Vitamin B Supplementation Does Not Slow Cognitive Decline in Alzheimer’s Disease
Despite a significant reduction in homocysteine levels, new research shows that supplementation with high-dose vitamins B6 and B12 and folic acid does not slow cognitive decline in patients with mild to moderate Alzheimer’s disease (AD).
The large, randomized, controlled clinical trial — the first study to address the impact of homocysteine reduction on cognitive and clinical decline in AD — showed vitamin supplementation given over 18 months reduced homocysteine levels by 31% in AD patients, but this had no effect on disease progression.
The study, conducted by the Alzheimer Disease Cooperative Study, a consortium of 40 US centers, is published in the October 15 issue of the Journal of the American Medical Association.
“The results indicate that individuals with mild to moderate Alzheimer’s disease and normal vitamin levels should not be treated with high-dose B vitamins,” principal investigator Paul S. Aisen, MD, from the University of California, San Diego, told Medscape Psychiatry.
No Disease-Modifying Effect
Previous research has shown that plasma levels of homocysteine are elevated in patients with AD. It is also well-known that supplementation with B vitamins, including B6, B12, and folic acid, lower plasma homocysteine levels.
Against this background, the group hypothesized that long-term supplementation with B vitamins may have a disease-modifying effect in AD.
To determine whether high-dose supplementation with folic acid and vitamins B6 and B12 for 18 months would slow the rate of decline in cognition, clinical status, function, and behavior, the researchers recruited individuals with mild to moderate AD.
Participants were age 50 years and older with a Mini-Mental State Examination (MMSE) score between 14 and 26 and had normal plasma levels of folate, vitamin B12, and homocysteine.
From 2003 to 2006, 409 individuals with a mean age of 76 years were randomized to receive either placebo (n = 169) or high-dose supplementation (n = 240) for 18 months. Active treatment consisted of 5-mg folic acid, 1-mg vitamin B12, and 25-mg vitamin B6 daily.
“The active treatment was selected to optimally reduce homocysteine levels, based on previous work by our group and others,” said Dr. Aisen.
Supplementation Not Justified
The primary outcome was the 18-month change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog), which includes evaluation of memory, attention, and language. A 25% reduction in ADAS-cog was defined as a significant benefit. Secondary outcomes included changes in MMSE and measures of quality of life.
At 18 months, levels of each vitamin increased over baseline in the active-treatment group, and homocysteine levels were significantly decreased compared with those in the placebo group.
The rate of change in the ADAS-cog score, however, did not differ between the treatment groups. There was also no significant difference between the 2 groups for any secondary outcome, including clinical status, function, or behavior.
In addition, adverse events, including symptoms of depression, were more common in the treated group than in the placebo group.
In an accompanying editorial, Robert J. Clarke, MD, and Derrick A. Bennett, PhD, both from Oxford University, in the United Kingdom, say that the reason the study failed to show any beneficial effect of B vitamins on cognitive decline is unclear.
However, they write, “until and unless new data suggest otherwise, there is insufficient evidence to justify routine use of homocysteine-lowering vitamin supplements for the prevention of Alzheimer’s disease and cognitive decline among individuals with normal vitamin status.”
Dr. Aisen has consulted for, received grant support from, and/or holds stock in the following pharmaceutical companies: Pfizer, Novartis, Janssen, Elan-Wyeth, Roche, Merck, Eli Lilly, Bristol-Myers Squibb, Schering-Plough, Neurochem, Medivation, GlaxoSmithKline, PamLab, Adlyfe, Neuro-Hitech, and Myriad. A complete list of disclosures is available in the original article.
Drs. Clarke and Bennett have disclosed no relevant financial relationships.