Fish Oil

Fish oil is a common term used to refer to two kinds of omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These omega-3 fats are usually found in fish, animal products, and phytoplankton.

The fatty acids EPA and DHA are involved in regulating various biological processes such as the inflammatory response, various metabolic signaling pathways, and brain function. They can be synthesized in the body from alpha-linolenic acid (ALA), but in small amounts for most people.

Fish oil causes a potent reduction in triglyceride levels and a more modest reduction in blood pressure in hypertensives. Despite this, long-term trials haven't found a reduction in the rate of cardiovascular events.

It appears to notably improve mood in people with major depression, though it's unclear if it has an effect in people with minor depression. EPA, in particular, seems to be the most effective omega-3 fatty acid for this purpose which suggests that the effects of fish oil are due to reducing neuroinflammation. Its anti-inflammatory benefits also seem to extend to reducing the symptoms of systemic lupus erythematosus. However, its benefits shouldn't be assumed to extend to inflammatory diseases in general.

Many fish oil supplements may contain harmful lipid peroxides (oxidized lipids that can damage cells), but it's unclear if this has notable consequences to health.

"Fish oil" refers to a solution of fatty acids where the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are dominant. Fish is by far the most common source for fish oil, hence the name, but an artificially manufactured EPA/DHA dominant mixture from any source could be considered fish oil. Typical fish oil can contain small amounts of other omega-3 fatty acids, usually DPA and fatty acids that don't belong to the omega-3 category. Alpha-linolenic acid (found most abundantly in nuts and seeds), is an omega-3 fatty acid that can be turned into EPA and DHA but is not itself a fish oil fatty acid.

Fish oil doses vary depending on the goal of supplementation. For general health, 250mg of combined EPA and DHA is the minimum dose and can be obtained via fish intake. The American Heart Association recommends 1g daily. If the goal of supplementation is to reduce soreness, a 6g dose, spread over the course of a day, will be effective.

Since fish oil is a combination of two different fatty acids, these numbers reflect a combined total. Total eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) consumption should come from a mix of real food and supplements. The more EPA and DHA is provided by the diet, the less supplementation is required.

Fish oil can be taken throughout the day. To minimize the "fish burp" taste, take fish oil with meals.

Pregnant women should increase their intake of DHA by at least 200mg a day, as long as there is no risk of elevated mercury levels.

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects fish oil has on your body, and how strong these effects are.

Grade	Level of Evidence [show legend]
	Robust research conducted with repeated double-blind clinical trials
	Multiple studies where at least two are double-blind and placebo controlled
	Single double-blind study or multiple cohort studies
	Uncontrolled or observational studies only

Level of Evidence ? The amount of high quality evidence. The more evidence, the more we can trust the results.	Outcome	Magnitude of effect ? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.	Consistency of research results ? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.	Notes
	Triglycerides	Strong	Very High See all 44 studies	Fish oil, both EPA and DHA, are reference drugs for the purpose of reducing triglycerides with highly reliable reductions in the range of 15-30% (higher reductions seen in persons with higher baseline triglycerides)
	Depression	Notable	Very High See all 23 studies	Fish oil supplementation has been noted to be comparable to pharmaceutical drugs (fluoxetine) in majorly depressed persons, but this may be the only cohort that experiences a reduction of depression. There is insufficient evidence to support a reduction of depressive symptoms in persons with minor depression (ie. not diagnosed major depressive disorder)
	ADHD in Children	Minor	Very High See all 9 studies	Supplemental DHA above 300mg appears to be effective in reducing ADHD symptoms in children when supplemented
	Blood Pressure	Minor	Very High See all 8 studies	May decrease blood pressure in persons with high blood pressure, but does not appear to have efficacy in persons with normal blood pressure
	HDL-C	Minor	Very High See all 27 studies	Mixed evidence, but a possible increase in HDL-C is seen with fish oil supplementation in unhealthy persons
	Inflammation	Minor	Moderate See all 17 studies	Highly mixed and unreliable influences on circulating inflammatory cytokines (although, due to immunosuppression on cellular adhesion factors, the overall effect may still be antiinflammatory)
	LDL-C	Minor	- See all 30 studies	A decrease has been noted in persons without high cholesterol in the first place, and the decreasing effect of statins appears to be augmented with fish oil. However, in persons at higher risk for cardiovascular disease due to high triglycerides and cholesterol (who more frequently use fish oil as therapy) it is possible LDL-C may actually be increased. The magnitude tends to be in the 5-10% range.
	Blood Glucose	-	High See all 19 studies	No significant alterations in fasting glucose are seen over time with fish oil supplementation
	C-Reactive Protein	-	Very High See all 16 studies	Although some decreases have been noted, the vast majority of the evidence suggests that there is no significant influence
	HbA1c	-	Moderate See all 10 studies	Although the majority of evidence suggests absolutely no influence on HbA1c, reductions have been reported and a lone case has noted a clinically irrelevant increase of HbA1c (secondary to the increase in glucose). Practically, there is unlikely to be any large changes
	Insulin Sensitivity	-	Very High See all 12 studies	No significant influence on insulin sensitivity seems to be the consensus, although there are isolated reports of both an increase and decrease (in response to a glucose tolerance test and fasting, respectively)
	Total Cholesterol	-	Very High See all 18 studies	Although some decreases have been noted, overall there does not appear to be a significant clinical reduction in total cholesterol like there is with triglycerides
	Weight	-	High See all 14 studies	For the most part, no significant influence on body weight over time
	Symptoms of Systemic Lupus Erythematosus	Notable	Very High See all 7 studies	The decrease in symptoms of lupus as assessed by SLAM-R and BILAG at times reaches up to 50% symptom reduction and tends to exceed 30%, and the first pilot studies noted remission in all subjects (although they have not been replicated since). Oddly, benefit may come from lower doses (160mg EPA and 140mg DHA) with higher doses conferring less benefit
	Cell Adhesion Factors	Minor	Low See all 8 studies	Appears to be able to reduce cellular adhesion factors (that draw immune cells into tissue to aid in inflammatory processes, reducing these is immunosuppressive) in elderly persons, while slightly increasing expression in youth
	Cortisol	Minor	Low See all 4 studies	A possible reducing effect of fish oil supplementation on cortisol
	Endothelial Function	Minor	Very High See all 4 studies	There appears to be a slight increase in vascular reactivity and blood vessel responsiveness that may be independent of both blood flow alterations and blood pressure
	Infant Birth Weight	Minor	Very High See 2 studies	There appears to be an increased infant birth weight in mothers that consume fish oil (or fish weekly) relative to no fish oil intake. Although earlier studies have suggested this may due to prolonging pregnancy, a recent RCT found an increase in birth weight independent of gestational age.
	Lipid Peroxidation	Minor	- See all 5 studies	Both increases and decreases in lipid peroxidation have been noted with fish oil supplementation, with the increases in peroxidation usually seen with high doses of fish oil paired with other oxidative stressors (such as marathon running)
	Natural Killer Cell Activity	Minor	High See all 3 studies	Although there do not appear to be changes in the amounts of NK cells in the body following fish oil, their activity appears to be a tad reduced
	Photoprotection	Minor	Very High See all 3 studies	There appears to be reduced risk of DNA damage, immunosuppression, and erythema in response to sunlight associated with fish oil consumption. Studies have only investigated higher doses (1,800mg EPA minimum) and it is unsure if these protective effects apply to lower doses
	Platelet Aggregation	Minor	High See all 4 studies	Possible decreases in platelet aggregation
	Symptoms of Bipolar Disorder	Minor	Very High See all 5 studies	There appears to be reduced depressive symptoms in bipolar disorder when the depression is of a large magnitude (similar to the anti-depressant effects of fish oil in general). There may not be a reduction in depressive symptoms with lower severity depression (a trend to increase has been noted) and manic symptoms do not appear to be significantly influenced.
	TNF-Alpha	Minor	High See all 6 studies	May decrease TNF-a
	vLDL-C	Minor	Very High See all 6 studies	May decrease vLDL cholesterol
	Apolipoprotein B	-	Moderate See all 6 studies	Although at least one study has noted a decrease, usually there is no significant changes
	B-Cell Count	-	Very High See all 3 studies	The overall quantity of B lymphocytes does not appear to be altered with fish oil supplementation
	Blood Flow	-	Moderate See all 5 studies	Although there is some counter evidence to suggest an improvement of small magnitude, most evidence suggest no significant changes in blood flow
	Insulin	-	Very High See all 10 studies	No significant influence on fasting insulin levels
	Insulin Secretion	-	Very High See all 5 studies	There does not appear to be an augmented insulin release from dietary carbohydrate nor an inherent insulin release from the pancreas associated with fish oil supplementation
	Muscle Soreness	-	High See all 3 studies	Although one study suggests a decrease, most evidence suggest no significant influence
	Natural Killer Cell Content	-	High See all 3 studies	Although one increase in NK cell content has been noted after exercise, the two studies using similar doses at rest have failed to find a significant influence on NK cell content
	Postpartum Depression	-	Very High See all 5 studies	There does not appear to be any unique effect of supplemental fish oil on postpartum depression. Fish oil in postpartum and perinatal periods follows the same motifs as other depressive states, with EPA being the active molecule but likely only of benefit in major depressive disorder
	Pre-Eclampsia Risk	-	Very High See 2 studies	There does not appear to be a significant protective effect against pre-eclampsia in women who supplement fish oil during pregnancy
	T Cell Count	-	High See all 4 studies	Although there is some evidence to suggest an immunosuppressive effect on T cells, most evidence suggest no significant effect. When the immunosuppresion does occur, it is due to the EPA content
	VO2 Max	-	Very High See all 3 studies	There is no evidence to support an improvement of VO2 max when fish oil is consumed alongside an exercise routine
	5-HEPE	Notable	- See study	5-HEPE is a catabolite of EPA, and its blood levels are increased following consumption of EPA in a dose-dependent manner
	Aggression	Minor	- See study	A decrease in aggression has been noted, which is thought to be secondary to improvements in mood state and general well being
	Anxiety	Minor	Very High See 2 studies	A decrease in anxiety has been noted in medical students
	Cerebral Blood Flow	Minor	- See study	Appears to improve cerebral blood flow and volume in persons with low dietary fish intake
	Cerebral Oxygenation	Minor	- See study	The increase in cerebral oxygenation appears to exist in otherwise healthy persons with low dietary fish intake, and appears to be secondary to improvements in blood flow in general
	Cognitive Decline	Minor	Very High See 2 studies	High dose (900 mg) DHA appears to be somewhat beneficial in reducing the rate of cognitive decline in elderly but otherwise healthy persons, but 350 mg DHA and 600 mg EPA has been seen to have no effect in those with concurrent age-related macular degeneration.
	Erythema	Minor	Very High See 2 studies	Ingestion of fish oil appears to prolong the time required for sunlight to induce reddening of the skin, and secondary to this fish oil ingestion above 1,800mg EPA is able to reduce the risk of sunburn.
	Exercise-Induced Oxidation	Minor	- See study	Exercise induced oxidation has been noted to be increased in elite athletes with fish oil supplementation
	Factor VII	Minor	- See study	An increase in serum Factor VII has been noted with fish oil supplementation
	General Oxidation	Minor	Moderate See 2 studies	May increase general oxidation in the body, but seems unreliable in doing so
	Homocysteine	Minor	Very High See 2 studies	May decrease homocysteine content
	Infant Death Risk	Minor	- See study	A reduced risk of death of infants after pregnancy has been noted with maternal consumption of fish oil, but this information is preliminary and needs replication (noted offhand in one study)
	Interleukin 2	Minor	Moderate See 2 studies	Mixed effects on IL-2 concentrations, with an increase noted when supplemented around exercise and no change noted at rest.
	Interleukin 6	Minor	- See study	A decrease in circulating IL-6 has been noted with fish oil supplementation
	Ketone Bodies	Minor	- See study	An increase in ketone bodies has been noted when fish oil is paired with a weight loss diet (relative to placebo)
	Leukotriene B5	Minor	Very High See 2 studies	An increase in LKB5 has been noted following fish oil supplementation
	Liver Fat	Minor	- See study	A possible decreasing effect of liver fat seen in persons with NAFLD
	Lymphocyte Count	Minor	- See study	A decrease in lymphocytic count has been noted in obese persons
	Memory	Minor	- See 2 studies	Possible improvements in memory
	Nitric Oxide	Minor	- See study	An increase in exercise-induced nitric oxide production has been noted
	Plasminogen Inhibitor 1	Minor	- See study	An increase in PAI-1 is noted with fish oil supplementation
	Processing Accuracy	Minor	- See study	An improvement in processing accuracy (assessed by amount of errors in a cognitive test) has been noted with fish oil in otherwise healthy adults that do not frequently consume fish products
	Prostaglandin J2a	Minor	- See study	An increase in prostaglandin J2A is noted with fish oil supplementation, which is thought to mediate a variety of fish oil's effects
	Reaction Time	Minor	- See study	A reduction in reaction time has been noted with fish oil supplementation in persons who consume low levels of fish in the diet
	Stress	Minor	- See study	Self-reported stress in distressed women given fish oil supplementation appears to be reduced
	Subjective Well-Being	Minor	Moderate See all 3 studies	An improvement in well being has been noted in nondepressed and nonelderly obese persons given fish oil supplementation to a small magnitude.
	Thromboxane B2	Minor	- See study	An increase in thromboxane B2 is noted with fish oil supplementation
	5-HETE	-	- See study	5-HETE is a catabolite of arachidonic acid (omega-6 fatty acids), and its serum levels do not appear to be significantly influenced by ingestion of fish oil supplementation despite an increase in EPA and DHA
	Adiponectin	-	Moderate See 2 studies	No significant influence on Adiponectin concentrations
	Apolipoprotein A	-	Very High See 2 studies	No significant influence on Apolipoprotein A concentrations
	Attention	-	Very High See 2 studies	Fish oil supplementation in otherwise healthy adults has failed to significantly influence attention processing
	Cognition of Offspring	-	- See study	Despite the importance of DHA in cognition of offspring (and absolute deprivation likely to reduce cognitive development), additional supplemental fish oil does not appear to be supported for further enhancing the cognition of offspring although it is plausible
	DHEA	-	- See study	No significant influence on DHEA sulfate in serum
	DNA Damage	-	Very High See 2 studies	Does not appear to influence DNA damage
	Exercise-Induced Immune Suppression	-	- See study	Does not appear to augment nor alleviate the immunosuppression that occurs during exercise in otherwise healthy persons
	Fat Mass	-	Very High See all 3 studies	No significant influence on fat mass with routine supplemental fish oil
	Fatigue	-	Moderate See 2 studies	No demonstrable benefit to fatigue
	Food Intake	-	Very High See 2 studies	There does not appear to be a significant influence of fish oil supplementation on food intake
	Fructosamine	-	- See study	No evidence to support an increase in fructosamine, which alongside HbA1c is thought to indicate pathology from elevated blood glucose (fish oil appears to elevate glucose, but does not appear to be associated with higher diabetes risk)
	Glucagon	-	- See study	No significant influence on plasma glucagon concentrations
	Heart Rate	-	- See study	No significant acute effect on heart rate seen with fish oil supplementation
	Interleukin 1-beta	-	- See study	No significant influence on circulating IL-1β concentrations
	Interleukin 5	-	- See study	No significant influence on circulating IL-5 concentrations
	Lean Mass	-	Very High See all 3 studies	No significant influence on lean mass associated with fish oil supplementation
	Leptin	-	Very High See 2 studies	No significant influence on Leptin in serum
	Leukotriene B4	-	Very High See 2 studies	No significant influence on LKB4 concentrations
	Liver Enzymes	-	- See study	No significant influence on liver enzymes noted
	Muscle Damage	-	- See study	No significant influence on biomarkers of muscle damage seen with fish oil supplementation
	Oxidation of LDL	-	Very High See 2 studies	No significant influence detected
	Proteinuria	-	- See study	Although a trend to reduce protein losses in the urine was noted (which would be kidney protective), this was a statistically insignificant and secondary to lupus treatment
	Sex Hormone Binding Globulin	-	- See study	No significant influence on SHBG levels
	Symptoms of Alzheimer’s	-	- See study	Despite the benefit seen with high dose DHA in cognitive decline, there does not appear to be a proven significant protective effect in persons already with Alzheimer's
	Testosterone	-	- See study	No detectable influence on testosterone levels in serum
	Fat Oxidation	Minor	- See study	An increase in fat oxidation (percentage of energy being taken from fat tissue) has been noted with fish oil supplementation
	Follicle-Stimulating Hormone	Minor	- See study	Effect occurs in normal-weight women, but not obese women.
	Bone Mineral Density	-	- See study	No significant influence on bone mineral density noted with fish oil supplementation
	Metabolic Rate	-	- See study	No significant influence on metabolic rate seen with fish oil supplementation
	Working Memory	-	- See study

Studies Excluded from Consideration

• Confounded with other fatty acids^[1]

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