Article

Let Astaxanthin be thy Medicine

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Abstract

Astaxanthin is known as a "marine carotenoid" and occurs in a wide variety of living organisms such as salmon, shrimp, crab, and red snapper. Astaxanthin antioxidant activity has been reported to be more than 100 times greater than that of vitamin E against lipid peroxidation and approximately 550 times more potent than that of vitamin E for singlet oxygen quenching. Astaxanthin exhibits no pro-oxidant activity and its main site of action is on/in the cell membrane. To date, various important benefits suggested for human health include immunomodulation, anti-stress, anti-inflammation, LDL cholesterol oxidation suppression, enhanced skin health, improved semen quality, attenuation of eye fatigue, increased sports performance and endurance, limiting exercised-induced muscle damage, and the suppression of the development of lifestyle related diseases such as obesity, atherosclerosis, diabetes, hyperlipidemia and hypertension. Recently, there has been an explosive increase worldwide in both the research and demand for natural astaxanthin in human health applications. Japanese clinicians are especially using astaxanthin extracted from the microalgae, Haematococcus pluvialis, as add-on supplementation for patients who are unsatisfied with conventional medications or cannot take other medications due to serious symptoms. For example, in heart failure or overactive bladder patients, astaxanthin treatment enhances patient's daily activity levels and QOL. Other ongoing clinical trials and case studies are examining chronic diseases such as non-alcoholic steatohepatitis, diabetes, diabetic nephropathy and CVD, as well as infertility, atopic dermatitis, androgenetic alopecia, ulcerative colitis and sarcopenia. In the near future, astaxanthin's role may be stated as, "Let astaxanthin be thy medicine".

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... canthaxanthin, zeaxanthin, lutein and b-carotene) as well as vitamins C and E (Miki et al. 1982;Terao 1989;Jorgensen & Skibsted 1993;Stewart et al. 2008;Ranga Rao et al. 2010). This carotenoid pigment has been proposed as 'super vitamin E' whereby the antioxidant activities are noted to be approximately 10 times stronger than those of other carotenoids and 500 times greater than a-tocopherol comparatively, while more efficiently assimilated at low-energetic expense (Miki 1991;Petit et al., 1997;Lorenz & Cysewski 2000;Naguib 2000;Goto et al. 2001;Chen et al. 2003;Dufosse et al. 2005;Yamashita 2015). It is scientifically understood that aquatic animals generally exhibit poor ability to biochemically synthesize astaxanthin and must be acquired in the diet. ...
... These findings strongly support the safety profile of astaxanthin for future human clinical trials. No observable serious side effects of astaxanthin have been recorded thus far in any of the published human clinical studies when administered to humans, and there is evidence of a suppression in biomarkers of inflammation and oxidative stress (Spiller & Dewell 2003;Kim & Chyun 2004;Iwabayashi et al. 2009;Satoh et al. 2009;Park et al. 2010;Fassett & Coombes 2011;Yamashita 2015). A growing body of research suggests that dietary astaxanthin supplementation could exert protective actions against atherosclerotic cardiovascular disease (CVD) via its potential as a therapeutic agent to ameliorate endothelial inflammation, oxidative stress, neutrophil functions, flexibility of red blood cell membranes, lipid and glucose metabolism (Macedo et al. 2010;Riccioni et al. 2012;Kishimoto et al. 2016). ...
Article
Astaxanthin is a high value keto-carotenoid pigment renowned for its commercial application in various industries comprising aquaculture, food, cosmetic, nutraceutical and pharmaceutical. Among the verified bio-resources of astaxanthin are red yeast Phaffia rhodozyma and green alga Haematococcus pluvialis. The supreme antioxidant property of astaxanthin reveals its tremendous potential to offer manifold health benefits among aquatic animals which is a key driving factor triggering the upsurge in global demand for the pigment. Numerous scientific researches devoted over a number of years have persistently demonstrated the instrumental role of astaxanthin in targeting several animal health conditions. This review article evaluates the current best available evidence to judge the beneficial usage of astaxanthin in aquaculture industry. Most apparent is the profound effect on pigmentation, where astaxanthin is frequently utilized as an additive in formulated diets to boost and improve the coloration of many aquatic animal species, and subsequently product quality and price. Moreover, the wide range of other physiological benefits that this biological pigment confers to these animals is also presented which include various improvements in survival, growth performance, reproductive capacity, stress tolerance, disease resistance and immune-related gene expression.
... Naguib reported a greater anti-oxidant activity of AST in comparison with different carotenoids like α-carotene, lycopene, lutein, and β-carotene [53]. In comparison to other anti-oxidants, AST anti-oxidant activity [54,55] is more than 100 times greater than that of vitamin E which has been exposed to LPO and about 550 times more capable than vitamin E in neutrilizing singlet oxygen [56]. Its anti-oxidants activity is 100-1000 fold higher than other photochemical agents [57,58], and is 100 fold more than a-tocopherol [12,59], zeaxanthin, lutein [53], [12] and β-carotene [55,60,61]. ...
... In comparison to other anti-oxidants, AST anti-oxidant activity [54,55] is more than 100 times greater than that of vitamin E which has been exposed to LPO and about 550 times more capable than vitamin E in neutrilizing singlet oxygen [56]. Its anti-oxidants activity is 100-1000 fold higher than other photochemical agents [57,58], and is 100 fold more than a-tocopherol [12,59], zeaxanthin, lutein [53], [12] and β-carotene [55,60,61]. Some researchers have revealed that although all-trans-isomer of AST predominates in nature, the cis isomer AST, especially 9-cis show a greater anti-oxidant potential compared to the trans isomer [51,62]. ...
Article
Astaxanthin (AST) is a potent lipid-soluble keto-carotenoid with auspicious effects on human health. It protects organisms against a wide range of diseases with excellent safety and tolerability. Various imperative biological activities in vitro and in vivo models have been suggested for AST. This review article is focused on the therapeutic potentials, biological activities and benefical health effects of AST. The pharmacological mechanisms of action of AST in the treatment and prevention of the peripheral and central nervous system diseases was also reviewed to provide new insights to researchers. Finally, we suggested a novel hypothesis for the mechanism of action of AST in neuropathic pain following spinal cord injury.
... That's why it is used as a stabilizer to sustain the high antioxidant capacities in both conditions [21,58]. The hydrogen atom at C3 methine of a terminal ring of ASX molecule acts as a radical-trapping site [59]. The terminal ring of ASX lies in the hydrophilic layers. ...
... This links the cell membrane from inside to outside, thus increasing the cell defense [58]. Most antioxidants have a high potential of quenching Reactive oxygen species and free radicals, including hydrogen peroxide, superoxide anion, singlet of the inner and outer side like vitamin E and β carotene or vitamin C, respectively [59]. Due to hydroxyl and keto groups in the same structure, ASX can effectively neutralize ROS. ...
Article
Astaxanthin is a ketocarotenoid, super antioxidant molecule. It has higher antioxidant activity than a range of carotenoids, thus has applications in cosmetics, aquaculture, nutraceuticals, therapeutics, and pharmaceuticals. Naturally, it is derived from Haematococcus pluvialis via a one‐stage process or two‐stage process. Natural astaxanthin significantly reduces oxidative and free‐radical stress as compared to synthetic astaxanthin. The present review summarizes all the aspects of astaxanthin, including its structure, chemistry, bioavailability, and current production technology. Also, this paper gives a detailed mechanism for the potential role of astaxanthin as nutraceuticals for cardiovascular disease prevention, skin protection, antidiabetic and anticancer, cosmetic ingredient, natural food colorant, and feed supplement in poultry and aquaculture. Astaxanthin is one of the high‐valued microalgae products of the future. However, due to some risks involved or not having adequate research in terms of long‐term consumption, it is still yet to be explored by food industries. Although the cost of naturally derived astaxanthin is high, it accounts for only a 1% share in total astaxanthin available in the global market. Therefore, scientists are looking for ways to cut down the cost of natural astaxanthin to be made available to consumers.
... Thanks to the polar-non-polar structure, astaxanthin can fit the hydrophobic polyene carbon chain inside the bilayer lipid cell membrane, and its polar terminal rings can be located near its surface ( Figure 2). In consequence, in comparison with other carotenoids, astaxanthin exhibits very high anti-oxidative activity in lipid systems [14]. ...
... Thanks to the polar-non-polar structure, astaxanthin can fit the hydrophobic polyene carbon chain inside the bilayer lipid cell membrane, and its polar terminal rings can be located near its surface ( Figure 2). In consequence, in comparison with other carotenoids, astaxanthin exhibits very high anti-oxidative activity in lipid systems [14]. Astaxanthin was found to protect membrane phospholipids and other lipids from peroxidation more effectively than β-carotene and lutein [16,17]. ...
Article
Full-text available
Xanthophyll astaxanthin, which is commonly used in aquaculture, is one of the most expensive and important industrial pigments. It is responsible for the pink and red color of salmonid meat and shrimp. Due to having the strongest anti-oxidative properties among carotenoids and other health benefits, natural astaxanthin is used in nutraceuticals and cosmetics, and in some countries, occasionally, to fortify foods and beverages. Its use in food technology is limited due to the unknown effects of long-term consumption of synthetic astaxanthin on human health as well as few sources and the high cost of natural astaxanthin. The article characterizes the structure, health-promoting properties, commercial sources and industrial use of astaxanthin. It presents the possibilities and limitations of the use of astaxanthin in food technology, considering its costs and food safety. It also presents the possibilities of stabilizing astaxanthin and improving its bioavailability by means of micro- and nanoencapsulation.
... β-carotene and vitamin C, being antioxidant, are located in both inside and outside of cell lipid layer of membrane. However, besides participation in the double-layer membrane, the presence of the cell both inside and outside gives ASTX better protection than others ( Figure 5) [54]. It is adduced in studies related to astaxhantin that ASTX decreases oxidant stress by inducing antioxidant enzymes, such as Nrf2, PI3K/Akt, SOD and glutathione, and their pathways [55][56][57][58]. ...
... Protection of ASTX against ROS in the double-layer membrane[54]. ...
... The conjugated double bonds at its center are responsible for its red color and, most important, for its high antioxidant capacity, as it donates the electrons that react with free radicals to convert them into more stable products, blocking free radical chain reactions [4]. Astaxanthin can also trap free radicals in its terminal ring moiety, in which the hydrogen atom at the C3 methine has been suggested to be a radical trapping site [92]. As astaxanthin shows both lipophilic and hydrophilic properties, this molecule is exposed to both the inside and outside of the cell, where it can scavenge radicals from the surface of the cell and at the interior of the phospholipid membrane (Fig. 2). ...
... As astaxanthin shows both lipophilic and hydrophilic properties, this molecule is exposed to both the inside and outside of the cell, where it can scavenge radicals from the surface of the cell and at the interior of the phospholipid membrane (Fig. 2). This feature makes astaxanthin unique when compared to other antioxidants, such as β-carotene or vitamin C, which can only reside within or outside the lipid bilayer membrane, respectively [92]. Indeed, studies have demonstrated that astaxanthin shows the highest antioxidant activity when compared to related carotenoids, being 10 times stronger. ...
Article
Astaxanthin is a natural C40 carotenoid with numerous reported biological functions, most of them associated with its antioxidant and anti-inflammatory activity, standing out from other antioxidants as it has shown the highest oxygen radical absorbance capacity (ORAC), 100-500 times higher than ⍺-tocopherol and a 10 times higher free radical inhibitory activity than related antioxidants (α-tocopherol, α-carotene, β -carotene, lutein and lycopene). In vitro and in vivo studies have associated astaxanthin´s unique molecular features with several health benefits, including neuroprotective, cardioprotective and antitumoral properties, suggesting its therapeutic potential for the prevention or co-treatment of dementia, Alzheimer, Parkinson, cardiovascular diseases and cancer. Benefits on skin and eye health promotion have also been reported, highlighting its potential for the prevention of skin photo-aging and the treatment of eye diseases like glaucoma, cataracts and uveitis. In this review, we summarize and discuss the currently available evidence on astaxanthin benefits, with a particular focus on human clinical trials, including a brief description of the potential mechanisms of action responsible for its biological activities.
... Cardiovascular disorders are responsible for a large number of deaths worldwide [5,156], and since they are often connected with oxidative stress and ROS, astaxanthin can be used in their prevention due to its strong antioxidative activity [126,[157][158][159]. Furthermore, the oral administration of astaxanthin reduced cholesterol in mice with immediate spread across the body [160]. ...
... Astaxanthin from natural sources has been suggested as safe for application with no adverse (mutagenic, carcinogenic, biochemical, and hematological) effects for humans [7,142,147,158]. However, there is a lack of literature on marine astaxanthin therapeutic applications and safety concerns since it is known that supplementation of different amounts and forms (natural and synthetic) exhibits different levels of bioactivities [159,[175][176][177]. Considering the safety issues, the allowed levels of astaxanthin in food supplements were 8 mg/day, and acceptable daily intake for adults ranged from 0.034 to 0.2 mg astaxanthin/kg body weight [178]. ...
Article
Full-text available
In recent years, the food, pharma, and cosmetic industries have shown considerable interest in bioactive molecules of marine origin that show high potential for application as nutraceuticals and therapeutic agents. Astaxanthin, a lipid-soluble and orange-reddish-colored carotenoid pigment, is one of the most investigated pigments. Natural astaxanthin is mainly produced from microalgae, and it shows much stronger antioxidant properties than its synthetic counterpart. This paper aims to summarize and discuss the important aspects and recent findings associated with the possible use of crustacean byproducts as a source of astaxanthin. In the last five years of research on the crustaceans and their byproducts as a source of natural astaxanthin, there are many new findings regarding the astaxanthin content in different species and new green extraction protocols for its extraction. However, there is a lack of information on the amounts of astaxanthin currently obtained from the byproducts as well as on the cost-effectiveness of the astaxanthin production from the byproducts. Improvement in these areas would most certainly contribute to the reduction of waste and reuse in the crustacean processing industry. Successful exploitation of byproducts for recovery of this valuable compound would have both environmental and social benefits. Finally, astaxanthin's strong biological activity and prominent health benefits have been discussed in the paper.
... In addition, the antioxidative capacity of AST has been obtained due to the polar-nonpolar structure of AST which could contain hydrophobic polyene carbon chains in the lipid bilayer cell membrane, while the polar terminal ring is placed near its surface [36]. ...
Article
Full-text available
Recent interest in carotenoids has increased due to their antioxidant and production performance. Astaxanthin (AST) is a xanthophyll carotenoid abundantly distributed in microalgae, which is described as a highly potent antioxidant. Therefore, recent studies have tended to investigate the role of antioxidants in improving metabolic processes and physiological functioning of the body. It is now evident that AST could significantly reduce free radicals and oxidative stress and help to maintain a healthy state. Moreover, AST also could improve the performance of broiler chicken by increasing the daily feed intake, followed by improvement in the food conversion rate.
... In this chapter, we mainly described astaxanthin, sponge extracts, SCSs and some secondary metabolites of marine fungi. Among them, astaxanthin has a strong antioxidant capacity and is promising in preventing diseases related to oxidative stress [204]. Recent studies have shown that astaxanthin reduces the area of atherosclerotic plaques in animals and exert anti-atherosclerotic effects by improving oxidative stress and lipid metabolism. ...
Article
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Atherosclerosis is a chronic disease characterized by lipid accumulation and chronic inflammation of the arterial wall, which is the pathological basis for coronary heart disease, cerebrovascular disease and thromboembolic disease. Currently, there is a lack of low-cost therapeutic agents that effectively slow the progression of atherosclerosis. Therefore, the development of new drugs is urgently needed. The research and development of marine-derived drugs have gained increasing interest from researchers across the world. Many marine organisms provide a rich material basis for the development of atherosclerotic drugs. This review focuses on the latest technological advances in the structures and mechanisms of action of marine-derived anti-atherosclerotic substances and the challenges of the application of these substances including marine polysaccharides, proteins and peptides, polyunsaturated fatty acids and small molecule compounds. Here, we describe the theoretical basis of marine biological resources in the treatment of atherosclerosis.
... 5 The most commonly used pigment commercially is synthetic astaxanthin. 6 The pigmentation studies in snappers are scarce. However, the inclusion of unesterified forms as Carophyll Pink TM has been studied in Australian snapper Pagrus auratus 7 and considered the need for pigmentation in spotted rose snapper. ...
Article
Full-text available
The purpose of this study was to evaluate the effects of increasing concentrations of astaxanthin (Carophyll Pink) on color and pigment content in the skin of Pacific red snapper. Wild organisms (163.0 to 176.0 g) were fed with experimental diets supplemented with 0, 25, 50 and 100 mg astaxanthin/kg (unesterified forms Carophyll Pink) for 30 days. It was found that the lowest values of L*, a*, b*, Cab* and H°ab were recorded in the wild Pacific red snapper and the higher values in AX100 treatment. The colors in the Pacific red snapper depend upon type and concentration of pigment in the skin. it was found that the application of unesterified (Carophyll Pinkt) in the diet improves the appearance of the Pacific red snapper giving it a salmon-colored hue (red-orange) mainly in the ventral area, in the treatments AX50 and AX100. The highest concentration of pigments was found in the dorsal > pectoral > ventral area.
... On the other hand, a single-blind placebo-controlled study showed that dietary supplement containing only AST with a dose of 4 mg per day led to significant improvements in human skin characterized by elasticity during a dermatologist's visual assessment [109]. The combination of oral supplementation with topical application resulted in significant improvements in skin wrinkles, age spot size, elasticity, skin texture, moisture, the content of the corneocyte layer, and the corneocyte condition [111]. ...
Article
Full-text available
As the leading causes of human disability and mortality, neurological diseases affect millions of people worldwide and are on the rise. Although the general roles of several signaling pathways in the pathogenesis of neurodegenerative disorders have so far been identified, the exact pathophysiology of neuronal disorders and their effective treatments have not yet been precisely elucidated. This requires multi-target treatments, which should simultaneously attenuate neuronal inflammation, oxidative stress, and apoptosis. In this regard, astaxanthin (AST) has gained growing interest as a multi-target pharmacological agent against neurological disorders including Parkinson's disease (PD), Alzheimer's disease (AD), brain and spinal cord injuries, neuropathic pain (NP), aging, depression, and autism. The present review highlights the neuroprotective effects of AST mainly based on its anti-inflammatory, antioxidative, and anti-apoptotic properties that underlies its pharmacological mechanisms of action to tackle neurodegeneration. The need to develop novel AST delivery systems, including nanoformulations, targeted therapy, and beyond, is also considered.
... It has diverse biological activities and potential health benefits (e.g. antioxidant, anti-inflammatory, and antitumour activities) to humans and animals and have been extensively investigated (Fakhri et al. 2018;Ng et al. 2020;Nouchi et al. 2020;Yamashita 2015). ...
Article
Full-text available
Astaxanthin is a natural pigment, known for its strong antioxidant activity and numerous health benefits to human and animals. Its antioxidant activity is known to be substantially greater than β-carotene and about a thousand times more effective than vitamin E. The potential health benefits have generated a growing commercial interest, and the escalating demand has prompted the exploration of alternative supply chain. Astaxanthin naturally occurs in many sea creatures such as trout, shrimp, and microalgae, some fungi, bacteria, and flowering plants, acting to protect hosts against environmental stress and adverse conditions. Due to the rapid growth and simple growth medium requirement, microbes, such as the microalga, Haematococcus pluvialis, and the fungus Xanthophyllomyces dendrorhous, have been developed to produce astaxanthin. With advances in metabolic engineering, non-carotenogenic microbes, such as Escherichia coli and Saccharomyces cerevisiae, have been pur-posed to produce astaxanthin and significant progress has been achieved. Here, we review the recent achievements in microbial astaxanthin biosynthesis (with reference to metabolic engineering strategies) and extraction methods, current challenges (tech-nical and regulatory), and commercialization outlook. Due to greenness, sustainability, and dramatic cost reduction, we envision microbial synthesis of astaxanthin offers an alternative means of production (e.g. chemical synthesis) in the near future.
... Since selenium is an essential cofactor for certain peroxidases, selenium supplementation might also be appropriate in this context [3]. Besides, other nutraceuticals with antioxidant properties such as ascorbic acid, spirulina and a blend of herbal extracts including Uncaria tomentosa, Endopleura uchi and Haematoccocus pluvialis could also contribute to reduce the oxidative stress [63,64,71,129,157]. ...
Article
Full-text available
The number of COVID-19 patients is still growing exponentially worldwide due to the high transmissibility of the SARS-CoV-2 virus. Therapeutic agents currently under investigation are antiviral drugs, vaccines, and other adjuvants that could relieve symptoms or improve the healing process. In this review, twelve therapeutic agents that could play a role in prophylaxis or improvement of the COVID-19-associated symptoms (as add-on substances) are discussed. Agents were identified based on their known pharmacologic mechanism of action in viral and/or nonviral fields and are postulated to interact with one or more of the seven known mechanisms associated with the SARS-CoV-2 virus: (i) regulation of the immune system; (ii) virus entrance in the cell; (iii) virus replication; (iv) hyperinflammation; (v) oxidative stress; (vi) thrombosis; and (vii) endotheliitis. Selected agents were immune transfer factor (oligo- and polypeptides from porcine spleen, ultrafiltered at <10 kDa; Imuno TF®), anti-inflammatory natural blend (Uncaria tomentosa, Endopleura uchi and Haematoccocus pluvialis; Miodesin®), zinc, selenium, ascorbic acid, cholecalciferol, ferulic acid, spirulina, N-acetylcysteine, glucosamine sulfate potassium hydrochloride, trans-resveratrol, and maltodextrin-stabilized orthosilicic acid (SiliciuMax®). This review gives the scientific background on the hypothesis that these therapeutic agents can act in synergy in the prevention and improvement of COVID-19-associated symptoms.
... Fourteen of the obtained 20 transformants were selected based on their colony size (AlCarS#1, 4,5,6,9,10,11,12,13,14,15,16,17,18). Colony PCR and gel electrophoresis revealed the corresponding bands (PCR product size, 261 bp) in AlCarS#1, 4, 5, 6, 9, 10, 11, 15, and 18. ...
Article
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Aurantiochytrium limacinum produces both docosahexaenoic acid (DHA) and astaxanthin, respectively. Organisms that produce these industrially important materials more efficiently than microalgae are currently needed. In this study, we overexpressed a putative homolog of CarS, which is involved in synthesizing the astaxanthin precursor, β-carotene, in A. limacinum to increase carotenoid synthesis with the goal of obtaining strains that produce large amounts of both DHA and carotenoids. AlCarS transformants #1 and #18 produced significantly increased amounts of astaxanthin as assessed according to culture (up to 5.8-fold) and optical density (up to 9.3-fold). The improved astaxanthin production of these strains did not affect their DHA productivity. Additionally, their CarS expression levels were higher than those of the wild-type strain, suggesting that CarS overexpression enhanced β-carotene production, which in turn improved astaxanthin productivity. Although cell yields were slightly decreased, these features will be valuable in health food, medical care, and animal feed fields.
... 51 Besides, other nutraceuticals with antioxidant properties such as Vitamin C, Spirulina and Astaxanthin can also contribute to reduce the oxidative stress. 51,66,67,[71][72][73][74] As a limitation of our study, we can point out the differences in age of the cohorts. Therefore, we can understand the data as a description of the fast times needed to recover from the most common COVID-19 symptoms, rather than a direct comparison between the cohorts. ...
Preprint
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Although a vast knowledge has already been gathered on the pathophysiology of COVID-19, there are still limited, non-optimal treatment options. In this paper, we describe a multicentre, retrospective, observational study to describe the course of SARS-CoV-2 disease in patients treated with ImmunoFormulation (IF), an add-on therapy developed to decrease duration of clinical symptoms. In parallel, a group of patients that did not receive IF was used for comparison (using standard of care treatment). A total of 39 patients were evaluated. Throughout the observational period, 90% of patients recovered in the IF cohort and 47.4% in the Control cohort (p=0.0057). From the symptoms with statistically significant differences, the duration of symptoms (i.e., the time to recover from it) was shorter in the IF cohort than in control cohort (in days, average), especially for fever (2.25 x 21.78), dry cough (4.38 x 24.00), dyspnoea (3.67 x 20.00), headache (2.00 x 26.50), diarrhoea (5.25 x 25.25), and weakness (1.92 x 23.30). This demonstrates a potential promising role of IF as adjuvant therapy on the evolution of symptomatology to COVID-19 patients.
... Besides its strong antioxidant activity, which is about 100 and 10 times greater than those of vitamin E and β-carotene, respectively, this carotenoid exhibits no pro-oxidative properties and free radicals can be trapped not only by the conjugated polyene chain, but also by the terminal ring moiety of the molecule. Moreover, it shows the unique ability to span the double layer of the cell membrane, providing better overall protection [12]. ...
Article
Haematococcus pluvialis is a green microalga that produces a considerable amount of carotenoids, mainly astaxanthin (ASTX), which is a powerful antioxidant compound. However, carotenoid compounds exhibit poor water solubility and high instability, which restrain their application in pharmaceutical products. Considering that, here we describe the encapsulation of Haematococcus pluvialis carotenoids into poly-lactide-co-glycolide nanocapsules (NC-ESHp), aiming to obtain an innovative topical product with antioxidant properties. Nanocapsules were prepared by the solvent displacement method and characterized according to size, zeta potential, total carotenoid content, and ASTX content. Poloxamer 407 was added to the colloidal dispersion to form a thermosensitive hydrogel (HG–NC–ESHp). Release studies demonstrated that the carotenoids were released from the gel system in a sustained way. In the DPPH scavenging assay, NC-ESHp15 exhibited an antioxidant activity 9-fold higher than ascorbic acid. These results indicated that the hydrogel developed may be a promising formulation to provide prolonged protection of the skin against the photo-oxidation process.
... Astaxanthin (3,3'-dihydroxy-β,β-carotene-4,4'-dione) is a naturally occurring carotenoid found in many native organisms, especially those living in the ocean. The red-orange colored astaxanthin, with its 13 conjugated double bonds, stands out mainly due to its much stronger antioxidant properties than other antioxidants commonly used as food additives, Abbreviations: ACA, acetyl-CoA acyltransferase; CBFD, carotenoid beta-ring 4-dehydrogenase; CrtW/BKT, β-carotene ketolase; CrtZ, β-carotene hydroxylase; DCW, dry cell weight; DMAPP, dimethylallyl diphosphate; DPPMVK, diphosphomevalonate kinase; DXR, 1-deoxy-D-xylulose5-phosphate reductoisomerase; DXS, 1-deoxy-D-xylulose-5-phosphate synthase; FDPPS, farnesyl diphosphate synthase; FPP, farnesyl diphosphate; G3P, glyceraldehyde-3-phosphate; GGPP, geranylgeranyl pyrophosphate; GGS, geranylgeranyl diphosphate synthase; HBFD, 4-hydroxy-beta-ring 4-dehydrogenase; HMGR, HMG-CoA reductase; HMGS, HMG-CoA synthase; IDI, isopentenyl diphosphate isomerase; IPP, isopentenyl diphosphate; IspD, 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase; IspE, 4-diphosphocytidyl-2-Cmethyl-D-erythritol kinase; IspF, 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase; IspG, (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase; IspH, 4hydroxy-3-methylbut-2-enyl diphosphate reductase; LYC, lycopene cyclase; MEP, 2-C-methyl-D-erythritol 4-phosphate; MVA, mevalonate; MVK, mevalonate kinase; P450, cytochrome P450 enzyme; PDS, phytoene desaturase; PEP, phosphoenol pyruvate; PPMVK, phosphomevalonate kinase; PSY, phytoene synthase; TAG, triacylglycerol; TCA cycle, tricarboxylic acid cycle; ZDS, zeta-carotene desaturase.. such as β-carotene, lycopene, lutein and α-tocopherol [2,3]. Astaxanthin also has important anti-aging [4,5], anti-atherosclerotic [6], anti-tumor [7][8][9] and anti-nerve injury properties [10], inhibits Helicobacter pylori infection [11][12][13][14], activates the immune response [15][16][17] and improves memory [18,19]. ...
Article
There is an increasing demand for astaxanthin in food, feed, cosmetics and pharmaceutical applications because of its superior anti-oxidative and coloring properties. However, naturally produced astaxanthin is expensive, mainly due to low productivity and limited sources. Reprogramming of microorganisms for astaxanthin production via metabolic engineering is a promising strategy. We primarily focus on the application of synthetic biology, enzyme engineering and metabolic engineering in enhancing the synthesis and accumulation of astaxanthin in microorganisms in this review. We also discuss the biosynthetic pathways of astaxanthin within natural producers, and summarize the achievements and challenges in reprogramming microorganisms for enhancing astaxanthin production. This review illuminates recent biotechnological advances in microbial production of astaxanthin. Future perspectives on utilization of new technologies for boosting microbial astaxanthin production are also discussed.
... 51 Besides, other nutraceuticals with antioxidant properties such as Vitamin C, Spirulina and Astaxanthin can also contribute to reduce the oxidative stress. 51,66,67,[71][72][73][74] As a limitation of our study, we can point out the differences in age of the cohorts. Therefore, we can understand the data as a description of the fast times needed to recover from the most common COVID-19 symptoms, rather than a direct comparison between the cohorts. ...
Preprint
Full-text available
Background Although a vast knowledge has already been gathered on the pathophysiology of COVID-19, there are still limited, non-optimal treatment options. In this context, agents that can act on prophylaxis or as adjuvants to the therapies are of high value. Methods In this paper, we describe a multicentre, retrospective, observational study to describe the course of SARS-CoV-2 disease in patients treated with ImmunoFormulation (IF), an add-on therapy developed to decrease duration of clinical symptoms. In parallel, a group of patients that did not receive IF was used for comparison (using standard of care treatment). A total of 39 patients were evaluated for their recovery rate, general symptoms and their severity, and adverse reactions. Results Throughout the observational period, 90% of patients recovered in the IF cohort and 47.4% in the Control cohort (p=0.0057). From the symptoms with statistically significant differences, the duration of symptoms (i.e., the time to recover from it) was shorter in the IF cohort than in control cohort (in days, average), especially for fever (2.25 x 21.78), dry cough (4.38 x 24.00), dyspnoea (3.67 x 20.00), headache (2.00 x 26.50), diarrhoea (5.25 x 25.25), and weakness (1.92 x 23.30). Conclusions This demonstrates a potential promising role of IF as adjuvant therapy on the evolution of symptomatology to COVID-19 patients.
... 50 Besides, other nutraceuticals with antioxidant properties such as Vitamin C, Spirulina and Astaxanthin can also contribute to reduce the oxidative stress. 50,65,66,[70][71][72][73] As a limitation of our study, we can point out the differences in age of the cohorts. Therefore, we can understand the data as a description of the fast times needed to recover from the most common COVID-19 symptoms, rather than a direct comparison between the cohorts. ...
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Background Although a vast knowledge has already been gathered on the pathophysiology of COVID-19, there are still limited, non-optimal treatment options. In this context, agents that can act on prophylaxis or as adjuvants to the therapies are of high value. Methods In this paper, we describe a multicentre, retrospective, observational study to describe the course of SARS-CoV-2 disease in patients treated with ImmunoFormulation (IF), an add-on therapy developed to decrease duration of clinical symptoms. In parallel, a group of patients that did not receive IF was used for comparison (using standard of care treatment). A total of 39 patients were evaluated for their recovery rate, general symptoms and their severity, and adverse reactions. Results Throughout the observational period, 90% of patients recovered in the IF cohort and 47.4% in the Control cohort (p=0.0057). From the symptoms with statistically significant differences, the duration of symptoms (i.e., the time to recover from it) was shorter in the IF cohort than in control cohort (in days, average), especially for fever (2.25 x 21.78), dry cough (4.38 x 24.00), dyspnoea (3.67 x 20.00), headache (2.00 x 26.50), diarrhoea (5.25 x 25.25), and weakness (1.92 x 23.30). Conclusions This demonstrates a potential promising role of IF as adjuvant therapy on the evolution of symptomatology to COVID-19 patients.
... The industrial demand for naturally produced astaxanthin is increasing because the number of people who prefer to use natural products for feeding livestock or fish is increasing; also, the nutraceutical and cosmetological applications for humans are widening. Haematococcus pluvialis is known as a natural astaxanthin source, and astaxanthin is commonly used for human application (Yamashita 2015;Shah et al. 2016). Phaffia rhodozyma has also been recognized to naturally produce astaxanthin (Johnson 2003), which is mainly used for the pigmentation of fish, meat, and eggs. ...
Chapter
Paracoccus carotinifaciens is an aerobic Gram-negative bacterium that exhibits motility by a peritrichous flagellum. It produces a carotenoid mixture containing astaxanthin as the main component. Selective breeding of P. carotinifaciens has been performed using classical techniques for mutation induction, such as chemical treatment and ultraviolet irradiation, and not using genetic engineering technology. The commercial production of astaxanthin with P. carotinifaciens has been established by optimizing fermentation medium and conditions in the process. Dehydrated P. carotinifaciens is used as a coloring agent for farmed fish and egg yolks. Compared with the administration of chemically synthesized astaxanthin, dehydrated P. carotinifaciens imparts more natural coloration, which is favored by consumers. In addition, astaxanthin-rich carotenoid extracts (ARE) derived from P. carotinifaciens are developed for human nutrition. Animal and clinical studies with ARE for evaluating its efficacy have been conducted and suggested that ARE would be useful for preventing anxiety, stomach ulcer, and retinal damage, as well as improving cognitive function. The efficacy is anticipated to result from not only astaxanthin but also other carotenoids in ARE, such as adonirubin and adonixanthin, in some studies. Hence, astaxanthin commercially produced with P. carotinifaciens has been applied widely in animals and humans.
... As a result, recent scientific research and studies have tended towards finding alternatives and practical solutions that reduce these obstacles by using safe natural additives in poultry diets such as carotenoids that are deposited within the body tissues and enhance the productive and immune performance [9,10] considered From the alga Haematococcus pluvialis is a safe natural substance and effective antioxidant according to the authorization issued by the European Food and Safety Authority (EFSA) and the Food and Allergy Committee (NDA) to use it as a food supplement for humans and animals [11], as its importance is due to its extension across the cell membrane (dual Layer) compared to other antioxidants whose effect is either in specific locations inside or outside the cell membrane [12,13]. It deals with an unspecified number of free radicals generated as a result of oxidative stress, inhibiting their action and protecting protein, fat and cell membranes from processes Oxidation [14,15] and disposal of hydrogen peroxide, which causes damage to all cell components such as lipids, proteins, and nucleic acids [16,17]Which improves the functions of the immune system [18,19], and in view of the immunological and therapeutic roles of Astaxanthin as a natural antioxidant and the presence of limited studies on the use of this substance in poultry diets, this study aimed to use Astaxanthin in poultry meat and to determine the optimal level of reduction From oxidative damage and maintaining the immune performance of broilers. ...
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This experiment was conducted at the poultry farm/Department of Animal Production/College of Agriculture/Al-Qasim Green University And for two experiments, The first for the period from 27/4/2019 to 7/6/2019 and the second from 1/7/2019 to 4/8/2019 for the second experiment to see the effect of adding different levels of astaxanthin to the broiler diet on some immune characteristics of broilers raised under environmental conditions Natural and elevated. Use 240 unsexed birds of one day age ROSS 308 strain, distributed randomly into five treatments by 48 birds/treatment and the birds of each treatment were divided into three replicates (16 birds/replicate). The chicks were fed on three diets that included the initiator, growth and final 23, 21.5 and 19.44% crude protein respectively, and the representative energy was 3000.5, 3100.7 and 3199.25 kcal/kg feed, respectively, in addition to the astaxanthin powder at levels 0, 10, 20, 30, 40 mg/kg of feed for T1, T2, T3, T4 and T5 treatments, respectively. The results of the first trial showed a significant superiority (P<0.05) for treatment T2 in the relative weight of the fabrichia gland and for the fabrichia index, and significant superiority for treatment T5 and T3 in the size standard of antibodies directed against Newcastle disease, while treatment T2 and T3 outperformed the size criterion of antibodies directed against camboro disease compared With the control treatment T1, and the second trial, the additional factors T2, T3, T4 and T5 achieved significant superiority (P<0.01) in all the immunological characteristics studied by treatment T1. It is concluded from this study that the addition of astaxanthin to the broiler meat diet led to an improvement in the immune characteristics of broilers raised under normal and elevated environmental temperatures.
Article
In this study, atmospheric and room temperature plasma and ultraviolet mutagenesis was studied for astaxanthin overproducing mutant. Phaffia rhodozyma mutant Y1 was obtained from the selection plate with 120 μmol/L diphenylamine as selection agent, and its carotenoid concentration and content were 54.38 mg/L and 5.38 mg/g, which were 19.02 % and 21.20 % higher than that of the original strain, respectively. Sugarcane bagasse hydrolysate was used for astaxanthin production by mutant Y1 at 22 °C and 220 rpm for 96 h, and the biomass and carotenoid concentration reached 12.65 g/L and 88.57 mg/L, respectively. Ultrasonication and cellulase were used to break cell wall and the parameters were optimized, achieving an astaxanthin extraction rate of 96.01 %. The present work provided a novel combined mutagenesis method for astaxanthin overproducing mutant and a green cell wall disruption process for astaxanthin extraction, which would play a solid foundation on the development of natural astaxanthin.
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Astaxanthin is a carotenoid widely found in marine organisms and microorganisms. With extensive use in nutraceuticals, cosmetics, and animal feed, astaxanthin will have the largest share in the global market for carotenoids in the near future. Owing to its unique molecular features, astaxanthin has excellent antioxidant activity and holds promise for use in biochemical studies. This review focuses on the observed health benefits of dietary astaxanthin, as well as its underlying bioactivity mechanisms. Recent studies have increased our understanding of the role of isomerization and esterification in the structure–function relationship of dietary astaxanthin. Gut microbiota may involve the fate of astaxanthin during digestion and absorption; thus, further knowledge is needed to establish accurate recommendations for dietary intake of both healthy and special populations. Associated with the regulation of redox balance and multiple biological mechanisms, astaxanthin is proposed to affect oxidative stress, inflammation, cell death, and lipid metabolism in humans, thus exerting benefits for skin condition, eye health, cardiovascular system, neurological function, exercise performance, and immune response. Additionally, preclinical trials predict its potential effects such as intestinal flora regulation and anti-diabetic activity. Therefore, astaxanthin is worthy of further investigation for boosting human health, and wide applications in the food industry.
Article
Aims: Astaxanthin-producing protist Aurantiochytrium limacinum can accumulate higher amounts of astaxanthin under light conditions; however, little is known about the impact of light exposure on its metabolism. Here, we investigated the transcriptional profile of A. limacinum under light conditions. Methods and results: Transcriptomic analyses revealed that 962 genes of A. limacinum showed a significant change in expression under light conditions, most of which (94.5%) were downregulated. Further, gene ontology enrichment analysis indicated that A. limacinum mainly downregulated genes associated with cell motility, proliferation, and gene expression processes, whose activities depend on ATP as an energy source. Additionally, the quantification of carotenoid and its transcripts suggested that β-carotene and astaxanthin biosynthesis pathways were rate-limiting and tightly regulated steps, respectively. In comparison, these processes were enhanced under light conditions. Conclusions: Considering that astaxanthin accumulation was highly correlated with reactive oxygen species (ROS) levels in microalgae, our results suggest that A. limacinum reduces ATP consumption to decrease the occurrence of ROS in mitochondria, while accumulating astaxanthin to prevent ROS damage. Significance and impact of study: This study provides novel insights into the impact of light exposure on A. limacinum metabolism, thereby facilitating a complete understanding of this protist for efficient astaxanthin production.
Article
Cardiovascular disease is the main contributor to morbidity and mortality worldwide. Based on its unique chemical features, the xanthophyll carotenoid astaxanthin is being proposed as a suitable preventive and therapeutic agent in cardiovascular disease. This review focuses on recent advances in astaxanthin research relevant to cardiovascular health and disease, i.e. its direct antioxidant, indirect antioxidant, anti-inflammatory, anti-hypertensive, anti-diabetic, renoprotective, lipid-lowering and anti-atherosclerotic activities in vitro and in vivo. Disparities in the biological activities and health benefits of astaxanthin observed in vitro (strong evidence), in animals (moderate evidence), and in humans (weak evidence) and the variety of astaxanthin sources hamper efforts to establish areas of astaxanthin application in human health care. A list of knowledge gaps and experimental pitfalls is proposed to overcome some of the short-comings in astaxanthin research.
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The singlet oxygen quenching activities among common hydrophilic and lipophilic antioxidants such as polyphenols, tocopherols, carotenoids, ascorbic acid, coenzyme Q10 and α-lipoic acid were recorded under the same test condition: the chemiluminescence detection system for direct 1O2 counting using the thermodissociable endoperoxides of 1,4-dimethylnaphthalene as 1O2 generator in DMF : CDCl3 (9 : 1). Carotenoids exhibited larger total quenching rate constants than other antioxidants, with astaxanthin showing the strongest activity. α-Tocopherol and α-lipoic acid showed considerable activities, whereas the activities of ascorbic acid, CoQ10 and polyphenols were only slight; these included capsaicin, probucol, edaravon, BHT and Trolox. This system has the potential of being a powerful tool to evaluate the quenching activity against singlet oxygen for various hydrophilic and lipophilic compounds.
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Astaxanthin, a xanthophyll carotenoid, accelerates lipid utilization during aerobic exercise, although the underlying mechanism is unclear. The present study investigated the effect of astaxanthin intake on lipid metabolism associated with peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in mice. Mice were divided into 4 groups: sedentary, sedentary and astaxanthin-treated, exercised, and exercised and astaxanthin-treated. After 2 weeks of treatment, the exercise groups performed treadmill running at 25 m/min for 30 min. Immediately after running, intermuscular pH was measured in hind limb muscles, and blood was collected for measurements. Proteins were extracted from the muscle samples and PGC-1α and its downstream proteins were measured by western blotting. Levels of plasma fatty acids were significantly decreased after exercise in the astaxanthin-fed mice compared with those fed a normal diet. Intermuscular pH was significantly decreased by exercise, and this decrease was inhibited by intake of astaxanthin. Levels of PGC-1α and its downstream proteins were significantly elevated in astaxanthin-fed mice compared with mice fed a normal diet. Astaxanthin intake resulted in a PGC-1α elevation in skeletal muscle, which can lead to acceleration of lipid utilization through activation of mitochondrial aerobic metabolism.
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Astaxanthin, one of the dominant carotenoids in marine animals, showed both a strong quenching effect against singlet oxygen, and a strong scavenging effect against free radicals. These effects are considered to be defence mechanisms in the animals for attacking these active oxygen species. The activities of astaxanthin are approximately 10 times stronger than those of other carotenoids that were tested, namely zeaxanthin, lutein, tunaxanthin, canthaxanthin and β-carotene, and 100 times greater than those of a tocopherol. Astaxanthin also showed strong activity as an inhibitor of lipid peroxidation mediated by these active forms of oxygen. From these results, astaxanthin has the properties of a “SUPER VITAMIN E”.
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The effects of the carotenoids β-carotene and astaxanthin on the peroxidation of liposomes induced by ADP and Fe2+ were examined. Both compounds inhibited production of lipid peroxides, astaxanthin being about 2-fold more effective than β-carotene. The difference in the modes of destruction of the conjugated polyene chain between β-carotene and astaxanthin suggested that the conjugated polyene moiety and terminal ring moieties of the more potent astaxanthin trapped radicals in the membrane and both at the membrane surface and in the membrane, respectively, whereas only the conjugated polyene chain of β-carotene was responsible for radical trapping near the membrane surface and in the interior of the membrane. The efficient antioxidant activity of astaxanthin is suggested to be due to the unique structure of the terminal ring moiety.
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We examined the effect of Astaxanthin (AST) on substrate metabolism and cycling time trial (TT) performance by randomly assigning 21 competitive cyclists to 28 d of encapsulated AST (4 mg/d) or placebo (PLA) supplementation. Testing included a VO2max test and on a separate day a 2 h constant intensity pre-exhaustion ride, after a 10 h fast, at 5% below VO2max stimulated onset of 4 mmol/L lactic acid followed 5 min later by a 20 km TT. Analysis included ANOVA and post-hoc testing. Data are Mean (SD) and (95% CI) when expressed as change (pre vs. post). Fourteen participants successfully completed the trial. Overall, we observed significant improvements in 20 km TT performance in the AST group (n=7; -121 s; 95% CI, -185, -53), but not the PLA (n=7; -19 s; 95% CI, -84, 45). The AST group was significantly different vs. PLA (P<0.05). The AST group significantly increased power output (20 W; 95% CI, 1, 38), while the PLA group did not (1.6 W; 95% CI, -17, 20). The mechanism of action for these improvements remains unclear, as we observed no treatment effects for carbohydrate and fat oxidation, or blood indices indicative of fuel mobilization. While AST significantly improved TT performance the mechanism of action explaining this effect remains obscure.
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The ketocarotenoid astaxanthin can be found in the microalgae Haematococcus pluvialis, Chlorella zofingiensis, and Chlorococcum sp., and the red yeast Phaffia rhodozyma. The microalga H. pluvialis has the highest capacity to accumulate astaxanthin up to 4-5% of cell dry weight. Astaxanthin has been attributed with extraordinary potential for protecting the organism against a wide range of diseases, and has considerable potential and promising applications in human health. Numerous studies have shown that astaxanthin has potential health-promoting effects in the prevention and treatment of various diseases, such as cancers, chronic inflammatory diseases, metabolic syndrome, diabetes, diabetic nephropathy, cardiovascular diseases, gastrointestinal diseases, liver diseases, neurodegenerative diseases, eye diseases, skin diseases, exercise-induced fatigue, male infertility, and HgCl₂-induced acute renal failure. In this article, the currently available scientific literature regarding the most significant activities of astaxanthin is reviewed.
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Astaxanthin (Ax), a carotenoid ubiquitously distributed in microorganisms, fish, and crustaceans, has been known to be a potent antioxidant and hence exhibit various physiological effects. We attempted in these studies to evaluate clinical toxicity and efficacy of long-term administration of a new Ax product, by measuring biochemical and hematological blood parameters and by analyzing brain function (using CogHealth and P300 measures). Ax-rich Haematococcus pluvialis extracts equivalent to 4, 8, 20 mg of Ax dialcohol were administered to 73, 38, and 16 healthy adult volunteers, respectively, once daily for 4 weeks to evaluate safety. Ten subjects with age-related forgetfulness received an extract equivalent to 12 mg in a daily dosing regimen for 12 weeks to evaluate efficacy. As a result, no abnormality was observed and efficacy for age-related decline in cognitive and psychomotor functions was suggested.
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Carotenoids are used for systemic photoprotection in humans. Regarding mechanisms underlying photoprotective effects of carotenoids, here we compared the modulation of UVA-related injury by carotenoids. Human dermal fibroblasts (HDF) were exposed to moderate doses of UVA, which stimulated apoptosis, increased levels of reactive oxygen species and thiobarbituric acid reactive substances, decreased antioxidant enzymes activities, promoted membrane perturbation, and induced the expression of heme oxygenase-1 (HO-1). The carotenoids astaxanthin (AX), canthaxanthin (CX) and beta-carotene (betaC) were delivered to HDF 24 h before exposure to UVA. Astaxanthin exhibited a pronounced photoprotective effect and counteracted all of the above-mentioned UVA-induced alterations to a significant extent. beta-Carotene only partially prevented the UVA-induced decline of catalase and superoxide dismutase activities, but it increased membrane damage and stimulated HO-1 expression. Moreover, betaC dose-dependently induced caspase-3 activity following UVA exposure. In contrast, CX had no effect on oxidative damage, except for HO-1 expression, which was augmented. Uptake of AX by fibroblasts was higher than that of the other two carotenoids. The photostability of the three compounds in fibroblasts was AX > CX > betaC. The data indicate that the oxo-carotenoid AX has a superior preventive effect towards photo-oxidative changes in cell culture.
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Dietary antioxidants may attenuate oxidative damage from strenuous exercise in various tissues. Beneficial effects of the antioxidant astaxanthin have been demonstrated in vitro, but not yet in vivo. We investigated the effect of dietary supplementation with astaxanthin on oxidative damage induced by strenuous exercise in mouse gastrocnemius and heart. C57BL/6 mice (7 weeks old) were divided into groups: rested control, intense exercise, and exercise with astaxanthin supplementation. After 3 weeks of exercise acclimation, both exercise groups ran on a treadmill at 28 m/min until exhaustion. Exercise-increased 4-hydroxy-2-nonenal-modified protein and 8-hydroxy-2'-deoxyguanosine in gastrocnemius and heart were blunted in the astaxanthin group. Increases in plasma creatine kinase activity, and in myeloperoxidase activity in gastrocnemius and heart, also were lessened by astaxanthin. Astaxanthin showed accumulation in gastrocnemius and heart from the 3 week supplementation. Astaxanthin can attenuate exercise-induced damage in mouse skeletal muscle and heart, including an associated neutrophil infiltration that induces further damage.
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We evaluated the effect of astaxanthin on visual function in 49 eyes of 49 healthy volunteers. They were over 40 years of age. They were divided into 4 groups matched for age and gender. Each group was given peroral astaxanthin once a day. The dosage was 0 mg, 2 mg, 4 mg, or 12 mg for each group. After ingestion of astaxanthin for consecutive 28 days, the uncorrected far visual acuity significantly improved in groups receiving 4 mg or 12 mg. The accommodation time significantly shortened in groups receiving 4 mg or 12 mg. There was no change in refraction, flicker fusion frequency, or pupillary reflex.
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Astaxanthin, a red carotenoid, has been known to possess excellent antioxidant activity and various biological activities, thereby attracting attention as a functional food material. The safety of astaxanthin administered orally has been demonstrated in human clinical studies for about ten years. In this review, we summarized the clinical studies related to safety, as well as studies on genotoxicity, and acute and subchronic toxicity, with a focus on AstaREAL, an astaxanthin product derived from Haematococcus pluvialis which has been reported in numerous human clinical studies to be safe and to have multiple health benefits. Furthermore, based on the latest research, we reviewed the effect of astaxanthin on drug-metabolizing enzymes involved in drug interactions, and concluded that the safety of H. pluvialis-derived astaxanthin, AstaREAL has been widely confirmed.
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The cosmetic effects on human skin by 4mg per day astaxanthin supplementation were demonstrated in a single blind placebo controlled study using forty-nine US healthy middle-aged women. There were significant improvements in fine lines/wrinkles and elasticity by dermatologist's assessment and in the moisture content by instrumental assessment at week 6 compares to base-line initial values.
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The present study was designed to investigate the effect of dietary supplementation with astaxanthin on physical performance. Forty healthy paramedic students were recruited for this test in a double blind placebo controlled study. In this study, we used algal meal (AstaREAL ® biomass) as astaxanthin supplementation. Twenty of the subjects received capsules filled with algal meal to provide 4 mg astaxanthin per capsule, whereas the other twenty received placebo capsules for six months. The physical parameters monitored were fitness, strength/endurance and strength/explosivity by standardized exercises. Before starting the dietary supplementation, base values for each of the subjects were obtained. At the end of the six month period of dietary supplementation, the average number of knee bendings (squats) increased by 27.05 (from 49.32 to 76.37) for subjects having received astaxanthin and by 9.0 (from 46.06 to 55.06) for the placebo subjects. Hence, the increase in the astaxanthin supplemented group was three times higher than that of the placebo group (P=0.047). None of the other parameters monitored differed significantly between the groups at the end of the study period. Based on this findings, it suggested that supplementation of astaxanthin is effective for the improvement of strength endurance that may lead to sports performance.
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Astaxanthin (Asx) is known to be a potent quencher of singlet oxygen and an efficient scavenger of superoxide anion. Therefore, Asx would be expected to be a useful antioxidant for the prevention of oxidative stress, a causative factor in severe diseases such as ischemic reperfusion injury. However, it is still unclear whether Asx has scavenging capability against the most potent reactive oxygen species (ROS), hydroxyl radical, because the hydrophobicity of Asx prevents analysis of hydroxyl radical scavenging ability in aqueous solution. In this study, to solve this problem, liposomes containing Asx (Asx-lipo), which could be dispersed in water, were prepared, and the scavenging ability of Asx-lipo for the hydroxyl radical was examined. The liposomal formulation enabled encapsulation of a high concentration of Asx. Asx-lipo gave a dose-dependent reduction of chemiluminescence intensity induced by hydroxyl radical in aqueous solution. Hydroxyl radical scavenging of Asx was more potent than α-tocopherol. The absorbance of Asx in the liposome decreased after reduction of hydroxyl radicals, indicating the direct hydroxyl radical scavenging by Asx. Moreover, Asx-lipo prevented hydroxyl radical-induced cytotoxicity in cultured NIH-3T3 cells. In conclusion, Asx has potent scavenging capability against hydroxyl radicals in aqueous solution, and this paper is the first report regarding hydroxyl radial scavenging by Asx.
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When oxygenic photosynthesis evolved, one of the key functions of carotenoids was to protect aerobic photosynthetic organisms against destruction by photodynamic sensitization. Aerobic photosynthesis would not exist without the coevolution of carotenoids alongside the chlorophylls. As carotenoids are abundant in nature, in many fruits and vegetables, they are able to react with excited states of appropriate energy and quench them, and they can react with free radicals according to their reactivity, redox potentials, and XÐH bond energies. This report concerns the bimolecular reactions of carotenoids with oxygen species, such as 3 O 2 , 1 O 2 , H , HO , À 2 , etc.
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Two human clinical studies were performed. One was an open-label non-controlled study involving 30 healthy female subjects for 8 weeks. Significant improvements were observed by combining 6 mg per day oral supplementation and 2 ml (78.9 μM solution) per day topical application of astaxanthin. Astaxanthin derived from the microalgae, Haematococcus pluvialis showed improvements in skin wrinkle (crow's feet at week-8), age spot size (cheek at week-8), elasticity (crow's feet at week-8), skin texture (cheek at week-4), moisture content of corneocyte layer (cheek in 10 dry skin subjects at week-8) and corneocyte condition (cheek at week-8). It may suggest that astaxanthin derived from H. pluvialis can improve skin condition in all layers such as corneocyte layer, epidermis, basal layer and dermis by combining oral supplementation and topical treatment. Another was a randomized double-blind placebo controlled study involving 36 healthy male subjects for 6 weeks. Crow's feet wrinkle and elasticity; and transepidermal water loss (TEWL) were improved after 6 mg of astaxanthin (the same as former study) daily supplementation. Moisture content and sebum oil level at the cheek zone showed strong tendencies for improvement. These results suggest that astaxanthin derived from Haematococcus pluvialis may improve the skin condition in not only in women but also in men.
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Previous studies have reported that astaxanthin (AXT) has antioxidative and anti-inflammatory effects in addition to its ability to shorten blood transit times. As laser speckle flowgraphy (LSFG) can noninvasively visualize the hemodynamics of the choroidal circulation, we used the technique to evaluate whether continuous ingestion of 12 mg of AXT per day could increase quantitative blood flow velocity. In this randomized, double-blind, placebo-controlled study, we examined 20 healthy volunteers who ingested 12 mg AXT or placebo capsules over a 4-week period. LSFG was measured in the right eyes of all subjects at pre-ingestion, and at 2 and 4 weeks after the treatment of AXT. LSFG values were used to calculate the square blur rate (SBR), which is a quantitative index of relative blood flow velocity. A significant increase of the macular SBR was seen 4 weeks after AXT ingestion when compared to the pre-ingestion values (Wilcoxon signed-rank test, P = 0.018). In contrast, no statistical difference in the macular SBR was detected in the placebo group (Friedman test, P = 0.598). No subjective or objective adverse events were found after the 12-mg AXT ingestion. Results suggest that administration of AXT over a 4-week period can elevate the choroidal blood flow velocity without any adverse effects.
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rights: 本文データは和漢医薬学会の許諾に基づき複製したものである We evaluated the effects of astaxanthin, a red carotenoid, on accommodation, critical flicker fusion (CFF), and pattern visual evoked potential (PVEP) in visual display terminal (VDT) workers. As controls, 13 non-VDT workers received no supplementation (Group A). Twenty-six VDT workers were randomized into 2 groups: Group B consisted of 13 subjects who received oral astaxanthin, 5 mg/day, for 4 weeks, and Group C consisted of 13 subjects who received an oral placebo, 5 mg/day, for 4 weeks. No significant difference in age was noted among the 3 groups. A double-masked study was designed in Groups B and C. Accommodation amplitude in Group A was 3.7± 1.5 diopters. Accommodation amplitudes (2.3±1.4 and 2.2±1.0 diopters) in Groups B and C before supplementation were significantly (p<0.05) lower than in Group A. Accommodation amplitude (2.8±1.6 diopters) in Group B after astaxanthin treatment was significantly (p<0.01) larger than before supplementation, while accommodation amplitude (2.3±1.1 diopters) in Group C after placebo supplementation was unchanged. The CFFs and amplitude and latency of P100 in PVEP in Group A were 45.0±4.2 Hz, 6.5±1.8μV, and 101.3±6.5 msec, respectively. The CFFs in Groups B and C before supplementation were significantly (p<0.05) lower than in Group A. The CCFs in Groups B and C did not change after supplementation. Amplitudes and latencies of P100 in PVEP in Groups B and C before supplementation were similar to those in Group A and did not change after supplementation. Findings of the present study indicated that accommodation amplitude improved after astaxanthin supplementation in VDT workers. 赤色カロチノイドの一種であるアスタキサンチンのvisual display terminal(VDT)作業者の調節力,中心フリッカー値,パターン視覚誘発電位に及ぼす影響を調べた。VDT作業を行わない13人をコントロールとした(Group A)。26人のVDT作業者を2群に無作為に分けた。Group Bはアスタキサンチン一日5mg 4週間内服した13人で,Group Cはアスタキサンチンを含有しないカプセルを4週間内服した13人とした。外見上同じカプセルでの内服投与を行った。結果:Group AはGroup B及びGroup Cと比較して,調節力,中心フリッカー値は有意に高い値であったが,パターン視覚誘発電位検査結果は,Group B,Cと有意差はなかった。Group Bでは,アスタキサンチンの投与前後で有意な調節力の改善がみられた(p<0.01)。しかし,中心フリッカー値,パターン視覚誘発電位に変化はみられなかった。Group Cでは,投与前後で,調節力,中心フリッカー値,パターン視覚誘発電位に変化はみられなかった。考察:VDT作業者では,非作業者と比べ調節力,中心フリッカー値が低下していることは以前より報告されており,今回の我々の研究でも同様の結果であった。VDT作業者で,アスタキサンチン非内服群では,調節力は投与前後で変化がなかったが,アスタキサンチンの内服群で,有意に調節力が改善した。VDT作業者の調節力の改善には,アスタキサンチンの内服が有効と考えられた。
Article
Effects of astaxanthin (AX) derived from H. pluvialis on human blood rheology were investigated in 20 adult men with a single-blind method. The experimental group was 57.5 +/- 9.8 years of age and the placebo group was 50.8 +/- 13.1 years of age. A blood rheology test that measures whole blood transit time was conducted using heparinized blood of the volunteers by a MC-FAN apparatus (microchannel array flow analyzer). After administration of AX 6 mg/day for 10 days, the values of the experimental group were decreased from 52.8 +/- 4.9 s to 47.6 +/- 4.2 s (p<0.01) and a comparison of the values between the experimental (47.6 +/- 4.2 s) and the placebo (54.2 +/- 6.7 s) groups showed a significant difference (p<0.05). There were no adverse effects resulting from the administration of AX 6 mg/day for 10 days. Informed consent was obtained from each subject.
Article
A growing body of scientific literature indicates that astaxanthin is a more powerful antioxidant than other carotenoids and vitamin E and may confer numerous health benefits. The purpose of this investigation was to conduct a human safety study with a Haematococcus pluvialis algal extract with high levels of astaxanthin. Thirty-five healthy adults age 35-69 years were enrolled in a randomized, double-blind, placebo-controlled trial of 8 weeks' duration. All participants took three gelcaps per day, one at each meal. Nineteen participants received gelcaps with an algal extract in safflower oil, containing 2 mg of astaxanthin each (treatment); 16 participants received gelcaps containing safflower oil only (placebo). Blood pressure and blood chemistry tests, including a comprehensive metabolic panel and cell blood count, were conducted at the beginning of the trial and after 4 and 8 weeks of supplementation. No significant differences were detected between the treatment and the placebo groups after 8 weeks of supplementation with the algal extract in the parameters analyzed, except for serum calcium, total protein, and eosinophils (P <.01). Although the differences in these three parameters were statistically significant, they were very small and are of no clinical importance. These results reveal that 6 mg of astaxanthin per day from a H. pluvialis algal extract can be safely consumed by healthy adults.
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RANKL is an essential factor for osteoclastogenesis. Amgen research group has developed AMG 162, a fully human monoclonal antibody to RANKL. The bone antiresorptive activity and safety of AMG 162 were evaluated in 49 healthy postmenopausal women (Phase I study). The effect of increasing amounts of AMG 162 on bone mineral density (BMD) was studied in 411 postmenopausal women with low BMD (Phase II study). A single subcutaneous dose of AMG 162 (1 mg/kg or 60 mg) suppressed bone resorption for more than 6 month without critical side effects (Phase I study), and increased BMD within 1 month in postmenopausal women (Phase II study).
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The biological benefits of certain carotenoids may be due to their potent antioxidant properties attributed to specific physico-chemical interactions with membranes. To test this hypothesis, we measured the effects of various carotenoids on rates of lipid peroxidation and correlated these findings with their membrane interactions, as determined by small angle X-ray diffraction approaches. The effects of the homochiral carotenoids (astaxanthin, zeaxanthin, lutein, beta-carotene, lycopene) on lipid hydroperoxide (LOOH) generation were evaluated in membranes enriched with polyunsaturated fatty acids. Apolar carotenoids, such as lycopene and beta-carotene, disordered the membrane bilayer and showed a potent pro-oxidant effect (>85% increase in LOOH levels) while astaxanthin preserved membrane structure and exhibited significant antioxidant activity (40% decrease in LOOH levels). These findings indicate distinct effects of carotenoids on lipid peroxidation due to membrane structure changes. These contrasting effects of carotenoids on lipid peroxidation may explain differences in their biological activity.
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Intracellular redox balance may affect nutrient metabolism in skeletal muscle. Astaxanthin, a carotenoid contained in various natural foods, exerts high antioxidative capacity in the skeletal muscles. The present study investigated the effect of astaxanthin on muscle lipid metabolism in exercise. ICR mice (8 weeks old) were divided into four different groups: sedentary, sedentary treated with astaxanthin, running exercise, and exercise treated with astaxanthin. After 4 weeks of treatment, exercise groups performed treadmill running. Astaxanthin increased fat utilization during exercise compared with mice on a normal diet with prolongation of the running time to exhaustion. Colocalization of fatty acid translocase with carnitine palmitoyltransferase I (CPT I) in skeletal muscle was increased by astaxanthin. We also found that hexanoyl-lysine modification of CPT I was increased by exercise, while astaxanthin prevented this increase. In additional experiment, we found that astaxanthin treatment accelerated the decrease of body fat accumulation with exercise training. Our results suggested that astaxanthin promoted lipid metabolism rather than glucose utilization during exercise via CPT I activation, which led to improvement of endurance and efficient reduction of adipose tissue with training.