Effect of astaxanthin supplementation on female fertility and reproductive outcomes: a systematic review and meta-analysis of clinical and animal studies.

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. However, the evidence is limited by the heterogeneity, risk of bias, and small sample size of the included studies.

Anti-Inflammatory and Antioxidant Properties of a New Mixture of Vitamin C, Collagen Peptides, Resveratrol, and Astaxanthin in Tenocytes: Molecular Basis for Future Applications in Tendinopathies.

Tendinopathy is one of the most frequent musculoskeletal disorders characterized by sustained tissue inflammation and oxidative stress, accompanied by extracellular matrix remodeling. Patients suffering from this pathology frequently experience pain, swelling, stiffness, and muscle weakness. Current pharmacological interventions are based on nonsteroidal anti-inflammatory drugs; however, the effectiveness of these strategies remains ambiguous. Accumulating evidence supports that oral supplementation of natural compounds can provide preventive, and possibly curative, effects. Vitamin C (Vit C), collagen peptides (Coll), resveratrol (Res), and astaxanthin (Asx) were reported to be endowed with potential beneficial effects based on their anti-inflammatory and antioxidant activities. Here, we analyzed the efficacy of a novel combination of these compounds (Mix) in counteracting proinflammatory (IL-1ß) and prooxidant (H2O2) stimuli in human tenocytes. We demonstrated that Mix significantly impairs IL-6-induced IL-1ß secretion, NF-κB nuclear translocation, and MMP-2 production; notably, a synergistic effect of Mix over the single compounds could be observed. Moreover, Mix was able to significantly counteract H2O2-triggered ROS production. Together, these results point out that Mix, a novel combination of Vit C, Coll, Resv, and Asx, significantly impairs proinflammatory and prooxidant stimuli in tenocytes, mechanisms that contribute to the onset of tendinopathies.

The effect of astaxanthin supplementation on inflammatory markers, oxidative stress indices, lipid profile, uric acid level, blood pressure, endothelial function, quality of life, and disease symptoms in heart failure subjects.

BACKGROUND: Heart failure is a chronic and progressive disease where the heart muscle is unable to pump enough blood and oxygen to meet the body's needs. Oxidative stress and inflammation are key elements in the development and progression of heart failure. Astaxanthin, a carotenoid, has strong anti-inflammatory and antioxidant effects that may protect the cardiovascular system. A study will evaluate the effect of astaxanthin supplementation on inflammatory status, oxidative stress, lipid profile, uric acid levels, endothelial function, quality of life, and disease symptoms in people with heart failure. METHODS: The current study is a double-blind controlled randomized clinical trial for 8 weeks, in which people with heart failure were randomly assigned to two groups: intervention (one capsule containing 20 mg of astaxanthin per day, n = 40) and placebo (one capsule containing 20 mg of maltodextrin per day, n = 40) will be divided. At the beginning and end of the intervention, uric acid, lipid profile, oxidative stress indices, inflammatory markers, blood pressure, nitric oxide, and anthropometric factors will be measured, and questionnaires measuring quality of life, fatigue intensity, shortness of breath, and appetite will be completed. SPSS version 22 software will be used for statistical analysis. DISCUSSION: There is a growing global interest in natural and functional food products. This RCT contributes to the expanding body of research on the potential benefits of astaxanthin in heart failure patients, including its antioxidant, lipid-lowering, and anti-inflammatory effects. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20200429047235N3. Registered on 26 March 2024.

Hepatoprotective effect of astaxanthin against cholestasis liver fibrosis induced by bile duct ligation in adult Wistar rats.

In this study, we evaluated the hepatoprotective effects of astaxanthin, a natural carotenoid, against the cholestatic liver fibrosis induced by bile duct ligation (BDL). Toward this end, male rats were subjected to BDL and treated with astaxanthin for 35 days. Afterwards, their serum and liver biochemical factors were assessed. Also, histopathological and immunohistochemical analyses were performed to determine the fibrosis and the expression levels of alpha-smooth muscle actin (α-SMA) and transforming growth factor beta (TGF-ß1) in the liver tissue. Based on the results, BDL caused a significant increase in liver enzyme levels, blood lipids, and bilirubin, while decreasing the activity of superoxide dismutase(SOD), catalase (CAT), and glutathione (GSH) enzymes. Also, in the BDL rats, hepatocyte necrosis, infiltration of inflammatory lymphocytes, and hyperplasia of bile ducts were detected, along with a significant increase in α-SMA and TGF-ß1 expression. Astaxanthin, however, significantly prevented the BDL's detrimental effects. In all, 10 mg/kg of this drug maintained the bilirubin and cholesterol serum levels of BDL rats at normal levels. It also reduced the liver enzymes' activity and serum lipids, while increasing the SOD, CAT, and GSH activity in BDL rats. The expression of α-SMA and TGF-ß1 in the BDL rats treated with 10 mg/kg of astaxanthin was moderate (in 34%-66% of cells) and no considerable cholestatic fibrosis was observed in this group. However, administrating the 20 mg/kg of astaxanthin was not effective in this regard. These findings showed that astaxanthin could considerably protect the liver from cholestatic damage by improving the biochemical features and regulating the expression of related proteins.

Astaxanthin attenuates diabetic kidney injury through upregulation of autophagy in podocytes and pathological crosstalk with mesangial cells.

Objectives: Astaxanthin (ATX) is a strong antioxidant drug. This study aimed to investigate the effects of ATX on podocytes in diabetic nephropathy and the underlying renal protective mechanism of ATX, which leads to pathological crosstalk with mesangial cells.Methods: In this study, diabetic rats treated with ATX exhibited reduced 24-h urinary protein excretion and decreased blood glucose and lipid levels compared to vehicle-treated rats. Glomerular mesangial matrix expansion and renal tubular epithelial cell injury were also attenuated in ATX-treated diabetic rats compared to control rats.Results: ATX treatment markedly reduced the α-SMA and collagen IV levels in the kidneys of diabetic rats. Additionally, ATX downregulated autophagy levels. In vitro, compared with normal glucose, high glucose inhibited LC3-II expression and increased p62 expression, whereas ATX treatment reversed these changes. ATX treatment also inhibited α-SMA and collagen IV expression in cultured podocytes. Secreted factors (vascular endothelial growth factor B and transforming growth factor-ß) generated by high glucose-induced podocytes downregulated autophagy in human mesangial cells (HMCs); however, this downregulation was upregulated when podocytes were treated with ATX.Conclusions: The current study revealed that ATX attenuates diabetes-induced kidney injury likely through the upregulation of autophagic activity in podocytes and its antifibrotic effects. Crosstalk between podocytes and HMCs can cause renal injury in diabetes, but ATX treatment reversed this phenomenon.

Astaxanthin Rescues Memory Impairments in Rats with Vascular Dementia by Protecting Against Neuronal Death in the Hippocampus.

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.

Randomized clinical trial of astaxanthin supplement on serum inflammatory markers and ER stress-apoptosis gene expression in PBMCs of women with PCOS.

Polycystic ovarian syndrome (PCOS) is related to pro-apoptotic and pro-inflammatory conditions generated by Endoplasmic reticulum (ER) stress. This study aimed to determine the effect of Astaxanthin (ASX), as carotenoid with potent antioxidant and anti-inflammatory properties, on serum inflammatory markers, apoptotic factors and ER stress-apoptotic genes in peripheral blood mononuclear cells (PBMCs) of women with PCOS. This randomized, double-blind clinical trial included 56 PCOS patients aged 18-40. For 8 weeks, subjects were randomly assigned to one of two groups: either 12 mg ASX (n = 28) or placebo (n = 28). Real-time PCR was used to quantify gene expression associated with ER stress-apoptosis in PCOS women's PBMCs. The levels of TNF-α, IL18, IL6 and CRP were determined by obtaining blood samples from all patients before and after the intervention using Enzyme-linked immunosorbent assay (ELISA). Also, the levels of active caspase-3 and caspase-8 were detected in the PBMC by ELISA kit. Furthermore, we evaluated the efficacy of ASX on disease symptoms. Following the 8-week intervention, ASX supplementation was able to reduce the expression of GRP78 (p = 0.051), CHOP (p = 0.008), XBP1 (p = 0.002), ATF4 (0.038), ATF6 (0.157) and DR5 (0.016) when compared to the placebo. However, this decrease was not statistically significant for ATF6 (p = 0.067) and marginally significant for GRP78 (p = 0.051). The levels of TNF-α (p = 0.009), IL-18 (p = 0.003), IL-6 (p = 0.013) and active caspase-3 (p = 0.012) were also statistically significant lower in the therapy group. However, there was no significant difference in CRP (p = 0.177) and caspase-8 (p = 0.491) levels between the treatment and control groups. In our study, ASX had no significant positive effect on BMI, hirsutism, hair loss and regularity of the menstrual cycle. It appears that ASX may benefit PCOS by changing the ER stress-apoptotic pathway and reducing serum inflammatory markers; however, additional research is required to determine this compound's potential relevance.

Astaxanthin Expedites the Healing of Acute Skin Wounds in Rats by Facilitating M2 Macrophage Polarization and Enhancing Collagen Secretion.

BACKGROUND: Facilitating the healing process of skin post-trauma is crucial for minimizing infection risks and reinstating normal tissue functionality. While past studies have established astaxanthin (ASX) as an effective compound in promoting wound healing, the precise mechanism of its action remains unclear. Consequently, the objective of this study was to explore the impact of ASX on the acute wound healing of rat skin by modulating macrophage polarization. METHODS: Eighteen male SD rats were randomly assigned to control, dimethylsulfoxide (DMSO), and ASX groups. Acute skin wounds were induced in the rats, and the effects of different treatments on wound area and healing were assessed. Hematoxylin-eosin (H&E) staining was employed to detect histopathological changes in the skin, while Masson staining was utilized to observe collagen expression. Immunohistochemistry was conducted to identify clusters of differentiation (CD) 206 macrophages in the tissues. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, IL-10, IL-4, and IL-13. The expression of inducible nitric oxide synthase (iNOS), arginase (Arg)-1, and mannose receptor C-type 1 (Mrc1) proteins in the injured skin of rats was assessed through Western blot analysis. RESULTS: On postoperative days 7 and 14, the ASX treatment demonstrated notable reductions in inflammatory cell infiltration and inflammatory cytokine expression when compared to the Control and DMSO groups. This was accompanied by evident improvements in the pathological changes in skin tissue, characterized by the regeneration of new epidermis, dermal repair, and increased thickness of granulation, contributing to enhanced scar formation. Furthermore, ASX therapy exhibited an upregulation in the expression levels of collagen I and collagen III, along with markers indicative of M2 macrophages. These findings collectively signify the accelerated progression of wound healing attributed to ASX intervention. CONCLUSIONS: In summary, these findings collectively indicate that ASX facilitates the healing of rat skin wounds by suppressing inflammatory responses and fostering M2 macrophage polarization. Consequently, ASX holds promise as a potentially effective drug for the treatment of skin wounds.

A marine-derived antioxidant astaxanthin as a potential neuroprotective and neurotherapeutic agent: A review of its efficacy on neurodegenerative conditions.

Astaxanthin is a potent lipid-soluble carotenoid produced by several different freshwater and marine microorganisms, including microalgae, bacteria, fungi, and yeast. The proven therapeutic effects of astaxanthin against different diseases have made this carotenoid popular in the nutraceutical market and among consumers. Recently, astaxanthin is also receiving attention for its effects in the co-adjuvant treatment or prevention of neurological pathologies. In this systematic review, studies evaluating the efficacy of astaxanthin against different neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebrovascular diseases, and spinal cord injury are analyzed. Based on the current literature, astaxanthin shows potential biological activity in both in vitro and in vivo models. In addition, its preventive and therapeutic activities against the above-mentioned diseases have been emphasized in studies with different experimental designs. In contrast, none of the 59 studies reviewed reported any safety concerns or adverse health effects as a result of astaxanthin supplementation. The preventive or therapeutic role of astaxanthin may vary depending on the dosage and route of administration. Although there is a consensus in the literature regarding its effectiveness against the specified diseases, it is important to determine the safe intake levels of synthetic and natural forms and to determine the most effective forms for oral intake.

The protective effect of Astaxanthin on scopolamine - induced Alzheimer's model in mice.

OBJECTIVES: To investigate the fundamental mechanisms of the neuroprotective impact of Astaxanthin (AST) in a mouse model of Alzheimer's disease (AD) induced by scopolamine. METHODS: This research constituted an in vivo animal study encompassing 36 adult male mice, divided into 6 groups: Control, 100 mg/kg AST, 2 mg/kg scopolamine (AD group), 100 mg/kg AST+2 mg/kg scopolamine, 3 mg/kg galantamine+2 mg/kg scopolamine, and 100 mg/kg AST+3 mg/kg galantamine+2 mg/kg scopolamine. After 14 days, the mice's short-term memory, hippocampus tissue, oxidative and inflammatory markers were evaluated. RESULTS: The AST demonstrated a beneficial influence on short-term memory and a reduction in acetylcholinesterase activity in the brain. It exhibited neuroprotective and anti-amyloidogenic properties, significantly decreased pro-inflammatory markers and oxidative stress, and reversed the decline of the Akt-1 and phosphorylated Akt pathway, a crucial regulator of abnormal tau. Furthermore, AST enhanced the effect of galantamine in reducing inflammation and oxidative stress. CONCLUSION: The findings indicate that AST may offer therapeutic benefits against cognitive dysfunction in AD. This is attributed to its ability to reduce oxidative stress, control neuroinflammation, and enhance Akt-1 and pAkt levels, thereby underscoring its potential in AD treatment strategies.

The Effects of Astaxanthin on Cognitive Function and Neurodegeneration in Humans: A Critical Review.

Oxidative stress is a key contributing factor in neurodegeneration, cognitive ageing, cognitive decline, and diminished cognitive longevity. Issues stemming from oxidative stress both in relation to cognition and other areas, such as inflammation, skin health, eye health, and general recovery, have been shown to benefit greatly from antioxidant use. Astaxanthin is a potent antioxidant, which has been outlined to be beneficial for cognitive function both in vitro and in vivo. Given the aforementioned promising effects, research into astaxanthin with a focus on cognitive function has recently been extended to human tissue and human populations. The present critical review explores the effects of astaxanthin on cognitive function and neurodegeneration within human populations and samples with the aim of deciphering the merit and credibility of the research findings and subsequently their potential as a basis for therapeutic use. Implications, limitations, and areas for future research development are also discussed. Key findings include the positive impacts of astaxanthin in relation to improving cognitive function, facilitating neuroprotection, and slowing neurodegeneration within given contexts.

Protective effect of astaxanthin on ANCA-associated vasculitis.

OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by inflammation and fibrinoid necrosis of medium and small vessels, and its pathogenesis is closely related to inflammation and oxidative stress. Astaxanthin (ATX) is a carotenoid with anti-inflammatory, antioxidant, and immunomodulatory effects. We hypothesized that ATX could play a role in AAV treatment. This study aimed to investigate whether ATX has a protective effect against AAV and to elucidate its regulatory mechanism. METHODS: In vitro experiments, neutrophils isolated from healthy people were treated with ATX or not and cultured with serum from myeloperoxidase (MPO) -ANCA-positive patients and healthy persons. The levels of IL-6 and TNF-α in neutrophil culture supernatant before and after stimulation were measured. Neutrophil extracellular traps (NETs) and intracellular reactive oxygen species (ROS) in neutrophils were detected after stimulation. In vivo study, experimental autoimmune vasculitis (EAV) rat models were established and then treated with ATX via intragastric administration for 6 consecutive weeks. Urinary erythrocytes, urinary proteins, and serum creatinine were detected and HE staining was performed to assess renal injury in rats. Lung hemorrhage was observed by gross dissection and microscopic Prussian blue staining. The level of serum MPO-ANCA was detected. Serum IL-6, TNF-α, superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) in rats were measured to explore the effects of ATX on oxidative stress and inflammation in EAV rats. The deposition of MPO in kidney and lung of rats was detected by immunohistochemistry. RESULTS: ATX significantly inhibited neutrophil secretion of inflammatory factors IL-6 and TNF-α. ATX reduced the elevated levels of ROS in neutrophils stimulated by serum from AAV patients and alleviated the release of NETs. ATX administration was observed to reduce the degree of hematuria, proteinuria, and glomerular crescent formation in EAV rats. The degree of pulmonary hemorrhage was significantly reduced. Besides, the serum levels of IL-6 and TNF-α were attenuated, and antioxidant SOD and GSH-px increased in serum. Pathological results showed that MPO deposition was decreased in lung and kidney tissues after ATX treatment. CONCLUSION: ATX could ameliorate the organ damages in EAV rats. It could serve as a hopeful therapy for AAV by its anti-inflammatory and anti-oxidative feature as a unique nature carotenoid.

Astaxanthin reduces inflammation and promotes a chondrogenic phenotype by upregulating SIRT1 in osteoarthritis.

OBJECTIVE: To investigate the effects of astaxanthin (AST) on mouse osteoarthritis (OA) and lipopolysaccharide (LPS)-induced ATDC5 cell damage and to explore whether SIRT1 protein plays a role. METHODS: In this study, some mouse OA models were constructed by anterior cruciate ligament transection (ACLT). Imaging, molecular biology and histopathology methods were used to study the effect of AST administration on traumatic OA in mice. In addition, LPS was used to stimulate ATDC5 cells to mimic the inflammatory response of OA. The effects of AST on the cell activity, inflammatory cytokines, matrix metalloproteinases and collagen type II levels were studied by CCK8 activity assay, reverse transcription polymerase chain reaction and protein imprinting. The role of SIRT1 protein was also detected. RESULTS: In the mouse OA model, the articular surface collapsed, the articular cartilage thickness and cartilage matrix protein abundance were significantly decreased, while the expression of inflammatory cytokines and matrix metalloproteinases was increased; but AST treatment reversed these effects. Meanwhile, AST pretreatment could partially reverse LPS-induced ATDC5 cell damage and upregulate SIRT1 expression, but this protective effect of AST was attenuated by concurrent administration of the SIRT1 inhibitor Ex527. CONCLUSION: AST can protect against the early stages of OA by affecting SIRT1 signalling, suggesting that AST might be a potential therapeutic agent for OA treatment.

Astaxanthin Inhibits STING Carbonylation and Enhances Antiviral Responses.

STING-mediated DNA sensing pathway plays a crucial role in the innate antiviral immune responses. Clarifying its regulatory mechanism and searching STING agonists has potential clinical implications. Although multiple STING agonists have been developed to target cancer, there are few for the treatment of infectious diseases. Astaxanthin, a natural and powerful antioxidant, serves many biological functions and as a potential candidate drug for many diseases. However, how astaxanthin combats viruses and whether astaxanthin regulates the cyclic GMP-AMP synthase-STING pathway remains unclear. In this study, we showed that astaxanthin markedly inhibited HSV-1-induced lipid peroxidation and inflammatory responses and enhanced the induction of type I IFN in C57BL/6J mice and mouse primary peritoneal macrophages. Mechanistically, astaxanthin inhibited HSV-1 infection and oxidative stress-induced STING carbonylation and consequently promoted STING translocation to the Golgi apparatus and oligomerization, which activated STING-dependent host defenses. Thus, our study reveals that astaxanthin displays a strong antiviral activity by targeting STING, suggesting that astaxanthin might be a promising STING agonist and a therapeutic target for viral infectious diseases.