Can You Take Melatonin and Ibuprofen Together?

No trial has tested melatonin with ibuprofen, and no source we read reports harm from the pair. Ibuprofen 400 mg lowered the body's own melatonin within 2 hours in a small study¹, yet 1,200 mg a day did not change sleep in 30 adults².

The better-documented risks with ibuprofen involve other supplements and medicines: those that affect bleeding, the kidneys or how fast ibuprofen leaves the body. This guide ranks them. For melatonin on its own, see our melatonin evidence page.

No source we read reports harm from short-term use, but the pair is untested. No trial has given a melatonin supplement together with ibuprofen, so this rests on what each does alone.

Does ibuprofen lower melatonin?

In the lab, yes, for the body's own melatonin. In a 1987 study, ibuprofen 400 mg taken at midnight lowered plasma melatonin after 2 hours, and the same dose at 6 pm delayed the nighttime rise¹. A 1996 series of experiments in 75 people found that aspirin and ibuprofen suppressed nighttime melatonin and flattened the normal fall in body temperature³. Daytime temperature was unaffected³.

None of these studies gave a melatonin supplement, so they cannot say whether the effect matters if you take one.

Does ibuprofen disrupt sleep?

The results conflict. A 1994 trial in 37 people found that aspirin and ibuprofen increased awakenings and lowered sleep efficiency, and ibuprofen delayed the deeper sleep stages⁴. Acetaminophen did not differ from placebo on any sleep measure in that trial⁴. A double-blind trial in 30 healthy adults gave ibuprofen 400 mg three times a day and found no significant change in sleep measured in a sleep laboratory or by self-report².

What does the NHS say?

The NHS lists NSAIDs, including ibuprofen, naproxen and diclofenac, among medicines to mention to a doctor or pharmacist before you take melatonin. Many medicines can raise or lower melatonin's drowsy effect⁵.

Is a night-time ibuprofen product the same thing?

No. One common night-time product pairs ibuprofen 200 mg with diphenhydramine citrate 38 mg as a sleep aid⁶. Its label says not to use it with any other product containing diphenhydramine, such as cold and allergy medicines⁶. Drowsiness will occur with it, and the label asks you to check with a doctor or pharmacist first if you take any other sleep aid⁶. That is the line that applies if you also take melatonin. The label also says not to use it in children under 12 and to ask a doctor first if you have trouble urinating from an enlarged prostate⁶.

The NHS adds that it does not have enough information to call non-drowsy herbal remedies and supplements safe with melatonin, and advises against herbal remedies that cause sleepiness⁵.

Could melatonin protect the stomach from NSAIDs?

One small study hints at it for aspirin. Twenty-one healthy men took aspirin 2 g a day for 11 days; those who also took melatonin 5 mg, 30 minutes before the aspirin, had significantly lower endoscopy lesion scores than those on aspirin alone⁷. The study used aspirin, not ibuprofen, with 7 men per group. Do not use melatonin as stomach protection.

Concerns with ibuprofen come from four mechanisms:

• Bleeding: ginkgo, garlic, ginger, vitamin E, fish oil and turmeric. The concern is added bleeding risk, and it rests mostly on case reports and lab data^{8, 9}.
• Absorption: magnesium hydroxide antacids. They speed up ibuprofen's absorption rather than blocking it¹⁰.
• Kidneys and potassium: NSAID use is linked to a higher risk of kidney injury and high potassium in older adults¹¹.
• Drug clearance: berberine slows the liver enzyme CYP2C9, which also clears the active form of ibuprofen^{12, 13}.

No source we read reports an interaction between ibuprofen and L-theanine, kava or ashwagandha. Each has its own safety notes, covered below. For melatonin, the NHS asks you to mention NSAIDs to a pharmacist⁵.

Possibly, but the proof is thin. Ibuprofen alone can cause stomach bleeding, and the label says the chance is higher if you take a blood thinner or another NSAID¹⁴.

A 2002 review warned that NSAIDs, particularly aspirin, may interact with herbs that affect platelets and so raise bleeding risk. It named ginkgo, garlic, ginger, bilberry, dong quai, feverfew, ginseng, turmeric, meadowsweet and willow⁸. It also said most of this rests on case reports, animal studies and lab data⁸. A 2012 review of garlic, ginkgo, ginger, ginseng, fish oil and vitamin E reached the same point: serious bleeds have been reported, but controlled studies are too limited to show a consistent effect alone or with drugs⁹.

What does the ginkgo evidence show?

• Trials: a meta-analysis of 18 randomized trials in 1,985 adults found no significant effect of standardized ginkgo extract on platelet aggregation or prothrombin time. A small drop in activated partial thromboplastin time in some subgroups was not clinically relevant¹⁵.
• Case reports: a systematic review found 15 reports of bleeding with ginkgo, including 8 intracranial bleeds. In 13 of the 15, other bleeding risks were present¹⁶.
• With ibuprofen: a case report describes a fatal brain bleed associated with ginkgo and ibuprofen¹⁷.

The systematic review concluded that the case reports suggest a possible causal association between ginkgo and bleeding, and that people with known bleeding risks should be counseled¹⁶. One case report cannot prove cause. We read only the title and indexing of the ibuprofen report, which has no abstract. See our ginkgo page for its other uses.

What about vitamin E, fish oil, garlic and ginger?

The NIH Office of Dietary Supplements says large doses of vitamin E can inhibit platelets, so taking them with anticoagulant or antiplatelet drugs such as warfarin can raise bleeding risk, especially with low vitamin K intake¹⁸. That fact sheet does not name NSAIDs, so the ibuprofen question is untested. Fish oil, garlic and ginger sit in the same 2012 review⁹.

If you take a prescription blood thinner, read our guide to blood thinners and supplements. Stop ibuprofen and get help if you feel faint, vomit blood, or have bloody or black stools¹⁴.

No trial has combined them, so the safety of the pair is untested. Trials have compared them instead, in knee osteoarthritis.

• Turmeric extract vs ibuprofen: 367 adults took ibuprofen 1,200 mg a day or Curcuma domestica extracts 1,500 mg a day for 4 weeks. The extracts were noninferior on total, pain and function scores. Abdominal pain was reported more often with ibuprofen¹⁹.
• Curcumin vs diclofenac: in 139 patients, curcumin 500 mg three times a day matched diclofenac 50 mg twice a day for pain over 28 days. Adverse effects occurred in 13% on curcumin and 38% on diclofenac²⁰.
• Pooled view: a meta-analysis of 7 trials in 797 people found curcuminoids beat placebo for knee pain but relieved pain less than ibuprofen. All trials were in Asia, with small samples²¹.

So turmeric is a plausible alternative for mild knee pain, not a proven match. Turmeric also appears on the 2002 list of herbs with antiplatelet activity⁸, which is the reason to mention it to a pharmacist if you take both. See curcumin and curcumin for knee pain.

Probably, but it is untested for magnesium supplements. Two small studies of magnesium hydroxide antacids found no loss of ibuprofen absorption. In 6 volunteers, magnesium hydroxide 850 mg raised the early ibuprofen level (area under the curve over the first hour) by 65% and the peak by 31%, and brought the peak about 0.5 hours sooner. The total absorbed did not rise¹⁰. The same dose changed neither ketoprofen nor diclofenac absorption¹⁰.

An aluminum and magnesium hydroxide suspension left ibuprofen's pharmacokinetics unchanged in 8 volunteers²².

Treat this as limited evidence. Both studies were single-dose antacid tests in a handful of healthy people. We found no study of magnesium glycinate, citrate or oxide with ibuprofen, and no naproxen data at all. Our guides cover magnesium, what not to take with it and magnesium with melatonin.

No study tested an NSAID with any supplement for kidney effects, but NSAIDs alone carry a kidney signal. A study of Ontario adults aged 66 and older matched 46,107 new NSAID users with 46,107 non-users. Within 30 days, acute kidney injury occurred in 0.82% of users and 0.59% of non-users (odds ratio 1.41), and high potassium in 0.40% and 0.27% (odds ratio 1.50)¹¹. Predictors included older age, lower kidney function, higher baseline potassium, and use of an ACE inhibitor, an angiotensin receptor blocker or a diuretic¹¹. The ibuprofen label also says to ask a doctor first if you have kidney disease or take a diuretic¹⁴.

Potassium supplements

No study tested a potassium supplement with an NSAID. Because higher baseline potassium was a predictor of trouble¹¹, ask a pharmacist before combining them, especially with blood pressure medicine. See potassium and our guide to blood pressure meds and supplements.

Creatine

No study paired creatine with an NSAID. A case report describes a healthy 24-year-old weight lifter who developed acute kidney failure with interstitial nephritis while taking creatine and several other supplements, and recovered after stopping them²³. A systematic review of 6 pooled studies concluded that creatine does not cause kidney damage at the amounts and durations studied, although its abstract also reports small statistical increases in serum creatinine and plasma urea²⁴. With kidney disease, check with a doctor before using either.

It might, though nobody has measured it. The enzyme CYP2C9 is a major route for clearing the active S form of ibuprofen. In 21 healthy volunteers who took ibuprofen 600 mg, carriers of the slow CYP2C9 *3/*3 genotype cleared S-ibuprofen at 1.52 L/h, against 3.25 L/h in *1/*1 carriers. Slow clearers also showed stronger inhibition of cyclooxygenase-1¹³.

In healthy men, berberine 300 mg three times a day for 2 weeks reduced CYP2C9, CYP2D6 and CYP3A4 activity. The losartan-to-metabolite ratio, a CYP2C9 marker, doubled¹². If that effect carries over to ibuprofen, ibuprofen would clear more slowly. That is an inference, not a finding, so tell your pharmacist if you take berberine daily.

None of the sources we read links these to ibuprofen. Their own safety notes still apply.

• Kava: the liver warning is about acetaminophen, not NSAIDs. The 2002 analgesic review links kava with higher liver risk alongside acetaminophen⁸. A review of 26 suspected kava liver cases found rare toxicity at recommended doses, with overdose, long treatment and other medicines raising the risk²⁵.
• Ashwagandha: five patients developed liver injury, mostly cholestatic, after 2 to 12 weeks. Liver tests normalized in 1 to 5 months in four of them²⁶.
• L-theanine: We found no interaction report with ibuprofen.

Is it bad to take melatonin every night?

Long-term trials of 6 months or more report few adverse events, and few of those were clinically significant. The authors still warn against complacency because double-blind placebo-controlled trials are scarce²⁷.

Does melatonin affect blood sugar?

A meta-analysis of randomized placebo-controlled trials found no significant change in fasting glucose (n = 603) and a small drop in fasting insulin (n = 278), with wide confidence intervals²⁸.

Can you take melatonin with Prozac or other antidepressants?

The NHS names fluvoxamine and amitriptyline, not fluoxetine (Prozac), among antidepressants to mention before taking melatonin⁵. If you also take ibuprofen, SSRIs plus NSAIDs raise the odds of upper stomach bleeding, as the 'Who should be careful?' section shows²⁹. Read our guide to SSRIs and supplements, and see the full list of sleep supplements.

Check with a doctor or pharmacist first if any of these apply:

• You take a prescription blood thinner or a steroid, or drink 3 or more alcoholic drinks a day: the ibuprofen label names each as raising the chance of stomach bleeding¹⁴.
• You take an SSRI antidepressant such as fluoxetine (Prozac): a pooled analysis of 19 studies found upper stomach bleeding odds of 1.66 to 1.68 with an SSRI alone and 4.25 with an SSRI plus an NSAID²⁹.
• You have heart disease, high blood pressure, liver cirrhosis or asthma, or have had a stroke: the label says to ask a doctor first, and warns that NSAIDs other than aspirin raise the risk of heart attack, heart failure and stroke¹⁴.
• You take aspirin for your heart or to prevent a stroke: ibuprofen may decrease that benefit¹⁴.
• You are 60 or older, or have had ulcers: the same label names both as raising the chance of stomach bleeding¹⁴.
• You have kidney disease or take a diuretic, ACE inhibitor or angiotensin receptor blocker: these were the main predictors of kidney injury and high potassium after starting an NSAID¹¹.
• You are pregnant or breast-feeding: the current label says to ask a health professional first, and not to use ibuprofen at 20 weeks or later in pregnancy unless a doctor directs it⁶.
• A child needs the dose: the label says to ask a doctor for children under 12¹⁴. No trial tested melatonin with ibuprofen in children. The night-time product is not for children under 12⁶.

Use these rules, in order:

1. Melatonin and ibuprofen: no source reports harm, so mention both to a pharmacist. Choose plain ibuprofen, not a night-time product with diphenhydramine, unless a pharmacist agrees^{6, 5}.
2. Magnesium: the antacid studies give no reason to separate it from ibuprofen, though magnesium supplements were not tested^{10, 22}.
3. Ginkgo, vitamin E, fish oil, garlic, ginger or turmeric: mention them to a pharmacist, especially if you take a blood thinner^{8, 9}.
4. Berberine: tell your pharmacist if you take it daily with ibuprofen¹².
5. Potassium or creatine: raise them if you have kidney disease or take a daily NSAID¹¹.
6. Ibuprofen: use the smallest effective dose, as the label directs, and stop and ask a doctor if pain lasts more than 10 days⁶.

We searched PubMed and the Firecrawl research index in October 2026 for studies of NSAIDs with melatonin, curcumin, ginkgo, magnesium, berberine, creatine, potassium, kava and ashwagandha. We read the records of 25 papers and cite 25. We also read the NHS melatonin interaction page, two ibuprofen drug labels on DailyMed and the NIH vitamin E fact sheet. We prioritized systematic reviews, randomized trials and drug labels, and used case reports only where nothing stronger exists.

The gaps are large: no trial has tested melatonin, magnesium, curcumin or berberine together with ibuprofen. Most bleeding-risk claims rest on case reports and lab data. Researched on 30 October 2026.

1. Surrall K, et al. Effect of ibuprofen and indomethacin on human plasma melatonin. J Pharm Pharmacol. 1987;39(10):840-3. doi:10.1111/j.2042-7158.1987.tb05129.x
2. Gengo F. Effects of ibuprofen on sleep quality as measured using polysomnography and subjective measures in healthy adults. Clin Ther. 2006;28(11):1820-6. doi:10.1016/j.clinthera.2006.11.018
3. Murphy PJ, et al. Nonsteroidal anti-inflammatory drugs alter body temperature and suppress melatonin in humans. Physiol Behav. 1996;59(1):133-9. doi:10.1016/0031-9384(95)02036-5
4. Murphy PJ, et al. Nonsteroidal anti-inflammatory drugs affect normal sleep patterns in humans. Physiol Behav. 1994;55(6):1063-6. doi:10.1016/0031-9384(94)90388-3
5. NHS. Taking melatonin with other medicines and herbal supplements. https://www.nhs.uk/medicines/melatonin/taking-melatonin-with-other-medicines-and-herbal-supplements/
6. DailyMed, U.S. National Library of Medicine. Ibuprofen and diphenhydramine citrate tablet, coated (nighttime pain reliever and sleep aid): Drug Facts label. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=658fc201-47c9-6a6d-8af9-6208298d43b4&audience=consumer
7. Konturek PC, et al. Melatonin and its precursor L-tryptophan prevent acute gastric mucosal damage induced by aspirin in humans. J Physiol Pharmacol. 2008;59 Suppl 2:67-75. https://pubmed.ncbi.nlm.nih.gov/18812629/
8. Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin Pharm Ther. 2002;27(6):391-401. doi:10.1046/j.1365-2710.2002.00444.x
9. Stanger MJ, et al. Anticoagulant activity of select dietary supplements. Nutr Rev. 2012;70(2):107-17. doi:10.1111/j.1753-4887.2011.00444.x Our study summary.
10. Neuvonen PJ. The effect of magnesium hydroxide on the oral absorption of ibuprofen, ketoprofen and diclofenac. Br J Clin Pharmacol. 1991;31(3):263-6. doi:10.1111/j.1365-2125.1991.tb05527.x
11. Nash DM, et al. Nonsteroidal anti-inflammatory drug use and risk of acute kidney injury and hyperkalemia in older adults: a population-based study. Nephrol Dial Transplant. 2019;34(7):1145-1154. doi:10.1093/ndt/gfz062
12. Guo Y, et al. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-7. doi:10.1007/s00228-011-1108-2
13. Kirchheiner J, et al. Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2. Clin Pharmacol Ther. 2002;72(1):62-75. doi:10.1067/mcp.2002.125726
14. DailyMed, U.S. National Library of Medicine. Ibuprofen 200 mg tablet, film coated: over-the-counter Drug Facts label. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=afa87bb5-7fcb-4ccd-acac-f7931242181f
15. Kellermann AJ, et al. Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy. 2011;31(5):490-502. doi:10.1592/phco.31.5.490 Our study summary.
16. Bent S, et al. Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature: a case report and systematic review of the literature. J Gen Intern Med. 2005;20(7):657-61. doi:10.1111/j.1525-1497.2005.0121.x
17. Meisel C, et al. Fatal intracerebral mass bleeding associated with Ginkgo biloba and ibuprofen. Atherosclerosis. 2003;167(2):367. doi:10.1016/s0021-9150(03)00015-7
18. National Institutes of Health, Office of Dietary Supplements. Vitamin E: Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/
19. Kuptniratsaikul V, et al. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study. Clin Interv Aging. 2014;9:451-8. doi:10.2147/CIA.S58535 Our study summary.
20. Shep D, et al. Safety and efficacy of curcumin versus diclofenac in knee osteoarthritis: a randomized open-label parallel-arm study. Trials. 2019;20(1):214. doi:10.1186/s13063-019-3327-2
21. Onakpoya IJ, et al. Effectiveness of curcuminoids in the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomized clinical trials. Int J Rheum Dis. 2017;20(4):420-433. doi:10.1111/1756-185X.13069
22. Gontarz N, et al. Effect of antacid suspension on the pharmacokinetics of ibuprofen. Clin Pharm. 1987;6(5):413-6. https://pubmed.ncbi.nlm.nih.gov/3665393/
23. Thorsteinsdottir B, et al. Acute renal failure in a young weight lifter taking multiple food supplements, including creatine monohydrate. J Ren Nutr. 2006;16(4):341-5. doi:10.1053/j.jrn.2006.04.025
24. de Souza E Silva A, et al. Effects of Creatine Supplementation on Renal Function: A Systematic Review and Meta-Analysis. J Ren Nutr. 2019;29(6):480-489. doi:10.1053/j.jrn.2019.05.004
25. Teschke R, et al. Kava hepatotoxicity: a clinical survey and critical analysis of 26 suspected cases. Eur J Gastroenterol Hepatol. 2008;20(12):1182-93. doi:10.1097/MEG.0b013e3283036768
26. Björnsson HK, et al. Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network. Liver Int. 2020;40(4):825-829. doi:10.1111/liv.14393
27. Besag FMC, et al. Adverse events in long-term studies of exogenous melatonin. Expert Opin Drug Saf. 2022;21(12):1469-1481. doi:10.1080/14740338.2022.2160444
28. Lauritzen ES, et al. Effects of daily administration of melatonin before bedtime on fasting insulin, glucose and insulin sensitivity in healthy adults and patients with metabolic diseases. A systematic review and meta-analysis. Clin Endocrinol (Oxf). 2021;95(5):691-701. doi:10.1111/cen.14576
29. Anglin R, et al. Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis. Am J Gastroenterol. 2014;109(6):811-9. doi:10.1038/ajg.2014.82