Brain Atrophy in Cognitively Impaired Elderly: The Importance of Long-chain ω-3 Fatty Acids
and B Vitamin Status in a Randomized Controlled Trial
Fredrik Jernerén, Amany K Elshorbagy, Abderrahim Oulhaj,
Stephen M Smith, Helga Refsum, and A David Smith
From the Oxford Project to Investigate Memory and Ageing (OPTIMA),
Department of Pharmacology,
University of Oxford, Oxford, United Kingdom;
|This study provides clarity to earlier studies that found that B vitamins and/or Omega-3 fatty acids were found to slow brain loss in areas of the brain associated with Alzheimer’s disease.
In a 2010 study, Smith et al.  (in the Oxford Project to Investigate Memory and Ageing study) gave 271 individuals with mild cognitive impairment high-dose B vitamins for 2 years. Pre- and post-MRI studies were done, and they demonstrated that the B vitamin group experienced 30-percent slower rates of brain atrophy, on average, and in some cases patients experienced reductions as high as 53 percent.
In a 2012 study, Bowman et al.  (in the Oregon Brain Aging Study) reviewed blood nutrient levels in 104 dementia-free elders. They found two nutrient biomarker patterns (NBPs) that were associated with more favorable cognitive and MRI measures: one was high plasma levels of the vitamins B, C, D, and E, and the second NBP was high plasma marine omega-3 fatty acids. They also demonstrated that high trans fat blood levels were associated with less favorable cognitive function and less total cerebral brain volumes.
When this article was pre-released, the New York Times ran a banner headline titled:
In a 2013 study, Douaud et al.  provided high-dose B-vitamin treatment to elderly subjects with increased dementia risk for 2 years. They found that B vitamins reduced brain shrinkage and reduced levels of plasma total homocysteine (tHcy). This is important because many cross-sectional and prospective studies have shown that high tHcy levels are associated with cognitive impairment, Alzheimer’s disease (AD), and vascular dementia.
The current study also helps explain why some trials that focused solely on the B vitamins or Omega-3s had mixed results. Apparently having high blood levels of BOTH the B vitamins AND Omega-3 fatty acids provides better results in preventing the deterioration of brain tissue in Alzheimer’s patients.
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 fatty acid 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 (<390 µmol/L). High baseline ω-3 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.
This trial was registered at www.controlled-trials.com as ISRCTN94410159.
© 2015 American Society for Nutrition.