Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004;291:565-75.
3,680 adults with cerebral infarction participated in a study of folic acid, vitamin B6 and vitamin B12 and stroke. Participants received a multivitamin containing the US recommended daily allowance of other vitamins and were randomly assigned to receive once-daily doses of either high-dose or low-dose amounts of the studied vitamins. Subjects were followed for a 2-year period. The high-dose group had a greater reduction in total homocysteine, however neither treatments lowered the risk of stroke, coronary heart disease events or death. Researchers suggest that further studies are necessary to understand the association between total homocysteine levels and vascular risk.
Van Guelpen B, Hultdin J, Johansson I, et al. Low folate levels may protect against colorectal cancer. Gut 2006;55(10):1461-6.
This prospective study was conducted to determine the association between folate levels and the risk of developing colorectal cancer. This is the first study to look at the plasma folate levels unlike the earlier ones that examined the benefits of oral folic acid supplementation. The study involved 226 persons with colorectal cancer and 437 matched controls from the Northersn Sweden Health and Disease Cohort. Researchers observed a bell-shaped association between plasma folate levels and the risk of colorectal cancer. Persons in the highest folate quintile were four times as likely to develop colorectal cancer compared to those in the lowest quintile. These results contradict the data available so far, but the low folate status of the subjects may be the reason. Further studies with long-term follow up are needed to confirm the benefits of folic acid supplementation.
Durga J, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 2007;369(9557):208-216.
In the Folic Acid and Carotid Intima-media Thickness (FACIT) trial, 818 participants (50-70 years of age) with homocysteine concentrations ranging from 13-26 ìmol/L randomly received placebo or folic acid (800 ìg daily) for 3 years during which cognitive function was assessed by 5 separate tests including memory, word fluency, and sensorimotor, complex, and information processing speeds. Participants that received folic acid experienced benefits in memory, speed of information processing, and sensorimotor speed as compared to those receiving placebo, indicating that folic acid supplementation may improve cognitive function in older adults. Further studies are necessary to determine if individuals with low or high homocysteine levels would also benefit in folic acid supplementation.
Connelly PJ, et al. A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease. Int J Geriatr Psychiatry 2008;23(2):155-160.A pilot randomized, double-blind, placebo-controlled study of 57 participants with Alzheimer's disease sought to determine if folic acid supplementation could improve the patients' response to cholinesterase inhibitors. Consecutive patients were either given placebo or folic acid (1 mg daily) and their Mini-Mental State Examination (MMSE) and Instrumental Activities of Daily Living (IADL) and Social Behavior (SB) scores as well as homocysteine levels were assessed at baseline and 3 and 6 months after treatment initiation. Although MMSE scores were not affected by folic acid supplementation, IADL and IADL/SB scores were. Further studies of larger population sizes will confirm whether folic acid supplementation is beneficial in the treatment of Alzheimer's disease.