Antioxidant effects of astaxanthin 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 the 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, enhances eye health, suppresses lipid peroxidation and atherosclerosis, enhances skin and brain health, and suppresses 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.

Full text

JOURNAL OF MOLECULAR PATHOPHYSIOLOGY, 2018
VOL 7, NO. 1, PAGE 1–6
10.5455/jmp.20180627120817
REVIEW ARTICLE Open Access
Anoxidant eects of astaxanthin in various diseases—a review
Lawson Ekpe1, Kenneth Inaku1, Victor Ekpe2
1Department of Chemical Pathology, University of Calabar, Calabar, Nigeria
2Drexel University, Philadelphia, PA
Contact Lawson Ekpe lawsonekpe2002@yahoo.com Department of Chemical Pathology, University of Calabar, Calabar, Nigeria.
© 2018 The Authors. This is an open access arcle under the CC BY license (hps://creavecommons.org/licenses/by/4.0/).
ABSTRACT
Background: Astaxanthin, a potent anoxidant carotenoid has been found to be highly
eecve in mopping up free radicals as it possesses an-oxidave, an-inammatory,
an-apoptoc, and other benecial pharmacological properes. Many chemical reac-
ons produce free radicals which are injurious to body cells, as they are the causes of
many diseases, disabilies, and death. Anoxidants suppress and mop up these circulat-
ing 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. Arcles related and linked to studies
involving astaxanthin were thoroughly searched and the references of such arcles were
also searched for informaon about astaxanthin in relaon to the medical applicaon.
Results: In various studies, astaxanthin has been found to be a potent carotenoid as an
anoxidant thereby protecve to the body as it prevents cancer, enhances eye health,
suppresses lipid peroxidaon and atherosclerosis, enhances skin and brain health, and
suppresses the formaon of complicaons of diabetes mellitus.
Conclusion: Astaxanthin, a highly potent xanthophylls carotenoid has mulple pharma-
cological properes, and oral supplements of this an-oxidant are protecve against a
wide range of diseases.
ARTICLE HISTORY
Received June 27, 2018
Accepted August 20, 2018
Published September 26, 2018
KEYWORDS
Astaxanthin; free radical;
anoxidant; cancer;
carotenoids
Introducon
Free radicals
Free radicals are molecules containing one or
more unpaired electrons which give a consid-
erable degree of chemical reactivity to it [1,2].
Most of these free radicals come from intracellu-
      -
ids. The plasma membranes of cells are potential
sources of free radicals [3,4]. Other ways of free
radical generation are exposure to ionizing radi-
ation, cigarette smoking, sunlight, drug inges-
tion, 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 results in increased hemolysis due to the
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 vitamins C and E and
glutathione. Astaxanthin is considered a potent
antioxidant.
Anoxidants
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’ reac-
tion. 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, anti-
oxidants are divided into two major groups:
Water soluble (hydrophilic)
       
  
cell cytosol and blood plasma. Examples of such are
vitamin C, glutathione, and catechins.

2 J Mol Pathophysiol • 2018 • Vol 7 • Issue 1
Lawson Ekpe, Kenneth Inaku, Victor Ekpe
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 evalu-
ated 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 of 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 identi-

lipid soluble and distinguished from all other carot-
enoids and has a molecular mass of 596.84 g/mol
with a formula of C40H52O4. It has conjugated dou-
ble bonds at its center—giving it, its antioxidant
effects [10,12].
Humans cannot synthesize astaxanthin in the
body [13]. Historically, Professor Basil Weedon’s
-
anthin 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,
     
Astaxanthin is present in most red-colored aquatic
organisms [13,15]. The primary sources of astax-
anthin in high concentrations are given below in
Table 1 [10].
Algae are the primary natural sources of astaxan-
thin in the aquatic food chain. The primary industrial
sources for natural astaxanthin are the microalgae
and Haematococcus pluvialis. Commercial astaxan-
thin for aquaculture is produced synthetically [10].
Historical Evolvement of Astaxanthin in
Medical Uses
Since its discovery in 1970, astaxanthin has evolved
through some technological processes to be use-
ful in everyday life uses. It is now mainly extracted
from Haematococcus pluvialis using high-pressure
     
spectrometry [16]. Currently, astaxanthin has
been approved as a food colorant in animal and
     
made by scientists to synthetically produce the
products of Haematococcus pluvialis. Lee et al. [18]
demonstrated that adding 1-aminocyclopropane-1-
carboxylic acid could enhance the accumulation of
astaxanthin while Shang et al. [19] suggested that
synthetic Haematococcus pluvialis production is
enhanced by using butylated hydroxyanisole.
Consumption of astaxanthin can reduce and
prevent various disorders in human and animals.
Synthetic astaxanthin has a dominant role in agri-
culture. The consumption of astaxanthin can reduce
or prevent the risk of various disorders in human
and animals. Synthetic astaxanthin is produced by
H. pluvialis through chemical syn-
thesis [20].
Mechanism of Acon of Astaxanthin
Usually, carotenoids are absorbed into body lipids
which are enhanced by high cholesterol. On absorp-
tion, astaxanthin mixes with bile acid to make
micelles and are incorporated into chylomicron.
Astaxanthin is then assimilated with lipoprotein
and transported to body tissues to protect cells such
as skin and lipid-based membrane against oxida-
tive damage [21]. Also, astaxanthin contains poly-
ene chain and multiple double bonds which quench
singlet oxygen and radicals to stop the reaction.
Antioxidant properties have been linked to their
chemical and physical interactions with cell mem-
branes. 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 met-
abolic syndrome, cancer health, and a whole lot
of other disease entities [23,24]. In general, with
regards to general antioxidant effects (free radi-
cal scavenging), astaxanthin is more than 65 times
Table 1. Showing the sources of astaxanthin.
Natural sources Concentraon of astaxanthin
(Parts per million)
Salmonids 5
Plankton 60
Krill 120
Arcc shrimp (P. borealis)1,200
Phaa yeast
(Xanthophyllomyces
dendrorhous)
10,000
Haematococcus pluvialis 40,000

www.jmolpat.com 3
Astaxanthin as an anoxidant
stronger than vitamin C and 50 times more power-
ful than vitamin E in protecting cell membranes. In
addition, astaxanthin has been shown to be more
effective than other carotenoids and other nutri-
ents at singlet oxygen quenching by being up to
800 times stronger than coenzyme Q, 6,000 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 [25]. Research suggests that
      -
matory, and neurodegenerative diseases [26,27].
Astaxanthin has been shown to play a role in sev-
eral diseases.
Cancer prevenon
Several research studies have deciphered that
astaxanthin exerts in activity such as anti-
proliferation, anti-apoptosis, and anti-invasion
via different molecules and pathways including
signal transducers and activator of transcrip-
tion 3 (STAT 3), nuclear factor kappa light chain
     
proliferator activator receptor gamma, and other
multiple mechanism of cancer effects. According
to Zhang et al., astaxanthin is thought to pro-
tect body tissues from oxidation and ultraviolet
     -
vation [28,29]. Astaxanthin also prevents can-
       
UV oxidant damage. It does this by promoting
early detection and destruction of cells that have
undergone malignant transformation by avoiding
immune surveillance [30,31]. Also, Jacobsson et al.
  
     -
vents the 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 [13,32,33].
Eye health
     
against eye-related macular degeneration (the most

conditions. Astaxanthin protects the eye against eye
fatigue, improves visual activity and depth percep-

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. Iwasaki
and Tahara [34] concluded that astaxanthin
reduces cataract formation, glaucoma, and macular
degeneration.
Prevenon of complicaons of diabetes mellitus
In 2015, a meta-analysis of data from 10 random-
       
supplementation with astaxanthin on plasma lipid
      
involving db/db mice, prevention of diabetic
nephropathy was noted on treatment with astaxan-
thin. It is found that chronic administration of astax-
anthin reduces the oxidative stress on the kidneys
and prevents renal cell damage. A dose of 6.8 mg
a day decreased the level of blood glucose [35–37].
Uchiyama et al. [38] and Ambati et al. [39] noted
that giving astaxanthin to obese or/and diabetic
animals experienced lower plasma glucose levels,
     -
mation and oxidative stress. In addition, astaxan-
thin enhanced the ability of the pancreas to secrete
insulin and slowed down the rate of diabetic
nephropathy [27,38,39].
Brain health/stroke/hypertension prevenon
     
been noted in experimental animals. It is known
to protect against stroke and hypertension and in
improving memory in vascular dementia [40–43].
Astaxanthin crosses the blood–brain barrier; hence,
protecting the brain [42]. At a given dose of 6–8 mg
daily, there was a reduction in blood pressure in
-
erties 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 improves
mental functions in rats, 50 mg/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 acvies
Astaxanthin is known to promote muscle endur-
ance and protects against muscle damage [46,47].
Astaxanthin limits exercise-induced skeletal mus-
cle damage in mice. It is now used by athletes to
enhance performance. The same properties that it

       

4 J Mol Pathophysiol • 2018 • Vol 7 • Issue 1
Lawson Ekpe, Kenneth Inaku, Victor Ekpe
 
supported [47–49]. This it does by reducing the pro-
duction and storage of lactic acid, reducing free rad-
ical, and supporting mitochondrial function [50].
Skin health
      
improves skin elasticity, protects against sun dam-
age, and prevents age spots and hyperpigmentation.
Astaxanthin works as an internal sunscreen of the

damage to skin cells [51]. It is a potent UV radiation
absorber [27]. Tominaga et al. in a study involving
38 healthy females gave 6 mg/day of astaxanthin
oral supplement and 2 ml/day topical astaxanthin
to the participating subjects. Their results showed
that the H. pluvialis-derived astaxanthin improved
skin conditions in all layers such as corneocyte
layer, epidermis, basal and dermis layer by combin-
ing oral and topical treatment [52]. Astaxanthin is
believed to offer skin protection through a number
of mechanisms. First, it is believed to block a cer-
tain amount of the 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 import-
ant 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 combina-
tion 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 1,000 times stron-
ger than lutein in preventing UV light-induced oxi-
dative stress [54].
Pepc ulcer disease prevenon
The ulcer-preventing ability was studied in
India when researchers [55,56] at Central Food
Technological Institute gave carotenoids and
astaxanthin esters orally at doses of 100, 250, and
5,000 mcg/kg to rats. After being fed antioxidants,
ethanol was then given to induce gastric ulcer in the
studied rats. The researchers noted that lipoxygen-
ase inhibitors in the rat cells were 23 times greater
when astaxanthin was given compared to admin-
istration of omeprazole, a proton-pump inhibitor
used for peptic ulcer disease management. They
concluded that free radicals scavenging activity of
astaxanthin found in H. pluvialis protects against
gastric mucosal injury [27,55,56].
Lipid peroxidaon/atherosclerosis prevenon
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 pro-
tein in the cardiovascular system, reducing tri-
glycerides, increasing high-density lipoprotein
cholesterol and adiponectin levels. In another
study done in Finland, Karppi et al. assessed the
effect of 3-month astaxanthin supplementation
on certain healthy non-smokers aged between
19 and 33 years. The intervention group received
two 4 mg capsules daily while the control received
      -
mentation with astaxanthin decreased the in vivo
oxidation of fatty acids in the healthy men [57]. In
another study by Jacobsson et al. [58], taking 6–8
mg daily of astaxanthin decreased the oxidation of
low-density lipoprotein cholesterol and prevented
it from atherogenic effect. It protects the vascular
      -
tects cholesterol from being oxidized. Astaxanthin
is thought to play a role in atherosclerosis preven-
      
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 anti-
oxidant. This single property has been found to be

from free radical scavenging, mitochondrial protec-

glycation [60,61].
With the advancement in technology, synthetic
production of astaxanthin by genetic engineering
will go a long way in supplying the needed astax-
anthin in both agricultural and medical uses. It is
believed that the extraction of astaxanthin from
its natural sources and synthetic-based forms will
play a great role in the management of patients
      
humans.
Conict of interest


www.jmolpat.com 5
Astaxanthin as an anoxidant
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6 J Mol Pathophysiol • 2018 • Vol 7 • Issue 1
Lawson Ekpe, Kenneth Inaku, Victor Ekpe
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