It really isn’t practical to try to take EVERYTHING …
Why We Take Astaxanthin
Here is a truly versatile nutrient
By Durk Pearson & Sandy Shaw
As you know if you read much of what is published on healthful nutraceuticals, there are many possible choices of natural substances that can contribute to your health. Yet, as we have noted before, it really isn’t practical to try to take EVERYTHING that is available that offers potential health advantages, making it necessary to pick and choose to design a regimen that will give you better health. We have the same problem as you do only worse because we are aware of an even larger number of potential supplements and there is no way on Earth that we can take all those things. We spend a considerable amount of our time evaluating our regimen and updating it when we become aware of potentially important new supplements. Here we will give you some reasons why one of the natural substances that we choose to take is ASTAXANTHIN.
One reason we take astaxanthin is its versatility, in that it has protective effects against a large number of processes that contribute to aging and age-associated diseases.
A Few Basic Facts About Astaxanthin
Astaxanthin is a carotenoid that is found in marine animals such as salmon and vegetables, as well as in flamingos that all get astaxanthin in their diet from algae. For instance, the astaxanthin content of wild salmon is 1.7 to 2.6 mg/100 g (Yasui, 2011). (The astaxanthin content of farmed salmon depends upon the amount of the carotenoid contained in their diet and, thus, will vary more than that of wild salmon.) The bioavailability of astaxanthin is enhanced in the presence of fat (take your supplemental astaxanthin with the fattiest meal(s) of the day) and its elimination half-life in humans is reported to be 15.9 +-5 hours (n=32) (Wang, 2013).
Astaxanthin Can Protect Against:
(A) Astaxanthin ameliorates lung fibrosis in vivo (Wang, 2013). This is an important form of protection because fibrosis occurs in many organs during the aging process and is a major cause of morbidity and mortality. It is well known that transforming growth factor beta (TGF-beta) is a major signaling molecule that contributes to fibrosis, which includes medical conditions ranging from physiological scarring of superficial skin wounds all the way to fatal idiopathic pulmonary fibrosis and to odd conditions such as Peyronnie’s, where fibrosis causes the penis to become bent and interferes with sexual intercourse. Fibrosis is difficult to treat once it has developed, so it is better to take supplements that help prevent it from developing in the first place. In one study (Wang, 2013), Sprague-Dawley rats were induced to develop lung fibrosis by treatment with bleomycin (a chemotherapeutic drug used to treat cancer). The rats thus treated also received low-dose astaxanthin (0.5 mg/mL, 1 mL/kg), median-dose astaxanthin (1 mg/mL, 1 mL/kg), or high dose astaxanthin (2 mg/mL, 1 mL/kg). A dexamethasone (a corticosteroid) treatment group was treated with 1 mg/mL, 1 mL/kg of dexamethasone. The controls did not receive bleomycin-induced fibrosis, but got an equal volume of saline.
The results showed that the astaxanthin groups (but especially the high-dose astaxanthin treatment) had significant reduction in the symptoms of fibrosis. The dexamethasone group also had significant reduction of the symptoms of fibrosis. In the cell culture part of this study, the researchers investigated the role of TGF-beta in the development of fibrosis. They found that the A549 cells underwent EMT (epithelial-mesenchymal transition) in response to TGF-beta, which involves changes such as a loss of E-cadherin expression, a key change in the fibrosis process. One of the effects of astaxanthin was to increase the expression of E-cadherin, which was part of how it inhibited the fibrotic changes induced by TGF-beta.
As the authors (Wang, 2013) noted in the introductory paragraph to their paper, “[n]ew antifibrotic methods and drugs are urgently needed because no effective treatment to improve patient survival has been developed to date.” The new data on astaxanthin suggests a way to help prevent fibrosis.
- Wang et al. Astaxanthin ameliorates lung fibrosis in vivo and in vitro by preventing transdifferentiation, inhibiting proliferation, and promoting apoptosis of activated cells. Food Chem Toxicol. 56:450-8 (2013).
ASTAXANTHIN IS NEUROPROTECTIVE
(B) Another important contribution of astaxanthin to health is as a neuroprotectant (Lieu, 2009). Parkinson’s disease is a neurodegenerative disorder that results from damage to and ultimately death of dopaminergic neurons in a specific area of the brain. Dopaminergic neurons are especially susceptible to oxidative damage. The study reported here (Lieu, 2009) involved treatment of dopaminergic SH-SY5Y cells with neurotoxic DHA hydroperoxides and 6-hydroxydopamine (6-OHDA), along with astaxanthin treatment.
The “pretreatment of SH-SY5Y cells with astaxanthin for 4 h resulted in a dose-dependent protection against DHA-OOH- or 6-OHDA-induced toxicity at the concentration of 25–100 nM range, and the most significant protection was found at the concentration of 100 nM.” This resulted in 65% (DHA-OOH) and 84% (6-OHDA) of the toxicity to the controls. DHA-OOH and 6-OHDA increased cytochrome c release (part of the apoptosis programmed cell death process) to 9-fold and 7-fold, respectively, relative to control. These increases were reduced to 2-fold and 3-fold of control, respectively, by astaxanthin treatment at a concentration of 100 nM.
Astaxanthin Improves Lipid Metabolism in Muscles of Mice During Exercise
(C) In a study (Aoi, 2008) in which mice were run to exhaustion on a treadmill, astaxanthin treatment for 4 weeks increased fat utilization during exercise as compared to mice doing the same exercise after 4 weeks on a regular diet (no astaxanthin supplementation). Moreover, the supplemented mice were able to run on the treadmill for a significantly longer period of time and had an accelerated decrease of body fat accumulation.
- Aoi et al. Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of oxidative CPT I modification. Biochem Biophys Res Commun. 366:892-7 (2008).
ASTAXANTHIN FOUND IN CELL MITOCHONDRIA
The most interesting thing to us in Lieu, 2009 was the fact that by HPLC analysis, “astaxanthin was detected at 0%, 9.42%, 7.9%, and 72.56% of the total administration levels in the cytosolic, mitochondrial, membrane fraction of the cells and the culture medium, respectively ...” This indicates that some of the astaxanthin concentrated in mitochondria, where it is likely to have contributed directly to the protection of mitochondria by astaxanthin against the oxidants used in the experiments. As we have mentioned before, most antioxidants do not provide much protection to mitochondria because they don’t get into these organelles. Hence, this is a particularly beneficial property of astaxanthin.
- Liu et al. Astaxanthin inhibits reactive oxygen species-mediated cellular toxicity in dopaminergic SH-SY5Y cells via mitochondria-targeted protective mechanism. Brain Res. 1254:18-27 (2009).
Anticoagulatory and Antiinflammatory
Effects of Astaxanthin in Diabetic Rats
As you likely know, diabetes is a common disorder that is associated with age and obesity and can be difficult to keep under control because it is not just a disorder of blood-borne sugar, but also of excess fatty acids in blood, liver, muscle, and other tissues. In this paper (Chan, 2012), astaxanthin reveals anti-coagulatory and antiinflammatory effects in diabetic rats, a model of human diabetes.
Many diseases of aging are associated with inflammation and hypercoagulability, an increased tendency for blood clots to form (as for example in cardiovascular disease and cancer). In this study (Chan, 2012), astaxanthin was used to treat rats that had developed diabetes as a result of streptozotocin treatment. As the researchers explain (Chan, 2012), plasminogen activator inhibitor-1 (PAI-1) is an important inhibitor of fibrinolysis (the breakdown of clots) that promotes the balance of coagulation and fibrinolysis so as to favor coagulation. One of the anti-coagulatory effects of astaxanthin was to reduce the levels of PAI-1 in the diabetic rats.
Chronic inflammation is an important factor contributing to the effects of diabetes. As the researchers explained, the inflammatory cytokines IL-6 and TNF-alpha (tumor necrosis factor-alpha) mediate the progression of inflammation, endothelial dysfunction, and hypercoagulation (Chan, 2012). Astaxanthin in this study substantially decreased the levels of IL-6 and TNF-alpha, as well as MCP-1 (a factor that activates monocytes and macrophages and attracts them to sites of injury, exacerbating inflammation) in the circulation and in the kidney.
Thus, conclude the authors (Chan, 2012), “[t]hese results support that astaxanthin could attenuate diabetes associated coagulatory, oxidative, and inflammatory stress.”
- Chan et al. Anticoagulatory and antiinflammatory effects of astaxanthin in diabetic rats. J Food Sci. 77(2):H76-H80 (2012).
Astaxanthin Reduces Inflammatory Effect of
Bacterial Eye Infection in Mouse Macrophages
Lipopolysaccharide (LPS) is a bacterial cell wall component that strongly stimulates immune system activity and, hence, activates the inflammatory aspects of immunity. A short period of such inflammation is beneficial, helping to clear the infection, but chronic inflammation is associated with many diseases, such as diabetes, cardiovascular disease, cancer, and arthritis, among others. A paper (Ohgami, 2003) was published in which the effect of astaxanthin on LPS-induced inflammation in the eyes of rats that developed uveitis (an eye infection) as a result of footpad injection of LPS. Astaxanthin or prednisolone (a corticosteroid) was administered intravenously at 30 minutes before, at the same time as, or 30 minutes after LPS treatment.
Astaxanthin suppressed the development of uveitis in a dose-dependent fashion. The anti-inflammatory effect of 100 mg/kg of astaxanthin was reported to be as powerful as that of 10 mg/kg prednisolone (a corticosteroid having a potent antiinflammatory effect). The authors found that the antiinflammatory effect of astaxanthin was a result of a decreased production of nitric oxide, decreased activity of inducible nitric oxide synthase and decreased production of PGE2 (an inflammatory prostaglandin) and TNF-alpha (tumor necrosis factor alpha, an inflammatory cytokine).
The authors suggest that astaxanthin may be a promising agent for the treatment of ocular inflammation.
- Ohgami et al. Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Invest Ophthalmol Vis Sci. 44:2694-701 (2003).
Astaxanthin in Mouse Food Inhibited Colitis
and Colitis-associated Colon Carcinogenesis Via
Reduction of Inflammatory Cytokines
Gastrointestinal inflammatory infections seem to be becoming all too common (to judge by the number of papers being published on them) without very effective treatments available. We were particularly interested to see this recent paper (Yasui, 2011) on the beneficial effects of astaxanthin on colitis and colitis-associated colon carcinogenesis in male mice.
The authors suggest, on the basis of the findings reported in their paper (Yasui, 2011) that astaxanthin should be considered as a candidate for the prevention of colitis and inflammation-associated colon carcinogenesis in humans.
Colitis was induced in male ICR mice by dextran sulfate sodium (DSS), commonly used in experimental studies to induce colitis or as a colon cancer promoter. Results included: The incidence of mucosal ulcer was decreased with increasing dose of astaxanthin at week 20. The decrease in mice fed the diet containing 200 ppm astaxanthin was statistically significant (p< 0.05). Dietary administration of astaxanthin at three different doses (50 ppm, 100 ppm, 200 ppm) significantly reduced the multiplicity of mucosal ulcers and dysplasia (hyperproliferation) at week 20. Treatment with the three different doses significantly reduced the incidence of adenocarcinoma (p<0.01). In a separate experiment that was a part of the study, dietary astaxanthin (astaxanthin contained in the mouse food) dose-dependently decreased colonic inflammation. 200 ppm astaxanthin was particularly effective as compared to group 1 (treated with dextran sulfate sodium but not receiving astaxanthin).
The authors observed that astaxanthin reduced NF-kappaB activation and suggest that this suppression of the master regulator of inflammation NF-kappaB may be the main pathway respnsible for the reduction of mouse colonic inflammation by astaxanthin. As the researchers noted. aberrant activation of NF-kappaB is associated with a number of chronic inflammatory diseases.” We have also reported a separate paper (Zhang, 2013) in our October 2013 issue that found that chronic overactivation of NF-kappaB in the hypothalamus appeared to be a major promoter of aging. Hence, reducing excess NF-kappaB signaling may have anti-aging effects.
- Yasui et al. Dietary astaxanthin inhibits colitis and colitis-associated colon carcinogenesis in mice via modulation of the inflammatory cytokines. Chem Biol Interact. 193:79-87 (2011).
- Zhang et al. Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH.
- Nature. 497:211-6 (2013).
Astaxanthin Protects Against Ischemic
(Reduced Blood Flow) Brain Injury in Rats
Here we mention one very useful protective effect of astaxanthin—it has been shown to protect the brain of rats from damage resulting from ischemia (reduced blood flow) as occurs in transient cerebrovascular incidents or even blood vessel occlusion in the brain as occurs in stroke.
A 2005 paper (Hussein, 2005) using a composition of 5.5% astaxanthin in an edible oil base (ASX-O) was used in a study of the effects of treatment against hypertension in stroke-prone spontaneously hypertensive rats. Five weeks of treatment significantly reduced blood pressure and also delayed the incidence of stroke. By day 4 post-treatment, the stroke rate was 60% in the controls and lower dose of ASX-O (5 mg/kg) group, whereas the group receiving 50 mg/kg of ASX-O showed no sign of stroke.
Studies of ischemic mice with ASX-O that were also included in the paper (Hussein, 2005) showed a shortened latency of mice reaching the platform in the Morris water maze test, where mice are dumped into a container of opaque water with a hidden platform allowing the mice to reach “safety” instead of having to keep treading water. In these mice, transient ischemia was induced by bilateral common carotid occlusion, a common technique for mimicking the effects of transient ischemic events, stroke, or vascular dementia. The transient ischemia caused cognitive and memory impairments. Pretreatment with ASX-O (55, 550 mg/kg) significantly ameliorated these impairments, shortening the time it took for mice to escape onto the platform.
A later paper (Shen, 2009) reported the results of experiments with adult rats that were given intracerebroventricular injections (injections directly into the brain) of astaxanthin or vehicle prior to a 60 minute middle cerebral artery occlusion. The astaxanthin treatment increased locomotor activity of the treated rats compared to the rats subject to occlusion but receiving only vehicle and also reduced the infarct area (brain cells killed) by the procedure in the astaxanthin treated rats compared to those receiving vehicle. The mechanistic studies of the authors suggested that the reduction of ischemia-related injury was mediated by inhibition of oxidative stress and glutamate release, and induction of mechanisms to protect cells from programmed cell death.
The researchers (Shen, 2009) suggested that astaxanthin might be clinically useful for patients vulnerable or prone to ischemic events. However, the route of administration used here (intracerebroventricular injections) can’t be directly compared to oral or even i.v. administration and, while convenient for treating rats, would probably be considered risky compared to safe oral administration in humans.
- Hussein et al. Antihypertensive and neuroprotective effects of astaxanthin in experimental animals. BIOL. PHARM. BULL. 28(1):47-52 (2005).
- Shen et al. Astaxanthin reduces ischemic brain injury in adult rats. FASEB J. 23:1958-1968 (2009)
Astaxanthin’s Diversity of Protective Mechanisms
Is a Factor In Its Favor When Designing a
Carotenoids are lipophilic (fat loving) substances, but those with a polar hydroxyl and keto functionalities (such as astaxanthin) have increased affinity for the lipid/water interface (Liang, 2009). This is the likely reason for the synergy of action seen between carotenoids. In this paper (Liang, 2009), researchers found that lycopene and especially beta carotene, which are both reported to be efficient radical scavengers, nevertheless have only small effects on the lag phase of lipid oxidation, while zeaxanthin and astaxanthin, less effective radical scavengers, are highly effective in increasing the lag phase of lipid oxidation. The researchers report that “combination of each of two less efficient but highly reducing antioxidants beta-carotene and lycopene with astaxanthin gave a clear synergistic effect for initiation of oxidation in the lipid phase ... and the length of lag phase ...” As oxidation of lipids is an important mechanism of aging, this synergy could be highly beneficial.
- Liang et al. Antioxidant synergism between carotenoids in membranes. Astaxanthin as a radical transfer bridge. Food Chem. 115:1437-42 (2009).
Effects of Astaxanthin on Sperm Function and Use in the Treatment of Male Infertility
In order for sperm to fertilize eggs, they must undergo a series of biochemical changes called capacitation. Reactive oxygen species (ROS) are crucially involved in this process, which causes cells to undergo a massive acrosome reaction. The researchers of a new study (Dona, 2013) tested the effects of incubating sperm cells in the presence or absence of increasing concentrations of astaxanthin or diamide. The results suggested to the authors that “Asta [astaxanthin] can be inserted in the membrane and therefore create capacitation-like membrane alteration which allow Tyr-P [tyrosine phosphorylation] of the head [of the sperm cell]. Once this has occurred, AR [acrosome reaction] can take place and involves a higher number of cells.”
The authors explain that “in seminal fluid it [astaxanthin] significantly decreases ROS production and has positive effects on some semen parameters and male fertility by increasing sperm concentration and linear velocity, thus ameliorating fertilizing power.” Another paper (Comhaire, 2005) studied astaxanthin as a possible treatment for male infertility and reported a positive effect of astaxanthin on sperm parameters and fertility, but suggested a larger trial to confirm these findings before making general recommendations.
- Dona et al. Effect of astaxanthin on human sperm capacitation. Mar Drugs. 11:1909-19 (2013).
- Comhaire et al. Combined conventional/antioxidant “Astaxanthin” treatment for male infertility: a double blind, randomized trial. Asian J Androl. 7(3):257-62 (2005).
Human Studies with Astaxanthin
Several short term, small size human clinical trials with most being randomized controlled trials using various doses of astaxanthin were reported in a recent review. (Kidd, 2011) For example, one trial with healthy non-obese human subjects found 6 mg a day of astaxanthin for 12 weeks to significantly increase HDL levels, while significantly increasing blood adiponectin levels and lowering triglycerides at 12 mg. a day for 12 weeks.
- Kidd. Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential. Altern Med Rev. 16(4):355-64 (2011)
Why Do We Take Astaxanthin?
Considering the evidence for a variety of potentially important beneficial effects of astaxanthin, do you wonder why the two of us use it on a daily basis? We currently take 12 mg once daily, preferably with meals containing some fat for better absorption.
Will Block is the publisher and editorial director of Life Enhancement magazine.