Tryptophan

Elevated tryptophan may be seen in high protein diets or supplementation. Stress, insulin resistance, magnesium or vitamin B6 deficiency, and increasing age can all inhibit the conversion of tryptophan to 5-HTP and elevate tryptophan.

Lack of nutrient cofactors (vitamin B6, riboflavin, iron, and heme) in several other tryptophan pathways can also contribute to elevations.

Lastly, glutaric aciduria is a rare inborn error of metabolism characterized by elevated tryptophan.

Low levels of essential amino acids may indicate a poor-quality diet, or maldigestion due to deficient digestive peptidase activity or pancreatic dysfunction.

Because some dietary tryptophan is converted to niacin, tryptophan-deficient diets have been associated with lower niacin production. Interestingly, niacin administration increased plasma tryptophan by 40%. Clinically, low serum tryptophan levels have been shown to correlate with depressive symptoms and cognitive impairment.

Tryptophan is involved in serotonin production via vitamin B6-dependent pathways resulting in the intermediate 5-hydroxytryptophan (5-HTP). 5-HTP is often used as a supplement for serotonin formation instead of tryptophan, which can be quickly metabolized in other pathways.

Serotonin is further metabolized to melatonin via methylation.

Because of these downstream conversions, therapeutic administration of 5-HTP has been shown to be effective for depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.