L-Tryptophan is one the nine essential amino acids, but is one of the least plentiful found in the standard American diet. It is believed to improve mood, focus, and sleep quality.
L-tryptophan is metabolized in the liver by the rate-limiting enzyme tryptophan hydroxylase where it is then converted to 5-HTP, at which point it can then freely cross the blood-brain barrier where it is finally converted to serotonin [1]. Whereas supplemental 5-HTP can directly and freely influence serotonin production, the rate-limiting nature of L-tryptophan encourages balanced levels of serotonin.
Serotonin is an agonist for several different serotonin receptors in the brain. Many antidepressant drugs developed over the past 30 years, known as selective serotonin re-uptake inhibitors (SSRIs), have been developed with the intention of keeping serotonin levels active in the brain by reducing the activity of the SERT protein [2].
L-Tryptophan Deficiency
Low levels of tryptophan have been associated with poor mood [3, 4].
Tryptophan deficiency can be the result of chronic inflammation, in which enzymes are unregulated that inhibit serotonin production, or, deficiency can likely be the result of a diet lacking in the amino acid tryptophan [5, 6, 7].
Additionally, deficiencies of magnesium or vitamin B6 can downregulate activity of the rate-limiting enzyme tryptophan hydroxylase which is required to convert L-Tryptophan to 5-HTP [8].
Effects on Mood
Tryptophan is a precursor to 5-HTP which is used to produce serotonin, a neurotransmitter thought to be responsible for mood, anxiety, fear, depression, and aggression [9, 10, 11, 12].
Effects on Anxiety
Serotonin appears to be involved with anxiety and panic attacks. Studies using a tryptophan depletion technique (thought to be a reliable method to reduce serotonin) in humans have shown that the body may be more sensitized to panic-related symptoms, reduced mood, and increased anxiety when serotonin is depleted [13, 14, 15].
Effects on Sleep
Serotonin is broken down and then processed into melatonin via methylation [16].
Melatonin is crucial for healthy sleep cycles and supplemental doses up to 3 mg have been shown to improve sleep quality and reduce symptoms of insomnia [17, 18]. Supplementation of melatonin has been shown to increase serotonin in animal models, and increases of melatonin from supplemental L-Tryptophan have been noted to varying degrees [19, 20].
Seasonal affective disorder, a form of depression caused by lack of sunlight in winter months, is tied to serotonin deficiency [21]. This is possibly due to excess melatonin production from serotonin as melatonin production is controlled by light exposure and the circadian rhythms [22].
Side Effects
Gastrointestinal effects such as nausea, heartburn, vomiting, stomach pain, and diarrhea have been reported in abnormally high doses.
Gupta, A., Sharma, P. K., Garg, V. K., Singh, A. K., & Mondal, S. C. (2013). Role of serotonin in seasonal affective disorder. European review for medical and pharmacological sciences, 17(1), 49-55.
Rosenthal, N. E., Sack, D. A., Jacobsen, F. M., James, S. P., Parry, B. L., Arendt, J., ... & Wehr, T. A. (1985). Melatonin in seasonal affective disorder and phototherapy. Journal of neural transmission. Supplementum, 21, 257-267.
