Tryptophan is interesting in that it is the sole precursor of the inhibitory neurotransmitter serotonin. The relative percentage of tryptophan in protein sources is small in comparison to the other amino acids (roughly 1%). Additionally, the degradation of tryptophan occurs via two pathways: the kynurenine pathway that is responsible for 90-95% of tryptophan degradation and the minor pathways that lead to serotonin and melatonin (serotonin synthesis). The kynurerine pathway leads to two metabolites, quinolinic and kynurenic acid, which act on the NMDA receptors (glutamate receptor) as either an agonist (neurotoxic) and antagonist (neuroprotective) respectively (1). Interestingly, the kynurenine pathway is involved in UV protection of the retina, which naturally declines with age (2). The kynurenine pathways is also involved in the formation of NAD and NADP necessary for redox reactions. To a lesser degree, tryptophan degradation along the kynurenine pathway is involved in niacin (B3) synthesis. (1,2)
Tryptophan uptake in the brain has been shown to be in competition with other amino acids, tryptophan being largely protein bound and will predominantly cross the blood brain barrier in the free form. Therefore, in a normal diet, the amount of tryptophan uptake to the brain is influenced by the amount of plasma tryptophan, relative to the amount of other amino acids, thereby contributing to a smaller synthesis of serotonin. Other factors that influence serotonin synthesis are B6 and magnesium deficiency, insulin resistance, and stress (3). However, the ratio of circulating plasma tryptophan to other competing amino acids appears to be the largest factor. Serotonin uptake in the brain has also been demonstrated to be increased by insulin stimulation or carbohydrate intake (1). In (Richard, 2009) review, the authors provide summaries of some early studies on the manipulation of tryptophan through diet: a study on three equivalent calorically high carbohydrate meals during the day demonstrated increased tryptophan ratio only after the first meal: BREAKFAST! And acute alcohol ingestion has also demonstrated a lowered ratio of tryptophan to amino acids, which in healthy individuals may not be a big difference, but could affect someone who is vulnerable to low serotonin production - are but a couple of examples. While dietary changes can have a small impact, they are unlikely to significantly contribute to increased serotonin clinically. (2,3)
What is also interesting is that immune stimulation (i.e. infections) and chronic stress can cause the degradation of tryptophan to favor the kynurenine pathway. It has been postulated that this could be a mechanism by which stress can affect things such as mental health, sleep, and digestion. Furthermore, one of the metabolites along this pathway, quinolinic acid, can increase oxidation stress, further contributing to dysregulation of the nervous system. Acute stress, on the other hand, appears to increase serotonin uptake to the brain, via increased sympathetic activity, but the underlying mechanism is unknown. (1,3) Which is why, contrary to what we would think, we cannot solely increase serotonin by increasing it's pool of synthesis. There appears to be other players at play! And the aspect of arousal, is one of them. (2)
The biochemistry and metabolism of tryptophan have been discovered from cellular and animal studies.
Tryptophan depletion studies in both animal and humans have demonstrated an increase in social aggressiveness. Findings from other studies point to increased agreeableness and decreased quarrelsomeness with increased tryptophan/serotonin. These studies do not point to a clear relationship of tryptophan-serotonin-mood in humans however. Low serotonin can contribute to low mood, but is not in itself a cause of low mood. It is suggested that improved social behavior in and of itself contributes to improved mood. (2)
A tryptophan depletion study in individuals suffering from obsessive compulsive disorder, who respond to standard SSRI, demonstrated that tryptophan depletion had not so much an effect on anxiety and other OCD symptoms, but could potentially be linked to a shift in "habitual responding" to goal-directed responding. This was observed because compared to placebo, those taking the tryptophan depletion drink demonstrated decreased perception control and an increase in interfering thoughts. (4)
Tryptophan has a rich history dating as far back as the 1900's. It was banned, put back on the market, made into a prescription only pill, and even has an entire journal dedicated to its research.
My goal here is not necessarily to say supplementing may be good or not good, or ok, but understanding these mechanisms can provide some insight into the understanding of things, and make connections about behavior.
1. Badawy, AAB. (2017) Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects. Int J Tryptophan Res. March 15: 10.
2. Young, SM. (2013). Acute tryptophan depletion in humans: a review of theoretical, practical, and ethical aspects. J PSychiatry Neurosci. 38(5):294-305.
3. Richard, DM et al. (2009). L-tryptophan, basic metabolic functions, behavioral research and therapeutic indications. Int J Tryptophan Res. March 23.
4. Hood, SD et al. (2017). Effects of tryptophan depletion on selective serotonin reuptake inhibitor-remitted patients with obsessive compulsive disorder. J Psychopharmacol. 31(12):1615-1623.