Understanding the correct dosage and timing for methylene blue (MB) is essential for maximizing its benefits while minimizing risks. While methylene blue is a powerful compound with neuroprotective, mitochondrial-enhancing, and cognitive effects, more is not necessarily better. In fact, there is a biphasic dose-response, meaning too much can reverse or negate its positive effects.

🔬 What the Research Says About Dosage

1. The Sweet Spot: 0.5–2 mg/kg body weight

The most consistently cited effective dosage range for cognitive and mitochondrial support lies between 0.5–2 mg/kg of body weight per day. Within this range:

• Low doses (~0.5 mg/kg) support mitochondrial respiration and cerebral blood flow.
• Mid-range doses (1–2 mg/kg) are used in many studies for cognitive enhancement and neuroprotection.
• High doses (>3 mg/kg) may produce oxidative stress and impair mitochondrial function, the opposite of what’s desired .

This biphasic dose response is confirmed in multiple animal and human models . Always err on the side of caution, especially when combining with other compounds.

2. High-dose caution

MB at doses above 5 mg/kg (used medically for methemoglobinemia or cyanide poisoning) should not be used without medical supervision. These levels increase risk of serotonin toxicity and monoamine oxidase inhibition, especially when combined with antidepressants .

⏰ Timing & Bioavailability

1. Half-life & Frequency

• The elimination half-life of methylene blue is approximately 5 to 24 hours, depending on the dose and individual metabolic factors.
• It’s often taken once per day, or split into two doses to maintain stable plasma concentrations.

2. Sublingual vs Oral

• Sublingual (under the tongue) delivery provides faster absorption and avoids first-pass liver metabolism.
• Oral capsules are slower to absorb and may be influenced by food intake.

Sublingual delivery is often preferred for nootropic purposes, especially in fasted states or before performance-related tasks .

🧠 Best Use Timing (Based on Goals)

⚖️ Finding Your Optimal Dose

Use body weight (in kg) × target mg/kg dose to calculate:

• Example: A 70 kg individual using 1 mg/kg → 70 mg per day.

Start low, assess your response, and scale carefully. Bioindividual factors such as liver health, drug interactions, and neurotransmitter status will influence how methylene blue affects you.

📌 Key Takeaways

• 0.5–2 mg/kg is the research-backed sweet spot.
• Avoid high doses unless medically supervised.
• Timing depends on goals: cognitive tasks, workouts, or general health.
• Sublingual administration offers fast, efficient absorption.
• Use caution with MAO inhibitors or SSRIs—interactions can be dangerous.