Dairy foods, calcium intakes, and risk of incident prostate cancer in Adventist Health Study-2.

BACKGROUND: Prostate cancer is the most common noncutaneous cancer in American males. Causal links between dairy, or dietary calcium, and this cancer are considered suggestive but limited. OBJECTIVES: To evaluate these associations in a large North American cohort, including many with no (or very low) dairy intake and much calcium from nondairy sources. METHODS: A prospective cohort study of 28,737 Seventh-day Adventist men in the United States and Canada, of whom 6389 were of black ethnicity. Diet was measured by FFQ, and 275 male participants also provided repeated 24-h dietary recalls as a calibration substudy. Incident cancers were mainly found by matching with cancer registries. Analyses used multivariable proportional hazards regressions and regression calibration for some analyses. RESULTS: In total, 1254 (190 advanced) incident prostate cancer cases were found during an average 7.8 y of follow-up. Men at the 90th percentile of dairy intake (430 g/d) compared with the 10th percentile (20.2 g/d) had higher prostate cancer risk (HR: 1.27; 95% CI: 1.12, 1.43). Similar findings, comparing the same g/d intakes, were demonstrated for advanced prostate cancers (HR: 1.38; 95% CI: 1.02, 1.88), for nonadvanced cases (HR: 1.27; 95% CI: 1.11, 1.45), in black participants (HR: 1.24; 95% CI: 0.98, 1.58), and when excluding vegan participants (HR: 1.22; 95% CI: 1.03, 1.43). Calibrated dairy (g/d) regressions (all participants and all prostate cancers), adjusting for dietary measurement error, found a HR of 1.75 (95% CI: 1.32, 2.32). Comparing 90th percentile intake to zero intakes (uncalibrated), the HR was 1.62 (95% CI: 1.26, 2.05). There was no evidence of an effect of higher (905 mg/d) compared with lower (349 mg/d) intakes of nondairy calcium (HR: 1.16; 95% CI: 0.94, 1.44). CONCLUSIONS: Men with higher intake of dairy foods, but not nondairy calcium, had a higher risk of prostate cancer compared with men having lower intakes. Associations were nonlinear, suggesting greatest increases in risk at relatively low doses.

The Biology of Veganism: Plasma Metabolomics Analysis Reveals Distinct Profiles of Vegans and Non-Vegetarians in the Adventist Health Study-2 Cohort.

It is unclear how vegetarian dietary patterns influence plasma metabolites involved in biological processes regulating chronic diseases. We sought to identify plasma metabolic profiles distinguishing vegans (avoiding meat, eggs, dairy) from non-vegetarians (consuming ≥28 g/day red meat) of the Adventist Health Study-2 cohort using global metabolomics profiling with ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS). Differences in abundance of metabolites or biochemical subclasses were analyzed using linear regression models, adjusting for surrogate and confounding variables, with cross-validation to simulate results from an independent sample. Random forest was used as a learning tool for classification, and principal component analysis was used to identify clusters of related metabolites. Differences in covariate-adjusted metabolite abundance were identified in over 60% of metabolites (586/930), after adjustment for false discovery. The vast majority of differentially abundant metabolites or metabolite subclasses showed lower abundance in vegans, including xanthine, histidine, branched fatty acids, acetylated peptides, ceramides, and long-chain acylcarnitines, among others. Many of these metabolite subclasses have roles in insulin dysregulation, cardiometabolic phenotypes, and inflammation. Analysis of metabolic profiles in vegans and non-vegetarians revealed vast differences in these two dietary groups, reflecting differences in consumption of animal and plant products. These metabolites serve as biomarkers of food intake, many with potential pathophysiological consequences for cardiometabolic diseases.

Ultra-processed food intake and animal-based food intake and mortality in the Adventist Health Study-2.

BACKGROUND: Both ultra-processed foods and animal-derived foods have been associated with mortality in some studies. OBJECTIVES: We aimed to examine the association of 2 dietary factors (ultra-processed foods and animal-based foods), adjusted for each other, with all-cause mortality. METHODS: The setting is an observational prospective cohort study in North America, recruited from Seventh-day Adventist churches, comprised of 95,597 men and women, yielding an analytic sample of 77,437 participants after exclusions. The exposure of interest was diet measured by FFQ, in particular 2 dietary factors: 1) proportion of dietary energy from ultra-processed foods (other processing levels and specific substitutions in some models) and 2) proportion of dietary energy from animal-based foods (red meat, poultry, fish, and eggs/dairy separately in some models). The main outcome was all-cause mortality. Mortality data through 2015 were obtained from the National Death Index. Analyses used proportional hazards regression. RESULTS: There were 9293 deaths. In mutually adjusted continuous linear models of both dietary factors (ultra-processed and animal-based foods), the HR for the 90th compared with the 10th percentile of the proportion of dietary energy from ultra-processed food was 1.14 (95% CI: 1.07, 1.21, comparing 47.7% with 12.1% dietary energy), whereas for animal-based food intake (meats, dairy, eggs) it was 1.01 (95% CI: 0.95, 1.07, comparing 25.0% with 0.4% dietary energy). There was no evidence of interaction (P = 0.36). Among animal-based foods, only red meat intake was associated with mortality (HR: 1.14; 95% CI: 1.08, 1.22, comparing 6.2% with 0% dietary energy). CONCLUSIONS: Greater consumption of ultra-processed foods was associated with higher all-cause mortality in this health-conscious Adventist population with many vegetarians. The total of animal-based food consumption (meat, dairy, eggs) was not associated with mortality, but higher red meat intake was. These findings suggest that high consumption of ultra-processed foods may be an important indicator of mortality.

Lower Utilization of Colorectal Cancer Screening Among Vegetarians, Adventist Health Study-2.

This study aims to examine lifestyle predictors of the utilization of colorectal cancer screening. Using modified Poisson regression, we studied self-reported colorectal cancer screening utilization (colonoscopy or fecal occult blood test) with various dietary and lifestyle characteristics among 33,922 subjects aged 51 + years in the Adventist Health Study-2, a large population-based prospective cohort study. According to the multivariable-adjusted models, vegetarians were less likely to report screening: vegans, prevalence ratio (PR) = 0.80 (95% confidence interval 0.77-0.83); lacto-ovo-vegetarians (0.95 [0.93-0.97]); and semi-vegetarians (0.97 [0.94-0.99]) compared to non-vegetarians. Blacks were more likely than non-Blacks to be screened (1.04 [1.02-1.06]) and males were less likely (0.93 [0.92-0.95]) to utilize the screening tests. Older subjects were more likely to be screened, and unmarried and divorced/widowed subjects were less likely to screen. Education, personal income, and BMI were positively associated with screening, with p-value for trend < 0.001 for all three variables. A family history of colorectal cancer was associated with higher screening prevalence (1.15 [1.12-1.17]). Our stratified analyses on race and gender with dietary patterns showed non-Hispanic White vegans (PR = 0.77 [0.74-0.81]) and male vegans (PR = 0.76 [0.72-0.81]) were least likely compliant with colorectal cancer screening (p = 0.009 and p = 0.04, respectively). Vegans may believe that their personal risk for colorectal cancer is low due to their healthy lifestyle, resulting in lack of compliance to colorectal cancer screening. It remains to be seen whether vegans in AHS-2 also experience higher incidence of colorectal cancer or are diagnosed at a later stage.

Validity of FFQ Estimates of Total Sugars, Added Sugars, Sucrose and Fructose Compared to Repeated 24-h Recalls in Adventist Health Study-2 Participants.

Sugar intake is a potentially important aspect of diet which has not previously been validated in the Adventist Health Study-2 (AHS-2). We sought to validate the food frequency questionnaire (FFQ) measurement of total sugars, added sugars, sucrose, and fructose against multiple 24-h dietary recalls (recalls) in AHS-2 participants. Food consumption data from a self-administered FFQ and six recalls from 904 participants were combined with nutrient profile data to estimate daily sugar intake. Validity was evaluated among all participants and by race. FFQ and recall means were compared and correlation coefficients (Spearman's, energy-adjusted log-transformed Pearson's, deattenuated Pearson's) were calculated. Mean total energy, total sugars, and fructose intake were higher in the FFQ, whereas added sugars and sucrose were higher in recalls. The energy-adjusted (log-transformed) deattenuated correlations among all participants were: total sugars (r = 0.42, 95% CI 0.32-0.52), added sugars (r = 0.50, 95% CI 0.36-0.59), sucrose (r = 0.32, 95% CI 0.23-0.42), and fructose (r = 0.50, 95% CI 0.40-0.59). We observed moderate validity for added sugars and fructose and low-moderate validity for total sugars and sucrose measured by the AHS-2 FFQ in this population. Dietary sugar estimates from this FFQ may be useful in assessing possible associations of sugars intake with health outcomes.

DNA Methylation Profiles of Vegans and Non-Vegetarians in the Adventist Health Study-2 Cohort.

We sought to determine if DNA methylation patterns differed between vegans and non-vegetarians in the Adventist Health Study-2 cohort. Genome-wide DNA methylation derived from buffy coat was profiled in 62 vegans and 142 non-vegetarians. Using linear regression, methylation of CpG sites and genes was categorized or summarized according to various genic/intergenic regions and CpG island-related regions, as well as the promoter. Methylation of genes was measured as the average methylation of available CpG's annotated to the nominated region of the respective gene. A permutation method defining the null distribution adapted from Storey et al. was used to adjust for false discovery. Differences in methylation of several CpG sites and genes were detected at a false discovery rate < 0.05 in region-specific and overall analyses. A vegan diet was associated predominantly with hypomethylation of genes, most notably methyltransferase-like 1 (METTL1). Although a limited number of differentially methylated features were detected in the current study, the false discovery method revealed that a much larger proportion of differentially methylated genes and sites exist, and could be detected with a larger sample size. Our findings suggest modest differences in DNA methylation in vegans and non-vegetarians, with a much greater number of detectable significant differences expected with a larger sample.

Ovarian Cancer Risk Factor Associations by Primary Anatomic Site: The Ovarian Cancer Cohort Consortium.

BACKGROUND: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites. METHODS: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests. RESULTS: Most associations did not vary by tumor site (P het ≥ 0.05). Associations between first pregnancy (P het = 0.04), tubal ligation (P het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases. CONCLUSIONS: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site. IMPACT: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

Lower rates of cancer and all-cause mortality in an Adventist cohort compared with a US Census population.

BACKGROUND: Previous research suggests that Adventists, who often follow vegetarian diets, live longer and have lower risks for many cancers than others, but there are no national data and little published comparative data for black subjects. METHODS: This study compared all-cause mortality and cancer incidence between the nationally inclusive Adventist Health Study 2 (AHS-2) and nonsmokers in US Census populations: the National Longitudinal Mortality Study (NLMS) and its Surveillance, Epidemiology, and End Results substudy. Analyses used proportional hazards regression adjusting for age, sex, race, cigarette smoking history, and education. RESULTS: All-cause mortality and all-cancer incidence in the black AHS-2 population were significantly lower than those for the black NLMS populations (hazard ratio [HR] for mortality, 0.64; 95% confidence interval [CI], 0.59-0.69; HR for incidence, 0.78; 95% CI, 0.68-0.88). When races were combined, estimated all-cause mortality was also significantly lower in the AHS-2 population at the age of 65 years (HR, 0.67; 95% CI, 0.64-0.69) and at the age of 85 years (HR, 0.78; 95% CI, 0.75-0.81), as was cancer mortality; this was also true for the rate of all incident cancers combined (HR, 0.70; 95% CI, 0.67-0.74) and the rates of breast, colorectal, and lung cancers. Survival curves confirmed the mortality results and showed that among males, AHS-2 blacks survived longer than white US subjects. CONCLUSIONS: Substantially lower rates of all-cause mortality and cancer incidence among Adventists have implications for the effects of lifestyle and perhaps particularly diet on the etiology of these health problems. Trends similar to those seen in the combined population are also found in comparisons of black AHS-2 and NLMS subjects.

Vegetarian Epidemiology: Review and Discussion of Findings from Geographically Diverse Cohorts.

Epidemiologic cohort studies enrolling a large percentage of vegetarians have been highly informative regarding the nutritional adequacy and possible health effects of vegetarian diets. The 2 largest such cohorts are the European Prospective Investigation into Cancer and Nutrition-Oxford (EPIC-Oxford) and the Adventist Health Study-2 (AHS-2). These cohorts are described and their findings discussed, including a discussion of where findings appear to diverge. Although such studies from North America and the United Kingdom have been important, the large majority of the world's vegetarians live in other regions, particularly in Asia. Findings from recent cohort studies of vegetarians in East and South Asia are reviewed, particularly the Tzu Chi Health Study and Indian Migration Study. Important considerations for the study of the health of vegetarians in Asia are discussed. Vegetarian diets vary substantially, as may associated health outcomes. Cohort studies remain an important tool to better characterize the health of vegetarian populations around the globe.

Red and Processed Meat and Mortality in a Low Meat Intake Population.

Associations of low-to-moderate consumption of red and processed meat with mortality would add to the evidence of possible adverse effects of these common foods. This study aims to investigate the association of red and processed meat intake with mortality. The Adventist Health Study-2 (AHS-2) is a prospective cohort study of ~96,000 Seventh-day Adventist men and women recruited in the US and Canada between 2002 and 2007. The final analytic sample after exclusions was 72,149. Cox proportional hazards regression was used and hazard ratios (HR) and confidence intervals (CI) were obtained. Diet was assessed by a validated quantitative food frequency questionnaire (FFQ), calibrated using six 24-h dietary recalls. Mortality outcome data were obtained from the National Death Index. During a mean follow-up of 11.8 years, there were 7961 total deaths, of which 2598 were Cardiovascular diseases (CVD) deaths and 1873 were cancer deaths. Unprocessed red meat was associated with risk of all-cause mortality (HR: 1.18; 95% CI: 1.07⁻1.31) and CVD mortality (HR: 1.26; 95% CI: 1.05⁻1.50). Processed meat alone was not significantly associated with risk of mortality. The combined intake of red and processed meat was associated with all-cause mortality (HR: 1.23; 95% CI: 1.11⁻1.36) and CVD mortality (HR: 1.34; 95% CI: 1.12⁻1.60). These findings suggest moderately higher risks of all-cause and CVD mortality associated with red and processed meat in a low meat intake population.

Next steps in studying the human microbiome and health in prospective studies, Bethesda, MD, May 16-17, 2017.

The National Cancer Institute (NCI) sponsored a 2-day workshop, "Next Steps in Studying the Human Microbiome and Health in Prospective Studies," in Bethesda, Maryland, May 16-17, 2017. The workshop brought together researchers in the field to discuss the challenges of conducting microbiome studies, including study design, collection and processing of samples, bioinformatics and statistical methods, publishing results, and ensuring reproducibility of published results. The presenters emphasized the great potential of microbiome research in understanding the etiology of cancer. This report summarizes the workshop and presents practical suggestions for conducting microbiome studies, from workshop presenters, moderators, and participants.

Unscrambling the relations of egg and meat consumption with type 2 diabetes risk.

Background: Meat intake is associated with increased risk of type 2 diabetes (T2D). It is not clear if egg intake is associated with T2D risk because purported associations may be due to concurrent consumption of eggs with meat. Objective: Our aim was to differentiate any associations between meat and egg consumption and the risk of T2D. Design: In this longitudinal study, 55,851 participants of the Adventist Health Study 2 who were free of diabetes provided demographic, anthropometric, and dietary data at baseline. Meat and egg intakes were assessed with a validated quantitative food-frequency questionnaire. Responses to 2 follow-up questionnaires determined incident T2D cases. Multivariate-adjusted logistic regression was used to determine relations between meat and egg intake and incident T2D. Results: T2D cases identified during a mean 5.3 y of follow-up totaled 2772. Meat intake of >0 to <25 g/d, ≥25 to <70 g/d, and ≥70 g/d significantly increased the risk of T2D compared with no meat intake (OR: 1.29; 95% CI: 1.16, 1.44; OR: 1.42; 95% CI: 1.25, 1.61; and OR: 1.65; 95% CI: 1.39, 1.96, respectively; P-trend < 0.0001). Egg intake compared with no egg intake was not associated with T2D risk. A significant meat-egg interaction (P = 0.019) showed that within every category of egg intake, there was an incremental rise in T2D risk as meat intake increased. However, within categories of meat intake, increasing egg intake did not increase the risk of T2D except among nonmeat-eaters consuming ≥5 eggs/wk (OR: 1.52; 95% CI: 1.09, 2.12). Conclusions: Meat consumption, but not egg consumption, is independently associated with T2D risk. Egg intake seems not to increase T2D risk further with meat intake. Our findings suggest that the purported egg-T2D risk relation in US populations may be biased due to failure to investigate egg-meat interactions. Further investigations are needed to ascertain T2D risk among nonmeat-eaters with high egg intakes.

Vegetarian dietary patterns and the risk of colorectal cancers.

IMPORTANCE: Colorectal cancers are a leading cause of cancer mortality, and their primary prevention by diet is highly desirable. The relationship of vegetarian dietary patterns to colorectal cancer risk is not well established. OBJECTIVE: To evaluate the association between vegetarian dietary patterns and incident colorectal cancers. DESIGN, SETTING, AND PARTICIPANTS: The Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96,354 Seventh-Day Adventist men and women recruited between January 1, 2002, and December 31, 2007. Follow-up varied by state and was indicated by the cancer registry linkage dates. Of these participants, an analytic sample of 77,659 remained after exclusions. Analysis was conducted using Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. The analysis was conducted between June 1, 2014, and October 20, 2014. EXPOSURES: Diet was assessed at baseline by a validated quantitative food frequency questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto-ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary pattern. MAIN OUTCOMES AND MEASURES: The relationship between dietary patterns and incident cancers of the colon and rectum; colorectal cancer cases were identified primarily by state cancer registry linkages. RESULTS: During a mean follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer were documented. The adjusted hazard ratios (HRs) in all vegetarians combined vs nonvegetarians were 0.78 (95% CI, 0.64-0.95) for all colorectal cancers, 0.81 (95% CI, 0.65-1.00) for colon cancer, and 0.71 (95% CI, 0.47-1.06) for rectal cancer. The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59-1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65-1.02); in pescovegetarians, 0.57 (95% CI, 0.40-0.82); and in semivegetarians, 0.92 (95% CI, 0.62-1.37) compared with nonvegetarians. Effect estimates were similar for men and women and for black and nonblack individuals. CONCLUSIONS AND RELEVANCE: Vegetarian diets are associated with an overall lower incidence of colorectal cancers. Pescovegetarians in particular have a much lower risk compared with nonvegetarians. If such associations are causal, they may be important for primary prevention of colorectal cancers.

Patterns of food consumption among vegetarians and non-vegetarians.

Vegetarian dietary patterns have been reported to be associated with a number of favourable health outcomes in epidemiological studies, including the Adventist Health Study 2 (AHS-2). Such dietary patterns may vary and need further characterisation regarding foods consumed. The aims of the present study were to characterise and compare the food consumption patterns of several vegetarian and non-vegetarian diets. Dietary intake was measured using an FFQ among more than 89 000 members of the AHS-2 cohort. Vegetarian dietary patterns were defined a priori, based on the absence of certain animal foods in the diet. Foods were categorised into fifty-eight minor food groups comprising seventeen major food groups. The adjusted mean consumption of each food group for the vegetarian dietary patterns was compared with that for the non-vegetarian dietary pattern. Mean consumption was found to differ significantly across the dietary patterns for all food groups. Increased consumption of many plant foods including fruits, vegetables, avocados, non-fried potatoes, whole grains, legumes, soya foods, nuts and seeds was observed among vegetarians. Conversely, reduced consumption of meats, dairy products, eggs, refined grains, added fats, sweets, snack foods and non-water beverages was observed among vegetarians. Thus, although vegetarian dietary patterns in the AHS-2 have been defined based on the absence of animal foods in the diet, they differ greatly with respect to the consumption of many other food groups. These differences in food consumption patterns may be important in helping to explain the association of vegetarian diets with several important health outcomes.

Vegetarian diets in the Adventist Health Study 2: a review of initial published findings.

The Adventist Health Study 2 is a large cohort that is well suited to the study of the relation of vegetarian dietary patterns to health and disease risk. Here we review initial published findings with regard to vegetarian diets and several health outcomes. Vegetarian dietary patterns were associated with lower body mass index, lower prevalence and incidence of diabetes mellitus, lower prevalence of the metabolic syndrome and its component factors, lower prevalence of hypertension, lower all-cause mortality, and in some instances, lower risk of cancer. Findings with regard to factors related to vegetarian diets and bone health are also reviewed. These initial results show important links between vegetarian dietary patterns and improved health.

Global epidemiology of obesity, vegetarian dietary patterns, and noncommunicable disease in Asian Indians.

An increase in noncommunicable disease (NCD) in India has been attributed to an epidemiologic transition whereby, due to urbanization, there is an increase in traditional cardiovascular disease risk factors such as obesity. Accumulated biomarker data on the "Asian Indian phenotype" identify central obesity, which occurs at a lower body mass index (BMI), as a particularly potent risk factor in Asian Indians. A revised WHO case definition for obesity in India [BMI (in kg/m(2)) >25] has identified an obesity epidemic that exceeds 30% in some cities and rivals that in Western nations. This review summarizes 2 key lines of evidence: 1) the emergence of an obesity epidemic in urban and rural India and its contribution to the NCD burden and 2) the role of a "nutrition transition" in decreasing the whole plant food content of diets in India and increasing risk of obesity and NCDs. We then present new epidemiologic evidence from Asian Indians enrolled in the Adventist Health Study 2 that raises the possibility of how specific whole plant foods (eg, nuts) in a vegetarian dietary pattern could potentially prevent obesity and NCDs in a target population of >1 billion persons.

Diet pattern and longevity: do simple rules suffice? A commentary.

Nutritionism reduces dietary advice to statements about a few nutrients, with sometimes unintended implications for science, industry, and the public. Although reductionist questions about nutrition are legitimate scientifically, a nutrient focus in the public arena forces the food industry to compete with the use of nutrient statements. Consumers must interpret information that may not be correct or relevant. The theory of food synergy, which postulates that the many constituents of individual foods and dietary patterns act together on health, leads to the idea that dietary policy would be clearer if it focused on foods. To illustrate this method, the food-based A Priori Diet Quality Score was described in the Iowa Women's Health Study; a substantial total mortality reduction for increasing quartiles of the score was found. The simple food-based rules implied in this a priori score support minimizing meat, salt, added sugar, and heavily processed foods while emphasizing phytochemical-rich foods. These principles could help improve nutrition policy, help industry to supply better food, and help to focus future scientific research. Although an understanding of what foods are best for health is a step forward in nutrition, other major challenges remain, including getting high-quality food to the masses and food sustainability.