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Bipolar Disorder

Your Brain on Omega 3: Balancing the O3 to O6 Ratio

New research shows lowering omega-6 fatty acids may help the brain.

Wikimedia Commons
Source: Wikimedia Commons

The fats we eat come in all sorts and sizes, from polyunsaturated to saturated, long, medium, short chain and sterols. Each of these categories of fats plays a role in our bodies, from calorie source to energy storage to hormones, and even as signaling molecules sending messages back and forth between the cells of the brain, the endocrine system, and the immune system. Mental health researchers have long been interested in the role of the long chain omega 3 fatty acids found in fish oil, for example, as it is so prevalent in our brains.

In recent years, with the advent of processed food and widespread use of vegetable oils, the amount of omega 3 and omega 6 fatty acids we are eating changed from a relatively equal amount to a hugely skewed ratio in favor of omega 6. Why does this matter? The answer to that question is, well, complicated, but can be roughly broken down to the fact that omega 3 fatty acids and omega 6 fatty acids have opposing roles as signaling molecules in the body. The omega 3 fatty acids are (in general) anti-inflammatory, while the omega 6 fatty acids are pro-inflammatory. For example, omega 6 fatty acid metabolites are responsible for increasing pain and swelling from an injury, and blocking this pathway using ibuprofen will reduce pain and swelling. Omega 3 fatty acids on the other hand tend to turn off these inflammatory signaling pathways. Both inflammation and undoing that inflammation are important in combating disease, injury, and maintaining a healthy bodily homeostasis.

In the brain these inflammatory pathways, if chronic and uncontrolled, can affect all sorts of processes that then go on to affect not only the health of the brain but the whole body. For example, omega 6 fatty acids are made into prostaglandin E2, a pro inflammatory molecule that affects sleep, reduces concentration, suppresses appetite, and leads to behaviors such as social withdrawal. These behaviors are common in sickness, such as a cold or flu, but are also common in depression. Prostaglandins also set off the “fight or flight” response to stress by inducing the brain to send out corticotropin-releasing hormone, which leads to downstream release of cortisol, adrenaline, and other stress hormones.

Now both omega 3 and omega 6 fatty acids are stored in cell membranes. To some extent this fact protects us from the hugely skewed dietary intake, as most of the long chain omega 3 we eat displaces the omega 6 filling up our cell membranes. Therefore consuming a little omega 3 can make up for a lot of omega 6. But could we improve the anti-inflammatory/inflammatory balance even more by restricting the omega 6 in the diet? As much as that would make perfect sense, research backing that conclusion has only recently popped up. A new paper from the Journal of Clinical Psychiatry makes an interesting case for a more balanced omega 3 to omega 6 ratio as being beneficial for bipolar disorder.

Much of the early clinical research on using fish oil for mood disorders was done for bipolar disorder, based on some animal and human post-mortem brain findings that increased long chain omega 6 fatty acids (arachidonic acid) and inflammation are increased in animal models and humans diagnosed with bipolar disorder. Later studies using neuroimaging and peripheral markers of inflammation also show increases in folks with bipolar disorder, especially during an acute episode.

Mood stabilizers such as anti-epileptic drugs are used to treat bipolar disorder and migraines as well. However, some anti-epilepsy drugs that work fine for seizures, such as topiramate and gabapentin, don’t work well for bipolar disorder. The ones that do work (like valproic acid and carbamazepine) and other anti-bipolar drugs such as lithium actually down regulate the omega 6 inflammatory cascade. Topiramate and gabapentin don’t.

Omega 3 supplements have a mixed record in clinical trials for both bipolar disorder and depression. In general, only supplements containing EPA or a mix of EPA+DHA have been beneficial (which is why I don’t recommend algae DHA product or DHA milk). The authors of the JCP paper question if omega 3 supplementation should be combined with a low omega 6 diet to see if this would work better for psychiatric purposes. Interestingly, a trial like this has been done for migraines, also a disease of increased inflammation and omega 6 cascade up-regulation in the brain. Not only did omega 3 supplement plus a low omega 6 diet help with decreasing migraine pain and number of migraines, a subsequent paper also showed increase in quality of life.

Wikimedia Commons
Source: Wikimedia Commons

It’s quite plausible that we could reduce symptoms of brain inflammatory diseases such as bipolar disorder, migraines and more by reducing the omega 6 fatty acids in our diet and increasing, by a small amount, long chain omega 3s. Such an intervention is unlikely to be harmful, as the major sources of omega 6 fatty acids in our diet are processed foods (chips, fries, and baked goods). As some researchers have shown, reducing omega 6 in the diet does reduce inflammatory metabolites in humans as well as increasing the bioavailability of omega 3s. Some other healthy foods, like nuts and poultry, are also high in omega 6, but since the idea is to reduce, not eliminate omega 6, moderate amounts of nuts and chicken should be fine. Certainly worth further study!

Copyright Emily Deans MD