Carnitine: The missing link to omega-3 supplementation for ADHD
Carnitine is one of the new "trendy" supplements out there today, due in part to the number of heart-healthy benefits that can be derived from it's usage (often alongside other new popular supplements such as Coenzyme Q10). I am not here to discourage these supplements, I definitely see a number of positives from taking them, but for this post I would like to address the topic on Carnitine and ADHD: Can Carnitine, with all of it's heart-healthy benefits, actually be useful in treating ADHD? Here are 10 possible reasons why carnitine may be a powerful new treatment option for ADHD and related disorders:
As a quick aside: Carnitine, like many other nutrients, can exist in different forms, one of which is acetylcarnitine. This form, actually has a number of metabolic roles, but for the sake of simplicity, I will not go into too much detail about the different forms of carnitine unless absolutely necessary.
As a quick aside: Carnitine, like many other nutrients, can exist in different forms, one of which is acetylcarnitine. This form, actually has a number of metabolic roles, but for the sake of simplicity, I will not go into too much detail about the different forms of carnitine unless absolutely necessary.
- Potential for boosting the effectiveness of omega-3 fatty acid supplementation: We have already discussed the theory and applications of omega-3's and their possible benefits as alternative non-pharmaceutical treatment options for ADHD. Nonetheless, despite the recent surge in population of omega-3's (including the ever-popular fish oil supplements), only marginal amounts of improvements as far as behavior and symptom reductions are often seen. A big possibility for this limited effectiveness may actually stem from missing pieces of the puzzle with regards to omega-3 metabolism. This may include a deficiency in carnitine. There is even some speculation that abnormalities in fatty acid metabolism may play a role in autism, and that carnitine levels may play a role in this. Given the degree of inter-relationship between autism and ADHD, this possible connection may be at least worth mentioning. In particular, carnitine plays an important role in the synthesis of the docosahexaenoic acid (DHA), and a carnitine deficiency can result in a reduction of this key nutrient. Like several other important fatty acids, DHA deficency is often seen in ADHD individuals.
- Carnitine may be beneficial for "refractory" ADHD (unresponsive to conventional pharmaceutical treatment): This one is somewhat surprising. Typically supplementation and "natural" measures can be tried, but if they fail, the more "heavy-hitting" pharmaceutical treatment options for ADHD are often employed. However, a Dutch study done by Van Oudheusden and Scholte which investigated the efficacy of carnitine in treating children with ADHD mentioned that carnitine was found to be effective in treating ADHD in children who were previously unresponsive to methylphenidate, clonidine or behavioral therapy treatments.
What's interesting is that this group found a strong connection between plasma carnitine levels and a reduction in behavior problems (i.e., those children who were able to build up higher levels of carnitine in the blood were more likely to show direct benefit with regards to ADHD symptoms, while those with lower blood levels exhibited more severe ADHD-like behavior). This strongly suggests the carnitine/ADHD connection and also highlights the fact that there is a relatively wide degree of variation among individuals as far as carnitine storage and metabolism is concerned. Even more interesting, this same group found that when carnitine treatment was discontinued, the negative ADHD symptoms re-appeared relatively soon (within 3-4 weeks), but upon re-administration of the previous carnitine doses, the behavioral problems quickly subsided again. - Potential for use for both inattentive and hyperactive/impulsive ADHD: The same study on carnitine treatment for ADHD noted that a decrease in aggression and conduct problems (which are often comorbid to or co-occur with the more hyperactive/impulsive side of ADHD) upon treatment with carnitine. Not to be outdone, another study found that carnitine was more useful in treating the inattentive subtype of ADHD. Interestingly, the inattentive ADHD study found that individuals with the combined subtype ADHD subtype (which includes high levels of both the inattentive and hyperactive/impulsive behaviors) actually showed a worsening of symptoms upon treatment with carnitine.
It's important to note that the Dutch study did see some improvement in inattentive symptoms as well, so it appears (at least for now), that carnitine may be more of benefit towards treating the inattentive aspects of ADHD. This may actually be in line with other studies which link carnitine treatment to increased energy (individuals with the inattentive form of ADHD are often more likely associated to be more lethargic as opposed to the bouncing-off-the-walls behavior typically exhibited by the hyperactive/impulsive or combined ADHD subtypes). - Carnitine as a memory booster: I am personally hesitant to suggest supplementation with generalized memory boosters for ADHD (multiple ADHD websites love to do this), due to the distinct nature of the disorder. Nevertheless, individuals with ADHD do typically exhibit deficiencies in working memory, and some studies on carnitine on memory improvement are of interest. There is evidence that memory improvement from carnitine treatment may be seen in certain sub-populations. For example, carnitine treatment improved visual memory and attention in Down Syndrome patients, but the same effects were not seen in non-Down Syndrome individuals. Additionally, carnitine has also been shown to be useful in Alzheimer's dementia. The possibility that unique subsections of the population may be particularly receptive is intriguing, to say the least.
- Carnitine may play a role in reducing toxicity of other psychiatric medications: We have previously addressed the possible association of ADHD and epilepsy. Valproic acid, an anti-epileptic medication (which is also used in treating bipolar disorders, which often has a fair amount of overlap with ADHD itself) has risks of toxicity. However, carnitine treatment of Valproic acid toxicity has been shown in a recent study. In general, carnitine can also help the body clear toxic carboxylic acids from its cells.
- Carnitine's lack of addiction potential compared to stimulant ADHD medications: One of the classic problems with many medications (including ADHD stimulant medications) is the potential for addiction. In general, addiction potential is increased by rapid uptake into and rapid clearance by the brain. Although much more rare than prescription medications, herbs and supplements may also be addiction forming. However, there is a relatively slow uptake of carnitine into the brain, which reduces its addiction potential to virtually zero. While not entirely significant (addictions of similar types of nutrients are almost non-existent), it is worth mentioning, if for no other reason than to inform those who are looking for non-prescription alternatives to ADHD some of the benefits to nutrient supplementation.
- Acetyl-carnitine may offer the brain an alternative energy source during glucose shortages: Multiple studies have found glucose deficiencies in key specific brain regions in ADHD patients. A study found that glucose can actually inhibit the uptake of acetyl-carnitine into the brain, indicating a similar metabolic pathway. This conclusion of acetyl-carnitine as an alternative energy source was reached by the authors, however, it has been backed up by a body of research from numerous other studies. This seems to indicate that carnitine and its various forms may offer a viable means of alternative energy for glucose-starved ADHD brains.
- Carnitine plays a role in acetylcholine (and possibly dopamine) synthesis: Acetylcholine is an important neuro-transmitter in the brain. While it often takes a back seat to more well-known ADHD-related neuro-signaling agents such as dopamine and norepinephrine, several stimulant drugs which alleviate ADHD symptoms may target acetylcholine-dependent pathways (interestingly, nicotine appears to have a high degree of interaction with the acetylcholine receptors, and is often a popular drug of choice in ADHD individuals, often as a means to "self-medicate").
It appears that carnitine can help offset acetylcholine deficiencies in the brain, especially with regards to neuro-degenerative diseases. These effects can be even more pronounced if carnitine is co-administered with other key nutrients such as S-Adenosylmethionine (SAMe) and N-Acetylcysteine (NAc). To do these other two nutrients justice with regards to their effects on ADHD and related disorders or illness, they will need to be covered in their own separate posts. Finally, it appears that carnitine also affects dopamine-related pathways as well, which has numerous potential implications for ADHD, given that dopamine shortages and metabolic differences in key brain regions are often associated with the disorder. - Improved circulation via administration of carnitine (and vitamin E?): There is a mounting body of evidence that supports the assertion that individuals with ADHD have reduced bloodflow to key regions of the brain necessary for maintaining focus, eliminating distractions and maintaining attention to specific tasks. Certain ADHD medications, such as methylphenidate (Ritalin, Concerta, Metadate, Daytrana), can actually alter patterns of cerebral bloodflow in ADHD patients. It appears that carnitine can also improve blood flow to brain tissue (the study refers to the term "ischemia", which is simply a reduction of blood supply via blood vessels). These effects may possibly be increased even further, when combined with vitamin E, as highlighted in the same study. Carnitine can also help reduce ischemia to the spinal cord.
- Carnitine helps maintain cell membrane integrity: Numerous diseases and disorders are the result of damages to (or "leaky") cell membranes. These membranes are comprised mainly of fats, with several different proteins interspersed among the fatty acids. Ample omega-3 fatty acids play a critical role in maintaining a structure to the cell membranes, which is one of the reasons why adequate carnitine levels are so beneficial. However, fatty acids are prone to oxidation (think of a damage similar to rusting or corrosion, but within the body), so adequate antioxidant levels are needed to maintain these key components of cell structure and overall health.
In addition to its numerous other roles, carnitine is considered to be an antioxidant. Dietary deficiencies, as well as environmental stresses can leave these membranes prone to damage, resulting in a whole slew of potential diseases and disorders, such as increased risks of viral infections, allergies, buildup of cellular toxins, impairment of blood flow (this is actually related to our previous point on carnitine and ischemia) etc. In addition, cells contain inner membranes, whose structure and function can also be dependent on carnitine.
This is a good question, which, unfortunately, does not carry a straight answer. There is no official "RDA" for carnitine at the moment. One group studying carnitine metabolism suggested a recommended daily dose of carnitine to be 200 mg/day. The Dutch study used a dose that was proportional to the patient's body weight, 100 mg of carnitine/kg body weight to be precise. This corresponded to a maximum of 4 grams of carnitine (note that this study was done in children) for the study. Dosage at this level corresponded to about a doubling in plasma carnitine concentration. With regards to side effects, there were relatively few, although one individual discontinued the study due to onset of a strange odor emanating from his skin. It was believed that this may be due to a buildup of a compound known as trimethylamine, which has a characteristic fishy, ammonia-like smell.
However, some of the effects in other studies were seen at only a fraction of these doses, such as some reporting effects such as significant improvements in attention at only 25 mg carnitine/kg body weight. 50 mg/kilogram body weight was the dosage used in a study that found carnitine to be effective in combating hyperactivity. These studies are simply rough estimates for amounts needed to suppress inattentive and hyperactive/impulsive behaviors associated with ADHD. As far as safety and toxicity issues are concerned, there are few published reports about dangerously high levels of carnitine. For a one-year study on the effects of carnitine for ADHD boys, a daily dose of 1 gram per day was found to be safe. This study recommended 20-50 mg carnitine per kg of body weight, which is roughly one fifth to one half of the levels used in the Dutch study.
Regional/Geographic effects on carnitine supplementation for ADHD: A mult-site study on the effects of carnitine on ADHD by Arnold and co-workers made an interesting observation. They studied the effects of carnitine on ADHD symptoms in children in 10 different sites across the United States, and found that significantly more pronounced effects were seen in 3 sites in Ohio and northern Kentucky. All of these sites were about 150 miles northwest of the Allegheny Mountains. The other parameters (age range, demographics, ethnicity, ADHD symptom scores, doses of carnitine, etc.) were similar to the other sites, and the researchers in the study offered no explanation for the findings and suggested the difference to be merely coincidental. While this is obviously a possibility, this blogger offers a possible explanation: the potential effects of interaction between carnitine and minerals or heavy metals.
One possibility may have to do with magnesium deficiency in this particular region. Some studies note that the soil in the Allegheny region is deficient in magnesium due to erosion or poor soil management. It is possible that this magnesium depletion in the soil may result in a higher prevalance to dietary magnesium deficiency in these geographic regions. We have demonstrated the effects of magnesium deficiency in ADHD in several previous posts, such as one on Magnesium Deficiency and Childhood ADHD. However, we have also seen that magnesium can often work in conjunction with other vitamins, minerals and antioxidants in treating ADHD as well. These highlights can be found in an earlier post on magnesium combination treatments and ADHD.
Some research has found that magnesium can boost the activity of the enzyme Acetyl-CoA carboxylase, which plays a significant role in fatty acid biosynethesis. A fatty derivative of carnitine can also push this same enzyme along. It is possible, therefore, that carnitine supplementation may take over some of the roles of the depleted magnesium, thereby freeing up magnesium for some of the other ADHD-fighting fuctions as previously noted. Of course this is just a personal hypothesis, but this blogger earnestly believes that there are a number of carnitine-mineral interactions that have not been studied extensively that warrant further investigation.
Carnitine does not act in isolation:
If you get nothing else out of this post or any of the other posts in this blog dealing with nutrition strategies for ADHD, please remember this: nutrient therapies often do not work because not all the pieces are in place. In other words, the different nutrients are highly interdependent, and a missing piece or two can sabotage the whole system. I personally believe that this is why a number of ADHD supplementation strategies do not work to their full potentials, because they are often missing key ingredients. Instead, for ADHD combination treatments to be effective, it is vital that we begin to understand all of the individual steps of nutrient metabolism and their affiliation with the disorder.
Just from this post alone, we have seen that carnitine has potential interactions with:
Omega-3 fatty acids
Vitamin E and other antioxidants
S-Adenosylmethionine (SAMe)
N-Acetylcysteine (NAc)
Magnesium
Glucose
Coenzyme Q10
Valproic acid (and other medications often used to ADHD or disorders which often show up alongside of it)
The point is, is that the various ADHD medications and treatment alternatives do not exist in a vacuum. One of the goals of this blog is to further elucidate the many interactions and factors at work in the different treatment strategies for ADHD. We need to consider all possible food-food, drug-drug, food-drug, food-supplement, drug-supplement and supplement-supplement interactions in order to tailor an effective treatment method for any individual. It is my belief that only then will we be truly able to see consistently effective individual treatments for ADHD and related disorders.