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Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial
Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD.. The American journal of clinical nutrition, 2015-04-15
Topic: Risk, prevention and care in population studies
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 ( 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.
Key findings
- Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia.
- 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 ( 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.
Why it matters
In a 2-year trial of 168 people aged 70+ with mild cognitive impairment, high-dose B vitamins slowed brain shrinkage on MRI by 40% compared with placebo, but only in people whose blood omega-3 levels were already high (above 590 μmol/L). In people with lower omega-3 levels there was no significant effect. The authors say this points to finding subgroups likely to benefit. It is a retrospective analysis of one trial, it measured brain shrinkage rather than dementia, and it does not show that B vitamins or omega-3 prevent Alzheimer's disease.
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Study details
- Participants83
- Effect size40.0%
- Evidence strengthLow
How this study scored 67/100
Published in a peer-reviewed journal, and it is a randomised controlled trial.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The American journal of clinical nutrition) |
| Journal's citation record | 3 / 4 | American Journal of Clinical Nutrition: journal h-index 499 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 83 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 5 / 7 | Cited 189 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.5 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 16.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 2 / 4 | Cited 34 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author A. David Smith: h-index 125 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25877495) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 67 / 100 | — |
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APA 7th
Jernerén, F., Elshorbagy, A. K., Oulhaj, A., Smith, S. M., Refsum, H., & Smith, A. D. (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. The American journal of clinical nutrition. https://doi.org/10.3945/ajcn.114.103283
Vancouver
Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD. Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. The American journal of clinical nutrition. 2015. doi:10.3945/ajcn.114.103283. PMID: 25877495.
BibTeX
@article{jerneren2015-25877495,
author = {Jernerén, F. and Elshorbagy, A. K. and Oulhaj, A. and Smith, S. M. and Refsum, H. and Smith, A. D.},
title = {{Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial}},
journal = {The American journal of clinical nutrition},
year = {2015},
doi = {10.3945/ajcn.114.103283},
pmid = {25877495},
url = {https://doi.org/10.3945/ajcn.114.103283}
}
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