Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease

Background: Elevated blood homocysteine is a risk factor for cardiovascular disease. A 5-[micro]mol/L increase is associated with an [approximately equals] 70% increase in relative risk of cardiovascular disease in adults. For patients with established risk factors, this risk is likely even greater. Objective: Effects of increased dietary folate and recommended intakes of vitamins B-12 and B-6 on serum total homocysteine (tHcy) were assessed in individuals at high risk of cardiovascular disease. Design: This trial was conducted at 10 medical research centers in the United States and Canada and included 491 adults with hypertension, dyslipidemia, type 2 diabetes, or a combination thereof. Participants were randomly assigned to follow a prepared meal plan (PMP; n = 244) or a self-selected diet (SSD: n = 247) for 10 wk, which were matched for macronutrient content. The PMP was fortified to provide [is greater than or equal to] 100% of the recommended dietary allowances for 23 micronutrients, including folate. Results: Mean folate intakes at 10 wk were 601 [+ or -] 143 [micro]g/d with the PMP and 270 [+ or -] 107 [micro]g/d with the SSD. With the PMP, serum tHcy concentrations fell from 10.8 [+ or -] 5.8 to 9.3 [+ or -] 4.9 [micro]mol/L (P [is less than] 0.0001) between weeks 0 and 10 and the change was associated with increased intakes of folate, vitamin B-12, and vitamin B-6 and with increased serum and red blood cell folate and serum vitamin B-12 concentrations, tHcy concentrations did not change significantly with the SSD. Conclusions: The PMP resulted in increased intakes and serum concentrations of folate and vitamin B-12. These changes were associated with reduced serum tHcy concentrations in persons at high risk of cardiovascular disease. Am J Clin Nutr 1999:70:881-7. KEY WORDS Homocysteine, dietary folate, vitamin B-12, vitamin B-6, cardiovascular disease, randomized clinical trial, humans