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In medicine, antioxidants are "naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissue".[1]

Antioxidant supplements include beta-carotene, vitamin A (retinol), vitamin C (ascorbic acid), vitamin E (tocopherols), and selenium.

Medical uses

Cancer prevention

Antioxidants do not appear to prevent cancers[2][3][4] in spite of early research that suggested benefit in secondary analyses[5].

Vascular disease prevention

Initially, observational cohort cohort studies such as the Nurses' Health Study found associations between self-reported consumption of vitamin C (ascorbic acid)[6] and vitamin E (α-tocopherol) and reductions in vascular disease.[7]

Cambridge Heart Antioxidant Study (CHAOS)[8] -
lack of dose-response gradient
  Nonfatal MI
Vitamin E 800 IU/day 2.0% (11/546)
Vitamin E 400 IU/day 0.6% (3/489)
Placebo 4.2% (41/967)

The Cambridge Heart Antioxidant Study (CHAOS) was an early randomized controlled trial of vitamin E and in spite of having worse baseline characteritics in the vitamin E group, found "in patients with angiographically proven symptomatic coronary atherosclerosis, alpha-tocopherol treatment substantially reduces the rate of non-fatal MI, with beneficial effects apparent after 1 year of treatment" and no effect oncardiovascular deaths.[8] As noted in the table, the lack of a dose-response gradient makes causation less likely. The study also had less patients in the control group for uncertain reasons in spite of randomization. This trial was published prior to trials adhering to the Consort Statement on the reporting of trials and thus readers cannot track patients through the trial's recruitment process.

In the year 2000, the HOPE study was the first negative randomized controlled trial of Vitamin E to be published.[9] The HOPE study used 400 IU of vitamin E and followed high-risk patients for a mean of 4.5 years. At the time of the HOPE study, 1 of every 8 Americans reported taking vitamin E supplements.[10]

Surprisingly, authors continued to cite positive results from earlier observations studies were refuted by the HOPE trial.[11] These authors often cited the earlier CHAOS study.[11]

In the year 2005, a meta-analysis concluded that Vitamin E supplementation may actually be harmful.[12] After this publication, sales of vitamin E fell by 33%.[13]

Subsequent trials confirmed the HOPE study.[14][15] Vitamins C (500 mg) and E (400 IU) did not benefit males in the Physicians' Health Study II randomized controlled trial which started recruitment in 1997 and followed patients for a mean of 8 years.[16] Vitamin E did not benefit women in the Women's Health Study randomized controlled trial which began recruitment in 1992 and followed women for an average of 10.1 years.[17]


  1. Anonymous (2023), Antioxidant (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. Gaziano JM, Glynn RJ, Christen WG, et al (January 2009). "Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial". JAMA 301 (1): 52–62. DOI:10.1001/jama.2008.862. PMID 19066368. Research Blogging.
  3. Lippman SM, Klein EA, Goodman PJ, et al (January 2009). "Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT)". JAMA 301 (1): 39–51. DOI:10.1001/jama.2008.864. PMID 19066370. Research Blogging.
  4. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C (2008). "Antioxidant supplements for preventing gastrointestinal cancers". Cochrane Database Syst Rev (3): CD004183. DOI:10.1002/14651858.CD004183.pub3. PMID 18677777. Research Blogging.
  5. (April 1994) "The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group". N. Engl. J. Med. 330 (15): 1029–35. PMID 8127329[e]
  6. Osganian SK, Stampfer MJ, Rimm E, et al (July 2003). "Vitamin C and risk of coronary heart disease in women". J. Am. Coll. Cardiol. 42 (2): 246–52. PMID 12875759[e]
  7. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC (May 1993). "Vitamin E consumption and the risk of coronary disease in women". N. Engl. J. Med. 328 (20): 1444–9. PMID 8479463[e]
  8. 8.0 8.1 Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ (March 1996). "Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS)". Lancet 347 (9004): 781–6. DOI:10.1016/S0140-6736(96)90866-1. PMID 8622332. Research Blogging.
  9. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P (January 2000). "Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators". N. Engl. J. Med. 342 (3): 154–60. PMID 10639540[e]
  10. Muth MK, Anderson DW, Domanico JL, Smith JB, Wendling B. Economic Characterization of the Dietary Supplement Industry. Washington, DC: Center for Food Safety and Administration, Food and Drug Administration; 1999.
  11. 11.0 11.1 Tatsioni A, Bonitsis NG, Ioannidis JP (December 2007). "Persistence of contradicted claims in the literature". JAMA 298 (21): 2517–26. DOI:10.1001/jama.298.21.2517. PMID 18056905. Research Blogging.
  12. Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (January 2005). "Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality". Ann. Intern. Med. 142 (1): 37–46. PMID 15537682[e]
  13. Tilburt JC, Emanuel EJ, Miller FG (September 2008). "Does the evidence make a difference in consumer behavior? Sales of supplements before and after publication of negative research results". J Gen Intern Med 23 (9): 1495–8. DOI:10.1007/s11606-008-0704-z. PMID 18618194. PMC 2518024. Research Blogging.
  14. (July 2002) "MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial". Lancet 360 (9326): 23–33. DOI:10.1016/S0140-6736(02)09328-5. PMID 12114037. Research Blogging.
  15. Waters DD, Alderman EL, Hsia J, et al (November 2002). "Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial". JAMA 288 (19): 2432–40. PMID 12435256[e]
  16. Sesso HD, Buring JE, Christen WG, et al (November 2008). "Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial". JAMA 300 (18): 2123–33. DOI:10.1001/jama.2008.600. PMID 18997197. Research Blogging.
  17. Lee IM, Cook NR, Gaziano JM, et al (July 2005). "Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial". JAMA 294 (1): 56–65. DOI:10.1001/jama.294.1.56. PMID 15998891. Research Blogging.