5-HTP

Serotonin pathway rationale. People with fibromyalgia have repeatedly been reported to show lower serotonin activity (e.g., reduced CSF 5-HIAA, the main serotonin metabolite). Because 5-HTP is the direct precursor to serotonin, supplementing it could raise central serotonin and potentially improve pain processing, sleep, and mood, which are all relevant in fibromyalgia. Wiley Online Library

Mechanistic fit with symptoms. Serotonin modulates slow-wave sleep and pain perception; low serotonin is associated with a reduced pain threshold—both key issues in fibromyalgia. 5-HTP increases serotonin availability and has been explored to improve tender point counts, pain severity, sleep, fatigue, and anxiety. Active Caldic

Context among standard therapies. Modern guidelines emphasise exercise, education/CBT, and certain medicines (duloxetine, milnacipran, pregabalin, low-dose amitriptyline). 5-HTP is not part of standard guideline-recommended care and evidence is limited/older—so it’s an optional adjunct to discuss with your clinician rather than a first-line therapy. AAFP

Dose used in the best-known fibromyalgia trial

• 100 mg, three times daily (TID) by mouth for 30 days. This double-blind, placebo-controlled study in 50 patients reported significant improvements in tender points, pain, sleep, fatigue, stiffness, and anxiety vs placebo. Active Caldic

Typical practical dosing/titration used in clinics/summaries

• Start 50–100 mg at night for a few days (to monitor tolerance), then increase to 100 mg 2–3×/day as tolerated. Many consumer-health references list adult ranges of 150–300 mg/day (sometimes higher in other indications), but fibromyalgia data most closely match 100 mg TID. Take with food if you get nausea. Examine

Timing

• If sleep is a major problem, reserve one dose 30–60 min before bedtime; the other dose(s) can be taken morning/afternoon. This exploits 5-HTP’s downstream effects on serotonin/melatonin that may support sleep. Examine

Duration

• The controlled trial lasted 30 days. If no meaningful benefit after 4–6 weeks, many clinicians would reconsider using it. (Evidence for longer-term efficacy is lacking.) Active Caldic

Product quality tips

• Choose a supplement from brands that are third-party tested (USP/NSF/Informed Choice) because historical contamination problems (see “Warnings”) have been reported with tryptophan-pathway products. The Lancet

Randomized controlled trial (1990).

• Caruso et al., J Int Med Res: 100 mg 5-HTP TID for 30 days vs placebo (n=50). Significant improvements in tender points, pain, sleep, fatigue, stiffness, and anxiety; adverse effects were mild and transient. Authors called for larger/longer trials. (Full text figures and dosing shown in the PDF.) Active Caldic

Mechanistic/biomarker backdrop. Multiple reports show reduced serotonin/tryptophan and CSF 5-HIAA in fibromyalgia compared with controls, supporting the serotonin-augmentation hypothesis that motivated the 5-HTP trial. Wiley Online Library

Current guideline perspective. Contemporary overviews of pharmacologic therapies for fibromyalgia highlight duloxetine, milnacipran, pregabalin (and sometimes low-dose amitriptyline) as medicines with moderate evidence for short-term pain relief; there is no substantial modern efficacy evidence for many other medicines/supplements, and 5-HTP is not recommended as standard care. Oxford Academic

Summary: There’s one small, older RCT suggesting benefit over 30 days, plus biological plausibility—but no robust, modern confirmatory trials. If you and your clinician choose to try 5-HTP, consider it an adjunct with a clear stop-rule if it doesn’t help.