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Antioxidants- relevant for life extension?

Harman published his free radical theory of aging in 1956 and in the following decades it slowly became probably the most popular explanation of the mechanism of aging (Ashok & Ali, 1999). Because the theory claims that reactive oxygen species damage macromolecules (more details in my previous article “Aging theories: Is there a unifying factor in aging?”), the effects of substances known as nutritional antioxidants have received a lot of attention. The underlying theory that has been long accepted says that antioxidants may  improve health (and eventually prolong lifespan) by lowering the level of oxidative stress present in the organism because they eliminate free radicals, usually by 'donating' a free electron.   
However, there is a controversy about validity of this theory because some researchers reached the opposite conclusion. They view reactive oxygen species as signal molecules important for mitochondrial processes and cellular communication (Hamanaka & Chandel, 2010; Ristow & Schmeisser, 2011). It becomes clear that reactive oxygen species are not necessarily always harmful  (Brigelius-Flohé, 2009). A research of EGCG from green tea suggested antioxidants may be potent agents causing reductive damage (Lu, Ou, & Lu, 2013). It was observed that antioxidant consumption may neutralize any positive outcomes of exercising (Ristow et al., 2009). According to the meta-analysis of available clinical data about vitamin supplementation, the consumption of beta-carotene, vitamin A, or vitamin E has been associated with higher all-cause mortality (Bjelakovic, Nikolova, Gluud, Simonetti, & Gluud, 2012). One Danish research group found association between supplemented folic acid and increased all-cause mortality (Roswall et al., 2012). On the other hand, other researchers did not identify any effects on mortality (Henríquez-Sánchez et al., 2015) or even found the inverse association (Zhao et al., 2016; Bastide et al., 2017). It is possible that some unknown factors are in play which lead to controversy and confusion caused by so many different results.

The most well-known antioxidant is probably L-ascorbic acid, so-called vitamin C. Human body is unable to synthesize it and its absence or deficiency in diet causes fatal disease known as scurvy. However, the level of vitamin C in blood plasma is strictly regulated by organism, therefore high oral doses of L-ascorbic acid in any form do not elevate its plasma levels accordingly (Padayatty et al., 2004). There has been a lot of research done about potential effects on aging-related diseases, but the currently available evidence does not support any benefits (“Vitamin C Fact Sheet for Health Professionals,” 2016). Although, according to some researchers, there is a potential to use L-ascorbic acid intravenously in cancer treatment (Padayatty, Riordan, Hewitt, Katz, Hoffer, & Levine, 2006).

Another antioxidant which received a lot of attention is alpha-tocopherol, the only form of vitamin E with high enough biological activity to meet human requirements. Recommended daily intake is less precisely determined, compared to vitamin C. No beneficial effects were confirmed in studies with high number of participants (“Vitamin E Fact Sheet for Health Professionals,” 2016), some researchers even proposed possible harmful effects, such as increased general mortality in supplemented groups (Bjelakovic, Nikolova, Gluud, Simonetti, & Gluud, 2007).

Carotenoids also display antioxidant properties, the most popular of them is beta-carotene, sometimes called provitamin A (“Vitamin A Fact Sheet for Health Professionals,” 2016). Unfortunately, no benefits have received sufficient support by multiple studies. And it has been suggested that beta-carotene was found to increase the risk of lung cancer and cardiovascular diseases (The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group, 1994; Goodman et al., 2004). Another molecule from this group is lycopene, results of studies are mixed but the data from The Health Professionals Follow-up Study indicate a reduced risk of prostate cancer (Giovannucci, Liu, Platz, Stampfer, & Willett, 2007). Lutein seems to decline age-related macular degeneration (Richer et al., 2004). Astaxanthin is the strongest carotenoid antioxidant (Ursoniu, Sahebkar, Serban, & Banach, 2015) and researchers claim it has beneficial effects on humans (Cohaire, Garem, Mahmoud, Eertmans, & Schoonjans, 2005) but no large study was yet concluded.

Plant polyphenols (and their most numerous subgroup flavonoids) are abundant in nature as well as in our diet, and are generally nontoxic (Yao et al., 2004; Manach, Scalbert, Morand, Remesy, & Jimenez, 2004). In spite of these facts, they received scientific attention only for a short period of time, compared to aforementioned antioxidants. It is worth to note that recent research shows their potential benefits go often well beyond antioxidant mechanism (Scalbert, Johnson, & Saltmarsh, 2005; Kim, Quon, & Kim, 2014; Srivastava & Mishra, 2015).

The grape derived flavonoid polyphenolic substance resveratrol became widely known in anti-aging circles but shows very little bioavailability in vivo (Goldberg, Yan, & Soleas, 2003) and no lifespan extension in mammals has been conclusively shown.

Good, popular and easy-to-access source of catechins and other flavonoids is tea. According to many studies, its chemical composition provides antioxidant, anticancer, neuroprotective, cardioprotective and other beneficial health effects (Fujiki et al., 1999; Rietveld & Wiseman, 2003; Caruana & Vassallo, 2015). EGCG, or epigallocatechin-3-gallate, is a major tea polyphenol (Nagle, Ferreira, & Zhou, 2006; Singh, Shankar, & Srivastava, 2011). Interestingly, bioavailability of tea polyphenols does not change with the addition of milk (Kyle, Morrice, McNeill, & Duthie, 2007).

Curcumin, the main physiologically active polyphenol of turmeric, shows antioxidant and anti-inflammatory properties in humans (Ursoniu, Sahebkar, Serban, & Banach, 2015) and exhibits high level of safety and tolerability (Gupta, Patchva, & Aggarwal, 2013). Although, its bioavailability is very poor if taken alone, but drastically increases by about 2000% if consumed with an addition of piperine (Shoba et al., 1998). Other promising techniques of enhanced drug delivery are also being investigated (Prasad, Tyagi, & Aggarwal, 2014).

The most important antioxidant for humans is probably endogenous glutathione which is abundantly present in our cells. It scavenges free radicals very efficiently, directly regulates immune functions and levels of oxidative stress (Wu, Fang, Yang, Lupton, & Turner, 2004; Pizzorno, 2014). Furthermore, recent research conducted on humans showed that daily glutathione consumption can significantly increase its body stores (Richie et al., 2014). N-acetylcysteine supplementation boosts glutathione biosynthesis (Pendyala & Creaven, 1995).

Alpha lipoic acid (and its reduced form, dihydrolipoic acid), another interesting endogenous antioxidant, is crucial for mitochondrial functions (Palaniappan & Dai, 2007). It is also a chelator substance as it has the ability to eliminate metal ions but do not cause metal depletion in organism. Alpha lipoic acid is able to reduce the oxidized forms of vitamin C and E (Gomes & Negrato, 2014). Orally supplemented lipoic acid accumulates in tissues and evidence suggests its antioxidant properties are indirect but still beneficial (Shat, Moreau, Smith, Smith, & Hagen, 2009).

Coenzyme Q10 plays a key role in mitochondrial and other metabolic processes. It displays antioxidant properties and can be supplemented orally (Littarru & Tiano, 2007). Aging related Q10 deficiency has been linked to cardiovascular diseases (Singh, Devaraj, & Jialal, 2007). Research showed that sufficient intake can prevent or treat these issues (Kumar, Kaur, Devi, & Mohan, 2009; Mortensen et al., 2014) but another review study calls for trials with better design (Flowers, Hartley, Todkill, Stranges, & Rees, 2013).

Melatonin also participates in the protection from oxidative damage by stimulation of glutathione production (Fusco, Colloca, Lo Monaco, & Cesari, 2007). Particularly high concentrations were found in cell nucleus and mitochondria (Aydogan, Yerer, & Goktas, 2006). Melatonin is well-known as a sleep hormone and in darkness is naturally produced by brain (Peuhkuri, Sihvola, & Korpela, 2012).

Typical age-related diseases are cardiovascular, cancer, type 2 diabetes, Alzheimer’s disease (Everitt et al., 2006). Interestingly, they cause about 90 percent of deaths annually in industrialized countries (de Grey, 2007). Therefore, if antioxidants were effective in reducing these health problems, we could claim they are relevant for life extension, even if they are not relevant for the extension of maximal lifespan. However, whether or not this is the case remains controversial, especially in the case of certain vitamins (as described above). One speculation would be that the contradicting results might be explained by the non-homogeneous of vitamins among the population (Semba, 2012). Antioxidants in the diet seem to be a necessity but the benefits of dietary supplement consumption remain questionable. Some supplements contain unnecessarily high doses which do not offer any benefits but may even lead to adverse effects. On the other hand, the health impact of some polyphenolic antioxidants seems to go well beyond their basic antioxidant mechanism (Scalbert, Johnson, & Saltmarsh, 2005). 


  • Anisimov, V. (2003). Effects of Exogenous Melatonin—A Review. Toxicologic Pathology, 31(6), 589-603. http://dx.doi.org/10.1080/01926230390257885
  • Ashok, B., & Ali, R. (1999). The aging paradox: free radical theory of aging. Experimental Gerontology, 34(3), 293-303. http://dx.doi.org/10.1016/s0531-5565(99)00005-4
  • Aydogan, S., Yerer, M., & Goktas, A. (2006). Melatonin and nitric oxide. Journal Of Endocrinological Investigation, 29(3), 281-287. http://dx.doi.org/10.1007/bf03345555
  • Bastide, N., Dartois, L., Dyevre, V., Dossus, L., Fagherazzi, G., Serafini, M., & Boutron-Ruault, M. (2016). Dietary antioxidant capacity and all-cause and cause-specific mortality in the E3N/EPIC cohort study. European Journal Of Nutrition, 56(3), 1233-1243. http://dx.doi.org/10.1007/s00394-016-1172-6
  • Bjelakovic, G., Nikolova, D., Gluud, L., Simonetti, R., & Gluud, C. (2007). Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention. JAMA, 297(8), 842. http://dx.doi.org/10.1001/jama.297.8.842
  • Bjelakovic, G., Nikolova, D., Gluud, L., Simonetti, R., & Gluud, C. (2012). Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Of Systematic Reviews. http://dx.doi.org/10.1002/14651858.cd007176.pub2
  • Brigelius-Flohé, R. (2009). Commentary: oxidative stress reconsidered. Genes & Nutrition, 4(3), 161-163. http://dx.doi.org/10.1007/s12263-009-0131-8
    de Grey, A. (2007). Life Span Extension Research and Public Debate: Societal Considerations. Studies In Ethics, Law, And Technology, 1(1). http://dx.doi.org/10.2202/1941-6008.1011
  • Everitt, A., Hilmer, S., Brand-Miller, J., Jamieson, H., Truswell, A., & Sharma, A. et al. (2006). Dietary approaches that delay age-related diseases. Clinical Interventions In Aging, 1(1), 11-31. http://dx.doi.org/10.2147/ciia.2006.1.1.11
  • Flowers, N., Hartley, L., & Rees, K. (2013). Co-enzyme Q10 supplementation for the primary prevention of cardiovascular disease. Cochrane Database Of Systematic Reviews. http://dx.doi.org/10.1002/14651858.cd010405
  • Fusco, D., Colloca, G., Lo Monaco, M., & Cesari, M. (2007). Effects of antioxidant supplementation on the aging process. Clinical Interventions In Aging, 2(3), 377-87.
  • Giovannucci, E., Liu, Y., Platz, E., Stampfer, M., & Willett, W. (2007). Risk factors for prostate cancer incidence and progression in the health professionals follow-up study. International Journal Of Cancer, 121(7), 1571-1578. http://dx.doi.org/10.1002/ijc.22788
  • Goldberg, D., Yan, J., & Soleas, G. (2003). Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clinical Biochemistry, 36(1), 79-87. http://dx.doi.org/10.1016/s0009-9120(02)00397-1
  • Gomes, M., & Negrato, C. (2014). Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Diabetology & Metabolic Syndrome, 6(1), 80. http://dx.doi.org/10.1186/1758-5996-6-80
  • Goodman, G., Thornquist, M., Balmes, J., Cullen, M., Meyskens, F., & Omenn, G. et al. (2004). The Beta-Carotene and Retinol Efficacy Trial: Incidence of Lung Cancer and Cardiovascular Disease Mortality During 6-Year Follow-up After Stopping -Carotene and Retinol Supplements. JNCI Journal Of The National Cancer Institute, 96(23), 1743-1750. http://dx.doi.org/10.1093/jnci/djh320
  • Gupta, S., Patchva, S., & Aggarwal, B. (2013). Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials. The AAPS Journal, 15(1), 195-218. http://dx.doi.org/10.1208/s12248-012-9432-8
  • Hamanaka, R., & Chandel, N. (2010). Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends In Biochemical Sciences, 35(9), 505-513. http://dx.doi.org/10.1016/j.tibs.2010.04.002
  • Henríquez-Sánchez, P., Sánchez-Villegas, A., Ruano-Rodríguez, C., Gea, A., Lamuela-Raventós, R., & Estruch, R. et al. (2015). Dietary total antioxidant capacity and mortality in the PREDIMED study. European Journal Of Nutrition, 55(1), 227-236. http://dx.doi.org/10.1007/s00394-015-0840-2
  • Karaaslan, C., & Suzen, S. (2015). Antioxidant Properties of Melatonin and its Potential Action in Diseases. Current Topics In Medicinal Chemistry, 15(9), 894-903. http://dx.doi.org/10.2174/1568026615666150220120946
  • Karasek, M. (2004). Melatonin, human aging, and age-related diseases. Experimental Gerontology, 39(11-12), 1723-1729. http://dx.doi.org/10.1016/j.exger.2004.04.012
  • Kim, H., Quon, M., & Kim, J. (2014). New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate. Redox Biology, 2, 187-195. http://dx.doi.org/10.1016/j.redox.2013.12.022
  • Kumar, A., Kaur, H., Devi, P., & Mohan, V. (2009). Role of coenzyme Q10 (CoQ10) in cardiac disease, hypertension and Meniere-like syndrome. Pharmacology & Therapeutics, 124(3), 259-268. http://dx.doi.org/10.1016/j.pharmthera.2009.07.003
  • Kyle, J., Morrice, P., McNeill, G., & Duthie, G. (2007). Effects of Infusion Time and Addition of Milk on Content and Absorption of Polyphenols from Black Tea. Journal Of Agricultural And Food Chemistry, 55(12), 4889-4894. http://dx.doi.org/10.1021/jf070351y
  • Littarru, G., & Tiano, L. (2007). Bioenergetic and Antioxidant Properties of Coenzyme Q10: Recent Developments. Molecular Biotechnology, 37(1), 31-37. http://dx.doi.org/10.1007/s12033-007-0052-y
  • Lu, L., Ou, N., & Lu, Q. (2013). Antioxidant Induces DNA Damage, Cell Death and Mutagenicity in Human Lung and Skin Normal Cells. Scientific Reports, 3(1). http://dx.doi.org/10.1038/srep03169
  • Manach, C., Scalbert, A., Morand, C., Remesy, C., & Jimenez, L. (2004). Polyphenols: food sources and bioavailability. The American Journal Of Clinical Nutrition, 79(5), 727-47.
  • Mortensen, S., Rosenfeldt, F., Kumar, A., Dolliner, P., Filipiak, K., & Pella, D. et al. (2014). The Effect of Coenzyme Q10 on Morbidity and Mortality in Chronic Heart Failure. JACC: Heart Failure, 2(6), 641-649. http://dx.doi.org/10.1016/j.jchf.2014.06.008
  • Nagle, D., Ferreira, D., & Zhou, Y. (2006). Epigallocatechin-3-gallate (EGCG): Chemical and biomedical perspectives. Phytochemistry, 67(17), 1849-1855. http://dx.doi.org/10.1016/j.phytochem.2006.06.020
  • Padayatty, S., Riordan, H., Hewitt, S., Katz, A., Hoffer, L., & Levine, M. (2006). Intravenously administered vitamin C as cancer therapy: three cases. Canadian Medical Association Journal, 174(7), 937-942. http://dx.doi.org/10.1503/cmaj.050346
  • Padayatty, S., Sun, H., Wang, Y., Riordan, H., Hewitt, S., & Katz, A. et al. (2004). Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use. Ann Intern Med, 140(7), 533-537.
  • Palaniappan, A., & Dai, A. (2007). Mitochondrial Ageing and the Beneficial Role of α-Lipoic Acid. Neurochemical Research, 32(9), 1552-1558. http://dx.doi.org/10.1007/s11064-007-9355-4
  • Pendyala, L., & Creaven, P. (1995). Pharmacokinetic and pharmacodynamic studies of N-acetylcysteine, a potential chemopreventive agent during a phase I trial. Cancer Epidemiology, Biomarkers And Prevention, 4(3), 245-51.
  • Peuhkuri, K., Sihvola, N., & Korpela, R. (2012). Dietary factors and fluctuating levels of melatonin. Food & Nutrition Research, 56(1), 17252. http://dx.doi.org/10.3402/fnr.v56i0.17252
  • Pizzorno, J. (2014). Glutathione!. Integrative Medicine (Encinitas), 13(1), 8-12.
  • Prasad, S., Tyagi, A., & Aggarwal, B. (2014). Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: the Golden Pigment from Golden Spice. Cancer Research And Treatment, 46(1), 2-18. http://dx.doi.org/10.4143/crt.2014.46.1.2
  • Reiter, R., Tan, D., Mayo, J., Sainz, R., Leon, J., & Czarnocki, Z. (2003). Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochimica Polonica, 50(4), 1129-1146.
  • Richer, S., Stiles, W., Statkute, L., Pulido, J., Frankowski, J., & Rudy, D. et al. (2004). Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry - Journal Of The American Optometric Association, 75(4), 216-229. http://dx.doi.org/10.1016/s1529-1839(04)70049-4
  • Richie, J., Nichenametla, S., Neidig, W., Calcagnotto, A., Haley, J., Schell, T., & Muscat, J. (2014). Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. European Journal Of Nutrition, 54(2), 251-263. http://dx.doi.org/10.1007/s00394-014-0706-z
  • Rietveld, A., & Wiseman, S. (2003). Antioxidant effects of tea: evidence from human clinical trials. Journal Of Nutrition, 133(10), 3285S-3292S.
  • Ristow, M., & Schmeisser, S. (2011). Extending life span by increasing oxidative stress. Free Radical Biology And Medicine, 51(2), 327-336. http://dx.doi.org/10.1016/j.freeradbiomed.2011.05.010
  • Ristow, M., Zarse, K., Oberbach, A., Kloting, N., Birringer, M., & Kiehntopf, M. et al. (2009). Antioxidants prevent health-promoting effects of physical exercise in humans. Proceedings Of The National Academy Of Sciences, 106(21), 8665-8670. http://dx.doi.org/10.1073/pnas.0903485106
  • Roswall, N., Olsen, A., Christensen, J., Hansen, L., Dragsted, L., Overvad, K., & Tjønneland, A. (2012). Micronutrient intake in relation to all-cause mortality in a prospective Danish cohort. Food & Nutrition Research, 56(1), 5466. http://dx.doi.org/10.3402/fnr.v56i0.5466
  • Scalbert, A., Johnson, I., & Saltmarsh, M. (2005). Polyphenols: antioxidants and beyond. The American Journal Of Clinical Nutrition, 81(1 Suppl), 215S-217S.
  • Shoba, G., Joy, D., Joseph, T., Majeed, M., Rajendran, R., & Srinivas, P. (1998). Influence of Piperine on the Pharmacokinetics of Curcumin in Animals and Human Volunteers. Planta Medica, 64(04), 353-356. http://dx.doi.org/10.1055/s-2006-957450
  • Singh, B., Shankar, S., & Srivastava, R. (2011). Green tea catechin, epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and clinical applications. Biochemical Pharmacology, 82(12), 1807-1821. http://dx.doi.org/10.1016/j.bcp.2011.07.093
  • Srivastava, T., & Mishra, S. (2015). Novel Function of Polyphenols in Human Health: A Review. Research Journal Of Phytochemistry, 9(3), 116-126. http://dx.doi.org/10.3923/rjphyto.2015.116.126
  • Tan, D., Chen, L., Poeggeler, B., Manchester, L., & Reiter, R. (1993). Melatonin: A potent endogenous hydroxyl radical scavenger. Endocrine Journal, (1), 57-60.
  • The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group. (1994). The Effect of Vitamin E and Beta Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers. New England Journal Of Medicine, 330(15), 1029-1035. http://dx.doi.org/10.1056/nejm199404143301501
  • Tomé-Carneiro, J., Larrosa, M., González-Sarrías, A., Tomás-Barberán, F., García-Conesa, M., & Espín, J. (2013). Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence. Current Pharmaceutical Design, 19(34), 6064-6093. http://dx.doi.org/10.2174/13816128113199990407
  • United States General Accounting Office. (2001). “Anti-Aging” Products Pose Potential for Physical and Economic Harm (p. 31). United States General Accounting Office. Retrieved from http://www.gao.gov/new.items/d011129.pdf
  • Ursoniu, S., Sahebkar, A., Serban, M., & Banach, M. (2015). Systematic review/Meta-analysis Lipid profile and glucose changes after supplementation with astaxanthin: a systematic review and meta-analysis of randomized controlled trials. Archives Of Medical Science, 2, 253-266. http://dx.doi.org/10.5114/aoms.2015.50960
  • Vitamin C Fact Sheet for Health Professionals. (2016). Ods.od.nih.gov. Retrieved 31 May 2017, from http://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/
  • Vitamin E Fact Sheet for Health Professionals. (2016). Ods.od.nih.gov. Retrieved 31 May 2017, from http://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/
  • Wu, G., Fang, Y., Yang, S., Lupton, J., & Turner, N. (2004). Glutathione metabolism and its implications for health. Journal Of Nutrition, 134(3), 489-92.
  • Yao, L., Jiang, Y., Shi, J., Tomas-Barberan, F., Datta, N., Singanusong, R., & Chen, S. (2004). Flavonoids in Food and Their Health Benefits. Plant Foods For Human Nutrition, 59(3), 113-122. http://dx.doi.org/10.1007/s11130-004-0049-7
  • Zhao, L., Zhang, Q., Zheng, J., Li, H., Zhang, W., Tang, W., & Xiang, Y. (2016). Dietary, circulating beta-carotene and risk of all-cause mortality: a meta-analysis from prospective studies. Scientific Reports, 6(1). http://dx.doi.org/10.1038/srep26983

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---- LongeCity comment ---
This article serves as a brief introduction into a complex and controversial topic in life extension science. For decades, anti-oxidants were almost synonymous with anti-aging. Current evidence suggests that the picture is more complex. Yet despite the potential for inefficiency and harm that antioxidants may pose, their role in modulating aging-related health cannot be ignored.
Continue the discussion of individual antioxidants in our supplements forum.