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Role of Astaxanthin in Sports Nutrition

Authors:
  • Cyanotech Corporation

Abstract

Strenuous exercise induces oxidative stress, inflammation, lipid peroxidation, and muscle damage. Natural astaxanthin is a potent antioxidant with anti-inflammatory properties. As such, astaxanthin supplementation may be important in sports nutrition. Natural astaxanthin has been documented to increase muscular strength and endurance in five out of six human clinical studies as well as four supporting animal trials. This chapter reviews the published studies on astaxanthin supplementation as they relate to sports nutrition.
Role of Astaxanthin in Sports Nutrition
Bob Capelli, Cyanotech Corporation, Kailua-Kona, Hawaii, USA
Gerald R. Cysewski, PhD, Cyanotech Corporation, Kailua-Kona,
Hawaii, USA
January, 2013
Corresponding Author: Bob Capelli, bcapelli@cyanotech.com 808.334.9415
Summary
Natural Astaxanthin is documented to increase strength and endurance in both human clinical
studies as well as supporting animal trials. In a study funded by Gatorade®, competitive cyclists
taking 4 mg per day of Natural Astaxanthin for 28 days improved cycling times by 5% and
power output by 15% on average. In earlier research, young men taking 4 mg per day of Natural
Astaxanthin for six months performed 62% more deep knee bends, increasing their strength and
endurance almost three times faster than the placebo group. In addition to improving strength
and endurance, Astaxanthin is an excellent supplement for athletes due to its intense and unique
antioxidant activity and its safe and natural anti-inflammatory effects. As an antioxidant, its
reach extends throughout the body to all organs and muscle tissue, combatting excessive free
radical production by athletes, and is many times stronger than other common antioxidants. As
an anti-inflammatory, it reduces six different inflammatory pathways and provides a safe
alternative to over-the-counter and prescription anti-inflammatories, most of which have serious
side effects. In conclusion, Natural Astaxanthin supplementation would be a great benefit to all
athletes and active people, particularly endurance athletes.
Key Words
Astaxanthin; Natural Astaxanthin; endurance; strength; antioxidant; anti-inflammatory; recovery.
Role of Astaxanthin in Sports Nutrition
Introduction
Natural Astaxanthin was released on the human nutrition market in the late 1990’s after
establishing safety parameters and being allowed for human use by the US Food & Drug
Administration. Based on research on its impressive antioxidant strength, Astaxanthin was
originally marketed as “The World’s Strongest Natural Antioxidant.” At that time, exploration
was just beginning to emerge as to Astaxanthin’s various other health benefits. (1). It was also
at that time that a very important human clinical study was done in Sweden by Dr. Curt
Malmsten validating Natural Astaxanthin’s ability to increase strength and endurance. (2). Since
then, additional research has further validated Astaxanthin’s ability to increase strength and
endurance in human and animal populations. New in-vitro work has surfaced showing the
extraordinary and unique ability of Astaxanthin to combat oxidation, of particular interest to
athletes who generate excessive levels of free radicals and wish to lengthen workouts and
improve recovery time. Furthermore, Astaxanthin is emerging as a safe and natural alternative to
over-the-counter and prescription anti-inflammatories to help with overuse injuries as well as
joint, tendon and muscle pain. (1). Although all of these factors can yield enormous benefits for
all types of athletes, no group is better suited for supplementation with Natural Astaxanthin than
endurance athletes. For this reason, Natural Astaxanthin has become an important tool in the
arsenal of many triathletes, marathon runners, long distance bicyclists and more. In this paper,
we will first analyze the existing literature on Astaxanthin’s ability to increase strength and
endurance, and then examine its antioxidant and anti-inflammatory properties and discuss how
these properties can benefit athletes.
Benefits of Astaxanthin for Athletes
Part 1: Strength & Endurance
The most important benefit that Natural Astaxanthin has for athletes is that it increases strength
and endurance. In the animal kingdom, the animal that has the greatest amount of Astaxanthin in
its body is the salmon. Astaxanthin concentrates to the highest levels in the muscles of the
salmon. It has been theorized that Astaxanthin is what gives the salmon the incredible strength
and endurance to swim upriver for weeks to spawn. In salmon, as in other species (including
humans), extremely high levels of free radicals are generated when exerting force. The presence
of a strong antioxidant such as Natural Astaxanthin in the fish’s muscle tissue can mitigate or
eliminate the excess free radicals generated by this extreme exertion of swimming up river for
weeks at a time. It appears that this same effect of Astaxanthin concentrating in the muscles
occurs in humans. The study done in Sweden we mentioned above verified what many early
users of Natural Astaxanthin were reporting—that they were getting stronger and increasing their
endurance when supplementing with Astaxanthin. The study was done with healthy male
students between the ages of seventeen and nineteen. The researcher used forty men with an
equal number (twenty) in the treatment group and in the placebo group. Each subject took one 4
mg capsule per day with a meal for six months.
The subjects’ strength was measured at the beginning of the experiment, halfway through (after
three months), and again at the end of the experiment (after six months) by counting the
maximum number of knee bends to a 90º angle that each subject could do. This was controlled
by an adjustable stool in a “Smith machine.” (The Smith machine is specifically designed for
measuring strength and endurance in clinical trials.) The subjects were properly warmed up for a
set time and in a similar manner before each strength measurement.
The results showed that, in six months, the students taking Natural Astaxanthin improved their
strength and endurance by 62%. This was achieved at the relatively low dose of only 4 mg per
day. The students taking a placebo increased their strength by 22%, which is normal for people in
this age group over a six month period, as they were generally involved in sports and physically
activity. Basically, Astaxanthin made these students stronger and increased their endurance
almost three times faster than the placebo group. (2).
Insert Figure 1.
The same researcher, Dr. Malmstem, teamed up with long term Natural Astaxanthin researcher
Dr. Ake Lignell in an article ten years later, also centered on strength and endurance. This 2008
publication cited several other supporting studies that had occurred over the last ten years since
Dr. Malmstem’s groundbreaking human clinical study. The summary of this article is a good tool
for understanding Natural Astaxanthin’s potential for athletes and active people:
"The marked improvement in strength/endurance would seem very interesting,
since it cannot be explained by improved fitness (step-up test) or improved lactic
acid tolerance (Wingate test). Furthermore, since there was no significant
increase in body weight, an increased muscle mass cannot be used to explain this
positive effect. Because of this, Astaxanthin seems to have a beneficial effect on
strength/endurance.
This is the first study in humans to show that Astaxanthin supplementation has a
positive effect on physical performance. The result of this study is supported by
earlier findings that Astaxanthin supplementation in mice increases swimming
time before exhaustion, and that biomarkers of muscle fatigue decrease in humans
after exercise due to Astaxanthin supplementation.
Further studies need to be designed to find the explanations to the mechanisms
behind the increased muscle endurance. It can be hypothesized that Astaxanthin
protects the membrane structures of the cells, like the mitochondrial membrane
against oxidative stress generated during heavy exercise and thereby preserves the
functionality of the muscle cells.” (3).
While these same results cannot be guaranteed for older people, they certainly indicate that
Astaxanthin increases strength and endurance. The hypothesis for how Astaxanthin helps in this
area: Mitochondrial organelles, which are numerous in muscle tissue, produce up to 95% of our
body’s energy by burning fatty acids and other substances. But this energy that is produced also
generates highly reactive free radicals. The free radicals, in turn, can damage cell membranes and
oxidize DNA. And the free radicals continue to impact the muscles even after we stop exercising
—they activate inflammatory markers which lodge in muscle tissue and cause soreness and
tiredness. According to the mitochondrial theory of aging, degradation done to the mitochondria
is due largely to oxidative damage. The damage done in the cell leaves the mitochondria
deficient of respiration and inefficient in producing energy. When a cell is no longer producing
energy optimally, the strength and endurance of the individual declines.
Because Astaxanthin is such a powerful antioxidant, it effectively scavenges the muscle tissue
for free radicals and eliminates singlet oxygen. During all strenuous physical activity, the body
produces large amounts of free radicals. The more strenuous the activity, the greater the
production of free radicals. (4,5,6) It is probable that the mechanism of action that enables
Natural Astaxanthin to make people stronger and increase their endurance is through its intense
antioxidant and anti-inflammatory activity in the energy-producing mitochondria.
An extremely significant human clinical trial on Natural Astaxanthin in 2011 was funded by
Gatorade Sports Science Institute. Being the world’s leading company in the sports drink
market, Gatorade’s interest in Astaxanthin is in the area of endurance and sports applications. For
this study, Gatorade used competitive cyclists, supplementing them with a placebo or 4 mg of
Natural Astaxanthin each day for four weeks. From the endurance athlete’s—or for that matter—
from any competitive athlete’s perspective, the results were excellent. In a 20 kilometer
(approximately 12.5 mile) cycling time trial, the performance of the subjects taking Astaxanthin
significantly improved, while the subjects taking placebo showed no improvement. Natural
Astaxanthin made these competitive cyclists on average 5% faster in only 28 days. Also, the
cyclists taking Astaxanthin demonstrated significant improvement in their power output, which
increased by 15% on average over the same 28 day period. (7). Although this study did not
establish a mechanism of action for Astaxanthin’s improvement in performance, strength and
endurance for these cyclists, the fact that it is the second human clinical trial showing that
Natural Astaxanthin can improve strength and endurance in and of itself is of particular
significance. Of particular interest to competitive athletes is the 5% improvement in speed in
less than a month. In many sports where fractions of a second separate gold medal winners from
silver, bronze and being off the podium, a potential 5% improvement is extraordinarily
significant.
Insert Figure 2.
A different kind of sports-related clinical study was done in Japan to measure Natural
Astaxanthin’s effect on lactic acid levels in the muscles. Lactic acid is an unwanted byproduct of
physical exertion; it deposits in the muscles and causes burning during exercise. The result of
reducing lactic acid levels is increased endurance. This study was also done with young men, all
twenty years old; the treatment group took 6 mg per day of Natural Astaxanthin for four weeks.
Lactic acid levels for both groups were measured before running 1200 meters and again two
minutes after running. The results were very positive: The young men taking Natural Astaxanthin
averaged 28.6% lower serum lactic acid after running 1200 meters compared to the placebo
group. (8).
There are animal studies that corroborate the human clinical trials cited above. One such study
done with mice was designed to measure the effects of Astaxanthin on endurance. The results
were similar to the endurance clinical trials in young men and in competitive cyclists:
Astaxanthin markedly increased endurance in mice. This study took course over a five week
period. Mice were divided into two groups and their endurance was tested by seeing how long
they could swim until exhaustion. The mice fed Astaxanthin showed a significant increase in
swimming time before exhaustion. Blood lactose levels were measured in both groups, and, as
expected, the levels of the Astaxanthin group were significantly lower than the control group.
Another effect measured was fascinating: Astaxanthin supplementation significantly reduced fat
accumulation. This is the first mention of such an effect and further proof is needed before
putting any credence into this potential benefit. The study’s authors suggested that Astaxanthin
enabled the mitochondria to burn more fat: “These results suggest that improvement in
swimming endurance by the administration of Astaxanthin is caused by an increase in utilization
of fatty acids as an energy source.” (9).
A subsequent mouse study backed up the results found in the human clinical trials discussed
above as well as earlier mouse trials. This study was set up to investigate the effects of
Astaxanthin supplementation on muscle lipid metabolism in mice that exercised heavily. The
outcome was that mice that were fed Astaxanthin for four weeks and then exercised 1) had better
fat utilization; 2) had longer running time until exhaustion; 3) had better muscle lipid metabolism
and 4) had reduced fat tissue. The researchers concluded that Astaxanthin supplementation led to
improvement in endurance. (10).
The last animal study that we’ll examine in the area of endurance is from the same group of
researchers as the mouse study above. This study took mice and ran them on a treadmill until
they were exhausted. The mice were separated into three different groups: Group A was the
control group that was not exercised at all and was not given Astaxanthin. Group B was
exercised until exhaustion, but was not given Astaxanthin either. Group C was exercised
similarly to Group B, but their diets were supplemented with Natural Astaxanthin. After the
exhaustive exercise, the mice were sacrificed and examined. Their heart muscles and calf
muscles were checked for oxidative damage. The researchers found that various markers of
oxidative damage were reduced in both the heart muscles and calf muscles of Group C. They
found a corresponding reduction of oxidation in the plasma as well. The cell membranes in the
treatment group’s calf and heart muscles suffered significantly less peroxidation damage. Also,
damage to DNA and proteins were significantly reduced in the mice supplemented with
Astaxanthin. Another effect noticed was better modulation of inflammation damage indicators
and serum creatine kinase. In fact, muscle inflammation was found to decrease by more than
50% in the mice given Astaxanthin. “Our data documented that Astaxanthin indeed is absorbed
and transported into skeletal muscle and heart in mice, even though most carotenoids accumulate
mainly in the liver and show relatively little distribution to other peripheral tissues, including
skeletal muscle and heart. This unique pharmacokinetic characteristic of Astaxanthin makes it
well suited to oxidative stress in gastrocnemius [calf] and heart…Thus, Astaxanthin attenuates
exercise-induced damage by directly scavenging reactive oxygen species and also by down-
regulating the inflammatory response.” (11).
This study proves, first of all, by examining the calf muscles and heart muscles of mice, that
Natural Astaxanthin actually reaches these two very spread out areas in the rodents’ bodies. The
authors point out that this is not the case with most other carotenoids. This is a unique and very
important difference between Natural Astaxanthin and other antioxidants and carotenoids: Many
cannot get throughout the body. Because of its shape and esterified nature (with fatty acids
attached to one or both ends of the molecule), Natural Astaxanthin has this tremendous
advantage—it travels to the far reaches of the body, into every organ—the brain, the heart, the
muscles and even the skin, fighting oxidation and inflammation and thereby protecting them.
The other key point that this study proved was that, once in these diverse areas of the body,
Astaxanthin was doing exactly what it’s supposed to do—eliminating free radicals, reducing
inflammation and preventing damage to DNA and cell membranes. This is one of the most
significant animal studies to date demonstrating the extensive and varied benefits of Natural
Astaxanthin in-vivo.
In summary, human clinical trials validate and pre-clinical animal trials corroborate strength and
endurance benefits for athletes who use Natural Astaxanthin. Highlights of these benefits
include:
5% time improvement for competitive cyclists using 4 mg Natural Astaxanthin per
day for 28 days
15% power output improvement for the same competitive cyclists using 4 mg
Natural Astaxanthin per day for 28 days
62% more deep knee bends by 17 19 year old men taking 4 mg Natural
Astaxanthin per day for six months
28.6% decrease in serum lactic acid in 20 year old men taking 6 mg Natural
Astaxanthin per day for six weeks when measured after a 1200 meter run
Human clinical results above are substantiated in animal trials
Additional potential benefits in animal trials include:
Reduced fat accumulation
Improved muscle lipid metabolism
Reduced markers for oxidative damage in heart and calf muscles after
heavy exercise
Reduced oxidation in the plasma
Reduced peroxidation damage to DNA and proteins
Improved modulation of inflammatory damage
Improved modulation of serum creatine kinase
Reduced muscle inflammation by 50%
Part 2: A Diverse and Unique Antioxidant
It is well documented that athletes, particularly endurance athletes and anyone doing heavy
workouts, generate extremely high levels of free radicals. Astaxanthin is a perfect supplement
for athletes who want to combat these increased levels of free radicals. Some potential benefits
of neutralizing free radicals are:
Faster recover
Increased length of workouts
Reduced muscle soreness
As cited above, increased endurance (1)
It is also well documented that Astaxanthin is an extremely powerful antioxidant. Countless in-
vitro studies comparing it to many other antioxidants such as Vitamin C, Vitamin E,
Pycnogenol®, green tea catechins, CoQ10, alpha lipoic acid, as well as other carotenoids (beta
carotene, lutein, lycopene) generally show Astaxanthin to be at minimum an order of magnitude
more powerful as an antioxidant. This is true regardless of the type of antioxidant test—whether
it be free radical elimination or singlet oxygen quenching—and the results are sometimes
staggering. For example, Astaxanthin proved to be 800X stronger than CoQ10; 550X stronger
than both green tea catechins and Vitamin E; and 6000X stronger than Vitamin C in eliminating
singlet oxygen. (12,13).
Insert Figure 3.
But Astaxanthin’s strength as an antioxidant is only one factor in why it is so different from other
antioxidants. In addition to being extraordinarily powerful, Astaxanthin, unlike many other
antioxidants, can:
Span the cell membrane and bring antioxidant protection to both the fat-soluble and
water-soluble parts of the cell
Travel throughout the entire body into all organs, muscle tissue and the skin
Bond with muscle tissue
Cross the blood-brain and blood-retinal barriers and bring antioxidant protection to the
eyes and brain
Never become a pro-oxidant (1)
The combination of outstanding antioxidant power; the ability to travel throughout the body and
protect organs vital to athletic performance like the heart, eyes and brain; the ability to bond with
muscle tissue; as well as the fact that it can never turn into a pro-oxidant and potentially cause
oxidation—as can happen with Vitamins C & E, zinc, and carotenoids like beta carotene,
lycopene and zeaxanthin (14,15)—make Astaxanthin an ideal choice as an antioxidant for
athletes.
Part 3: Anti-Inflammatory Activity of Astaxanthin
In addition to being a powerful and unique antioxidant, Astaxanthin also possesses anti-
inflammatory activity to help athletes with joint, tendon and muscle soreness. Once again, there
is a distinguishing factor between Astaxanthin and other anti-inflammatories: Natural
Astaxanthin is safe.
If you consider current anti-inflammatory products on the market, most have serious side effects.
Aspirin has anti-inflammatory effects, but prolonged use can cause stomach bleeding and ulcers.
Non-steroidal anti-inflammatory drugs (NSAID’s) such as acetaminophen (Tylenol®) can cause
liver damage. And prescription anti-inflammatory drugs such as Vioxx® and Celebrex® can
cause heart problems. Vioxx was taken off the market and its manufacturer Merck & Co. lost
almost $5 billion in lawsuits related to deaths it caused. In fact, the American Journal of
Medicine reported that NSAID’s contribute to roughly 16,500 deaths and more than 100,000
hospitalizations each year. (16). Yet after many years of consumer use and extensive safety
studies, Natural Astaxanthin has never been documented to have any side effect or
contraindication. It is a safe alternative in the high-risk category of anti-inflammatories.
One possible reason why Astaxanthin is safe compared to alternative anti-inflammatories is that
it works on several different inflammatory pathways, but in a less concentrated way than the
other anti-inflammatories. Astaxanthin is documented to suppress the production of each of
these inflammatory causing agents in our bodies:
1. Tumor necrosis factor-alpha
2. Prostaglandin E-2
3. Nitric oxide
4. Interleukin 1-B
5. Cox-1 enzyme
6. Cox-2 enzyme (17,18,19,20,21)
The most recent of these five studies citing Astaxanthin’s multiple pathways in combatting
inflammation found activity on all six of the pathways listed above, and called Astaxanthin’s
anti-inflammatory activity “remarkable.” (21). Working in a gentler manner on six different
causes of inflammation is much safer than working intensely on one cause (as is the case with
Vioxx and Celebrex which work intensely on the Cox-2 enzyme). Professor of Medicine and
Neurology Greg Cole, PhD from the University of California at Los Angeles explains, “While
anti-inflammatory drugs usually block a single target molecule and reduce its activity
dramatically, natural anti-inflammatories gently tweak a broader range of inflammatory
compounds. You’ll get greater safety and efficacy reducing five inflammatory mediators by 30%
than by reducing one by 100%. (22).
Conclusions
Natural Astaxanthin is documented to increase strength and endurance in both human clinical
studies as well as supporting animal trials. In a study funded by Gatorade®, competitive cyclists
taking 4 mg per day of Natural Astaxanthin for 28 days improved cycling times by 5% and
power output by 15% on average. In earlier research, young men taking 4 mg per day of Natural
Astaxanthin for six months performed 62% more deep knee bends. In addition to improving
strength and endurance, Astaxanthin is an excellent supplement for athletes due to its intense and
unique antioxidant activity and its safe and natural anti-inflammatory effects. As an antioxidant,
its reach extends throughout the body to all organs and muscle tissues, combatting excessive free
radical production by athletes, and is many times stronger than other common antioxidants. As
an anti-inflammatory, it reduces six different inflammatory pathways and provides a safe
alternative to over-the-counter and prescription anti-inflammatories, most of which have serious
side effects. In conclusion, Natural Astaxanthin would be a great benefit to all athletes and
active people, particularly endurance athletes.
References
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T. (2008). “Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of
oxidative CPT I modification.” Biochemical and Biophysical Research Communications.
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11. Aoi, W., Naito, Y., Sakuma, K., Kuchide, M., Tokuda, H., Maoka, T., Toyokuni, S., Oka, S.,
Yasuhara, M., Yoshikawa, T. (2003). “Astaxanthin limits exercise-induced skeletal and cardiac
muscle damage in mice,” Antioxidants & Redox Signaling. 5(1):139-44.
12. Nishida, Y., Yamashita, E., Miki, W. (2007). “Comparison of Astaxanthin’s singlet oxygen
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annual meeting on Carotenoid Research held at Osaka, Japan on September 6 & 7, 2007.
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19. Choi, SK., Park, YS., Choi, DK., Chang, HI. (2008). “Effects of Astaxanthin on the production of
NO and the expression of COX-2 and iNOS in LPS-stimulated BV2 microglial cells.” Journal of
Microbiology and Biotechnology. 18(12):1990-6.
20. Saki, S., Sugawara, T., Matsubara, K., Hirata, T. (2009). “Inhibitory effect of carotenoids on the
degranulation of mast cells via suppression of antigen-induced aggregation of high affinity IgE
receptors.” The Journal of Biological Chemistry. 284(41):28172-9.
21. Kishimoto, Y., Tani, M., Uto-Kondo, H., Iizuak, M., Saita, E., Sone, H., Kurata, H., Kondo, K.
(2010). “Astaxanthin suppresses scavenger receptor expression and matrix metalloproteinase
activity in macrophages.” European Journal of Nutrition. 49(2):119-26.
22. Cole, G. (2005). Professor of Medicine and Neurology at UCLA, as reported to Anne
Underwood, Newsweek Magazine, “Special Summer Issue,” August 2005. Pg. 26-28.
Figure 1.
Figure 2.
Figure 3.
... Research by Nishida et al. (2007) revealed that astaxanthin has a singlet oxygen quenching capability 800 times greater than ubiquinone (antioxidant present in most cells in the body). These initial results have led to further studies, which have concluded antilipid peroxidation activities in vitro (Leite et al. 2010), anticancer properties in vitro and in vivo with rodent models (Tanaka et al. 2012), immune system boosting activity (Bolin et al. 2010), eye health maintenance (Guerin et al. 2003;Piermarocchi et al. 2012), alleviation of arthritic symptoms (Capelli et al. 2013b), and protection against cognitive decline (Katagiri et al. 2012;Satoh et al. 2009). In mice models, H. pluvialis astaxanthin has been shown to inhibit the growth of Astaxanthin has the capacity to cross the blood-brain barrier to provide antioxidant protection to the brain and eyes. ...
... Most studies of H. pluvialis-derived astaxanthin have been in vitro and in animal models, and the efficacy has been well proven (Guerin et al. 2003;Visioli and Artaria 2017;Yuan et al. 2011). In addition, the health benefits of astaxanthin in human patients have been extensively reported: improvements in muscle endurance through reduced lactic acid and increased respiratory and sympathetic nervous system activities (Capelli et al. 2013b), antioxidant potential in bilateral cataract patients (Hashimoto et al. 2014), improved immune response and a reduction in inflammation and oxidative stress (Park et al. 2010), cognitive improvements with increased response time and accuracy of completing tasks (Katagiri et al. 2012;Satoh et al. 2009), cosmetic benefits through improvements in skin elasticity and a reduction in wrinkles (Tominaga et al. 2012), and improvements in semen quality with an associated increase in pregnancy rates (Elgarem et al. 2002;Comhaire et al. 2005). However, with regard to anticancer, cardiovascular health claims for the alleviation of oxidative stress in humans, and benefits in ocular health that have been reported in vitro and in vivo, no conclusive statements can be deduced, and further study is warranted. ...
Chapter
Astaxanthin is commercially sold as a pigment for animal feed and as an antioxidant for the nutraceutical sector. Astaxanthin is predominantly manufactured synthetically from petrochemicals but is also obtained from the chlorophyte Haematococcus pluvialis (Haematococcus lacustris). The petrochemical-derived synthetic alternative has conventionally been used, attributable to its lower cost ($1300–1800 kg⁻¹). However, it is inferior as an antioxidant, prohibited for direct human consumption, and may cause toxicity in the final product. Conventionally, astaxanthin from H. lacustris is produced in a two-stage production process, incorporating a green and red stage for maximising growth and astaxanthin production, respectively, but a one-stage process has been proposed. The H. lacustris-derived astaxanthin industry has been a commercial success, but several constraints have arisen including contamination issues, relatively low biomass and astaxanthin productivities, high downstream processing costs, and photobleaching issues in the red stage. These constraints need to be addressed for the production of astaxanthin from H. lacustris for the aquaculture sector. Alternatively, through the exploitation of an alternative life cycle stage, red motile macrozooids can be formed lacking the thick walls of aplanospores. It is envisaged that the red motile macrozooids could be harvested and fed as a whole-cell product directly to the aquaculture sector rich in astaxanthin and polyunsaturated fatty acids, bypassing the cell disruption and extraction steps to deliver bioavailable astaxanthin as a biobased feed.
... Although carotenoids cannot be synthesised by most animals de novo, animals have the ability to convert the ingested carotenoid into different structures via specific metabolic conversion pathways (Maoka 2011;Weaver et al. 2018). Carotenoids have strong antioxidant activity, with astaxanthin being the champion amongst them all (Miki 1991;Naguib 2000), therefore there is a strong focus on astaxanthin as a nutraceutical in combatting human diseases, in enhancing sports performance, as supplement in cosmetics and in the food industry (Zu Berstenhorst et al. 2009;Yuan et al. 2011;Capelli et al. 2013;Ranga Rao et al. 2014;Gwaltney-Brant 2021). As such, reports on natural sources of astaxanthin, appropriate extraction methods, and the chemical synthesis of astaxanthin, have remained hot topics (Maoka 2011;Ranga Rao et al. 2014;Nguyen et al. 2017;Ahmadkelayeh and Hawboldt 2020;Nunes et al. 2021). ...
... It also lowers the risk of neurodegenerative disorders like Alzheimer's and Parkinson's disease [334,335]. It is also known as a natural superfood that can increase stamina and speed up muscle recovery and ultimately boost athletic performance [336]. Chlorella zofingiensis and ...
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Microalgal biomass has been proved to be a sustainable source for biofuels including bio-oil, biodiesel, bioethanol, biomethane, etc. One of the collateral benefits of integrating the use of microalgal technologies in the industry is microalgae’s ability to capture carbon dioxide during the application and biomass production process and consequently reducing carbon dioxide emissions. Although microalgae are a feasible source of biofuel, industrial microalgae applications face energy and cost challenges. To overcome these challenges, researchers have been interested in applying the bio-refinery approach to extract the important components encapsulated in microalgae. This review discusses the key steps of microalgae-based biorefinery including cultivation and harvesting, cell disruption, biofuel and value-added compound extraction along with the detailed technologies associated with each step of biorefinery. This review found that suitable microalgae species are selected based on their carbohydrate, lipid and protein contents and selecting the suitable species are crucial for high-quality biofuel and value-added products production. Microalgae species contain carbohydrates, proteins and lipids in the range of 8% to 69.7%, 5% to 74% and 7% to 65% respectively which proved their ability to be used as a source of value-added commodities in multiple industries including agriculture, animal husbandry, medicine, culinary, and cosmetics. This review suggests that lipid and value-added products from microalgae can be made more economically viable by integrating upstream and downstream processes. Therefore, a systematically integrated genome sequencing and process-scale engineering approach for improving the extraction of lipids and co-products is critical in the development of future microalgal biorefineries.
... The EFSA on the other hand in a recent scientific opinion by FEEDAP recommended an ADI of 0.2 mg/kg bw/day (equivalent to 12 mg/ day for 60 kg adult) taking into account an uncertainty factor of 200, which replaces the previous 0.034 mg/kg bw/day (equivalent to about 2 mg/day for a 60 kg adult) established in 2014 (EFSA FEEDAP Panel 2019). The FDA likewise revised its ADI from the initial 6-7 mg/day to 12 mg/day (Brendler and Williamson 2019;Capelli et al. 2013). Generally, the ADI, as set by national regulatory authorities varies even among countries within the EU; ranging from 4 mg/day in Spain (AESAN 2012) to 12 mg/day in New Zealand, Australia, Canada and South Korea (Brendler and Williamson 2019). ...
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Diabetes remains a major health emergency in our entire world, affecting hundreds of millions of people worldwide. In conjunction with its much-dreaded complications (e.g., nephropathy, neuropathy, retinopathy, cardiovascular diseases, etc.) it substantially reduces the quality of life, increases mortality as well as economic burden among patients. Over the years, oxidative stress and inflammation have been highlighted as key players in the development and progression of diabetes and its associated complications. Much research has been devoted, as such, to the role of antioxidants in diabetes. Astaxanthin is a powerful antioxidant found mostly in marine organisms. Over the past years, several studies have demonstrated that astaxanthin could be useful in the treatment and management of diabetes. It has been shown to protect β-cells, neurons as well as several organs including the eyes, kidney, liver, etc. against oxidative injuries experienced during diabetes. Furthermore, it improves glucose and lipid metabolism along with cardiovascular health. Its beneficial effects are exerted through multiple actions on cellular functions. Considering these and the fact that foods and natural products with biological and pharmacological activities are of much interest in the 21st-century food and drug industry, astaxanthin has a bright prospect in the management of diabetes and its complications.
... According to the European Food Safety Authority, the current acceptable daily intake of ASX is 0.034 mg·kg −1 ·d −1 , which is equivalent to 2.38 mg·d −1 in a 70-kg human (3,4). In 2011, the FDA allowed the usage of ASX at a concentration up to 12 mg per daily serving (5). However, it is important to note that these are suggested upper safe levels of use, not dietary guidelines. ...
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Astaxanthin (ASX) is a naturally occurring xanthophyll carotenoid. Both in vitro and in vivo studies have shown that it is a potent antioxidant with anti-inflammatory properties. Lung cancer is the leading cause of cancer death worldwide, whereas other lung diseases such as chronic obstructive pulmonary disease, emphysema, and asthma are of high prevalence. In the past decade, mounting evidence has suggested a protective role for ASX against lung diseases. This article reviews the potential role of ASX in protecting against lung diseases, including lung cancer. It also summarizes the underlying molecular mechanisms by which ASX protects against pulmonary diseases, including regulating the nuclear factor erythroid 2–related factor/heme oxygenase-1 pathway, NF-κB signaling, mitogen-activated protein kinase signaling, Janus kinase–signal transducers and activators of transcription-3 signaling, the phosphoinositide 3-kinase/Akt pathway, and modulating immune response. Several future directions are proposed in this review. However, most in vitro and in vivo studies have used ASX at concentrations that are not achievable by humans. Also, no clinical trials have been conducted and/or reported. Thus, preclinical studies with ASX treatment within physiological concentrations as well as human studies are required to examine the health benefits of ASX with respect to lung diseases.
... The effects of natural AX in humans have been reviewed in more than 20 publications over the last 10 years and include studies on antioxidation, hepatoprotection, eye function, skin health, immune response, inflammation, gastric ulcer, cardiovascular system, muscle endurance, cancer, central nervous system, male fertility, metabolic syndrome, diabetes, and mitochondrial dysfunction (Ekpe, Fassett et al., 2008, Fassett & Coombes, 2012Galasso et al., 2018;Visioli & Artaria, 2017;Brown, Gough, Deb, Sparks, & McNaughton, 2018;Capelli, Jenkins, & Cysewski, 2013;Davinelli, Nielsen, & Scapagnini, 2018;Kim & Kim, 2018;. ...
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Astaxanthin (AX)‐containing preparations are increasingly popular as health food supplements. Evaluating the maximum safe daily intake of AX is important when setting dose levels for these products and currently, there are discrepancies in recommendations by different regulatory authorities. We have therefore conducted a review of approved dose levels, clinical trials of natural AX, and toxicological studies with natural and synthetic AX. Recommended or approved doses varied in different countries and ranged between 2 and 24 mg. We reviewed 87 human studies, none of which found safety concerns with natural AX supplementation, 35 with doses ≥12 mg/day. An acceptable daily intake (ADI) of 2 mg as recently proposed by European Food Safety Authority was based on a toxicological study in rats using synthetic AX. However, synthetically produced AX is chemically different from natural AX, so results with synthetic AX should not be used in assessing natural AX safety. In addition, few safety studies have been conducted in either humans or animals with synthetic AX. We therefore recommend the ADI for natural AX to be based only on studies conducted with natural AX and further studies to be conducted with synthetic AX (including human clinical trials) to establish a separate ADI for synthetic AX.
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Objective This study aimed to ascertain the effects of astaxanthin (ASX) in an experimental necrotizing enterocolitis (NEC) model using rat pups. Study Design Forty-two pups born from five Wistar albino rats were randomly divided into three groups as the control group, NEC + placebo (saline), and NEC + ASX. Pups in the NEC + ASX group were given 100 mg/kg/day oral ASX from day 1 to day 4 of the study. Saline of 2 mL/kg was given to the NEC + placebo group. Histopathological, immunohistochemical (caspase-3), and biochemical evaluations including the total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), glutathione (GSH), lipid hydroperoxide (LPO), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and nuclear factor erythroid 2–related factor 2 (Nfr-2) activities were all performed. Results A better survival rate and weight gain were demonstrated in the NEC + ASX group (p < 0.05). In the histopathological evaluation, the severity of intestinal damage was significantly reduced in the NEC + ASX group, as well as decreased apoptosis (enzyme-linked immunosorbent assay [ELISA] for caspase-3; p = 0.001). The biochemical analyses of intestinal tissue TOS, oxidative stress index (OSI; TOS/TAS), IL-1β, LPO, 8-OHdG, AOPP, caspase-3 (p < 0.001 for all), and TNF-α and MPO (p = 0.001 for both parameters) levels were lower in the NEC + ASX group than in the NEC + placebo group. Nrf-2, TAS, GSH, and SOD levels were higher in the NEC + ASX group than in the NEC + placebo group (p = 0.001, 0.001, <0.001, and 0.01, respectively). Conclusion ASX treatment has been shown to effectively reduce the severity of intestinal damage in NEC due to its antioxidant, anti-inflammatory, and antiapoptotic properties. Key Points
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This study investigated the effect of dietary supplemented synthetic, and shrimp shell meal (SSM) derived natural astaxanthin combination on growth, digestive and metabolic enzyme activities, antioxidative status, physio-metabolic responses, and skin colouration of high valued discus (Symphysodon aequifasciatus) advanced juveniles reared in captive condition. Four isonitrogenous (50% crude protein), isolipidic (9% ether extract), and isocaloric (around 400 kcal digestible energy/100g) experimental diets viz. Control (only synthetic astaxanthin, without SSM), T1 (15% SSM + synthetic astaxanthin), T2 (20% SSM + synthetic astaxanthin), T3 (25% SSM + synthetic astaxanthin) were prepared and fed to satiation level twice daily for 90 days. Results indicated significantly (P<0.05) higher weight gain percentage, FER, SGR, and PER and lower FCR in T2 and T3 groups compared to control. Combination effect of synthetic and natural astaxanthin significantly (P<0.05) enhanced the protease activity, hematological parameters, and levels of serum immune parameters and decreased activities of amylase, hepatic and muscle MDH, LDH, ALT, AST with hepatic and gill SOD, CAT and serum glucose level with the most pronounced effects in T3 group. Significantly (P<0.05) highest values of L*, a*, b*, chroma, and hue angle in the T3 group indicated their brightest skin colouration. Therefore, the study concluded that synthetic and SSM derived natural astaxanthin combinations at levels of 71.5 and 28.5 mg/kg, respectively, can be effectively supplemented in ornamental fish diets for improving their growth, health status, and skin colouration.
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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.
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http://www.appleacademicpress.com/phytochemicals-from-medicinal-plants-scope-applications-and-potential-health-claims/9781771887953
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Prolonged physical exercise results in transient elevations of biochemical markers of muscular damage. This study examined the effect of short-term maximal exercise on these markers, homocysteine levels (Hcy), and total antioxidant status (TAS) in trained subjects. Eighteen male football players participated in this study. Blood samples were collected 5-min before and 3-min after a 30-s Wingate test. The results indicated that plasma biochemical markers of muscle injury increased significantly after the Wingate test (P<0.05). Moreover, significant increase of white blood Cells and their main subpopulations (i.e. monocytes, neutrophiles, and lymphocytes) (P<0.001) has been observed. Likewise, uric acid, total bilirubin, and TAS increased significantly after exercise (P<0.05). However, Hcy levels were unaffected by the Wingate test (for 3-min post-exercise measurement). Short-term maximal exercise (e.g. 30-s Wingate test) is of sufficient intensity and duration to increase markers of muscle damage, and TAS; but not Hcy levels. Increases in the selected enzymes probably come primarily from muscle damage, rather than liver damage. Moreover, increase of TAS confirms the Wingate test induced oxidative stress.
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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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To understand the roles of carotenoids as singlet oxygen quenchers in marine organisms, quenching activities of eight major carotenoids, astaxanthin, canthaxanthin, β-carotene, zeaxanthin, lutein, tunaxanthin, fucoxanthin and halocynthiaxanthin were examined according to the method using a thermodissociable endoperoxide of 1,4-dimethylnaphthalene as a singlet oxygen generator. The second-order rate constant for the singlet oxygen quenching activity by each carotenoid was determined, suggesting that an increasing number of conjugated double bonds in carotenoid was proportional to greater quenching activity. The quenching activity of each carotenoid was found to be approximately 40 to 600 times greater than that of α-tocopherol. The potency of these carotenoids suggests that they may play a role in protecting marine organisms from active oxygen species.
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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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Reactive oxygen species are potentially damaging molecules. An important function of antioxidants is to intercept harmful triplet states, in order to prevent the formation of singlet oxygen, or to quench singlet oxygen directly. However, antioxidants are also reactive towards other active oxygen species such as the hydroxyl radical, the superoxide anion and the non-excited oxygen ground state in the presence of radical initiators. It is well known that flavonoids and carotenoids show strong antioxidant properties. Polyenes and carotenoids are the best known among the compounds that quench singlet oxygen by efficient energy transfer. A large number of modified, synthetic analogues and derivatives have been synthesised to prepare even better quenchers than the natural carotenoids. Phenols are also excellent chain-breaking antioxidants. Recently, many indigoid dyes (including bacterial indigoids) were studied, with the remarkable result that most, but not all, members of this class of chromophores quench singlet oxygen at the diffusion limit and some of them are excellent radical traps. It has been shown in this study that a quantitative assessment of antioxidant properties of flavonoids, carotenoids, phenols and natural indigoids can be achieved using the following three assays: (1) oxygen pressure dependence; (2) peroxide formation; (3) singlet oxygen quenching. Reactivities towards both excited states and ground state radicals can be properly described by these assays. The remarkable role of -carotene as an ‘unusual antioxidant’ (Burton GW and Ingold KU, Science 224: 569–573 (1984)) in reactions using various oxygen pressures becomes clearer. The so-called ‘pro-oxidant effects’ concern primarily the antioxidant itself and its degradation, since no or very little damage to the substrate occurs in this type of experiment. Three main categories of antioxidants may be classified: (1) excellent antioxidants that perfectly quench excited states as well as ground state radicals (eg actinioerythrol, astaxanthin); (2) good antioxidants that strongly inhibit peroxide formation but are less efficient in quenching excited states (eg flavonols, tocopherols) or lead to considerable degradation of the antioxidant itself (eg -carotene, lycopene); (3) moderate antioxidants that fail to excel in both reactivities (eg -carotene, flavone).© 2001 Society of Chemical Industry
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Carotenoids can be effective singlet oxygen quenchers and inhibit free-radical induced lipid peroxidation. A remarkable property of β-carotene (1a) is the change from an antioxidant to a prooxidant depending on oxygen pressure and concentration. In the present study a considerable number of carotenoids (1a, 2c, 2d, 2e, 3a, 4a, 5a, 6a, 7a, 8a, 8h, 8i, 8j, 9f, 10a, 11a, 12g) was investigated using two independent approaches: 1. Comparison of their effects on inhibition of the free-radical oxidation of methyl linoleate, and 2. The direct study of the effect of oxygen partial pressure upon their rates of oxidation. It is shown that some carotenoids (7a, 8a) are even more effective than the well-known compounds β-carotene (1a) and astaxanthin (5a) and are powerful antioxidants without any prooxidative property. Different carotenoids display different behaviour depending on chain length and end groups. The influence of these functional groups on the antioxidative reactivity is discussed.
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Astaxanthin is a red carotenoid pigment which has significant potential for antioxidant activity. The macrophages in atherosclerotic lesions, known as activated macrophages, express scavenger receptors responsible for the clearance of pathogenic lipoproteins. In addition, the expression and secretion of proteolytic enzymes, matrix metalloproteinases (MMPs), and pro-inflammatory cytokines are remarkably promoted in activated macrophages. In this study, we investigated the effects of astaxanthin on the expression of scavenger receptors, MMPs, and pro-inflammatory cytokines in macrophages. THP-1 macrophages were incubated with 5-10 microM astaxanthin for 24 h. The expression levels of scavenger receptors, MMPs, and pro-inflammatory cytokines were determined by Western blot analysis or real-time RT-PCR. The MMP-9 and -2 activities were examined by gelatin zymography and total MMP activity was measured by fluorometry. We found that astaxanthin remarkably decreased the class A scavenger receptor and CD36 expression in the protein and mRNA levels. Astaxanthin also reduced MMP-1, -2, -3, -9, -12, and -14 activity and expression. The mRNA expression of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 were significantly suppressed by astaxanthin. Furthermore, astaxanthin inhibited the phosphorylation of nuclear factor-kappaB. These results indicate that astaxanthin has inhibitory effects on macrophage activation, such as scavenger receptors up-regulation, MMPs activation, and pro-inflammatory cytokines secretion.
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Astaxanthin has shown antioxidant, antitumor, and antiinflammatory activities; however, its molecular action and mechanism in the nervous system have yet to be elucidated. We examined the in vitro effects of astaxanthin on the production of nitric oxide (NO), as well as the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Astaxanthin inhibited the expression or formation of nitric oxide (NO), iNOS and COX-2 in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Astaxanthin also suppressed the protein levels of iNOS and COX-2 in LPS-stimulated BV2 microglial cells. These results suggest that astaxanthin, probably due to its antioxidant activity, inhibits the production of inflammatory mediators by blocking iNOS and COX-2 activation or by the suppression of iNOS and COX-2 degradation.
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Exercise induces free radical formation in muscle and liver, and oxidative damage, such as lipid peroxidation. The amount of damage depends on exercise intensity, training state and the tissue examined and can be reduced through dietary supplementation of antioxidants such as vitamin E and possibly coenzyme Q10. Supplementation with antioxidants does not increase maximal aerobic capacity or maximal exercise capacity; effects on endurance capacity are unclear. Deficiency of vitamin E or vitamin C greatly reduces endurance capacity, whereas selenium deficiency has no effect on endurance capacity. In studies by the authors, urinary output of the oxidatively damaged RNA base 8-hydroxyguanosine was not affected by several submaximal exercise bouts nor by supplementation with vitamins E and C and beta-carotene in moderately trained humans. In rats, endurance training caused an increase in oxidative damage, as measured by the protein carbonyl concentration of muscle, but not liver. Muscle protein carbonyl concentration returned to normal on detraining. These results indicate that the search for oxidative damage due to exercise and the effects of antioxidant manipulation on such damage should ideally involve examination of several indices of oxidative damage in various tissues after exercise and training.
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A growing amount of evidence indicates that free radicals play an important role as mediators of skeletal muscle damage and inflammation after strenuous exercise. It has been postulated that the generation of oxygen free radicals is increased during exercise as a result of increases in mitochondrial oxygen consumption and electron transport flux, inducing lipid peroxidation. The literature suggests that dietary antioxidants are able to detoxify the peroxides produced during exercise, which could otherwise result in lipid peroxidation, and that they are capable of scavenging peroxyl radicals and therefore may prevent muscle damage. Endogenous antioxidant enzymes also play a protective role in the process of lipid peroxidation. The studies reviewed (rodent and human) show significant increases of malondialdehyde (a product of lipid peroxidation) after exercise to exhaustion, and also favourable changes in plasma antioxidant levels and in antioxidant enzyme activity. In trained individuals and trained rats, the antioxidant enzyme activity increases markedly. In this way, the increased oxidative stress induced by exercise is compromised by increased antioxidant activity, preventing lipid peroxidation. Human studies have shown that dietary supplementation with antioxidant vitamins has favourable effects on lipid peroxidation after exercise. Although several points of discussion still exist, the question whether antioxidant vitamins and antioxidant enzymes play a protective role in exercise-induced muscle damage can be answered affirmatively. The human studies reviewed indicate that antioxidant vitamin supplementation can be recommended to individuals performing regular heavy exercise. Moreover, trained individuals have an advantage compared with untrained individuals, as training results in increased activity of several major antioxidant enzymes and overall antioxidant status. However, future studies are needed in order to be able to give more specific information and recommendations on this topic.