Benefits of B vitamin supplementation in reducing the effects of Mild Cognitive Impairment in elderly people are dependent on their EPA & DHA status

July 24, 2015

Mild Cognitive Impairment (MCI) is a condition in elderly people associated with a higher risk of developing dementia. At present, there are no effective pharmacological treatments for Alzheimer’s Disease (AD), so scientists are now concentrating their efforts on finding effective interventions in the pre-clinical stages of dementia, such as MCI.

A new paper from Jerneren et al. reworks data from a human double-blinded, randomized controlled trial that had shown that homocysteine-lowering B vitamins were able to reduce brain shrinkage in people with MCI. They found the beneficial effect was highly dependent on the patients’ plasma docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) status. In the highest DHA/EPA tertile, brain atrophy rates were reduced by an average of 40%, whereas there was no reduction at all in the lowest tertile.

The identification of elderly people at higher risk of developing dementia is an important challenge for clinicians. The ability to diagnose individuals suffering mild cognitive impairment (MC I) is thought to be important in achieving this.

Enhanced plasma concentrations of homocysteine are a useful biomarker in the diagnosis of MCI. Homocysteine is a metabolic product of the amino acid methionine, with elevated levels appearing in the body as a result ofoxidative stress (2). Brain shrinkage is believed to be faster in dementia patients with sustained high levels of homocysteine and low plasma vitamin B12 levels.

The current paper (1) is a reworking of data from the VITACOG trial carried out in the Oxford area in 2004 to 2006 (3). One hundred and thirty-three subjects aged 70 years or over with an MCI diagnosis were given an intervention of B vitamins (0.8 mg folic acid, 0.5 mg Vitamin B12 and 20 mg vitamin B6) daily for two years. Brain volumes were determined by cranial MRI scans at baseline and after the intervention. The study showed that the intervention group had lower levels of homocysteine and suffered less brain atrophy.

However, a recent meta-analysis by Clark et al. (4) found no significant effect with regard to homocysteine lowering with B vitamins and global cognitive function. A probable reason for this was the considerable heterogeneity of the included studies. It seemed reasonable to take a more detailed look at some of the specific subgroups (2).

The new paper (1) looked retrospectively at the effects of circulating plasma EPA and DHA levels in the VITAGOG cohort. The reason for this is that the optimal utilization and distribution of marine omega-3 fatty acids requires sufficient B vitamin status and low homocysteine levels (2). The new Jerneren et al. paper (1) was able to show that the beneficial effects of B vitamins in reducing brain atrophy was strongly dependent on the patient’s omega-3 status. The tertile with the highest marine omega-3 fatty acid plasma concentrations (˃ 590 µmol/L) showed a reduction in atrophy rate of 40% in comparison with the placebo group. The subjects in the tertile with the lowest baseline marine omega-3 concentrations (˂ 390 µmol/L) did not achieve any reduction in the rate of brain shrinkage from the B vitamin supplementation. 


  1. Jeneren F, Elshorbagy AK, Ouljah A et al, “Brain atrophy in cognitively impaired elderly : the importance of long-chain omega -3 fatty acids and B vitamin status in a randomized controlled trial”, Am J Clin Nutr 2015; 102:215-21
  2. Blasko B, “Interaction of omega-3 fatty acids with B vitamins in slowing the progression of brain atrophy: identifying the elderly at risk”, Am J Clin Nutr 2015; 102:7-8.
  3. Smith AD, Smith SM, De Jager CA et al. “Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial”. PLoS ONE 2010; 5:e12244. 
  4. Clarke R, Bennett D, Parish S et al., “Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals”; Am J Clin Nutr 2014; 100:657-66.