Adventist Health Study-2 Research Articles

Letter to the editor concerning: Stroke and diets: A review

Dear Editor, It is with great interest that we read the recently published review entitled “Stroke and Diets” in the Tzu Chi Medical Journal[1]. The authors provide a concise and up-to-date discussion on the role of different dietary patterns in the prevention of stroke. Lin et al. concluded that “vegetarian (meatless) diets have a significant impact on major risk factors of stroke” and highlighted their importance in both stroke prevention and management. We agree that plant-based diets are beneficial with regard to stroke risk factor management (including hypertension, obesity, and atrial fibrillation[2]), yet we also believe that it is of paramount importance to differentiate between different plant-based eating patterns in greater detail. In particular, the lacto-ovo-vegetarian diet (which includes dairy products such as milk, cheese, and yoghurt) and the vegan diet (defined by the absence of all animal foods) may have different effects on several established stroke risk factors. The Adventist Health Study-2 cited by Lin revealed that lacto-ovo-vegetarians had a significantly higher body mass index (25.7 ± 5.1 kg/m 2) than those consuming a vegan diet (23.6 ± 4.4 kg/m2)[3]. Diabetes, another major stroke risk factor, was also found more frequently in vegetarians than in vegans [Figure 1] [3].Figure 1: Prevalence of type-2-diabetes (in %) among different dietary patterns in the Adventist Health Study-2One important difference between both dietary patterns is that vegan diets exclude cheese, a food high in (saturated) fat and sodium. Excessive intake of both of these nutrients has been frequently associated with an increased stroke risk[4]. The higher cheese (and subsequently sodium) intake in vegetarians also served as one of several potential explanations why vegetarians were shown to have higher rates of hemorrhagic and total stroke than omnivores in the EPIC-Oxford study[5]. Of note, this study has been often criticized for combining vegetarians and vegans in the same group and a recent cohort study by Chiu et al. revealed opposite finding[6]. A Taiwanese vegetarian diet was associated with a lower risk of ischemic and hemorrhagic strokes[6]. Yet, the low number of daily dairy servings in this examined Taiwanese cohort (compared to European or American vegetarian cohorts) warrants special consideration. Taiwanese vegetarians had a median daily intake of only 0.2 dairy servings (1 serving of dairy was defined as 8 g protein) per day, whereas EPIC-Oxford vegetarians consumed significantly more: 232.3 (±207.3) ml dairy milk and 26.8 (±25.4) g dairy cheese per day[5]. This raises the question whether the comparably low dairy intake is potentially a unique feature to the Taiwanese vegetarian diet? Is it not conceivable that this substantial difference (and the implied reduction in daily saturated fat and sodium intake) could mediate some of the health effects of the Taiwanese vegetarian diet? Finally, it would also be interesting whether the authors are aware of different stroke risk profiles of Taiwanese vegetarians (consuming few dairy products) and Taiwanese vegans (avoiding all dairy products)? Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Vegetarian Dietary Patterns and Cognitive Function among Older Adults: The Adventist Health Study-2

We explored effects on cognitive function of following plant-based vegetarian compared with non-vegetarian dietary patterns in otherwise healthy older community-dwelling members of the Adventist Health Study-2 cohort (n = 132). Cognition was assessed using a comprehensive neuropsychological battery; a principal components analysis derived processing speed, executive function, and memory/language factors. Mild memory impairment (MMI) (n = 26, 19.7%) was identified by memory tests. Vegetarians consumed (a) meats, fish, and dairy <1 time/month, (b) dairy ≥1 time/month and meats, and fish <1 time/month, or (c) fish ≥1 time/month, no limits on dairy, and meats <1 time/month. Dietary patterns were determined at baseline, for each decade, and at cognitive assessment; a diet stability score was calculated. Factor scores were not different between vegetarians and non-vegetarians, nor was dietary pattern associated with a lower odds of MMI. A more stable diet over the life course was associated with better memory/language [β = 0.021 SE(β) = 0.008; p = 0.01]. This exploratory study did not support differences in processing speed, executive function, or memory/language abilities between vegetarians and non-vegetarians but did suggest that a more stable dietary pattern which was characteristic of vegetarians was associated with better memory/language abilities.

Dietary patterns and hip fracture in the Adventist Health Study 2: combined vitamin D and calcium supplementation mitigate increased hip fracture risk among vegans

Concerns regarding the adequacy of vegetarian diets with respect to fracture risk continue. We aimed to explore the influence of 5 previously defined dietary patterns on hip fracture risk and whether this association is modified by concomitant calcium and vitamin D supplementation. The Adventist Health Study 2 is a prospective cohort study in which participants were enrolled during 2002-2007; proportional hazards regression analyses were used to estimate fracture risk. Participants reside throughout the United States and Canada. A total of 34,542 non-Hispanic white peri- and postmenopausal women and men 45 y and older responded to the biennial hospital history form and were followed for a median of 8.4 y. The study identified 679 incident hip fractures during 249,186 person-years of follow-up. Fracture risk varied according to dietary pattern, with a clear effect modification by concurrent supplementation with both vitamin D and calcium. In multivariable models, including adjustment for calcium and vitamin D supplementation, female vegans had 55% higher risk of hip fracture (HR: 1.55; 95% CI: 1.06, 2.26) than nonvegetarians (NVEGs), whereas there was no association between diet pattern and hip fracture risk in men. When further stratifying females on supplement use with both vitamin D and calcium, vegans taking both supplements were at no greater risk of hip fracture than the subjects with other dietary patterns including the NVEGs. Without combined supplementation of both vitamin D and calcium, female vegans are at high risk of hip fracture. However, with supplementation the excessive risk associated with vegans disappeared. Further research is needed to confirm the adequacy of a vegan diet supplemented with calcium and vitamin D with respect to risk of fracture.

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.

The effectiveness of plant-based nutrition in the treatment of arterial hypertension

In the treatment of hypertension, an important role is played by the modification of the lifestyle of patients, especially the correction of their diet. Plant nutrition has the ability to improve blood pressure in such patients. However, a large number of types of vegetarian diets leave open the question of which of them is the best in the treatment of arterial hypertension.The aim of the study was to analyze the literature on the effectiveness of different plant-based diets in the treatment of hypertension and to determine whether the complete absence of animal products in a vegetarian diet is necessary to achieve a significant beneficial effect on blood pressure. The paper analyzes the data of many scientific studies and meta-analyses: the team of scientists from the University of Warwick; Dietary Approaches to Stop Hypertension (DASH) research group; a prospective study of coronary risk in young adults (Coronary Artery Risk Development in Young Adults, CARDIA); analysis of three prospective cohorts - Nurses 'Health Study I (NHS I), Nurses' Health Study II (NHS II), and Health Professionals Follow-up Study (HPFS); calibration sub-study Adventist Health Study-2 (AHS-2). The most common plant-based diets and their effect on blood pressure were analyzed: high-fruit and vegetable diet, high-fiber diet, Nordic, lacto-ovo-vegetarian, Mediterranean, vegan and DASH diets. All scientists confirm a positive correlation between the consumption of animal meat and the risk of developing hypertension and/or difficulties in its treatment.Conclusion. The study of literature data allows us to conclude about the important role of plant foods in the prevention and treatment of hypertension. The best results in lowering blood pressure were demonstrated by diets with a complete absence of animal products.

Validation of estimated glycaemic index and glycaemic load, stratified by race, in the Adventist Health Study-2 (AHS-2).

Few studies have validated FFQ estimates of dietary glycaemic index (GI) and load (GL). We investigated how well our estimates of overall GI and GL from FFQs correlate with estimates from repeated 24 h recall data to validate overall GI and GL in the Adventist Health Study-2 (AHS-2). The AHS-2 is a prospective population-based cohort of 95 873 Seventh-day Adventist adult church members enrolled from 2002 to 2007 to investigate diet, cancer and mortality. A 204-item FFQ was used to assess race- and gender-specific validity of GI and GL and 24 h recall data, from the calibration sub-study, were used as the reference. The 734 calibration study participants were randomly selected by church and included approximately equal numbers of blacks and whites but were otherwise similar to the whole cohort with respect to gender, age, education and vegetarian status. The deattenuated correlation coefficients for overall GI ranged from 0·19 (95 % CI -0·06, 0·53) in black men to 0·46 (95 % CI 0·40, 0·60) in black women, with both non-black men and women falling between those values (0·45 (95 % CI 0·35, 0·65) and 0·38 (95 % CI 0·27, 0·57), respectively). GL correlations were somewhat higher for all study participants. When looking at the entire cohort, the deattenuated validity correlation value for overall GI was (r 0·38, 95 % CI 0·36, 0·47) and GL was (r 0·39, 95 % CI 0·34, 0·49). Our findings support the cautious use of our FFQ in epidemiological studies when assessing associations of overall GI and GL with disease risk. However, observed differences by race should be considered when interpreting results.

Environmental Impacts of Foods in the Adventist Health Study-2 Dietary Questionnaire

The objective of this study was to use life cycle assessment to estimate the environmental impacts (from farm to factory gate) of the 198 hard-coded line-items included in the food frequency questionnaire of the Adventist Health Study-2 survey and to assess differences among food groups. Life cycle inventories were created using existing data sources and primary data, and their global warming potential (GWP), land use, and water consumption impacts were assessed using the ReCiPe 2016 methodology. In addition to presenting the impacts according to weight and protein content across food groups, we include the novel addition of presenting impacts according to the NOVA classification indicating various levels of processing. Food categories were compared based on one kilogram of edible food, protein food sources were compared based on one kilogram of protein, and NOVA comparisons were based on one serving. In general, meats had the highest environmental impacts per both weight and protein content, while the lowest overall impacts per kilogram came from fruits. Meat analogs had the lowest overall impacts per kilogram of protein, contrary to expectations that additional processing would result in higher environmental impacts when compared to whole plant-based foods. Per serving, ultra-processed foods had the highest GWP, processed foods the highest land use, and minimally processed foods the highest water consumption. Results from this analysis were consistent with other studies. Results from this study suggest that meat and ultra-processed foods have the overall worst environmental impacts, but high water consumption in some minimally processed foods means that those should be carefully considered as well.

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.

Vegetarian diets, circulating miRNA expression and healthspan in subjects living in the Blue Zone.

A long-term vegetarian diet plays a role in the longevity and maintenance of the healthspan, but the underlying mechanisms for these observations are largely unknown. Particularly, it is not known whether a long-term vegetarian dietary pattern may affect the circulating miRNA expression in such a way as to modulate the healthspan. The Adventist Health Study-2 (AHS-2) cohort includes a large number of older adults who primarily follow vegetarian dietary patterns and reside in Loma Linda, California, one of five “Blue Zones” in the world in which a higher proportion of the population enjoys a longer than average lifespan. We performed miRNA-seq in 96 subjects selected from the AHS-2 cohort with different dietary patterns. We identified several differentially expressed miRNAs between vegetarians and non-vegetarians, which are involved in immune response and cytokine signaling, cell growth and proliferation as well as age-related diseases such as cardiovascular diseases and neurodegenerative diseases. Overall, our study showed that a vegetarian diet modulates aging-associated circulating miRNAs in a sex-dependent manner of differential expression for certain miRNAs, which may be related in a beneficial manner to the healthspan. Further investigation is needed to validate these miRNAs as potential biomarkers for diet-modulated longevity in humans.

The Association Between Phytosterol Intake and Breast Cancer Incidence in the Adventist Health Study-2 Cohort

Abstract Objectives Breast cancer is the most diagnosed form of cancer among American women. Worldwide, it is second only to lung cancer. Phytosterols are phytochemicals found in plant foods that have potential benefits for breast cancer. Research on phytosterols and cancer associations to date has been limited to breast cancer cell lines and animal studies, and the results have been promising. Our objective is to examine the association between breast cancer incidence and phytosterol intake in the Adventist Health Study-2, a large cohort in North America. Methods The present study estimated the association between phytosterol intake and breast cancer incidence in 52,734 females who were part of the Adventist Health Study 2 (AHS-2) cohort. Breast cancer cases (n = 1050) were ascertained with tumor registries from 2008 to 2014. Phytosterols content in foods was quantified by using USDA 17 and other published sources. These values were used to estimate phytosterol intake from food intake assessed by a self-administered food frequency questionnaires (FFQ). Results Hazard ratios were below the null, but statistically non-significant for β-sitosterol [HR = 0.77, 95%CI (0.44–1.36)], campesterol [HR = 0.84, 95%CI (0.46–1.55)], stigmasterol [HR = 0.76 (0.46–1.26)], and total phytosterol [HR = 0.77, 95%CI (0.43–1.40)]. In premenopausal women, HRs ranged between 0.95–1.72; in postmenopausal women, HRs were below the null, ranging between 0.67–0.83. In both premenopausal and postmenopausal women, HRs were statistically non-significant. Conclusions The inverse association between phytosterol consumption and breast cancer incidence appears uncertain. The uncertainty possibly could be due to lack of power or measurement error. Additional epidemiological studies with a larger number of breast cancer cases, improved phytosterol intake estimates, or both are needed. Funding Sources Unilever Research &amp;Development, Vlaardingen, The Netherlands.

Tomato consumption and intake of lycopene as predictors of the incidence of prostate cancer: the Adventist Health Study-2.

Studies have controversially suggested that prostate cancer, the most common cancer among Western men, is less common among those with a high intake of tomato products and lycopene. We examine multivariable associations between the intake of tomatoes and lycopene, and risk of prostate cancer. In a prospective study of 27,934 Adventist men without prevalent cancer, Cox proportional hazard regression analyses were used to address the objectives. Dietary measurement error was partially corrected with regression calibration. 1226 incident cases of prostate cancer, 355 of them aggressive, were identified during 7.9years of follow-up. Consumption of canned and cooked tomatoes more than four times a week was associated with a HR = 0.72 (95% CI 0.55, 0.94, P = 0.02) comparing to risk in those never consuming this food. Treating this as a continuous variable, adjusting for confounders, produces a similar result, HR = 0.86 (95% CI 0.75, 0.99), comparing 64g/day with zero intakes (questionnaire data). Regression calibration, although less precise, suggests a yet stronger and statistically significant inverse relationship, comparing a 24-h dietary recall intake of 71g/day canned and cooked tomato product, with zero intake. Uncalibrated multivariable-adjusted competing risk analyses do not find differences in tomato associations between aggressive and non-aggressive prostate cancers although power for aggressive cancers is limited. Consumption of canned and cooked tomatoes may reduce the risk of prostate cancer. These products contain more available lycopene. However, an observational study cannot exclude confounding by some unidentified, prostate cancer preventive factor. Clinical Trial Registry: ClinicalTrials.gov Identifier: NCT03615599.

Adverse childhood experiences and depressive symptoms: Protective effects of dietary flavonoids

ObjectivesAdverse childhood experiences (ACEs) are associated with increased inflammation, stress, and depression. Diet patterns rich in flavonoids may buffer the effects of ACEs on depression through neuroprotective mechanisms. No studies have examined the protective effects of dietary flavonoids on depressive symptoms after ACEs. We examine the relationships among ACEs, perceived stress, depressive symptoms, and flavonoid intake in older adults. MethodsIn this longitudinal cohort study, flavonoid intake was provided by 6404 Seventh-day Adventist adults in North America who, as part of the Adventist Health Study-2, completed a validated food frequency questionnaire in 2002–6. ACEs, perceived stress, and depressive symptoms were assessed in the Biopsychosocial Religion and Health Study in 2006–7 and 2010–11. Bootstrapping models predicting depression were tested after controls. ResultsACEs were associated with adult depressive symptoms and perceived stress mediated this relationship. A moderated mediation model indicates that flavonoid intake buffers the association between perceived stress and depressive symptoms after ACEs. Flavonoid consumption was negatively associated with depressive symptoms (β = −0.034, p = .03). As ACEs increased by one standard deviation, depressive symptoms increased through the interaction of perceived stress and flavonoids when flavonoids were consumed a standard deviation below the mean (effect = 0.040 SD, BC 95% CI [0.030, 0.052]). Depressive symptoms were lower for those that consumed flavonoids a standard deviation above the mean (effect =. 035 SD, BC 95% CI [0.025, 0.046]). ConclusionA varied diet rich in flavonoids may reduce depressive symptoms associated with perceived stress following ACEs exposure.

Associations of Circulating Methylmalonic Acid and Vitamin B-12 Biomarkers Are Modified by Vegan Dietary Pattern in Adult and Elderly Participants of the Adventist Health Study 2 Calibration Study.

ABSTRACTBackgroundElevated plasma methylmalonic acid (MMA) is a functional biomarker of vitamin B-12 status but limited information is available on its prevalence in US vegetarians.ObjectivesThe study examines the prevalence of plasma MMA ≥0.27 µmol/L in those consuming vegetarian diets, its associations with vitamin B-12 intake and biomarkers, and the modifying effect of vegetarian patterns on these associations.MethodsIn this cross-sectional study (n = 785), concentrations of MMA, vitamin B-12, holotranscobalamin (holoTC), and homocysteine (Hcy) were determined in participants of the calibration substudy of the Adventist Health Study 2 (AHS-2). Vitamin B-12 intake from food, fortified food, and supplements was assessed by six 24-h recalls. Regression models were used to estimate ORs of having high MMA as related to vitamin B-12 status biomarkers, vitamin B-12 intake, and dietary pattern.ResultsThe prevalence of low vitamin B-12 status defined by serum vitamin B-12 <148 pmol/L, holoTC <35 pmol/L, MMA ≥0.27 and ≥0.37 μmol/L, or Hcy ≥15 μmol/L, and the OR of having high MMA did not differ by dietary pattern, possibly due to intake from fortified food and supplements. Total daily vitamin B-12 intake in the second tertile range of 4.4–14.5 μg/d reduced the likelihood of elevated MMA by 69%; and a doubling of vitamin B-12 intake was associated with a 4.3% decrease in plasma MMA. The association between log plasma MMA and biomarkers was modified by diet, with the vegan pattern showing an ∼3-fold stronger association with log serum vitamin B-12 and Hcy than did the nonvegetarian pattern.ConclusionsThe prevalence of vitamin B-12 intake <2.0 μg/d was 15.2% in vegans, 10.6% in lacto-ovo-vegetarians, and 6.5% in nonvegetarians. Given the irreversible neurological consequences of vitamin B-12 inadequacy, the importance of regular supplemental vitamin B-12 intake in adult and elderly individuals is stressed.

Observed Physical Function Is Associated With Better Cognition Among Elderly Adults: The Adventist Health Study-2.

Lifestyle factors may individually protect against the development of mild cognitive impairment. We investigate the relationships between both self-reported physical activity and measured physical function with cognition in a population of elderly adults, more than half of whom follow vegetarian dietary patterns. Otherwise healthy adults (n = 127, mean age 74.9 ± 7.9 years, 61.3% current vegetarians) were assessed using a comprehensive neuropsychological battery. A principal components analysis derived processing speed, executive function, and memory/language factors. Participants reported current levels of vigorous physical activity on questionnaires, and physical function and mobility were measured with the Physical Performance Test (PPT) and Timed Up and Go (TUG) Test. Generalized linear models estimated β coefficients for cross-sectional associations between cognitive factors and indicators of physical abilities and self-reported physical activity. Better physical function indicated by PPT was associated with higher scores on the processing speed factor (β = 0.21 SDs for each 4.4-point increase in PPT score; p = 0.02). Faster TUG times were also associated with higher processing speed factor scores (β = 0.21 SDs increase for each 2.8 second less TUG time; p = 0.02). Self-reported levels of vigorous physical activity were not associated with any area of cognitive function; the association between PPT, TUG and processing speed was independent of physical activity. Associations between PPT and TUG and processing speed were stronger among participants who followed vegetarian dietary patterns. Better physical function may have an effect on cognition in a context of healthy lifestyles.

Multiple Health Benefits and Minimal Risks Associated with Vegetarian Diets.

Understand the current prevalence, health benefits, and health risks of vegetarian diets. Since the publishing of the Adventist Health Study 2 in 2013, there have been several prospective diet studies demonstrating and challenging the health benefits and risks of the vegetarian diet. The definition of the vegetarian diet has become more specific over time and requires standardization for research purposes. Despite an uptrend in sales rates of plant-based foods per year, a 2018 Gallup poll showed overall stagnation of the percentage of self-reported vegetarians and vegans compared to percentages obtained 6 years prior. Compared to the Adventist Health Study, more recent vegetarian diet studies have demonstrated significant although smaller risk reductions for mortality in cardiovascular disease, cerebrovascular disease, diabetes mellitus, and chronic kidney disease. Recent studies have correlated certain food groups with early death or increased longevity. In addition, the vegetarian health risks of deficiencies of protein, omega-3 fatty acids, vitamin D, vitamin B12, iron, calcium, and zinc are explored.

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.

Comment on “Plasma, Urine, and Adipose Tissue Biomarkers of Dietary Intake Differ between Vegetarian and Non-Vegetarian Diet Groups in the Adventist Health Study-2”

Comment on “Plasma, Urine, and Adipose Tissue Biomarkers of Dietary Intake Differ between Vegetarian and Non-Vegetarian Diet Groups in the Adventist Health Study-2”

Patterns of amino acid intake are strongly associated with cardiovascular mortality, independently of the sources of protein.

The intake of specific amino acids (AA) has been associated with cardiovascular health, but amino acids are consumed together as dietary protein. Here we investigated the association between identified patterns of amino acid intake and cardiovascular mortality. A total of 2216 cardiovascular deaths among 79838 men and women from the Adventist Health Study-2 were included in our analysis. Baseline dietary patterns based on the participants' amino acids intakes were derived by factor analysis. Using Cox regression analyses, we estimated multivariate-adjusted hazard ratios (HRs) adjusted for sociodemographic and lifestyle factors and other dietary components. Three patterns of amino acids were identified. Factor 1 was positively associated with cardiovascular disease (CVD) mortality [hazard ratio (HR)Q5-Q1: 1.62, 98.75% confidence interval (CI): 1.15, 2.28; P-trend <0.001]; and Factors 2 and 3 were inversely associated with CVD mortality (HR Q5-Q1 Factor 2: 0.74, 98.75% CI: 0.53, 1.04; P-trend <0.01 and HR Q5-Q1 Factor 3: 0.65, 98.75% CI: 0.44, 0.95; P-trend <0.05]. The associations with Factor 1 (with high loadings on indispensable amino acids such as branched chain amino acids, lysine, methionine) and Factor 3 (with high loadings on non-indispensable amino acids, namely arginine, glycine, aspartate+asparagine) remained significant after further adjustment for nutrient intake and for the five protein source patterns identified previously (HR Q5-Q1: 1.56 (0.99, 2.45) and 0.55 (0.35, 0.85); P-trends < 0.01). Indispensable AA have a positive and some non-indispensable AA have a negative, independent, strong association with the risk of cardiovascular mortality.

Dairy Milk Is Associated with Increased Risk of Breast Cancer in the Adventist Health Study-2 (AHS-2) Cohort (P05-026-19)

ObjectivesAssociations between diet and risk of breast cancer have been difficult to identify. Dairy milk has been hypothesized as a possible cause based on ecological data, also its sex hormone content (70% of dairy cows are pregnant), and likely ability to raise levels of insulin-like growth factor-1. We tested the dairy-breast cancer hypothesis in the Adventist Health Study-2 (AHS-2) cohort. MethodsAHS-2 is a national cohort that includes 61,000 Adventist women, of whom 52,795 formed an analytic cohort after exclusions. Many of these women did not consume dairy or consumed in minimal amounts, but more than half (i.e., the non-vegetarians) consumed dairy in usual amounts, on average. Soymilk was also consumed by many. Consumption of dairy, other foods and covariates was assessed from an extensive food frequency, health habits, and medical history questionnaire at study baseline (2002–7). During follow-up 1057 incident breast cancers were observed largely by matching with state cancer registries. Statistical analyses used proportional hazards regressions, adjusting for reproductive and other possible lifestyle risk factors. A calibration study with repeated 24-hour dietary recalls allowed for regression calibration. ResultsComparing 90th to 10th percentiles of intake, dairy milk was associated with a hazard ratio (HR) of 1.41 (95% CI: 1.15–1.72; P = 0.001), rising to 2.56 (95% CI:1.51–4.99; P < 0.001) with the less biased but less precise regression calibration procedure. Models substituting median intakes of soymilk for dairy milk (medians of users) predicted a HR of 0.66 (95% CI:0.51–0.85; P < 0.001). No associations were seen with cheese or yogurt. Associations were non-linear with steeper rises in breast cancer risk at intakes of dairy milk up to ¾ cup/day. No clear indication of protection was seen for soymilk after adjustment for dairy. ConclusionsIn this population, dairy milk consumption is clearly associated with risk of breast cancer after adjusting for soy intake. This was not the case for cheese (known to have lower hormone content). More work is needed to define possible mechanisms. Those at higher risk of breast cancer may gain advantage by limiting milk intake and considering dairy substitutes. Funding SourcesNational Institutes of Health, 1UO1CA152939]; World Cancer Research Fund (U.K.), grant 2009/93.

Differences in DNA Methylation Patterns Between Vegans and Non-vegetarians in the AHS-2 Cohort (FS11-06-19)

ObjectivesIt is unclear how diets differing in content of animal products affect DNA methylation patterns. We sought to determine if DNA methylation patterns differed between vegans and non-vegetarians in the Adventist Health Study-2 (AHS-2) cohort. MethodsDNA methylation was profiled using the Infinium Human Methylation 450 K BeadChip in white blood cells of 137 participants in the AHS-2 cohort classified as vegan (57) or non-vegetarian (80) based on validated diet history data. Linear regression models were generated to test associations between diet pattern and methylation, where the response variable represented methylation intensity for individual CpG sites. This was repeated for sites separated into gene regions or in relation to CpG islands. CpG methylation was also averaged across each gene. The permutation-identified null distribution, false discovery rate of Storey et al was used to adjust for multiple testing. ResultsA total of 53,809 individual CpG sites were estimated to be differentially methylated (non-null). Of these, with this small sample, we could individually identify only up to 5.5% (differing by gene region) at FDR <0.05. A vegan diet was associated almost exclusively with hypomethylation of individual CpG sites. Significant CpG sites numbered 2504 within CpG islands, 749 and 13 CpG sites 0–200 base pairs or 201–1500 base pairs upstream of the transcription start site (TSS200 and TSS1500), respectively, and 51 and 458 sites falling within the 5’ UTR and first exon, respectively. The greatest difference in methylation was observed for sites mapping to TSS200 and CpG islands, where methylation was 9.2% lower in vegans. No differences were found when CpG methylation was averaged to obtain a cumulative value for all sites (no FDR criterion) within each gene region. A total of 328 genes (averaging all methylation regions) were significantly hypomethylated in vegans relative to non-vegetarians at FDR <0.05. The greatest number of genes were hypomethylated when considering methylation of only CpG islands, followed by the TSS200, first exon, and TSS1500 regions. ConclusionsOur findings suggest substantial differences in methylation of CpG sites and genes, particularly in regulatory regions, between vegans and non-vegetarians, with a preponderance of hypomethylation among vegans. Funding SourcesNational Institute of Health, National Cancer Institute, World Cancer Research Fund (UK).