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Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease^1,2,3

¹ From the Division of Metabolism, Endocrinology, and Nutrition, the Department of Medicine, and the Interdisciplinary Nutrition Sciences Program, University of Washington, Seattle; the Laboratory of Cardiovascular Diseases, Oregon Regional Primate Research Center, Beaverton; the Division of Nephrology, Hypertension, and Clinical Pharmacology, the Department of Medicine, Oregon Health Sciences University, Portland; the Nutrition Department, College of Health and Human Development, Pennsylvania State University, University Park; the Division of Endocrinology, Diabetes, and Nutrition, St Luke's–Roosevelt Hospital, Columbia University, New York; the Hypertension Program, University of Alabama at Birmingham; the Division of Endocrinology/Hypertension, Wayne State University Medical Center, Detroit; the Division of Clinical Nutrition, the Department of Nutrition and Metabolism, University of California, Davis Medical Center, Davis; the Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada; and the Clinical Research Group of Oregon, Portland.

Background: Elevated blood homocysteine is a risk factor for cardiovascular disease. A 5-µmol/L increase is associated with an 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 100% of the recommended dietary allowances for 23 micronutrients, including folate.

Results: Mean folate intakes at 10 wk were 601 ± 143 µg/d with the PMP and 270 ± 107 µg/d with the SSD. With the PMP, serum tHcy concentrations fell from 10.8 ± 5.8 to 9.3 ± 4.9 µmol/L (P < 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.

Key Words: Homocysteine • dietary folate • vitamin B-12 • vitamin B-6 • cardiovascular disease • randomized clinical trial • humans

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