Dietary interventions through supplementation with antioxidant compounds

  • Vanja Todorović University of Belgrade – Faculty of Pharmacy, Department of Bromatology
  • Brižita Djordjević University of Belgrade – Faculty of Pharmacy, Department of Bromatology
Keywords: dietary intervention, dietary supplements, antioxidant activity, diseases, ageing, athletes


Dietary supplements (DS) are manufactured products consisting of one or more dietary ingredients; they are intended to supplement the diet and provide additional nutrients or other beneficial compounds that are lacking or insufficient in a regular diet. Dietary supplements containing antioxidant compounds have been shown to have positive effects in various (pato)physiological processes, i.e., any condition that is fundamentally redox imbalanced (cardiovascular diseases, cancer, aging, intense exercise). The most common antioxidants in dietary supplements are clearly antioxidant micronutrients such as vitamin C, vitamin E, zinc, and selenium, but also various secondary plant compounds, including polyphenols and carotenoids. The dosage of antioxidants administered through dietary supplements may not always be optimal, so some dietary interventions through supplementation with antioxidant compounds have been shown to have an effect that it is limited, or completely absent. Therefore, any dietary supplementation should be done only under appropriate guidance from health care professionals to ensure that it is safe, effective, and appropriate for the individual's condition and needs.


1.          Magni P, Bier DM, Pecorelli S, Agostoni C, Astrup A, Brighenti F, et al. Perspective: Improving Nutritional Guidelines for Sustainable Health Policies: Current Status and Perspectives. Adv Nutr Bethesda Md. 2017 Jul;8(4):532–45.

2.          WHO [Internet]. [cited 2023 May 30]. Available from:

3.          NIH [Internet]. [cited 2023 May 30]. Available from:

4.          Antioxidant Supplement Market Report [Internet]. [cited 2023 May 30]. Available from:

5.          Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, et al. Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer: The Women’s Health Study: A Randomized Controlled Trial. JAMA. 2005 Jul 6;294(1):56.

6.          Milman U, Blum S, Shapira C, Aronson D, Miller-Lotan R, Anbinder Y, et al. Vitamin E Supplementation Reduces Cardiovascular Events in a Subgroup of Middle-Aged Individuals With Both Type 2 Diabetes Mellitus and the Haptoglobin 2-2 Genotype: A Prospective Double-Blinded Clinical Trial. Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):341–7.

7.          Al-Khudairy L, Flowers N, Wheelhouse R, Ghannam O, Hartley L, Stranges S, et al. Vitamin C supplementation for the primary prevention of cardiovascular disease. Cochrane Heart Group, editor. Cochrane Database Syst Rev. 2017 Mar 16;2017(3). doi: 10.1002/14651858.CD011114.pub2

8.          Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, et al. The SU.VI.MAX Study: A Randomized, Placebo-Controlled Trial of the Health Effects of Antioxidant Vitamins and Minerals. Arch Intern Med. 2004 Nov 22;164(21):2335.

9.          Grabež M, Škrbić R, Stojiljković MP, Vučić V, Rudić Grujić V, Jakovljević V, et al. A prospective, randomized, double-blind, placebo-controlled trial of polyphenols on the outcomes of inflammatory factors and oxidative stress in patients with type 2 diabetes mellitus. Rev Cardiovasc Med. 2022 Feb 11;23(2):057.

10.       Dludla PV, Ziqubu K, Mabhida SE, Mazibuko-Mbeje SE, Hanser S, Nkambule BB, et al. Dietary Supplements Potentially Target Plasma Glutathione Levels to Improve Cardiometabolic Health in Patients with Diabetes Mellitus: A Systematic Review of Randomized Clinical Trials. Nutrients. 2023 Feb 14;15(4):944.

11.       Grodstein F. A Randomized Trial of Beta Carotene Supplementation and Cognitive Function in MenThe Physicians’ Health Study II. Arch Intern Med. 2007 Nov 12;167(20):2184.

12.       Kryscio RJ, Abner EL, Caban-Holt A, Lovell M, Goodman P, Darke AK, et al. Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer’s Disease by Vitamin E and Selenium Trial (PREADViSE). JAMA Neurol. 2017 May 1;74(5):567.

13.       Kantor ED, Rehm CD, Du M, White E, Giovannucci EL. Trends in Dietary Supplement Use Among US Adults From 1999-2012. JAMA. 2016 Oct 11;316(14):1464.

14.       Poljsak B, Milisav I. The Role of Antioxidants in Cancer, Friends or Foes? Curr Pharm Des. 2019 Mar 29;24(44):5234–44.

15.       Yasueda A, Urushima H, Ito T. Efficacy and Interaction of Antioxidant Supplements as Adjuvant Therapy in Cancer Treatment: A Systematic Review. Integr Cancer Ther. 2016 Mar;15(1):17–39.

16.       Farhood B, Goradel NH, Mortezaee K, Khanlarkhani N, Salehi E, Nashtaei MS, et al. Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization. Clin Transl Oncol. 2019 Mar;21(3):268–79.

17.       Ambrosone CB, Zirpoli GR, Hutson AD, McCann WE, McCann SE, Barlow WE, et al. Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221). J Clin Oncol. 2020 Mar 10;38(8):804–14.

18.       A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation With Vitamins C and E, Beta Carotene, and Zinc for Age-Related Macular Degeneration and Vision Loss: AREDS Report No. 8. Arch Ophthalmol. 2001 Oct 1;119(10):1417.

19.       Chew EY, Clemons TE, SanGiovanni JP, Danis RP, Ferris FL, Elman MJ, et al. Secondary Analyses of the Effects of Lutein/Zeaxanthin on Age-Related Macular Degeneration Progression: AREDS2 Report No. 3. JAMA Ophthalmol. 2014 Feb 1;132(2):142.

20.       Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Eyes and Vision Group, editor. Cochrane Database Syst Rev. 2017 Jul 30;2017(9). doi: 10.1002/14651858.CD000254.pub4

21.       Jeukendrup AE, Gleeson M. Sport nutrition. Third edition. Champaign, IL: Human Kinetics; 2019.

22.       Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, et al. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr. 2008 Jan;87(1):142–9.

23.       Klein EA, Thompson IM, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, et al. Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011 Oct 12;306(14):1549.

24.       Hidaka T, Fujii K, Funahashi I, Fukutomi N, Hosoe K. Safety assessment of coenzyme Q 10 (CoQ 10 ). BioFactors. 2008;32(1–4):199–208.

25.       Dudašova Petrovičova O, Stanković I, Milinković N, Dopsaj V, Đorđević B, Dopsaj M. Effects of 6-Week Supplementation with GliSODin on Parameters of Muscle Damages, Metabolic, and Work Performance at International Level Rowers after Specific Maximal Effort. Biology. 2022 Sep 30;11(10):1437.

26.       Petrovic S, Arsic A, Glibetic M, Cikiriz N, Jakovljevic V, Vucic V. The effects of polyphenol-rich chokeberry juice on fatty acid profiles and lipid peroxidation of active handball players: results from a randomized, double-blind, placebo-controlled study. Can J Physiol Pharmacol. 2016 Oct;94(10):1058–63.

27.       Bojarczuk A, Dzitkowska-Zabielska M. Polyphenol Supplementation and Antioxidant Status in Athletes: A Narrative Review. Nutrients. 2022 Dec 29;15(1):158.

28.       Djordjevic B, Baralic I, Kotur-Stevuljevic J, Stefanovic A, Ivanisevic J, Radivojevic N, et al. Effect of astaxanthin supplementation on muscle damage and oxidative stress markers in elite young soccer players. J Sports Med Phys Fitness. 2012 Aug;52(4):382–92.

29.       Brown DR, Gough LA, Deb SK, Sparks SA, McNaughton LR. Astaxanthin in Exercise Metabolism, Performance and Recovery: A Review. Front Nutr. 2018 Jan 18;4:76.

30.       Baralic I, Stojmenovic T, Andjelkovic M, Djordjevic B, Dikic N, Radojevic-Skodric S, et al. Effect of combined antioxidant treatment on oxidative stress, muscle damage and sport performance in female basketball players. Srp Arh Celok Lek. 2019;147(11–12):729–35.

31.       Angelo G, Drake VJ, Frei B. Efficacy of Multivitamin/mineral Supplementation to Reduce Chronic Disease Risk: A Critical Review of the Evidence from Observational Studies and Randomized Controlled Trials. Crit Rev Food Sci Nutr. 2015 Dec 6;55(14):1968–91.

32.       Bjelakovic G, Nikolova D, Gluud C. Antioxidant Supplements to Prevent Mortality. JAMA. 2013 Sep 18;310(11):1178.

33.       Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013 Dec 17;159(12):824–34.

34.       Kuszak AJ, Hopp DC, Williamson JS, Betz JM, Sorkin BC. Approaches by the US National Institutes of Health to support rigorous scientific research on dietary supplements and natural products. Drug Test Anal. 2016 Mar;8(3–4):413–7.

35.       Myung SK, Ju W, Cho B, Oh SW, Park SM, Koo BK, et al. Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials. BMJ. 2013 Jan 18;346(jan18 1):f10–f10.

36.       Ye Y, Li J, Yuan Z. Effect of Antioxidant Vitamin Supplementation on Cardiovascular Outcomes: A Meta-Analysis of Randomized Controlled Trials. Hernandez AV, editor. PLoS ONE. 2013 Feb 20;8(2):e56803.

37.       Vrolijk MF, Opperhuizen A, Jansen EHJM, Godschalk RW, Van Schooten FJ, Bast A, et al. The shifting perception on antioxidants: The case of vitamin E and β-carotene. Redox Biol. 2015 Apr;4:272–8.

38.       Cohen PA. The Supplement Paradox: Negligible Benefits, Robust Consumption. JAMA. 2016 Oct 11;316(14):1453.

39.       Bast A, Haenen GRMM. Ten misconceptions about antioxidants. Trends Pharmacol Sci. 2013 Aug;34(8):430–6.

40.       Halliwell B. Free radicals and antioxidants – quo vadis? Trends Pharmacol Sci. 2011 Mar;32(3):125–30.

41.       Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J. Vitamin C exhibits pro-oxidant properties. Nature. 1998 Apr;392(6676):559–559.

42.       Panel on Dietary Antioxidants and Related Compounds, Subcommittee on Upper Reference Levels of Nutrients, Subcommittee on Interpretation and Uses of Dietary Reference Intakes, Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids [Internet]. Washington, D.C.: National Academies Press; 2000 [cited 2023 Jun 16]. Available from:

43.       Shahidi F, De Camargo A. Tocopherols and Tocotrienols in Common and Emerging Dietary Sources: Occurrence, Applications, and Health Benefits. Int J Mol Sci. 2016 Oct 20;17(10):1745.

44.       de la Lastra CA, Villegas I. Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications. Biochem Soc Trans. 2007 Nov 1;35(5):1156–60.

45.       Poljsak B, Milisav I. The Neglected Significance of “Antioxidative Stress.” Oxid Med Cell Longev. 2012;2012:1–12.

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