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Impact of Aging on Metabolic Changes in the Ketotic Rat Brain: Glucose, Oxidative and 4-HNE Metabolism.
Zhang Y, Xu K, Kerwin T, LaManna JC, Puchowicz M.
Adv Exp Med Biol. 2018;1072:21-25. doi: 10.1007/978-3-319-91287-5_4.
PMID: 30178318
Abstract
Neuroprotection by ketosis is thought to be associated with improved mitochondrial function, decreased reactive oxygen species (ROS) and apoptotic and inflammatory mediators, and increased protective pathways. Oxidative injury to cells is often associated with lipid peroxidation. Accumulation of intermediary products of lipid peroxidation includes 4-hydroxynonenal (HNE; a toxic lipid peroxidation intermediate). We investigated the metabolic effects of diet-induced ketosis on cerebral metabolic rate of glucose (CMRglc), Acetyl-coA, and HNE concentrations in young and aged rats. Rats (3 months old and 18 months old) were randomly assigned to two groups, ketogenic (high fat, carbohydrate restricted; KG) or standard lab-chow (STD) diet for 4 weeks. CMRglc was measured using 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (PET). Cerebral metabolic rates of glucose (μmol/min per 100 g) was determined in the brain using Gjedde-Patlak analysis. Acetyl-coA, glutamate and HNE concentrations in cortical tissues were measured using mass spectrometry. We observed a 30% reduction of CMRglc in young ketotic rats, whereas CMRglc in the aged on the KG diet was similar to the STD groups. We observed no differences in cortical Acetyl-coA concentrations between the groups. Glutamate concentrations were significantly reduced in the aged STD group, but recovered in the KG group, compared to the young. Brain ketone body concentrations were highest in the young KG rats (tenfold vs STD), whereas ketone body levels in the aged KG brains were 30% of the young KG. The lack of KG diet effect on CMRglc in the aged rats was not expected. Also noted was that, in the aged rats, HNE levels were not elevated as we had expected. Together these findings suggest that oxidative metabolism may be reduced in the aged.

Benefits and Risks of Nonsteroidal Anti-inflammatory Drugs: Methodologic Limitations Lead to Clinical Uncertainties.
Rane MA, Foster JG, Wood SK, Hebert PR, Hennekens CH.
Ther Innov Regul Sci. 2018 Sep 3:2168479018794159. doi: 10.1177/2168479018794159. [Epub ahead of print]
PMID: 30176739
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) include traditional (tNSAIDs), such as ibuprofen, naproxen, and diclofenac, as well as selective cyclooxygenase-2 inhibitors (COXIBs), principally celecoxib. COXIBs were developed to decrease gastrointestinal side effects. Recently, the US Food and Drug Administration strengthened its warning about the risks of non-aspirin NSAIDs on myocardial infarction and stroke. The Cyclooxygenase 2 and Non-Steroidal Anti-Inflammatory Drug Trialist collaboration conducted a comprehensive worldwide meta-analysis using individual patient data exploring the risks of various COXIBs and NSAIDs on cardiovascular disease (CVD). Recently, the results of the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trial were published that tested risks of COXIBs and NSAIDs on CVD. Generally, data from meta-analyses of trials not designed a priori to test hypotheses are less reliable than large-scale randomized trials to test small to moderate benefits or harm. When the sample size is large, randomization provides control of confounding not possible to achieve in any observational study. Further, observational studies, and especially claims data, have inherent confounding by indication larger than the effects being sought. Nonetheless, trials must be of sufficient size and duration and achieve high compliance and follow-up to avoid bias and confounding. In this regard, PRECISION has high rates of nonadherence and losses to follow-up that may have introduced bias and confounding. At present, therefore, it may be most prudent for clinicians to remain uncertain about benefits and risks of these drugs and make individual clinical judgments for each of their patients.
KEYWORDS:
PRECISION; cardiovascular
>>>>>>>>>>>>>>>>>>>>
FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes
[ 7-9-2015 ]
https://www.fda.gov/Drugs/DrugSafety/ucm451800.htm

Coffee, Caffeine Metabolism Genotype, and Disease Progression in Localized Prostate Cancer Patients Managed with Active Surveillance.
Gregg JR, Lopez DS, Reichard C, Zheng J, Wu W, Ye Y, Chapin B, Kim J, Daniel CR, Davis J.
J Urol. 2018 Sep 1. pii: S0022-5347(18)43796-2. doi: 10.1016/j.juro.2018.08.048. [Epub ahead of print]
PMID: 30179617
Abstract
PURPOSE:
Active surveillance (AS) is increasingly used as a management strategy for localized prostate cancer. Coffee intake has been associated with lower prostate cancer incidence; and we assessed whether coffee was associated with disease progression in men on AS.
MATERIALS AND METHODS:
Patients with newly diagnosed Gleason score (GS) 6 or 7 prostate cancer were enrolled on a prospective AS protocol for at least 6 months and completed a baseline dietary assessment (n=411). The AS protocol included a biennial monitoring regimen with disease progression defined as an increase in GS. Cox proportional hazards models were used to evaluate associations of coffee intake with progression-free survival. Patient genotype in the caffeine metabolism-related SNP rs762551 was also evaluated.
RESULTS:
Median follow-up was 36 months (range 6 - 126), and 76/411 (18.5%) had GS progression. In the multivariable model adjusting for PSA, age and tumor length, compared to 0 cups/day, <1 cup (HR 0.85, 95%CI 0.40-1.71), 1-1.9 cups (HR 0.64, 95%CI 0.29-1.43), 2-3.9 cups (HR 0.71, 95%CI 0.35-1.47), and ≥4 cups (HR 1.67, 95%CI 0.81-3.45) were not significantly associated with progression-free survival (P for non-linearity = 0.01). Patients with low/moderate coffee intake and the AA "fast caffeine metabolizer" genotype were less likely to experience grade progression, as compared to non-consumers (HR 0.36, 95% CI 0.15-0.88, P=0.03).
CONCLUSIONS:
Low to moderate coffee intake appears safe in men on AS for localized prostate cancer. Further work is needed to determine if high consumption is associated with shorter progression-free survival in sensitive groups.
KEYWORDS:
Prostatic neoplasms; caffeine; coffee; genetic variation; risk

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A Dietary Intervention to Lower Serum Levels of IGF-I in BRCA Mutation Carriers.
Pasanisi P, Bruno E, Venturelli E, Morelli D, Oliverio A, Baldassari I, Rovera F, Iula G, Taborelli M, Peissel B, Azzolini J, Manoukian S.
Cancers (Basel). 2018 Sep 4;10(9). pii: E309. doi: 10.3390/cancers10090309.
PMID: 30181513
http://www.mdpi.com/2072-6694/10/9/309/htm
Abstract
BACKGROUND:
Insulin-like growth factor I (IGF-I) and other markers of insulin resistance (IRm) might influence the penetrance of BRCA gene mutation. In a demonstration project on BRCA mutation carriers we tested the effect of the 'Mediterranean diet', with moderate protein restriction, on serum levels of IGF-I and IRm.
METHODS:
BRCA mutation carriers, with or without breast cancer, aged 18⁻70 years and without metastases were eligible. After the baseline examinations, women were randomized to an active dietary intervention or to a control group. The intervention group attended six full days of life-style intervention activities (cookery classes followed by lunch, sessions of walking for 45 min and nutritional conferences) over the next six months.
RESULTS:
213 BRCA mutation carriers completed the six-month study. Women in the intervention group (110) showed major changes in all the parameters under study. They significantly lost weight (p < 0.001), fat mass (p = 0.002), with reduced hip circumference (p = 0.01), triglycerides (p = 0.02) and IGF-I (p = 0.02) compared with controls. They also had a significantly higher levels of insulin-like growth factor-binding protein 3 (IGFI-BP3) (p = 0.03) and a lower IGF-I/IGFI-BP3 ratio (p = 0.04). The reduction of serum levels of IGF-I was significantly associated with the reduction in the consumption of animal products (p = 0.04).
CONCLUSIONS:
Women in the intervention group showed significant improvements in IGF-I and in other IRm that might influence the penetrance of BRCA mutations.
KEYWORDS:
BRCA genes; IGF-I; diet; mutation carriers; penetrance
>>>>>>>>>>>>>>>>>
"In humans, calorie restriction alone does not seem to significantly lower IGF-I; protein restriction
is also required [36]. Men and women belonging to the Calorie Restriction Society, in fact, who
consume a fairly large amount of protein, had lower levels of several biomarkers of cardiovascular
risk, but not of IGF-I [36]. IGF-I, however, was markedly reduced in raw food vegetarians, who have
very low protein consumption (0.9 g/kg body weight) [37]. Fontana et al. [38] persuaded six members
of the Calorie Restriction Society to reduce their protein intake from 24% to about 10% for three weeks.
This resulted in plasma IGF-I falling from 194 ng/mL to 152 ng/mL. Therefore, protein restriction
might be effective in reducing IGF-I."

Physical fitness and dementia risk in the very old: a study of the Lothian Birth Cohort 1921.
Sibbett RA, Russ TC, Allerhand M, Deary IJ, Starr JM.
BMC Psychiatry. 2018 Sep 4;18(1):285. doi: 10.1186/s12888-018-1851-3.
PMID: 30180830
https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-018-1851-3
https://bmcpsychiatry.biomedcentral.com/track/pdf/10.1186/s12888-018-1851-3
Abstract
BACKGROUND:
Previous studies have demonstrated that individual measures of fitness - such as reduced pulmonary function, slow walking speed and weak handgrip - are associated with an increased risk of dementia. Only a minority of participants included in these studies were aged over 80. The aim of this study was therefore to investigate the association between physical fitness and dementia in the oldest old.
METHODS:
Subjects (n = 488) were enrolled in the Lothian Birth Cohort 1921 and aged 79 at baseline. Dementia cases arising after enrolment were determined using data from death certificates, electronic patient records and clinical reviews. Fitness measures included grip strength, forced expiratory volume in 1 s (FEV1) and walking speed over 6 m, measured at 79 years. Dementia risk associated with each fitness variable was initially determined by logistic regression analysis, followed by Cox regression analysis, where death was considered as a competing risk. APOE ε4 status, age, sex, height, childhood IQ, smoking, history of cardiovascular or cerebrovascular disease, hypertension and diabetes were included as additional variables. Cumulative incidence graphs were calculated using Aalen-Johansen Estimator.
RESULTS:
Although initial results indicated that greater FEV1 was associated with an increased risk of dementia (OR (odds ratio per unit increase) 1.93, p = 0.03, n = 416), taking into account the competing risk of mortality, none of the fitness measures were found to be associated with dementia; FEV1 (HR (hazard ratio per unit increase) 1.30, p = 0.37, n = 416), grip strength (HR 0.98, p = 0.35, n = 416), walking speed (HR 0.99, p = 0.90, n = 416). The presence of an APOE ɛ4 allele was however an important predictor for dementia (HR 2.85, p < 0.001, n = 416). Cumulative incidence graphs supported these findings, with an increased risk of dementia for APOE ɛ4 carriers compared with non-carriers. While increased FEV1 was associated with reduced risk of death, there was no reduction in risk for dementia.
CONCLUSIONS:
In contrast to previous studies, this study found that lower fitness beyond age 79 was not a risk factor for subsequent dementia. This finding is not explained by those with poorer physical fitness, who would have been more likely to develop dementia, having died before onset of dementia symptoms.
KEYWORDS:
Cohort studies; Dementia; Fitness; Risk factors; Terms

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Dietary protein restriction reprograms tumor associated macrophages and enhances immunotherapy.
Orillion AR, Damayanti NP, Shen L, Adelaiye-Ogala R, Affronti HC, Elbanna M, Chintala S, Ciesielski MJ, Fontana L, Kao C, Elzey BD, Ratliff TL, Nelson DE, Smiraglia DJ, Abrams SI, Pili R.
Clin Cancer Res. 2018 Sep 6. pii: clincanres.0980.2018. doi: 10.1158/1078-0432.CCR-18-0980. [Epub ahead of print]
PMID: 30190370
Abstract
PURPOSE:
Diet and healthy weight are established means of reducing cancer incidence and mortality. However, the impact of diet modifications on the tumor microenvironment (TME) and antitumor immunity are not well-defined. Immunosuppressive tumor-associated macrophages (TAMs) are associated with poor clinical outcomes and are potentially modifiable through dietary interventions. We tested the hypothesis that dietary protein restriction modifies macrophage function toward antitumor phenotypes.
EXPERIMENTAL DESIGN:
Macrophage functional status under different tissue culture conditions and in vivo was assessed by Western blot, immunofluorescence, qRT-PCR, and cytokine array analyses. Tumor growth in the context of protein or amino acid (AA)-restriction and immunotherapy, namely a survivin peptide-based vaccine or a PD-1 inhibitor, was examined in animal models of prostate (RP-B6Myc) and renal (RENCA) cell carcinoma. All tests were two-sided.
RESULTS:
Protein or AA-restricted macrophages exhibited enhanced tumoricidal, pro-inflammatory phenotypes, and in two syngeneic tumor models, protein or AA-restricted diets elicited reduced TAM infiltration, tumor growth, and increased response to immunotherapies. Further, we identified a distinct molecular mechanism by which AA-restriction reprograms macrophage function via a ROS/mTOR centric cascade.
CONCLUSIONS:
Dietary protein restriction alters TAM activity and enhances the tumoricidal capacity of this critical innate immune cell type, providing the rationale for clinical testing of this supportive tool in patients receiving cancer immunotherapies.

Insulin-like growth factor-I concentration and risk of prostate cancer: results from the European Prospective Investigation into Cancer and Nutrition.
Price AJ, Allen NE, Appleby PN, Crowe FL, Travis RC, Tipper SJ, Overvad K, Grønbæk H, Tjønneland A, Johnsen NF, Rinaldi S, Kaaks R, Lukanova A, Boeing H, Aleksandrova K, Trichopoulou A, Trichopoulos D, Andarakis G, Palli D, Krogh V, Tumino R, Sacerdote C, Bueno-de-Mesquita HB, Argüelles MV, Sánchez MJ, Chirlaque MD, Barricarte A, Larrañaga N, González CA, Stattin P, Johansson M, Khaw KT, Wareham N, Gunter M, Riboli E, Key T.
Cancer Epidemiol Biomarkers Prev. 2012 Sep;21(9):1531-41. doi: 10.1158/1055-9965.EPI-12-0481-T. Epub 2012 Jul 3.
PMID: 22761305 Free PMC Article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749609/pdf/emss-53860.pdf
Abstract
BACKGROUND:
High circulating insulin-like growth factor-I (IGF-I) concentrations have been associated with increased risk for prostate cancer in several prospective epidemiological studies. In this study, we investigate the association between circulating IGF-I concentration and risk of prostate cancer over the long term in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
METHODS:
In a nested case-control design, 1,542 incident prostate cancer cases from eight European countries were individually matched to 1,542 controls by study center, age at recruitment, duration of follow-up, time of day, and duration of fasting at blood collection. Conditional logistic regression models were used to calculate risk for prostate cancer associated with IGF-I concentration, overall and by various subgroups.
RESULTS:
Circulating IGF-I concentration was associated with a significant increased risk for prostate cancer [OR for highest vs. lowest quartile, 1.69; 95% confidence interval (CI), 1.35-2.13; P(trend) = 0.0002]. This positive association did not differ according to duration of follow-up [ORs for highest vs. lowest quartile were 2.01 (1.35-2.99), 1.37 (0.94-2.00), and 1.80 (1.17-2.77) for cancers diagnosed <4, 4-7, and >7 years after blood collection, respectively (P(heterogeneity) = 0.77)] or by stage, grade, and age at diagnosis or age at blood collection (all subgroups P(heterogeneity) >0.05).
CONCLUSION:
In this European population, high circulating IGF-I concentration is positively associated with risk for prostate cancer over the short and long term.
IMPACT:
As IGF-I is the only potentially modifiable risk factor so far identified, research into the effects of reducing circulating IGF-I levels on subsequent prostate cancer risk is warranted.
>>>>>>>>>>>>>>>>>>>>>>
Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 concentrations and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition.
Allen NE, Key TJ, Appleby PN, Travis RC, Roddam AW, Rinaldi S, Egevad L, Rohrmann S, Linseisen J, Pischon T, Boeing H, Johnsen NF, Tjønneland A, Grønbaek H, Overvad K, Kiemeney L, Bueno-de-Mesquita HB, Bingham S, Khaw KT, Tumino R, Berrino F, Mattiello A, Sacerdote C, Palli D, Quirós JR, Ardanaz E, Navarro C, Larrañaga N, Gonzalez C, Sanchez MJ, Trichopoulou A, Travezea C, Trichopoulos D, Jenab M, Ferrari P, Riboli E, Kaaks R.
Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1121-7.
PMID: 17548673 Free Article
http://cebp.aacrjournals.org/content/16/6/1121.long
Abstract
BACKGROUND:
Some studies suggest that elevated serum insulin-like growth factor (IGF)-I concentrations are associated with an increased risk of prostate cancer and, in particular, with an increased risk of advanced-stage prostate cancer.
METHODS:
We analyzed the association between prediagnostic serum concentrations of IGF-I and IGF-binding protein-3 (IGFBP-3) and prostate cancer risk in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. This study includes 630 incident prostate cancer cases and 630 matched control subjects. Odds ratios and their 95% confidence intervals (95% CI) were calculated for prostate cancer risk associated with increasing IGF-I and IGFBP-3 concentrations using conditional logistic regression.
RESULTS:
The risk of total prostate cancer in the highest versus the lowest third of serum peptide concentration was 1.35 (95% CI, 0.99-1.82; Ptrend = 0.08) for IGF-I, 1.39 (95% CI, 1.02-1.89; Ptrend = 0.12) for the IGF-I residuals after adjusting for IGFBP-3, 1.22 (95% CI, 0.92-1.64; Ptrend = 0.38) for IGFBP-3, and 1.01 (95% CI, 0.74-1.37; Ptrend = 0.75) for the IGFBP-3 residuals after adjusting for IGF-I. There was no significant difference in the association of peptide hormones and prostate cancer by stage of disease, although the association of serum IGF-I concentration with risk was slightly stronger for advanced-stage disease; the odds ratio for the highest versus the lowest third was 1.65 (95% CI, 0.88-3.08; Ptrend = 0.21) for IGF-I and 1.76 (95% CI, 0.92-3.40; Ptrend = 0.11) for IGF-I adjusted for IGFBP-3.
CONCLUSIONS:
In this large nested case-control study, serum IGF-I concentration is not strongly associated with prostate cancer risk, although the results are compatible with a small increase in risk, particularly for advanced-stage disease; no association for IGFBP-3 was observed.

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Amusing.

Two sets of conclusions on essentially the same subject -- possible correlation of serum IGF1 levels with prostate cancer risk -- based on portions of the same study, reaching different conclusions (the two are, or are not, significantly positively correlated).

Perhaps a more careful statistical analysis of this material might be justified.

 ?

   --  Saul

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Saul,

 

10 minutes ago, Saul said:

Perhaps a more careful statistical analysis of this material might be justified.

If you read Al's first (2012) paper, you'll see that it was a more careful analysis of the data from the second (2007) paper, along with more data from the same population of European men, including a longer follow-up and hence more cases of prostate cancer (1542 vs. 630)  among the men they've been following in EPIC.

It looks like (unsurprisingly) higher total and free IGF-1 is positively correlated with later diagnosis of prostate cancer in this population.

--Dean

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Various Leisure-Time Physical Activities Associated With Widely Divergent Life Expectancies:The Copenhagen City Heart Study.
Schnohr P, O'Keefe JH, Holtermann A, Lavie CJ, Lange P, Jensen GB, Marott JL.
Mayo Clin Proc. 2018 Aug 31. pii: S0025-6196(18)30538-X. doi: 10.1016/j.mayocp.2018.06.025. [Epub ahead of print]
PMID: 30193744
Abstract
OBJECTIVE:
To evaluate the differential improvements in life expectancy associated with participation in various sports.
PATIENTS AND METHODS:
The Copenhagen City Heart Study (CCHS) is a prospective population study that included detailed questionnaires regarding participation in different types of sports and leisure-time physical activity. The 8577 participants were followed for up to 25 years for all-cause mortality from their examination between October 10, 1991, and September 16, 1994, until March 22, 2017. Relative risks were calculated using Cox proportional hazards models with full adjustment for confounding variables.
RESULTS:
Multivariable-adjusted life expectancy gains compared with the sedentary group for different sports were as follows: tennis, 9.7 years; badminton, 6.2 years; soccer, 4.7 years; cycling, 3.7 years; swimming, 3.4 years; jogging, 3.2 years; calisthenics, 3.1 years; and health club activities, 1.5 years.
CONCLUSION:
Various sports are associated with markedly different improvements in life expectancy. Because this is an observational study, it remains uncertain whether this relationship is causal. Interestingly, the leisure-time sports that inherently involve more social interaction were associated with the best longevity-a finding that warrants further investigation.

Fat intake during pregnancy and risk of preeclampsia: a prospective cohort study in Denmark.
Arvizu M, Afeiche MC, Hansen S, Halldorsson TF, Olsen SF, Chavarro JE.
Eur J Clin Nutr. 2018 Sep 7. doi: 10.1038/s41430-018-0290-z. [Epub ahead of print]
PMID: 30194370
Abstract
BACKGROUND:
Previous studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), may decrease the risk of preeclampsia, but many suffer from important methodological limitations.
METHODS:
We prospectively examined the association between fat intake during pregnancy and preeclampsia and among 65,220 singleton pregnancies in the Danish National Birth Cohort (1996-2002). Women were asked to report their diet around gestation week 20 with a food frequency questionnaire. Preeclampsia diagnosis was obtained via linkage with the Danish National Patient Registry. We estimated relative risks (RR) and 95% confidence intervals (95% CI) of preeclampsia and severe preeclampsia according to fat intake using logistic regression models with generalized estimating equations to account for repeated pregnancies per woman while adjusting for potential confounders.
RESULTS:
We documented 1302 cases of preeclampsia, including 301 cases of severe preeclampsia. Intake of long-chain omega-3 fatty acids was associated to preeclampsia. Women in the top quintile of DHA intake had a lower risk of preeclampsia (RR 0.67 (0.51-0.89)) and severe preeclampsia (RR 0.46 (0.25-0.83)) than women in the bottom quintile. Women who met daily recommended intake of EPA+DHA according to the Dietary Guidelines for Americans (≥250 mg/day), had a lower risk of severe preeclampsia (RR 0.77 (0.60-0.99)), but not of preeclampsia (RR 0.93 (0.82-1.05)). Conversely, ALA intake was associated with higher risk of severe preeclampsia (RR 1.71 (1.07-2.75)).
CONCLUSIONS:
Higher intake of DHA is inversely related to preeclampsia and severe preeclampsia, whereas ALA increases the risk of severe preeclampsia among Danish women.

Dietary carbohydrate quality and quantity in relation to the incidence of type 2 diabetes: A prospective cohort study of middle-aged and older Korean adults.
Lee KW, Lyu J, Park JK, Jo C, Kim SS.
Nutrition. 2018 May 24;57:245-251. doi: 10.1016/j.nut.2018.04.011. [Epub ahead of print]
PMID: 30195245
https://sci-hub.tw/10.1016/j.nut.2018.04.011
Abstract
OBJECTIVES:
This study aimed to investigate whether dietary glycemic load (GL), glycemic index (GI), and carbohydrate intake were prospectively associated with incident type 2 diabetes mellitus (T2DM) in a middle-aged and older Korean populations.
METHODS:
Data from the Korean Genome and Epidemiology Study were used. A total of 7294 Korean adults ages 40 y to 69 y and with no previous diagnosis of T2DM or cancer at baseline were followed for 10 y. Dietary GL, GI, and carbohydrate intake were estimated on the basis of participants' responses to a validated, semiquantitative, food-frequency questionnaire at baseline. T2DM was defined according to the World Health Organization and International Diabetes Federation criteria.
RESULTS:
During 7.7 y (56 377 person-years) of follow-up time, 1259 participants (17.3%) developed T2DM. Grain and its products (particularly refined and whole grains) were the greatest contributors to dietary GL. In the multivariable Cox models, dietary GL was differentially associated with T2DM risk by sex. Men in the highest quintile demonstrated a higher risk of T2DM incidence than did those with the lowest, energy-adjusted, dietary GL (hazard ratio for fifth vs. first quarter = 1.26; 95% confidence interval, 1.05-1.52; P for trend < 0.05) but no association between dietary GL and the risk of T2DM was observed in women. Similar to the findings from the main models, the effect of dietary GL on T2DM incidence according to body mass index, abdominal obesity, and physical activity levels differed substantially by sex.
CONCLUSIONS:
High GL diets may increase the risk of the development of T2DM in middle-aged and older Korean men but not in women. Nutrition education and emphasis on self-monitoring of dietary carbohydrate quality and quantity of overall diets is necessary in the middle-aged and older Korean populations.
KEYWORDS:
Dietary glycemic load; KoGES; Korean adults; Prospective studies; Type 2 diabetes

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22 hours ago, Dean Pomerleau said:

Saul,

 

If you read Al's first (2012) paper, you'll see that it was a more careful analysis of the data from the second (2007) paper, along with more data from the same population of European men, including a longer follow-up and hence more cases of prostate cancer (1542 vs. 630)  among the men they've been following in EPIC.

It looks like (unsurprisingly) higher total and free IGF-1 is positively correlated with later diagnosis of prostate cancer in this population.

--Dean

Hi Dean!

Yes, you're right.

  --  Saul

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What's the difference? A gender perspective on understanding educational inequalities in all-cause and cause-specific mortality.
van Hedel K, van Lenthe FJ, Oude Groeniger J, Mackenbach JP.
BMC Public Health. 2018 Sep 10;18(1):1105. doi: 10.1186/s12889-018-5940-5.
PMID: 30200912
https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-018-5940-5
Abstract
BACKGROUND:
Material and behavioural factors play an important role in explaining educational inequalities in mortality, but gender differences in these contributions have received little attention thus far. We examined the contribution of a range of possible mediators to relative educational inequalities in mortality for men and women separately.
METHODS:
Baseline data (1991) of men and women aged 25 to 74 years participating in the prospective Dutch GLOBE study were linked to almost 23 years of mortality follow-up from Dutch registry data (6099 men and 6935 women). Cox proportional hazard models were used to calculate hazard ratios with 95% confidence intervals, and to investigate the contribution of material (financial difficulties, housing tenure, health insurance), employment-related (type of employment, occupational class of the breadwinner), behavioural (alcohol consumption, smoking, leisure and sports physical activity, body mass index) and family-related factors (marital status, living arrangement, number of children) to educational inequalities in all-cause and cause-specific mortality, i.e. mortality from cancer, cardiovascular disease, other diseases and external causes.
RESULTS:
Educational gradients in mortality were found for both men and women. All factors together explained 62% of educational inequalities in mortality for lowest educated men, and 71% for lowest educated women. Yet, type of employment contributed substantially more to the explanation of educational inequalities in all-cause mortality for men (29%) than for women (- 7%), whereas the breadwinner's occupational class contributed more for women (41%) than for men (7%). Material factors and employment-related factors contributed more to inequalities in mortality from cardiovascular disease for men than for women, but they explained more of the inequalities in cancer mortality for women than for men.
CONCLUSIONS:
Gender differences in the contribution of employment-related factors to the explanation of educational inequalities in all-cause mortality were found, but not of material, behavioural or family-related factors. A full understanding of educational inequalities in mortality benefits from a gender perspective, particularly when considering employment-related factors.
KEYWORDS:
Education; Gender differences; Mortality; Socioeconomic inequalities

Dietary fiber intake and risks of proximal and distal colon cancers: A meta-analysis.
Ma Y, Hu M, Zhou L, Ling S, Li Y, Kong B, Huang P.
Medicine (Baltimore). 2018 Sep;97(36):e11678. doi: 10.1097/MD.0000000000011678.
PMID: 30200062
Abstract
The purpose of this study was to conduct a systematic review and meta-analysis of studies investigating the relationship between dietary fiber intake and subsite-specific colon cancer.The PubMed database was searched to identify relevant cohort studies published from inception to August 2016 in order to examine individually the association between dietary fiber intake and the risk of proximal colon cancer (PCC), and that between dietary fiber intake and the risk of distal colon cancer (DCC). We searched the reference lists of the studies included in our analysis as well as those listed in the published meta-analyses. A random-effects model was used to compute summary risk estimates. Heterogeneity was assessed using I and Q statistics. Publication bias was assessed with the Egger's and Begg's tests, with a P value of P < .10 indicating publication bias. All statistical tests were 2-sided.We identified and included 11 prospective cohort studies in the final meta-analysis. The risks of PCC and DCC among individuals in the highest dietary fiber intake quartile/quintile were 14% (relative risk [RR] = 0.86, 95% confidence interval [CI] = 0.78-0.95) and 21% (RR = 0.79, 95% CI = 0.71-0.87) lower, respectively, than those among individuals with the lowest dietary fiber intake. In a subgroup analysis, the inverse association observed in the sex-based subgroup was apparent only for men with PCC. Dietary fiber intake was inversely associated with DCC for both men and women. In addition, dietary fiber intake appeared to be inversely associated with PCC only in European countries, whereas this association was observed for DCC in both European countries and the United States.Our findings reveal that dietary fiber intake is associated inversely with the risk of both PCC and DCCs.

Green Tea, Coffee, and Caffeine Consumption Are Inversely Associated with Self-Report Lifetime Depression in the Korean Population.
Kim J, Kim J.
Nutrients. 2018 Sep 1;10(9). pii: E1201. doi: 10.3390/nu10091201.
PMID: 30200434
Abstract
This study investigated the associations of green tea, coffee, and caffeine consumption with self-report lifetime depression in the Korean population using data from the Korean National Health and Nutrition Examination Survey. In total, 9576 participants (3852 men and 5724 women) aged 19 years or older were selected for the present study. Green tea, coffee, and caffeine consumption levels were assessed with a validated food frequency questionnaire. Multivariate logistic regression analysis was used to determine the odds ratios (OR) and 95% confidence intervals (CIs) for depression according to green tea, coffee, and caffeine consumption. Frequent green tea consumers (≥3 cups/week) had 21% lower prevalence of depression (OR = 0.79, 95% CI = 0.63⁻0.99, p for trend = 0.0101) than green tea non-consumers after adjustment for potential confounders. Likewise, frequent coffee drinkers (≥2 cups/day) had 32% lower prevalence of depression (OR = 0.68, 95% CI = 0.55⁻0.85, p for trend = 0.0026) than coffee non-drinkers after adjustment for potential confounders. Also, participants in the highest quartile of caffeine consumption had 24% lower prevalence of depression than those in the lowest quartile (OR = 0.76, 95% CI = 0.62⁻0.92, p for trend = 0.0032). Frequent consumption of green tea, coffee, or caffeine was associated with a reduced prevalence of self-report lifetime depression in Korean adults. A prospective study and randomized clinical trials should be conducted to confirm the inverse relationships of green tea and coffee consumption with risk of depression.
KEYWORDS:
caffeine; coffee; depression; green tea

Prospective Associations of Erythrocyte Composition and Dietary Intake of n-3 and n-6 PUFA with Measures of Cognitive Function.
Bigornia SJ, Scott TM, Harris WS, Tucker KL.
Nutrients. 2018 Sep 6;10(9). pii: E1253. doi: 10.3390/nu10091253.
PMID: 30200655
http://www.mdpi.com/2072-6643/10/9/1253/htm
Abstract
Polyunsaturated fatty acid (PUFA) consumption is recommended as part of a healthy diet, but evidence of the impact of individual species and biological concentrations on cognitive function is limited. We examined prospective associations of PUFA erythrocyte composition and dietary intake with measures of cognitive function among participants of the Boston Puerto Rican Health Study (aged 57 years). Erythrocyte and dietary PUFA composition were ascertained at baseline and associated with 2-year scores on the Mini-Mental State Exam (MMSE) (n = 1032) and cognitive domain patterns derived from a battery of tests (n = 865), as well as with incidence of cognitive impairment. Erythrocyte and dietary n-3 PUFA were not significantly associated with MMSE score. However, total erythrocyte and dietary n-3 very-long-chain fatty acids (VLCFA), and intake of individual species, were associated with better executive function (P-trend < 0.05, for all). There was evidence that greater erythrocyte n-6 eicosadienoic acid concentration was associated with lower MMSE and executive function scores (P-trend = 0.02). Only erythrocyte arachidonic acid (ARA) concentration predicted cognitive impairment (Odds Ratio = 1.26; P = 0.01). Among Puerto Rican adults, we found that n-3 VLCFA consumption may beneficially impact executive function. Further, these findings provide some evidence that n-6 metabolism favoring greater ARA tissue incorporation, but not necessarily dietary intake, could increase the risk of cognitive impairment.
KEYWORDS:
Boston Puerto Rican Health Study; cognitive function; erythrocyte fatty acids; omega-3 fatty acids; omega-6 fatty acids

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Physical activity attenuates the impact of poor physical, mental, and social health on total and cardiovascular mortality in older adults: a population-based prospective cohort study.
Higueras-Fresnillo S, Cabanas-Sánchez V, García-Esquinas E, Rodríguez-Artalejo F, Martinez-Gomez D.
Qual Life Res. 2018 Sep 11. doi: 10.1007/s11136-018-1974-5. [Epub ahead of print]
PMID: 30206816
http://sci-hub.tw/http://link.springer.com/10.1007/s11136-018-1974-5
Abstract
PURPOSE:
To examine the separate and joint associations of physical activity and levels of physical, mental, and social health with long-term all-cause and cardiovascular disease (CVD) mortality in older adults.
METHODS:
A cohort of 4008 individuals representative of the non-institutionalized population of Spain aged 60 years and older was analyzed. Information on physical activity was self-reported. Physical and mental health were assessed with the SF-36 questionnaire, and social health with a 4-item score on network structure and social engagement. Participants were categorized as being in a good, intermediate, or poor health according to tertiles of the score in each health dimension. Analyses were performed with Cox regression and adjusted for main confounders, including levels in the other two health dimensions.
RESULTS:
Over a median follow-up of 14 years, a total of 1811 deaths occurred, 674 due to CVD. Hazard ratios (95% confidence interval) for all-cause mortality were 1.35 (1.18-1.55), 1.18 (1.02-1.36), and 1.37 (1.18-1.58) for poor vs. good physical, mental, and social health, respectively (all p trend < 0.001). Being physically active was associated with a 28% (15-39%), 31% (19-42%), and 19% (5-31%) lower all-cause mortality in participants with poor physical, mental, and social health, respectively. In each health dimension, physically active individuals with poor health showed a similar or lower all-cause mortality than those who had intermediate or good health but were physically inactive. Results for CVD mortality were similar to those for all-cause death.
CONCLUSIONS:
Physical activity might attenuate the excess all-cause and CVD mortality associated with poor physical, mental, and social health.
KEYWORDS:
Aging; Health; Mortality; Older adults; Physical activity

The Gut-Brain Axis in Alzheimer's Disease and Omega-3. A Critical Overview of Clinical Trials.
La Rosa F, Clerici M, Ratto D, Occhinegro A, Licito A, Romeo M, Iorio CD, Rossi P.
Nutrients. 2018 Sep 8;10(9). pii: E1267. doi: 10.3390/nu10091267. Review.
PMID: 30205543
Abstract
Despite intensive study, neurodegenerative diseases remain insufficiently understood, precluding rational design of therapeutic interventions that can reverse or even arrest the progressive loss of neurological function. In the last decade, several theories investigating the causes of neurodegenerative diseases have been formulated and a condition or risk factor that can contribute is described by the gut-brain axis hypothesis: stress, unbalanced diet, and drugs impact altering microbiota composition which contributes to dysbiosis. An altered gut microbiota may lead to a dysbiotic condition and to a subsequent increase in intestinal permeability, causing the so-called leaky-gut syndrome. Herein, in this review we report recent findings in clinical trials on the risk factor of the gut-brain axis in Alzheimer's disease and on the effect of omega-3 supplementation, in shifting gut microbiota balance towards an eubiosis status. Despite this promising effect, evidences reported in selected randomized clinical trials on the effect of omega-3 fatty acid on cognitive decline in Alzheimer's disease are few. Only Mild Cognitive Impairment, a prodromal state that could precede the progress to Alzheimer's disease could be affected by omega-3 FA supplementation. We report some of the critical issues which emerged from these studies. Randomized controlled trials in well-selected AD patients considering the critical points underlined in this review are warranted.
KEYWORDS:
Alzheimer’s disease; cognitive impairment; microbiota; neurodegeneration; neuroinflammation; omega-3
https://www.ncbi.nlm.nih.gov/pubmed/17030655

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Red cell distribution width and common disease onsets in 240,477 healthy volunteers followed for up to 9 years.
Pilling LC, Atkins JL, Kuchel GA, Ferrucci L, Melzer D.
PLoS One. 2018 Sep 13;13(9):e0203504. doi: 10.1371/journal.pone.0203504. eCollection 2018.
PMID: 30212481
Abstract
Higher Red Blood Cell Distribution Width (RDW or anisocytosis) predicts incident coronary artery disease (CAD) plus all-cause and cardiovascular mortality, but its predictive value for other common diseases in healthy volunteers is less clear. We aimed to determine the shorter and longer term associations between RDW and incident common conditions in participants free of baseline disease, followed for 9 years. We undertook a prospective analysis of RDW% using 240,477 healthy UK Biobank study volunteers aged 40-70 years at baseline, with outcomes ascertained during follow-up (≤9 years). Participants were free of anemia, CAD, type-2 diabetes, stroke, hypertension, COPD, and any cancer (except non-melanoma skin cancer) at baseline. Survival models (with competing Hazards) tested associations with outcomes from hospital admission records and death certificates. High RDW (≥15% variation, n = 6,050) compared to low (<12.5% n = 20,844) was strongly associated with mortality (HR 3.10: 95% CI 2.57 to 3.74), adjusted for age, sex, smoking status, education level, mean cell volume and hemoglobin concentration. Higher RDW was also associated with incident CAD (sub-HR 1.67: 1.40 to 1.99), heart failure, peripheral vascular disease, atrial fibrillation, stroke, and cancer (sHR 1.37: 1.21 to 1.55; colorectal cancer sHR 1.92: 1.36 to 2.72), especially leukemia (sHR 2.85: 1.63 to 4.97). Associations showed dose-response relationships, and RDW had long-term predictive value (≥4.5 years after assessment) for the majority of outcomes, which were similar in younger and older persons. In conclusion, higher RDW predicted onsets of a wide range of common conditions as well as mortality in a large healthy volunteer cohort. RDW is not just a short term predictor, as high levels were predictive 4.5 to 9 years after baseline in healthy volunteers. The wide range of outcomes reflects known RDW genetic influences, including diverse disease risks. RDW may be a useful clinical marker for inclusion in wellness assessments.

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Acute Effects of Dietary Carbohydrate Restriction on Glycemia, Lipemia and Appetite Regulating Hormones in Normal-Weight to Obese Subjects.
Samkani A, Skytte MJ, Thomsen MN, Astrup A, Deacon CF, Holst JJ, Madsbad S, Rehfeld JF, Krarup T, Haugaard SB.
Nutrients. 2018 Sep 12;10(9). pii: E1285. doi: 10.3390/nu10091285.
PMID: 30213037
http://www.mdpi.com/2072-6643/10/9/1285/htm
Abstract
Postprandial responses to food are highly dependent on the macronutrient composition of the diet. We investigated the acute effects of transition from the recommended moderately high carbohydrate (HC) diet towards a carbohydrate-reduced high-protein (CRHP) diet on postprandial glycemia, insulinemia, lipemia, and appetite-regulating hormones in non-diabetic adults. Fourteen subjects, including five males (Mean ± SD: age 62 ± 6.5; BMI 32 ± 7.6 kg/m²; hemoglobin A1c (HbA1c) 40 ± 3.0 mmol/mol; HOMA2-IR 2.1 ± 0.9) were included in this randomized, cross-over study. Iso-caloric diets were consumed for two consecutive days with a median wash-out period of 21 days (range 2⁻8 weeks) between diets (macronutrient energy composition: CRHP/HC; 31%/54% carbohydrate, 29%/16% protein, 40%/30% fat). Postprandial glucose, insulin secretion rate (ISR), triglycerides (TGs), non-esterified fatty acids (NEFAs), and satiety ratings were assessed after ingestion of breakfast (Br) and lunch (Lu), and gut hormones and glucagon were assessed after ingestion of Br. Compared with the HC diet, the CRHP diet reduced peak glucose concentrations (Br 11%, p = 0.024; Lu 11%, p < 0.001), glucose excursions (Br 80%, p = 0.20; Lu 85%, p < 0.001), and ISR (Br 31%; Lu 64%, both p < 0.001) whereas CRHP, as compared with HC, increased glucagon-like peptide-1 (Br 27%, p = 0.015) and glucagon values (Br 249%, p < 0.001). NEFA and TG levels increased in the CRHP diet as compared with the HC diet after Br, but no difference was found after Lu (NEFA Br 22%, p < 0.01; TG Br 42%, p = 0.012). Beta-cell glucose sensitivity, insulin clearance, cholecystokinin values, and subjective satiety ratings were unaffected. It is possible to achieve a reduction in postprandial glycemia and insulin without a deleterious effect on beta-cell glucose sensitivity by substituting part of dietary carbohydrate with iso-caloric protein and fat in subjects without type 2 diabetes mellitus (T2DM). The metabolic effects are more pronounced after the second meal.
KEYWORDS:
carbohydrate reduction; postprandial glucose metabolism; second-meal effect

Wholegrain Intake and Risk of Type 2 Diabetes: Evidence from Epidemiological and Intervention Studies.
Della Pepa G, Vetrani C, Vitale M, Riccardi G.
Nutrients. 2018 Sep 12;10(9). pii: E1288. doi: 10.3390/nu10091288. Review.
PMID: 30213062
http://www.mdpi.com/2072-6643/10/9/1288/htm
Abstract
Type 2 diabetes mellitus (T2DM) is one of the most common metabolic diseases and represents a leading cause of morbidity and mortality because of its related complications. The alarming rise in T2DM prevalence worldwide poses enormous challenges in relation to its social, economic, and a clinical burden requiring appropriate preventive strategies. Currently, lifestyle modifications-including approaches to promote a moderate body weight reduction and to increase regular physical exercise-are the first crucial intervention for T2DM prevention. In the light of the difficulty in reducing body weight and in long-term maintenance of weight loss, quality changes in dietary patterns-in terms of macro and micronutrient composition-can also strongly affect the development of T2DM. This may provide a more practical and suitable preventative approach than simply implementing caloric restriction. Along this line, there is increasing evidence that wholegrain consumption in substitution of refined grains is associated with a reduction of the incidence of several non-communicable chronic diseases. The aim of the present review is to summarize the current evidence from observational and randomized controlled clinical trials on the benefits of wholegrain on T2DM prevention and treatment. Plausible mechanisms by which wholegrain could act on glucose homeostasis and T2DM prevention are also evaluated. Altogether, the totality of the available evidence supports present dietary recommendations promoting wholegrain foods for the prevention and treatment of T2DM.
KEYWORDS:
diabetes diet; diabetes prevention; plasma glucose; plasma insulin; type 2 diabetes mellitus; wholegrain

The role of dietary sodium on autoimmune diseases: The salty truth.
Sharif K, Amital H, Shoenfeld Y, MaACR.
Autoimmun Rev. 2018 Sep 10. pii: S1568-9972(18)30204-0. doi: 10.1016/j.autrev.2018.05.007. [Epub ahead of print] Review.
PMID: 30213699
Abstract
Autoimmune diseases are a group of heterogeneous condition that occur secondary to the intrinsic loss of tolerance to self- antigens. In genetically susceptible individuals, the complex interplay of environmental factors and epigenetic deregulations have been proposed to drive disease etiopathogenesis. Various environmental variables have been identified including viral infections, exposure to pollutants, stress and dietary factors. Sodium, a major constituent of salt is essential for mammalian physiology. However, high salt intake may play a role in the development of autoimmune diseases. Several lines of evidence point toward the role of high sodium intake in reversing the suppressive effects of Regulatory T cells (Tregs) and instead promote cellular shift toward T-helper (Th)-1 and Th17 pro-inflammatory phenotypes. These effects have been attributed to cascade of events that ultimately results in downstream activation of serum glucocorticoid kinase 1 (Sgk1). In vivo, various autoimmune animal models have confirmed the role of high sodium diet in the emergence and the exacerbation of autoimmune conditions including for instance Experimental Autoimmune Encephalomyelitis model for multiple sclerosis, MRL/lpr mouse model for lupus nephritis, collagen induced arthritis model for rheumatoid arthritis, and dextran sulfate sodium induced colitis, and TNBS-induced colitis models for Crohn's disease. Clinical epidemiological studies are scarce. High sodium intake was associated with increased risk of rheumatoid arthritis disease emergence. In multiple sclerosis, some studies suggest a relation to clinical exacerbation rates however other studies did not corroborate these results. Taken together, high dietary salt intake plays a role in the spectrum of autoimmune disease etiology. Further research is warranted to better characterize such relationship and assist in identifying individuals that would benefit from dietary salt restriction.
KEYWORDS:
Autoimmunity; Dietary salt; Regulatory T cells (Tregs); Sodium; T-helper 17 (Th17)

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Benefits of time-restricted feeding.
Greenhill C.
Nat Rev Endocrinol. 2018 Sep 14. doi: 10.1038/s41574-018-0093-2. [Epub ahead of print] No abstract available.
PMID: 30218015
https://sci-hub.tw/10.1038/s41574-018-0093-2
"New research utilizing timerestricted
feeding (TRF) now
shows that metabolic homeostasis
is maintained as a result of the
circadian clock’s control of daily
rhythms in feeding and fasting.
Amandine Chaix and colleagues
used three different mouse models
of altered circadian rhythms: wholebody
knockout of Cry1 and Cry2;
liver-specific knockout of Bmal1;
and liver-specific knockout of
Nr1d1 and Nr1d2 (also known as
Rev-erbα and Rev-erbβ). The mice were
fed a high-fat diet either ad libitum or
under TRF (9 or 10hours during the
dark phase); mice in both groups ate
the same amount of calories.
Under ad libitum conditions,
the control and mutant mice gained
weight and exhibited metabolic
abnormalities. Importantly, the
mutant mice on TRF were protected
from weight gain and metabolic
abnormalities. The researchers also
conducted extensive transcriptome
and metabolome analyses, which
showed that TRF reduced the
accumulation of lipids in the liver
and enhanced cellular defences
against metabolic stress.
In addition, the mutant mice
on an ad libitum diet were found
to have an inflexible respiratory
exchange ratio, suggesting that the
mice were unable to switch between
using carbohydrates and fats for fuel.
By contrast, mutant mice on TRF
showed normal diurnal patterns in
the respiratory exchange ratio.
“Our study shows that TRF
protects clock mutant mice from
obesity, fatty liver, dyslipidaemia
and glucose intolerance without
changes in activity or caloric intake,”
explains corresponding author
Satchidananda Panda. “TRF restores
rhythms in feeding and fasting,
metabolic pathways and
nutrient-sensing pathways.”
The authors note that their
study raises many questions that
need to be answered. For instance,
how the circadian clock regulates
feeding rhythms is unclear and
the effects of TRF in old animals
and over long periods of time
are unknown. “Nevertheless,
the impact of TRF in delaying
onset of metabolic diseases
in circadian mutant mice will
have significant mechanistic
and translational impact,”
concludes Panda."
>>>>>>>>>>>>>>>>>>>>
Time-Restricted Feeding Prevents Obesity and Metabolic Syndrome in Mice Lacking a Circadian Clock.
Chaix A, Lin T, Le HD, Chang MW, Panda S.
Cell Metab. 2018 Aug 17. pii: S1550-4131(18)30505-9. doi: 10.1016/j.cmet.2018.08.004. [Epub ahead of print]
PMID: 30174302
Abstract
Increased susceptibility of circadian clock mutant mice to metabolic diseases has led to the idea that a molecular clock is necessary for metabolic homeostasis. However, these mice often lack a normal feeding-fasting cycle. We tested whether time-restricted feeding (TRF) could prevent obesity and metabolic syndrome in whole-body Cry1;Cry2 and in liver-specific Bmal1 and Rev-erbα/β knockout mice. When provided access to food ad libitum, these mice rapidly gained weight and showed genotype-specific metabolic defects. However, when fed the same diet under TRF (food access restricted to 10 hr during the dark phase) they were protected from excessive weight gain and metabolic diseases. Transcriptome and metabolome analyses showed that TRF reduced the accumulation of hepatic lipids and enhanced cellular defenses against metabolic stress. These results suggest that the circadian clock maintains metabolic homeostasis by sustaining daily rhythms in feeding and fasting and by maintaining balance between nutrient and cellular stress responses.
KEYWORDS:
cell response to stress; circadian clock; circadian clock mutant mice; feeding-fasting rhythms; hepatic metabolomics; hepatic transcriptomics; metabolic diseases; metabolic homeostasis; metabolic syndrome; time-restricted feeding

Changes in fat mass and fat-free-mass are associated with incident hypertension in four population-based studies from Germany.
Ittermann T, Werner N, Lieb W, Merz B, Nöthlings U, Kluttig A, Tiller D, Greiser KH, Vogt S, Thorand B, Peters A, Völzke H, Dörr M, Schipf S, Markus MRP.
Int J Cardiol. 2018 Sep 8. pii: S0167-5273(18)33772-0. doi: 10.1016/j.ijcard.2018.09.035. [Epub ahead of print]
PMID: 30217425
https://sci-hub.tw/10.1016/j.ijcard.2018.09.035
Abstract
BACKGROUND:
We estimated the association of changes in body weight, waist circumference (WC), fat mass (FM) and fat-free mass (FFM) with changes in blood pressure and incident hypertension using data from four German population-based studies.
METHODS:
We analyzed data from 4467 participants, aged 21 to 82 years not taking antihypertensive medication and not having type 2 diabetes mellitus or a history of myocardial infarction at baseline and follow-up, from four population-based studies conducted in Germany. Body weight, WC, and blood pressure were measured at baseline and follow-up (median follow-up of the single studies 4 to 7 years). FM and FFM were calculated based on height-weight models derived from bioelectrical impedance studies. Hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg. Confounder-adjusted linear and logistic regressions were used to associate changes in anthropometric markers with changes in blood pressure, incident hypertension, and incident normalization of blood pressure.
RESULTS:
In a pooled dataset including all four studies, increments in body weight, WC, FM, and FFM were statistically significantly associated with incident hypertension and changes in systolic and diastolic blood pressure over time. Decreases in body weight, FM, and FFM were significantly associated with incident normalization of blood pressure.
CONCLUSIONS:
Our data suggests that the well-established association between obesity and blood pressure levels might be more related to body composition rather than to total body weight per se. Our findings indicate that gaining or losing FFM has substantial impact on the development or reversion of hypertension.
KEYWORDS:
Body composition; Fat mass; Fat-free mass; Hypertension; Obesity; Overweight

Association of dairy intake with cardiovascular disease and mortality in 21 countries from five continents (PURE): a prospective cohort study.
Dehghan M, Mente A, Rangarajan S, Sheridan P, Mohan V, Iqbal R, Gupta R, Lear S, Wentzel-Viljoen E, Avezum A, Lopez-Jaramillo P, Mony P, Varma RP, Kumar R, Chifamba J, Alhabib KF, Mohammadifard N, Oguz A, Lanas F, Rozanska D, Bostrom KB, Yusoff K, Tsolkile LP, Dans A, Yusufali A, Orlandini A, Poirier P, Khatib R, Hu B, Wei L, Yin L, Deeraili A, Yeates K, Yusuf R, Ismail N, Mozaffarian D, Teo K, Anand SS, Yusuf S; Prospective Urban Rural Epidemiology (PURE) study investigators.
Lancet. 2018 Sep 11. pii: S0140-6736(18)31812-9. doi: 10.1016/S0140-6736(18)31812-9. [Epub ahead of print]
PMID: 30217460
https://sci-hub.tw/10.1016/S0140-6736(18)31812-9
Abstract
BACKGROUND:
Dietary guidelines recommend minimising consumption of whole-fat dairy products, as they are a source of saturated fats and presumed to adversely affect blood lipids and increase cardiovascular disease and mortality. Evidence for this contention is sparse and few data for the effects of dairy consumption on health are available from low-income and middle-income countries. Therefore, we aimed to assess the associations between total dairy and specific types of dairy products with mortality and major cardiovascular disease.
METHODS:
The Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort study of individuals aged 35-70 years enrolled from 21 countries in five continents. Dietary intakes of dairy products for 136 384 individuals were recorded using country-specific validated food frequency questionnaires. Dairy products comprised milk, yoghurt, and cheese. We further grouped these foods into whole-fat and low-fat dairy. The primary outcome was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were calculated using multivariable Cox frailty models with random intercepts to account for clustering of participants by centre.
FINDINGS:
Between Jan 1, 2003, and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major cardiovascular events [n=5855]) during the 9·1 years of follow-up. Higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of the composite outcome (HR 0·84, 95% CI 0·75-0·94; ptrend=0·0004), total mortality (0·83, 0·72-0·96; ptrend=0·0052), non-cardiovascular mortality (0·86, 0·72-1·02; ptrend=0·046), cardiovascular mortality (0·77, 0·58-1·01; ptrend=0·029), major cardiovascular disease (0·78, 0·67-0·90; ptrend=0·0001), and stroke (0·66, 0·53-0·82; ptrend=0·0003). No significant association with myocardial infarction was observed (HR 0·89, 95% CI 0·71-1·11; ptrend=0·163). Higher intake (>1 serving vs no intake) of milk (HR 0·90, 95% CI 0·82-0·99; ptrend=0·0529) and yogurt (0·86, 0·75-0·99; ptrend=0·0051) was associated with lower risk of the composite outcome, whereas cheese intake was not significantly associated with the composite outcome (0·88, 0·76-1·02; ptrend=0·1399). Butter intake was low and was not significantly associated with clinical outcomes (HR 1·09, 95% CI 0·90-1·33; ptrend=0·4113).
INTERPRETATION:
Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort.

Predicting mixed-meal measured glycaemic index in healthy subjects.
Ballance S, Knutsen SH, Fosvold ØW, Fernandez AS, Monro J.
Eur J Nutr. 2018 Sep 14. doi: 10.1007/s00394-018-1813-z. [Epub ahead of print]
PMID: 30218140
https://sci-hub.tw/https://link.springer.com/article/10.1007/s00394-018-1813-z
Abstract
PURPOSE:
To determine the influence of meal composition on the glycaemic impact of different carbohydrate staples, and the accuracy of "adjusted calculated meal GI" compared with "measured mixed-meal GI".
METHODS:
In a non-blind randomized crossover trial fasted healthy subjects consumed four dinner-type mixed meals of realistic serving size comprising a carbohydrate staple of either mashed potato, pasta, rice or a glucose drink, combined with fixed portions of boiled carrots, poached salmon and herb sauce. Blood samples collected between 0 and 180 min were analysed for glucose and insulin concentrations. Adjusted calculated meal GI values were determined against a 50 g reference glucose drink, and compared to corresponding measured mixed-meal GIs, supplemented with data from four previous mixed-meal postprandial glycaemic response studies.
RESULTS:
The common carbohydrate staples, and the glucose drink, ingested as part of the salmon mixed meal induced a significantly lower post-prandial relative glycaemic response (RGR) and concurrent higher relative insulin response than the same amount of staple eaten alone. Adjusted calculated mixed-meal GI closely predicted measured mixed-meal GI in healthy subjects for 15 out of 17 mixed meals examined, showing the need to account for effects of fat and protein when predicting measured mixed-meal GI. Further, we showed the validity of using customarily consumed food amounts in mixed-meal postprandial RGR study design.
CONCLUSIONS:
Adjusted calculated mixed-meal GI appears a useful model to predict measured mixed-meal GI in healthy subjects and with further development and validation could aid nutrition research and rational design of healthy meals for personalized nutrition and particular consumer groups.
KEYWORDS:
Blood sugar; Insulin; Meal; Pasta; Potato; Rice; Starch

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https://sci-hub.tw/10.1007/s10552-018-1058-4
Metformin use and incidence cancer risk: evidence for a selective protective effect against liver cancer.
Murff HJ, Roumie CL, Greevy RA, Hackstadt AJ, McGowan LED, Hung AM, Grijalva CG, Griffin MR.
Cancer Causes Control. 2018 Sep;29(9):823-832. doi: 10.1007/s10552-018-1058-4. Epub 2018 Jul 18.
PMID: 30022336
Abstract
PURPOSE:
Several observational studies suggest that metformin reduces incidence cancer risk; however, many of these studies suffer from time-related biases and several cancer outcomes have not been investigated due to small sample sizes.
METHODS:
We constructed a propensity score-matched retrospective cohort of 84,434 veterans newly prescribed metformin or a sulfonylurea as monotherapy. We used Cox proportional hazard regression to assess the association between metformin use compared to sulfonylurea use and incidence cancer risk for 10 solid tumors. We adjusted for clinical covariates including hemoglobin A1C, antihypertensive and lipid-lowering medications, and body mass index. Incidence cancers were defined by ICD-9-CM codes.
RESULTS:
Among 42,217 new metformin users and 42,217 matched-new sulfonylurea users, we identified 2,575 incidence cancers. Metformin was inversely associated with liver cancer (adjusted hazard ratio [aHR] = 0.44, 95% CI 0.31, 0.64) compared to sulfonylurea. We found no association between metformin use and risk of incidence bladder, breast, colorectal, esophageal, gastric, lung, pancreatic, prostate, or renal cancer when compared to sulfonylurea use.
CONCLUSIONS:
In this large cohort study that accounted for time-related biases, we observed no association between the use of metformin and most cancers; however, we found a strong inverse association between metformin and liver cancer. Randomized trials of metformin for prevention of liver cancer would be useful to verify these observat

Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice.
Contreras-Duarte S, Chen P, Andía M, Uribe S, Irarrázaval P, Kopp S, Kern S, Marsche G, Busso D, Wadsack C, Rigotti A.
Biol Res. 2018 Sep 15;51(1):34. doi: 10.1186/s40659-018-0183-6.
PMID: 30219096
Abstract
BACKGROUND AND AIMS:
Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice.
METHODS AND RESULTS:
Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice.
CONCLUSIONS:
Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.
KEYWORDS:
Atherosclerosis; HDL; Serum lipids; Vitamin C and E

[That was more than one sachet sucralose per kg body weight.  It is a lot.]
The not-so-sweet effects of sucralose on blood sugar control     
M Yanina Pepino
The American Journal of Clinical Nutrition, Volume 108, Issue 3, 1 September 2018, Pages 431–432, https://doi.org/10.1093/ajcn/nqy205
Published: 11 September 2018
http://sci-hub.tw/10.1093/ajcn/nqy205
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Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial     
Alonso Romo-Romo; Carlos A Aguilar-Salinas; Griselda X Brito-Córdova ; Rita A Gómez-Díaz; Paloma Almeda-Valdes
The American Journal of Clinical Nutrition, Volume 108, Issue 3, 1 September 2018, Pages 485–491, https://doi.org/10.1093/ajcn/nqy152
Published: 11 September 2018  Article history
https://sci-hub.tw/10.1093/ajcn/nqy152
ABSTRACT
Background
Recently, the absence of metabolic effects from nonnutritive sweeteners has been questioned.
Objective
The aim of this study was to evaluate the effects of sucralose consumption on glucose metabolism variables.
Design
We performed a randomized controlled trial involving healthy subjects without comorbidities and with a low habitual consumption of nonnutritive sweeteners (n = 33/group).
Methods
The intervention consisted of sucralose consumption as 15% of Acceptable Daily Intake every day for 14 d using commercial sachets. The control group followed the same procedures without any intervention. The glucose metabolism variables (insulin sensitivity, acute insulin response to glucose, disposition index, and glucose effectiveness) were evaluated by using a 3-h modified intravenous-glucose-tolerance test before and after the intervention period.
Results
Individuals assigned to sucralose consumption showed a significant decrease in insulin sensitivity with a median (IQR) percentage change of −17.7% (−29.3% to −1.0%) in comparison to −2.8% (−30.7% to 40.6%) in the control group (P= 0.04). An increased acute insulin response to glucose from 577 mU · L-1· min (350–1040 mU · L-1· min) to 671 mU · L-1· min (376–1010 mU · L-1· min) (P = 0.04) was observed in the sucralose group for participants with adequate adherence.
Conclusions
Sucralose may have effects on glucose metabolism, and our study complements findings previously reported in other trials. Further studies are needed to confirm the decrease in insulin sensitivity and to explore the mechanisms for these metabolic alterations. This trial was registered at www.clinicaltrials.gov as NCT02589002.
nonnutritive sweeteners, insulin resistance, sweetening agents, sucralose, glucose intolerance, intravenous glucose tolerance test

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Temporal Changes in a Novel Metric of Physical Activity Tracking (Personal Activity Intelligence) and Mortality: The HUNT Study, Norway.

Kieffer SK, Croci I, Wisløff U, Nauman J.

Prog Cardiovasc Dis. 2018 Sep 15. pii: S0033-0620(18)30189-0. doi: 10.1016/j.pcad.2018.09.002. [Epub ahead of print] Review.

PMID: 30227185
http://sci-hub.tw/http://www.sciencedirect.com/science/article/pii/S0033062018301890
Abstract
BACKGROUND:
Personal Activity Intelligence (PAI) is a novel activity metric that translates heart rate variations during exercise into a weekly score. Weekly PAI scores assessed at a single point in time were found to associate with lower risk of premature cardiovascular disease (CVD) mortality in the general healthy population. However, to date, the associations between long-term longitudinal changes in weekly PAI scores and mortality have not been explored.
PURPOSE:
The aim of the present study was to prospectively examine the association between change in weekly PAI scores estimated 10 years apart, and risk of mortality from CVD and all-causes.
METHODS:
We performed a prospective cohort study of 11,870 men and 13,010 women without known CVD in Norway. By using data from the Nord-Trøndelag Health Study (HUNT) PAI was estimated twice, ten years apart (HUNT1 1984-86 and HUNT2 1995-97). Mortality was followed-up until December 31, 2015. Adjusted hazard ratios (AHR) and 95% confidence intervals (CI) for death from CVD and all-causes related to temporal changes in PAI were estimated using Cox regression analyses.
RESULTS:
During a mean (SD) of 18 (4) years of follow-up, there were 4782 deaths, including 1560 deaths caused by CVD. Multi-adjusted analyses demonstrated that participants achieving a score of ≥100 PAI at both time points had 32% lower risk of CVD mortality (AHR 0.68; CI: 0.54-0.86) for CVD mortality and 20% lower risk of all-cause mortality (AHR 0.80; CI: 71-0.91) compared with participants obtaining <100 weekly PAI at both measurements. For participants having <100 PAI in HUNT1 but ≥100 PAI in HUNT2, the AHRs were 0.87 (CI: 0.74-1.03) for CVD mortality, and 0.86 (CI: 0.79-0.95) for all-cause mortality. We also found an inverse linear relationship between change in PAI and risk of CVD mortality among participants with 0 PAI (P < 0.01), and ≤50 PAI (P = 0.04) in HUNT1, indicating that an increase in PAI over time is associated with lower risk of mortality. Excluding the first three years of follow-up did not substantially alter the findings. Increasing PAI score from <100 PAI in HUNT1 to ≥100 PAI in HUNT2 was associated with 6.6 years gained lifespan.
CONCLUSION:
Among men and women without known CVD, an increase in PAI score and sustained high PAI score over a 10-year period was associated with lower risk of mortality.
KEYWORDS:
Activity tracking; Cardiovascular disease mortality; Physical activity promotion; Prevention

Substitution of red meat with poultry or fish and risk of type 2 diabetes: a Danish cohort study.
Ibsen DB, Warberg CK, Würtz AML, Overvad K, Dahm CC.
Eur J Nutr. 2018 Sep 17. doi: 10.1007/s00394-018-1820-0. [Epub ahead of print]
PMID: 30225630
Abstract
PURPOSE:
We examined associations between substitution of red meat (total, processed and unprocessed, low fat and high fat) with poultry or fish and substitution of processed red meat with unprocessed red meat and the risk of type 2 diabetes.
METHODS:
A cohort of 53,163 participants from the Danish Diet, Cancer and Health study were followed for incident type 2 diabetes (6879 cases; median follow-up time 15.4 years). Diet was assessed by a validated 192-item food frequency questionnaire at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for type 2 diabetes associated with specified food substitutions of 150 g/week.
RESULTS:
Replacing total red meat with fish was associated with a lower risk of type 2 diabetes [HR 0.96 (95% CI 0.94, 0.99)] as was replacement of processed red meat with poultry or fish [HR poultry 0.96 (95% CI 0.93, 0.99)]; HR fish 0.94 [(95% CI 0.91, 0.97)]. Replacing low fat red meat or high fat red meat with fish was associated with a lower risk of type 2 diabetes whereas similar substitutions, with poultry, were not. Replacing processed red meat with unprocessed red meat was also associated with a lower risk of type 2 diabetes [HR 0.96 (95% CI 0.93, 0.99)].
CONCLUSIONS:
Replacing processed red meat with poultry, replacing total or processed red meat with fish, and replacing processed red meat with unprocessed red meat were all associated with a lower risk of type 2 diabetes.
KEYWORDS:
Fish; Poultry; Prospective studies; Red meat; Substitution models; Type 2 diabetes mellitus

Mineralocorticoid Antagonism Enhances Brown Adipose Tissue Function In Humans: A Randomized Placebo-controlled Cross-over Study.
Thuzar M, Law WP, Dimeski G, Stowasser M, Ho KK.
Diabetes Obes Metab. 2018 Sep 17. doi: 10.1111/dom.13539. [Epub ahead of print]
PMID: 30225967
Abstract
AIM:
To investigate whether mineralocorticoid (MC) antagonism enhances brown adipose tissue (BAT) function in humans.
MATERIALS & METHODS:
In a randomized double-blind cross-over design, 10 healthy adults (2 men, 8 women) underwent two weeks of spironolactone (100mg/day) and placebo treatments with an intervening 2-week wash-out. BAT function was assessed in response to cooling and to a mixed meal. Metabolic activity was measured by fluoro-deoxyglucose (FDG) uptake (maximal standardized uptake value, SUVmax ) using PET-CT, thermogenic activity by measuring skin temperatures overlying supraclavicular (SCL) BAT depots using infrared thermography, and postprandial metabolism by measuring energy production rate (EPR) and lipid synthesis using indirect calorimetry.
RESULTS:
During cooling, BAT metabolic activity (SUV 6.30±2.16 vs 3.98±1.34; P<0.05) and volume (54.9±22.8 vs 21.6±11.8 cm3 ; P<0.05) were significantly higher, and mean SCL temperature fell by a smaller degree (-0.3±0.2 vs -0.9±0.20 C; P=0.05) with spironolactone treatment. A mixed meal increased SCL temperature and EPR. The postprandial rise in SCL temperature (+0.4±0.1 vs +0.1±0.10 C; P<0.05) but not EPR was greater during spironolactone treatment. Postprandial lipid synthesis occurred in three subjects during placebo but none during spironolactone treatment (P=0.06).
CONCLUSION:
MC antagonism enhanced human BAT function in response to cooling and to a meal during which lipid synthesis was suppressed. As postprandial EPR comprises energy dissipated as heat and energy required to store nutrients, the reduction in lipid synthesis during MC antagonism is a likely consequence of concurrent stimulation of BAT thermogenesis. The shift of energy usage from storage to heat dissipation indicates that MC antagonists may have therapeutic benefit for obesity.
KEYWORDS:
brown adipose tissue; brown fat; humans; lipids; lipogenesis; metabolism; mineralocorticoid; regulation; spironolactone; thermogenesis

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Adherence to Mediterranean Diet and Risk of Cancer: An Updated Systematic Review and Meta-Analysis.
Schwingshackl L, Schwedhelm C, Galbete C, Hoffmann G.
Nutrients. 2017 Sep 26;9(10). pii: E1063. doi: 10.3390/nu9101063. Review.
PMID: 28954418 Free PMC Article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5691680/
Abstract
The aim of the present systematic review and meta-analysis was to gain further insight into the effects of adherence to Mediterranean Diet (MedD) on risk of overall cancer mortality, risk of different types of cancer, and cancer mortality and recurrence risk in cancer survivors. Literature search was performed using the electronic databases PubMed, and Scopus until 25 August 2017. We included randomized trials (RCTs), cohort (for specific tumors only incidence cases were used) studies, and case-control studies. Study-specific risk ratios, hazard ratios, and odds ratios (RR/HR/OR) were pooled using a random effects model. Observational studies (cohort and case-control studies), and intervention trials were meta-analyzed separately. The updated review process showed 27 studies that were not included in the previous meta-analysis (total number of studies evaluated: 83 studies). An overall population of 2,130,753 subjects was included in the present update. The highest adherence score to a MedD was inversely associated with a lower risk of cancer mortality (RRcohort: 0.86, 95% CI 0.81 to 0.91, I² = 82%; n = 14 studies), colorectal cancer (RRobservational: 0.82, 95% CI 0.75 to 0.88, I² = 73%; n = 11 studies), breast cancer (RRRCT: 0.43, 95% CI 0.21 to 0.88, n = 1 study) (RRobservational: 0.92, 95% CI 0.87 to 0.96, I² = 22%, n = 16 studies), gastric cancer (RRobservational: 0.72, 95% CI 0.60 to 0.86, I² = 55%; n = 4 studies), liver cancer (RRobservational: 0.58, 95% CI 0.46 to 0.73, I² = 0%; n = 2 studies), head and neck cancer (RRobservational: 0.49, 95% CI 0.37 to 0.66, I² = 87%; n = 7 studies), and prostate cancer (RRobservational: 0.96, 95% CI 0.92 to 1.00, I² = 0%; n = 6 studies). Among cancer survivors, the association between the adherence to the highest MedD category and risk of cancer mortality, and cancer recurrence was not statistically significant. Pooled analyses of individual components of the MedD revealed that the protective effects appear to be most attributable to fruits, vegetables, and whole grains. The updated meta-analysis confirms an important inverse association between adherence to a MedD and cancer mortality and risk of several cancer types, especially colorectal cancer. These observed beneficial effects are mainly driven by higher intakes of fruits, vegetables, and whole grains. Moreover, we were able to report for the first time a small decrease in breast cancer risk (6%) by pooling seven cohort studies.
KEYWORDS:
Mediterranean Diet; cancer; meta-analysis; systematic review update
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Adherence to Mediterranean diet and risk of cancer: an updated systematic review and meta-analysis of observational studies.
Schwingshackl L, Hoffmann G.
Cancer Med. 2015 Dec;4(12):1933-47. doi: 10.1002/cam4.539. Epub 2015 Oct 16. Review.
PMID: 26471010 Free PMC Article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123783/
Abstract
The aim of the present systematic review and meta-analysis of observational studies was to gain further insight into the effects of adherence to Mediterranean Diet (MD) on overall cancer mortality, incidence of different types of cancer, and cancer mortality risk in cancer survivors. Literature search was performed using the electronic databases PubMed, and EMBASE until 2 July 2015. We included either cohort (for specific tumors only incidence cases were used) or case-control studies. Study specific risk ratios, hazard ratios, and odds ratios (RR/HR/OR) were pooled using a random effect model. The updated review process showed 23 observational studies that were not included in the previous meta-analysis (total number of studies evaluated: 56 observational studies). An overall population of 1,784,404 subjects was included in the present update. The highest adherence score to an MD was significantly associated with a lower risk of all-cause cancer mortality (RR: 0.87, 95% CI 0.81-0.93, I(2) = 84%), colorectal cancer (RR: 0.83, 95% CI 0.76-0.89, I(2) = 56%), breast cancer (RR: 0.93, 95% CI 0.87-0.99, I(2) =15%), gastric cancer (RR: 0.73, 95% CI 0.55-0.97, I(2) = 66%), prostate cancer (RR: 0.96, 95% CI 0.92-1.00, I(2) = 0%), liver cancer (RR: 0.58, 95% CI 0.46-0.73, I(2) = 0%), head and neck cancer (RR: 0.40, 95% CI 0.24-0.66, I(2) = 90%), pancreatic cancer (RR: 0.48, 95% CI 0.35-0.66), and respiratory cancer (RR: 0.10, 95% CI 0.01-0.70). No significant association could be observed for esophageal/ovarian/endometrial/and bladder cancer, respectively. Among cancer survivors, the association between the adherence to the highest MD category and risk of cancer mortality, and cancer recurrence was not statistically significant. The updated meta-analyses confirm a prominent and consistent inverse association provided by adherence to an MD in relation to cancer mortality and risk of several cancer types.
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Mediterranean diet adherence and risk of pancreatic cancer: A pooled analysis of two Dutch cohorts.
Schulpen M, Peeters PH, van den Brandt PA.
Int J Cancer. 2018 Sep 19. doi: 10.1002/ijc.31872. [Epub ahead of print]
PMID: 30230536
Abstract
Studies investigating the association of Mediterranean diet (MD) adherence with pancreatic cancer risk are limited and had inconsistent results. We examined the association between MD adherence and pancreatic cancer incidence by pooling data from the Netherlands Cohort Study (NLCS, 120852 subjects) and the Dutch cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-NL, 40011 subjects). MD adherence was assessed using alternate and modified Mediterranean diet scores (aMED and mMED, respectively), including and excluding alcohol. After median follow-ups of 20.3 (NLCS) and 19.2 (EPIC-NL) years, 449 microscopically confirmed pancreatic cancer (MCPC) cases were included in study-specific multivariable Cox models. Study-specific estimates were pooled using a random-effects model. MD adherence was not significantly associated with MCPC risk in pooled and study-specific analyses, regardless of sex and MD score. Pooled hazard ratios (95% confidence interval) for high (6-8) compared to low (0-3) values of mMED excluding alcohol were 0.66 (0.40 - 1.10) in men and 0.94 (0.63 - 1.40) in women. In never smokers, mMED excluding alcohol seemed to be inversely associated with MCPC risk (non-significant). However, no association was observed in ever smokers (pheterogeneity =0.03). Hazard ratios were consistent across strata of other potential effect modifiers. Considering MD scores excluding alcohol, mMED-containing models generally fitted better than aMED-containing models, particularly in men. Although associations somewhat differed when all pancreatic cancers were considered instead of MCPC, the overall conclusion was similar. In conclusion, MD adherence was not associated with pancreatic cancer risk in a pooled analysis of two Dutch cohorts.
KEYWORDS:
Mediterranean diet; cohort study; epidemiology; pancreatic cancer

Omega-3 fatty acids in coronary heart disease: Recent updates and future perspectives.
Ajith TA, Jayakumar TG.
Clin Exp Pharmacol Physiol. 2018 Sep 19. doi: 10.1111/1440-1681.13034. [Epub ahead of print] Review.
PMID: 30230571
Abstract
Incidence of coronary heart disease (CHD) increases worldwide with varying etiological factors. In addition to the control of risk factors, dietary modification has been recommended to reduce the prevalence. Omega-3 (ω-3) fatty acids (FAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of fish oil are beneficial for the prevention of CHD. The effect can be ascribed to anti-inflammatory, vasodilating, antiarrhythmic, antihypertensive activities and lowering of triacyl glycerol level. The American Heart Association advises two fish meals per week in subjects without CHD or supplementation of 1 g of EPA plus DHA per day in subjects with CHD. Despite the beneficial effects of EPA/DHA reported in some of the clinical trials, results of many others were inconsistent that can be ascribed to short duration of studies, low doses of ω-3 FAs, variations in the EPA:DHA ratio, selection of patients with different risk factors or interaction of ω-3 FAs with drugs used in the therapy. Therefore, well designed clinical trials in various populations are warranted. This article discusses the current update and future prospective of ω-3 FAs in CHD.
KEYWORDS:
Omega-3 fatty acids; coronary heart disease; cyclooxygenase; lipoxygenase; myocardial infarction

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High-Fat Feeding Improves Anxiety-Type Behavior Induced by Ovariectomy in Rats.
Dornellas APS, Boldarine VT, Pedroso AP, Carvalho LOT, de Andrade IS, Vulcani-Freitas TM, Dos Santos CCC, do Nascimento CMDPO, Oyama LM, Ribeiro EB.
Front Neurosci. 2018 Sep 3;12:557. doi: 10.3389/fnins.2018.00557. eCollection 2018.
PMID: 30233288
https://www.frontiersin.org/articles/10.3389/fnins.2018.00557/full
Abstract
Menopause-induced changes may include increased incidence of both depression/anxiety and obesity. We hypothesized that behavioral changes that may develop after ovarian failure could be related to neurochemical and metabolic aspects affected by this condition and that high-fat intake may influence these associations. The present study investigated in rats the effects of ovariectomy, either alone or combined with high-fat diets enriched with either lard or fish-oil, on metabolic, behavioral and monoaminergic statuses, and on gene expression of neuropeptides and receptors involved in energy balance and mood regulation. Female rats had their ovaries removed and received either standard chow (OvxC) or high-fat diets enriched with either lard (OvxL) or fish-oil (OvxF) for 8 weeks. The Sham group received only chow diet. Ovariectomy increased feed efficiency and body weight gain and impaired glucose homeostasis and serotonin-induced hypophagia, effects either maintained or even accentuated by the lard diet but counteracted by the fish diet. The OvxL group developed obesity and hyperleptinemia. Regarding components of hypothalamic serotonergic system, both ovariectomy alone or combined with the fish diet increased 5-HT2C expression while the lard diet reduced 5-HT1B mRNA. Ovariectomy increased the anxiety index, as derived from the elevated plus maze test, while both high-fat groups showed normalization of this index. In the forced swimming test, ovariectomy allied to high-lard diet, but not to fish-oil diet, reduced the latency to immobility, indicating vulnerability to a depressive-like state. Linear regression analysis showed hippocampal AgRP to be negatively associated with the anxiety index and hypothalamic AgRP to be positively associated with the latency to immobility. These AgRp gene expression associations are indicative of a beneficial involvement of this neuropeptide on both depression and anxiety measures. The present findings demonstrate metabolic, neurochemical and behavioral alterations after ovaries removal and highlight a positive effect of high-fat feeding on the anxiety-like behavior shown by ovariectomized animals. Since the polyunsaturated ômega-3 intake (fish diet), unlike the saturated fat intake (lard diet), failed to induce deleterious metabolic or neurochemical consequences, further studies are needed focusing on the potential of this dietary component as an adjuvant anxiolytic agent after menopause.
KEYWORDS:
fish-oil; hippocampus; hypothalamus; lard; neuropeptides; serotonin

Swallowing function in advanced age.
Jardine M, Miles A, Allen J.
Curr Opin Otolaryngol Head Neck Surg. 2018 Sep 17. doi: 10.1097/MOO.0000000000000485. [Epub ahead of print]
PMID: 30234658
Abstract
PURPOSE OF REVIEW:
To present current literature regarding swallowing function in advanced age, including healthy ageing, dysphagia and trends in multidisciplinary team service delivery.
RECENT FINDINGS:
Normative studies support swallowing efficiency but greater variability in healthy advanced age, through to 100 years old. Deviations from normative data and symptoms of dysphagia leading to aspiration or nutritional risk, imply swallowing disorder, rather than simply the ageing process. Quantitative and qualitative studies are emerging that promote management of swallow dysfunction for an ageing society, including innovative assessment, home treatment, swallowing exercise and optimized mealtimes.
SUMMARY:
Current literature on swallowing function in advanced age provides multidisciplinary perspectives and initiatives, with clear commitment to improving quality of life for older adults. The diversity of the older population and serious consequences of swallowing difficulties calls for routine screening tools for swallowing impairment and malnutrition risk. Representation of 'oldest old' in future normative studies is essential to guide swallowing management in adults over 85 years old.

Pharmaceutical Intervention of Aging.
Qian M, Liu B.
Adv Exp Med Biol. 2018;1086:235-254. doi: 10.1007/978-981-13-1117-8_15.
PMID: 30232763
https://sci-hub.tw/10.1007/978-981-13-1117-8_15
Abstract
The aging population represents a significant worldwide socioeconomic challenge. Aging is an inevitable and multifactorial biological process and primary risk factor for most age-related diseases, such as cardiovascular diseases, cancers, type 2 diabetes mellitus (T2DM), and neurodegenerative diseases. Pharmacological interventions targeting aging appear to be a more effective approach in preventing age-related disorders compared with the treatments targeted to specific disease. In this chapter, we focus on the latest findings on molecular compounds that mimic caloric restriction (CR), supplement nicotinamide adenine dinucleotide (NAD+) levels, and eliminate senescent cells, including metformin, resveratrol, spermidine, rapamycin, NAD+ boosters, as well as senolytics. All these interventions modulate the determinants and pathways responsible for aging/longevity, such as the kinase target of rapamycin (TOR), AMP-activated protein kinase (AMPK), sirtuins, and insulin-like growth factor (IGF-1) signaling (Fig. 15.1).
KEYWORDS:
Age-related diseases; Aging; Pharmaceutical intervention

Marital satisfaction and mortality in the United States adult population.
Whisman MA, Gilmour AL, Salinger JM.
Health Psychol. 2018 Sep 20. doi: 10.1037/hea0000677. [Epub ahead of print]
PMID: 30234318
Abstract
OBJECTIVE:
The present study examined the association between marital satisfaction and all-cause mortality in a large, representative sample of American adults. Gender was evaluated as a potential moderator of this association.
METHOD:
Ratings of marital satisfaction from married adults <90 years of age (N = 19,246) were extracted from the 1978 - 2010 waves of the General Social Survey and linked to mortality data from the National Death Index. Discrete-time survival analysis was used to evaluate the association between marital satisfaction and mortality.
RESULTS:
After statistically adjusting for demographic variables, the odds of dying for married individuals who described their marriage as very happy or pretty happy were significantly lower than the odds of dying for married individuals who described their marriage as not too happy. The association between marital satisfaction and mortality was not moderated by gender.
CONCLUSIONS:
The significant prospective association between marital satisfaction and mortality suggests that reducing marital dissatisfaction may increase longevity. Further longitudinal research is warranted to (a) replicate the current findings, and (b) evaluate whether increasing marital satisfaction through clinical intervention increases longevity.

Association between maternal gluten intake and type 1 diabetes in offspring: national prospective cohort study in Denmark.
Antvorskov JC, Halldorsson TI, Josefsen K, Svensson J, Granström C, Roep BO, Olesen TH, Hrolfsdottir L, Buschard K, Olsen SF.
BMJ. 2018 Sep 19;362:k3547. doi: 10.1136/bmj.k3547.
PMID: 30232082
Abstract
OBJECTIVE:
To examine the association between prenatal gluten exposure and offspring risk of type 1 diabetes in humans.
DESIGN:
National prospective cohort study.
SETTING:
National health information registries in Denmark.
PARTICIPANTS:
Pregnant Danish women enrolled into the Danish National Birth Cohort, between January 1996 and October 2002, MAIN OUTCOME MEASURES: Maternal gluten intake, based on maternal consumption of gluten containing foods, was reported in a 360 item food frequency questionnaire at week 25 of pregnancy. Information on type 1 diabetes occurrence in the participants' children, from 1 January 1996 to 31 May 2016, were obtained through registry linkage to the Danish Registry of Childhood and Adolescent Diabetes.
RESULTS:
The study comprised 101 042 pregnancies in 91 745 women, of whom 70 188 filled out the food frequency questionnaire. After correcting for multiple pregnancies, pregnancies ending in abortions, stillbirths, lack of information regarding the pregnancy, and pregnancies with implausibly high or low energy intake, 67 565 pregnancies (63 529 women) were included. The average gluten intake was 13.0 g/day, ranging from less than 7 g/day to more than 20 g/day. The incidence of type 1 diabetes among children in the cohort was 0.37% (n=247) with a mean follow-up period of 15.6 years (standard deviation 1.4). Risk of type 1 diabetes in offspring increased proportionally with maternal gluten intake during pregnancy (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 g/day increase of gluten). Women with the highest gluten intake versus those with the lowest gluten intake (≥20 v <7 g/day) had double the risk of type 1 diabetes development in their offspring (adjusted hazard ratio 2.00 (95% confidence interval 1.02 to 4.00)).
CONCLUSIONS:
High gluten intake by mothers during pregnancy could increase the risk of their children developing type 1 diabetes. However, confirmation of these findings are warranted, preferably in an intervention setting.

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Relative Protein Intake and Physical Function in Older Adults: A Systematic Review and Meta-Analysis of Observational Studies.
Coelho-Júnior HJ, Milano-Teixeira L, Rodrigues B, Bacurau R, Marzetti E, Uchida M.
Nutrients. 2018 Sep 19;10(9). pii: E1330. doi: 10.3390/nu10091330. Review.
PMID: 30235845
Abstract
(1) Background: The present work aims to conduct a systematic review and meta-analysis of observational studies, in order to investigate the association of relative protein intake and physical function in older adults; (2) Methods: Observational studies, that investigated the association between protein intake and physical function in older adults, were retrieved from MEDLINE, SCOPUS, CINAHL, AgeLine, EMBASE, and Cochrane-CENTRAL. Two independent researchers conducted study selection and data extraction; (3) Results: Very high protein intake (≥1.2 g/kg/day) and high protein intake (≥1.0 g/kg/day) groups showed better lower limb physical functioning and walking speed (WS) performance, respectively, in comparison to individuals who present relative low protein (<0.80 g/kg/day) intake. On the other hand, relative high protein intake does not seem to propitiate a better performance on isometric handgrip (IHG) and chair rise in comparison to relative low protein intake. In addition, there were no significant differences in the physical functioning of high and middle protein intake groups; (4) Conclusions: In conclusion, findings of the present study indicate that a very high (≥1.2 g/kg/day) and high protein intake (≥1.0 g/kg/day) are associated with better lower-limb physical performance, when compared to low protein (<0.80 g/kg/day) intake, in community-dwelling older adults. These findings act as additional evidence regarding the potential need to increase protein guidelines to above the current recommendations. However, large randomized clinical trials are needed to confirm the addictive effects of high-protein diets (≥1.0 g/kg/day) in comparison to the current recommendations on physical functioning. All data are available in the Open ScienceFramework.
KEYWORDS:
physical function; protein intake; sarcopenia

Alcohol abuse kills 3 million a year globally, most of them men: WHO
28 per cent of death were due to injuries like traffic accidents, self-harm and interpersonal violence
Thomson Reuters · Posted: Sep 21, 2018 
https://www.cbc.ca/news/health/alcohol-related-deaths-1.4833011
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Alcohol responsible for more hospital admissions than heart attacks last year: report
Measurement could be 'an important indicator for monitoring public health'
Sherry Noik · CBC News · Posted: Jun 22, 2017
https://www.cbc.ca/news/health/alcohol-hospital-admissions-1.4172091

Association Between Alcohol Intake and Cardiac Remodeling.
Rodrigues P, Santos-Ribeiro S, Teodoro T, Gomes FV, Leal I, Reis JP, Goff DC Jr, Gonçalves A, Lima JAC.
J Am Coll Cardiol. 2018 Sep 25;72(13):1452-1462. doi: 10.1016/j.jacc.2018.07.050.
PMID: 30236306
https://sci-hub.tw/10.1016/j.jacc.2018.07.050
Abstract
BACKGROUND:
Alcohol-induced cardiotoxicity is incompletely understood. Specifically, the long-term impact of alcohol use on ventricular remodeling or dysfunction, its modulators, and effect thresholds among young adults remain controversial.
OBJECTIVES:
The authors sought to evaluate a potential relationship between alcohol intake and cardiac remodeling, assessed by echocardiography, over 20 years of follow-up.
METHODS:
Among the CARDIA (Coronary Artery Risk Development in Young Adults) study cohort, the authors studied all subjects without baseline heart disorders who provided adequate information on their drinking habits and underwent echocardiographic evaluation at years 5 and 25 of the study. The echocardiographic outcomes were left ventricular (LV) ejection fraction, indexed LV end-diastolic volume and LV mass, and left atrial diameter. Participants were grouped according to their weighted-average weekly drinking habits. An additional analysis used the estimated cumulative alcohol consumption. Regression models and multivariable fractional polynomials were used to evaluate the association between alcohol consumption and the outcomes.
RESULTS:
Among the 2,368 participants, alcohol consumption was an independent predictor of higher indexed LV mass (p = 0.014) and indexed LV end-diastolic volume (p = 0.037), regardless of sex. No significant relationship between alcohol intake and LV ejection fraction was found. Drinking predominantly wine was associated with less cardiac remodeling and there was a nonsignificant trend for a harmful effect of binge drinking.
CONCLUSIONS:
After 20 years of follow-up, alcohol intake was associated with adverse cardiac remodeling, although it was not related with LV systolic dysfunction in this initially healthy young cohort. Our results also suggest that drinking predominantly wine associates with less deleterious findings in cardiac structure.
KEYWORDS:
alcohol; alcoholic cardiomyopathy; cardiac remodeling; heart failure; ventricular dilatation; ventricular function

Dietary Antioxidants, Circulating Antioxidant Concentrations, Total Antioxidant Capacity, and Risk of All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Observational Studies.
Jayedi A, Rashidy-Pour A, Parohan M, Zargar MS, Shab-Bidar S.
Adv Nutr. 2018 Sep 20. doi: 10.1093/advances/nmy040. [Epub ahead of print]
PMID: 30239557
Abstract
The associations of various dietary or circulating antioxidants with the risk of all-cause mortality in the general population have not been established yet. A systematic search was performed in PubMed and Scopus, from their inception up to October 2017. Prospective observational studies reporting risk estimates of all-cause mortality in relation to dietary intake and/or circulating concentrations of antioxidants were included. Random-effects meta-analyses were conducted. Forty-one prospective observational studies (total n = 507,251) involving 73,965 cases of all-cause mortality were included. The RRs of all-cause mortality for the highest compared with the lowest category of circulating antioxidant concentrations were as follows: total carotenes, 0.60 (95% CI: 0.46, 0.74); vitamin C, 0.61 (95% CI: 0.53, 0.69); selenium, 0.62 (95% CI: 0.45, 0.79); β-carotene, 0.63 (95% CI: 0.57, 0.70); α-carotene, 0.68 (95% CI: 0.58, 0.78); total carotenoids, 0.68 (95% CI: 0.56, 0.80); lycopene, 0.75 (95% CI: 0.54, 0.97); and α-tocopherol, 0.84 (95% CI: 0.77, 0.91). The RRs for dietary intakes were: total carotenoids, 0.76 (95% CI: 0.66, 0.85); total antioxidant capacity, 0.77 (95% CI: 0.73, 0.81); selenium, 0.79 (95% CI: 0.73, 0.85); α-carotene, 0.79 (95% CI: 0.63, 0.94); β-carotene, 0.82 (95% CI: 0.77, 0.86); vitamin C, 0.88 (95% CI: 0.83, 0.94); and total carotenes, 0.89 (95% CI: 0.81, 0.97). A nonsignificant inverse association was found for dietary zinc, zeaxanthin, lutein, and vitamin E. The nonlinear dose-response meta-analyses demonstrated a linear inverse association in the analyses of dietary β-carotene and total antioxidant capacity, as well as in the analyses of circulating α-carotene, β-carotene, selenium, vitamin C, and total carotenoids. The association appeared to be U-shaped in the analyses of serum lycopene and dietary vitamin C. The present study indicates that adherence to a diet with high antioxidant properties may reduce the risk of all-cause mortality. Our results confirm current recommendations that promote higher intake of antioxidant-rich foods such as fruit and vegetables.

Effect of psyllium (Plantago ovata) fiber on LDL cholesterol and alternative lipid targets, non-HDL cholesterol and apolipoprotein B: a systematic review and meta-analysis of randomized controlled trials.
Jovanovski E, Yashpal S, Komishon A, Zurbau A, Blanco Mejia S, Ho HVT, Li D, Sievenpiper J, Duvnjak L, Vuksan V.
Am J Clin Nutr. 2018 Sep 15. doi: 10.1093/ajcn/nqy115. [Epub ahead of print]
PMID: 30239559
Abstract
BACKGROUND:
Studies have identified viscous dietary fiber as potentially attenuating cholesterol, including psyllium, which reduces LDL cholesterol and thus may complement cardiovascular disease (CVD) treatment.
OBJECTIVES:
The aims of this study were to update evidence on the effect of psyllium on LDL cholesterol and to provide an assessment of its impact on alternate markers: non-HDL cholesterol and apolipoprotein B (apoB).
DESIGN:
Medline, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials were searched through 3 October 2017. Independent reviewers extracted relevant data and assessed risk of bias. We included randomized controlled trials with a duration of ≥3 wk that assessed the effect of psyllium on blood lipids in individuals with or without hypercholesterolemia. Data were pooled by using the generic inverse variance method with random-effects models and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by Cochran's Q statistic and quantified by the I2 statistic. Overall quality of the evidence was assessed by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.
RESULTS:
We included 28 trials in our analysis (n = 1924). Supplementation of a median dose of ∼10.2 g psyllium significantly reduced LDL cholesterol (MD = -0.33 mmol/L; 95% CI: -0.38, -0.27 mmol/L; P < 0.00001), non-HDL cholesterol (MD = -0.39 mmol/L; 95% CI: -0.50, -0.27 mmol/L; P < 0.00001), and apoB (MD = -0.05 g/L; 95% CI: -0.08, -0.03 g/L; P < 0.0001). Effect estimates for LDL cholesterol and non-HDL cholesterol were graded as moderate quality on the basis of downgrades for inconsistency and graded as high quality for apoB.
CONCLUSION:
Psyllium fiber effectively improves conventional and alternative lipids markers, potentially delaying the process of atherosclerosis-associated CVD risk in those with or without hypercholesterolemia. 

Alcohol Intake and Colorectal Cancer Risk in the Multiethnic Cohort Study.
Park SY, Wilkens LR, Setiawan VW, Monroe KR, Haiman CA, Le Marchand L.
Am J Epidemiol. 2018 Sep 15. doi: 10.1093/aje/kwy208. [Epub ahead of print]
PMID: 30239578
Abstract
To investigate the association of alcohol intake with colorectal cancer risk by race/ethnicity as well as sex, lifestyle-related factors, alcoholic beverage type, and anatomical subsite, we analyzed data from 190,698 African Americans, Native Hawaiians, Japanese Americans, Latinos and whites in the Multiethnic Cohort Study, with 4,923 incident cases during a 16.7-year follow-up period (1993-2013). In multivariate Cox regression models, the hazard ratio (HR) was 1.16 (95% confidence interval (CI): 1.01, 1.34) for 15.0‒29.9 g/day of alcohol and 1.28 (95% CI: 1.12, 1.45) for ≥30.0 g/day in men, and 1.06 (95% CI: 0.85, 1.32) and 1.15 (95% CI: 0.92, 1.43), respectively, in women, compared with nondrinkers (P for heterogeneity by sex = 0.74). An increased risk was apparent in Native Hawaiians, Japanese Americans, Latinos and whites, and in individuals with body mass index <25.0 kg/m2, never use of nonsteroidal anti-inflammatory drugs, and lower intake of dietary fiber and folate. Beer and wine, but not liquor, consumption was positively related to colorectal cancer risk. The association was stronger for rectum and left colon than right colon tumors. Our findings suggest that the positive association between alcohol and colorectal cancer varies by race/ethnicity, lifestyle factors, alcoholic beverage type, and anatomical subsite of tumors.

Long-term consumption of fruits and vegetables and risk of chronic obstructive pulmonary disease: a prospective cohort study of women.
Kaluza J, Harris HR, Linden A, Wolk A.
Int J Epidemiol. 2018 Sep 18. doi: 10.1093/ije/dyy178. [Epub ahead of print]
PMID: 30239739
Abstract
BACKGROUND:
Fruits and vegetables, due to high antioxidant capacity, may protect the lung from oxidative damage caused by tobacco smoke and potentially prevent chronic obstructive pulmonary disease (COPD). Only one study based on baseline diet has examined fruit and vegetable consumption in relation to risk of COPD, and no previous studies have examined long-term diet.
METHODS:
We investigated whether long-term fruit and vegetable consumption was associated with COPD incidence among 34 739 women (age 48-83 years) in the population-based prospective Swedish Mammography Cohort. Fruit and vegetable consumption was assessed twice (1987, 1997) with a self-administered questionnaire. Cases of COPD were identified by linkage to the Swedish health register. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS:
During follow-up from 2002 to 2014, 1512 women were diagnosed with COPD. Long-term fruit was associated with lower risk of COPD; women in the highest vs lowest quintile of consumption (≥2.5 vs <0.8 servings/day) had a 37% lower risk of COPD (95% CI: 25-48%; P-trend < 0.0001). No association was observed with long-term vegetable intake. Current and ex-smokers with low long-term consumption of fruits (<1 serving/day) in comparison to never smokers with high consumption (≥3 servings/day) had a 38-fold (HR: 38.1; 95% CI: 20.2-71.7) and 13-fold (HR: 12.5, 95% CI: 6.5-24.1) higher risk of COPD, respectively. However, no significant interaction between smoking status and fruit intake in relation to COPD incidence was observed (P-interaction = 0.95).
CONCLUSIONS:
In this prospective cohort of middle-age and older women, long-term consumption of fruits but not vegetables was inversely associated with COPD incidence.

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Protein synthesis signaling in skeletal muscle is refractory to whey protein ingestion during a severe energy deficit evoked by prolonged exercise and caloric restriction.
Martin-Rincon M, Perez-Suarez I, Pérez-López A, Ponce-González JG, Morales-Alamo D, de Pablos-Velasco P, Holmberg HC, Calbet JAL.
Int J Obes (Lond). 2018 Sep 21. doi: 10.1038/s41366-018-0174-2. [Epub ahead of print]
PMID: 30242237
Abstract
BACKGROUND:
Exercise and protein ingestion preserve muscle mass during moderate energy deficits.
OBJECTIVE:
To determine the molecular mechanisms by which exercise and protein ingestion may spare muscle mass during severe energy deficit (5500 kcal/day).
DESIGN:
Fifteen overweight, but otherwise healthy men, underwent a pre-test (PRE), caloric restriction (3.2 kcals/kg body weight/day) + exercise (45 min one-arm cranking + 8 h walking) for 4 days (CRE), followed by a control diet (CD) for 3 days, with a caloric content similar to pre-intervention while exercise was reduced to less than 10,000 steps per day. During CRE, participants ingested either whey protein (PRO, n = 8) or sucrose (SU, n = 7) (0.8 g/kg body weight/day). Muscle biopsies were obtained from the trained and untrained deltoid, and vastus lateralis.
RESULTS:
Following CRE and CD, serum concentrations of leptin, insulin, and testosterone were reduced, whereas cortisol and the catabolic index (cortisol/total testosterone) increased. The Akt/mTor/p70S6K pathway and total eIF2α were unchanged, while total 4E-BP1 and Thr37/464E-BP1 were higher. After CRE, plasma BCAA and EAA were elevated, with a greater response in PRO group, and total GSK3β, pSer9GSK3β, pSer51eIF2α, and pSer51eIF2α/total eIF2α were reduced, with a greater response of pSer9GSK3β in the PRO group. The changes in signaling were associated with the changes in leptin, insulin, amino acids, cortisol, cortisol/total testosterone, and lean mass.
CONCLUSIONS:
During severe energy deficit, pSer9GSK3β levels are reduced and human skeletal muscle becomes refractory to the anabolic effects of whey protein ingestion, regardless of contractile activity. These effects are associated with the changes in lean mass and serum insulin, testosterone, and cortisol concentrations.

NADH Dehydrogenase Subunit-2 237 Leu/Met Polymorphism Influences the Association of Coffee Consumption with Serum Chloride Levels in Male Japanese Health Checkup Examinees: An Exploratory Cross-Sectional Analysis.
Kokaze A, Ishikawa M, Matsunaga N, Karita K, Yoshida M, Ochiai H, Shirasawa T, Yoshimoto T, Minoura A, Oikawa K, Satoh M, Hoshino H, Takashima Y.
Nutrients. 2018 Sep 20;10(10). pii: E1344. doi: 10.3390/nu10101344.
PMID: 30241386
http://www.mdpi.com/2072-6643/10/10/1344/htm
Abstract
BACKGROUND:
Nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism has been shown to modify the association of coffee consumption with the risk of hypertension, dyslipidemia, and abnormal glucose tolerance, and low serum chloride levels have been shown to be associated with all-cause and cardiovascular disease mortality. Therefore, the purpose of the present study was to investigate whether ND2-237 Leu/Met polymorphism influences the association of coffee consumption with serum chloride levels in male Japanese health checkup examinees.
METHODS:
From among individuals visiting the hospital for a regular medical checkup, 402 men (mean age ± standard deviation, 53.9 ± 7.8 years) were selected for inclusion in the study. After ND2-237 Leu/Met genotyping, we conducted an exploratory cross-sectional study to examine the combined association of ND2-237 Leu/Met polymorphism and coffee consumption with serum electrolyte levels.
RESULTS:
After adjusting for age, body mass index, habitual smoking, alcohol consumption, green tea consumption, and antihypertensive medication, coffee consumption significantly increased serum chloride levels (p for trend = 0.001) in men with the ND2-237Leu genotype. After these adjustments, the odds ratios (ORs) for low levels of serum chloride, defined as <100 mEq/L, were found to be dependent on coffee consumption (p for trend = 0.001). In addition, the OR for low levels of serum chloride was significantly lower in men with the ND2-237Leu genotype who consumed ≥4 compared with <1 cup of coffee per day (OR = 0.096, 95% confidence interval = 0.010⁻0.934; p = 0.044). However, neither serum chloride levels nor risk of low levels of serum chloride appeared to be dependent on coffee consumption.
CONCLUSIONS:
The results suggest that ND2-237 Leu/Met polymorphism modifies the association of coffee consumption with serum chloride levels in middle-aged Japanese men.
KEYWORDS:
NADH dehydrogenase; cardiovascular disease; coffee consumption; gene-diet interaction; longevity; polymorphism; serum chloride levels

High calcium intake in men not women is associated with all-cause mortality risk: Melbourne Collaborative Cohort Study.
Rodríguez AJ, Scott D, Khan B, Hodge A, English DR, Giles GG, Abrahamsen B, Ebeling PR.
Arch Osteoporos. 2018 Sep 21;13(1):101. doi: 10.1007/s11657-018-0518-5.
PMID: 30242518
Abstract
The risk of mortality associated with high dietary calcium is uncertain. Unlike a highly publicised study in Swedish women, high dietary calcium intake in men-not women-was associated with increased all-cause mortality.
PURPOSE:
The association of dietary calcium with mortality is controversial. A study of women from the Swedish Mammography Cohort (SMC) suggested higher calcium was associated with higher mortality risk, whilst a study of Australian adults from the Melbourne Collaborative Cohort Study (MCCS) suggested higher intakes were associated with lower mortality risk. Thus, we aimed to perform a sex-specific re-analysis of the MCCS to evaluate the association of dietary calcium with mortality outcomes and directly compare hazard estimates (95% confidence intervals) in women with those from the SMC.
METHODS:
A prospective cohort study of community-dwelling Australian adults was conducted, in which 34,627 individuals (women 20,834 (60.2%); mean ± SD, age = 54 ± 8 years) were included at baseline after excluding those with prevalent cardiovascular (CV) disease, cancer or incomplete data. Energy-adjusted dietary calcium was categorised into the following levels of consumption (mg/day): < 600, 600-999, 1000-1399 and ≥ 1400. Mortality from all-causes, any cardiovascular disease and myocardial infarction was determined. Mortality hazards relative to intakes were estimated to be of 600-999 mg/day.
RESULTS:
In women, hazard estimates for calcium intake of ≥ 1400 mg/day did not reach significance for all-cause (HR = 0.85; 0.66, 1.10) or CV (HR = 1.10; 0.69, 1.81) mortality in adjusted models. In men, intakes of ≥ 1400 mg/day were associated with a 42% increased all-cause mortality risk (HR = 1.42; 1.02, 1.99). There was a trend toward increased CV mortality (HR = 1.83; 0.94, 3.55).
CONCLUSION:
Contrary to findings from a similar study conducted in Swedish women, Australian women, after adjustment for cofounders showed no increase in mortality risk with high calcium intakes possibly reflecting differences in calcium handling dynamics, diet or lifestyle factors between the two countries. We identified an increased risk for men.
KEYWORDS:
All-cause mortality; Calcium; Cardiovascular disease; Cohort study; Diet

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Kieneker LM, Eisenga MF, Gansevoort RT, de Boer RA, Navis G, Dullaart RPF, Joosten MM, Bakker SJL.
Mayo Clin Proc. 2018 Sep 20. pii: S0025-6196(18)30411-7. doi: 10.1016/j.mayocp.2018.05.028. [Epub ahead of print]
PMID: 30244812
Abstract
The positive relationship between sodium intake and blood pressure is well established. However, results of observational studies on dietary sodium intake and risk of stroke are inconsistent. Moreover, prospective studies with multiple 24-hour urine samples for accurate estimation of habitual sodium intake are scarce. We examined the association of urinary sodium excretion (UNaV) as an accurate estimate of intake with risk of stroke. We studied 7330 individuals free of cardiovascular events at baseline in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, a prospective, population-based cohort of Dutch men and women. The UNaV was measured in two 24-hour urine specimens at baseline (1997-1998) and two specimens during follow-up (2001-2003). Baseline median UNaV was 137 mmol/24 h (interquartile range, 106-171 mmol/24 h). During a median follow-up of 12.5 years (interquartile range, 11.9-12.9 years), a total of 183 stroke events occurred. An inverse association between UNaV and risk of stroke was observed after adjustment for age and sex (hazard ratio per 1-SD [51 mmol/24 h] decrement, 1.36; 95% CI, 1.11-1.65), which remained independent of additional adjustment for anthropometric, dietary, lifestyle, and other potential confounding factors (HR, 1.44; 95% CI, 1.14-1.82). After adjustment for potential mediators (systolic blood pressure and antihypertensive medication, plasma renin, aldosterone, and sodium levels), the association of UNaV with risk of stroke remained unchanged, with HRs (95% CIs) of 1.44 (1.14-1.82), 1.50 (1.18-1.90), 1.54 (1.21-1.97), and 1.49 (1.17-1.90), respectively. This prospective study revealed an association of low UNaV with an increased risk of stroke.

Rapamycin but not acarbose decreases age-related loss of outer hair cells in the mouse Cochlea.
Altschuler RA, Kanicki A, Martin C, Kohrman DC, Miller RA.
Hear Res. 2018 Sep 7;370:11-15. doi: 10.1016/j.heares.2018.09.003. [Epub ahead of print]
PMID: 30245283
Abstract
Adding rapamycin or acarbose to diet at 9-10 months of age has been shown to significantly increase life span in both male and female UM-HET3 mice. The current study examined cochleae of male and female UM-HET3 mice at 22 months of age to determine if either treatment also influenced age-related loss of cochlear hair cells. A large loss of cochlear outer hair cells was observed at 22 months of age in untreated mice in both apical and basal halves of the cochlear spiral. Addition of acarbose to diet had no significant effect on the amount of outer hair cell loss at 22 months of age or in its pattern, with large loss in both apical and basal halves. The addition of rapamycin to diet, however, significantly reduced outer hair cell loss in the basal half of the cochlea at 22 months of age when compared to untreated mice. There was no significant difference between male and female mice in any of the conditions. Age-related outer hair cell loss in the apical cochlea precedes outer hair cell loss in the base in many mouse strains. The results of the present study suggest that rapamycin but not acarbose treatment can delay age-related loss of outer hair cells at doses at which each drug increases life span.
KEYWORDS:
Acarbose; Age-related hearing loss; Aging; Auditory; Cochlea; Rapamycin

Estradiol and leptin have separate but additive anorexigenic effects and differentially target fat mass in rats.
Côté I, Green SM, Yarrow JF, Conover CF, Toklu HZ, Morgan D, Carter CS, Tümer N, Scarpace PJ.
J Neuroendocrinol. 2018 Sep 23:e12646. doi: 10.1111/jne.12646. [Epub ahead of print]
PMID: 30246441
Abstract
We recently showed that male compared to female rats exhibit lower hypophagia and body weight (BW) loss following central leptin delivery, suggesting a role for estradiol in leptin responsiveness. Addressing this, we delivered Ob (Leptin) or GFP (Control) gene into the brain of male rats that were simultaneously treated with estradiol or Vehicle. In a reciprocal approach, we compared estradiol-deficient (Ovx) to intact females (Sham) that received Leptin or Control vector. Changes in food intake (FI), BW, and body composition were examined. In males, estradiol and Leptin resulted in lower cumulative food intake (15%) and endpoint body weight (5%) but rats receiving dual treatment (Estradiol-Leptin) ate 28% less and weighed 22% less than Vehicle-Control. Changes in FI were unique to each treatment, with a rapid decrease in Vehicle-Leptin followed by gradual renormalization. In contrast, hypophagia in Estradiol-Control was of lower amplitude and sporadic. Leptin selectively targeted fat mass and endpoint abdominal fat mass was 65-80% lower compared to their respective Control groups. In females, both Leptin groups had lower body weight (endpoint values 20% lower than Control groups) with the highest extent in Sham animals (endpoint value was 28% less in Sham-Leptin than in Sham-Control). Ovx rats rapidly started regaining their lost BW reminiscent of the pattern in males. Leptin rapidly and robustly reduced fat mass with endpoint values 30-35% less than Control treated animals. It appears that Leptin and estradiol decreased FI and BW through different mechanisms, with the pattern of Estradiol-Leptin reminiscent of that observed in females and with the pattern of Ovx-Leptin, reminiscent of that observed in males. Estrogen status did not influence initial fat mass loss by Leptin. It can be concluded that estradiol modulates long-term response to central leptin overexpression but its actions on energy homeostasis are additive and independent of those of leptin.
KEYWORDS:
Estradiol; Female; Leptin; Male; Weight loss

Do dietary amino acid ratios predict risk of incident hypertension among adults?
Teymoori F, Asghari G, Farhadnejad H, Mirmiran P, Azizi F.
Int J Food Sci Nutr. 2018 Sep 24:1-9. doi: 10.1080/09637486.2018.1515183. [Epub ahead of print]
PMID: 30246590
Abstract
In the current study, we investigated the association between dietary amino acid ratios and the 3-year incidence of hypertension, conducted in the framework of the Tehran Lipid and Glucose Study with 4287 adults(41.9% men), aged 20-70 y. Dietary intakes of amino acids were assessed using a valid and reliable food frequency questionnaire and reported as percentage of protein. Then amino acid ratios including Leu.Ser/Thr.Trp, Leu/Trp, Leu/Thr, and Ser/Thr were calculated. We identified 429(10%) cases of hypertension during 3.1 y of follow up. The adjusted OR of the highest quartile of dietary Leu.Ser/Thr.Trp intake was 1.48 (95%CI:1.04-2.09, P for trend:0.02) compared with the lowest one. Furthermore, the OR of hypertension in the highest, compared with the lowest quartile of the leu/Thr ratio(2.19 vs 2.02) was 1.46(1.01-2.12), P for trend = 0.07. Our findings suggest that high dietary intakes of Leu.Ser/Thr.Trp ratio were associated with higher risk of incident hypertension and BP levels.
KEYWORDS:
Hypertension; blood pressure; leucine; serine; threonine; tryptophan

Protein Intake and Functional Integrity in Aging: The Framingham Heart Study Offspring.
Hruby A, Sahni S, Bolster D, Jacques PF.
J Gerontol A Biol Sci Med Sci. 2018 Sep 24. doi: 10.1093/gerona/gly201. [Epub ahead of print]
PMID: 30247514
Abstract
BACKGROUND:
Higher protein intake is linked to maintenance of muscle mass and strength, but few studies have related protein to physical function and disability in aging.
METHODS:
In participants of the Framingham Heart Study Offspring, we examined associations between protein intake (g/d), estimated from food frequency questionnaires, and maintenance of functional integrity, as a functional integrity score based on responses to 17 questions from Katz Activities of Daily Living, Nagi, and Rosow-Breslau questionnaires, repeated up to five times (1991/1995-2011/2014) over 23 years of follow-up. Cox proportional hazard models were used to estimate risk of incident loss of functional integrity (functional integrity score ≤ 15th percentile).
RESULTS:
In 2,917 participants (age 54.5 [9.8] years), baseline protein intake was 77.2 (15.6) g/d. The functional integrity score (baseline, mean 98.9, range 82.4-100.0) was associated with objective performance (gait speed, grip strength) and lower odds of falls, fractures, and frailty. Across follow-up, there were 731 incident cases of loss of functional integrity. In fully adjusted models, participants in the highest category of protein intake (median 92.2 g/d) had 30% lower risk of loss of functional integrity (hazard ratio [95% confidence interval] 0.70 [0.52, 0.95], p trend = .03), versus those with the lowest intake (median 64.4 g/d). However, sex-stratified analyses indicated the association was driven by the association in women alone (hazard ratio [95% confidence interval] 0.49 [0.32, 0.74], p trend = .002) and was nonsignificant in men (hazard ratio [95% confidence interval] 1.14 [0.70, 1.86], p trend = .59).
CONCLUSIONS:
Higher protein intake was beneficially associated with maintenance of physical function in middle-aged, high-functioning U.S. adults over the span of two decades. This association was particularly evident in women.

Changes in Types of Dietary Fats Influence Long-term Weight Change in US Women and Men.
Liu X, Li Y, Tobias DK, Wang DD, Manson JE, Willett WC, Hu FB.
J Nutr. 2018 Sep 22. doi: 10.1093/jn/nxy183. [Epub ahead of print]
PMID: 30247611
Abstract
BACKGROUND:
The relation between dietary fat intake and body weight remains controversial. Few studies have examined long-term changes in types of dietary fat and weight change in longitudinal studies.
OBJECTIVE:
The objective of this study was to examine associations between intake of different types of fat and long-term weight change in US women and men.
METHODS:
The association between changes in consumption of varying types of fat and weight change was examined every 4 y through the use of multivariate models adjusted for age, baseline body mass index, and change in percentage energy from protein, intake of cereal fiber, fruits, and vegetables, alcohol use, and other lifestyle covariates in 3 prospective US cohorts, including 121,335 men and women free of diabetes, cardiovascular disease, cancer, or obesity over a 20- to 24-y follow-up. Dietary intakes and body weight were assessed via validated questionnaires. Cohort-specific results were pooled with the use of a random-effect meta-analysis.
RESULTS:
Compared with equivalent changes in carbohydrate intake, a 5% increase in energy from saturated fatty acid (SFA) and a 1% increase in energy from trans-fat were associated with 0.61 kg (95% CI: 0.54, 0.68 kg) and 0.69 kg (95% CI: 0.56, 0.84 kg) greater weight gain per 4-y period, respectively. A 5% increase in energy from polyunsaturated fatty acid (PUFA) was associated with less weight gain (-0.55 kg; 95% CI: -0.81, -0.29 kg). Increased intake of monounsaturated fatty acid (MUFA) from animal sources by 1% was associated with weight gain of 0.29 kg (95% CI: 0.25, 0.33 kg), whereas MUFA from plant sources was not associated with weight gain.
CONCLUSIONS:
Different dietary fats have divergent associations with long-term weight change in US men and women. Replacing saturated and trans-fats with unsaturated fats, especially PUFAs, contributes to the prevention of age-related weight gain.

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Associations of adult-attained height and early life energy restriction with postmenopausal breast cancer risk according to estrogen and progesterone receptor status.
Elands RJ, Offermans NS, Simons CC, Schouten LJ, Verhage BA, van den Brandt PA, Weijenberg MP.
Int J Cancer. 2018 Sep 25. doi: 10.1002/ijc.31890. [Epub ahead of print]
PMID: 30252931
Abstract
Adult-attained height is a marker for underlying mechanisms, such as cell growth, that may also influence postmenopausal breast cancer (BC) risk, perhaps specifically hormone-sensitive BC subtypes. Early life energy restriction may inhibit these mechanisms, resulting in shorter height and a reduced postmenopausal BC risk. 62,573 women from the Netherlands Cohort Study, 55-69 years old, completed a self-administered questionnaire in 1986, and were followed-up for 20.3 years (case-cohort: Nsubcohort =2438; Ncases =3354). Cox multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated for BC risk overall and by estrogen and progesterone receptor subtypes in relation to height and early life energy restriction during the Hunger Winter, War Years, and Economic Depression. Although energy restriction can only influence longitudinal growth in women exposed before and/or during the growth spurt, it may also influence BC risk when occurring after the growth spurt, possibly through different growth processes. Therefore, Cox analyses were additionally conducted according to timing of energy restriction in relation to the growth spurt. Height was associated with an increased BC risk (HRper 5cm =1.07, 95%CI:1.01-1.13), particularly hormone receptor-positive BC. Energy restriction before and/or during the growth spurt was associated with a decreased hormone receptor-positive BC risk. Energy restriction during the Hunger Winter increased the estrogen receptor-negative BC risk regardless of the timing of energy restriction. In conclusion, Height and energy restriction before and/or during the growth spurt were both associated with hormone receptor-positive BC risk, in the direction as expected, indicating critical exposure windows for hormonal growth-related mechanisms.
KEYWORDS:
adult-attained height; breast cancer epidemiology; energy restriction; estrogen receptor status; progesterone receptor status

Relevance of the Glycemic Index and Glycemic Load for Body Weight, Diabetes, and Cardiovascular Disease.
Vega-López S, Venn BJ, Slavin JL.
Nutrients. 2018 Sep 22;10(10). pii: E1361. doi: 10.3390/nu10101361. Review.
PMID: 30249012
https://www.mdpi.com/2072-6643/10/10/1361/htm
Abstract
Despite initial enthusiasm, the relationship between glycemic index (GI) and glycemic response (GR) and disease prevention remains unclear. This review examines evidence from randomized, controlled trials and observational studies in humans for short-term (e.g., satiety) and long-term (e.g., weight, cardiovascular disease, and type 2 diabetes) health effects associated with different types of GI diets. A systematic PubMed search was conducted of studies published between 2006 and 2018 with key words glycemic index, glycemic load, diabetes, cardiovascular disease, body weight, satiety, and obesity. Criteria for inclusion for observational studies and randomized intervention studies were set. The search yielded 445 articles, of which 73 met inclusion criteria. Results suggest an equivocal relationship between GI/GR and disease outcome. The strongest intervention studies typically find little relationship among GI/GR and physiological measures of disease risk. Even for observational studies, the relationship between GI/GR and disease outcomes is limited. Thus, it is unlikely that the GI of a food or diet is linked to disease risk or health outcomes. Other measures of dietary quality, such as fiber or whole grains may be more likely to predict health outcomes. Interest in food patterns as predictors of health benefits may be more fruitful for research to inform dietary guidance.
KEYWORDS:
body weight; carbohydrates; chronic disease risk; glycemic index; glycemic load; glycemic response; satiety; type 2 diabetes

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Rapamycin prevents thoracic aortic aneurysm and dissection in mice.
Zhou B, Li W, Zhao G, Yu B, Ma B, Liu Z, Xie N, Fu Y, Gong Z, Dai R, Zhang X, Kong W.
J Vasc Surg. 2018 Sep 22. pii: S0741-5214(18)31780-4. doi: 10.1016/j.jvs.2018.05.246. [Epub ahead of print]
PMID: 30253896
Abstract
OBJECTIVE:
The purpose of this study was to investigate whether rapamycin inhibits the development of thoracic aortic aneurysm and dissection (TAAD) in mice.
METHODS:
Three-week-old C57BL/6J male mice were fed a normal diet and randomized into a control group (n = 6), β-aminopropionitrile fumarate (BAPN) group (Gp A; n = 15), BAPN plus rapamycin (5 mg) group (Gp B; n = 8), and BAPN plus rapamycin (10 mg) group (Gp C; n = 8). Gp A, Gp B, and Gp C were administered BAPN (1 g/kg/d) for 4 weeks. One week after BAPN administration, Gp B and Gp C were treated with rapamycin (5 mg/kg/d or 10 mg/kg/d) through gavage for 21 days. Thoracic aortas were harvested for Western blot and immunofluorescence staining at day 14 and for morphologic and histologic analyses at day 28.
RESULTS:
BAPN treatment induced TAAD formation in mice. The incidence of TAAD in control, Gp A, Gp B, and Gp C mice was 0%, 80%, 25%, and 37.5%, respectively. Smaller thoracic aortic diameters (ascending aorta and arch) were observed in Gp B and Gp C mice than in Gp A mice (Gp B vs Gp A: ascending aorta, ex vivo, 1.07 ± 0.21 mm vs 1.80 ± 0.67 mm [P < .05]; aortic arch, ex vivo, 1.51 ± 0.40 mm vs 2.70 ± 1.06 mm [P < .05]; Gp C vs Gp A: ascending aortas, ex vivo, 1.10 ± 0.33 mm vs 1.80 ± 0.67 mm [P < .05]; aortic arch, ex vivo, 1.55 ± 0.56 mm vs 2.70 ± 1.06 mm [P < .05]). TAAD mice exhibited elastin fragmentation, abundant inflammatory cell infiltration, and significantly increased matrix metalloproteinase production in the aorta, and rapamycin treatment alleviated these changes. The protein levels of p-S6K and p-S6 in TAAD aortic tissues increased significantly, whereas they were suppressed by rapamycin.
CONCLUSIONS:
Rapamycin suppressed TAAD formation, probably by inhibition of mechanistic target of rapamycin signaling and reduction of inflammatory cell infiltration and matrix metalloproteinase 9 production. Targeting of the mechanistic target of rapamycin signaling pathway using rapamycin may be a favorable modulation for the clinical treatment of TAAD.
KEYWORDS:
Inflammatory cells; Matrix metalloproteinases; Rapamycin; Thoracic aortic aneurysm and dissection; mTOR

Primary prevention of dementia: from modifiable risk factors to a public brain health agenda?
Hussenoeder FS, Riedel-Heller SG.
Soc Psychiatry Psychiatr Epidemiol. 2018 Sep 25. doi: 10.1007/s00127-018-1598-7. [Epub ahead of print] Review.
PMID: 30255384
Abstract
INTRODUCTION:
With large numbers of people affected, no treatment in sight and continuing demographic change, the prevention of dementia is becoming a central public health issue.
METHODS:
We conducted a systematic meta-review including systematic reviews and meta-analyses of longitudinal observational studies on modifiable risk and protective factors for dementia published over the last 5 years.
RESULTS:
Compelling evidence on a number of modifiable risk factors, mostly lifestyle factors, is available from longitudinal observational studies to inform primary preventive efforts.
DISCUSSION:
Evidence stemming from preventive RCTs is limited. However, multi-domain interventions addressing a variety of risk factors at once seem promising with regard to high-risk individuals (selective preventive approach). However, we argue that it is time to move forward and discuss a public brain health agenda as a universal preventive approach. Based on a risk reduction strategy, the public brain health agenda suggests the following ten key actions: (1) increase physical activity, (2) foster social integration, (3) improve education and foster lifelong learning, (4) provide mentally stimulating workplaces, (5) foster a cognitively active lifestyle, (6) propose a healthy Mediterranean-like diet, (7) reduce alcohol consumption, (8) stop smoking, (9) prevent, diagnose and treat chronic conditions, and (10) reduce anticholinergic medication in the elderly.
KEYWORDS:
Brain health agenda; Dementia; Prevention; Risk factors; Systematic review

Fruit and vegetable intake and pancreatic cancer risk in a population-based cohort study in Japan.
Yamagiwa Y, Sawada N, Shimazu T, Yamaji T, Goto A, Takachi R, Ishihara J, Iwasaki M, Inoue M, Tsugane S.
Int J Cancer. 2018 Sep 26. doi: 10.1002/ijc.31894. [Epub ahead of print]
PMID: 30255932
Abstract
Oxidative stress and chronic inflammation are potential pathogenic factors of pancreatic cancer. Although fruits and vegetables are abundant in antioxidants and anti-inflammatory constituents, the reported associations between fruit and vegetable intake and pancreatic cancer risk have been inconsistent. Here, we investigated the association between fruit and vegetable intake and pancreatic cancer risk as part of the Japan Public Health Center-based Prospective Study. The analysis included 90,185 participants who responded to a medical and lifestyle questionnaire during 1995-1998. Associations between fruit and vegetable intake and pancreatic cancer risk were evaluated with Cox proportional hazards models. Additional analyses were stratified by smoking status and body mass index. During follow-up (median duration, 16.9 years), 577 participants were diagnosed with pancreatic cancer. In multivariate-adjusted models, pancreatic cancer risk was inversely associated with total fruit intake (highest vs. lowest intake quartile; hazard ratio


: 0.74, 95% confidence interval [CI]: 0.57-0.95, P-trend: 0.115) and positively associated with total vegetable intake (HR: 1.30, 95% CI: 1.01-1.66, P-trend: 0.150). For total fruit intake, the inverse association with pancreatic cancer risk was more apparent in never smokers (HR: 0.67, 95% CI: 0.47-0.97, P-trend: 0.034). For total vegetable intake, the positive association was statistically significant in ever smokers (HR: 1.49, 95% CI: 1.01-2.19, P-trend: 0.044) and statistically non-significant in never smokers. In summary, total fruit intake and total vegetable intake had inverse and positive associations, respectively, with pancreatic cancer risk. Vegetable intake may correlate with increased risk partly because of the influence of smoking on vegetable intake. This article is protected by copyright.
KEYWORDS:
Body mass index; Japan Public Health Center-based Prospective Study; dietary factor; smoking

Masked hypertension incidence and risk factors in a prospective cohort study.
Trudel X, Brisson C, Gilbert-Ouimet M, Duchaine CS, Dalens V, Talbot D, Milot A.
Eur J Prev Cardiol. 2018 Sep 26:2047487318802692. doi: 10.1177/2047487318802692. [Epub ahead of print]
PMID: 30256672
Abstract
Aims Masked hypertension may affect up to 30% of the general population and is associated with a high cardiovascular disease risk. No previous study has examined the incidence of masked hypertension and its risk factors. The study aim was to determine the incidence of masked hypertension and to examine its related risk factors. Methods This is a cohort study including 1836 initially normotensive participants followed up on average for 2.9 years. Blood pressure was measured using Spacelabs 90207. Manual blood pressure was defined as the mean of the first three readings taken at rest. Ambulatory blood pressure was defined as the mean of the next readings recorded every 15 minutes during daytime working hours. Masked hypertension incidence at follow-up was defined as manual blood pressure less than 140 and less than 90 mmHg and ambulatory blood pressure at least 135 or at least 85 mmHg. Generalised estimating equations were used. Results The cumulative incidence of masked hypertension was 10.3% and was associated with male gender (relative risk (RR) 1.51, 95% confidence interval (CI) 1.18-1.94), older age (RR40-49 years 1.56, 95% CI 1.16-2.11, RR≥50 years 1.50, 95% CI 1.06-2.10), higher education (RRcollege 1.31, 95% CI 1.03-1.65), body mass index (RR≥27 1.43, 95% CI 1.11-1.85), smoking (RR 1.51, 95% CI 1.09-2.010) and alcohol intake (RR≥6/week 1.65, 95% CI 1.13-2.03). Conclusion The present study is the first to identify risk factors for the incidence of masked hypertension. Current guidelines for hypertension detection recommend ambulatory blood pressure in patients with an elevated blood pressure reading at the clinic. As it is impractical to measure ambulatory blood pressure in all normotensive patients, factors identified in the present study should be considered for the screening of at-risk individuals and for primary prevention of masked hypertension.
KEYWORDS:
Masked hypertension; ambulatory blood pressure; epidemiology; prospective cohort study; risk factors

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Associations of Body Composition with Blood Pressure and Hypertension.
Ye S, Zhu C, Wei C, Yang M, Zheng W, Gan D, Zhu S.
Obesity (Silver Spring). 2018 Sep 27. doi: 10.1002/oby.22291. [Epub ahead of print]
PMID: 30260578
Abstract
OBJECTIVE:
The present study investigated the associations of body composition, including skeletal muscle and fat mass, with blood pressure (BP) and hypertension.
METHODS:
Data from 3,130 participants aged 18 to 80 years were analyzed. Body composition and total skeletal muscle (TSM) were measured or calculated based on dual-energy x-ray absorptiometry. Multivariate linear and logistic regression models were used to analyze the associations of TSM, body fat percentage, android to gynoid fat ratio, and leg and arm lean body mass (LBM) with BP and hypertension. The Wald test was used to estimate the differences in the coefficients.
RESULTS:
TSM indices, body fat percentage, and android to gynoid fat ratio were significantly associated with higher odds ratio for prehypertension and hypertension, except for TSM/weight, after controlling for potential confounders. The standardized beta coefficients of arm LBM indices for systolic and diastolic BP were higher than relevant indices of leg LBM.
CONCLUSIONS:
Different indices of TSM, especially in arm LBM, were all positively associated with elevated BP, prehypertension, and hypertension in Chinese adults, after considering potential confounding factors, including body fat and fat distribution. Future longitudinal studies are warranted to confirm our findings.

Association of Dietary Fatty Acids with Blood Lipids is Modified by Physical Activity in Adolescents: Results from the GINIplus and LISA Birth Cohort Studies.
Harris CP, von Berg A, Berdel D, Bauer CP, Schikowski T, Koletzko S, Heinrich J, Schulz H, Standl M.
Nutrients. 2018 Sep 25;10(10). pii: E1372. doi: 10.3390/nu10101372.
PMID: 30257483
https://www.mdpi.com/2072-6643/10/10/1372/htm
Abstract
The role of consuming different types of fatty acids (FA) at the expense of carbohydrates (CHO), on the blood lipid profile of adolescents is largely unknown, as is the modulating effect of different levels of physical activity (PA). Children from the GINIplus and LISA birth cohorts, with complete data on dietary FA (assessed by food-frequency questionnaires), objectively-measured PA (assessed by accelerometers) and blood lipids (lipoprotein cholesterol and triglycerides) at age 15 years, were included (N = 837). Sex-stratified associations between dietary FA and blood lipids were assessed by linear regression in substitution models which represented isocaloric replacements of CHO with saturated FA (SFA), monounsaturated FA (MUFA), n-3 polyunsaturated FA (PUFA) or n-6 PUFA. To assess the interactions with PA, analyses were then performed stratified by tertiles of different PA levels (sedentary, lifestyle, moderate-to-vigorous (MVPA)). Both sexes presented a significant inverse association between MUFA and triglycerides, and females a direct association between n-3 PUFA and high-density lipoprotein. Stratifying by PA tertiles, associations were mainly restricted to participants with the lowest levels of lifestyle PA, or the highest time spent sedentary. The effects of dietary FA on the lipid profile vary in an activity-specific manner, emphasizing possible synergistic roles of diet and PA.
KEYWORDS:
MVPA; adolescents; blood lipids; carbohydrates; fatty acids; lifestyle; physical activity; sedentary; substitution

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Telomere Length and All-Cause Mortality: A Meta-analysis.
Wang Q, Zhan Y, Pedersen NL, Fang F, Hägg S.
Ageing Res Rev. 2018 Sep 22. pii: S1568-1637(18)30123-5. doi: 10.1016/j.arr.2018.09.002. [Epub ahead of print] Review.
PMID: 30254001
https://sci-hub.tw/10.1016/j.arr.2018.09.002
Abstract
Telomere attrition is associated with increased morbidity and mortality of various age-related diseases. Reports of association between telomere length (TL) and all-cause mortality remain inconsistent. In the present study, a meta-analysis was performed using published cohort studies and un-published data from the Swedish Twin Registry (STR). Twenty-five studies were included: four STR cohorts (12,083 individuals with 2517 deaths) and 21 published studies. In the STR studies, one standard deviation (SD) decrement of leukocyte TL corresponded to 13% increased all-cause mortality risk (95% confidence interval [CI]: 7%-19%); individuals in the shortest TL quarter had 44% higher hazard (95% CI: 27%-63%) than those in the longest quarter. Meta-analysis of all eligible studies (121,749 individuals with 21,763 deaths) revealed one SD TL decrement-associated hazard ratio of 1.09 (95% CI: 1.06-1.13); those in the shortest TL quarter had 26% higher hazard (95% CI: 15%-38%) compared to the longest quarter, although between-study heterogeneity was observed. Analyses stratified by age indicated that the hazard ratio was smaller in individuals over 80 years old. In summary, short telomeres are associated with increased all-cause mortality risk in the general population. However, TL measurement techniques and age at measurement contribute to the heterogeneity of effect estimation.
KEYWORDS:
all-cause mortality; epidemiology; meta-analysis; telomere length
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Telomere length measurement as a clinical biomarker of aging and disease.
Fasching CL.
Crit Rev Clin Lab Sci. 2018 Sep 28:1-23. doi: 10.1080/10408363.2018.1504274. [Epub ahead of print]
PMID: 30265166
https://sci-hub.tw/https://www.tandfonline.com/doi/full/10.1080/10408363.2018.1504274
Abstract
Telomere length measurement is increasingly recognized as a clinical gauge for age-related disease risk. There are several methods for studying blood telomere length (BTL) as a clinical biomarker. The first is an observational study approach, which directly measures telomere lengths using either cross-sectional or longitudinal patient cohorts and compares them to a population of age- and sex-matched individuals. These direct traceable measurements can be considered reflective of an individual's current health or disease state. Escalating interest in personalized medicine, access to high-throughput genotyping and resulting acquisition of large volumes of genetic data corroborates the second method, Mendelian randomization (MR). MR employs telomere length-associated genetic variants to indicate predisposition to disease risk based on the genomic composition of the individual. When assessed from cells in the bloodstream, telomeres can show variation from their genetically predisposed lengths due to environmental-induced changes. These alterations in telomere length act as an indicator of cellular health, which, in turn, can provide disease risk status. Overall, BTL measurement is a dynamic marker of biological health and well-being that together with genetically defined telomere lengths can provide insights into improved healthcare for the individual.
KEYWORDS:
Leukocyte; Mendelian randomization; age-related disease; all-cause mortality; cardiovascular disease; observational studies; telomere length

Associations between self-reported periodontal disease, assessed using a very short questionnaire, cardiovascular disease events and all-cause mortality in a contemporary multi-ethnic population: The Multi-Ethnic Study of Atherosclerosis (MESA).
Gonzalez-Navarro B, Pintó-Sala X, Corbella E, Jané-Salas E, Miedema MD, Yeboah J, Shea S, Nasir K, Comin-Colet J, Corbella X, Lopez-López J, Blumenthal RS, Blaha MJ, Cainzos-Achirica M.
Atherosclerosis. 2018 Sep 20;278:110-116. doi: 10.1016/j.atherosclerosis.2018.09.026. [Epub ahead of print]
PMID: 30265891
https://sci-hub.tw/10.1016/j.atherosclerosis.2018.09.026
Abstract
BACKGROUND AND AIMS:
Periodontal disease (PD) is believed to be associated with cardiovascular disease (CVD) events. Nevertheless, the additive prognostic value of PD for the prediction of CVD events beyond traditional risk factors is unclear, particularly when self-reported using a short questionnaire.
METHODS:
In the community-based, multicenter, prospective, Multi-Ethnic Study of Atherosclerosis (MESA), PD was assessed at baseline using a two-item questionnaire. We used Cox proportional hazards regression models to evaluate the independent associations between self-reported PD and coronary heart disease (CHD), CVD events, and all-cause death. In addition, the area under the receiver-operator characteristic curve (AUC) was calculated for each of the study endpoints, for models including traditional CVD risk factors alone and models including traditional CVD risk factors plus information on PD. Subgroup analyses were performed stratifying by age and tobacco use.
RESULTS:
Among the 6640 MESA participants, high education level, high income, and access to healthcare were more frequent among individuals who self-reported PD. In multivariable analyses, null associations were observed between self-reported PD and incident CVD events, CHD events, and all-cause mortality; and self-reported PD did not improve risk prediction beyond traditional CVD risk factors in terms of AUC, for any of the three study endpoints. Subgroup analyses were consistent with the overall results.
CONCLUSIONS:
Our findings suggest that the prevalence of self-reported PD may be strongly influenced by educational status and other socioeconomic features. In this context, self-reported PD does not improve CVD risk assessment when evaluated using a brief questionnaire. Future studies should prioritize objective, dental health-expert assessments of PD.
KEYWORDS:
Cardiovascular disease; Periodontal disease; Periodontitis

Prospective Analysis of Vegetable Amount and Variety on the Risk of All-Cause and Cause-Specific Mortality among US Adults, 1999⁻2011.
Conrad Z, Thomson J, Jahns L.
Nutrients. 2018 Sep 27;10(10). pii: E1377. doi: 10.3390/nu10101377.
PMID: 30261669
https://www.mdpi.com/2072-6643/10/10/1377/htm
Abstract
The Dietary Guidelines for Americans 2015⁻2020 (DGA) provides recommendations for consuming a specific amount and variety of vegetables, but no studies have assessed the relationship between DGA-recommended vegetable variety and risk of mortality. We prospectively assessed the relationship between vegetable amount and variety and the risk of mortality using nationally-representative survey data (n = 29,133). Hazard ratios were estimated using survey-weighted, multivariate, Cox-proportional hazards models. Mean follow-up time was 6.5 years (12.8 years maximum). Total deaths from all causes were 2861, which included 829 deaths from cardiometabolic disease (556 coronary heart disease, 170 stroke, and 103 diabetes). Compared to individuals who reported consuming the greatest amount of vegetables daily, those with the least intake had a 78% greater risk of mortality from all causes (HR: 1.78, 95% CI: 1.29⁻2.47), a 68% greater risk of death from cardiovascular disease (1.68, 1.08⁻2.62), and an 80% greater risk of death from coronary heart disease (1.80, 1.09⁻2.08). No relationships were observed between vegetable variety and risk of all-cause or cause-specific mortality. Greater vegetable amount, but not variety, was associated with a reduced risk of mortality from all causes, cardiovascular disease, and coronary heart disease. Additional large-scale longitudinal studies with repeated measures of dietary exposure are needed.
KEYWORDS:
cardiometabolic; cardiovascular; heart disease; index; mortality; survival; variety; vegetable

Hiding negative trials by pooling them: a secondary analysis of pooled-trials publication bias in FDA-registered antidepressant trials.
de Vries YA, Roest AM, Turner EH, de Jonge P.
Psychol Med. 2018 Sep 28:1-7. doi: 10.1017/S0033291718002805. [Epub ahead of print]
PMID: 30261934
Abstract
BACKGROUND:
Previous studies on reporting bias generally examined whether trials were published in stand-alone publications. In this study, we investigated whether pooled-trials publications constitute a specific form of reporting bias. We assessed whether negative trials were more likely to be exclusively published in pooled-trials publications than positive trials and examined the research questions, individual trial results, and conclusions presented in these articles.
METHODS:
Data from a cohort of 105 randomized controlled trials of 16 antidepressants were extracted from earlier publications and the corresponding Food and Drug Administration (FDA) reviews. A systematic literature search was conducted to identify pooled-trials publications.
RESULTS:
We found 107 pooled-trials publications that reported results of 23 (72%) of 32 trials not published in stand-alone publications. Only two (3.8%) of 54 positive trials were published exclusively in pooled-trials publications, compared with 21 (41.1%) of 51 negative trials (p < 0.001). Thirteen (12%) of 107 publications had as primary aim to present data on the trial's primary research question (drug efficacy compared with placebo). Only four of these publications, reporting on five (22%) trials, presented individual efficacy data for the primary research question. Additionally, only five (5%) of 107 pooled-trials publications had a negative conclusion.
CONCLUSIONS:
Compared with positive trials, negative trials of antidepressants for depression were much more likely to be reported exclusively in pooled-trials publications. Pooled-trials publications flood the evidence base with often-redundant articles that, instead of addressing the original primary research question, present (positive) results on secondary questions. Therefore, pooled-trials publications distort the apparent risk-benefit profile of antidepressants.
KEYWORDS:
Antidepressants; bias; depression; pooled-trials publication bias

Marine n-3 Fatty Acids and the Risk of Peripheral Arterial Disease.
Lasota AN, Grønholdt MM, Bork CS, Lundbye-Christensen S, Overvad K, Schmidt EB.
J Am Coll Cardiol. 2018 Oct 2;72(14):1576-1584. doi: 10.1016/j.jacc.2018.07.045.
PMID: 30261957
Abstract
BACKGROUND:
The content of marine n-3 polyunsaturated fatty acids (PUFAs) in adipose tissue is considered a long-term biomarker for the body's endogenous exposure to seafood.
OBJECTIVES:
This study sought to examine associations between the content of marine n-3 PUFAs in adipose tissue and the risk of incident peripheral arterial disease (PAD).
METHODS:
In this case-cohort study based on data from the Danish Diet, Cancer and Health cohort, adipose tissue biopsies were taken from the buttocks of all participants at baseline. After a median follow-up of 13.5 years, 870 validated cases of PAD were identified and included together with a randomly drawn subcohort of 3,204 participants using weighted Cox regression. Adipose tissue samples were analyzed by gas chromatography.
RESULTS:
In multivariable analyses using the lowest quintile as the reference and adjusting for established risk factors for PAD, we found a statistically significant lower rate of PAD in the highest quintile of eicosapentaenoic acid (EPA) (hazard ratio {HR}: 0.55; 95% confidence interval [CI]: 0.41 to 0.74) and a nonsignificant lower rate for docosahexaenoic acid (HR: 0.79; 95% CI: 0.59 to 1.06). We observed a lower rate of PAD, when comparing the highest quintile of the combined EPA and docosahexaenoic acid with the reference (HR: 0.71; 95% CI: 0.53 to 0.96). In contrast, docosapentaenoic acid had an HR of 1.31 (95% CI: 0.97 to 1.77) in the highest quintile.
CONCLUSIONS:
A high content of marine n-3 PUFAs in adipose tissue, in particular EPA, was associated with a lower risk of incident PAD.
KEYWORDS:
adipose tissue; case-cohort study; docosahexaenoic acid; eicosapentaenoic acid; marine n-3 polyunsaturated fatty acids

Habitual consumption of soy protein and isoflavones and risk of metabolic syndrome in adults ≥ 40 years old: a prospective analysis of the Korean Multi-Rural Communities Cohort Study (MRCohort).
Woo HW, Kim MK, Lee YH, Shin DH, Shin MH, Choi BY.
Eur J Nutr. 2018 Sep 27. doi: 10.1007/s00394-018-1833-8. [Epub ahead of print]
PMID: 30264377
Abstract
PURPOSE:
Although considerable attention has been paid to the potential benefits of soy protein and isoflavones for preventing metabolic syndrome (MetS) and its components, findings linking habitual consumption of these factors to MetS are limited. This study aimed to evaluate the association of MetS incidence with habitual intake of soy protein/isoflavones among Korean men and women aged ≥ 40 years old who did not have MetS at baseline (n = 5509; 2204 men and 3305 women).
METHODS:
Dietary intake of soy protein/isoflavones at baseline and average consumption during follow-up were used.
RESULTS:
A significant inverse association between dietary intake and incidence of MetS was found in women (incidence rate ratios, IRR = 0.60, 95% CI = 0.46-0.78, P for trend = 0.0094 for the highest quintile of average soy protein intake compared with the lowest quintile; IRR = 0.57, 95% CI = 0.44-0.74, P for trend = 0.0048 for the highest quintile of average isoflavones intake compared with the lowest quintile). A tendency towards an inverse association was also found in men, although it was not significant for the highest quintile (IRR = 0.80, 95% CI = 0.58-1.11, P for trend = 0.9759, comparing the lowest to the highest quintile of average soy protein intake; IRR = 0.73, 95% CI = 0.53-1.01, P for trend = 0.8956, comparing the lowest to the highest quintile of average isoflavones intake). In terms of individual abnormalities, a significant inverse association was found between soy protein and isoflavones and the incidence of low-high-density lipoprotein cholesterol in both men and women. Abdominal obesity and elevated blood pressure were inversely related to soy protein/isoflavones only in women, and an inverse association of elevated triglyceride appeared only in men.
CONCLUSION:
Our findings suggest that habitual intake of soy protein and isoflavones is inversely associated with the risk of MetS and its components. There is likely to be a reverse J-shaped association of average intake with MetS.
KEYWORDS:
Isoflavones; Korea; Metabolic syndrome; Prospective; Soy protein

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Associations of clothing size, adiposity and weight change with risk of postmenopausal breast cancer in the UK Women's Cohort Study (UKWCS).
Moy FM, Greenwood DC, Cade JE.
BMJ Open. 2018 Sep 28;8(9):e022599. doi: 10.1136/bmjopen-2018-022599.
PMID: 30269068
https://bmjopen.bmj.com/content/bmjopen/8/9/e022599.full.pdf
Abstract
OBJECTIVES:
Breast cancer is associated with overweight and obesity after menopause. However, clothing size as a proxy of adiposity in predicting postmenopausal breast cancer is not widely studied. We aimed to explore the relationships between postmenopausal breast cancer risk with adipose indicators (including clothing sizes) and weight change over adulthood.
DESIGN:
Prospective cohort study.
SETTING:
England, Wales and Scotland.
PARTICIPANTS:
17 781 postmenopausal women from the UK Women's Cohort Study.
PRIMARY OUTCOME MEASURE:
Incident cases of malignant breast cancers (International Classification of Diseases (ICD) 9 code 174 and ICD 10 code C50).
RESULTS:
From 282 277 person-years follow-up, there were 946 incident breast cancer cases with an incidence rate of 3.35 per 1000 women. Body mass index (HR: 1.04; 95% CI: 1.02 to 1.07), blouse size (HR: 1.10; 1.03 to 1.18), waist circumference (HR: 1.07; 1.01 to 1.14) and skirt size (HR: 1.14;1.06 to 1.22) had positive associations with postmenopausal breast cancer after adjustment for potential confounders. Increased weight over adulthood (HR: 1.02; 1.01 to 1.03) was also associated with increased risk for postmenopausal breast cancer.
CONCLUSIONS:
Blouse and skirt sizes can be used as adipose indicators in predicting postmenopausal breast cancer. Maintaining healthy body weight over adulthood is an effective measure in the prevention of postmenopausal breast cancer.
KEYWORDS:
Uk women cohort; blouse size; post-menopausal breast cancer; skirt size; weight change

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BMI, Waist Circumference and All-Cause Mortality in a Middle-Aged and Elderly Chinese Population.
Hu H, Wang J, Han X, Li Y, Wang F, Yuan J, Miao X, Yang H, He M.
J Nutr Health Aging. 2018;22(8):975-981. doi: /10.1007/s12603-018-1047-z.
PMID: 30272102
Abstract
OBJECTIVE:
To investigate the association of obesity and all-cause mortality in a sample of middle-aged and elderly population.
DESIGN AND SETTING:
Information of participants was collected in the Dongfeng-Tongji study, a perspective cohort study of Chinese occupational population. The main outcome was risk of death after 8.5 years of follow-up.
PARTICIPANTS AND MEASUREMENTS:
We examined the association of BMI, waist circumference (WC, and waist-height ratio (WHtR) with all-cause mortality in the Dongfeng-Tongji cohort study (n=26,143). Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality. Area under the receiver operating characteristic curves and net reclassification improvement (NRI) were used to calculate the power of prediction models.
RESULTS:
During a mean of 8.5 years of follow-up, 2,246 deaths were identified. There is a U-shaped association of BMI with all-cause mortality in the middle-aged and elderly Chinese population. Compared with individuals with normal BMI, underweight was positively (HR=2.16, 95% CI: 1.73, 2.69) while overweight (HR=0.75, 95% CI: 0.67, 0.84) and obesity (HR=0.67, 95% CI: 0.56, 0.79) were negatively associated with all-cause mortality after adjustment for potential confounders including WC. In contrast, WC (Q5 vs. Q1, HR=1.55, 95% CI: 1.29, 1.86) and WHtR (Q5 vs.Q1, HR=1.69, 95% CI: 1.40, 2.04) were positively associated with mortality after further adjustment for BMI (P trend < 0.001). Addition of both BMI and WC into the all-cause mortality predictive model significantly increased AUC (P =0.0002) and NRI (NRI = 2.57%, P = 0.0007).
CONCLUSIONS:
BMI and WC/WHtR were independently associated with all-cause mortality after mutual adjustment. Combination of BMI and WC/WHtR improved the predictive ability of all-cause mortality risk in the middle-aged and elderly population.

The Diurnal Timing of Starvation Differently Impacts Murine Hepatic Gene Expression and Lipid Metabolism - A Systems Biology Analysis Using Self-Organizing Maps.
Rennert C, Vlaic S, Marbach-Breitrück E, Thiel C, Sales S, Shevchenko A, Gebhardt R, Matz-Soja M.
Front Physiol. 2018 Sep 10;9:1180. doi: 10.3389/fphys.2018.01180. eCollection 2018.
PMID: 30271348
Abstract
Organisms adapt their metabolism and draw on reserves as a consequence of food deprivation. The central role of the liver in starvation response is to coordinate a sufficient energy supply for the entire organism, which has frequently been investigated. However, knowledge of how circadian rhythms impact on and alter this response is scarce. Therefore, we investigated the influence of different timings of starvation on global hepatic gene expression. Mice (n = 3 each) were challenged with 24-h food deprivation started in the morning or evening, coupled with refeeding for different lengths and compared with ad libitum fed control groups. Alterations in hepatocyte gene expression were quantified using microarrays and confirmed or complemented with qPCR, especially for lowly detectable transcription factors. Analysis was performed using self-organizing maps (SOMs), which bases on clustering genes with similar expression profiles. This provides an intuitive overview of expression trends and allows easier global comparisons between complex conditions. Transcriptome analysis revealed a strong circadian-driven response to fasting based on the diurnal expression of transcription factors (e.g., Ppara, Pparg). Starvation initiated in the morning produced known metabolic adaptations in the liver; e.g., switching from glucose storage to consumption and gluconeogenesis. However, starvation initiated in the evening produced a different expression signature that was controlled by yet unknown regulatory mechanisms. For example, the expression of genes involved in gluconeogenesis decreased and fatty acid and cholesterol synthesis genes were induced. The differential regulation after morning and evening starvation were also reflected at the lipidome level. The accumulation of hepatocellular storage lipids (triacylglycerides, cholesteryl esters) was significantly higher after the initiation of starvation in the morning compared to the evening. Concerning refeeding, the gene expression pattern after a 12 h refeeding period largely resembled that of the corresponding starvation state but approached the ad libitum control state after refeeding for 21 h. Some components of these regulatory circuits are discussed. Collectively, these data illustrate a highly time-dependent starvation response in the liver and suggest that a circadian influence cannot be neglected when starvation is the focus of research or medicine, e.g., in the case of treating victims of sudden starvation events.
KEYWORDS:
circadian regulation; hepatocyte; refeeding; self-organizing map; starvation

Mediterranean diet and mortality in the elderly: a prospective cohort study and a meta-analysis.
Bonaccio M, Di Castelnuovo A, Costanzo S, Gialluisi A, Persichillo M, Cerletti C, Donati MB, de Gaetano G, Iacoviello L.
Br J Nutr. 2018 Oct;120(8):841-854. doi: 10.1017/S0007114518002179. Epub 2018 Aug 30.
PMID: 30157978
Abstract
The Mediterranean diet (MD) has been associated with prolonged survival in the general population, but no meta-analysis has apparently investigated the potential health benefits in relation to mortality in the elderly. We performed a longitudinal analysis on 5200 individuals aged ≥65 years identified within the general population recruited in the Moli-sani study cohort (2005-2010). Adherence to the MD was appraised by the a priori Mediterranean diet score (MDS; range 0-9). Survival estimates were derived using Cox regression and competing risk models. For the meta-analysis, PubMed and Scopus databases were searched from inception until April 2018 to identify prospective studies on the MD and death risk in the elderly. Over a median follow-up of 8·1 years, a total of 900 deaths were ascertained in the elderly sub-sample of the Moli-sani cohort. A one-point increase in the MDS was associated with lower risk of all-cause, coronary artery disease/cerebrovascular and non-cardiovascular/non-cancer mortality (multi-variable hazard ratio (HR)=0·94; 95 % CI 0·90, 0·98; HR=0·91; 95 % CI 0·83, 0·99 and HR=0·89; 95 % CI 0·81, 0·96, respectively). In a meta-analysis of seven prospective studies, including our results, for a total of 11 738 participants and 3874 deaths, one-point increment in MDS was associated with 5 % (4-7 %) lower risk of all-cause death. An inverse linear dose-response relationship was found from a meta-analysis including three studies. In conclusion, a prospective cohort study and a meta-analysis showed that closer adherence to the MD was associated with prolonged survival in elderly individuals, suggesting the appropriateness for older persons to adopt/preserve the MD to maximise their prospects for survival.
KEYWORDS:
HR hazard ratio; ICD International Classification of Diseases; MD Mediterranean diet; MDS Mediterranean diet score; Elderly; Mediterranean diet; Meta-analyses; Moli-sani Study; Mortality
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http://www.cardiacrehabilitation.org.uk/docs/Mediterranean Diet Score Tool.pdf

Vitamin D insufficiency predicts mortality among older men, but not women: A nationwide retrospective cohort from Thailand.
Srinonprasert V, Chalermsri C, Chailurkit LO, Ongphiphadhanakul B, Aekplakorn W.
Geriatr Gerontol Int. 2018 Oct 2. doi: 10.1111/ggi.13529. [Epub ahead of print]
PMID: 30280463
https://sci-hub.tw/10.1111/ggi.13529
Abstract
AIM:
Previous studies on the association between low vitamin D level and increased mortality mainly came from high-income countries. The primary objective of the present study was to examine the effect of sex on the association between 25-hydroxyvitamin D2 and D3 and mortality among community-dwelling older people in Thailand.
METHODS:
A cohort of individuals aged ≥60 years from the Thai 4th National Health Examination Survey carried out in 2008 were followed and linked to a vital registry in 2015. Data regarding comorbid diseases, physical activity and serum vitamin D were obtained at the baseline assessment. Factors associated with all-cause mortality were determined using Cox proportional hazards models.
RESULTS:
A total of 1268 participants with a median age of 74.0 years (interquartile range 67.0-81.0) were included. The prevalence of vitamin D insufficiency was 24.5% and 43.9% in men and women, respectively. Vitamin D insufficiency was significantly associated with all-cause mortality only among men (adjusted HR 1.77, 95% CI 1.25-2.51), but not women. Analysis of 25-hydroxyvitamin D3 divided into tertiles also showed an association with an adjusted HR of 1.83 (95% CI 1.23-2.72) for the lowest tertile in men. Diabetes was an effect modifier for low serum vitamin D and male sex, with HR 3.34 (95% CI 1.76-6.33, P < 0.001) in diabetic men with vitamin D insufficiency.
CONCLUSIONS:
Low serum vitamin D is an independent risk factor for increased mortality in community-dwelling Thai older men. Further randomized controlled study to investigate the benefit of vitamin D3 supplementation in older persons, particularly men, is warranted. Geriatr Gerontol Int 2018; ••: ••-••.
KEYWORDS:
Thailand; mortality; older persons; serum 25-hydroxyvitamin D3; vitamin D insufficiency

Aging, Cell Senescence, and Chronic Disease: Emerging Therapeutic Strategies.
Tchkonia T, Kirkland JL.
JAMA. 2018 Sep 17. doi: 10.1001/jama.2018.12440. [Epub ahead of print] No abstract available.
PMID: 30242336
https://sci-hub.tw/10.1001/jama.2018.12440

Aging as a Biological Target for Prevention and Therapy.
Barzilai N, Cuervo AM, Austad S.
JAMA. 2018 Sep 17. doi: 10.1001/jama.2018.9562. [Epub ahead of print] No abstract available.
PMID: 30242337
https://sci-hub.tw/10.1001/jama.2018.9562

From Lifespan to Healthspan.
Olshansky SJ.
JAMA. 2018 Sep 17. doi: 10.1001/jama.2018.12621. [Epub ahead of print] No abstract available.
PMID: 30242384
https://sci-hub.tw/10.1001/jama.2018.12621

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