Effect of topical application of methylsulfonylmethane (MSM), EDTA on pitting edema and oxidative stress in a double blind, placebo-controlled study

Cell Mol Biol (Noisy-le-grand). 2011 Feb 12;57(1):62-9.


No pharmacological treatment exists for lower extremity pitting edema, characterized by inflammation, found in chronic venous insufficiency. Treatment with EDTA, an effective metal chelator, was explored because it can modulate free calcium and iron and prevent further free radical production. However, EDTA may not effectively penetrate the cell membrane, hence methylsulfonylmethane(MSM), reported to facilitate transmembrane transport, was added. The effect of topical application of a lotion containing MSM+EDTA was assessed in two phases of a double blind, placebo controlled clinical trial. In phase 1, patients having swelling in the lower extremities were randomly distributed to receive the MSM+EDTA lotion or a placebo (vehicle) alone. In the second phase, patients were given MSM as placebo followed by MSM+EDTA lotion for 2 weeks. The circumference of calf, ankle and foot for both legs were found to decline significantly after 2 weeks of application of the lotion/ but not placebo, and total antioxidant capacity (FRAP) and lipid peroxidation products (MDA), assayed in blood, showed decline in oxidative stress. Application of MSM alone increased the swelling. Thus EDTA+MSM offers an efficacious treatment for lower extremity pitting edema, through reduction in oxidative stress.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Topical
  • Adult
  • Aged
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use*
  • Chelating Agents / administration & dosage
  • Chelating Agents / therapeutic use*
  • Dimethyl Sulfoxide / administration & dosage
  • Dimethyl Sulfoxide / therapeutic use*
  • Double-Blind Method
  • Edema / drug therapy*
  • Edema / pathology
  • Edetic Acid / administration & dosage
  • Edetic Acid / therapeutic use*
  • Humans
  • Leg / pathology
  • Middle Aged
  • Oxidative Stress / drug effects*
  • Sulfones / administration & dosage
  • Sulfones / therapeutic use*


  • Anti-Inflammatory Agents
  • Chelating Agents
  • Sulfones
  • Edetic Acid
  • dimethyl sulfone
  • Dimethyl Sulfoxide