Don’t give up on fish oil just yet. New studies show great promise

In the 1970s Danish researchers Hans Bang and Jørn Dyerberg found that the Inuit, whose diet consisted mainly of the meat and blubber of seal and whale and relatively small amounts of oily fish, were substantially protected against cardiovascular disease and most of the diseases now thought to be driven by chronic inflammation.

The Danes believed that this protection was related to the omega-3 fatty acids in the Inuits’ diet. Other scientists subsequently showed that omega-3s were metabolised in the body to form anti-inflammatory mediators such as resolvins and neuroprotectins, which function pretty much as their names suggest; epidemiological studies consistently linked fish consumption to improved health; a couple of clinical trials suggested that fish oil could reduce cardiovascular deaths — and the omega-3 fatty acids took off, becoming the poster child for improved health through nutrition. A Harvard study, which calculated that omega-3 deficiency was killing 96,000 Americans a year, drove omega-3 awareness even higher.

Today, millions of health-conscious consumers swallow purified and deodorised fish oil capsules in the belief that these encapsulate the Inuit diet, and will help keep them healthy. Their faith in fish oil supplements may, however, be dangerously misplaced. To begin with, Bang and Dyerberg’s original work has been undermined by more stringent reviews of their Inuit mortality data. More seriously, fish oil increasingly appears to be double-edged.

The Inuit traditionally consumed their food raw or dried. Sophisticated urbanites would rather swallow purified, deodorised fish oil capsules than spend their evenings chewing seal blubber, but highly processed fish oil capsules are a long way from the Eskimo diet.

Scientists at the University of Tromso have shown that the industrial processes used to extract and purify fish oil remove the trace ingredients in fish that cause problems for supplement manufacturers — but which likely played a critical role in conferring the possible health benefits of the Inuit diet. Removing these trace compounds reduces the omega-3s’ anti-inflammatory effects, probably by leaving them vulnerable to oxidation, which turns them into pro-inflammatory compounds. Worryingly, there is evidence that older mice and men, many of whom take an omega-3 supplement, are intrinsically more vulnerable to its potentially pro-inflammatory effects. And the clinical evidence is problematic.

Even the most ardent omega-3 supporters concede that since the early successes of DART-1 and GISSI, the results of randomised clinical trials have been mixed.

DART-2, a prospective study of 3,114 men with angina under 70 years of age, was a disappointment. Men advised to eat oily fish, and particularly those supplied with fish oil capsules, had a higher risk of cardiac death. A subsequent large meta-analysis found that supplements of omega–3 capsules were not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association. There were also negative findings in the JELLIS, GISSI-HF, ALPHA-OMEGA, OMEGA, SU.FO.OM and ORIGIN trials; further studies have found that fish oils do not protect against Alzheimer’s or age-related macular degeneration.

While fish oil capsules look increasingly discredited, eating oily fish still appears to have some effect in reducing all-cause and coronary heart mortality, so there is an emerging argument for eschewing capsules and eating wild salmon, herring and mackerel, if not whale and seal. But there may be a problem here too; some scientists believe that due to pollution issues, eating fish is not as cardio-protective as it used to be. Recent events at Fukushima have strengthened this argument.

A preferred strategy may be to combine purified fish oils with an appropriate antioxidant. Vitamin E, the antioxidant most commonly used, is not the right candidate. It may protect fragile fish oils while they are in the capsule, but it does not protect them adequately once they have been consumed — and can act as a pro-oxidant. There is an alternative antioxidant, ignored until very recently, which does a far better job.

Omega-3s, which are produced by the cold-water seaweeds at the base of the marine food pyramid, survive passage through the food chain into humans because they are so well protected. What protects them is fat-soluble antioxidants produced by those same seaweeds. These antioxidants are polyphenols, called phlorotannins. The phlorotannins are extremely effective in protecting omega-3 fatty acids, so much so that they are being developed for use in industrial fish processing. They also exert an array of effects that are powerfully anti-inflammatory in their own right, and in ways that perfectly complement the anti-inflammatory effects of the omega-3s.

There are only two types of fat-soluble polyphenols that play a significant role in human nutrition; the phlorotannins, and a group of related compounds found in olives. The olive polyphenols are now regarded as playing a key role in the health-promoting benefits of the Mediterranean diet, and it seems probable that the marine polyphenols are equally beneficial.

The phlorotannins are potent anti-inflammatory agents with vaso- and cardio-protective properties in vitro and in vivo. They also display anti-allergy, anti-hypertensive, anti-diabetic, anti-Alzheimer and anti-cancer activity. It seems increasingly likely that many of the health benefits associated with the traditional Inuit diet, and which were attributed to omega-3 fatty acids, were at least partly due to their co-ingestion of phlorotannins. This would explain why trials of fish oil failed; pharmaceutically-minded scientists took a binary weapon, and in their reductionist way decided that only omega-3s were relevant. But by filtering out the phlorotannins, they threw out the baby with the bathwater.

Along with colleagues in northern Europe I have witnessed the clinical results of using a combination of omega-3s and olive polyphenols in over 2,000 subjects, and seen a consistent reduction of symptoms related to chronic inflammation. Seeing the alleviation of chronic pain, essential hypertension, allergic symptoms and a range of chronic conditions has been moving and exciting. Case histories do not constitute proof, however, and clinical trials are very much needed. Hopefully, we will see these initiated within the year.

Dr Paul Clayton is a Fellow at the Institute of Food, Brain and Behaviour, Oxford


  • bob sheridan

    Something fishy about this story. And the non-scientific “trust me” endorsement of the alleged benefits of the omega3/polyphenol approach smells of snake oil rather than fish oil. The IFBB website gives no info on who is behind this organisation. And who is P.R. Clayton?? Clayton has published only one article in the ‘peer reviewed’ literature, and that was a review rather than original research. Clayton’s co-author in that review shares an equally barren record of scientific publications.

    The last paragraph of the review’s abstract states: “The authors believe that due to such issues as dietary shift, it may now be inadvisable to prescribe or sell purified ω3 highly unsaturated fatty acids supplements, unless the appropriate co-factors are included.”

    I wonder who funded this work?

    • flavonoid

      Your questions are reasonable, and deserve answers. So …

      The journal article was not funded, as stated in the relevant (and mandatory) section of the article itself, and sprang from curiosity about conflicting data sets. For my publishing record, visit Pubmed. If you are genuinely curious, blend fish oil and high polyphenol olive oil at about 5:1, and try it yourself at a dose sufficient to your 6:3 ratio down below 3. There are self-use tests which measure this. The mix of oils tastes bad, but is surprisingly effective in alleviating the symptoms of chronic inflammation.

      • bob sheridan

        Thank you for your response. I did in fact search PubMed before posting my comment. A single review article on the topic of omega3 was all I could find. Reassuring to hear that you believe your approach to be “surpringly effective”, although I think I prefer to wait for some real evidence. Others less critical of questionable unsubstantiated claims may choose otherwise.

        • flavonoid

          Bob, There is real evidence, and there is real evidence. As a scientist with a pharma background, I look for well-powered RCT’s, and am a firm believer in EBM – even though we know this is an aspiration rather than a reality. As someone with a strong clinical orientation, I am also convinced by the large numbers of very coherent case histories, which also happen to be in line with theoretical aspects i.e. m.o.a. data.

    • Tarek

      A well performed review in invaluable in assessing evidence. Original research is of course the most laudable goal but covers anything from a case report to an RCT which I’m sure you’ll agree all differ greatly in utility and evidence-strength.