6,144
Views
3
CrossRef citations to date
0
Altmetric
Review Article

L-Arginine supplementation in pregnancy: a systematic review of maternal and fetal outcomes

ORCID Icon, , &
Article: 2217465 | Received 07 Dec 2022, Accepted 19 May 2023, Published online: 31 May 2023

References

  • Garovic VD, Dechend R, Easterling T, et al. Hypertension in pregnancy: diagnosis, blood pressure goals, and pharmacotherapy: a scientific statement from the American Heart Association. Hypertension. 2022;79(2):e21–e41.
  • Saving mothers’ lives: reviewing maternal deaths to make motherhood safer: 2006–2008. BJOG Int J Obstet Gynaecol. 2011;118:1–203.
  • Ananth CV, Vintzileos AM. Maternal-fetal conditions necessitating a medical intervention resulting in preterm birth. Am J Obstet Gynecol. 2006;195(6):1557–1563.
  • Morgan T. Role of the placenta in preterm birth: a review. Am J Perinatol. 2016;33(3):258–266.
  • Goto E. Meta-regression analysis to evaluate relationships between maternal blood levels of placentation biomarkers and low delivery weight. Int J Gynaecol Obstet. 2018;142(2):148–155.
  • Gaccioli F, Lager S. Placental nutrient transport and intrauterine growth restriction. Front Physiol. 2016;7:40.
  • Nigam J, Misra V, Singh P, et al. Histopathological study of placentae in low birth weight babies in India. Ann Med Health Sci Res. 2014;4(Suppl 2):S79–S83.
  • Goto E. Effects of prenatal oral l-arginine on birth outcomes: a meta-analysis. Sci Rep. 2021;11(1):22748.
  • PRISMA transparent reporting of systematic reviews and meta-analyses; 2021 [accessed 2022 Nov 18]. Available from: https://prisma-statement.org/
  • Zhu Q, Yue X, Tian Q-Y, et al. Effect of l-Arginine supplementation on blood pressure in pregnant women: a meta-analysis of placebo-controlled trials. Hypertens Pregnancy. 2013;32(1):32–41.
  • SIGO. I Disordini Ipertensivi in Gravidanza: Classificazione, Diagnosi e Terapia. Raccomandazioni di Buona Pratica Clinica AIPE (Associazione Italiana Preeclampsia); 2020 [accessed 2022 Dec]. Available from: https://www.sigo.it/wp-content/uploads/2020/11/RaccomandazioniAIPE-Disordini_Ipertensivi_Gravidanza.pdf
  • Fetal growth restriction. Obstet Gynecol. 2021;137(2):e16–e28.
  • Borisova LV, Martinussen PE, Rydland HT, et al. Public evaluation of health services across 21 European countries: the role of culture. Scand J Public Health. 2017;45(2):132–139.
  • Battaglia C, Regnani G, Marsella T, et al. Adjuvant L-arginine treatment in controlled ovarian hyperstimulation: a double-blind, randomized study. Hum Reprod. 2002;17(3):659–665.
  • Battaglia C, Salvatori M, Maxia N, et al. Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients. Hum Reprod. 1999;14(7):1690–1697.
  • Monari F, Menichini D, Pignatti L, et al. Effect of L-arginine supplementation in pregnant women with chronic hypertension and previous placenta vascular disorders receiving aspirin prophylaxis: a randomized control trial. Miner Obstet Gynecol. 2021;73(6):782–789.
  • Shen S, Hua C. Effect of L-arginine on the expression of bcl-2 and bax in the placenta of fetal growth restriction. J Matern Neonatal Med. 2011;24(6):822–826.
  • Neri I, Mazza V, Galassi MC, et al. Effects of L-arginine on utero-placental circulation in growth-retarded fetuses. Acta Obstet Gynecol Scand. 1996;75(3):208–212.
  • Xiao XM, Li LP. L-Arginine treatment for asymmetric fetal growth restriction. Int J Gynaecol Obstet. 2005;88(1):15–18.
  • So S, Yamaguchi W, Murabayashi N, et al. Beneficial effect of L-arginine in women using assisted reproductive technologies: a small-scale randomized controlled trial. Nutr Res. 2020;82:67–73.
  • Sieroszewski P, Suzin J, Karowicz-Bilińska A. Ultrasound evaluation of intrauterine growth restriction therapy by a nitric oxide donor (L-arginine). J Matern Neonatal Med. 2004;15(6):363–366.
  • Singh S, Singh A, Sharma D, et al. Effect of L-Arginine on nitric oxide levels in intrauterine growth restriction and its correlation with fetal outcome. Indian J Clin Biochem. 2015;30(3):298–304.
  • Ropacka M, Szymanski P, Kowalska J, et al. Effect of oral supplementation with nitric oxide donor on fetomaternal hemodynamic. Ultrasound Obstet Gynecol. 2007;30(4):632–632.
  • Winer N, Branger B, Azria E, et al. L-Arginine treatment for severe vascular fetal intrauterine growth restriction: a randomized double-bind controlled trial. Clin Nutr. 2009;28(3):243–248.
  • Hladunewich MA, Derby GC, Lafayette RA, et al. Effect of L-Arginine therapy on the glomerular injury of preeclampsia. Obstet Gynecol. 2006;107(4):886–895.
  • Rytlewski K, Olszanecki R, Korbut R, et al. Effects of prolonged oral supplementation with L-arginine on blood pressure and nitric oxide synthesis in preeclampsia. Eur J Clin Invest. 2005;35(1):32–37.
  • Staff AC, Berge L, Haugen G, et al. Dietary supplementation with L-arginine or placebo in women with pre-eclampsia. Acta Obstet Gynecol Scand. 2004;83(1):103–107.
  • Rytlewski K, Olszanecki R, Lauterbach R, et al. Effects of oral L-arginine on the pulsatility indices of umbilical artery and Middle cerebral artery in preterm labor. Eur J Obstet Gynecol Reprod Biol. 2008;138(1):23–28.
  • Valdivia-Silva JE, López-Molina K, Macedo R. Efecto de la terapia temprana con L-arginina en el crecimiento intrauterino restringido en la preclampsia. Estudio aleatorizado en mujeres latinoamericanas. Prog Obstet Ginecol. 2009;52(2):89–98.
  • Neri I, Blasi I, Facchinetti F. Effects of acute L-arginine infusion on non-stress test in hypertensive pregnant women. J Mat Fet Neonat Med. 2004;16(1):23–26.
  • Facchinetti F, Saade GR, Neri I, et al. L-Arginine supplementation in patients with gestational hypertension: a pilot study. Hypertens Pregnancy. 2007;26(1):121–130.
  • Neri I, Jasonni VM, Gori GF, et al. Effect of L-arginine on blood pressure in pregnancy-induced hypertension: a randomized placebo-controlled trial. J Matern Neonatal Med. 2006;19(5):277–281.
  • Vadillo-Ortega F, Perichart-Perera O, Espino S, et al. 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:d2901.
  • Camarena Pulido EE, García Benavides L, Panduro Barón JG, et al. Efficacy of L-arginine for preventing preeclampsia in high-risk pregnancies: a double-blind, randomized, clinical trial. Hypertens Pregnancy. 2016;35(2):217–225.
  • Neri I, Monari F, Sgarbi L, et al. L-Arginine supplementation in women with chronic hypertension: impact on blood pressure and maternal and neonatal complications. J Matern Neonatal Med. 2010;23(12):1456–1460.
  • Facchinetti F, Neri I, Genazzani AR. L-Arginine infusion reduces preterm uterine contractions. J Perinat Med. 1996;24(3):283–285.
  • Petrella E, Pignatti L, Neri I, et al. The L-arginine/nitric oxide pathway is impaired in overweight/obese pregnant women. Pregnancy Hypertens. 2014;4(2):150–155.
  • Crane AR, Redden RR, Van Emon ML, et al. Impacts of supplemental arginine on the reproductive performance of fall lambing ewes. J Anim Sci. 2016;94(8):3540–3549.
  • Sales F, Sciascia Q, van der Linden DS, et al. Intravenous maternal L-arginine administration to twin-bearing ewes, during late pregnancy, is associated with increased fetal muscle mTOR abundance and postnatal growth in twin female lambs. J Anim Sci. 2016;94(6):2519–2531.
  • De Boo HA, Van Zijl PL, Smith DEC, et al. Arginine and mixed amino acids increase protein accretion in the growth-restricted and normal ovine fetus by different mechanisms. Pediatr Res. 2005;58(2):270–277.
  • Mateo RD, Wu G, Moon HK, et al. Effects of dietary arginine supplementation during gestation and lactation on the performance of lactating primiparous sows and nursing piglets. J Anim Sci. 2008;86(4):827–835.
  • Mateo RD, Wu G, Bazer FW, et al. Dietary L-Arginine supplementation enhances the reproductive performance of gilts. J Nutr. 2007;137(3):652–656.
  • Li J, Xia H, Yao W, et al. Effects of arginine supplementation during early gestation (day 1 to 30) on litter size and plasma metabolites in gilts and sows. J Anim Sci. 2015;93(11):5291–5303.
  • Kelley DE, Warren LK, Mortensen CJ. Oral L-arginine supplementation impacts several reproductive parameters during the postpartum period in mares. Anim Reprod Sci. 2013;138(3–4):233–240.
  • Madsen JG, Mueller S, Kreuzer M, et al. Milk replacers supplemented with either L-arginine or L-carnitine potentially improve muscle maturation of early reared low birth weight piglets from hyperprolific sows. Animal. 2018;12(1):43–53.
  • Quesnel H, Quiniou N, Roy H, et al. Supplying dextrose before insemination and L-arginine during the last third of pregnancy in sow diets: effects on within-litter variation of piglet birth weight. J Anim Sci. 2014;92(4):1445–1450.
  • Garbossa CAP, Júnior FMC, Silveira H, et al. Effects of ractopamine and arginine dietary supplementation for sows on growth performance and carcass quality of their progenies. J Anim Sci. 2015;93(6):2872–2884.
  • Bérard J, Bee G. Effects of dietary L-arginine supplementation to gilts during early gestation on foetal survival, growth and myofiber formation. Animal. 2010;4(10):1680–1687.
  • Li X, Bazer FW, Johnson GA, et al. Dietary supplementation with L-arginine between days 14 and 25 of gestation enhances embryonic development and survival in gilts. Amino Acids. 2014;46(2):375–384.
  • Sun L, Zhang H, Fan Y, et al. Metabolomic profiling in umbilical venous plasma reveals effects of dietary rumen-protected arginine or N-carbamylglutamate supplementation in nutrient-restricted Hu sheep during pregnancy. Reprod Domest Anim. 2017;52(3):376–388.
  • Sun L, Zhang H, Wang Z, et al. Dietary rumen-protected arginine and N-carbamylglutamate supplementation enhances fetal growth in underfed ewes. Reprod Fertil Dev. 2018;30(8):1116–1127.
  • Zhang H, Sun L, Wang Z, et al. N-carbamylglutamate and L-arginine improved maternal and placental development in underfed ewes. Reproduction. 2016;151(6):623–635.
  • Gao K, Jiang Z, Lin Y, et al. Dietary l-arginine supplementation enhances placental growth and reproductive performance in sows. Amino Acids. 2012;42(6):2207–2214.
  • Li X, Bazer FW, Johnson GA, et al. Dietary supplementation with 0.8% L-Arginine between days 0 and 25 of gestation reduces litter size in gilts. J Nutr. 2010;140(6):1111–1116.
  • Bass BE, Bradley CL, Johnson ZB, et al. Influence of dietary-arginine supplementation of sows during late pregnancy on piglet birth weight and sow and litter performance during lactation. J Anim Sci. 2017;95(1):248–256.
  • Peine JL, Jia G, Van Emon ML, et al. Effects of maternal nutrition and rumen-protected arginine supplementation on ewe performance and postnatal lamb growth and internal organ mass. J Anim Sci. 2018;96(8):3471–3481.
  • Bursztyn M, Podjarny E, Dahan R, et al. Insulin‐induced hypertension, L‐arginine, and endothelial nitric oxide synthase in pregnant rats. Hypertens Pregnancy. 2003;22(3):267–274.
  • Sharkey LC, McCune SA, Yuan O, et al. Spontaneous pregnancy-induced hypertension and intrauterine growth restriction in rats. Am J Hypertens. 2001;14(10):1058–1066.
  • Podjarny E, Bursztyn M, Rashed G, et al. Chronic exogenous hyperinsulinaemia-induced hypertension in pregnant rats: effect of chronic treatment with l-arginine. Clin Sci. 2001;100(6):667–671.
  • Helmbrecht GD, Farhat MY, Lochbaum L, et al. L-arginine reverses the adverse pregnancy changes induced by nitric oxide synthase inhibition in the rat. Am J Obstet Gynecol. 1996;175(4 Pt 1):800–805.
  • Altun ZS, Uysal S, Guner G, et al. Effects of oral L‐arginine supplementation on blood pressure and asymmetric dimethylarginine in stress‐induced preeclamptic rats. Cell Biochem Funct. 2008;26(5):648–653.
  • da Costa CMB, de Freitas MRB, Brazão V, et al. Does l-arginine availability during the early pregnancy alters the immune response of Trypanosoma cruzi infected and pregnant Wistar rats? Exp Parasitol. 2014;142:59–66.
  • Groten T, Lehmann T, Städtler M, et al. Effect of pentaerythritol tetranitrate (PETN) on the development of fetal growth restriction in pregnancies with impaired uteroplacental perfusion at midgestation—a randomized trial. Am J Obstet Gynecol. 2023;228(1):84.e1–84.e12.
  • Duckitt K, Thornton S. Nitric oxide donors for the treatment of preterm labour. Cochrane Database of Syst. Rev. 2002;(3):CD002860.
  • Nanetti L, Giannubilo S, Raffaelli F, et al. Nitric oxide and peroxynitrite platelet levels in women with small-for-gestational-age fetuses. BJOG. 2008;115(1):14–21.
  • McDonald CR, Cahill LS, Gamble JL, et al. Malaria in pregnancy alters l-arginine bioavailability and placental vascular development. Sci Transl Med. 2018;10(431):eaan6007.
  • Tran N-T, Amarger V, Bourdon A, et al. Maternal citrulline supplementation enhances placental function and fetal growth in a rat model of IUGR: involvement of insulin-like growth factor 2 and angiogenic factors. J Matern Neonatal Med. 2017;30(16):1906–1911.
  • Gemmel M, Sutton EF, Brands J, et al. L-Citrulline supplementation during pregnancy improves perinatal and postpartum maternal vascular function in a mouse model of preeclampsia. Am J Physiol Regul Integr Comp Physiol. 2021;321(3):R364–R376.
  • Bourdon A, Hannigsberg J, Misbert E, et al. Maternal supplementation with citrulline or arginine during gestation impacts fetal amino acid availability in a model of intrauterine growth restriction (IUGR). Clin Nutr. 2020;39(12):3736–3743.
  • Hsu C-N, Tain Y-L. Impact of arginine nutrition and metabolism during pregnancy on offspring outcomes. Nutrients. 2019;11(7):1452.
  • Barker D. The fetal and infant origins of adult disease. BMJ. 1990;301(6761):1111.
  • McNeal CJ, Meininger CJ, Wilborn CD, et al. Safety of dietary supplementation with arginine in adult humans. Amino Acids. 2018;50(9):1215–1229.
  • Ivy JL. The use of L-arginine supplements for cardiovascular disease and related disorders is questionable. Nov Tech Nutr Food Sci. 2020;5(1):406–412.
  • Schulman SP, Becker LC, Kass DA, et al. L-Arginine therapy in acute myocardial infarction. JAMA. 2006;295(1):58–64.
  • Pels A, Derks J, Elvan-Taspinar A, et al. Maternal sildenafil vs placebo in pregnant women with severe early-onset fetal growth restriction. JAMA Netw Open. 2020;3(6):e205323.
  • Institute of Medicine. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. Washington (DC): The Natlional Academies Press; 2005.
  • Schönfeldt HC, Gibson Hall N. Dietary protein quality and malnutrition in Africa. Br J Nutr. 2012;108(S2):S69–S76.
  • Gernand AD, Schulze KJ, Stewart CP, et al. Micronutrient deficiencies in pregnancy worldwide: health effects and prevention. Nat Rev Endocrinol. 2016;12(5):274–289.
  • Kurpad AV, Kao C, Dwarkanath P, et al. In vivo arginine production and nitric oxide synthesis in pregnant Indian women with normal and low body mass indices. Eur J Clin Nutr. 2009;63(9):1091–1097.
  • de Castro Barbosa T, Jiang LQ, Zierath JR, et al. L-Arginine enhances glucose and lipid metabolism in rat L6 myotubes via the NO/c-GMP pathway. Metabolism. 2013;62(1):79–89.
  • Hu S, Han M, Rezaei A, et al. L-Arginine modulates glucose and lipid metabolism in obesity and diabetes. Curr Protein Pept Sci. 2017;18(6):599–608.
  • Hadi A, Arab A, Moradi S, et al. The effect of L-arginine supplementation on lipid profile: a systematic review and meta-analysis of randomised controlled trials. Br J Nutr. 2019;122(9):1021–1032.
  • Jobgen WS, Fried SK, Fu WJ, et al. Regulatory role for the arginine–nitric oxide pathway in metabolism of energy substrates. J Nutr Biochem. 2006;17(9):571–588.