The Human Upgrade with Dave Asprey

Episode 1366: The Methylene Blue Episode | Solo Biohacking Masterclass
Release Date: November 20, 2025
Host: Dave Asprey

Episode Overview

In this solo masterclass, Dave Asprey—founder of Bulletproof and long-time biohacker—dives deep into the science, potential, and cautions of methylene blue, a decades-old synthetic compound that has recently surged in popularity within biohacking and longevity circles. Asprey explores how it functions as a mitochondrial enhancer and neuroprotective agent, who might benefit, who should avoid it, how to use it effectively, and where it sits among other advanced biohacks.

Key Discussion Points & Insights

Introduction to Methylene Blue

• What is It?
  • A synthetic blue dye first created in 1876; widely used in medicine for its antiseptic and antimalarial properties.
  • Known as “the world’s first fully synthetic dye.”
  • Used historically from dyeing fabrics to treating malaria and psychiatric conditions.
  • Currently FDA approved for methemoglobinemia, a rare blood disorder.
    • [06:38] "It was a dye, and medicine took it over. This started all the way back in 1876 by a guy named Heinrich Caro."
• Biohacker’s Interest:
  • Rediscovered for mitochondrial enhancement, cognitive performance, neuroprotection, and mood stabilization.
  • "Methylene blue can boost mitochondrial function, it can support your mood, and it can improve resilience under stress. But it doesn't always work for everyone." [03:40]

How Methylene Blue Works in the Body

• Mitochondrial Multi-tool:

  • Acts as an alternative electron carrier, particularly aiding complex I and III in the mitochondrial electron transport chain.
  • At low doses: protective and restorative; at high doses: becomes a pro-oxidant and potentially toxic.
  • "I like to think of methylene blue as like jumper cables for your mitochondria. The right dose, you get steady power. Wrong dose, you probably just short the system." [10:54]

• Redox Cycling:

  • Methylene blue alternates between oxidized (blue) and reduced (clear) states inside the body, keeping ATP production and electron flow smooth even under stress.
  • "Methylene blue acts as a redox cycler. When it's blue, it's oxidized; when it's reduced leuko methylene blue, it's clear. So inside your body, it goes blue, clear, blue, clear." [20:59]

Mood, Neurotransmission, and Cautions

• Old-line MAO Inhibitor:

  • Functions as a monoamine oxidase inhibitor—affecting breakdown of serotonin, dopamine, and norepinephrine.
  • Mood “lift” can be both subtle and pronounced, depending on dose, but this isn’t always a positive if misused.
    • "If you take a high dose of methylene blue and say, 'Oh, I feel so good,' that's not your mitochondria—now you're not depressed." [09:40]

• Serotonin Syndrome Warning:

  • Never combine methylene blue with psychedelics or SSRIs; can trigger life-threatening serotonin syndrome.
    • "So first warning—no methylene blue if you're going to party this weekend or you’re going to go on a spiritual journey." [18:59]
    • "I've been with people who've had serotonin syndrome ... you don't want to experience that. It is life threatening." [32:21]

Who Should and Should Not Use Methylene Blue

• Do Not Use If:
  • On SSRIs (unless supervised in a tapering protocol)
  • Planning to use psychedelics
  • Pregnant, breastfeeding, or under 18
  • Have G6PD deficiency (common in some African, Mediterranean, and Asian populations—get tested)
    • "If you're from one of those genetic populations, you should get a genetic test ... methylene blue pops your red blood cells like balloons." [35:09]
• When to Consider It:
  • If you have mitochondrial dysfunction (chronic infections, toxic exposures, cognitive challenges)
  • As a performance or resilience booster (after foundational health is addressed)

Dosing, Usage, and Best Practices

• Start Low, Go Slow:
  • Biohacking range: 0.5–2 mg total per day (not per kg); medical doses are much higher and not recommended for self-experimentation.
    • "So most biohackers are around, you know, 2 milligrams per day... start at 0.5 to 1 milligram per day and just track your energy, your mood, your clarity, your sleep." [39:09]
  • Results follow a “Goldilocks” inverted U-shaped curve; too much becomes counterproductive.
• Synergy with Other Biohacks:
  • Enhances effects of red light therapy (apply red or near-infrared light 30–90 minutes after methylene blue for added mitochondrial boost).
  • Works well with fasting, cold plunges, ketosis, and creatine.
    • "Fasting, cold plunges or ketosis pair very well with methylene blue." [49:30]
• Timing:
  • Take in the morning or early afternoon; late dosing can disrupt sleep.

Sourcing and Quality Considerations

• Use Only Pharmaceutical Grade:
  • Avoid aquarium-grade methylene blue (contains heavy metals).
  • Look for USP (United States Pharmacopeia) or compounded pharmacy versions.
    • "There's tons of cheap methylene blue out there and only some of it is pharmaceutical grade ... USP means United States Pharmacopoeia Standards." [45:48]

Potential Benefits Supported by Research

• Brain function: Improves working memory, attention, and may protect against dementia in animal and some human studies ([23:41], [56:30])
• Mood: Adjunct in depression and bipolar (older studies)
• Fertility: Early studies suggest mitochondrial support for eggs and sperm (not a direct fertility supplement)
• Neuroplasticity: Increases dendritic spine density (in animal models), potentially enhancing learning capacity
• Skin: May increase collagen synthesis (can be used topically in low doses)
• Vision: Lowers retinal cell oxidative stress in early research

Notable Quotes & Memorable Moments

• On Precision and Personalization:
  "Two people can take exactly the same dose and have opposite effects." [38:15]

• On Responsibility:
  "You are your own health daddy. So, without warning and that incredibly freeing responsibility that you have, let's talk about what methylene blue might do for you when you might not want to use it." [04:26]

• On Caution:
  "This is one of those frosting or sprinkles on the cupcake. It’s not the cupcake itself, if you know what I’m saying." [12:44]

Timestamps for Important Segments

• Intro, Longevity Vision: [00:00–03:40]
• What is Methylene Blue, Origins: [06:38–11:12]
• Mechanisms of Action in Mitochondria: [13:30–21:00]
• Mood, MAO Inhibition, and Dangers: [16:00–20:36]
• Synergies (Red Light, Fasting, Creatine, etc.): [48:44–51:33]
• Dosing Guidelines: [39:00–41:20]
• Fertility & Libido Discussion: [53:10–57:30]
• Warnings (SSRIs, Psychedelics, G6PD, Children): [32:21–36:07]
• Sourcing & Quality: [45:48–47:12]
• Topical Uses & Collagen: [60:00–62:12]

Final Takeaways (in Dave Asprey’s words)

"Methylene blue might be good for you, it might not be good for you. Don’t use it with psychedelics. Start with a low dose. Track your sleep; look if it’s overstimulating you and it’s okay to use it and not use it. I do not use it every day ... I use it a couple times a week when I get around to it." [65:11]

Additional Practical Tips

• Store methylene blue in airtight glass, away from light (amber bottle preferred).
• Blue urine and tongue are common side effects; doses affect their intensity.
• Do not rely on methylene blue as a foundational supplement—address minerals, fat-soluble vitamins, sleep, and lifestyle first.

This episode is a comprehensive guide for anyone considering methylene blue as a biohack. Asprey provides nuanced, practical, and safety-conscious advice for those curious about this compound’s potential for the brain, mood, and longevity.

For further resources or Dave’s product recommendations, visit:

• daveasprey.com/NB
• daveasprey.com/saffron

End of Summary