Versatile Cell Membrane Protection
The molecular character of this natural astaxanthin especially equips it to become incorporated into working cell membranes. The molecule is long and thin, with both ends having “polar” groups that are compatible with water but the middle segment being “nonpolar” and not water-compatible.1 This specific molecular layout allows astaxanthin to insert into cell membranes without substantially changing the membrane structure.2 In this way astaxanthin differs from other carotenoids which distort the membrane’s structure and thereby make it more vulnerable to damage from “free radical” or other toxic influences. Within the membrane astaxanthin provides potent protection against free radical or other toxic attack.
2-5 All cells have membranes, and membranes manage most of the processes important for life.6 Every cell membrane is an ultrathin, extended, double molecular sheet of lipids, into which are inserted enzymes and other catalytic proteins.6,7 The proteins’ metabolic activities unavoidably generate highly reactive “free radicals” of oxygen, nitrogen, sulfur or carbon within the membrane or at its surface.7-9 The astaxanthin in cell membranes helps protect against all such byproducts of normal metabolism.
3-5 The double lipid layers of cell membranes can resemble micro-railroad tracks as seen under a microscope.6 Each astaxanthin molecule likely spans the membrane’s two layers, rather like ties span a railroad track.1 This positions them to intercept and neutralize free radicals, whether these are at the membrane’s edge or within its core.2,5
The most common threats to membrane integrity are oxygen free radicals (oxyradicals, for short). Astaxanthin’s ability to protect against oxyradicals was clearly illustrated in an experiment with rofecoxib. This pharmaceutical is known to cause oxyradicals to initiate reactions that destroy membranes (called “peroxidation”). In experiments with membranes created in the laboratory, astaxanthin totally blocked rofecoxib’s damage and actually switched the membrane into anti-peroxidative balance.10
Astaxanthin also fights free radicals differently from most other antioxidants. Rather than donate electrons, as most antioxidants do, astaxanthin neutralizes radicals by taking electrons from them.10 This property gives the astaxanthin molecule better stability than other antioxidants, and therefore it can remain active longer in the membrane. Astaxanthin’s membrane presence very likely provides backup for the more delicate membrane antioxidants such as tocopherols (vitamin E) and ubiquinone (“CoQ”).
Protects and Enhances the Mitochondria
Mitochondria are our microscopic energy powerhouses. They have two membranes crammed with proteins that specialize in making energy (ATP). Mitochondria make over 90% of the body’s energy, using over 85% of the body’s oxygen supply.7,9 But these oxygen molecules are highly reactive and a small percentage become oxyradicals.8,9 Some are neutralized by antioxidant enzymes, but others escape to directly attack the mitochondrial membranes or to propagate other reactive molecules that do damage.4,8
Experimental studies indicate astaxanthin conserves and promotes the critical bioenergy function of mitochondria. In a study with dogs and cats, astaxanthin given by mouth became more concentrated in the membranes of the mitochondria than in other cell membranes.12 In experiments with cultured cells astaxanthin lowered the mitochondria’s oxyradical production rate,13,14 and at concentrations achievable in the body by dietary supplementation.15Astaxanthin also increased the mitochondria’s resistance to toxic challenge and even increased their ATP energy output.13,14
Overweight or obese individuals tend to have an unhealthy dominance of free radical activity over antioxidant capacity ( “oxidative stress”). In a 2011 double blind trial,16 a group of overweight or obese subjects received astaxanthin (5 mg per day) for three weeks, while a control group with normal weight received no astaxanthin. The astaxanthin group experienced significant lowering of two measures related to oxyradical membrane damage: blood malondialdehyde was down 35% and blood isoprostanes was 65% lowered. Their blood SOD (superoxide dismutase, a key antioxidant enzyme) doubled in activity and the blood total antioxidant capacity markedly increased, entering the more healthy range of the control group.
Astaxanthin therefore has a universally protective effect on cell membranes in general and the membranes of mitochondria in particular, with potential to improve mitochondria ’s energy production efficiency. These benefits of astaxanthin for the body’s most fundamental life processes seemingly translate into a broad spectrum of clinical benefit.
Supports Memory and Other Higher Brain Functions
In a small clinical trial, astaxanthin was shown to improve memory and other higher brain functions (“cognition”).17 Ten healthy men aged 50-69 who had been complaining of forgetfulness received astaxanthin at 12 mg per day for 12 weeks. On computerized cognition tests their attention, memory and other cognitive functions improved significantly, as did their stimulus response time. Various other experimental studies support these findings.18-22
Astaxanthin at human physiological levels improved the memory and learning performance of mice in water maze tests.18 In cultured nerve cells it protected the mitochondria against oxyradical attack,19,20 and the cell as a whole against attack from outside toxins.21 Astaxanthin also stimulated cultured stem cells to mature into functioning nerve cells.22
Improves Vision and Relieves Eye Fatigue
Astaxanthin has been extensively researched in Japan for its support of vision. In several double blind and other clinical trials, published in Japanese, astaxanthin at 6 mg per day significantly improved visual sharpness in healthy volunteers (reviewed in Yuan, 201123 and Kajita, 200924). Other trials published in English show astaxanthin also can relieve eye fatigue and vision problems related to aging.
Extended work at computer monitors is known to cause eyestrain, blurring and other vision problems. One double blind trial compared astaxanthin (5 mg per day) versus a placebo, against eyestrain in young Japanese VDT (visual display terminal) workers.25 Astaxanthin significantly improved eye muscle accommodation, which closely equated to relief from eyestrain. In another clinical trial astaxanthin (6 mg per day, for 4 weeks) significantly improved eye muscle functions in middle-aged subjects.24 Eyestrain improved, as did related symptoms including difficulty to see near objects, blurred vision, and shoulder and low back stiffness.
Supports Cardiovascular Health
Astaxanthin can improve the human blood lipid profile. In a double blind, placebo-controlled trial on subjects with high triglyceride levels, astaxanthin (at 6 mg or 12 mg per day for 12 weeks) significantly elevated HDL (high-density lipoprotein) cholesterol, an effect consistent with lowering of cardiovascular risk.26 Astaxanthin taken at 12 mg per day also significantly lowered triglycerides and increased blood adiponectin levels. Adiponectin is a hormone that is produced by adipose tissue and helps regulate healthy insulin sensitivity, healthy inflammatory response, and heart health.27
Abnormally low blood adiponectin is also linked to problems with blood sugar management.27 In a small clinical trial, astaxanthin (16 mg per day, for 12 weeks) significantly elevated adiponectin and significantly lowered glycohemoglobin (HbA1c), indicating a favorable effect on blood glucose management.28
Astaxanthin also may improve body fat metabolism. In a double blind trial, overweight or obese subjects aged 20-65 years received a beverage providing either 6 mg astaxanthin per day, or no astaxanthin, for 12 weeks.29 Computer tomographic (CT) scanning reported a significant reduction in abdominal subcutaneous and total fat.
As people age their red blood cells can become more susceptible to free radical attack.30 This can impair the red cell oxygen carrying capacity and potentially compromise oxygen supply to the tissues. In a 2011 double blind trial, healthy subjects aged 50-69 years received either astaxanthin (at 6 or 12 mg per day), or a placebo, for 12 weeks.31 Compared to placebo, astaxanthin significantly lowered hydroperoxides (oxyradical products) in the red cells and the plasma. The 6 mg dose worked just as well as did the 12 mg dose.
In another human study astaxanthin improved a measure of blood flow.32 Healthy middleaged men were randomly chosen to receive either astaxanthin (6 mg per day) or a placebo, for ten days. Blood was collected from a vein in the elbow area, then a precisely measured amount was forced under pressure through a set of very fine tubes about the width of capillaries. The time required to traverse these capillary-type tubes was measured (blood transit time). The astaxanthin group showed significantly lower transit time at the end of the trial, indicating their blood was flowing more freely. The researchers concluded astaxanthin can improve the capillary circulation.
Promotes Healthy, Integrated Immune Response
Astaxanthin promotes healthy immune competence. In a 2010 double blind trial, young healthy women received astaxanthin at a 2, or 8 mg per day dose for 8 weeks.33 Astaxanthin at 2 mg per day significantly increased the total T cell numbers, while the 8 mg per day dose significantly increased natural killer cell activity, enhanced lymphocyte proliferation in response to stimulation, and enhanced the skin delayed type hypersensitivity (DTH) response to injected tuberculin. From these findings the researchers concluded astaxanthin promoted both cell mediated and antibody mediated immunity, and promoted immune competence overall.
In this trial blood CRP (C-reactive protein) was significantly lowered, by the 2 mg per day dose.33 Both the 2 mg per day and the 8 mg per day doses also significantly lowered plasma 8-OHdG (8- hydroxy-2’-deoxyguanosine), indicating astaxanthin also reduced ongoing DNA damage in the body. These are further indications of astaxanthin’s potent protective powers. Judging from this trial, the most effective dose for immune support in women may lie between 2 and 8 mg per day.
Astaxanthin can improve immune balance in the skin. In a double blind trial, subjects with troubling skin immune hypersensitivities received astaxanthin (12 mg per day) or a placebo, for 4 weeks.29 Astaxanthin proved significantly more effective than placebo at improving symptoms related to overall quality of life, and the associated feelings of anxiety. DNA damage (as urine 8- OHdG) also was significantly reduced, a further indication of astaxanthin’s protective efficacy in humans.
Counters Oxidative Stress Related to Aging
A 2009 trial recruited postmenopausal women aged 65 years or younger, and selected 20 of them with above-average oxidative stress—a relative excess of free radical activity over antioxidant capacity, as measured in their blood.34 These women then received astaxanthin (12 mg per day) for 12 weeks. Astaxanthin significantly increased their blood antioxidant capacity, and lowered their systolic and diastolic blood pressures. The group reported significant improvement of “tired eyes,” “stiff shoulders,” “constipation,” and “cold skin,” and “difficulty in falling asleep.”
Astaxanthin’s capacity to counter free radicals, and its plethora of benefits for memory and other brain functions, vision, cardiovascular health, insulin and blood sugar management, and immunity all suggest this is a premier nutrient for overall healthy aging. Astaxanthin provides profound support for cell membrane integrity and the mitochondria’s crucial energy production, both of which are core features of the well recognized free radical theory of aging.35 By protecting membranes and facilitating mitochondrial efficiency,36,37 astaxanthin promotes our health and wellbeing at every stage of life.
Scientific References:
1. Fassett RG, Coombes JS. Astaxanthin: a potential therapeutic agent in cardiovascular disease. Marine Drugs 2011;9:447-465.
2. McNulty HP, Byun J, Lockwood SF, others. Differential effect of carotenoids on lipid peroxidation due to membrane interactions. Biochim Biophys Acta 2007;1768:167-174.
3.
Naguib YM. Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem 2000;48:1150-1154.
4.
Mortensen A, Skibsted LH, Truscott TG. The interaction of dietary carotenoids with radical species. Arch Biochem Biophys 2001;385:13-19.
5.
Goto S, Kogure K, Abe K, others. Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. Biochim Biophys Acta 2001;1512:251-258.
6.
Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell (Fourth Edition). New York: Garland Science; 2002.
7.
Hulbert AJ. Membrane fatty acids as pacemakers of animal metabolism. Lipids 2007;42:811-819.
8.
Levine SA, Kidd PM. Antioxidant Adaptation:Role in Free Radical Pathology. San Leandro, CA: Allergy Research Group;1985.
9.
Shigenaga MK, Hagen TM, Ames BN. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 1994;91:10771-10778.
10.
Mason RP, Walter MF, McNulty HP, others. Rofecoxib increases susceptibility of human LDL and membrane lipids to oxidative damage: a mechanism of cardiotoxicity. J Cardiovasc Pharmacol 2006;47:S7-S14.
11.
Martinez A, Rodriguez-Girones MA, Barbosa A, Costas M. Donator acceptor map for carotenoids, melatonin and vitamins. J Phys Chem A 2008;112:9037-9042.
12.
Park JS, Kim HW, Mathison BD, others. Astaxanthin uptake in domestic dogs and cats. Nutr Metab 2010;7:52 (8 pages).
13.
Wolf AM, Asoh S, Hiranuma H, others. Astaxanthin protects mitochondrial redox state and functional integrity against oxidative stress. J Nutr Biochem 2010;21:381-389.
14.
Lu YP, Liu SY, Sun H, others. Neuroprotective effect of astaxanthin on H(2)O(2)-induced neurotoxicity in vitro and on focal cerebral ischemia in vivo. Brain Res 2010;1360:40-48.
15.
Karppi J, Rissanen TH, Nyyssonen K, others. Effects of astaxanthin supplementation on lipid peroxidation. Int J Vit Nutr Res 2007;77:3-11.
16.
Choi HD, Kim JH, Kvu-Youn Y, Shin WG. Effects of astaxanthin on oxidative stress in overweight and obese adults. Phytother Res 2011;Apr 8 (Epub ahead of print).
17.
Satoh A, Tsuji S, Okada Y, others. Preliminary clinical evaluation of toxicity and efficacy of a new astaxanthin-rich Haematococcus pluvialis extract. J Clin Biochem Nutr 2009;44:280-284.
18.
Zhang X, Pan L, Wei X, others. Impact of astaxanthin-enriched algal powder of Haematococcus pluvialis on memory improvement in BALB/c mice. Environ Geochem Hlth 2007;29:483-489.
19.
Kim J-H, Choi W, Lee, J-H, others. Astaxanthin inhibits H2O2-mediated apoptotic cell death in mouse neural progenitor cells via modulation of P38 and MEK signaling pathways. J Microbiol Biotechnol 2009;19:1355-1363.
20.
Lu Y-P, Liu S-Y, Sua H, others. Neuroprotective effect of astaxanthin on H2O2-induced neurotoxicity in vitro and on focal cerebral ischemia in vivo. Brain Res 2010;1360:40-48.
21.
Liu X, Osawa T. Astaxanthin protects neuronal cells against oxidative damage and is a potent candidate for brain food. Forum Nutr 2009;61:129-135.
22.
Kim JH, Nam S-W, Kim BW, others. Astaxanthin improves the proliferative capacity as well as the osteogenic and adipogenic differentiation potential in neural stem cells. Food Chem Toxicol 2010;48:1741-1745.
23.
Yuan J-P, Peng J, Yin K, Wang J-H. Potential health-promoting effects of astaxanthin. Mol Nutr Food Res 2011;55:150-165.
24.
Kajita M, Tsukahara H, Kato M. The effects of a dietary supplement containing astaxanthin on the accommodation function of the eye in middle-aged and older people. Med Consult New Remedies 2009;46:89-93 (English translation from Japanese).
25.
Nagaki Y, Hayasaka S, Yamada T, others. Effects of astaxanthin on accommodation, critical flicker fusion, and pattern visual evoked potential in visual display terminal workers. J Trad Med 2002;19:170-173.
26.
Yoshida H, Yanai H, Ito K, others. Administration of natural astaxanthin increases serum HDL-cholesterol and adiponectin in subjects with mild hyperlipidemia. Atheroscler 2010;219:520-523.
27.
Kajikawa Y, Ikeda M, Takemoto S, others. Association of circulating levels of leptin and adiponectin with metabolic syndrome and coronary heart disease. Int Heart J 2011;52:17-22.
28.
Uchiyama A, Okada Y. Clinical efficacy of astaxanthin-containing Haematococcus pluvialis extract for the volunteers at risk of metabolic syndrome. J Clin Biochem Nutr 2008;43 Suppl 1:390-393.
29.
Satoh A, Ishikura M, Murakami N, others. The innovation of technology for microalgae cultivation. In, Biotechnology in Functional Foods and Nutraceuticals, ed Bagchi D, Lau FC, Ghosh DK. Boca Raton, FL:CRC Press; 2010.
30.
Marotta F, Pavasuthipaisit K, Yoshida C, others. Relationship between aging and susceptibility of erythrocytes to oxidative damage. Rejuvenation Res 2006;9:227-230.
31.
Nakawaga K, Kiko T, Miyazawa T, others. Antioxidant effect of astaxanthin on phospholipid peroxidation in human erythrocytes. Br J Nutr 2011 Jan 31;1-9 [Epub ahead of print]
32.
Miyawaki H, Takahashi J, Tsukahara H, Takehara I. Effects of astaxanthin on human blood rheology. J Clin Biochem Nutr 2008;43:69-74.
33.
Park JS, Chyun JH, Kim YK, others. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab 2010;7:18 (10 pages).
34.
Iwabayashi M, Fujioka N, Nomoto K, others. Efficacy and safety of eight-week treatment with astaxanthin in individuals screened for increased oxidative stress burden. Anti-Aging Medicine 2009;6:15-21.
35.
Harman D. Free radical theory of aging. An update: increasing the functional life span. Ann NY Acad Sci 2006;1067:10-21.
36.
Hulbert AJ, Pamplona R, Buffenstein R, Buttemer WA. Life and death: metabolic rate, membrane composition, and life span of animals. Physiol Rev 2007;87:1175-1213.
Pieczenik SR, Neustadt J. Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol 2007;83:84-92. |
