Intact cognition is crucial for functional independence for people of any age. Unfortunately, due to subtle signs and symptoms of cognitive decline, cognitive impairment may go unnoticed for years, and clinical diagnoses are often made late into disease progression. In the absence of treatments and cures for dementia and other forms of cognitive decline, a lot of focus has been placed on prevention strategies and managing risk factors.
Certain nutrients and nutraceuticals have been touted as “brain foods” in the media, with particular focus landing on a few, such as omega-3 fatty acids and B vitamins. Let’s look at some more recent studies examining how omega-3s and B vitamins might impact cognitive health and aging and determine if they are worth the brainpower hype.
Omega-3s & Cognitive Aging
Omega-3 fatty acids are part of neuronal cell membranes and are implicated in several cerebral functions. Some of these functions include increased synaptic development and functionality, the growth of new neurons (neurogenesis), the retention of gray and white brain matter, and the overall enhancement of cognitive activity. Omega-3 fatty acids include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).
DHA is one of the most important fatty acids in the brain, constituting over 90% of the omega-3s and 10-20% of the total lipids in the brain. DHA is incorporated at the synaptic terminals, mitochondria, and endoplasmic reticula, where it can modulate processes like membrane fluidity, the release of neurotransmitters, gene expression, myelination, neuroinflammation, and neuronal growth.
Observational studies suggest that a dietary lifestyle enriched with omega-3s reduces the risk of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. However, randomized trials have provided conflicting results. Similarly, studies have identified an association between low levels of omega-3 and cognitive impairment. Yet, the effects of omega-3 supplementation on cognitive outcomes in randomized clinical trials are controversial.
Because of the contradictory findings in the literature concerning the effects of omega-3s on cognitive aging, two researchers published a systematic review in 2019 to find an answer. This review includes randomized controlled trials using DHA, EPA, or both combined in aged adults or elder subjects with or without mild cognitive impairment. Ten of the fourteen studies showed positive outcomes in at least one domain of cognitive function. Therefore, these researchers concluded that omega-3 supplementation might be considered a therapeutic and preventative tool for cognitive aging.
Two other recent studies have found similar results. A 2020 prospective study included over 1200 participants who were non-demented at the time of baseline measurements and followed for detection and incident of dementia over 17 years. The researchers found that higher levels of plasma EPA + DHA were consistently associated with a lower risk of dementia, and lower decline in global cognition, memory, and medial temporal lobe volume.
Moreover, a study published in 2022 found Alzheimer’s disease patients with lower baseline DHA levels were associated with a higher risk of cognitive decline two years later. Although current literature provides compelling evidence for a relationship between omega-3s and improved cognitive outcomes, other studies still offer conflicting results, making it challenging to draw definitive conclusions and recommendations.
B vitamins and Cognitive Aging
The link between B vitamins and cognition appears to be related to homocysteine (Hcy). Epidemiological studies show that elevated plasma Hcy levels are a strong modifiable risk factor for cognitive decline via direct neurotoxic or vascular mechanisms. Vascular contributions to cognitive impairment and dementia are the second most common cause, affecting up to 40% of dementia patients. Furthermore, elevated Hcy has also been associated with white matter damage, brain atrophy, neurofibrillary tangles, and dementia.
Early studies have found that B vitamins, particularly folate and B12, are involved in eliminating Hcy and that low B vitamins and elevated Hcy levels are associated with Alzheimer’s disease.
Although the connection between B vitamins and Hcy levels exists, there is still controversy regarding whether B vitamins’ reduction of Hcy levels affects cognitive outcomes. Several systematic reviews and meta-analyses on this topic have been performed recently, and they disagree.
One recent review by Wang et al. concluded that B vitamin supplementation is associated with slowing cognitive decline, with a few stipulations. After reviewing 95 different studies, they found that B vitamins may slow cognitive decline (1) when supplementation was provided long term >12 months, (2) in the non-dementia population, and (3) dietary folate (B9) had a more significant impact than B12 or B6 on lowering dementia risk. This meta-analysis suggests that B vitamins can slow cognitive decline when intervention, particularly with B9, is received early and for a long duration.
Another recent review by Li et al. confirmed these findings. After reviewing 21 randomized controlled trials, the authors concluded that B vitamin supplementation might delay the cognitive decline of elderly adults and recommended B vitamin supplements as a preventative addition for people with or without cognitive impairment.
Yet another review by Behrens et al. found no overall evidence that oral B vitamin supplementation would prevent cognitive decline. Interestingly, a different review and meta-analysis published in 2020 found that B vitamin benefits for global cognition were geographically specific, with significant effects experienced only in people from certain regions. Ultimately, many researchers have concluded that it’s not possible at this time to make any definitive conclusions or recommendations regarding the duration or dosage of B vitamins for beneficial effects on cognition.
Combining Omega-3s and B-vitamins for Cognitive Health
While studies investigating the effect of omega-3s and B vitamins on cognitive decline have yielded mixed results, it has been hypothesized that the efficacy of B vitamin supplementation may depend on omega-3 status. A group of researchers in the Netherlands published an analysis in February of 2022 exploring this hypothesis. Are both B vitamins and omega-3s needed for best results?
The study was conducted as a posthoc analysis within the B-proof trial, a randomized, double-blind placebo-controlled trial investigating the effect of folic acid and B12 on fracture incidence in older individuals. While the study’s primary outcome was fracture incidence, cognitive functioning was measured as a secondary outcome.
The participants included cognitively healthy subjects aged 65 years and older with elevated homocysteine levels. For two years, participants in one group received a daily tablet with 0.5 mg of vitamin B12 + 0.4mg of folic acid + 600IU of vitamin D. The other group received a placebo tablet that only included 600IU of vitamin D.
Cognitive functioning was assessed at baseline and after two years of intervention. Of the participants included in this study (n=2,919), an analysis was completed on a subsample (n=191) from whom fatty acid data were collected at baseline. Baseline omega-3 fatty acids DHA and EPA concentrations were divided into tertials for comparison.
The researchers found that global cognition in the treatment group improved more over time than in the placebo group, regardless of omega-3 status. Yet, there was little difference in treatment effects of B vitamins between the low, middle, and high omega-3 fatty acid tertials.
However, once analyzing the treatment effects of DHA and EPA separately, it becomes evident that the efficacy of B vitamin supplementation on global cognition may be related more specifically to plasma DHA levels. The report concluded that B vitamin supplementation was more effective than placebo in maintaining global cognitive functioning in participants in the high DHA tertial. At the same time, individuals with lower plasma DHA levels experienced no difference.
The study’s authors suggested a mechanism to explain why B vitamin supplementation was more effective in individuals with higher DHA status. As we have already learned, B vitamins are essential in regulating Hcy levels. Without adequate B vitamins, levels of Hcy, and its precursor, S-adenosyl homocysteine (SAH), increase. High SAH levels slow the rate of phosphatidylcholine (PC) development. PC plays a crucial role in transporting omega-3 fatty acids to the brain. Therefore, adequate B vitamin status is required for sufficient PC production, which in turn transports omega-3s to the brain. Omega-3s, particularly DHA, increase membrane fluidity which is imperative for transmitting signals and proper brain functioning.
A recent analysis has concluded that individuals with higher DHA levels experience greater cognitive benefits from B vitamin supplementation than those with lower DHA levels. Therefore, combined omega-3 and B vitamin supplementation may be more beneficial for improving cognitive outcomes than either supplement alone.
The best way to know if you need omega-3 or B vitamin supplementation is to test your current levels. If you are receiving adequate amounts from a whole food diet, supplements are not necessary at this time. However, if you are deficient in either, supplementation may be beneficial to both short- and long-term cognitive outcomes. More studies in cognitively healthy populations are required to determine optimal levels of B vitamins and omega-3s for peak cognitive outcomes.