Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Dietary antioxidants in inflammatory arthritis: do they have any role in etiology or therapy?

Abstract

Rheumatoid arthritis is an autoimmune-mediated inflammatory disease of unknown etiology, and is characterized by joint pain and soft-tissue swelling. The role of dietary antioxidants in the prevention and amelioration of symptoms in inflammatory joint disease has been of interest for many years. Epidemiological studies provide evidence of a link between dietary antioxidant intake and the likelihood of developing inflammatory arthritis. Interventional studies of antioxidant supplementation in established disease have been inconclusive overall; however, the quality of such studies has often been poor. The pathways by which antioxidant compounds might act are now better understood. In this Review, we explore not only some of the accepted mechanisms of antioxidant function but also outline some concepts that could aid further investigation of the potential therapeutic role of dietary antioxidants in inflammatory arthritis.

Key Points

  • Oxidative stress is frequently related to diseases that have an inflammatory component, such as inflammatory arthritis

  • Epidemiological evidence suggests that dietary antioxidants can diminish the oxidative stress associated with inflammatory arthritis

  • Dietary antioxidants might confer protective properties through mechanisms unrelated to conventional antioxidant properties

  • Future research is needed to clarify the mechanisms of action of dietary antioxidants, their bioavailability in humans and the quantities required to promote health

  • Current evidence does not support the use of antioxidant nutraceuticals in the management of inflammatory arthritis

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: The course of inflammatory polyarthritis.
Figure 2: Schematic diagram showing the inflamed rheumatoid joint and the activation of neutrophils therein.
Figure 3: Chemical structures of three dietary antioxidants.
Figure 4: A mechanism by which antioxidant micronutrients might exert anti-inflammatory activity—modulation of the activity of the redox-regulated transcription factor NFκB.

References

  1. 1

    Symmons DP et al. (1994) The incidence of rheumatoid arthritis in the United Kingdom: results from the Norfolk Arthritis Register. Br J Rheumatol 33: 735–739

    CAS  Article  Google Scholar 

  2. 2

    Karlson EW et al. (2008) Associations between human leukocyte antigen, PTPN22, CTLA4 genotypes and rheumatoid arthritis phenotypes of autoantibody status, age at diagnosis and erosions in a large cohort study. Ann Rheum Dis 67: 358–363

    CAS  Article  Google Scholar 

  3. 3

    Symmons DPM et al. (2000) Early inflammatory polyarthritis: results from the Norfolk Arthritis Register with a review of the literature. I. Risk factors for the development of inflammatory polyarthritis and rheumatoid arthritis. Rheumatology (Oxford) 39: 835–843

    CAS  Article  Google Scholar 

  4. 4

    Aho K and Heliövaara M (2004) Risk factors for rheumatoid arthritis. Ann Med 36: 242–251

    CAS  Article  Google Scholar 

  5. 5

    Pattison DJ et al. (2004) Does diet have a role in the aetiology of rheumatoid arthritis? Proc Nutr Soc 63: 137–143

    CAS  Article  Google Scholar 

  6. 6

    Arts IC and Hollman PC (2005) Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr 81 (Suppl 1): 317S–325S

    CAS  Article  Google Scholar 

  7. 7

    Halliwell B and Gutteridge JMC (1999) Free Radicals in Biology and Medicine (edn 3) New York: Oxford University Press, USA

    Google Scholar 

  8. 8

    Sies H (1997) Preface. In Antioxidants in Disease Mechanisms and Therapy, xxiii (Eds Packer et al.) London: Academic Press

    Google Scholar 

  9. 9

    Winyard PG et al. (2005) Oxidative activation of antioxidant defence. Trends Biochem Sci 30: 453–461

    CAS  Article  Google Scholar 

  10. 10

    Jones OTG and Hancock JT (2000) The NADPH oxidase of neutrophils and other cells. In Free Radicals and Inflammation, 21–46 (Eds Winyard PG et al.) Basel: Birkhauser

    Chapter  Google Scholar 

  11. 11

    Karunasinghe N et al. (2006) Hemolysate thioredoxin reductase and glutathione peroxidase activities correlate with serum selenium in a group of New Zealand men at high prostate cancer risk. J Nutr 136: 2232–2235

    CAS  Article  Google Scholar 

  12. 12

    Rinehart JF et al. (1936) Reduced ascorbic acid content of blood plasma in rheumatoid arthritis. Proc Soc Exp Bol Med 35: 347–350

    Article  Google Scholar 

  13. 13

    Fairburn K et al. (1992) Alpha-tocopherol, lipids and lipoproteins in knee-joint synovial fluid and serum from patients with inflammatory joint disease. Clin Sci (Lond) 83: 657–664

    CAS  Article  Google Scholar 

  14. 14

    Lunec J and Blake DR (1985) The determination of dehydroascorbic acid and ascorbic acid in the serum and synovial fluid of patients with rheumatoid arthritis (RA). Free Radic Res Commun 1: 31–39

    CAS  Article  Google Scholar 

  15. 15

    Canter PH et al. (2007) The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a systematic review of randomized clinical trials. Rheumatology (Oxford) 46: 1223–1233

    CAS  Article  Google Scholar 

  16. 16

    Edmonds SE et al. (1997) Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial. Ann Rheum Dis 56: 649–655

    CAS  Article  Google Scholar 

  17. 17

    Winrow VR et al. (1993) Free radicals in inflammation: second messengers and mediators of tissue destruction. Br Med Bull 49: 506–522

    CAS  Article  Google Scholar 

  18. 18

    Bjelakovic G et al. (2007) Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297: 842–857

    CAS  Article  Google Scholar 

  19. 19

    Willett WC et al. (1995) Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr 61 (Suppl 6): 1402S–1406S

    CAS  Article  Google Scholar 

  20. 20

    Sköldstam L et al. (2003) An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis. Ann Rheum Dis 62: 208–214

    Article  Google Scholar 

  21. 21

    McKellar G et al. (2007) A pilot study of a Mediterranean-type diet intervention in female patients with rheumatoid arthritis living in areas of social deprivation in Glasgow. Ann Rheum Dis 66: 1239–1243

    CAS  Article  Google Scholar 

  22. 22

    Pattison DJ et al. (2004) The role of diet in susceptibility to rheumatoid arthritis: a systematic review. J Rheumatol 31: 1310–1319

    CAS  PubMed  Google Scholar 

  23. 23

    Linos A et al. (1999) Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables? Am J Clin Nutr 70: 1077–1082

    CAS  Article  Google Scholar 

  24. 24

    Pattison DJ et al. (2004) Vitamin C and the risk of developing inflammatory polyarthritis: a prospective nested case control study. Ann Rheum Dis 63: 843–847

    CAS  Article  Google Scholar 

  25. 25

    Cerhan JR et al. (2003) Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older women. Am J Epidemiol 157: 345–354

    Article  Google Scholar 

  26. 26

    Pedersen M et al. (2005) Diet and risk of rheumatoid arthritis in a prospective cohort. J Rheumatol 32: 1249–1252

    PubMed  Google Scholar 

  27. 27

    Shapiro JA et al. (1996) Diet and rheumatoid arthritis in women: a possible protective effect of fish consumption. Epidemiology 7: 256–263

    CAS  Article  Google Scholar 

  28. 28

    Pattison DJ et al. (2005) Dietary beta-cryptoxanthin and inflammatory polyarthritis: results from a population-based prospective study. Am J Clin Nutr 82: 451–455

    CAS  Article  Google Scholar 

  29. 29

    Heliövaara M et al. (1994) Serum antioxidants and risk of rheumatoid arthritis. Ann Rheum Dis 53: 51–53

    Article  Google Scholar 

  30. 30

    Comstock GW et al. (1997) Serum concentrations of alpha-tocopherol, beta-carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis 56: 323–325

    CAS  Article  Google Scholar 

  31. 31

    Knekt P et al. (2000) Serum selenium, serum alpha-tocopherol, and the risk of rheumatoid arthritis. Epidemiology 11: 402–405

    CAS  Article  Google Scholar 

  32. 32

    Bashir S et al. (1993) Oxidative DNA damage and cellular sensitivity to oxidative stress in human autoimmune diseases. Ann Rheum Dis 52: 659–666

    CAS  Article  Google Scholar 

  33. 33

    Tak PP (2000) Rheumatoid arthritis and p53: how oxidative stress might alter the course of inflammatory diseases. Immunol Today 21: 78–82

    CAS  Article  Google Scholar 

  34. 34

    Eggleton P et al. (2008) Consequence of neo-antigenicity of the 'altered self'. Rheumatology (Oxford) 47: 567–571

    CAS  Article  Google Scholar 

  35. 35

    Reddanna P et al. (1985) Inhibition of 5-lipoxygenase by vitamin E. FEBS Lett. 193: 39–43

    CAS  Article  Google Scholar 

  36. 36

    Douglas C et al. (1986) Vitamin E inhibits platelet phospholipase A2 . Biochim Biophys Acta 876: 639–645

    CAS  Article  Google Scholar 

  37. 37

    Azzi A (2007) Molecular mechanism of alpha-tocopherol action. Free Radical Biol Med 43: 16–21

    CAS  Article  Google Scholar 

  38. 38

    Stocker R and Keaney JF Jr (2004) Role of oxidative modifications in atherosclerosis. Physiol Rev 84: 1381–1478

    CAS  Article  Google Scholar 

  39. 39

    Premkumar K and Bowlus CL (2004) Ascorbic acid does not increase the oxidative stress induced by dietary iron in C3H mice. J Nutr 134: 435–438

    CAS  Article  Google Scholar 

  40. 40

    Hultqvist M et al. (2006) A new arthritis therapy with oxidative burst inducers. PLoS Med 3: e348

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank Joanna Tarr for her help with preparing Figure 2.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Dorothy J Pattison.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Pattison, D., Winyard, P. Dietary antioxidants in inflammatory arthritis: do they have any role in etiology or therapy?. Nat Rev Rheumatol 4, 590–596 (2008). https://doi.org/10.1038/ncprheum0920

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing