Fish Oil: How much is too much?

Question

Many physicians and laypeople extol the virtues of Fish Oil supplements.

But how much is too much, and why?

Let's assume the fish oil is being ingested by a healthy adult, and that the fish oil has been purified to remove mercury.

Answer 1

Many people are quite gullible.
_{(Just general observation, not a a comment on the question or the asker.)}

Whatever the marketing section of the industries' propaganda unit tells the public, supplements can only augment so much in a good diet.

The FDA once said that 3g of fish oil daily is generally recognised as safe (GRAS) and there is a number of studies out there with differing dosages tried.

But that is misleading, not in the least because of the "let's assume" part in the question above. These supplements have side-effects, even if 'pure' and manufactured to the highest standards. No single nutrient can be assayed in complete isolation. They interact on multiple levels and the rest of the diet is as much an influence on outcomes, as are genetics, the microbiome and other environmental or lifestyle factors.

"The virtues of fish oil: "For what would anyone need this supplement?

Omega-3 fatty acids for depression in adults? At present, we do not have sufficient high quality evidence to determine the effects of n-3PUFAs as a treatment for MDD. Our primary analyses suggest a small-to-modest, non-clinically beneficial effect of n-3PUFAs on depressive symptomology compared to placebo; however the estimate is imprecise, and we judged the quality of the evidence on which this result is based to be low/very low.

Poly-unsaturated fatty acid supplementation for drug-resistant epilepsy? The existing evidence, which consists of only three small studies, is not enough to support the use of PUFA supplementation in addition to routine antiepileptic medications to improve seizure control or quality of life in people with drug-resistant epilepsy.

Omega 3 fatty acids for prevention and treatment of cardiovascular disease? There is not enough evidence to say that people should stop taking rich sources of omega 3 fats, but further high quality trials are needed to confirm the previously suggested protective effect of omega 3 fats for those at increased cardiovascular risk

The review shows that it is not clear whether dietary or supplemental omega 3 fats (found in oily fish and some vegetable oils) alter total deaths, cardiovascular events (such as heart attacks and strokes) or cancers in the general population, or in people at risk of, or with, cardiovascular disease. When the analysis was limited to fish-based or plant-based, dietary or supplemental omega 3 fats there was still no evidence of reduction in deaths or cardiovascular events in any group.

These are just a few examples. Fish oil is not just a magic pill that is equally beneficial for anyone in every circumstance. And as so often "taking much will do much good" does simply not apply.

Why is this the case? Randomised clinical control trials have shown…

That things are a bit more complicated when in comes to humans and their nutrition as to arrive at a meaningful result in these trials when the focus is on isolated substances, components, or ingredients.

Take Lipid peroxidation during n-3 fatty acid and vitamin E supplementation in humans:

The results demonstrate that supplementing the diet with n-3 fatty acids resulted in an increase in lipid peroxidation, as measured by plasma MDA release and lipid peroxide products, which was not suppressed by vitamin E supplementation.

Reductionist nutrition studies are valuable tools to find, explore, or explain basic mechanisms. But it is inappropriate to grab every one such study and start selling stuff based on these findings:

Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet:

Our genome adapts slowly to changing conditions of existence. Many diseases of civilisation result from mismatches between our Paleolithic genome and the rapidly changing environment, including our diet. The objective of the present study was to reconstruct multiple Paleolithic diets to estimate the ranges of nutrient intakes upon which humanity evolved. A database of, predominantly East African, plant and animal foods (meat/fish) was used to model multiple Paleolithic diets, using two pathophysiological constraints (i.e. protein < 35 energy % (en%) and linoleic acid (LA) >1·0 en%), at known hunter–gatherer plant/animal food intake ratios (range 70/30–30/70 en%/en%). We investigated selective and non-selective savannah, savannah/aquatic and aquatic hunter–gatherer/scavenger foraging strategies. We found (range of medians in en%) intakes of moderate-to-high protein (25–29), moderate-to-high fat (30–39) and moderate carbohydrates (39–40). The fatty acid composition was SFA (11·4–12·0), MUFA (5·6–18·5) and PUFA (8·6–15·2). The latter was high in α-linolenic acid (ALA) (3·7–4·7 en%), low in LA (2·3–3·6 en%), and high in long-chain PUFA (LCP; 4·75–25·8 g/d), LCP n-3 (2·26–17·0 g/d), LCP n-6 (2·54–8·84 g/d), ALA/LA ratio (1·12–1·64 g/g) and LCP n-3/LCP n-6 ratio (0·84–1·92 g/g). Consistent with the wide range of employed variables, nutrient intakes showed wide ranges. We conclude that compared with Western diets, Paleolithic diets contained consistently higher protein and LCP, and lower LA. These are likely to contribute to the known beneficial effects of Paleolithic-like diets, e.g. through increased satiety/satiation. Disparities between Paleolithic, contemporary and recommended intakes might be important factors underlying the aetiology of common Western diseases. Data on Paleolithic diets and lifestyle, rather than the investigation of single nutrients, might be useful for the rational design of clinical trials. […]

The fish oil fatty acids EPA and DHA (and their derivatives), vitamin D (1,25-dihydroxyvitamin D) and vitamin A (retinoic acid) are examples of nutrients that act in concert, while each of these has multiple actions(7,8).

Consequently, the criteria for establishing optimum nutrient intakes via randomised controlled trials (RCT) with single nutrients at a given dose and with a single end point have serious limitations. They are usually based upon poorly researched dose–response relationships, and typically ignore many possible nutrient interactions and metabolic interrelationships.

For instance, the adequate intake of linoleic acid (LA) to prevent LA deficiency depends on the concurrent intakes of α-linolenic acid (ALA), γ-LA and arachidonic acid (AA). Consequently, the nutritional balance on which our genome evolved is virtually impossible to determine using the reigning paradigm of ‘evidence-based medicine’ with RCT.

The last sentence is a bit extreme in its wording but highlights very well the almost fraudulent 'jumping onto a soap box' attitude that the supplement industry apparently cannot resist since its creation.

The German Federal Institute for Risk Assessment reached in 2009 the point to issues a warning and called for a maximum dosage of around 1-2g daily equivalent of 100g salmon. Overdosing on these pharmakons would increase multiple risks, like increased bleeding, decreased immune system function, premature death for patients with pre-existing heart disease etc.

Giving one single number to avoid overdoing it seems more than difficult. In this case it is not only the total dose response relationship to consider. This also about the ratio (mainly of fatty acids) and unavoidable interactions with other supplements, medications and normal food, which is now also sometimes fortified. As a general rule of thumb: consider an Inuit or Japanese gut and body, trained or habituated to large amounts of sea fish, whose owner also really likes eating fish. The equivalent amount of fish oil in supplements might be a good orientation for staying in the 'not detrimental' range.

There is no reason to abstain from fish. There is no doubt we do not eat enough omega-3 fatty acids – compared to the ratio of omega 6. Just lowering omega-6 PUFAs seems to be a much safer and cheaper way to achieve what the extolers want to achieve. Staying away from the industry's omega-6 rich food abolishes the perceived or real need for the industry's supplements?

This is not to say that (even supplemented) omega-3, whether from fish oil or from elsewhere is totally useless, ineffective or wholly dangerous. In a clinical setting under good supervision and control of the individual and his lab results even high doses of fish oil will likely prove to be of substantial value in a wide range of applications. Everyone should be able to decide this for himself. But the industry has to be kept under the strictest regulation and harshly enforced quality control. The primary target for improving health has to be a sensible diet. We just don't know it any better.