Thursday, November 20, 2008

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:

  • 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.