Skip to main content
Search
Search
    Quick Search anywhere
    Quick search in Citations
Advanced Search
Skip main navigationClose Drawer MenuOpen Drawer Menu
Previous article
Review

Effects of Astaxanthin Supplementation on Oxidative Stress

A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Published Online:April 15, 2019https://doi.org/10.1024/0300-9831/a000497

Abstract

Abstract. A systematic review and meta-analysis was conducted in six databases from 1948 to 2015 to assess the antioxidant activity of astaxanthin in humans. Nine randomized controlled trials were included in the systematic review. Results of meta-analysis revealed a borderline significant antioxidant effect of astaxanthin between the intervention and control groups, with a malondialdehyde-lowering effect for lipid peroxidation (p = 0.050). However, the data included here are insufficient. When compared with the baseline in intervention groups, the meta-analysis suggested that astaxanthin supplements significantly decreased plasma malondialdehyde {Standard mean difference (SMD) −1.32 μmol/L [95% CI −1.92, −0.72]; p < 0.0001} and isoprostane (SMD −3.10 ng/mL [95% CI −4.69, −1.51]; p < 0.0001). However, they increased superoxide dismutase (SMD 1.57 U/mL [95% CI 0.57, 2.56]; p = 0.002) and total antioxidant capacity (SMD 0.77 mmol 95% CI [0.12, 1.43]; p = 0.018). For dosage subgroup analysis, high dose (≥20 mg/day) of astaxanthin showed significant antioxidant effect (on total antioxidant capacity, isoprostane, and superoxide dismutase, p < 0.05). However, low dose (<20 mg/day) showed no significant effect (p > 0.05). Further duration subgroup analysis indicated that astaxanthin showed antioxidant effect after a 3-week intervention (p < 0.001), whereas this effect was not observed after a 12-week or 3-month intervention (on isoprostane and superoxide dismutase, p > 0.05). This review suggested that the antioxidant effect of astaxanthin on humans is unclear.

References

  • 1 Shukla, V., Mishra, S.K., & Pant, H.C. (2011) Oxidative stress in neurodegeneration. Adv. Pharmacol. Sci. 2011, 1–13. First citation in articleCrossref, Google Scholar

  • 2 Sies, H., & Jones, D.P. (2007) Oxidative Stress. Encyclopedia of Stress. (vol. 3 pp. 45–48). Elsevier. First citation in articleCrossref, Google Scholar

  • 3 Uki, M., Ninkovi, M., & Jovanovi, M. (2008) Oxidative stress - clinical diagnostic significance. J. Med. Biochem. 27, 409–425. First citation in articleCrossref, Google Scholar

  • 4 Schriner, S.E., Linford, N.J., Martin, G.M., Treuting, P., Ogburn, C.E., Emond, M., Coskun, P.E., Ladiges, W., Wolf, N., Van Remmen, H., Wallace, D.C., & Rabinovitch, P.S. (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. 308, 1909–1911. First citation in articleCrossref Medline, Google Scholar

  • 5 Dzau, V.J., Antman, E.M., Black, H.R., Hayes, D.L., Manson, J.E., Plutzky, J., Popma, J.J., & Stevenson, W. (2006) The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part ii: clinical trial evidence (acute coronary syndromes through renal disease) and future directions. Circulation. 114, 2871–2891. First citation in articleCrossref Medline, Google Scholar

  • 6 Serrano, M., & Blasco, M. (2007) Cancer and ageing: convergent and divergent mechanisms. Nat. Rev. Mol. Cell Biol. 8, 715–722. First citation in articleCrossref Medline, Google Scholar

  • 7 Houstis, N., Rosen, E.D., & Lander, E.S. (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. 440, 944–948. First citation in articleCrossref Medline, Google Scholar

  • 8 Beal, M.F. (2003) Bioenergetic approaches for neuroprotection in parkinson ‘ s disease. Ann Neurol. 53, 39–48. First citation in articleCrossref, Google Scholar

  • 9 Brezezinska-Slebodzinska, E., Slebodzinski, A.B., Pietras, B., & Wieczorek, G. (1995) Antioxidant effect of vitamin e and glutathione on lipid peroxidation in boar semen plasma. Biol. Trace Elem. Res. 47, 69–74. First citation in articleCrossref Medline, Google Scholar

  • 10 Sindhu, E.R., Preethi, K.C., & Kuttan, R. (2010) Antioxidant activity of carotenoid lutein in vitro and in vivo. Indian J. Exp. Biol. 48, 843. First citation in articleMedline, Google Scholar

  • 11 Bohm, F., Edge, R., Mcgarvey, D.J., & Truscott, T.G. (1998) Beta-carotene with vitamins e and c offers synergistic cell protection against nox. Febs Letters. 436, 387–389. First citation in articleCrossref Medline, Google Scholar

  • 12 Chen, K., Suh, J., Carr, A.C., Morrow, J.D., Zeind, J., & Frei, B. (2001) Vitamin c suppresses oxidative lipid damage in vivo, even in the presence of iron overload. Am. J. Physiol. – Endocrinol. Metab. 279, 1406–1412. First citation in articleCrossref, Google Scholar

  • 13 Darr, D., Combs, S., Dunston, S., Manning, T., & Pinnell, S. (1992) Topical vitamin c protects porcine skin from ultraviolet radiation-induced damage. Br. J. Dermatol. 127, 247–253. First citation in articleCrossref Medline, Google Scholar

  • 14 Xavier, S.M., Barbosa, C.O., Barros, D.O., Silva, R.F., Oliveira, A.A., & Freitas, R.M. (2007) Vitamin c antioxidant effects in hippocampus of adult wistar rats after seizures and status epilepticus induced by pilocarpine. Neurosci. Lett. 420, 76–79. First citation in articleCrossref Medline, Google Scholar

  • 15 Cocate, P.G., Natali, A.J., Alfenas, R.C., De, O.A., Dos Santos, E.C., & Hermsdorff, H.H. (2015) Carotenoid consumption is related to lower lipid oxidation and dna damage in middle-aged men. Br. J. Nutr. 114, 1–8. First citation in articleCrossref Medline, Google Scholar

  • 16 Carty, J.L., Bevan, R., Waller, H., Mistry, N., Cooke, M., Lunec, J., & Griffiths, H.R. (2000) The effects of vitamin c supplementation on protein oxidation in healthy volunteers. Biochem. Biophys. Res. Commun. 273, 729–735. First citation in articleCrossref Medline, Google Scholar

  • 17 Yusuf, S., Dagenais, G., Pogue, J., Bosch, J., & Sleight, P. (2000) Vitamin e supplementation and cardiovascular events in high-risk patients. the heart outcomes prevention evaluation study investigators. N. Engl. J. Med. 342(3), 154–160. First citation in articleCrossref Medline, Google Scholar

  • 18 Heart Protection Study Collaborative Group. (2002) Mrc/bhf heart protection study of antioxidant vitamin supplementation in 20, 536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 360, 23–33. First citation in articleCrossref Medline, Google Scholar

  • 19 Miller, E.R., Pastorbarriuso, R., Dalal, D., Riemersma, R.A., Appel, L.J., & Guallar, E. (2005) Meta-analysis: high-dosage vitamin e supplementation may increase all-cause mortality. Ann. Intern. Med. 142, 37–47. First citation in articleCrossref Medline, Google Scholar

  • 20 Stanner, S.A., Hughes, J., & Buttriss, C.K.J. (2004) A review of the epidemiological evidence for the ‘antioxidant hypothesis’. Public Health Nutr. 7, 407–422. First citation in articleCrossref Medline, Google Scholar

  • 21 Steinhubl, S.R. (2008) Why have antioxidants failed in clinical trials? Am. J. Cardiol. 101, 14–19. First citation in articleCrossref, Google Scholar

  • 22 Fassett, R.G., & Coombes, J.S. (2009) Astaxanthin, oxidative stress, inflammation and cardiovascular disease. Future Cardiol. 5, 333–342. First citation in articleCrossref Medline, Google Scholar

  • 23 Fassett, R.G., & Coombes, J.S. (2012) Astaxanthin in cardiovascular health and disease. Molecules. 17, 2030–2048. First citation in articleCrossref Medline, Google Scholar

  • 24 Lee, S., & Min, D. (1990) Effects, quenching mechanisms, and kinetics of carotenoids in chlorophyll-sensitized photooxidation of soybean oil. J. Agric. Food Chem. 38, 1630–1634. First citation in articleCrossref, Google Scholar

  • 25 Shmidzu, N., Goto, M., & Miki, W. (1996) Carotenoids as singlet oxygen quenchers in marine organisms. Fish Sci. 62, 134–137. First citation in articleCrossref, Google Scholar

  • 26 Mcnulty, H., Jacob, R.F., & Mason, R.P. (2008) Biologic activity of carotenoids related to distinct membrane physicochemical interactions. Am. J. Cardiol. 101, 20–29. First citation in articleCrossref Medline, Google Scholar

  • 27 Kochi, T., Shimizu, M., Sumi, T., Kubota, M., Shirakami, Y., Tanaka, T., & Moriwaki, H. (2014) Inhibitory effects of astaxanthin on azoxymethane-induced colonic preneoplastic lesions in c57/bl/ksj-db/db mice. BMC Gastroenterol. 14, 212. First citation in articleCrossref Medline, Google Scholar

  • 28 Guo, S.X., Zhou, H.L., Huang, C.L., You, C.G., Fang, Q., Wu, P., Wang, X.G., & Han, C.M. (2015) Astaxanthin attenuates early acute kidney injury following severe burns in rats by ameliorating oxidative stress and mitochondrial-related apoptosis. Mar. Drugs. 13, 2105–2123. First citation in articleCrossref Medline, Google Scholar

  • 29 Fassett, R.G., & Coombes, J.S. (2011) Astaxanthin: A potential therapeutic agent in cardiovascular disease. Mar. Drugs. 9, 447–465. First citation in articleCrossref Medline, Google Scholar

  • 30 Iwamoto, T., Hosoda, K., Hirano, R., Kurata, H., Matsumoto, A., Miki, W., Kamiyama, M., Itakura, H., Yamamoto, S., & Kondo, K. (2000) Inhibition of low-density lipoprotein oxidation by astaxanthin. J. Atheroscler. Thromb. 7, 216–222. First citation in articleCrossref Medline, Google Scholar

  • 31 Rufer, C.E., Moeseneder, J., Briviba, K., Rechkemmer, G., & Bub, A. (2008) Bioavailability of astaxanthin stereoisomers from wild (oncorhynchus spp.) and aquacultured (salmo salar) salmon in healthy men: a randomised, double-blind study. Br. J. Nutr. 99, 1048–1054. First citation in articleCrossref Medline, Google Scholar

  • 32 Haematococcus, A., Spiller, G.A., & Dewell, A. (2003) Safety of an astaxanthin-rich haematococcus pluvialis algal extract: a randomized clinical trial. J. Med. Food. 6, 51–56. First citation in articleCrossref Medline, Google Scholar

  • 33 Chen, J., Song, Y., & Zhang, L. (2013) Effect of lycopene supplementation on oxidative stress: an exploratory systematic review and meta-analysis of randomized controlled trials. J. Med. Food. 16, 361–374. First citation in articleCrossref Medline, Google Scholar

  • 34 Betteridge, D.J. (2000) What is oxidative stress? Metabolism. 49, 3–8. First citation in articleCrossref Medline, Google Scholar

  • 35 Shuster, J.J. (2011) Review: Cochrane handbook for systematic reviews for interventions, Version 5.1.0, published 3/2011. Julian P.T Higgins and Sally Green, Editors. Res. Synth. Methods. 2, 126–130. First citation in articleCrossref, Google Scholar

  • 36 Kiehna, E.N., Starke, R.M., Pouratian, N., & Dumont, A.S. (2010) Standards for reporting randomized controlled trials in neurosurgery. J. Neurosurg. 114, 280–285. First citation in articleCrossref Medline, Google Scholar

  • 37 Hsu, Y.M., Lai, C.H., Chang, C.Y., Fan, C.T., Chen, C.T., & Wu, C.H. (2008) Characterizing the lipid-lowering effects and antioxidant mechanisms of tomato paste. Biosci. Biotechnol. Biochem. 72, 677–685. First citation in articleCrossref Medline, Google Scholar

  • 38 European Food Safety Authority. (2014) Scientific Opinion on the safety of astaxanthin-rich ingredients (AstaREAL A1010 and AstaREAL L10) as novel food ingredients. EFSA J. 12, 1–35. First citation in articleGoogle Scholar

  • 39 Rosenberg, M.S. (2005) The file-drawer problem revisited: a general weighted method for calculating fail-safe numbers in meta-analysis. Evolution (N.Y). 59, 464–468. First citation in articleCrossref Medline, Google Scholar

  • 40 Baralic, I., Andjelkovic, M., Djordjevic, B., Dikic, N., Radivojevic, N., Suzin-Zivkovic, V., Radojevic-Skodric, S., & Pejic, S. (2015) Effect of astaxanthin supplementation on salivary iga, oxidative stress, and inflammation in young soccer players. Evidence-based Complementary and Alternative Medicine. 2015, 41–46. First citation in articleCrossref, Google Scholar

  • 41 Baralic, I., Djordjevic, B., Dikic, N., Kotur-Stevuljevic, J., Spasic, S., Jelic-Ivanovic, Z., Radivojevic, N., Andjelkovic, M., & Pejic, S. (2013) Effect of astaxanthin supplementation on paraoxonase 1 activities and oxidative stress status in young soccer players. Phytotherapy Research Ptr. 27, 1536–1542. First citation in articleMedline, Google Scholar

  • 42 Djordjevic, B., Baralic, I., Kotur-Stevuljevic, J., Stefanovic, A., Ivanisevic, J., Radivojevic, N., Andjelkovic, M., & Dikic, N. (2012) Effect of astaxanthin supplementation on muscle damage and oxidative stress markers in elite young soccer players. J. Sports Med. Phys. Fitness. 52, 382–392. First citation in articleMedline, Google Scholar

  • 43 Nakagawa, K., Kiko, T., Miyazawa, T., Carpentero Burdeos, G., Kimura, F., Satoh, A., & Miyazawa, T. (2011) Antioxidant effect of astaxanthin on phospholipid peroxidation in human erythrocytes. Br. J. Nutr. 105, 1563–1571. First citation in articleCrossref Medline, Google Scholar

  • 44 Karppi, J., Rissanen, T.H., Nyyssonen, K., Kaikkonen, J., Olsson, A.G., Voutilainen, S., & Salonen, J.T. (2007) Effects of astaxanthin supplementation on lipid peroxidation. Int. J. Vitam. Nutr. Res. 77, 3–11. First citation in articleLink, Google Scholar

  • 45 Peng, L., Zhao, P., Li, B., Zhang, J., & Huang, C. (2011) Antioxidant effects and impact on human health of astaxanthin. Chinese J. Food Hyg. 23, 313–316. First citation in articleGoogle Scholar

  • 46 Kim, J.H., Chang, M.J., Choi, H.D., Youn, Y.-K., Kim, J.T., Oh, J.M., & Shin, W.G. (2011) Protective Effects of Haematococcus Astaxanthin on Oxidative Stress in Healthy Smokers. J. Med. Food. 14, 1469–1475. First citation in articleCrossref Medline, Google Scholar

  • 47 Choi, H.D., Kim, J.H., Chang, M.J., Kyu-Youn, Y., & Shin, W.G. (2011) Effects of astaxanthin on oxidative stress in overweight and obese adults. Phyther. Res. 25, 1813–1818. First citation in articleCrossref Medline, Google Scholar

  • 48 Choi, H.D., Youn, Y.K., & Shin, W.G. (2011) Positive effects of astaxanthin on lipid profiles and oxidative stress in overweight Subjects. Plant Foods Hum. Nutr. 66, 363–369. First citation in articleCrossref Medline, Google Scholar

  • 49 Park, J.S., Chyun, J.H., Kim, Y.K., Line, L.L., & Chew, B.P. (2010) Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr. Metab. (Lond). 7, 18. First citation in articleCrossref Medline, Google Scholar

  • 50 Gaweł, S., Wardas, M., Niedworok, E., & Wardas, P. (2004) Malondialdehyde (mda) as a lipid peroxidation marker. Wiad. Lek. 57, 453–455. First citation in articleMedline, Google Scholar

  • 51 Repetto, M., Semprine, J., & Boveris, A. (2012) Lipid peroxidation: chemical mechanism, biological implications and analytical determination. Lipid peroxidation. (vol 1, pp 29). InTech. First citation in articleCrossref, Google Scholar

  • 52 Nielsen, F., Mikkelsen, B.B., Nielsen, J.B., Andersen, H.R., & Grandjean, P. (1997) Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin. Chem. 43, 1209–1214. First citation in articleCrossref Medline, Google Scholar

  • 53 Kadiiska, M.B., Gladen, B.C., Baird, D.D., Graham, L.B., Parker, C.E., Ames, B.N., Basu, S., FitzGerald, G.A., Lawson, J.A., Marnett, L.J., Morrow, J.D., Murray, D.M., Plastaras, J., Roberts, L.J., Rokach, J., Shigenaga, M.K., Sun, J., Walter, P.B., Tomer, K.B., Barrett, J.C., & Mason, R.P. (2005) Biomarkers of oxidative stress study: III. effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in ccl4 poisoning. Free Radic. Biol. Med. 38, 711–718. First citation in articleCrossref Medline, Google Scholar

  • 54 Kadiiska, M.B., Gladen, B.C., Baird, D.D., Dikalova, A.E., Sohal, R.S., Hatch, G.E., Jones, D.P., Mason, R.P., & Barrett, J.C. (2000) Biomarkers of oxidative stress study: are plasma antioxidants markers of ccl4 poisoning? Free Radic. Biol. Med. 28, 838–845. First citation in articleCrossref Medline, Google Scholar

  • 55 Kadiiska, M.B., Gladen, B.C., Baird, D.D., Germolec, D., Graham, L.B., Parker, C.E., Nyska, A., Wachsman, J.T., Ames, B.N., Basu, S., Brot, N., FitzGerald, G.A., Floyd, R.A., George, M., Heinecke, J.W., Hatch, G.E., Hensley, K., Lawson, J.A., Marnett, L.J., Morrow, J.D., Murray, D.M., Plastaras, J., Roberts, L.J., Rokach, J., Shigenaga, M.K., Sohal, R.S., Sun, J., Tice, R.R., Van Thiel, D.H., Wellner, D., Walter, P.B., Tomer, K.B., Mason, R.P., & Barrett, J.C. (2005) Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of ccl 4 poisoning? Free Radic. Biol. Med. 38, 698–710. First citation in articleCrossref Medline, Google Scholar

  • 56 Khoubnasabjafari, M., Ansarin, K., & Jouyban, A. (2015) Reliability of malondialdehyde as a biomarker of oxidative stress in psychological disorders. Bioimpacts. 5, 123–127. First citation in articleMedline, Google Scholar

  • 57 Montuschi, P., Barnes, P.J., & Roberts, L.J. (2004) Isoprostanes: markers and mediators of oxidative stress. FASEB J. 18, 1791–1800. First citation in articleCrossref Medline, Google Scholar

  • 58 Roberts, L.J., & Morrow, J.D. (2000) Measurement of F 2-isoprostanes as an index of oxidative stress in vivo. Free Radic. Biol. Med. 28, 505–513. First citation in articleCrossref Medline, Google Scholar

  • 59 Barros, M.P., Pinto, E., Colepicolo, P., & Pedersen, M. (2001) Astaxanthin and peridinin inhibit oxidative damage in Fe2+-loaded liposomes: scavenging oxyradicals or changing membrane permeability? Biochem. Biophys. Res. Commun. 288, 225–232. First citation in articleCrossref Medline, Google Scholar

  • 60 Kurashige, M., Okimasu, E., Inoue, M., & Utsumi, K. (1989) Inhibition of oxidative injury of biological membranes by astaxanthin. Physiol. Chem. Phys. Med. NMR. 22, 27–38. First citation in articleGoogle Scholar

  • 61 Chitchumroonchokchai, C., Bomser, J.A., Glamm, J.E., & Failla, M.L. (2004) Xanthophylls and alpha-tocopherol decrease UVB-induced lipid peroxidation and stress signaling in human lens epithelial cells. J. Nutr. 134, 3225–3232. First citation in articleCrossref Medline, Google Scholar

  • 62 Kidd, P. (2011) Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential. Altern. Med. Rev. 16, 355–364. First citation in articleMedline, Google Scholar

  • 63 Sies, H. (2007) Total Antioxidant Capacity: Appraisal of a Concept. J. Nutr. 137, 1493–1495. First citation in articleCrossref Medline, Google Scholar

  • 64 Sautin, Y.Y., & Johnson, R.J. (2008) Uric acid: the oxidant-antioxidant paradox. Nucleosides, Nucleotides and Nucleic Acids. 27, 608–619. First citation in articleCrossref Medline, Google Scholar

  • 65 Prochazkova, D., Bousova, I., & Wilhelmova, N. (2011) Antioxidant and prooxidant properties of flavonoids. Fitoterapia. 82, 513–523. First citation in articleCrossref Medline, Google Scholar

  • 66 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., Willett, W., & Peto, R. (1996) Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N. Engl. J. Med. 334, 1145–1149. First citation in articleCrossref Medline, Google Scholar

  • 67 Aris, A., Leblanc, S., Ouellet, A., & Moutquin, J.M. (2008) Detrimental effects of high levels of antioxidant vitamins c and e on placental function: considerations for the vitamins in preeclampsia (VIP) trial. J. Obstet. Gynaecol. Res. 34, 504–511. First citation in articleCrossref Medline, Google Scholar

  • 68 Versari, D., Daghini, E., Rodriguez-Porcel, M., Sattler, K., Galili, O., Pilarczyk, K., Napoli, C., Lerman, L.O., & Lerman, A. (2006) Chronic antioxidant supplementation impairs coronary endothelial function and myocardial perfusion in normal pigs. Hypertension. 47, 475–481. First citation in articleCrossref Medline, Google Scholar

  • 69 Gerardi, G., Usberti, M., Martini, G., Albertini, A., Sugherini, L., Pompella, A., & Lorenzo, D.D. (2002) Plasma total antioxidant capacity in hemodialyzed patients and its relationships to other biomarkers of oxidative stress and lipid peroxidation. Clin. Chem. Lab. Med. 40, 104–110. First citation in articleCrossref Medline, Google Scholar

  • 70 Del Rio, D., Stewart, A.J., & Pellegrini, N. (2005) A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr. Metab. Cardiovasc. Dis. 15, 316–328. First citation in articleCrossref Medline, Google Scholar