Little Support for Oral B Vitamins in Alzheimer Disease

Ingredients in the proprietary nutritional drink Souvenaid, which its developers claim work synergistically to rejuvenate neuronal synapses in Alzheimer disease, include several B vitamins. (For necessary background on Souvenaid development and negative trials of omega-3 fatty acids [another ingredient in Souvenaid] in AD, go here and here.)

The rationale for using vitamins B6,* B9 (folic acid), and B12 specifically in AD is to reduce levels of homocysteine, an independent risk factor for AD. However, a directed PubMed search provides little evidence of the benefit of oral B-vitamin supplementation in dementing disorders. A total of 4 randomized, double-blind, placebo-controlled trials were discovered, in which 1 or more of these vitamins were assessed in patients with AD.

Published in 2007, a Thai study enrolled 89 AChEI-treated individuals with mild-to-moderate AD, all of whom had normal folic acid and vitamin B12 levels. The daily, oral administration of B12 500 mg and a multivitamin containing B6 (5 mg) and folic acid (1 mg) provided no statistically significant cognitive benefits at 26 weeks (measured by using the 11-item ADAS-cog); nor was the ability to perform activities of daily living (ADLs) affected. Negative clinical benefits were observed despite the reduction of homocysteine levels in treated AD patients.

A smaller UK pilot study, reported in 2008, revealed that folic-acid supplementation in 57 AChEI-treated AD outpatients improved the ability to perform instrumental ADLs and social behavior (a combined outcome) at 6 months; but daily folic acid did not significantly alter cognition (measured with the MMSE).

The same year, JAMA published results of an 18-month multicenter US study of 409 individuals with mild-to-moderate AD and normal folic-acid, B12, and homocysteine levels. Randomized, oral supplementation with B6 (25 mg/d), folic acid (5 mg/d), and B12 (1 mg/d) reduced homocysteine levels but had no effect on cognitive decline (measured with the ADAS-cog) in 340 "completers." Curiously depression was more likely to occur in supplemented patients.

Finally last year a multicenter Dutch study was printed, in which "vascular care" was assessed in 130 outpatients with AD and evidence of cerebrovascular disease on brain images. The combined, randomized treatment of aspirin, folic acid, and B6 provided no statistical benefits with respect to measures of cognition, dementia-related disabilities, or behavioral problems at 2 years. Rates of institutionalization were also comparable between patients who received vascular care and those who didn't. 

ADAS-cog = Alzheimer's Disease Assessment Scale, cognitive subscale; AChEI = acetylcholinesterase inhibitor (eg, Aricept [donepezil]); MMSE = Mini-Mental State Examination.

* It should be noted the B6 supplementation is associated with a dose-dependent peripheral neuropathy (for instance see Berger et al and Parry and Bredesen). The Food and Nutrition Board of the Institute of Medicine recommends that daily B6 intake should not exceed 100 mg.

Photograph: Atrophied brain of person with AD from National Institute on Alcohol Abuse and Alcoholism.