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In the news: B Vitamins Needed for Cognitive Benefits of Omega-3 in Alzheimer’s? B Vitamins Needed for Cognitive Benefits of Omega-3 in Alzheimer’s?

B Vitamins Needed for Omega-3 Brain Benefits?

Population health studies have linked the intake of long-chain omega-3 fatty acids with a lower risk of Alzheimer’s disease (AD), while animal studies have shown that these fatty acids, DHA in particular, can reduce Alzheimer’s-like brain disease. However, intervention trials testing whether EPA/DHA can slow the cognitive decline in mild cognitive impairment (MCI) or early to moderate AD have yielded mixed results.

Recent work by a team of Swedish researchers from Uppsala University offers some insight into why these studies may have produced conflicting results. Their work indicates that the protective effect of omega-3 fatty acids is influenced by the status of B vitamins.

In an earlier study (1), the Swedish team conducted a post-hoc analysis of the 2-year long VITACOG study – a randomized, double-blind, placebo-controlled study
evaluating the effect of moderately-high dose B vitamins (folic acid, 0.8 mg; vitamin B6, 20 mg; vitamin B12, 0.5 mg) in elderly participants with MCI.

The analysis showed that the protective effect of the B vitamins on brain atrophy rates depended upon initial plasma levels of DHA and EPA.

In those with high plasma DHA + EPA at the study’s start, the B vitamin treatment slowed the rate of brain atrophy by 40% compared with placebo – notable since a faster rate of brain atrophy is characteristic of those with MCI who go on to develop AD.

In the present study (2), the researchers performed a post-hoc analysis of another trial in patients with mild to moderate AD, the OmegAD study. This trial, also randomized and controlled, evaluated the effect of omega-3 (2300 mg DHA + EPA daily) on cognitive out-comes: changes in the Mini-Mental State Examination and the Alzheimer’s Disease Assessment Scale.

While the supplemental fatty acids did not significantly delay cognitive decline overall in this 6-month study, a small patient group with mild AD did experience cognitive benefits.

The Swedish team sought to determine whether interactions between initial homocysteine levels (a measure of B vitamin status) and the supplemental omega-3s could have played a role in the observed cognitive and functional outcomes.

Compared to those with higher homocysteine levels (and lower B vitamin status), participants with levels below 11.7 mmol/L saw a 7.1% improvement in cognitive performance p = 0.03) and a 22.3% reduction on the rating scale of dementia vs. placebo (p = 0.009).

The authors conclude that the effect of omega-3 supple-mentation on measures of cognitive performance and clinical status could be dependent on having sufficient levels of B vitamins.

How do the Omega-3s and B Vitamins Interact?

Omega-3 fatty acids, particularly DHA, is concentrated in neuronal membranes in the brain, while folate and vitamins B6 and B12 are necessary for producing monoamine neurotransmitters, phospholipids and nucleotides. Importantly, these B vitamins are required to form phosphatidyl choline which is necessary to carry DHA and EPA across the blood brain barrier.

Interestingly, AD and age-related macular degeneration (AMD) share some epidemiological, genetic, molecular and clinical links. For instance, AD and AMD share the underlying factors of oxidative stress and neuro-inflammation. Beta-amyloid, the main component of senile plaques and a hallmark of AD, is also an important component of drusen, the hallmark of AMD. Perhaps future studies evaluating the effects of omega-3 fatty acids in AD, MCI and AMD should take into account the functional B-vitamin status of participants.

References

1. Jerneren F, et al. 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. 102: 215–21, 2015.
2. Jerneren F, et al. Homocysteine status modifies the treatment effect of omega-3 fatty acids on cognition in a randomized clinical trial in mild to moderate Alzheimer's disease: The OmegAD Study. J Alz Dis 69:189–97, 2019.