Is Melatonin Anti-Inflammatory? What Trials Found Beyond Sleep

A sleep hormone with a second job?

Your brain makes melatonin at night. It is the hormone that helps set your body clock.1 Many people take it as a pill for sleep or jet lag.7

Melatonin also plays a part in the immune system, and lab and animal studies suggest it calms inflammation.1 But for years, few human trials had tested that.1 That gap is the reason for this article. A pill many people already own for sleep could, in theory, do a second job. Does it?

First, two terms. CRP (C-reactive protein) is the inflammation marker your doctor is most likely to test, and IL-6 is a signaling protein your body uses to turn inflammation up. A meta-analysis pools many trials into one answer.

Can melatonin reduce inflammation?

The largest review we found pooled 31 trials with 1,517 people, published in 2021. Melatonin lowered IL-1, IL-6, IL-8 and TNF, all signals that push inflammation up.1 CRP did not move.1

Across 31 trials, melatonin lowered IL-6 and related signals, but CRP did not move.From a 2021 meta-analysis in Brain Behav Immun

The team then checked their work. When they set aside trials with outsize results, IL-1, IL-6 and IL-8 still came out lower, but TNF no longer did.1

A second review, from 2020, pooled 13 trials with 749 people. Melatonin lowered TNF and IL-6. Its effect on CRP was borderline and could have been chance.2 The trials in that review also disagreed with each other to a very high degree.2

So the answer to the big question is a careful yes for some signals, and a shrug for CRP.

Who were the trials in?

This is where the picture sharpens, because the trials with the clearest results were mostly in people who were already living with a disease that keeps inflammation running high.

In 6 trials of people with metabolic syndrome and related conditions, melatonin lowered CRP and IL-6, but not TNF.3 In 14 trials with 823 people with diabetes, it lowered CRP, TNF, IL-1 and IL-6.4 A 2025 review of 63 randomized trials on heart and metabolic health found CRP fell by 0.59 mg/L on average, with IL-6 and TNF lower too.5

Then there is multiple sclerosis (MS), an autoimmune disease where the immune system attacks the nerves. A 2026 review of 10 studies with 435 people found melatonin did not reduce relapses, disability or new damage on brain scans.6 Small studies hinted at better sleep, mood and inflammation markers, but those results were inconsistent and rarely repeated.6 Every outcome was rated low or very low certainty.6

We found no trial that tested melatonin on inflammation in healthy people as its main question. So if you are healthy and your CRP is normal, these trials do not tell you much about what melatonin would do for you.

Does melatonin help you sleep?

Here the evidence is firmer. A 2017 meta-analysis found the most convincing use was helping people with insomnia fall asleep faster, and resetting sleep timing in people whose body clock runs late.8

Timing seems to matter as much as dose. A 2024 review of 26 randomized trials found that the effect on falling asleep and on total sleep time peaked at 4 mg a day.9 The authors suggested taking it about 3 hours before bed, rather than the common habit of 2 mg 30 minutes before.9

Sleep and inflammation are linked. A 2016 review of 72 studies with more than 50,000 people found that poor sleep was linked to higher CRP and IL-6.10 Short-term sleep loss in the lab, though, did not raise those markers.10 So better sleep might be one route by which melatonin calms inflammation. None of the reviews we read tested that idea.

Is melatonin safe at higher doses?

Most of the inflammation trials used higher doses than a typical sleep pill, so this matters. A 2022 review looked at 79 trials of 10 mg or more, with 3,861 people.7 Of those trials, 29 (37%) never said whether side effects happened.7 In the few trials with the best methods, melatonin did not raise serious side effects but did raise drowsiness, headache and dizziness.7

The MS review adds a warning. Doses from 0.5 to 25 mg a day were generally well tolerated.6 But at 300 mg a day, 3 of 4 people taking melatonin developed high liver enzymes, which went away once they stopped.6

The bottom line

Melatonin was always a sleep hormone first. The trials add a second chapter: lower IL-6 and related signals across dozens of small studies, a CRP drop in people with diabetes and metabolic syndrome, and no clear change in CRP across the largest pool of trials. That is real, but early. For most people, melatonin is still what the label says: a tool for getting to sleep. Use it that way. Any calm it brings to your blood work is a bonus the science has not yet pinned down.