Can methylene blue cause leg cramping and fatigue?

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Last updated: June 24, 2025View editorial policy

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From the Research

Methylene blue can potentially cause leg cramping and fatigue as side effects, though these are not among the most commonly reported reactions. When used medicinally, methylene blue may cause side effects including headache, dizziness, nausea, vomiting, and discoloration of urine and stool. Muscle pain, cramping, and fatigue have been reported by some patients, particularly at higher doses. These symptoms may occur because methylene blue affects mitochondrial function and can interfere with cellular energy production in some individuals. The medication works by altering redox reactions in the body, which can impact muscle function and energy levels. If you experience persistent leg cramping or unusual fatigue while taking methylene blue, you should contact your healthcare provider, as dosage adjustment or alternative treatments may be necessary. These symptoms are more likely to occur in patients with underlying conditions like G6PD deficiency or those taking certain medications that interact with methylene blue, such as serotonergic drugs 1. A recent study published in 2022 found that intra-articular injection of methylene blue was a safe and effective therapy for patients with lumbar facet joint syndrome, with no severe adverse side effects reported 2. However, it is essential to note that the study did not specifically investigate the incidence of leg cramping and fatigue as side effects. In general, methylene blue is considered to be well-tolerated, but caution is needed in patients with certain underlying conditions or those taking interacting medications 3, 4. Some key points to consider when taking methylene blue include:

  • Monitoring for signs of serotonin toxicity, particularly when taking serotonergic drugs 3
  • Reporting any persistent or unusual side effects to your healthcare provider
  • Being aware of potential interactions with other medications
  • Following the recommended dosage and administration guidelines to minimize the risk of adverse effects.

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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