Neurodegeneration

How B Vitamins and Omega-3s Could Prevent Cognitive Decline

Several recent studies suggest that the effectiveness of alleviating cognitive deficits with omega-3s in older adults depends on vitamin B levels.

By Daniel R. Miranda, Ph.D.

Key Points: 

  • Alleviating cognitive decline with omega-3s may only occur with adequate B vitamin levels. 
  • Vitamins B6, B9, and B12 break down the amino acid homocysteine, allowing for omega-3s to be incorporated into the membranes of brain cells.

As we age, our brains progressively atrophy (deteriorate, shrink, degenerate), leading to cognitive decline. Cognitive decline can be described as the age-related deterioration in faculties such as learning, memory, and problem-solving. These cognitive deficits can progress to more severe stages, from mild cognitive impairment to Alzheimer’s disease and other forms of dementia.

When it comes to preventing or delaying the progression of cognitive decline, many studies have pointed to omega-3 polyunsaturated fatty acids as a promising single-nutrient solution. The most well-studied omega-3s are DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid), which are found in fish oil. However, the evidence doesn’t consistently show that older adults with cognitive deficits benefit from omega-3s, namely DHA and EPA. There are several potential reasons for this, but a few studies published within the last three months suggest that B vitamins are the culprit.

Omega-3s and B Vitamins Need Each Other

Upon analyzing the results from fourteen previous studies (meta-analysis), the authors of a report in the April issue of the British Journal of Nutrition concluded that omega-3s might only be beneficial for improving cognition in older adults if vitamin B levels are adequate. Similarly, in a study published in the June issue of the European Journal of Nutrition, van Soest and colleagues showed that vitamin B9 and B12 treatment improved cognitive performance in older adults but only if they had high levels of DHA in their blood. 

(van Soest et al., 2022 | European Journal of Nutrition) B Vitamin Treatment Improves Cognition only with High DHA. Cognitive performance did not significantly improve (go above zero) with any level of EPA in response to B-vitamin treatment (dark gray) compared to placebo (light gray). However, cognitive performance was improved with high levels of DHA and B-vitamin treatment.

The above studies suggest that adequate levels of both omega-3s and B vitamins are needed to improve cognition in older adults. However, there is one catch to the von Soest study, as the participants were chosen based on their high homocysteine levels. Homocysteine is a non-protein amino acid and intermediate metabolite that can be measured from our blood. It has been associated with many diseases, including nervous system and cardiovascular disease. In a report from the May issue of the Journal of Nutrition, Health & Aging, Maltais and colleagues showed that omega-3 treatment only improves cognitive performance in older adults when they have low homocysteine levels.

What’s Does Homocysteine have to do with B Vitamins and Omega-3s?

Vitamins B12, B9, and B6 are involved in metabolizing homocysteine, thus lowering homocysteine levels. Notably, high homocysteine levels are associated with an increased risk of dementia. Furthermore, studies show that B vitamins reverse brain atrophy and cognitive deficits only in individuals with elevated homocysteine levels (and adequate omega-3s). Hence, lowering homocysteine levels with B vitamins seems necessary for receiving the benefits of omega-3s. 

How does this work? Homocysteine, B vitamins, and omega-3s share a common cellular pathway. This pathway leads to the synthesis of phosphatidylcholine (PC) — a species of fat (lipid) that is a major component of cell membranes. Our cells, including brain cells are enveloped within these cellular membranes, which can potentially alter the efficiency of the cell. Without omega-3s, PC will contain other fats, possibly leading to brain cell inefficiencies. When homocysteine levels are low, PC is enriched with omega-3s. However, when homocysteine levels are too high, omega-3s are no longer incorporated into PC.

(Smith et al., 2021 | The American Journal of Clinical Nutrition) Interface Between Omega-3s, B Vitamins, and Homocysteine. Vitamin B12, B9, and B6 aid in the conversion of homocysteine to the amino acids methionine and cysteine, allowing for the synthesis of phosphatidylcholine (PC) rich in omega-3s. When homocysteine levels are too high, omega-3 enriched PC is blocked from being synthesized.

While the role of omega-3 enriched PC is unknown, sufficient levels of it may be needed for optimal brain function. Studies have shown that high levels of DHA-enriched PC are associated with a reduced risk of Alzheimer’s disease and cognitive impairment. Additionally, patients with Alzheimer’s and cognitive impairment exhibit selective depletion of DHA-enriched PC.

Which Omega-3 is Best for Preventing Cognitive Decline?

Aging is associated with reduced brain omega-3s, and poor omega-3 status has repeatedly been linked to cognitive decline. Some studies show that treatment with omega-3s can improve cognitive function, slow rates of cognitive decline, and lower the risk of developing dementia. However, not all clinical studies consistently show that omega-3s alleviate cognitive deficits. The studies mentioned above have brought the importance of B vitamins to light, but does the type omega-3 also matter?

DHA seems important for cognition as it regulates the generation of new neurons and their connections, modulating the signaling between them. A recent study showed that higher DHA levels slowed cognitive decline in Alzheimer’s disease patients. As mentioned above, DHA-enriched PC could be driving the benefits of omega-3s. Additionally, the findings of van Soest and colleagues suggest that DHA is more important than EPA when it comes to improving cognition in older adults. Therefore, overall, it would seem DHA is better for preventing cognitive decline than EPA, but more studies comparing the two are needed. 

Supplementing with Omega-3s and B Vitamins

The studies summarized here focus on a specific pathway that warrants further investigation. Omega-3s are known to have anti-inflammatory and antioxidant effects that may not depend on this pathway and still delay the aging process. However, the association between omega-3s and cognitive decline cannot be ignored, and now it seems that B vitamins play a key role in their effectiveness. More basic research studies, along with clinical studies designed to examine the synergetic effect of omega-3s and B vitamins on cognition in older adults with low vs. high homocysteine levels will support the relevance of this pathway and its role in cognitive decline. 

The precise dosage of EPA, DHA, and B vitamins needed to improve cognition still needs to be worked out and likely depends on the stage of cognitive impairment. Between the three most recent studies mentioned, the dosage of DHA ranged from 400 mg to 1,700 mg, EPA from 112.5 to 600 mg, folic acid (synthetic B9)/ folate (natural B9) from 400 to 1000 µg, vitamin B12 from 3 to 500 µg, and vitamin B6 from 1 to 20 mg. Some of these studies used formulations containing other ingredients such as 15 µg of vitamin D. Thus if going by the highest dosages, 1,700 mg of DHA, 600 mg of EPA, 0.5 mg of vitamin B12, 1 mg of vitamin B9, and 20 mg of vitamin B6 might help with improving cognition.

Model & Dosage

Model: Older adults with varying levels of cognitive decline

Dosage (oral): 1,700 mg DHA, 600 mg EPA, 0.5 mg B12, 1 mg B9, and 20 mg B6

Source

Fairbairn P, Dyall SC, Tsofliou F. The Effects of Multi-Nutrient Formulas containing a Combination of Omega-3 Polyunsaturated Fatty Acids and B vitamins on Cognition in the older adult: A Systematic Review and Meta-analysis. Br J Nutr. 2022 Apr 27:1-42. doi: 10.1017/S0007114522001283. Epub ahead of print. PMID: 35473808.

van Soest APM, van de Rest O, Witkamp RF, Cederholm T, de Groot LCPGM. DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. Eur J Nutr. 2022 Jun 15. doi: 10.1007/s00394-022-02924-w. Epub ahead of print. PMID: 35704085.

Maltais M, de Souto Barreto P, Bowman GL, Smith AD, Cantet C, Andrieu S, Rolland Y. Omega-3 Supplementation for the Prevention of Cognitive Decline in Older Adults: Does It Depend on Homocysteine Levels? J Nutr Health Aging. 2022;26(6):615-620. doi: 10.1007/s12603-022-1809-5. PMID: 35718871.

Smith AD, Jernerén F, Refsum H. ω-3 fatty acids and their interactions. Am J Clin Nutr. 2021 Apr 6;113(4):775-778. doi: 10.1093/ajcn/nqab013. PMID: 33711096.

Mora I, Arola L, Caimari A, Escoté X, Puiggròs F. Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging. Int J Mol Sci. 2022 Mar 23;23(7):3472. doi: 10.3390/ijms23073472. PMID: 35408832; PMCID: PMC8998232.

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