The Role of Amino Acids in Mood Regulation: A Functional Medicine Perspective

Dietary amino acids play a crucial role in influencing various brain functions. In addition to their critical roles in energy metabolism, tissue growth and repair, immune function, and digestion, amino acids play a significant role in mood regulation and mental health through their involvement in hormone and neurotransmitter synthesis. The protein composition of a single meal can impact the uptake of amino acids into the brain and the synthesis of neurotransmitters. (32) 

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What Are Amino Acids?

In understanding the basics of amino acids, it is crucial to recognize their fundamental role in various physiological functions within the body. Amino acids are the building blocks of proteins, essential for synthesizing enzymes, hormones, and neurotransmitters. They contribute to the structural integrity of tissues, organs, and muscles, playing a pivotal role in overall health.

Amino acids are broadly categorized into two types: essential and non-essential. Essential amino acids are those that the body cannot synthesize and must be obtained through dietary sources. There are nine essential amino acids: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. In nutrition, a "complete protein" contains all nine essential amino acids. (26) 

On the other hand, non-essential amino acids can be synthesized by the body, even if we do not get them from dietary sources. However, this does not diminish their importance, as they are still vital for supporting various bodily functions. Non-essential amino acids include alanine, asparagine, aspartic acid, glutamic acid, and tyrosine. (2, 26)

Some amino acids are termed conditionally essential. This means that they are non-essential except in times of illness, stress, and periods of growth. Conditionally essential amino acids include arginine, cysteine, glutamine, tyrosine, glycine, proline, and serine. (2, 26)

Amino Acids and The Brain

Neurotransmitters are chemical messengers that transmit signals between neurons in the central nervous system to facilitate communication between nerve cells. Neurotransmitters are involved in a wide range of physiological processes, including motor control, sensory perception, cognitive function, and mood regulation. Imbalances or dysregulation in neurotransmitter levels can contribute to the development of various psychiatric and mental health conditions. (12)

Amino acids serve as essential building blocks in neurotransmitter synthesis. In particular, the aromatic amino acids – tryptophan, tyrosine, and phenylalanine – serve as precursors for the neurotransmitters serotonin, dopamine, and noradrenaline, which are key players in mood regulation. (32) 

Glutamate, another dietary amino acid, acts as neurotransmitter along with being a precursor for gamma-aminobutyric acid (GABA). Both glutamate and GABA are involved in mood regulation, but the direct link between dietary intake and their impact on brain functions is not fully understood. (32)

Tryptophan

Serotonin, also called 5-hydroxytryptamine (5-HT), is synthesized by the hydroxylation of tryptophan to 5-hydroxy-L-tryptophan (5-HTP), followed by the decarboxylation to 5-HT. Enzymatic cofactors required for these reactions include iron, folic acid, vitamin B6, and magnesium. (13)

Reduced serotonin levels are linked to anxiety, depression, other mental health disorders, sleep problems, and digestive issues (13, 34).  

Phenylalanine & Tyrosine

Catecholamines, encompassing dopamine, norepinephrine, and epinephrine, are molecules that act as both neurotransmitters and hormones. The synthesis pathway of catecholamines begins with the conversion of phenylalanine to tyrosine. Tyrosine serves as the precursor for synthesizing dopamine and norepinephrine, where it first undergoes a series of conversions to form dopamine. Once dopamine is created, it can undergo additional enzymatic modifications to give rise to norepinephrine. Essential cofactors for the reactions involved in this synthesis pathway include iron, folic acid, vitamin B6, vitamin C, and copper. 

Dopamine depletion is associated with feelings of fatigue, apathy, low mood, poor concentration, and the tendency to withdraw from social interactions (14). 

Low levels of norepinephrine can cause lethargy, lack of concentration, ADHD, and depression (3). 

Amino Acids and Mood Disorders

The most common nutritional deficiencies observed in patients with mental health disorders are amino acids, omega-3 fatty acids, and B vitamins. Results of clinical studies support the notion that amino acid supplementation is often helpful in treating mood disorders, including anxiety and depression. (24)

A small, randomized 2015 crossover study concluded that college students eating a diet high in L-tryptophan experience improved mood, as noted by fewer symptoms of anxiety, irritability, and depression, compared to those eating a diet low in L-tryptophan. A 2021 systematic review that included 11 studies investigating the effects of supplemental tryptophan on mood concluded taking 0.14-3 grams of tryptophan daily, in addition to dietary intake, is effective in decreasing anxiety and increasing positive mood.  

DLPA is a combination of D- and L- forms of phenylalanine. DLPA has been studied as an adjunctive therapy for depression with positive clinical outcomes. Small clinical trials have found that 50-200 mg of DLPA daily effectively reduces feelings of agitation, sluggishness, and depressed mood in as quickly as 15-20 days (5, 19). Other trials have compared DLPA to pharmacologic antidepressant therapy, revealing its ability to enhance positive clinical outcomes when used in conjunction with drug monotherapy. Furthermore, DLPA shows a comparative advantage by having fewer associated side effects than prescription medications. (4, 7) 

A 2017 study investigated the impact of a dietary supplement formulated with tyrosine, tryptophan, and blueberry extract during the early postpartum period. The researchers found that women who took the supplement over postpartum days 3-5 had dramatically reduced rates of postpartum depression compared to those who did not receive the supplement.

Dietary Sources of Amino Acids

Maintaining optimal amino acid status through a nutritious diet is fundamental for supporting overall health, cognitive function, and preventing various health conditions associated with amino acid deficiencies. Dietary sources of the amino acids emphasized in this article are listed below:

Tryptophan Sources

• Fish and Seafood: salmon, tuna, tilapia, lobster
• Meat and Poultry: beef, chicken, turkey
• Legumes: soybeans, tofu
• Nuts and Seeds: pumpkin seeds, chia seeds, walnuts
• Grains: quinoa, oats (6) 

Phenylalanine Sources

• Animal Products: beef, pork, turkey, fish, eggs
• Dairy: milk, cheese
• Grains: wheat, oats, quinoa, barley, rye 
• Lentils, nuts, and seeds (31) 

Tyrosine Sources

• Animal Products: chicken, turkey, fish, eggs
• Dairy: milk, cheese, yogurt
• Soy Products: edamame, tofu
• Legumes, Nuts, and Seeds: peanuts, almonds, lima beans, pumpkin seeds, sesame seeds
• Fruits and Vegetables: seaweed, avocado, banana (35)

Functional Medicine Approach to Amino Acid Balance

Functional medicine takes a personalized and comprehensive approach to addressing amino acid imbalances, recognizing the intricate connections between nutrition, biochemistry, and overall health. In addressing amino acid balance, functional medicine emphasizes personalized dietary strategies tailored to an individual's unique biochemical needs. This approach involves assessing specific amino acid profiles through advanced testing (discussed below) and then devising personalized diets that optimize the intake of deficient or imbalanced amino acids. Additionally, supplementation with targeted amino acids may be recommended to address specific deficiencies identified through these diagnostic assessments. Lifestyle changes, including stress management, are also incorporated into holistic protocols to support overall amino acid balance, as evidence shows that acute and chronic stress affect amino acid levels.

Lab Testing for Amino Acid Levels

Various options exist for testing amino acid levels to diagnose amino acid imbalances. 

Organic Acid Test (OAT)

The Organic Acids Test (OAT) by Mosaic Diagnostics is a comprehensive diagnostic tool that indirectly assesses amino acid levels by analyzing urine organic acid metabolites. This test provides valuable insights into the metabolic pathways and can reveal imbalances in amino acid metabolism. In the context of mood regulation, the OAT can help identify abnormalities or deficiencies in key neurotransmitter amino acid precursors and vitamin/mineral cofactors that are essential for neurotransmitter synthesis. If the OAT reveals imbalances in amino acid or neurotransmitter metabolism, healthcare providers can design a treatment plan to address these deficiencies. This may involve recommending specific dietary changes or supplements to restore optimal levels. 

Micronutrient Panel

A micronutrient panel, such as the Cellular Micronutrient Assay by Cell Science Systems, is a diagnostic tool that directly evaluates the levels of various essential vitamins, minerals, and amino acids in the body, offering a comprehensive overview of an individual's nutritional status. In the context of amino acids and mood regulation, a micronutrient panel can provide valuable insights into potential deficiencies or imbalances that may contribute to mood disorders. Similarly to the OAT, the results from a micronutrient panel can guide treatment plans by identifying nutritional areas of concern and helping healthcare professionals design targeted interventions.

Integrating Amino Acid Therapy with Other Treatments

A holistic approach to mood regulation recognizes that various factors, including genetic, psychological, and social elements, influence mental health. A functional medicine approach to mental health focuses on finding the root cause of symptoms and designing an integrative treatment plan incorporating nutrition, botanical medicine, exercise, sleep hygiene, and mind-body modalities alongside traditional treatment interventions. This comprehensive strategy aims to alleviate symptoms and promote long-term mental well-being by addressing the root causes of imbalances.

Other dietary supplements can be used alongside amino acid therapy to support endogenous biosynthesis pathways of neurotransmitters holistically and support mental health and cognitive function. As mentioned above, iron, magnesium, copper, and B vitamins 6, 9, and 12 are essential cofactors for the enzymes involved in neurotransmitter synthesis. Clinical studies show that supplementation with magnesium and vitamins B6, B12, and folate are associated with reduced symptoms of anxiety and/or depression over time (8, 28, 33). 

Bright light exposure, specifically through light therapy or phototherapy, has shown promising results in the treatment of depression, particularly seasonal affective disorder (SAD). Light therapy involves exposure to a bright light, typically mimicking natural sunlight, and is designed to regulate circadian rhythms and improve mood. (37)

An overwhelming body of evidence points to the positive relationship between exercise and mood. Exercise reduces symptoms by promoting the release of endorphins, which act as natural mood lifters, and improving blood flow and oxygenation to the brain. Physical activity also helps to regulate the stress hormone cortisol, contributing to a more balanced stress response. (22, 37)

Potential Risks and Considerations

While amino acid supplementation can offer various health benefits, it is crucial to be aware of potential risks and side effects associated with their use. Overconsumption of certain amino acids, especially through supplementation, can lead to imbalances in the overall amino acid profile, potentially causing adverse effects. For instance, excessive intake of branched-chain amino acids (BCAAs) may cause digestive upset or affect blood sugar levels. (20) 

Phenylketonuria (PKU) is a rare genetic disorder characterized by the body's inability to process phenylalanine due to a deficiency in the enzyme required to break it down. Without this enzyme, phenylalanine levels can become elevated in the blood and lead to the accumulation of harmful byproducts, which can negatively affect the brain. Patients with PKU require a low-phenylalanine diet, and phenylalanine supplementation would be contraindicated in this population. (29) 

Arginine is an amino acid that promotes the proliferation of some viruses. Following a low-arginine diet and avoiding arginine-containing supplements during viral illnesses and outbreaks is often recommended. (36)

Professional guidance is essential to ensure the safe and effective use of amino acid supplements. Healthcare providers, including registered dietitians or nutritionists, can assess individual needs, considering factors like age, health conditions, and medications, to provide personalized dosing recommendations to ensure the safe use of amino acid supplements.

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The Role of Amino Acids in Mood Regulation

Amino acids are an important nutritional factor in mood regulation, serving as building blocks for neurotransmitters that influence emotional health. A functional medicine approach recognizes the interconnectedness of nutrition, biochemistry, and mood. By embracing amino acids as integral components of mental health, individuals can consider tailored interventions, including dietary modifications and supplementation, to optimize neurotransmitter synthesis and support overall emotional balance.