Intended for healthcare professionals

CCBYNC Open access

Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial

BMJ 2011; 342 doi: (Published 19 May 2011) Cite this as: BMJ 2011;342:d2901
  1. Felipe Vadillo-Ortega, professor1,
  2. Otilia Perichart-Perera, titular researcher2,
  3. Salvador Espino, associate professor of obstetrics and gynaecology2,
  4. Marco Antonio Avila-Vergara, associate professor of obstetrics and gynaecology3,
  5. Isabel Ibarra, associate professor4,
  6. Roberto Ahued, professor of obstetrics and gynaecology2,
  7. Myrna Godines, associate professor of obstetrics and gynaecology1,
  8. Samuel Parry, associate professor and chief of division of maternal-fetal medicine5,
  9. George Macones, Mitchell and Elaine Yanow professor and head of obstetrics and gynaceology56,
  10. Jerome F Strauss, professor of obstetrics and gynaecology and dean of School of Medicine7
  1. 1Department of Experimental Medicine, School of Medicine, Universidad Nacional, Autonoma de Mexico, Torre de Investigacion, 3er Piso, Ciudad Universitaria, Mexico, D F 04510
  2. 2Instituto Nacional de Perinatologia Isidro Espinosa de los, Reyes, Mexico
  3. 3Universidad Autonoma de Sinaloa, Mexico
  4. 4Instituto de Investigaciones Biomedicas, UNAM, Mexico
  5. 5Department of Obstetrics and Gynaecology, University of Pennsylvania, Philadelphia, PA, USA
  6. 6Department of Obstetrics and Gynaecology, Washington University, St Louis, MO, USA
  7. 7Department of Obstetrics and Gynaecology, Virginia Commonwealth University, Richmond, VA, USA
  1. Correspondence to: F Vadillo-Ortega felipe.vadillo{at}
  • Accepted 28 March 2011


Objective To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk.

Design Randomised, blinded, placebo controlled clinical trial.

Setting Tertiary public hospital in Mexico City.

Participants Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery.

Interventions Supplementation with a medical food—bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo—during pregnancy.

Main outcome measure Development of pre-eclampsia/eclampsia.

Results 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ2=19.41; P<0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ2=3.76; P=0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P=0.004; absolute risk reduction 0.09, 0.05 to 0.14).

Conclusions Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to …

View Full Text