OVERVIEW
· Whichever way we look at it, we’re faced with a massive burden of mental health problems in the modern world.
· Could our modern-day diet be messing with our brains?
· We explore whether the modern-day epidemics of depression, antisocial behaviour and dementia could be curbed by simple dietary changes?
· In particular, we hone in on fish and its omega-3 fat content, and reveal whether it really is ‘brain food’.
We don’t hear all that much about mental illness. It is a pretty scary thing after all. When it comes to dinner party etiquette, it’s said that of all the subjects to keep quiet about, mental health tops the list, above politics, sex or religion. Despite attempts to increase awareness, we have to admit that mental illness remains a taboo for many of us. You might be forgiven then for not knowing the shocking numbers. Mental illness is a greater health burden in the Western world than any other disease, including cancer and heart disease. Across 30 European countries in a typical year, it’s estimated that around 165 million people (we’re talking 38% of the total population of these countries) will have a fully developed mental illness1. One in four adults in the USA is suffering from a mental illness, and nearly half will develop at least one mental illness in their lifetime2. If that’s all not too much, let’s add in the economic cost of mental illness, which in the USA was $300 billion in 2002, and we can only presume that’s got a whole lot worse since2.
There’s no getting away from it: our mental wellbeing in the twenty-first century is in crisis. The burden of brain disorders we now face is unnerving. It’s a complex problem, with many different opinions as to how we arrived at this dire state of affairs. But how often do we stop to think that the physical and the mental may not be so disconnected after all, and that the food, and specifically the fats, we eat could be affecting our grey matter?
Depression – not all in the mind
Across 30 European countries, the number of people affected by major depression is a shocking 30 million1, and around one in ten in the USA are depressed, right now3. We’ve got a serious problem on an epic scale. There are various drugs touted for depression, but they’re not much to shout about. Just take the most popular class, selective serotonin reuptake inhibitors (SSRIs for short), where we see a reported 27% discontinuation rate4 and less than 60% of those who complete a course finding benefit5. So it’s pretty interesting to see that there’s a strong correlation between a nation’s fish consumption and the prevalence of depression6. In fact, the annual prevalence of major depression shows close to a 60-fold variation across countries6. What that means is that countries such as Japan, with a high intake of fish, have the lowest rates of depression, whereas countries with a low intake of fish, like the USA and much of Europe, have the highest. Even within a country, consuming more fish has been shown to correlate with less chance of having depressive symptoms7.
These might be mere correlations but they make you sit up and listen. Of course, we’ve got to ask, is it biologically plausible? Well, there can be little doubt that omega-3 fish oils are critical for both the structure and function of the brain, and importantly, they play a role in how our potent brain messengers – neurotransmitters – work8. So it does seem feasible that they could affect our mood. Indeed, when researchers have looked at the actual levels of omega-3 fats in depressed patients, they find lower quantities9, and what’s more, the lower the level of omega-3, the worse the depression10. Results from studies like these imply that depression is associated with a low intake and/or some sort of abnormal metabolism of omega-3 fats. So, the plot thickens.
Let’s up the ante and take a look at the results from more definitive, cut-and-dried, intervention studies. It’s not difficult to find studies that show clear benefits from giving supplements of omega-3 fish oils to depressed patients. In a four-week study, giving patients with depression 2g of EPA per day (a specific type of omega-3 fat found in fish oil), alongside their ongoing antidepressant treatment, resulted in significant benefit in depressive symptoms11. Another study in patients with persistent depression despite treatment, found that supplementation with 1g per day of EPA resulted in better outcomes on each of the three ratings scales of depression used, compared with those receiving placebos12. These encouraging findings from omega-3 fish oil supplements have also been observed in childhood depression13, as well as depression during pregnancy14.
The problem is, however, that a bunch of other studies haven’t found benefits from fish oil supplements15,16,17,18, so you’d be forgiven for thinking that, overall, the evidence is all a bit shaky. When we have conflicting evidence like this, the best thing to do is to perform a meta-analysis, which basically involves collecting all the relevant studies together and looking for any overall effect. And in September 2011 that’s exactly what was done. A meta-analysis of 13 of the relevant and best RCTs of fish oil and major depression was published in the journal Molecular Psychiatry5. The authors described the results as ‘sobering’. While early trials showed much promise, the inclusion of later more rigorously conducted studies showed ‘that omega-3 FAs (fatty acids) have, at most, minimal efficacy in treating depression’. So that’s apparently that – fish oils are ineffective.
Well, that is if you excuse an oversight. Molecular Psychiatry was not the only journal to publish a meta-analysis of fish oils and major depression that month – The Journal of Clinical Psychiatry was also in on the act. They examined 15 RCTs (12 of which were the same as the first meta-analysis, so largely the same body of evidence). However, they took a different and more intricate approach to the literature. Building on previous evidence19, they didn’t take fish oils as a whole, instead they examined the individual constituents EPA and DHA. And this time, it gave some very different findings. The thing is, when it comes to fish oils, EPA and DHA are structurally very similar but biologically different. Lump all the studies together and you might easily miss this fact. And here’s the thing. It looks likely that it’s EPA that’s effective in depression, while DHA is not only ineffective, it blocks EPA’s activity. And this is exactly what was borne out in the meta-analysis published in The Journal of Clinical Psychiatry20.
The authors found that it was only when EPA was given at levels greater than 60% of the total amount of EPA/DHA that a beneficial effect was observed in depression. As well as this, EPA appears to exert a ‘U’-shaped curve, with effects seen only when EPA is in the range of 200–2,200mg greater than DHA. Giving more doesn’t do the job. Quite why EPA appears to confer benefits for depression and DHA doesn’t, and why the benefit is diminished at high doses, isn’t terribly well understood.
It’s not a simple matter of indiscriminately upping your fish oil intake. The idea that omega-3s might compete among themselves has received little attention. It looks increasingly likely that for a therapeutic effect in depression, you should be backing EPA over DHA.
While existing pharmacological treatments for depression are reasonably effective, they are not without limitations and side effects. Combining antidepressant drug therapy with EPA may significantly enhance efficacy, while reducing side effects11,21.
Unfortunately, most of the studies in this field have been small, and there can be no doubt that we need more in the way of large-scale, well-conducted trials. But bearing in mind the appalling rates of depression we now experience across all walks of society, we think any measures that can safely lower this burden should be promoted. And when all’s said and done, there’s a compelling case for us all to be regularly including oily fish in our diets and bumping up our omega-3 intakes in a bid to bolster our mental wellbeing and put a dent in the soaring depression rates. As for those suffering with depression, there is a persuasive case for including a supplement of 1g per day of EPA as part of a comprehensive treatment approach.
Depression is strongly linked with other chronic illnesses such as cardiovascular disease, diabetes, immunological abnormalities, multiple sclerosis, cancer and osteoporosis22. Increasing intake of oily fish/fish oils could also be beneficial in reducing many of these health problems.
Crime and nourishment
If the dearth of omega-3 fats in our modern diet could be affecting our mood, is it possible that it could be affecting our behaviour, too? In an experiment with Capuchin monkeys, when their dietary omega-3 availability was reduced, they were observed to develop severe behavioural disturbances, violence and self-inflicted injury23. Okay, we’re not monkeys, but it does raise some questions. It’s all too easy to just assume that our diets are completely separate from, and unrelated to, our behaviour. After all, suggesting what we eat can affect such abstract things as our thoughts, emotions, behaviours and actions appears to be bizarre. Yet the incontrovertible truth is that good nutrition is essential for many aspects of brain function24. Which leads us to ask a pretty outlandish question: could there be a nutritional component to aggressive and anti-social behaviour?
And the answer looks to be a big yes. Those countries with the highest intake of seafood have the lowest levels of homicide25. A high dietary intake of DHA and consumption of oily fish have been associated with a lower likelihood of hostility in young adults26. In substance abusers EPA (2.25g per day) and DHA (500mg per day) for three months produced significant decreases in anger and anxiety levels27. Giving EPA (1g per day) to women with borderline personality disorder reduced their aggression and severity of depression28.
You start to get the picture, which leads us on to two intriguing studies that have ignited interest in how our intake of nutrients can modify behaviour. A study of 231 prisoners at a young offenders institute in Aylesbury in the UK, found that administering nutritional supplements – providing broadly the daily needs of vitamins and minerals, along with essential fatty acids – resulted in a 26% reduction in offences compared to those not receiving the supplements29. Indeed, those prisoners who took the nutritional supplements for at least two weeks committed 37% fewer serious offences (e.g. violence).
These findings have been replicated in a second rigorous study involving 221 young adult offenders incarcerated in eight Dutch prisons. Daily supplementation with a combination of vitamins and minerals (a standard multivitamin, similar to the UK study) and fatty acids (including 400mg of both EPA and DHA) for 30–90 days was investigated. Despite the prisoners not perceiving any change in their behaviour, there was a 34% reduction in reported incidents in those receiving the supplements, compared with a 14% increase in the control group30.
Now prison food might not have the best reputation, but the fact is that many criminals are likely to have a better dietary status during imprisonment than they do out on the streets, especially for those prisoners with a drug and/or alcohol addiction30. We can only wonder what the implications are for anti-social behaviour among swathes of society with our modern-day diets deficient in omega-3 fats and other key micronutrients. With tongue only slightly in cheek, perhaps it’s high time we revolutionized the whole business of custodial sentencing by bringing in a plea of ‘not guilty by reason of malnourishment, Your Honour’. Maybe it would act as the catalyst for the integration of nutrition-based strategies for both the prevention of criminal behaviour and a more enlightened rehabilitation of offenders.
Some, although not all, children with symptoms of ADHD (attention deficit hyperactivity disorder) are likely to benefit from omega-3 supplementation, and EPA, rather than DHA, is likely to be most effective in such cases31.
Oiling the brain
For most people, the spectre of dementia in later life is simply terrifying. The fact that it is a disease process spanning many years, indeed decades, has got researchers interested in whether its initiation and progression could be lessened through diet. And what food do you think is right up there at the top of the list? Of course, we’re talking fish, and most notably its rich concentration of the omega-3 fat DHA. With ageing, and especially among patients with Alzheimer’s disease, DHA levels in the brain tend to decrease32, which opens up the suggestion that a drop in DHA might contribute to the slowdown in memory and other cognitive functions with age.
Established wisdom has it that the decline in our cognitive faculties doesn’t begin until old age, with no cognitive decline before the age of 60. However, a recent study of British civil servants shows that it is already evident in middle age, starting from the age of 45, and possibly even earlier33. Once again, this illustrates how important it is to start prevention early by following a healthy diet and lifestyle.
The results of numerous epidemiological studies support this theory34. Famously, a prospective study from a geographically defined community in Chicago reported that subjects who consumed fish once per week or more had 60% less risk of Alzheimer’s disease compared with those who rarely or never ate fish35. Accompanying these findings are results from the Hordaland Health Study, a large population-based study of elderly people in Western Norway, which showed that consumers of fish had better cognitive function than non-consumers, and furthermore that this was strongly dose-dependent, with the maximum effect observed at an intake of approximately 75g of fish per day36.
So how might fish be working its magic? There are lots of fancy ‘mechanisms’ to explain just how omega-3 fish oils, most notably DHA, reduce the risk of dementia. Topping the list are their anti-inflammatory effects (noting that chronic inflammation is a hallmark of Alzheimer’s disease)37. Additionally, DHA inhibits the production, accumulation and toxicity of amyloid ß, the characteristic ‘plaque’ that builds up in the brain in Alzheimer’s disease38. DHA is also thought to interfere with tau kinases and tau pathology, which are regarded as integral aspects of the neurodegenerative process34. We could go on…
There’s just one snag, and this is that intervention trials of fish oils in patients with Alzheimer’s disease have largely been ineffective. This is obviously disappointing, but perhaps not so surprising. Once again, we have to delve a bit deeper into the research to really understand what’s going on here.
DHA is vital for brain development in early growth and the degree of uptake has been linked to visual development, social skills, motor skills and cognitive functioning. It’s very likely that it is in youth, even childhood, that we reach what we could call our ‘peak brain development’; thereafter the developmental ‘window’ is closed and all we can do then is try to slow the decline in our mental functioning as we age. This might be by a healthy diet and lifestyle, including, as we’ve just seen, a regular intake of fish rich in omega-3 fats. But when Alzheimer’s disease is established, it may simply be too late. It’s a case of closing the stable door after the horse has bolted.
But there are some glimmers of hope in the research. An RCT in Sweden found that while DHA supplementation in 174 elderly individuals with Alzheimer’s disease produced no overall benefit after six months, when confined to those with very mild Alzheimer’s, DHA was shown to arrest the decline in cognitive functioning39. A small-scale RCT examined fish oil supplements (EPA 1,080mg and DHA 720mg) in participants with mild to moderate Alzheimer’s disease and those with much earlier mild cognitive impairment. Using the ADAS-cog test (a cognitive functioning test for Alzheimer’s disease), no benefit was found from supplementation in Alzheimer patients, but those with mild cognitive impairment showed notable improvement40. In an RCT of 485 adults (average age 70) with mild memory problems, supplementation of 900mg per day DHA for 24 weeks resulted in participants making significantly fewer errors on a test that measured learning and memory performance compared with those who took a placebo41.
So what about studies in healthy older people without signs of Alzheimer’s disease? A well-conducted RCT of 867 cognitively healthy participants aged between 70 and 79 investigated whether a daily dose of EPA (200mg) and DHA (500mg) would slow the decline of cognitive functioning compared to olive oil42. Unfortunately, no answers were forthcoming because cognitive functioning did not decline in either group. The authors noted that the group receiving olive oil were actually getting enough dietary DHA already, which really only tells us what we already know. We’re not necessarily talking about the need for fish oil supplements to gain benefits, as data from epidemiological studies report that as little as one meal of fish per week appears to proffer a significant protective effect35. Yet we only have to look at data from the UK to see that three-quarters of people don’t consume any oily fish43.
To sum all this up, let’s look at a review of the evidence, which concluded that ‘omega-3 fatty acids… cannot be recommended for patients who have already developed dementia’ but endorsed ‘fish consumption two to three times per week and/or the use of long-chain omega-3 fatty acid supplements such as DHA–EPA in elderly individuals who are looking for ways to maintain their cognitive function as they age32.’
Of course, it would be foolish to reduce the potential benefits of fish to just its omega-3 content. After all, fish has a lot of other good things going on too that could ultimately prove to be neuro-protective, notably a rich offering of nutrients including niacin, vitamin D, vitamin B12 and selenium44,45,46,47,48.
Regular fish consumption, alongside other components of a Mediterranean-style diet – rich in healthy unsaturated oils, fruit and vegetables, nuts, whole grains, other flavonoid-rich foods, and light-to-moderate intake of wine, but low in trans fats and sugar – looks like the best bet for an overall protective diet against dementia49,50.
With 81 million people expected to suffer with dementia by 204051, any lifestyle changes we can introduce to stem this mounting burden on our health are more than welcome. It doesn’t require popping a ton of pills, just simply getting some fish into our diet on a regular basis.
THE PARTING SHOT
When it comes to ‘brain’ food, fish is quite the catch. But do we have to rely on all this fancy science to tell us what cultures around the world have known since time immemorial? All we’re actually doing is catching up with something that’s been embedded in religious and spiritual traditions for millennia, where fish is commonly portrayed as nirvana, a pure and sacred food associated with peace and healing52. Way before science came along, the antidepressant and calming properties of fish, and its rich content of omega-3 fats, seem to have been well known to our cultural and religious traditions. And it’s high time we opened our eyes to this.
SUMMARY AND RECOMMENDATIONS
· Contrary to popular belief, the foods we eat can affect our mood, emotions and behaviours and, indeed, improve the way the brain functions with age.
· Patients with depression should discuss the appropriateness of including a supplement of EPA (1g per day) as part of their treatment with their medical practitioner, as it may help to improve symptoms and reduce the risk of other health problems linked to depression.
· Increasing the intake of omega-3 fish oils, alongside a broad range of essential vitamins and minerals, may also improve behavioural problems and reduce aggressive and anti-social behaviour.
· When it comes to the ageing brain, eating oily fish at least once per week helps stave off dementia and cognitive decline.