5-HTP supplements: serotonin, evidence and interaction risks

A 2020 review in the International Journal of Molecular Sciences describes 5-HTP as both a drug and a natural component of some dietary supplements. The body makes it from tryptophan using an enzyme called tryptophan hydroxylase, and decarboxylation turns it into serotonin, the messenger involved in mood, memory, reward and sleep. Serotonin is then converted to melatonin, which helps regulate the sleep-wake cycle. Making 5-HTP is the rate-limiting step in this chain, which is the reason supplement makers focus on it.

Chemical synthesis is not economically practical at scale, so commercial 5-HTP is usually extracted from the seeds of Griffonia simplicifolia. The review notes that extraction and measurement of 5-HTP in plant material is laborious and sensitive to other compounds, which is relevant to how consistent the content of a given capsule is.

The same review reports that most clinical trials have looked at depression, anxiety, panic attacks and sleep disorders, with some work on obesity and migraine. Early studies suggested 5-HTP could act as an antidepressant with relatively few side effects, and the authors mention a small crossover trial showing improvement in depressive symptoms against placebo. They describe this as preliminary evidence, and they also report that some of the earlier work combined 5-HTP with other drugs such as monoamine oxidase inhibitors or decarboxylase inhibitors, which is not how supplements are taken.

The NHS description of depression treatment centres on talking therapies, antidepressants and lifestyle measures, and mentions St John's wort as an example of a herbal remedy that doctors do not recommend because the active ingredients vary between brands and batches and it interacts with other medicines. 5-HTP is not part of NHS care. Anyone with persistent low mood, loss of interest or thoughts of self-harm should see a GP, and in a crisis contact NHS 111, Samaritans or emergency services.

Serotonin syndrome is a medication-induced state of excess serotonergic activity. The review describes its triad of altered mental state, autonomic disturbance and neuromuscular abnormalities. It is most often linked with antidepressants, and the review notes that an excess of 5-HTP could be responsible for the same picture.

The NHS page on SSRI antidepressants lists the things that can interact with them, including other antidepressants, some anti-inflammatory medicines, alcohol, certain recreational drugs and St John's wort. A product that raises serotonin through another route belongs on the same list of things to check. Anyone taking antidepressants or other medicines that act on serotonin should ask a pharmacist before adding 5-HTP, and should seek urgent help for confusion, agitation, sweating or a racing heart, tremor or muscle stiffness.

• Tell the prescriber about every supplement, including those bought online.

• Do not stop an antidepressant to switch to a supplement; the NHS advises talking to your doctor, who will agree a plan to reduce the dose gradually.

• The review also reports dose-dependent stomach upset as the commonest side effect, with nausea and vomiting at higher intakes.

L-tryptophan was suspended as a dietary supplement in 1989 after eosinophilia-myalgia syndrome, a rare and sometimes fatal condition with severe muscle pain and raised eosinophil counts, was traced to contaminated synthetic tryptophan from a single manufacturer. The review says toxic impurities have also been discussed for 5-HTP preparations and that this is why accurate chemical analysis has been developed. It adds that, apart from one unresolved case, no definitive toxicity cases have emerged despite about twenty years of worldwide use.

That is reassuring but not a guarantee for any individual capsule. Supplement quality varies, and the FSA advises caution with online marketplaces, where it can be hard to know who is selling a product and where it came from.

The FSA states that food supplements should not be sold with claims to prevent, treat or cure a medical condition, that anyone pregnant, breastfeeding, with a medical condition or taking prescribed medicines should check with a GP first, and that if you feel unwell after a supplement you should stop it and seek advice. I did not find a UK regulator page that sets out how each 5-HTP product is classified, so labels, the seller and a pharmacist are the practical checks.

Mood and sleep problems have many causes, including thyroid disease, anaemia, medicines, alcohol and sleep disorders, so a supplement should not delay assessment.