Fish Oil is an UltraProcessed Food

Sun Tzu may (or may not) have said, ‘If you wait by the river long enough, the bodies of your enemies will float by.’  A scientific version might read, ‘If you sit in the commons room long enough, the shades of your old ideas will float by.’

This is certainly true of nutrition.

In the 1980’s, beta carotene was the best supplement for smokers because it protected them from lung cancer. I tried to get my pipe-smoking father to take them, but he wouldn’t do it. This was exasperating; I was studying for my PhD at the time and my shiny young mind could see the logic behind the carrot-coloured capsules.

Preclinical work carried out in the 70’s had shown that diets rich in carotenoids were cancer-protective (ie 1). Within a few years, large epidemiological studies found that in people who consumed a diet containing high levels of beta carotene, the risk of lung cancer was markedly reduced (2-3). Short-term trials subsequently suggested that a beta-carotene supplement could reduce DNA damage in the sputum of heavy smokers (4).

The great epidemiologist Sir Richard Peto urged caution (2): ‘It is most unlikely that this inverse cancer risk association will disappear entirely with future observational studies, but the inverse association may be an artifact, due merely to association of β-carotene ingestion with some truly protective dietary habit(s) or component(s) or avoidance of some truly harmful habits or components.’

But nobody wanted to hear this.

Beta carotene as a nutritional amulet for cancer prevention practically sold itself. Keep on smoking, feed your addiction, pop a pill, relax, was the message. Almost all the nutrition companies at the time advertised beta carotene supplements for smokers, although it’s hard to find references now; the records have been thoroughly sanitized. Because in 1994 and then again in 1996, the results of two prospective trials brought it all to a coughing, spluttering halt.

The famous ATBC (6) and CARET (7) studies showed, entirely counter-intuitively, that beta carotene supplements increased the risk of lung cancer in smokers. The later SU.VI. MAX (8) and VITAL (9) trials were not particularly reassuring, and after it was discovered that beta carotene oxidized in the lungs of smokers to form potentially carcinogenic epoxides (ie 10), the jig was up (11).

Today, the World Cancer Research Fund and other authorities strongly advise smokers not to take beta carotene supplements (12).

With the benefit of hindsight, it seems that Sir Richard Peto was right. The same diet that contained higher levels of beta carotene also contained higher levels of many other phytonutrients, some of these – such as the polyphenols and fibers – with stronger chemoprotective data behind them.

Cocooned within this dense nutrient and antioxidant background, beta carotene was manifestly not harmful and may even have contributed to the overall positive effect of a healthy diet. More specifically, there are other compounds in a healthy diet such as vitamin C and the polyphenols which protect or chaperone beta carotene, and keep it in its therapeutically active form (13, 14).

Many of us were too invested in beta carotene at the time, however, and too invested in the philosophy and practice of magic bullets (15, 16), to be able to concede. Ah, we said, the beta carotene used in these trials was synthetic, and contained a different mix of stereoisomers than occur in foods. If only natural carotene had been used, the results would have been different.

How wrong we were. How wrong I was. And now, I’m feeling deja vu all over again.

As beta carotene’s star was fading, fish oil was just starting to fly. Pioneering work had been done by the Danes August and Marie Krogh, who studied metabolism and diet in the Inuit during an expedition to Greenland in 1908 (17). 60 years later another two Danish physiologists, Hans Olaf Bang and Jørn Dyerberg, further researched the traditional Inuit diet of whale and seal meat and blubber and inferred that it was the high levels of omega 3 PUFAs in these foods that provided the known cardioprotective benefits (18, 19). 

A group of trials carried out at the turn of the century suggested that fish oil could protect against coronary artery disease, ventricular arrhythmias and heart attacks (ie 20-23). Around the same time, high fish consumption was found to be positively associated with a range of improved health outcomes (ie 24).

Professor Michael Crawford published his important works on the importance of omega 3 PUFAs for the developing infant brain (ie 25), others followed (ie 26). 3-PUFAs became the new beta carotene. Industry climbed aboard, and by 2023 the global fish oil market, based exclusively on 3-PUFAs, had reached USD 3.08 billion (27).

Lately, however, the fish oil story has been floundering.

Firstly, an extending series of clinical trials of fish oil generated null findings (28) and secondly, a further group of studies has thrown up some potentially very serious adverse effects (ie 29-31). Fish oil supplements may, according to these studies, increase the risk of atrial fibrillation (29), lung cancer (30, 31), and progressive brain damage (32, 33).

These negative findings are all contested (ie 34-35), and it may simply mean that we have to start taking a more nuanced view, ie one that takes into account individual genetic factors (ie 37), but doubts have set in. For example, current National Institute for Health and Care Excellence (NICE) guidelines no longer recommend taking fish oil supplements to prevent heart and circulatory diseases (38).

If fish oil doesn’t reduce the risk of disease, while at the same time possibly increasing the risk of adverse outcomes, it has a null or negative therapeutic index. In that case, fish oil should not be sold in the pharmacies, over the counter or over the internet.

When the clinical data become too confusing, I always go back to mechanism. I was trained as a pharmacologist, after all, so what does the pharmacology say?

There is a huge difference between oily fish and fish oil (39, 40). When you eat a filet of oily fish (or a portion of marine mammal), you are consuming an immensely complex and biologically potent mix of nutrients (ie 41, 42). The omega 3’s are only two compounds among the hundreds present in a mackerel or Minke.

In the production of fish oil standardised to omega 3’s, most of these ancillary compounds are jettisoned. It is an industrial process of up to 11 steps including degumming, neutralisation, bleaching, deodorization … (43). At the end of this process is an ultraprocessed food, stripped of the omega 3’s natural chaperone compounds which would otherwise protect the fragile polyunsaturated fatty acids as they pass through the marine food webs (42, 43), and through you (44-46).

Removing the omega-3’s chaperones, which are probably lipophenols, changes everything.

After you swallow fish oil, a significant amount of the EPA and DHA is oxidised in the circulation and in the liver before it can be integrated into the cell membranes. This is why fish oil seldom achieves the 6:3 ratios and 3-index values needed to exert a significant anti-inflammatory effect (47). This explains why fish oils don’t work (28).

Then, it gets more serious. The oxidation of EPA and DHA in the body has negative effects of its own.

In people who consume whole fish, levels of toxic PUFA oxidation products such as hexenals and nonenals do not appear – but they do in those who take fish oil supplements (44-46). These oxidation products are arrhythmogenic, cytotoxic and mutagenic (44-46). Atrial fibrillation, brain damage, lung cancer … (29-33)?

For me, the brain health story brings it home. The positive effects of whole fish on brain health are quite consistent (ie 48, 49); after all, whole fish provide the omega 3’s required for brain structure and anti-inflammatory tone, where the lipophenols also make a contribution (51-52). Plus all nine essential amino acids (in a highly digestible format), vitamins D and B12, iron, calcium, zinc, iodine, selenium and more.

These benefits stand in contrast to the recently reported negative effects of ultraprocessed fish oil supplements on brain health (32, 33).

Fish oil is increasingly reminiscent, to me, of the other ultraprocessed food that is a beta carotene supplement.

So where does this leave us?

Humans evolved eating whole foods, providing rich networks of combinatorial compounds which are the very opposite of the magic bullets the current medical model is founded on. Our metabolisms are geared to these kinds of dietary intakes, and when we consume such diets we gain relative freedom from non-communicable, degenerative disease (53, 54).

Today’s industrial diet has shifted from nutrient-dense and calorie-light to calorie-dense and nutrient-light. It has also changed from anti-inflammatory to pro-inflammatory, from fibre-rich to fibre-poor and from low glycemic load to excessively high glycemic load. The idea that we can rectify the resulting profound metabolic dysregulation with two overly purified and therefore vulnerable omega-3 PUFAs is absurd on its face, and a hangover of pharmaceutical thinking.

I am no romantic, but there is merit is a return to whole foods. If we wish to add nutrient supplements to our inflammatory, dysbiotic and depleted lives, we should at the very least ensure that these products are formulated in such a way as to reproduce the benefits of the original. And here, we can learn from babes and sucklings.

Consider the way in which infant formula has evolved over the decades. When starting from the premise that infant formula should reproduce as accurately as possible the physiological effects of breast milk (55), Michael Crawford’s pioneering work on 3-PUFAs (25) set the modern standard. But it goes back further than that, and the science is still developing today.

In 1891 Paul Ehrlich (the zauberkugel man) first reported that immunity could be transmitted through breast-feeding (56, 57). Breast milk was eventually found to contain innate immune-primers (58) and microbiome modulators (59), and it was not too long before 1-3, 1-6 beta glucans and prebiotic fibers were added, cautiously, to the better formulas (60, 61).

We should view omega 3’s though the same lens. It is past time to upgrade fish oil, put those vitally important chaperones back into the mix, purge the damaging oxidation products and recapitulate the benefits of oily fish within evidence-based pharmaco-nutritional supplements.

This is not just a puff for the few companies who have already done so, but a plea for the entire fish oil industry to mend their ways, and to help mend our broken public health.

References:

1. Epstein JH. Effects of beta-carotene on ultraviolet induced cancer formation in the hairless mouse skin. Photochem Photobiol. 1977 Feb;25(2):211-3.
2. Peto R, Doll R, Buckley JD, Sporn MB. Can dietary beta-carotene materially reduce human cancer rates? Nature. 1981 Mar 19;290(5803):201-8. 
3. Steinmetz KA, Potter JD. Vegetables, fruit, and cancer. I. Epidemiology. Cancer Causes Control. 1991 Sep;2(5):325-57. 
4. Steinmetz KA, Potter JD. Vegetables, fruit, and cancer. II. Mechanisms. Cancer Causes Control. 1991 Nov;2(6):427-42.
5. van Poppel G, Kok FJ, Hermus RJ. Beta-carotene supplementation in smokers reduces the frequency of micronuclei in sputum. Br J Cancer. 1992 Dec;66(6):1164-8.
6. Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994 Apr 14;330(15):1029-35. 
7. Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, Keogh JP, Meyskens FL, Valanis B, Williams JH, Barnhart S, Hammar S. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996 May 2;334(18):1150-5.
8. Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, Roussel AM, Favier A, Briançon S. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004 Nov 22;164(21):2335-42.
9. Satia JA, Littman A, Slatore CG, Galanko JA, White E. Long-term use of beta-carotene, retinol, lycopene, and lutein supplements and lung cancer risk: results from the VITamins And Lifestyle (VITAL) study. Am J Epidemiol. 2009 Apr 1;169(7):815-28.
10. Palozza P, Serini S, Trombino S, Lauriola L, Ranelletti FO, Calviello G. Dual role of beta-carotene in combination with cigarette smoke aqueous extract on the formation of mutagenic lipid peroxidation products in lung membranes: dependence on pO2. Carcinogenesis. 2006 Dec;27(12):2383-91.
11. Goralczyk R. Beta-carotene and lung cancer in smokers: review of hypotheses and status of research. Nutr Cancer. 2009;61(6):767-74.
12. https://www.wcrf.org/research-policy/evidence-for-our-recommendations/supplements/
13. Gomboeva SB, Gessler NN, Shumaev KB, Khomich TI, Moiseenok AG, Bykhovskii VY. Some natural and synthetic antioxidants as stabilizers of beta-carotene conversion into vitamin A. Biochemistry (Mosc). 1998 Feb;63(2):185-90. 
14. Unten L, Koketsu M, Kim M. Antidiscoloring Activity of Green Tea Polyphenols on β-Carotene. J. Agric. Food Chem. 1997, 45, 6, 2009–2012
15. https://drpaulclayton.eu/blog/the-doctor-is-out/
16. https://drpaulclayton.eu/blog/the-doctor-is-out-pt-2-the-bugs-are-back-in-town/
17. Krogh A, Krogh M. (1913). A study of the diet and metabolism of Eskimos undertaken in 1908 on an expedition to Greenland. Meddelelser om Grønland, 51, 1–52.
18. Dyerberg J, Bang HO. Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet. 1979 Sep 1;2(8140):433-5.
19. Dyerberg J. Coronary heart disease in Greenland Inuit: a paradox. Implications for western diet patterns. Arctic Med Res. 1989 Apr;48(2):47-54.
20. Stone NJ. The Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardio (GISSI)-Prevenzione Trial on fish oil and vitamin E supplementation in myocardial infarction survivors. Curr Cardiol Rep. 2000 Sep;2(5):445-51. 
21. Lemaitre RN, King IB, Mozaffarian D, Kuller LH, Tracy RP, Siscovick DS. n-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study. Am J Clin Nutr. 2003 Feb;77(2):319-25. 
22. Leaf A, Albert CM, Josephson M, Steinhaus D, Kluger J, Kang JX, Cox B, Zhang H, Schoenfeld D; Fatty Acid Antiarrhythmia Trial Investigators. Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake. Circulation. 2005 Nov 1;112(18):2762-8.
23. Jacobson TA. Beyond lipids: the role of omega-3 fatty acids from fish oil in the prevention of coronary heart disease. Curr Atheroscler Rep. 2007 Aug;9(2):145-53. 
24. Mendivil CO. Fish Consumption: A Review of Its Effects on Metabolic and Hormonal Health. Nutr Metab Insights. 2021 Jun 3;14:11786388211022378.
25. Crawford MA, Hassam AG, Williams G. Essential fatty acids and fetal brain growth. Lancet. 1976;1:452–453.
26. Willatts P, Forsyth JS, DiModugno MK, Varma S, Colvin M. Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age. Lancet. 1998 Aug 29;352(9129):688-91. 
27. Grand View Research. Fish Oil Market (2024 – 2030). Viewed 22.5.2026 https://www.grandviewresearch.com/industry-analysis/fish-oil-market
28. https://drpaulclayton.eu/blog/fish-oil-upgrade-to-snake-oil/
29. Gencer B, Djousse L, Al-Ramady OT, Cook NR, Manson JE, Albert CM. Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. Circulation. 2021 Dec 21;144(25):1981-1990. 
30. Zhao H, Wu S, Luo Z, Liu H, Sun J, Jin X. The association between circulating docosahexaenoic acid and lung cancer: A Mendelian randomization study. Clin Nutr. 2022 Nov;41(11):2529-2536. 
31. Takezaki T, Inoue M, Kataoka H, Ikeda S, Yoshida M, Ohashi Y, Tajima K, Tominaga S. Diet and lung cancer risk from a 14-year population-based prospective study in Japan: with special reference to fish consumption. Nutr Cancer. 2003;45(2):160-7.
32. Wei BZ, Li L, Dong CW, Tan CC; Alzheimer’s Disease Neuroimaging Initiative; Xu W. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers. Am J Clin Nutr. 2023 Jun;117(6):1096-1109.
33. Karakaya E, Berber B, Eskiocak O, Edwards J, Barker RB, Jamil S, Li W, Abdul Y, Ericsson M, Stein T, McKee A, Ergul A, Beyaz S, Albayram O. Eicosapentaenoic acid reprograms cerebrovascular metabolism and impairs repair after brain injury, with relevance to chronic traumatic encephalopathy. Cell Rep. 2026 Mar 25:11
34. Manson JE, Bassuk SS, Cook NR, Lee IM, Mora S, Albert CM, Buring JE; VITAL Research Group. Vitamin D, Marine n-3 Fatty Acids, and Primary Prevention of Cardiovascular Disease Current Evidence. Circ Res. 2020 Jan 3;126(1):112-128. 
35. Wang C, Ding Y, Hu Q, Wang B, Xie S, Yang Z, Zhang Z, Dai D, Xiong A, Sun R, Ling Y, Qiu L, Yu F, Xie Z, Peng M. Omega-6/Omega-3 Ratio as a Protective Factor in Lung Cancer: A Mendelian Randomization Study on Polyunsaturated Fatty Acids and Lung Adenocarcinoma Risk. J Cancer. 2025 Jun 12;16(8):2649-2662
36. Dighriri IM, Alsubaie AM, Hakami FM, Hamithi DM, Alshekh MM, Khobrani FA, Dalak FE, Hakami AA, Alsueaadi EH, Alsaawi LS, Alshammari SF, Alqahtani AS, Alawi IA, Aljuaid AA, Tawhari MQ. Effects of Omega-3 Polyunsaturated Fatty Acids on Brain Functions: A Systematic Review. Cureus. 2022 Oct 9;14(10):e30091.
37. Zuo X, Kiyasu Y, Liu Y, Deguchi Y, Liu F, Moussalli M, Tan L, Wei B, Wei D, Yang P, Shureiqi I. Colorectal 15-Lipoxygenase-1 as a Host Factor Determining the Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Colorectal Tumorigenesis in Mice. Cell Mol Gastroenterol Hepatol. 2025;19(12):101607.
38. Cardiovascular disease: risk assessment and reduction, including lipid modification. London: National Institute for Health and Care Excellence (NICE); 2023 Dec 14. PMID: 38564551. 
39. Clayton PR, Ladi S. From alga to omega; have we reached peak (fish) oil? J R Soc Med. 2015 Sep;108(9):351-7.
40. https://drpaulclayton.eu/blog/thanks-for-all-the-fish/
41. Mendivil CO. Fish Consumption: A Review of Its Effects on Metabolic and Hormonal Health. Nutr Metab Insights. 2021 Jun 3;14:11786388211022378.
42. Noreen S, Hashmi B, Aja PM, Atoki AV. Health benefits of fish and fish by-products-a nutritional and functional perspective. Front Nutr. 2025 May 9;12:1564315.
43. FAO Technical Guide on Fish Meal and Oil. . https://openknowledge.fao.org/server/api/core/bitstreams/0695bbe2-aa69-4a8e-837f-9297d543f626/content/X6899E04.htm
44. https://drpaulclayton.eu/uncategorised/ice-fishing/
45. https://drpaulclayton.eu/blog/watch-your-six/
46. https://drpaulclayton.eu/blog/autoimmunity/
47. Zinzino in-house data, in pre-publication.
48. Kokubun K, Nemoto K, Yamakawa Y. Fish Intake May Affect Brain Structure and Improve Cognitive Ability in Healthy People. Front Aging Neurosci. 2020 Mar 20;12:76.).
49. Satizabal CL, Himali JJ, Beiser AS, Ramachandran V, Melo van Lent D, Himali D, Aparicio HJ, Maillard P, DeCarli CS, Harris WS, Seshadri S. Association of Red Blood Cell Omega-3 Fatty Acids With MRI Markers and Cognitive Function in Midlife: The Framingham Heart Study. Neurology. 2022 Dec 5;99(23):e2572-e2582.
50. Al Rihani SB, Darakjian LI, Kaddoumi A. Oleocanthal-Rich Extra-Virgin Olive Oil Restores the Blood-Brain Barrier Function through NLRP3 Inflammasome Inhibition Simultaneously with Autophagy Induction in TgSwDI Mice. ACS Chem Neurosci. 2019 Aug 21;10(8):3543-3554.
51. Moine E, Boukhallat M, Cia D, Jacquemot N, Guillou L, Durand T, Vercauteren J, Brabet P, Crauste C. New lipophenols prevent carbonyl and oxidative stresses involved in macular degeneration. Free Radic Biol Med. 2021 Jan;162:367-382.
52. Crauste C, Rosell M, Durand T, Vercauteren J. Omega-3 polyunsaturated lipophenols, how and why? Biochimie. 2016 Jan;120:62-74. 
53. https://drpaulclayton.eu/blog/the-drugs-dont-work/
54. Clayton P, Rowbotham J. How the mid-Victorians worked, ate and died. Int J Environ Res Public Health. 2009 Mar;6(3):1235-53.
55. Martin CR, Ling PR, Blackburn GL. Review of Infant Feeding: Key Features of Breast Milk and Infant Formula. Nutrients. 2016 May 11;8(5):279. 
56. Ehrlich P. Experimentelle Untersuchangen über Immunität. I. ueber ricin. Dtsch Med Wochenschr. 1891;32:1.
57. Ehrlich P. Experimentelle Untersuchangen über Immunität. II. Üeber abrin. Dtsch Med Wochenschr. 1891;44:1.
58. Goldman AS, Smith CW. Host resistance factors in human milk. J Pediatr. 1973 Jun;82(6):1082-90. 
59. Boudry G, Charton E, Le Huerou-Luron I, Ferret-Bernard S, Le Gall S, Even S, Blat S. The Relationship Between Breast Milk Components and the Infant Gut Microbiota. Front Nutr. 2021 Mar 22;8:629740.
60. Li F, Jin X, Liu B, Zhuang W, Scalabrin D. Follow-up formula consumption in 3- to 4-year-olds and respiratory infections: an RCT. Pediatrics. 2014 Jun;133(6):e1533-40.
61. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 1995; 125:1401-12