In 2018, why would anyone take fish oil?

The global market for this stuff is reckoned to be closing in on $13 billion per year (1), and in some parts of the world fish oil is almost a religion. Scandawegians, for example, drink Møllers Tran from birth to the grave, and regard it as a sacrament. But why do they do that? Not only are Møllers Tran and the other fish oils utterly disgusting, they are also utterly ineffective. 

Fish oil has a talismanic value, perhaps, and may bind your anxieties (it has some effect in alleviating depressive states), but that is all. If you are taking fish oil to ward off heart attacks, dementia or strokes, you are no better than the medieval man (or woman) who carried around a splinter of the true cross, or a bone fragment from some saint or other, to fend off evil spirits.

What does evil consist of today? Take a look at the supplement business. Unscrupulous companies are pouring rivers of inoffensive fish through giant mangles, squeezing out the oil and flogging this junk to unwary customers, even though they (the companies) know that their products are useless. In the process they hoover up 20 – 25 million tonnes of oily fish every year, chipping away at marine ecosystems, contributing to global fish stock depletion, and passing off their shoddy products as health-protective.

The Cochrane Collaboration recently released a meta-analysis to determine whether or not omega-3 supplements reduced the risk of coronary heart disease. After comparing 79 trials involving 112,059 people, the researchers could find ‘little or no difference to risk of cardiovascular events, coronary heart deaths, coronary heart disease events, stroke or heart irregularities’. (2)

Even more recently, the VITAL study – a huge prospective randomized and placebo-controlled clinical trial – found that in a population of 26,000 adults, given 1 gram of fish oil /day for 5 years, there was no reduction of heart disease or cancer (3).

Eating oily fish, however, is consistently associated with better health outcomes. An analysis of 20 studies involving hundreds of thousands of participants found that eating approximately one to two 3-ounce servings of fatty fish a week—salmon, herring, mackerel, anchovies, or sardines—reduces the risk of dying from heart disease by 36 percent (4)

What is wrong with this picture?

Well, the VITAL study has some serious problems. The docs measured the omega 3 index in plasma but did not, bizarrely, measure the omega 3 index in cell membranes, or cell membrane 6:3 ratios, both of which are more accurate guides to whether you are getting the fatty acids to the sites where they actually work.

We do not know, therefore, what impact –if any – the fish oil had on cell membrane composition, the proximal phase of the inflammazone, and peri-cellular inflammation. But that does not matter because they got the dose wrong, so wrong that they could not have generated therapeutic 6:3 ratios in the cell membranes even if they had wanted to!

Assuming that the average body weight of the trial subjects was around 80 kg (5), it would have taken 8.5 g of standard 32% fish oil to bring the cell membrane 6:3 ratio below 5 (6), a ratio recommended, for example, by the Nordic Council of Health ministers (7). But the docs who designed the VITAL trial used a dose of 1 gram / day of 84% fish oil just because it was the dose recommended by the American Heart Association for cardio-protection (8), demonstrated to be beneficial and to have minimal side effects in a secondary prevention population (9). That is a mere 30% of the pharmacologically appropriate dose!!

These seem to me to be very grave issues, but they are not the major problem. The real flaw in this paper, in my view, was that the intervention was wrongly conceived and incorrectly formulated..

The intervention, the drug (!) Omacor, was pure omega 3 fish oil stabilised with 4mg of d-alpha tocopherol. 

Vitamin E is almost certainly the wrong antioxidant for long chain omega 3’s. It is pretty hopeless at preventing them from oxidative stress (10), and under certain circumstances it becomes a pro-oxidant. This is probably why vitamin E is NOT the antioxidant chosen by nature to protect omega 3 HUFA’s. Nature’s choice is phlorotannin, a lipid-soluble polyphenol that protects the omega 3’s produced by marine algae so well that it used to preserve fish (11). Phlorotannin sticks rigorously to the omega 3’s, acting as a chaperone so effectively that it travels with them from the marine algae through the krill, pelagic fish, larger fish, marine mammals and carries them safely all the way to the apex predator (ie us) when we eat whale, or fish. 

The lipid-soluble polyphenol acts as a chaperone in the body too. If you take Balance oil, the lipid-soluble olive polyphenols carry the omega 3’s we swallow safely through the gut, the portal circulation, the liver and the bloodstream before depositing them into the membranes of the cells in our peripheral tissues.

When the polyphenol gets into our peripheral tissues it dons a second hat, and becomes a powerful anti-inflammatory agent with actions that complement those of the omega 3’s (ie 12, 13, 14). 

To go back to the massive VITAL trial, this raises yet another red flag. If you look at the trial design you will see that they used for their placebo – olive oil! As olive oil contains the anti-inflammatory polyphenols, this may not have been a true placebo at all; and if the olive oil did have any protective effects, however slight, these would have minimized or even cancelled out any protective effects that the tiny dose of fish oil might have otherwise had. I believe the trial designers would have had a better chance of a positive result if they had given their victims the fish oil capsule AND the olive oil capsule together. 

The Omacor would have made a fine placebo.

Fish oil does not work well, because the fish oil industry strips the polyphenols out of the fish oil and leaves it naked, shivering and vulnerable.

Balance oil adds the polyphenols back in and that is why it does work, and extremely effectively, as so many of us have witnessed in friends, families and ourselves.

Are these clinicians deliberately trying to hold back the pharmaconutritional tide with their ridiculous trial designs – or is it just me?

There is one more piece of evidence that I cannot leave out, and that is the REDUCE-IT trial. This recently gained a good deal of publicity when the authors declared a significant reduction in heart attacks in patients who received Vascepa, a pharmaceutical product which contains a fraction of fish oil called Icosapent Ethyl, or EPA, without the DHA (15).

In this trial, Vascepa reduced the incidence of Major Adverse Cardiovascular Events (MACE), from 22% in the placebo group down to 17.2% in the Vascepa group. This has been described as a breakthrough, but I am unimpressed. I am not surprised that the trial showed some positive effects because at least in this instance the dose of omega 3’s was in the right ballpark, and EPA does have anti-inflammatory effects; but the fact that almost 1 in 5 of the patients in the treatment group still experienced a major cardiovascular event indicates that this is not an optimal intervention. The mid-Victorians had MACE at levels of only 10% of ours (16), and this suggests that if you use the right combination of nutrients, you can get twice as much protection as Vascepa seems to offer.

I want to do better than 17.2%. And from what I have seen, I am quite certain that we can achieve more IF we combine the right dose of the omega 3 HUFA’s, both EPA and DHA, with the right polyphenols.

The REDUCE-IT trial was funded by Amarin Pharma, the company that sells Vascepa. Vascepa is a form of fish oil that has a pharmaceutical license, which makes it easier for clinicians to use it in a study than natural fish oil. They argue that EPA is better than natural fish oil because it has ‘better’ effects on the cholesterol profile, ie it does not raise LDL cholesterol levels. However, given that cholesterol levels are not particularly good risk markers, and the role of polyphenols in alleviating endothelial dysfunction, I do not believe that it is the best tool for the job. And I think Balance is.

If I had cardiovascular risk factors, I would stake my life on it.

P.S. 

References:

1. https://www.marketsandmarkets.com/Market-Reports/fishmeal-and-fish-oil-market-52416251.html?gclid=CjwKCAiAz7TfBRAKEiwAz8fKOA6e215cz8Pds-1ZepoT7ppR5RqQqApg7Pu8cxPTYyl08yu6F1KSgRoC0AQQAvD_BwE
2. Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KHO, AlAbdulghafoor FK, Summerbell CD, Worthington HV, Song F, Hooper L. Omega 3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2018, Issue 7. Art. No.: CD003177.
3. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Albert CM, Gordon D, Copeland T, D’Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE; VITAL Research Group.   Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. 2018, November 10, 2018
   DOI: 10.1056/NEJMoa1811403
4. Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA. 2006; 296:1885-99.
5. https://news.gallup.com/poll/102919/average-american-weighs-pounds-more-than-ideal.aspx
6. Marangoni F, Colombo C, Galli C. A method for the direct evaluation of the fatty acid status in a drop of blood from a fingertip in humans: applicability to nutritional and epidemiological studies. Anal Biochem. 2004 Mar 15;326(2):267-72.
7. Nordic Council of Ministers. Nutritional Recommendations ‘05 
8. Kris-Etherton PM, Harris WS, Appel LJ; American Heart Association. Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002 Nov 19;106(21):2747-57. 
9. GISSI-Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico). Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the GISSI-Prevenzione trial. Lancet. 1999;354:447-455
10. Oil stability index, AOCS Official Method Cd12b-92, Average of 3 analysis at 70 C SINTEF – Fisheries & Aquaculture – 2010
11. Wang T 2009. Industry Research Thesis, Open University, Iceland.  ISBN 978-9979-9928-3-7

http://skemman.is/stream/get/1946/4139/11867/1/Final_fixed.pdf

12. Rosillo MÁ, Alarcón-de-la-Lastra C, Castejón ML, Montoya T, Cejudo-Guillén M, Sánchez-Hidalgo M. Polyphenolic extract from extra virgin olive oil inhibits the inflammatory response in IL-1β-activated synovial fibroblasts. Br J Nutr. 2018 Oct 26:1-8.
13. Aparicio-Soto M, Sánchez-Hidalgo M, Cárdeno A, Rosillo MÁ, Sánchez-Fidalgo S, Utrilla J, Martín-Lacave I, Alarcón-de-la-Lastra C. Dietary extra virgin olive oil attenuates kidney injury in pristane-induced SLE model via activation of HO-1/Nrf-2 antioxidant pathway and suppression of JAK/STAT, NF-κB and MAPK activation. J Nutr Biochem. 2016 Jan;27:278-88.
14. Scoditti E, Nestola A, Massaro M, Calabriso N, Storelli C, De Caterina R, Carluccio MA. Hydroxytyrosol suppresses MMP-9 and COX-2 activity and expression in activated human monocytes via PKCα and PKCβ1 inhibition. Atherosclerosis. 2014 Jan;232(1):17-24.
15. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2018 Nov 10. doi: 10.1056/NEJMoa1812792.
16. Clayton P, Rowbotham J. How the mid-Victorians worked, ate and died. Int J Environ Res Public Health. 2009 Mar;6(3):1235-53.