Is Fish Oil Omega-3's Good for Brain Health?

Fish oil is a popular over-the-counter supplement extracted from fatty fish like sardines, anchovies, mackerel and salmon.

Fish oil primarily contains two types of omega-3 fatty acids — eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are well known for their heart health and skin benefits. Among other parameters, like blood glucose, brain function depends on brain structure, brain perfusion, and, in some cases, on the absence of inflammatory processes⁽¹⁾.

In addition, the fatty acid composition of a cell’s membrane impacts on physical stability, signal transduction, ion channel behavior, and a host of other cell properties and functions⁽¹⁾.

This is where omega-3s play a crucial role.

What are fish oil omega-3s?

Omega-3 fatty acids are polyunsaturated fats responsible for most of the brain and mental health benefits of fish oil. These two fatty acids (EPA & DHA) are constituents of cell membranes and have powerful anti-inflammatory function within the body.

In addition, they are well known for their critical roles in human development and heart health⁽¹⁾.

In the human diet, EPA and DHA are almost exclusively found in fatty fish and fish oil. Because most people do not consume the recommended amounts of fish, many people likely fall short of getting enough EPA and DHA in their diets⁽²⁾.

Relevance of EPA and DHA to the Brain

Building and Maintaining Brain: The conversion of plant-derived alpha-linolenic acid (ALA) to DHA is minimal in humans, as is formation of DHA from EPA⁽³⁾.

ALA is found in several food sources, such as walnuts, flaxseeds, chia seeds, canola oil, soybeans and soybean oil.  However, the conversion of ALA to EPA and DHA is not efficient in humans, with estimates reporting that less than 10% of the amount of ALA you consume is converted to EPA or DHA⁽⁴⁾.

This percentage decreases more as we age.

Hence, taking fish oil may be a good option, especially for individuals who do not eat much fish but are still interested in gaining the health benefits of omega-3 fatty acids.

Brain perfusion: Brain perfusion is crucial to overall brain function. The brain utilizes about 20% of the blood pumped by the heart, with white matter receiving some 25, and gray matter receiving some 90 mL/100g/min⁽⁵⁾.

Arteries and arterioles are responsible for perfusing the brain with blood, which are modulated by vasoactive molecules, some of them derivatives of EPA, and some derivatives of DHA. In addition, obstructions to brain perfusion (e.g. embolus, arterial plaque) are less riskier at higher blood levels of EPA and DHA compared to lower blood levels⁽⁶⁾.
 
Inflammatory Processes in Brain: Some issues in brain function result from regional inflammatory processes, like major depression. Both EPA and DHA reduce severity of inflammation, with mechanisms and/or metabolites mitigating development of inflammation, as well as facilitating resolution of inflammation.

How do Omega-3s affect the brain?

The omega-3 fatty acids EPA and DHA are critical for normal brain function and development throughout all stages of life. Fatty acids are integral components of biological membranes, and influence membrane fluidity, ion transport, and other functions⁽⁷⁾.

The neuronal cell membrane is no exception; the central nervous system (CNS) has the highest concentration of phospholipids in the body.

EPA and DHA seem to have crucial roles in the developing baby’s brain.

Several studies show a correlation between pregnant women’s fish intake or fish oil use with higher scores for their children on tests of intelligence and brain function in early childhood⁽⁸⁾.

These fatty acids are also vital for maintaining normal brain function throughout life. They are abundant in the cell membranes of brain cells, preserving cell membrane health and facilitating communication between brain cells⁽⁹⁾.

Interestingly, when animals are fed diets without omega-3 fatty acids, the amount of DHA in their brains decreases, and they tend to experience learning and memory deficits⁽¹⁰⁾.
 
In addition, lower levels of DHA in the blood have been associated with smaller brain size, which is a sign of accelerated brain aging. In fact, evidence indicates that lower red blood cell DHA levels are associated with smaller brain volumes and a “vascular” pattern of cognitive impairment even in persons free of clinical dementia⁽¹¹⁾.

Clearly, it is important to make sure you get enough omega-3 fatty acids to avoid some of these detrimental effects on brain function and development.

Omega-3 and memory loss

Although there is no compelling evidence that omega-3 supplements like fish oil improve brain function in people with Alzheimer’s disease; server studies indicate fish oil may improve brain function in people with more mild types of brain conditions like mild cognitive impairment or age-related cognitive decline⁽¹²⁾.

Although these conditions are not as severe as Alzheimer’s disease, they still culminate in memory loss and sometimes other types of impaired brain function.

As an example, one study gave 485 older adults with age-related cognitive decline either 900 mg of DHA or a placebo every day.  After 24 weeks, the individuals taking DHA performed better on memory and learning tests.

This study concluded that DHA is a beneficial supplement that supports cognitive health with aging⁽¹³⁾.

Based on the evidence to date, fish oil supplements may be most beneficial when people start taking them in the early stages of brain function decline. It seems that if you wait too long, fish oil may be of little benefit to the brain.

Omega-3 mechanisms of action

The biological mechanisms through which omega-3 might exert beneficial effects on the brain can be broadly divided into vascular and nonvascular pathways.

DHA and EPA exert several favorable effects on the vasculature, including:

• - Blood pressure reduction
• - Lowering the risk of thrombosis
• - Reducing inflammation
• - Lowering serum triglyceride levels

Given that vascular risk factors (i.e., cerebral atherosclerosis, and stroke) are associated with a higher risk of incident dementia⁽¹⁴⁾, omega-3 may delay cognitive and structural brain aging by some combination of these mechanisms.

The omega-3 composition of both lipid rafts and caveolae is known to influence membrane function and the activities of membrane-bound proteins⁽¹⁵⁾, suggesting another potential mechanism of action.

Other roles of omega-3 PUFAs may be more directly linked to the neurodegenerative pathogenesis of Alzheimer’s disease, including reduction of amyloid-β production, synaptic protection by reducing neuro-inflammation and oxidative damage, by increasing levels of brain-derived neurotrophic factor, and through reduction of potentially excitotoxic arachidonic acid (omega-6) levels⁽¹⁶⁾.

Should you take fish oil for your brain?

Based on the evidence available, you may want to consider taking fish oil if you have experienced a mild decline in brain function or been diagnosed with depression. Although there are other health benefits of taking fish oil, these two groups of people will likely see the most benefits as far as brain and mental health are concerned.

One area of research that is needed is in the optimal dosage of fish oil required to get the best effects.

There are no official recommendations on the amount of fish oil needed. Dosages used in research varied from study to study.

The Food and Drug Administration (FDA) set a safe upper limit for the intake of omega-3 fatty acid supplements at 3,000 mg per day. The European Food Safety Authority set their recommendation a little higher, at no more than 5,000 mg per day.

A good starting point is 1,000-2,000 mg of omega-3 fatty acids from fish oil daily.

This is well under the recommended upper limit. It’s crucial to read and understand labels carefully when evaluating fish oil supplements. A 1,000 mg capsule of fish oil might contain less than 500 mg of actual omega-3, but this amount varies from brand to brand.

Although fish oil supplement are considered safe under dosages mentioned above, you should inform your physician before starting fish oil supplements.

Due to their potential effects on blood clotting, this is especially important if you are currently taking blood-thinning medications or have a surgery in the near future.

References:
1.    Godos, J., et al., Diet and Mental Health: Review of the Recent Updates on Molecular Mechanisms. Antioxidants (Basel), 2020. 9(4).
2.    Yanni Papanikolaou, J.B., Carroll Reider, Victor L Fulgoni, U.S. adults are not meeting recommended levels for fish and omega-3 fatty acid intake: results of an analysis using observational data from NHANES 2003-2008. Nutr J, 2014. 13(31).
3.    Greupner, T., et al., Effects of a 12-week high-alpha-linolenic acid intervention on EPA and DHA concentrations in red blood cells and plasma oxylipin pattern in subjects with a low EPA and DHA status. Food Funct, 2018. 9(3): p. 1587-1600.
4.    Gerster, H., Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)? Int J Vitam Nutr Res, 1998. 68(3): p. 159-73.
5.    C., V.S., ω-3 Fettsäuren und Hirnfunktion. Orthomol. Med., 2016. 2: p. 6-10.
6.    Budoff, M.J., et al., Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial. Eur Heart J, 2020. 41(40): p. 3925-3932.
7.    Florent-Bechard, S., et al., Towards a nutritional approach for prevention of Alzheimer's disease: biochemical and cellular aspects. J Neurol Sci, 2007. 262(1-2): p. 27-36.
8.    Oken, E., et al., Maternal fish consumption, hair mercury, and infant cognition in a U.S. Cohort. Environ Health Perspect, 2005. 113(10): p. 1376-80.
9.    Dyall, S.C., Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci, 2015. 7: p. 52.
10.    Innis, S.M., Dietary (n-3) fatty acids and brain development. J Nutr, 2007. 137(4): p. 855-9.
11.    Tan, Z.S., et al., Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology, 2012. 78(9): p. 658-64.
12.    Mazereeuw, G., et al., Effects of omega-3 fatty acids on cognitive performance: a meta-analysis. Neurobiol Aging, 2012. 33(7): p. 1482 e17-29.
13.    Yurko-Mauro, K., et al., Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement, 2010. 6(6): p. 456-64.
14.    Viswanathan, A., W.A. Rocca, and C. Tzourio, Vascular risk factors and dementia: how to move forward? Neurology, 2009. 72(4): p. 368-74.
15.    Ma, D.W., et al., n-3 PUFA and membrane microdomains: a new frontier in bioactive lipid research. J Nutr Biochem, 2004. 15(11): p. 700-6.
16.    Cole, G.M. and S.A. Frautschy, DHA may prevent age-related dementia. J Nutr, 2010. 140(4): p. 869-74.