Change in habitual intakes of flavonoid-rich foods and mortality in US males and females.

BACKGROUND: Higher baseline intakes of flavonoid-rich foods and beverages are associated with a lower risk of chronic disease and mortality in observational studies. However, associations between changes in intakes and mortality remain unclear. We aimed to evaluate associations between 8-year changes in intakes of (1) individual flavonoid-rich foods and (2) a composite measure (termed the 'flavodiet') of foods and beverages that are known to be main contributors to flavonoid intake and subsequent total and cause-specific mortality. METHODS: We evaluated associations between 8-year changes in intakes of (1) individual flavonoid-rich foods and (2) a novel 'flavodiet' score and total and cause-specific mortality. We included 55,786 females from the Nurses' Health Study (NHS) and 29,800 males from the Health Professionals Follow-up Study (HPFS), without chronic disease at baseline in our analyses. Using multivariable-adjusted Cox proportional hazard models, we examined associations of 8-year changes in intakes of (1) flavonoid-rich foods and (2) the flavodiet score with subsequent 2-year lagged 6-year risk of mortality adjusting for baseline intakes. Data were pooled using fixed-effects meta-analyses. RESULTS: We documented 15,293 deaths in the NHS and 8988 deaths in HPFS between 1986 and 2018. For blueberries, red wine and peppers, a 5%, 4% and 9% lower risk of mortality, respectively, was seen for each 3.5 servings/week increase in intakes while for tea, a 3% lower risk was seen for each 7 servings/week increase [Pooled HR (95% CI) for blueberries; 0.95 (0.91, 0.99); red wine: 0.96 (0.93, 0.99); peppers: 0.91 (0.88, 0.95); and tea: 0.97 (0.95, 0.98)]. Conversely, a 3.5 servings/week increase in intakes of onions and grapefruit plus grapefruit juice was associated with a 5% and 6% higher risk of total mortality, respectively. An increase of 3 servings per day in the flavodiet score was associated with an 8% lower risk of total mortality [Pooled HR: 0.92 (0.89, 0.96)], and a 13% lower risk of neurological mortality [Pooled HR: 0.87 (0.79, 0.97)], after multivariable adjustments. CONCLUSIONS: Encouraging an increased intake of specific flavonoid-rich foods and beverages, namely tea, blueberries, red wine, and peppers, even in middle age, may lower early mortality risk.

The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial.

BACKGROUND: Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT). METHODS: In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3-4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues. RESULTS: Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: - 2.7%, green-MED: - 3.9%) and waist circumference (MED: - 4.7%, green-MED: - 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: - 4.2%, MED: - 6.0%, green-MED: - 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss (p < 0.05, multivariate models). CONCLUSIONS: A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03020186.

The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial.

BACKGROUND: Previous studies have linked the Mediterranean diet (MED) with improved cardiometabolic health, showing preliminary evidence for a mediating role of the gut microbiome. We recently suggested the Green-Mediterranean (Green-MED) diet as an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake. Here, we investigated the effects of MED interventions on the gut microbiota and cardiometabolic markers, and the interplay between the two, during the initial weight loss phase of the DIRECT-PLUS trial. METHODS: In the DIRECT-PLUS study, 294 participants with abdominal obesity/dyslipidemia were prospectively randomized to one of three intervention groups: healthy dietary guidelines (standard science-based nutritional counseling), MED, and Green-MED. Both isocaloric MED and Green-MED groups were supplemented with 28g/day walnuts. The Green-MED group was further provided with daily polyphenol-rich green tea and Mankai aquatic plant (new plant introduced to a western population). Gut microbiota was profiled by 16S rRNA for all stool samples and shotgun sequencing for a select subset of samples. RESULTS: Both MED diets induced substantial changes in the community structure of the gut microbiome, with the Green-MED diet leading to more prominent compositional changes, largely driven by the low abundant, "non-core," microorganisms. The Green-MED diet was associated with specific microbial changes, including enrichments in the genus Prevotella and enzymatic functions involved in branched-chain amino acid degradation, and reductions in the genus Bifidobacterium and enzymatic functions responsible for branched-chain amino acid biosynthesis. The MED and Green-MED diets were also associated with stepwise beneficial changes in body weight and cardiometabolic biomarkers, concomitantly with the increased plant intake and reduced meat intake. Furthermore, while the level of adherence to the Green-MED diet and its specific green dietary components was associated with the magnitude of changes in microbiome composition, changes in gut microbial features appeared to mediate the association between adherence to the Green-MED and body weight and cardiometabolic risk reduction. CONCLUSIONS: Our findings support a mediating role of the gut microbiome in the beneficial effects of the Green-MED diet enriched with Mankai and green tea on cardiometabolic risk factors. TRIAL REGISTRATION: The study was registered on ClinicalTrial.gov ( NCT03020186 ) on January 13, 2017.

The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS).

BACKGROUND: The effect of diet on age-related brain atrophy is largely unproven. OBJECTIVES: We aimed to explore the effect of a Mediterranean diet (MED) higher in polyphenols and lower in red/processed meat (Green-MED diet) on age-related brain atrophy. METHODS: This 18-mo clinical trial longitudinally measured brain structure volumes by MRI using hippocampal occupancy score (HOC) and lateral ventricle volume (LVV) expansion score as neurodegeneration markers. Abdominally obese/dyslipidemic participants were randomly assigned to follow 1) healthy dietary guidelines (HDG), 2) MED, or 3) Green-MED diet. All subjects received free gym memberships and physical activity guidance. Both MED groups consumed 28 g walnuts/d (+440 mg/d polyphenols). The Green-MED group consumed green tea (3-4 cups/d) and Mankai (Wolffia-globosa strain, 100 g frozen cubes/d) green shake (+800 mg/d polyphenols). RESULTS: Among 284 participants (88% men; mean age: 51 y; BMI: 31.2 kg/m2; APOE-ε4 genotype = 15.7%), 224 (79%) completed the trial with eligible whole-brain MRIs. The pallidum (-4.2%), third ventricle (+3.9%), and LVV (+2.2%) disclosed the largest volume changes. Compared with younger participants, atrophy was accelerated among those ≥50 y old (HOC change: -1.0% ± 1.4% compared with -0.06% ± 1.1%; 95% CI: 0.6%, 1.3%; P < 0.001; LVV change: 3.2% ± 4.5% compared with 1.3% ± 4.1%; 95% CI: -3.1%, -0.8%; P = 0.001). In subjects ≥ 50 y old, HOC decline and LVV expansion were attenuated in both MED groups, with the best outcomes among Green-MED diet participants, as compared with HDG (HOC: -0.8% ± 1.6% compared with -1.3% ± 1.4%; 95% CI: -1.5%, -0.02%; P = 0.042; LVV: 2.3% ± 4.7% compared with 4.3% ± 4.5%; 95% CI: 0.3%, 5.2%; P = 0.021). Similar patterns were observed among younger subjects. Improved insulin sensitivity over the trial was the parameter most strongly associated with brain atrophy attenuation (P < 0.05). Greater Mankai, green tea, and walnut intake and less red and processed meat were significantly and independently associated with reduced HOC decline (P < 0.05). Elevated urinary concentrations of the polyphenols urolithin-A (r = 0.24; P = 0.013) and tyrosol (r = 0.26; P = 0.007) were significantly associated with lower HOC decline. CONCLUSIONS: A Green-MED (high-polyphenol) diet, rich in Mankai, green tea, and walnuts and low in red/processed meat, is potentially neuroprotective for age-related brain atrophy.This trial was registered at clinicaltrials.gov as NCT03020186.

Consumption of Olive Oil and Risk of Total and Cause-Specific Mortality Among U.S. Adults.

BACKGROUND: Olive oil consumption has been shown to lower cardiovascular disease risk, but its associations with total and cause-specific mortality are unclear. OBJECTIVES: The purpose of this study was to evaluate whether olive oil intake is associated with total and cause-specific mortality in 2 prospective cohorts of U.S. men and women. METHODS: The authors used multivariable-adjusted Cox proportional-hazards models to estimate HRs for total and cause-specific mortality among 60,582 women (Nurses' Health Study, 1990-2018) and 31,801 men (Health Professionals Follow-up Study, 1990-2018) who were free of cardiovascular disease or cancer at baseline. Diet was assessed by a semiquantitative food frequency questionnaire every 4 years. RESULTS: During 28 years of follow-up, 36,856 deaths occurred. The multivariable-adjusted pooled HR for all-cause mortality among participants who had the highest consumption of olive oil (>0.5 tablespoon/day or >7 g/d) was 0.81 (95% CI: 0.78-0.84) compared with those who never or rarely consumed olive oil. Higher olive oil intake was associated with 19% lower risk of cardiovascular disease mortality (HR: 0.81; 95% CI: 0.75-0.87), 17% lower risk of cancer mortality (HR: 0.83; 95% CI: 0.78-0.89), 29% lower risk of neurodegenerative disease mortality (HR: 0.71; 95% CI: 0.64-0.78), and 18% lower risk of respiratory disease mortality (HR: 0.82; 95% CI: 0.72-0.93). In substitution analyses, replacing 10 g/d of margarine, butter, mayonnaise, and dairy fat with the equivalent amount of olive oil was associated with 8%-34% lower risk of total and cause-specific mortality. No significant associations were observed when olive oil was compared with other vegetable oils combined. CONCLUSIONS: Higher olive oil intake was associated with lower risk of total and cause-specific mortality. Replacing margarine, butter, mayonnaise, and dairy fat with olive oil was associated with lower risk of mortality.

Olive Oil Consumption and Cardiovascular Risk in U.S. Adults.

BACKGROUND: Olive oil intake has been associated with lower risk of cardiovascular disease (CVD) in Mediterranean populations, but little is known about these associations in the U.S population. OBJECTIVES: This study sought to examine whether olive oil intake is associated with total CVD, coronary heart disease (CHD), and stroke risk. METHODS: This study included 61,181 women from the Nurses' Health Study (1990 to 2014) and 31,797 men from the Health Professionals Follow-up Study (1990 to 2014) who were free of cancer, heart disease, and stroke at baseline. Diet was assessed using food frequency questionnaires at baseline and then every 4 years. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 24 years of follow-up, this study documented 9,797 incident cases of CVD, including 6,034 CHD cases and 3,802 stroke cases. After adjusting for major diet and lifestyle factors, compared with nonconsumers, those with higher olive oil intake (>0.5 tablespoon/day or >7 g/day) had 14% lower risk of CVD (pooled HR: 0.86; 95% CI: 0.79 to 0.94) and 18% lower risk of CHD (pooled HR: 0.82; 95% CI: 0.73 to 0.91). No significant associations were observed for total or ischemic stroke. Replacing 5 g/day of margarine, butter, mayonnaise, or dairy fat with the equivalent amount of olive oil was associated with 5% to 7% lower risk of total CVD and CHD. No significant associations were observed when olive oil was compared with other plant oils combined. In a subset of participants, higher olive oil intake was associated with lower levels of circulating inflammatory biomarkers and a better lipid profile. CONCLUSIONS: Higher olive oil intake was associated with lower risk of CHD and total CVD in 2 large prospective cohorts of U.S. men and women. The substitution of margarine, butter, mayonnaise, and dairy fat with olive oil could lead to lower risk of CHD and CVD.

A prospective study of tea and coffee intake and risk of glioma.

Tea and coffee have antioxidant and neuroprotective effects. Observational studies suggest that tea and coffee intake may reduce cancer risk, but data on glioma risk are inconclusive. We evaluated the association between tea, coffee and caffeine intake and glioma risk in the female Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII) and the male Health Professionals Follow-Up Study (HPFS). Cumulative intake was derived from validated quadrennial food frequency questionnaires. Glioma cases were confirmed by medical record review. Multivariable-adjusted hazard ratios of glioma by beverage intake category were estimated using Cox proportional hazards models. We documented 554 incident cases of glioma (256 in NHS, 87 in NHSII and 211 in HPFS). Compared to <1 cup/week, higher tea consumption was borderline inversely associated with glioma risk in pooled cohorts (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.49-1.10 for >2 cups/day, p-trend = 0.05), but not in women (HR = 0.74, 95% CI: 0.47-1.18 for >2 cups/day, p-trend = 0.11) or men (HR = 0.70, 95% CI: 0.30-1.60 for >2 cups/day, p-trend = 0.30) separately. Overall, we observed no significant associations between caffeinated, decaffeinated or total coffee intake and glioma risk. There were no material differences in the results with baseline values, 8-year lagged responses, or when limited to glioblastoma (n = 362). In three large prospective cohort studies, tea intake was borderline inversely associated with glioma risk. No significant associations were observed for coffee intake and glioma risk. These results merit further exploration in prospective studies.

The Effect of Wolffia globosa Mankai, a Green Aquatic Plant, on Postprandial Glycemic Response: A Randomized Crossover Controlled Trial.

OBJECTIVE: To compare the postprandial and overnight glycemic response using a novel green aquatic plant thought to provide a dietary source for high-quality protein, with an iso-carbohydrate/protein/caloric dairy shake. RESEARCH DESIGN AND METHODS: This is a randomized controlled crossover trial among 20 abdominally obese participants (age 51.4 years; fasting plasma glucose 110.9 mg/dL), who were allocated to replace dinner with either, first, a green shake containing Wolffia globosa duckweed (Mankai: specific-strain) or an iso-carbohydrate/protein/calorie yogurt shake. A 2-week flash glucose-monitoring system was used to assess postmeal glucose dynamics (6 net administration days; 97 observation days in total). We further obtained from each participant dietary/daily activity/satiety scale/sleep logs. Participants were recruited from the green-Mediterranean diet arm of the 18-month Dietary Intervention Randomized Controlled Trial-Polyphenols Unprocessed (DIRECT-PLUS) study. RESULTS: Wolffia globosa Mankai elicited a lower postprandial glucose peak compared with yogurt (∆peak = 13.4 ± 9.2 vs. 19.3 ± 15.1 mg/dL; P = 0.044), which occurred later (77.5 ± 29.2 vs. 59.2 ± 28.4 min; P = 0.037) and returned faster to baseline glucose levels (135.8 ± 53.1 vs. 197.5 ± 70.2 min; P = 0.012). The mean post-net incremental area under the curve (netAUC) was lower with Wolffia globosa up to 60 and 180 min (netAUC 60 min: 185.1 ± 340.1 vs. 441.4 ± 336.5 mg/dL/min, P = 0.005; netAUC 180 min: 707.9 ± 1,428.5 vs. 1,576.6 ± 1,810.1 mg/dL/min, P = 0.037). A Wolffia globosa-based shake replacing dinner resulted in lower next-morning fasting glucose levels (83.2 ± 0.8 vs. 86.6 ± 13 mg/dL; P = 0.041). Overall, postprandial glucose levels from the shake administration until the next morning were lower in the Wolffia globosa Mankai green shake compared with the yogurt shake (P < 0.001). Overnight sleep duration was similar (378.2 ± 22.4 vs. 375.9 ± 28.4 min; P = 0.72), and satiety rank was slightly higher for the Wolffia globosa shake compared with the yogurt shake (7.5 vs. 6.5; P = 0.035). CONCLUSIONS: Wolffia globosa Mankai duckweed may serve as an emerging alternative plant protein source with potential beneficial postprandial glycemic effects.

A Green-Mediterranean Diet, Supplemented with Mankai Duckweed, Preserves Iron-Homeostasis in Humans and Is Efficient in Reversal of Anemia in Rats.

BACKGROUND: Decreased dietary meat may deplete iron stores, as plant-derived iron bioavailability is typically limited. OBJECTIVES: We explored the effect of a low-meat Mediterranean (green-MED) diet, supplemented with Wolffia globosa duckweed (Mankai: rich in protein and iron) as a food source for humans, on iron status. We further examined the iron bioavailability of Mankai in rats. METHODS: Two hundred and ninety-four abdominally obese/dyslipidemic [mean age = 51.1 y; body mass index (kg/m2) = 31.3; 88% men] nonanemic participants were randomly assigned to physical activity (PA), PA + MED diet, or PA + green-MED diet. Both isocaloric MED groups consumed 28 g walnuts/d and the low-meat green-MED group further consumed green tea (800 mL/d) and Mankai (100 g green shake/d). In a complementary animal experiment, after 44 d of an iron deficiency anemia-inducing diet, 50 female rats (age = 3 wk; Sprague Dawley strain) were randomly assigned into: iron-deficient diet (vehicle), or vehicle + iso-iron: ferrous gluconate (FG) 14, Mankai 50, and Mankai 80 versions (1.7 mg · kg-1 · d-1 elemental iron), or FG9.5 and Mankai 50-C version (1.15 mg · kg-1 · d-1 elemental iron). The specific primary aim for both studies was changes in iron homeostasis parameters. RESULTS: After 6 mo of intervention, iron status trajectory did not differ between the PA and PA + MED groups. Hemoglobin modestly increased in the PA + green-MED group (0.23 g/dL) compared with PA (-0.1 g/dL; P < 0.001) and PA + MED (-0.1 g/dL; P < 0.001). Serum iron and serum transferrin saturation increased in the PA + green-MED group compared with the PA group (8.21 µg/dL compared with -5.23 µg/dL and 2.39% compared with -1.15%, respectively; P < 0.05 for both comparisons), as did folic acid (P = 0.011). In rats, hemoglobin decreased from 15.7 to 9.4 mg/dL after 44 d of diet-induced anemia. After depletion treatment, the vehicle-treated group had a further decrease of 1.3 mg/dL, whereas hemoglobin concentrations in both FG and Mankai iso-iron treatments similarly rebounded (FG14: +10.8 mg/dL, Mankai 50: +6.4 mg/dL, Mankai 80: +7.3 mg/dL; FG9.5: +5.1 mg/dL, Mankai 50-C: +7.1 mg/dL; P < 0.05 for all vs. the vehicle group). CONCLUSIONS: In humans, a green-MED low-meat diet does not impair iron homeostasis. In rats, iron derived from Mankai (a green-plant protein source) is bioavailable and efficient in reversal of anemia. This trial was registered at clinicaltrials.gov as NCT03020186.

Is high vitamin B12 status a cause of lung cancer?

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre-diagnostic circulating vitamin B12 concentrations in a nested case-control study, complemented with a Mendelian randomization (MR) approach in an independent case-control sample. We used pre-diagnostic biomarker data from 5183 case-control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre-diagnostic blood samples from the nested case-control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12 ] = 1.15, 95% confidence interval (95%CI) = 1.06-1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD ] = 1.08, 95%CI = 1.00-1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.

A 24-year prospective study of dietary α-linolenic acid and lethal prostate cancer.

Several meta-analyses have attempted to determine the relationships between intake of α-linolenic acid (ALA) and prostate cancer, but results were inconclusive. 47,885 men aged 40-75 years without prior cancer in the Health Professionals Follow-Up Study were prospectively followed from 1986 to 2010. Intake of ALA was determined from validated food frequency questionnaires every 4 years. We used multivariate Cox proportional hazards models to estimate hazard ratios (HR) with 95% confidence intervals (CIs) for lethal prostate cancer (distant metastasis or prostate cancer death). 386 lethal prostate cancers were diagnosed in the pre-PSA era (before February, 1994) and 403 cancers in the PSA era. Intake of ALA was associated with increased risk of lethal prostate cancer in the pre-PSA era (comparing top to bottom quintile of intake, multivariate-adjusted HR = 1.78; 95% CI = 1.22-2.06; ptrend = 0.003), but not in the PSA era (HR = 0.81; 95% CI = 0.56-1.17; ptrend = 0.53), and the difference in associations was statistically significant (p for interaction = 0.02). Mayonnaise, a primary food source of ALA intake in our cohort, was likewise only significantly associated with lethal prostate cancer in the pre-PSA era. Among many other fatty acids that are correlated with ALA due to shared food sources, none was associated with lethal prostate cancer in the pre-PSA era. In conclusion, higher intake of ALA was associated with an increased risk of lethal prostate cancer in the pre-PSA era, but not in the PSA era. Potential reasons for the differential associations warrant further investigation.

Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations.

Background: Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies.Objective: We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions.Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory.Results: Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and α-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users.Conclusions: The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.

Selenium and Prostate Cancer: Analysis of Individual Participant Data From Fifteen Prospective Studies.

BACKGROUND: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade. METHODS: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. RESULTS: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08). CONCLUSIONS: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.

Association of Religious Service Attendance With Mortality Among Women.

IMPORTANCE: Studies on the association between attendance at religious services and mortality often have been limited by inadequate methods for reverse causation, inability to assess effects over time, and limited information on mediators and cause-specific mortality. OBJECTIVE: To evaluate associations between attendance at religious services and subsequent mortality in women. DESIGN, SETTING, AND PARTICIPANTS: Attendance at religious services was assessed from the first questionnaire in 1992 through June 2012, by a self-reported question asked of 74 534 women in the Nurses' Health Study who were free of cardiovascular disease and cancer at baseline. Data analysis was conducted from return of the 1996 questionnaire through June 2012. MAIN OUTCOMES AND MEASURES: Cox proportional hazards regression model and marginal structural models with time-varying covariates were used to examine the association of attendance at religious services with all-cause and cause-specific mortality. We adjusted for a wide range of demographic covariates, lifestyle factors, and medical history measured repeatedly during the follow-up, and performed sensitivity analyses to examine the influence of potential unmeasured and residual confounding. RESULTS: Among the 74 534 women participants, there were 13 537 deaths, including 2721 owing to cardiovascular deaths and 4479 owing to cancer deaths. After multivariable adjustment for major lifestyle factors, risk factors, and attendance at religious services in 1992, attending a religious service more than once per week was associated with 33% lower all-cause mortality compared with women who had never attended religious services (hazard ratio, 0.67; 95% CI, 0.62-0.71; P < .001 for trend). Comparing women who attended religious services more than once per week with those who never attend, the hazard ratio for cardiovascular mortality was 0.73 (95% CI, 0.62-0.85; P < .001 for trend) and for cancer mortality was 0.79 (95% CI, 0.70-0.89; P < .001 for trend). Results were robust in sensitivity analysis. Depressive symptoms, smoking, social support, and optimism were potentially important mediators, although the overall proportion of the association between attendance at religious services and mortality was moderate (eg, social support explained 23% of the effect [P = .003], depressive symptoms explained 11% [P < .001], smoking explained 22% [P < .001], and optimism explained 9% [P < .001]). CONCLUSIONS AND RELEVANCE: Frequent attendance at religious services was associated with significantly lower risk of all-cause, cardiovascular, and cancer mortality among women. Religion and spirituality may be an underappreciated resource that physicians could explore with their patients, as appropriate.

Higher visceral adiposity is associated with an enhanced early thermogenic response to carbohydrate-rich food.

BACKGROUND: Studies examining the dynamics of the thermic effect of feeding (TEF) of specific food items and the relationship of TEF to visceral adiposity are limited. METHODS: We measured resting energy expenditure (REE) and early-TEF (40-min postprandial, e-TEF) after 8-h fast by indirect calorimetry in 40 obese men, and imaged abdominal fat tissues by magnetic resonance imaging. Each participant was examined on two occasions, 3-weeks apart. At each examination we measured fasting REE and then postprandial REE following the isocaloric [∼380 kcal] consumption of either 56 gr walnuts [(8% carbohydrates; 84% fat, of which 72% polyunsaturated fat)], or 5-slices (150gr) of whole-grain bread (48% carbohydrates; 32% fat). e-TEF was calculated as the area under the curve between the fasting and postprandial tests. RESULTS: Participants had a mean age of 45 ± 8 years, body-mass-index (BMI) = 31.1 ± 3.8 kg/m(2), total abdominal fat area = 901.4 ± 240 cm(2), visceral fat area (VAT) = 260 ± 102.9 cm(2), fasting REE = 1854 ± 205 kcal, REE/kg = 19.39 ± 1.73 kcal/kg, and respiratory quotient (RQ, CO2 eliminated/O2 consumed) = 0.82 ± 0.04. Individuals who exhibited increased e-TEF (top ΔAUC median) to bread had higher VAT (299 cm(2) vs. 223 cm(2); p = 0.024) and higher BMI (32.4 kg/m(2) vs. 30.0 kg/m(2); p = 0.013), compared to their peers with the lower e-TEF response (ΔAUC below median). As expected, postprandial e-TEF was higher after whole-grain bread consumption [ΔAUC = +14 kcal/40min] compared to walnuts [ΔAUC = -2 kcal/40 min; p < 0.001]. CONCLUSIONS: Higher early thermic effect of high-carbohydrate food, likely reflecting digestion, early absorption and/or sympathetic tone (rather than metabolic utilization (oxidation)), associates with visceral adiposity. Future studies are required to determine if this association represents an added causality between early carbohydrate processing and visceral fat accumulation.

Carotenoids, vitamin A, vitamin C, vitamin E, and folate and risk of self-reported hearing loss in women.

BACKGROUND: Higher intake of certain vitamins may protect against cochlear damage from vascular compromise and oxidative stress, thereby reducing risk of acquired hearing loss, but data are limited. OBJECTIVE: We prospectively examined the relation between carotenoids, vitamin A, vitamin C, vitamin E, and folate intake and risk of self-reported hearing loss in women. DESIGN: This prospective cohort study followed 65,521 women in the Nurses' Health Study II from 1991 to 2009. Baseline and updated information obtained from validated biennial questionnaires was used in Cox proportional hazards regression models to examine independent associations between nutrient intake and self-reported hearing loss. RESULTS: After 1,084,598 person-years of follow-up, 12,789 cases of incident hearing loss were reported. After multivariable adjustment, we observed modest but statistically significant inverse associations between higher intake of ß-carotene and ß-cryptoxanthin and risk of hearing loss. In comparison with women in the lowest quintile of intake, the multivariable-adjusted RR of hearing loss among women in the highest quintile was 0.88 (95% CI: 0.81, 0.94; P-trend < 0.001) for ß-carotene and 0.90 (95% CI: 0.84, 0.96; P-trend < 0.001) for ß-cryptoxanthin. In comparison with women with folate intake 200-399 µg/d, very low folate intake (<200 µg/d) was associated with higher risk (RR: 1.19; 95% CI: 1.01, 1.41), and higher intake tended to be associated with lower risk (P-trend = 0.04). No significant associations were observed for intakes of other carotenoids or vitamin A. Higher vitamin C intake was associated with higher risk; in comparison with women with intake <75 mg/d, the RR among women with vitamin C intake ≥1000 mg/d (mainly supplemental) was 1.22 (95% CI: 1.06, 1.42; P-trend = 0.02). There was no significant trend between intake of vitamin E intake and risk. CONCLUSION: Higher intakes of ß-carotene, ß-cryptoxanthin, and folate, whether total or from diet, are associated with lower risk of hearing loss, whereas higher vitamin C intake is associated with higher risk.

Selenium supplementation and prostate cancer mortality.

BACKGROUND: Few studies have evaluated the relation between selenium supplementation after diagnosis and prostate cancer outcomes. METHODS: We prospectively followed 4459 men initially diagnosed with nonmetastatic prostate cancer in the Health Professionals Follow-Up Study from 1988 through 2010 and examined whether selenium supplement use (from selenium-specific supplements and multivitamins) after diagnosis was associated with risk of biochemical recurrence, prostate cancer mortality, and, secondarily, cardiovascular disease mortality and overall mortality, using Cox proportional hazards models. All P values were from two-sided tests. RESULTS: We documented 965 deaths, 226 (23.4%) because of prostate cancer and 267 (27.7%) because of cardiovascular disease, during a median follow-up of 8.9 years. In the biochemical recurrence analysis, we documented 762 recurrences during a median follow-up of 7.8 years. Crude rates per 1000 person-years for prostate cancer death were 5.6 among selenium nonusers and 10.5 among men who consumed 140 or more µg/day. Crude rates per 1000 person-years were 28.2 vs 23.5 for all-cause mortality and 28.4 vs 29.3 for biochemical recurrence, for nonuse vs highest-dose categories, respectively. In multivariable analyses, men who consumed 1 to 24 µg/day, 25 to 139 µg/day, and 140 or more µg/day of supplemental selenium had a 1.18 (95% confidence interval [CI] = 0.73 to 1.91), 1.33 (95% CI = 0.77 to 2.30), and 2.60-fold (95% CI = 1.44 to 4.70) greater risk of prostate cancer mortality compared with nonusers, respectively, P trend = .001. There was no statistically significant association between selenium supplement use and biochemical recurrence, cardiovascular disease mortality, or overall mortality. CONCLUSION: Selenium supplementation of 140 or more µg/day after diagnosis of nonmetastatic prostate cancer may increase risk of prostate cancer mortality. Caution is warranted regarding usage of such supplements among men with prostate cancer.

Total antioxidant intake in relation to prostate cancer incidence in the Health Professionals Follow-Up Study.

Epidemiologic evidence on the association of antioxidant intake and prostate cancer incidence is inconsistent. Total antioxidant intake and prostate cancer incidence have not previously been examined. Using the ferric-reducing antioxidant potential (FRAP) assay, the total antioxidant content (TAC) of diet and supplements was assessed in relation to prostate cancer incidence. A prospective cohort of 47,896 men aged 40-75 years was followed from 1986 to 2008 for prostate cancer incidence (N = 5,656), and they completed food frequency questionnaires (FFQs) every 4 years. A FRAP value was assigned to each item in the FFQ, and for each individual, TAC scores for diet, supplements and both (total) were calculated. Major contributors of TAC intake at baseline were coffee (28%), fruit and vegetables (23%) and dietary supplements (23%). In multivariate analyses for dietary TAC a weak inverse association was observed [highest versus lowest quintiles: 0.91 (0.83-1.00, p-trend = 0.03) for total prostate cancer and 0.81 (0.64-1.01, p-trend = 0.04) for advanced prostate cancer]; this association was mainly due to coffee. No association of total TAC on prostate cancer incidence was observed. A positive association with lethal and advanced prostate cancers was observed in the highest quintile of supplemental TAC intake: 1.28 (0.98-1.65, p-trend < 0.01) and 1.15 (0.92-1.43, p-trend = 0.04). The weak association between dietary antioxidant intake and reduced prostate cancer incidence may be related to specific antioxidants in coffee, to nonantioxidant coffee compounds or other effects of drinking coffee. The indication of increased risk for lethal and advanced prostate cancers with high TAC intake from supplements warrants further investigation.