Astaxanthin

Objective: Seaweed and microalgae provide antioxidants, polyunsaturated fatty acids, and bioactive compounds that may enhance exercise performance and accelerate recovery. However, evidence remains inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of algae-derived supplementation on exercise performance and physiological recovery outcomes in healthy and athletic adults. Methods: This review was registered in PROSPERO (CRD420251166723) and conducted in accordance with PRISMA 2020 guidelines. PubMed, Web of Science, Embase, Cochrane Library, EBSCO, and CNKI were systematically searched for randomized controlled trials (RCTs) evaluating algae supplementation in exercise contexts. Inclusion and exclusion criteria were defined based on the PICOS framework. Primary outcomes included VO2max, Time to exhaustion (TTE), maximal power output (WRmax), Time-Trial (TT) performance, and creatine kinase (CK). Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup, sensitivity, and publication bias analyses were performed. Results: Twenty-two RCTs (n = 822) investigating Spirulina, Chlorella, brown-algal polysaccharides, or astaxanthin met inclusion criteria. Algae supplementation showed a suggestive improvement in VO2max (SMD = 0.88, 95% CI: 0.00-1.75) and significantly improved in TTE (SMD = 1.06, 95% CI: 0.16-1.96), with smaller effects on WRmax (SMD = 0.29, 95% CI: 0.03-0.55), and no significant benefit for TT performance (SMD = -0.27, 95% CI: -0.74 to 0.21). Regarding recovery, CK concentrations were significantly reduced (SMD = -0.78, 95% CI: -1.28 to -0.28). Subgroup analysis suggested greater effects for Chlorella supplementation, higher dosages, and aerobic training contexts; reductions in muscle-damage markers were more evident following resistance exercise. Sensitivity analyses supported the robustness of the main findings with minimal evidence of publication bias. Conclusions: Algae-derived supplements-particularly Spirulina and Chlorella-may modestly enhance aerobic exercise performance and attenuate exercise-induced muscle damage under certain conditions. Eff

The use of antioxidants in cryopreservation media has been shown to improve post-thaw sperm quality and male fertility in several credible meta-analyses. However, to our knowledge, no review has specifically examined the impact of astaxanthin, a potent antioxidant, on sperm quality after freezing. This meta-analysis and systematic review aims to investigate how astaxanthin affects sperm parameters during the freeze-thaw process. A thorough search of electronic databases (PubMed, Scopus, and Web of Science) was conducted up until July 1, 2024. Random-effects models were used to synthesize the data, and the quality and heterogeneity of the evidence were assessed. Our findings show that while astaxanthin improved sperm viability and morphology, there was no significant improvement in total motility (MD = 5.67, 95% CI: -7.49 to 18.84, p = 0.40) or DNA damage (MD = -12.07, 95% CI: -25.72 to 1.57, p = 0.08) after thawing. However, significant increases were observed in progressive motility (MD = 6.79, 95% CI: 3.37 to 10.21, p = 0.00) and sperm viability during thawing (MD = 7.56, 95% CI: 4.91 to 10.21, p = 0.00). Astaxanthin also significantly improved the percentage of sperm with normal morphology (MD = -24.53, 95% CI: -45.25 to -3.81, p = 0.02). Additionally, sperm kinematic parameters including VAP (MD = 3.71, 95% CI: 0.65 to 6.77, p = 0.02) and VCL (MD = 3.37, 95% CI: 1.19 to 5.54, p = 0.00) were significantly improved, while no significant differences were observed for VSL, LIN, and STR.A descriptive synthesis of redox status, metabolic activity, MMP measures, and apoptosis was conducted.These findings suggest that astaxanthin supplementation can significantly improve sperm viability, morphology, and certain kinematic parameters during the freeze-thaw process. However, due to the small sample sizes, risk of bias, and significant heterogeneity, further studies are needed to confirm these results. © 2026. The Author(s).

BACKGROUND AND AIMS: Carotenoids are known for their beneficial effects in improving chronic diseases through their antioxidant properties. However, there has been no meta-analysis on the effects of carotenoids on liver enzymes and the evidence is inconsistent. So, this study aimed to evaluate the effects of carotenoid supplementation on liver enzyme levels in adults. METHODS: Through November 2024, the PubMed, Scopus and Web of Science electronic databases were searched for eligible trials evaluating the carotenoid supplementation effects on the Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and Gamma-glutamyl transferase (GGT). The 95% confidence intervals (CIs) and weighted mean differences (WMDs) were calculated using the random effects model. As part of standard methods, dose-response, meta-regressions, sensitivity, and publication bias analyses were performed. Evidence certainty was assessed using GRADE (Grading of Recommendations for Assessment, Development, and Evaluation). RESULTS: Of the 15 studies (20 arms; n = 757), 7 included healthy participants, while 8 involved non-healthy individuals, including 4 studies on prediabetes or diabetes. Pooled estimates indicated non-significant effects of carotenoid supplementation on all enzymes including ALT (WMD: -2.25 IU/L, 95%CI: -4.84,0.34, P = 0.089), AST (WMD: -0.46 IU/L, 95%CI: -1.25,0.34, P = 0.259), ALP (WMD: -0.34 IU/L, 95%CI: -6.89,6.21, P = 0.918) and GGT (WMD: -0.43 IU/L, 95%CI: -3.06,2.21, P = 0.751) levels non-significantly. Significant reductions in ALT levels occurred in < 12 weeks (P = 0.028), BMI ≥ 25 (P = 0.045), and among non-healthy participants (P = 0.015). AST levels were significantly reduced in non-healthy participants (P = 0.003) with ages > 50 (P = 0.003) as well as GGT levels (P = 0.011) in non-healthy participants. CONCLUSION: Carotenoid supplementation might be beneficial in reducing liver enzymes, especially in non-healthy participants and in those with a BMI ≥ 25 kg/m2. However, more trials with standard methods are required. PROSPERO REGISTERATION CODE: CRD42024612956. © 2025. The Author(s).

OBJECTIVES: We conducted a systematic review and meta-analysis to assess the effects of carotenoid supplementation on glycemic indices, and the certainty of evidence. METHODS: A systematic literature search in PubMed, SCOPUS, ISI-Web of Science, and Cochrane Library was conducted from inception up to Jun 17, 2024. Randomized controlled trials (RCTs) investigating the effect of carotenoid supplementation on circulating glycemic parameters were included. Records were excluded when studies reported the effect of co-interventions with other nutrients, did not provide mean differences (MDs) and standard deviations (SD) for outcomes, or administered whole food rather than supplements of carotenoids. Summary mean differences (MDs) and 95% CI between intervention and control groups were estimated using a random-effects model. The risk of bias of the included studies was assessed using the Risk of Bias 2.0 (RoB 2.0) tool. RESULTS: Overall, 36 publications with 45 estimated effect sizes were included in the meta-analyses. The overall findings showed an improvement in fasting blood glucose (FBG) (MD = -4.54 mg/dl; 95% CI: -5.9, -3.2; n = 45), and hemoglobin A1C (HbA1C) (MD = -0.25% (95% CI: -0.4, -0.11; n = 22) in the intervention group in comparison with the control group. Moreover, in individuals with type 2 diabetes (T2D), interventions with astaxanthin and fucoxanthin led to a reduction in FBG by 4.36 mg/dl (95% CI: -6.13, -2.6; n = 10). The findings also showed that the intervention with crocin reduced FBG levels by 13.5 mg/dl (95% CI: -15.5, -7.8; n = 5), and HbA1C by 0.55% (95% CI: -0.77, -0.34; n = 5) in individuals with T2D. However, the certainty of evidence was very low. CONCLUSION: Carotenoid's supplementation improved glycemic parameters especially in people with T2D. However. the certainty of evidence was very low, mainly due to small sample size, and indirectness. Therefore, no specific recommendations can be provided at present and well-designed RCTs are required. REGISTRY URL: https://www.crd.york.ac.uk/PROSPERO/ REGISTRY NUMBER: CRD42021285084 REGISTRY AND REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYSES: PROSPERO ID: CRD42021285084. © 2024. The A

Polycystic ovary syndrome (PCOS) is a prevalent gynecological-endocrinological disorder characterized by hyperandrogenism, menstrual irregularities, and metabolic disturbances. Recent research has highlighted the role of oxidative stress and chronic inflammation in exacerbating PCOS symptoms and impeding reproductive outcomes. Astaxanthin, a potent antioxidant found in marine organisms, has been suggested as a potential therapeutic intervention due to its ability to reduce oxidative stress and inflammation. This meta-analysis systematically reviews randomized controlled trials assessing the impact of astaxanthin supplementation on oxidative stress and reproductive outcomes in women with PCOS. Data from four trials were analyzed, focusing on markers of oxidative stress and reproductive health metrics. The meta-analysis utilized fixed and random-effects models to synthesize results, with heterogeneity assessed using Chi-square and I2 statistics. The findings indicate that while astaxanthin significantly improves markers of total antioxidant capacity (TAC) in follicular fluid, it does not show a consistent effect on other oxidative stress biomarkers such as malondialdehyde (MDA), catalase (CAT), or superoxide dismutase (SOD). Reproductive outcomes, including oocyte quality and the number of high-quality embryos, showed moderate improvements, although effects on fertilization rates and pregnancy outcomes were insignificant. The analysis highlights variability in study designs and dosing, suggesting a need for further research with standardized protocols and larger sample sizes. Future studies should focus on determining optimal dosing, exploring mechanistic pathways, and investigating the combined effects of astaxanthin with other interventions. Longitudinal studies are needed to assess long-term benefits and safety, and personalized approaches could enhance treatment efficacy for individuals with PCOS. © 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

CONTEXT: Oxidative stress (OS) plays a harmful role in female reproduction and fertility. Several studies explored various dietary interventions and antioxidant supplements, such as astaxanthin (AST), to mitigate the adverse effects of OS on female fertility. Ameliorative effects of AST on female fertility and the redox status of reproductive organs have been shown in several animal and clinical studies. OBJECTIVES: The main objective of present systematic review and meta-analysis of both animal and clinical studies was to provide a comprehensive overview of the current evidence on the effects of AST on female fertility and reproductive outcomes. The effect of AST on redox status, inflammatory and apoptotic markers in reproductive organs were included as the secondary outcomes. DATA SOURCES: We systematically searched electronic databases including PubMed, Scopus, and Web of Science, until January 1, 2024, using specified search terms related to AST, female reproductive performance, and infertility, considering the diverse synonyms found in the literature for interventional studies that compared oral AST supplementation with placebo or control in human or animal models. DATA EXTRACTION: Two independent reviewers extracted data on study characteristics, outcomes, and risk of bias. We pooled the results using random-effects models and assessed the heterogeneity and quality of evidence. We descriptively reported the data from animal models, as meta-analysis was not possible. DATA ANALYSIS: The meta-analysis of clinical trials showed that AST significantly increased the oocyte maturation rate (MD: 8.40, 95% CI: 4.57 to 12.23, I2: 0%) and the total antioxidant capacity levels in the follicular fluid (MD: 0.04, 95% CI: 0.02 to 0.06, I2: 0%). The other ART and pregnancy outcomes and redox status markers did not show statistically significant changes. The animal studies reported ameliorative effects of AST on redox status, inflammation, apoptosis, and ovarian tissue histomorphology. CONCLUSION: This systematic review shows that AST supplementation may improve assisted reproductive technology outcomes by enhancing oocyte quality and reducing OS in the reproductive organs

The efficacy of functional lipids with antioxidant properties in reducing cardiovascular risk has not been consistent. Randomized controlled trials (RCTs) reporting estimates for the effects of antioxidant functional lipid supplementations on cardiometabolic risk factors were searched up to 1 May 2024. Overall, antioxidant lipid supplementations, compared with placebo, had favorable effects on systolic blood pressure (lycopene: -1.95 [-3.54, -0.36] mmHg), low-density lipoprotein cholesterol (n6 fatty acid: -0.39 [-0.71, -0.06] mmol/L; astaxanthin: -0.11 [-0.21, -0.01] mmol/L), high-density lipoprotein cholesterol (n3 fatty acid: 0.20 [0.13, 0.27] mmol/L; n6 fatty acid: 0.08 [0.01, 0.14] mmol/L; astaxanthin: 0.13 [0.05, 0.21] mmol/L), total cholesterol (n6 fatty acid: -0.24 [-0.37, -0.11] mmol/L; astaxanthin: -0.22 [-0.32, -0.12] mmol/L; beta-carotene: -0.13 [-0.23, -0.04] mmol/L), triglyceride (n3 fatty acid: -0.37 [-0.47, -0.28] mmol/L; astaxanthin: -0.46 [-0.83, -0.10] mmol/L), and fasting blood insulin (astaxanthin: -2.66 [-3.98, -1.34] pmol/L). The benefits of antioxidant lipid supplementations appeared to be most evident in blood pressure and blood lipids in participants with different cardiometabolic health statuses. Notably, n9 fatty acid increased triglyceride and hemoglobin A1C in the total population, which increases CVD risk. Antioxidant lipid supplementations ameliorate cardiometabolic risk factors, while their effect may depend on type and cardiometabolic health status. Long-term RCTs are needed to corroborate risk-benefit ratios across different antioxidant functional lipid supplementation settings.

According to previous studies, astaxanthin exerts various biological effects due to its anti-inflammatory and antioxidant capabilities; however, its effects on liver enzymes have not yet been well elucidated. Therefore, we conducted a meta-analysis to assess astaxanthin's effects on liver enzymes. A systematic literature search was conducted using scientific databases including PubMed, Scopus, Web of Science, the Cochrane databases, and Google Scholar up to February 2023 to find relevant randomized controlled trials (RCTs) examining the effects of astaxanthin supplementation on alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP). A random-effects model was used for the estimation of the pooled weighted mean difference (WMD). Overall, we included five trials involving 196 subjects. The duration of the intervention was between 4 and 48 weeks, and the dose was between 6 and 12 mg/day. ALT levels increased in the intervention group compared to the control group following astaxanthin supplementation (WMD: 1.92 U/L, 95% CI: 0.16 to 3.68, P=0.03), whereas supplementation with astaxanthin had a non-significant effect on AST (WMD: 0.72 U/L, 95% CI: -0.85 to 2.29, P=0.36), GGT (WMD: 0.48 U/L, 95% CI: -2.71 to 3.67, P=0.76), and ALP levels (WMD: 2.85 U/L, 95% CI: -7.94 to 13.63, P=0.60) compared to the placebo group. Our data showed that astaxanthin supplementation increases ALT concentrations in adults without affecting the levels of other liver enzymes. Further long-term and well-designed RCTs are necessary to assess and confirm these findings.

Dietary astaxanthin supplementation has been demonstrated to have many beneficial and health-promoting effects. The purpose of this systematic review and meta-analysis was to assess the effect of astaxanthin supplementation on fatigue, cognition, and exercise efficiency. A total of 11 randomized controlled trials (RCTs) with 346 healthy participants were included. The random effects model and pooled standardized mean difference (SMDs) were used according to Hedge's g for the meta-analysis, and a meta-regression was also conducted. The results of the two existing studies showed a positive trend for astaxanthin in subjective fatigue relief. The effects of astaxanthin supplementation for 8-12 weeks on cognitive accuracy were marginally significant (SMD: .12; 95% CI: -.02-.26) and on reaction time was not significant (SMD: -.08; 95% CI: -.26 to .10). Remarkably, astaxanthin supplementation combined with regular training could enhance the fat oxidation (SMD: 2.56; 95% CI: 1.24-3.89), and significantly improve the physical performance (SMD: .62; 95% CI: .17-1.06). The subgroup analysis further showed significantly greater benefits when performing the aerobic exercises performance (SMD: .45; 95% CI: .13-.76), when the dose was ≥ 20 mg (SMD: .37; 95% CI: .11-.63), and when the supplementation duration was > 12 weeks (SMD: .66; 95% CI: .13-.63). We conclude that astaxanthin supplementation could significantly enhance aerobic exercise efficiency, especially at higher doses and for longer durations. Further studies based on large sample sizes are imperatively warranted.

The use of medication is effective in managing metabolic syndrome (MetS), but side effects have led to increased attention on using nutraceuticals and supplements. Astaxanthin shows positive effects in reducing the risk of MetS, but results from individual studies are inconclusive. This systematic review summarizes the latest evidence of astaxanthin in adults with risk factors of MetS. A systematic search of English and Chinese randomized controlled trials in 14 electronic databases from inception to 30 June 2021 was performed. Two reviewers independently screened the titles and abstracts, and conducted full-text review, quality appraisal, and extraction of data. Risk of bias was assessed by PEDro. A total of 7 studies met the inclusion criteria with 321 participants. Six studies were rated to have excellent methodological quality, while the remaining one was rated at good. Results show marginal effects of astaxanthin on reduction in total cholesterol and systolic blood pressure, and a significant attenuating effect on low-density lipoprotein cholesterol. Further robust evidence is needed to examine the effects of astaxanthin in adults at risk of MetS.

Background. Research indicates that omega-3 fatty acids, resveratrol, astaxanthin, and coenzyme Q10 (CoQ10) possess anti-inflammatory properties, and their vascular benefits have been well-documented. This is a pilot study aimed at comprehensively evaluating the potential impact of the compound fish oil capsules on the microcirculation of multiple organs. Methods. In a triple-blind, randomized, placebo-controlled trial, 64 hypertensive patients were randomly assigned to either the compound fish oil (FO) group or the corn oil (CO) group (n = 32 per group) for a 3-week intervention. Participants were required to consume 2 capsules of the corresponding oil daily. The microcirculation functions of the heart, skin, and brain were examined by transthoracic Doppler echocardiography (TTDE), laser Doppler flowmetry (LDF), and magnetic resonance imaging (MRI), respectively. Data were primarily analyzed according to an intention-to-treat approach. Findings. In the left anterior descending artery (LAD), the end-diastolic velocity (EDV) and peak diastolic velocity (PDV) significantly increased in the FO group. The mean differences in change were 1.95 (0.13, 3.77; p = 0.036) and 2.95 (0.48, 5.41; p = 0.020), respectively. The resistance index (RI) showed a decreasing trend in the FO group, but the result was non-significant (p = 0.071). No significant differences were observed in blood pressure, brain and skin microcirculation parameters among the different groups. Interpretation. Compound fish oil capsules did not significantly improve RH. But compound fish oil capsules improved EDV and PDV levels in the LAD of hypertensive patients.

Polycystic ovary syndrome (PCOS) is a major risk factor for ovarian hyperstimulation syndrome (OHSS) during controlled ovarian stimulation (COS). Oxidative stress and inflammation, mediated by the advanced glycation end products (AGE)-receptor for AGE (RAGE)-nuclear factor kappa-B (NFκB) pathway, contribute to OHSS development and impaired oocyte quality. Astaxanthin (AST), a potent antioxidant, may modulate this pathway. In this exploratory pilot trial using a triple‑blind, randomized, placebo‑controlled design, 44 PCOS patients at high risk for OHSS were assigned to receive AST (n = 22) or placebo (n = 22) adjunct to the COS regimen. COS was performed using a gonadotropin-releasing hormone (GnRH) antagonist protocol with individualized gonadotropin dosing. Stimulation characteristics, gonadotropin dose, and follicle distribution were comparable between groups. The mean number of retrieved oocytes was slightly higher with AST, and the oocyte maturity rate (OMR) was significantly greater. Estradiol and progesterone levels on trigger day were lower in the AST group, though not statistically significant. Molecular analyses showed reduced RAGE expression, a lower phosphorylated inhibitor of kappa-B (pIκB)/inhibitor of kappa-B (IκB) ratio in granulosa cells (GCs), and significantly decreased interleukin-6 (IL-6) in follicular fluid (FF), with vascular endothelial growth factor (VEGF) showing a downward trend. These findings suggest that AST supplementation may improve COS outcomes and favorably modulate inflammatory pathways, with potential to reduce OHSS risk in high-risk PCOS patients. However, this pilot trial was not powered enough to confirm the primary OHSS endpoint, and larger studies are required for validation.Trial registration: Registration ID: IRCT20231028059882N2; Registration date: 2024-06-15; Update date: 2025-03-16; Direct Access Link: https://irct.behdasht.gov.ir/trial/77250 . © 2026. The Author(s).

Type 2 diabetes mellitus (T2DM) is driven by oxidative stress (OS) and inflammation (IF), accelerating disease progression. This study examined whether combined aerobic and resistance training (CT) and astaxanthin (AST) supplementation synergistically improve oxidant and inflammatory status as well as metabolic indices in T2DM, focusing on the mediatory role of Humanin (HN) and microRNAs (miRNA-122, miRNA-126-3p, and miRNA-146a). Ninety women with T2DM were randomly assigned to six groups (n = 15 each): control (C), placebo (P), AST supplementation (S), combined training (CT), CT + placebo (CT + P), and CT + AST supplementation (CT + S). CT, CT + P and CT + S groups underwent an 8-week training program (eight exercises, three sessions per week). Groups and CT + S groups received 8 mg/day of AST. OS markers, inflammatory cytokines, HN levels, miRNAs expression, fasting blood glucose (FBG), insulin resistance (HOMA-IR), lipid profile, and hemoglobin A1c (HbA1c) were assessed. Both CT and AST enhanced antioxidant defenses and reduced IF, with CT + S showing the best effects. HN levels increased significantly in CT and CT + S (p < 0.05). MiRNA-126-3p and miRNA-146a were upregulated, while miRNA-122 was downregulated in CT + S compared to other groups. Lipid profile improved with both interventions, with CT + S yielding the highest increases in HDL and triglycerides. FBG, IR, and HbA1c improved significantly in CT groups but remained unchanged with S group. The metabolic and anti-inflammatory benefits of CT and AST in T2DM may mediated by the effects of HN on mitochondrial function and insulin signaling, together with miRNA-mediated regulation of lipid metabolism, endothelial health, and innate immunity. Targeting these molecular pathways may improve therapeutic strategies for diabetes management. © 2025. The Author(s).

BACKGROUND AND AIMS: Chronic heart failure (HF) is often linked to increased oxidative stress and metabolic issues like high uric acid, which can worsen outcomes. Astaxanthin (ASX), a strong antioxidant, may help reduce these harmful effects. This study aimed to investigate the effects of ASX supplementation on oxidative stress markers as the primary outcome and clinical symptoms in patients with HF. METHODS: In this randomized, double-blind, placebo-controlled clinical trial, 80 patients with HF were enrolled and randomly assigned to receive either ASX (20 mg/day) or a placebo (20 mg/day of maltodextrin) for 8 weeks. Biomarkers including total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD), serum UA, and clinical symptoms (dyspnea, fatigue, appetite) were assessed pre-and post-intervention. RESULTS: After eight weeks, compared to the placebo group, participants receiving ASX supplementation showed a significant increase in TAC (0.12 vs. -0.04 mmol/L, P = 0.002) and SOD levels (156.92 vs. 36.14 U/mL, P < 0.001). In contrast, the ASX group demonstrated significantly greater reductions in MDA (-2.19 vs. -0.68 nmol/L, P < 0.001) and serum UA levels (-1.82 vs. -0.63 mg/dl, P = 0.003) compared to placebo. Furthermore, among ASX treated patients, improvements in dyspnea and fatigue were statistically significant (P < 0.001), while the increase in appetite was only marginally significant (P = 0.071). CONCLUSION: These findings suggest that ASX supplementation may be effective in improving oxidative stress biomarkers and clinical status in patients with HF. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20200429047235N3. Registered on 26 March 2024, prior to the enrollment of the first participant. http://irct.behdasht.gov.ir/trial/75913 . © 2025. The Author(s).

OBJECTIVE: To investigate the effect of krill oil (KO) supplementation during alternate-day fasting (ADF) on body composition and muscle function in healthy adults with overweight. METHODS: In a randomized trial, during the 8-week ADF, participants consumed four capsules per day containing krill oil (KO group) or vegetable oil (placebo group). Each capsule of KO contained 191 mg EPA, 94 mg DHA, 78 mg choline, and 100 mcg astaxanthin. Body mass, fat-free mass (FFM), and handgrip strength (HGS) were measured before and after the intervention. Data were analyzed using ANOVA. RESULTS: The study was completed by 41 (25 women and 16 men) participants (age: 39 ± 10 years, BMI: 31.1 ± 4.2 kg/m2). Body weight reduction was not different (p > 0.05) between groups (KO, -4.6 ± 1.4 kg; Placebo, -4.5 ± 1.9 kg). The KO group had no change (p > 0.05) in FFM (-0.2 ± 0.9 kg) or HGS (-0.2 ± 0.5 kg). The placebo group experienced a reduction (p < 0.05) in FFM (-1.2 ± 2.0 kg) and HGS (-0.9 ± 0.7 kg). Changes in FFM and HGS were different (p < 0.05) between groups. CONCLUSIONS: KO supplementation during body weight loss attenuates the decline in FFM and muscle strength. TRIAL REGISTRATION: ClinicalTrials.gov Identifier (NCT06001632). © 2025 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.

Rheumatoid Arthritis (RA) is a chronic, systemic inflammatory disease that results in joint destruction and progressive disability. This study aimed to determine the effect of astaxanthin (ASX) on clinical outcomes, quality of life, and inflammatory factors in patients with RA. In this randomized, triple-blind, placebo-controlled clinical trial, 60 patients with RA were randomly allocated into two groups and given either 20 mg day-1 of ASX supplement in the intervention group (n = 30) or placebo in the control group (n = 30) for 8 weeks. Fasting blood samples were obtained from patients at the beginning and end of the intervention to measure the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6). Clinical symptoms were also measured, including the pain intensity based on the visual analogue scale (VAS), Disease Activity Score 28 (DAS-28), and Health Assessment Questionnaire (HAQ). In the intervention group compared to the control group after the intervention, DAS-28, HAQ, ESR, and CRP levels were significantly reduced (P < 0.05), and the pain intensity was marginally significantly reduced. The significant differences in DAS-28, HAQ, and ESR levels persisted even after adjusting for baseline values and other covariates. However, no significant differences in the pain intensity and CRP levels were found after controlling for confounding factors (P > 0.05). The IL-6 level did not change in either group by the end of the study, and the difference between the two groups also was not statistically significant (P > 0.05). This study demonstrated the beneficial effects of ASX on some important clinical outcomes, quality of life, and inflammatory factors in patients with RA. Including it as part of their treatment plan could significantly aid in managing their condition.

Obesity increases the risk for insulin resistance (IR) and type-2 diabetes. Lifestyle interventions (LI) and dietary supplementation can help mitigate IR. We investigated the effect of calanus oil (CO) supplementation, combined with LI, on glucose homeostasis in obese subjects. CO, a novel marine oil, contains omega-3 fatty acid wax esters as well as plant sterols and astaxanthin. In the double-blind, randomized, placebo-controlled 12-week intervention study, 266 subjects with distinct IR phenotypes were assigned to four groups: 2 g CO/day, 4 g CO/day, 2 g CO/day + LI, and placebo. The effect of CO on HOMA index reduction was influenced by the initial (t0) squared HOMA index (interaction p = 0.011). A post hoc test showed significant improvement with 2 g CO/day + LI (estimated marginal means [EMM] 95% confidence interval [CI]: -0.19 [-0.80-0.41], p = 0.021). Secondary analysis revealed that 4 g CO/day had significant effects in subjects with mild IR (HOMA index 2.5-5.0) (EMM [95% CI]: -0.76 [-1.53-0.03], p = 0.043). CO supplementation improved glucose homeostasis, with effects varying by dose, combination with LI, and IR phenotype.

INTRODUCTION: This study assessed the effects of astaxanthin supplementation on chronic and acute digital eye strain in school-aged children (10-14 years) and evaluated its safety. While previous studies focused on adults, this study examined astaxanthin's effects on developing eyes. METHODS: A randomized, double-blind, placebo-controlled trial was conducted over 84 days involving 64 children engaged in ≥ 4 h of screen time daily and experiencing mild to moderate computer vision syndrome (CVS) symptoms as indicated by a CVS-Questionnaire (CVS-Q) score ≥ 8 and < 19. Participants received a daily 4-mg astaxanthin soft capsule for 84 days. Primary outcomes were measured using CVS-Q, while secondary outcomes included visual fatigue Likert scale (VFLS), visual acuity, spherical equivalence, near point of accommodation, near exophoria, dry eye intensity, pupil size, stereopsis, blinking frequency, immunity, and safety variables. RESULTS: Of the 64 participants (mean age 11.5-11.7 years), 35 were male and 29 were female. Astaxanthin supplementation significantly improved CVS-Q scores after 84 days (- 4.00 ± 4.05 arbitrary units (A.U.) from baseline, p < 0.0001) compared to placebo (- 1.72 ± 3.61 A.U., p < 0.05), a 20% between group difference. The mean VFLS scores were significantly lower in the astaxanthin group (11.55 ± 5.78 A.U.) compared to placebo (15.78 ± 7.12 A.U., p = 0.01), showing a 27% improvement after 84 days. Stereopsis improved significantly after acute visual load at 28 and 84 days (p < 0.05, p < 0.0001 vs. placebo, respectively), and pupillary light reflex improved after 84 days (p < 0.05 vs. placebo). Tear production increased after 14, 56, and 84 days (p < 0.05, p < 0.001, and p < 0.001 vs. baseline, respectively) in the astaxanthin group, with no significant intergroup difference in the Schirmer I test, visual acuity, spherical equivalence, near point of accommodation, near exphoria, immune markers, or safety variables. CONCLUSION: Astaxanthin supplementation effectively reduced chronic and acute digital eye strain, while enhancing objective measures of visual performance in school-aged children, underscoring the benefits of astaxanthin in pediatric

RATIONALE: Firefighters are at risk for cardiovascular disease due to occupational-related inflammation, oxidative stress, and lifestyle practices. Astaxanthin (AX) possesses anti-inflammatory/antioxidant and purported ergogenic properties. This study examined the impact of supplementing the diet with 12 mg/d AX for four weeks on markers of inflammation, oxidative stress, cardiometabolic health, exercise capacity, and occupation-related performance in career firefighters. METHODS: In a randomized, double-blinded, placebo-controlled, crossover fashion, 15 male career firefighters (34.5 ± 7.4 years; 177.7 ± 7.0 cm; 95.6 ± 12.0 kg; 30.1 ± 2.9 kg/m2; 11.03 ± 6.85 years of service) ingested 12 mg/d of AX (AstaReal®, AstaReal AB, Nacka, SWE) or placebo (PLA) for four weeks while following a standardized resistance training program. After each treatment, testing sessions were completed to assess inflammatory markers, oxidative stress markers, cardiopulmonary exercise capacity, and performance to a fire ground test (FGT) consisting of nine fire suppressive activities. Data were analyzed using general linear model (GLM) analysis with repeated measures. Clinical significance was assessed via mean changes from baseline with 95% confidence intervals. RESULTS: Analysis of mean percent changes from baseline revealed that AX supplementation lessened the inflammatory response to to performing an incremental maximal exercise test and attenuated increases in interleukin-1β, cortisol, and uric acid in response to performing fire suppressive activities compared to when they ingested PLA. However, most of these effects were within groups rather than between groups. Additionally, there was evidence that AX ingestion increased the ventilatory anaerobic threshold. Four weeks of AX supplementation did not significantly affect fasting markers of oxidative stress, blood lipids, performance during the FGT, general clinical chemistry panels, or self-reported side effects. CONCLUSIONS: Results provide some evidence that AX supplementation may help mediate occupation-related inflammation in response to high-intensity, short-duration exercise in firefighters. More research is warranted to dete

BACKGROUND: Poor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR. METHODS: In this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone < 1.2 ng/ml or antral follicle count < 5) undergoing intracytoplasmic sperm injection were enrolled. Patients were assigned to receive either 12 mg/day AST or placebo for eight weeks. All patients underwent a gonadotropin-releasing hormone antagonist regimen for COS. ART outcomes were compared between groups. Blood serum and follicular fluid (FF) were analyzed for OS markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], and malondialdehyde [MDA]), and pro-inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) via enzyme-linked immunosorbent assay kits, and cell-free DNA [cfDNA] (apoptotic marker) via ALU quantitative polymerase chain reaction. RESULTS: After the intervention, the AST group exhibited a significant elevation in serum (P = 0.013) and TAC (P = 0.030), accompanied by a significant reduction in serum MDA (P = 0.005). No significant differences between AST and placebo groups were observed in OS markers in FF. AST group showed significant reductions in the serum IL-6 (P < 0.001), IL-8 (P = 0.001), and VEGF (P = 0.002) levels following AST therapy. In the AST group, FF levels of IL-6 (P = 0 < 001), IL-8 (P = 0.036), VEGF (P = 0.006), and cfDNA (P < 0.001) were significantly lower than in the placebo group. Between-group comparisons showed significant differences in the alterations of serum SOD (P = 0.027), IL-6 (P < 0.001), and IL-8 (P =

BACKGROUND: Central nervous system oxygen toxicity (CNS-OT) is a critical concern for Navy divers using closed-circuit rebreathers who are subjected to prolonged exposure to hyperbaric oxygen levels. We explored the potential of specific dietary supplements, caffeine, and astaxanthin, to delay the onset of CNS-OT. METHODS: Experiments were conducted using male C57BL/6 mice exposed to pure oxygen at 507 kPa, with latency to tonic-clonic seizures recorded. Mice were orally administered caffeine (1.25, 2.5, or 5 mg/ kg), astaxanthin (8 mg/kg), or a vehicle (water). RESULTS: Caffeine and astaxanthin significantly extended the latency period to seizure onset (p<0.03). Notably, combining caffeine and astaxanthin (p<0.001 vs. control) provided better protection against CNS-OT than either substance alone. CONCLUSION: Our results suggest that administering caffeine and astaxanthin before hyperbaric oxygen exposure delays hyperoxia-induced seizures.

Bone cancer pain (BCP) is a complex condition that severely affects patients' quality of life, and its treatment remains challenging. Astaxanthin, a potent antioxidant with anti-inflammatory and neuroprotective effects, and celecoxib, a selective COX-2 inhibitor, have shown synergistic effects in various disease models, but their potential in BCP is unclear. In this study, a mouse BCP model was used to evaluate the analgesic effects of astaxanthin alone and combined with celecoxib on pain-related behaviors, including mechanical allodynia, thermal hyperalgesia, and spontaneous leg-lifting. The combination showed significant synergistic analgesic effects. Transcriptomic data from the Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed genes (DEGs), and nine core genes were screened by integrating DEGs with BCP-related targets. Machine learning methods (LASSO, random forest, SVM) and cross-validation identified CASP1 and TLR7 as key genes. Immune infiltration analysis, gene immune cell correlation, and molecular docking further supported the therapeutic potential of the drug combination and the importance of CASP1 and TLR7. This study provides new molecular targets and candidate drugs for BCP treatment, laying a foundation for future research.

This in vivo study performed in rat adjuvant arthritis aims to advance the understanding of astaxanthin's therapeutic properties for the possible treatment of rheumatoid arthritis (RA) in monotherapy and along with the standard RA treatment, methotrexate (MTX), in combination therapy. The main goal was to elucidate astaxanthin's full therapeutic potential, evaluate its dose dependency, and compare its effects in monotherapy with other carotenoids such as β-carotene and β-cryptoxanthin (KXAN). Moreover, potential differences in therapeutic activity caused by using different sources of astaxanthin, synthetic (ASYN) versus isolated from Blakeslea trispora (ASTAP), were evaluated using one-way ANOVA (Tukey-Kramer post hoc test). KXAN was the most effective in reducing plasma MMP-9 levels in monotherapy, significantly better than MTX, and in reducing hind paw swelling. The differences in the action of ASTAP and ASYN have been observed across various biometric, anti-inflammatory, and antioxidative parameters. In combined therapy with MTX, the ASYN + MTX combination proved to be better. These findings, especially the significant anti-arthritic effect of KXAN and ASYN + MTX, could be the basis for further preclinical studies.

BACKGROUND: Hormonal receptor positive (HR+) breast cancer is the most commonly diagnosed molecular subtype of breast cancer; which showed good response to doxorubicin (DOX)-based chemotherapy. Eugenol (EUG) and astaxanthin (AST) are natural compounds with proved epigenetic and immunomodulatory effects in several cancer cell lines. This study has been initiated to investigate the molecular mechanism (s) whereby EUG and AST could enhance DOX cytotoxicity in MCF7 cells. METHODS: Cytotoxic activity of DOX alone and combined with either 1 mM EUG or 40 μM AST was performed using sulphorhodamine-B assay in MCF7 cells. Global histones acetylation and some immunological markers were investigated using ELISA, western blotting and quantitative RT-PCR techniques. Functional assay of multidrug resistance was performed using rhodamine 123 and Hoechst 3342 dyes. Flow cytometry with annexin V and propidium iodide were used to assess the change in cell cycle and apoptosis along with the expression of some differentiation, apoptosis and autophagy proteins. RESULTS: DOX alone resulted in concentration-dependent cytotoxicity with IC50 of 0.5 μM. Both EUG and AST significantly increased DOX cytotoxicity which is manifested as a significant decrease in DOX IC50 from 0.5 μM to 0.088 μM with EUG and to 0.06 μM with AST. Combinations of DOX with 1 mM EUG or 40 μM AST significantly increased the level of histones acetylation and histone acetyl transferase expression, while reduced the expression of aromatase and epidermal growth factor receptor (EGFR) when compared with 0.25 μM DOX alone. Also both combinations showed higher uptake of rhodamine but lower of Hoechst stains, along with increased the percentage of caspase 3, and decreased the expression of CK7 and LC3BI/II ratio. EUG combination induced IFγ but reduced TNFα causing shifting of cells from G2/M to S and G0/ G1 phases. Combination of DOX with EUG induced apoptosis through the higher BAX/ BCl2 ratio, while with AST was through the increase in caspase 8 expressions. CONCLUSION: EUG and AST potentiated the anticancer activity of DOX through epigenetic histones acetylation along with the immunonomodulation of different apoptotic

Astaxanthin (Asx) is known to be a potent quencher of singlet oxygen and an efficient scavenger of superoxide anion. However, the scavenging activity of Asx toward the hydroxyl radical was currently unclear because the high lipophilicity of Asx prevents analysis of such activity in water. Liposomes containing Asx (Asx-lipo) were previously shown to be dispersed in water. Analysis of the hydroxyl radical scavenging activity of Asx-lipo demonstrated a dose-dependence in water, with the effect of Asx being more potent than the vitamin E α-tocopherol (α-T). Furthermore, liposomes co-encapsulating Asx and vitamin E derivatives, namely tocotrienols (T3), showed a synergistic elimination effect on singlet oxygen and hydroxyl radical, although the antioxidative activity of liposomes co-encapsulating Asx and α-T was lower than the calculated additive value of each independent activity. A calculation of the most stable structure of Asx in the presence of α-T or T3, suggested that only T3 was able to hydrogen bond with Asx, and the Asx polyene chain partially interacting with the α-T3 triene chain, which could explain the synergistic effect between Asx and T3, but not Asx and α-T. This review introduces the hydroxyl radical scavenging activity of Asx, and its synergistic effect with T3.

The metabolism of aflatoxin B1 (AFB1) generates reactive oxygen species (ROS) that destroys hepatocytes. Meanwhile, astaxanthin (AX) is known to have stronger antioxidative activity than other carotenoids. This study aimed to investigate hepatoprotective role of AX from AFB1-induced toxicity in rat by histopathological study and immunohistochemistry of Cu/Zn-SOD (SOD1) which acts as the first enzyme in antioxidative reaction against cell injury from ROS. Twenty Wistar rats were randomly divided into 4 groups. The control and AFB1 groups were gavaged by water for 7 days followed by a single DMSO and 1 mg/kg AFB1, respectively. The AXL+ AFB1 and AXH+ AFB1 groups were given of 5 mg/kg and 100 mg/kg AX for 7 days before 1 mg/kg AFB1 administration. The result showed significantly elevated liver weight per 100 g body weight in AFB1 group. The histopathological finding revealed vacuolar degeneration, necrosis, megalocytosis and binucleation of hepatocytes with bile duct hyperplasia in AFB1 group. The severities of pathological changes were sequentially reduced in AXL+AFB1 and AXH+AFB1 groups. Most rats in AXH+AFB1 group owned hypertrophic hepatocytes and atypical proliferation of cholangiocytes which are adaptive responses to severe hepatocyte damage. The SOD1 expression was also significantly higher in AXH+AFB1 group than solely treated AFB1 and AXL+AFB1 groups. In conclusion, AX alleviated AFB1-induced liver damage in rat by stimulating SOD1 expression and transdifferentiation of cholangiocytes in dose dependent manner.

The combination of carotenoids and doxorubicin (DOX) selectively alters oxidative stress-mediated apoptosis in breast cancer cells. Primarily, cytotoxic efficiency of carotenoids (β-carotene, BC; lutein, LUT; astaxanthin, AST; or fucoxanthin, FUCO) either with or without a minimal cytotoxic dose of DOX was evaluated in MCF-7 (0.12 μM) and MDA-MB-231 cells (0.28 μM). The higher cell growth inhibition of BC and/or LUT with DOX was selected for testing in further cell-based assays. Low-dose DOX significantly enhanced cytotoxicity in carotenoid (<5 μM)-treated cells compared to high-dose DOX (>1 μM) or carotenoid (20 μM) treatment alone. Depleted glutathione, increased lipid peroxides and increased ROS levels in cells confirmed the cytotoxic effect. Furthermore, mitochondrial dysfunction, cell growth arrest at G0/G1 phase and caspase cascades as well as up- and down-regulated expression levels of related proteins (p21, p27, Bax, p53, Bcl-2, and cyclin D1) revealed the synergistic effect of carotenoid and DOX treatment on ROS-mediated apoptosis. These observations demonstrated increased apoptosis in BC + DOX/LUT + DOX-treated cells due to the pronounced pro-oxidant action. Interestingly, normal breast epithelial cells (MCF 10A) exposed to similar treatments resulted in non-significant cytotoxicity. These newly observed mechanistic differences of anticancer drugs on the mitigation of toxicity with carotenoids may provide insight into the targeting of cancer therapy.

Increasing evidence suggests that dietary carotenoids may reduce the risk of breast cancer. However, anti-breast cancer effects of carotenoids have been controversial, albeit understudied. Here, we investigated the effects of specific carotenoids on a wide range of breast cancer cell lines, and found that among several carotenoids (including β-carotene, lutein, and astaxanthin), lutein significantly inhibits breast cancer cell growth by inducing cell-cycle arrest and caspase-independent cell death, but it has little effect on the growth of primary mammary epithelial cells (PmECs). Moreover, lutein-mediated growth inhibition of breast cancer cells is quantitatively similar to that induced by chemotherapeutic taxanes, paclitaxel and docetaxel, and exposure to lutein plus taxanes additively inhibits breast cancer cell growth. Analysis of mechanisms showed that lutein treatment significantly increases the intracellular reactive oxygen species (ROS) production in triple-negative breast cancer (TNBC) cells, but not in normal PmECs. Lutein-induced growth inhibition is also attenuated by the radical oxygen scavenger N-acetyl cysteine, suggesting a role for ROS generation in the growth inhibitory effect of lutein on TNBC cells. Additionally, we found that the p53 signaling pathway is activated and HSP60 levels are increased by lutein treatment, which may contribute partly to the induction of growth inhibition in TNBC cells. Our findings show that lutein promotes growth inhibition of breast cancer cells through increased cell type-specific ROS generation and alternation of several signaling pathways. Dietary lutein supplementation may be a promising alternative and/or adjunct therapeutic candidate against breast cancer.

This study investigated the synergistic efficacy of keto-carotenoid astaxanthin (AST, from shrimp) plus hydrocarbon (β-carotene, BC) and hydroxyl (lutein, L) carotenoids (from greens) on molecular events in MCF-7 cells. MCF-7 cells were treated with either of carotenoid (20 μM, AST or BC or L) separately or the mixture of them (an equimolar concentration of carotenoids mixture, CM) or saponified carotenoid extract from shrimp (SSCE) for 48 h and analyzed cellular uptake, cytotoxicity, and apoptosis. The IC50 and combination-index values of AST co-treatment with a lower concentration of BC and L (5 μM) exhibited enhanced cytotoxicity and oxidative stress as compared with individual carotenoids or SSCE. Further, higher cellular uptake/accumulation of AST along with BC and L found to synergistically induce apoptosis through modulation of cyclin D1, p53, Bax and Bcl-2 expressions by arresting cell cycle at G0/G1 phase. Further, CM or SSCE treatments are unlikely to affect proliferation of normal breast epithelial cells (MCF-10A). The results of selective killing of MCF-7 cells demonstrated a greater insight on the synergistic effect of shrimp AST plus BC and L. It is concluded that consumption of shrimp along with green leafy vegetables helps in combating cancer chemoprevention.

Despite the widespread use of the five major xanthophylls astaxanthin, β-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin as dietary supplements, there have been no studies regarding their inhibitory effects on hepatic UDP-glucuronosyltransferases (UGTs). Here, we evaluated the inhibitory potential of these xanthophylls on the seven major human hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7 and UGT2B15) in vitro by LC-MS/MS using specific marker reactions in human liver microsomes (except UGT2B15) or recombinant supersomes (UGT2B15). We also predicted potential dietary supplement-drug interactions for β-cryptoxanthin via UGT1A1 inhibition. We demonstrated that astaxanthin and zeaxanthin showed no apparent inhibition, while the remaining xanthophylls showed only weak inhibitory effects on the seven UGTs. β-Cryptoxanthin mildly inhibited UGT1A1, UGT1A3, and UGT1A4, with IC50 values of 18.8 ± 2.07, 28.3 ± 4.40 and 34.9 ± 5.98 μM, respectively. Canthaxanthin weakly inhibited UGT1A1 and UGT1A3, with IC50 values of 38.5 ± 4.65 and 41.2 ± 3.14 μM, respectively; and lutein inhibited UGT1A1 and UGT1A4, with IC50 values of 45.5 ± 4.01 and 28.7 ± 3.79 μM, respectively. Among the tested xanthophyll-UGT pairs, β-cryptoxanthin showed the strongest competitive inhibition of UGT1A1 (Ki, 12.2 ± 0.985 μM). In addition, we predicted the risk of UGT1A1 inhibition in vivo using the reported maximum plasma concentration after oral administration of β-cryptoxanthin in humans. Our data suggests that these xanthophylls are unlikely to cause dietary supplement-drug interactions mediated by inhibition of the hepatic UGTs. These findings provide useful information for the safe clinical use of the tested xanthophylls.