The Medical Research of Astaxanthin © Copyright 2012 Cyanotech Corporation All rights reserved Compiled and edited by: Bob Capelli Stephanie Keily Julia Linhart Gerald R. Cysewski, PhD Editor’s Note: The publisher of this paper, Cyanotech Corporation, is the producer of BioAstin® Natural Astaxanthin. Cyanotech wishes to make it clear that none of the animal studies referenced in this paper were sponsored by Cyanotech. Our company policy is to sponsor medical research as human clinical trials, exclusively with subjects recruited as willing volunteers. We do not condone animal experimentation; yet animal studies done by others are reported in this paper in order that the reader may fully understand the ongoing medical research and the potential benefits of Astaxanthin in human nutrition. Publisher’s Note: The information contained within is for educational purposes only; it is not to be taken as medical advice or as an attempt to sell a particular product. People with medical problems or questions should consult a health professional. Information in this book is not intended to diagnose, treat, cure or prevent any disease. 1 Table of Contents I. Introduction……………………………………………………………………3 II. Antioxidant……………………………………………………………………4 III. Anti-Inflammatory: Joint, Tendon and Muscle Health….…………………..67 IV. Skin Health: Internal Beauty and UV Protection……………………………85 V. Eye Health……………………………………………..……………………102 VI. Neuroprotective (Brain)…………………………………………………….129 VII. Cardioprotective (Heart)……………………………………………….…...150 VIII. Immunity……………………………………………………………………199 IX. Cancer Prevention and Tumor Reduction…………………………………..218 X. Diabetes……………………………………………………………………..254 XI. Ulcers and Gastrointestinal Health……………………………………........270 XII. Applications for Athletes: Strength, Endurance, Energy, Recovery………282 XIII. Additional Areas of Astaxanthin Research……………………………..…..297 • General Health • Weight Loss • Hepatoprotective (Liver) • Renal Protective (Kidney) • Prostate Health • Male Fertility • Asthma • Candida • Toxicity • Neural Stem Cells • Bioavailability • Anti-Aging • Safety 2 Introduction The body of medical research on Astaxanthin is fast approaching critical mass for several diverse applications. Over the last decade in particular, the amount of studies done by private researchers and universities throughout the world has escalated. The intense interest in undertaking new research on Astaxanthin is a direct result of the remarkable qualities of this fascinating molecule. Cyanotech Corporation* feels that it is important to have a library of this research available for interested persons; hence we have created this document. Below the reader will find selected research abstracts on the health benefits of Astaxanthin. It was not practical to include full studies due to the substantial amount of literature available; however, with these abstracts, the reader will obtain a working knowledge of potential applications for Astaxanthin in human nutrition. The abstracts are presented according to health benefit as noted in the table of contents. In the case of studies that focused on more than one health benefit, the study is categorized according to the primary area of research within the abstract. Any questions may be directed to Cyanotech Corporation, Kailua-Kona, Hawaii, USA, by e-mail at [email protected] or by telephone at 808.326.1353. * Cyanotech Corporation is the world leader in microalgae technology. Cyanotech produces BioAstin Natural Astaxanthin at its 90 acre (40 hectare) microalgae farm on the pristine Kona Coast of Hawaii. 3 Antioxidant Carotenoid Science, Vol.11, 2007, 16-20 Quenching Activities of Common Hydrophilic and Lipophilic Antioxidants against Singlet Oxygen Using Chemiluminescence Detection System Yasuhiro Nishida*, Eiji Yamashita and Wataru Miki Institute for Food Science Research, Japan The singlet oxygen quenching activities among common hydrophilic and lipophilic antioxidants such as polyphenols, tocopherols, carotenoids, ascorbic acid, coenzyme Q10 and α-lipoic acid were recorded under the same test condition: the chemiluminescence detection system for direct 1O2 counting using the thermodissociable endoperoxides of 1,4-dimethylnaphthalene as 1O2 generator in DMF : CDCl3 (9 : 1). Carotenoids exhibited larger total quenching rate constants than other antioxidants, with astaxanthin showing the strongest activity. α-Tocopherol and α-lipoic acid showed considerable activities, whereas the activities of ascorbic acid, CoQ10 and polyphenols were only slight; these included capsaicin, probucol, edaravon, BHT and Trolox. This system has the potential of being a powerful tool to evaluate the quenching activity against singlet oxygen for various hydrophilic and lipophilic compounds. Antioxidant 4 Adapted from Nishida, Yamashita, Miki, Carotenoid Science, Vol. 11, 2007, 16-20 (in Japanese) Astaxanthin has exceptional antioxidant activity to combat singlet oxygen when compared to other antioxidants. In particular, Astaxanthin can be used to defend against singlet oxygen damage for eye and skin health, which are especially susceptible to UV damage and aging effects. Singlet oxygen is an active oxygen species generated in human skin by exposure to ultraviolet radiation (UV) that causes skin damage and eye damage. In this study, Astaxanthin extracted from Haematococcus microalgae powerfully quenched singlet oxygen. Results show that the quenching effect of Astaxanthin is 800 times greater than coenzyme Q10. Astaxanthin was also about 75 times greater than alpha lipoic acid, about 550 times greater than green tea catechins and about 6000 times greater than Vitamin C. Antioxidant 5 Carotenoids as Singlet Oxygen Quenchers in Marine Organisms Shimidzu, Gogo, Miki, 1995. Fisheries Science 62(1), 134-137 Results indicated that Astaxanthin was significantly stronger than all other antioxidants tested as singlet oxygen quenchers. Among the results Astaxanthin was shown to be 550X stronger than Vitamin E; 11X stronger than Beta-Carotene; 2.75X stronger than Lutein. Antioxidant 6 OXYGEN FREE RADICAL SCAVENGING ABILITIES OF VITAMINS C, E, β-CAROTENE, PYCNOGENOL, GRAPE SEED PROANTHOCYANIDIN EXTRACT AND ASTAXANTHINS IN VITRO Debasis Bagchi, Ph.D. Pharmacy Sciences, Creighton University School of Health Sciences, June 2001 Summary: Natural Astaxanthin (as BioAstin® from Cyanotech) showed significantly higher free radical scavenging activity than all other antioxidants tested. Results on a pure active basis were as follows: Natural Astaxanthin Alternate Antioxidant Multiple of Greater Free Radical Scavenging Activity BioAstin Vitamin C 65X stronger BioAstin Vitamin E 14X stronger BioAstin Beta Carotene 54X stronger BioAstin Pycnogenol® 18X stronger BioAstin Synthetic Astaxanthin 21X stronger Antioxidant 7 Comparison of Astaxanthin’s Singlet Oxygen Quenching Activity with Common Fat and Water Soluble Antioxidants United States Patent Application 20060217445 Kind Code A1 Chew; Boon P. ; et al. September 28, 2006 Natural astaxanthin extract reduces DNA oxidation Abstract Provided herein are methods for reducing oxidative DNA damage in a subject, by administering to the subject astaxanthin, for instance a natural, astaxanthin- enriched extract from Haematococcus pluvialis. It is shown that doses as low as 2 mg/day, given orally to a human subject for a period of four weeks, is sufficient to reduced measurable endogenous oxidative DNA damage by about 40%. Antioxidant 8 Phytother Res. 2009 Jun 22. [Epub ahead of print] Cytoprotective role of astaxanthin against glycated protein/iron chelate-induced toxicity in human umbilical vein endothelial cells. Nishigaki I, Rajendran P, Venugopal R, Ekambaram G, Sakthisekaran D, Nishigaki Y. NPO International Laboratory of Biochemistry, 1-166 Uchide, Nakagawa-ku Nagoya 454-0926, Japan. Astaxanthin (ASX), a red carotenoid pigment with no pro-vitamin A activity, is a biological antioxidant that occurs naturally in a wide variety of plants, algae and seafoods. This study investigated whether ASX could inhibit glycated protein/iron chelate-induced toxicity in human umbilical-vein endothelial cells (HUVEC) by interfering with ROS generation in these cells. Glycated fetal bovine serum (GFBS) was prepared by incubating fetal bovine serum (FBS) with high- concentration glucose. Stimulation of cultured HUVECs with 50 mm 1 mL of GFBS significantly enhanced lipid peroxidation and decreased antioxidant enzyme activities and levels of phase II enzymes. However, preincubation of the cultures with ASX resulted in a marked decrease in the level of lipid peroxide (LPO) and an increase in the levels of antioxidant enzymes in an ASX concentration-dependent manner. These results demonstrate that ASX could inhibit LPO formation and enhance the antioxidant enzyme status in GFBS/iron chelate-exposed endothelial cells by suppressing ROS generation, thereby limiting the effects of the AGE-RAGE interaction. The results indicate that ASX could have a beneficial role against glycated protein/iron chelate-induced toxicity by preventing lipid and protein oxidation and increasing the activity of antioxidant enzymes. PMID: 19548280 [PubMed - as supplied by publisher] Antioxidant 9 Biochim Biophys Acta. 2001 Jun 6;1512(2):251-8. Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. Goto S, Kogure K, Abe K, Kimata Y, Kitahama K, Yamashita E, Terada H. Faculty of Pharmaceutical Sciences, University of Tokushima, Japan. [email protected] The effects of the carotenoids beta-carotene and astaxanthin on the peroxidation of liposomes induced by ADP and Fe(2+) were examined. Both compounds inhibited production of lipid peroxides, astaxanthin being about 2-fold more effective than beta-carotene. The difference in the modes of destruction of the conjugated polyene chain between beta-carotene and astaxanthin suggested that the conjugated polyene moiety and terminal ring moieties of the more potent astaxanthin trapped radicals in the membrane and both at the membrane surface and in the membrane, respectively, whereas only the conjugated polyene chain of beta-carotene was responsible for radical trapping near the membrane surface and in the interior of the membrane. The efficient antioxidant activity of astaxanthin is suggested to be due to the unique structure of the terminal ring moiety. Publication Types: PMID: 11406102 [PubMed - indexed for MEDLINE] Antioxidant 10