Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone

N Engl J Med. 1993 Oct 14;329(16):1158-63. doi: 10.1056/NEJM199310143291604.


Background: Benzopyrones can reduce the volume of high-protein edema fluid by stimulating proteolysis. These compounds provide a method for removing excess protein and its consequent edema and reduce its clinical sequelae, such as chronic inflammation and secondary infections.

Methods: We conducted a randomized, double-blind, placebo-controlled, crossover trial of 5,6-benzo-[alpha]-pyrone in 31 patients with postmastectomy lymphedema of the arm and 21 patients with lymphedema of the leg of various causes (this agent, also known as 56 BaP, 1,2-benzopyrone, or coumarin, is not an anticoagulant). The patients received 400 mg of the active drug or placebo, each for six months.

Results: During the placebo period, lymphedema often worsened, especially in the arms. Measurements of limb volume showed that the active drug reduced the mean amount of edema fluid in the arms from 46 percent above normal to 26 percent above normal (P < 0.001) and the amount in the legs from 25 percent to 17 percent above normal (P < 0.001). The circumference of the arms was reduced from 17 percent to 13 percent above normal, and the circumference of the legs from 11 percent to 7 percent above normal (P < 0.001). The softness of the limb tissue was increased (P < 0.001), and elevated skin temperatures were reduced (P < 0.001). There were fewer attacks of secondary acute inflammation (P = 0.01). Bursting pains and feelings of hardness were decreased, as were feelings of tightness, tension, swelling, and heaviness; limb mobility also improved. The active drug was preferred to the placebo by 93 percent of the patients (P < 0.001). Side effects--mild nausea or diarrhea--occurred in seven patients taking the active drug. None withdrew from the trial, and the side effects disappeared after the first month of therapy.

Conclusions: 5,6-Benzo-[alpha]-pyrone results in slow but safe reduction of lymphedema of the extremities.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arm / pathology
  • Chronic Disease
  • Coumarins / adverse effects
  • Coumarins / therapeutic use*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Leg / pathology
  • Lymphedema / drug therapy*
  • Lymphedema / pathology
  • Lymphedema / physiopathology
  • Male
  • Middle Aged
  • Skin Temperature


  • Coumarins
  • coumarin