Methylene Blue for Endurance: What the Science Says

Imagine pushing through mental fog or muscle fatigue: not with caffeine or creatine, but with a century-old blue compound that’s making a quiet comeback in neuroscience labs and performance circles. Did we say quiet? Well...not really since January of this year! 

Methylene blue, once used to dye textiles and treat infections, is now under the scientific spotlight for its potential to enhance endurance: not just physically, but cognitively and metabolically as well. With new clinical studies revisiting its mechanisms and benefits, high performers and biohackers are increasingly turning to methylene blue for that extra edge.

But is it safe? And does the science really back the hype?

Let’s explore why methylene blue is gaining hype, and what to watch out for.

The Science-Backed Potential

Methylene blue is best known for treating methemoglobinemia, a condition where red blood cells can't release oxygen effectively. It has been explored as a potential option in managing distributive shock, particularly in cases where conventional therapies are ineffective [1]. Recent evidence suggests it may have much broader benefits, especially for endurance and performance.

1. Boosting Cellular Energy

Methylene blue enhances mitochondrial respiration by bypassing damaged segments of the electron transport chain, specifically at complex IV (cytochrome c oxidase), and supports ATP production [2]. This is a game-changer in endurance, where mitochondrial efficiency directly affects how long and hard the body and brain can perform.

In 2021, a study showed that a single low dose of methylene blue enhanced fMRI activity (a brain imaging technique that tracks blood flow in the brain) in brain regions responsible for sustained attention and memory, suggesting enhanced oxygen usage and brain efficiency under cognitive load [3].

2. Protecting the Brain Under Stress

In surgical patients, a single 2 mg/kg dose of methylene blue administered after anesthesia induction significantly reduced postoperative cognitive dysfunction and delirium, a sign that methylene blue supports neuroprotection during extreme stress [3].

Interestingly, these protective effects aren't limited to acute stress. In another trial, patients with bipolar disorder who were experiencing residual depression and cognitive fatigue saw significant improvements in mood and anxiety levels when treated with higher-dose methylene blue, without triggering mania [4].

This suggests that methylene blue may support long-term brain resilience in populations under chronic psychological stress as well. 

3. Improving Memory and Focus

Methylene blue has also shown potential to support focus and memory in healthy people. It was demonstrated that a low dose performed better on memory tests and showed more brain activity in areas linked to attention and recall. Just one dose was enough to boost mental performance by about 7%, suggesting methylene blue might help the brain work more efficiently when under pressure [5]. 

While large-scale studies are still limited, these early findings have sparked growing interest in methylene blue's potential as a cognitive enhancer. Its ability to support memory, attention, and mental clarity, especially under pressure, is now being explored in wellness, longevity, and performance circles.

Why Everyone’s Talking About It

While methylene blue is not yet approved for performance enhancement, interest is growing among:

• Biohackers looking for a mitochondrial upgrade. 
• Founders and shift workers fighting brain fog
• High-altitude adventurers using it to improve oxygen efficiency
• Longevity communities experimenting with it as a neuroprotective agent
• People with chronic complex medical illnesses who have been struggling

In niche forums and podcasts, methylene blue is being talked about in the same breath as creatine, NMN, and red light therapy, especially for its role in photobiomodulation as a light-activated mitochondrial enhancer. In fact, researchers have found that methylene blue and red light may work even better together. One study showed that both boost energy production in cells by acting on the same mitochondrial enzyme, but in slightly different ways. When combined, they may enhance memory and brain performance more than either one alone. That’s part of why methylene blue is gaining attention in longevity circles and brain-hacking protocols that include red light therapy [6].

Before you dive in, it’s worth knowing what you’re really working with. Methylene blue can do a lot, but it’s not a magic pill, and using it wisely makes all the difference.

Smart Use Starts Here

Methylene blue is also a monoamine oxidase inhibitor or MAOI, which means it can interact with antidepressants and other serotonergic agents, increasing the risk of serotonin syndrome [7]. It also poses a risk for individuals with G6PD deficiency, potentially triggering hemolytic anemia [8]. 

If you’re taking medications like sertraline, fluoxetine, escitalopram, venlafaxine, or amitriptyline, methylene blue should be avoided unless you're under direct medical supervision. Likewise, anyone with a personal or family history of G6PD deficiency, or those unsure of their status, should speak to their healthcare provider and consider testing. 

Additionally, higher doses haven’t always led to better outcomes. Some studies, particularly in Alzheimer’s research, found that increasing the dose didn’t enhance results, and in a few cases, it appeared to interfere with the intended benefits [5,6]. The optimal dose in these studies was 8 mg twice daily. 

As with most powerful compounds, more is not better. Most studies showing benefit use low doses (< 3 mg/kg), often referred to as the “therapeutic window” for methylene blue; however, doses on the lower side — 4 mg to 25 mg (not weight-based) — are often all that are needed to see significant improvements in mitochondrial dysfunction. 

You may want to consider higher doses — around 1 mg/kg or greater — for acute or chronic infections, or even more severe mitochondrial dysfunction, but these doses are best guided by a practitioner. 

When to Take It

Methylene blue isn’t your typical 4 PM pre-workout. Because it can feel subtly activating, the best time to dose is in the morning: ideally 30 to 60 minutes before your workout, deep work block, or any endurance challenge (mental or physical). If you train later in the day, try your first few doses earlier and track how it affects your sleep, focus, or recovery.

Pro tip: If you’re new to methylene blue or want to start at a lower dose, then start with 1/4 troche of Just Blue, Troscriptions' pure methylene blue buccal troche! It’s an easy way to ease in, especially if you’re tracking your response.

Some users report improved clarity, reduced “energy dips,” and more consistent output during both cardio and resistance training sessions. If you're training fasted or doing endurance work, methylene blue helps your mitochondria work more efficiently, giving you better oxygen use and less perceived fatigue, and longer to lactate threshold [6].

What to Pair It With (and What to Avoid)

You don’t need to overhaul your nutrition, but you can support methylene blue's effects by focusing on cell-friendly fuel:

• Avocados, eggs, and fatty fish (great for brain + mitochondria)
• Berries and dark leafy greens (antioxidant support without heavy sugar load)
• Hydration, because methylene blue may subtly shift how your body handles oxygen, and you want your blood volume on point
• Even supplementing with micronutrients that support mitochondrial function, like B-vitamins, minerals, and antioxidants like glutathione, may be helpful

Avoid mixing methylene blue with medications like Prozac, Zoloft, or Effexor, or anything that affects serotonin, dopamine, or norepinephrine unless cleared by a doctor [9]. And you may want to skip it (or decrease it) on days you’re stacking heavy nootropics or stimulants, especially if you don’t know how you react.

Track Like You Train

If you track macros, personal records, or sleep, treat methylene blue the same way. Keep a short log of...

• Time of dose
• Workout type + performance notes (mental or physical workouts!)
• Mental clarity or fatigue level
• Sleep quality that night (including HRV, if you train)
• Inflammation, pain, and mood

The goal isn’t perfection: it’s pattern recognition. If you’re getting better endurance, more steady output, less inflammation and brain fog, or smoother recovery, you’ll know it’s working for you, not just in theory.

Know the Compound. Own the Results.

Methylene blue isn’t just a quirky dye from the past; it’s a compound with real potential to enhance endurance, cognitive performance, and metabolic resilience. From surgical recovery to brain-boosting studies in healthy adults, the research is building. And while it’s not a miracle cure (or a shortcut), methylene blue may offer a new way to train longer, think clearer, and recover better, when used with care.

But like any tool, the outcome depends on the user. It’s not about taking more: it’s about knowing your “why,” understanding your body, and respecting the science.

Try it. Track it. Know your body. That’s where real performance begins.

And if you’re curious where to start, Just Blue offers a physician-formulated, pharmaceutical-grade, and precision-dosed buccal troche to brighten your focus, decrease inflammation, and boost your energy and endurance.

No guesswork. Just the benefits, backed by research, ready to meet your goals when you are.

A note on methylene blue quality from Dr. Scott here (hint: liquids are not a good idea): https://www.instagram.com/reel/DMfxhBrswA4/?utm_source=ig_web_copy_link&igsh=MzRlODBiNWFlZA==

Additionally, here are some previous methylene blue articles that may be of interest:

• Methylene Blue as a Nootropic: Science, Potential, and Usage
• Methylene Blue: Sorting out the Fishy Headlines
• How to take methylene blue orally to optimize health
• Methylene Blue and Red Light: The Colors of Neuroprotection
  
• The MAOI-Methylene Blue Connection: A Breakthrough in Mood Enhancement
• Methylene Blue for Jet Lag
• The Effects of Methylene Blue Usage on Hormones
• Methylene Blue: Unlocking Its Potential in the Fight Against Breast Cancer
• Methylene Blue for Detoxification: Methemoglobinemia, Mitochondrial Toxins, and More
• Methylene Blue for Human Skin: Anti-Aging, Regeneration, and More
• Methylene Blue: Enhancing Cellular Energy Metabolism via Cytochrome C Oxidase

References

1. Jang DH, Nelson LS, Hoffman RS. Methylene blue for distributive shock: a potential new use of an old antidote. J Med Toxicol. 2013;9(3):242-249. doi:10.1007/s13181-013-0298-7

2. Rodriguez P, Zhou W, Barrett DW, et al. Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain. Radiology. 2016;281(2):516-526. doi:10.1148/radiol.2016152893

3. Deng Y, Wang R, Li S, et al. Methylene blue reduces incidence of early postoperative cognitive disorders in elderly patients undergoing major non-cardiac surgery: An open-label randomized controlled clinical trial. J Clin Anesth. 2021;68:110108. doi:10.1016/j.jclinane.2020.110108

4. Alda M, McKinnon M, Blagdon R, et al. Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study. Br J Psychiatry. 2017;210(1):54-60. doi:10.1192/bjp.bp.115.173930

5. Rodriguez P, Zhou W, Barrett DW, et al. Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain. Radiology. 2016;281(2):516-526. doi:10.1148/radiol.2016152893

6. Rojas JC, Bruchey AK, Gonzalez-Lima F. Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. Prog Neurobiol. 2012;96(1):32-45. doi:10.1016/j.pneurobio.2011.10.007

7. Naylor GJ, Martin B, Hopwood SE, Watson Y. A two-year double-blind crossover trial of the prophylactic effect of methylene blue in manic-depressive psychosis. Biol Psychiatry. 1986;21(10):915-920. doi:10.1016/0006-3223(86)90265-9

8. Guild R, Rapport D. Calorigenic action of methylene blue during muscular exercise. Proc Soc Exp Biol Med. 1936;34(4):459-461. doi:10.3181/00379727-34-8658C.

9. U.S. Food and Drug Administration. FDA Drug Safety Communication: Updated information about the drug interaction between methylene blue (methylthioninium chloride) and serotonergic psychiatric medications. FDA. Published October 20, 2011. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-updated-information-about-drug-interaction-between-methylene-blue