Tryptophan

Tryptophan is an essential amino acid. It has been implicated in playing a role in obesity because of its function as a precursor to various neurotransmitters that regulate homeostasis in the body. Once tryptophan is ingested, it can be converted to serotonin by serotonergic neurons in the brain. Serotonin neurons can affect the brain function of food intake—the serotonin neurons participate in the neuronal pathway that reduces the intake of food. Therefore, any abnormal metabolism of tryptophan could potentially be one of many causes of obesity and normalizing the level of tryptophan and correcting the abnormal metabolism pathway of tryptophan and serotonin can be considered a treatment for the obese.

Tryptophan is required in human diet and it is often found in dairy, meat, seeds, and nuts. It is mainly involved in protein synthesis; however, it can serve as a precursor to neurotransmitters or niacin. Tryptophan has been recognized to play a possible role in obesity due to its ability to convert to serotonin—serotonin has been known to participate in controlling sleep, appetite, mood, sexual behavior, and pain sensation. Serotonin neurons in the brain control appetite and a negative correlation is observed between the level of stimulation of those neurons and the amount of food intake.

When tryptophan is ingested as part of diet, it can be metabolized in various ways. First, tryptophan is normally modified to one of the two metabolites: 5-hydroxytryptophan or N-formylkynurenine. In the presence of the enzyme tryptophan 5-monooxygenase, tryptophan is converted to 5-hydroxytryptophan, which will be further metabolized to serotonin with the help of vitamin B6. Under certain conditions, such as stress, elevated cortisol level, vitamin B6 deficiency, or a high dosage of tryptophan (above 2,000 mg), the pathway to the production of N-formylkynurenine is preferred, reducing the amount of available serum tryptophan and 5-hydroxytryptophan.

Because serotonin is impermeable to the blood–brain barrier and needs to be synthesized by neuronal cells in the central nervous system after the uptake of tryptophan, the decreased availability of tryptophan in the central nervous system may compromise the adequate production of serotonin. Furthermore, lowered proportion of tryptophan to five other amino acids—tyrosine, phenylalanine, valine, leucine, and isoleucine, all of which share the same transporter molecule with tryptophan—can negatively affect the production of serotonin.

The serum concentration of tryptophan can fluctuate based on a variety of factors including stress and dieting. The drop in the serum concentration of tryptophan will lead to the reduced uptake of the amino acid by the central nervous system, which will in turn result in a decreased level of serotonin in the central nervous system due to its heavy dependence on the concentration of tryptophan to produce serotonin in the central nervous system. Because 5-hydroxytryptophan can readily cross the blood–brain barrier and serves as a precursor to serotonin, 5-hydroxytryptophan is being studied as an agent that reduces food intake by increasing the availability of serotonin.