In a review of natural product-derived treatments for ADHD, Ahn et al. (2016) explain how the amino acids glycine, L-theanine, L-tyrosine, taurine, acetyl-L-carnitine (ALC), GABA, 5-hydroxytryptophan (5-HTP), are all considered potential complementary ADHD interventions. The authors’ review was thorough, but since we don’t take anything at face value, let’s take a deeper look at each one of these amino acids, how they might help, and studies that have demonstrated their efficacy.
As I have mentioned in my previous posts, each individual with ADHD is unique. This means that what works for one may not work for all, because individual causes for ADHD will vary. You know your child best, and you know yourself best. That being said, considering the dangers of stimulant medications, I believe natural therapies are certainly worth trying under the supervision of your health care provider. Consistency is key. Some may experience immediate results, but some may need to be consistent and give the body time to adjust. Let us begin.
Glycine is an inhibitory (calming) neurotransmitter and it plays a role in regulating the motor and sensory information that permits movement, vision, and hearing. It modulates excitatory neurotransmission by increasing the effect of glutamate (the most abundant neurotransmitter in the brain) and also plays a role in transporting GABA (our primary inhibitory neurotransmitter) between neurons. In essence, L-Glycine is essential for proper brain balance of GABA and glutamate. A disruption of this balance has been implicated as a potential cause for ADHD, and drugs that promote that balance are being researched (Malapati et al., 2015). In fact, stimulant medications greatly increase the amount of glutamate in the brains of healthy people, and may be part of the reason that they work for children with ADHD (Brown University, 2018). It is logical to supplement with a calming amino acid that supports this balance.
Glycine is one of the three amino acid precursors of the most powerful antioxidant glutathione (produced by the liver). According to Aksoy et al. (2016), there is significantly increased oxidative stress in children with ADHD. Supporting their ability to combat that oxidative stress by supplying adequate glutathione precursors is essential. The other two glutathione precursors are L-cysteine and L-glutamate.
“Balance between excitatory glutamate and inhibitory GABA neurotransmitter is essential and critical for proper development and functioning of brain.” – Current Medicinal Chemistry, Malapati et al., 2015
I know you may want to rush out and buy some glutathione, but the body does not utilize glutathione well if taken directly. It is better to support the body’s ability to synthesis it. NAC (N-acetyl-cysteine) is another powerful supplement that supports glutathione production in the liver. I will be posting more about glutathione in the future.
GABA is an amino acid and a neurotransmitter that has a calming effect on the brain. Crocetti et al (2012) studied brain scans and found children with ADHD have reduced concentrations of GABA. So why not take GABA? It appears GABA supplements do not cross the blood brain barrier very effectively in ADHD. It is better to take the GABA precursors L-Theanine, L-Glutamine, and Vitamin B6 in its activated form P5P. Taking the precursors gives the brain what it needs to make adequate GABA.
One study in which boys age 8 to 12 years old were given 400mg L-theanine daily demonstrated that L-Theanine may represent a safe and important adjunctive therapy in ADHD (Juneja et al, 2011). Theanine is able to cross the blood brain barrier and has been proven to alleviate symptoms of anxiety and improve ADHD symptoms by helping to regulate dopamine and serotonin as well as increase the production of inhibitory (calming) neurotransmitters (Lardner, 2014; Ahn et al., 2016). L-Theanine has been proven to improve cognitive function including learning, attention, and memory (Lardner, 2014).
One theory for the cause of ADHD is rather than an issue with the quantity of available dopamine and norepinephrine, there is some kind of disturbance in the blood brain barrier that does not allow enough of the amino acid tryptophan to be transported across it (Ahlin et al., 2011). Tryptophan deficiency within the brain would not necessarily appear in typical blood work. To clarify, a person may have plenty of tryptophan circulating in their blood, but if the blood brain barrier won’t let enough of it in, there is a brain deficiency (and there is not currently an easy, available, and safe way to study brain deficiencies). And if there is a brain deficiency of tryptophan it can be assumed that there is also a serotonin deficiency since the brain utilizes tryptophan to create serotonin. This would disturb the serotonin-dopamine balance, which plays a role in ADHD symptoms.
It seems reasonable that supplementing with L-tryptophan would increase the available circulating tryptophan, and potentially allow more of it to cross the blood brain barrier.
To read more on L-Tryptophan and the serotonin-dopamine balance in ADHD read my previous post L-Tryptophan for ADHD: Amino Acids Reduce Symptoms
“Taurine is an amino acid made in the liver from cysteine that is known to play a role in the brain by eliciting a calming effect.” Lakhan & Vieira, Nutrition Journal, 2008
In an animal study, taurine reduced hyperactivity symptoms so significantly that it was proposed as an alternative treatment for ADHD (Chen et al., 2017).
Ripps and Shen (2012) emphasize the importance of taurine in their article “Review: Taurine: A “very essential” amino acid.” The authors explain that taurine is vital for normal brain development, for the protection of neurons and cells from toxic agents, for modulation of brain activity, and for modulation of intracellular calcium (Ripps & Shen, 2012). It also meets many criteria for consideration as a neurotransmitter, although a specific receptor site for taurine has yet to be found (Ripps & Shen, 2012). Kim and Schaffer (2018) further confirm the importance of taurine in their article “Effects and Mechanisms of Taurine as a Therapeutic Agent.” They explain that taurine is anti-inflammatory, antioxidant, lowers cholesterol, helps to treat cardiovascular disease and high blood pressure, regulates energy metabolism, regulates gene expression, and even inhibits brain injury in stroke and Alzheimer’s disease (Kim & Schaffer, 2018). I was unable to find any studies that specifically focused on taurine for ADHD, however studies and reviews do demonstrate that it is a GABA and L-glycine agonist (we have already discussed the research on GABA and L-Glycine for ADHD above). It is clearly vital for brain and overall health. I expect to see research on taurine and ADHD in the future.
ALC and L-Carnitine are used to transport fatty acids into cell mitochondria. The body can change ALC into L-carnitine as needed, and visa versa (it can also change L-carnitine into ALC). The importance of essential fatty acids for overall health (especially brain and heart health) has been well established. Indeed, essential fatty acid (EFA) supplementation is also extremely beneficial for ADHD (stay tuned for future post on EFAs). Here we are focusing on how ALC helps us properly utilize those healthy fats.
“Treatment with carnitine significantly decreased the attention problems and aggressive behavior in boys with ADHD.” Van Oudheusden & Scholte, PLEFA Journal, 2002
Another study found that in Fragile X Syndrome (FXS) children with ADHD, treatment with ALC at doses of 20-50 mg/kg/day was very effective and considered a safe alternative to the use of stimulant drugs for the treatment of ADHD in FXS children (Calvani et al., 2008).
In a study on boys and girls ages 5 through 12, Amato et al. (2007) found that Acetyl-L-Carnitine supplementation at weight-based doses from 500 to 1500 mg twice per day was more effective for inattentiveness than for hyperactivity.
L-tyrosine increases catecholamine production. Ahn et al. (2016) explain that ADHD is associated with disruption in catecholaminergic function in the brain. In fact, stimulant medications seem to mimic catecholamines as well as increase dopamine and norepinephrine levels, which seems to restore catecholamine balance. The problem is that these medications are dangerous, damage the liver, and damage long term brain health. By contrast, L-tyrosine is an amino acid found in protein-rich foods that we eat every day. L-tyrosine is the amino acid that is required for the production of dopamine, norepinephrine, and epinephrine. Cofactors include B6 (P5P), vitamin C, iron, and copper. Check your child’s multivitamin to be sure these cofactors are present, or be sure that your child is eating healthy foods that are rich in these nutrients. If you are not sure how much B6 is safe for supplementation, here is the chart for established upper intakes according to the National Institutes of Health (2018):
One retrospective study by Hinz et al. (2011) demonstrated that the use of a protocol including L-Tyrosine, 5-HTP and the necessary cofactors resulted in significant improvement of ADHD symptoms in 77% of study participants. They monitored neurotransmitter levels via urine testing during the stages of the study, and concluded that their results were actually superior to that of stimulant medication studies. Hinz et al. (2011) emphasize:
“Even if the finding was that use of serotonin and dopamine amino acid precursors with OCT assay interpretation was equal to reported efficacy values found with atomoxetine and methylphenidate, it is asserted that this approach would be superior because it does not share the adverse reactions, potential depletion of neurotransmitters, and neurotoxicity concerns reported with the group of drugs prescribed for ADHD treatment.”
5-HTP is a naturally occurring amino acid derived from the African plant known as Griffonia simplicifolia. It is able to cross the blood brain barrier, and it is a precursor to serotonin production (keep in mind that our bodies make melatonin from serotonin). Serotonin also plays a role in regulating dopamine. Kennealy, Patrick, and Seo (2008) explain that serotonin deficit could lead to symptoms of dopamine excess, and visa versa.
Dr. Hinz and his colleagues propose that an imbalance between serotonin and dopamine is the cause for a variety of disorders, including ADHD. They use urine testing to guide amino acid therapy and to evaluate if their amino acid protocol achieves the intended balance. As I mentioned above, the study demonstrates that balancing these neurotransmitters appears to significantly reduce or eliminate ADHD symptoms. I strongly recommend that you work with your health care provider if you want to try the L-tyrosine/5-HTP amino acid therapy. For information purposes, here is the Hinz protocol according to the 2011 study (link found in references). Patients start with level one, if symptoms are relieved they do not advance to level 2. If symptoms persist on level one dosing, the patient is advanced to level two dosing. If symptoms resolve, they do not advance. You get the idea. If symptoms persist even after level three dosing, the patient is reevaluated. Important to mention is that supplementing with only one of these may result in further imbalance.
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Ahlin, A., Bejerkenstedt, L., Fernell, E., … (2011). Altered tryptophan and alanine transport in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD): an in vitro study. Retrieved from https://behavioralandbrainfunctions.biomedcentral.com/articles/10.1186/1744-9081-7-40
Ahn, H., Ahn, J., Cheong, J., & Pena, I. (2016). Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757677/
Aksoy, N., Basmaci Kandemir, S., Bilinc, H., Kandemir, H., Kilicaslan, F., Savik, E., & Sezen, H. (2016). Increased oxidative stress in children with attention deficit hyperactivity disorder. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26886057
Amato, A., Arnold, L., Bozzolo, H., Cook, A., Crowl, L., Hollway, J., . . . Zhang, D. (2007). Acetyl-L-carnitine (ALC) in attention-deficit/hyperactivity disorder: a multi-site, placebo-controlled pilot trial. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/18315451
Brown University. (2018). ADHD drugs increase brain glutamate, predict positive emotion in healthy people. Retrieved from https://news.brown.edu/articles/2018/03/glutamate
Calvani, M., Chiurazzi, P., Cocchi, E., D’Iddio, S., Frontera, M., Garbarino, E., . . . & Vernacotola, S. (2008). A double-blind, parallel, multicenter comparison of L-acetylcarnitine with placebo on the attention deficit hyperactivity disorder in fragile X syndrome boys. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/18286595
Chen, L., Chen, V., Chou, H., Hsu, T., Tzang, B., & Weng, J. (2017). Effects of taurine on resting-state fMRI activity in spontaneously hypertensive rats. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507323/
Crocetti, D., Edden, R., Gilbert, D., Mostofski, S., & Zhu, H. (2012). Reduced GABA concentration in Attention-Deficit/Hyperactivity Disorder. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970207/
Hinz, M., Neff, R., Stein, A., Uncini, T., & Weinberg, R. (2011). Treatment of attention deficit hyperactivity disorder with monoamine amino acid precursors and organic cation transporter assay interpretation. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035600/
Juneja, L., Kapoor, M., & Lyon, M. (2011). The effects of L-theanine (Suntheanine) on objective sleep quality in boys with Attention Deficit Hyperactivity Disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Retrieved from http://archive.foundationalmedicinereview.com/publications/16/4/348.pdf
Kennealy, P., Patrick, C., & Seo, D. (2008). Role of Serotonin and Dopamine System Interactions in the Neurobiology of Impulsive Aggression and its Comorbidity with other Clinical Disorders. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612120/
Kim, H. & Schaffer, S. (2018). Effects and Mechanisms of Taurine as a Therapeutic Agent. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933890/
Lakhan, S. & Vieira, K. (2008). Nutritional therapies for mental disorders. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248201/
Lardner, A. (2014). Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23883567/
Malapati, A., Purkayastha, P., Sriram, D., & Yogeeswari P. (2015). A Review on GABA/Glutamate Pathway for Therapeutic Intervention of ASD and ADHD. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25666800
Ripps, H. & Shen, W. (2012). Review: Taurine: A “very essential” amino acid. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501277/
Van Oudheusden, L. & Scholte, H. (2002). Efficacy of carnitine in the treatment of children with attention-deficit hyperactivity disorder. Retrieved from https://www.plefa.com/article/S0952-3278(02)90378-9/pdf