5-HTP vs Melatonin: what to choose and for whom

On forums 5-HTP and melatonin are often recommended as interchangeable «natural sleep aids», and sometimes advised to be taken both at once. The editorial team considers this approach simplistic: these substances have different indications, a different evidence base and very different risks of interactions. Below is a practical breakdown of for whom and in which situation each remedy is more appropriate, and for whom it is better to refrain from both.

Start with the goal

If your problem is falling asleep at the «wrong» time, jet lag or a disrupted schedule after night shifts, this is about the circadian rhythm. For this goal it is specifically melatonin that has been studied, and it logically comes first.

If, however, you are looking for a remedy for mood, reducing cravings for sweets or «serotonin support», this is no longer about sleep. 5-HTP was studied precisely in these directions, although there is little evidence of effectiveness, and in depression self-medication is unacceptable.

Some people buy 5-HTP for sleep, counting on it being converted into melatonin. Biochemically this is possible, but melatonin synthesis is regulated by darkness and pineal gland enzymes, so an increase in serotonin does not guarantee better sleep.

Therefore the first practical rule: for sleep choose a remedy that has been studied for sleep; for mood — see a specialist, not «serotonin» supplements.

Who is better suited by melatonin

For those who often fly across time zones — athletes at away competitions, business travelers. The Cochrane review confirmed that melatonin reduces the manifestations of jet lag.

For people with delayed sleep phase who regularly cannot fall asleep until late at night. Clinical guidelines on circadian disorders support properly timed melatonin intake for them.

For people aged 55 and over with insomnia, to whom a doctor may prescribe prolonged-release melatonin. For this group there is a prescription form registered in the EU.

For those who cannot take serotonergic remedies: melatonin does not raise serotonin levels and carries no risk of serotonin syndrome, although it has its own interactions that should be discussed with a doctor.

For whom 5-HTP may be considered — and with what cautions

5-HTP is sometimes considered by adults without psychiatric diagnoses and not taking medications who are interested in its possible effect on appetite and satiety. The evidence base here is small and consists mainly of old short studies.

For treating depression 5-HTP is not a justified choice: the Cochrane review found no sufficient evidence, and for depression there are effective treatment methods that a doctor should select.

For sleep 5-HTP has no advantages over melatonin, and gastrointestinal side effects — nausea, discomfort, diarrhea — occur noticeably more often.

The main caution: 5-HTP must not be combined with antidepressants, tramadol, triptans, MAO inhibitors, linezolid and other agents that raise serotonin, because of the risk of serotonin syndrome.

Map of choice by situation

For convenience the editorial team has summarized typical scenarios in a table.

The editorial team does not advise combining 5-HTP and melatonin without a doctor: the total sedative effect is hard to predict, and there are no quality safety and effectiveness studies for such a combination.

Product quality and practical advice

For both supplements the quality of manufacture is critical. Analysis of melatonin supplements showed that the actual content may differ significantly from what is stated, and in some products serotonin was found. For 5-HTP the purity of the raw material has historically been important.

• Choose products with independent laboratory quality control.
• Athletes who undergo doping control should give preference to certified products.
• Do not exceed the doses indicated by the manufacturer, and do not take sleep aids together with alcohol.
• After taking a sleep aid do not drive a car if you feel drowsy.

Any new supplement should be assessed by a clear criterion: what exactly should change and over what period. If the goal is not achieved in 2–3 weeks, it is better to stop taking it and discuss the problem with a doctor.

Finally, the basic steps — a stable time of going to bed and waking, a dark cool bedroom, giving up caffeine in the second half of the day — remain the most effective and safe for anyone.

Editorial conclusions

For sleep problems — jet lag, a shifted schedule, insomnia in older age — melatonin is the more justified choice with a better evidence base.

5-HTP has no convincing advantages for sleep, has more stomach side effects and a serious risk of interactions with serotonergic medications.

People who take antidepressants, have depression, are pregnant or breastfeeding should discuss both remedies only with a doctor.

The editorial team also recommends our materials on the differences between 5-HTP and melatonin at the biochemical level, on melatonin and magnesium and on glycine for sleep.

References

1. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev. 2002;(2):CD001520.
2. Auger RR, Burgess HJ, Emens JS, Deriy LV, Thomas SM, Sharkey KM. Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders. J Clin Sleep Med. 2015;11(10):1199–1236.
3. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198.
4. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112–1120.
5. Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006;109(3):325–338.
6. Erland LA, Saxena PK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. J Clin Sleep Med. 2017;13(2):275–281.
7. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JE. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307–349.