5-Hydroxytryptophan (5-HTP)

5-Hydroxytryptophan, commonly abbreviated as 5-HTP, is a naturally-occurring derivative of the amino acid tryptophan.¹ It is instrumental in the production of serotonin, a neurotransmitter pivotal to mood and social behavior.

Adequate serotonin levels in the brain are associated with well-being and contentment, while depleted levels can contribute to depression and other mood disorders.

The potential benefits of 5-HTP include:¹

• Reducing caloric intake;
• Assisting in portion control and curbing snacking habits;
• Facilitating serotonin synthesis, which plays a role in satiety.

What Is 5-HTP?

5-HTP is synthesized in the body from tryptophan, an essential amino acid derived from dietary sources like eggs, cheese, salmon, nuts, and soy. However, merely consuming foods rich in tryptophan doesn’t guarantee a significant rise in 5-HTP levels due to the competition from other amino acids entering the brain. 5-HTP, when contrasted with tryptophan, can readily traverse the blood-brain barrier, thereby enhancing serotonin production.¹
Research since the 1970s has substantiated 5-HTP’s pivotal role in serotonin synthesis. A preliminary study from that era indicated that 5-HTP supplementation might favorably influence mood. Researchers observed that 5-HTP supplementation correlated with a 35% mood enhancement, in stark contrast to a 6% mood decline in the placebo group.²
While the 1970s study indicated the potential benefits of 5-HTP, there wasn’t an immediate surge in its supplementation, likely due to its high cost during that period. Today, 5-HTP has become more accessible and affordable to the general public. Modern 5-HTP supplements are derived from the seeds of the African plant, Griffonia simplicifolia. These supplements are both effective and bioavailable, with studies suggesting that as much as 70% of supplemental 5-HTP is successfully absorbed into the bloodstream.

How 5-HTP Might Benefit the Brain

Serotonin Production

5-HTP plays a crucial role in elevating serotonin levels, especially given that tryptophan, its precursor, can be redirected towards niacin or protein synthesis. An advantage of 5-HTP over tryptophan is its ability to easily cross the blood-brain barrier³. Furthermore, 5-HTP is more effective than tryptophan alone as a supplement, mainly because 5-HTP directly contributes to serotonin synthesis without the self-regulatory limitations encountered with L-tryptophan. To gauge the effectiveness of drugs in increasing serotonin synthesis or bioavailability, researchers use the 5-HTP-induced syndrome test, wherein the effectiveness is determined by the minimal dose of 5-HTP required to induce “serotonin syndrome”⁴.

Panic/Anxiety

There is a clear link between serotonin levels and panic episodes. While tryptophan depletion might not always precipitate panic attacks, it appears to increase sensitivity to panic-like symptoms, suggesting that serotonin serves a protective role in the short term⁵. In one study, both unmedicated panic disorder patients and healthy participants were given 200mg of 5-HTP prior to a 35% CO2 test (a method to induce panic). The study found that 5-HTP provided protective effects against the induced panic in both groups, particularly in those diagnosed with panic disorder⁵.

Mechanism of Action

L-5-Hydroxytryptophan (5-HTP) is produced endogenously in the body from the amino acid L-tryptophan with the assistance of the enzyme tryptophan hydroxylase. Another enzyme, aromatic amino acid decarboxylase, then converts 5-HTP into serotonin (5-hydroxytryptamine/5-HT). This neurotransmitter plays crucial roles in mood regulation, appetite control, and various cognitive functions. The metabolism of L-tryptophan can follow different pathways, depending on the body’s requirements. Consequently, ingesting 5-HTP might increase serotonin levels more effectively than taking L-tryptophan directly⁶. This easy crossing of the blood-brain barrier by 5-HTP makes it a promising therapeutic agent for conditions like depression. The beneficial effects of 5-HTP supplementation are believed to arise from enhanced serotonin concentrations in the brain. Subsequently, serotonin can be converted into melatonin, a hormone secreted by the pineal gland, vital for sleep regulation and circadian rhythms. Factors such as exposure to bright light can suppress melatonin production, whereas darkness promotes its secretion.

Recommended Dosage

Continuous use of 5-HTP should be approached with caution, as excessive levels might lead to a condition called serotonin syndrome, characterized by excessive serotonin in the brain⁷. The European Food Safety Authority (EFSA) advises taking two 150mg tablets daily with meals. If the primary goal is to improve sleep quality, it’s recommended to take one dose approximately an hour before bedtime⁷.

1. Supplements in Review. 2016, April 6. “What Are Neurotransmitters – And How Can I Make Mine Better?” https://supplementsinreview.com/nootropic/what-are-neurotransmitters/.

2. van Praag, H. M., J. Korf, L. C. Dols, and T. Schut. 1972. “A Pilot Study of the Predictive Value of the Probenecid Test in Application of 5-Hydroxytryptophan as Antidepressant.” Psychopharmacologia 25 (1): 14–21. https://doi.org/10.1007/BF00422612.

3. Wyatt, R. J., V. Zarcone, K. Engelman, W. C. Dement, F. Snyder, and A. Sjoerdsma. 1971. “Effects of 5-Hydroxytryptophan on the Sleep of Normal Human Subjects.” Electroencephalography and Clinical Neurophysiology 30 (6): 505–9. https://doi.org/10.1016/0013-4694(71)90147-7.

4. Pellow, Janice, Elizabeth M. Solomon, and Candice N. Barnard. 2011. “Complementary and Alternative Medical Therapies for Children with Attention-Deficit/Hyperactivity Disorder (ADHD).” Alternative Medicine Review: A Journal of Clinical Therapeutic 16 (4): 323–37.

5. Schruers, Koen, Rob van Diest, Thea Overbeek, and Eric Griez. 2002. “Acute L-5-Hydroxytryptophan Administration Inhibits Carbon Dioxide-Induced Panic in Panic Disorder Patients.” Psychiatry Research 113 (3): 237–43. https://doi.org/10.1016/s0165-1781(02)00262-7.

6. Schruers, Koen, Rob van Diest, Thea Overbeek, and Eric Griez. 2002. “Acute L-5-Hydroxytryptophan Administration Inhibits Carbon Dioxide-Induced Panic in Panic Disorder Patients.” Psychiatry Research 113 (3): 237–43. https://doi.org/10.1016/s0165-1781(02)00262-7.

7. EFSA. 2011. “Scientific Opinion on the Substantiation of Health Claims Related to 5-Hydroxytryptophan (5-HTP) and Increase in Satiety Leading to a Reduction in Energy Intake (ID 4223) Pursuant to Article 13(1) of Regulation (EC) No 1924/2006.” EFSA Journal, 9 (6): 2198. Accessed September 8, 2022. https://doi.org/10.2903/j.efsa.2011.2198.