Astaxanthin Ameliorates Inflammation, Oxidative Stress, and Reproductive Outcomes in Endometriosis Patients Undergoing Assisted Reproduction: A Randomized, Triple-blind Placebo-controlled Clinical Trial

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2023 Apr 6

PMID 37020589

Authors

Sahar Rostami

Ashraf Alyasin

Mojtaba Saedi

Saeid Nekoonam

Mahshad Khodarahmian

Ashraf Moeini

Fardin Amidi

Affiliations

Soon will be listed here.

Abstract

Purpose: In a randomized, triple-blind, placebo-controlled clinical trial (RCT) including 50 infertile women with endometriosis candidate for assisted reproductive techniques (ART), we studied the effect of Astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and early pregnancy outcomes.

Methods: Before and after 12 weeks of AST treatment (6 mg per day), blood serum and follicular fluid (FF) samples were collected from 50 infertile women with endometriosis stage III/IV undergoing ART. Pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and OS markers (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT], and total antioxidant capacity [TAC]) were measured in the serum and FF. ART outcomes were also compared between the groups.

Results: Increased serum levels of TAC (398.661 ± 57.686 . 364.746 ± 51.569; P = 0.004) and SOD (13.458 ± 7.276 . 9.040 ± 5.155; P = 0.010) were observed after AST therapy in the treatment group. Furthermore, serum MDA (14.619 ± 2.505 . 15.939 ± 1.512; P = 0.031) decreased significantly following antioxidant treatment. In addition, significantly lower serum levels of IL-1β (4.515 ± 0.907 . 6.8760 ± 0.8478; P = 0.000), IL-6 (5.516 ± 0.646 . 5.0543 ± 0.709; P = 0.024) and TNF-α (2.520 ± 0.525 . 2.968 ± 0.548; P = 0.038) were observed after AST treatment. In addition, AST supplementation led to an improved number of oocytes retrieved (14.60 ± 7.79 . 9.84 ± 6.44; P = 0.043), number of mature (MII) oocytes (10.48 ± 6.665 . 6.72 ± 4.3; P = 0.041), and high-quality embryos (4.52 ± 2.41 . 2.72 ± 2.40; P = 0.024).

Conclusion: AST pretreatment can modulate inflammation and OS in endometriosis-induced infertile patients. ART outcomes also improved after 12 weeks of AST therapy. Our results suggest that AST can be a potential therapeutic target for infertile patients with endometriosis undergoing ART.

Citing Articles

Astaxanthin Alleviates Oxidative Stress in Mouse Preantral Follicles and Enhances Follicular Development Through the AMPK Signaling Pathway.

He J, Zhong Y, Li Y, Liu S, Pan X Int J Mol Sci. 2025; 26(5).

PMID: 40076863 PMC: 11900623. DOI: 10.3390/ijms26052241.

Assisted Reproduction Technologies (ART): Impact of Mitochondrial (Dys)function and Antioxidant Therapy.

Ferreira F, Teixeira J, Lidon F, Cagide F, Borges F, Pereira R Animals (Basel). 2025; 15(3).

PMID: 39943058 PMC: 11815877. DOI: 10.3390/ani15030289.

The Key Nutrients in the Mediterranean Diet and Their Effects in Inflammatory Bowel Disease: A Narrative Review.

Deleu S, Becherucci G, Godny L, Mentella M, Petito V, Scaldaferri F Nutrients. 2024; 16(23).

PMID: 39683595 PMC: 11644409. DOI: 10.3390/nu16234201.

Meta-analysis and network pharmacology studies of the clinical efficacy of Guizhi Fuling capsules/pills combined with dienogest in treating endometriosis.

Qin Y, Yang X, Zhao Q, Tang X, Zhao H, Jiao Y Medicine (Baltimore). 2024; 103(49):e40528.

PMID: 39654212 PMC: 11630926. DOI: 10.1097/MD.0000000000040528.

Hot-Melt Extrusion Drug Delivery System-Formulated Extracts Regulate Inflammation and Oxidative Stress in Lipopolysaccharide-Stimulated Macrophages.

Gil T, Sim H, Lee H, Ryu S, Baek J, Kim D Mar Drugs. 2024; 22(11).

PMID: 39590792 PMC: 11595552. DOI: 10.3390/md22110512.

References

Eslami M, Esfandyari S, Aghahosseini M, Rashidi Z, Hosseinishental S, Brenjian S . Astaxanthin Protects Human Granulosa Cells against Oxidative Stress through Activation of NRF2/ARE Pathway and Its Downstream Phase II Enzymes. Cell J. 2021; 23(3):319-328. PMC: 8286460. DOI: 10.22074/cellj.2021.7222. View

Mate G, Bernstein L, Torok A . Endometriosis Is a Cause of Infertility. Does Reactive Oxygen Damage to Gametes and Embryos Play a Key Role in the Pathogenesis of Infertility Caused by Endometriosis?. Front Endocrinol (Lausanne). 2018; 9:725. PMC: 6281964. DOI: 10.3389/fendo.2018.00725. View

Gonzalez-Ramos R, Van Langendonckt A, Defrere S, Lousse J, Colette S, Devoto L . Involvement of the nuclear factor-κB pathway in the pathogenesis of endometriosis. Fertil Steril. 2010; 94(6):1985-94. DOI: 10.1016/j.fertnstert.2010.01.013. View

Park J, Chyun J, Kim Y, Line L, Chew B . Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab (Lond). 2010; 7:18. PMC: 2845588. DOI: 10.1186/1743-7075-7-18. View

Pasqualotto E, Agarwal A, Sharma R, Izzo V, Pinotti J, Joshi N . Effect of oxidative stress in follicular fluid on the outcome of assisted reproductive procedures. Fertil Steril. 2004; 81(4):973-6. DOI: 10.1016/j.fertnstert.2003.11.021. View

Cacciottola L, Donnez J, Dolmans M . Can Endometriosis-Related Oxidative Stress Pave the Way for New Treatment Targets?. Int J Mol Sci. 2021; 22(13). PMC: 8267660. DOI: 10.3390/ijms22137138. View

Asimakopoulos B, Demirel C, Felberbaum R, Waczek S, Nikolettos N, Koster F . Concentrations of inflammatory cytokines and the outcome in ICSI cycles. In Vivo. 2010; 24(4):495-500. View

Bedaiwy M, Shahin A, AbulHassan A, Goldberg J, Sharma R, Agarwal A . Differential expression of follicular fluid cytokines: relationship to subsequent pregnancy in IVF cycles. Reprod Biomed Online. 2007; 15(3):321-5. DOI: 10.1016/s1472-6483(10)60346-x. View

Alijotas-Reig J, Esteve-Valverde E, Ferrer-Oliveras R, Llurba E, Gris J . Tumor Necrosis Factor-Alpha and Pregnancy: Focus on Biologics. An Updated and Comprehensive Review. Clin Rev Allergy Immunol. 2017; 53(1):40-53. DOI: 10.1007/s12016-016-8596-x. View

10.

Yamaguchi K, Mandai M, Toyokuni S, Hamanishi J, Higuchi T, Takakura K . Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress. Clin Cancer Res. 2008; 14(1):32-40. DOI: 10.1158/1078-0432.CCR-07-1614. View

11.

Naguib Y . Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem. 2000; 48(4):1150-4. DOI: 10.1021/jf991106k. View

12.

Clower L, Fleshman T, Geldenhuys W, Santanam N . Targeting Oxidative Stress Involved in Endometriosis and Its Pain. Biomolecules. 2022; 12(8). PMC: 9405905. DOI: 10.3390/biom12081055. View

13.

Rahmioglu N, Fassbender A, Vitonis A, Tworoger S, Hummelshoj L, DHooghe T . World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: III. Fluid biospecimen collection, processing, and storage in endometriosis research. Fertil Steril. 2014; 102(5):1233-43. PMC: 4230639. DOI: 10.1016/j.fertnstert.2014.07.1208. View

14.

de Ziegler D, Borghese B, Chapron C . Endometriosis and infertility: pathophysiology and management. Lancet. 2010; 376(9742):730-8. DOI: 10.1016/S0140-6736(10)60490-4. View

15.

Spiller G, Dewell A . Safety of an astaxanthin-rich Haematococcus pluvialis algal extract: a randomized clinical trial. J Med Food. 2003; 6(1):51-6. DOI: 10.1089/109662003765184741. View

16.

Prieto L, Quesada J, Cambero O, Pacheco A, Pellicer A, Codoceo R . Analysis of follicular fluid and serum markers of oxidative stress in women with infertility related to endometriosis. Fertil Steril. 2012; 98(1):126-30. DOI: 10.1016/j.fertnstert.2012.03.052. View

17.

Choi H, Kim J, Chang M, Kyu-Youn Y, Shin W . Effects of astaxanthin on oxidative stress in overweight and obese adults. Phytother Res. 2011; 25(12):1813-8. DOI: 10.1002/ptr.3494. View

18.

Gupta S, Goldberg J, Aziz N, Goldberg E, Krajcir N, Agarwal A . Pathogenic mechanisms in endometriosis-associated infertility. Fertil Steril. 2008; 90(2):247-57. DOI: 10.1016/j.fertnstert.2008.02.093. View

19.

Baralic I, Djordjevic B, Dikic N, Kotur-Stevuljevic J, Spasic S, Jelic-Ivanovic Z . Effect of astaxanthin supplementation on paraoxonase 1 activities and oxidative stress status in young soccer players. Phytother Res. 2012; 27(10):1536-42. DOI: 10.1002/ptr.4898. View

20.

. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997; 67(5):817-21. DOI: 10.1016/s0015-0282(97)81391-x. View