OJOG  Vol.4 No.9 , June 2014
Efficacy of Magnesium and Alpha Lipoic Acid Supplementation in Reducing Premature Uterine Contractions
Abstract: Objective: Premature uterine contractions represent one of the major symptoms related to preterm labor. So far, primary prevention of preterm labor is based on the early identification of symptoms and on pharmacological treatments which are prone of several secondary effects. In this double-blinded, randomized, placebo-controlled trial, the efficacy of a supplementation of magnesium and alpha-lipoic acid has been evaluated. Methods: Three hundred pregnant women at 14 - 34 weeks of gestation were enrolled and randomly divided to receive a daily single tablet containing a supplement of magnesium and alpha-lipoic acid (DAV®LoLiPharmasrl, Rome-Italy) or placebo until delivery. The incidence of episodes of preterm uterine contraction, associated or not with pain, as well as maternal need of hospitalization was evaluated. Results: Magnesium and lipoic acid supplementation was effective to significantly reduce the incidence of preterm uterine contractions compared to placebo. In particular, 52% of women who received the supplementation reported no symptoms of preterm uterine contractions throughout pregnancy, and persistent episodes of uterine contractions were significantly reduced compared to placebo (20% vs 60%, respectively). Furthermore, only 20% of subjects who received the supplementation required hospitalization, while it has been necessary for 40% of women who received placebo. Conclusions: Our findings suggest that supplementation with magnesium and lipoic acid is effective in reducing the incidence of premature uterine contraction and related episodes of hospitalization, compared to placebo. Nevertheless, further studies based on larger cohorts of patients are necessary to confirm the efficacy of these preliminary results.
Cite this paper: Parente, E. , Colannino, G. and Ferrara, P. (2014) Efficacy of Magnesium and Alpha Lipoic Acid Supplementation in Reducing Premature Uterine Contractions. Open Journal of Obstetrics and Gynecology, 4, 578-583. doi: 10.4236/ojog.2014.49082.

[1]   Iams, J.D., Newman, R.B., Thom, E.A., Goldenberg, R.L., Mueller-Heubach, E., Moawad, A., et al. (2002) Frequency of Uterine Contractions and the Risk of Spontaneous Preterm Delivery. The New England Journal of Medicine, 346, 250-255.

[2]   Carson, R.J. (2004) Detection and Prevention of Premature Labour. Neuro Endocrinology Letters, 25, 35-41.

[3]   Hubinont, C. and Debieve, F. (2011) Prevention of Preterm Labour: 2011 Update on Tocolysis. Journal of Pregnancy, 2011, 941057.

[4]   Groom, K.M. (2007) Preterm Labour. Pharmacological Prevention of Prematurity. Best Practice & Research Clinical Obstetrics & Gynaecology, 21, 843-856.

[5]   Pochwat, B., Szewczyk, B., Sowa-Kucma, M., Siwek, A., Doboszewska, U., Piekoszewski, W., et al. (2013) Antidepressant-Like Activity of Magnesium in the Chronic Mild Stress Model in Rats: Alterations in the NMDA Receptor Subunits. International Journal of Neuropsychopharmacology, 17, 1-13.

[6]   Sowa-Kucma, M., Szewczyk, B., Sadlik, K., Piekoszewski, W., Trela, F., Opoka, W., et al. (2013) Zinc, Magnesium and NMDA Receptor Alterations in the Hippocampus of Suicide Victims. Journal of Affective Disorders, 151, 924-931.

[7]   Hall, D.G., Mc Jr., G.H., Corey, E.L. and Thornton Jr., W.N. (1959) The Effects of Magnesium Therapy on the Duration of Labor. American Journal of Obstetrics and Gynecology, 78, 27-32.

[8]   Kurzel, R.B. (1991) Serum Magnesium Levels in Pregnancy and Preterm Labor. American Journal of Perinatology, 8, 119-127.

[9]   Lemancewicz, A., Laudanska, H., Laudanski, T., Karpiuk, A. and Batra, S. (2000) Permeability of Fetal Membranes to Calcium and Magnesium: Possible Role in Preterm Labour. Human Reproduction, 15, 2018-2022.

[10]   Fomin, V.P., Gibbs, S.G., Vanam, R., Morimiya, A. and Hurd, W.W. (2006) Effect of Magnesium Sulfate on Contractile Force and Intracellular Calcium Concentration in Pregnant Human Myometrium. American Journal of Obstetrics and Gynecology, 194, 1384-1390.

[11]   Pearson, P.J., Evora, P.R., Seccombe, J.F. and Schaff, H.V. (1998) Hypomagnesemia Inhibits Nitric Oxide Release from Coronary Endothelium: Protective Role of Magnesium Infusion after Cardiac Operations. The Annals of Thoracic Surgery, 65, 967-972.

[12]   Phillippe, M. (1998) Cellular Mechanisms Underlying Magnesium Sulfate Inhibition of Phasic Myometrial Contractions. Biochemical and Biophysical Research Communications, 252, 502-507.

[13]   Hurd, W.W., Natarajan, V., Fischer, J.R., Singh, D.M., Gibbs, S.G. and Fomin, V.P. (2002) Magnesium Sulfate Inhibits the Oxytocin-Induced Production of Inositol 1,4,5-Trisphosphate in Cultured Human Myometrial Cells. American Journal of Obstetrics and Gynecology, 187, 419-424.

[14]   Raddatz, G. and Bisswanger, H. (1997) Receptor Site and Stereospecifity of Dihydrolipoamide Dehydrogenase for Rand S-Lipoamide: A Molecular Modeling Study. Journal of Biotechnology, 58, 89-100.

[15]   Packer, L., Tritschler, H.J. and Wessel, K. (1997) Neuroprotection by the Metabolic Antioxidant Alpha-Lipoic Acid. Free Radical Biology & Medicine, 22, 359-378.

[16]   Kawagoe, Y., Sameshima, H., Ikenoue, T., Yasuhi, I. and Kawarabayashi, T. (2011) Magnesium Sulfate as a SecondLine Tocolytic Agent for Preterm Labor: A Randomized Controlled Trial in Kyushu Island. Journal of Pregnancy, 2011, Article ID: 965060.

[17]   Popper, L.D., Batra, S.C. and Akerlund, M. (1989) The Effect of Magnesium on Calcium Uptake and Contractility in the Human Myometrium. Gynecologic and Obstetric Investigation, 28, 78-81.

[18]   Mizuki, J., Tasaka, K., Masumoto, N., Kasahara, K., Miyake, A. and Tanizawa, O. (1993) Magnesium Sulfate Inhibits Oxytocin-Induced Calcium Mobilization in Human Puerperal Myometrial Cells: Possible Involvement of Intracellular Free Magnesium Concentration. American Journal of Obstetrics and Gynecology, 169, 134-139.

[19]   Tica, V.I., Tica, A.A., Carlig, V. and Banica, O.S. (2007) Magnesium Ion Inhibits Spontaneous and Induced Contractions of Isolated Uterine Muscle. Gynecological Endocrinology: The Official Journal of the International Society of Gynecological Endocrinology, 23, 368-372.

[20]   Coudray, C., Rambeau, M., Feillet-Coudray, C., Gueux, E., Tressol, J.C., Mazur, A., et al. (2005) Study of Magnesium Bioavailability from Ten Organic and Inorganic Mg Salts in Mg-Depleted Rats Using a Stable Isotope Approach. Magnesium Research: Official Organ of the International Society for the Development of Research on Magnesium, 18, 215-223.

[21]   Boylan, L.M. and Spallholz, J.E. (1990) In Vitro Evidence for a Relationship between Magnesium and Vitamin B-6. Magnesium Research: Official Organ of the International Society for the Development of Research on Magnesium, 3, 79-85.

[22]   Snegovskikh, V., Park, J.S. and Norwitz, E.R. (2006) Endocrinology of Parturition. Endocrinology and Metabolism Clinics of North America, 35, 173-191.

[23]   Smith, R., Van Helden, D., Hirst, J., Zakar, T., Read, M., Chan, E.C., Palliser, H., Grammatopoulos, D., Nicholson, R. and Parkington, H.C. (2007) Pathological Interactions with the Timing of Birth and Uterine Activation. Australian & New Zealand Journal of Obstetrics & Gynaecology, 47, 430-437.

[24]   Moore, R.M., Novak, J.B., Kumar, D., Mansour, J.M., Mercer, B.M. and Moore, J.J. (2009) Alpha-Lipoic Acid Inhibits Tumor Necrosis Factor-Induced Remodeling and Weakening of Human Fetal Membranes. Biology of Reproduction, 80, 781-787.

[25]   Moore, R.M., Schatz, F., Kumar, D., Mercer, B.M., Abdelrahim, A., Rangaswamy, N., et al. (2010) Alpha-Lipoic Acid Inhibits Thrombin-Induced Fetal Membrane Weakening in Vitro. Placenta, 31, 886-892.

[26]   Kim, H.S., Kim, H.J., Park, K.G., Kim, Y.N., Kwon, T.K., Park, J.Y., Lee, K.U., Kim, J.G. and Lee, I.K. (2007) α-Lipoic Acid Inhibits Matrix Metalloproteinase-9 Expression by Inhibiting NF-κB Transcriptional Activity. Experimental & Molecular Medicine, 39, 106-113.