Omega-3 Fatty Acids

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Omega-3 fatty acids are a class of polyunsaturated fatty acid compounds that have ore than one double bond in their backbone. Research has shown that dietary supplementation with omega-3 fatty acids carry benefits including improved memory, reduced symptoms of depression, decreases in triglyceride levels, and decreases in blood pressure.1The most commonly used omega-3 fatty acids are eicosapentaenoic acid (EPA), docosahexaneoic acid (DHA), and alpha-linoleic acid (ALA). EPA and DHA are typically extracted from fish, while ALA is typically found in vegetable oil, nuts, flaxseed oils and grass-fed animal fats.

Pharmacology of Omega-3 Fatty Acids

Omega-3 fatty acids are a family of polyunsaturated fatty acid molecules. These are fatty acids that contain more than one double bond in their backbone, specifically starting after the third carbon on the chain. The most commonly used and studied omega-3 fatty acids are α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).


Examples of omega-3 fatty acids include α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

The omega-3 fatty acids are important constituents of the cell membrane – the dynamic interface between cells and the rest of the body. Deficiency of omega-3 fatty acids has been correlated with increased risk of multiple mental health disorders, including depression, bipolar disorder, schizophrenia, and others. While no causal relationship has been established, these evidence show that nutritional support could be useful in ameliorating some types of cognitive dysfuction.

DHA Synapse

DHA is >30% of the lipid composition of the neural cell membrane. DHA helps promote fluidity at critical synaptic junctions – allowing dynamic molecular processes to take place


DHA and EPA both have positive effects on the body. DHA generally produces more cognitive benefits such as improvements in working memory or attention. On the other hand, EPA tends to better for lowering blood cholesterol levels as well as improving the immune response. Most nutritional omega-3 fatty acid supplements have a 2:1 ratio of DHA to EPA, or vice versa.

Omega-3 Fatty Acids and Mental Performance

Some evidence suggests that omega-3 fatty acids carry neuroprotective effects against memory loss that usually comes with old age. DHA in particular has been known to increase blood flow as well as reduce aggregation of amyloid plaque in brain neurons as well as in reduce plaque aggregation in blood vessels.


Omega-3 polyunsaturated fatty acids can help to prevent atherosclerotic plaque buildup in blood vessels, as well as to prevent amyloid plaque buildup in brain neurons.


Some evidence suggests that dietary supplementation of omega-3 fatty acids in older adults may help to augment memory function. A 24-week long study involving 46 participants between the ages of 55 and 90, showed that dietary supplementation with 1.8g/day of omega-3 fatty acid (1080g EPA and 720mg DHA), resulted in an improvement in the Clinician Interview-Based Impression of Change plus caregiver input (CIBIC-plus) evaluation for dementia patients, but not the ADAS-cog and MMSE tests for cognitive function, as compared to placebo.

Regarding risks for Alzheimer’s disease, there is conflicting evidence as to whether or not omega-3 fatty acid dietary supplementation can reduce rates of developing Alzheimer’s disease in many large-scale clinical studies. Various studies show correlations of decreased rates of Alzheimer’s development in patients undergoing dietary supplementation of omega-3 fatty acids, but without statistically significant effects and the effects across studies vary.

Studies of dietary DHA manipulation and school performance in children have shown interesting results. In a 2007 study of 780 children, nutrient supplementation of iron, zinc, folate, vitamins A, B6, B12, C, DHA + EPA, significantly improved tests of verbal learning and memory in a subset of the children. Though difficult to tease apart the influence of EPA and DHA alone, this evidence represents a starting point for future analyses of DHA intervention and cognitive performance.


A study on 49 participants, in which 33 were given dietary supplementation of omega-3 for 55 days, and 16 were given a placebo for 35 days, showed that omega-3 supplementation resulted in improved attention in the participants who had the omega-3 supplementation. Specifically, participants noticed a mean decrease of 50 milliseconds in a sustained attention task. In this experiment, attention was measured by the Zimmermann & Fimm Attention Test procedure.11

Omega-3 Fatty Acids and Physical Health

Cardiovascular effects

Various large scale studies have showed beneficial effects of omega-3 fatty acids on cardiovascular health. For example, a large scale study in over 11,000 patients showed that dietary supplementation in of omega-3 fatty acids in patients recently suffering myocardial infarction, resulted in a 10% decrease in relative risk of exhibiting a second myocardial infarction. Furthermore, there was a 14% decrease in relative risk of death, and a 20% decrease in fatal events.

A study in over 18,000 patients in Japan with cholesterol levels of over 6.5 mmol/L showed that dietary supplementation with EPA (1.8g/day) along with statin medications resulted in significantly fewer rates of major coronary events, as compared to a statin only control group. In the EPA group, there was an overall 19% decrease in major coronary events, as well as a 25% decrease in levels of low-density lipoproteins.


The JELIS study on over 18,000 hypercholesterolemic patients showed that dietary supplementation of omega-3 fatty acids for 1.8g/day led to significantly lower rates of major coronary events.


Evidence suggests that healthy dosages of omega-3 fatty acid supplementation can carry beneficial anti-inflammatory effects. Previous scientific evidence suggests that increased omega-3 fatty acid intake (EPA and DHA) is associated with reductions in incidence of diseases involving inflammation, including cardiovascular disease, inflammatory bowel disease, cancer and rheumatoid arthritis.

Omega-3 Fatty Acids and Exercise

There are synergistic relationships between exercise and DHA, that have been shown to improve cognitive processes greater than either intervention alone. Animal models have shown that exercise, combined with DHA, can increase expression of neurotrophic factors important for cognitive health such as brain derived neurotophic factor (BDNF).


exercise & DHA synergy

In animal models, exercise and DHA improve brain derived neurotrophic factor (BDNF) mediated plasticity, and spatial learning, more than either alone. Furthermore, exercise can counteract the effects of a negative, high fat (HF) diet, on BDNF mediated plasticity.

Differences in Adults and Children

Omega-3 fatty acid supplementation has been linked to differences in learning and behavior among children. A study in 26 children with ADHD found that children who recieved supplementation of omega-3 fatty acids exhibited decreases in several aspects on the Conner’s subscales for ADHD symptoms including cognitive problems, inattention, hyperactivity, anxiousness and social problems. Another study on 493 schoolchildren, found that low blood levels of omega-3 fatty acids was linked to poor cognitive performance (as measured by reading ability) and behavioral problems as rated by Conner’s ADHD scales, DSM-IV scales for attention and hyperactivity, as well as subjectively by schoolteachers.

Optimal ratios of EPA/DHA

Many supplements on the market contain a blend of EPA and DHA. Furthermore, many studies for cognition and other health effects use a blend of EPA and DHA as the intervention. The ratios of DHA to EPA in various studies for cognition have ranged from 1-to-2 to 2-to-1. For example, several studies of omega-3 fatty acids on Alzheimer’s disease have used blends of 1.7 g DHA and 0.7 g EPA daily as the intervention. The optimal ratio for achieving peak cognitive effects is an interesting question, although there is not a conclusive, rigorously validated optimal ratio at this point in time.

Adverse Effects of Omega-3 Fatty Acids

There are no major severe adverse effects of omega-3 fatty acids, when taken in normal quantities. Some research suggests that extreme excess consumption of omega-3 fatty acids may lead to potentially negative cardiovascular effects.

Some human studies have investigated potential negative effects of omega-3 fatty acids when taken in excess. For example, one study in which adults were supplemented with EPA (between 1.65 to 4.95 g daily) over 12 weeks, found that high intake of omega-3 fatty acids in older adults may lead to suppressed immune responses to infection, as measured by the change in neutrophil respiratory burst in response to E. coli (a test in which levels of active neutrophils, an important immune cell for destroying pathogens, are measured in the blood).It was suggested that there may be a dose dependent response of EPA to immunomodulation in older adults, as the the same study showed decreased neutrophil activation with increases in EPA supplementation, with up to a 15% decrease for an intake of 4g/day EPA. In younger adults, there were not significant changes in the magnitude of neurophil respiratory burst with intake up to 4g/day.


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