Benefits of α‑lipoic acid in high‑risk pregnancies (Review)

Petca,Aida; Bot,Mihaela; Maru,Nicoleta; Calo,Ioana Gabriela; Borislavschi,Andreea; Dumitrascu,Mihai Cristian; Petca,Razvan-Cosmin; Sandru,Florica; Zvanca,Mona Elena

doi:10.3892/etm.2021.10666

Benefits of α‑lipoic acid in high‑risk pregnancies (Review)

Authors:
- Aida Petca
- Mihaela Bot
- Nicoleta Maru
- Ioana Gabriela Calo
- Andreea Borislavschi
- Mihai Cristian Dumitrascu
- Razvan-Cosmin Petca
- Florica Sandru
- Mona Elena Zvanca
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Affiliations: Department of Obstetrics and Gynecology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Obstetrics and Gynecology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Anatomy, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Obstetrics and Gynecology, Elias Emergency University Hospital, 011461 Bucharest, Romania, Department of Urology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Dermatology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
Published online on: August 31, 2021 https://doi.org/10.3892/etm.2021.10666
Article Number: 1232

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Abstract

α‑Lipoic acid (ALA) is a natural molecule that is inconsistently synthesized by the human body and must be provided from exogenous sources, such as food and dietary supplements. Once absorbed, the oxidized form of ALA is transformed into its reduced form, dihydrolipoic acid (DHLA). ALA/DHLA exert direct and indirect antioxidant, anti‑inflammatory and fine immunomodulatory effects. ALA/DHLA reduce the levels of pro‑inflammatory cytokines (IL‑1β, IL‑6, IL‑8 and IL‑17), while increasing the secretion of anti‑inflammatory cytokines (IL‑10). They also inhibit cyclooxygenase 2, thereby decreasing the secretion of prostaglandin E2 and nitrogen oxide, and reducing the risk of miscarriage in the first trimester of pregnancy. In patients at risk of abortion, administration of ALA from the first trimester has shown efficacy by accelerating subchorionic hematoma resorption, with a significant decrease in the accompanying abdominal pain. ALA has been proven to be efficient in maintaining the length of the cervix and keeping it closed following one episode of premature labor. Preeclampsia is a dysfunction caused by abnormal placentation and an excessive maternal inflammatory response, leading to extreme hypoxia in the placental bed and exaggerated oxidative stress, with release of oxygen free radicals. Oxidative stress plays a key role in the development of preeclampsia and intrauterine growth restriction. The hypothesis of antioxidant supplementation may play an essential part in disease prevention and fetal neuroprotection.

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1	Reed LJ: A trail of research from lipoic acid to alpha-keto acid dehydrogenase complexes. J Biol Chem. 276:38329–38336. 2001.PubMed/NCBI View Article : Google Scholar
2	Parente E, Colannino G, Picconi O and Monastra G: Safety of oral alpha-lipoic acid treatment in pregnant women: A retrospective observational study. Eur Rev Med Pharmacol Sci. 18:4219–4227. 2017.PubMed/NCBI
3	Smith AR, Shenv SV, Widlansky M, Suh JH and Hagen TM: Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem. 11:1135–1146. 2004.PubMed/NCBI View Article : Google Scholar
4	Mayr JA, Feichtinger RG, Tort F, Ribes A and Sperl W: Lipoic acid biosynthesis defects. J Inherit Metab Dis. 37:553–563. 2014.PubMed/NCBI View Article : Google Scholar
5	Monastra G, De Gazia S, Cilaker Micili S, Goker A and Unfer V: Immunomodulatory activities of alpha lipoic acid with a special focus on its efficacy in preventing miscarriage. Expert Opin Drug Deliv. 13:1695–1708. 2016.PubMed/NCBI View Article : Google Scholar
6	Gorąca A, Huk-Kolega H, Piechota A, Keniewska P, Ciejka E and Skibska B: Lipoic acid-biological activity and therapeutic potential. Pharmacol Rep. 63:849–858. 2011.PubMed/NCBI View Article : Google Scholar
7	Biewenga GP, Haenen GR and Bast A: The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 29:315–331. 1997.PubMed/NCBI View Article : Google Scholar
8	Hermann R, Niebch G, Borbe HO, Fieger-Büschges H, Ruus P, Nowak H, Riethmüller-Winzen H, Peukert M and Blume H: Enantioselective pharmacokinetics and bioavailability of different racemic α-lipoic acid formulations in healthy volunteers. Eur J Pharm Sci. 4:167–174. 1996.
9	Kliman HJ and Milano KM: The majority of miscarriages are caused by genetic abnormalities. Fertil Steril. 100(S306)2013.
10	Kwak-Kim J, Yang KM and Gilman-Sachs A: Recurrent pregnancy loss: A disease of inflammation and coagulation. J Obstet Gynaecol Res. 35:609–622. 2009.PubMed/NCBI View Article : Google Scholar
11	Christiansen OB, Nielsen HS and Kolte AM: Inflammation and miscarriage. Semin Fetal Neonatal Med. 11:302–308. 2006.PubMed/NCBI View Article : Google Scholar
12	Yassaee F, Shekarriz-Foumani R, Afsari S and Fallahian M: The effect of progesterone suppositories on threatened abortion: A randomized clinical trial. J Reprod Infertil. 15:147–151. 2014.PubMed/NCBI
13	Wada H, Shintani D and Ohlrogge J: Why do mitochondria synthesize fatty acids? Evidence for involvement in lipoic acid production. Proc Natl Acad Sci USA. 94:1591–1596. 1997.PubMed/NCBI View Article : Google Scholar
14	Teichert J and Preiss R: HPLC-methods for determination of lipoic acid and its reduced form in human plasma. Int J Clin Pharmacol Ther Toxicol. 30:511–512. 1992.PubMed/NCBI
15	Duhig K, Chappell LC and Shennan AH: Oxidative stress in pregnancy and reproduction. Obstet Med. 9:113–116. 2016.PubMed/NCBI View Article : Google Scholar
16	Toy H, Camuzcuoglu H, Camuzcuoglu A, Celik H and Aksoy N: Decreased serum prolidase activity and increased oxidative stress in early pregnancy loss. Gynecol Obstet Invest. 69:122–127. 2010.PubMed/NCBI View Article : Google Scholar
17	Safronova VG, Matveeva NK, Avkhacheva NV, Sidel'nikova VM, Van'ko LV and Sukhikh GT: Changes in regulation of oxidase activity of peripheral blood granulocytes in women with habitual abortions. Bull Exp Biol Med. 136:257–260. 2003.PubMed/NCBI View Article : Google Scholar
18	Spector A, Huang RR, Yan GZ and Wang RR: Thioredoxin fragment 31-36 is reduced by dihydrolipoamide and reduces oxidized protein. Biochem Biophys Res Commun. 150:156–162. 1988.PubMed/NCBI View Article : Google Scholar
19	Salehi B, Berkay Yılmaz Y, Antika G, Boyunegmez Tumer T, Fawzi Mahomoodally M, Lobine D, Akram M, Riaz M, Capanoglu E, Sharopov F, et al: Insights on the Use of α-lipoic acid for therapeutic purposes. Biomolecules. 9:9–356. 2019.PubMed/NCBI View Article : Google Scholar
20	Shay KP, Moreau RF, Smith EJ and Hagen TM: Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 1790:1149–1160. 2009.PubMed/NCBI View Article : Google Scholar
21	Luckheeram RV, Zhou R, Verma AD and Xia B: CD4⁺ T cells: Differentiation and functions. Clin Dev Immunol. 2012(925135)2012.PubMed/NCBI View Article : Google Scholar
22	Torchinsky A, Shepshelovich J, Orenstein H, Zaslavsky Z, Savion S, Carp H, Fein A and Toder V: TNF-alpha protects embryos exposed to developmental toxicants. Am J Reproduct Immunol. 49:159–168. 2003.PubMed/NCBI View Article : Google Scholar
23	Wang W, Sung N, Gilman-Sachs A and Kwak-Kim J: T Helper (Th) cell profiles in pregnancy and recurrent pregnancy losses: Th1/Th2/Th9/Th17/Th22/Tfh cells. Front Immunol. 11(2025)2020.PubMed/NCBI View Article : Google Scholar
24	Bauer S, Pollheimer J, Hartmann J, Husslein P, Aplin JD and Knöfler M: Tumor necrosis factor-alpha inhibits trophoblast migration through elevation of plasminogen activator inhibitor-1 in first-trimester villous explant cultures. J Clin Endocrinol Metabol. 89:812–822. 2004.PubMed/NCBI View Article : Google Scholar
25	Renaud SJ, Postovit LM, Macdonald-Goodfellow SK, McDonald GT, Caldwell JD and Graham CH: Activated macrophages inhibit human cytotrophoblast invasiveness in vitro. Biol Reprod. 73:237–243. 2005.PubMed/NCBI View Article : Google Scholar
26	Vitoratos N, Papadias C, Economou E, Makrakis E, Panoulis C and Creatsas G: Elevated circulating IL-1beta and TNF-alpha, and unaltered IL-6 in first-trimester pregnancies complicated by threatened abortion with an adverse outcome. Mediators Inflamm. 2006(30485)2006.PubMed/NCBI View Article : Google Scholar
27	Saito S, Nakashima A, Shima T and Ito M: Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol. 63:601–610. 2010.PubMed/NCBI View Article : Google Scholar
28	Prins JR, Gomez-Lopez N and Robertson SA: Interleukin-6 in pregnancy and gestational disorders. J Reprod Immunol. 95:1–14. 2012.PubMed/NCBI View Article : Google Scholar
29	Chatterjee P, Chiasson VL, Bounds KR and Mitchell BM: Regulation of the anti-inflammatory cytokines Interleukin-4 and Interleukin-10 during pregnancy. Front Immunol. 5(253)2014.PubMed/NCBI View Article : Google Scholar
30	Kaminski VD, Ellwanger JH, Matte MCC, Savaris RF, Vianna P and Chies JAB: IL-17 blood levels increase in healthy pregnancy but not in spontaneous abortion. Mol Biol Rep. 45:1565–1568. 2018.PubMed/NCBI View Article : Google Scholar
31	Lombardelli L, Logiodice F, Aguerre-Girr M, Kullolli O, Haller H, Casart Y, Berrebi A, L'Faqihi-Olive FE, Duplan V, Romagnani S, et al: Interleukin-17-producing decidual CD4+ T cells are not deleterious for human pregnancy when they also produce interleukin-4. Clin Mol Allergy. 14(1)2016.PubMed/NCBI View Article : Google Scholar
32	Nakashima A, Ito M, Shima T, Bac ND, Hidaka T and Saito S: Accumulation of IL-17-positive cells in decidua of inevitable abortion cases. Am J Reprod Immunol. 64:4–11. 2010.PubMed/NCBI View Article : Google Scholar
33	Wang WJ, Hao CF, Yi-Lin Yin GJ, Bao SH, Qiu LH and Lin QD: Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol. 84:164–170. 2010.PubMed/NCBI View Article : Google Scholar
34	Liu YS, Wu L, Tong XH, Wu LM, He GP, Zhou GX, Luo LH and Luan HB: Study on the relationship between Th17 cells and unexplained recurrent spontaneous abortion. Am J Reprod Immunol. 65:503–511. 2010.PubMed/NCBI View Article : Google Scholar
35	Osorio F, Leibund Gut-Landmann S, Lochner M, Lahl K, Sparwasser T, Eberl G and Reis e Sousa C: DC activated via dectin-1 convert Treg into IL-17 producers. Eur J Immunol. 38:3274–3281. 2008.PubMed/NCBI View Article : Google Scholar
36	Liu HP, Cao AT, Feng T, Li Q, Zhang W, Yao S, Dann SM, Elson CO and Cong Y: TGF-β converts Th1 cells into Th17 cells through stimulation of Runx1 expression. Eur J Immunol. 45:1010–1018. 2015.PubMed/NCBI View Article : Google Scholar
37	Attia M, Essa EA, Zaki RM and Elkordy AA: An overview of the antioxidant effects of ascorbic acid and alpha lipoic acid (in liposomal forms) as adjuvant in cancer treatment. Antioxidants (Basel). 9(359)2020.PubMed/NCBI View Article : Google Scholar
38	Porcaro G, Brillo E, Giardina I and Di Iorio R: Alpha Lipoic Acid (ALA) effects on subchorionic hematoma: Preliminary clinical results. Eur Rev Med Pharmacol Sci. 19:3426–3432. 2015.PubMed/NCBI
39	Costantino M, Guaraldi C and Costantino D: Resolution of subchorionic hematoma and symptoms of threatened miscarriage using vaginal alpha lipoic acid or progesterone: Clinical evidences. Eur Rev Med Pharmacol Sci. 20:1656–1663. 2016.PubMed/NCBI
40	Di Tucci C, Di Feliciantonio M, Vena F, Capone C, Schiavi MC, Pietrangeli D, Muzii L and Benedetti Panici P: Alpha lipoic acid in obstetrics and gynecology. Gynecol Endocrinol. 34:729–733. 2018.PubMed/NCBI View Article : Google Scholar
41	Pashaj A, Xia M and Moreau R: α-Lipoic acid as a triglyceride-lowering nutraceutical. Can J Physiol Pharmacol. 93:1029–1041. 2015.PubMed/NCBI View Article : Google Scholar
42	Parente E, Colannino G and Ferrara P: Efficacy of magnesium and alpha lipoic acid supplementation in reducing premature uterine contractions. Open J Obstet Gynecol. 4:578–583. 2014.
43	Carson RJ: Detection and prevention of premature labour. Neuro Endocrinol Lett. 25 (Suppl 1):S35–S41. 2004.PubMed/NCBI
44	Hubinont C and Debieve F: Prevention of preterm labour: 2011 update on tocolysis. J Pregnancy. 2011(941057)2011.PubMed/NCBI View Article : Google Scholar
45	Connon CJ, Nakamura T, Hopkinson A, Quantock A, Yagi N, Doutch J and Meek KM: The biomechanics of amnion rupture: An X-ray diffraction study. PLoS One. 2(e1147)2007.PubMed/NCBI View Article : Google Scholar
46	Snegovskikh V, Park JS and Norwitz ER: Endocrinology of parturition. Endocrin Metabol Clin North Am. 35:173–191. 2006.PubMed/NCBI View Article : Google Scholar
47	Moore RM, Novak JB, Kumar D, Mansour JM, Mercer BM and Moore JJ: Alpha-Lipoic Acid inhibits tumor necrosis factor-induced remodeling and weakening of human fetal membranes. Biol Reprod. 80:781–787. 2008.PubMed/NCBI View Article : Google Scholar
48	Moore RM, Schatz F, Kumar D, Mercer BM, Abdelrahim A, Rangaswamy N, Bartel C, Mansour JM, Lockwood CJ and Moore JJ: Alpha-lipoic acid inhibits thrombin-induced fetal membrane weakening in vitro. Placenta. 31:886–892. 2010.PubMed/NCBI View Article : Google Scholar
49	Grandi G, Pignatti L, Ferrari F, Dante G, Neri I and Facchinetti F: Vaginal alpha-lipoic acid shows an anti-inflammatory effect on the cervix, preventing its shortening after primary tocolysis. A pilot, randomized, placebo-controlled study. J Matern Fetal Neonatal Med. 30:2243–2249. 2017.PubMed/NCBI View Article : Google Scholar
50	Vitrano G, Mocera G, Guardino M, Giallombardo V and Venezia R: Oral plus vaginal alpha-lipoic acid in women at risk for preterm delivery. IJMDAT. 1(e104)2018.
51	Wei SQ, Fraser W and Luo ZC: Inflammatory cytokines and spontaneous preterm birth in asymptomatic women: A systematic review. Obstet Gynecol. 116:393–401. 2010.PubMed/NCBI View Article : Google Scholar
52	Kim HS, Kim HJ, Park KG, Kim YN, Kwon TK, Park JY, Lee KU, Kim JG and Lee IK: Alpha-lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-kappaB transcriptional activity. Exp Mol Med. 39:106–113. 2007.PubMed/NCBI View Article : Google Scholar
53	Myatt L and Cui X: Oxidative stress in the placenta. Histochem Cell Biol. 122:369–382. 2004.PubMed/NCBI View Article : Google Scholar
54	Walsh SW and Wang Y: Secretion of lipid peroxides by the human placenta. Am J Obstet Gynecol. 169:1462–1466. 1993.PubMed/NCBI View Article : Google Scholar
55	Redman CW and Sargent IL: Placental debris, oxidative stress and preeclampsia. Placenta. 21:597–602. 2000.PubMed/NCBI View Article : Google Scholar
56	McKinney ET, Shouri R, Hunt RS, Ahokas RA and Sibai BM: Plasma, urinary, and salivary 8-epi-prostaglandin f2alpha levels in normotensive and preeclamptic pregnancies. Am J Obstet Gynecol. 183:874–877. 2000.PubMed/NCBI View Article : Google Scholar
57	Aouache R, Biquard L, Vaiman D and Miralles F: Oxidative stress in preeclampsia and placental diseases. Int J Mol Sci. 19(1496)2018.PubMed/NCBI View Article : Google Scholar
58	Buonocore G, Perrone S and Tataranno ML: Oxygen toxicity: Chemistry and biology of reactive oxygen species. Semin Fetal Neonatal Med. 15:186–190. 2010.PubMed/NCBI View Article : Google Scholar
59	Poston L, Igosheva N, Mistry HD, Seed PT, Shennan AH, Rana S, Karumanchi SA and Chappell LC: Role of oxidative stress and antioxidant supplementation in pregnancy disorders. Am J Clin Nutr. 94 (6 Suppl):1980S–1985S. 2011.PubMed/NCBI View Article : Google Scholar
60	Lewen A, Matz P and Chan PH: Free radical pathways in CNS injury. J Neurotrauma. 17:871–890. 2000.PubMed/NCBI View Article : Google Scholar
61	Gug C, Rațiu A, Navolan D, Drăgan I, Groza IM, Păpurică M, Vaida MA, Mozoș I and Jurcă MC: Incidence and spectrum of chromosome abnormalities in miscarriage samples: A retrospective study of 330 cases. Cytogenet Genome Res. 158:171–183. 2019.PubMed/NCBI View Article : Google Scholar
62	Wolz P and Krieglstein J: Neuroprotective effects of alpha-lipoic acid and its enantiomers demonstrated in rodent models of focal cerebral ischemia. Neuropharmacology. 35:369–375. 1996.PubMed/NCBI View Article : Google Scholar
63	Mei XH and Yang YW: Neuroprotective effects of α-lipoic acid against hypoxic-ischemic brain injury in neonatal rats. Trop J Pharm Res. 16:1051–1058. 2017.
64	Miller SL, Wallace EM and Walker DW: Antioxidant therapies: A potential role in perinatal medicine. Neuroendocrinology. 96:13–23. 2012.PubMed/NCBI View Article : Google Scholar