L-tryptophan

L-tryptophan is sold as a «natural sleep aid» on the hypothesis of melatonin synthesis from tryptophan via serotonin. Small 1970s-1980s RCTs showed mild reduction in sleep latency at 1–3 g doses before bed; modern evidence is weak. AASM 2021 and SES 2016 list CBT-I first-line for chronic insomnia; L-tryptophan is in no international sleep guideline. If L-tryptophan was recommended for chronic insomnia instead of CBT-I or workup for sleep apnoea and restless legs syndrome, consider seeking a second opinion. It is also important to check whether the patient takes serotonergic drugs – serotonin syndrome risk.

ICD-10: G47.0 · ICD-11: 7A00

L-tryptophan supplement is sold as a «natural antidepressant» promising a «safe SSRI alternative». Evidence base in mild-to-moderate depression is insufficient: Cochrane 2002 did not confirm clinically meaningful efficacy. NICE 2022 and SEP 2014 list CBT and SSRIs first-line for mild-to-moderate depression; L-tryptophan is not included. Main risk: self-combination with an antidepressant, tramadol or triptans – serotonin syndrome (tachycardia, hyperthermia, myoclonus, rigidity, confusion). A separate documented harm is the historical eosinophilia-myalgia syndrome epidemic with fatalities, after which the FDA removed L-tryptophan from over-the-counter sale. Unproven benefit against real harm is a net-minus, so it is not recommended. If L-tryptophan was recommended for depression instead of a psychiatric consultation, consider seeking a second opinion.

ICD-10: F32.0 · ICD-11: 6A70.0

L-tryptophan is sold as a «natural anxiolytic» on the «tryptophan → serotonin → anxiety reduction» hypothesis. Evidence in anxiety disorders is weak: a significant fraction of tryptophan goes to the kynurenine pathway rather than serotonin, and CNS effect is unpredictable. NICE CG113 lists SSRIs and CBT first-line for anxiety disorders. Main risk: combination with SSRIs, tramadol or triptans – serotonin syndrome. EMS (eosinophilia-myalgia syndrome) after the 1989 outbreak, which had fatalities and led to an FDA over-the-counter ban, continues to be reported in isolated cases. Unproven benefit against documented harm is a net-minus, so it is not recommended. If L-tryptophan was recommended for GAD or panic attacks instead of a psychiatric consultation, consider seeking a second opinion.

ICD-10: F41.9 · ICD-11: 6B0Z

L-tryptophan is sold for weight loss and appetite control on the idea that the body turns it into serotonin and that serotonin signals fullness. Controlled trials do not back this up: in people with obesity the supplement added no weight loss over placebo, and at usual doses it did not change hunger. EFSA reviewed the claim that L-tryptophan helps maintain a normal body weight, found no cause-and-effect relationship, and rejected the claim. Harm, by contrast, is documented: in 1989 tryptophan supplements caused an epidemic of eosinophilia-myalgia syndrome (more than 1500 cases and dozens of deaths), and combining it with SSRI antidepressants has triggered serotonin syndrome. With no proven benefit and a cited harm profile, talk to your doctor before use if you take any serotonergic medication and consider a second opinion.