Several randomized controlled trials have been performed utilizing omega-3 fatty acids as a monotherapy for depression, or as augmentation therapy (added to an antidepressant for major depressive disorder.)  Two recent meta-analyses aggregated these data, and found that there is evidence for an anti-depressant effect of omega-3 fatty acids when used in conjunction with anti-depressant medications for depression; however, there was evidence of publication bias in favor of positive studies.  That is, a normal distribution of the effect sizes showed an absence of small, negative studies that have been published.  The available evidence from randomized controlled trials is modest, but does support a role for omega-3 fatty acids as an augmentation therapy for depression.  However, randomized controlled trials do not at this time support a role for omega-3 fatty acids in monotherapy for major depressive disorder, nor for boosting “subclinical depression” (which is to say depressed mood that does not meet the criteria for major depressive disorder.)

Problem with Randomized Controlled Trials

All of these studies involve very short time courses (e.g. supplementation over the course of approximately twelve weeks.)  The epidemiological data suggests that it is the overall consumption of omega-3 fatty acids over years to a lifetime that has a protective effect.  None of our randomized controlled trials are done over a long enough time period to determine the full effect of omega-3 fatty acids on mood.

Conclusion: Omega-3 Fatty Acids Have a Protective Effect

It is important to aggregate the evidence across a range of different types of studies, including epidemiological, cellular and molecular in addition to randomized controlled trials.  When that is done, the potential effect of Omega-3 fatty acids on depression and other mood disorders looks to be far greater than the available evidence from randomized, controlled trials.  As the Committee on Research on Psychiatric Treatments of the American Psychiatric Association recently concluded, “The preponderance of epidemiologic and tissue compositional studies supports a protective effect of omega-3 EFA intake, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).”

There is mounting evidence, as more and more research is done into Alzheimer’s Disease and related neurodegenerative disorders, that diet plays a large role in the development of brain disorders later in life. What you eat matters, but what you make sure not to eat matters as well.

And despite the focus in the United States on the importance of protein in our diets, more and more evidence seems to indicate that regularly consuming high levels of protein (such as deriving >50% of ones calories from protein) can have adverse effects. The landmark research study, The China Study, examining the role of diet (and dietary protein) in health is what I consider to be essential reading for anyone interested in the link between diet and health.

For more information on the research study on high protein diets and brain mass – published in the Journal of Molecular Neurodegeneration, check here:

Dietary composition modulates brain mass and amyloid beta levels in a mouse model of aggressive Alzheimer’s amyloid pathology

Correlation Between Fish Consumption and Major Depression

In this classic article to the Lancet, JR Hibbeln demonstrated that there was an inverse correlation between annual fish consumption in a country, and that country’s incidence of depression (Hibbeln, 1998.)  As you can see from the graph, those countries that consumed the most fish per capita, such as Japan, had the lowest rates of depression.  Vice versa, those countries where people consumed the lowest amount of fish, such as the United States, had the highest rates of depression per capita.  Of course, correlation is not causation – the fact that two things are linked does not mean one causes the other.  For that reason, epidemiological studies such as this one must be confirmed by other methodologies: mechanistic studies in cell cultures, animal models of illness, and randomized clinical trials.  Research on why fish consumption might help prevent depression has focused on omega-3 fatty acids.  Cellular studies have confirmed that Omega-3 fatty acids, found mostly in certain kinds of fish, but also in walnuts, soybeans, flaxseed, and some other plants, are integral components of the cell membrane of brain cells.  Without adequate omega-3’s, membrane dysfunction may lead to cellular dysfunction, and from cellular dysfunction to conditions such as depression.

Next week: what randomized clinical trials show about omega-3 consumption and depression!

Hints from Humans that Turmeric Protects Memory

One provocative report from the  American Journal of Epidemiology in 2006 suggests that increased curry consumption in human populations is associated with a lowered risk for developing cognitive impairment, including memory loss, as one ages. Although this was a retrospective study using a population from Singapore these results are exciting, in part since most curries in Singapore are yellow curries which contain turmeric. Therefore, there is evidence that consuming turmeric prevents memory loss. In fact, people who ate curry “often” (once a month or more) were nearly half as likely to have cognitive impairment than were people who ate curry “rarely” (once every 6 months). Though more research needs to be done, these are encouraging results.

Ever gone out for a night on the town and had a few too many drinks? Ever woken up the next morning with a really bad headache? Well, the source of that headache wasn’t the alcohol you drank. (Well, the alcohol played a part, for sure.) But when you drank all that alcohol, it actually causes dehydration to occur in your brain. (That’s why the best way to stave off a hangover is to drink lots of water while you are drinking the alcohol… but that’s a discussion for another time.) Alcohol causes your brain to dehydrate and the pounding headache the next day is your parched, thirsty brain screaming at you to drink lots of water.

So just make it a habit: keep your brain nice and hydrated on a regular basis. So much of what we eat and drink can dehydrate us – coffee is one example – so make sure water is a part of your everyday routine.

How Lack of Sleep Can Decrease Brain Health and Increase Alzheimer’s Risk

Recent research done by Dr. David M. Holtzman at the Washington University School of Medicine has shown a correlation between lack of sleep and the development of Alzheimer’s Disease. One of the clear indicators of Alzheimer’s Disease is beta-amyloid plaques in the brain. These plaques interfere with brain function and cause the dementia associated with Alzheimer’s. Dr. Holtzman’s research team subjected mice to sleep deprivation, limiting them to 4 hours of sleep per day and found an increase in the development of plaques in the brain. Over time, this can cause a serious decline in overall brain health.

Some of the mice were then given a new drug for insomnia, which put the mice to sleep for greater time periods. Lower levels of plaque-forming proteins were measured in the mice, indicative of more positive long-term outcomes.

Additionally, Dr. Holtzman tested healthy males to measure levels of beta-amyloid during both waking and sleeping hours, and found the beta-amyloid levels were lower during sleep cycles than when the men were awake. A conclusion can be inferred that greater will will lead to lower overall levels of beta-amyloid, and a lower chance of developing Alzheimer’s disease.

Other Options Besides Sleeping Pills May be Better Alternatives

Although sleeping pills can induce sleep, it is not necessarily known whether sleep induced by sleeping pills is most conducive to brain health. A healthy diet to maintain brain nutrition, a normal sleep schedule, and exercise to induce natural tiredness and drowsiness may be the best answers to long-term prevention of Alzheimer’s and dementia.

At this point, what specifically causes Alzheimer’s Disease is not well understood. We know some of the contributing factors, but the interaction of these factors in the brain is complicated. However, it is reasonable to assume that providing your body and mind with adequate sleep will increase overall brain health, body health, and general well-being. It is just one of the things you can do to significantly improve your quality of life.