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.

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.

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.

BACKGROUND: Elevated plasma methylmalonic acid (MMA) is a functional biomarker of vitamin B-12 status but limited information is available on its prevalence in US vegetarians. OBJECTIVES: The 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. METHODS: In 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. RESULTS: The 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. CONCLUSIONS: The 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.

Comparison of polyphenol intakes according to distinct dietary patterns and food sources in the Adventist Health Study-2 cohort.

Evidence suggests a relationship between polyphenol intake and health benefits. Polyphenol intake among a large US cohort with diverse dietary practices ranging from meatless to omnivorous diets has not been previously evaluated. The primary aim of this study was to compare polyphenol intakes of several vegetarian and non-vegetarian dietary patterns and to assess phenolic intake by food source. To characterise dietary intake, a FFQ was administered to 77 441 participants of the Adventist Health Study-2. Dietary patterns were defined based on the absence of animal food consumption as vegan, lacto-ovo-vegetarian, pesco-vegetarian, semi-vegetarian and non-vegetarian. Polyphenol intakes were calculated based on chromatography-derived polyphenol content data of foods from Phenol-Explorer, US Department of Agriculture databases and relevant literature. Results revealed a mean unadjusted total polyphenol intake of 801 (sd 356) mg/d, and the main foods contributing to polyphenol intakes were coffee, fruits and fruit juices. Total polyphenol intake differed significantly between dietary patterns, with phenolic acids from coffee contributing the greatest variation. The dominant classes and sources of dietary polyphenols differed between vegetarian and non-vegetarian diets. Flavonoid intake was the highest among pesco-vegetarians, and phenolic acid intake was the highest among non-vegetarians. In addition, coffee consumers appeared to have a different dietary profile than non-coffee consumers, including greatly reduced contribution of fruits, vegetables and legumes to total phenolic intake. Coffee drinkers were more likely to be non-vegetarians, which explained several of these observations. Further evaluating these differences may be important in identifying relationships between plant-based diets and health outcomes.

Determinants of serum 25 hydroxyvitamin D levels in a nationwide cohort of blacks and non-Hispanic whites.

OBJECTIVE: To develop algorithms predicting serum 25 hydroxyvitamin D [s25(OH)D] for a large epidemiological study whose subjects come from large geographic areas, are racially diverse and have a wide range in age, skin types, and month of blood sample collection. This will allow a regression calibration approach to determine s25(OH)D levels replacing the more costly method of collection and analysis of blood samples. STUDY DESIGN AND SETTING: Questionnaire data from a subsample of 236 non-Hispanic whites (whites) and 209 blacks from the widely dispersed Adventist Health Study-2 (n = 96,000) were used to develop prediction algorithms for races separately and combined. A single blood sample was collected from each subject, at different times throughout the year. RESULTS: Models with independent variables age, sex, BMI, skin type, UV season, erythemal zone, total dietary vitamin D intake, and sun exposure factor explained 22 and 31% of the variance of s25(OH)D levels in white and black populations, respectively (42% when combined). UV season and erythemal zone determined from measured UV radiation produced models with higher R (2) than season and latitude. CONCLUSION: Combining races with a term for race and using variables with measured UV radiation capture the variance in s25(OH)D levels better than analyzing races separately.

Serum 25-hydroxyvitamin D status of vegetarians, partial vegetarians, and nonvegetarians: the Adventist Health Study-2.

BACKGROUND: Vegans and other vegetarians who limit their intake of animal products may be at greater risk of vitamin D deficiency than nonvegetarians, because foods providing the highest amount of vitamin D per gram naturally are all from animal sources, and fortification with vitamin D currently occurs in few foods. OBJECTIVE: We assessed serum 25-hydroxyvitamin D [s25(OH)D] concentrations and factors affecting them in vegetarians, partial vegetarians, and nonvegetarians in a sample of calibration study subjects from the Adventist Health Study-2. DESIGN: Food-frequency questionnaires and sun-exposure data were obtained from 199 black and 229 non-Hispanic white adults. We compared s25(OH)D concentration, dietary and supplemental vitamin D intake, and sun exposure in the different dietary groups. RESULTS: We found no significant difference in s25(OH)D by vegetarian status for either white or black subjects. Among whites, dietary vitamin D intake and sun behavior were different between vegetarian groups, but there was no difference in skin type distribution. Among blacks, no significant differences were observed for any of these variables between vegetarian groups. The mean (+/-SD) s25(OH)D was higher in whites (77.1 +/- 10.33 nmol/L) than in blacks (50.7 +/- 27.4 nmol/L) (P < 0.0001). CONCLUSIONS: s25(OH)D concentrations were not associated with vegetarian status. Other factors, such as vitamin D supplementation, degree of skin pigmentation, and amount and intensity of sun exposure have greater influence on s25(OH)D than does diet.

Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies.

BACKGROUND: Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, require substitution of other macronutrients to maintain energy balance. OBJECTIVE: We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age. Using substitution models, our aim was to clarify whether energy from unsaturated fatty acids or carbohydrates should replace energy from SFAs to prevent CHD. DESIGN: This was a follow-up study in which data from 11 American and European cohort studies were pooled. The outcome measure was incident CHD. RESULTS: During 4-10 y of follow-up, 5249 coronary events and 2155 coronary deaths occurred among 344,696 persons. For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from carbohydrates, there was a modest significant direct association between carbohydrates and coronary events (hazard ratio: 1.07; 95% CI: 1.01, 1.14); the hazard ratio for coronary deaths was 0.96 (95% CI: 0.82, 1.13). MUFA intake was not associated with CHD. No effect modification by sex or age was found. CONCLUSION: The associations suggest that replacing SFAs with PUFAs rather than MUFAs or carbohydrates prevents CHD over a wide range of intakes.

Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: a pooled analysis of 8 prospective studies.

Intakes of vitamins A, C and E and folate have been hypothesized to reduce lung cancer risk. We examined these associations in a pooled analysis of the primary data from 8 prospective studies from North America and Europe. Baseline vitamin intake was assessed using a validated food-frequency questionnaire, in each study. We calculated study-specific associations and pooled them using a random-effects model. During follow-up of 430,281 persons over a maximum of 6-16 years in the studies, 3,206 incident lung cancer cases were documented. Vitamin intakes were inversely associated with lung cancer risk in age-adjusted analyses; the associations were greatly attenuated after adjusting for smoking and other risk factors for lung cancer. The pooled multivariate relative risks, comparing the highest vs. lowest quintile of intake from food-only, were 0.96 (95% confidence interval (CI) 0.83-1.11) for vitamin A, 0.80 (95% CI 0.71-0.91) for vitamin C, 0.86 (95% CI 0.76-0.99) for vitamin E and 0.88 (95% CI 0.74-1.04) for folate. The association with vitamin C was not independent of our previously reported inverse association with beta-cryptoxanthin. Further, vitamin intakes from foods plus supplements were not associated with a reduced risk of lung cancer in multivariate analyses, and use of multivitamins and specific vitamin supplements was not significantly associated with lung cancer risk. The results generally did not differ across studies or by sex, smoking habits and lung cancer cell type. In conclusion, these data do not support the hypothesis that intakes of vitamins A, C and E and folate reduce lung cancer risk.

Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts.

BACKGROUND: Epidemiologic studies have suggested a lower risk of coronary heart disease (CHD) at higher intakes of fruit, vegetables, and whole grain. Whether this association is due to antioxidant vitamins or some other factors remains unclear. OBJECTIVE: We studied the relation between the intake of antioxidant vitamins and CHD risk. DESIGN: A cohort study pooling 9 prospective studies that included information on intakes of vitamin E, carotenoids, and vitamin C and that met specific criteria was carried out. During a 10-y follow-up, 4647 major incident CHD events occurred in 293 172 subjects who were free of CHD at baseline. RESULTS: Dietary intake of antioxidant vitamins was only weakly related to a reduced CHD risk after adjustment for potential nondietary and dietary confounding factors. Compared with subjects in the lowest dietary intake quintiles for vitamins E and C, those in the highest intake quintiles had relative risks of CHD incidence of 0.84 (95% CI: 0.71, 1.00; P=0.17) and 1.23 (1.04, 1.45; P=0.07), respectively, and the relative risks for subjects in the highest intake quintiles for the various carotenoids varied from 0.90 to 0.99. Subjects with higher supplemental vitamin C intake had a lower CHD incidence. Compared with subjects who did not take supplemental vitamin C, those who took >700 mg supplemental vitamin C/d had a relative risk of CHD incidence of 0.75 (0.60, 0.93; P for trend <0.001). Supplemental vitamin E intake was not significantly related to reduced CHD risk. CONCLUSIONS: The results suggest a reduced incidence of major CHD events at high supplemental vitamin C intakes. The risk reductions at high vitamin E or carotenoid intakes appear small.

Long-term almond supplementation without advice on food replacement induces favourable nutrient modifications to the habitual diets of free-living individuals.

Epidemiological and metabolic studies have shown that regular nut consumption may protect against risk of heart disease and diabetes. None has investigated the effect of adding nuts to a self-selected habitual diet (containing little or no nuts) on dietary patterns. The present study evaluated the impact of long-term almond supplementation in healthy men (n 43) and women (n 38) aged 25-70 years on nutrient profile and nutrient displacement. All subjects were followed for 1 year. During the first 6 months, subjects followed their habitual diets; in the second 6 months, subjects added almonds to their diets. Diets were assessed by seven random 24 h telephone diet recalls during each diet period. On average, the almond supplement was 52 g/d (about forty-two nuts) containing 1286 kJ. When subjects changed from their habitual diet to the almond-supplemented diet, the intakes of MUFA, PUFA, fibre, vegetable protein, alpha-tocopherol, Cu and Mg significantly (P<0.05) increased by 42, 24, 12, 19, 66, 15 and 23% respectively; the intakes of trans fatty acids, animal protein, Na, cholesterol and sugars significantly (P<0.05) decreased by 14, 9, 21, 17 and 13% respectively. These spontaneous nutrient changes closely match the dietary recommendations to prevent cardiovascular and other chronic diseases. Displacement estimates for total energy, total protein, total fat, SFA, MUFA, PUFA, total fibre, Ca, Fe, Mg, P, K, Zn and alpha-tocopherol ranged from 16 to 98%; the estimates for total food weight, carbohydrate, sugars and Se were >245%. A daily supplement of almonds can induce favourable nutrient modifications for chronic disease prevention to an individual's habitual diet.

Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies.

BACKGROUND: Studies in animals have suggested that calcium may reduce the risk of colorectal cancer. However, results from epidemiologic studies of intake of calcium or dairy foods and colorectal cancer risk have been inconclusive. METHODS: We pooled the primary data from 10 cohort studies in five countries that assessed usual dietary intake by using a validated food frequency questionnaire at baseline. For most studies, follow-up was extended beyond that in the original publication. The studies included 534 536 individuals, among whom 4992 incident cases of colorectal cancer were diagnosed between 6 and 16 years of follow-up. Pooled multivariable relative risks for categories of milk intake and quintiles of calcium intake and 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. RESULTS: Milk intake was related to a reduced risk of colorectal cancer. Compared with the lowest category of intake (<70 g/day), relative risks of colorectal cancer for increasing categories (70-174, 175-249, and > or =250 g/day) of milk intake were 0.94 (95% CI = 0.86 to 1.02), 0.88 (95% CI = 0.81 to 0.96), and 0.85 (95% CI = 0.78 to 0.94), respectively (P(trend)<.001). Calcium intake was also inversely related to the risk of colorectal cancer. The relative risk for the highest versus the lowest quintile of intake was 0.86 (95% CI = 0.78 to 0.95; P(trend) =.02) for dietary calcium and 0.78 (95% CI = 0.69 to 0.88; P(trend)<.001) for total calcium (combining dietary and supplemental sources). These results were consistent across studies and sex. The inverse association for milk was limited to cancers of the distal colon (P(trend)<.001) and rectum (P(trend) =.02). CONCLUSION: Higher consumption of milk and calcium is associated with a lower risk of colorectal cancer.