Life Extension Update
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VISP trial revisited
Some of our readers may be familiar with the results of the Vitamin Intervention for Stroke Prevention (VISP) trial which were published in the February 4, 2004 issue of the Journal of the American Medical Association (JAMA). The conclusion of the JAMA report was that a trial of so-called "high dose" and low dose folic acid, vitamin B6, and vitamin B12, given to lower total homocysteine levels had no effect on vascular outcomes during the two year follow-up period. However, a new report entitled, "Vitamin Intervention for Stroke Prevention Trial, An Efficacy Analysis," published in the November 2005 issue of the American Heart Association journal Stroke concluded that a higher intake of vitamin B12 in a subgroup of participants was protective against ischemic stroke, coronary artery disease and death.
J. David Spence, MD of the Stroke Prevention and Atherosclerosis Research Center, Roberts Research Institute in London, Ontario, and coauthors from the VISP Statistical Coordinating Center and Harvard School of Public Health wrote that there were several possible explanations for the lack of efficacy of vitamins to reduce vascular risk in the VISP trial. Folate fortification of grains in North America has reduced the number of people with very low blood folate levels to less than 1 percent of the population, which has lowered plasma homocysteine levels. This would reduce the difference in homocysteine levels between high dose and low dose groups in the study, and could have influenced the apparent effect of the supplements. Additionally, although a multivitamin containing the recommended daily intake (RDI) for all vitamins except those included in the study was distributed to all participants, the RDI of vitamin B12 was given to subjects in the low dose group, and participants with low serum levels of the vitamin were given B12 injections. The authors also noted that the dose of vitamin B12 in the high dose group was only 400 micrograms per day, which may have been too low to be effective for older individuals whose ability to absorb vitamin B12 is frequently abnormal. Furthermore, although individuals on dialysis were excluded from the study, some of the participants had significant renal impairment which could render them unable to respond well to supplementation.
For the current analysis, a subgroup of 2,155 of the original subjects were selected who would be more likely to respond to vitamin therapy. The investigators found a 21 percent lower risk of ischemic stroke, coronary disease or death in participants who received the higher dose of the supplements compared to the lower dose. Analysis of blood levels found that those whose levels were in the top 50 percent and who received the high dose supplements experienced the best overall outcome, while those whose B12 levels were in the lowest half who received the low dose regimen had the worst outcome.
Analysis of total homocysteine levels as they related to serum vitamin B12 levels suggested that levels of the vitamin sufficient to maintain low homocysteine are higher than those commonly regarded as adequate. The authors conclude that "Higher doses of B12, and other treatments to lower total homocysteine may be needed for some patients."
Cardiovascular disease causes 44% of all deaths in the United States. Alzheimer's dementia affects 4 million Americans now, and is expected to increase sharply as the population ages. Both cardiovascular and Alzheimer's disease have now been linked to the accumulation of a toxic amino acid called homocysteine. Vitamin supplement users have assumed they are being protected against homocysteine overload, but this article will expose that fallacy and recommend a scientific course of action to follow.
The medical establishment woke up to the dangers of homocysteine when the New England Journal of Medicine (April 9, 1998) and the Journal of the American Medical Association (JAMA, Dec. 18, 1996) published articles suggesting that vitamin supplements be used to lower homocysteine levels. This same message was published by the Life Extension Foundation 18 years earlier (Anti-Aging News, Nov. 1981, 85-86).
Some cardiologists suggest that coronary artery disease patients take a multivitamin supplement to lower their homocysteine levels. Patients who follow this advice, but fail to have their blood tested for homocysteine, could be making a fatal mistake.
The Life Extension Foundation has uncovered a flaw in the theory that a person can blindly take vitamin supplements to adequately reduce homocysteine levels. While folic acid, vitamin B12, B6, and trimethylglycine (TMG) all lower homocysteine levels, it is impossible for any individual to know if he or she is taking the proper amount of nutrients without a homocysteine blood test.
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