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

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. 

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.

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.