Monday, January 12, 2009

Omega 3 Fatty Acids and ADHD: The Theory Behind the Practice

How Omega 3 Fatty Acids work and their influence on ADHD

In the past couple of posts, we have examined the connections between ADHD and alcoholism. We will continue this discussion shortly, when we begin to investigate specific genes of overlap between the two. One of these genes, whose products are thought to be affected by alcohol consumption, and appears to have some degree of influence on ADHD is called the Fatty Acid Desaturase 2 gene. We will be investigating this gene in the next post, but I want to preface it with a bit of a background information as to why fatty acids, especially the famous omega 3's, are believed to be so attractive as potential natural treatments for managing ADHD (as well as a host of other disorders).

Since ADHD is so strongly affiliated with the nervous system, the physical composition of this system is extremely important when considering some of the implications for this order. Keep in mind that the brain is over 60% fat in humans and other mammals.

Additionally, during the brain developmental stages, neurons are coated with an insulation of sorts, a fatty material called myelin. This whole process is called myelination. When this myelination process is complete, a neural connection can be up to 100's of times more efficient, and signaling through these connections can become exponentially faster. During the teen years, this myelination process often runs rampant, as the brain begins to hardwire itself for greater efficiency. That is why it is so crucial to develop these key connections early in life, before this myelination process begins.

Given the importance of fat in the myelination process, and the overall abundance of fat in the brain as a whole, the nervous system is extremely influenced by fat composition obtained from dietary means. Cell membranes, which are the outer protective layers of cells (in all parts of the body) are also comprised of fatty materials. Among these are omega-3 fatty acids and omega-6 fatty acids.

**Please note: the rest of this post deals primarily with the biochemistry of omega-3 fatty acids and their impact on cell structure and function, and their connection to disorders like ADHD. If you are just interested in general strategies on omega-3 supplementation, you can skip to the end of the post, where I have listed 6 tips to increase your chances of effective treatments. If you want a bit more background as to why I am giving these suggestions, please continue reading!

These two types of fatty acids each have unique structures, which means that their incorporation into the cell membrane also affects its structure. For example, omega 3's typically take on a more curvy shape, and omega 6's are often more "straight" and narrow. Because of these shape differences, the omega-3 rich regions of the cell membrane are more prone to forming "gaps" in the cell membrane, making this whole region more "fluid". However, the straighter, more rigid, omega-6 regions of cell membranes make for tighter and smaller gaps, making the cell membrane less flexible. Numerous studies have shown that fatty acid composition in cell membranes is directly affected by dietary intake of omega-3 fatty acids.

Among the omega 3-fatty acids, perhaps the most important is called alpha-linolenic acid (ALA). The human body is unable to produce this type of fat, so it must be obtained via dietary measures. The body can then convert ALA to two other types of omega-3 fatty acids, DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid). Both DHA and EPA can be incorporated into cell membranes, giving them a more flexible conformation. Not surprisingly, all three of these omega-3's (ALA, DHA and EPA) are currently popular supplements and health-food items. Supplementation with EPA and DHA-rich fish oil has been shown to boost levels of these omega-3's in the cell membrane.

Keep in mind that many of these studies of omega-3 incorporation into cell membranes typically involve blood cells as opposed to nerve cells. However, there have been a few recent findings supporting the incorporation of supplemented DHA into neuronal cells in mammalian systems. Additionally, dietary differences in omega-3 fatty acids has also been shown to influence the ratio of these to other fats in the brain in rat model studies of ADHD, and possibly influence learning behaviors.

The makeup and rigidity of the cell membrane is very important for proper functioning among cells in the nervous system. Gaps, such as those from omega 3 fatty acid regions, allow easier passage of key materials in and out of cells. Among these key openings are a type of passageway, made up of protein-based structures called ion channels. We will see in later posts that ion channels play a huge role in a number of diseases and disorders, including those which involve the nervous system (including ADHD). It is believed that these ion channels are not directly influenced by omega 3's and other fatty acids but rather by the tension on the cell membrane caused by these fats. Therefore, the right amount of tension, governed by the fatty acid composition is thought to regulate ion channel function is necessary for proper cell function.

Additionally, these ion channels are able to change shape, allowing the membranes of different cells to "fuse together" at specified times. This allows for adequate conductance of electrical signals and facilitates communication in-between cells. However, with a more rigid structure (i.e. from one that is deficient in omega 3 fatty acids), this lack of flexibility impairs the ability of these ion channels to change to the optimal conformations necessary for this fusion process. As a result, functional cell-cell communication is hampered. This too, is thought to be a factor in disorders such as ADHD (which will be discussed in future posts).

Perhaps the biggest effect that cell membrane integrity has to do with ADHD is its influence on the signaling agent dopamine. It has repeatedly been shown that ADHD is intricately connected to dopamine-based signaling methods and systems. The role of dopamine on ADHD is especially pronounced in specific brain regions such as the prefrontal cortex, in which this key neurotransmitter is often deficient. Numerous animal studies have shown that a deficiency of omega-3 fatty acids can lead to reduced dopamine function in the prefrontal cortex.

Interestingly, there has been a reported increase in dopamine levels in omega-3 deficient animals in another brain region called the nucleus accumbens. The reason this is somewhat intriguing is that the prefrontal cortex and the nucleus accumbens are thought to work in different directions, in an oppositional sort of way. Some studies suggest that this "ADHD" brain region, the prefrontal cortex inhibits the nucleus accumbens. As a result, a dopamine deficiency in the prefrontal cortex could lead to less inhibition and higher dopamine levels in the nucleus accumbens brain region. This confers the idea that the prefrontal cortex is often deficient in free levels of the important neurotransmitter dopamine.

When addressing ways to "naturally" treat deficits with regards to any type of disease or disorder, it is often tempting to "supplement" the problem away. Because of the dopamine deficiency in the prefrontal cortex, combined with the fact that omega-3 fatty acid deficiencies have repeatedly been seen in ADHD brains, it is easy to jump to the conclusion that rampant supplementation with fish oils and other omega-3 rich sources can make negative symptoms of this disorder go away.

However, research has indicated that although individuals with ADHD have been shown to have plasma deficiencies of omega-3 fatty acids, the cause is not likely to be a dietary omega-3 deficiency. Only a few limited studies have actually suggested direct reduction of ADHD symptoms with omega-3 fatty acid supplementation. For example, based changes in teacher rating scores on ADHD symptoms, children who took EPA and DHA supplements did show noticeable reductions in ADHD symptoms. Interestingly, this same study found that the effects of antioxidant vitamin E were also a large factor.

Even if these studies above hold true for the general population, numerous others have shown omega-3 supplementation to be effective in reducing ADHD symptoms. What is confusing is that this method has proven successful in some instances, while doing little-to-nothing in other cases. As a result, we are left with the big question, why? It appears that the answer may lie in the genes of the individual.

Fatty acid desaturase genes are responsible for coding for a series of enzymes of the same name. These fatty acid desaturase enzymes are important for the metabolism of omega-3 fatty acids. Deficiencies in fatty acid desaturase enzymes are not limited exclusively to genes. We now know that external chemical factors such as maternal alcohol use can also reduce the activities of these key enzyme systems. As a result, omega-3 metabolism suffers. Our next post will deal almost exclusively with this topic.

Before we go, I would like to list a few strategies to follow if you're interested in exploring omega-3 fatty acids as a treatment option for ADHD. Of course there is no guarantee that this treatment method will work, but here are a few pointers to stack the deck in your favor:

***Please note: You may be wondering why I am not giving specific dosage recommendations for omega-3's. There are two main reasons: 1.) There are still no clear-cut established daily amounts, and with the information I currently have, I am not fully comfortable in recommending a numerical amount, and 2.) Due to so many other factors at work (such as age, gender, disease status, cardiovascular health, genetic background, total caloric intake, and other dietary choices), omega-3 recommendations do not follow a one-size-fits-all model. However, a better option is to keep a good balance between omega-3 levels and intake levels of other fats. Since dietary fat intake plays a huge role on hormonal functions, overall ratios and balance play as much of a role as total amounts. Nevertheless, if you're looking for a rough estimate, many of the sources out there generally suggest levels of around 1-2 grams (on the higher end of this for men and the lower end for women) total of omega-3 fatty acids per day.

  1. Take a mixture of omega-3 fatty acids, not just one kind. Since ALA is the omega-3 precursor (mentioned above) to EFA and DHA, it might be tempting to just take ALA and let it convert to these other omega-3's in the body. However, this conversion process is slow and inefficient, as the enzyme system involved results in less than 1% of the ALA being converted to EPA and even less (since EPA goes through a series of steps using other enzymes to convert itself to DHA) to DHA.
  2. Don't omega-3 overload. This is extremely important. Many well-meaning treatment methods for ADHD and related disorders often try to force down high levels of these seemingly benign substances to "cure" these disorders. However, an omega-3 overdose can also cause problems. These enzymes (which are the same desaturase enzymes will will be discussing in the next post), operate by a mechanism called negative feedback. This means that if omega-3 levels are too high, the activity of these enzymes is significantly reduced, and the conversion processes listed in suggestion #1 are greatly impaired.
  3. On the other hand, keep a good balance between omega-3 fatty acids and omega-6 fatty acids. Recommendations may vary, but most sources recommend between a 1:1 and 2:1 ratio of omega-6's to omega-3's. Unfortunately, most Western industrialized diets have a much more skewed ratio, often upwards of 10:1 or even 50:1 in favor of the omega-6's. This imbalance, too, will affect enzyme activity in the omega-3 conversion process. As mentioned above, a balance of these dietary fats is essential for maintaining proper structure and integrity of cell membranes. While this is a bit of oversimplification, fats from marine sources are typically much greater in omega-3's and fats from land animals is higher in omega-6's (and another class of fats called omega-9's, which the body can actually produce from the other 2).
  4. Keep your vitamin E levels up to speed. Since the brain is comprised of high levels of fat, it is one of the most oxidation-prone organs in the entire body. A number of neurodegenerative diseases such as Alzheimer's are thought to be products of this oxidation process. While all antioxidants have some benefits, vitamin E appears to be one of the best with regards to brain health. This is in part because it is a fat-soluble vitamin (unlike vitamin C, which, in its most common form, is not). I mentioned in the study above on a reduction of ADHD symptoms based on teacher evaluations after omega-3 supplementation that vitamin E levels were also a major factor in the study.
  5. On the other hand, don't go overboard on the vitamin E. General daily amount recommendations and upper limits (a bit high in my opinion for the upper limits, try to stay well under these upper boundaries), and food and supplement sources of vitamin E can be found here. While a number of antioxidants are water-soluble, like vitamin C (which can easily be flushed out of the system and much tougher to overdose on), vitamin E can build up to toxic levels in the body much more easily. An alternative strategy is to take sufficient levels of vitamin C, which can help "recycle" vitamin E and enhance it's positive antioxidant effects while reducing the likelihood of toxicity.
  6. This should go without saying, but eliminate alcohol intake if you are pregnant. We will spend our next entire post on the negative effects of maternal alcohol consumption on these desaturase enzymes which are needed to convert dietary omega-3's to ones which can be used by the cells. This is another possible link between alcohol and ADHD, a topic which we have been exploring in quite a bit of depth as of late.