Obstet Gynecol Sci.  2024 Jan;67(1):17-29. 10.5468/ogs.23206.

The effect of alpha-lipoic acid supplementation on anthropometric, glycemic, lipid, oxidative stress, and hormonal parameters in individuals with polycystic ovary syndrome: a systematic review and meta-analysis of randomized clinical trials

• Abu-Zaid A
• Baradwan S
• Bukhari IA
• Alyousef A
• Abuzaid M
• Saleh SAK
• Adly HM
• Alomar O
• Al-Badawi IA

• KMID: 2550483
• DOI: http://doi.org/10.5468/ogs.23206

Abstract

This systematic review and meta-analysis aimed to examine the effect of the antioxidant alpha-lipoic acid (ALA) on various cardiometabolic risk factors and hormonal parameters in patients with polycystic ovary syndrome (PCOS). We searched PubMed, EMBASE, SCOPUS, Cochrane Library, and Web of Science databases without language restrictions until May 2023 to find randomized controlled trials (RCTs) that assessed the impact of ALA supplementation on anthropometric, glycemic, lipid, oxidative stress, and hormonal parameters in women with PCOS. Outcomes were summarized using the standardized mean difference (SMD) and 95% confidence interval (CI) in a random-effects model. An I² statistic of >60% established significant between-study heterogeneity. The overall certainty of the evidence for each outcome was determined using the grading of recommendations, assessment, development, and evaluations system. Seven RCTs met the inclusion criteria. The ALA group had significant reductions in fasting blood sugar (fasting blood sugar (FBS), n=7 RCTs, SMD, -0.60; 95% CI, -1.10 to -0.10; I²=63.54%, moderate certainty of evidence) and homeostatic model assessment for insulin resistance (homeostatic model assessment of insulin resistance (HOMA-IR), n=4 RCTs, SMD, -2.03; 95% CI, -3.85 to -0.20; I²=96.32%, low certainty of evidence) compared with the control group. However, significant differences were observed between the groups in body mass index, insulin, estrogen, follicle-stimulating hormone, luteinizing hormone, testosterone, low-density lipoprotein, highdensity lipoprotein, triglyceride, total cholesterol, malondialdehyde, or total antioxidant capacity profiles. ALA supplementation improves FBS and HOMA-IR levels in women with PCOS. ALA consumption is an effective complementary therapy for the management of women with PCOS.

Keyword

Thioctic acid; Inositol; Polycystic ovary syndrome; Cardiometabolic risk factors

Figure

• 

  Fig. 1 The preferred reporting items for systematic reviews and meta-analyses flow diagram. RCT, randomized controlled trial. *The electronic databases were searched from their inception until May 15, 2023.

• 

  Fig. 2 The effect of alpha-lipoic acid intake on body mass index (A), fasting blood sugar (B), insulin (C), homeostatic model assessment for insulin resistance (D), estrogen (E), follicle-stimulating hormone (F), luteinizing hormone (G), and testosterone (H) in women with polycystic ovary syndrome. SD, standard deviation; SMD, standardized mean difference; CI, confidence interval; REML, restricted maximum likelihood.

Reference

References

1. Joham AE, Norman RJ, Stener-Victorin E, Legro RS, Franks S, Moran LJ, et al. Polycystic ovary syndrome. Lancet Diabetes Endocrinol. 2022; 10:668–80.

2. Heshmati J, Sepidarkish M, Morvaridzadeh M, Farsi F, Tripathi N, Razavi M, et al. The effect of cinnamon supplementation on glycemic control in women with polycystic ovary syndrome: a systematic review and meta-analysis. J Food Biochem. 2021; 45:e13543.

3. Moradi N, Bidgoli SA, Chaichian S. Ovarian cysts disappear after 14-day oral regimen of Korean red ginseng extract in letrozole-induced polycystic ovarian syndrome. Obstet Gynecol Sci. 2021; 64:274–83.

4. Naz MSG, Tehrani FR, Majd HA, Ahmadi F, Ozgoli G, Fakari FR, et al. The prevalence of polycystic ovary syndrome in adolescents: a systematic review and meta-analysis. Int J Reprod Biomed. 2019; 17:533–42.

5. Riestenberg C, Jagasia A, Markovic D, Buyalos RP, Azziz R. Health care-related economic burden of polycystic ovary syndrome in the United States: pregnancy-related and long-term health consequences. J Clin Endocrinol Metab. 2022; 107:575–85.

6. Louwers YV, Laven JSE. Characteristics of polycystic ovary syndrome throughout life. Ther Adv Reprod Health. 2020; 14:2633494120911038.

7. Salehpour S, Hosseini S, Nazari L, Hosseini M, Saharkhiz N. The effect of vitamin D supplementation on insulin resistance among women with polycystic ovary syndrome. JBRA Assist Reprod. 2019; 23:235–8.

8. Karimi E, Heshmati J, Shirzad N, Vesali S, Hosseinzadeh-Attar MJ, Moini A, et al. The effect of synbiotics supplementation on anthropometric indicators and lipid profiles in women with polycystic ovary syndrome: a randomized controlled trial. Lipids Health Dis. 2020; 19:60.

9. Romualdi D, Versace V, Lanzone A. What is new in the landscape of insulin-sensitizing agents for polycystic ovary syndrome treatment. Ther Adv Reprod Health. 2020; 14:2633494120908709.

10. Glintborg D, Andersen M. Medical treatment and comorbidity in polycystic ovary syndrome: an updated review. Curr Opin Endocr Metab Res. 2020; 12:33–40.

11. Costantini D. Understanding diversity in oxidative status and oxidative stress: the opportunities and challenges ahead. J Exp Biol. 2019; 222(Pt 13):jeb194688.

12. Shan H, Luo R, Guo X, Li R, Ye Z, Peng T, et al. Abnormal endometrial receptivity and oxidative stress in polycystic ovary syndrome. Front Pharmacol. 2022; 13:904942.

13. Abudawood M, Tabassum H, Alanazi AH, Almusallam F, Aljaser F, Ali MN, et al. Antioxidant status in relation to heavy metals induced oxidative stress in patients with polycystic ovarian syndrome (PCOS). Sci Rep. 2021; 11:22935.

14. Sandhu JK, Waqar A, Jain A, Joseph C, Srivastava K, Ochuba O, et al. Oxidative stress in polycystic ovarian syndrome and the effect of antioxidant N-acetylcysteine on ovulation and pregnancy rate. Cureus. 2021; 13:e17887.

15. Pakniat H, Lalooha F, Movahed F, Boostan A, Khezri MB, Hedberg C, et al. The effect of ginger and metoclopramide in the prevention of nausea and vomiting during and after surgery in cesarean section under spinal anesthesia. Obstet Gynecol Sci. 2020; 63:173–80.

16. Zonooz SR, Hasani M, Morvaridzadeh M, Pizarro AB, Heydari H, Yosaee S, et al. Effect of alpha-lipoic acid on oxidative stress parameters: a systematic review and meta-analysis. J Funct Foods. 2021; 87:104774.

17. Rahimlou M, Asadi M, Banaei Jahromi N, Mansoori A. Alpha-lipoic acid (ALA) supplementation effect on glycemic and inflammatory biomarkers: a systematic review and meta-analysis. Clin Nutr ESPEN. 2019; 32:16–28.

18. Fogacci F, Rizzo M, Krogager C, Kennedy C, Georges CMG, Knežević T, et al. Safety evaluation of α-lipoic acid supplementation: a systematic review and meta-analysis of randomized placebo-controlled clinical studies. Antioxidants (Basel). 2020; 9:1011.

19. Maciejczyk M, Żebrowska E, Nesterowicz M, Żendzian-Piotrowska M, Zalewska A. α-Lipoic acid strengthens the antioxidant barrier and reduces oxidative, nitrosative, and glycative damage, as well as inhibits inflammation and apoptosis in the hypothalamus but not in the cerebral cortex of insulin-resistant rats. Oxid Med Cell Longev. 2022; 2022:7450514.

20. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015; 4:1.

21. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions. Chichester: John Wiley & Sons;2019.

22. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008; 336:924–6.

23. Asa E, Janatifar R, Soltani MA, Verdi A, Janbazi M. Effect of alpha-lipoic acid on blood hormonal parameters and follicular fluid oxidative stress factors in infertile women with polycystic ovary syndrome undergoing intracytoplasmic sperm injection. Qom Univ Med Sci J. 2020; 14:49–58.

24. Cianci A, Panella M, Fichera M, Falduzzi C, Bartolo M, Caruso S. d-chiro-Inositol and alpha lipoic acid treatment of metabolic and menses disorders in women with PCOS. Gynecol Endocrinol. 2015; 31:483–6.

25. Fruzzetti F, Benelli E, Fidecicchi T, Tonacchera M. Clinical and metabolic effects of alpha-lipoic acid associated with two different doses of myo-inositol in women with polycystic ovary syndrome. Int J Endocrinol. 2020; 2020:2901393.

26. Ivanova LA. Influence of thioctic acid on the hyperinsulinemia and ovarian volume in female patients with polycystic ovary syndrome. Open J Endocr Metab Dis. 2015; 5:37.

27. Jannatifar R, Piroozmanesh H, Sahraei SS, Asa E. Combination of alpha lipoic acid and metformin supplement improve assisted reproductive technologies outcomes in polycystic ovary syndrome patients. Anat Cell Biol. 2022; 55:239–46.

28. Rago R, Marcucci I, Leto G, Caponecchia L, Salacone P, Bonanni P, et al. Effect of myo-inositol and alpha-lipoic acid on oocyte quality in polycystic ovary syndrome non-obese women undergoing in vitro fertilization: a pilot study. J Biol Regul Homeost Agents. 2015; 29:913–23.

29. Hamed BM, El-Sayed YAE, El-Ghazawy SS, Mohamed AI. Effects of thioctic acid on the hyperinsulinemia and ovarian volume in female patients with polycystic ovary syndrome. Egyptian J Hosp Med. 2023; 90:2728–33.

30. Laganà AS, Monti N, Fedeli V, Gullo G, Bizzarri M. Does alpha-lipoic acid improve effects on polycystic ovary syndrome? Eur Rev Med Pharmacol Sci. 2022; 26:1241–7.

31. Namazi N, Larijani B, Azadbakht L. Alpha-lipoic acid supplement in obesity treatment: a systematic review and meta-analysis of clinical trials. Clin Nutr. 2018; 37:419–28.

32. Kucukgoncu S, Zhou E, Lucas KB, Tek C. Alpha-lipoic acid (ALA) as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials. Obes Rev. 2017; 18:594–601.

33. Vajdi M, Abbasalizad Farhangi M. Alpha-lipoic acid supplementation significantly reduces the risk of obesity in an updated systematic review and dose response meta-analysis of randomised placebo-controlled clinical trials. Int J Clin Pract. 2020; 74:e13493.

34. Mahmoudi-Nezhad M, Vajdi M, Farhangi MA. An updated systematic review and dose-response meta-analysis of the effects of α-lipoic acid supplementation on glycemic markers in adults. Nutrition. 2021; 82:111041.

35. Mohammadi V, Khorvash F, Feizi A, Askari G. Does alpha-lipoic acid supplementation modulate cardiovascular risk factors in patients with stroke? A randomized, double-blind clinical trial. Int J Prev Med. 2018; 9:34.

36. Najafi N, Mehri S, Ghasemzadeh Rahbardar M, Hosseinzadeh H. Effects of alpha lipoic acid on metabolic syndrome: a comprehensive review. Phytother Res. 2022; 36:2300–23.

37. Aiassa V, Del Rosario Ferreira M, Villafañe N, Eugenia D’Alessandro M. α-Linolenic acid rich-chia seed modulates visceral adipose tissue collagen deposition, lipolytic enzymes expression, insulin signaling and GLUT-4 levels in a diet-induced adiposity rodent model. Food Res Int. 2022; 156:111164.

38. Kaviyani N, Keshavarz SA, Abbasi B. Effect of alphalipoic acid supplementation on glycemic control in the patients with metabolic syndrome: a randomized clinical trial [Internet]. Research Square. c2020; [cited 2023 May 17]. Available from: https://doi.org/10.21203/rs.3.rs-37045/v1 .

39. Jacob S, Henriksen EJ, Schiemann AL, Simon I, Clancy DE, Tritschler HJ, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung. 1995; 45:872–4.

40. Diane A, Mahmoud N, Bensmail I, Khattab N, Abunada HA, Dehbi M. Alpha lipoic acid attenuates ER stress and improves glucose uptake through DNAJB3 cochaperone. Sci Rep. 2020; 10:20482.

41. Capece U, Moffa S, Improta I, Di Giuseppe G, Nista EC, Cefalo CMA, et al. Alpha-lipoic acid and glucose metabolism: a comprehensive update on biochemical and therapeutic features. Nutrients. 2023; 15:18.

42. Elbadawy AM, Abd Elmoniem RO, Elsayed AM. Alpha lipoic acid and diabetes mellitus: potential effects on peripheral neuropathy and different metabolic parameters. Alexandria J Med. 2021; 57:113–20.

43. Dugbartey GJ, Alornyo KK, Adams I, Atule S, Obeng-Kyeremeh R, Amoah D, et al. Targeting hepatic sulfane sulfur/hydrogen sulfide signaling pathway with α-lipoic acid to prevent diabetes-induced liver injury via upregulating hepatic CSE/3-MST expression. Diabetol Metab Syndr. 2022; 14:148.

44. Zeng M, Xu J, Zhang Z, Zou X, Wang X, Cao K, et al. Htd2 deficiency-associated suppression of α-lipoic acid production provokes mitochondrial dysfunction and insulin resistance in adipocytes. Redox Biol. 2021; 41:101948.

45. Lee SJ, Kim SH, Kang JG, Kim CS, Ihm SH, Choi MG, et al. Alpha-lipoic acid inhibits endoplasmic reticulum stress-induced cell death through PI3K/Akt signaling pathway in FRTL5 thyroid cells. Horm Metab Res. 2011; 43:445–51.

46. Kra G, Daddam JR, Moallem U, Kamer H, Mualem B, Levin Y, et al. Alpha-linolenic acid modulates systemic and adipose tissue-specific insulin sensitivity, inflammation, and the endocannabinoid system in dairy cows. Sci Rep. 2023; 13:5280.

47. Mohammed MA, Mahmoud MO, Awaad AS, Gamal GM, Abdelfatah D. Alpha lipoic acid protects against dexamethasone-induced metabolic abnormalities via APPL1 and PGC-1 α up regulation. Steroids. 2019; 144:1–7.

48. Kim MS, Park JY, Namkoong C, Jang PG, Ryu JW, Song HS, et al. Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Nat Med. 2004; 10:727–33.

49. Lee WJ, Song KH, Koh EH, Won JC, Kim HS, Park HS, et al. Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochem Biophys Res Commun. 2005; 332:885–91.

50. Park KG, Min AK, Koh EH, Kim HS, Kim MO, Park HS, et al. Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. Hepatology. 2008; 481477–86.