Astaxanthin

Following on from my last article on DHA and the relevance between the modern day dietary lack of this essential PUFA and the recent significance regarding gene expression in certain pathologies that are emerging, I thought I would highlight another nutrient that is very much in the current research spotlight, Astaxanthin. The amount of studies done throughout the world has escalated and the intense interest in undertaking new research on Astaxanthin is a direct result of the remarkable biological qualities of this nutrient. Astaxanthin is one of a group of natural pigments called xanthophylls, a part of the carotenoid family and has many biochemical functions, its scope and benefits within the body’s systems are diverse. This is one of my favourite nutrients, and it first caught my eye several years ago when I discovered its biological potential in retinal health and eye disorders above and beyond other carotenoids.

Carotenoids are a group of approximately 700 natural lipid-soluble pigments that are only produced by phytoplankton, algae, plants, and a limited number of fungi and bacteria with diverse biological functions. In plants and algae, carotenoids serve both photosynthetic and photoprotective roles as part of their survival mechanisms. In animals, carotenoids are effective chain-breaking antioxidants and singlet oxygen quenchers, and some also serve as precursors for retinoids (vitamin A). (1) Some carotenoids also appear to have effects on cell communication and proliferation in animals. (2) Because animals cannot synthesize carotenoids de novo, they must obtain them from dietary sources. (3) Animals have adapted to exploit the potent antioxidant properties of carotenoids. One familiar example is seen in the cold-water fish that selectively accumulate astaxanthin from their diet and deposit this red pigment in their flesh to protect lipid tissues from peroxidation, a harmful form of oxidation. We recognize this in the flesh of salmon, shellfish and trout as a healthy pink to red glow. Astaxanthin is also found in microalgae, krill, shrimp, crayfish, crustaceans and some plants.

With the diverse loss of many traditional foods and herbs from our clients diets there is the inevitable lack of many important plant components, together with a loss of biological synergism and bioactive mechanisms so crucial for function in human health. It is a pity that the ‘power of food’ which our ancestors harnessed so successfully has been in our modern life forgotten, not realised, or properly utilised to defend us and help us adapt against the constant environmental battles we all face. If only people knew the extent of how food substances such as Astaxanthin acted within the body and how they can truly manipulate health as a result. As NT’s we get frustrated with the poor and inadequate range of foods our clients eat especially in the lack of the huge array of colourful fruit and vegetables that are on offer.

Diets are often lacking in carotenoid rich foods and certainly Astaxanthin which is nature’s super carotenoid is not prevalent. Fish is no exception, where our clients might eat little or no fish, white fish being the predominant variety if it appears at all within the dietary questionnaire, and any oily fish intake is usually confined to purchase of tins with an occasional piece of supermarket salmon seen lurking in the weekly intake. Salmon, the principal dietary source of astaxanthin is an important component of the traditional diets of Eskimos and certain coastal tribes in North America; these groups have shown unusually low prevalence of cancer. This low cancer incidence has been attributed to the high levels in salmon of certain fatty acids, yet it is possible that astaxanthin has played a role in cancer chemoprevention among these peoples as well. (4,5)

Antioxidant - There are clear links between human cancers and diet.(6,7) A number of substances naturally occurring in foodstuffs, particularly antioxidant compounds in plant products have shown promise as potential chemopreventive agents.(8-11) Among these phytonutrients, the yellow, orange and red carotenoid pigments have sparked much interest. Among the carotenoids, astaxanthin is of particular interest in health management due to its unique structural and chemical properties. (12-14) At the cellular level astaxanthin accumulates in the membranes of cells and mitochondria. Astaxanthin’s unique structure enables the molecule to span the double layer membrane and consequently, expose itself both to the interior as well as the exterior of the cell. (Fig 1) By localizing itself in the membranes, astaxanthin protects membrane components like proteins and lipids from ROS medi-ated oxidation.

Astaxanthin is fat soluble and is carried by fat molecules directly to tissues and organs in the body such as the retina, brain, breast tissue, prostate tissue, and skeletal muscles. Harmful reactive oxygen species such as singlet oxygen, superoxide, peroxyl and hydroxyl radicals are commonly formed as a consequence of photo-oxidation, physiological stress and normal immune system functions. These oxidants collectively contribute to aging and degenerative diseases such as cancer and atherosclerosis through oxidation of DNA, proteins and lipids. (15-17) Antioxidant compounds can decrease mutagenesis, and thus carcinogenesis, both by decreasing oxidative damage to DNA and by decreasing oxidant-stimulated cell division. (16) Fig 1

Astaxanthin protects cells against oxidation; it has a very quenching effect against singlet oxygen dissipating the energy as heat and has a powerful scavenging ability for lipid and free radicals effectively breaking peroxide chain reactions. (18-22) Astaxanthin has exceptional antioxidant activity when compared to other antioxidants. In a 2007 study astaxanthin extracted from Haematococcus microalgae powerfully quenched singlet oxygen and results showed that the quenching effect of astaxanthin was far greater than coenzyme Q10, alpha-lipoic acid, green tea catechins and vitamin C. (23) A growing body of scientific literature reveals significant evidence that astaxanthin surpasses the antioxidant benefits of beta-carotene, zeaxanthin, canthaxanthin and vitamin E. (24)

At low oxygen partial pressures, diverse carotenoids effectively inhibit oxidation reactions, and their anti-oxidative abilities increase with increasing carotenoid concentration. As oxygen levels are increased, however, their antioxidant potential typically decreases. (25-27) Certain carotenoids, notably beta-carotene but also lycopene, exhibit unusual behaviour; beyond a threshold carotenoid concentration, they actually decrease in antioxidant ability with increasing carotenoid concentration, and this effect is further exacerbated at high oxygen levels. (27-30)

This pro-oxidant behaviour of beta-carotene appears to be related to its degradation products and their potential to be involved in radical chain reactions, and may help to explain the unexpected increase in lung cancer deaths among smokers supplemented with this carotenoid. It has been suggested that these negative results should not have been wholly unexpected. Rather than individual agents, the total diet and all its constituents need to be considered in determining nutrient factors related to cancer risk incidence. (31) The xanthophylls zeaxanthin, canthaxanthin and especially astaxanthin are considered pure antioxidants because they exhibit little or no pro-oxidative behaviour even at high carotenoid concentration and high oxygen tension.

Astaxanthin has exhibited potent antioxidant, immunomodulating and enzyme inducing properties, all of which suggest a potential role for this carotenoid in the prevention of cancer. Moreover, its unique structural properties and its lack of pro-oxidant activity make it a prime candidate for further investigation in this area of human health. (26, 29, 30, 32) *There was a negative Daily Mail report on the beta-carotene/lung cancer trial last week without the full explanation of why there was a negative effect, see above.

Skin Health - When skin is irradiated with ultraviolet light it causes photo-oxidative damage induced by the formation of reactive oxygen species such as singlet oxygen, superoxide radical and peroxide radicals. This photo-oxidative stress damages cellular lipids, proteins and DNA and is considered to contribute to erythema, premature aging of the skin, photodermatoses and skin cancers. Skin is damaged over time by extensive and on-going exposure to the sun’s harmful rays. These ultraviolet rays can cause premature aging of the skin, wrinkles, dry skin, age spots and freckles. By preventing UV damage, skin can be protected from these conditions. And there is evidence that natural astaxanthin not only prevents UV damage from occurring, but may actually help to reverse these external signs of aging from the inside out.

Natural astaxanthin is an effective internal sunscreen that protects the skin from damage caused by exposure to UV light. This has been demonstrated in animal models as well as in a human clinical trial. Sunburn is actually an inflammatory process. When the skin becomes inflamed by exposure to UV light, the inflammation becomes visible through reddening. This is not too different from some other forms of inflammation where the outward appearance manifests as reddening. Swollen ankles, inflamed cuts and abrasions and arthritic hands can all appear red from inflammation. So when our body’s largest organ, the skin, turns red, we know that inflammation has taken place. Skin was tested before supplementation began to see how much UV light was needed to cause erythema (reddening of the skin; sunburn). Then, subjects were supplemented with 4 mg of natural astaxanthin per day for two weeks. After the two week supplementation period was over, the subjects once again underwent the skin reddening test. The pre-supplementation and post-supplementation scores were then compared. The result was that in only two weeks at a standard dose of just 4 mg per day, there was a statistically significant increase in the amount of time necessary for UV radiation to redden the skin. This result is particularly promising because astaxanthin has a cumulative effect in the body - it builds up in the organs over time. Two weeks is a relatively short time for astaxanthin to concentrate in the body’s largest organ, the skin. Yet this study proved that in just two weeks natural astaxanthin was already working as an internal sunscreen.

Astaxanthin’s anti-inflammatory action is a major contributory factor to its effect as an internal sunscreen. In addition to its protective properties, there is strong evidence that natural astaxanthin has curative properties for the skin and serves as an internal beauty supplement. While more research is needed in this area, it certainly appears that astaxanthin has great potential as a component of an anti-aging supplement and to improve and protect skin. (33) Anti-inflammatory- oxidative stress and inflammation play an integral role in the pathophysiology of many chronic diseases. Astaxanthin, probably due to its antioxidant activity, inhibits the production of a variety of inflammatory mediators by blocking NF-kappaB activation and as a consequent suppression of IKKactivity and I(kappa)B-alpha degradation. (34)

A small health survey showed that over 80 percent of people who noted back pain (and symptoms from rheumatoid and osteoarthritis arthritis), reported a substantial improvement when supplementing with astaxanthin. (35) Previous studies have provided data suggesting that daily use of natural astaxanthin can positively address inflammatory conditions such as rheumatoid arthritis and carpal tunnel syndrome. In one study, the effect of a microalgae extract containing natural astaxanthin, on C-reactive protein was evaluated. It was found that after daily use for eight weeks C-reactive protein (CRP) was significantly lowered in the treatment group as compared to the placebo group. This correlation of reduced CRP and use of astaxanthin may suggest that daily use can help reduce CRP and possibly lower inflammation levels in the body. (36)

In 2002 in the Journal of the American College of Nutrition a study showed that after receiving astaxanthin for only eight weeks, RA sufferers showed a 35 per cent improvement in pain levels, as well as a 40 per cent improvement in their ability to perform daily activities. In another study it was found that grip strength measurements (GSM) for those on astaxanthin were significantly improved. This correlation of improved GSM and use of natural astaxanthin may suggest that daily use can help alleviate pain associated with Tennis Elbow, and increase mobility. (37)

Cardiovascular protection -Oxidative stress and inflammation are implicated in several different manifestations of cardiovascular disease (CVD). They are generated, in part, from the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that activate transcriptional messengers, such as nuclear factor-kappaB, tangibly contributing to endothelial dysfunction, the initiation and progression of atherosclerosis, irreversible damage after ischemic reperfusion, and even arrhythmia, such as atrial fibrillation. Results from multiple species support the antioxidant/anti-inflammatory properties of astaxanthin, establishing it as an appropriate candidate for development as a therapeutic agent for cardiovascular oxidative stress and inflammation. (38)

Astaxanthin has been shown to accumulate primarily in the blood plasma LDL and VLDL lipoproteins with a slightly lower concentration in the HDL, thereby providing protection against oxidation. (39)  A randomized, placebo-controlled human study also suggests that astaxanthin consumption ameliorates triglyceride and HDL-cholesterol in correlation with increased adiponectin in humans. (40)

Muscle and Joint Health - Oxidative stress has harmful effects on muscle health causing muscle pain, weakness and fatigue. A recent published review describes the research on astaxanthin for muscle endurance. Results from human and model studies have shown that astaxanthin increases muscle endurance, lowers lactic acid and might prevent muscle atrophy in aging. The effects of astaxanthin on muscle are explained by its ability to protect membranes from oxidation and thereby enhance mitochondrial function where energy is produced and reduce inflammation and muscle damage. (41)

Salmon depend on astaxanthin for their incredible endurance when travelling hundreds of miles to reach their spawning grounds often for days without food so it is not surprising that astaxanthin is favoured by athletes to increase strength and stamina, reduce recovery time and prevent joint and muscle soreness after exercise. In a new randomized, double blind study 14 competitive amateur cyclists performed a 20 km maximal biking test before and 28 days after treatment. Participants received supplementation of 4 mg/day of astaxanthin or placebo. The results were outstanding and the group treated with astaxanthin were biking 121 seconds faster after the treatment period while in the meantime the placebo group were biking more slowly. (42)

Antioxidants that can cross the blood-brain barrier are essential for people as they get older to protect the brain and central nervous system. Astaxanthin crosses the blood-brain barrier and the blood-retinal barrier (beta-carotene and lycopene do not), which brings antioxidant and anti-inflammatory protection to eyes, brain and central nervous system.

Eye Health - Dr.Tso of the Wilmer Eye Institute at Johns Hopkins University has clearly demonstrated that astaxanthin is the significant carotenoid when it comes to protecting eyes. He discovered that astaxanthin easily crosses into the tissues of the eye and exerts its effects safely and with more potency than any of the other carotenoids, without adverse reactions. Specifically, Tso determined astaxanthin could ameliorate or prevent light induced damage, photoreceptor cell damage, ganglion cell damage, and damage to the neurons of the inner retinal layers. He concluded that astaxanthin supplementation could be effective in preventing or treating a whole host of eye diseases, including:

 Age-related macular degeneration (ARMD)
 Diabetic neuropathy
 Cystoid macular oedema
 Central retinal arterial and venous occlusion
 Glaucoma
 Inflammatory eye diseases (i.e., retinitis, iritis, keratitis, scleritis, etc.)

Other researchers have since confirmed Dr.Tso's finding that astaxanthin is the most powerful antioxidant ever discovered for eye health, giving your eyes an additional layer of long-term protection. Astaxanthin was also found to reduce ocular inflammation in eyes with uveitis by down regulating proinflammatory factors and by inhibiting the NF-kappaB dependent signalling pathway. (43)

Brain Health-Recent research has validated astaxanthin’s ability to protect our central nervous system. A great deal of this research has been centred on the neuroprotective benefits of astaxanthin. Two human clinical trials were undertaken in Japan in the last two years in this area. The first study took ten elderly subjects with age-related forgetfulness and administered 12 mg of astaxanthin each day for 12 weeks. The researchers found efficacy for age-related decline in cognitive and psychomotor function. (44)

The second study was randomized, double-blind and placebo-controlled; a state of the art study in human volunteers. After 12 weeks at either 6 mg or 12 mg daily astaxanthin dosages, subjects were found to have decreased levels of phospholipid hydroperoxides (which accumulate in people suffering from dementia), as well as improved erythrocyte antioxidant status. The researchers concluded that astaxanthin supplementation may contribute to the prevention of dementia in humans as we age. (45)

There have been several other studies in the last two years showing evidence that Astaxanthin may be the very best supplement for brain health:
Human brain cells were subjected to an oxidative stress-induced neuronal cell damage system at Nagoya University in Japan. Significant protection was found in cells pre-treated with astaxanthin. Additionally, pre-treatment with Astaxanthin inhibited the generation of reactive oxygen species. The authors concluded: The neuroprotective effect of Astaxanthin is suggested to be dependent upon its antioxidant potential and mitochondria protection; therefore, it is strongly suggested that treatment with astaxanthin may be effective for oxidative stress-associated neurodegeneration and a potential candidate for natural brain food. (46) A different set of researchers in the USA at University of Pittsburgh Medical School also found astaxanthin to have neuroprotective effects; they too attributed this to its potent antioxidant activity. (47) Researchers at a biotechnology university in Taiwan concluded that Astaxanthin could be used as a potent neuron protectant and as a therapy for early stages of Alzheimers disease. (48)

Astaxanthin can protect against damage from ischemia (Ischemia is the condition where there is a deficient supply of blood to the brain as a result of an obstruction of the arteries which results in stroke, brain cell death and impaired brain function). The researchers attributed astaxanthin benefits to its intense antioxidant activity. (49) Another study found that pre-treatment with astaxanthin 5 hours and again 1 hour before ischemia provided protection against brain damage. (50) Astaxanthin was found to be a potent agent against neurodegenerative disorders. (51) Brain cell death was reduced by astaxanthin. (52) Astaxanthin displayed an ability to improve the proliferation of neural stem cells. (53)

Blood pressure is a causative factor for many diseases including some associated with the eyes and brain. Researchers examined the effects of astaxanthin on stroke-prone rats. They found after five weeks of continuous supplementation, the incidence of stroke was delayed in the treated group. Next, they established a possible mechanism for these results in-vitro, which they believed to be nitric oxide suppression. The ischemic mice were fed astaxanthin only once - just one hour before the ischemia was induced. Remarkable results were seen in the treated group - the mice performed better in a maze designed as a learning performance test. “The present results suggest that astaxanthin can attenuate the development of hypertension and may help to protect the brain from stroke and ischemic insult. In addition, astaxanthin showed neuroprotective effects at relatively high doses by preventing the ischemia-induced impairment of spatial memory in mice.

This effect is suggested to be due to the significant antioxidant property of astaxanthin on ischemia-induced free radicals and their consequent pathological cerebral and neural effects. The current result indicates that astaxanthin may have beneficial effects in improving memory in vascular dementia." It appears that astaxanthin actually made these mice with restricted blood flow to their brains smarter by improving their memory. A similar study had been done previously and was published in Carotenoid Science; this study also demonstrated that Astaxanthin could prevent brain damage due to ischemia. (54-57)

Evidence shows astaxanthin holds great promise for those wishing to prevent cognitive diseases and maintain general brain health. In particular, daily supplementation with astaxanthin may have benefits for those wishing to protect their brains as they age as our aging population sees growing numbers of Alzheimer’s patients, stroke sufferers and people afflicted by dementia caused by other factors. Immune Health -Singlet oxygen is also cytotoxic to the immune system by virtue of its ability to catalyse production of free radicals. This action can facilitate degradation of macrophage cell membranes resulting in dysfunction and reduced efficiency of phagocytosis. (58) Carotenoids have been shown to enhance both the non-specific and specific immune system and protect cell membranes and cellular DNA from mutation. (59)

Astaxanthin enhances the release of interleukin-1 alpha and tumour necrosis factor alpha in mice greater than canthaxanthin and beta-carotene. The conclusion of one study was that astaxanthin had the best cytokine-inducing activity and may provide an immunomodulating role. (60) Astaxanthin has a significant enhancing action on antibody production when cells are presented with antigens. Other carotenoids such as zeaxanthin, lutein, lycopene and canthaxanthin did not have the same effect. (61) Astaxanthin modulates immune response, inhibits cancer cell growth, reduces bacterial load and gastric inflammation in H.Pylori infection, and protects against UVA-induced oxidative stress in vitro and rodent models. (62,63) In a recent study it showed that dietary astaxanthin enhanced immune response and decreased a DNA oxidative damage biomarker and inflammation in young healthy females. (64)

Male Fertility - Other research has been undertaken on fertility where natural astaxanthin from Haematococcus Algae has been shown in a double blind, placebo controlled clinical trial to improve fertility in infertile men. This study was conducted on men who were diagnosed as infertile due to abnormal sperm quality. The experimental group received 16 mg of natural astaxanthin per day for three months. The results were an improvement in conception rate in the experimental group by 478% over the placebo group. It was concluded that supplementation with natural astaxanthin improved the quality of the spermatozoa, which is suggested to be the plausible explanation for the increased frequency of conception. (65)

Prostate Health - Inhibition of 5alpha-reductase has been reported to decrease the symptoms of benign prostate hyperplasia (BPH) and possibly inhibit or help treat prostate cancer. Saw Palmetto berry lipid extract (SPLE) is reported to inhibit 5alphareductase and decrease the clinical symptoms of BPH. Epidemiologic studies report that carotenoids such as lycopene may inhibit prostate cancer. In one study low levels of astaxanthin have been found to inhibit 5alpha-reductase and decrease the growth of human prostatic cancer cells. Astaxanthin added to Saw Palmetto berry lipid (SPLE) extract showed greater inhibition of 5alpha-reductase than SPLE alone in vitro. (66)

Summary on the main health benefits of Astaxanthin
 Boosting immune function
 Improving cardiovascular health by reducing C-Reactive Proteins (CRP), reducing triglycerides, and increasing beneficial HDL
 Protecting the eyes
 Protecting the brain
 Reducing risk of cancer (including cancers of the breast, colon, bladder and mouth) by stimulating apoptosis (cancer cell death) and inhibiting lipid peroxidation
 Improving recovery from spinal cord and other central nervous system injuries
 Reducing inflammation
 Improving endurance, workout performance and recovery
 Helping to stabilize blood sugar, thereby protecting the kidneys
 Relieving indigestion and reflux
 Improving fertility by increasing sperm strength and sperm count
 Prevent sunburn, and protection from the damaging effects of radiation
 Reducing oxidative damage to DNA
 Reducing symptoms from Pancreatitis, Multiple Sclerosis, Carpal tunnel syndrome, Rheumatoid Arthritis, Parkinson's disease, Lou Gehrig's dis-ease, and neurodegenerative diseases.

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