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ANTIOXIDANT EFFECTS OF ATAXANTHIN IN VARIOUS DISEASES
A REVIEW
ABSTRACT:
BACKGROUND: Astaxanthin, a potent antioxidant carotenoid has been found to be highly
effective in mopping up free radicals as it possesses anti-oxidative, anti-inflammatory, anti-
apoptotic and other beneficial pharmacological properties. Many chemical reactions produce
free radicals which are injurious to body cells, as they are the causes of many diseases,
disabilities and death. Antioxidants suppress and mop up these circulating free radicals.
METHOD: This review was done by a comprehensive literature search using internet search
engines linked to academics such as ebsco, pubmed, google scholar,etc.They were assessed
on topics related to astaxanthin. Articles related and linked to studies involving astaxanthin
were thoroughly searched and the references of such articles were also searched for
information about astaxanthin in relation to medical application.
RESULTS: In various studies astaxanthin has been found to be a potent carotenoid as an
antioxidant thereby protective to the body as it prevents cancer, enhance eye health, suppress
lipid peroxidation and atherosclerosis, enhance skin and brain health and suppress the
formation of complications of diabetes mellitus.
CONCLUSION: Astaxanthin, a highly potent xanthophylls carotenoid has multiple
pharmacological properties and oral supplements of this anti-oxidant are protective against a
wide range of diseases.
KEYWORDS: Astaxanthin, free radical, antioxidant, cancer, carotenoids
INTRODUCTION
FREE RADICALS
Free radicals are molecules containing one or more unpaired electrons which give a
considerable degree of chemical reactivity to it [1,2]. Most of these free radicals come from
intracellular and extracellular processes in biological fluids. The plasma membranes of cells
are potential sources of free radicals [3,4]. Other ways of free radical generation are:
exposure to ionizing radiation, cigarette smoking, drug ingestion, and exposure of red blood
cells to chemicals such as acetyl phenylhydrazine and hydrogen peroxide (H2O2)[5].
Exposure of some neonates to oxidants such as dusting powder and camphor balls result in
increased haemolysis due to generation of free radicals [6].Free radicals are injurious to body
cells and tissues and need to be mopped up by antioxidants .Various sources of antioxidants
exist such as vitamin C,E and gluthatione. Astxanthin is considered a potent antioxidant.
ANTIOXIDANTS
Antioxidants are protective against free radicals such that the possible detrimental
effects of these free radicals that are generated are kept on check. Hence, antioxidants
stabilize free radicals’ reaction. Some antioxidants may be enzymes such as glutathione
reductase, superoxide dismutase, and catalase [7]. Dietary antioxidants also exist such as
vitamins A, C, E, and beta carotene.
Generally, antioxidants are divided into two major groups:
Water Soluble (Hydrophilic): Which are potent in blood, intracellular fluid (ICF), and
extracellular fluid (ECF). They react with oxidants in the cell cytosol and blood plasma.
Examples of such are vitamin C, glutathione, and catechins. Lipid Soluble (Hydrophobic):
They are localized to cellular membranes and lipoproteins. These include vitamins A, E, and
beta carotene [5,8]. Generally, antioxidants are helpful in preventing or delaying cell
damage as they mop up free radicals generated from cellular processes. Several antioxidants
have been evaluated such as vitamin C (ascorbic acid), vitamin E (tocopherol), beta carotene,
selenium, lycopene and astaxanthin [8,9].
ASTAXANTHIN
Astaxanthin is a lipophilic terpene which is made up from carbon precursors [10,11].
It is a metabolite of zeaxanthin and canthaxanthin, containing hydroxyl and ketone functional
groups [10,11]. Astaxanthin, being a xanthophyll carotenoid is chemically identified as 3, 3’-
dihydroxy-B, B1-Carotene-4, 4-Dione. It is lipid soluble and distinguished from all other
carotenoids, and has a molecular mass of 596.84 g/mol with a formula of C40H52O4. It has
conjugated double bonds at its centre – giving it, its antioxidant effects [10, 12].
Humans cannot synthesize astaxanthin in the body [13]. Historically, Professor Basil
Weedon’s group was the first to prove the structure of astaxanthin by synthesis in 1970[14].
Like all other carotenoids, astaxanthin is absorbed alongside fatty acids via passive diffusion
into the intestinal epithelium [15].Sources of astaxanthin are yeasts, krill, trout, microalgae,
shrimps, and crayfish. Astaxanthin is present in most red-coloured aquatic organisms [13,
15]. The primary sources of astaxanthin in high concentrationsare given below [10].
Natural Sources
Concentration of Astaxanthin (Parts per
million)
Salmonids
5
Plankton
Krill
60
120
Arctic shrimp
1200
(P. borealis)
Phaffia yeast
(Xanthophyllomyces dendrorhous)
10,000
Haemococcus pluvialis
40,000
Algae are the primary natural sources of astaxanthin in the aquatic food chain. The
primary industrial sources for natural astaxanthin are the microalgae, Haemococus pluvialis.
Commercial astaxanthin for aquaculture are produced synthetically [10].
HISTORICAL EVOLVEMENT OF ASTAXANTHIN IN MEDICAL USES
Since its discovery in 1970, astaxanthin has evolved through some technological
processes to be useful in everyday life uses. It is now mainly extracted from haematococcus
using high pressure liquid chromatography and identified by mass spectrometry [16].
Currently, astaxanthine has been approved as a food colorant in animal and fish feed
[17].Over the years, attempts have been made by scientists to synthetically produce the
products of Haemococcus pluvialis. Lee et al demonstrated that, adding 1-
aminocyclopropane-1-carboxylic acid could enhance the accumulation of astaxanthin, while
Shang et al suggested that synthetic Haemococcus pluvialis production is enhanced by using
butylated hydroxyanisole[18,19].
Consumption of astaxanthin can reduce, and prevent various disorders in human and
animals. Synthetic astaxanthin has a dominant role in agriculture. The consumption of
astaxanthin can reduce or prevent risk of various disorders in human and animals. Synthetic
astaxanthin are produced by phaffe yeast and H.pluviali through chemical synthesis [20].
MECHANISM OF ACTION OF ASTAXANTHIN
Usually, carotenoids are absorbed into body lipids which are enhanced by high
cholesterol. On absorption, astaxanthin mixes with bile acid to make micelles and are
incorporated into chylomicron. Astaxanthin is then assimiliated with lipoprotein and
transported to body tissues to protect cells, and lipid-based membrane against oxidative
damage [21]. Also, astaxanthin contain polyene chain and multiple double bonds which
quench singlet oxygen and radicals to stop reaction. Antioxidant properties have been linked
to their chemical and physical interactions with cell membrames. The polyene chain in
astaxanthin mops up free radicals in the cell membrane [22].
REVIEW OF MEDICAL USES OF ASTAXANTHIN
Over 50 clinical and experimental studies show that astaxanthin is important in
cardiovascular health, eye health, brain health, sports-related activities, skin health, diabetes
mellitus and metabolic syndrome, cancer health and a whole lot of other disease entities
[23,24]. In general, with regards to general antioxidant effects (free radical scavenging),
astaxanthin are more than 65 times stronger than vitamin C, and 50 times more powerful than
vitamin E in protecting cell membranes. In addition, astaxanthin has been shown to be more
effective than other carotenoids and other nutrients at singlet oxygen quenching by being up
to 800 times stronger than coenzyme Q, 6000 times greater than Vitamin C, 550 times more
powerful than green tea catechins, and 11 times stronger than beta carotene.It is also found to
be 2.75 times stronger than lutein. Research suggests that astaxanthin may be beneficial in
immune, inflammatory and neurodegenerative diseases [25,26, 27]. Astaxanthin has been
shown to play a role in several diseases.
CANCER PREVENTION
Several researches have deciphered that astaxanthine exerts in activity such as anti-
proliferation, anti-apoptosis and anti-invasion, via different molecules and pathways
including signal transducers and activator of transcription 3(STAT 3), nuclear factor Kappa
light chain enhancer of activated β-cell (NF-Kβ), and peroxisome proliferator activator
receptor gamma (PPAR-γ),and other multiple mechanism of cancer effects.According to
Zhang et al, astaxanthin is thought to protect body tissues from oxidation and ultraviolet
damage through suppression of NF-KB activation[28,29]. Astaxanthin also prevents cancer
initiation by protecting the body DNA from ultraviolet oxidant damage. This it does, by
promoting early detection and destruction of cells that have undergone malignant
transformation by avoiding immune surveillance [30,31]. Also, other reaserchers(Yuan et al,
Palozza et al, and Nagendraprablu et al)confirm that astaxanthin prevents tumor from
spreading by reducing tumor production of tissue-melting proteins and blocks the rapid cell
replication of tumors in their growth phase by stopping the cancer cell reproductive cycle
and enhancing apoptosis[13,28,32,33].
EYE HEALTH
Health benefits of astaxanthin includes protection against eye-related macular
degeneration (the most common cause of blindness), and inflammatory eye conditions.
Astaxanthin protects the eye against eye- fatigue, improves visual activity and depth
perception and increases blood flow to eye tissues.
Astaxanthin does this because it crosses the blood-retinal barrier hence protecting the
eyes. These antioxidant properties have protective effects on the eyes, protecting it against
cataract, macular degeneration and even blindness. Tsuneto and Akihiko concluded that
astaxanthin reduces cataract formation, glaucoma and macular degeneration [34].
PREVENTION OF COMPLICATIONS OF DIABETES MELLITUS
In 2015, Meta analysis of data from 10 randomized control studies showed a
significant effect of supplementation with astaxanthin on plasma lipid profile and fasting
glucose. In another research, involving db/db mice, prevention of diabetic nephropathy was
noted on treatment with astaxanthin. It is found that chronic administration of astaxanthin
reduces the oxidative stress on the kidneys, and prevents renal cell damage. A dose of 6.8mg
a day decreased the level of blood glucose [35, 36, 37]. Uchiyama et al and Ambati et al
noted that giving astaxanthin to obese or/and diabetic animals experienced lower plasma
glucose levels, improved insulin sensitivity and reduced inflammation and oxidative stress
[33]. In addition, astaxanthin enhanced the ability of the pancreas to secrete insulin and
slowed down the rate of diabetic nephropathy [27,38, 39].
BRAIN HEALTH/STROKE/HYPERTENSION PREVENTION
Neuro-protective effects of astaxanthin have also been noted in experimental animals.
It is known to protect against stroke and hypertension and in improving memory in vascular
dementia as noted by Hussein et al [40, 41,42,43]. Astaxanthin crosses the blood brain barrier
hence protecting the brain. At a given dose of 6-8mg daily, there was a reduction in blood
pressure in studied individuals [35,36,37]. Neuroprotective properties of the marine
carotenoid, astaxanthin and omega -3-fatty acid are seen as prospective future combinations
[44]. Fassett et al further noted that astaxanthin protects against aging and improve mental
functions in rats, 50mg/kg astaxanthin oil reduced both systolic and diastolic blood pressure
in spontaneously hypertensive rats/mrc-cp rats (a model for metabolic syndrome)[45].
SPORTS-RELATED ACTIVITIES
Astaxanthin is known to promote muscle endurance and protects against muscle
damage [46,47]. Astaxanthin limits exercise - induced skeletal muscle damage in mice. It is
now used by athletes to enhance performance. The same properties it has that make it
beneficial for salmon to swim upstream are beneficial to humans looking to accomplish feats
of endurance. This finding is well supported by Ikeuchi et al [47,48,49]. This it does by
reducing the production and storage of lactic acid, reducing free radical, and supporting
mitochondrial function [50].
SKIN HEALTH
Astaxanthin reduces the fine lines and wrinkles, improves skin elasticity, protects
against sun damage and prevents age-spots and hyperpigmentation. Astaxanthin works as an
internal sunscreen of sort; since it reduces inflammation, and reduces ultraviolet damage to
skin cells [51]. It is a potent ultraviolet radiation absorber [27]. Tominaga et al in a study
involving 38 healthy females gave 6mg/day of astaxanthin oral supplement and 2mls per day
topical astaxanthin to the participating subjects. Their results showed that the H.pluvialis-
derived astaxanthin improved skin conditions in all layers such as corneolyte layer,
epidermis, basal and dermis layer by combining oral and topical treatment [52]. Astaxanthin
is believed to offer skin protection through a number of mechanisms. First, it is believed to
block a certain amount of the ultraviolet (UV) radiation acting directly on the skin. Secondly,
it neutralizes the free radicals induced by the UV radiation. Thirdly, it appears to inhibit the
induction of matrix metalloproteinase (MMP) by UV light.MMP is thought to be an
important factor in sun damage and skin aging [53]. In yet another study in 1998, Savoure et
al also noted that astaxanthin, when given alone or in combination with retinol, substantially
reduced/prevented photo-aging of the skin. This study in rats also showed that astaxanthin
was found to be 100 times stronger than beta carotene and 1000 times stronger than lutein in
preventing UV light –induced oxidative stress [54].
PEPTIC ULCER DISEASE (PUD) PREVENTION
The ulcer-preventing ability was studied in India when researchers (Kamath et al) at
Central Food Technological Institute gave total carotenoids and astaxanthin esters orally at
doses of 100, 250, 5000mcg/kg to rats. After being fed antioxidants, ethanol was then given
to induce gastric ulcer in the studied rats. The researchers noted that lipoxygenase inhibitors
in the rat cells were 23 times greater when astaxanthin was given, compared to administration
of omeprazole, a proton-pump inhibitor used for PUD management. They concluded that free
radicals-scavenging activity of astaxanthin found in H. pluvialis protects against gastric
mucosal injury [27,55,56].
LIPID PEROXIDATION/ATHEROSCLEROSIS PREVENTION
Astaxanthin is thought to inhibit lipid peroxidation and simultaneously simulate
cancer cells, making it effective for treating breast, colon, and bladder cancers. Also,
astaxanthin reduces C-reactive protein (CRP) in the cardiovascular system, reducing
triglycerides, increasing high density lipoprotein (HDL) cholesterol and adiponectin levels. In
another study, done in Finland, Karppi et al assessed the effect of three-month astaxanthin
supplementation on certain healthy non-smokers aged between 19-33 years. The intervention
group received two 4mg capsules daily, while the control received placebo. Their findings
suggest that the supplementation with astaxanthin decreased the in-vivo oxidation of fatty
acids in the healthy men [57]. In yet another study by Jacobsson et al, taking 6-8mg of daily
of astaxanthin decreased the oxidation of low density lipoprotein- cholesterol and prevented it
from atherogenic effect [58]. It protects the vascular lining, promotes improved blood flow,
and protects cholesterol from being oxidized. Astaxanthin is thought to play a role in
atherosclerosis prevention due to it antioxidant and anti-inflammatory effects in endothelial
cells. Dysfunction of both systems in these cells produces a pro-atherogenic state [17, 45, 59].
CONCLUSION
From its discovery till now, astaxanthin has been found to be a useful antioxidant
which has the potential of mopping up free radicals. The chemical structure of astaxanthin
makes it an excellent antioxidant. This single property has been found to be beneficial to
man. These protective effects range from free radical scavenging, mitochondrial protection,
anti-inflammatory effects and protection from glycation [60,61].
With the advancement in technology, synthetic production of astaxanthin by genetic
engineering will go a long way in supplying the needed astaxanthin in both agricultural and
medical uses. It is believe that extraction of astaxanthin from its natural sources and
synthetic-based forms will play a great role in the management of patients because of its large
pharmacological benefits to man.
CONFLICT OF INTEREST: None declared
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