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Dietary vinegar prevents kidney stone recurrence via epigenetic regulations.
Zhu W, Liu Y, Lan Y, Li X, Luo L, Duan X, Lei M, Liu G, Yang Z, Mai X, Sun Y, Wang L, Lu S, Ou L, Wu W, Mai Z, Zhong D, Cai C, Zhao Z, Zhong W, Liu Y, Sun Y, Zeng G.
EBioMedicine. 2019 Jun 12. pii: S2352-3964(19)30379-2. doi: 10.1016/j.ebiom.2019.06.004. [Epub ahead of print]
PMID: 31202812
https://www.ebiomedicine.com/article/S2352-3964(19)30379-2/pdf
Abstract
BACKGROUND:
Epidemiological evidence of over 9000 people suggests that daily intake of vinegar whose principal bioactive component is acetic acid is associated with a reduced risk of nephrolithiasis. The underlying mechanism, however, remains largely unknown.
METHODS:
We examined the in vitro and in vivo anti-nephrolithiasis effects of vinegar and acetate. A randomized study was performed to confirm the effects of vinegar in humans.
FINDINGS:
We found individuals with daily consumption of vinegar compared to those without have a higher citrate and a lower calcium excretion in urine, two critical molecules for calcium oxalate (CaOx) kidney stone in humans. We observed that oral administration of vinegar or 5% acetate increased citrate and reduced calcium in urinary excretion, and finally suppressed renal CaOx crystal formation in a rat model. Mechanism dissection suggested that acetate enhanced acetylation of Histone H3 in renal tubular cells and promoted expression of microRNAs-130a-3p, -148b-3p and -374b-5p by increasing H3K9, H3K27 acetylation at their promoter regions. These miRNAs can suppress the expression of Nadc1 and Cldn14, thus enhancing urinary citrate excretion and reducing urinary calcium excretion. Significantly these mechanistic findings were confirmed in human kidney tissues, suggesting similar mechanistic relationships exist in humans. Results from a pilot clinical study indicated that daily intake of vinegar reduced stone recurrence, increased citrate and reduced calcium in urinary excretion in CaOx stone formers without adverse side effects.
INTERPRETATION:
Vinegar prevents renal CaOx crystal formation through influencing urinary citrate and calcium excretion via epigenetic regulations. Vinegar consumption is a promising strategy to prevent CaOx nephrolithiasis occurrence and recurrence.
KEYWORDS:
Acetate; Calcium; Citrate; Epigenetic regulation; Nephrolithiasis; Vinegar; microRNA

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Effects of the DASH Diet and Sodium Intake on Bloating: Results From the DASH-Sodium Trial.
Peng AW, Juraschek SP, Appel LJ, Miller ER 3rd, Mueller NT.
Am J Gastroenterol. 2019 Jun 17. doi: 10.14309/ajg.0000000000000283. [Epub ahead of print]
PMID: 31206400
Abstract
INTRODUCTION:
Bloating is one of the most common gastrointestinal complaints. Evidence has linked fiber and sodium to bloating; however, randomized trials examining these diet components are lacking. Here, we used a randomized trial to examine the effects of the high-fiber DASH diet and dietary sodium intake on abdominal bloating. We hypothesized that both the high-fiber DASH diet and higher sodium intake would increase bloating.
METHODS:
The DASH-Sodium trial (1998-1999) randomized healthy adults to a high-fiber (32 g/d) DASH or low-fiber (11 g/d) Western diet (control). On their assigned diet, participants ate 3 sodium levels (50, 100, and 150 mmol/d at 2100 kcal) in 30-day periods in random order, with 5-day breaks between each period. The participants reported the presence of bloating at baseline and after each feeding period. Statistical analyses included log-binomial models to evaluate the risk of bloating.
RESULTS:
Of 412 participants (mean age 48 years; 57% women; 57% black), 36.7% reported bloating at baseline. Regardless of the diet, high sodium intake increased the risk of bloating (risk ratio = 1.27; 95% confidence interval: 1.06-1.52; P = 0.01). The high-fiber DASH diet also increased the risk of bloating over all sodium levels (risk ratio = 1.41; 95% confidence interval: 1.22-1.64; P < 0.001). The effect of high-fiber DASH on bloating was greater in men than in women (P for interaction = 0.001).
DISCUSSION:
Higher dietary sodium increased bloating, as did the high-fiber DASH diet. Although healthful high-fiber diets may increase bloating, these effects may be partially mitigated by decreasing dietary sodium intake. Future research is needed to explore mechanisms by which sodium intake and diet can influence bloating.

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Sex Differences In Postprandal Responses To Different Dairy Products On Lipoprotein Subclasses: A Randomized Controlled Cross-Over Trial.
Hansson P, Holven KB, Øyri LKL, Brekke HK, Gjevestad GO, Thoresen M, Ulven SM.
Br J Nutr. 2019 Jun 18:1-25. doi: 10.1017/S0007114519001429. [Epub ahead of print]
PMID: 31208475
Abstract
Men have earlier first time event of coronary heart disease, and higher postprandial triglyceride response, compared to women. The aim of this exploratory sub-study was to investigate if intake of meals with the same amount of fat from different dairy products affects postprandial lipoprotein subclasses differently in healthy women and men. Thirty-three women and 14 men were recruited to a randomized controlled cross-over study with four dairy meals consisting of butter, cheese, whipped cream or sour cream, corresponding to 45 grams of fat (approximately 60 energy percent). Blood samples were taken at 0, 2, 4 and 6 hours postprandially. Lipoprotein subclasses were measured using nuclear magnetic resonance, and analyzed using a linear mixed model. Sex had a significant impact on the response in M-VLDL (P=0.04), S-LDL (P=0.05), XL-HDL (P=0.009), and L-HDL (P=0.001) particle concentration (P), with women having an overall smaller increase in M-VLDL-P, a larger decrease in S-LDL-P, and a larger increase in XL-, and L-HDL-P compared to men, independent of meal. Men showed a decrease in XS-VLDL-P compared to women after intake of sour cream (P&lt;0.01). In men only, XS-VLDL-P decreased after intake of sour cream compared to all other meals (vs. butter: P=0.001; vs. cheese: P&lt;0.04; vs. whipped cream: P=0.006). Meals with the same amount of fat from different dairy products induce different postprandial effects on lipoprotein subclass concentrations in men and women.
KEYWORDS:
CHD Coronary heart disease CRP C-reactive protein CVD Cardiovascular disease E% Energy percent HDL-C High-density lipoprotein-cholesterol iAUC Incremental area under the curve IDL Intermediate-density lipoprotein IS Ischemic stroke L Large LDL-C Low-density lipoprotein-cholesterol LPL Lipoprotein lipase M Medium MFGM Milk fat globule membrane MI Myocardial infarction P Particle concentration S Small TC Total cholesterol TG Triglyceride TRL Triglyceride-rich lipoprotein XL Very large XS Very small XXL Extremely large; HDL; LDL; VLDL; butter; cheese; cream; dairy matrix; lipoprotein subclasses; postprandial; sex differences; sour cream

Joint Analysis of Metabolite Markers of Fish Intake and Persistent Organic Pollutants in Relation to Type 2 Diabetes Risk in Swedish Adults.
Shi L, Brunius C, Bergdahl IA, Johansson I, Rolandsson O, Donat Vargas C, Kiviranta H, Hanhineva K, Åkesson A, Landberg R.
J Nutr. 2019 Jun 18. pii: nxz068. doi: 10.1093/jn/nxz068. [Epub ahead of print]
PMID: 31209490
Abstract
BACKGROUND:
There is conflicting evidence regarding the association between fish intake and type 2 diabetes (T2D) incidence, possibly owing to measurement errors in self-reported intake and coexposure to persistent organic pollutants (POPs) present in fish.
OBJECTIVE:
The aim of this study was to identify plasma metabolites associated with fish intake and to assess their association with T2D risk, independently of POPs, in Swedish adults.
METHODS:
In a case-control study nested in the Swedish Västerbotten Intervention Programme, fasting plasma samples from 421 matched T2D case-control pairs of men and women aged 30-60 y at baseline and 10-y follow-up samples from a subset of 149 pairs were analyzed using untargeted metabolomics. Moreover, 16 plasma POPs were analyzed for the 149 pairs who had repeated samples available. Fish-related plasma metabolites were identified using multivariate modelling and partial correlation analysis. Reproducibility of metabolites and metabolite patterns, derived via principal component analysis (PCA), was assessed by intraclass correlation. A unique component of metabolites unrelated to POPs was dissected by integrating metabolites and POPs using 2-way orthogonal partial least squares regression. ORs of T2D were estimated using conditional logistic regression.
RESULTS:
We identified 31 metabolites associated with fish intake that had poor to good reproducibility. A PCA-derived metabolite pattern strongly correlated with fish intake (ρ = 0.37, P < 0.001) but showed no association with T2D risk. Integrating fish-related metabolites and POPs led to a unique metabolite component independent of POPs, which tended to be inversely associated with T2D risk (OR: 0.75; 95% CI: 0.54, 1.02, P = 0.07). This component mainly consisted of metabolites reflecting fatty fish intake.
CONCLUSIONS:
Our results suggest that fatty fish intake may be beneficial for T2D prevention, after removing the counteractive effects of coexposure to POPs in Swedish adults. Integrating metabolite markers and POP exposures appears a promising approach to advance the understanding of associations between fish intake and T2D incidence.
EYWORDS:
O2PLS modeling; fish biomarkers; metabolomics; nested case-control study; persistent organic pollutants; type 2 diabetes

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Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis.
Barbarawi M, Kheiri B, Zayed Y, Barbarawi O, Dhillon H, Swaid B, Yelangi A, Sundus S, Bachuwa G, Alkotob ML, Manson JE.
JAMA Cardiol. 2019 Jun 19. doi: 10.1001/jamacardio.2019.1870. [Epub ahead of print]
PMID: 31215980
https://sci-hub.tw/10.1001/jamacardio.2019.1870
Abstract
IMPORTANCE:
Observational studies have reported an association between low serum vitamin D levels and elevated risk of cardiovascular disease (CVD) events, but such studies cannot prove causation because of possible unmeasured confounding.
OBJECTIVE:
We conducted a meta-analysis of randomized clinical trials that tested the association of vitamin D supplementation with reduced CVD events and all-cause mortality.
DATA SOURCES:
Literature search through PubMed, the Cochrane Library, and Embase was completed by 2 reviewers from each database's inception to December 15, 2018.
STUDY SELECTION:
Inclusion criteria were randomized clinical trials that reported the effect of long-term (≥1 year) vitamin D supplementation on CVD events and all-cause mortality. Studies that did not include cardiovascular outcomes were excluded.
DATA EXTRACTION AND SYNTHESIS:
Data were abstracted independently by 2 authors. Random-effects models were used to report the risk ratios (RRs) and 95% CIs.
MAIN OUTCOMES AND MEASURES:
Major adverse cardiovascular events was the primary outcome, and rates of myocardial infarction, stroke or cerebrovascular accident, CVD mortality, and all-cause mortality were the secondary end points.
RESULTS:
Twenty-one randomized clinical trials were included (including 83 291 patients, of whom 41 669 received vitamin D and 41 622 received placebos). The mean (SD) age of trial participants was 65.8 (8.4) years; 61 943 (74.4%) were female. Only 4 trials had prespecified CVD as a primary end point. Vitamin D supplementation compared with placebo was not associated with reduced major adverse cardiovascular events (RR, 1.00 [95% CI, 0.95-1.06]; P = .85) nor the secondary end points of myocardial infarction (RR, 1.00 [95% CI, 0.93-1.08]; P = .92), stroke (RR, 1.06 [95% CI, 0.98-1.15]; P = .16), CVD mortality (RR, 0.98 [95% CI, 0.90-1.07]; P = .68), or all-cause mortality (RR, 0.97 [95% CI, 0.93-1.02]; P = .23). Results were generally consistent by sex, baseline 25-hydroxyvitamin D level, vitamin D dosage, formulation (daily vs bolus dosing), and presence or absence of concurrent calcium administration.
CONCLUSIONS AND RELEVANCE:
In this updated meta-analysis, vitamin D supplementation was not associated with reduced major adverse cardiovascular events, individual CVD end points (myocardial infarction, stroke, CVD mortality), or all-cause mortality. The findings suggest that vitamin D supplementation does not confer cardiovascular protection and is not indicated for this purpose.

Omega-3 fatty acids and cognitive decline: a systematic review.
Marti Del Moral A, Fortique F.
Nutr Hosp. 2019 Jun 19. doi: 10.20960/nh.02496. [Epub ahead of print]
PMID: 31215788
Abstract
In a growing elderly population, Mild Cognitive Impairment (MCI) and Age Related Cognitive Decline (ARCD) are increasing in prevalence worldwide. In the search for food compounds able to ameliorate this condition, it has been postulated that n-3 Long Chain Polyunsaturated Fatty Acids (n-3 LCPUFA), also known as omega-3, consumption could have a positive effect in the prevention or therapy of these cognitive declines. This current systematic review studies the relationship between n-3 LCPUFAs and cognitive status in aged adult and elder populations to determine whether there is or not a positive effect of n-3 LCPUFAs supplementation on cognitive decline. A search of Randomized Controlled Trials (RCTs) related with the relationship between cognitive impairment and n-3 LCPUFA (Docosahexaenoic Acid, Eicosapentanoic Acid or combined) supplementation was conducted through PubMed database from January, 2010 to December, 2017 following the PRISMA statement. Interventional studies which included aged adults or elder subjects with or without MCI and with no previous intake of Fish Oil Supplements (FOS) were included. Ten out of the fourteen RCTs reviewed showed positive outcome on at least one domain of cognitive function (working memory, executive function, verbal memory, short-term memory, perceptual speed, etc.). This Systematic Review concludes that omega-3 supplementation might have a positive effect on cognitive function. Thus, n-3 LCPUFAs could be used as a preventive or therapeutic tool for cognitive decline in aged or elder adults.

Duration and life-stage of antibiotic use and risk of cardiovascular events in women.
Heianza Y, Zheng Y, Ma W, Rimm EB, Albert CM, Hu FB, Rexrode KM, Manson JE, Qi L.
Eur Heart J. 2019 Apr 24. pii: ehz231. doi: 10.1093/eurheartj/ehz231. [Epub ahead of print]
PMID: 31216010
Abstract
AIMS:
Growing data suggest that antibiotic exposure is associated with a long-lasting alteration in gut microbiota, and may be related to subsequent cardiovascular disease (CVD). We investigated associations of life-stage and duration of antibiotic exposure during adulthood with subsequent CVD events.
METHODS AND RESULTS:
This study included 36 429 women initially free of CVD and cancer from the Nurses' Health Study. We estimated hazard ratios (HRs) for CVD (a composite endpoint of coronary heart disease or stroke) according to duration of antibiotic use in young (age 20-39), middle (age 40-59), and late (age 60 and older) adulthood. During an average of 7.6 years of follow-up, 1056 participants developed CVD. Women with long-term use of antibiotics (for ≥2 months) in late adulthood had a significantly increased risk of CVD (HR 1.32, 95% confidence interval 1.03-1.70) after adjustment for covariates (such as demographic factors, diet and lifestyle, reasons for antibiotic use, overweight or obesity, disease status, and other medication use), as compared to women who did not use antibiotics in this life-stage. Longer duration of antibiotic use in middle adulthood was also related to higher risk of CVD (P trend = 0.003) after controlling for these covariates. There was no significant relationship between the use in young adulthood and the risk of CVD.
CONCLUSION:
In this study which examined the antibiotic use in different life-stages, longer duration of exposure to antibiotics in the middle and older adulthood was related to an increased risk of future CVD events among elderly women at usual risk.
KEYWORDS:
Antibiotics; Cardiovascular disease; Risk factors

Tea Consumption and Health Outcomes: Umbrella Review of Meta-Analyses of Observational Studies in Humans.
Yi M, Wu X, Zhuang W, Xia L, Chen Y, Zhao R, Wan Q, Du L, Zhou Y.
Mol Nutr Food Res. 2019 Jun 19:e1900389. doi: 10.1002/mnfr.201900389. [Epub ahead of print] Review.
PMID: 31216091
https://sci-hub.tw/10.1002/mnfr.201900389
Abstract
SCOPE:
We sought to conduct an umbrella review to study the strength and validity of associations between tea consumption and diverse health outcomes.
METHODS AND RESULTS:
Meta-analyses of observational studies examining associations between tea consumption and health outcomes in all human populations and settings were screened. The umbrella review identified 96 meta-analyses with 40 unique health outcomes. Tea consumption showed more benefits than harms to health in this review. Dose-response analyses of tea consumption indicated reduced risks of total mortality, cardiac death, coronary artery disease, stroke and type 2 diabetes mellitus with increment of 2 to 3 cups per day. Beneficial associations were also found for several cancers, skeletal, cognitive, and maternal outcomes. Harmful associations were found for esophageal and gastric cancer when the temperature of intake was more than 55-60°C.
CONCLUSION:
Tea consumption, except for very hot tea, seems generally safe at usual levels of intake, with summary estimates indicating the largest reduction for diverse health outcomes at two to three cups per day. Generally, tea consumption seems more beneficial than harmful in this umbrella review. Randomized controlled trials are further needed to understand whether the observed associations are causal. This article is protected by copyright. All rights reserved.
KEYWORDS:
health; meta-analysis; tea consumption; umbrella review

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Diet-Related Metabolites Associated with Cognitive Decline Revealed by Untargeted Metabolomics in a Prospective Cohort.
Low DY, Lefèvre-Arbogast S, González-Domínguez R, Urpi-Sarda M, Micheau P, Petera M, Centeno D, Durand S, Pujos-Guillot E, Korosi A, Lucassen PJ, Aigner L, Proust-Lima C, Hejblum BP, Helmer C, Andres-Lacueva C, Thuret S, Samieri C, Manach C.
Mol Nutr Food Res. 2019 Jun 20:e1900177. doi: 10.1002/mnfr.201900177. [Epub ahead of print]
PMID: 31218777
https://sci-hub.tw/10.1002/mnfr.201900177
Abstract
SCOPE:
Untargeted metabolomics may reveal preventive targets in cognitive aging, including within the food metabolome.
METHODS AND RESULTS:
A case-control study nested in the prospective Three-City study included participants aged ≥65 years and initially free of dementia. We contrasted 209 cases of cognitive decline and 209 controls (matched for age, gender and educational level) with slower cognitive decline over up to 12 years. Using a bootstrap-enhanced LASSO regression on the baseline serum metabolomes analyzed with LC-QTOF, we identified a signature of 22 metabolites associated with subsequent cognitive decline. The signature included three coffee metabolites, a biomarker of citrus intake, a cocoa metabolite, two metabolites putatively derived from fish and wine, three medium-chain acylcarnitines, glycodeoxycholic acid, lysoPC(18:3), trimethyllysine, glucose, cortisol, creatinine and arginine. Adding the 22 metabolites to a reference predictive model for cognitive decline (conditioned on age, gender and education and including ApoE-ε4, diabetes, BMI and number of medications) substantially increased the predictive performance: cross-validated Area Under the Receiver Operating Curve = 75% [95% CI 70-80%] compared to 62% [95% CI 56-67%].
CONCLUSIONS:
Our untargeted metabolomics study supports a protective role of specific foods (e.g., coffee, cocoa, fish) and various alterations in the endogenous metabolism responsive to diet in cognitive aging.
KEYWORDS:
aging; coffee; cognitive decline; dietary biomarkers; untargeted metabolomics

Effect of Chronic Krill Oil Supplement on Seizures Induced by Pentylenetetrazole in the Hippocampus of Adult Rats with Previous Febrile Seizures.
Medina-Ceja L, Villalpando-Vargas F, Girón de la Cruz GI, Lara-Vazquez AM, Flores-Mancilla L, Salazar-Sánchez JC, Morales-Villagrán A.
J Food Sci. 2019 Jun 19. doi: 10.1111/1750-3841.14679. [Epub ahead of print]
PMID: 31218711
Abstract
We evaluated the effect of krill oil (KO) supplement on seizures induced by pentylenetetrazole (PTZ) in animals with previous febrile seizures (FSs) induced by hyperthermia to determine its effectiveness in seizure susceptibility and as an anticonvulsant. Male Wistar rats with FS separated into water (W, 1 mL), palm oil (PO, 300 mg/kg, total volume 1 mL), or KO (300 mg/kg, total volume 1 mL) groups. All drugs were administered chronically via the intragastric route. Electrical activity was recorded by intracranial EEG simultaneously with convulsive behavior. All animals' brains were processed by immunofluorescence against GFAP, NeuN, and connexins (Cx); cellular quantification was performed in hippocampus and pyramidal or granular layer thickness was evaluated with cresyl violet (CV) staining. The results showed a significant delay in convulsive behavior and a slight increased survival time after PTZ administration in the group treated with KO compared with PO and W groups. The epileptiform activity showed high amplitude and frequency, with no significant differences between groups, nor were there differences in the number and duration of discharge trains. KO and PO increased the number of astrocytes and the number of neurons compared with the W group. KO and PO decreased the expression of Cx36 without affecting Cx43 expression or the thickness of layers. Based on these data, we consider it important to perform more experiments to determine the anticonvulsant role of KO, taking into account the partial effect found in this study. KO could be used as a coadjuvant of traditional anticonvulsive treatments. PRACTICAL APPLICATION: In this study was evaluated the anticonvulsive effect of a chronic krill oil (KO) supplement in animals with seizures. Results showed that KO had partial anticonvulsive effects measured by EEG activity and convulsive behavior analysis. These data justify further research that looks at KO supplementation as a prospective coadjuvant of pharmacologic management of seizure disorder.
KEYWORDS:
GFAP; connexins; hippocampus; krill oil supplement; pentylenetetrazole; seizures

Influence of Diets with Varying Essential/Nonessential Amino Acid Ratios on Mouse Lifespan.
Romano C, Corsetti G, Flati V, Pasini E, Picca A, Calvani R, Marzetti E, Dioguardi FS.
Nutrients. 2019 Jun 18;11(6). pii: E1367. doi: 10.3390/nu11061367.
PMID: 31216646
https://www.mdpi.com/2072-6643/11/6/1367/htm
Abstract
An adequate intake of essential (EAA) and non-essential amino acids (NEAA) is crucial to preserve cell integrity and whole-body metabolism. EAA introduced with diet may be insufficient to meet the organismal needs, especially under increased physiological requirements or in pathological conditions, and may condition lifespan. We therefore examined the effects of iso-caloric and providing the same nitrogenous content diets, any diet containing different stoichiometric blends of EAA/NEAA, on mouse lifespan. Three groups of just-weaned male Balb/C mice were fed exclusively with special diets with varying EAA/NEAA ratios, ranging from 100%/0% to 0%/100%. Three additional groups of mice were fed with different diets, two based on casein as alimentary proteins, one providing the said protein, one reproducing the amino acidic composition of casein, and the third one, the control group, was fed by a standard laboratory diet. Mouse lifespan was inversely correlated with the percentage of NEAA introduced with each diet. Either limiting EAA, or exceeding NEAA, induced rapid and permanent structural modifications on muscle and adipose tissue, independently of caloric intake. These changes significantly affected food and water intake, body weight, and lifespan. Dietary intake of varying EAA/NEAA ratios induced changes in several organs and profoundly influenced murine lifespan. The balanced content of EAA provided by dietary proteins should be considered as the preferable means for "optimal" nutrition and the elevated or unbalanced intake of NEAA provided by food proteins may negatively affect the health and lifespan of mice.
KEYWORDS:
amino acids intake; diet; essential amino acids; extended lifespan; mice

Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss.
Hyde PN, Sapper TN, Crabtree CD, LaFountain RA, Bowling ML, Buga A, Fell B, McSwiney FT, Dickerson RM, Miller VJ, Scandling D, Simonetti OP, Phinney SD, Kraemer WJ, King SA, Krauss RM, Volek JS.
JCI Insight. 2019 Jun 20;4(12). pii: 128308. doi: 10.1172/jci.insight.128308. eCollection 2019 Jun 20.
PMID: 31217353
Abstract
BACKGROUNDMetabolic syndrome (MetS) is highly correlated with obesity and cardiovascular risk, but the importance of dietary carbohydrate independent of weight loss in MetS treatment remains controversial. Here, we test the theory that dietary carbohydrate intolerance (i.e., the inability to process carbohydrate in a healthy manner) rather than obesity per se is a fundamental feature of MetS.METHODSIndividuals who were obese with a diagnosis of MetS were fed three 4-week weight-maintenance diets that were low, moderate, and high in carbohydrate. Protein was constant and fat was exchanged isocalorically for carbohydrate across all diets.RESULTSDespite maintaining body mass, low-carbohydrate (LC) intake enhanced fat oxidation and was more effective in reversing MetS, especially high triglycerides, low HDL-C, and the small LDL subclass phenotype. Carbohydrate restriction also improved abnormal fatty acid composition, an emerging MetS feature. Despite containing 2.5 times more saturated fat than the high-carbohydrate diet, an LC diet decreased plasma total saturated fat and palmitoleate and increased arachidonate.CONCLUSIONConsistent with the perspective that MetS is a pathologic state that manifests as dietary carbohydrate intolerance, these results show that compared with eucaloric high-carbohydrate intake, LC/high-fat diets benefit MetS independent of whole-body or fat mass.
>>>>>>>>>>>>>>>>
FUNDINGDairy Management Inc. and the Dutch Dairy Association.
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KEYWORDS:
Lipoproteins; Metabolism; Obesity

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Can Healthy Diets, Regular Exercise, and Better Lifestyle Delay the Progression of Dementia in Elderly Individuals?
George EK, Reddy PH.
J Alzheimers Dis. 2019 Jun 17. doi: 10.3233/JAD-190232. [Epub ahead of print]
PMID: 31227652
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss and multiple cognitive impairments. Current healthcare costs for over 50 million people afflicted with AD are about $818 million and are projected to be $2 billion by 2050. Unfortunately, there are no drugs currently available that can delay and/or prevent the progression of disease in elderly individuals and in AD patients. Loss of synapses and synaptic damage are largely correlated with cognitive decline in AD patients. Women are at a higher lifetime risk of developing AD encompassing two-thirds of the total AD afflicted population. Only about 1-2% of total AD patients can be explained by genetic mutations in APP, PS1, and PS2 genes. Several risk factors have been identified, such as Apolipoprotein E4 genotype, type 2 diabetes, traumatic brain injury, depression, and hormonal imbalance, are reported to be associated with late-onset AD. Strong evidence reveals that antioxidant enriched diets and regular exercise reduces toxic radicals, enhances mitochondrial function and synaptic activity, and improves cognitive function in elderly populations. Current available data on the use of antioxidants in mouse models of AD and antioxidant(s) supplements in diets of elderly individuals were investigated. The use of antioxidants in randomized clinical trials in AD patients was also critically assessed. Based on our survey of current literature and findings, we cautiously conclude that healthy diets, regular exercise, and improved lifestyle can delay dementia progression and reduce the risk of AD in elderly individuals and reverse subjects with mild cognitive impairment to a non-demented state.
KEYWORDS:
Alzheimer’s disease; amyloid-beta; antioxidant enriched diet; healthcare cost; healthy diets; mitochondria; phosphorylated tau; reactive oxygen species; regular exercise

Meat consumption in midlife and risk of cognitive impairment in old age: the Singapore Chinese Health Study.
Jiang YW, Sheng LT, Pan XF, Feng L, Yuan JM, Pan A, Koh WP.
Eur J Nutr. 2019 Jun 21. doi: 10.1007/s00394-019-02031-3. [Epub ahead of print]
PMID: 31227861
Abstract
PURPOSE:
Epidemiological studies directly investigating the association between different types of meat intake and cognitive impairment are limited. We, therefore, examined this association in the Singapore Chinese Health Study.
METHODS:
In total, 16,948 participants were included in analysis. Diet was measured by a 165-item semiquantitative food-frequency questionnaire at baseline (1993-1998) when participants were 45-74 years. Cognitive impairment was defined using a Singapore modified version of Mini-Mental State Examination during follow-up three visits (2014-2016) when participants were 61-96 years. Multivariable logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI).
RESULTS:
Cognitive impairment was present in 2443 (14.4%) participants. Compared to the lowest quartile, the highest quartile of red meat intake was associated with increased risk of cognitive impairment (OR 1.16, 95% CI 1.01-1.32, P for trend = 0.009), while the corresponding value for poultry intake was 0.89 (95% CI 0.78-1.02, P for trend = 0.10). Higher fresh fish/shellfish was associated with a lower risk of cognitive impairment (OR 0.88, 95% CI 0.77-1.00, P for trend = 0.03), while preserved fish/shellfish intake was associated with a higher risk (OR 1.19, 95% CI 1.04-1.36, P for trend = 0.01).
CONCLUSION:
This study found that a higher intake of red meat in midlife was associated with increased likelihood of cognitive impairment in later life, while substitution of red meat intake with poultry or fresh fish/shellfish was associated with reduced risk.
KEYWORDS:
Cognitive impairment; Cohort study; Fish/shellfish; Poultry; Red meat

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Relationship Between Serum Alpha-Tocopherol and Overall and Cause-Specific Mortality.
Huang J, Weinstein SJ, Yu K, Männistö S, Albanes D.
Circ Res. 2019 Jun 21;125(1):29-40. doi: 10.1161/CIRCRESAHA.119.314944. Epub 2019 May 6.
PMID: 31219752
Abstract
RATIONALE:
Although there has been a long-standing interest in the human health effects of vitamin E, a comprehensive analysis of the association between circulating vitamin E and long-term mortality has not been conducted.
OBJECTIVE:
Determine whether serum α-tocopherol (the predominant form of vitamin E) is related to long-term overall and cause-specific mortality and elucidate the dose-response relationships with better quantification of the associations.
METHODS AND RESULTS:
We conducted a biochemical analysis of 29 092 participants in the ATBC Study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention) that originally tested vitamin E and β-carotene supplementation. Serum α-tocopherol was measured at baseline using high-performance liquid chromatography, and during a 30-year follow-up we identified 23 787 deaths, including deaths from cardiovascular disease (9867), cancer (7687), respiratory disease (2161), diabetes mellitus (119), injuries and accidents (1255), and other causes (2698). After adjusting for major risk factors, we found that men with higher serum α-tocopherol had significantly lower all-cause mortality (hazard ratios=0.83, 0.79, 0.75, and 0.78 for quintile 2 (Q2)-Q5 versus Q1, respectively; Ptrend<0.0001), and significantly decreased mortality from cardiovascular disease, heart disease, stroke, cancer, respiratory disease, and other causes, with risk reductions from 17% to 47% for the highest versus lowest quintile. The α-tocopherol association with overall mortality was similar across subgroups of smoking intensity, years of smoking, alcohol consumption, trial supplementation, and duration of follow-up. The association was, however, significantly modified by baseline age and body mass index, with stronger inverse associations for younger men and men with a lower body mass index ( Pinteraction≤0.006).
CONCLUSIONS:
In this long-term prospective cohort study, higher baseline serum α-tocopherol biochemical status was associated with lower risk of overall mortality and mortality from all major causes. Our data support the long-term health benefits of higher serum α-tocopherol for overall and chronic disease mortality and should be replicated in other more diverse populations.
KEYWORDS:
epidemiology; mortality; multivariate analysis; risk factors; vitamin E

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A single dose of dietary nitrate increases maximal knee extensor angular velocity and power in healthy older men and women.
Coggan AR, Hoffman RL, Gray DA, Moorthi RN, Thomas DP, Leibowitz JL, Thies D, Peterson LR.
J Gerontol A Biol Sci Med Sci. 2019 Jun 20. pii: glz156. doi: 10.1093/gerona/glz156. [Epub ahead of print]
PMID: 31231758
Abstract
BACKGROUND:
Aging results in reductions in maximal muscular strength, speed, and power, which often lead to functional limitations highly predictive of disability, institutionalization, and mortality in the elderly. This may be partially due to reduced nitric oxide (NO) bioavailability. We therefore hypothesized that dietary nitrate (NO3-), a source of NO via the NO3- → nitrite (NO2 ) → NO enterosalivary pathway, could increase muscle contractile function in older subjects.
METHODS:
Twelve healthy older (age 71±5 y) men and women were studied using a randomized, double-blind, placebo-controlled, crossover design. After fasting overnight, subjects were tested 2 h after ingesting beetroot juice containing or devoid of 13.4±1.6 mmol NO3-. Plasma NO3- and NO2 and breath NO were measured periodically, and muscle function was determined using isokinetic dynamometry.
RESULTS:
NO3- ingestion increased (P<0.001) plasma NO3-, plasma NO2 , and breath NO by 1051±433%, 138±149%, and 111±115%, respectively. Maximal velocity of knee extension increased (P<0.01) by 10.9±12.1%. Maximal knee extensor power increased (P<0.05) by 4.4±7.8%.
CONCLUSIONS:
Acute dietary NO3- intake improves maximal knee extensor angular velocity and power in older individuals. These findings may have important implications for this population, in whom diminished muscle function can lead to functional limitations, dependence, and even premature death.
KEYWORDS:
Nitric oxide; blood pressure; isokinetic dynamometry; nitrite

The effect of melatonin supplementation on lipid profile and anthropometric indices: A systematic review and meta-analysis of clinical trials.
Loloei S, Sepidarkish M, Heydarian A, Tahvilian N, Khazdouz M, Heshmati J, Pouraram H.
Diabetes Metab Syndr. 2019 May - Jun;13(3):1901-1910. doi: 10.1016/j.dsx.2019.04.043. Epub 2019 Apr 23. Review.
PMID: 31235113
Abstract
BACKGROUND:
Epidemiological evidence suggests that melatonin has some effects on the serum lipid. However, these results are controversial. The aim of this systematic review and meta-analysis is to examine the effect of melatonin supplement on dyslipidemia and anthropometric indices.
METHODS:
We searched electronic databases including Medline, Embase, Scopus, Web of Science and Cochrane Library up to Des 2018 without any language restriction. To compare the effects of melatonin with placebo, differences in standardized means difference (SMD) with 95% confidence intervals (95% CI) were pooled using random effects model.
RESULTS:
Twelve trials including 641 participants included in meta-analysis finally. The dose of melatonin was reported at 0.8-30 mg. Comparing with the control group, melatonin may improve low density lipoprotein cholesterol (LDL-C) (-0.31 mmol/L, 95% CI (-0.61, 0.01), P = 0.049, I2 = 42%) and triglyceride (TG) level (SMD = -0.45 mmol/L; 95% CI, -0.77, -0.13, P = 0.006, I2 = 47%). No significant effect of melatonin on high density lipoprotein cholesterol (HDL-C) and anthropometric indices was found.
CONCLUSIONS:
The results of our systematic review and Meta-analyzes showed that supplementation of melatonin could be effective in improving lipid parameters and should be considered in the prevention of cardiovascular disease, although the effect of this supplement on anthropometric indices needs further investigation.
KEYWORDS:
Body mass index; Body weight; Cholesterol; HDL; LDL; Melatonin

Differential effects of diet composition and timing of feeding behavior on rat brown adipose tissue and skeletal muscle peripheral clocks.
de Goede P, Sen S, Oosterman JE, Foppen E, Jansen R, la Fleur SE, Challet E, Kalsbeek A.
Neurobiol Sleep Circadian Rhythms. 2017 Sep 18;4:24-33. doi: 10.1016/j.nbscr.2017.09.002. eCollection 2018 Jan.
PMID: 31236504
Abstract
The effects of feeding behavior and diet composition, as well as their possible interactions, on daily (clock) gene expression rhythms have mainly been studied in the liver, and to a lesser degree in white adipose tissue (WAT), but hardly in other metabolic tissues such as skeletal muscle (SM) and brown adipose tissues (BAT). We therefore subjected male Wistar rats to a regular chow or free choice high-fat-high sugar (fcHFHS) diet in combination with time restricted feeding (TRF) to either the light or dark phase. In SM, all tested clock genes lost their rhythmic expression in the chow light fed group. In the fcHFHS light fed group rhythmic expression for some, but not all, clock genes was maintained, but shifted by several hours. In BAT the daily rhythmicity of clock genes was maintained for the light fed groups, but expression patterns were shifted as compared with ad libitum and dark fed groups, whilst the fcHFHS diet made the rhythmicity of clock genes become more pronounced. Most of the metabolic genes in BAT tissue tested did not show any rhythmic expression in either the chow or fcHFHS groups. In SM Pdk4 and Ucp3 were phase-shifted, but remained rhythmically expressed in the chow light fed groups. Rhythmic expression was lost for Ucp3 whilst on the fcHFHS diet during the light phase. In summary, both feeding at the wrong time of day and diet composition disturb the peripheral clocks in SM and BAT, but to different degrees and thereby result in a further desynchronization between metabolically active tissues such as SM, BAT, WAT and liver.
KEYWORDS:
Brown adipose tissue (BAT); Soleus muscle (SM); Time-restricted feeding (TRF); desynchronization; free choice High-fat High-sugar (fcHFHS)

Physical activity trajectories and mortality: population based cohort study.
Mok A, Khaw KT, Luben R, Wareham N, Brage S.
BMJ. 2019 Jun 26;365:l2323. doi: 10.1136/bmj.l2323.
PMID: 31243014
https://www.bmj.com/content/bmj/365/bmj.l2323.full.pdf
Abstract
OBJECTIVE:
To assess the prospective associations of baseline and long term trajectories of physical activity on mortality from all causes, cardiovascular disease, and cancer.
DESIGN:
Population based cohort study.
SETTING:
Adults from the general population in the UK.
PARTICIPANTS:
14 599 men and women (aged 40 to 79) from the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort, assessed at baseline (1993 to 1997) up to 2004 for lifestyle and other risk factors; then followed to 2016 for mortality (median of 12.5 years of follow-up, after the last exposure assessment).
MAIN EXPOSURE:
Physical activity energy expenditure (PAEE) derived from questionnaires, calibrated against combined movement and heart rate monitoring.
MAIN OUTCOME MEASURES:
Mortality from all causes, cardiovascular disease, and cancer. Multivariable proportional hazards regression models were adjusted for age, sex, sociodemographics, and changes in medical history, overall diet quality, body mass index, blood pressure, triglycerides, and cholesterol levels.
RESULTS:
During 171 277 person years of follow-up, 3148 deaths occurred. Long term increases in PAEE were inversely associated with mortality, independent of baseline PAEE. For each 1 kJ/kg/day per year increase in PAEE (equivalent to a trajectory of being inactive at baseline and gradually, over five years, meeting the World Health Organization minimum physical activity guidelines of 150 minutes/week of moderate-intensity physical activity), hazard ratios were: 0.76 (95% confidence interval 0.71 to 0.82) for all cause mortality, 0.71 (0.62 to 0.82) for cardiovascular disease mortality, and 0.89 (0.79 to 0.99) for cancer mortality, adjusted for baseline PAEE, and established risk factors. Similar results were observed when analyses were stratified by medical history of cardiovascular disease and cancer. Joint analyses with baseline and trajectories of physical activity show that, compared with consistently inactive individuals, those with increasing physical activity trajectories over time experienced lower risks of mortality from all causes, with hazard ratios of 0.76 (0.65 to 0.88), 0.62 (0.53 to 0.72), and 0.58 (0.43 to 0.78) at low, medium, and high baseline physical activity, respectively. At the population level, meeting and maintaining at least the minimum physical activity recommendations would potentially prevent 46% of deaths associated with physical inactivity.
CONCLUSIONS:
Middle aged and older adults, including those with cardiovascular disease and cancer, can gain substantial longevity benefits by becoming more physically active, irrespective of past physical activity levels and established risk factors. Considerable population health impacts can be attained with consistent engagement in physical activity during mid to late life.

Dietary Protein Quantity, Quality, and Exercise Are Key to Healthy Living: A Muscle-Centric Perspective Across the Lifespan.
Burd NA, McKenna CF, Salvador AF, Paulussen KJM, Moore DR.
Front Nutr. 2019 Jun 6;6:83. doi: 10.3389/fnut.2019.00083. eCollection 2019. Review.
PMID: 31245378
https://www.bmj.com/content/bmj/365/bmj.l2323.full.pdf
Abstract
A healthy eating pattern, regardless of age, should consist of ingesting high quality protein preferably in adequate amounts across all meals throughout the day. Of particular relevance to overall health is the growth, development, and maintenance of skeletal muscle tissue. Skeletal muscle not only contributes to physical strength and performance, but also contributes to efficient macronutrient utilization and storage. Achieving an optimal amount of muscle mass begins early in life with transitions to "steady-state" maintenance as an adult, and then safeguarding against ultimate decline of muscle mass with age, all of which are influenced by physical activity and dietary (e.g., protein) factors. Current protein recommendations, as defined by recommended dietary allowances (RDA) for the US population or the population reference intakes (PRI) in Europe, are set to cover basic needs; however, it is thought that a higher protein intake might be necessary for optimizing muscle mass, especially for adults and individuals with an active lifestyle. It is necessary to balance the accurate assessment of protein quality (e.g., digestible indispensable amino acid score; DIAAS) with methods that provide a physiological correlate (e.g., established measures of protein synthesis, substrate oxidation, lean mass retention, or accrual, etc.) in order to accurately define protein requirements for these physiological outcomes. Moreover, current recommendations need to shift from single nutrient guidelines to whole food based guidelines in order to practically acknowledge food matrix interactions and other required nutrients for potentially optimizing the health effects of food. The aim of this paper is to discuss protein quality and amount that should be consumed with consideration to the presence of non-protein constituents within a food matrix and potential interactions with physical activity to maximize muscle mass throughout life.
KEYWORDS:
adolescents; aging-old age-seniors; anabolic; children; leucine; muscle protein synthesis/breakdown; skeletal muscle mass

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Association between grains, gluten and the risk of colorectal cancer in the Cancer Prevention Study-II Nutrition Cohort.
Um CY, Campbell PT, Carter B, Wang Y, Gapstur SM, McCullough ML.
Eur J Nutr. 2019 Jun 25. doi: 10.1007/s00394-019-02032-2. [Epub ahead of print]
PMID: 31240448
Abstract
PURPOSE:
Evidence supports a role of whole grains in colorectal cancer (CRC) prevention, but the association between gluten intake and CRC risk in healthy populations is unclear. We examined the association of grain and gluten intake with risk of CRC overall and by subsite among Cancer Prevention Study-II Nutrition Cohort participants.
METHODS:
In 1999, 50,118 men and 62,031 women completed food frequency questionnaires assessing grain intake. Gluten intake was estimated using the protein content of grain products. Multivariable-adjusted hazards ratio (HR) and 95% confidence interval (CI) of CRC risk were estimated using Cox proportional hazards regression.
RESULTS:
During follow-up through 2013, 1742 verified CRC cases occurred. For the highest vs. lowest quintiles of whole grain intake, HRs (95% CIs) of CRC risk were 0.77 (0.61-0.97; P trend = 0.03) among men and 1.10 (95% CI 0.88-1.36; P trend = 0.14) among women (P interaction by sex = 0.01). Men in the highest vs. lowest quintile of whole grain intake had a 43% lower risk of rectal cancer (HR = 0.57, 95% CI 0.35-0.93, P trend = 0.04). Gluten intake was not associated with CRC risk overall (HR = 1.10, 95% CI 0.93-1.32, P trend = 0.10), but was associated with risk of proximal colon cancer among men and women, combined (HR = 1.37, 95% CI 1.07-1.75, quintile 5 vs. 1, P trend = 0.001) and separately. Refined grains and grain-based sweets were not associated with CRC risk.
CONCLUSIONS:
We found that higher whole grain intake was associated with lower CRC risk among older US men, but not women. The positive association of gluten intake with the risk of proximal colon cancer deserves further study.
KEYWORDS:
Cohort study; Colorectal cancer; Gluten; Refined grains; Whole grains

Are dietary amino acids prospectively predicts changes in serum lipid profile?
Teymoori F, Asghari G, Salehi P, Sadeghian S, Mirmiran P, Azizi F.
Diabetes Metab Syndr. 2019 May - Jun;13(3):1837-1843. doi: 10.1016/j.dsx.2019.04.013. Epub 2019 Apr 17.
PMID: 31235103
Abstract
BACKGROUND:
Besides of dietary fat and carbohydrate, amino acids(AAs), as constituent components of dietary protein have been related with serum lipid levels. This study aims to examine the association between dietary AAs and prospective changes in serum lipid profile in adults.
METHODS:
Analyses were conducted on 3881 participants aged, 18-75 years of Tehran lipid and Glucose study, at baseline (2008-2011) and were followed for 3 years (2011-2014) to ascertain serum lipid profile changes. Dietary intakes of AAs were collected at baseline using food frequency questionnaire. Multiple linear regression adjusted for age, sex, body mass index, physical activity, smoking and daily intakes of energy, total fat, and fiber were used.
RESULTS:
The median(IQR) changes in triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were 6.0(-19.0, -35.5), 9.0(7.0, -24.0), 1.0(-3.0, -6.0), and 5.2(-8.0, -18.6) mg/dl, respectively. Higher intakes of isoleucine, lysine, tyrosine, alanine, threonine, methionine, valine, histidine, aspartic acid, and branched chain, alkaline, and alcoholic AAs were positively associated with TGs-changes in the final adjusted model, whereas tryptophan, glutamic acid, and acidic AAs were negatively related to TG-changes. Alanine and tryptophan were associated with higher and lower LDL-C-changes, respectively. Lysine, alanine, methionine, aspartic acid, and alkaline AAs showed positive association with changes in TC, whereas tryptophan and glutamic acid had a negative association with TC-changes.
CONCLUSION:
Our findings showed that some dietary amino acids have the potential to increase or decrease serum lipid profile.
KEYWORDS:
Amino acid; High density lipoprotein cholesterol; Low density lipoprotein cholesterol; Total cholesterol; Triglyceride

Mixed Spices at Culinary Doses Have Prebiotic Effects in Healthy Adults: A Pilot Study.
Lu QY, Rasmussen AM, Yang J, Lee RP, Huang J, Shao P, Carpenter CL, Gilbuena I, Thames G, Henning SM, Heber D, Li Z.
Nutrients. 2019 Jun 25;11(6). pii: E1425. doi: 10.3390/nu11061425.
PMID: 31242596
[pdf availed from Medline site.]
Abstract
Spices were used as food preservatives prior to the advent of refrigeration, suggesting the possibility of effects on microbiota. Previous studies have shown prebiotic activities in animals and in vitro, but there has not been a demonstration of prebiotic or postbiotic effects at culinary doses in humans. In this randomized placebo-controlled study, we determined in twenty-nine healthy adults the effects on the gut microbiota of the consumption daily of capsules containing 5 g of mixed spices at culinary doses by comparison to a matched control group consuming a maltodextrin placebo capsule. The 16S ribosomal RNA sequencing data were used for microbial characterization. Spice consumption resulted in a significant reduction in Firmicutes abundance (p < 0.033) and a trend of enrichment in Bacteroidetes (p < 0.097) compared to placebo group. Twenty-six operational taxonomic units (OTUs) were different between the spice and placebo groups after intervention. Furthermore, there was a significant negative correlation between fecal short-chain fatty acid propionate concentration and Firmicutes abundance in spice intervention group (p < 0.04). The production of individual fecal short-chain fatty acid was not significantly changed by spice consumption in this study. Mixed spices consumption significantly modified gut microbiota, suggesting a prebiotic effect of spice consumption at culinary doses.
KEYWORDS:
dietary intervention; firmicutes; gut microbiota; prebiotic effect; short-chain fatty acids; spices

Cumulative Meta-Analysis of the Soy Effect Over Time.
Jenkins DJA, Blanco Mejia S, Chiavaroli L, Viguiliouk E, Li SS, Kendall CWC, Vuksan V, Sievenpiper JL.
J Am Heart Assoc. 2019 Jul 2;8(13):e012458. doi: 10.1161/JAHA.119.012458. Epub 2019 Jun 27.
PMID: 31242779
Abstract
Background Soy protein foods have attracted attention as useful plant protein foods with mild cholesterol-lowering effects that are suitable for inclusion in therapeutic diets. But on the basis of the lack of consistency in significant cholesterol reduction by soy in 46 randomized controlled trials, the US Food and Drug Administration (FDA) is reassessing whether the 1999 heart health claim for soy protein should be revoked. Methods and Results We have, therefore, performed a cumulative meta-analysis on the 46 soy trials identified by the FDA to determine if at any time, since the 1999 FDA final rule that established the soy heart health claim, the soy effect on serum cholesterol lost significance. The cumulative meta-analysis for both total cholesterol and low-density lipoprotein cholesterol demonstrated preservation of the small, but significant, reductions seen both before and during the subsequent 14 years since the health claim was originally approved. For low-density lipoprotein cholesterol, the mean reduction in 1999 was -6.3 mg/dL (95% CI, -8.7 to -3.9 mg/dL; P=0.00001) and remained in the range of -4.2 to -6.7 mg/dL ( P=0.0006 to P=0.0002, respectively) in the years after 1999. At no time point did the total cholesterol or low-density lipoprotein cholesterol reductions lose significance or were the differences at individual time points in the cumulative meta-analysis significantly different from those seen in 1999 when the health claim was approved. Conclusions A cumulative meta-analysis of the data selected by the FDA indicates continued significance of total cholesterol and low-density lipoprotein cholesterol reduction after soy consumption and supports the rationale behind the original soy FDA heart health claim.
KEYWORDS:
US Food and Drug Administration heart health claim; cholesterol reduction; soy protein

Almond Consumption and Risk Factors for Cardiovascular Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Lee-Bravatti MA, Wang J, Avendano EE, King L, Johnson EJ, Raman G.
Adv Nutr. 2019 Jun 27. pii: nmz043. doi: 10.1093/advances/nmz043. [Epub ahead of print]
PMID: 31243439
Abstract
Evidence suggests that eating nuts may reduce the risk of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating almond consumption and risk factors for CVD. MEDLINE, Cochrane Central, Commonwealth Agricultural Bureau, and previous systematic reviews were searched from 1990 through June 2017 for RCTs of ≥3 wk duration that evaluated almond compared with no almond consumption in adults who were either healthy or at risk for CVD. The most appropriate stratum was selected with an almond dose closer to 42.5 g, with a control most closely matched for macronutrient composition, energy intake, and similar intervention duration. The outcomes included risk factors for CVD. Random-effects model meta-analyses and subgroup meta-analyses were performed. Fifteen eligible trials analyzed a total of 534 subjects. Almond intervention significantly decreased total cholesterol (summary net change: -10.69 mg/dL; 95% CI: -16.75, -4.63 mg/dL), LDL cholesterol (summary net change: -5.83 mg/dL; 95% CI: -9.91, -1.75 mg/dL); body weight (summary net change: -1.39 kg; 95% CI: -2.49, -0.30 kg), HDL cholesterol (summary net change: -1.26 mg/dL; 95% CI: -2.47, -0.05 mg/dL), and apolipoprotein B (apoB) (summary net change: -6.67 mg/dL; 95% CI: -12.63, -0.72 mg/dL). Triglycerides, systolic blood pressure, apolipoprotein A1, high-sensitivity C-reactive protein, and lipoprotein (a) showed no difference between almond and control in the main and subgroup analyses. Fasting blood glucose, diastolic blood pressure, and body mass index significantly decreased with almond consumption of >42.5 g compared with ≤42.5 g. Almond consumption may reduce the risk of CVD by improving blood lipids and by decreasing body weight and apoB. Substantial heterogeneity in eligible studies regarding almond interventions and dosages precludes firmer conclusions.
KEYWORDS:
blood lipids; hypercholesterolemia; hyperglycemia; hypertension; meta-analysis; metabolic syndrome; obesity; risk factors; systematic review

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Branched-chain amino acid and branched-chain ketoacid ingestion increases muscle protein synthesis rates in vivo in older adults: a double-blind, randomized trial.
Fuchs CJ, Hermans WJH, Holwerda AM, Smeets JSJ, Senden JM, van Kranenburg J, Gijsen AP, Wodzig WKHW, Schierbeek H, Verdijk LB, van Loon LJC.
Am J Clin Nutr. 2019 Jun 28. pii: nqz120. doi: 10.1093/ajcn/nqz120. [Epub ahead of print]
PMID: 31250889
Abstract
BACKGROUND:
Protein ingestion increases muscle protein synthesis rates. However, limited data are currently available on the effects of branched-chain amino acid (BCAA) and branched-chain ketoacid (BCKA) ingestion on postprandial muscle protein synthesis rates.
OBJECTIVE:
To compare the impact of ingesting 6 g BCAA, 6 g BCKA, and 30 g milk protein (MILK) on the postprandial rise in circulating amino acid concentrations and subsequent myofibrillar protein synthesis rates in older males.
METHODS:
In a parallel design, 45 older males (age: 71 ± 1 y; BMI: 25.4 ± 0.8 kg/m2) were randomly assigned to ingest a drink containing 6 g BCAA, 6 g BCKA, or 30 g MILK. Basal and postprandial myofibrillar protein synthesis rates were assessed by primed continuous l-[ring-13C6]phenylalanine infusions with the collection of blood samples and muscle biopsies.
RESULTS:
Plasma BCAA concentrations increased following test drink ingestion in all groups, with greater increases in the BCAA and MILK groups compared with the BCKA group (P < 0.05). Plasma BCKA concentrations increased following test drink ingestion in all groups, with greater increases in the BCKA group compared with the BCAA and MILK groups (P < 0.05). Ingestion of MILK, BCAA, and BCKA significantly increased early myofibrillar protein synthesis rates (0-2 h) above basal rates (from 0.020 ± 0.002%/h to 0.042 ± 0.004%/h, 0.022 ± 0.002%/h to 0.044 ± 0.004%/h, and 0.023 ± 0.003%/h to 0.044 ± 0.004%/h, respectively; P < 0.001), with no differences between groups (P > 0.05). Myofibrillar protein synthesis rates during the late postprandial phase (2-5 h) remained elevated in the MILK group (0.039 ± 0.004%/h; P < 0.001), but returned to baseline values following BCAA and BCKA ingestion (0.024 ± 0.005%/h and 0.024 ± 0.005%/h, respectively; P > 0.05).
CONCLUSIONS:
Ingestion of 6 g BCAA, 6 g BCKA, and 30 g MILK increases myofibrillar protein synthesis rates during the early postprandial phase (0-2 h) in vivo in healthy older males. The postprandial increase following the ingestion of 6 g BCAA and BCKA is short-lived, with higher myofibrillar protein synthesis rates only being maintained following the ingestion of an equivalent amount of intact milk protein.
KEYWORDS:
aging; anabolism; chronic kidney disease; dietary protein; leucine; milk; sarcopenia; α-ketoisocaproic acid

Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort.
Aglago EK, Huybrechts I, Murphy N, Casagrande C, Nicolas G, Pischon T, Fedirko V, Severi G, Boutron-Ruault MC, Fournier A, Katzke V, Kühn T, Olsen A, Tjønneland A, Dahm CC, Overvad K, Lasheras C, Agudo A, Sánchez MJ, Amiano P, Huerta JM, Ardanaz E, Perez-Cornago A, Trichopoulou A, Karakatsani A, Martimianaki G, Palli D, Pala V, Tumino R, Naccarati A, Panico S, Bueno-de-Mesquita B, May A, Derksen JWG, Hellstrand S, Ohlsson B, Wennberg M, Van Guelpen B, Skeie G, Brustad M, Weiderpass E, Cross AJ, Ward H, Riboli E, Norat T, Chajes V, Gunter MJ.
Clin Gastroenterol Hepatol. 2019 Jun 25. pii: S1542-3565(19)30669-X. doi: 10.1016/j.cgh.2019.06.031. [Epub ahead of print]
PMID: 31252190
Abstract
BACKGROUND & AIMS:
There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
METHODS:
Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs.
RESULTS:
Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend=.005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend=.009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend=.016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend=.010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend<.001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity=.026).
CONCLUSIONS:
In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
KEYWORDS:
epidemiologic; omega 3; seafood; tumorigenesis

Associations of diet soda and non-caloric artificial sweetener use with markers of glucose and insulin homeostasis and incident diabetes: the Strong Heart Family Study.
Jensen PN, Howard BV, Best LG, O'Leary M, Devereux RB, Cole SA, MacCluer JW, Ali T, Lee ET, Yeh FL, Yeh J, Umans JG, Fretts AM.
Eur J Clin Nutr. 2019 Jun 28. doi: 10.1038/s41430-019-0461-6. [Epub ahead of print]
PMID: 31253876
Abstract
BACKGROUND/OBJECTIVES:
Non-caloric artificial sweeteners (NAS) are marketed as healthier alternatives to sugar, but the relationship between consumption of NAS and development of diabetes is unclear. This study assessed the associations of diet soda and NAS consumption with (1) early markers of insulin and glucose homeostasis (cross-sectionally) and (2) incident diabetes (over an average of 8 years of follow-up) among American Indians, a population with high rates of obesity.
SUBJECTS/METHODS:
The study population included Strong Heart Family Study participants without cardiovascular disease or diabetes who participated in the 2007-2009 study exam (n = 1359). Diet soda and NAS consumption were assessed using a Block food frequency questionnaire and supplemental NAS questionnaire at the study exam. Fasting plasma glucose and insulin were measured during the study exam after a 12-h overnight fast. Participants were followed for incident diabetes through December 2017 using a single phone interview and medical record review; diabetes was identified by self-report and confirmed by documentation in medical records. Associations of diet soda and NAS consumption with fasting insulin, glucose, and incident diabetes were assessed using generalized estimating equations (fasting insulin and glucose analyses) and parametric survival models with Weibull distributions (incident diabetes analyses).
RESULTS:
Just under half of participants reported regularly consuming diet soda (40%) or using NAS to sweeten their beverages (41%). During an average 8 years of follow-up, we identified 98 cases of incident diabetes. After correction for multiple comparisons, there were no statistically significant associations of reported diet soda and NAS consumption with fasting insulin, fasting glucose, or incident diabetes.
CONCLUSIONS:
Although reported consumption of diet soda and NAS were high, neither were associated with diabetes risk.

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Moderate Protein Restriction Protects Against Focal Cerebral Ischemia in Mice by Mechanisms Involving Anti-inflammatory and Anti-oxidant Responses.
de Carvalho TS, Sanchez-Mendoza EH, Nascentes LM, Schultz Moreira AR, Sardari M, Dzyubenko E, Kleinschnitz C, Hermann DM.
Mol Neurobiol. 2019 Jul 1. doi: 10.1007/s12035-019-01679-6. [Epub ahead of print]
PMID: 31257559
https://link.springer.com/content/pdf/10.1007%2Fs12035-019-01679-6.pdf
Abstract
Food composition influences stroke risk, but its effects on ischemic injury and neurological deficits are poorly examined. While severe reduction of protein content was found to aggravate neurological impairment and brain injury as a consequence of combined energy-protein malnutrition, moderate protein restriction not resulting in energy deprivation was recently suggested to protect against perinatal hypoxia-ischemia. Male C57BL6/j mice were exposed to moderate protein restriction by providing a normocaloric diet containing 8% protein (control: 20% protein) for 7, 14, or 30 days. Intraluminal middle cerebral artery occlusion was then induced. Mice were sacrificed 24 h later. Irrespective of the duration of food modification (that is, 7-30 days), protein restriction reduced neurological impairment of ischemic mice revealed by a global and focal deficit score. Prolonged protein restriction over 30 days also reduced infarct volume, brain edema, and blood-brain barrier permeability and increased the survival of NeuN+ neurons in the core of the stroke (i.e., striatum). Neuroprotection by prolonged protein restriction went along with reduced brain infiltration of CD45+ leukocytes and reduced expression of inducible NO synthase and interleukin-1β. As potential mechanisms, increased levels of the NAD-dependent deacetylase sirtuin-1 and anti-oxidant glutathione peroxidase-3 were noted in ischemic brain tissue. Irrespective of the protein restriction duration, a shift from pro-oxidant oxidative stress markers (NADPH oxidase-4) to anti-oxidant markers (superoxide dismutase-1/2, glutathione peroxidase-3 and catalase) was found in the liver. Moderate protein restriction protects against ischemia in the adult brain. Accordingly, dietary modifications may be efficacious strategies promoting stroke outcome.
KEYWORDS:
Cerebral metabolism; Ischemic stroke; Middle cerebral artery occlusion; Neuroprotection; Oxidative stress; Protein intake

Associations of overweight and metabolic health with successful aging: 32-year follow-up of the Helsinki Businessmen Study.
Jyväkorpi SK, Urtamo A, Strandberg AY, von Bonsdorff M, Salomaa V, Kivimäki M, Luotola K, Strandberg TE.
Clin Nutr. 2019 Jun 21. pii: S0261-5614(19)30266-3. doi: 10.1016/j.clnu.2019.06.011. [Epub ahead of print]
PMID: 31256807
Abstract
BACKGROUND & AIMS:
Prognostic significance of metabolically healthy overweight and obesity (MHO) is under debate. However the relationship between MHO and health-related quality of life (HRQoL) is less studied. We compared successful aging (longevity plus HRQoL) in men with MHO, metabolically healthy normal weight (MHN) and metabolically unhealthy overweight and obesity (MUO).
METHODS:
In the Helsinki Businessmen Study longitudinal cohort, consisting of men born 1919 to 1934. In 1985/86, overweight (BMI≥25 kg/m2) and metabolic health were determined in 1309 men (median age 60 years). HRQoL was assessed using RAND-36/SF-36 in 2000 and 2007, and all-cause mortality retrieved from registers up to 2018. The proportion of men reaching 90 years was also calculated.
RESULTS:
Of the men, 469 (35.8%), 538 (41.1%), 276 (21.1%), and 26 (2.0%) were MHN, MHO, MUO and MUN, respectively. During the 32-year follow-up, 72.3% men died. With MHN as reference, adjusted hazard ratio with all-cause mortality was 1.08 (95% confidence interval [CI] 0.93 to 1.27) for MHO, and 1.18 (95% CI 0.95 to 1.47) for MUO. During follow-up, 273 men reached 90 years. With MHN as reference, adjusted odds ratio for MHO was 0.82 (95% CI 0.59 to 1.14) and 0.62 (95% CI 0.41 to 0.95) for MUO. Men in MHN group scored generally highest in RAND-36 HRQoL subscales in 2000 and 2007, of those significantly better in Physical functioning, Role physical, Role emotional, Bodily Pain, and General health sub-scales compared to MHO group in 2000.
CONCLUSIONS:
As compared to MHN, MHO in late midlife does not increase mortality, but impairs odds for successful aging.
KEYWORDS:
Metabolically healthy overweight and obesity; Metabolically unhealthy overweight and obesity; Nonagenarians; Quality of life; RAND-36; Successful aging

Genetic and life-style risk factors for advanced liver disease among men and women.
Sahlman P, Nissinen M, Puukka P, Jula A, Salomaa V, Männistö S, Lundqvist A, Valsta L, Perola M, Färkkilä M, Åberg F.
J Gastroenterol Hepatol. 2019 Jul 1. doi: 10.1111/jgh.14770. [Epub ahead of print]
PMID: 31260143
Abstract
BACKGROUND & AIMS:
Liver disease is traditionally categorized as alcoholic and non-alcoholic. We studied various risk factors predictive of advanced non-viral liver disease in general population and analyzed the interaction between these factors and alcohol consumption.
METHODS:
Persons without underlying liver disease who participated in the Health2000 or FINRISK studies 1992-2012 comprised a cohort of 41260 individuals. Pattern of alcohol consumption and metabolic, life-style-related and anthropometric parameters were analyzed with Cox regression analysis using severe liver disease hospitalization, cancer or death as end-point. Viral liver diseases were excluded.
RESULTS:
355 liver events occurred during the mean 12.4-year follow-up (511789 person-years). In the multivariate model, age (HR 1.03, p=0.0083 for men, HR 1.04, p=0.0198 for women), waist-hip ratio (WHR) (HR 1.52, p=0.0006 for men, HR 1.58, p=0.0167 for women) PNPLA3 mutations (HR 1.9, p=0.024 for men, HR 2.7, p=0.0109 for women) and weekly binge drinking (HR 2.4, p=0.0024 for men, HR 7.4, p<0.0001 for women) predicted development of severe liver disease. Among men, diabetes (HR 2.7, p=0.0002), average alcohol consumption (HR for 10g/d 1.1, p=0.0022) non-married status (HR 1.9, p=0.0397 for single and HR 2.4, p=0.0002 for widow/separated) and serum HDL (HR 2.2, p=0.0022) and non-HDL cholesterol (HR 1.2, p=0.0237) were additional risk factors. Alcohol intake increased the risk especially among persons with high WHR (p for interaction 0.009).
CONCLUSIONS:
Age, PNPLA3 haplotype and WHR increase the risk for development of severe liver disease. We found strong synergism between alcohol and central obesity. Binge drinking is an additional risk factor.
KEYWORDS:
alcohol; cirrhosis; liver disease; risk factor

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Garlic Consumption and All-Cause Mortality among Chinese Oldest-Old Individuals: A Population-Based Cohort Study.
Shi X, Lv Y, Mao C, Yuan J, Yin Z, Gao X, Zhang Z.
Nutrients. 2019 Jun 30;11(7). pii: E1504. doi: 10.3390/nu11071504.
PMID: 31262080
https://www.mdpi.com/2072-6643/11/7/1504/htm
Abstract
In vitro and in vivo experimental studies have shown garlic has protective effects on the aging process; however, there is no evidence that garlic consumption is associated with all-cause mortality among oldest-old individuals (≥80 years). From 1998 to 2011, 27,437 oldest-old participants (mean age: 92.9 years) were recruited from 23 provinces in China. The frequencies of garlic consumption at baseline and at age 60 were collected. Cox proportional hazards models adjusted for potential covariates were constructed to estimate hazard ratios (HRs) relating garlic consumption to all-cause mortality. Among 92,505 person-years of follow-up from baseline to September 1, 2014, 22,321 participants died. Participants who often (≥5 times/week) or occasionally (1-4 times/week) consumed garlic survived longer than those who rarely (less than once/week) consumed it (p < 0.001). Participants who consumed garlic occasionally or often had a lower risk for mortality than those who rarely consumed garlic at baseline; the adjusted HRs for mortality were 0.92(0.89-0.94) and 0.89(0.85-0.92), respectively. The inverse associations between garlic consumption and all-cause mortality were robust in sensitivity analyses and subgroup analyses. In this study, habitual consumption of garlic was associated with a lower all-cause mortality risk; this advocates further investigation into garlic consumption for promoting longevity.
KEYWORDS:
elderly; garlic; mortality; oldest old; survival

Dietary Vitamin B6 Intake Associated with a Decreased Risk of Cardiovascular Disease: A Prospective Cohort Study.
Jeon J, Park K.
Nutrients. 2019 Jun 29;11(7). pii: E1484. doi: 10.3390/nu11071484.
PMID: 31261898
https://www.mdpi.com/2072-6643/11/7/1504/htm
Abstract
Although the biological mechanisms underlying the beneficial effects of vitamin B6 on cardiovascular disease (CVD) have been reported on, epidemiological studies have yielded controversial results, and data on the Korean population are limited. This study examined the association between dietary vitamin B6 intake and CVD incidence in Koreans. A total of 9142 participants of the Korean Genome and Epidemiology Study, aged 40-69 years, who did not have CVD or cancer at the baseline were included in the analysis. Dietary data were assessed using a validated semi-quantitative food frequency questionnaire. CVD incidence was assessed using biennial questionnaires and confirmed through repeated personal interviews. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression models. After multivariate adjustment, a higher vitamin B6 intake was significantly associated with a decreased CVD risk in men (HR: 0.44; 95% CI: 0.25-0.78); no such association was observed in women. Dose-response analysis confirmed the presence of inverse linearity between vitamin B6 intake and CVD incidence in men (p for nonlinearity = 0.3). A higher dietary intake level of vitamin B6 was associated with a reduced CVD risk in Korean men. These observations require further verification in other populations.
KEYWORDS:
cardiovascular disease; cohort study; men; vitamin B6

Effects of Omega-3-Polyunsaturated Fatty on Endothelial Function in Patients with Peripheral Arterial Disease: A Randomized, Placebo-Controlled, Double-Blind Trial.
Hammer A, Moertl D, Schlager O, Matschuck M, Seidinger D, Koppensteiner R, Steiner S.
Br J Nutr. 2019 Jul 2:1-20. doi: 10.1017/S0007114519001582. [Epub ahead of print]
PMID: 31262371
Abstract
As only limited evidence is available for potential benefits of omega-3 polyunsaturated fatty acids (n3-PUFA) supplementation in patients with peripheral arterial disease (PAD), we studied the effects of 4g n3-PUFA on endothelial function and inflammatory markers. Seventy patients with stable PAD classified as Rutherford stage 2 or 3 and good control of cardiovascular factors were randomized to receive either 4g n3-PUFA or placebo daily for 3 months in a double-blind fashion. Primary endpoint was endothelial function assessed by flow-mediated vasodilation (FMD). In addition, ankle-brachial index (ABI), maximum and pain-free walking distances were determined. Lipid parameters including omega-3 index reflecting n3-PUFA intake as well as pro-inflammatory, endothelial and platelet activation markers were measured over the same time interval. After 3 months of treatment with 4g n3-PUFA daily a significant improvement of FMD was observed compared to placebo (n3-PUFA, median (IQR): Δ 3.7% (-1.8, 7.1) vs. placebo: Δ -0.5% (-6.5, 3.0), P=0.01 between the groups). After a 3 months wash out period this benefit was not sustained (n3-PUFA, median (IQR): Δ 0.6% (-2.2, 5.6) vs. placebo: Δ -0.9% (-6.6, 6,7), P=0.20). In response to n3-PUFA, an improvement of lipid parameters with a pronounced increase of omega-3 index was seen. No changes were found for other parameters. In conclusion, in patients with PAD, 4g/d n3-PUFA improved endothelial function but not walking capacity. Thus, N3-PUFA supplementation might be a potential candidate for reduction of the excess CV risk in PAD patients, which needs testing in large scale trials. 
KEYWORDS:
endothelial function; peripheral arterial disease; polyunsaturated fatty acids

Relation of Vegetarian Dietary Patterns With Major Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.
Glenn AJ, Viguiliouk E, Seider M, Boucher BA, Khan TA, Blanco Mejia S, Jenkins DJA, Kahleová H, Rahelić D, Salas-Salvadó J, Kendall CWC, Sievenpiper JL.
Front Nutr. 2019 Jun 13;6:80. doi: 10.3389/fnut.2019.00080. eCollection 2019.
PMID: 31263700
Abstract
Background: Vegetarian dietary patterns are recommended for cardiovascular disease (CVD) prevention and management due to their favorable effects on cardiometabolic risk factors, however, the role of vegetarian dietary patterns in CVD incidence and mortality remains unclear. Objective: To update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy, we undertook a systematic review and meta-analysis of the association of vegetarian dietary patterns with major cardiovascular outcomes in prospective cohort studies that included individuals with and without diabetes using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Methods: MEDLINE, EMBASE, and Cochrane databases were searched through September 6th, 2018. We included prospective cohort studies ≥1 year of follow-up including individuals with or without diabetes reporting the relation of vegetarian and non-vegetarian dietary patterns with at least one cardiovascular outcome. Two independent reviewers extracted data and assessed study quality (Newcastle-Ottawa Scale). The pre-specified outcomes included CVD incidence and mortality (total CVD, coronary heart disease (CHD) and stroke). Risk ratios for associations were pooled using inverse variance random effects model and expressed as risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q-statistic) and quantified (I 2-statistic). The overall certainty of the evidence was assessed using GRADE. Results: Seven prospective cohort studies (197,737 participants, 8,430 events) were included. A vegetarian dietary pattern was associated with reduced CHD mortality [RR, 0.78 (CI, 0.69, 0.88)] and incidence [0.72 (0.61, 0.85)] but were not associated with CVD mortality [0.92 (0.84, 1.02)] and stroke mortality [0.92 (0.77, 1.10)]. The overall certainty of the evidence was graded as "very low" for all outcomes, owing to downgrades for indirectness and imprecision. Conclusions: Very low-quality evidence indicates that vegetarian dietary patterns are associated with reductions in CHD mortality and incidence but not with CVD and stroke mortality in individuals with and without diabetes. More research, particularly in different populations, is needed to improve the certainty in our estimates.
KEYWORDS:
GRADE; cardiovascular disease; meta-analysis; prospective cohort studies; systematic review; vegetarian dietary patterns; vegetarian diets

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Low fasting glucose and future risks of major adverse outcomes in people without baseline diabetes or cardiovascular disease: a systematic review and meta-analysis.
Liao HW, Saver J, Yeh HC, Chen CS, Wu YL, Lee M, Ovbiagele B.
BMJ Open. 2019 Jul 1;9(7):e026010. doi: 10.1136/bmjopen-2018-026010.
PMID: 31266835
https://bmjopen.bmj.com/content/bmjopen/9/7/e026010.full.pdf
Abstract
OBJECTIVE:
To investigate the link between low fasting blood glucose levels and all-cause mortality and cardiovascular outcomes among people without baseline diabetes or cardiovascular disease.
DESIGN:
Systematic review and meta-analysis.
DATA SOURCES:
PubMed and Embase (1966-February 2019).
SELECTION CRITERIA:
Prospective cohort studies were included for meta-analysis if they reported adjusted HRs with 95% CIs for associations between risk of all-cause mortality, stroke, major cardiovascular events, coronary heart disease and low fasting glucose levels (<4.6 mmol/L and/or 4.0 mmol/L, respectively) versus normal fasting glucose levels.
DATA EXTRACTION AND STATISTICAL ANALYSIS:
Two independent reviewers extracted data from eligible studies. Heterogeneity was assessed by p value of χ2 tests and I2. We assessed four characteristics for each included study based on items developed by the US Preventive Task Force, as well as the modified checklist used in previous studies.
RESULTS:
Eleven articles (consisting of 129 prospective cohort studies) with 2 674 882 participants without diabetes and cardiovascular disease at baseline were included in this meta-analysis. Pooled results from the random effects model showed increased risks of all-cause mortality (HR: 1.56; 95% CI 1.09 to 2.23), total stroke (HR: 1.08, 95% CI 1.03 to 1.13) and ischaemic stroke (HR: 1.06, 95% CI 1.01 to 1.10), and major cardiovascular events (HR: 1.05, 95% CI 1.03 to 1.07) among people with a fasting glucose <4.0 mmol/L, as compared with people with normal fasting glucose. The less stringent low fasting glucose level, <4.6 mmol/L, was not associated with increased risk of any endpoints.
DISCUSSION AND CONCLUSIONS:
Among people without baseline diabetes or cardiovascular disease, a fasting blood glucose level of <4.0 mmol/L is associated with increased risk of all-cause mortality, major cardiovascular events and stroke.
KEYWORDS:
epidemiology; primary care; public health
 

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Nut and Peanut Butter Consumption and Mortality in the National Institutes of Health-AARP Diet and Health Study.
Amba V, Murphy G, Etemadi A, Wang S, Abnet CC, Hashemian M.
Nutrients. 2019 Jul 2;11(7). pii: E1508. doi: 10.3390/nu11071508.
PMID: 31269682
[pdf aviled from Medline abstract.]
Abstract
Although previous studies have shown inverse associations between nut consumption and mortality, the associations between nut consumption and less common causes of mortality have not been investigated. Additionally, about 50% of peanut consumption in the US is through peanut butter but the association between peanut butter consumption and mortality has not been thoroughly evaluated. The National Institutes of Health-AARP (NIH-AARP) Diet and Health Study recruited 566,398 individuals aged 50-71 at baseline in 1995-1996. A food-frequency questionnaire was used to evaluate nut and peanut butter consumption. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals for mortality using the non-consumers as reference groups and three categories of consumption. After excluding subjects with chronic diseases at baseline, there were 64,464 deaths with a median follow-up time of 15.5 years. We observed a significant inverse association between nut consumption and overall mortality (HR C4 vs C1 = 0.78, 95% CI = 0.76, 0.81, p ≤ 0.001). Nut consumption was significantly associated with reduced risk of cancer, cardiovascular, respiratory, infectious, renal and liver disease mortality but not with diabetes or Alzheimer's disease mortality. We observed no significant associations between peanut butter consumption and all-cause (HR C4 vs C1 = 1.00, 95% CI = 0.98, 1.04, p = 0.001) and cause-specific mortality. In a middle-aged US population, nut intake was inversely associated with all-cause mortality and certain types of cause-specific mortality. However, peanut butter consumption was not associated with differential mortality.
KEYWORDS:
NIH-AARP Diet and Health Study; cancer; cardiovascular disease; chronic liver disease; mortality; nut; peanut butter; respiratory disease

Role of diet in type 2 diabetes incidence: umbrella review of meta-analyses of prospective observational studies.
Neuenschwander M, Ballon A, Weber KS, Norat T, Aune D, Schwingshackl L, Schlesinger S.
BMJ. 2019 Jul 3;366:l2368. doi: 10.1136/bmj.l2368.
PMID: 31270064
Abstract
OBJECTIVE:
To summarise the evidence of associations between dietary factors and incidence of type 2 diabetes and to evaluate the strength and validity of these associations.
DESIGN:
Umbrella review of systematic reviews with meta-analyses of prospective observational studies.
DATA SOURCES:
PubMed, Web of Science, and Embase, searched up to August 2018.
ELIGIBILITY CRITERIA:
Systematic reviews with meta-analyses reporting summary risk estimates for the associations between incidence of type 2 diabetes and dietary behaviours or diet quality indices, food groups, foods, beverages, alcoholic beverages, macronutrients, and micronutrients.
RESULTS:
53 publications were included, with 153 adjusted summary hazard ratios on dietary behaviours or diet quality indices (n=12), food groups and foods (n=56), beverages (n=10), alcoholic beverages (n=12), macronutrients (n=32), and micronutrients (n=31), regarding incidence of type 2 diabetes. Methodological quality was high for 75% (n=115) of meta-analyses, moderate for 23% (n=35), and low for 2% (n=3). Quality of evidence was rated high for an inverse association for type 2 diabetes incidence with increased intake of whole grains (for an increment of 30 g/day, adjusted summary hazard ratio 0.87 (95% confidence interval 0.82 to 0.93)) and cereal fibre (for an increment of 10 g/day, 0.75 (0.65 to 0.86)), as well as for moderate intake of total alcohol (for an intake of 12-24 g/day v no consumption, 0.75 (0.67 to 0.83)). Quality of evidence was also high for the association for increased incidence of type 2 diabetes with higher intake of red meat (for an increment of 100 g/day, 1.17 (1.08 to 1.26)), processed meat (for an increment of 50 g/day, 1.37 (1.22 to 1.54)), bacon (per two slices/day, 2.07 (1.40 to 3.05)), and sugar sweetened beverages (for an increase of one serving/day, 1.26 (1.11 to 1.43)).
CONCLUSIONS:
Overall, the association between dietary factors and type 2 diabetes has been extensively studied, but few of the associations were graded as high quality of evidence. Further factors are likely to be important in type 2 diabetes prevention; thus, more well conducted research, with more detailed assessment of diet, is needed.

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Beware of the margarita burn: the unfortunate side effect of limes and sun
'I woke up the next morning and I was in pain. I was crying my eyes out.'
Ariel Fournier · CBC News · Posted: Jul 07, 2019
https://www.cbc.ca/news/canada/edmonton/beware-of-the-margarita-burn-the-unfortunate-side-effect-of-limes-and-sun-1.5200862

A randomized controlled trial contrasting the effects of 4 low-calorie sweeteners and sucrose on body weight in adults with overweight or obesity.
Higgins KA, Mattes RD.
Am J Clin Nutr. 2019 May 1;109(5):1288-1301. doi: 10.1093/ajcn/nqy381.
PMID: 30997499
Abstract
BACKGROUND:
Low-calorie sweeteners (LCSs) provide sweetness with little or no energy. However, each LCS's unique chemical structure has potential to elicit different sensory, physiological, and behavioral responses that affect body weight.
OBJECTIVE:
The purpose of this trial was to compare the effects of consumption of 4 LCSs and sucrose on body weight, ingestive behaviors, and glucose tolerance over a 12-wk intervention in adults (18-60 y old) with overweight or obesity (body mass index 25-40 kg/m2).
METHODS:
In a parallel-arm design, 154 participants were randomly assigned to consume 1.25-1.75 L of beverage sweetened with sucrose (n = 39), aspartame (n = 30), saccharin (n = 29), sucralose (n = 28), or rebaudioside A (rebA) (n = 28) daily for 12 wk. The beverages contained 400-560 kcal/d (sucrose treatments) or <5 kcal/d (LCS treatments). Anthropometric indexes, energy intake, energy expenditure, appetite, and glucose tolerance were measured at baseline. Body weight was measured every 2 wk with energy intake, expenditure, and appetite assessed every 4 wk. Twenty-four-hour urine collections were completed every 4 wk to determine study compliance via para-aminobenzoic acid excretion.
RESULTS:
Of the participants enrolled in the trial, 123 completed the 12-wk intervention. Sucrose and saccharin consumption led to increased body weight across the 12-wk intervention (Δweight = +1.85 ± 0.36 kg and +1.18 ± 0.36 kg, respectively; P ≤ 0.02) and did not differ from each other. There was no significant change in body weight with consumption of the other LCS treatments compared with baseline, but change in body weight for sucralose was negative and significantly lower compared with all other LCSs at week 12 (weight difference ≥ 1.37 ± 0.52 kg, P ≤ 0.008). Energy intake decreased with sucralose consumption (P = 0.02) and ingestive frequency was lower for sucralose than for saccharin (P = 0.045). Glucose tolerance was not significantly affected by any of the sweetener treatments.
CONCLUSIONS:
Sucrose and saccharin consumption significantly increase body weight compared with aspartame, rebA, and sucralose, whereas weight change was directionally negative and lower for sucralose compared with saccharin, aspartame, and rebA consumption. LCSs should be categorized as distinct entities because of their differing effects on body weight.
KEYWORDS:
appetite; energy intake; glycemia; ingestive behavior; low-calorie sweeteners; obesity; overweight; sweetness

Restricting carbohydrates at breakfast is sufficient to reduce 24-hour exposure to postprandial hyperglycemia and improve glycemic variability.
Chang CR, Francois ME, Little JP.
Am J Clin Nutr. 2019 May 1;109(5):1302-1309. doi: 10.1093/ajcn/nqy261.
PMID: 30968140
Abstract
BACKGROUND:
The breakfast meal often results in the largest postprandial hyperglycemic excursion in people with type 2 diabetes.
OBJECTIVE:
Our purpose was to investigate whether restricting carbohydrates at breakfast would be a simple and feasible strategy to reduce daily exposure to postprandial hyperglycemia.
DESIGN:
Adults with physician-diagnosed type 2 diabetes [n = 23; mean ± SD age: 59 ± 11 y; glycated hemoglobin: 6.7% ± 0.6%; body mass index (kg/m2): 31 ± 7] completed two 24-h isocaloric intervention periods in a random order. Participants consumed one of the following breakfasts: 1) a very-low-carbohydrate high-fat breakfast (LCBF; <10% of energy from carbohydrate, 85% of energy from fat, 15% of energy from protein) or 2) a breakfast with dietary guidelines-recommended nutrient profile (GLBF; 55% of energy from carbohydrate, 30% of energy from fat, 15% of energy from protein), with the same lunch and dinner provided. Continuous glucose monitoring was used to assess postprandial glucose responses over 24 h, and visual analog scales were used to assess ratings of hunger and fullness.
RESULTS:
The LCBF significantly reduced postprandial hyperglycemia after breakfast (P < 0.01) and did not adversely affect glycemia after lunch or dinner. As such, overall postprandial hyperglycemia (24-h incremental area under the glucose curve) and glycemic variability (mean amplitude of glycemic excursions) were reduced with the LCBF (24-h incremental area under the glucose curve: -173 ± 361 mmol/L; P = 0.03; mean amplitude of glycemic excursions: -0.4 ± 0.8 mmol/L · 24 h; P = 0.03) compared with the GLBF. Premeal hunger was lower before dinner with the LCBF than with the GLBF (P-interaction = 0.03).
CONCLUSIONS:
A very-low-carbohydrate high-fat breakfast lowers postbreakfast glucose excursions. The effects of this simple strategy appear to be sufficient to lower overall exposure to postprandial hyperglycemia and improve glycemic variability. Longer-term interventions are warranted.
KEYWORDS:
LCHF; continuous glucose monitoring; diabetes glycemic control; macronutrient

Habitual coffee consumption and risk of falls in 2 European cohorts of older adults.
Machado-Fragua MD, Struijk EA, Ballesteros JM, Ortolá R, Rodriguez-Artalejo F, Lopez-Garcia E.
Am J Clin Nutr. 2019 May 1;109(5):1431-1438. doi: 10.1093/ajcn/nqy369.
PMID: 31005970
Abstract
BACKGROUND:
Habitual coffee consumption has been associated with lower risk of type 2 diabetes, cardiovascular disease, and sarcopenia, which are strong risk factors of falls. In addition, caffeine intake stimulates attention and vigilance, and reduces reaction time. Therefore, a protective effect of coffee on the risk of falling can be hypothesized.
OBJECTIVES:
The aim of this study was to examine the association between habitual coffee consumption and the risk of ≥1 falls, injurious falls, and falls with fracture in older people.
METHODS:
Data were taken from 2964 participants aged ≥60 y from the Seniors-ENRICA (Study on Nutrition and Cardiovascular Risk in Spain) cohort and 8999 participants aged ≥60 y from the UK Biobank cohort. In the Seniors-ENRICA study, habitual coffee consumption was assessed with a validated diet history in 2008-2010, and falls were ascertained up to 2015. In the UK Biobank study, coffee was measured with 3-5 multiple-pass 24-h food records starting in 2006, and falls were assessed up to 2016.
RESULTS:
A total of 793 individuals in Seniors-ENRICA and 199 in UK Biobank experienced ≥1 fall during follow-up. After multivariable adjustment for major lifestyle and dietary risk factors and compared with daily consumption of <1 cup of coffee, the pooled HR for ≥1 fall was 0.75 (95% CI: 0.52, 1.07) for total coffee consumption of 1 cup/d and 0.74 (95% CI: 0.62, 0.90) for ≥2 cups/d (P-trend = 0.001). The corresponding figures for caffeinated coffee were 0.67 (95% CI: 0.42, 1.07) and 0.70 (95% CI: 0.56, 0.87) (P-trend < 0.001). Decaffeinated coffee was not associated with risk of falling in the analyzed cohorts. In Seniors-ENRICA, there was a tendency to lower risk of injurious falls among those consuming caffeinated coffee (HR: 0.83; 95% CI: 0.68, 1.00 for 1 cup/d; HR: 0.83; 95% CI: 0.64, 1.09 for ≥2 cups/d; P-trend = 0.09). No association was observed between caffeinated or decaffeinated coffee consumption and risk of falls with fracture.
CONCLUSIONS:
Habitual coffee consumption was associated with lower risk of falling in older adults in Spain and the United Kingdom.
KEYWORDS:
Seniors-ENRICA; UK Biobank; coffee; cohort study; falls; older population

Dietary proteins and protein sources and risk of death: the Kuopio Ischaemic Heart Disease Risk Factor Study.
Virtanen HEK, Voutilainen S, Koskinen TT, Mursu J, Kokko P, Ylilauri MPT, Tuomainen TP, Salonen JT, Virtanen JK.
Am J Clin Nutr. 2019 May 1;109(5):1462-1471. doi: 10.1093/ajcn/nqz025.
PMID: 30968137
Abstract
BACKGROUND:
Previous studies investigating protein intake in relation to mortality have provided conflicting results.
OBJECTIVE:
We investigated the associations of dietary protein and protein sources with risk of disease death in the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study.
METHODS:
The study population consisted of 2641 Finnish men, aged 42-60 y at baseline in 1984-1989. We estimated protein intakes with 4-d dietary records at baseline and collected data on disease deaths from the national Causes of Death Register. Cox proportional hazards regression models were used to estimate HRs and 95% CIs.
RESULTS:
During the average follow-up of 22.3 y, we observed 1225 deaths due to disease. Higher intakes of total protein and animal protein had borderline statistically significant associations with increased mortality risk: multivariable-adjusted HR (95% CI) in the highest compared with the lowest quartile for total protein intake = 1.17 (0.99, 1.39; P-trend across quartiles = 0.07) and for animal protein intake = 1.13 (0.95, 1.35; P-trend = 0.04). Higher animal-to-plant protein ratio (extreme-quartile HR = 1.23; 95% CI: 1.02, 1.49; P-trend = 0.01) and higher meat intake (extreme-quartile HR = 1.23; 95% CI: 1.04, 1.47; P-trend = 0.01) were associated with increased mortality. When evaluated based on disease history at baseline, the association of total protein with mortality appeared more evident among those with a history of type 2 diabetes, cardiovascular disease, or cancer (n = 1094) compared with those without disease history (n = 1547) (P-interaction = 0.05 or 0.07, depending on the model). Intakes of fish, eggs, dairy, or plant protein sources were not associated with mortality.
CONCLUSIONS:
Higher ratio of animal to plant protein in diet and higher meat intake were associated with increased mortality risk. Higher total protein intake appeared to be associated with mortality mainly among those with a predisposing disease.
KEYWORDS:
animal protein; dairy; dietary protein; meat; men; mortality; plant protein; prospective study

Soy, Soy Isoflavones, and Protein Intake in Relation to Mortality from All Causes, Cancers, and Cardiovascular Diseases: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.
Nachvak SM, Moradi S, Anjom-Shoae J, Rahmani J, Nasiri M, Maleki V, Sadeghi O.
J Acad Nutr Diet. 2019 Jul 2. pii: S2212-2672(19)30362-4. doi: 10.1016/j.jand.2019.04.011. [Epub ahead of print]
PMID: 31278047
Abstract
OBJECTIVE:
We conducted a systematic review and dose-response meta-analysis of prospective studies to summarize findings on the associations between intakes of soy, soy isoflavones, and soy protein and risk of mortality from all causes, cancers, and cardiovascular diseases.
METHODS:
Online databases were systematically searched to identify relevant articles published earlier than May 2018. We applied restricted cubic splines using random-effects analysis to assess dose-response associations. Between-study heterogeneity was assessed by I2 value and Cochrane Q test. Potential publication bias was assessed by visual inspection of funnel plots and Begg regression test.
RESULTS:
In total, 23 prospective studies with an overall sample size of 330,826 participants were included in the current systematic review and the meta-analysis. Soy/soy products consumption was inversely associated with deaths from cancers (pooled relative risk 0.88, 95% CI 0.79 to 0.99; P=0.03; I2=47.1%, 95% CI 0.0% to 75.4%) and cardiovascular diseases (pooled effect size: 0.85, 95% CI 0.72 to 0.99; P=0.04; I2=50.0%, 95% CI 0.0% to 77.6%). Such significant associations were also observed for all-cause mortality in some subgroups of the included studies, particularly those with higher quality. In addition, higher intake of soy was associated with decreased risk of mortality from gastric, colorectal, and lung cancers as well as ischemic cardiovascular diseases. Participants in the highest category of dietary soy isoflavones intake had a 10% lower risk of all-cause mortality compared with those in the lowest category. We also found that a 10-mg/day increase in intake of soy isoflavones was associated with 7% and 9% decreased risk of mortality from all cancers and also breast cancer respectively. Furthermore, a 12% reduction in breast cancer death was indicated for each 5-g/day increase in consumption of soy protein. However, intake of soy protein was not significantly associated with all-cause and cardiovascular diseases mortality.
CONCLUSIONS:
Soy and its isoflavones may favorably influence risk of mortality. In addition, soy protein intake was associated with a decreased risk in the mortality of breast cancer. Our findings may support the current recommendations to increase intake of soy for greater longevity.
KEYWORDS:
Cancer; Isoflavones; Meta-analysis; Mortality; Soy foods

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Aspirin Efficacy in Primary Prevention: A Meta-analysis of Randomized Controlled Trials.
Barbarawi M, Kheiri B, Zayed Y, Gakhal I, Al-Abdouh A, Barbarawi O, Rashdan L, Rizk F, Bachuwa G, Alkotob ML.
High Blood Press Cardiovasc Prev. 2019 Jul 6. doi: 10.1007/s40292-019-00325-5. [Epub ahead of print] Review.
PMID: 31280451
Abstract
INTRODUCTION:
The role of aspirin as a means of primary prevention remains controversial.
AIM:
We have conducted a meta-analysis of all randomized controlled trials (RCTs) to evaluate the role of aspirin in primary prevention.
METHODS:
Literature search was performed via PubMed, Embase, and the Cochrane Library for all related RCTs. All-cause mortality was the primary endpoint. Secondary endpoints included major adverse cardiovascular events (MACE), myocardial infarction (MI), cardiovascular mortality, cerebrovascular events, and bleeding events. We used a random effects model to report the risk ratios (RRs) with 95% confidence intervals (CIs).
RESULTS:
Our analysis included 17 RCTs (164,862 patients; 83,309 received aspirin and 81,744 received placebo). Our study did not demonstrate any significant reduction in all-cause mortality for patients treated with aspirin when compared with placebo (RR 0.97; 95% CI 0.93-1.01; P = 0.13). Sensitivity analysis performed by excluding healthy elderly (≥ 65) showed significant reductions in all-cause mortality in the aspirin-treated patients (RR 0.94; 95% CI 0.90-0.99; P = 0.01). There were no significant differences between both groups regarding cardiovascular mortality and cerebrovascular events (P > 0.05). However, aspirin-treated patients significantly reduced MACE and MI events (RR 0.89; 95% CI 0.85-0.93; P < 0.001 and RR 0.88; 95% CI 0.78-0.98; P = 0.02, respectively), respectively. However, aspirin was associated with a significantly higher incidence of bleeding, including major bleeding and intracranial bleeding (P < 0.001).
CONCLUSIONS:
Aspirin use in primary prevention has resulted in a lower incidence of MACE and MI without significantly effecting cerebrovascular events. However, aspirin was associated with a higher bleeding risk. Use of aspirin as a means of primary prevention should be thoroughly discussed with patients and pursued based on the risk of cardiovascular disease while also considering bleeding risk.
KEYWORDS:
Aspirin; Cardiovascular disease; Meta-analysis; Primary prevention

Fried food consumption and risk of coronary artery disease: The Million Veteran Program.
Honerlaw JP, Ho YL, Nguyen XT, Cho K, Vassy JL, Gagnon DR, O'Donnell CJ, Gaziano JM, Wilson PWF, Djousse L; VA Million Veteran Program.
Clin Nutr. 2019 Jun 5. pii: S0261-5614(19)30219-5. doi: 10.1016/j.clnu.2019.05.008. [Epub ahead of print]
PMID: 31279615
Abstract
INTRODUCTION:
Previous studies of the relationship between fried food consumption and coronary artery disease (CAD) have yielded conflicting results. We tested the hypothesis that frequent fried food consumption is associated with a higher risk of incident CAD events in Million Veteran Program (MVP) participants.
METHODS:
Veterans Health Administration electronic health record data were linked to questionnaires completed at MVP enrollment. Self-reported fried food consumption at baseline was categorized: (<1, 1-3, 4-6 times per week or daily). The outcome of interest was non-fatal myocardial infarction or CAD events. We fitted a Cox regression model adjusting for age, sex, race, education, exercise, smoking and alcohol consumption.
RESULTS:
Of 154,663 MVP enrollees with survey data, mean age was 64 years and 90% were men. During a mean follow-up of approximately 3 years, there were 6,725 CAD events. There was a positive linear relationship between frequency of fried food consumption and risk of CAD (p for trend 0.0015). Multivariable adjusted hazard ratios (95% CI) were 1.0 (ref), 1.07 (1.01-1.13), 1.08 (1.01-1.16), and 1.14 (1.03-1.27) across consecutive increasing categories of fried food intake.
CONCLUSIONS:
In a large national cohort of U.S. Veterans, fried food consumption has a positive, dose-dependent association with CAD.
KEYWORDS:
Coronary artery disease; Nutrition; Population science

Long-term dietary fiber intake and risk of chronic obstructive pulmonary disease: a prospective cohort study of women.
Szmidt MK, Kaluza J, Harris HR, Linden A, Wolk A.
Eur J Nutr. 2019 Jul 6. doi: 10.1007/s00394-019-02038-w. [Epub ahead of print]
PMID: 31280344
Abstract
PURPOSE:
Until now, only two prospective cohort studies have investigated dietary fiber intake in relation to risk of chronic obstructive pulmonary disease (COPD), but neither examined long-term fiber intake. Both studies reported that total fiber intake was associated with decreased COPD risk; however, results for specific fiber sources were inconsistent. Thus, we prospectively evaluated the association between baseline and long-term intake of dietary fiber and COPD risk in a population-based prospective cohort of 35,339 Swedish women.
METHODS:
Dietary fiber intake was assessed in 1987 and 1997 with a food frequency questionnaire. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS:
During follow-up (2002-2014), 1557 COPD cases were identified via linkage to the Swedish National Patient Register. Long-term high dietary fiber intake (≥ 26.5 vs. < 17.6 g/day) was associated with a 30% (95% CI 17-41%) lower risk of COPD. For specific fiber sources, cereal (≥ 16.3 vs. < 9.4 g/day; HR 0.67, 95% CI 0.55-0.81) and fruit fiber (≥ 7.6 vs. < 2.6 g/day; HR 0.65, 95% CI 0.5-0.81), but not vegetable fiber intake (≥ 5.4 vs. < 2.2 g/day; HR 1.03, 95% CI 0.81-1.28) were associated with lower COPD risk. Current and ex-smokers with low long-term total fiber intake (< 17.6 g/day) compared to never smokers with high intake (≥ 26.5 g/day) had a 33-fold (95% CI 23.6-46.6) and tenfold (95% CI 7.0-16.3), respectively, higher risk of COPD.
CONCLUSIONS:
Our findings indicate that high fiber intake is a modifiable lifestyle factor which may decrease COPD risk primarily in current and ex-smokers.
KEYWORDS:
Chronic obstructive pulmonary disease; Diet; Dietary fiber; Epidemiology; Prospective cohort study

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Gonadal hormones influence core body temperature during calorie restriction.
Cintron-Colon R, Shankar K, Sanchez-Alavez M, Conti B.
Temperature (Austin). 2019 Apr 26;6(2):158-168. doi: 10.1080/23328940.2019.1607653. eCollection 2019.
PMID: 31286026
https://sci-hub.tw/https://www.tandfonline.com/doi/full/10.1080/23328940.2019.1607653
Abstract
During calorie restriction (CR), endotherms adjust several physiological processes including the decrease of core body temperature (Tb) and reduction of energy expenditure. We recently found that CR-induced hypothermia is regulated in a sex-dependent manner in mice with lowered central insulin-like growth factor receptor signaling. Here, we describe the contribution of sex hormones to CR-induced hypothermia in wild type C57BL6 mice by measuring Tb of female and male mice following bilateral gonadectomy and hormonal replacement. Specifically, we evaluated the effects of progesterone (P4), 17-ß estradiol (E2), a combination of both (P4 + E2) in females and of 5-α dihydrotestosterone (5-α DHT) in males. Gonadectomy resulted in an earlier and stronger CR-induced hypothermia in both sexes. These effects were fully antagonized in females by E2 replacement, but not by P4, which had only minor and partial effects when used alone and did not prevent the action of E2 during CR when both hormones were given in combination. 5-α-DHT had only minor and transient effects on preventing the reduction of Tb during CR on gonadectomized male mice. These findings indicate that gonadal hormones contribute to sex-specific regulation of Tb and energy expenditure when nutrient availability is scarce. Abbreviations: AL: ad libitum; ANOVA: analysis of variance; CR: calorie restriction; E2: 17-ß estradiol; GNX: gonadectomy or gonadectomized; IGF-1R: insulin-like growth factor 1 receptor; POA: preoptic area; P4: progesterone; RM: repeated measures; SD: standard deviation; SEM: standard error of mean; Tb: core body temperature; WT: wildtype; 5-α DHT: 5-α dihydrotestosterone.
KEYWORDS:
Hypothermia; calorie restriction; estradiol; gonadal hormones; gonadectomy; temperature

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Alcohol intake, specific alcoholic beverages, and risk of hip fractures in postmenopausal women and men age 50 and older.
Fung TT, Mukamal KJ, Rimm EB, Meyer HE, Willett WC, Feskanich D.
Am J Clin Nutr. 2019 Jul 9. pii: nqz135. doi: 10.1093/ajcn/nqz135. [Epub ahead of print]
PMID: 31287144
Abstract
BACKGROUND:
Although a number of studies have examined the association between alcohol intake and hip fractures, few have considered specific alcoholic beverages separately.
OBJECTIVES:
We prospectively assessed total alcohol and specific alcoholic beverage consumption and risk of hip fractures in US men and women.
METHODS:
Health, lifestyle information, and hip fractures were self-reported on biennial questionnaires between 1980 and 2014 in 75,180 postmenopausal women from the Nurses' Health Study, and between 1986 and 2014 in 38,398 men aged ≥50 y from the Health Professionals Follow-Up Study. Diet was assessed approximately every 4 y with a semiquantitative FFQ. RRs were computed for hip fracture using Cox proportional hazards models, adjusting for potential confounders.
RESULTS:
We ascertained 2360 incident low trauma hip fractures in women and 709 in men. Among women, RRs for low trauma hip fractures compared with nondrinkers were 0.89 (95% CI: 0.80, 0.99) for an average daily consumption of <5.0 g, 0.81 (95% CI: 0.70, 0.94) for 5.0 to <10.0 g, 0.83 (95% CI: 0.71, 0.96) for 10.0 to <20.0 g, and 0.93 (95% CI: 0.78, 1.10) for ≥20.0 g. Among men, risk declined linearly with higher alcohol consumption (P-trend = 0.002). Multivariable RR compared with nondrinkers was 0.77 (95% CI: 0.59, 1.01), 0.69 (0.49, 0.96), and 0.67 (0.48, 0.95) for an average intake of 10 g/d to <20 g/d, 20 g/d to <30 g/d, and 30.0 g/d or more, respectively. In women, the alcoholic beverage most significantly associated with hip fracture risk was red wine (RR per serving = 0.59; 95% CI: 0.45, 0.79). In men, there was no clear association with specific alcoholic beverages.
CONCLUSION:
In these 2 US cohorts, low to moderate alcohol consumption, when compared with no consumption, was associated with a lower risk of hip fractures, particularly with red wine consumption among women.
KEYWORDS:
alcohol; beer; epidemiology; fractures; liquor; nutrition; wine

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JULY 10, 2019 / 4:39 PM / A DAY AGO
Study finds possible link between sugary drinks and cancer
Kate Kelland
https://www.reuters.com/article/us-health-cancer-sugar/study-finds-possible-link-between-sugary-drinks-and-cancer-idUSKCN1U52QN
>>>>>>>>>>>>>>>>>>>
Sugary drink consumption and risk of cancer: results from NutriNet-Santé prospective cohort
BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l2408 (Published 10 July 2019)
Eloi Chazelas, intern1,  Bernard Srour, epidemiologist1,  Elisa Desmetz, intern
https://www.bmj.com/content/366/bmj.l2408
https://www.bmj.com/content/bmj/366/bmj.l2408.full.pdf

Associations of blood pressure categories defined by 2017 ACC/AHA guidelines with mortality in China: Pooled results from three prospective cohorts.
Liu N, Yang JJ, Meng R, Pan XF, Zhang X, He M, Li H, Gao YT, Xiang YB, Shu XO, Zheng W, Wu T, Yu D, Pan A.
Eur J Prev Cardiol. 2019 Jul 9:2047487319862066. doi: 10.1177/2047487319862066. [Epub ahead of print]
PMID: 31288541
https://sci-hub.tw/10.1177/2047487319862066
Abstract
BACKGROUND:
The recent American College of Cardiology/American Heart Association guidelines for high blood pressure lowered the hypertension criteria from systolic/diastolic blood pressure (SBP/DBP) of 140/90 mmHg or greater to 130/80 mmHg or greater, while the potential impact of the change on Chinese adults remains unclear.
DESIGN:
A pooled prospective cohort analysis.
METHODS:
Included were 154,407 Chinese adults from three prospective cohorts, which measured blood pressure at baseline and follow-up visits, and tracked death events by linkages to medical insurance system or vital statistics registries. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS:
During a total follow-up of 1,718,089 person-years, 14,692 deaths were documented including 5086 cardiovascular deaths (1277 ischaemic heart disease and 2509 cerebrovascular disease deaths). Compared to normal blood pressure (SBP/DBP < 120/80 mmHg), newly defined stage 1 hypertension (SBP/DBP 130-139/80-89 mmHg) was associated with increased cardiovascular mortality (HR 1.40, 95% CI 1.16-1.69; HR 1.36, 95% CI 1.12-1.65 for ischaemic heart disease mortality; HR 1.53, 95% CI 1.18-2.00 for cerebrovascular mortality), but not with all-cause mortality (HR 1.04, 95% CI 0.89-1.21). Stage 2 hypertension (SBP/DBP ≥ 140/90 mmHg) showed significant associations with cardiovascular disease and all-cause mortality, while elevated blood pressure (SBP 120-129 mmHg and DBP < 80 mmHg) showed null associations. The associations were stronger in adults younger than 65 years and adults without pre-existing cardiovascular disease compared with their counterparts (P for heterogeneity < 0.05).
CONCLUSIONS:
The newly defined stage 1 hypertension is associated with an increased risk of cardiovascular disease mortality in the Chinese population, particularly among younger adults and those without a history of cardiovascular disease.
KEYWORDS:
Blood pressure; Chinese; cardiovascular disease; cohort study; hypertension; mortality

Dietary Choline is Positively Related to Overall and Cause-Specific Mortality: Results from Individuals of the National Health and Nutrition Examination Survey and Pooling Prospective Data.
Mazidi M, Katsiki N, Mikhailidis DP, Banach M.
Br J Nutr. 2019 Jul 10:1-22. doi: 10.1017/S0007114519001065. [Epub ahead of print]
PMID: 31288869
Abstract
Little is known about the association between dietary choline intake and mortality. We evaluated the link between choline consumption and overall as well as cause-specific mortality by using both individual data and pooling prospective studies by meta-analysis and systematic review. Furthermore, adjusted means of cardiometabolic risk factors across choline intake quartiles were calculated. Data from the National Health and Nutrition Examination Survey (1999-2010) were collected. Adjusted Cox regression was performed to determine the risk ratio (RR) and 95 % CI (95 % CI), as well as random-effects models and generic inverse variance methods to synthesise quantitative and pooling data, followed by a leave-one-out method for sensitivity analysis. After adjustments, we found that individuals consuming more choline had worse lipid profile and glucose homeostasis, but lower CRP levels (p &lt; 0·001 for all comparisons) with no significant differences in anthropometric parameters and blood pressure. Multivariable Cox regression models revealed that individuals in the highest quartile (Q4) of choline consumption had a greater risk of total (23 %), cardiovascular disease (CVD) (33 %) and stroke (30 %) mortality compared with the first quartile (Q1) (p &lt; 0·001 for all comparison). These results were confirmed in a meta-analysis, showing that choline intake was positively and significantly associated with overall (RR: 1·12, 95 % CI: 1·08-1·17, I2: 2·9) and CVD (RR: 1·28, 95 % CI: 1·17-1·39, I2: 9·6) mortality risk. In contrast, the positive association between choline consumption and stroke mortality became non-significant (RR: 1·18, 95 % CI: 0·97-1·43, p = 0·092, I2: 1·1). Our findings shed light on the potential adverse effects of choline intake on selected cardiometabolic risk factors and mortality risk.
KEYWORDS:
Cardiovascular mortality; Choline; Glucose homeostasis; Inflammation; Lipids; Overall mortality; Stroke mortality

PM2.5 air pollution and cause-specific cardiovascular disease mortality.
Hayes RB, Lim C, Zhang Y, Cromar K, Shao Y, Reynolds HR, Silverman DT, Jones RR, Park Y, Jerrett M, Ahn J, Thurston GD.
Int J Epidemiol. 2019 Jul 10. pii: dyz114. doi: 10.1093/ije/dyz114. [Epub ahead of print]
PMID: 31289812
Abstract
BACKGROUND:
Ambient air pollution is a modifiable risk factor for cardiovascular disease, yet uncertainty remains about the size of risks at lower levels of fine particulate matter (PM2.5) exposure which now occur in the USA and elsewhere.
METHODS:
We investigated the relationship of ambient PM2.5 exposure with cause-specific cardiovascular disease mortality in 565 477 men and women, aged 50 to 71 years, from the National Institutes of Health-AARP Diet and Health Study. During 7.5 x 106 person-years of follow up, 41 286 cardiovascular disease deaths, including 23 328 ischaemic heart disease (IHD) and 5894 stroke deaths, were ascertained using the National Death Index. PM2.5 was estimated using a hybrid land use regression (LUR) geostatistical model. Multivariate Cox regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CI).
RESULTS:
Each increase of 10  μg/m3 PM2.5 (overall range, 2.9-28.0  μg/m3) was associated, in fully adjusted models, with a 16% increase in mortality from ischaemic heart disease [hazard ratio (HR) 1.16; 95% CI 1.09-1.22] and a 14% increase in mortality from stroke (HR 1.14; CI 1.02-1.27). Compared with PM2.5 exposure <8  μg/m3 (referent), risks for CVD were increased in relation to PM2.5 exposures in the range of 8-12  μg/m3 (CVD: HR 1.04; 95% CI 1.00-1.08), in the range 12-20  μg/m3 (CVD: HR 1.08; 95% CI 1.03-1.13) and in the range 20+ μg/m3 (CVD: HR 1.19; 95% CI 1.10-1.28). Results were robust to alternative approaches to PM2.5 exposure assessment and statistical analysis.
CONCLUSIONS:
Long-term exposure to fine particulate air pollution is associated with ischaemic heart disease and stroke mortality, with excess risks occurring in the range of and below the present US long-term standard for ambient exposure to PM2.5 (12  µg/m3), indicating the need for continued improvements in air pollution abatement for CVD prevention.
KEYWORDS:
Air pollution; cardiovascular disease; mortality

Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials.
Akhlaghi M, Ghasemi Nasab M, Riasatian M, Sadeghi F.
Crit Rev Food Sci Nutr. 2019 Jul 10:1-15. doi: 10.1080/10408398.2019.1635078. [Epub ahead of print]
PMID: 31290343
Abstract
Background: Osteoporosis is a common bone disease characterized by reduced bone mass resulting from continuous bone resorption. Methods: PubMed, Scopus, and Embase were searched to find published trials on the effect of soy isoflavones on bone mineral density (BMD) and bone turnover markers (bone-specific alkaline phosphatase, osteocalcin, osteoprotegerin, pyridinoline, deoxypyridinoline, C-telopeptide, and N-telopeptide). Random-effects inverse-variance model was used to calculate the pooled effects. Results: A total of 5313 articles were found, screened, and assessed for eligibility, and finally 52 trials were included in the meta-analysis. Consumption of soy isoflavones caused significant improvement in BMD of lumbar spine (mean difference (MD) = 0.76%; 95% CI: 0.09, 1.42%; p = 0.03), hip (MD = 0.22%; 95% CI: 0.02, 0.42%; p = 0.04), and femoral neck (MD = 2.27%; 95% CI: 1.22, 3.31%; p < 0.001). Subgroup analysis showed that in all 3 sites, the improvement was significant in normal weight subjects and interventions longer than a year, although trial location and dosage were also factors influencing isoflavones' impact on BMD. Among markers of bone turnover, osteoprotegerin (MD = 5.79; 95% CI: 3.08, 8.51 pg/ml; p < 0.001), pyridinoline (MD = -5.13; 95% CI: -7.76, -2.50 nmol/mmol; p < 0.001), and C-telopeptides (MD = -0.08; 95% CI: -0.16, -0.00 ng/ml; p = 0.04) were favorably affected by isoflavones while osteocalcin and bone alkaline phosphatase did not change. Subgroup analysis of bone markers showed that in overweight/obese individuals and dosages <90 mg/day, isoflavones are more effective. Conclusions: Soy isoflavones prevent osteoporosis-related bone loss in any weight status or treatment duration. They increase BMD in normal weight subjects and diminish bone resorption in overweight/obese individuals. Although bone resorption may be decelerated over short-term isoflavone consumption, periods longer than a year are probably needed to affect BMD. Isoflavones also appear benefits on bone in any dose or subjects' ethnicity.
KEYWORDS:
BMD; Isoflavones; bone; bone mineral density; bone resorption; bone turnover markers

Prospective associations between beverage intake during the midlife and subclinical carotid atherosclerosis: The Study of Women's Health Across the Nation.
Wang D, Karvonen-Gutierrez CA, Jackson EA, Elliott MR, Appelhans BM, Barinas-Mitchell E, Bielak LF, Baylin A.
PLoS One. 2019 Jul 10;14(7):e0219301. doi: 10.1371/journal.pone.0219301. eCollection 2019.
PMID: 31291324
Abstract
BACKGROUND:
The potential impacts of beverage intake during the midlife on future subclinical atherosclerosis among women are unclear. The aim of this study was to evaluate the prospective associations between the intakes of eight beverage groups and subclinical carotid atherosclerosis in midlife women.
METHODS:
Data came from the Study of Women's Health Across the Nation, a multicenter, multiethnic, and prospective cohort study. A total of 1,235 midlife women had measures of subclinical carotid atherosclerosis and repeatedly beverage intake data collected using a validated food frequency questionnaire. Beverages were aggregated into eight groups, including coffee, tea, sugar-sweetened beverages, artificially sweetened beverages, fruit juices, whole milk, milk with lower fat content, and alcoholic beverages. The associations of beverage intake with common carotid artery intima-media thickness (CCA-IMT) and adventitial diameter (CCA-AD) were estimated using linear models; the associations with carotid plaque were estimated using log-binomial models.
RESULTS:
Coffee intake was associated with CCA-IMT in an inverted J-shaped pattern. After adjusting for covariates, women with >0 to <1 cup/day and 1 to <2 cups/day of coffee intake had a 0.031 mm (95% CI: 0.012, 0.051) and a 0.027 mm (95% CI: 0.005, 0.049) larger CCA-IMT, respectively, than coffee non-drinkers. Women who consumed ≥2 cups/day of coffee did not have significantly different CCA-IMT than non-drinkers. There was an inverse linear association between moderate alcoholic beverages intake and CCA-IMT (P-trend = 0.014). Whole milk intake had inverted U-shaped associations with CCA-IMT and carotid plaque. No significant associations were found between other beverage groups and subclinical atherosclerosis.
CONCLUSIONS:
In midlife women, occasional coffee intake may be associated with more subclinical atherosclerosis while moderate alcoholic beverages intake may be associated with less subclinical atherosclerosis. Future work should focus on the determination of the optimal beverage intake profile for maximum cardiovascular benefits in midlife women.

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Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Incident Diabetes and Microvascular Disease.
Cardenas A, Hivert MF, Gold DR, Hauser R, Kleinman KP, Lin PD, Fleisch AF, Calafat AM, Ye X, Webster TF, Horton ES, Oken E.
Diabetes Care. 2019 Jul 11. pii: dc182254. doi: 10.2337/dc18-2254. [Epub ahead of print]
PMID: 31296647
Abstract
OBJECTIVE:
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are suspected endocrine disruptors widely detected across populations. We examine the extent to which PFASs are associated with diabetes incidence and microvascular disease. Secondarily, we tested whether a lifestyle intervention modifies associations and decreases concentrations.
RESEARCH DESIGN AND METHODS:
We analyzed data from a prospective cohort of 957 participants from the Diabetes Prevention Program (DPP) trial and Outcomes Study (DPPOS). At baseline, participants were randomized to an intensive lifestyle intervention of diet, physical activity, and behavior modification or a placebo medication. We quantified plasma concentrations of six PFASs at baseline and 2 years after randomization. Participants were monitored for ∼15 years, repeatedly tested for diabetes, and evaluated for microvascular disease at the end of the follow-up.
RESULTS:
A doubling in baseline Sb-PFOA concentration was associated with a 14% increase in diabetes risk for the placebo (hazard ratio {HR} 1.14, 95% CI 1.04, 1.25) but not in the lifestyle intervention group (HR 1.01, 95% CI 0.92, 1.11, P interaction = 0.11). Mean change in plasma baseline branched perfluorooctanoic acid concentration was greater for the placebo (0.96 ng/mL; 95% CI 0.71, 1.22) compared with the lifestyle intervention group (0.31 ng/mL; 95% CI 0.14, 0.48) 2 years after randomization. Each doubling in N-ethyl-perfluorooctane sulfonamido acetic acid was associated with 17% greater odds of prevalent microvascular disease (OR 1.17, 95% CI 1.05, 1.31), and a similar association was observed for perfluorodimethylhexane sulfonic acid (OR 1.18, 95% CI 1.04, 1.35), regardless of treatment.

CONCLUSIONS:
Some plasma PFASs were associated with diabetes and microvascular disease. Our results suggest that exercise and diet may attenuate the diabetogenic association of PFASs.

Effects of Dietary Protein Quantity on Bone Quantity following Weight Loss: A Systematic Review and Meta-analysis.
Wright CS, Li J, Campbell WW.
Adv Nutr. 2019 Jul 13. pii: nmz058. doi: 10.1093/advances/nmz058. [Epub ahead of print]
PMID: 31301138
Abstract
Research supports the hypothesis that higher total protein intake during weight loss promotes retention of lean soft tissue, but the effect of dietary protein quantity on bone mass, a lean hard tissue, is inconsistent. The purpose of this systematic review and meta-analysis was to assess the effect of dietary protein quantity [higher protein (HP): ≥25% of energy from protein or ≥1.0 g · kg body wt-1 · d-1; normal protein (NP): <25% of energy from protein or <1.0 g · kg body wt-1 · d-1] on changes in bone mineral density (BMD) and content (BMC; total body, lumbar spine, total hip, femoral neck) following a prescribed energy restriction. We hypothesized that an HP diet would attenuate the loss of BMD/BMC following weight loss in comparison to an NP diet. Two researchers systematically and independently screened 2366 publications from PubMed, Cochrane, Scopus, CINAHL, and Web of Science Core Collection and extracted data from 34 qualified publications. Inclusion criteria included the following: 1) healthy subjects ≥19 y; 2) a prescribed energy restriction; 3) measurements of total protein intake, BMD, and BMC; and 4) an intervention duration of ≥3 mo. Data from 10 of the 34 publications with 2 groups of different total protein intakes were extracted and used to conduct a random-effects model meta-analysis. A majority of publications (59%) showed a decrease in bone quantity following active weight loss, regardless of total protein intake. Statistically, the loss of total BMD (P = 0.016; weighted mean difference: +0.006 g/cm2; 95% CI: 0, 0.011 g/cm2) and lumbar spine BMD (P = 0.019; weighted mean difference: +0.017 g/cm2; 95% CI: 0.001, 0.033 g/cm2) was attenuated with an HP versus an NP weight-loss diet. However, the clinical significance is questionable given the modest weighted mean difference and study duration. Higher total protein intake does not exacerbate but may attenuate the loss of bone quantity following weight loss.
KEYWORDS:
bone mineral content; bone mineral density; dietary protein; energy restriction; lean hard tissue; meta-analysis; systematic review; total protein intake; weight loss

Food as medicine: Selenium enriched lentils offer relief against chronic arsenic poisoning in Bangladesh.
Smits JE, Krohn RM, Akhtar E, Hore SK, Yunus M, Vandenberg A, Raqib R.
Environ Res. 2019 Jun 28;176:108561. doi: 10.1016/j.envres.2019.108561. [Epub ahead of print]
PMID: 31299617
https://sci-hub.tw/10.1016/j.envres.2019.108561
Abstract
Chronic arsenic (As) exposure is a major environmental threat to human health affecting >100 million people worldwide. Low blood selenium (Se) increases the risk of As-induced health problems. Our aim was to reduce As toxicity through a naturally Se-rich lentil diet. In a randomized, double-blind, placebo-control trial in Bangladesh, 405 participants chronically exposed to As were enrolled. The intervention arm (Se-group) consumed Se-rich lentils (55 μg Se/day); the control arm received lentils of similar nutrient profile except with low Se (1.5 μg Se/day). Anthropometric measurements, blood, urine and stool samples, were taken at baseline, 3 and 6 months; hair at baseline and 6 months after intervention. Morbidity data were collected fortnightly. Measurements included total As in all biological samples, As metabolites in urine, and total Se in blood and urine. Intervention with Se-rich lentils resulted in higher urinary As excretion (p = 0.001); increased body mass index (p ≤ 0.01), and lower incidence of asthma (p = 0.05) and allergy (p = 0.02) compared to the control group. The Se-group demonstrated increased excretion of urinary As metabolite, dimethylarsinic acid (DMA) at 6 months compared to control group (p = 0.008). Consuming Se-rich lentils can increase As excretion and improve the health indicators in the presence of continued As exposure.
KEYWORDS:
Arsenic; Arsenic metabolites; Dietary intervention; Morbidity; Selenium; Toxicity

Dietary Fat Intake and the Risk of Skin Cancer: A Systematic Review and Meta-Analysis of Observational Studies.
Ruan L, Cheng SP, Zhu QX.
Nutr Cancer. 2019 Jul 12:1-11. doi: 10.1080/01635581.2019.1637910. [Epub ahead of print]
PMID: 31298947
Abstract
We conducted a meta-analysis to evaluate the association between fat intake and the risk of three major types of skin cancer including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). A comprehensive search of PubMed and EMBASE was performed to identify all relevant observational studies published up to December 1, 2018. Specific odds ratio (OR) or relative risk (RR) estimates for the highest versus the lowest intake of dietary fat and 95% confidence intervals (CI) from the included studies were pooled using random effect model. Three prospective cohort studies (175,675 participants and 30,915 BCC cases, 4,106 SCC cases and 1,638 CMM cases) and nine case-control studies (328 BCC cases, 493 SCC cases, 1,547 CMM cases and 2,660 controls) were identified. The pooled results indicated that dietary consumption of total fat and saturated fat were not associated with three major types of skin cancer. High consumption of monounsaturated fat was significantly associated with a decreased risk of BCC (RR: 0.90, 95% CI: 0.85-0.96) and high level of polyunsaturated fat intake was potentially positively associated with SCC (RR: 1.19, 9

[Call me a skeptic, but to me, a fatty acid from an animal or plant source is the same.]
Plant-sourced and animal-sourced monounsaturated fatty acid intakes in relation to mortality: a prospective nationwide cohort study.
Mao L, Zhang Y, Wang W, Zhuang P, Wu F, Jiao J.
Eur J Nutr. 2019 Jul 11. doi: 10.1007/s00394-019-02048-8. [Epub ahead of print]
PMID: 31297602
https://sci-hub.tw/10.1007/s00394-019-02048-8
Abstract
PURPOSE:
Monounsaturated fatty acids (MUFAs) are typical components of various plant-sourced and animal-sourced foods. However, the associations of MUFA consumption from different sources with mortality remain unclear. This study aimed to investigate the relationships between MUFA intakes from plant and animal sources and mortality.
METHODS:
A total of 14,305 participants from China Health and Nutrition Survey were prospectively followed up for 14 years. Dietary intake of MUFAs was assessed by 3-day 24-h dietary records in each round. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS:
A total of 1006 deaths occurred during 199,091 person-years of follow-up. Intake of total MUFAs was not associated with mortality (P-trend = 0.17). The plant-sourced MUFA intake was strongly associated with lower mortality [HRQ4vsQ1 (95% CI) 0.72 (0.58-0.89); P-trend = 0.008], whereas animal-sourced MUFA intake showed no significant association. Likewise, oleic acid (OA) and palmitoleic acid (PA) intakes from plant sources were also inversely associated with mortality [HRQ4vsQ1 (95% CI) 0.66 (0.52-0.84) for OA and 0.73 (0.59-0.91) for PA], while animal-sourced OA and PA were not related to mortality. Theoretically replacing saturated fatty acids (SFAs) (5% of total energy) with isocaloric plant-sourced MUFAs was associated with 15% (95% CI 5-25%) lower mortality. In addition, 18% (95% CI 10-26%) lower mortality was observed when theoretically replacing the sum of SFAs and animal-sourced MUFAs with isocaloric plant-sourced MUFAs.
CONCLUSIONS:
Intakes of MUFAs, including OA and PA, from plant but not animal sources were associated with lower total mortality. These findings suggested the importance of consuming MUFAs from plant-based foods for overall health.
KEYWORDS:
Animal sources; China Health and Nutrition Survey; Monounsaturated fatty acids; Mortality; Plant sources

Pregnancy dietary cholesterol intake, major dietary cholesterol sources, and the risk of gestational diabetes mellitus: A prospective cohort study.
Wu Y, Sun G, Zhou X, Zhong C, Chen R, Xiong T, Li Q, Yi N, Xiong G, Hao L, Yang N, Yang X.
Clin Nutr. 2019 Jun 28. pii: S0261-5614(19)30272-9. doi: 10.1016/j.clnu.2019.06.016. [Epub ahead of print]
PMID: 31296343
Abstract
BACKGROUND & AIMS:
The Scientific Report of 2015 Dietary Guidelines Advisory Committee recommended the elimination of dietary cholesterol limits. However, cholesterol intake increases during pregnancy and studies regarding the association between dietary cholesterol and gestational diabetes mellitus (GDM) are limited. We evaluate the association of total dietary cholesterol and different sources of cholesterol intake during pregnancy, with GDM risk and blood glucose levels in a Chinese prospective cohort study.
METHODS:
A total of 2124 pregnant women from the Tongji Maternal and Child Health Cohort was included. A validated semi-quantitative food frequency questionnaire was used to assess dietary cholesterol intake prior to GDM diagnosis. GDM was diagnosed by the 75-g 2-h oral glucose tolerance test. Cubic-restricted spline function and logistic regression analyses were used to evaluate the association between dietary cholesterol intake during pregnancy and GDM. Generalized linear models were conducted to examine the associations of cholesterol intake with fasting blood glucose (FBG), 1-h post-load blood glucose (PBG) and 2-h PBG.
RESULTS:
The average dietary cholesterol intake was 379.1 mg/d, and cholesterol from eggs explained 64.2% of the variability. Total dietary cholesterol intake and cholesterol from eggs rather than other foods, were linearly associated with GDM risk, with adjusted OR for GDM of 2.10 (95%CI: 1.24, 3.58) for total cholesterol intake and 1.83 (95%CI: 1.08, 3.07) for cholesterol from eggs comparing the highest versus lowest quintile. A 100-mg/d increase in total cholesterol and cholesterol from eggs intake were associated with an increased GDM risk by 18% and 16%, respectively. Moreover, higher maternal dietary total cholesterol could increase FBG and 1-h PBG, while cholesterol from eggs increased FBG only.
CONCLUSION:
Higher dietary cholesterol from eggs intake during pregnancy was associated with greater risk of GDM.
KEYWORDS:
Cohort study; Dietary cholesterol; Gestational diabetes mellitus; Pregnancy nutrition; Pregnant women

Effect of low-ratio n-6/n-3 PUFA on blood glucose: a meta-analysis.
Li N, Yue H, Jia M, Liu W, Qiu B, Hou H, Huang F, Xu T.
Food Funct. 2019 Jul 11. doi: 10.1039/c9fo00323a. [Epub ahead of print]
PMID: 31292599
Abstract
OBJECTIVE:
The aim of this meta-analysis was to investigate the effect of increasing dietary low-ratio n-6/n-3 polyunsaturated fatty acid (PUFA) intake on blood glucose and other related indicators.
METHODS:
We systematically searched randomized controlled trials of low-ratio n-6/n-3 PUFA intervention on PubMed, Embase, Cochrane library and related references up to August 2018. The change values were calculated as the weighted mean difference (WMD) by using a random-effect model.
RESULTS:
Eleven randomized controlled trials were included. No significant effect of dietary low-ratio n-6/n-3 PUFA supplementation was observed on fasting blood glucose (WMD: 0.057 mmol L-1; 95% CI: -0.090 to 0.204 mmol L-1), insulin (WMD: -0.757 mIU L-1; 95% CI: -2.419 to 0.904 mIU L-1), insulin resistance index (WMD: -0.201; 95% CI: -0.566 to 0.165), and glycosylated hemoglobin (WMD: -0.063%; 95% CI: -0.061 to 0.186%). Subgroup analysis showed that the effect of low-ratio n-6/n-3 PUFA on the reduction of the plasma insulin level in North America (WMD: -3.473 mIU L-1; 95% CI: -5.760 to -1.185 mIU L-1) was more obvious than that in Asian countries (WMD: -0.797 mIU L-1; 95% CI: -2.497 to 0.902 mIU L-1) and European countries (WMD: -0.063 mIU L-1; 95% CI: -0.061 to 0.186 mIU L-1). In the subgroup of diabetic subjects, low-ratio n-6/n-3 PUFA supplementation can decrease the plasma insulin level (WMD: -3.010 mIU L-1; 95% CI: -5.371 to -0.648 mIU L-1) and insulin resistance index (WMD: -0.460; 95% CI: -0.908 to -0.012). When the intervention period was longer than 8 weeks, low-ratio n-6/n-3 PUFA supplementation could also decrease the plasma insulin level (WMD: -2.782 mIU L-1; 95% CI: -4.946 to -0.618 mIU L-1). No significant publication bias was observed for all blood glucose and other related indicators as suggested by Begg's test and Egger's test.
CONCLUSION:
Our meta-analysis found that low-ratio n-6/n-3 PUFA supplementation could improve the glucose metabolism by reducing the insulin and insulin resistance in the diabetic patients. Low-ratio n-6/n-3 PUFA supplementation could reduce the plasma insulin level when the supplementation duration was longer than 8 weeks.

New Trend in Old-Age Mortality: Gompertzialization of Mortality Trajectory.
Gavrilov LA, Gavrilova NS.
Gerontology. 2019 May 20:1-7. doi: 10.1159/000500141. [Epub ahead of print] Review.
PMID: 31295741
Abstract
There is great interest among gerontologists, demographers, and actuaries in the question concerning the limits to human longevity. Attempts at getting answers to this important question have stimulated many studies on late-life mortality trajectories, often with opposing conclusions. One group of researchers believes that mortality stops growing with age at extreme old ages, and that hence there is no fixed limit to the human life span. Other studies found that mortality continues to grow with age up to extreme old ages. Our study suggests a possible solution to this controversy. We found that mortality deceleration is best observed when older, less accurate life span data are analyzed, while in the case of more recent and reliable data there is a persistent mortality growth with age. We compared the performance (goodness of fit) of two competing mortality models - the Gompertz model and the Kannisto ("mortality deceleration") model - at ages of 80-105 years using data for 1880-1899 single-year birth cohorts of US men and women. The mortality modeling approach suggests a transition from mortality deceleration to the Gompertzian mortality pattern over time for both men and women. These results are consistent with the hypothesis about disappearing mortality deceleration over time due to improvement in the accuracy of age reporting. In the case of more recent data, mortality continues to grow with age even at very old ages. This observation may lead to more conservative estimates of future human longevity records.
KEYWORDS:
Age misreporting; Biodemography; Gompertz law; Kannisto model; Late-life mortality; Longevity; Mortality deceleration; Old age

Acute effect of Finnish sauna bathing on brachial artery flow-mediated dilation and reactive hyperemia in healthy middle-aged and older adults.
Gravel H, Coombs GB, Behzadi P, Marcoux-Clément V, Barry H, Juneau M, Nigam A, Gagnon D.
Physiol Rep. 2019 Jul;7(13):e14166. doi: 10.14814/phy2.14166.
PMID: 31293098
Abstract
Regular Finnish sauna bathing is associated with a reduced risk of all-cause and cardiovascular mortality in middle-aged and older adults. Potential acute physiological adaptations induced by sauna bathing that underlie this relationship remain to be fully elucidated. The purpose of this study was to determine if typical Finnish sauna sessions acutely improve brachial artery flow-mediated dilation (FMD) and reactive hyperemia (RH) in healthy middle-aged and older adults. Using a randomized crossover design, FMD and RH were evaluated in 21 healthy adults (66 ± 6 years, 10 men/11 women) before and after each of the following conditions: (1) 1 × 10 min of Finnish sauna bathing (80.2 ± 3.2°C, 23 ± 2% humidity); (2) 2 × 10 min of sauna bathing separated by 10 min of rest outside the sauna; (3) a time control period (10 min of seated rest outside the sauna). FMD was taken as the peak change from baseline in brachial artery diameter following 5 min of forearm ischemia, whereas RH was quantified as both peak and area-under-the-curve forearm vascular conductance postischemia. FMD was statistically similar pre to post 1 × 10 min (4.69 ± 2.46 to 5.41 ± 2.64%, P = 0.20) and 2 × 10 min of sauna bathing (4.16 ± 1.79 to 4.55 ± 2.14%, P = 0.58). Peak and area-under-the-curve forearm vascular conductance were also similar following both sauna interventions. These results suggest that typical Finnish sauna bathing sessions do not acutely improve brachial artery FMD and RH in healthy middle-aged and older adults.
KEYWORDS:
Aging; flow-mediated dilation; heat

Contribution of protein intake and its interaction with physical activity to transitions between disability states and to death in very old adults: the Newcastle 85+ Study.
Mendonça N, Kingston A, Granic A, Hill TR, Mathers JC, Jagger C.
Eur J Nutr. 2019 Jul 10. doi: 10.1007/s00394-019-02041-1. [Epub ahead of print]
PMID: 31292749
Abstract
INTRODUCTION:
Growth in the number of very old (≥ 85 years) adults will likely lead to increased prevalence of disability. Our aim was to determine the contribution of protein intake, and the interaction between protein intake and physical activity (PA), to the transition between disability states and to death in the very old using the Newcastle 85+ Study.
METHODS:
The analytic sample comprised of 717 older adults aged 85 years at baseline and living in the community. Protein intake was estimated with 2 × 24-h multiple pass recalls (24 h-MPR) at baseline. Disability was measured as difficulty performing 17 activities of daily living (ADL) at baseline, at 18, 36, and 60 months, and defined as having difficulties in one or more ADL. The contribution of protein intake [g/kg adjusted body weight/day (g/kg aBW/d)] to transition probabilities to and from disability, and to death over 5 years was examined by multi-state models adjusted for key health covariates.
RESULTS:
Participants were expected to spend 0.8 years (95% CI 0.6-1.0) disability-free and 2.8 years (95% CI 2.6-2.9) with disability between the ages 85 and 90 years. One unit increase in protein intake (g/kg aBW/d) halved the likelihood of incident disability (HR 0.44, 95% CI 0.24-0.83) but not for other transitions. Similar reductions in disability incidence were also found in individuals with protein intake ≥ 0.8 (HR 0.50, 95% CI 0.31-0.80) and ≥ 1 g/kg aBW/d (HR 0.49, 95% CI 0.33-0.73). Participants with high PA and protein intake ≥ 1 g/kg aBW/d were less likely to transition from disability-free to disability than those within the same PA level but with protein intake < 1 g/kg aBW/d (HR 0.45, 95% CI 0.28-0.72).
CONCLUSION:
Higher protein intake, especially in combination with higher physical activity, may delay the incidence of disability in very old adults.
KEYWORDS:
Disability; Malnutrition; Multi-state; PROMISS; Physical activity; Protein; Transitions; ‘Aged, 80 and over’

Quantity and quality of mental activities and the risk of incident mild cognitive impairment
Janina Krell-Roesch, Jeremy A. Syrjanen, Maria Vassilaki, Mary M. Machulda, Michelle M. Mielke, David S. Knopman, Walter K. Kremers, Ronald C. Petersen, Yonas E. Geda
First published July 10, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007897
https://n.neurology.org/content/neurology/early/2019/07/10/WNL.0000000000007897.full.pdf
Abstract
Objective To investigate whether timing, number, and frequency of mentally stimulating activities in midlife and late life are associated with the risk of incident mild cognitive impairment (MCI).
Methods We conducted a prospective cohort study in the setting of the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota, including 2,000 individuals aged ≥70 years who were cognitively unimpaired at baseline and were followed for a median of 5.0 years. Participants completed a self-reported survey on timing, number, and frequency of engagement in 5 mentally stimulating activities (reading books, computer use, social activities, playing games, craft activities) at baseline.
Results The risk of incident MCI was significantly reduced for participants who engaged in social activities (hazard ratio [95% confidence interval] 0.80 [0.64–0.99]) and playing games (0.80 [0.66–0.98]) in both late life and midlife combined. Using a computer was associated with a decreased risk regardless of timing (not late life but midlife: 0.52 [0.31–0.88]; late life but not midlife: 0.70 [0.56–0.88]; late life and midlife: 0.63 [0.51–0.79]). Craft activities were associated with a reduced risk of incident MCI only when carried out in late life but not midlife (0.58 [0.34–0.97]). Furthermore, engaging in a higher number of activities in late life was associated with a significantly reduced risk of incident MCI (any 2 activities: 0.72 [0.53–0.99], any 3: 0.55 [0.40–0.77], any 4: 0.44 [0.30–0.65], all 5: 0.57 [0.34–0.96]).
Conclusion Engaging in a higher number of mentally stimulating activities, particularly in late life, is associated with a decreased risk of MCI among community-dwelling older persons.

Association between greater leg length and increased incidence of colorectal cancer: the atherosclerosis risk in communities (ARIC) study.
Onyeaghala G, Lutsey PL, Demerath EW, Folsom AR, Joshu CE, Platz EA, Prizment AE.
Cancer Causes Control. 2019 Aug;30(8):791-797. doi: 10.1007/s10552-019-01192-0. Epub 2019 Jun 4.
PMID: 31165420
Abstract
PURPOSE:
Previous studies have reported that taller people have an increased risk of colorectal cancer (CRC). We examined the association of two height components-leg length and sitting height-with CRC risk in 14,532 individuals aged 45-64 years in the Atherosclerosis Risk in Communities study.
METHODS:
Anthropometrics were measured at baseline (1987-1989). Incident CRC cases (n = 382) were ascertained from 1987 to 2012. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios for CRC and colon cancer across quintiles of sex-specific leg length and sitting height.
RESULTS:
The highest (versus the lowest) quintile of leg length was associated with a 36% greater CRC risk (p-trend = 0.04), and 51% greater colon cancer risk (p-trend = 0.01). For the top four quintiles combined, risk was increased by 34% for CRC and by 45% for colon cancer versus the lowest quintile. Total height and sitting height were not significantly associated with CRC or colon cancer risk. A small number of cases (n = 57) limited our ability to conduct subgroup analyses for rectal cancer.
CONCLUSIONS:
A positive association of leg length with CRC and colon cancer risk suggests that biological mechanisms leading to greater leg length during puberty may explain the association between taller height and CRC.
KEYWORDS:
ARIC; Colorectal cancer; Leg length; Prospective cohort; Risk

Soy and tea intake on cervical cancer risk: the Singapore Chinese Health Study.
Paul P, Koh WP, Jin A, Michel A, Waterboer T, Pawlita M, Wang R, Yuan JM, Butler LM.
Cancer Causes Control. 2019 Aug;30(8):847-857. doi: 10.1007/s10552-019-01173-3. Epub 2019 Jun 1.
PMID: 31154549
Abstract
PURPOSE:
Soy isoflavones and tea catechins have immunomodulating and chemopreventive properties relevant for cervical carcinogenesis; however, there are limited epidemiologic data on the relationship of soy and tea consumption with cervical cancer risk. The aim of our study was to examine effects of soy and tea intake on cervical cancer risk among Singapore Chinese women.
METHODS:
The association between intake of soy and tea drinking and cervical cancer risk was investigated in a prospective, population-based cohort of 30,744 Chinese women in Singapore with an average 16.7 years of follow-up and 312 incident cervical cancer cases. Multivariable proportional hazard models were used to estimate hazard ratio (HR) and 95% confidence interval (CI) of cervical cancer associated with intake levels of soy and tea.
RESULTS:
High intake of soy alone was associated with a statistically borderline significant 20% reduced risk of cervical cancer (HR 0.80, 95% CI 0.61, 1.05) while green tea alone was not (HR 0.97, 95% CI: 0.76, 1.22). In stratified analysis, high intake of soy was associated with a statistically significant decrease in cervical cancer risk among green tea drinkers (HR 0.43; 95% CI 0.28, 0.69) but not among non-drinkers of green tea. The difference in the soy-cervical cancer risk association between green tea drinkers and non-drinkers was statistically significant (p for interaction = 0.004). This inverse association between soy intake and cervical cancer risk remained after further adjustment for human papillomavirus serostatus. Black tea consumption was not associated with cervical cancer risk.
CONCLUSIONS:
These findings suggest that a protective effect of soy against cervical cancer development may depend on green tea constituents.
KEYWORDS:
Black tea; Cervical cancer; Green tea; Soy; Soy isoflavone

Anticoagulants and cancer mortality in the Finnish randomized study of screening for prostate cancer.
Kinnunen PTT, Murtola TJ, Talala K, Taari K, Tammela TLJ, Auvinen A.
Cancer Causes Control. 2019 Aug;30(8):877-888. doi: 10.1007/s10552-019-01195-x. Epub 2019 Jun 17.
PMID: 31209595
Abstract
PURPOSE:
Anticoagulants may reduce mortality of cancer patients, though the evidence remains controversial. We studied the association between different anticoagulants and cancer death.
METHODS:
All anticoagulant use during 1995-2015 was analyzed among 75,336 men in the Finnish Randomized Study of Screening for Prostate Cancer. Men with prevalent cancer were excluded. Multivariable Cox regression was performed to compare risk of death from any cancer and disease-specific death from 9 specific cancer types between (1) anticoagulant users overall and (2) warfarin users compared to anticoagulant non-users and (3) warfarin or (4) low-molecular-weight heparins (LMWH) compared to users of other anticoagulants. Medication use was analyzed as time-dependent variable to minimize immortal time bias. 1-, 2- and 3-year lag-time analyses were performed.
RESULTS:
During a median follow-up of 17.2 years, a total of 27,233 men died of whom 8033 with cancer as the primary cause of death. In total, 32,628 men (43%) used anticoagulants. Any anticoagulant use was associated with an increased risk of cancer death (HR = 2.50, 95% CI 2.37-2.64) compared to non-users. Risk was similar independent of the amount, duration, or intensity of use. The risk increase was observed both among warfarin and LMWH users, although not as strong in warfarin users. Additionally, cancer-specific risks of death were similar to overall cancer mortality in all anticoagulant categories.
CONCLUSION:
Our study does not support reduced cancer mortality among anticoagulant users. Future studies on drug use and cancer mortality should be adjusted for anticoagulants as they are associated with significantly higher risk of cancer death.
KEYWORDS:
Anticoagulant; Cancer mortality; Cohort; Low-molecular weight heparins; Warfarin

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Association of Lifestyle and Genetic Risk With Incidence of Dementia.
Lourida I, Hannon E, Littlejohns TJ, Langa KM, Hyppönen E, Kuzma E, Llewellyn DJ.
JAMA. 2019 Jul 14. doi: 10.1001/jama.2019.9879. [Epub ahead of print]
PMID: 31302669
https://sci-hub.tw/10.1001/jama.2019.9879
Abstract
IMPORTANCE:
Genetic factors increase risk of dementia, but the extent to which this can be offset by lifestyle factors is unknown.
OBJECTIVE:
To investigate whether a healthy lifestyle is associated with lower risk of dementia regardless of genetic risk.
DESIGN, SETTING, AND PARTICIPANTS:
A retrospective cohort study that included adults of European ancestry aged at least 60 years without cognitive impairment or dementia at baseline. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016 or 2017.
EXPOSURES:
A polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption, categorized into favorable, intermediate, and unfavorable lifestyles.
MAIN OUTCOMES AND MEASURES:
Incident all-cause dementia, ascertained through hospital inpatient and death records.
RESULTS:
A total of 196 383 individuals (mean [SD] age, 64.1 [2.9] years; 52.7% were women) were followed up for 1 545 433 person-years (median [interquartile range] follow-up, 8.0 [7.4-8.6] years). Overall, 68.1% of participants followed a favorable lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Twenty percent had high polygenic risk scores, 60% had intermediate risk scores, and 20% had low risk scores. Of the participants with high genetic risk, 1.23% (95% CI, 1.13%-1.35%) developed dementia compared with 0.63% (95% CI, 0.56%-0.71%) of the participants with low genetic risk (adjusted hazard ratio, 1.91 [95% CI, 1.64-2.23]). Of the participants with a high genetic risk and unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) developed dementia compared with 0.56% (95% CI, 0.48%-0.66%) of participants with low genetic risk and favorable lifestyle (hazard ratio, 2.83 [95% CI, 2.09-3.83]). There was no significant interaction between genetic risk and lifestyle factors (P = .99). Among participants with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) of those with a favorable lifestyle developed dementia compared with 1.78% (95% CI, 1.38%-2.28%) with an unfavorable lifestyle (hazard ratio, 0.68 [95% CI, 0.51-0.90]).
CONCLUSIONS AND RELEVANCE:
Among older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk. A favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk.

Meat intake and risk of hepatocellular carcinoma in two large US prospective cohorts of women and men.
Ma Y, Yang W, Li T, Liu Y, Simon TG, Sui J, Wu K, Giovannucci EL, Chan AT, Zhang X.
Int J Epidemiol. 2019 Jul 13. pii: dyz146. doi: 10.1093/ije/dyz146. [Epub ahead of print]
PMID: 31302687
Abstract
BACKGROUND:
Epidemiological evidence on the associations between meat intake and risk of hepatocellular carcinoma (HCC) was limited and inconsistent.
METHODS:
We prospectively examined the association between consumption of meats and meat mutagens with HCC risk using data from the Nurses' Health Study and the Health Professionals Follow-up Study. Cox proportional-hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for known liver-cancer risk factors.
RESULTS:
During up to 32 years of follow-up, we documented 163 incident HCC cases. The HRs of HCC for the highest vs the lowest tertile intake levels were 1.84 (95% CI: 1.16-2.92, Ptrend = 0.04) for processed red meats and 0.61 (95% CI: 0.40-0.91, Ptrend = 0.02) for total white meats. There was a null association between unprocessed red meats and HCC risk (HR = 1.06, 95% CI: 0.68-1.63, Ptrend = 0.85). We found both poultry (HR = 0.60, 95% CI: 0.40-0.90, Ptrend = 0.01) and fish (HR = 0.70, 95% CI: 0.47-1.05, Ptrend = 0.10) were inversely associated with HCC risk. The HR for HCC risk was 0.79 (95% CI: 0.61-1.02) when 1 standard deviation of processed red meats was substituted with an equivalent amount of poultry or fish intake. We also found a suggestive positive association of intake of meat-derived mutagenicity or heterocyclic amines with risk of HCC.
CONCLUSIONS:
Processed red meat intake might be associated with higher, whereas poultry or possibly fish intake might be associated with lower, risk of HCC. Replacing processed red meat with poultry or fish might be associated with reduced HCC risk.
KEYWORDS:
Red meat; cohort study; fish; hepatocellular carcinoma; poultry; processed red meat

Effect of urinary sodium-to-potassium ratio change on blood pressure in participants of the longitudinal health of adults study - ELSA-Brasil.
Pereira TSS, Mill JG, Griep RH, Sichieri R, Molina MDCB.
Medicine (Baltimore). 2019 Jul;98(28):e16278. doi: 10.1097/MD.0000000000016278.
PMID: 31305409
https://journals.lww.com/md-journal/fulltext/2019/07120/Effect_of_urinary_sodium_to_potassium_ratio_change.22.aspx
Abstract
To assess the effect of changing the sodium to potassium (Na/K) ratio on blood pressure at 4 years of follow-up.The measurements were carried out under identical conditions in two study periods (2008-2010 and 2012-2014). Urinary excretion of sodium and potassium (mmol/L) over 12 nocturnal hours was used to calculate the Na/K ratio and categorized by quintile. The 24-hour sodium and potassium intake was estimated using a validated equation. The mean BP was calculated from 3 measurements after 5 minutes of rest. Of the 15,105 participants at baseline, 14,014 completed the first follow-up. Participants without validated urine collection (n = 5,041), using antihypertensive medication (n = 3,860) at either time points or reporting bariatric surgery during follow-up (n = 45) were excluded. The differences between follow-up and baseline values were calculated for BP and the Na/K ratio. Analyses were stratified by sex and adjusted for confounding variables.Sodium intake did not change from baseline, but potassium intake increased by approximately 150 mg in both sexes (P < .001), with a consequent reduction of the Na/K ratio. The highest quintile of change in the Na/K ratio was associated with greater variation in BP. When adjusted for covariates, it is possible to observe an increase in SBP in women from the third quintile of the Na/K ratio, in men this increase was observed from the fourth quintile. However, for DBP this increase is observed from the third quintile in both men and women.Increase in SBP was observed in women from the third quintile of the Na/K ratio, in men this increase is observed from the fourth quintile. However, for DBP this increase is observed from the third quintile in both men and women. The Na/K ratio demonstrated a greater association in BP.

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Genetic background, epigenetic factors and dietary interventions which influence human longevity.
Costa D, Scognamiglio M, Fiorito C, Benincasa G, Napoli C.
Biogerontology. 2019 Jul 15. doi: 10.1007/s10522-019-09824-3. [Epub ahead of print] Review.
PMID: 31309340
Abstract
Longevity is mainly conditioned by genetic, epigenetic and environmental factors. Different genetic modifications seem to be positively associated to longevity, including SNPs in SIRT1, APOE, FOXO3A, ACE, ATM, NOS1 and NOS2 gene. Epigenetic changes as DNA hyper- and hypo-methylation influence significantly human longevity by activating/deactivating different genes involved in physiological mechanisms. Several studies have confirmed that centenarians have a lower DNA methylation content compared to young subjects, which showed more homogeneously methylated DNA region. Also the up-regulation of miR-21 seems to be more associated with longevity in different populations of long-lived subjects, suggesting its role as potential epigenetic biomarkers. A non-pharmacological treatment that seems to contrast age-related diseases and promote longevity is represented by dietary intervention. It has been evaluated the effects of dietary restriction of both single nutrients or total calories to extend lifespan. However, in daily practice it is very difficult to guarantee adherence/compliance of the subjects to dietary restriction and at the same time avoid dangerous nutritional deficiencies. As consequence, the attention has focused on a variety of substances both drugs and natural compounds able to mime the beneficial effects of caloric restriction, including resveratrol, quercetin, rapamycin, metformin and 2-deoxy-D-glucose.
KEYWORDS:
Calorie restriction mimetic; Dietary restriction; Epigenetic mechanism; Genetic modification; Longevity; Longevity molecular biomarkers

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Dairy Product Consumption and Prostate Cancer Risk in the United States.
Preble I, Zhang Z, Kopp R, Garzotto M, Bobe G, Shannon J, Takata Y.
Nutrients. 2019 Jul 16;11(7). pii: E1615. doi: 10.3390/nu11071615.
PMID: 31315238
Abstract
An ongoing controversy exists regarding the effect of dairy products on prostate cancer risk in observational studies. We prospectively investigated the associations between dairy product consumption and prostate cancer risk among men in the United States. After calculating pre-diagnostic intake of individual or subgroups of dairy products using a validated food frequency questionnaire, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for pathologically-verified cases of incident prostate cancer among men, overall, or stratified by severity. Among 49,472 men, 4134 were diagnosed with prostate cancer during an average follow-up period of 11.2 years. The median total dairy intake was 101 g/1000 kcal. Consumption of total, individual, or subgroups of dairy products was not statistically significantly associated with prostate cancer risk overall (HR = 1.05, 95% CI = 0.96-1.15 comparing the highest with lowest quartile) or stratified by severity, except for regular-fat dairy product intake with late-stage prostate cancer risk (HR = 1.37, 95% CI = 1.04-1.82 comparing the highest with lowest quartile) and 2%-fat milk intake with advanced prostate cancer risk (HR = 1.14, 95% CI = 1.02-1.28 comparing the higher than median intake with no intake group). Our findings do not support the previously reported harmful impact of dairy consumption on overall prostate cancer risk among men in the United States.
KEYWORDS:
United States; dairy products; prostate cancer risk
 
Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition.
Christakoudi S, Kakourou A, Markozannes G, Tzoulaki I, Weiderpass E, Brennan P, Gunter M, Dahm CC, Overvad K, Olsen A, Tjønneland A, Boutron-Ruault MC, Madika AL, Severi G, Katzke V, Kühn T, Bergmann MM, Boeing H, Karakatsani A, Martimianaki G, Thriskos P, Masala G, Sieri S, Panico S, Tumino R, Ricceri F, Agudo A, Redondo-Sánchez D, Colorado-Yohar SM, Mokoroa O, Melander O, Stocks T, Häggström C, Harlid S, Bueno-de-Mesquita B, van Gils CH, Vermeulen RCH, Khaw KT, Wareham NJ, Tong TYN, Freisling H, Johansson M, Lennon H, Aune D, Riboli E, Trichopoulos D, Trichopoulou A, Tsilidis KK.
Int J Cancer. 2019 Jul 18. doi: 10.1002/ijc.32576. [Epub ahead of print]
PMID: 31319002
Abstract
Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HR) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating centre and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR=1.12 (1.08-1.17) per 10mmHg higher SBP and HR=1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR=1.16 (1.07-1.26) (SBP), HR=1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR=1.08 (1.04-1.12) (SBP), HR=1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, post-menopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC, or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR=0.91 (0.82-1.00) and lymphomas: HR=0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.
KEYWORDS:
Europe; association; cancer; cohort; epidemiology; hypertension; morphology; risk factors

 

Edited by AlPater

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Risks of light and moderate alcohol use in fatty liver disease - follow-up of population cohorts.
Åberg F, Puukka P, Salomaa V, Männistö S, Lundqvist A, Valsta L, Perola M, Färkkilä M, Jula A.
Hepatology. 2019 Jul 19. doi: 10.1002/hep.30864. [Epub ahead of print]
PMID: 31323122
Abstract
The effects of alcohol use in non-alcoholic fatty-liver disease are unclear. We investigated the impact of alcohol use in fatty liver disease on incident liver, cardiovascular, and malignant disease, and death. Study comprised 8345 persons with hepatic steatosis (fatty-liver index >60) who participated in the health-examination surveys (FINRISK 1992-2012 or Health 2000), with available data on baseline alcohol intake. Main exclusions were baseline clinical liver disease, viral hepatitis, ethanol intake >50g/day, and current abstainers. Data were linked with national registers for hospital admissions, malignancies and death regarding liver, cardiovascular, and malignant disease, and all-cause death. Adjustment were for multiple confounders. Alcohol consumption showed a dose-dependent risk increase for incident advanced liver disease and malignancies. Consuming 10-19g/day of alcohol in general, or 0-9g/day as non-wine beverages, doubled the risk for advanced liver disease compared to lifetime abstainers. In contrast, alcohol intake up to 49g/day was associated with a 22-40% reduction of incident CVD. We observed a J-shaped association between alcohol intake and all-cause death with a maximal risk reduction of 21% (95%CI 5-34%) at alcohol intake of 0-9g/day compared to lifetime abstainers. However, these benefits on CVD and mortality were only observed in never smokers. Alcohol intake above 30g/day yielded increased risk estimates for mortality compared to lifetime abstainers. In a subpopulation with longitudinal data, alcohol intake remained stable over time in >80% of subjects. CONCLUSION: Even low alcohol intake in fatty liver disease is associated with increased risks for advanced liver disease and cancer. Low to moderate alcohol use is associated with reduced mortality and CVD risk, but only among never smokers. This article is protected by copyright.
KEYWORDS:
NAFLD ; cancer; cardiovascular; liver cirrhosis; mortality

Effects of Multiple Cycles of Weight Loss and Regain on the Body-Weight Regulatory System in Rats.
Rosenbaum JL, Frayo RS, Melhorn SJ, Cummings DE, Schur EA.
Am J Physiol Endocrinol Metab. 2019 Jul 19. doi: 10.1152/ajpendo.00110.2019. [Epub ahead of print]
PMID: 31322412
Abstract
OBJECTIVE:
We studied the effects of multiple cycles of weight loss and regain on the defended body weight in rats.
METHODS:
36 male Wistar rats were divided into 3 weight-matched groups: weight cyclers (n=18), ad libitum-fed controls (n=9), and maturity controls (n=9). Cyclers underwent four rounds of 20% weight loss from 50% caloric restriction, each cycle followed by recovery to stable plateau weight on ad libitum feeding. Controls ate ad libitum. Maturity controls ate ad libitum then weight cycled the final two rounds to evaluate the effect of age in later cycles.
RESULTS:
Cyclers post-diet plateau weight became progressively lower than that of controls. With each weight-loss, ghrelin increased, while insulin and leptin decreased; the magnitude of these changes did not differ across cycles. After 4 rounds, cyclers weight (504+7 vs. 540+22 g; P<0.05) and percent body fat (11.7 vs. 15.2%; P<0.05) were lower than in controls. After a 4-mo follow-up period of ad libitum feeding, cyclers maintained a lower total fat-pad mass versus controls (8.6+0.5 vs. 15.9+3.6 g; P<0.01) and a lower glucose area-under-the-curve on oral glucose tolerance tests (P<0.05).
CONCLUSIONS:
Repeated weight-loss cycles exerted positive effects, durably lowering defended levels of body adiposity and improving glucose tolerance.
KEYWORDS:
ghrelin; weight cycling; weight maintenance

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