Written by Taylor Woosley, Staff Writer. 12-week supplementation of 6 mg astaxanthin significantly increased serum TAC (p = 0.004) and SOD (p = 0.010) and significantly decreased TNF-α levels (p = 0.038) compared to placebo. 

stomach painEndometriosis is a chronic, inflammatory condition associated with debilitating chronic pelvic pain estimated to affect 6%-10% of women of reproductive age1. A series of alterations of inflammatory cells, cytokines, and chemokines are present in endometriotic lesions, forming an inflammatory environment2. Endometriosis-associated infertility stems from a complex interaction between endometriosis subtype, altered pelvic anatomy, adhesions, disrupted ovarian reserve/function, and compromised endometrial receptivity3.

Astaxanthin is a naturally occurring xanthophyll carotenoid found in microalgae, crustaceans, and fish, which acts as a powerful antioxidant4. Research on astaxanthin shows that it can neutralize reactive oxygen species and reactive nitrogen species within the body’s cells which lead to oxidative damage5. Furthermore, astaxanthin has reported anti-inflammatory responses through blocking the NF-ĸB dependent signaling pathway and forestalling gene expression of downstream inflammatory mediators such as IL-1β, IL-6, and tumor necrosis factor-α (TNF-α)6.

Rostami et al. conducted a prospective, parallel, randomized, triple-blind, placebo-controlled trial to analyze the effect of astaxanthin supplementation on oxidative stress, inflammation, and reproductive outcomes in subjects with endometriosis that are undergoing assisted reproductive technique (ART), the main treatment option for endometriosis-induced infertility. Subject inclusion consisted of subjects aged 20 to 40 years old who were experiencing infertility caused by stage III/IV endometriosis confirmed by video laparoscopy and histopathological tests, with regular menstrual cycles, with 18.5 < BMI < 30 kg/m2, and no history of surgical treatments.

Participants were randomly assigned to either the astaxanthin (AST) (n = 25) or placebo (n = 25) groups. Those in the AST group consumed 6 mg of oral AST daily, while the placebo group consumed a similar looking capsule for a total of 12 weeks. Treatment began on day 1 of two menstrual cycles before starting controlled ovarian stimulation (COS) until oocyte pick-up (OPU). All participants partook in a routine gonadotropin-releasing hormone (GnRH) antagonist ovarian stimulation protocol alongside the AST or placebo administration. Recombinant follicle-stimulating hormone (rFSH) was administered (150-300 IU/day) at the beginning of the cycle and serial transvaginal sonography (TVS) was conducted to assess the ovarian response.

Subjects were instructed to maintain normal lifestyle habits and to refrain from taking nutritional supplements except for prenatal folic acid. Supplement adherence and possible side effects were monitored via weekly phone calls and monthly visits. Blood samples were obtained before and after the intervention (on the day of OPU) to analyze oxidative stress markers (serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) activities) and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Follicular fluid (FF) sample measurements were aspirated from the first follicle during the OPU. ART outcomes were assessed by retrieving oocytes two hours following OPU to analyze for quality and maturity.

An independent sample t-test was performed to compare AST and placebo groups. Student’s paired t-test was utilized to compare pre- and post-intervention markers in both groups. Fisher’s exact and Pearson’s chi-squared tests were used to compare chemical, clinical, and multiple pregnancy rates. No significant differences in age, BMI, duration of infertility, and hormone levels were noted at baseline between the two groups. Significant findings of the study are as follows:

  • The AST group experienced increased serum levels of TAC (p = 0.004) and SOD (p = 0.010), along with decreased serum MDA (p = 0.031) at the end of treatment compared to baseline.
  • Regarding cytokine parameters, treatment with AST significantly lowered serum levels of IL-1β (p = 0.000) and TNF-α (p = 0.038). However, there were no significant differences in the FF IL-1β levels between the placebo and AST groups after the intervention (all P > 0.05).
  • Ovarian stimulation parameters and ART outcome results show that AST therapy significantly improved the number of oocytes retrieved (p = 0.043), the number of MII oocytes (p = 0.041), and high-quality embryos (p = 0.024).

Results of the study show that astaxanthin administration significantly increased serum TAC and SOD levels and significantly decreased FF TNF-α and IL-1β levels compared to placebo. Further research should continue to explore the benefits of astaxanthin administration for inflammatory-based disorders. Study limitations include the lack of generalizability of results because only subjects undergoing assisted reproduction were involved with the study and the small sample size.

Source: Rostami, Sahar, Ashraf Alyasin, Mojtaba Saedi, Saeid Nekoonam, Mahshad Khodarahmian, Ashraf Moeini, and Fardin Amidi. “Astaxanthin ameliorates inflammation, oxidative stress, and reproductive outcomes in endometriosis patients undergoing assisted reproduction: A randomized, triple-blind placebo-controlled clinical trial.” Frontiers in Endocrinology 14 (2023): 1144323.

© 2023 Rostami, Alyasin, Saedi, Nekoonam, Khodarahmian, Moeini and Amidi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

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Posted December 4, 2023.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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