Association of tea and coffee consumption and biliary tract cancer risk: The Biliary Tract Cancers Pooling Project.

BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Systemic Lupus Erythematosus and the Ratio of Omega-3 to Omega-6 Fatty Acids Consumption among Women in the Adventist Health Study-2.

OBJECTIVE: To assess the associations of omega-3 and omega-6 fatty acids consumption, and the ratio between the two, with self-reported doctor told Systemic Lupus Erythematosus (SLE) diagnosis. Further, to assess whether initiation of omega-3 supplements intake was related to time/year of SLE diagnosis. METHODS: Data from 42,398 women in the Adventist Health Study-2 cohort were used for this cross-sectional study. Unconditional logistic regression modeling was used for all analyses with the following candidate covariates: age, race, education, smoking, and body mass index (BMI). RESULTS: Compared to non-cases, participants with a diagnosis of SLE reported higher intakes of total omega-3 fatty acids and about the same intakes of omega-6 fatty acids. Overall, they had higher ratios of omega-3 to omega-6 fatty acids. When assessing odds ratios of SLE diagnosis by quartiles of omega-3 to omega-6 and DHA+EPA to omega-6, there was a positive significant trend (p trend = 0.005). Additionally, among those reporting intake of fish oil, 87% had initiated fish oil consumption around the time of SLE diagnosis. SLE was more likely to occur among Black women compared to White women, among ever smokers compared to never smokers, among overweight women compared to women with normal/underweight, and among women 50-59 years compared to those 30-49 year old. When a smaller 6 year follow-up study identified 64 incident SLE cases and assessed their omega-3 intake at baseline (6 years earlier and before the SLE diagnosis) their intake of omega-3 and fish oil was no different than among non-cases. CONCLUSION: We observed a significant positive association between the ratio of omega-3 to omega-6 fatty acids consumption and prevalence of SLE. Among those with prevalent SLE, their year of starting supplementation of omega-3 and fish oil was closely linked to year of SLE diagnosis. Further, baseline intake of omega-3 fatty acids was not increased among 64 incident SLE cases identified during 6 years of follow-up. Our surprising finding can best be explained by reverse causation. This could be an example of how public health information is assimilated and acted upon by a health conscious public.

Proportional troponin changes and risk for outcomes with intervention strategies in non-ST-elevation acute coronary syndrome across kidney function.

AIMS: This analysis evaluates whether proportional serial cardiac troponin (cTn) change predicts benefit from an early versus delayed invasive, or conservative treatment strategies across kidney function in non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Patients diagnosed with NSTE-ACS in the Veterans Health Administration between 1999 and 2022 were categorized into terciles (<20%, 20 to ≤80%, >80%) of proportional change in serial cTn. Primary outcome included mortality or rehospitalization for myocardial infarction at 6 and 12 months, in survivors of index admission. Adjusted hazard ratio (HR) with 95% confidence Intervals (95% confidence interval [CI]) were calculated for the primary outcome for an early invasive (≤24 h of the index admission), delayed invasive (>24 h of index admission to 90-days postdischarge), or a conservative management. RESULTS: Chronic kidney disease (CKD) was more prevalent (45.3%) in the lowest versus 42.2% and 43% in middle and highest terciles, respectively (p < 0.001). Primary outcome is more likely for conservative versus early invasive strategy at 6 (HR: 1.44, 95% CI: 1.37-1.50) and 12 months (HR: 1.44, 95% CI: 1.39-1.50). A >80% proportional change demonstrated HR (95% CI): 0.90 (0.83-0.97) and 0.93 (0.88-1.00; p = 0.041) for primary outcome at 6 and 12 months, respectively, when an early versus delayed invasive strategy was used, across CKD stages. CONCLUSIONS: Overall, the invasive strategy was safe and associated with improved outcomes across kidney function in NSTE-ACS. Additionally, >80% proportional change in serial troponin in NSTE-ACS is associated with benefit from an early versus a delayed invasive strategy regardless of kidney function. These findings deserve confirmation in randomized controlled trials.

Plasma metabolomics profiles in Black and White participants of the Adventist Health Study-2 cohort.

BACKGROUND: Black Americans suffer disparities in risk for cardiometabolic and other chronic diseases. Findings from the Adventist Health Study-2 (AHS-2) cohort have shown associations of plant-based dietary patterns and healthy lifestyle factors with prevention of such diseases. Hence, it is likely that racial differences in metabolic profiles correlating with disparities in chronic diseases are explained largely by diet and lifestyle, besides social determinants of health. METHODS: Untargeted plasma metabolomics screening was performed on plasma samples from 350 participants of the AHS-2, including 171 Black and 179 White participants, using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and a global platform of 892 metabolites. Differences in metabolites or biochemical subclasses by race were analyzed using linear regression, considering various models adjusted for known confounders, dietary and/or other lifestyle behaviors, social vulnerability, and psychosocial stress. The Storey permutation approach was used to adjust for false discovery at FDR < 0.05. RESULTS: Linear regression revealed differential abundance of over 40% of individual metabolites or biochemical subclasses when comparing Black with White participants after adjustment for false discovery (FDR < 0.05), with the vast majority showing lower abundance in Blacks. Associations were not appreciably altered with adjustment for dietary patterns and socioeconomic or psychosocial stress. Metabolite subclasses showing consistently lower abundance in Black participants included various lipids, such as lysophospholipids, phosphatidylethanolamines, monoacylglycerols, diacylglycerols, and long-chain monounsaturated fatty acids, among other subclasses or lipid categories. Among all biochemical subclasses, creatine metabolism exclusively showed higher abundance in Black participants, although among metabolites within this subclass, only creatine showed differential abundance after adjustment for glomerular filtration rate. Notable metabolites in higher abundance in Black participants included methyl and propyl paraben sulfates, piperine metabolites, and a considerable proportion of acetylated amino acids, including many previously found associated with glomerular filtration rate. CONCLUSIONS: Differences in metabolic profiles were evident when comparing Black and White participants of the AHS-2 cohort. These differences are likely attributed in part to dietary behaviors not adequately explained by dietary pattern covariates, besides other environmental or genetic factors. Alterations in these metabolites and associated subclasses may have implications for the prevention of chronic diseases in Black Americans.

Sialic acids Neu5Ac and KDN in adipose tissue samples from individuals following habitual vegetarian or non-vegetarian dietary patterns.

Sialic acids (Sias) are a class of sugar molecules with a parent nine-carbon neuraminic acid, generally present at the ends of carbohydrate chains, either attached to cellular surfaces or as secreted glycoconjugates. Given their position and structural diversity, Sias modulate a wide variety of biological processes. However, little is known about the role of Sias in human adipose tissue, or their implications for health and disease, particularly among individuals following different dietary patterns. The goal of this study was to measure N-Acetylneuraminic acid (Neu5Ac), N-Glycolylneuraminic acid (Neu5Gc), and 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN) concentrations in adipose tissue samples from participants in the Adventist Health Study-2 (AHS-2) and to compare the abundance of these Sias in individuals following habitual, long-term vegetarian or non-vegetarian dietary patterns. A method was successfully developed for the extraction and detection of Sias in adipose tissue. Sias levels were quantified in 52 vegans, 56 lacto-vegetarians, and 48 non-vegetarians using LC-MS/MS with Neu5Ac-D-1,2,3-13C3 as an internal standard. Dietary groups were compared using linear regression. Vegans and lacto-ovo-vegetarians had significantly higher concentrations of Neu5Ac relative to non-vegetarians. While KDN levels tended to be higher in vegans and lacto-ovo-vegetarians, these differences were not statistically significant. However, KDN levels were significantly inversely associated with body mass index. In contrast, Neu5Gc was not detected in human adipose samples. It is plausible that different Neu5Ac concentrations in adipose tissues of vegetarians, compared to those of non-vegetarians, reflect a difference in the baseline inflammatory status between the two groups. Epidemiologic studies examining levels of Sias in human adipose tissue and other biospecimens will help to further explore their roles in development and progression of inflammatory conditions and chronic diseases.

Left ventricular diastolic abnormalities in vegetarians compared with non-vegetarians.

Vegetarians have less hypertension, diabetes mellitus and obesity, hence possibly lower risk of congestive heart failure (HF). We studied associations between vegetarian diets and echocardiographic markers of stage B HF. In a cross-sectional study, dietary pattern was ascertained by a validated FFQ. Echocardiograms were interpreted using standardised criteria. Participants were free-living subjects in Southern California who were older Adventist Health Study-2 cohort members. After exclusions, 133 subjects aged >60 years were enrolled. Their mean age was 72·7 (sd 8·7) years, 48·1 % were female, 32 % were African American and 71 % were vegetarian. Non-vegetarians had higher body weight (80·3 (sd 15·17) kg v. 71·3 (sd 16·2), P < 0·005), body surface area (1·92 (sd 0·24) m2v. 1·81 (sd 0·22) m2, P = 0·01) and prevalence of hypertension (63 % v. 47 %, P = 0·10). Adjusting for age, sex, race and physical activity, it is found that vegetarians had greater echocardiographic mitral annular e' velocity (a measure of left ventricular (LV) relaxation) 7·44 v. 6·48 (non-vegetarian) cm/s (P = 0·011) and a yet greater contrast when vegans (7·66 cm/s, P = 0·011) were the group of interest. The ratio mid-to-late-diastolic mitral flow velocity (E/A) was also higher in vegans compared with non-vegetarians (1·02 and 0·84, respectively, P = 0·008). Mediation analyses suggested these associations may be partly related to higher blood pressures and BMI in the non-vegetarians. We conclude that vegetarians, especially vegans, appear to have better LV relaxation and fewer diastolic abnormalities than others. As dietary exposure is modifiable, one may speculate pending further investigation about the potential for reduction of stage B HF and later mortality.

The association between dietary patterns and a doctor diagnosis of systemic lupus erythematosus: the Adventist Health Study-2.

OBJECTIVE: The aim of our study was to assess the association between a diagnosis of Systemic Lupus Erythematosus (SLE) and dietary pattern as well as demographic factors among subjects in the Adventist Health Study-2 (AHS-2) cohort. METHODS: Multivariable logistic regression modeling was used to assess the association between prevalence of self-reported SLE and dietary patterns (vegetarian, pesco-vegetarian and non-vegetarian). Potential confounding variables included were age, gender, race, education, and smoking history among 77,795 AHS-2 participants. RESULTS: There was a dose-response association between the prevalence of SLE with vegetarian diets, ordered by content of animal meats. The stricter vegetarians had 25% lower odds of reporting that they were currently being treated for SLE (OR = 0.75, 95% CI 0.56, 1.02) with intermediate levels for the pesco-vegetarians who eat fish (OR 0.88, 95% CI 0.57, 1.36), compared to non-vegetarians. As expected, there were also significant associations between the prevalence of SLE with sex, race, age, and smoking. Significantly fewer men were diagnosed with SLE compared to women (OR = 0.14, 95% CI: 0.08, 0.22). Compared to non-Hispanic Whites, non-Hispanic Blacks were significantly more likely to report a diagnosis of SLE (OR 1.69, 95% CI 1.29, 2.21). A significantly lower proportion of 30-39 year olds (OR 0.51, 95% CI 0.29, 0.90) reported a diagnosis of SLE when compared to those 60 or older. Also, ever smokers were more likely to report prevalent SLE than those who had never smoked (OR 1.71, 95% CI 1.27, 2.31). CONCLUSION: We found that vegetarians had lower odds of doctor-diagnosed SLE with an increasing trend in prevalence from stricter vegetarians to pesco-vegetarians to non-vegetarians. We also note that the association with other demographic factors in AHS-2 was similar to that found in other studies. Future studies may focus on assessing the incidence and severity of the disease among vegetarians and non-vegetarians.

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.

Lower Compliance with Cervical Cancer Screening Guidelines Among Vegetarians in North America.

Cervical cancer is preventable and treatable through regular screening and follow-up. However, the utilization of cervical cancer screening may vary widely based on individual lifestyles. The purpose of this study was to examine the differences in the adherence to cervical cancer screening guidelines in various dietary groups. Our study included 21,376 women from the United States and Canada, aged 30-69 from the Adventist Health Study-2, a large population-based prospective cohort study. Modified Poisson regression with robust variance estimation was used to determine the prevalence ratios of cervical cancer screening behavior in participants following five different dietary patterns (non-vegetarians, semi-vegetarians, pesco-vegetarians, lacto-ovo-vegetarians, and vegans). All analyses were adjusted for age, race/ethnicity, marital status, education, personal income, body mass index, smoking, alcohol use, exercise, and family history of all female cancer. Vegetarians, in general, had similar screening prevalence as non-vegetarians. However, vegans were 16% less likely to have had a Pap test compared to non-vegetarians (prevalence ratio (PR) = 0.84, 95% confidence interval 0.81-0.86). Women who were younger, Black, married, more educated, had a family history of all female cancer, had a higher income, and exercise reported higher compliance to a Pap test. It remains to be seen whether vegan women in Adventist Health-2 experience a higher incidence of cervical cancer or are diagnosed at a later stage compared to non-vegetarians.

Cancer risk in living kidney donors.

Living kidney donors are screened for transmissible diseases including cancer. Outcomes following donation are excellent, but concern exists regarding development of chronic kidney disease, and cancer risk is unknown. We used linked transplant and cancer registry data to identify incident cancers among 84,357 kidney donors in the United States (1995-2017). We compared risk with the general population using standardized incidence ratios (SIRs). For selected cancers, we used Poisson regression to compare donors with 47,451 Adventist Health Study 2 (AHS-2) participants, who typically have healthy lifestyles. During follow-up, 2843 cancers were diagnosed in donors, representing an overall deficit (SIR 0.79, 95%CI 0.76-0.82). None of 46 specified cancer sites occurred in excess relative to the general population, and 15 showed significant deficits (SIR < 1.00). Compared with AHS-2 participants, donors had similar incidence of liver cancer, melanoma, breast cancer, and non-Hodgkin lymphoma but, starting 7 years after donation, elevated incidence of colorectal cancer (adjusted incidence rate ratio 2.07, 95%CI 1.54-2.79) and kidney cancer (2.97, 1.58-5.58, accounting for the presence of a single kidney in donors). Elevated kidney cancer incidence may reflect adverse processes in donors' remaining kidney. Nonetheless, cancer risk is lower than in the general population, suggesting that enhanced screening is unnecessary.

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.

Dietary Animal to Plant Protein Ratio Is Associated with Risk Factors of Metabolic Syndrome in Participants of the AHS-2 Calibration Study.

BACKGROUND: Few research studies have focused on the effects of dietary protein on metabolic syndrome and its components. Our objective was to determine the relationship between the type of dietary protein intake and animal to plant (AP) protein ratio with metabolic syndrome and its components. METHODS: This population-based study had a cross sectional design and conducted on 518 participants of the Adventist Health Study 2 (AHS-2) Calibration Study. Two sets of three dietary 24-h recalls were obtained six months apart. Anthropometric measures and biochemical tests were performed in clinics. Regression calibration models were used to determine the association of type of dietary protein with metabolic syndrome and its components (raised triglyceride, raised blood pressure, reduced high-density lipoprotein cholesterol (HDL), raised fasting blood glucose and increased waist circumference). RESULTS: The likelihood of metabolic syndrome was lower in those with higher total dietary protein and animal protein intake (p = 0.02).Total protein (ß = 0.004, [95%CI: 0.002, 0.007]), animal protein intake (ß = 0.004, [95%CI: 0.001, 0.007]) and AP protein intake ratio (ß = 0.034, [95%CI: 0.021, 0.047]) were positively associated with waist circumference. Higher AP protein ratio was related to higher fasting blood glucose (ß = 0.023, [95%CI: 0.005, 0.041]). CONCLUSION: Our study suggests that considering a significant amount of plant protein as a part of total dietary protein has beneficial effects on cardiometabolic risk factors.

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.

Omega-3 fatty acids are associated with blood-brain barrier integrity in a healthy aging population.

In aging populations, omega-3 polyunsaturated fatty acids (PUFAs) have been associated with better cognitive function, slower rates of cognitive decline, and lower risk of developing dementia. Animal studies have shown that diets rich in omega-3 PUFAs reduce blood-brain barrier (BBB) disruption associated with aging, but this has yet to be observed in humans. Forty-five healthy subjects (mean age, 76 years) were recruited and underwent cognitive assessment (verbal learning and memory, language, processing speed, executive function, and motor control) and measurement of PUFAs. Forty of the same subjects also underwent magnetic resonance imaging (MRI) to measure BBB integrity (Ktrans using dynamic contrast-enhanced MRI). The long chain omega-3 score (DHA+EPA) was negatively correlated with Ktrans values in the internal capsule, indicating higher omega-3 levels were associated with greater BBB integrity in this region (r = -0.525, p = .004). Trends were observed for a positive correlation between the long chain omega-3 score and both memory and language scores, but not with executive function, speed, or motor control. The omega-6 score was not significantly correlated with any cognitive scores or Ktrans values. The significant correlations between long chain omega-3 levels and BBB integrity provide a possible mechanism by which omega-3 PUFAs are associated with brain health.

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

BACKGROUND: Concerns regarding the adequacy of vegetarian diets with respect to fracture risk continue. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

OBJECTIVE: 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). DESIGN: 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. SETTING: 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. PARTICIPANTS: 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. RESULTS: 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). CONCLUSIONS: 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.

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.

Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project.

BACKGROUND & AIMS: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. METHODS: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. RESULTS: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only. CONCLUSION: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. LAY SUMMARY: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.