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Astaxanthin in Cardiovascular Health and Disease
Abstract and Figures
Oxidative stress and inflammation are established processes contributing to cardiovascular disease caused by atherosclerosis. However, antioxidant therapies tested in cardiovascular disease such as vitamin E, C and β-carotene have proved unsuccessful at reducing cardiovascular events and mortality. Although these outcomes may reflect limitations in trial design, new, more potent antioxidant therapies are being pursued. Astaxanthin, a carotenoid found in microalgae, fungi, complex plants, seafood, flamingos and quail is one such agent. It has antioxidant and anti-inflammatory effects. Limited, short duration and small sample size studies have assessed the effects of astaxanthin on oxidative stress and inflammation biomarkers and have investigated bioavailability and safety. So far no significant adverse events have been observed and biomarkers of oxidative stress and inflammation are attenuated with astaxanthin supplementation. Experimental investigations in a range of species using a cardiac ischaemia-reperfusion model demonstrated cardiac muscle preservation when astaxanthin is administered either orally or intravenously prior to the induction of ischaemia. Human clinical cardiovascular studies using astaxanthin therapy have not yet been reported. On the basis of the promising results of experimental cardiovascular studies and the physicochemical and antioxidant properties and safety profile of astaxanthin, clinical trials should be undertaken.
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... None membrane rigidity water permeability Antioxidant role 1 O2 quenching 800 times > coenzyme Q 6000 times > vitamin C 550 times > green tea catechins, 11 times > -carotene [59] Natural 50 times > synthetic not reported Free radical scavenger 65 times > vitamin C 50 times > vitamin E [60] Natural 20 times > synthetic [61] Toxicity NOAEL (no observed adverse effect levels) natural AST is 465 and 557 mg/kg/day in male and female rats respectively. The repeated-dose oral toxicity in pregnant mice showed LD50 > 20 g/kg [66] Up to 500 mg/kg/day for 14 days on Wistar rats no observed adverse effects were registered. ...
... AST can neither be converted into vitamin A nor synthesized de novo by animals; 269 therefore, it must be consumed in the diet [94]. Through feeding, AST is present in egg 270 yolks, feathers from flamingos, canaries and chickens, and it confers salmon, shrimp and 271 lobster shells their distinctive colour and plays key metabolic effects (Table 1) [59]. In hu-272 man consumption, it is employed as food supplements and cosmetic ingredients. ...
Carotenoids are natural products regulated by the food sector, currently used as feed dyes and as antioxidants in dietary supplements and composing functional foods for human consumption. Of the nearly one thousand carotenoids described to date, only retinoids, derived from beta carotene, have the status of drug and are regulated by the pharmaceutical sector. In this review, we address a novel field: the transformation of xanthophylls-particularly the highly marketed astaxanthin and the practically unknown bacterioruberin-in therapeutic agents by altering their pharmacokinetics, biodistribution, and pharmacodynamics through their formulation as nanomedicines. The antioxidant activity of xanthophylls is mediated by routes different from those of the classical oral anti-inflammatory drugs such as corticosteroids and non-steroidal anti-inflammatory 19 drugs (NSAIDs): remarkably, xanthophylls lack therapeutic activity but also lack toxicity. Formulated as nanomedicines, xanthophylls gain therapeutic activity, by mechanisms other than increased bioavailability. Loaded into ad-hoc tailored nanoparticles to protect their structure throughout storage and during gastrointestinal transit or skin penetration, xanthophylls can be targeted and delivered to selected inflamed cell groups, achieving a massive intracellular concentration after endocytosis of small doses of the formulation. Most first reports showing the activities of oral and topical anti-inflammatories xanthophyll-based nanomedicines against chronic diseases such as inflammatory bowel disease, psoriasis, atopic dermatitis, and dry eye disease emerged between 2020 and 2023. Here we discuss in detail their preclinical performance-mostly targeted vesicular and polymeric nanoparticles-on cellular models and in vivo. The results, although preliminary, are auspicious enough to speculate their potential use upon oral or topical administration in the treatment of chronic inflammatory diseases.
... A supplement containing AXT may preserve skin problems caused by environmental damage and prevent age-related skin degradation [70]. Chalyk et al. [74] observed that the oxidative stress indicator, malondialdehyde (MDA), reduced after a human trial participant received a daily dose of 4 mg of AXT. This experimental study showed a reduction of MDA level by 11.2% on the 15th day and 21.7% on the 29th day [70,71]. ...
... Orally administered AXT was demonstrated to decrease BP in SHR rats by reducing nitric oxide end products. Also, this is because of its potential effects in decreasing the accumulation of elastin in the aorta and attenuating atherosclerosis by reducing the wall-to-lumen ratio of coronary arteries [74]. There is also growing research evidence supporting the benefits of AXT in other cardiovascular aspects. ...
Astaxanthin (AXT) is a red fat-soluble pigment found naturally in aquatic animals, plants, and various microorganisms and can be manufactured artificially using chemical catalysis. AXT is a xanthophyll carotenoid with a high potential for scavenging free radicals. Several studies have investigated AXT efficacy against diseases such as neurodegenerative, ocular, skin, and cardiovascular hypertension, diabetes, gastrointestinal and liver diseases, and immuno-protective functions. However, its poor solubility, low stability to light and oxygen, and limited bioavailability are major obstacles hindering its wide applications as a therapeutic agent or nutritional supplement. Incorporating AXT with nanocarriers holds great promise in enhancing its physiochemical properties. Nanocarriers are delivery systems with several benefits, including surface modification, bioactivity, and targeted medication delivery and release. Many approaches have been applied to enhance AXT’s medicinal effect, including solid lipid nanoparticles, nanostructured lipid carriers (NLCs) and polymeric nanospheres. AXT nano-formulations have demonstrated a high antioxidant and anti-inflammatory effect, significantly affecting cancer in different organs. This review summarizes the most recent data on AXT production, characterization, biological activity, and therapeutic usage, focusing on its uses in the nanotechnology era.
Graphical abstract
... Astaxanthin is present in several living creatures, including salmon, trout, crayfish and prawns, many of which are found in the maritime ecosystem [86,87]. Fungi such as Phaffia rhodozyma and Xanthophyllomyces dendrorhous are also among the sources of astaxanthin [88,89]. medication [82,83]. ...
... Astaxanthin is present in several living creatures, including salmon, trout, crayfish and prawns, many o which are found in the maritime ecosystem [86,87]. Fungi such as Phaffia rhodozyma and Xanthophyllomyces dendrorhous are also among the sources of astaxanthin [88,89]. The modification of the chemical structure of the esterified moieties can improve the water solubility and/or dispersibility of synthetic carotenoid analogues [90]. ...
Protein is one of the essential macronutrients required by all living things. The breakdown of protein produces monomers known as amino acids. The concept of conjugating natural compounds with amino acids for therapeutic applications emerged from the fact that amino acids are important building blocks of life and are abundantly available; thus, a greater shift can result in structural modification, since amino acids contain a variety of sidechains. This review discusses the data available on amino acid–natural compound conjugates that were reported with respect to their backgrounds, the synthetic approach and their bioactivity. Several amino acid–natural compound conjugates have shown enhanced pharmacokinetic characteristics, including absorption and distribution properties, reduced toxicity and increased physiological effects. This approach could offer a potentially effective system of drug discovery that can enable the development of pharmacologically active and pharmacokinetically acceptable molecules.
... These initial results have led to further studies, which have concluded anti-lipid peroxidation activities in human individuals , anticancer properties (Tanaka et al., 2012), immune system boosting activity (Bolin et al., 2010), eye health maintenance (Guerin et al., 2003;Piermarocchi et al., 2012) and protection against cognitive decline (Satoh et al., 2009;Katagiri et al., 2012). The health benefits and published evidence suggest astaxanthin is safe and orally bioavailable (Fassett and Coombes, 2012), whilst having no provitamin A activity (which can lead to hypervitaminosis A toxicity) (Jyonouchi et al., 1995). ...
... The commercial sector producing H. pluvialis derived astaxanthin is well established. There have been no adverse effects associated with the administration of H. pluvialis derived astaxanthin reported to date (Spiller and Dewell, 2003;Satoh et al., 2009;Fassett and Coombes, 2012) and large-scale production has successfully been employed by several leading companies. Nevertheless, problems in large-scale production of H. pluvialis have arisen and this is why H. pluvialis is the focal organism for this study. ...
Astaxanthin is commercially sold as a pigment for animal feed and as an antioxidant for the nutraceutical sector. Astaxanthin is predominantly manufactured synthetically from
petrochemicals but is also obtained from the Chlorophyte Haematococcus pluvialis. Synthetic astaxanthin has a retail price of $2000/kg. H. pluvialis derived astaxanthin has a higher antioxidant potential than the synthetic form and can be sold for up to $100,000/kg for nutraceutical grade astaxanthin. Commercially, astaxanthin from H. pluvialis is produced in a two-stage production process, incorporating a green and red stage for maximising growth and astaxanthin production respectively. The H. pluvialis derived astaxanthin industry has been a commercial success, but several constraints have arisen including contamination issues, high extraction costs, requirements for high light for outdoor production in the red stage, and photo-bleaching issues in the red stage. In this study following a programme of strain selection, a prototype two-stage autotrophic process for astaxanthin production using H. pluvialis SAG 34/1d was developed. The green and red stages were optimised for the selection of red motile macrozooids rather than aplanospores. Several problems have been alleviated using this prototype production process, offering the potential to be manufactured indoors in the UK and other temperate locations. Under the conditions tested the red motile macrozooids formed did not exhibit photo-bleaching. The red motile macrozooids lacked the thick walls of aplanospores and therefore astaxanthin was bioavailable without the requirement for an extraction process. In addition the red motile macrozooids are not known to be susceptible to the chytrid Paraphysoderma sedebokerensis, a devastating pathogen specific to H. pluvialis. It is envisaged that the red motile macrozooids could be harvested and fed as a whole-cell product directly to the animal feed and aquaculture sectors, or furthermore sold as a synergistic blend of carotenoids and polyunsaturated fatty acids (PUFAs) for the nutraceutical industry.
... The impact of astaxanthin and its beneficial effects on animal and human metabolism have been reported elsewhere. 1 In particular, it can be used as a nutritional supplement, as well as an antioxidant and anti-cancer 2 agent, coupled with additional effects of preventing diabetes, 3 cardiovascular diseases 4 and neuropathy. 5 The coloring and antioxidant properties of astaxanthin have been linked to its molecular structure, 6 notably the presence of double bonds in an aliphatic chain of 40 carbon atoms. ...
Background:
Astaxanthin (ASTA) is a kind of food-derived active ingredients (FDAI) with functions of antioxidant, antidiabetic, and nontoxicity, but its poor solubility and low bioavailability hinder further application in food industry. In this study, through inclusion technologies, micellar solubilization and electrospray, we prepared astaxanthin nanoparticles before optimizing the formulation to regulate micelles' physical and chemical properties. We accomplished the preparation of astaxanthin nanoparticle delivery system based on single needle electrospray technology through the usage of 2-hydroxypropyl-β-cyclodextrin (HPCD) and Soluplus®(Sol) for the improvement of the release behavior of the nanocarrier.
Results:
Through this experiment, we successfully prepared astaxanthin nanoparticles with a particle size of about 80 nm, which was further verified with SEM and TEM. Besides, the encapsulation of astaxanthin molecules into the carrier nanoparticles was verified via the results of ATR-IR and XRD techniques. The in vitro release behavior of astaxanthin nanoparticles was different in media that contained 0.5% Tween 80 (pH 1.2, 4.5 and 6.8) buffer solution and distilled water. Also, we carried out the pharmacokinetic study of astaxanthin nanoparticles, wherein, it was observed that astaxanthin nanoparticle showed an effect of immediate release and significant improved bioavailability.
Conclusion:
2-hydroxypropyl-β-cyclodextrin and Soluplus® were used in this work as a hydrophilic nano-carrier, which could provide a simple way to encapsulate natural function food with improving the solubility and bioavailability of poorly water-soluble ingredient. This article is protected by copyright. All rights reserved.
... ATX, a natural antioxidant that is a xanthophyll carotenoid of the carotenoid family member, is predominantly found in marine organisms or water plants such as fungi, microalgae, and other seafood. [7,8] It is reported to be the only carotenoid, which can pass the blood-brain barrier and get into the parenchyma by transcytosis to date. [7] Higher antioxidant activity than other similar carotenoid molecules (α-and β-carotene, lycopene, vitamin E, and lutein) is the other favored feature of ATX. ...
... Studies have shown that ASTE is a potent natural activator of the AMPK pathway. [40][41][42] AMPKα is a central regulation of body energy balance gene by modifying lots of mRNA expression, including HMGCOA-R and LXRα 43 . A down-regulation of HMGCOA-R can reduce the rate of chole-sterol synthesis. ...
Scope: Atherosclerosis (AS) is the leading cause of ischemic disease. However, the anti-AS effects of astaxanthin and its potential mechanisms remain unclear. This study is aimed to investigate the function of astaxanthin-rich extract (ASTE) on AS and gut microbiota as well as the difference from atorvastatin (ATO) in apolipoprotein E-deficient (ApoE-/-) mice. Methods and results: Wild type (WT) and ApoE-/- mice were divided into seven groups: the low-fat diet (LFD) and high-fat diet (HFD) groups (in both types) as well as three ApoE-/- groups based on HFD added with two doses of ASTE and one dose of ATO, respectively. After 30 weeks of intervention, results showed that ASTE significantly inhibited body weight increase, lipids accumulation in serum/liver, and AS-lesions in the aorta. Furthermore, fundus fluorescein angiography and retinal CD31 immunohistochemical staining showed that ASTE could alleviate the occurrence of AS-retinopathy. H&E staining showed that ASTE could protect the colon's mucosal epithelium from damage. The gas chromatographic and gene expression analyses showed that ASTE promoted the excretion of fecal acidic and neutral sterols from cholesterol by increasing LXRα, CYP7A1, and ABCG5/8 and decreasing FXR, NPC1L1, ACAT2, and MTTP expressions. Remarkably, the ASTE administration maintained the gut barrier by enhancing gene expression of JAM-A, Occludin, and mucin2 in the colon and reshaped gut microbiota with the feature of blooming Akkermansia. Conclusion: Our results suggested that ASTE could prevent AS in both macrovascular and/or microvascular as well as used as novel prebiotics by supporting the bile acid excretion and growth of Akkermansia.
Gut microbiota plays a crucial role in regulating the response to immune checkpoint therapy, therefore modulation of the microbiome with bioactive molecules like carotenoids might be a very effective strategy to reduce the risk of chronic diseases. This review highlights the bio-functional effect of carotenoids on Gut Microbiota modulation based on a bibliographic search of the different databases. The methodology given in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) has been employed for developing this review using papers published over two decades considering keywords related to carotenoids and gut microbiota. Moreover, studies related to the health-promoting properties of carotenoids and their utilization in the modulation of gut microbiota have been presented. Results showed that there can be quantitative changes in intestinal bacteria as a function of the type of carotenoid. Due to the dependency on several factors, gut microbiota continues to be a broad and complex study subject. Carotenoids are promising in the modulation of Gut Microbiota, which favored the appearance of beneficial bacteria, resulting in the protection of villi and intestinal permeability. In conclusion, it can be stated that carotenoids may help to protect the integrity of the intestinal epithelium from pathogens and activate immune cells.
Radiation-induced lung injury (RILI) is one of the common complications of radiotherapy for chest tumors and nuclear radiation accidents. The excessive reactive oxygen species induced by radiation is the main mediator. So far, the effective prevention and treatment for RILI are still lacking. Astaxanthin is a carotenoid that belongs to red natural lutein family and is commonly found in Marine organisms such as shrimp, oysters and salmon. It has been confirmed that astaxanthin has strong antioxidant and anti-inflammatory properties, therefore we speculated that astaxanthin may be a potential treatment for RILI. First, with a mice model of RILI, the protected effects of astaxanthin were observed. Furthermore, the experiments in vitro were performed by detecting apoptosis. As a result, astaxanthin protects the RILI, inhibits the process of pulmonary fibrosis, and reduces the elevation of inflammatory factors. The experiments in vitro demonstrated that astaxanthin could reduce radiation-induced apoptosis and especially inhibit activation of apoptosis pathway. In conclusion, astaxanthin could protect RILI of mice, which is mediated by inhibiting activation of apoptosis pathway.
It has been suggested that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease, cancer, and other adverse outcomes. METHODS: 20,536 UK adults (aged 40-80) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) or matching placebo. Intention-to-treat comparisons of outcome were conducted between all vitamin-allocated and all placebo-allocated participants. An average of 83% of participants in each treatment group remained compliant during the scheduled 5-year treatment period. Allocation to this vitamin regimen approximately doubled the plasma concentration of alpha-tocopherol, increased that of vitamin C by one-third, and quadrupled that of beta-carotene. Primary outcomes were major coronary events (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity. FINDINGS: There were no significant differences in all-cause mortality (1446 [14.1%] vitamin-allocated vs 1389 [13.5%] placebo-allocated), or in deaths due to vascular (878 [8.6%] vs 840 [8.2%]) or non-vascular (568 [5.5%] vs 549 [5.3%]) causes. Nor were there any significant differences in the numbers of participants having non-fatal myocardial infarction or coronary death (1063 [10.4%] vs 1047 [10.2%]), non-fatal or fatal stroke (511 [5.0%] vs 518 [5.0%]), or coronary or non-coronary revascularisation (1058 [10.3%] vs 1086 [10.6%]). For the first occurrence of any of these "major vascular events", there were no material differences either overall (2306 [22.5%] vs 2312 [22.5%]; event rate ratio 1.00 [95% CI 0.94-1.06]) or in any of the various subcategories considered. There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause. INTERPRETATION: Among the high-risk individuals that were studied, these antioxidant vitamins appeared to be safe. But, although this regimen increased blood vitamin concentrations substantially, it did not produce any significant reductions in the 5-year mortality from, or incidence of, any type of vascular disease, cancer, or other major outcome.
To understand the roles of carotenoids as singlet oxygen quenchers in marine organisms, quenching activities of eight major carotenoids, astaxanthin, canthaxanthin, β-carotene, zeaxanthin, lutein, tunaxanthin, fucoxanthin and halocynthiaxanthin were examined according to the method using a thermodissociable endoperoxide of 1,4-dimethylnaphthalene as a singlet oxygen generator. The second-order rate constant for the singlet oxygen quenching activity by each carotenoid was determined, suggesting that an increasing number of conjugated double bonds in carotenoid was proportional to greater quenching activity. The quenching activity of each carotenoid was found to be approximately 40 to 600 times greater than that of α-tocopherol. The potency of these carotenoids suggests that they may play a role in protecting marine organisms from active oxygen species.
Background. Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables, as well as high serum levels of vitamin E (alpha-tocopherol) and beta carotene, are associated with a reduced risk of lung cancer. Methods. We performed a randomized, double-blind, placebo-controlled primary-prevention trial to determine whether daily supplementation with alpha-tocopherol, beta carotene, or both would reduce the incidence of lung cancer and other cancers. A total of 29,133 male smokers 50 to 69 years of age from southwestern Finland were randomly assigned to one of four regimens: alpha-tocopherol (50 mg per day) alone, beta carotene (20 mg per day) alone, both alpha-tocopherol and beta carotene, or placebo. Follow-up continued for five to eight years. Results. Among the 876 new cases of lung cancer diagnosed during the trial, no reduction in incidence was observed among the men who received alpha-tocopherol (change in incidence as compared with those who did not, -2 percent; 95 percent confidence interval, -14 to 12 percent). Unexpectedly, we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not (change in incidence, 18 percent; 95 percent confidence interval, 3 to 36 percent). We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer. Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not. Beta carotene had little or no effect on the incidence of cancer other than lung cancer. Alpha- tocopherol had no apparent effect on total mortality, although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not. Total mortality was 8 percent higher (95 percent confidence interval, 1 to 16 percent) among the participants who received beta carotene than among those who did not, primarily because there were more deaths from lung cancer and ischemic heart disease. Conclusions. We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene. In fact, this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects.
Background:
It has been suggested that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease, cancer, and other adverse outcomes.
Methods:
20,536 UK adults (aged 40-80) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) or matching placebo. Intention-to-treat comparisons of outcome were conducted between all vitamin-allocated and all placebo-allocated participants. An average of 83% of participants in each treatment group remained compliant during the scheduled 5-year treatment period. Allocation to this vitamin regimen approximately doubled the plasma concentration of alpha-tocopherol, increased that of vitamin C by one-third, and quadrupled that of beta-carotene. Primary outcomes were major coronary events (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity.
Findings:
There were no significant differences in all-cause mortality (1446 [14.1%] vitamin-allocated vs 1389 [13.5%] placebo-allocated), or in deaths due to vascular (878 [8.6%] vs 840 [8.2%]) or non-vascular (568 [5.5%] vs 549 [5.3%]) causes. Nor were there any significant differences in the numbers of participants having non-fatal myocardial infarction or coronary death (1063 [10.4%] vs 1047 [10.2%]), non-fatal or fatal stroke (511 [5.0%] vs 518 [5.0%]), or coronary or non-coronary revascularisation (1058 [10.3%] vs 1086 [10.6%]). For the first occurrence of any of these "major vascular events", there were no material differences either overall (2306 [22.5%] vs 2312 [22.5%]; event rate ratio 1.00 [95% CI 0.94-1.06]) or in any of the various subcategories considered. There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause.
Interpretation:
Among the high-risk individuals that were studied, these antioxidant vitamins appeared to be safe. But, although this regimen increased blood vitamin concentrations substantially, it did not produce any significant reductions in the 5-year mortality from, or incidence of, any type of vascular disease, cancer, or other major outcome.
