The effect of vitamin B6 on cognition.

BACKGROUND

Micronutrient status can affect cognitive function at all ages. Vitamin deficiencies could influence memory function and might contribute to age-associated cognitive impairment and dementia. Vitamin B6, comprising three chemically distinct compounds pyridoxal, pyridoxamine, and pyridoxine, is involved in the regulation of mental function and mood. Vitamin B6 is also an essential homocysteine re-methylation cofactor, and deficiency is associated with increase in blood homocysteine levels. Homocysteine is a risk factor for cerebrovascular disease and may also have directly toxic effects on neurons of the central nervous system. Neuropsychiatric disorders including seizures, migraine, chronic pain and depression have been linked to vitamin B6 deficiency. Epidemiological studies indicate that poor vitamin B6 status is common among older people. Hyperhomocysteinaemia has been suggested as a cause or mechanism in the development Alzheimer's disease and other forms of dementia. Supplementation with B vitamins including vitamin B6 has been shown to reduce blood homocysteine levels.

OBJECTIVE

To assess the efficacy of vitamin B6 supplementation in reducing the risk of developing cognitive impairment by older healthy people, or improving cognitive functioning of people with cognitive decline and dementia, whether or not vitamin B6 deficiency has been diagnosed.

METHODS

The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 20 May 2003 using the terms: vitamin B6, pyridoxine, pyridoxamine, pyridoxal. For relevant trials on healthy elderly people MEDLINE, EMBASE and CENTRAL were searched using the previously mentioned terms as well as the term cognit *

METHODS

All unconfounded, double-blind randomized controlled trials in which the intervention with vitamin B6 was compared with placebo for healthy older people or people with cognitive decline or dementia. The primary outcome of interest was the efficacy of vitamin B6 supplementation on cognitive function.

METHODS

The two reviewers independently evaluated all studies identified as possibly meeting the criteria for inclusion. One reviewer independently extracted the data. Studies were rated for their overall quality. The weighted mean differences between treatment and placebo groups, with 95% confidence intervals, were calculated for each outcome. Review Manager version 4.2 was used to analyse the variance.

RESULTS

No trials of vitamin B6 involving people with cognitive impairment or dementia were found. The two trials included in the review (Bryan 2002; Deijen 1992) used a double-blind, randomized, placebo-controlled design and involved 109 healthy older people. One trial restricted enrolment to women and the other to men. Vitamin B6 supplementation and healthy older women: Bryan 2002 enrolled 211 healthy women from various age groups into a 5-week study. The trial was of multifactorial design with folic acid, vitamin B12, vitamin B6 and placebo in its four arms. Twelve healthy women aged 65 to 92 years received 75 mg vitamin B6 orally per day and were compared with 21 healthy women who were allocated to placebo. No statistically significant benefits from vitamin B6 on mood or cognition were observed. Vitamin B6 supplementation and healthy older men: Deijen 1992 recruited 76 healthy men aged 70 to 79 years. They were divided into 38 matched pairs, one member of each pair randomly allocated to 20 mg of vitamin B6 (pyridoxine hydrochloride) per day for 12 weeks the other to placebo. No statistically significant differences between treatment and placebo were found in their effects on cognition or mood. Effect of vitamin B6 supplementation on vitamin B6 status: Deijen 1992 reported that 20 mg of pyridoxine hydrochloride per day for 12 weeks increased blood vitamin B6 activity as assessed as by plasma pyridoxal-5'-phosphate (WMD 238, 95%CI 211.58 to 264.42, P<0.00001) and erythrocyte enzyme asparate aminotransferase (WMD 0.43, 95%CI 0.30 to 0.56, P<0.00001). Effect of vitamin B6 supplementation on blood homocysteine concentration: Neither of the included trials measured homocysteine levels. Drop-outs: All participants allocated to vitamin B6 or placebo completed the trial protocol. Adverse Events: No adverse effects were reported. Effect of vitamin B6 on carer burden, care costs and institutionalization rate: We found no trials in which these outcomes were assessed.

CONCLUSIONS

This review found no evidence for short-term benefit from vitamin B6 in improving mood (depression, fatigue and tension symptoms) or cognitive functions. For the older people included in one of the two trials included in the review, oral vitamin B6 supplements improved biochemical indices of vitamin B6 status, but potential effects on blood homocysteine levels were not assessed in either study. This review found evidence that there is scope for increasing some biochemical indices of vitamin B6 status among older people. More randomized controlled trials are needed to explore possible benefits from vitamin B6 supplementation for healthy older people and those with cognitively impairment or dementia.