August 13, 2018
Carotenoids belong to the category of lipid-soluble terpenes (as a tetraterpenoid) compounds. There are more than 1,100 known carotenoid compounds, and they are split into two classes: carotenes (which are unoxygenated and include α-carotene, β-carotene and lycopene) and xanthophylls (which contain oxygen), such as astaxanthin, canthaxanthin, lutein and zeaxanthin. Carotenoids are found in high concentrations in plants, algae and microorganisms. Humans cannot synthesize them and therefore are required to ingest them in their diet. The carotenoids that have been most studied for human health include astaxanthin, beta-carotene, lycopene, lutein and zeaxanthin.
Empirical formula: C40H52O4
Molecular weight: 596.84 g/mol (molar mass)
Astaxanthin, a deep reddish-orange color compound, was first identified and isolated in 1938 by Richard Kuhn. He had a laboratory on the Neckar River (Germany). When studying lobsters to determine what gave them their color, he named the carotenoid astaxanthin—“asta” (from Astacus gammarus, the scientific name for lobster) and “xanthin” (from xanthophyll, which is the class in which astaxanthin belongs). Kuhn was awarded the 1938 Nobel Prize in Chemistry for his work on carotenoids and vitamins.
Astaxanthin possesses two identical asymmetric atoms at C-3 and C-3’ making possible for three optical isomers (with all-trans configuration) to exist on the molecular chain: (3S,3’S), (3R,3’S) and (3R,3’R). Two of the stereoisomers (3S,3′S) and (3R,3′R) are the most abundant in nature.
There are two forms of astaxanthin: free and esterified. Astaxanthin may be esterified with different fatty acids, such as palmitic, oleic, stearic or linoleic acid; it may also be free (with non-esterified hydroxyl groups), but this makes it much more unstable and susceptible to oxidation. The esterified form is reportedly the most predominant in nature and sold commercially; however, the free form can also be found.1 Regardless of which form is ingested, only the free form is found in human blood.2,3,4
Commercial astaxanthin is mainly derived from three sources: Xanthophyllomyces dendrorhous (yeast, formerly called Phaffia rhodozyma), Haematococcus pluvialis (microalgae) and through chemical synthesis (synthetic). Phaffia produces mainly the (3R,3′R)-isomer; H. pluvialis biosynthesizes the (3S,3′S)-isomer; and synthetic astaxanthin comprises a racemic mixture of isomers (3S,3′S) (3R,3′S) and (3R,3′R) typically in 1:2:1 ratios.
Natural astaxanthin is a carotenoid produced naturally in microalgae, yeast, bacteria and fungi, and found in microalgae, yeast, salmon, trout, krill, lobster, shrimp, crayfish and crustaceans. In the aquatic environment, microalgae are consumed by zooplankton, insects or crustaceans, which accumulate astaxanthin and, in turn, are ingested by fish.
Synthetic production of astaxanthin is not preferred in some cases because synthetic astaxanthin contains a racemic mixture of stereoisomers. It is produced chemically (synthesized by combining isophorone and C10-dialdehyde together in several reactive steps). Synthetic astaxanthin is non-esterified, whereas astaxanthin in algae is always esterified.
Astaxanthin is primarily used as a dietary supplement for human consumption and as a feed supplement (pigmentation/colorant) for salmon, crabs, shrimp, chickens and egg production. Astaxanthin cannot be produced by humans; it must be ingested via diet or supplementation, like the other carotenoids.
To date, there are more than 1,000 peer-reviewed papers published in scientific journals studying the health effects of astaxanthin. Most research studies to date have used dosages between 2 mg and 24 mg daily.
Astaxanthin is a very strong antioxidant. The unique structure of astaxanthin allows it to span biological membranes and act as an antioxidant by reducing free radicals, therefore stabilizing them.5,6 Astaxanthin as an antioxidant is 550 times stronger than vitamin E in singlet oxygen quenching.7
Astaxanthin also improves plasma lipid antioxidant activity; the levels of blood plasma 12- and 15-hydroxy fatty acids lipids were reduced statistically and significantly in the astaxanthin group.8
Antihypertensive, neuroprotective effects
In a double-blind, placebo-controlled study conducted in Japan, 20 healthy postmenopausal women who ingested 12 mg/d astaxanthin for four weeks experienced reductions of systolic and diastolic blood pressure by 7% and 4%, respectively.9
Astaxanthin’s anti-inflammatory properties are closely related to its antioxidant activity.
Among benefits, astaxanthin has shown its ability to reduce levels of C-reactive protein (CRP), a marker of inflammation in the body. The study showed a correlation between daily use of astaxanthin for eight weeks and significantly lowered CRP compared to placebo.10 One ongoing project at the University of Eastern Finland in Kuopio investigated the effect of astaxanthin supplementation on lipid peroxidation. The astaxanthin group had a significant drop in the levels of hydroxy fatty acids (which increase inflammation) as compared to the placebo group. Further, astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans.11
Results from a study published in 2004 in BioFactors showed a lower level of blood glucose in diabetic mice treated with astaxanthin than in a non-treated group; the antioxidative activity of astaxanthin reduced stress on the kidneys and prevented renal cell damage.12 The researchers concluded astaxanthin may be useful in preventing diabetic nephropathy.
A 2009 study, published in the Journal of Agricultural and Food Chemistry, reported the benefits of astaxanthin for diabetics. The study showed the antioxidant power of astaxanthin can protect cells against oxidative damage caused by high glucose (sugar) levels. High blood sugar levels and oxidative stress are associated with complications common among diabetics, including kidney disease, neuropathy (nerve damage) and diabetic retinopathy (vision problems).13
A Japanese study showed astaxanthin has the potential to inhibit inflammation-mediated skin deterioration, such as wrinkle formation and seasonal skin moisture decline, thereby retarding the progression of skin aging.14
Results from a study by scientists in Rome, Italy, compared several carotenoids to see how they protected skin against the damaging effects of ultraviolet (UV) rays from the sun.15 According to the study, published in Experimental Dermatology, fibroblasts from skin were treated with carotenoids before being exposed to UVA, with only astaxanthin showing a significant photoprotective effect, modulating most of the UVA-induced injuries.15,16
Astaxanthin has been found to prevent or slow three of the most common eye diseases: age-related macular degeneration (AMD), glaucoma and eye strain.
The human retina naturally contains the carotenoids lutein and zeaxanthin, molecules closely related to astaxanthin. Supplementation with all three carotenoids has been shown to improve visual acuity and contrast detection in people with early AMD.17
Studies of patients with AMD revealed significant improvements in retinal electrical outputs following supplementation with astaxanthin and other carotenoids.18
Glaucoma, an increase in the pressure of fluid inside the eyeball, eventually results in retinal cell death from oxidant damage and loss of blood flow. Astaxanthin restores retinal parameters to normal in eyes with experimentally induced glaucoma.19
Working for long periods at visual display terminals reportedly induces various visual problems such as eye strain, blurring and diplopia (double vision). In a double-blind study performed in Japan, four weeks of supplementation with 5 mg/d astaxanthin led to a 46% reduction of eye strain and higher accommodation amplitude in visual display terminal.20
Astaxanthin is a promising compound for human health and nutrition applications, but more information and research is needed. Different producers recommend different astaxanthin dosage levels for various health conditions. Because there have not been enough studies to determine the ideal dose of astaxanthin, there are no standardized dosage recommendations. Doses of up to 50 mg/d of astaxanthin have been tolerated (the exact toxicity and upper limit is also not known).
Some studies have suggested the lowest “no observed adverse effect” level is 40 mg/kg bodyweight/d. An acceptable daily intake (ADI) is conventionally derived using a 100-fold safety factor applied to the lowest without observed adverse effects. This equates to an ADI intake of 0.4 mg/kg bodyweight/d for a person.
Robin Koon is Executive Vice-President at Best Formulations (bestformulations.com), has more than 35 years of pharmaceutical experience in clinical pharmacy, as a retail drug chain executive overseeing operations, in managed-care, and manufacturing.
Yanai H et al. “Antihypertensive effects of astaxanthin.” Integr Blood Press Control. 2008;1:1–3.
Satoh A et al. “Preliminary Clinical Evaluation of Toxicity and Efficacy of A New Astaxanthin-rich Haematococcus pluvialis Extract.” J Clin Biochem Nutr. 2009 May;44(3):280–284.
Østerlie M et al. “Plasma appearance and distribution of astaxanthin E/Z and R/S isomers in plasma lipoproteins of men after single dose administration of astaxanthin.” J Nutr Biochem. 2000;11(10):482-90.
Coral-Hinostroza GN et al. “Plasma appearance of unesterified astaxanthin geometrical E/Z and optical R/S isomers in men given single doses of a mixture of optical 3 and 3'R/S isomers of astaxanthin fatty acyl diesters.” Comp Biochem Physiol C Toxicol Pharmacol. 2004 Oct;139(1-3):99-110.
Hussein G et al. “Antihypertensive potential and mechanism of action of astaxanthin: III. Antioxidant and histopathological effects in spontaneously hypertensive rats.” Biol Pharm Bull. 2006 Apr;29(4):684-8.
Ambati R et al. “Astaxanthin: Sources, Extraction, Stability, Biological Activities and Its Commercial Applications—A Review.” Mar Drugs. 2014 Jan;12(1):128–152.
Shimidzu N, Goto M, Miki W. “Carotenoids as Singlet Oxygen Quenchers in Marine Organisms.” Fisheries Science. 1996;62:134-37.
Karpi et al. “Effects of astaxanthin supplementation on lipid peroxidation.” International Journal for Vitamin and Nutrition Research. 2007;77:3-11.
Hussein et al. “Astaxanthin, a Carotenoid with Potential in Human Health and Nutrition.” J Nat Prod. 2006;69(3):443-449.
Spiller et al. “Effect of daily use natural astaxanthin on C-reactive protein.” 2006. Health Research & Studies Center. Los Altos, CA.
Park J et al. “Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans.” Nutrition & Metabolism. 2010;7:18.
Naito Y et al. “Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice.” 2008. DOI: 10.1002/biof.5520200105.
Kim TJ et al. “Protection against Oxidative Stress, Inflammation, and Apoptosis of High-Glucose-Exposed Proximal Tubular Epithelial Cells by Astaxanthin.” Journal of Agricultural and Food Chemistry. 2009;57(19):8793–97.
Tominaga K et al. “Protective effects of astaxanthin on skin deterioration.” Journal of Clinical Biochemistry and Nutrition. 2017;61(1):33–39.
Lyons NM, O’Brien NM. Modulatory effects of an algal extract containing astaxanthin on UVA-irradiated cells in culture. J Dermatol Sci. 2002 Oct;30(1):73-84.
Hama S, Takahashi K, Inai Y, et al. Protective effects of topical application of a poorly soluble antioxidant astaxanthin liposomal formulation on ultraviolet-induced skin damage. J Pharm Sci. 2012 Aug;101(8):2909-16.
Piermarocchi S et al. “Carotenoids in Age-Related Maculopathy Italian Study (CARMIS): two-year results of a randomized study.” Eur J Ophthalmol. 2012 Mar-Apr;22(2):216-25.
Parisi et al. “Carotenoids and antioxidants in age-related maculopathy Italian study: multifocal electroretinogram modifications after 1 year.” Ophthalmology. 2008 Feb;115(2):324-33 e2.
Cort et al. “Suppressive effect of astaxanthin on retinal injury induced by elevated intraocular pressure.” Regul Toxicol Pharmacol. 2010 Oct;58(1):121-30.
Nagaki et al. “Effects of Astaxanthin on accommodation, critical flicker fusion, and pattern visual evoked potential in visual display terminal workers.” Journal of Traditional Medicines. 2002;19 (5):170-173.
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