Episode 190: Methylene blue/Part 2 of Matthew Schuster and Eric Zaltas

A brief synopsis of the episode's main discussions and takeaways as well as extended references

Author

Jeff Sankoff
February 13, 2026

Should you be considering a commercial dye product as a means of enhancing endurance performance? You probably won’t be surprised to learn that yet again, health and wellness influencers are not interested in science but rather, just promoting their own narratives….

Table of Contents

Methylene blue as a supplement to enhance endurance performance

Methylene blue has gained attention in endurance sport circles as a potential performance-enhancing supplement, largely because of its intriguing effects on cellular energy metabolism. In laboratory settings, methylene blue can act as an alternative electron carrier in the mitochondrial electron transport chain, theoretically improving oxidative phosphorylation efficiency and reducing the buildup of reactive oxygen species. This has led to claims that it can boost aerobic capacity, delay fatigue, and enhance endurance.

On the Medical Mailbag in this episode we sought to tease fact from the fiction being promoted by practitioners on the fringe of actual science based medicine and determine if this is something worth pursuing.

The reality, you won’t be too surprised to learn, is far more modest. Most evidence supporting methylene blue’s performance benefits comes from animal studies, in vitro experiments, or clinical contexts involving mitochondrial dysfunction or acute medical conditions. High-quality human studies in healthy, trained endurance athletes are scarce. Where human data exist, they tend to show minimal or inconsistent effects on exercise performance, particularly when compared with well-established interventions such as training adaptation, carbohydrate availability, altitude exposure, or caffeine.

There are also practical and safety considerations. Methylene blue is a prescription medication at many doses and can interact with serotonergic drugs, increasing the risk of serotonin syndrome (serotenergic drugs are common antidepressants and serotonin syndrome is a potentially fatal condition). At higher doses, it may impair rather than enhance mitochondrial function and can cause side effects including gastrointestinal distress and headache. It is also on the World Anti-Doping Agency (WADA) Monitoring Program, signaling regulatory interest.

In short, methylene blue is biochemically interesting but currently unsupported as a reliable endurance performance supplement. For most athletes, the hype outpaces the evidence.

Matthew Schuster and Eric Zaltas-back for Part 2 of their interview

Our guests, Matthew Shuster and Eric Zaltas, the masterminds behind Addra Labs, are back for the second part of their interview (part 1 can be heard in episode 189) to enlighten us on why protein is not just for bodybuilders but is crucial for endurance athletes too. Forget about the tired old narrative that carbs are king—these guys are flipping the script and showing us how protein can be the unsung hero of recovery and performance. They unpack the latest research suggesting that endurance athletes might need a whopping 1.8 grams of protein per kilogram of body weight. It’s time to put down those bland protein shakes and pay attention to what you’re really fueling your body with. This episode is packed with insights on how to optimize your nutrition to get the most out of your training without turning into the Hulk. 

Now while I do not do product endorsements on this program and I have not personally tried Addra’s bars myself, I do want to share a coupon code that Matthew and Eric have made available to TriDoc Podcast listeners and newsletter subscribers. If you head over to their website and enter the code recovery25 at checkout you will receive 25% off your first order. I hope you will check it out and let me know what you think.

Episode takeaways:

  • Protein is not just for bodybuilders; endurance athletes really need it for recovery and performance, but too much can lead to unwanted weight gain.

  • Methylene blue is touted as a miracle supplement for athletes, but the science doesn’t really back it up, and using it could be more harmful than good.

  • Recent studies suggest that endurance athletes might need even more protein than previously thought, highlighting the importance of proper nutrition post-workout.

  • The podcast offers a fresh perspective on the absurdity of health influencers, reminding us to be cautious about who we trust with our wellness advice.

References used for the MMB

Methylene Blue 101: How It Works and Side Effects

WebMD

Key Points:

  •  Methylene blue, originally used for dyeing purposes, began being used as a treatment for malaria ~125 years ago

  • Its only FDA-approved use began in 2016 for the treatment of methemoglobinemia, where a dose or two of methylene blue is dissolved and infused via IV

  • Methemoglobinemia, also known as “baby blue syndrome”, is a blood disorder caused by exposure to medication, drugs, or chemicals that prevent red blood cells from delivering oxygen to tissues, causing lips, skin, tongue, and nail beds to turn blue

  • Methylene blue increases oxygen delivery by reducing methemoglobin to hemoglobin

  • Methylene blue can cause hemolysis and worsen conditions for those with glucose-6-phosphate dehydrogenase (G6PD) deficiency

  • It can cause side effects, including chest pain, confusion, dizziness, and stomach pain, or interfere with medications, so it is important to discuss risks with a doctor

  • Beyond FDA-approved use, off-label and experimental use have targeted its potential as an antidote for nitrite or aniline poisoning, cognitive booster, cancer detector, disinfectant, and anti-aging agent.

What to know about methylene blue

Harvard Health Publishing Article by Leslie Goldman, MPH

Key Points:

  • Methylene blue is one of the oldest organic dyes, which was originally used as a textile dye

  • This synthetic dye has a history of being used for medical purposes

  • It is structurally similar to tricyclic antidepressants, and its interaction could be fatal if used by a person who is already taking certain antidepressants

  • Methylene blue has been shown to enhance mitochondrial efficiency 

  • The idea that methylene blue slows cellular aging, prevents cancer, reduces the risk of incurable neurological disorders, and enhances energy, mood, focus, and memory has surfaced, but the evidence is inconclusive

  • Some studies, such as one by a researcher from Texas A&M claimed that its use led to an 8% decrease in blood flow to the human brain

  • Purchasing unregulated supplements and consuming them is very different from utilizing the product under the supervision of a medical provider

  • Researchers have identified impurities in industrial- and chemical-grade methylene blue, making them inappropriate for human/animal consumption

  • It is necessary to note that methylene blue could pose significant risks

Why Athletes Are Turning to Methylene Blue for Performance and Recovery 

King’s Pharmacy and Compounding Center article

Key Points:

  • The King’s Pharmacy and Compounding Center specializes in compounding methylene blue for athletic support

  • They claim that the capsules, liquid/sublingual drops, and supplement options they provide are pharmaceutical-grade without impurities

  • The article notes that they work closely with sports physicians, fitness coaches, and integrative medicine specialists

  • This article notes that Methylene Blue enhances ATP production through improved mitochondrial efficiency and oxygen utilization

  • They claim the methylene blue is especially beneficial for endurance athletes, functional fitness competitors, high-performance lifters, and those recovering from training burnout or injury because of the following reasons:

    • “Increases cellular energy output – Methylene Blue helps mitochondria produce ATP more effectively.

    • Improves oxygen usage – More oxygen means better endurance and less fatigue.

    • Enhances mental clarity under pressure – Great for athletes in high-focus environments.

    • Reduces oxidative stress – Protects tissues from damage during intense exertion.

      • Reduced DOMS (Delayed Onset Muscle Soreness)

      • Shortened post-training recovery window

      • Improved muscle repair and tissue oxygenation

      • More consistent energy levels during training cycles”

NADclinic website, Methylene Blue page

Key Points:

  • Methylene Blue acts as an electron donor in the ETC, which enhances cellular metabolism, which boosts energy levels and cognitive performance

  • Its ability to support oxygen delivery and utilization enhances endurance and recovery

  • Recommended dosage is 0.5-1mg/kg of body weight

Intranasal methylene blue administration confers neuroprotection in rats subjected to exhaustive exercise training

Peng et al. 2025

Key Points:

  • Some evidence suggests the negative effects of exercise-induced fatigue on the nervous system

  • In this study, rat models were used to assess whether intranasal methylene blue could prevent exercise-induced neurological deficits

  • The study showed that exhaustive exercise resulted in reduced locomotor activity, increased anxiety-like behaviors, and impaired spatial memory, associated with loss of neurons, synaptic proteins/myelin sheath, gliosis, compromised mitochondrial morphology, and the activation of apoptotic pathways.

  • However, some neuroprotective effects of methylene blue were demonstrated.

  • Sample staining and analysis of apoptotic markers in this study showed that nasal methylene blue administration mitigated mitochondrial morphological changes in rats exposed to 10 days of exhaustive swimming by inhibiting the activation of apoptotic pathways and glial cells.

  • Methylene blue may help to reduce the neurological damage caused by exhaustive exercise.

  • The direct effect of methylene blue on athletic performance was not addressed through this study design.

  • The neuroprotective potential of methylene blue has been shown in previous studies.

Introduction: This study assessed the potential for methylene blue to prevent neurological deficits induced by exhaustive exercise. 

Methods: Male Sprague-Dawley rats acclimated for 14 days before experimentation. 2 months old rats randomized into control (in water, no exercise) (n=6), exhaustive swimming exercise (n=7), or exhaustive swimming exercise with nasal methylene blue administration (n=7).  Swimming acclimation of 3 days prior to exhaustive testing of 10 consecutive days for 2h with 3% of body weight attached to tail. Methylene blue administered nasally after each training session. 1% MB solution (10mg/ml) diluted in 0.9% saline. Control and exercise only group administered 0.9% saline. Mazes used to evaluate anxiety-like behaviors as well as spatial learning and memory. Tissues collected after experiment and stained to quantify surviving neurons.

Results: MB improved time to exhaustion and physical condition of rats, improved anxiety-like behaviors and spatial memory abilities, and prevented hippocampal neuron loss while inhibiting activation of apoptotic pathways, prevented loss of striatial neurons and myelin protein, and significantly inhibited the exercise-induced loss of dendritic and synaptic proteins in rats exposed to exhaustive training. Exhaustive exercise also induced excessive activation of glial cells in both the hippocampal and striatal regions and increased mitochondrial fragmentation and disrupted morphology, while the methylene blue inhibited this effect.

Effect of methylene blue on cardiac output response to exercise in dogs

Imai et al. 1986

Key Points:

  • Only had access to the abstract of this paper

  • This study assessed the effect of methylene blue (4mg/kg before exercise, followed by 0.15mg/kg/min) on cardiac output during exercise

  • Dogs were treated with treadmill exercise (2.5 mph and 5 mph, 6% incline, 20 min each) and treated with intravenous saline or methylene blue

  • Another group of dogs were treated with methylene blue without exercise 

  • Since methylene blue changes cellular oxidation states, the goal was to understand whether changes in redox potential induced by methylene blue could alter cardiac output during mild to moderate exercise 

  • Methylene blue reduced lactate-to-pyruvate ratios, but showed little to no effect on cardiac output, HR, arterial pressure, and rate of change in ventricular pressure

  • Exercise doubled cardiac output and increased O2 consumption in both saline and methylene blue conditions, but increased lactate-to-pyruvate levels were only observed in the exercise group with no methylene blue administration

  • While methylene blue can affect redox balance, it does not enhance cardiac output during exercise, suggesting that methylene blue will not enhance performance through changes in cardiac output

Behavioral, Physiological and Biochemical Hormetic Responses to the Autoxidizable Dye Methylene Blue

Bruchey et al. 2008

Key Points:

  • This review addresses the dose-dependent behavioral, physiological, and biochemical effects of methylene blue administration

  • Methylene blue’s biological properties have been investigated for over 120 years

  • Currently most used for methemoglobinemia, septic shock, encephalopathy, and ischemia

  • Methylene blue is an autoxidizable dye that can accept electrons in its oxidized form and acts as an electron donor in its reduced, leukomethylene blue form

  • It can act as an antioxidant in the mitochondria, where ROS are formed

  • While methylene blue has been shown to increase cytochrome oxidase activity at low and intermediate doses, it decreases cytochrome oxidase activity at higher doses

  • At higher dose situations, they can take away electrons from the ETC 

  • Methylene blue’s in vitro hormetic dose-response relationship has been shown as below

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