5-HTP: Serotonin, Sleep and Mood Claims, Contamination and Safety Concerns

Urgent first: serotonin syndrome

5-HTP raises the raw material the body uses to make serotonin, so it belongs in the same safety conversation as other serotonin-affecting medicines and supplements. Serotonin syndrome is a potentially life-threatening reaction. MedlinePlus says it most often occurs when two or more medicines or drugs that affect the body's level of serotonin are taken together. [1] A 2006 review of 5-HTP lists serotonin syndrome and eosinophilia-myalgia syndrome as its main safety issues. [2]

Signs can include agitation, fast heartbeat, high blood pressure, diarrhea, fever, heavy sweating, tremor, and overactive reflexes. If you have symptoms, contact a provider right away. [1] For severe symptoms, call 911. If you take an antidepressant or other prescribed medicine, do not stop it on your own. Talk to your prescriber first. [1] For an overdose or poisoning in the US, call Poison Help at 1-800-222-1222.

What it is

5-HTP (5-hydroxytryptophan) is the immediate precursor of serotonin and is made in the body from the essential amino acid tryptophan. [3] It is not an amino acid that builds proteins. For tryptophan itself, see Tryptophan.

5-HTP versus tryptophan

Both are linked to serotonin. A 2002 Cochrane review pooled them because few trials existed. [4] Its findings therefore cannot be split between the two. We found no head-to-head 5-HTP versus tryptophan comparison in the sources we read: proper evidence not found (we searched PubMed for reviews of 5-HTP and tryptophan).

What the research found

1. Depression

   Unclear

   Cochrane (2002): of 108 trials found, only two (64 patients) were good enough to include. These substances beat placebo, but the evidence was too poor to be conclusive. [4]

   Insufficient; old review

2. Sleep

   Unclear

   An American Academy of Sleep Medicine review (2005) assessed 5-HTP among nonprescription insomnia products and said rigorous data supporting benefit were not found for most such supplements. [5]

   Insufficient; old review

3. Migraine, fibromyalgia, weight

   Unclear

   Proper evidence not found. We searched PubMed for 5-HTP reviews on migraine, fibromyalgia and obesity and did not find a review we could read.

   Not established

The Cochrane authors also said that alternative antidepressants exist that have been proven effective and safe, so the clinical usefulness of 5-HTP and tryptophan is limited. [4] Low mood needs assessment: see stress, anxiety, burnout and depression. In the US, call or text 988 if you are in crisis.

Contamination and the EMS history

L-tryptophan was withdrawn as a supplement in 1989 after an outbreak of eosinophilia-myalgia syndrome (EMS), a potentially fatal illness, traced to contaminated synthetic tryptophan from a single manufacturer. [3] Because 5-HTP is chemically related to tryptophan, it has been watched closely for safety. [3]

The evidence is divided:

• A 2004 safety review said no definitive toxicity cases had emerged in 20 years of worldwide use, with one possible unresolved case, and that a minor "peak X" reported in some samples lacked credibility. [3]


• Lab analyses found otherwise. All eight commercial 5-HTP samples tested in a 1999 study contained three or more contaminants of the "peak X" family. [6] A 2003 study identified one as 4,5-tryptophan-dione, a putative neurotoxin, and said this gave some cause for concern about commercial preparations. [7]


• The Cochrane authors said the possible link between these substances and the potentially fatal EMS has not been elucidated. [4]

These samples are from the late 1990s and early 2000s. Recent independent testing of current products: proper evidence not found in the sources we read. See product quality and contamination.

Medicine and condition cautions

• Antidepressants and other serotonin-affecting medicines (also some migraine and cough medicines): ask your prescriber or pharmacist before using 5-HTP. [1]
• Carbidopa. In a 1980 case report, a scleroderma-like illness developed in one patient treated with 5-HTP and carbidopa for a movement disorder. [8] A 2006 review notes that carbidopa can block 5-HTP's conversion to serotonin in the periphery of the body. [2] This is a single case, not proof of risk, but a reason to avoid unsupervised combinations.
• Pregnancy, breastfeeding, children, kidney disease, liver disease, and surgery: not described in the sources we read. Ask a clinician. See supplements before surgery.
• Duplicate ingredients. Sleep or mood blends may contain several serotonin-related ingredients; see amounts and duplicate ingredients.

We give no personal amount. For sleep, see Natural sleep aids compared.