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

Felipe Vadillo-Ortega, Otilia Perichart-Perera, Salvador Espino, Marco Antonio Avila-Vergara, Isabel Ibarra, Roberto Ahued, Myrna Godines, Samuel Parry, George Macones, Jerome F Strauss, Felipe Vadillo-Ortega, Otilia Perichart-Perera, Salvador Espino, Marco Antonio Avila-Vergara, Isabel Ibarra, Roberto Ahued, Myrna Godines, Samuel Parry, George Macones, Jerome F Strauss

Abstract

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 (χ(2) = 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 (χ(2) = 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 the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846.

Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: funding for the study from the Bill and Melinda Gates Foundation, National Institutes of Health, and CONACyT; no relationships with any companies that might have an interest in the submitted work in the previous three years; and no non-financial interests that may be relevant to the submitted work.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787966/bin/vadf756783.f1_default.jpg
Flow diagram of trial

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