Clinical uses of L-tyrosine in naturopathic medicine

What is Tyrosine and what is it used for?

L-Tyrosine, commonly referred to as just tyrosine, is a conditionally essential amino acid that the body makes from another amino acid, phenylalanine. Tyrosine is essential for the production of a family of neurotransmitters called catecholamines that includes epinephrine, norepinephrine, and dopamine.¹ Neurotransmitters are cell messengers that send signals from neurons to other cells in the body and in this case, play a role in mood regulation, memory, and alertness. Additionally, tyrosine is a precursor to thyroid hormone and melanin synthesis.¹

Recommended Dietary Allowance (RDA) for Tyrosine

Technically, there isn’t an RDA established for tyrosine and most people meet their needs by eating a variety of protein rich foods. In specific instances, supplementation may be necessary. Most studies utilize a dose of 100-150 milligrams per one kilogram of body weight in adults, but this varies for children and individuals with phenylketonuria.¹ It is best practice to take tyrosine supplements on an empty stomach since other amino acids may interfere with its absorption.

Food Sources of Tyrosine

Tyrosine can be found in a variety of animal and plant foods, including almonds, avocado, banana, beef, dairy, eggs, fish, lima beans, and soy products.¹

Signs of Tyrosine Deficiency

Tyrosine is considered conditionally essential because it’s made from the amino acid phenylalanine. When adequate phenylalanine is consumed from the diet, the body readily converts it to tyrosine. Therefore, a dietary deficiency in phenylalanine may lead to insufficient tyrosine.

The most common cause of a phenylalanine deficiency is the disorder of amino acid metabolism called phenylketonuria (PKU). People with PKU can’t break down phenylalanine, allowing it to build up in the body and accumulate in the bloodstream. Too much phenylalanine can be toxic to the nervous system and result in intellectual and developmental disabilities. The primary intervention for PKU is limiting foods containing phenylalanine which includes all high protein foods and may lead to a tyrosine deficiency.

Another risk factor for tyrosine deficiency is excess stress since prolonged periods of stress open the floodgates of catecholamines and over time, lead to their depletion. Some studies suggest that supplemental L-tyrosine can attenuate this response. Symptoms of a deficiency include hypothyroidism, low blood pressure, fatigue, learning and behaviors disorders, and depression.¹

Signs of Tyrosine Excess

Tyrosine toxicity is typically the result of over supplementation or a functional metabolic block in the thyroid, catecholamine, or melanin pathways that result in a buildup of tyrosine. Another cause of elevated tyrosine is a deficiency of copper, iron, iodine, vitamin C, or vitamin B6 since they are necessary cofactors for its conversion to the appropriate catecholamines. Symptoms of excess tyrosine include hyperthyroidism, depression, brain fog, nausea, headache, fatigue, and heartburn.¹ Clinically I do see some patients experience anxiety when taking tyrosine supplements, especially in patients with MAOA or COMT single nucleotide polymorphisms (SNP’s).

Safety of L-tyrosine

L-tyrosine supplements are generally recognized as safe by the FDA, but may interact with medications such as Levodopa, monoamine oxidase inhibitors, and thyroid hormones.² Studies on long term tyrosine use are not robust enough to draw any conclusions. As always, supplements should only be considered under the supervision of a medical provider.

In my medical opinion, L-tyrosine supplementation is safe, but not always well-tolerated. I would consider L-tyrosine supplementation in teenagers or late elementary-aged children (8+), watching carefully for signs of agitation or anxiety.

What is the difference between tyrosine and L-tyrosine?

L-tyrosine specifically refers to the natural form of the amino acid, and the “L” designation indicates the specific stereochemistry of the molecule. In organic chemistry, molecules can exist in different forms called enantiomers, which are mirror images of each other. The L- and D- prefixes are used to distinguish between the two enantiomers. The best way of describing this is to say that molecules have different “handedness,” just as our right and left hands are identical, but are mirror forms of one another. The L-form is the biologically active form that is used in protein synthesis and various biochemical reactions in the body.

Clinical uses of L-tyrosine in naturopathic medicine

Stress

Since tyrosine is the precursor to the catecholamines, it has a direct effect on the brain’s ability to synthesize dopamine and norepinephrine.³ In animal studies, stress increases the release of catecholamines and may result in their depletion, but supplementing with L-tyrosine may attenuate this effect.³ It’s important to note that tyrosine supplements appear to enhance the release of catecholamines only when the neurons are firing at an increased rate due to stress.³

One well researched effect of tyrosine supplementation is preventing cognitive decline caused by physical stress from extreme cold, high altitude, and extended wakefulness.³ Tyrosine supplements are often marketed as stress relieving and people may assume this applies to all types of stress. It’s important to note that the most significant effects are in preventing cognitive decline associated with physical stress, not psychosocial stress.³

Fatigue

Tyrosine may be associated with fatigue through its effect on the catecholamines since we know catecholamine depletion is associated with more fatigue.⁴ One study found improvements in alertness in individuals using tyrosine supplements during times of sleep deprivation.⁵ In this study, the usual performance declines in psychomotor tasks associated with sleep loss were improved in individuals who missed one night of sleep but supplemented with 300 mg of tyrosine.⁵ Rather than boosting energy, it seems that tyrosine decreases mental fatigue and improves cognitive functions like memory, learning, and alertness during stressful situations when one may be more prone to fatigue.

Depression

Tyrosine may impact depression, again through its influence on the catecholamines. Several animal studies have shown improvements in depression following L-tyrosine supplementation, particularly in depressive behaviors induced by cold exposure or hyperthermia (physical stress).

Another study on rats found positive behavioral results after treatment with L-tyrosine and the researchers attributed these results to a restoration of the basal levels of cerebral norepinephrine.⁶

In a human trial, healthy volunteers were administered a comprehensive neuropsychological battery of tests after being randomly assigned a balanced amino acid mixture or the same mixture without tyrosine and phenylalanine. Those who took the mixture void of tyrosine and phenylalanine were less content and more apathetic than the control group. Furthermore, they demonstrated a sad latency bias compared to the control group who exhibited a happy latency bias.⁷ Unsurprisingly, there was a marked reduction in cerebral tyrosine availability in the group who took the mixture void of tyrosine and phenylalanine.⁷

However, other human trials have not found statistically significant evidence supporting the use of tyrosine in adults with major depression.⁸ Although the results remain inconclusive in human trials, it’s likely that L-tyrosine can have a positive role in depression management by supplying the dietary precursors to norepinephrine and dopamine. Until there is more conclusive research, I recommend using L-tyrosine supplementation cautiously under the guidance of a trained naturopathic physician. I have found L-tyrosine to be most helpful in patients with mixed severe fatigue and depression. In patients with classic depression (anhedonia, lack of motivation, anxiety, insomnia, etc), other serotonergic herbs or supplements are significantly more helpful, in my opinion.

Mental clarity

Studies have found tyrosine supportive for mental clarity by promoting a number of tasks such as cognitive flexibility, multitasking, updating and monitoring working memory, stopping on time, and convergent thinking.⁹ Cognitive studies have found tyrosine loading to counteract the depletions in working memory and information processing that are triggered by stressful conditions like extreme weather or excessive cognitive load.¹⁰ Tyrosine protects against the pitfalls of demanding situations by neutralizing depleted brain catecholamine levels, i.e. refilling the brain’s tank of neurotransmitters!¹⁰ In short, increasing tyrosine intake during physically or mentally challenging conditions can benefit the aspects of cognition that are under catecholaminergic control and enhance cognitive function.¹⁰

Summary:

Tyrosine is an amino acid that plays an essential role in the production of catecholamines, thyroid hormones, and melanin. Most people consume enough tyrosine by eating a number of animal and plant foods, especially those that are rich in protein, but individuals with PKU will likely require a supplement. Supplementing with appropriate doses of tyrosine is generally recognized as safe but should still be supervised by a medical provider.

The clinical applications of tyrosine supplementation are limited and do not include trials on children. Tyrosine has been shown to prevent cognitive decline associated with extreme physical stress and sleep deprivation and enhance mental clarity in cognitively challenging circumstances. Evidence surrounding tyrosine use in depression remains inconclusive and thus prioritizing tyrosine rich foods is the safest way to support catecholamine production for mood regulation. In short, tyrosine has notable cognitive benefits during demanding situations by increasing the availability of catecholamines. Although clinical trials on tyrosine supplements in children are limited, prioritizing tyrosine rich foods during stressful times may be beneficial for their mood, mental clarity, and energy!

References:

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7. McLean, A., Rubinsztein, J.S., Robbins, T.W.et al. The effects of tyrosine depletion in normal healthy volunteers: implications for unipolar depression. Psychopharmacology 171, 286-297 (2004).
8. Gelenberg AJ, Wojcik JD, Falk WE, et al. Tyrosine for depression: a double-blind trial. J Affect Disord. 1990;19(2):125-132. doi:10.1016/0165-0327(90)90017-3
9. Steenbergen L, Sellaro R, Hommel B, Colzato LS. Tyrosine promotes cognitive flexibility: evidence from proactive vs. reactive control during task switching performance. Neuropsychologia. 2015;69:50-55. doi:10.1016/j.neuropsychologia.2015.01.022
10. Hase A, Jung S, Rot M. Behavioral and Cognitive Effects of Tyrosine Intake in Healthy Human Adults. Pharmacology Biochemistry and Behavior. 2015;133:1-6
11. Colzato LS, Jongkees BJ, Sellaro R, Hommel B. Working memory reloaded: tyrosine repletes updating in the N-back task. Front Behav Neurosci. 2013;7:200. Published 2013 Dec 16. doi:10.3389/fnbeh.2013.00200