There has been a flood of media reports recently that cast doubt over the benefits of fish oil for a range of health conditions, as well as for general wellbeing. As nutrition scientists here at Igennus we unpick each of these studies to understand the science, strengths and weaknesses and often spot misinterpretations, not usually in the studies themselves, but typically in terms of how they are reported by the media. When, however, a highly influential clinician and thought leader, such as Chris Kresser, announces a 180 degree shift in his attitude towards ‘fish oil’ (see article), we feel it is time to clarify how omega-3 studies should be interpreted and understood. For the record we have, from day one, advocated identifying EPA and DHA as distinct and independent actives – with the latest backlash against omega-3 in depression being the perfect example; it is pure or predominantly EPA interventions at doses of 1000mg that have been reported in studies  and meta-analyses [2,3,4] that have been shown to be highly effective in depression, not omega-3 (as EPA plus DHA). Sadly, the media has reported a recent depression analysis and declared that fish oil is ineffective in depression and neglected to report on any pure EPA studies that do offer strong benefits.
Limitations of meta-analyses
Whilst meta-analyses are considered the ‘gold standard’ when it comes to evaluating a given area of research, they are still vulnerable to several methodological flaws. We must remember that a meta-analysis examines the merits of existing research and thus the validity of and ability to generalise about findings are dependent on a number of factors relating to the strengths of the studies they evaluate, including:
- The appropriate classification of a nutrient (for example, most fish oil studies examine the benefits of ‘omega-3’ but we deem this an inappropriate and insufficient classification of two biologically distinct fatty acids, EPA and DHA , liable to ‘flattening’ the effects of each nutrient)
- Variations in dosage of the specific nutrient
- Variations in baseline blood plasma levels of EPA and DHA in study participants, affecting degree of response [6,7]
- Wide variation in study duration (typically anything less than 3 months is insufficient to produce meaningful changes to cellular fatty acid composition)
Choose your opinion leaders carefully! What is an ‘expert’?
In order to make informed decisions about the best nutritional medicine practices it is all too easy to pick our ‘guru’ and follow their counsel to the letter. Well, why wouldn’t you? I am guilty of it myself; Chris Kresser is someone with a wealth of clinical experience and a vast archive of technical, referenced nutrition science articles; he always cites research papers and critically reviews the evidence-based protocols to provide the key take home messages for a wide range of followers. BUT even the best ‘guru’ is often, at some point, misinformed about specialist areas, or at least not quite as up-to-date as they might believe, since it is quite impossible to be an expert in ALL things health and nutrition. At Igennus, we identify as omega-3 specialists; more specifically, we are EPA and inflammation specialists – we’ve been researching EPA and its application for 11 years almost exclusively. So we are by no means experts in all other areas of nutrition science, although we’re more than qualified to report on such science and our nutritionists are trained scientists who read much more widely during working hours and privately for their own interest. But we’re quite modest about what we claim to be ‘expert’ in. Not everyone is quite so modest, however; many companies, clinicians and researchers identify as and claim to be expert in a wider range of areas than we deem is even possible – but that may depend on your standards for ‘expert’.
Consider for a minute that your average academic ‘expert’ dedicates every waking hour of their professional lives to one relatively small and often quite niche area of research. You would not dream of asking Professor Philip Calder– one of the most highly cited and world renowned omega-3 research experts  – to give his informed opinion on the best approach to treating Lyme disease, for example – he may have some knowledge of the topic, but it would be more appropriate to seek his opinion on all things ‘omega-3’. So why, then, do we rely on ‘gurus’ for the final word on the latest nutrition study, when they often happen to be clinicians, not research scientists, and whose very professional existence requires them to have knowledge and experience of a very broad range of clinical health interventions. Certainly, their basic manifestos and recommendations, and even their more tailored ‘tried and tested’, ‘developed-over-years-of-clinical-practice’, ‘personalised’ protocols can make sense and work for the majority of the ill health afflicted western world, but why is it that when it comes to more cutting-edge, complex and controversial areas, people take their word as gospel? Objectively speaking, we can see that a clinician is seemingly much more independent and less prone to bias; we aren’t sure, however, that qualifies them as ‘expert’ on nutrition science research – they could not possibly have invested anywhere near the same amount of time into nutrition research as a researcher or indeed even a scientist working for a company such as Igennus, where we dedicate every working hour to reading, reporting and educating on omega-3 science.
Working not only for one of the leading clinical fatty acid manufacturers with over 12 years’ experience in health research but also privately for 5 years as a clinical nutrition practitioner, I have a real passion to educate on informed, critically reviewed and honest science, hence my zeal to clarify and correct the so-called evidence behind the recent headlines. In the following sections I explain what you really need to know about ‘fish oil’, what this even means when media headlines report on ‘fish oil studies’, the best type of fish oil, whether we should all be consuming EPA and/or DHA, the omega-6:3 ratio and how to determine if fish oil is useful and safe.
Who should take fish oil?
Even as the body of research into fish oil, omega-3 and EPA & DHA grows, there are still no firm conclusions being made about who should take fish oil. Much of the recent negative press (coming mostly out of the US) has focused on the fact that, despite widespread understanding, recent meta-analyses do not in fact show consistent benefits for a range of conditions previously thought to benefit considerably from fish oil intake – in particular, heart and brain health. What these reporters and researchers are not telling us (because even they are not aware of it) is that there are many reasons why omega-3s do not work for everyone, in every condition, all the time. As we are only just discovering what these factors are, it means that most of the existing research, and most of the papers included in current meta-analyses, have not taken these factors into account, meaning many of the potentially positive effects of EPA and DHA are essentially being cancelled out.
The key factors that determine whether or not ‘omega-3’ offers health benefits include:
• The dose given
• The length of time fish oil is taken for
• The ratio of omega-3 fats EPA and DHA in the oil given
• The concentration of the oil given (higher % concentration is absorbed better than lower % concentration!)
• The dose of the individual fats given
• Whether the population in question is actually at risk for the condition being targeted
And, perhaps most importantly:
• Whether or not the participants chosen for the study actually need omega-3 in the first place.
In order to understand why these factors impact study outcomes, we need to take a step back and understand a little more about fish oils themselves.
What is fish oil? It’s about time we distinguish EPA and DHA!
Too often, the terms fish oil, omega-3, EPA and DHA seem to be used interchangeably and this error alone affects the conclusion as to who will benefit. Fish oil is really the raw oil that is extracted from the liver or body of the fish. Fish oil contains all of the omega fats, together with the vitamins, minerals and other non-omega fats such as saturates found in whole fish. These fish oils contain only about 30% omega-3 per total volume of oil, meaning you have to take a high number of capsules to get a decent omega-3 dose from fish oil. The current UK recommended omega-3 intake is 450mg, so if you wanted to get this with standard fish oil you would need to take 2 capsules of 1000 mg fish oil capsules daily.
Omega-3 fish oil, often just called omega-3, is still technically ‘fish oil’, but it has been concentrated slightly to remove a large portion of the non-omega-3 fats so that more of what you are swallowing are the desired EPA and DHA fatty acids. Most of these oils contain between 50-60% EPA + DHA plus some ALA and other omegas – these oils are a step closer to making sure you get a decent dose of omega-3 per capsule. Most will provide 500-600mg EPA and or DHA per 1000mg of fish oil.
Finally, there are EPA and DHA isolates, which are highly concentrated from the original fish oil; these are the oils we use at Igennus. These isolates ensure you get as much EPA and DHA per gram of oil as possible to maximise the amount that is absorbed and taken up into cells. Most concentrated omega-3 oils contain actives upwards of 70%, meaning there is significantly less of ‘other fats’ present in the oil. These oils provide between 700-900mg of EPA and DHA per 1000 mg of fish oil, making it possible to achieve higher, more therapeutically effective doses for high intensity support. These oils also tend to have different EPA to DHA ratios compared with ‘standard’ fish oil, in order to maximise the specific benefits of either of these two fats in specific areas of health.
Why is the ratio of EPA to DHA important?
It is extremely important to understand and take account of the difference between various types of oils and between EPA and DHA, because the best type, ratio and dose for a given individual will differ, depending on factors such as age, body weight, diet and lifestyle, as well as what specific health benefits they are seeking from ‘fish oil’.
If you are happy, healthy, young, active, eat an optimal diet containing 2-3 oily fish portions per week and do not currently have any symptoms of poor health but are interested in taking fish oil for ‘insurance purposes’, then a good old standard fish oil might just be adequate. This will ensure you get some additional omega-3 EPA and DHA in your diet, plus all the other lovely fats that fish can provide without removing anything that can keep you in ‘balance’.
If you don’t consume 3 portions of oily fish or have a few mild niggles and ailments, or you are starting to feel a bit stiff, achey and concerned about any areas of your health, then you likely need a more intense level of support and so choosing a more concentrated omega-3 oil would be more appropriate.
If you have a specific health condition, eat no fish or have a highly stressful life, poor diet and rarely move then you are going to need high intensity, targeted support and will need a high dose, high concentration, specialist EPA to DHA ratio containing omega-3 fish oil isolate.
If you are pregnant, have an irregular heart beat or have existing brain injury, including cognitive decline or Alzheimer’s, you need to consume higher levels of DHA than most people – at least 250mg of DHA daily.
If you exercise lots or lead a very stressful lifestyle, have a mental health condition (e.g. depression, bipolar disorder, schizophrenia ), high blood pressure, high risk of cardiovascular illness, an inflammatory-based condition or are recovering from cancer, then you need to make sure all or most of your high dose omega-3 is made up of EPA.
Also depending on your current omega-3 levels and your ratio of omega-6 to 3, and specifically AA to EPA ratio (an accurate measure of inflammation), then the type of omega-3s and the dose you need will also be different.
[9, 10, 11, 12, 13…there are many, many more]
Is the omega-6 to 3 ratio still a useful thing to measure?
Having a healthy omega-6 to 3 ratio is something that has been drummed into us for the last decade and whilst it is still a useful indicator of overall general health and disease risk, we know a lot more than we did 10 years ago about the unique effect EACH omega-6 and 3 fatty acid has on our health.
Today we know the key omega-3s that benefit our health are EPA and DHA – these are the long-chain fats found in fish.
We also know that having a little of the shorter chain plant-derived omega-3s such as ALA and SDA is also good for our health and so consuming some of these from nuts and seeds is advisable.
In terms of omega-6, we know that high LA and AA levels are possible whilst having very little GLA. A high AA level is known to increase the amount of inflammation within the body, but this only becomes problematic when our total omega-3, and specifically EPA, levels are low. EPA directly competes with AA’s pro-inflammatory actions and so helps reduce the risk of chronic illness and disease associated with unresolved and unnecessary inflammation. If we have a healthy EPA level, then having a good level of GLA (a health promoting anti-inflammatory omega-6) is a really good thing.
It is now widely recognised that just looking at total omega-6 to 3 levels is not as useful as once thought, as it does not tell us the types of omega-3s and 6s that make up this number. It is possible to have a higher than ‘ideal’ omega-6 to 3 ratio but a low AA to EPA ratio, which would not be a major cause for concern. Understanding the total EPA + DHA in our cells (known as the omega-3 index ), together with our AA to EPA ratio, the amount of GLA, the omega-6 to 3 ratio and the other fats that make up our cells gives us a much more comprehensive overview of cell and total body health.
Understanding omega-3 biomarkers: how does this affect how we interpret research outcomes?
I’ve explained above how different people benefit from different types of fish oil at different times of life, according to their unique needs. The trouble with much research is that not only do most studies not take this into consideration when they are being designed, meaning the fish oil given might not be the ‘best’ for the study group and desired outcome, but when we conduct meta-analyses of the existing ‘evidence’, this further dilutes any variations seen between the different studies included, therefore cancelling out any potential result.
As things currently stand, each ‘omega-3’ or ‘fish oil’ trial conducted has used a different dose, with a different EPA and DHA content, at a different concentration in very different groups of people. This is what is known as a lack of heterogeneity and is a big problem in nutrition research as it makes it very difficult to compare results, since the studies are not ‘like for like’ .
If each study is using a very different omega-3 formula (dose, ratios & concentration) and testing outcomes very differently on a group of people who do not share the same diet, lifestyle and disease risk, then how can we possibly conclude that fish oil or omega-3 are not beneficial?
Many of the studies being published at the moment started 2-5 years ago and so, by default, were designed before the knowledge we possess today and the growing interest in personalised nutrition. As a result, many studies have not taken into consideration the key factors that affect the outcomes.
• The dose given – we now know that for most conditions, high doses of 1-3g EPA or EPA/DHA are needed to see benefits, so many of the recent studies don’t deliver nearly enough. In addition, depending on a person’s current omega-3 levels and their weight, the dose they will need to see benefits will differ significantly. This, to date, has never been planned into study design and probably never will be, as logistically it is just too complex .
• The length of time omega-3 is taken for – it is now widely recognised that the minimum time you need to take omega-3 is 3 months. This is just to get EPA and DHA into your cells where they are needed to take effect. You then need to maintain omega-3 levels in the cell in order to see prolonged and noticeable changes to health markers. Depending on the severity of the health concern and the amount of omega-3 needed to reset cell levels, this can take upwards of 6 months for real benefits to become apparent. Lots of studies often dose for between 1-6 months (for cost and compliance reasons) and so the participants never reach the point where cell omega-3 levels have reached ‘active’.
• The ratio of omega-3 EPA and DHA in the oil given – depending on the condition being treated, the exact type of omega-3 is important, so if researchers are giving 1g omega-3 for a condition with an inflammatory basis (such as depression), of which 600mg is DHA and 400mg is EPA, this will most likely be negative . Similarly, we know now that DHA can raise LDL cholesterol while EPA helps to reduce it, so giving a high DHA oil to people with already high LDL cholesterol will only make it higher and lead to conclusions that fish oil is ‘bad’ for cholesterol . Had high doses of EPA been given, LDL cholesterol would have reduced and fish oil would be seen as ‘good’. If researchers do not consider the type of fat most relevant to the condition they are trying to target, then it is no surprise many studies and meta-analyses produce neutral or negative results.
• The concentration of the oil given – again this is rarely considered, as more focus is given on the dose provided by the oil, but studies do show that the more ‘other fats’ you take with your ‘active’ fats, the more you are diluting the potential for these important fats to be absorbed and utilised by the body. This is because fat absorption and uptake mechanisms are shared between all omega fats – in other words, the unwanted other fats get in the way and essentially block the active fats from being absorbed. This is why, for therapeutic reasons, taking a high concentration oil often results in better outcomes and greater cellular enrichment of omega-3 .
• The dose of the individual fats given – with the above in mind, it makes sense that if different fats result in different benefits, you need to take an ‘optimal’ dose of the fat that is going to directly target the biological mechanisms underpinning the health issue being addressed. Once you have identified which fat is best, you then need to give a high enough dose of that fat to elicit the benefits associated.
• Whether the population in question is actually at risk for the condition being prevented – saying this may seem silly but, believe it or not, some of the recent studies have looked at the benefit of taking omega-3 for conditions such as brain or heart diseases but used a population that were not actually at high risk for developing those conditions. Nutrition is not a magic bullet and if we do not need the nutrient, or are not likely to develop the condition being investigated, it is not surprising the results of these studies are often neutral.
• Whether or not the study participants actually need omega-3 in the first place. This ties in with dose but is, frustratingly, one of the major factors contributing to negative research outcomes. Just because a nutrient may be beneficial for a health condition does not mean giving it to everyone with that condition will result in benefits. This is because not everyone’s manifestation of this condition is likely to be as a result of low levels of the nutrient being tested. If someone has healthy omega-3 levels, giving them more is unlikely to offer benefits for a given health concern. In rare cases we have seen omega-3 levels that are too high – although this is quite unlikely unless you are eating a paleo type diet and consuming copious amounts of fish whilst taking omega-3 capsules too; remember, it is possible to have too much of a good thing!
Whilst this may be a lot to take in, I hope the above gives you a much clearer picture of what the research is really telling us and that just because a meta-analysis shows that something does not work in a given area, it does not ‘prove’ something does not work, nor that there are no benefits to be had from supplementing with omega-3s EPA and DHA (our Opti-O-3 fatty acid blood spot test has shown that even those with excellent diets, consuming oily fish, plenty of vegetables and grass-fed meats and low amounts of vegetable oils and grains can have suboptimal cellular omega-3 levels!).
So which omega-3s and how much do you need?
The best way to understand if you need omega-3 fatty acids and which type (EPA/DHA or both) would be best for you is to get a full fatty acid profile test carried out. The best ones currently available are offered by us at Igennus Healthcare Nutrition (the Opti-O-3 blood spot fatty acid profile) in the UK and OmegaQuant in the US. Both of these tests measure not only your omega-6 to 3 ratio, which can be a useful overall indicator of long-term health, but also your omega-3 index (the % of EPA and DHA in your cells out of total fat – a very useful marker of your omega-3 health and cell structure) together with your AA to EPA ratio, which tells you your body’s ability to cope with inflammation – a factor known to play a major role in the onset and progression of many modern health conditions.
Armed with your omega-3 index level, together your body weight, it is then possible to calculate exactly how much omega-3 EPA and DHA you need to raise your cell levels to what is considered ‘health positive’. Our test does this for you and we also look at the EPA to DHA ratio in your cells, as well as your GLA levels, and help you to understand which fats you need most.
This really is currently the only way to truly determine if and how much omega-3 you need. It is really easy to provide a sample with a simple pin prick blood spot test that can be carried out at home.
If you can’t test for any reason, then you might want to head over to our health section to find out what we recommend for your specific concerns. Alternatively give us a call!
Choose your influencers for their specialist expertise!
By now, I hope you can clearly see that someone who does not spend every moment of every day buried in omega-3 nutrition research is less likely to come across the most cutting-edge and up to date studies. Whilst media gurus and clinical experts offer a lot to the world of evidence-based medicine, it is always important to have a few knowledgeable, impartial research resources and experts to follow, to help you get the full picture and make informed choices about your health. It is yours, after all, and you want to guard it with the best knowledge available.
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2. Sublette ME1, Ellis SP, Geant AL, Mann JJ.Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry. 2011 Dec;72(12):1577-84. doi: 10.4088/JCP.10m06634. Epub 2011 Sep 6.
3. Grosso G1, Pajak A2, Marventano S3, Castellano S1, Galvano F1, Bucolo C1, Drago F1, Caraci F4. Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS One. 2014 May 7;9(5):e96905. doi: 10.1371/journal.pone.0096905. eCollection 2014.
4. Martins JG: EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. Journal of the American College of Nutrition 2009, 28:525-542.
5. Russell FD, Burgin-Maunder CS: Distinguishing health benefits of eicosapentaenoic and docosahexaenoic acids. Marine drugs 2012, 10:2535-2559.
6. Harris WS, Varvel SA, Pottala JV, Warnick GR, McConnell JP: Comparative effects of an acute dose of fish oil on omega-3 fatty acid levels in red blood cells versus plasma: implications for clinical utility. Journal of clinical lipidology 2013, 7:433-440.
7. Kohler A, Bittner D, Low A, von Schacky C: Effects of a convenience drink fortified with n-3 fatty acids on the n-3 index. The British journal of nutrition 2010, 104:729-736.
9. Verlengia R, Gorjao R, Kanunfre CC, Bordin S, de Lima TM, Martins EF, Newsholme P, Curi R: Effects of EPA and DHA on proliferation, cytokine production, and gene expression in Raji cells. Lipids 2004, 39:857-864.
10. Anderson BM1, Ma DW. Are all n-3 polyunsaturated fatty acids created equal? Lipids Health Dis. 2009 Aug 10;8:33. doi: 10.1186/1476-511X-8-33.
11. Gorjão R1, Azevedo-Martins AK, Rodrigues HG, Abdulkader F, Arcisio-Miranda M, Procopio J, Curi R. Comparative effects of DHA and EPA on cell function. Pharmacol Ther. 2009 Apr;122(1):56-64. doi: 10.1016/j.pharmthera.2009.01.004. Epub 2009 Feb 12.
12. Sierra S1, Lara-Villoslada F, Comalada M, Olivares M, Xaus J. Dietary eicosapentaenoic acid and docosahexaenoic acid equally incorporate as decosahexaenoic acid but differ in inflammatory effects. Nutrition. 2008 Mar;24(3):245-54. doi: 10.1016/j.nut.2007.11.005.
13. Russell FD1, Bürgin-Maunder CS. Distinguishing health benefits of eicosapentaenoic and docosahexaenoic acids. Mar Drugs. 2012 Nov 13;10(11):2535-59. doi: 10.3390/md10112535.
14. Harris WS1. The omega-3 index: clinical utility for therapeutic intervention. Curr Cardiol Rep. 2010 Nov;12(6):503-8. doi: 10.1007/s11886-010-0141-6.
15. Harris WS: Pushing the limits with omega-3 fatty acids. Trends in cardiovascular medicine 2015.
16. Laidlaw M, Cockerline CA, Rowe WJ. A randomized clinical trial to determine the efficacy of manufacturers’ recommended doses of omega-3 fatty acids from different sources in facilitating cardiovascular disease risk reduction. Lipids in Health and Disease. 2014;13:99. doi:10.1186/1476-511X-13-99.
17. C. Torrejon, U.J. Jung, and R.J. Deckelbaum. N-3 Fatty Acids and Cardiovascular Disease: Actions and Molecular Mechanisms. Prostaglandins Leukot Essent Fatty Acids. 2007 ; 77(5-6): 319–326.
18. Bryhn M1, Hansteen H, Schanche T, Aakre SE. The bioavailability and pharmacodynamics of different concentrations of omega-3 acid ethyl esters. Prostaglandins Leukot Essent Fatty Acids. 2006 Jul;75(1):19-24. Epub 2006 Jun 27.