Drug & supplement interaction

5-htp + Metformin

Metformin brand names: Glucophage, Metformin.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between 5-htp and Metformin in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

5-htp and Metformin

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Metformin and 5-htp in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

5-htp safety at a glance

5-htp overall Use caution May help some people but can cause side effects and affects serotonin, so use with care and professional guidance.
Pregnancy Avoid Not enough safety information; avoid during pregnancy.
Breastfeeding Avoid Not enough safety information; avoid while breastfeeding.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Metformin and 5-htp? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Metformin

Interactions in our licensed database are recorded against drug classes, not just single drug names. Metformin is filed under 5 classifications — including organic cation transporter 2 (oct2) substrates, antidiabetes drugs, oral drugs. 5-htp has documented interactions with 3 drug classes — the most serious being carbidopa (lodosyn) (moderate), cns depressants (moderate) and serotonergic drugs (moderate) — and none of Metformin’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

5-htp Does Interact With Other Medications

5-htp has 398 moderate known drug interactions in our database — Metformin isn’t one of them. If you take anything else, check it against the full list below.

Moderate 398 No known interaction 2,432 (incl. Metformin)
Taking anything else?

Check Another of Your Medications Against 5-htp

Covers the 2,830 medications we’ve checked against 5-htp. Pick one to open its full report.

What to actually watch for

No Interaction Found — But Data Suggests 5-htp and Metformin May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do.

  • Flushing Additional detail

    5-htp

    “Orally, 5-HTP has been reported to cause urticaria, other allergic-type skin reactions, and flushing. A scleroderma-like illness was reported in a 70-year-old man who had been taking 5-HTP 1400 mg daily and carbidopa 150 mg daily for 20 months. Elevated serotonin levels may be linked to this condition.”

    5-htp · Natural Medicines adverse-effect record, reported in myasthenia gravis.

    4 sources cited
    1. 2204. Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. Headache 2000;40:451-6.
    2. 30000. Takahashi S, Kondo H, Kato N. Effect of l-5-hydroxytryptophan on brain monoamine metabolism and evaluation of its clinical effect in depressed patients. J Psychiatr Res 1975;12:177-87. PubMed
    3. 30140. Chase, T. N., Ng, L. K., and Watanabe, A. M. Parkinson's disease. Modification by 5-hydroxytryptophan. Neurology 1972;22(5):479-484.
    4. 1403. Sternberg EM, Van Woert MH, Young SN, et al. Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. N Engl J Med 1980;303:782-7. PubMed

    Metformin

    Listed in the ADVERSE REACTIONS section of the FDA label for Metformin. Read the label on DailyMed ›

  • Bloating or gas Additional detail

    5-htp

    “Orally, 5-HTP has been reported to cause gastrointestinal side effects such as nausea, vomiting, abdominal or epigastric pain, heartburn, constipation, diarrhea, flatulence, anorexia, and taste alteration at any dose. Severity may be dose-dependent and also related to how quickly doses are increased. Some data suggests that these effects may diminish or disappear with continued use of 5-HTP.”

    5-htp · Natural Medicines adverse-effect record, reported in anorexia.

    6 sources cited
    1. 2203. Poldinger W, Calanchini B, Schwarz W. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology 1991;24:53-81.
    2. 2204. Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. Headache 2000;40:451-6.
    3. 30000. Takahashi S, Kondo H, Kato N. Effect of l-5-hydroxytryptophan on brain monoamine metabolism and evaluation of its clinical effect in depressed patients. J Psychiatr Res 1975;12:177-87. PubMed
    4. 30112. Jangid P, Malik P, Singh P, Sharma M, Gulia AK. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr 2013;6:29-34. PubMed
    5. 30114. Ceci F, Cangiano C, Cairella M, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm 1989;76:109-17. PubMed
    6. 30125. Angst J, Woggon B, Schoepf J. The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study. Arch Psychiatr Nervenkr 1977;224:175-86. DOI

    Metformin

    Listed in the ADVERSE REACTIONS section of the FDA label for Metformin. Read the label on DailyMed ›

  • Sweating Additional detail

    5-htp

    “Orally, palpitations have been reported with 5-HTP. Conversely, bradycardia has been reported in patients taking 5-HTP 0.4-2 grams daily in combination with carbidopa 100-300 mg daily. In patients with schizophrenia, a combination of 5-HTP in doses up to 6 grams daily and carbidopa 150 mg daily was associated with diaphoresis and mild diastolic hypotension, especially when doses were increased at a rate faster than 2…”

    5-htp · Natural Medicines adverse-effect record, reported in hypotension.

    5 sources cited
    1. 30076. Iovieno, N., Dalton, E. D., Fava, M., and Mischoulon, D. Second-tier natural antidepressants: review and critique. J Affect.Disord. 2011;130(3):343-357. PubMed
    2. 30130. De Benedittis G, Massei R. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. J Neurosurg Sci 1985;29:239-48.
    3. 30167. Bastard, J., Truelle, J. L., and Emile, J. [Effectiveness of 5 hydroxy-tryptophan in Parkinson's disease]. Nouv Presse Med 9-11-1976;5(29):1836-1837.
    4. 30132. Van Woert, M. H., Rosenbaum, D., Howieson, J., and Bowers, M. B., Jr. Long-term therapy of myoclonus and other neurologic disorders with L-5- hydroxytryptophan and carbidopa. N Engl J Med 1-13-1977;296(2):70-75. PubMed
    5. 30183. Wyatt, R. J., Vaughan, T., Kaplan, J., Galanter, M., and Green, R. 5-Hydroxytryptophan and chronic schizophrenia. In: Barchas J and Usdin E. Serotonin and Behavior. New York: Acedemic Press;1973.

    Metformin

    Listed in the ADVERSE REACTIONS section of the FDA label for Metformin. Read the label on DailyMed ›

  • Muscle pain Additional detail

    5-htp

    “Symptoms suggestive of eosinophilia myalgia syndrome (EMS) have been reported in some patients using 5-HTP. In one case, a woman was exposed to 5-HTP, tetrahydrobiopterin, carbidopa, and levodopa while administering them to her children for 2 years. Her diagnosis was not confirmed, and the validity of the tests performed on the 5-HTP product has been questioned.”

    5-htp · Natural Medicines adverse-effect record, reported in myalgia.

    6 sources cited
    1. 902. Michelson D, Page SW, Casey R, et al. An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan. J Rheumatol 1994;21:2261-5.
    2. 10084. Johnson KL, Klarskov K, Benson LM, et al. Presence of peak X and related compounds: the reported contaminant in case related 5-hydroxy-L-tryptophan associated with eosinophilia-myalgia syndrome. J Rheumatol 1999;26:2714-7.
    3. 30178. Auffret, M., Comte, H., and Bene, J. Eosinophilia-myalgia syndrome induced by L-5 hydroxytryptophane: about three cases. Fund Clin Pharmacol 2013;Suppl 1(120):poster P2-204.
    4. 88174. Das YT, Bagchi M, Bagchi D, Preuss HG. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett 2004;150:111-22. PubMed
    5. 90927. Michelson D, Page SW, Casey R, et al. An eosinophilia-myaligia syndrome related disorder associated with exposure to l-5-hydroxytryptophan. J Rheumatol 1994;21(12):2261-5.
    6. 919. U.S. Food and Drug Administration. Impurities confirmed in dietary supplement 5-hydroxy-L-tryptophan. FDA Talk Paper, August 31, 1998; T98-48.

    Metformin

    Listed in the ADVERSE REACTIONS section of the FDA label for Metformin. Read the label on DailyMed ›

  • Tiredness / Dizziness / Headache Additional detail

    5-htp

    “Orally, 5-HTP has been reported to cause drowsiness, dizziness, insomnia, fatigue, and headache.”

    5-htp · Natural Medicines adverse-effect record, reported in cluster headache.

    3 sources cited
    1. 30076. Iovieno, N., Dalton, E. D., Fava, M., and Mischoulon, D. Second-tier natural antidepressants: review and critique. J Affect.Disord. 2011;130(3):343-357. PubMed
    2. 30112. Jangid P, Malik P, Singh P, Sharma M, Gulia AK. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr 2013;6:29-34. PubMed
    3. 30132. Van Woert, M. H., Rosenbaum, D., Howieson, J., and Bowers, M. B., Jr. Long-term therapy of myoclonus and other neurologic disorders with L-5- hydroxytryptophan and carbidopa. N Engl J Med 1-13-1977;296(2):70-75. PubMed

    Metformin

    Listed in the ADVERSE REACTIONS section of the FDA label for Metformin. Read the label on DailyMed ›

  • Diarrhea / Vomiting / Nausea Additional detail

    5-htp

    Recorded for 5-htp in the same Natural Medicines adverse-effect record shown under Tiredness / Dizziness / Headache above.

    Metformin

    Listed in the ADVERSE REACTIONS section of the FDA label for Metformin. Read the label on DailyMed ›

Reported for 5-htp but not commonly for Metformin: stomach pain, hallucinations, severe muscle breakdown and constipation.

Effects for Metformin come from the ADVERSE REACTIONS section of its FDA label; effects for 5-htp come from the Natural Medicines adverse-effect record, quoted above. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

From our Q&A

Questions About 5-htp or Metformin

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers 5-htp or Metformin, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Metformin

This page covers 5-htp only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Metformin page lists 258 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Siberian Cocklebur (major), Acai (moderate), African Wild Potato (moderate) and Agaricus Mushroom (moderate).

By severity: 2 major · 217 moderate · 39 minor.

From our pharmacist’s overview on the Metformin page

“Siberian cocklebur is the ingredient I most want anyone taking metformin (Glucophage) to know about. It has caused severe low blood sugar in people, documented in humans, and it should not be combined with any glucose-lowering medication.”

Reviewed by 2 · Jul 18, 2026

Open the Metformin interaction page

One more smart check

Taking 5-htp as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,651 real supplement products containing 5-htp, each one broken down to its full ingredient list — and combination products often carry several ingredients besides 5-htp. Even though 5-htp itself has no known interaction with Metformin, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where 5-htp and Metformin Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement 5-htp
Top 10%

#124 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Metformin
Top 1%

#29 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every 5-htp reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The 5-htp and Metformin records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About 5-htp

What is 5-htp?

5-htp
  • Low mood or depression
  • Anxiety and stress
  • Sleep problems
  • Migraine headaches
  • Fibromyalgia
  • Appetite or weight management

5-HTP is a compound your body uses to make serotonin, and people take it as a supplement hoping to improve mood, sleep, and headaches. Some early research is promising, but the overall evidence is limited and not conclusive. Because it can affect serotonin and may interact with medicines, talk to your pharmacist or doctor before using it.

Seeds (Griffonia simplicifolia) used as the natural source; the supplement is the purified amino acid · Capsules, tablets, time-release tablets

An interaction check asks whether these two react with each other — it does not ask whether 5-htp is a good idea for someone in your situation. Here is what our 5-htp record says about it on its own.

5-htp: dosing

There is no official, standardized dose of 5-HTP that has been firmly established for any condition. Products vary widely in strength and form, including some time-release versions.The safest approach is to follow the directions on the product label and to start low. If you do not notice a benefit or you have side effects, stop and talk to a healthcare professional.

From our 5-htp monograph — the full record covers uses, side effects and every documented interaction.

Read the full 5-htp monograph & all interactions
Medication

About Metformin

What Is Metformin Used For?

Brand names: Glucophage, Metformin

Metformin is used to improve blood sugar (glucose) control in people with type 2 diabetes mellitus. It is always used together with diet and exercise, not instead of them.

Metformin hydrochloride tablets and oral solution are approved for adults and children 10 years and older. Metformin hydrochloride extended-release tablets — including brands such as Fortamet, Glumetza, and Metformin Hydrochloride Extended Release — are approved for adults only.

See full Metformin drug information
Keep checking

Other Drugs & 5-htp

Browse every other medication we’ve checked against 5-htp — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
398Moderate
0Minor
2,431No known interaction
398 Moderate 2,431 No interaction
Moderate

398 interactions

Showing 60 of 398 moderate interactions — see all 398 on the 5-htp page.

No interaction 2,431 drugs checked — show the list

We also checked 5-htp against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,431 medications checked with no known interaction — see the full 5-htp list.

See the full 5-htp interactions page
See every supplement checked against Metformin, ranked by severity
Evidence & sources

5-htp References

The 32 references that drive our 5-htp monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Birdsall TC. 5-Hydroxytryptophan: A Clinically-Effective Serotonin Precursor. Altern Med Rev 1998;3:271-80.
  2. Michelson D, Page SW, Casey R, et al. An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan. J Rheumatol 1994;21:2261-5.
  3. Cangiano C, Ceci F, Cancino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr 1992;56:863-7. PubMed
  4. U.S. Food and Drug Administration. Impurities confirmed in dietary supplement 5-hydroxy-L-tryptophan. FDA Talk Paper, August 31, 1998; T98-48.
  5. Sternberg EM, Van Woert MH, Young SN, et al. Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. N Engl J Med 1980;303:782-7. PubMed
  6. Poldinger W, Calanchini B, Schwarz W. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology 1991;24:53-81.
  7. Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. Headache 2000;40:451-6.
  8. U. S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements. Information Paper on L-Tryptophan and 5-hydroxy-L-tryptophan, February 2001.
  9. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  10. Johnson KL, Klarskov K, Benson LM, et al. Presence of peak X and related compounds: the reported contaminant in case related 5-hydroxy-L-tryptophan associated with eosinophilia-myalgia syndrome. J Rheumatol 1999;26:2714-7.
  11. Takahashi S, Kondo H, Kato N. Effect of l-5-hydroxytryptophan on brain monoamine metabolism and evaluation of its clinical effect in depressed patients. J Psychiatr Res 1975;12:177-87. PubMed
  12. Iovieno, N., Dalton, E. D., Fava, M., and Mischoulon, D. Second-tier natural antidepressants: review and critique. J Affect.Disord. 2011;130(3):343-357. PubMed
  13. den Boer JA, Westenberg HG. Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder. Psychiatry Res 1990;31:267-78. PubMed
  14. Jangid P, Malik P, Singh P, Sharma M, Gulia AK. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr 2013;6:29-34. PubMed
  15. Ceci F, Cangiano C, Cairella M, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm 1989;76:109-17. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking 5-htp and Metformin Together: Common Questions

Is it safe to take 5-htp with Metformin?
We do not list a known interaction between 5-htp and Metformin. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Do 5-htp and Metformin have any of the same side effects?
Yes — our sources link each of them separately to 10 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
How was the 5-htp and Metformin combination checked?
Interactions in our licensed database are recorded against drug classes. Metformin is filed under 5 classifications, and 5-htp has documented interactions with 3 drug classes — none of Metformin's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does 5-htp interact with any other medications?
Yes. 5-htp has 398 documented drug interactions in our database — Metformin is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Metformin interact with any supplements?
Yes. Metformin has documented interactions with 258 supplements in our database — 5-htp is not one of them. The Metformin interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

5-htp monograph Uses, safety profile, and every drug interaction in one place Metformin drug information The full plain-English guide to this medication Metformin supplement interactions Every supplement checked against Metformin, ranked by severity Supplement interaction checker Check any supplement or product against your medications Browse medications A–Z Every drug we’ve checked against herbs & supplements References The 32 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Metformin and 5-htp?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.