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Cognitively impaired brain atrophy was slowed 40 percent by Omega-3 and B vitamins – RCT July 2015

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

Am J Clin Nutr July 2015, vol. 102 no. 1 215-221
Fredrik Jernerén 3, fredrik.jerneren at pharm.ox.ac.uk, Amany K Elshorbagy 3,4, Abderrahim Oulhaj 5, Stephen M Smith 6, Helga Refsum 3,7, and A David Smith 3
3From the Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, University of Oxford, Oxford, United Kingdom;
4Department of Physiology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt;
5Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates;
6Functional Magnetic Resonance Imaging of the Brain Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; and
7Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway

↵1 Supported by grants from the Charles Wolfson Charitable Trust, The Medical Research Council, Norwegian Research Council, Norman Collisson Foundation, Alzheimer's Research UK, Henry Smith Charity, John Coates Charitable Trust, Thames Valley Dementias and Neurodegenerative Diseases Research Network of the National Institute for Health Research, the Sidney and Elizabeth Corob Charitable Trust, and Meda AB/Recip AB.

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.

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