The Manganese and Hyperactivity Connection

In a previous post, we examined whether lead exposure was responsible for worsening ADHD symptoms. We saw that there is a solid (although still somewhat hypothetical) connection between lead and hyperactive behavior. This lead to the blog's conclusion that high lead levels (the exact amount is still hotly debated, but a federal recommendations appear to be headed to a cutoff of around 10 micrograms lead/deciliter of blood. This converts roughly to half of a gram of lead total in the entire blood supply in the average adult male, or less than half a gram of lead total in a child's blood). This post can be found here.



A follow-up post suggested that adequate iron intake can help counteract some of lead's negative effects on ADHD and related symptoms through a variety of possible mechanisms. A link to this blog post can be found here.



Now it appears that another metal may be connected to hyperactivity. While the connection between manganese and hyperactivity appears to be more strained that that between lead and hyperactivity, it is at least worth mentioning. Additionally, manganese seems to be less tied to actual ADHD behavior (including inattention and impulse control problems alongside hyperactivity), and more towards generalized hyperactivity. Nevertheless, like the post on lead and hyperactivity mentioned previously, there at least remains that possibility that unhealthy buildup of manganese in the body may lead to hyperactive behavior. This could, at least hypothetically, "push" an individual with the predominantly inattentive form of ADHD to more of a mixed or combined subtype of ADHD, which includes hyperactive/impulsive behavior as well. A study of French Canadian children who lived in an area with naturally high levels of manganese found a significant tie-in between high manganese levels and hyperactive behavior. A summary of that study can be found here. Some key points of the article (along with some of my thoughts and comments) are listed below:

• Hair samples, while not a perfect method of evaluating manganese intake, is typically a good indicator of overall manganese exposure. This was the method used in the study of children in a region of Quebec, Canada with naturally high manganese levels in the drinking water. Children whose drinking water source came from a well with higher manganese levels showed consistently higher manganese levels in their hair samples.

• 46 children, ages 6-15 were examined in the study. Most were previously non-medicated and untreated for ADHD or related conditions before the study.

• A strong positive correlation was seen between high manganese levels in the hair and oppositional behavior scores in the children, as based on the teacher rating scale mentioned above. This was done using a form of the revised Connner's Teacher rating scales (a common method used for diagnosing ADD, ADHD and related symptoms and behaviors). For a brief synopsis of the different elements or categories of Conner's rating scales, please click here. Briefly, oppositional is characterized by "angry" or "annoyed" temperament as well as "rule-breaking" behavior.

• Additionally, an even stronger statistical correlation was seen between high manganese hair levels (above the study threshold level of 3 millionths of a gram of manganese per gram of hair sample, which was established based on detection methods and previous studies) and hyperactivity. Here, hyperactivity is characterized by restlessness and the inability to sit still, impulsive behavior and the inability to maintain adequate focus for a given task.

• Every single child who displayed the necessary score to be considered "hyperactive" or "oppositional" had manganese levels above the study cutoff amount of 3 millionths of a gram of manganese per gram of hair. Additionally, a large majority (11 of 13), who tested above the critical score for ADHD risk had manganese levels above the cutoff mark mentioned above.

• In contrast, cognitive problems (i.e. difficulty concentrating, slow learning, poor organizational skills) did not seem to be linked to manganese levels based on the study. Hypothetically, this suggests that high manganese exposure, should it be a factor in the onset and symptomology of ADHD, would likely be aligned or affiliated more with the hyperactive/impulsive subtype of ADHD and less towards the inattentive form of ADHD.

• Interestingly, the high degree of connection between high manganese levels and hyperactivity or oppositional behavior was not present in an analogous Conners Parent rating scale as it was for the teacher rating scale. While it may be simply due to differences in observational patterns and previous history with the children (i.e. parents may be more "accustomed" to specific behaviors based on long-terms relationships, or may be less objective in identifying problem behaviors in their children for a study), this should raise some questions to the replicability of this study and its findings. Additionally, it is possible that some of these observed behaviors are more relevant to an academic setting, and solutions such as trying to reduce manganese exposure at home, may provide more benefits in the classroom than at home. None of these should be ruled out as possibilities.

• ***Blogger's note: The following 2 points was addressed briefly in the manganese article, are rather long and complex and stray slightly off-topic. They can be omitted if necessary. Nonetheless, I think there are some interesting affiliations between this post, which deals primarily with manganese and common symptoms seen in ADHD and related disorders, and previous posts, which have dealt with genes associated with ADHD.
• Signaling and proper communication in the nervous system is dependent on certain chemicals such as GABA (which is also important for proper muscle tone and function) as well as dopamine and their respective systems or "targets". These complex systems in the body have been shown to be effected by high manganese levels. The negative effects of high manganese exposure are thought to work through these very systems. A quick summary of a study done on this can be found here.
• Interestingly, the very systems associated with these two agents (GABA and dopamine) are also thought to be affiliated with hyperactivity. A summary and link to the full article on this can be found here. Note that this study investigated a genetic connection between these systems and the onset of ADHD. Some of the genes indicated in this paper have been investigated in previous posts on this blog. Among these are the DRD4 gene, the DRD5 gene, and the DAT gene.

• We have seen previously in recent blog posts that there is a possible correlation between lead and hyperactive behavior thought to be associated with ADHD. However, the likelihood of interference from other environmental toxins on the outcome of the study was thought to be minimal. The area was investigated, and found to have relatively low levels of toxic metals such as lead, mercury or arsenic.

• There appear to be slight but noticeable differences based on age and sex. Based on the teacher (but not parent) rating scales, older children appeared to have more severe symptoms of ADHD behavior, hyperactivity, cognitive impairment and oppositional behavior. While the effects were relatively small, there remains the possibility that cumulative exposure to elevated levels of manganese can lead to increased impairment over time. However, I am personally not comfortable in making this assertion based solely on the limited scope of this study.

• What I did find interesting was the fact that girls showed substantially higher manganese concentrations in their hair samples than did boys. I am intrigued by the possibility that there may be hormonal reasons behind this, especially given the context of a previous post which mentioned that magnesium has a tendency to be stored better in females due to the effects of estrogen, and iron levels are thought to be lower in females due to menstruation as well as other effects.

• Alluding to this same earlier post, we have seen that iron is thought to counteract some of the negative effects of lead on hyperactivity and related ADHD behaviors. Interestingly, iron absorption in the body has been found to be hampered by manganese, based on a 2003 study. While the amount of iron in the water was found to be high in the French Canadian study, it is entirely possible that the manganese levels were sufficient to counteract these effects. It is unfortunate that the study did not take blood samples to investigate possible iron deficiencies in the subjects.

While the study made several noteworthy observations, there are too many loose ends and questions left to be answered before determining whether manganese can pose similar risks to lead as far as inducing hyperactive behavior and ADHD-related symptoms. As of now, we are unsure whether the effects were do more to interference with iron absorption (given that numerous studies have shown that individuals with ADHD are typically iron deficient) or through a non-iron-based regulation of the GABA and dopamine pathways mentioned above. Further clouding this is the fact that iron itself plays a key role in dopamine synthesis and manufacturing.

As of now, my conclusion is that there is a possible correlation between high manganese and ADHD (especially the hyperactive form), but this connection is much weaker than that of lead (which is debatable in its own right at the moment). It certainly appears that manganese is more tolerable and overall more benign than lead, at least with regards to similar levels of exposure.

Unlike lead, manganese is actually a trace element micronutrient (i.e., it's good for the body at low levels). Manganese-rich foods include teas, beans, nuts and many types of whole grains. Additionally, excess manganese can be cleared more easily from the body than can lead. While common sources are food and drinking water (with water thought to be a more potent source of intake than food), inhalation is also a common mode of entry. This is especially true of specific occupations such as welders. Typical blood manganese levels hover around 1 microgram of manganese/deciliter of blood. This roughly translates into about .05 grams total manganese in the bloodstream.

It is easy and often tempting to try to assimilate anything and everything to a disorder such as ADHD. Many professionals and researchers often fall into this trap. However, I caution against this, since this clouds the picture as to what the real underlying causes of the disorder might be. That is why I urge restraint before passing judgment on this particular metal, at least in regards to its causative role with respect to ADHD and related disorders.

Certainly, manganese toxicity is a problem, with the deleterious effects of manganism (sometimes referred to as "manganese poisoning" and is characterized by loss of balance and coordination and impaired reaction timing) going back hundreds of years and still seen in certain metal-related occupations such as welding. Nevertheless, the relative ease of excretion of manganese (at least when compared to other heavy metals such as lead) and somewhat higher limits of tolerability make it a possible foe in the ADHD symptom world, but not a powerful one, at least for the time being.

In the next post, we will be shifting gears a bit and looking into the connection between celiac disease and ADHD and its degree of association with specific symptoms of the disorder.

Using Iron to Combat the Effects of Lead in ADHD

In the previous post, we were discussing the potential connection between lead exposure early in life and the subsequent onset of ADHD symptoms. We saw that higher lead levels are more likely to be associated with the hyperactive or impulsive symptoms of ADHD than the inattentive symptoms. At the moment, the amount of lead necessary to precipitate these negative symptoms is debatable, especially when individual variations are taken into account. However, a rough estimate of upper level lead limits can be found here. At the end of the post, I alluded to the fact that iron supplementation either via diet or pills may be effective as a possible treatment option. I will go into some of the details here:

Iron supplementation has been found to be useful in multiple cases regarding ADHD. Numerous studies have indicated that a large percentage of individuals with ADHD are iron deficient. Iron is responsible, among other things, for the synthesis and regulation of levels of the key brain chemical dopamine. Dopamine deficiencies are often seen in multiple brain regions (especially in the area behind the forehead, called the prefrontal cortex) in individuals with ADHD. Additionally, iron is a key component of hemoglobin, which is responsible for carrying oxygen in the blood to other organs and tissues in the body. Not surprisingly, many ADHD individuals have lower than average oxygen levels delivered to their brains.

Finally, other co-existing or comorbid disorders of ADHD also have been associated with iron deficiencies. One of the most notable is Restless Leg Syndrome (RLS), which is characterized by unwanted leg movements during rest, and is thought to be a major contributing factor to many types of sleep disorders and impairments. Individuals with ADHD have been shown to suffer from Restless Leg Syndrome at disproportionately high frequencies, when compared to the general population and iron deficiency may be a key contributing factor to Restless Leg Syndrome seen alongside ADHD.

However, one of the unexpected benefits of iron, especially with regards to ADHD, is its potentially protective role in reducing the negative effects of early lead exposure. In a couple of correspondences in the August 2007 edition of the journal Environmental Health Perspectives, some key findings were summarized involving the protective role of iron to lead-induced damage. One of them (based on previous literature) reported on how lead can negatively impact levels of free dopamine (which is often correlated with ADHD, as many of the positive effects derived from most stimulant medications is due to their abilities to boost levels of dopamine in between neuron cells).

Additionally, lead is also thought to inhibit the interactions of dopamine and its targets as lead can alter the presence of these targets or dopamine receptors. Both of these reduce proper dopamine function, and it is thought that adequate levels iron can offset some of these negative effects (on the flip side, iron deficiencies are thought to exacerbate several of these negative occurrences). Finally, iron is also thought to restore a balance in the blood-brain barrier, which serves as a sort of controlled gateway, regulating the passage of nutrients and necessary neuro-signaling chemicals into (as well as keeping toxic substances out of) the brain. The role of iron is thought to restore and offset some of the negative and damaging effects of lead on the blood-brain barrier, which is especially sensitive to toxins during the early stages of life and childhood.


There is some dispute and controversy over some of these findings, however. Another study (which is frequently cited in numerous journals on toxins/heavy metals and ADHD or cognitive disorders) was done on the protective effects of iron and zinc on Mexican schoolchildren exposed to lead showed no statistically significant results as far as improving cognitive function.

While I do not advocate excessive iron supplementation, (watch for upper limits which are described here), I do strongly suggest that pregnant and nursing mothers, as well as children and adults with ADHD do ensure that their iron intake is adequate. It is interesting to note that magnesium deficiency is also affiliated with increased ADHD symptoms. Due to the role of estrogen in improving magnesium retention, women require less daily magnesium than do men (a table of recommended daily magnesium intake can be found here). However, in iron, the opposite is true. Several factors, including less efficient iron binding and loss of iron due to menstruation and pregnancy result in higher iron requirements in pre-menopausal women. A summary of recommended iron levels for men women and children can be found here.

In addition to the potential role of iron in protecting against lead damage, will be discussing how boosting iron intake can offset the effects of ADHD and other related comorbid disorders in future posts.

Does Lead Exposure Cause ADHD?

Many of these findings were based off of an original journal article regarding prenatal tobacco and lead exposure and the onset of ADHD by Braun and coworkers in the December 2006 issue of the journal Environmental Health Perspectives. For a quick synopsis of this article on lead and ADHD, please click here. Interestingly, this same group also published more recent papers on the effects of lead on conduct disorders, which are often comorbid to ADHD cases. This should be especially relevant for pregnant or nursing mothers. For more information on ADHD and pregnancy, please check out the collection of posts on this blog addressing the topic, which can be found here.

While the relevance of several studies regarding the effects of lead on ADHD and cognitive dysfunction is called into question, often because the lead-levels reflect a much higher exposure than what is often faced by the general population, a relatively large study done recently indicates that even moderately high blood lead levels show a strong correlation with ADHD. This suggests either one of two things:

• Other unknown or "hidden" factors were present in the lead-based studies which were the major contributors to impaired mental function and disorders such as ADHD. Even with lower lead levels, these under riding factors were still present, and therefore the major contributing causes to the disorder were still present.

OR

• The sensitivity to lead exposure in children is even higher than previously thought.

An important question we should be asking ourselves is "Does lead exposure beyond a certain point trigger specific ADHD symptoms, or is there an increase in ADHD behavior across the board?".

ADHD is often defined by two major components, the hyperactive/impulsive component and the inattentive component. Based on a recent publication by Nigg and coworkers in the February 2008 Journal of Biological Psychiatry, it appears that the hyperactive/impulsive component of ADHD predominates based on exposure to lead.

Interestingly, the children investigated in the study above were of the inattentive subtype or the combined subtype (both inattentive and hyperactive/impulsive) of ADHD. Based on these results, it is my personal opinion that a child who, under other circumstances may otherwise be of the ADHD inattentive subtype, could instead fall into the ADHD Combined Subtype if he/she is exposed to a specific quantity of lead during the prenatal or early childhood stages of development. Furthermore, I propose that, had the individuals in the study have been of the predominantly Hyperactive/Impulsive Subtype of ADHD, the results would have shown that lead exposure beyond a critical thresh hold would have exacerbated the already-negative hyperactive behaviors for this particular subtype.

In addition to the negative effects surrounding the hyperactive elements of ADHD, the study also found a correlation between low-level lead exposure and child IQ's. This, of course, has been a hotly debated topic for years. While other factors may clearly be at work (lead exposure is often higher in areas with lower socioeconomic status, which is also a factor often correlated with lower IQ scores), the results of numerous studies, many of them recent, still support a strong possible connection.

Theoretically, then, by significantly reducing the prenatal or early-developmental exposure to lead, a child may be at least partially shielded from negative symptoms such as a lower IQ and hyperactive behavior. However, for individuals with the predominantly inattentive form of ADHD, these lead-restrictive measures would be less effective in addressing their inattentive behaviors. Therefore, it is my opinion that reducing lead exposure due to prenatal intervention, iron therapy, or, even possibly chelation methods (both of which will be discussed in future posts), would be most effective for treating the Hyperactive/Impulsive and Combined subtypes of ADHD and less effective for the Predominantly Inattentive ADHD Subtype.

While we should be careful not to overplay or overhype the lead/ADHD connection (especially given the fact that overall lead exposure risks have gone down throughout most of the world in recent years due to the uses of unleaded gasoline and lead-based paint, among other things), it is important to recognize that there is still a statistically significant connection between the two, at least according to a number of recent studies. The Nigg paper, mentioned above, found a strong correlation with hyperactive ADHD-like behavior at much lower lead levels (much closer to the average levels found in much of the United States) than those in most previous studies. This information is particularly important to pregnant mothers, since it has been demonstrated that the negative effects of lead, and other heavy metals and toxins are more harmful on developing brains and nervous systems than to mature ones. The protective effects of reducing lead exposure to mitigate the negative symptoms of ADHD, should not, in this blogger's opinion, be overlooked.

In the next post, we will be discussing how treatment or supplementation with iron may be able to offset some of these harmful effects of early lead exposure on ADHD, should they occur.

Magnesium Combination Treatments for ADHD

The previous 3 posts have all addressed the role of magnesium in the causes and treatment of ADHD and related disorders. Here I will address some of the guidelines as to how to boost the effectiveness of magnesium treatments in ADHD patients. This will include information on which forms are the best and which other compounds or nutrients, when used in combination with magnesium, can help the absorption and processing of this key mineral. Please keep in mind that these are recommendations and findings compiled from hundreds of medical journal articles and clinical studies. Do not take these suggestions as medical advice until you consult with your physician!

Some guidelines are listed below:

• Based on age, gender and a few other factors, recommended amounts of magnesium levels range from 80 to 420 mg/day. For a detailed breakdown on the amount recommended for you, please check out this link here. Due to the role of estrogen, which helps in the retention of magnesium, females typically require less of this nutrient than males.



• Several forms of magnesium are available. These include magnesium chloride, magnesium oxide, magnesium lactate and magnesium aspartate. A study on human absorption patterns showed that magnesium oxide had much poorer absorption than the other three forms. Other forms include magnesium sulfate, magnesium hydroxide, magnesium acetyltaurinate, magnesium citrate, and magnesium carbonate.


• Of potential interest is the form magnesium acetyltaurinate. This form contains both magnesium and a chemically modified version of the substance taurine. Taurine, which is often seen in energy-boosters and “memory” drinks, has been shown to aid the absorption of magnesium into cells in mammals (as do several other compounds such as vitamin B6). It is important to note that this study was done in rats as opposed to humans, but, due to the high crossover of nutrient absorption and metabolism between the two species, I feel that this finding is at least worth mentioning. Although a rarer (and often more expensive) form of the mineral, magnesium acetyltaurinate may essentially provide “two-for-one” deal, thereby making it superior to other magnesium forms. Note that this conclusion is merely hypothetical at this point and should be treated as such. Nevertheless, with the support of your physician, it may be a strategy worthy of investigation for treatment of ADHD and related disorders.

• In a recent post, we have seen how elevated levels of the compound kynurenine can lead to numerous difficulties and exacerbate the symptoms of ADHD and related disorders. A derivative of niacin (short for nicotinic acid or vitamin B3), which is called nicotinamide, has been shown to reduce the unwanted high levels of kynurenine, especially in the brain. Additionally, it has also been shown to reduce spasms in the blood vessels, thereby improving blood flow to the brain and reducing the likelihood of a brain hemorrhage and stroke. These findings are summarized in a journal article by BL Grimaldi (an abstract of the article can be found here).

• As previously mentioned, vitamin B6 (pyridoxine) can boost the absorption of magnesium. We have seen in an earlier post that zinc can be used to boost the effectiveness of methylphenidate (Ritalin, Concerta), in certain cases. Additionally, zinc is required for optimal function of certain enzymes needed to process vitamin B6 such as pyridoxal kinase. Not surprisingly, zinc deficiencies are common in individuals with ADHD and related comorbid disorders. Vitamin B6 boosts the effectiveness of magnesium, vitamin B3 helps offset the buildup of unwanted levels of kynurenine, which is often seen in magnesium deficient individuals, and zinc aids in the processing of vitamin B6. Thus we're beginning to see how all of these vital nutrients do not act merely in isolation, but rather how they can work together to reduce the negative symptoms of ADHD and related disorders.

• We have seen above that vitamin B3 can offset the buildup of unwanted kynurenine, which can be induced through magnesium deficiency. However, there are other key nutrients which are often reduced through prolonged periods of inadequate magnesium intake. Depleted levels of many antioxidants are often seen and need to be replenished. Among these are vitamin C, vitamin E and glutathione.

• Glutathione, which is manufactured in the body, is among the most widespread and potent antioxidants used in the body. However, in order to stay in it's "de-oxidized" functional form, it needs help from dietary antioxidants. Vitamins C and E work with each other as well as with glutathione to keep adequate "pools" of glutathione available for the body's natural antioxidant defenses. Inadequate levels of glutathione can lead to the onset of numerous diseases, damage to the outer covering of cells and tissues, allergies, asthma, neural dysfunction and a wide array of other disorders. Magnesium deficiencies place unwanted stress on the body and reduce the body's available levels of glutathione. Thus, vitamin C and E are needed to "repair" this damage. Recommended levels of these two vitamins can be found here for vitamin E and here for vitamin C. These levels reflect recent changes in which the recommended doses of both vitamins have been bumped up.

• ***Blogger's note: You may have read a number of references or seen a number of websites for ADHD and multiple other ailments touting the benefits of compounds such as pycnogenol (also known as French Maritime Pine Bark Extract), and grape-seed extract. As of now, I am neutral as far as using products such as these. However, it is important to note that the majority of the benefits derived from treatments such as these are due to their antioxidant effects, which are quite powerful by the way (however, other functions besides mere antioxidant effects have been suggested and are entirely possible). Additionally, these supplements can be quite costly. It is this blogger's opinion that similar effects and benefits can be seen with vitamin C and E supplementation for a cheaper price. Nonetheless, the large number of studies supporting the effectiveness of pycnogenol and grape-seed extract does warrant further investigation and potential success as an ADHD treatment option. With you're doctor's permission, pycnogenol or grape seed extract may be worthy of a trial run.
  

• One final ingredient which is highly recommended for adding to the "pile" of nutrients for ADHD and related treatments is lecithin. The reason I personally hold in in such high regards is that it restores multiple components which may have been compromised by prolonged magnesium deficiency. Among these are essential omega 3 fatty acids (which are often found to be compromised in a wide range of diseases and disorders such as depression, heart disease, asthma, allergies, blood clotting and strokes, ADHD, multiple other neural disorders, Tourette's, chronic inflammation, and a whole slew of other ailments) such as alpha-linolenic acid, which is sometimes abbreviated as ALA.

• Additionally, lecithin provides rich levels of inositol which is a special type of sugar which is often listed as a B-vitamin (however, by definition, it is not, since inositol, unlike vitamins, can be synthesized in the body. Nevertheless, it functionally behaves in a manner similar to several other B vitamins and is therefore sometimes classified as such), as several key agents necessary for proper cellular structure and neuronal function. These agents include phosphatidylcholine (which is needed to maintain cell structure, helps regulate breakdown of fats, and is also used to help cells communicate with each other), phostphatidylinositol (which is also required for cell communication or signaling), and phosphatidyl ethanolamine (which is a fatty tissue found in high concentrations in the brain, spinal cord and throughout the nervous system). Inositol itself is also a key "messenger" by facilitating cell-cell communication.

• In addition to their utilization for cell structure and cell membrane integrity, some of these agents (namely inositol) have been shown to be effective antidepressants, having similar effectiveness and modes of action to the SSRI (selective serotonin re-uptake inhibitor) class of antidepressant medications. A summary of some of these findings can be found in a review by Grimaldi (abstract of article listed here). There is no official recommended amount for lecithin, but two tablespoons of the granular form are often administered by physicians. For good natural sources of lecithin, please click here.

• While it provides many absorption-related benefits, magnesium can reduce the absorption and effectiveness of certain antibiotics such as tetracylcine. If you are taking this antibiotic for a short period of time, you may want to consider temporarily reducing your magnesium intake/supplementation.



• Additionally, people with kidney disorders often have difficulty processing and removing magnesium from the system. It is imperative that this is discussed with a physician before deciding on magnesium supplementation.

The main idea of this post is to introduce to you the importance of including all of the pieces of the nutrient puzzle for treating ADHD and related disorders. A quick list of nutrients which must often be used in conjunction include: magnesium, vitamin B6, vitamin B3 (niacin), zinc, antioxidants (vitamin C and E, pycnogenol, grape-seed extract), and multiple components of lecithin (inositol, omega-3 fatty acids, and neuro-regulating agents and their derivatives). To summarize:

1. Magnesium deficiency is thought to be a common underlying cause to ADHD and related comorbid disorders. Increasing magnesium intake via diet or supplementation can offset some of these problems. Recommended magnesium levels and natural sources can be found here.
2. Vitamin B6 boosts the uptake of magnesium into cells. Additionally, an enzyme which helps absorb vitamin B6, called alkaline phosphatase, requires magnesium to function properly. Therefore, vitamin B6 and magnesium function in a cooperative manner, and enhance each other's effectiveness. Recommended vitamin B6 levels and natural sources can be found here.
3. In addition to magnesium, several enzymes required for the processing and proper metabolism of vitamin B6 need adequate zinc levels to function properly. Recommended zinc levels and natural sources can be found here.
4. Deficiencies of magnesium can lead to a harmful buildup of kynurenine. Treatment with vitamin B3 (niacin), can offset some of these harmful effects. Recommended vitamin B3 (niacin) levels and natural sources can be found here.
5. Magnesium deficiency can cause a depletion of antioxidants (especially glutathione) in the body. Increasing the intake of antioxidants such as vitamin C and vitamin E (which complement each other and work great together in tandem), grape-seed extract or pycnogenol can replenish and restore the proper antioxidant balance to the system. Recommended levels and natural sources can be found here for vitamin C and here for vitamin E. No official levels for grape-seed extract or pycnogenol have been established, but common treatment levels and dosage information can be found here for pycnogenol and here for grape-seed extract.
6. Low magnesium levels can also result in depleted amounts of several key fats or fatty-like substances necessary for proper nerve (as well as other types of) cell structure and function, as well as proper cell-cell communication. Lecithin is a great source of many of these deficient components, and is a good replacement method of treatment. There is no official recommended daily amount for lecithin, but for more information on common dosage levels of lecithin please click here.

You have hopefully seen how these key ingredients all work together and how a deficiency in even one of these can inhibit the effectiveness of the other nutritional agents.

Keep in mind that all of these can be obtained from natural food sources. It is not my intention to turn anyone into a "supplement popper". However, if your dietary patterns leave you prone to deficiencies in any of these nutrients, I do recommend supplementation. However, please check with your doctor before doing any of these treatment suggestions. Also, keep in mind that this list is not extensive. I will be discussing some other essential nutrients (such as iron, whose low levels are often connected to ADHD and related disorders) in future blog posts.

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.