1. Introduction

Methylene blue is a versatile compound with a long history in medicine, dating back to the late 19th century. Originally developed as a dye, it has evolved into a pharmaceutical agent used for treating specific medical conditions and, more recently, explored as a dietary supplement for potential cognitive and mitochondrial benefits. This guidebook provides a thorough overview of methylene blue, including its uses, dosage guidelines, safety considerations, and more. All information is based on current medical knowledge as of August 2025, drawing from reliable sources such as Mayo Clinic, NCBI, FDA, and peer-reviewed studies.

Important Disclaimer: This guide is for informational purposes only and is not a substitute for professional medical advice. Always consult a healthcare provider before using methylene blue, especially for supplementation purposes, as it is not FDA-approved for many off-label uses. Self-administration can lead to serious risks.

2. What is Methylene Blue?

Methylene blue (also known as methylthioninium chloride) is a synthetic thiazine dye that acts as a redox agent. It can donate and accept electrons, making it useful in treating conditions involving oxidative stress or impaired oxygen delivery in the blood. In medical settings, it is available as an injectable solution (e.g., ProvayBlue™) or oral formulations. For supplementation, it is often sold as USP-grade capsules, tablets, or liquid solutions.

 

• • Chemical Properties: Water-soluble, appears as a dark blue powder or crystals.

• • Mechanism of Action: In low doses, it enhances mitochondrial function and acts as an antioxidant; in higher doses, it can become pro-oxidant. It inhibits guanylate cyclase, reducing cyclic GMP levels, which helps in conditions like vasoplegia.

3. Medical Uses

Methylene blue is FDA-approved primarily for treating acquired methemoglobinemia, a condition where blood cannot properly carry oxygen due to oxidized hemoglobin. Other medical applications include:

 

• • Methemoglobinemia: Rapidly reduces methemoglobin levels by converting ferric iron (Fe³⁺) to ferrous iron (Fe²⁺) in hemoglobin.

• • Vasoplegic Syndrome: Used in cardiac surgery to manage low blood pressure; preoperative or intraoperative administration.

• • Ifosfamide-Induced Neurotoxicity: Acts as an electron acceptor to prevent encephalopathy.

• • Antimalarial: Effective against Plasmodium falciparum, especially in resistant strains.

• • Other: Dye for surgical marking (e.g., sentinel lymph nodes), treatment of priapism, and investigational uses in Alzheimer’s disease and photodynamic therapy for infections or cancer.

4. Supplementation Uses (Off-Label)

While not FDA-approved for these purposes, methylene blue is increasingly used as a supplement for potential nootropic (cognitive-enhancing) and anti-aging effects. Emerging research suggests benefits in:

 

• • Cognitive Enhancement: May improve memory, focus, and mood by supporting mitochondrial energy production and reducing oxidative stress.

• • Mitochondrial Support: Enhances cellular energy (ATP) production, potentially aiding conditions like fatigue or neurodegenerative diseases.

• • Antioxidant Effects: At low doses, it acts as an antioxidant; higher doses may have pro-oxidant effects for targeted therapies.

• • Other Potential Benefits: Investigated for depression, anxiety, and skin health, but evidence is limited and anecdotal.

Note: These uses are experimental and should only be pursued under medical supervision due to risks.

5. Dosage Guidelines

Dosage varies by use, administration route, and body weight. Always base calculations on lean body weight for accuracy. Start low and monitor for effects. Below are tables for key uses, with weights in kilograms (kg) and pounds (lbs; 1 kg ≈ 2.2 lbs).

5.1 Treatment of Methemoglobinemia (Intravenous, Medical Use)

Dosage: 1-2 mg/kg IV over 5-30 minutes. Repeat after 1 hour if methemoglobin >30% or symptoms persist (max total: 7 mg/kg). Administered under medical supervision.

Weight (kg)	Weight (lbs)	Low Dose (1 mg/kg, mg)	High Dose (2 mg/kg, mg)
50	110	50	100
60	132	60	120
70	154	70	140
80	176	80	160
90	198	90	180
100	220	100	200

5.2 Oral Supplementation (e.g., Cognitive Enhancement, Mitochondrial Support)

Dosage: 0.5-4 mg/kg/day, divided into 1-2 doses. Start at 0.5 mg/kg and titrate up. Not for long-term use without monitoring; typical range for adults: 10-60 mg/day.

Weight (kg)	Weight (lbs)	Low Dose (0.5 mg/kg, mg)	High Dose (4 mg/kg, mg)
50	110	25	200
60	132	30	240
70	154	35	280
80	176	40	320
90	198	45	360
100	220	50	400

5.3 Other Doses

 

• • Vasoplegic Syndrome: 1.5-2 mg/kg IV over 20-60 minutes.

• • Antimalarial: 36-72 mg/kg over 3 days (oral).

• • Ifosfamide Neurotoxicity: 50 mg IV every 4-6 hours (prophylactic/therapeutic).

6. Administration Methods

 

• • Intravenous (IV): For medical emergencies; slow infusion to avoid pain at injection site.

• • Oral: Capsules, tablets, or diluted liquid (e.g., 0.5% solution in 100-200 mL water) with food to reduce GI upset. Use USP-grade only; avoid industrial dyes.

• • Topical/Subcutaneous: Rarely for supplementation; used in photodynamic therapy.

• • Timing: For supplementation, take in the morning to avoid sleep interference.

7. Side Effects

Common (usually mild and temporary):

 

• • Blue-green urine/stool.

• • Nausea, vomiting, diarrhea.

• • Skin/mouth discoloration.

• • Headache, dizziness.

Serious (at high doses >5-7 mg/kg):

 

• • Methemoglobinemia (paradoxical).

• • Hemolytic anemia (especially in G6PD deficiency).

• • Cardiac arrhythmias, hypotension.

• • Serotonin syndrome (confusion, agitation, fever).

8. Safety and Precautions

 

• • Safe Dose Threshold: <2 mg/kg is generally safe; >7 mg/kg risks toxicity.

• • Monitoring: Check methemoglobin levels, kidney function, and G6PD status before use. Pulse oximetry may be inaccurate (shows falsely low oxygen).

• • Special Populations: Avoid in neonates (risk of hyperbilirubinemia), pregnant/breastfeeding women, or those with renal impairment.

• • Long-Term Use: Limited data; monitor for accumulation and side effects.

9. Drug Interactions

 

• • Serotonergic Drugs: High risk of serotonin syndrome with SSRIs, SNRIs, MAOIs, or tricyclics. Avoid combination or use low doses under supervision.

• • Anticoagulants: May increase bleeding risk.

• • Dapsone: Enhances hemolysis.

• • Other: Interferes with heparin; consult pharmacist for full list.

10. Contraindications

 

• • G6PD deficiency (risk of severe hemolysis).

• • Hypersensitivity to methylene blue.

• • Severe renal insufficiency.

• • Concurrent use with certain psychiatric medications without monitoring.

• • Heinz body anemia.

11. How to Obtain and Store

 

• • Obtaining: Prescription for medical use; over-the-counter or online for USP-grade supplements (e.g., from compounding pharmacies). Verify purity (≥99% pharmaceutical grade).

• • Storage: Keep in a cool, dark place; protect from light to prevent degradation. Shelf life: 2-3 years if stored properly.

12. References and Further Reading

This guide draws from authoritative sources. For the latest updates, consult healthcare professionals or visit sites like PubMed, FDA, or Mayo Clinic. Specific citations are inline throughout. If you need calculations for a specific weight or use, provide details for personalized guidance!