000054
Letter to the Editor
Antioxidants - friend or foe?
Meffert
Meffert
Hans
H
Prof. Dr. med.
Dermatologisches Zentrum Berlin, Potsdamer Chaussee 80, D-14129 Berlin, Deutschland, Tel.: 0049-30-2821475Dermatologisches Zentrum, Berlin, Germanyhttp://www.dermatologie-berlin.de
hans.meffert@web.de
author
German Medical Science GMS Publishing House
Düsseldorf
ANTIOXIDANTS
metabolism
pharmacology
therapeutic use
OXIDANTS
therapeutic use
metabolism
pharmacology
ASCORBIC ACID
therapeutic use
metabolism
pharmacology
BETA CAROTENE
therapeutic use
metabolism
pharmacology
VITAMIN E
therapeutic use
metabolism
pharmacology
VITAMIN A
therapeutic use
metabolism
pharmacology
FOOD ADDITIVES
metabolism
pharmacology
therapeutic use
DIETARY SUPPLEMENTS
SKIN AGING
drug effects
ANTICARCINOGENIC AGENTS
metabolism
pharmacology
FREE RADICALS
metabolism
pharmacology
SKIN NEOPLASMS
prevention & control
NEOPLASMS
prevention & control
REVIEW
HUMANS
ANIMALS
610
20080718
20080903
engl
1612-3174
6
GMS German Medical Science
GMS Ger Med Sci
09
Text
Particularly in the field of advertising and in popular scientific journals, antioxidants such as β-carotene (from carrots) or lycopenes (from tomatoes) and the <![CDATA[vitamins C</PlainText></TextGroup> and E are one-sidedly portrayed as substances capable of offering protection against cancer or ageing because they diminish or prevent the effects of free radicals.</Pgraph>
<Pgraph>However, free radicals should by no means be considered as being exclusively destructive. On the contrary, processes such as energy metabolism (in the respiratory chain) and the defence of neutrophilic granulocytes against pathogens and foreign bodies depend on the formation of free radicals <TextLink reference="1"></TextLink>, <TextLink reference="2"></TextLink>.</Pgraph>
<Pgraph>For this reason alone, it has to be expected that a supply of antioxidants may also cause considerable undesired effects to the skin and the organism.</Pgraph>
<Pgraph>In addition, “under certain conditions, some anti-oxidants can also exhibit a pro-oxidant mechanism of action” <TextLink reference="3"></TextLink>, e.g. β-carotene <TextLink reference="3"></TextLink> or vitamin C <TextLink reference="4"></TextLink>, with the question “When is an antioxidant not an antioxidant?” <TextLink reference="4"></TextLink>. </Pgraph>
<Pgraph>Many people with above-average consumption of fruits and vegetables undoubtedly demonstrate a lower risk of developing lung cancer. However about 10 years ago, completely unexpectedly two studies on highly dosed β<TextGroup><PlainText>-carotene</PlainText></TextGroup> supplementation had to be abandoned because the risk of lung cancer in smokers had unforeseeably increased following β-carotene supplementation. Further studies in vitro and in vivo were interpreted as showing β-carotene to act as an anticarcinogen, whereas its oxidation product acted as a carcinogen, possibly related to the instability of the β-carotene molecule in the free radical-rich environment in the lungs of cigarette smokers <TextLink reference="5"></TextLink>.</Pgraph>
<Pgraph>In a large-scale, multicenter, double-blind, placebo-controlled clinical trial on prevention, 864 persons, whose colon polyps had been removed, received 25 mg of <TextGroup><PlainText>β-carotene</PlainText></TextGroup> or placebo combined with 1000 mg <TextGroup><PlainText>vitamin C</PlainText></TextGroup> + 400 mg vitamin E or placebo on a daily basis. After four years, the following observations could be made concerning supplementation of β-carotene and the development of colon polyps:</Pgraph>
<Pgraph>
<UnorderedList>
<ListItem level="1">pronounced reduction of the risk for non-smokers and those abstaining from alcohol</ListItem>
<ListItem level="1">slightly increased risk for smokers or alcohol consumers</ListItem>
<ListItem level="1">a doubling of the risk for people who smoke cigarettes and consume more than one alcoholic beverage per day <TextLink reference="6"></TextLink>.</ListItem>
</UnorderedList>
</Pgraph>
<Pgraph>Further clinical studies showed that β-carotene supplementation caused no change in the incidence of non-melanoma skin cancer. As H. S. Black reported, after a β-carotene supplemented diet even a significant exacerbation of the UV-carcinogenesis occurred. A photoprotective effect was not achieved <TextLink reference="7"></TextLink>.</Pgraph>
<Pgraph>The artificial supply of antioxidants into the human skin poses further questions. In everyday life, on holidays or at work, large amounts of optical radiation can penetrate into the skin and modify the effects of antioxidants. It has been known for a long time that large quantities of free radicals can be generated in human skin as a result of UV irradiation <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>. </Pgraph>
<Pgraph>The World Cancer Research Fund carried out the largest ever inquiry into lifestyle and cancer, and issued several recommendations. They include the recommendation not to use nutrient supplements for cancer prevention since the risks/benefits ratio cannot be confidently predicted and there may be unexpected and uncommon adverse effects. Increasing the consumption of the relevant nutrients by means of the usual diet should be preferred <TextLink reference="10"></TextLink>. </Pgraph>
<Pgraph>The current fact sheet of the U.S. National Cancer Institute states as key points <TextLink reference="11"></TextLink>: “Laboratory and animal research has shown antioxidants help prevent the free radical damage that is associated with cancer. However, results from recent studies in people (clinical trials) are not consistent. Antioxidants are provided by a healthy diet that includes a variety of fruits and vegetables.” </Pgraph>
<Pgraph>A systematic review and meta-analysis of the Cochrane Hepato-Biliary Group, Copenhagen <TextLink reference="12"></TextLink>, which included 68 randomised trials with 232,606 participants (385 publications) concluded: “Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.”</Pgraph>
<Pgraph>So far, no adequate randomised, placebo-controlled, multicenter studies or even meta-analyses have emerged which can shed light on the question of whether antioxidants applied in or on the skin can alter phenomena such as ageing or carcinogenesis of the skin in an unfavourable or favourable sense. We still do not know how UV, visible light and infrared or portions or combinations of these may act on modified concentrations of various antioxidants and on their components in the skin. This is a considerable challenge to the field of dermatological research. Or, to quote H. S. Black: "At<Mark2> present, beta-carotene use as a dietary supplement for photoprotection should be approached cautiously</Mark2>” <TextLink reference="7"></TextLink>.</Pgraph>
</TextBlock>
<References linked="yes">
<Reference refNo="1">
<RefAuthor>Salganik RI</RefAuthor>
<RefTitle>The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population</RefTitle>
<RefYear>2001</RefYear>
<RefJournal>J Am Coll Nutr</RefJournal>
<RefPage>464S-472S</RefPage>
<RefTotal>Salganik RI. The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J Am Coll Nutr. 2001;20(5 Suppl):464S-472S.</RefTotal>
</Reference>
<Reference refNo="2">
<RefAuthor>Zeisel SH</RefAuthor>
<RefTitle>Free radicals: the pros and cons of antioxidants. Antioxidants suppress apoptosis</RefTitle>
<RefYear>2004</RefYear>
<RefJournal>J Nutr</RefJournal>
<RefPage>3179S-3180S</RefPage>
<RefTotal>Zeisel SH. Free radicals: the pros and cons of antioxidants. Antioxidants suppress apoptosis. J Nutr. 2004;134(11):3179S-3180S.</RefTotal>
</Reference>
<Reference refNo="3">
<RefAuthor>Valko M</RefAuthor>
<RefAuthor>Izakovic M</RefAuthor>
<RefAuthor>Mazur M</RefAuthor>
<RefAuthor>Rhodes CJ</RefAuthor>
<RefAuthor>Telser J</RefAuthor>
<RefTitle>Role of oxygen radicals in DNA damage and cancer incidence</RefTitle>
<RefYear>2004</RefYear>
<RefJournal>Mol Cell Biochem</RefJournal>
<RefPage>37-56</RefPage>
<RefTotal>Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem. 2004;266(1-2):37-56. DOI:10.1023/B:MCBI.0000049134.69131.89</RefTotal>
</Reference>
<Reference refNo="4">
<RefAuthor>Duarte TL</RefAuthor>
<RefAuthor>Lunec J</RefAuthor>
<RefTitle>Review: When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C</RefTitle>
<RefYear>2005</RefYear>
<RefJournal>Free Radic Res</RefJournal>
<RefPage>671-86</RefPage>
<RefTotal>Duarte TL, Lunec J. Review: When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C. Free Radic Res. 2005;39(7):671-86. DOI:10.1080/10715760500104025</RefTotal>
<RefLink>http://dx.doi.org/10.1080/10715760500104025</RefLink>
</Reference>
<Reference refNo="5">
<RefAuthor>Wang XD</RefAuthor>
<RefAuthor>Russell RM</RefAuthor>
<RefTitle>Procarcinogenic and anticarcinogenic effects of beta-carotene</RefTitle>
<RefYear>1999</RefYear>
<RefJournal>Nutr Rev</RefJournal>
<RefPage>263-72</RefPage>
<RefTotal>Wang XD, Russell RM. Procarcinogenic and anticarcinogenic effects of beta-carotene. Nutr Rev. 1999;57(9 Pt 1):263-72.</RefTotal>
</Reference>
<Reference refNo="6">
<RefAuthor>Baron JA</RefAuthor>
<RefAuthor>Cole BF</RefAuthor>
<RefAuthor>Mott L</RefAuthor>
<RefAuthor>Haile R</RefAuthor>
<RefAuthor>Grau M</RefAuthor>
<RefAuthor>Church TR</RefAuthor>
<RefAuthor>Beck GJ</RefAuthor>
<RefAuthor>Greenberg ER</RefAuthor>
<RefTitle>Neoplastic and antineoplastic effects of beta-carotene on colorectal adenoma recurrence: results of a randomized trial</RefTitle>
<RefYear>2003</RefYear>
<RefJournal>J Natl Cancer Inst</RefJournal>
<RefPage>717-22</RefPage>
<RefTotal>Baron JA, Cole BF, Mott L, Haile R, Grau M, Church TR, Beck GJ, Greenberg ER. Neoplastic and antineoplastic effects of beta-carotene on colorectal adenoma recurrence: results of a randomized trial. J Natl Cancer Inst. 2003;95(10):717-22.</RefTotal>
</Reference>
<Reference refNo="7">
<RefAuthor>Black HS</RefAuthor>
<RefTitle>Pro-carcinogenic activity of beta-carotene, a putative systemic photoprotectant</RefTitle>
<RefYear>2004</RefYear>
<RefJournal>Photochem Photobiol Sci</RefJournal>
<RefPage>753-8</RefPage>
<RefTotal>Black HS. Pro-carcinogenic activity of beta-carotene, a putative systemic photoprotectant. Photochem Photobiol Sci. 2004;3(8):753-8. DOI:10.1039/b316438a</RefTotal>
<RefLink>http://dx.doi.org/10.1039/b316438a</RefLink>
</Reference>
<Reference refNo="8">
<RefAuthor>Meffert</RefAuthor>
<RefAuthor>H</RefAuthor>
<RefAuthor>Lohrisch I</RefAuthor>
<RefTitle>Untersuchung der Lipidperoxidation menschlicher Haut in vitro [Lipid peroxidation of the human skin in vitro]</RefTitle>
<RefYear>1971</RefYear>
<RefJournal>Dermatol Monatsschr</RefJournal>
<RefPage>338-344</RefPage>
<RefTotal>Meffert, H, Lohrisch I. Untersuchung der Lipidperoxidation menschlicher Haut in vitro [Lipid peroxidation of the human skin in vitro]. Dermatol Monatsschr. 1971;157(5):338-344.</RefTotal>
</Reference>
<Reference refNo="9">
<RefAuthor>Meffert H</RefAuthor>
<RefAuthor>Diezel W</RefAuthor>
<RefAuthor>Sönnichsen N</RefAuthor>
<RefTitle>Stable lipid peroxidation products in human skin: detection, ultraviolet light-induced increase, pathogenic importance</RefTitle>
<RefYear>1976</RefYear>
<RefJournal>Experientia</RefJournal>
<RefPage>1397-8</RefPage>
<RefTotal>Meffert H, Diezel W, Sönnichsen N. Stable lipid peroxidation products in human skin: detection, ultraviolet light-induced increase, pathogenic importance. Experientia. 1976;32(11):1397-8. DOI:10.1007/BF01937397</RefTotal>
<RefLink>http://dx.doi.org/10.1007/BF01937397</RefLink>
</Reference>
<Reference refNo="10">
<RefAuthor>World Cancer Research Fund</RefAuthor>
<RefAuthor>American Institute for Cancer Research</RefAuthor>
<RefTitle></RefTitle>
<RefYear>2007</RefYear>
<RefBookTitle>Food, nutrition, physical activity, and the prevention of cancer: a global perspective</RefBookTitle>
<RefPage></RefPage>
<RefTotal>World Cancer Research Fund, American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Washington DC: AICR; 2007.</RefTotal>
</Reference>
<Reference refNo="11">
<RefAuthor>National Cancer Institute</RefAuthor>
<RefAuthor>U.S. National Institutes of Health</RefAuthor>
<RefTitle></RefTitle>
<RefYear>2004</RefYear>
<RefBookTitle>Antioxidants and cancer prevention: fact shee</RefBookTitle>
<RefPage></RefPage>
<RefTotal>National Cancer Institute, U.S. National Institutes of Health. Antioxidants and cancer prevention: fact sheet. Online available from: http://www.cancer.gov/cancertopics/factsheet/antioxidantsprevention [posted 08.01.2003, updated 28.07.2004].</RefTotal>
<RefLink>http://www.cancer.gov/cancertopics/factsheet/antioxidantsprevention</RefLink>
</Reference>
<Reference refNo="12">
<RefAuthor>Bjelakovic G</RefAuthor>
<RefAuthor>Nikolova D</RefAuthor>
<RefAuthor>Gluud LL</RefAuthor>
<RefAuthor>Simonetti RG</RefAuthor>
<RefAuthor>Gluud C</RefAuthor>
<RefTitle>Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis</RefTitle>
<RefYear>2007</RefYear>
<RefJournal>JAMA</RefJournal>
<RefPage>842-57</RefPage>
<RefTotal>Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007;297(8):842-57. Erratum in: JAMA. 2008;299(7):765-6. DOI:10.1001/jama.297.8.842</RefTotal>
<RefLink>http://dx.doi.org/10.1001/jama.297.8.842</RefLink>
</Reference>
</References>
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