Omega-3 fatty acid supplements and cognitive decline

Monday 13 May 2013 5:30PM (view full episode)

The omega-3 fatty acid supplement industry is huge - from fish oil to krill, from your heart to your brain. But do these supplements really protect our brains from age related cognitive decline?

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Today, a test of how sweet you are, so go and find a chewy lolly if you have one close by, don't eat it, and we'll do this experiment later. Plus a handy tip or two about how to get kids to eat their vegies.

And eating your fish, or at least your fish oil or omega-3 fatty acid supplements. Do they really protect your brain as some think they do?

Here's Alan Dangour of the London School of Hygiene and Tropical Medicine.

Alan Dangour: We conducted a study on the benefits of fish oil supplementation in later life. It has long been thought that if you eat a lot of fish, and especially these particular long-chain omega-3 fatty acids that are in fish, especially oily fish, that there is some benefit from eating those fish and especially for brain function. You know, people have often said if you eat a lot of fish it's good for your brain, and there is lots of evidence from cross-sectional studies, so surveys and also studies where you follow people up for a long time, that those people who eat more fish tend to have better brain function. But of course really the key question is if you supplement people with fish oil in a randomised design, so you are giving some people fish oil and some people a placebo, is there a benefit for brain function?

Norman Swan: Which also goes to cause and effect rather than some association that you might get. There might be something about you that makes you eat more fish.

Alan Dangour: That's precisely right. So people who eat a lot of fish tend to be healthier in all sorts of other ways, and if they are eating fish then what are they not eating instead. And there is concern about large intakes of saturated fat, for example, from meat which is the obvious substitute for fish in lots of people's diets. So people who eat a lot of fish tend to be healthier, they are more active, and they are more educated. And really the only way to test whether it's the fish itself which improves cognitive function is to conduct one of these randomised controlled trials.

Norman Swan: I've heard people who are believers in omega-3 fatty acids fight to the death over several kinds of omega-3 fatty acids, there's eicosapentaenoic acid…I can't remember what DHA stands for…

Alan Dangour: Docosahexaenoic acid, yes.

Norman Swan: People say, oh, you've tried that omega-3 fatty acid supplement but it didn't have DHA in it so therefore that's why it didn't work.

Alan Dangour: There's a lot of debate about this and the jury is largely out, and of course there are believers who say you must have DHA in your supplement or you must have EPA. There's no really good evidence either way on that. In fish, especially in oily fish there are large amounts of EPA and DHA, the two main long-chain omega-3 fatty acids. And they are very special because they are really only available in fish, although obviously the fish get them from algae, so there are certain algal forms of these oils you can also buy. There is no really good evidence that one is better than the other.

Norman Swan: What did you give in your study, in your trial?

Alan Dangour: We gave a mixture of DHA and EPA, but we especially gave a little bit more DHA than you would normally find in fish because there is evidence that DHA is neuroprotective.

Norman Swan: So this was a randomised controlled trial, and what outcomes were you looking at?

Alan Dangour: We were looking at cognitive decline. We expected people to decline over the course of the two years of intervention. These were people aged over 70 at the start of the studies and we wanted to see whether or not the fish oil would slow the cognitive decline in the intervention group.

Norman Swan: So they were normal, healthy people.

Alan Dangour: That's exactly right. So these were screened people, they were screened for heart disease, they were screened for diabetes and they were screened for their cognitive function. And at baseline they all performed well.

Norman Swan: And did the control group decline much? I mean, two years is not a very long time.

Alan Dangour: Well, there is the nub of the problem. Unfortunately the control group didn't decline very much at all, and I think that's one of the key learnings that we got out of this study. This was the largest study ever undertaken. About 860 people were randomised onto this study, it was a two-year intervention, and we expected a small amount of decline in the placebo group and we hoped…the hypothesis was that the fish oil would stop that decline. Unfortunately we were unable to detect any significant change in either arm of the study over the course of the two years, suggesting either of course that the fish oil made no difference, or suggesting that we should have done this study for longer.

There are lots of troubles with trials and you have to realise the limitations of studies like this. A limitation is of course that people who join trials tend to be interested in their health, the sort of worried well. So they are people who really care about their own health. They are likely to be more healthy, and in fact over the course of the study we would have expected something like 30 or 40 people, because it's an old cohort, 30 or 40 people to die. And over the course of the study I think less than 20 people died, so we had a very healthy group. They were a very highly educated group as well, they performed much better than their peers, their age-matched peers would have done.

Norman Swan: Probably typical of the group who would take omega-3 fatty acid supplements.

Alan Dangour: That's exactly it. So you can also say that that is a key learning. What we've learned is that those people who are most likely to buy the supplements are actually those who least need them, because certainly for cognitive function there is no evidence from our trial to suggest there is a benefit.

Norman Swan: So you've gone the next step up in quality of evidence. So randomised controlled trials are pretty high up in terms of if you are wanting to know whether something works or not, but the next level up is where you combine different randomised controlled trials in what's called a systematic review, when you add up all…you know, maybe thousands of cases rather than just a few hundred to see what results you got. And you've just recently published a systematic review of all the trials that are available.

Alan Dangour: That's right. At the very top of the evidence pyramid are systematic reviews where you bring together all of the evidence from the available studies. And we conducted a systematic review for the Cochrane group. For that we identified three trials that have ever been published in cognitively healthy older people who were given fish oils or a placebo. There was a smallish trial which lasted six months, there was our trial which lasted two years, and there was a large trial which was actually the primary outcome was heart disease but they had a strong cognitive function arm as well in that, and that gave fish oil in the form of a fortified margarine versus an ordinary margarine with no fish oil.

And if you look at the totality of the evidence, which included more than 4,000 older people aged over 65 and supplemented for up to 40 months, there was absolutely no evidence of a benefit of fish oil. So obviously very disappointing because we are really desperate to find cures for dementia and cognitive decline, and unfortunately from the Cochrane review we were unable to find any benefits at all.

Norman Swan: And did you get any data at all on things like depression? Because people have said that omega-3 fatty acids have an antidepressant effect.

Alan Dangour: There has been a systematic review which has looked at all of the evidence on depression, and it's quite equivocal; there's no really strong evidence on that front either that there is a benefit for depression. The suggested evidence from the systematic review is that those people who are more depressed seem to benefit a little bit more than those people who are less depressed, but I think at the moment a lot of the studies are really very small on fish oil and depression.

Norman Swan: So omega-3 fatty acids have bombed on heart disease. If they work at all it's just by replacing saturated fats, it's not a benefit like that. They don't seem to reduce sudden death. There doesn't seem to be an effect on cognitive impairment. What is left for this beleaguered industry producing these omega-3 fatty acids?

Alan Dangour: That's a very good question. All of these things do seem to go in phases. You know, there's a lot of excitement about a particular nutrient for a time, and then lots of research goes into that area, and then unfortunately with a lot of these things the evidence is somewhat disappointing. I mean, if you look at antioxidants, vitamin C or other antioxidants, actually the evidence there is also very disappointing. There's a lot of work going on on arthritis and joint pains which may show some benefits.

Norman Swan: But at vastly increased doses.

Alan Dangour: Absolutely. The question of course is, is a Western diet, where all of these trials have been conducted, is a Western diet already so rich in these oils that additional supplementation makes no difference? To date none of the studies have been long enough for a really important effect to be demonstrated. But all departments of health recommend the consumption of fish, and whether it's because it's a substitute to meat or whether it's because of the oils in these fish or other nutrients such as zinc or selenium in these fish, there are clear benefits.

Norman Swan: And any harm in these trials? Because people have said it might increase the risk of haemorrhage and haemorrhagic stroke.

Alan Dangour: Yes, I have a professor colleague who once took 15 grams of fish oils a day for about two or three weeks, which is an enormously high dose of course, and he got constant nosebleeds and the cat started following him around the house he said. But certainly in the trials that I have undertaken and the trials we included in our Cochrane review, the adverse effects are really things like flatulence and a slight upset tummy, and actually the evidence of adverse effect was quite balanced between the placebo and the intervention arm.

Norman Swan: You spend some of your time looking at nutrition in poorer countries. What sort of interventions are you looking at? Because presumably we're talking about much less sophisticated approaches to get huge benefits.

Alan Dangour: It's quite interesting to reflect on the different research that is being done in high income and low income countries. It is shameful there are still 3.5 million children every year who die of under-nutrition. This is an outrage and we must take this much more seriously. I spend a lot of time now thinking about research on agriculture. There is clear evidence that stimulating the agricultural sector in poor countries has a benefit for nutrition outcomes of those children in those countries, and there's a lot of work now going on into identifying the right strategies to stimulate the agriculture sector or innovations in agriculture such as bio-fortified crops. Those are crops which are selected, not genetically bred but selected to have higher levels of particular nutrients like vitamin A or iron, or the use of fertilisers that contains zinc, for example. The zinc gets into the plant and the plant is consumed by the children. So these are very simple, straightforward strategies. There is now beginning to be an evidence base to suggest that they are effective in treating under-nutrition, especially in children and pregnant women. And the situation is untenable. We cannot continue like this, it's completely outrageous.

Norman Swan: And when you say stimulate agriculture, you mean people have left the land and you are encouraging them to return?

Alan Dangour: In a lot of poor countries the vast majority of the population live in rural communities and are farmers…

Norman Swan: So what do you mean by stimulating agriculture then?

Alan Dangour: Stimulating it to be better, for yields to be greater, for the productivity to be enhanced, for the quality of the crop to be better, for the crop not to be lost through pests and through fungus. There is a huge opportunity in many parts of Africa and Asia for there to be much greater development of the agriculture sector, stimulation of its potential to meet the needs for food and good quality food and nutrition, and to ensure food and nutrition security in poor countries. And that need is not being met because there is insufficient infrastructure, there is insufficient access to markets, there is insufficient knowledge, there is insufficient fertilisers, seeds, whatever. There's a huge need to improve access to those sorts of things. And that comes with good quality governance and ensuring that aid money is well spent and national budgets are well spent, but there's also a huge amount of research that needs to be done to ensure that we identify cost-effective strategies for improving nutrition.

And the evidence recently published suggests that households that plant, for example, crops rich in vitamin A—orange fleshed sweet potatoes is the best example—those households, the women and children eat more of these orange fleshed sweet potato and there is a biological benefit in that the women and children in those households have raised vitamin A levels in their serum. So, a clear link between agriculture and a nutrition outcome.

Norman Swan: Alan Dangour of the London School of Hygiene and Tropical Medicine.

You're listening to the Health Report here on RN, with me, Norman Swan.

Still to come, your sweet test, so have that chewy lolly ready.



Dr Alan Dangour
Senior Lecturer
London School of Hygiene and Tropical Medicine


Dr Norman Swan
Brigitte Seega

Comments (9)

Add your comment

  • David Richards :

    13 May 2013 10:21:41pm

    This study is underpowered. Also the average daily supplementation of fish oil in the Cochrane meta-analysis was only 1.5g/day. The WHO recommends 2-3g daily intake. The problem with control studies with omega-3 is that they can't control for incidental intake.

    The Framingham Study found a 39% reduction in dementia in the quintile with the highest levels of DHA & EPA measured in their blood. Mozzafarian from Harvard - 30% reduction in all cause mortality, including 40% reduction in stroke risk in the highest quintile.

      • David Wyatt :

        16 May 2013 10:47:59am

        Thanks David Richards. ....good points.
        I wondered what you would make of this omega oil report.

  • David Richards :

    16 May 2013 4:10:30pm

    Thanks David,

    Eric Topol has just commented on the GISSI study that found no benefit. Interestingly previous GISSI studies in secondary prevention trials had demonstrated benefit, but this was a primary prevention study.

    However the study was flawed again because 40% of the participants were taking statin therapy.

  • martina enzo :

    18 May 2013 11:41:09am

    Humans should not eat krill. It's food for whales and other threatened species. Baleen whales cannnot eat anything else, but humans are highly adaptive omnivores and have many options.The krill fishery already faces serious threats from global warming and overfishing. Exploiting krill for some alleged health benefit is yet another middle class obscenely exploitative act. Eat fish if you will but leave the krill alone.

      • keith buckland :

        19 May 2013 3:39:38am

        Interesting. Replies interesting as well. Good on you Martina Enzo pointing out that krill is whale food. I've been pointing this out since it became a 'fad' to consume it. The natropath at the local health food store has had my speil on behalf of rhe whales.

  • David Richards :

    19 May 2013 4:43:29pm

    Krill oil contains only about 1/3 the amount of DHA/ EPA contained in a standard fish oil capsule. You pay a lot more for a lot less!

      • David Wyatt :

        22 May 2013 4:53:28pm


  • David Richards :

    26 May 2013 11:01:32pm

    You could be right David but Omacor has the runs on the board in the sense it has been used in clinical trials for more than 10years with favourable outcome. As such it has been approved for use by the FDA in the management of post-MI patients as it has demonstrated improved survival without any significant side effects - no warnings whatsoever in fact, which is pretty rare for any agent.

  • David Richards :

    27 May 2013 6:42:53am

    I should add that regular fish oils are considered complementary medicines and are treated by the TGA essentially as foods. As such there's no requirement to demonstrate efficacy, simply to show that they're being produced and handled in a way that is not doing to cause direct harm, e.g.. that they're being stored properly, etc. So OTC's may not contain anywhere near the dosages they claim and may contain other things that are not labelled or disclosed.

    Omacor has demonstrated efficacy and so the TGA has given approval of omacor as a prescription medicine. This means it must contain over 90% or so of the stated ingredients. I think the real problem is the lack of control of OTC products.