Methylene Blue and Exercise: What the Research Does and Does Not Show

Short answer: no published study we could find shows that methylene blue improves strength, muscle growth, or endurance in healthy people who lift or train. There are mitochondrial studies in cells, a few animal studies that touch on muscle or exercise, and some human brain-imaging work. That is the whole map. Nobody has run the gym trial.

• What is studied: mitochondrial respiration in cultured cells and isolated rat tissue, a 1986 dog treadmill experiment, rat and mouse muscle or tendon models, and brain blood flow and metabolism in healthy humans.
• What is unproven: any gain in strength, hypertrophy, VO2, endurance, or recovery in healthy lifters. A 2023 imaging study in healthy volunteers actually found lower brain blood flow and oxygen metabolism after methylene blue, not higher.
• What to watch: methylene blue inhibits monoamine oxidase A in lab tests, and reviews link it to serotonin toxicity with serotonergic drugs. We have not seen any study that tests it alongside pre-workout blends.

Important: The FDA label for methylene blue injection (Provayblue) warns about serotonin syndrome with serotonergic medications, including SSRIs and MAOIs. Review the full adverse medications list before use. We do not give doses in this article. Talk to your healthcare provider.

Search interest in methylene blue for the gym comes from one idea: mitochondria make the energy your muscles use, methylene blue interacts with the mitochondrial electron transport chain, so it must help training. The first half of that is real science. The last step is a guess. For background on the mechanism itself, see our explainer on how methylene blue works.

A 2018 review describes methylene blue as able to reroute electrons in the mitochondrial chain directly from NADH to cytochrome c, which the authors say increases complex IV activity while limiting oxidative stress (Tucker et al., Molecular Neurobiology, 2018). That review is about neuroprotection and the evidence it summarizes is mostly cell and animal work on brain conditions, not muscle performance.

In cultured human fibroblasts (skin-derived cells), methylene blue at very low concentrations raised complex IV by about 30 percent and cellular oxygen consumption by 37 to 70 percent in the authors' experiments (Atamna et al., FASEB Journal, 2008). In mitochondria isolated from rat hearts, a low concentration of methylene blue increased oxygen consumption, and its effect on hydrogen peroxide release depended on which fuel the mitochondria were given (Duicu et al., Canadian Journal of Physiology and Pharmacology, 2017).

Here is every exercise or muscle related animal study we found and what each one actually measured. We searched PubMed on September 30, 2026 using methylene blue with terms for exercise, skeletal muscle, fatigue, endurance, and oxygen consumption.

Two results matter most. First, the 1986 dog experiment is the closest thing to a direct test of methylene blue during exercise, and it did not show a change in the cardiac output and oxygen consumption relationship. Second, the positive muscle result is in a mouse model of ALS, where the muscle was already failing. Neither one is a reason to expect a stronger set of squats.

Gym forums often pair methylene blue with a pump or vasodilation story, as if more nitric oxide means more blood to the muscle. The published work we found points the other way in the one muscle preparation we could check. In rat cremaster arterioles, methylene blue inhibited dilation to acetylcholine and nitric oxide, and the authors tied this to superoxide generation outside the cells (Wolin et al., Journal of Pharmacology and Experimental Therapeutics, 1990). That is a rat vessel study under anesthesia, so it does not prove what happens in a training human either. The point is narrower: the pump claim has no supporting human data, and the nearest animal data does not support it.

We found no randomized or controlled human trial of methylene blue with an exercise, strength, endurance, VO2, or muscle outcome in healthy people. Searching for it in several ways returned animal work, case reports, and unrelated hits. No study is not proof of no effect, but it does mean nobody can promise you one.

What human data exist is about the brain, and it is not a clean win for the energy story.

• Singh et al., Journal of Cerebral Blood Flow and Metabolism, 2023: in a small group of healthy human volunteers and in rats, intravenous methylene blue reduced global cerebral blood flow and, in humans, reduced the cerebral metabolic rate of oxygen. The authors had expected the opposite. They suggest the clinically relevant concentrations may have a hormetic effect, meaning higher amounts inhibit instead of enhance, and that healthy brains with normal metabolism may have little room to improve.
• Rodriguez et al., Brain Imaging and Behavior, 2017: in a randomized, double-blind, placebo-controlled fMRI study in healthy adults, a single low oral dose was associated with lower cerebral blood flow in a task-related network and stronger resting-state connectivity in regions linked to perception and memory. The authors call for more work. It says nothing about muscle or athletic output.

Methylene blue is also an old, well studied drug in medicine. That history is about clinical uses under medical care, not about lifting. If you want the timing side of how people use it day to day, see the best time to take methylene blue, and keep in mind that it does not rest on gym trials either.

This is the part we would want a lifter to read twice. In tests on purified human enzyme, methylene blue was a potent, reversible inhibitor of monoamine oxidase A, and the authors linked that to the serotonin toxicity reported when it is given to patients on SSRIs (Ramsay et al., British Journal of Pharmacology, 2007). A 2011 review concluded that 13 of 14 reported cases of central nervous system toxicity with methylene blue met the criteria for serotonin toxicity, and advised very careful thought about stopping serotonin reuptake inhibitors before using it (Gillman, Journal of Psychopharmacology, 2011). Those cases involved clinical intravenous use, so they do not tell us how oral supplement use behaves. They do tell us the mechanism is real.

Where does that leave a pre-workout shaker? Nobody knows. Many pre-workout blends are stimulant-heavy, some include ingredients that act on monoamine systems, and we are not aware of any study that tests methylene blue with them. That is a reason to read labels, not a reason to assume it is fine. Check the ingredient list against the adverse medications list, read our methylene blue drug interactions guide, and ask your pharmacist or prescriber. For the caffeine side of the comparison, see our methylene blue vs pre-workout comparison.

If you compete in a tested sport, do not treat this article, or any supplement label, as clearance. We could not confirm from a primary source how any specific anti-doping code treats methylene blue, so we are not going to guess. Check your governing body's current prohibited list directly and ask the body before you use it.

Separately, a supplement that is fine under a rulebook can still interact with the medications you take. Both checks matter.

For the record, here is what would actually answer the gym question. A placebo-controlled, double-blind trial in healthy trained adults, with a pre-registered primary outcome such as time to exhaustion, VO2 max, or one-rep max, repeated across training weeks, with serotonergic drug use screened out and safety tracked. Until something like that is published, the accurate word for methylene blue and performance is unproven.

If your goal is getting more out of training, the boring levers still have the human evidence: progressive load, protein intake, sleep, and consistency. Methylene blue does not replace any of them.

Skip methylene blue, or talk to your healthcare provider first, if you:

• Take an SSRI, SNRI, MAOI, or any other serotonergic medication (risk of serotonin toxicity, per the sources above)
• Are stacking it with a stimulant-heavy or multi-ingredient pre-workout and have not checked the ingredients
• Have G6PD deficiency or are unsure of your status (see our G6PD deficiency guide)
• Are pregnant or nursing
• Are expecting it to add to your lifts or your run times. The research does not back that expectation.

Review the full adverse medications list and consult your healthcare provider before starting methylene blue in any form.

Nutricel sells methylene blue as capsules and as a 1% liquid, plus a mushroom blend. None of them are sold as sports or performance products, and nothing in this article is a recommendation to use one for training. Your provider, not us, should set the amount. Our lab reports are on the third-party test reports page.

If you and your provider decide methylene blue fits your situation, this is how our products differ:

Blue Boost is our core formula: 12mg of methylene blue per capsule with Vitamin C Ester and organic cacao.

Blue Immune combines methylene blue with copper, NAC, grass-fed beef liver, and vitamins A, C, and E.

Blue Shroom pairs methylene blue with six organic mushroom extracts including lion's mane, reishi, cordyceps, chaga, shiitake, and turkey tail.

Blue Renew is built around GlyNAC (glycine and N-acetyl cysteine) alongside methylene blue.

Blue Remove combines zeolite, curcumin, and nattokinase with methylene blue.

Blue Liquid is USP-grade methylene blue in a dropper bottle (1%, 10mg per mL).

Methylene blue has real mitochondrial chemistry behind it. It does not have a single human trial showing better lifting, bigger muscles, or longer endurance. The nearest experiments are a 1986 dog study that found no change in the cardiac output and oxygen consumption relationship, a rat study about brain damage after exhaustive running, a mouse disease model, and human brain imaging that found lower cerebral blood flow and oxygen metabolism in healthy volunteers.

If anyone sells methylene blue to you as a gym supplement, they are getting ahead of the evidence. Keep your expectations modest, watch the serotonergic medication issue, and keep your provider in the loop.

Mitochondria and Cell Studies

Exercise, Muscle and Blood Flow Studies in Animals

Human Brain Imaging

Serotonin and MAO

Further Reading

Sam Carlson, Marketing Developer at Nutricel

Sam is a marketing developer at Nutricel who writes the Nutricel Insights series to help our customers understand methylene blue and make informed choices, translating the published research into plain language. Sam is not a medical professional, and these articles are intended as education rather than medical advice. Every figure in this piece is tied to the studies listed in the references, and you should always speak with your healthcare provider before starting any supplement.