Associations of Circulating Methylmalonic Acid and B12 Biomarkers are Modified by Vegan Dietary Pattern in Adult and Elderly Participants of 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 micromol/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 /=0.27 and >/=0.37 mumol/L, or Hcy >/=15 mumol/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 mug/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 approximately 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 mug/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.