High-dose B vitamin supplementation and progression of subclinical atherosclerosis: a randomized controlled trial
Howard N Hodis, Wendy J Mack, Laurie Dustin, Peter R Mahrer, Stanley P Azen, Robert Detrano, Jacob Selhub, Petar Alaupovic, Chao-ran Liu, Ci-hua Liu, Juliana Hwang, Alison G Wilcox, Robert H Selzer, BVAIT Research Group, Howard N Hodis, Peter R Mahrer, Alex Sevanian, Martha Charlson, Sandra Engle, Christine Gesselman, Thelma LaBree, Moss Moss, Charlene Moya, Jan St John, MaryAnn Spahn, Frank Watcher, Liny Zurbrugg, Robert Browning, Phyllis Scutella, Robert H Selzer, Zenaida Lee, Chao-ran Liu, Ci-hua Liu, Alison G Wilcox, Clifford Martizorena, Tom Pham, Donna Proby, John Vicario, Robert Detrano, Christopher Dailing, Agnes Papa, Wendy J Mack, Nicole Aguirre, Stanley P Azen, Laurie Dustin, Molly Hubbard, Michael Hutchinson, George Martinez, Olga Morales, Christina Trujillo, Juliana Hwang, Orlando Bolusan, Gail Izumi, Arletta Ramirez, Jacob Selhub, Petar Alaupovic, Meir Stampfer, B Greg Brown, Joan Hilton, Joanna Badinelli, Andre J Premen, Howard N Hodis, Wendy J Mack, Laurie Dustin, Peter R Mahrer, Stanley P Azen, Robert Detrano, Jacob Selhub, Petar Alaupovic, Chao-ran Liu, Ci-hua Liu, Juliana Hwang, Alison G Wilcox, Robert H Selzer, BVAIT Research Group, Howard N Hodis, Peter R Mahrer, Alex Sevanian, Martha Charlson, Sandra Engle, Christine Gesselman, Thelma LaBree, Moss Moss, Charlene Moya, Jan St John, MaryAnn Spahn, Frank Watcher, Liny Zurbrugg, Robert Browning, Phyllis Scutella, Robert H Selzer, Zenaida Lee, Chao-ran Liu, Ci-hua Liu, Alison G Wilcox, Clifford Martizorena, Tom Pham, Donna Proby, John Vicario, Robert Detrano, Christopher Dailing, Agnes Papa, Wendy J Mack, Nicole Aguirre, Stanley P Azen, Laurie Dustin, Molly Hubbard, Michael Hutchinson, George Martinez, Olga Morales, Christina Trujillo, Juliana Hwang, Orlando Bolusan, Gail Izumi, Arletta Ramirez, Jacob Selhub, Petar Alaupovic, Meir Stampfer, B Greg Brown, Joan Hilton, Joanna Badinelli, Andre J Premen
Abstract
Background and purpose: Although plasma total homocysteine (tHcy) levels are associated with cardiovascular disease, it remains unclear whether homocysteine is a cause or a marker of atherosclerotic vascular disease. We determined whether reduction of tHcy levels with B vitamin supplementation reduces subclinical atherosclerosis progression.
Methods: In this double-blind clinical trial, 506 participants 40 to 89 years of age with an initial tHcy >8.5 micromol/L without diabetes and cardiovascular disease were randomized to high-dose B vitamin supplementation (5 mg folic acid+0.4 mg vitamin B(12)+50 mg vitamin B(6)) or matching placebo for 3.1 years. Subclinical atherosclerosis progression across 3 vascular beds was assessed using high-resolution B-mode ultrasonography to measure carotid artery intima media thickness (primary outcome) and multidetector spiral CT to measure aortic and coronary artery calcium (secondary outcome).
Results: Although the overall carotid artery intima media thickness progression rate was lower with B vitamin supplementation than with placebo, statistically significant between-group differences were not found (P=0.31). However, among subjects with baseline tHcy >or=9.1 micromol/L, those randomized to B vitamin supplementation had a statistically significant lower average rate of carotid artery intima media thickness progression compared with placebo (P=0.02); among subjects with a baseline tHcy <9.1 micromol/L, there was no significant treatment effect (probability value for treatment interaction=0.02). B vitamin supplementation had no effect on progression of aortic or coronary artery calcification overall or within subgroups.
Conclusions: High-dose B vitamin supplementation significantly reduces progression of early-stage subclinical atherosclerosis (carotid artery intima media thickness) in well-nourished healthy B vitamin "replete" individuals at low risk for cardiovascular disease with a fasting tHcy >or=9.1 micromol/L.
Trial registration: ClinicalTrials.gov NCT00114400.
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Source: PubMed