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Brain atrophy in cognitively impaired elderly: the importance of long-chain omega-3 fatty acids and B vitamin status in a randomized controlled trial.

Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD (2015) Am J Clin Nutr.  102(1) 215-21. doi: 10.3945/ajcn.114.103283. Epub 2015 Apr 15. 

Web URL: View this and related abstracts via PubMed here.

Abstract:

BACKGROUND:

Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia.

OBJECTIVE:

We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG).

DESIGN:

This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fattyacid concentrations.

RESULTS:

There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group).

CONCLUSIONS:

The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials. 

FAB RESEARCH COMMENT:

The pioneering clinical trial 'VITACOG', led by researchers at Oxford University, found that age-related cognitive decline and brain shrinkage in older adults with mild cognitive impairment was significantly slowed by supplementation with B vitamins (B6, B12 and folate). For the initial trial report, see:


In this further analysis of the trial data, the researchers found that the B vitamin treatment reduced cognitive decline and brain shrinkage only in participants who had higher blood levels of the long-chain Omega-3 fatty acids 
EPA and DHA (found in fish and seafood). 

No improvements were seen in particpants whose initial omega-3 status was low.  However, the beneficial effect of the B vitamins in those with higher blood omega-3 was so pronounced that this led to a significant treatment effect for the study sample as a whole, as initially reported.

This important finding highlights that nutrients work synergistically - not in isolation - and that adequate supplies of both B vitamins and long-chain omega-3 are needed to prevent age-related cognitive decline and dementia, and the physical brain shrinkage associated with these conditions. 

It also offers a possible explanation for the failure of some previous trials of B vitamin supplementation for brain health and cognition, and illustrates the importance of considering subgroups in the design and analysis of clinical trials, as well as overall nutritional status. 


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For more information about the VITACOG trial and the larger research programme of which it formed a part, see:  
OPTIMA - VITACOG

See also: