Effects of Astaxanthin Supplementation on Oxidative Stress
A Systematic Review and Meta-Analysis of Randomized Controlled Trials
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 (2011) Oxidative stress in neurodegeneration. Adv. Pharmacol. Sci. 2011, 1–13.
2 (2007) Oxidative Stress. Encyclopedia of Stress. (vol. 3 pp. 45–48). Elsevier.
3 (2008) Oxidative stress - clinical diagnostic significance. J. Med. Biochem. 27, 409–425.
4 (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. 308, 1909–1911.
5 (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.
6 (2007) Cancer and ageing: convergent and divergent mechanisms. Nat. Rev. Mol. Cell Biol. 8, 715–722.
7 (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. 440, 944–948.
8 (2003) Bioenergetic approaches for neuroprotection in parkinson ‘ s disease. Ann Neurol. 53, 39–48.
9 (1995) Antioxidant effect of vitamin e and glutathione on lipid peroxidation in boar semen plasma. Biol. Trace Elem. Res. 47, 69–74.
10 (2010) Antioxidant activity of carotenoid lutein in vitro and in vivo. Indian J. Exp. Biol. 48, 843.
11 (1998) Beta-carotene with vitamins e and c offers synergistic cell protection against nox. Febs Letters. 436, 387–389.
12 (2001) Vitamin c suppresses oxidative lipid damage in vivo, even in the presence of iron overload. Am. J. Physiol. – Endocrinol. Metab. 279, 1406–1412.
13 (1992) Topical vitamin c protects porcine skin from ultraviolet radiation-induced damage. Br. J. Dermatol. 127, 247–253.
14 (2007) Vitamin c antioxidant effects in hippocampus of adult wistar rats after seizures and status epilepticus induced by pilocarpine. Neurosci. Lett. 420, 76–79.
15 (2015) Carotenoid consumption is related to lower lipid oxidation and dna damage in middle-aged men. Br. J. Nutr. 114, 1–8.
16 (2000) The effects of vitamin c supplementation on protein oxidation in healthy volunteers. Biochem. Biophys. Res. Commun. 273, 729–735.
17 (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.
18 . (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.
19 (2005) Meta-analysis: high-dosage vitamin e supplementation may increase all-cause mortality. Ann. Intern. Med. 142, 37–47.
20 (2004) A review of the epidemiological evidence for the ‘antioxidant hypothesis’. Public Health Nutr. 7, 407–422.
21 (2008) Why have antioxidants failed in clinical trials? Am. J. Cardiol. 101, 14–19.
22 (2009) Astaxanthin, oxidative stress, inflammation and cardiovascular disease. Future Cardiol. 5, 333–342.
23 (2012) Astaxanthin in cardiovascular health and disease. Molecules. 17, 2030–2048.
24 (1990) Effects, quenching mechanisms, and kinetics of carotenoids in chlorophyll-sensitized photooxidation of soybean oil. J. Agric. Food Chem. 38, 1630–1634.
25 (1996) Carotenoids as singlet oxygen quenchers in marine organisms. Fish Sci. 62, 134–137.
26 (2008) Biologic activity of carotenoids related to distinct membrane physicochemical interactions. Am. J. Cardiol. 101, 20–29.
27 (2014) Inhibitory effects of astaxanthin on azoxymethane-induced colonic preneoplastic lesions in c57/bl/ksj-db/db mice. BMC Gastroenterol. 14, 212.
28 (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.
29 (2011) Astaxanthin: A potential therapeutic agent in cardiovascular disease. Mar. Drugs. 9, 447–465.
30 (2000) Inhibition of low-density lipoprotein oxidation by astaxanthin. J. Atheroscler. Thromb. 7, 216–222.
31 (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.
32 (2003) Safety of an astaxanthin-rich haematococcus pluvialis algal extract: a randomized clinical trial. J. Med. Food. 6, 51–56.
33 (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.
34 (2000) What is oxidative stress? Metabolism. 49, 3–8.
35 (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.
36 (2010) Standards for reporting randomized controlled trials in neurosurgery. J. Neurosurg. 114, 280–285.
37 (2008) Characterizing the lipid-lowering effects and antioxidant mechanisms of tomato paste. Biosci. Biotechnol. Biochem. 72, 677–685.
38 . (2014) Scientific Opinion on the safety of astaxanthin-rich ingredients (AstaREAL A1010 and AstaREAL L10) as novel food ingredients. EFSA J. 12, 1–35.
39 (2005) The file-drawer problem revisited: a general weighted method for calculating fail-safe numbers in meta-analysis. Evolution (N.Y). 59, 464–468.
40 (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.
41 (2013) Effect of astaxanthin supplementation on paraoxonase 1 activities and oxidative stress status in young soccer players. Phytotherapy Research Ptr. 27, 1536–1542.
42 (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.
43 (2011) Antioxidant effect of astaxanthin on phospholipid peroxidation in human erythrocytes. Br. J. Nutr. 105, 1563–1571.
44 (2007) Effects of astaxanthin supplementation on lipid peroxidation. Int. J. Vitam. Nutr. Res. 77, 3–11.
45 (2011) Antioxidant effects and impact on human health of astaxanthin. Chinese J. Food Hyg. 23, 313–316.
46 (2011) Protective Effects of Haematococcus Astaxanthin on Oxidative Stress in Healthy Smokers. J. Med. Food. 14, 1469–1475.
47 (2011) Effects of astaxanthin on oxidative stress in overweight and obese adults. Phyther. Res. 25, 1813–1818.
48 (2011) Positive effects of astaxanthin on lipid profiles and oxidative stress in overweight Subjects. Plant Foods Hum. Nutr. 66, 363–369.
49 (2010) Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr. Metab. (Lond). 7, 18.
50 (2004) Malondialdehyde (mda) as a lipid peroxidation marker. Wiad. Lek. 57, 453–455.
51 (2012) Lipid peroxidation: chemical mechanism, biological implications and analytical determination. Lipid peroxidation. (vol 1, pp 29). InTech.
52 (1997) Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin. Chem. 43, 1209–1214.
53 (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.
54 (2000) Biomarkers of oxidative stress study: are plasma antioxidants markers of ccl4 poisoning? Free Radic. Biol. Med. 28, 838–845.
55 (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.
56 (2015) Reliability of malondialdehyde as a biomarker of oxidative stress in psychological disorders. Bioimpacts. 5, 123–127.
57 (2004) Isoprostanes: markers and mediators of oxidative stress. FASEB J. 18, 1791–1800.
58 (2000) Measurement of F 2-isoprostanes as an index of oxidative stress in vivo. Free Radic. Biol. Med. 28, 505–513.
59 (2001) Astaxanthin and peridinin inhibit oxidative damage in Fe2+-loaded liposomes: scavenging oxyradicals or changing membrane permeability? Biochem. Biophys. Res. Commun. 288, 225–232.
60 (1989) Inhibition of oxidative injury of biological membranes by astaxanthin. Physiol. Chem. Phys. Med. NMR. 22, 27–38.
61 (2004) Xanthophylls and alpha-tocopherol decrease UVB-induced lipid peroxidation and stress signaling in human lens epithelial cells. J. Nutr. 134, 3225–3232.
62 (2011) Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential. Altern. Med. Rev. 16, 355–364.
63 (2007) Total Antioxidant Capacity: Appraisal of a Concept. J. Nutr. 137, 1493–1495.
64 (2008) Uric acid: the oxidant-antioxidant paradox. Nucleosides, Nucleotides and Nucleic Acids. 27, 608–619.
65 (2011) Antioxidant and prooxidant properties of flavonoids. Fitoterapia. 82, 513–523.
66 (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.
67 (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.
68 (2006) Chronic antioxidant supplementation impairs coronary endothelial function and myocardial perfusion in normal pigs. Hypertension. 47, 475–481.
69 (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.
70 (2005) A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr. Metab. Cardiovasc. Dis. 15, 316–328.