The chemical structures of EPA and DHA are very similar and they compete for uptake and processing resources. During digestion, the triglyceride molecules in standard fish oil are broken down into a mono glycerol and two free fatty acids, small enough to be absorbed into cells of the gut lining. More often than not, DHA is the fatty acid that remains attached to the glycerol backbone, meaning in essence that DHA gets a ‘free pass’ into the gut, while the remaining free fatty acids (more often EPA) must reattach onto a glycerol molecule or risk being oxidised and used as fuel. The implication of this is that DHA levels in our cells are often concentrated at the expense of EPA after absorption when taking EPA and DHA in the standard ratio of 1.5 to 1.
The conversion of ALA to EPA and further to DHA in humans has been reported to be limited, but varies with individuals. Women have higher ALA-to-DHA conversion efficiency than men, which is presumed to be due to the lower rate of use of dietary ALA for beta-oxidation. One preliminary study showed that EPA can be increased by lowering the amount of dietary linoleic acid, and DHA can be increased by elevating intake of dietary ALA.
Increasing ALA intake probably makes little or no difference to all‐cause mortality (RR 1.01, 95% CI 0.84 to 1.20, 19,327 participants; 459 deaths, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and it may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low‐quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low‐quality evidence), and probably reduces risk of CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs), and arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear.
A 2014 meta-analysis of eleven trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and of eight trials with patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo. The study concluded that: "The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD."
A tremendous body of research has been conducted on these important nutrients since it was first discovered in the 1950s that fish oil offered many health benefits and that these benefits were attributable to a type of polyunsaturated fat called omega-3. Despite the volumes of research on omega-3s, it is only in recent years (within the last 15 years or so) that the actions of EPA and DHA have come to be understood individually. Researchers now often investigate the actions of EPA and DHA individually rather than together, no longer simply under the generic label omega-3 as they are widely referred to.
There’s evidence that points to the mechanism behind the effects of fish oil on body composition, showing that fat burning at rest is increased with 6 grams/day of fish oil supplementation, and additional research suggests that higher omega-3 levels may be helpful for enhancing satiety during weight loss efforts. Other evidence suggests that fat loss may be a side-effect of the reduction in inflammation that fish oil can help with. Any way you look at it, supporting your dietary habits with 4 or more grams of fish oil per day is probably a good idea!
A group out of India conducted a study published in Cancer Chemotherapy and Pharmacology based on the premise that “fish oil rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anti-cancer drugs.” The study found that using 5-Fluorouracil (5-FU) to treat colorectal cancer along with fish oil increased the survival rate in carcinogen-treated animals. Researchers also found that the fish oil ameliorated hematologic depression, along with gastrointestinal, hepatic and renal toxicity caused by the 5-FU. (15)
It seems that infancy and childhood are some of the most important periods of time in a person’s life to get plenty omega-3s in their diet, probably because of the amount of long-chain fatty acids found in the brain and retina. It’s crucial for developing babies and children to get a good amount of DHA and EPA so their brains and eyes develop fully and properly. (78)
Augood, C., Chakravarthy, U., Young, I., Vioque, J., de Jong, P. T., Bentham, G., Rahu, M., Seland, J., Soubrane, G., Tomazzoli, L., Topouzis, F., Vingerling, J. R., and Fletcher, A. E. Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration. Am J Clin Nutr 2008;88(2):398-406. View abstract.
Fish oil supplements vary in the amounts and ratios of DHA and EPA they contain. For example, salmon oil naturally contains more DHA than EPA; a supplement derived from algae may only contain DHA. Krill oil contains significant amounts of both EPA and DHA. Read the labels and remember whatever supplement you buy, it must have at least 600 mg of DHA.
46. Gajos G, Rostoff P, Undas A, Piwowarska W. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol. 2010;55:1671–8. [PubMed]
Some research indicates that people who eat more seafood may have a reduced risk of cognitive decline. However, omega-3 supplements haven’t been shown to help prevent cognitive impairment or Alzheimer’s disease or to improve symptoms of these conditions. For example, a large NIH-sponsored study completed in 2015 indicated that taking EPA and DHA supplements did not slow cognitive decline in older adults. The people studied were participants in a larger eye disease study, and all of them had age-related macular degeneration (AMD).
Participants treated with a daily dose of 2000 mg or more of omega-3 PUFAs showed a significantly greater association of treatment with reduced anxiety symptoms. In addition, participants receiving supplements containing less than 60% EPA showed a significant association, but not those receiving supplements containing 60% or more EPA. The depression literature supports the clinical benefits of EPA-enriched formulations (≥60% or ≥50%) compared with placebo for the treatment of clinical depression.9,13,73-75 This opposite effect of EPA-enriched formations on anxiety and depression is intriguing and possibly linked to a distinct underlying mechanism of omega-3 PUFAs. Exploration of the effects of omega-3 PUFAs on anxiety symptoms is just beginning and studies assessing the dose response anxiolytic effects of omega-3 PUFAs have not yet been performed. Further phase 2 trials of anxiety symptoms among participants with neuropsychiatric illness or physical illness should aim to determine the optimal dose.
For slowing weight loss in patients with cancer: 30 mL of a specific fish oil product (ACO Omega-3, Pharmacia, Stockholm, Sweden) providing 4.9 grams of EPA and 3.2 grams of DHA daily for 4 weeks has been used. 7.5 grams of fish oil daily providing EPA 4.7 grams and DHA 2.8 grams has been used for about 6 weeks. In addition, two cans of a fish oil nutritional supplement containing 1.09 grams of EPA and 0.96 grams of DHA per can have been used daily for up to 7 weeks.
Although results from studies regarding the disease processes of AD seem to be promising, there are conflicting data regarding the use of omega-3 fatty acids in terms of cognitive function. Neuropsychiatric symptoms accompany AD from early stages and tend to increase with the progression of the disease (55). An analysis of 174 patients randomized to a placebo group or to a group with mild to moderate AD (MMSE score ≥15) treated with daily DHA (1.7 g) and EPA (0.6 g) found that at 6 mo, the decline in cognitive function did not differ between the groups. Yet, in a subgroup with very mild cognitive dysfunction (n = 32, MMSE score >27), they observed a significant reduction in the MMSE decline rate in the DHA+EPA-supplemented group compared with the placebo group (47). Another study that looked at DHA supplementation in individuals with mild to moderate AD used the Alzheimer's Disease Assessment Scale–Cognitive subscale, which evaluates cognitive function on a 70-point scale in terms of memory, attention, language, orientation, and praxis. This study found that DHA supplementation had no beneficial effect on cognition during the 18-mo trial period for the DHA group vs. placebo (56).
Fish oil is a concentrated source of omega-3 fats, which are also called ω-3 fatty acids or n-3 fatty acids. To get more scientific, omega-3s are long-chain polyunsaturated fatty acids, or PUFAs. Our bodies are able to make most of the fats we need need, but that’s not true for omega-3 fatty acids. When it comes to these essential fats, we need to get them from omega-3 foods or supplements.
Fish oil is also extremely beneficial for pregnant women and their children. Throughout pregnancy and also while breastfeeding, a woman’s omega-3 needs are even higher than usual. According to the American Pregnancy Association, most U.S. women are deficient in EPA and especially DHA going into pregnancy and get even more depleted during pregnancy, as the placenta supplies the fetus with DHA from the mother’s tissue. Omega-3 DHA is a critical building block of the fetal brain, eyes and nervous system. Once the baby is born, omega-3s continue to be vital to healthy brain development and immune function. (30)
Only fish and breast milk contain all the members of the omega-3 family, including its two main stars, EPA and DHA. Because Americans as a rule consume far too few omega-3s from fish or fish oil, it’s no surprise that the majority of Americans have low omega-3 index levels as well. A recent study of global omega-3 index levels found that an estimated 95% of Americans (with the exception of folks from Alaska) had an omega-3 index of 4 or below, putting them in the high risk category (5, 6, 7).
Omega-3 FA most likely reduce serum triglyceride levels by modulating very-low-density lipoprotein (VLDL) and chylomicron metabolism. There is a consistent finding in the literature that the end effect of fish oil is decreased hepatic secretion of VLDL17—the major endogenous source of triglycerides. This effect occurs most likely through multiple mechanisms, including: (1) decreased synthesis of triglycerides because these omega-3 FA may not be the preferred substrates of the enzyme diacylglycerol O-acyltransferase,18 or they may interact with nuclear transcription factors that control lipogenesis19; cellular metabolism consequently shifts toward a decrease in triglyceride synthesis and an increase in FA oxidation; and (2) the promotion of apolipoprotein B degradation in the liver through the stimulation of an autophagic process.20 This means that fewer VLDL particles can be assembled and secreted. Fish oil may also accelerate VLDL and chylomicron clearance21 by inducing lipoprotein lipase activity.22
Davidson, M. H., Stein, E. A., Bays, H. E., Maki, K. C., Doyle, R. T., Shalwitz, R. A., Ballantyne, C. M., and Ginsberg, H. N. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther 2007;29(7):1354-1367. View abstract.
First, EPA inhibits the enzyme that produces arachidonic acid. Second, EPA impedes the release of arachidonic acid from cell membranes (where it is stored) and its metabolization once it is released. Without this release and metabolization, your body can’t make eicosanoids. The result is lower risk of the inflammation that would have been caused by all that arachidonic acid going to eicosanoids.
Schilling, J., Vranjes, N., Fierz, W., Joller, H., Gyurech, D., Ludwig, E., Marathias, K., and Geroulanos, S. Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids, and nucleotide-enriched enteral feeding: a randomized prospective comparison with standard enteral and low calorie/low fat i.v. solutions. Nutrition 1996;12(6):423-429. View abstract.
We’ve written about the dose necessary to achieve measurable benefits before. However, a person’s actual omega-3 intake can be tricky to estimate. Even if you eat at least two servings of fatty fish per week, as the American Heart Association recommends (10), your fish might contain more or less omega-3s depending on the fish species, the time of year, and how you cook it. Even taking fish oil supplements isn’t always straightforward, as dose can be impacted by numerous bioavailability factors, as well as genetics, age, gender, medication-use and lifestyle.
Infant development. There is some evidence that mothers who eat fish or take fish oil supplements during pregnancy may improve some aspects of their baby's mental development. Taking fish oil during breast-feeding does not have this effect. However, feeding infants formula fortified with fish oil appears to improve some aspect of the baby's vision by the age of 2 months.