Omega-3 Oxidation in ADHD: A Problem with Supplementation?

Here are 4 reasons why omega-3/fish oil/flax seed oil often fails for treating ADHD and how some simple strategies can maximize omega-3 supplementation's effectiveness for therapeutic treatment of the disorder:

One of the most common recent trends in the natural treatment world of ADHD is omega-3 fatty acid supplementation. A number of studies appear to provide at least a theoretical basis for omega-3 fatty acid supplementation for ADHD as a valid natural treatment option. Fish oils, flax oils, and a variety of marine and seed oils are are showing up and rapidly disappearing off the shelves in grocery and health food stores.

Along with all of the pronounced cardiovascular improvements, a number of concerned parents are reaching for these omega-3's as natural treatment options for other dysfunctions, including ADHD and depression. A number of journal articles and research studies seem to support the use of omega-3 fatty acid supplementation as a viable alternative treatment method for attention deficit and or hyperactivity disorders (although not, perhaps at the complete level of stimulant medications).

Lost in the shuffle, however, is the million dollar question: Does omega-3 supplementation actually work in practice?

A number of parents will quickly jump to one side or another on this issue. Some swear by the effects, while others have written off this treatment alternative altogether.

I would like to distill some of the information I have gathered on the subject for this blog post. I personally believe that manipulation and treatment strategies for disorders such as ADHD using dietary fats is still in its infancy. Beyond their caloric content and to a degree beyond most other foodstuffs, fatty acids are often capable of making or breaking our systems hormonally and metabolically. Omega-3's are no different.

Recent findings suggest that fatty acid imbalances in children with ADHD may not be due as much to fatty acid intake, but rather a difference in metabolism of these fats.

In my personal line of work, I have seen at least 4 major factors (there are certainly more beyond these 4, for sure), which can severely hamper the effectiveness of omega-3 fatty acid treatment for ADHD and related disorders. They are:

1. Insufficient nutrient cofactors (or "helpers" for the enzymes that metabolize fatty acids). These include key vitamins and minerals, many whose supplementation, coincidentally, is often linked to improvement in ADHD symptoms.
2. Genetic factors in which lower amounts of of active enzymes key in the omega-3 metabolic pathway are present: A relatively new body of research suggests that individuals with ADHD manufacture different levels of these enzymes than the general population. This is one of many ways in which genetics may play a factor in the disorder.
3. Multiple fats competing for the same enzymes and pathways: The metabolism of different types of fatty acids can be complex. Different fats often share the same enzymes to form their respective products, so an imbalance in dietary intake of certain fats often means an imbalance in their products. This can have wide-reaching effects, such as a heightened state of inflammatory processes and disorders (such as heightened allergies), which coincidentally or not, are often seen at higher rates in ADHD patients. In other words, supplementation with omega-3 fats may be offset if a person's diet also contains high levels of "competing" fats.
   
4. Fatty acid oxidation: One of the most damaging negative side effects. Omega-3's, as great as they are for overall cell health, are often especially prone to oxidative damage. This damage, of course, can be at least partially stopped by ensuring that the body has adequate stores of antioxidant nutrients which are capable of acting on cell membranes and other common destinations of omega-3's.
   

Having highlighted these 4 factors on how well we can maximize the "omega-3 effect" on ADHD and related disorders, we can see that one of them (genetics) is largely beyond our control. However, we can also see that 3 of these 4 factors do fall under our control, at least somewhat, by dietary intervention. Add on these 3 helping factors, and you increase the chance of reducing unwanted ADHD symptoms and behaviors through omega-3 manipulation.

Before we begin, let's get a brief background on omega-3's and other fatty acids and how they relate to disorders such as ADHD.

A background on fatty acid ratios and ADHD:

You may be familiar with some of the following fatty acid "buzzwords" being thrown around recently: ALA, DHA, EPA, etc. These are simply abbreviations of much more lengthy names of major types of fatty acid which are either obtained in the diet or produced by metabolism of other fats.

Here is a quick summary on some of these important fatty acids and why they may be important with regards to ADHD and related disorders:

ALA: Short for Alpha Linolenic Acid, ALA is an omega-3 fatty acid. It can be obtained via dietary means including green vegetables, walnuts, soybeans and several types of seeds (kiwi seeds, flax seed or linseed are especially high in ALA).

One of the main reasons ALA is so important is that it can be converted to other key fatty acids such as EPA and DHA, which will be addressed shortly (essentially it acts as starting material for these other fats). It is therefore relatively versatile among the omega-3's, so maintaining adequate levels of this fat is important. It is important to keep in mind, however, that this conversion process is relatively inefficient, even with the help of important enzymes. As a result, many choose to supplement with these other fats which occur "down the line" directly. Nevertheless, due to its nutritive properties and versatility, maintaining adequate pools of ALA through consumption of the above-mentioned dietary staples is of great potential use.

DHA: Short for Docosahexaenoic Acid, DHA is another important omega-3 fat. It is found in green vegetables as well, as well as several types of meat and animal products (including milk from free range animals who graze on greens instead of feed lots). Of the omega-3's DHA is one of the most critical fatty acids for optimal brain health and nervous function. Low levels of DHA have been linked to cognitive decline and neurodegenerative diseases such as Alzheimer's Disease. DHA is also important for eye health, but is also susceptible to oxidation (which will be discussed in the last section). Interestingly, DHA is believed to play a role in protecting the nervous system from oxidative stress.

EPA: Short for Eicosapentaenoic Acid (not the Environmental Protection Agency, although this fat does play a protective role in several key functions!), EPA is another important omega-3 fatty acid. It is found in significant levels in breast milk (another major plus to breast-feeding) and oily fish such as sardines, mackerel, cod liver and salmon. Most of the fish oil treatments for ADHD rely heavily on this omega-3. It is important to note that this omega-3 is not often found in high levels in farmed fish who obtain their food primarily from non-algae sources. This is because it is the algae itself, which contains most of the EPA.

EPA is unique in that it's effect may be more far-reaching than many other omega-3's. At least some research suggests EPA has a protective effect against depressive disorders including suicide, inflammatory conditions (DHA does this as well, making both EPA and DHA good potential candidates for ADHD patients with a concurrent inflammatory condition such as allergies), and may even combat certain types of cancer.

As an interesting aside, there is also some evidence that EPA (at very high doses) may interact with an important type of enzyme called CYP2D6. This enzyme is actually responsible for metabolizing a number of drugs including amphetamines (for ADHD) and a number of antidepressants (including Prozac or fluoxetine as well as Tofranil or imipramine), so extremely high doses of EPA may actually interfere with these medications. Additionally, some studies suggest that higher levels of EPA may reduce levels of natural killer cells (which play a big role in fighting off invading foreign bodies) in older adults. However, to reiterate, most of these observations were seen at high doses beyond the common range of dietary or supplemental levels.

Blogger's note: I found an excellent review article about ALA, EPA and DHA for those of you who are interested. It can be found here. Although a bit lengthy and technical, it greatly expands on our above discussion.

Now that we have given some background into some of the key omega-3 fatty acids and their functional roles, let's return to the four factors listed in the beginning of this blog on how omega-3 supplementation's effectiveness can be hindered.

Factor #1: Insufficient supporting nutrients for the conversion process:
The ALA to DHA and EPA conversion process involves a number of steps and a number of enzymes. These enzymes, however, do not function in a vacuum, but rather rely on a number of common vitamin and mineral "cofactors" to optimize their function. Some of these cofactors necessary to optimize function of these fatty acid conversion enzymes include magnesium, zinc, vitamin B6, and vitamin C. We have seen in previous posts how magnesium, zinc, and vitamin B6 supplementation may be helpful in ADHD cases, especially if nutrient deficiencies are suspected.

Factor #2: Deficiencies in the enzyme systems themselves:
Another possibility in the fatty acid metabolic differences in individuals with ADHD may be due to malfunctioning or lower enzyme activity, even if the above mentioned cofactors are in place. Lending credence to this hypothesis is the fact that certain forms of genes responsible for "coding" for these important enzymes are seen at higher levels in ADHD patients. One of these genes is called fatty acid desaturase 2 gene, or FADS2.

It's important to note 2 things here:

1. The FADS2 gene is believed to code for an important enzyme delta-6 desaturase. This enzyme is critical in several fatty acid conversion processes, such as ALA to DHA. As we will see in the next section, this same enzyme, delta-6 desaturase is also used in another fatty acid conversion process, LA to AA.

2. At least some genetic evidence suggests that some forms of the FADS2 gene are seen at abnormally high rates in individuals with ADHD. This hints at a potential association between ADHD and the FADS2 gene.

Please keep in mind that these genetic factors are a bit more tenuous than the other ones. This is good news, because it suggests that even more control of the disorder may lie in the diet instead of the genes (at least with regards to omega-3 levels and ADHD). However, it is also important to note that the body of research on this topic is constantly shifting and changing.

Factor #3 on omega-3 supplementation for ADHD: Different fats share the same enzyme (delta-6 desaturase):

Factor #1 tells us that if we want to be serious about getting the most out of omega-3 supplementation for ADHD and related disorders, we had better make sure that we are supplying the enzymes which churn out this important omega-3 conversion process with the necessary nutrients or "cofactors" (vitamins C and B6, magnesium and zinc, to name a few). Without these helping nutrients in place, the enzymes cannot do their job nearly as effectively, and many of the nutritionally based benefits of omega-3's may be lost.

Factor #2 states that expression of some of these enzymes (and the subsequent activity level of these fatty-acid metabolizing enzymes, such as delta-6 desaturase) is contingent on specific genes, such as the FADS2 gene. Certain forms of this gene are believed to appear at higher levels in the ADHD population. Unfortunately, this is a genetic factor, meaning that there is little we can do about this process.

However, a third factor with regards to manipulating enzyme systems involved in omega-3 fatty acid supplementation and subsequent metabolism is within our control, at least to a certain extent. This involves tilting the scale or balance of dietary fats which compete for the same enzyme system. Let me explain:

The typical conversion of the omega-3 fatty acid ALA (alpha linolenic acid, see description at the top of this post) to the important fatty acid DHA utilizes the enzyme delta-6 desaturase. Yes, this is the same delta-6 desaturase enzyme which is coded by the FADS2 gene in factor #2 (and whose expression may, at least indirectly be associated with ADHD by genetic factors). However, the conversion of other fats in the body also share this enzyme for their conversion process (think of 2 construction workers who need to share the same power tool at the same time, but for completely different sections of the project). One of these other "competing" fats is linoleic acid (abbreviated as "LA", be careful, unlike alpha linolenic acid, this fat is spelled without the "n"). LA requires this same enzyme delta-6 desaturase to undergo a conversion process to another important product called arachidonic acid (AA).

Please don't get too tripped up on all of these lengthy names, terms and abbreviations. The important thing to remember here, is that many different processes, including metabolizing different types of fats, often share the same enzyme systems. As a result, these different fats often "compete" for the same enzymes, and significant dietary imbalances of one type of fat over another may often lead to an imbalance of "output" or products of these fatty acids.

Arachidonic acid (a non-omega 3 fatty acid) is responsible for a number of necessary processes, including some of the inflammatory responses described earlier, but it is important to note that it is possible to build up an over-abundance of this, which can play a role in the buildup of unnecessary or chronic levels of inflammation. This is believed to be at least partly responsible for inflammatory diseases and disorders such as allergies (as an interesting side note, allergies are seen at higher levels in individuals with ADHD than within the general population).

To summarize this point, the conversion of alpha-linolenic acid (ALA, which is an omega-3) to DHA must "compete" alongside the Linoleic acid (LA, a non omega-3) to Arachidonic acid pathway for the same enzyme (delta-6 desaturase). If excessive amounts of non omega-3 fatty acids are consumed (which is typical in most Western diets), then this crucial ALA to DHA process is hampered. Of course an imbalance on the other side (too many omega-3's) is also a possible, but given the dietary makeup in much of the industrialized world, this is often highly unlikely.

So, to summarize Factor#3: Omega-3 supplementation, such as with fish oil, flaxseed oil or ALA is often compromised by the concurrent intake of high amounts of other fats, throwing off the delicate balance of dietary fatty acid intake.

Finally, there is one other extremely important factor, which is the main topic of this post. Factor #4 involves the fatty acid oxidation process.

Factor #4: Is ADHD an "oxidative" condition?

While numerous studies have linked ADD and ADHD to lower blood level ratios of of omega-3's and various essential fatty acids, some others are suggesting that the actual oxidation of these fatty acids may also be a problem in children with attention deficit disorders.

Omega 3's are especially prone to fatty acid oxidation (as anyone who uses pure, untreated omega-3 rich oils can attest, these oils quickly become rancid and have a much shorter shelf-life than the processed "partially hydrogenated" oils). This is actually one of the main reasons why trans fats came about. They are tougher to oxidize by bacterial systems than the "natural" fats and thus have a longer shelf life. Unfortunately, a lot of the health problems stemming from trans-fats is due to many of the same reasons (our bodies aren't quite sure how to process, break down or metabolize these fats).

One of the major targets of omega-3's is that they are able to incorporate into cell membranes. In general, omega-3 fatty acids make the cell membranes more flexible or fluid, while other fats often make these same membranes more rigid or hard, which can compromise the integrity of the cell membrane and the overall cell health. However, like omega-3 cooking oils, these cell membranes are constantly exposed to oxidative damage. This includes cells in the nervous system, which are highly "fatty", and thus extremely susceptible to oxidative damage. This is why it is so important to not just provide the nerve cells with abundant supplies of omega-3's to incorporate into their membranes but also protected omega-3's (that is to say, omega-3 fatty acids accompanied by adequate antioxidant protection).

Therefore, for disorders involving the nervous system, including ADHD, it is imperative that sufficient antioxidants are available to protect these key cell systems. Simply taking omega-3's, fish oils, etc. in an antioxidant-deficient state is less effective at best, and neuro-damaging at its worst. I personally believe that omitting antioxidant protection is the single-greatest saboteur of omega-3, fish oil, or flax oil supplementation's effectiveness for treating diseases and disorders such as ADHD.

So which antioxidants should we be taking?

Vitamin C readily comes to mind as one of the cheapest and most well-known antioxidants. However, one strike against this vitamin is that it typically exists in a water-soluble form (that is, it mixes well with water, and is why it is easily flushed out of the system and needs to be replaced on a daily basis. It is also a main reason why it difficult to overdose on vitamin C, since excess amounts can simply be flushed away with water). Remember that omega-3's are still fats, and that fatty substances often do not mix or interact well with water. Thus, vitamin C, at least in isolation, is not the best option for protecting these essential fats. A fat-soluble antioxidant may be a better option here.

Enter vitamin E. Unlike vitamin C, vitamin E is a fat-soluble vitamin, which has a greater potential to interact with fatty substances such as omega-3-laden membranes in the nervous system and other cells. Even better, vitamin E and vitamin C work well in tandem, helping recycle each others' antioxidant pools after countering oxidative-damaging agents in the nervous system and other parts of the body. This is evidenced by a number of studies which indicate that vitamin C can help recycle vitamin E levels.

Recommended daily amounts (and toxic levels) can be found here for vitamin C and vitamin E.

Finally, I would like to address one of the more recent "wonder-nutrient" brain foods which may pose therapeutic benefits for ADHD and related disorders: Pycnogenol/pine bark extract. There is some debate as to why this may be an effective natural ADHD treatment, but much of the evidence suggests that the effectiveness of pycnogenol for ADHD lies in its antioxidant properties.

So the key take-home messages from this post are as follows:

1. Omega-3 fatty acids show a significant amount of potential as natural ADHD treatment options (although they are often not nearly as potent as medication treatments in a number of cases).
2. Omega-3's rely on enzyme systems to do their job. Genetics can play a role in the functionality and effectiveness in some of these key enzymes.
3. In order for these omega-3 metabolizing enzymes to function, nutritional "cofactors" are required. These include most of the B vitamins, vitamin C, and important minerals or metals such as zinc or magnesium. Other cofactors, such as biotin (found in eggs) are also necessary agents to make many of these enzymes run smoothly. Deficiencies in these nutrients compromise enzyme integrity and can ultimately limit the effectiveness of omega-3 supplementation for ADHD and related disorders.
4. Omega-3's compete with other fats for many of the same enzymes and enzyme systems. They often produce competing products, so an overall balance of fatty acids is imperative. Taking a couple of fish oil capsules will not be enough to offset a diet chock full of unhealthy saturated or trans fats. Chronic inflammation disorders such as allergies, asthma, etc. can be a sign of (but are by no means the exclusive reason of) omega-3 deficiencies or an indication of an imbalance in fatty acid intake or metabolism.
5. It is imperative that these omega-3's be protected by adequate antioxidant levels in the body, as omega-3 fatty acids are often extremely prone to damage by oxidation, especially in the nervous system. Vitamin C/E combos, as well as other powerful antioxidants such as bio-flavonoids in colorful fruits, vegetables, teas, etc. are especially helpful in this regard, and should be taken as seriously as the omega-3's themselves as natural treatment strategies for ADHD.
   

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.

Dietary Magnesium and ADHD Comorbid Disorders

This is the third in a three-part series on the effects of magnesium intake on ADHD. We have seen previously how ADHD can be associated with dietary magnesium deficiencies, and how supplementation with magnesium can prove helpful. We have also seen that taking in vitamin B6 can boost magnesium's absorption into cells, improving its effectiveness for treating ADHD. The co-dependence of magnesium and vitamin B6 is reciprocated, as the enzyme alkaline phosphatase helps absorb the usable form of vitamin B6 into tissues in the body. This important enzyme requires magnesium to function properly.


We have also seen in previous posts that ADHD is often not an isolated condition. Accompanying symptoms such as Tourette's, bedwetting, sleep disorders, depression, allergies and an array of other comorbid disorders are often seen alongside ADHD. Some of these disorders also show statistically-low blood levels of key nutrients. Although this does not guarantee a common underlying nutritional deficiency as the root cause of both ADHD and these other disorders, it does suggest that we give a closer look to some of these overlapping factors.


In the case of ADHD and Tourette's, we see a shared deficiency in the essential mineral magnesium. Keep in mind that Tourette's has a huge overlap with both the OCD (Obsessive Compulsive Disorder) and ADHD. In fact, some estimates place up to 90% of individuals with Tourette's in the ADHD category. While I personally find that figure to be a little high, it is important that we see the magnitude of overlap of these two comorbid disorders, especially since they both share a noticeable connection with low magnesium levels.


Most of this post draws from information from an article in the journal Medical Hypotheses by BL Grimaldi. A summary can be found here. As the name of the journal suggests, this information is not based on a controlled clinical study, but rather a literature investigation combing through over a dozen different disorders and abnormalities commonly associated with Tourette's. ADHD is one of them, as are other common ADHD comorbid disorders such as allergies, Restless Leg Syndrome, seizures, depression, migraine headaches, teeth-grinding and obsessive compulsive disorder.


While all of these symptoms have some sort of connection to a magnesium or vitamin B6 deficiency, three of the strongest tell-tale signs are migraine headaches, allergies (especially on the skin), and hypersensitivity/hyperexcitability (negative over-reactions to stimuli such as touch. Erratic, jerky movements (not seizure-like, or tic-like, but rather rigid, jerky movements in he body, and the hands in particular) can also be caused by low magnesium levels. A study on magnesium-deficient rats showed high levels of inflammation and redness, especially in the ears. While a similar study (at least to the best of this author's knowledge) has not been done on humans, the prominence and rapid onset of this potentially key tell-tale sign should not be overlooked.


Some other key findings of the article are listed below:

• Magnesium deficiencies correlate with muscle spasms and over-excitability. In the last post, we saw that magnesium deficiencies were more associated with the impulsive or hyperactive components of ADHD than the inattentive component of the disorder.

• Estrogen helps the body take up and store magnesium, which is a big reason why men need higher levels of this key mineral than do women. Interestingly, the relative occurrence of both ADHD and Tourette's is much higher in males than in females.

• There is a genetic region on the 11th chromosome called 11q23 which has been linked to both magnesium retention and loss as well as Tourette's. Interestingly, this genetic region is relatively close to another region called 11q22, which is possibly connected with ADHD, based on some studies. This suggests that, the magnesium deficiency connection may not be entirely dietary, as there may be an underlying genetic factor at work behind low magnesium levels, Tourette's and ADHD. This relationship is relatively strong with magnesium and Tourette's, with the relationship with ADHD being more tenuous.

• We have seen in the last post how vitamin B6 and magnesium serve as complementary ADHD treatments. Additionally, this article mentions that both these key nutrients are essential for an important enzyme called kynurenase. Kynurenase breaks down the compound kynurenine. We do not want to have high levels of kynurenine around, because high levels of this interfere with the balance of a number of brain chemicals which, at imbalanced levels are connected with ADHD, Tourette's and various other related disorders. Two of these important brain chemicals that need to be balanced are GABA (which will be discussed in future posts) and dopamine, which are extremely important neurochemicals tied in to ADHD in a number of different ways.

• Additionally, low levels of kynurenase (and thus high levels of kynurenine) can indirectly result in low levels of the important brain chemical serotonin (which is very important for both specific types of ADHD as well as depression and Obsessive Compulsive Disorders). Several individuals with specific types of ADHD or depression take the supplement L-tryptophan, which is converted to serotonin in the body. Low levels of the enzyme kynurenase can result in a poor tryptophan to serotonin conversion, so inadequate kynurenase levels can invalidate L-tryptophan supplementation effectiveness. Therefore, low levels of magnesium and vitamin B6 can result in compromised activity of a key enzyme that helps maintain balanced levels of important chemicals in key brain regions which are often unbalanced in individuals with ADHD.

• Hormonal surges, especially those that occur during puberty (such as testosterone), can also can lead to an unwanted increase in kynurenine (see previous 2 points for the negative effects of this). This is especially true for vitamin B6 deficiencies. Therefore, it it imperative that adolescents, especially those with or prone to disorders such as ADHD, OCD or Tourette's to make sure they have adequate levels of vitamin B6, either through diet or supplementation. Additional information on sources and recommended levels of this vitamin can be found here.

• Additionally, kynurenine can result in constriction of blood vessels, reducing blood flow to key areas. Since individuals with ADHD often have restricted blood flow to specific brain regions (the frontal region behind the forehead is a common site), higher levels of kynurenine due to magnesium and vitamin B6 deficiencies can contribute to or worsen one of the underlying causes of the disorder.

• Finally, high levels of kynurenine can increase uncontrolled hyperactive behavior and amplify some of the negative effects of caffeine.

• In addition to affecting serotonin levels, low magnesium levels can alter the targets of serotonin, also called serotonin receptors. This can result in migraine headaches, making migraines a possible warning sign of low magnesium levels (it is suggested that up to 50% of migraine cases are connected to significantly low levels of a key form of magnesium).

• For Tourette's-like behavior, stimulant medications used to treat ADHD can exacerbate tics and other symptoms of Tourette's (see a related post on this topic here). This may pose as a problem for the large number of individuals who suffer from both Tourette's and ADHD. These effects are magnified even further if the individual is under some type of physical or emotional stress. Unfortunately, low magnesium levels can also prolong stress or anxiety by tripping some key target regions in the brain such as the amygdala (which is located in the center of the brain and is an important site of emotions and memory generation). As a result, low magnesium levels, combined with ADHD stimulant medications can both lead to and increase the duration of negative anxiety and stress in the body. This in turn can worsen tics and other negative symptoms associated with Tourette's Syndrome.

• Following approximately 2 weeks of magnesium deficiency, histamine and other pro-inflammatory agents begin to appear. The result is often some type of allergic reaction. Not surprisingly, allergies are a common side effect of both ADHD and Tourette's. Interestingly, some of these agents, such as histamine, can counteract some of the functions of vitamin B6, thereby propagating the negative magnesium/B6 deficiency cycle. On top of this, the heightened allergic response can stimulate the anxiety regions in the brain (see the previous point), which in turn, boosts prolonged anxiety and stress levels even further.

• Finally, low magnesium levels can trigger a product called Substance P, which, among other things, can boost itching of the skin, the desire to use profanity (one of the less-frequent, but most-associated signs of Tourette's), and even unhealthy sexual obsession. Not surprisingly, individuals with both Tourette's and ADHD are much more prone to risky sexual behavior. Substance P also reduces the body's ability to absorb an important nutrient called inositol, which is essentially a cross between a sugar and a B vitamin. Inositol plays a number of critical roles, including neural function, balancing fat stores in the liver, detoxifying the body, and preventing cholesterol buildup in arteries. As we can see, reducing the presence or activity of this key nutrient and limiting its absorption into cells due to magnesium and vitamin B6 deficiencies (as well as other factors) can have prolific and far-reaching negative effects on many of the body's systems.

Due to the current length of this post, I will stop here. In the next post, I will wrap up a few more things with magnesium and accompanying nutrients and their critical role in ADHD and related disorders. I just wanted to highlight the fact that these effects are far-reaching, and can have serious implications in the overall health of an individual. One month ago, I knew next-to-nothing about the many roles of magnesium, but as of now, I consider it one of the most underrated nutrients out there. Stay tuned for the next blog post, where we will discuss which forms of this key mineral are the best for supplementation, as well as which other ingredients to take alongside of it to maximize its effectiveness for treating ADHD and some of its comorbid disorders.