ASTAXANTHIN: King of the Carotenoids

Carotenoids are a family of natural fat-soluble nutrients important for antioxidant defense. You’ve probably heard of some of them: beta-carotene, lycopene, lutein, zeaxanthin. If you eat a fruit or vegetable that is red, orange or yellow, odds are carotenoids are responsible for the vibrant color. (Pineapple, peaches, nectarines, tomatoes, papaya, apricots, carrots, watermelons, pumpkin, sweet potatoes… you get the point.) They do also appear in disguise sometimes, masked by chlorophyll, in dark green leafy vegetables like spinach, broccoli, collard greens, and kale.

Aside from food, some of the most beautiful colors in nature are brought to you by carotenoids: the pink flamingo, scarlet ibis, canary, lady bug, pink crustaceans and salmon, and many flowers all owe their “wow” factor to carotenoids.

Scarlet Ibis

While over 600 carotenoids have been identified in nature, fewer than 50 are part of the human diet. Humans cannot synthesize carotenoids and must ingest them via algae, plants, fungi and seafood.1

Most of the health benefits of carotenoids are associated with their action as antioxidants: they protect cells and tissues from the effects of free radicals.

Carotenoids are “kamikaze” antioxidants. In other words, carotenoids are not regenerated like other antioxidants such as Vitamin E or Coenzyme Q10; they are degraded in the process of neutralizing free radicals or reactive oxygen species. A typical carotenoid molecule like lycopene or beta-carotene can sustain more than 20 free radical “hits” by lipid radicals before it is completely destroyed.2

Carotenoids are not soluble in water. Therefore, they are transported in blood by low-density lipoproteins (LDL) together with other fat-soluble substances like vitamin E or cholesterol. When the LDL reaches cells of the skin epidermis and dermis, carotenoids are transferred by means of lipoprotein receptors on the cell surface. In this way, they offer skin protection against free radical damage from UV radiation.

There are two types of carotenoids (based on chemical structure): carotenes and xanthopylls. Lycopene and beta-carotene are examples of carotenes, while lutein, zeaxanthin, and astaxanthin are xanthopyll carotenoids.

Carotenoids exert varying effects according to their polarity and hence, how they configure with cellular membranes.3 This is, in fact, what makes astaxanthin the most “special” of the carotenoids (as far as humans are concerned):

novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am J Cardiol 2008;101(suppl):58D-68D.

As we see in the illustration above, astaxanthin has a unique structure: the polar end groups overlap the polar edges of the cell membrane, while the nonpolar middle fits the membrane’s nonpolar interior. This allows Astaxanthin to protect the cell membrane against free radical or other oxidative attack in a way that no other antioxidant can. The polar structures are called ionone rings, and have tremendous capacity for eliminating free radicals or other oxidants—as an anti-oxidant, astaxanthin is 11 times more potent than beta-carotene, and 550 times more potent than alpha-tocopherol!   Because it’s structure allows it to lie across the cell membrane, astaxanthin has the ability to neutralize free radical or other oxidant activity in both the nonpolar (“hydrophobic”) center of the membrane, as well as along the polar (hydrophilic) boundary zones.4

A particularly elegant experiment done in 2007 established astaxanthin’s superiority over other carotenoids in protecting cell membranes:

McNulty et al created models of cell membranes in a lab, using phosphatidylcholine and a small amount of cholesterol, at ratios similar to natural cell membranes. Then they introduced astaxanthin, zeaxanthin, lutein, beta-carotene, or lycopene to these model membranes and monitored what happened to the membranes. They also generated oxidative stress by gently increasing the temperature of the system. With the exception of astaxanthin, the carotenoids all disrupted the phospholipid packing and worsened peroxidative breakdown.  And the two went together: the greater the membrane disruption by a carotenoid, the greater was its peroxidative effect.  Only astaxanthin reduced peroxidation (by 41 percent) and only astaxanthin preserved the membrane structure.5

Lutein and beta-carotene are non-polar, and therefore cause disorder of the membrane structure and oxidation of lipids.5,6 In contrast, astaxanthin is polar, and preserves the structure of the membrane. These contrasting effects may explain the different outcomes seen in clinical and experimental studies. The non-polar beta-carotene has not been found to have any beneficial effects on cardiovascular disease 711 and is actually pro-oxidant at higher doses 12. An addition, both beta carotene and lutein were shown to increase the risk of cancer in human studies. In experimental studies the polar astaxanthin has myocardial preservation effects but this is yet to be confirmed in human clinical trials. 13-15   Both its high potency and polar properties make astaxanthin an attractive nutraceutical for further investigation in atherosclerotic cardiovascular disease where antioxidant cellular protection may be of clinical benefit.16

So what does this mean for us? Are there studies showing real benefit– studies in humans, not rats or test tubes? Yes. In an excellent 2011 article,27 Parris Kidd reviewed the human studies on astaxanthin, which suggest the following benefits:

Astaxanthin lowers oxidative stress—not just in a test tube, but in real people. 17

In a small 2011 study, overweight individuals were randomized to receive astaxanthin and were compared to a control group with normal body weight (BMI <25.0 kg/m2) who received no intervention.21 The researchers measured markers of oxidative stress in the blood. At baseline, the obese individuals had significantly higher levels of two oxidative biomarkers: malondialdehyde (MDA) and isoprostanes (ISP). At the same time, plasma levels of two antioxidant measures – superoxide dismutase (SOD) and total antioxidant capacity (TAC) – were significantly lower in obese participants. In other words, the antioxidant defenses were down in the obese patients. After three weeks, the astaxanthin group showed significant lowering of oxidative markers MDA and ISP (both p<0.01), and they also had significant increases in SOD and TAC (p<0.001). Marked improvements on all four measures caused the overweight and obese subjects to become statistically indistinguishable from the control group, suggesting that astaxanthin supplementation lowered oxidative stress and improved aspects of the antioxidant defense system.   In another double-blind trial, astaxanthin also significantly lowered C-reactive protein (CRP), a biomarker of systemic inflammation that we measure in all of our patients at PhysioAge. The same trial also investigated astaxanthin’s immune system benefits.18 They found that natural killer cell cytotoxic activity increased on astaxanthin, as did lymphocyte proliferation in response to appropriate (mitogen) stimulation (p<0.05 for both). In other words, immune system responses improved. This has implications not just for fighting off infection, but for fighting off cancer.

Astaxanthin improves blood lipids

Sixty-one people were recruited into a double-blind randomized controlled trial of astaxanthan vs placebo.19 Astaxanthin significantly increased HDL-cholesterol (the so-called “good cholesterol”; higher is better) and significantly lowered triglycerides, compared to placebo.

Positive Effects on Circulation

As people age, their red blood cells can be more susceptible to oxidative attack, resulting in damage to the red blood cell membranes, which impairs the ability of the red blood cells to carry oxygen through the body. In a 2011 double-blind RCT20, healthy subjects, ages 50-69 years (n=30), were randomly allocated to receive astaxanthin or placebo for 12 weeks. Astaxanthin significantly lowered RBC hydroperoxide levels (p<0.05).

Another interesting study looked at whether Astaxanthin could improve blood flow.21 Venous blood was forced using mild pressure through tiny “microchannels,” each just seven millionths of a meter wide, approximating the diameter of an red lood cell and the width of a capillary. The time required to traverse these capillary-type tubes under a set pressure was termed the transit time. Twenty men were randomly allocated to receive either astaxanthin or a placebo for 10 days. They tested their transit time both before and after the ten day period. Upon retest, the astaxanthin group had significantly faster transit time (p<0.05) compared to placebo. This is a small study, but it suggests astaxanthin could potentially improve microcirculation.

Improvements in Memory and Reaction Time

Astaxanthin might improve cognitive function. In a small, open-label trial, 10 healthy men ages 50-69, who had been complaining of forgetfulness, received astaxanthin (12 mg/day) for 12 weeks.22 On a computerized test designed to accurately detect early cognitive deterioration (“CogHealth”), they showed improvement in reaction time, attention, and working memory.

Improved Mitochondrial Function

The mitochondria are known as the “powerhouses” of your cells. They have double membranes crammed with proteins that utilize oxygen to generate energy. However, having a constantly working reactor does present risks: a small portion of this oxygen escapes catalytic control and is transformed into electronically excited reactive oxygen species (ROS, also known as “free radicals”). Our antioxidant defenses do their best to neutralize these free radicals, but some evade neutralization and damage the mitochondrial membranes.23. Mitochondrial decline due to cumulative ROS damage has been suggested as a major contributor to the aging process. 24
In a series of experiments with various cultured cell lines,25 astaxanthin improved cell survival under oxidative stress. Astaxanthin reduced the mitochondria’s endogenous production of oxygen radicals and protected the mitochondria against a decline in membrane function that typically occurs over time in these cultures. But astaxanthin’s benefits went even further: it increased mitochondrial activity by increasing oxygen consumption without increasing generation of ROS. It actually made the mitochondria more effective.   The researchers then inserted into the mitochondria another molecular probe that measured their ability to conserve glutathione and re-reduce oxidized biomolecules.25 The mitochondria were then challenged with hydrogen peroxide (H2O2), a reactive oxygen species (ROS) that should normally oxidize and reverse this redox state. Astaxanthin was found to protect against the H2O2 oxidant effect. Its capacities both to protect mitochondria and to boost their energy efficiency should stimulate further research into this nutrient’s potential for possible anti-aging effects. It should be clear now why we wanted astaxanthin in our new supplement Packs. Human trials suggest that it is among the most beneficial of the antioxidants, and almost certainly the most beneficial carotenoid. It seems to protect and improve the function of your mitochondria, which is highly significant as mitochondrial decay is one of the major contributors to the aging process. In addition, astaxanthin may benefit memory, blood lipids, circulation, and immune function, and help prevent metabolic syndrome.26 We added 10mg of astaxanthin to the PhysioAge Premium Packs: not just a token amount, but an amount consistent with what was effective in the studies listed above.
Show me the REFERENCES.

1. Sandmann, G. Carotenoid biosynthesis in microorganisms and plants. Eur. J. Biochem. 1994, 223, 7–24.
2. Tsuchiya et al., 1994.
3. McNulty, H.; Jacob, R.F.; Mason, R.P. Biologic activity of carotenoids related to distinct membrane physicochemical interactions. Am. J. Cardiol. 2008, 101, 20D–29D.
4. Fassett RG, Coombes JS. Astaxanthin: a potential therapeutic agent in cardiovascular disease. Mar Drugs 2011;9:447-465.
5. McNulty HP, Byun J, Lockwood SF, et al. Differential effects of carotenoids on lipid peroxidation due to membrane interactions. X-ray diffraction analysis. Biochim Biophys Acta 2007;1768:167-174.
6. McNulty, H.; Jacob, R.F.; Mason, R.P. Biologic activity of carotenoids related to distinct membrane physicochemical interactions. Am. J. Cardiol. 2008, 101, 20D–29D.
7. Brown, B.G.; Zhao, X.Q.; Chait, A.; Fisher, L.D.; Cheung, M.C.; Morse, J.S.; Dowdy, A.A.; Marino, E.K.; Bolson, E.L.; Alaupovic, P.; et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N. Engl. J. Med. 2001, 345, 1583––1592.
8. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J. Med. 1994, 330, 1029–1035. 9. Omenn, G.S.; Goodman, G.E.; Thornquist, M.D.; Balmes, J.; Cullen, M.R.; Glass, A.; Keogh, J.P.; Meyskens, F.L.; Valanis, B.; Williams, J.H.; et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N. Engl. J. Med. 1996, 334, 1150––1155. 10. Lee, I.M.; Cook, N.R.; Manson, J.E.; Buring, J.E.; Hennekens, C.H. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: The Women’s Health Study. J. Natl. Cancer Inst. 1999, 91, 2102––2106.
11. Hennekens, C.H.; Buring, J.E.; Manson, J.E.; Stampfer, M.; Rosner, B.; Cook, N.R.; Belanger, C.; LaMotte, F.; Gaziano, J.M.; Ridker, P.M.; et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N. Engl. J. Med. 1996, 334, 1145–1149
12. Burton, G.W.; Ingold, K.U. beta-Carotene: An unusual type of lipid antioxidant. Science 1984, 224, 569–573.
13. Lauver, D.A.; Driscoll, E.M.; Lucchesi, B.R. Disodium disuccinate astaxanthin prevents carotid artery rethrombosis and ex vivo platelet activation. Pharmacology 2008, 82, 67––73.
14. Gross, G.J.; Lockwood, S.F. Cardioprotection and myocardial salvage by a disodium disuccinate astaxanthin derivative (Cardax). Life Sci. 2004, 75, 215–224. 15. Gross, G.J.; Hazen, S.L.; Lockwood, S.F. Seven day oral supplementation with Cardax (disodium disuccinate astaxanthin) provides significant cardioprotection and reduces oxidative stress in rats. Mol. Cell. Biochem. 2006, 283, 23–30.
16. Pashkow, F.J.; Watumull, D.G.; Campbell, C.L. Astaxanthin: A novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am. J. Cardiol. 2008, 101, 58D–68D.

17. Choi HD, Kim JH, Chang MJ, et al. Effects of astaxanthin on oxidative stress in overweight and obese adults. Phytother Res 2011 Apr 8.

18. Park JS, Chyun JH, Kim YK, et al. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab (Lond) 2010;7:18.
19. Yoshida H, Yanai H, Ito K, et al. Administration of natural astaxanthin increases serum HDL-cholesterol and adiponectin in subjects with mild hyperlipid- emia. Atherosclerosis 2010;209:520-523.

20. Nakagawa K, Kiko T, Miyazawa T, et al. Antioxidant effect of astaxanthin on phospholipid peroxidation in human erythrocytes. Br J Nutr 2011;105:1563-1571.
21. Miyawaki H, Takahashi J, Tsukahara H, Takehara I. Effects of astaxanthin on human blood rheology. J Clin Biochem Nutr 2008;43:69-74. 22. Satoh A, Tsuji S, Okada Y, et al. Preliminary clinical evaluation of toxicity and efficacy of a new astaxanthin-rich Haematococcus pluvialis extract. J Clin Biochem Nutr 2009;44:280-284.

23. Shigenaga MK, Hagen TM, Ames BN. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci U S A 1994;91:10771-10778.

24. Harman D. Free radical theory of aging: an update: increasing the functional life span. Ann N Y Acad Sci 2006;1067:10-21.

25. Wolf AM, Asoh S, Hiranuma H, et al. Astaxanthin protects mitochondrial redox state and functional integrity against oxidative stress. J Nutr Biochem 2010;21:381-389.

26. 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;43:390-393.

27. Kidd. Astaxanthin, Cell Membrane Nutrient with Diverse Clinical Benefits and Anti-Aging Potential. Altern Med Rev 2011;16(4):355-364

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