Food and Behaviour Research

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B Vitamins and Omega-3 Fatty Acids Against Cognitive Decline

Josh Conway


This post-hoc analysis indicated that efficacy of B-vitamin supplementation in slowing cognitive decline relates to DHA status, with individuals with higher plasma DHA levels benefitting more from vitamin B12 and folic acid use.


Once again, detailed analysis of clinical trial findings reveals that any benefits of B vitamin supplementation for cognitive function in older adults depend on omega-3 status - i.e. that omega-3 and B vitamins work together synergistically to support brain health.

Specifically, researchers found that high blood levels of the long-chain omega-3 DHA were linked with significant benefits for cognitive performance (across a wide range of measures) after supplementation with vitamin B12 and folic acid vs placebo.  However, no effect of the B vitamins was found for those participants with only medium or low DHA levels at baseline.

For the related research article please see:

Synergistic effects of omega-3 and B vitamins for cognition in older adults were first reported in the Oxford Vitacog trial - when it was found that only those with the highest blood levels of long chain omega-3 (EPA/DHA) at baseline showed benefits from 2-years of supplementation with vitamins B6, B12 and folate vs placebo.

Although the original trial did find a significant effect of the B vitamins across the whole population studied - with significant reductions in both physical brain shrinkage and clinical measures of cognitive decline - further analysis revealed that this effect was entirely attributable to those with higher omega-3 status at baseline:

These findings led the same researchers to re-analyse data from the first ever trial of omega-3 for Alzheimer's disease - which confirmed that the oppostie was also true: i.e. that any benefits of omega-3 for slowing cognitive decline depended on the B vitamin status of these patients at baseline (as indexed by homocysteine - a toxic byproduct of normal metabolism that builds up when B6, B12 or folate is lacking). See:

This clinical trial evidence, showing that supplementation with both B vitamins and long-chain omega-3 could help to reduce the ever-increasing burden of age-related cognitive decline and dementia (and also benefit physical health), now needs following up with definitive trials.

However, this very relevant article by a researcher in this field (following the publication of the groundbreaking Vitacog results) explains the extraordinary difficulties facing researchers in trying to obtaining funding for studies in this area:

For further information on this subject please see:

See also:

20/06/2022 - Lifespan

A post-hoc analysis of previous results

The researchers came to their conclusion after analyzing the results of the B-proof trial, a Dutch study conducted between October 2008 and March 2013. This study was originally geared towards discovering the effectiveness of folic acid and vitamin B12 supplements; the researchers obtained their omega-3 results by analyzing deep-frozen blood plasma samples taken at the time of the study.
The researchers were able to collect the data they needed from nearly 200 people in total, approximarly half of which were in the placebo group. The average age of this group was about 71 and a half, although people in the treatment group were an average of two years younger than people in the placebo group.
This study focused on two specific omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). For each of these measurements, and for a combined measurement, the participants in each group were divided into three tertiles: low, middle, and high.
The researchers describe the cognitive measurements conducted in this test as an “extensive battery”, as they included short-term memory tasks such as digit and word memorization, long-term memory tasks such as letter-word recall, and detailed cognitive tests such as the trail-making test and the symbol-to-digit marking test. It also included the famous Stroop color-word test, in which a word written represents a different color than the ink it’s written in, such as the word “green” written in yellow.
At the beginning of the study, the baseline cognitive ability of participants in the low, middle, and high omega-3 fatty acid groups did not differ significantly.

One particular fatty acid shows a difference

Vitamin B supplementation appeared to be slightly associated with higher overall scores on cognitive tests after two years, although the difference was not statistically significant. This was independent of how much EPA was in the bloodstream.
However, the results were much different when examining DHA. In the middle and low DHA groups, cognitive ability was much less affected with vitamin B12 supplements. People with high levels of DHA did much better than the other two tertiles in the vitamin B12 group; in this analysis, a combination of vitamin B12 supplements and high levels of the omega 3 fatty acid DHA was shown to be significantly correlated with cognitive health.

This combination was correlated with scores on all of the cognitive tests; there was no individual subcomponent of cognitive performance that particularly stood out.


The researchers compare their results to those of other studies. One study, VITACOG, also showed a significant link between B vitamin supplements and omega-3 fatty acids in reducing cognitive decline [1] and brain atrophy [2]. A different post-hoc study showed that a combination of low homocysteine, an amino acid that is broken down by B vitamins, and omega-3 supplementation is associated with reduced cognitive decline [3]. These studies focused on people with cognitive impairment, while this new study was on cognitively healthy adults.

Pulling from other prior research, the researchers offer multiple biochemical explanations as to why DHA might be so important, such as ways in which B vitamin supplementation spurs the transfer of omega 3 fatty acids to the brain [4].
However, as a post-hoc analysis, this particular study can only show correlation, not prove causation, and the original cohorts were not powered for this analysis. As the researchers point out, a multifactorial clinical study is required to prove that vitamin B12 and DHA interact to improve cognitive performance in healthy older adults.