Treating ADHD with Magnesium and Vitamin B6

In the last post, we examined how magnesium levels are tied to ADHD and how supplementation with magnesium can potentially help for the disorder. We will be adding one more step to this process by including the role of vitamin B6 into the mix of magnesium treatment for ADHD. Vitamin B6 has been shown to improve the absorption of magnesium as well as other minerals into cells, allowing higher levels of this key mineral to be attained. Essentially, this allows smaller doses of magnesium to be taken by making the intake process more efficient. Additionally, B vitamins have their own set of properties and numerous studies have linked the B vitamin family to improved mental function.

A study was done on the effectiveness of the Magnesium/Vitamin B6 combination treatment for ADHD. While the subjects of this study were young children, many of these results can carry over to adult cases of ADHD. A quick synopsis of the original publication can be found here. I will summarize some of the key points here:

• Individuals with ADHD have lower than normal levels of magnesium inside their blood cells than do individuals without the disorder. However, magnesium levels in the serum (liquid part of the blood which does not include the blood cells) were not tied to ADHD. Since Vitamin B6 helps get the magnesium into the blood cells, it is a key ingredient in treating ADHD with Magnesium.

• Low magnesium levels can also lead to irritability (which is also a potential side effect of Vitamin B6 supplementation by itself. This is another reason why taking Magnesium and B6 together can be useful). Hyperactivity, inattention, aggressive behavior and sleep problems are also associated with low magnesium levels. It also has been tied to reduced blood flow to the brain, which is a common phenomena frequently seen in brain scans of ADHD individuals.

• Treatment with magnesium and vitamin B6 reduced negative symptoms of inattention, aggressiveness and hyperactivity in a study of young children (average age around 6-7 years old). The amounts used were 6 mg/kg/day for magnesium and 0.6mg/kg/day for vitamin B6. This is roughly 100-200 mg of magnesium, which is in line with the recommended amounts (see here for these numbers) and around 10-20 mg for Vitamin B6.

• Although most ADHD symptoms were improved with Magnesium/Vitamin B6 treatment, the most improvement was seen in hyperactivity. Thus this Magnesium/Vitamin B6 treatment combination would likely have the most success in the Hyperactive Impulsive or Combined ADHD subtypes.

• Symptom improvements were seen the most in individuals who had higher (closer to normal) magnesium levels to begin with. This suggests that there may be some type of minimum threshold in cells or tissues that must be attained to achieve the desired results. This supports the idea that Magnesium/Vitamin B6 should be more of a long-term treatment strategy for ADHD, as opposed to a "quick fix".

• It also suggests that it may take awhile (2 months or more, based on some of the study's parameters) for the full effectiveness to kick in. This was further supported by the fact that when treatment was discontinued, the undesired ADHD symptoms returned within a few weeks. The good news behind this is that missing a day will not have the pronounced immediate effects of missing a day of a stimulant medication for ADHD.

• Speaking of stimulant medications, the article referenced other studies which noted that stimulant medications such as dextroamphetamine and methylphenidate boost magnesium levels in the blood. This is important to note, especially for individuals who already take ADHD stimulant medications. It is possible that combining these meds with magnesium/vitamin B6 supplementation can lead to magnesium levels above the upper limit. Please consult your physician before taking Magnesium/Vitamin B6, especially if you are already taking stimulant medications for ADHD. For more information on magnesium overdose and its symptoms, please click here.

This study presents compelling evidence that deficits in just one mineral can be a major factor in the onset of ADHD. It also suggests that a relatively simple treatment via slight dietary changes or supplementation can produce significant results in treating ADHD. Although the study had some flaws (relatively short duration, few test subjects and minimal placebo controls), the results are difficult to overlook.

In our next post, we will investigate the role of magnesium in some of the other disorders that frequently occur alongside ADHD, also known as ADHD comorbid disorders.

Magnesium Deficiency and Childhood ADHD

Magnesium Levels and the Connection to ADHD
In the last blog post, we talked about how an iodine deficiency in pregnant women can lead to ADHD and other cognitive dysfunctions in children. Iodine is just one of the many key nutrients that have been correlated with a worsening of ADHD-like symptoms. The effects of deficiencies for more well-known minerals such as iron and zinc are widely published. Low levels of both of these minerals have been associated with the onset of ADHD, and will be discussed in later posts. However, a lesser-known but equally important mineral relevant to ADHD and overall brain function is magnesium. There have been multiple studies linking low levels this key nutrient to an increased onset of ADHD.

Signs and Symptoms of Inadequate Magnesium Intake
Magnesium actually shares a functional overlap with iodine as far as proper bodily function is concerned. It plays a crucial role in maintaining function in a number of enzymes and other essential proteins. Additionally, like iodine, magnesium is essential for adequate bone health as well as maintaining adequate body temperature and energy levels. There are a number of signs of magnesium deficiencies which actually mask symptoms of other diseases, but some of the most distinctive signs of low magnesium levels are unexplained ulcers in the mouth area. Additionally, while allergies and asthma occur at higher levels in individuals with ADHD as comorbid disorders, the presence of ADHD, allergies, asthma and fibromyalgia (high levels of constant pain and sensitivity to touch) can be due to inadequate magnesium levels in the body.

Frequency of Magnesium Deficiencies and Recommended Daily Amounts
Like iodine, magnesium deficiencies are relatively common in industrialized countries. In children, these trends are even more ominous, with some estimates placing up to 90% of children in the magnesium deficient category. Recommended amounts typically fall within 280 to 400 mg per day, with men requiring slightly higher amounts than women. Seeds and nuts are among the best sources of this vital nutrient, with one of the best options being pumpkin and squash seeds (1 ounce provides about a third of the recommended daily amount).

**Please keep in mind that the recommended magnesium levels of 280 to 400 mg are for adults and older children. For newborns (around 30 mg/day) to children under 9 (130 mg/day), the requirements are lower. While there are no "food-based" upper limits for magnesium, there are for supplements. This is due to in part to different absorption patterns of the different magnesium forms in supplements as opposed to foods. Please click here to see some tables for recommended and upper limits of magnesium for children. Also, keep in mind that certain antacids and laxatives contain high levels of magnesium already, so please follow the upper limit max for supplements.

Treating ADHD with Magnesium Supplementation
Given the relatively low consumption of these foods by individuals in westernized countries, as well as the prevalence of nut allergies, supplementation with magnesium is another good option.
While both of the main components of ADHD (inattention and impulsivity/hyperactivity) are both associated with low levels of magesium, it appears that the hyperactivity factor is even more pronounced. The effectiveness of magnesium treatment is boosted by another key nutrient in the family of B vitamins, namely Vitamin B6. My next blog post will go into more detail about this treatment combination for ADHD.

Iodine deficiency or ADHD?

We have alluded to the fact in previous posts that ADHD symptoms can sometimes either be triggered or mimicked by nutrient deficiencies. If this is the case, then we can argue that by increasing the levels of these nutrients via food intake or supplements could ameliorate some of the negative features of the disorder.

While vitamin, mineral, protein and omega 3 fatty acid deficiencies often steal the spotlight for dietary intervention strategies for ADHD, there is another, less-heralded connection and treatment that deserves considerable attention. According to multiple journal articles, reviews and studies, there appears to be a correlation between an iodine deficiency and an increased likelihood of developing ADHD.

One such study on ADHD and iodine was published in the Journal of Endocrinology and Metabolism in 2004 by Vermiglio and coworkers. This study found that mothers who were iodine deficient were more likely to give birth to children with ADHD. While numerous nutritional deficiencies are often predominantly linked to Third World countries, Iodine deficiencies are surprisingly common in industrialized nations. Although little attention is often paid to this topic, the results of an iodine deficiency can be quite severe.

Since the thyroid gland and the hormones it secretes are heavily dependent on this key nutrient, low levels of iodine can lead to problems such as poor circulation and body temperature regulation, reduced energy levels, inhibited brain development and dysfunction, improper calcium levels in the blood and bones, and impaired immune function.

In a nutshell, the study examined the rates of ADHD in children who lived in 2 different regions, a relatively Iodine-rich region (where iodine deficiencies were more commonplace) and and Iodin-poor region. The 10-year study, which had a relatively small sample size, found that the rates of ADHD born to mothers at risk for facing an iodine deficiency was significantly higher than the rates of those born to mothers in a more iodine-sufficient environment. Furthermore, IQ scores were statistically lower in the low-iodine group.

We need to be careful not to lump ADHD into a general category of cognitive decline. After all, a very large percentage of individuals with the disorder are of average or above-average intelligence.

The overall mechanism of low iodine and the onset of ADHD is not completely clear, but there is a known correlation between low hormone levels (those secreted by the thyroid gland) and ADHD. Other studies, including one in the New England Journal of Medicine, have shown that individuals with a built-in resistance to thyroid hormones have higher incidences of ADHD. Individuals with a specific genetic mutation to the thyroid receptor-beta gene, are resistant to specific thyroid hormones and have roughly 3 times the risk of developing ADHD than the general population.

In the low iodine study, it appears that there was a bias towards hyperactive and impulsive behavior (as opposed to inattentive behavior), but with the small sample size used in the study, we should not put too much weight into this possible connection. Nevertheless, it is at least worth mentioning. Additionally, abnormal weight gain can also be a sign of an iodine deficiency, so an unexplained increase in weight accompanied by an increase in ADHD symptom severity may be due to an iodine deficiency and thyroid dysfunction.

Simple clinical tests can be done to determine whether an individual is iodine deficient and/or has thyroid dysfunction. One of the most common measuring devices is testing for the levels of TSH or Thyroid Stimulating Hormone. If an individual has underactive thyroid function (such as that caused by insufficient iodine intake), then the body tries to compensate for this by boosting thyroid function through increasing levels of TSH. Therefore, high levels of TSH correlate with an abnormally low thyroid function. Not surprisingly, in the pregnancy study on ADHD and iodine deficiency, mothers of ADHD children typically had elevated levels of TSH.

So how do we boost dietary iodine levels quickly and efficiently (the recommended daily amount is 150 micrograms, if that number means anything to you!)? One of the easiest ways is to replace common refined table salt with either iodized salt, or iodine-rich sea salt. Ocean fish and seaweed are also good bets as iodine-rich food sources.

One particularly good piece of information is that the developing fetus is surprisingly resilient to early stages of iodine deficiency in the mother if the iodine deficiency is corrected before the third trimester of pregnancy. Since the effects of an iodine deficient diet can be severe to both mother and child, I highly recommend pregnant mothers to switch to iodized salts or sea salt during the pregnant and nursing stages. This simple practice can significantly reduce the risk of ADHD and cognitive dysfunction in their child's future.

Natural Treatments to Try Before ADHD Medication

We have been spending a lot of time recently on medications for ADHD. However, one question we should always be asking ourselves is: "Are medications always necessary?".

Believe it or not, there are a number of nutritional deficiencies that can trigger ADHD-like symptoms or worsen the disorder. There are definitely instances where merely fixing key nutritional imbalances over a period of a few weeks can lead to positive results.

Before we go any further, we need to examine how this all works out. It helps to think of ADHD as a puzzle, where one or more pieces are missing. If we can correctly fill in the missing puzzle piece(s), then we can treat the disorder. Of course this is oversimplifying it a bit, and no, nutritional and "natural" strategies do not always work. Nevertheless, I believe they are grossly under-utilized. After all, if a vitamin supplement gave the same results as an amphetamine-based drug, which one would you choose for you or your child? The answer is a no-brainer.

Based on a keynote article on Ritalin vs. supplement treatments for ADHD, which is frequently cited by the "natural cures for ADHD" crowd, we see compelling (albeit limited) evidence that natural supplementation can be as effective as Ritalin for treating ADHD. It sounds intriguing, but it is also important to note that too much weight is often placed on this study. Why? Because all of this information is based on the results of only 20 individuals (10 whom took the Ritalin and 10 who took the dietary supplements). Of course we should not discount the research because of a small sample size, but out of the millions who suffer from ADHD, do we really want to hinge a bunch of expectations on 20 individuals? Nevertheless, the results are worth reporting and are due much further investigation.

Here are 9 different possibilities cited by the article for nutritional deficiencies or environmental factors which could affect the onset of ADHD (I subdivided one of the categories, there are only 8 in the original article). I will list them here, and investigate each one in more detail in later posts:

1. Food allergies and food additives
2. Toxic effects of heavy metals or environmental contaminants
3. Protein-carbohydrate imbalances
4. Mineral deficiencies or imbalances
5. Fatty acid deficiencies or imbalances
6. Amino acid deficiencies or imbalances
7. Thyroid dysfunction and iodine deficiencies
8. B vitamin deficiencies
9. Antioxidant levels, including phytonutrients and polyphenols (found in fruits, vegetables, coffee, teas, wines, beer and a few other sources).

Increasing Concerta Medication Dosage: Benefits and Risks

In the last post, we introduced the concept of dosage windows for ADHD medications. In other words, we see that the dosage level of an ADHD medication can be of equal importance to the type of medication used. For more info on this topic, please check out the blog site of Dr. Charles Parker called CorePsychBlog. It is extremely well-organized, concise, and easy to follow, in my humble opinion. This is where I was first introduced to the "window" concept of medications, the term which I have borrowed for the last couple of posts.

This post is meant to expound on the dosage principle in the context of on of the more popular ADHD stimulant medications currently on the market, Concerta (slow-release methylphenidate). We will be drawing information from a few key articles, including one from the 2003 Journal of Pediatrics by Mark A. Stein and coworkers. A copy of the original online journal containing a summary of this article can be found here.

If you do not have time to read all of this post, feel free to skip to the last paragraph at the bottom of the page to get the overall message of this blog entry. If you are looking for more detail, I have addressed the key points made in this article in the major points below:

• The drug Concerta releases the active methylphenidate ingredient into the system at slowly increasing levels over roughly a 12-hour period. The overall effect is similar to that of the traditional tri-daily methylphenidate medication.

• The article studied the positive and negative effects of this medication in 5 to 16 year-old children under three different common prescription doses, 18, 36 and 54 milligram doses. These children were of average or above-average IQ, with about 1/3 being diagnosed as Learning Disabled. About two-thirds of the children had never taken any type of stimulant medication for ADHD before the study.

• Noticeable differences were seen between different ADHD subtypes. For the Inattentive subtype, lower levels doses were optimal, while for the Combined subtype (inattention plus impulsive behavior plus hyperactivity), higher amounts were typically optimal. When the effects of co-occuring disorders such as oppositional defiance (ODD) and learning disabilities were factored out to focus in the ADHD itself, the subtype differences were even greater. This underscores the need for proper subtype diagnosis as opposed to just labeling an individual ADHD.

• For the Primarily Inattentive (PI) subtype of ADHD, the inattention difficulties improved most dramatically with the first 18 mg of medication. Beyond this dosage, only slight effects were seen. This is in agreement with another earlier study which analyzed different doses of another form of methylphenidate for treating ADHD. For the accompanying hyperactivity and impulsive behavioral symptoms (which are often present in the inattentive subtype, just not at the same elevated level of the Combined subtype) were most effectively reduced with the first 18 mg of the medication. While the effectiveness of higher doses leveled off, slight but noticeable improvements were also seen as medication dosage was increased from 18 to 36 mg. At 54 mg, however, improvements stopped or even regressed. This suggests that the "sweet spot" for the Inattentive Subtype of ADHD is somewhere around 18 mg (or slightly higher). Note that Concerta is also available in the 27 mg level, a dosage which was not tested in the study.

• In contrast to the Inattentive Subtype, where the greatest gains were seen from 0 to 18 mg of Concerta, for the Combined Subtype of ADHD, the greatest overall boost in effectivness was seen between 36 to 54 mg. Based on the trends of the graphs in the paper, as well as data from other studies, it appears that doses beyond 54 mg may still be of benefit for several individuals with the combined subtype. In other words, treatment of individuals with the Combined ADHD Subtype typically requires at least 18 mg more medication than those of the Inattentive Subtype (see note at end of the post for an important caveat and exception to this).

• Negative side effects of the medication were minimal at low (18 mg) to middle (36 mg) doses. However, beyond 36 mg, these negative side effects became more pronounced.

• Sleep problems (such as insomnia) began at the 36 mg dosage for Concerta, with the most pronounced effects seen in younger and smaller children.

• Noticeable appetite suppression was seen even at low doses (from 0 to 18 mg), especially for younger and smaller children. However, the overall severity of this was limited. However, the percentage of children who experienced "severe" appetite suppression dramatically increased between 36 to 54 mg treatments of Concerta.

• At 36 mg, the presence of or increase in tics (see related post on ADHD and tics) was seen, and a further increase was seen for some children at the 54 mg dosage.

• None of the dosage levels corresponded to blood pressure increases, and only minimal increases in pulse rates were seen. Compare this to another post on the cardiovascular risks of ADHD stimulant medications.

• A much earlier study on the ADHD medication methylphenidate (an earlier non-Concerta form) suggested that while hyperactive behavior continued to improve at higher doses, the ability to perform cognitive tasks decreased at higher levels of medication. While these effects were difficult to duplicate in future studies, it does suggest an upper limit for certain medications in which going above may lead to a reduction in improvement. We have seen similar effects in previous posts (see the "upside down U curve" in point #6 for tyrosine and clozapine treatment for ADHD here as an example).

A caveat and final blogger's note: Based on the conclusions of the study, it appears that going above the 54 mg limit may be beneficial for certain individuals of the Combined Subtype. While the data of the study may support this, it is important to note that the study only lasted 3 weeks. As a result, long-term effects of high doses of medication were unable to be observed. Additionally, we saw in one of the points above that negative side effects began to creep in at the 36-54 mg level. Based on other blog posts with regards to risk factors of certain ADHD medications as well as potential medication side effects, I urge you to err on the side of caution, especially on issues concerning young and small children (who are at much greater risk for developing severe side effects). In the above study, the highest dosage (54 mg of Concerta) was omitted for the smallest study participant as a precautionary measure.

A quick overall summary of this post: It is imperative that we take ADHD subtype seriously. The take-home message of this blog post should be that lower doses of methylphenidate are often optimal individuals with the Inattentive subtype for ADHD, while those of the Hyperactive-Impulsive (not studied in the above journal article) and Combined subtypes of ADHD typically require significantly higher levels of medication.