Earlier this month, Blackmores Institute published an article entitled 'Cochrane Review Debunked as Fake Science', which looked at the latest Cochrane review on Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.
This headline and the claims that follow it (included in full below) are both inaccurate and highly misleading. Cochrane reviews are recognised internationally as representing the gold standard for high quality, trusted evidence. The Omega 3 review is one of a series of reviews Cochrane is conducting at the request of the World Health Organisation.
The scientific standards and methodological rigour required to publish a Cochrane review represent the antithesis of ‘fake science’, yet this headline immediately conveys the opposite notion. This is both unreasonable and potentially damaging - particularly in the current climate of anti-science sentiment and the dismissal of inconvenient facts as ‘fake news’.
Dr Lee Hooper, lead author of the Omega 3 Review, has compiled a detailed response to each of the claims made in the Blackmores article, as follows:
|Blackmores’ claim: Review underpowered - many studies used less than optimal dose|
“There are several issues with this review, firstly, the highest dose used in the trials reviewed is 1000mg. This is an issue because for 1000 mg of active EPA+DHA from fish oil ingested, one only sees about 50 percent increase into the safe zone of the omega-3 index score (i.e. greater than 8 percent) and if 500mg is used you are only going to see about 10 percent of people taking that dose ‘get over the line’ – if there is 100 percent compliance.”
The authors of Cochrane’s Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease review looked very hard for dose effects - if EPA and DHA work, you would expect greater effects where greater doses were used. Contrary to Dr Colquhoun’s suggestion, the review does show that many trials provided over 1g (1000mg) of EPA and DHA per day. Nine trials provided over 2400mg/day - of which two provided more than 4400mg/d.
Of the 79 trials included in the review, 71 of them assessed effects of the longer chain omega 3 fats (EPA and DHA). Of these:
Therefore we had a good range of doses - most trials gave more than 1000mg/d, and if there were different effects at higher doses we should have been able to see those effects.
There was no dose effect – we did not see different (or any) effects when doses were higher compared to studies where doses were lower. We analysed this in two different ways, subgrouping by dose and running meta-regressions. There was no more effect in high dose studies than in low dose studies.
Blackmores’ claim: Omega 3 index and supplement compliance should have been considered.
“This is important because we are talking about a supplement, not a drug which has a known absorption profile in the body which allows the variations in individuals to be minimised. With any supplement three things need to be considered – intake, absorption, and metabolism – before drawing conclusions. The omega index score is an important part of understanding the effect of omega-3 in the body.”
The omega-3 index reflects the relative amount of omega-3 fatty acids within red blood cell membranes and is measured by analysing blood samples. A safe zone of between four and eight percent is often referred to when interpreting the omega-3 index with scores in this range or greater being associated with a 30 percent decrease in cardiovascular disease.
Dr Colquhoun points out that the studies reviewed were not drug trials with clear-cut absorption profiles, but rather studies on a supplement which is affected in a number of ways such as by individual absorption and background intake through diet which means attempting to analyse outcome data is not feasible.
“Essential fatty acids are necessary in the body for normal brain and neurological development and in a study of the elderly in the United States, increasing omega-3 levels was associated with increased survival,” Dr Colquhoun explained.
The studies in our review represent the way that long chain omega-3 supplements are usually taken. If a normal person purchases EPA and DHA supplements they aren’t tested for red blood cell membrane EPA or DHA, they take the dose they purchase. The fatty acids are incorporated into their body fats (including the red cell membranes) over time – there have been some good studies of this.
One reason we only included studies of at least 1 year in duration into our systematic review is that while the fat in most parts of the body in most people equilibrates (reflects) the new EPA and DHA intake within a few weeks, a few people take a bit longer – up to 6 months to build up expected levels of EPA and DHA in all parts of their bodies. We included trials of at least a year so that all participants will have had time for that equilibration to occur and any benefits of this to be reflected in the health outcomes we were measuring.
Blackmores’ claim: Unhelpful to suggest clinical conclusions from such a broad review.
According to Dr Colquhoun, another major flaw with this review is that it is drawing conclusions on cardiovascular outcomes when the studies included in the meta-analysis were not designed to measure clinical outcomes.
“This is the second time the author of this recent review has conducted a meta-analysis of the fish oil studies. No new studies have been published since the first meta-analysis and it is not possible to draw clinical outcomes from the existing body of work.”
All of the included studies in our systematic review randomised participants to take omega 3 or a control for at least 1 year. Any cardiovascular events or deaths that occurred in these trials during the supplementation period are indeed useful in telling us what the effects of the omega 3 are on health.
We published a systematic review on this topic in 2004 with 48 trials. This time we were able to include 79 trials, as many more have been published – an additional 31 trials. We have added in the additional studies that have been published recently.
Blackmores’ claim: Studies with therapeutic dosages will provide more informed results. .
Two new randomised controlled trials with over 10,000 participants in each are due for completion in the coming months and are expected to provide new evidence to support the role of fish oil in cardiovascular disease.
“These two trials will be the first new trials on fish oil in five years with significant numbers and significant dose and will be an important contribution to the body of evidence on EPA and DHA derived from fish,” Dr Colquhoun said.
There are omega 3 trials being published regularly, but Dr Colquhoun is right that some very large ones are due to be published soon. Like him, we await their results with interest.
Blackmores’ claim: No doubt about the many health benefits of fish oil. .
Blackmores Institute Director Dr Lesley Braun added: “Fish oil is extremely well researched for a range of health benefits including heart health, joint health, and even cognitive decline. However, these benefits are all dose-dependent and also depend on good absorption. As with any medicine, taking the right amount is vital.
Meta-analyses like this paint a very broad picture, making it difficult to interpret the results from a clinical perspective, particularly when under-dosing is involved. It is clear that doses used were less than optimal, time frames are considered relatively short when looking at major endpoints such as all-cause mortality, there was no consideration about absorption which is significantly influenced by things such as form used and whether taken with food or not. Finally, the researchers stated they did not take into account baseline omega 3 levels which is an important factor.
Australians should not be concerned by this study as there is no doubt about the many health benefits of fish oil and omega-3s. If they are taking fish oil for a specific benefit, they should be mindful that they are getting enough for it to be therapeutic, and if using supplements, it is important that they be taken as directed and they are good quality products to get the most benefit.”
We have discussed dose above. Dr Braun mentions duration – all of our trials (including over 112,000 people) were for at least one year, most were longer and some were as long as 8 years. We did not find different effects with different doses (as above) or greater effects in longer trials. If omega 3 works, but is taking a while to provide health benefits, then we would expect greater effects to be seen in longer trials. As with dose we looked very carefully for these but did not see any hint of them in our systematic review (again we used both subgrouping and meta-regression to look for these effects). The research tells us that you can take high doses for long periods and still not see beneficial effects on our hearts or circulation.
This review is part of a series we are conducting at the request of the World Health Organization. In the other reviews (which will be finalised and published over the next couple of months) the effects of omega 3 fats on cognition, depression and several other important health outcomes will be published.
Dr Lee Hooper, lead author concludes with the conclusions from the review itself:
“This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate and high-quality evidence suggests that increasing EPA and DHA has little or no effect on mortality or cardiovascular health (evidence mainly from supplement trials). Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias.”
For more information on the Omega 3 review and a summary of global media coverage visit Cochrane.org. You can also listen to Dr Lee Hooper discuss the review findings with Dr Norman Swan on this week's ABC RN Health Report.