Background: Inverse associations have been reported between homocysteine concentrations and poor cognitive performance in several cross-sectional studies of healthy elderly subjects. Folate supplementation with or without vitamins B-12 and B-6 is an effective means of lowering homocysteine concentrations. Mood disturbances, from mild mood changes to clinical depression, are common in older populations. Several studies have shown that depressed people have lower levels of folate and vitamin B-12 and higher levels of homocysteine than non-depressed people. Improvement of mood has been reported in depressed people following supplementation with folic acid. Clinical trials are required to determine if lowering homocysteine concentration with vitamins improves cognitive function and/or mood in healthy elderly participants.
Objective: The primary aim of this research project was to carry-out a 2 year randomised, double-blind, placebo-controlled trial to determine if a supplement containing folate (1mg L-Mefolinic acid), vitamin B-12 (500(mu)g) and vitamin B-6 (10mg) improves scores or prevents decline on tests of cognition in a group of healthy older people ([greater than or equal to]̲ 65 years) with a plasma homocysteine concentration [greater than or equal to]̲13 (mu)mol/L. A second aim of this study was to determine if homocysteine lowering vitamins improved scores on tests of mood in this group.
Methods: Four hundred and sixty-five individuals, aged 65 and over, were recruited from Dunedin and surrounds, and asked to attend a screening clinic and provide a fasting blood sample. Two-hundred and seventy-six volunteers with a plasma homocysteine concentration [greater than or equal to]13(mu)mol/L were randomised to take either a combination of 1mg L-Mefolinic acid, 500(mu)g vitamin B-12 and 10mg vitamin B-6 or placebo for 2 years. A battery of cognitive tests and indices of mood was administered at baseline, one year, and two years. A fasting blood sample was collected at baseline and every six months thereafter.
Results: From baseline to 6 months of the intervention, homocysteine concentrations decreased by 37.5%, from 16.7 to 10.5 (mu)mol/L in the vitamin supplemented group and then plateaued. In the vitamin supplemented group there was a 181% increase in red blood cell folate concentration from a mean of 977 to 2752 nmol/L, and a 90.1% increase in plasma vitamin B-12 (from a mean 283 to 538 (mu)mol/L) over the study period of two years.
In the vitamin supplemented group there was a trend to poorer performance on almost all tests of cognition compared to placebo group. The vitamin group was 8% slower on Part B of the Reitan Trail Making Test, a test of speeded attention, mental tracking, visual search and mental flexibility (p=0.009). The vitamin group scored significantly lower on tests of short-term recall, Weschler Paragraphs (p=0.03) after 2 years, and the Rey Auditory Verbal Learning Test ((p=0.04) after one year, than the placebo group. There was no difference in mood score by treatment in this largely non-depressed group.
Conclusion: These results suggest a detrimental effect of high dose homocysteine lowering vitamin supplements on cognitive function in healthy older people. These results need to be confirmed in other randomised controlled trials.
| Identifer | oai:union.ndltd.org:ADTP/217569 |
| Date | January 2006 |
| Creators | McMahon, Jennifer A., n/a |
| Publisher | University of Otago. Department of Human Nutrition |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://policy01.otago.ac.nz/policies/FMPro?-db=policies.fm&-format=viewpolicy.html&-lay=viewpolicy&-sortfield=Title&Type=Academic&-recid=33025&-find), Copyright Jennifer A. McMahon |
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