal versus lowest serum and dietary magnesium level was 0.70 (95% CI: 0.57-0.85) and 0.86 (95% CI: 0.77-0.94). We noted a significant association between increasing serum magnesium levels (per 0.1-mg/dL increase) and risk of CVD (RR: 0.93, 95% CI: 0.88-0.97) and CHD (RR: 0.90, 95% CI: 0.84-0.96) and between dietary magnesium levels (per 100-mg/d increase) and risk of CVD (RR: 0.90, 95% CI: 0.83-0.96) and CHD (RR: 0.92, 95% CI: 0.82-0.98). Serum/dietary Mg level comparisons presented a 7%-10% decrease in CVD/CHD risk. The dose-response meta-analyses showed linear relationships between serum magnesium and CVD (Pnonlinearity = 0.833) or CHD (Pnonlinearity = 0.193) and dietary magnesium and CVD (Pnonlinearity = 0.463) or CHD (Pnonlinearity = 0.440).
CONCLUSIONS:
Increasing dietary magnesium or serum magnesium level is linearly and inversely associated with the risk of total CVD and CHD events.

Hearing Impairment, Household Composition, Marital Status, and Mortality among U.S. Adults.
Denney JT, Boardman JD.
J Gerontol B Psychol Sci Soc Sci. 2019 Dec 9. pii: gbz157. doi: 10.1093/geronb/gbz157. [Epub ahead of print]
PMID: 31814013
https://watermark.silverchair.com/gbz157.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAApEwggKNBgkqhkiG9w0BBwagggJ-MIICegIBADCCAnMGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMRZWOp0XGk7aiwYB1AgEQgIICRFO5MTZXsGqWZ1v4MCZo2nYtNgcQZFFD5u1TINKmHeXiTVAd0iM19uMLd7V8S1F-BEly0thuLOCLZdhqxbcrrocqdZC5N3Heq4pCWb0WVTwrtP0umiljrCVhZYzqHoc5fAywE510bqNl5P3KUyw8T3PHag0CVHuYEyMuxAIK5jFI0Oz_yXmdjzfHcCkzX4EfY37pWql0qA0TZzrHwn09fMKyRhtI2Op7BygIZKxbFndAzK_kP2HaJaVyvRL5lMz1HqxBNme-bUyqOL52m-a9EK6OVLMD5gqlPne7eguXKjsyT8fQfzngsLXi0YrOefW2AixI5HEWKJJaDlgxUzQldoO2foo8rfD9PuUJ0hI4t4qgEMFrYUaxuAs119WiI5pU6BBq8LKPduAmGXpn4VHduMDdO7X4mlFtFeHTJhXWNZ-RAqJ8HrJ--aKCFA7MkRrBDpTAzbhBqBkmavHBHFq6loDG1L5Qr7KP6wV5P8thZT_deSUtDMtFZTrTXZLXjOan3aRTFA0n4B0gemi1CZcLFQfRyM3UJe91Zv_Cvb-HWKZbuoHPUbR1iferjzn8vQqAQG4pfaLRcgadHnaai-2UiJr9jF51_ZTrhWgMG9pNn7hjsBHophDUy-OLT3YAqCL1wEsGNFZk9bpIzT0B0rCtltqNg2bXkKCSDUCrD9clxm7pVPCeHn9VmBGCJ85Z8afd0XsmcYP0pTwxJjJPj2hp3n9tfp_J6oOVje0PL2rDH_ASD3BapxZ8aD24xR4iZ83vQCcOxaM
Abstract
OBJECTIVE:
This study investigates associations between hearing impairment, household composition, marital status, and all-cause mortality for a representative sample of United States adults aged 40 and older (N = 198,902).
METHOD:
We use data from 11 waves of the National Health Interview Survey (2004-2014) linked to prospective mortality status through 2015. The risk of mortality over the follow-up period is estimated using Cox proportional hazard models.
RESULTS:
Compared to those with good to excellent hearing, adults with moderate to severe hearing impairments and deaf adults had 11% and 21% higher risk of death from any cause over the follow-up period, respectively. Household composition and marital status, as indicators of household social support systems, associated independently with the risk of mortality but did not substantively change the association between hearing impairment and mortality.
DISCUSSION:
Hearing impairment represents an important contributor to the length of life for adults age 40 and older, independent of other important and established determinants of mortality.
KEYWORDS:
Hearing Impairment; Household Composition; Marital Status; Mortality

Premature mortality attributable to socioeconomic inequality in England between 2003 and 2018: an observational study.
Lewer D, Jayatunga W, Aldridge RW, Edge C, Marmot M, Story A, Hayward A.
Lancet Public Health. 2019 Dec 5. pii: S2468-2667(19)30219-1. doi: 10.1016/S2468-2667(19)30219-1. [Epub ahead of print]
PMID: 31813773
Abstract
BACKGROUND:
Low socioeconomic position is consistently associated with increased risk of premature death. The aim of this study is to measure the aggregate scale of inequality in premature mortality for the whole population of England.
METHODS:
We used mortality records from the UK Office for National Statistics to study all 2 465 285 premature deaths (defined as those before age 75 years) in England between Jan 1, 2003, and Dec 31, 2018. Socioeconomic position was defined using deciles of the Index of Multiple Deprivation: a measure of neighbourhood income, employment, education levels, crime, health, availability of services, and local environment. We calculated the number of expected deaths by applying mortality rates in the least deprived decile to other deciles, within the strata of age, sex, and time. The mortality rates attributable to socioeconomic inequality was defined as the difference between the observed and expected deaths. We also used life table modelling to estimate years-of-life lost attributable to socioeconomic inequality.
FINDINGS:
35·6% (95% CI 35·3-35·9) of premature deaths were attributable to socioeconomic inequality, equating to 877 082 deaths, or one every 10 min. The biggest contributors were ischaemic heart disease (152 171 excess deaths), respiratory cancers (111 083) and chronic obstructive pulmonary disease (83 593). The most unequal causes of death were deaths due to tuberculosis, opioid use, HIV, psychoactive drugs use, viral hepatitis, and obesity, each with more than two-thirds attributable to inequality. Inequality was greater among men and peaked in early childhood and at age 40-49 years. The proportion of deaths attributable to inequality increased during the study period, particularly for women, because mortality rates among the most deprived women (excluding cardiovascular diseases) plateaued, and for some diseases increased. A mean of 14·4 months of life before age 75 years are lost due to socioeconomic inequality.
INTERPRETATION:
One in three premature deaths are attributable to socioeconomic inequality, making this our most important public health challenge. Interventions that address upstream determinants of health should be prioritised.

A little stress in the first years of life extends the lifespan, as shown in research on intestinal worms
BY
ISAAC NOVAK
DECEMBER 5, 2019
https://upnewsinfo.com/2019/12/05/a-little-stress-in-the-first-years-of-life-extends-the-lifespan-as-shown-in-research-on-intestinal-worms/
>>>>>>>>>>>>>>>>>
Developmental ROS individualizes organismal stress resistance and lifespan.
Bazopoulou D, Knoefler D, Zheng Y, Ulrich K, Oleson BJ, Xie L, Kim M, Kaufmann A, Lee YT, Dou Y, Chen Y, Quan S, Jakob U.
Nature. 2019 Dec 4. doi: 10.1038/s41586-019-1814-y. [Epub ahead of print]
PMID: 31801997
Abstract
A central aspect of aging research concerns the question of when individuality in lifespan arises1. Here we show that a transient increase in reactive oxygen species (ROS), which occurs naturally during early development in a subpopulation of synchronized Caenorhabditis elegans, sets processes in motion that increase stress resistance, improve redox homeostasis and ultimately prolong lifespan in those animals. We find that these effects are linked to the global ROS-mediated decrease in developmental histone H3K4me3 levels. Studies in HeLa cells confirmed that global H3K4me3 levels are ROS-sensitive and that depletion of H3K4me3 levels increases stress resistance in mammalian cell cultures. In vitro studies identified SET1/MLL histone methyltransferases as redox sensitive units of the H3K4-trimethylating complex of proteins (COMPASS). Our findings implicate a link between early-life events, ROS-sensitive epigenetic marks, stress resistance and lifespan.