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Review article: Biomedical intelligence

Vol. 145 No. 4546 (2015)

How the Mediterranean diet and some of its components modulate inflammatory pathways in arthritis

  • Francesca Oliviero
  • Paolo Spinella
  • Ugo Fiocco
  • Roberta Ramonda
  • Paolo Sfriso
  • Leonardo Punzi
Cite this as:
Swiss Med Wkly. 2015;145:w14190


Arthritis encompasses a heterogeneous group of diseases characterised by inflammation that leads not only to joint damage, bone erosion, severe pain and disability, but also affects other organs of the body, resulting in increased morbidity and mortality. Although the mechanisms underlying the pathogenesis of joint diseases are for the most part unknown, a number of nutrient and non-nutrient components of food have been shown to affect the inflammatory process and, in particular, to influence clinical disease progression.

The Mediterranean diet model has already been linked to a number of beneficial health effects: both fat and non-fat components of the Mediterranean dietary pattern have been shown to exert important anti-inflammatory activities by affecting the arachidonic acid cascade, the expression of some proinflammatory genes, and the activity of immune cells. N-3 polyunsaturated fatty acids, in particular, have been shown to affect lymphocyte and monocyte functions, crucially involved in adaptive and innate immunity.

Although some aspects concerning the mechanisms of action through which the Mediterranean diet pattern exerts its beneficial effects remain to be elucidated, arthritis patients may potentially benefit from it in view of their increased cardiovascular risk and the treatment they require which may have side effects.


  1. Preedy VR, Watson RR, eds. The Mediterranean Diet: An Evidence-Based Approach. Academic Press; 2015.
  2. Sofi F, Macchi C, Abbate R, Gensini GF, Casini A. Mediterranean diet and health. Biofactors. 2013;39:335–42.
  3. Wolf AD, Pfleger B. Burden of Major Musculoskeletal Conditions. Policy and Practice. Special Theme-Bone and Joint Decade 2000-2010. Bulletin of the World Health Organization. 2003;81:646–56.
  4. Ingegnoli F, Gualtierotti R, Artusi C, Lubrano E. Focus on the potential effects of treatments for spondylarthritides on cardiovascular risk. Expert Rev Clin Immunol. 2014;10:307–15.
  5. John H, Kitas G. Inflammatory arthritis as a novel risk factor for cardiovascular disease. Eur J Intern Med 2012;23:575-579.
  6. Bhole V, Krishnan E. Gout and the heart. Rheum Dis Clin North Am. 2014;40:125–43.
  7. Husted JA, Thavaneswaran A, Chandran V, Eder L, Rosen CF, Cook RJ, et al. Cardiovascular and other comorbidities in patients with psoriatic arthritis: a comparison with patients with psoriasis. Arthritis Care Res (Hoboken). 2011;63:1729–3.
  8. Ramonda R, Lo Nigro A, Modesti V, Nalotto L, Musacchio E, Iaccarino L, et al. Atherosclerosis in psoriatic arthritis. Autoimmun Rev. 2011;10:773–8.
  9. Pattison DJ, Symmons DP, Young A. Does diet have a role in the aetiology of rheumatoid arthritis? Proc Nutr Soc. 2004;63:137–43.
  10. Choi HK. Dietary risk factors for rheumatic diseases. Curr Opin Rheumatol. 2005;17:141–6.
  11. Firestein GS. The T cell cometh: interplay between adaptive immunity and cytokine networks in rheumatoid arthritis. J Clin Invest. 2004;114:471–4.
  12. Alamanos Y, Voulgari PV, Drosos AA. Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review. Semin Arthritis Rheum. 2006;36:182–8.
  13. Drosos AA, Lanchbury JS, Panayi GS, Moutsopoulos HM. Rheumatoid arthritis in Greek and British patients. A comparative clinical, radiologic, and serologic study. Arthritis Rheum. 1992;35:745–8.
  14. González Cernadas L, Rodríguez-Romero B, Carballo-Costa L. Importance of nutritional treatment in the inflammatory process of rheumatoid arthritis patients; a review. Nutr Hosp. 2014;29:237–45.
  15. Linos A, Kaklamani VG, Kaklamani E, Koumantaki Y, Giziaki E, Papazoglou S, et al. Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables? Am J Clin Nutr. 1999;70:1077–8.
  16. Pedersen M, Stripp C, Klarlund M, Olsen SF, Tjønneland AM, Frisch M. Diet and risk of rheumatoid arthritis in a prospective cohort. J Rheumatol. 2005;32:1249–52.
  17. Symmons D, Harrison B. 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). 2000;39:835–43.
  18. Hu Y, Costenbader KH, Gao X, Al-Daabil M, Sparks JA, Solomon DH, et al. Sugar-sweetened soda consumption and risk of developing rheumatoid arthritis in women. Am J Clin Nutr. 2014;100:959–67.
  19. Benito-Garcia E, Feskanich D, Hu FB, Mandl LA, Karlson EW. Protein, iron, and meat consumption and risk for rheumatoid arthritis: a prospective cohort study. Arthritis Res Ther. 2007;9:R16.
  20. Rosell M, Wesley AM, Rydin K, Klareskog L, Alfredsson L; EIRA study group. Dietary fish and fish oil and the risk of rheumatoid arthritis. Epidemiology. 2009;20:896–901.
  21. Jin Z, Xiang C, Cai Q, Wei X, He J. Alcohol consumption as a preventive factor for developing rheumatoid arthritis: a dose response meta-analysis of prospective studies. Ann Rheum Dis. 2014;73:1962–7.
  22. Sundström B, Johansson I, Rantapää-Dahlqvist S. Diet and alcohol as risk factors for rheumatoid arthritis: a nested case-control study. Rheumatol Int. 2015;35(3):533–9.
  23. Boyer GS, Templin DW, Cornoni-Huntley JC, Everett DF. Prevalence of spondyloarthropathies in Alaskan Eskimos. J Rheumatol. 1994;21:2292–7.
  24. Sundström B, Wallberg-Jonsson S, Johansson G. Diet, disease activity, and gastrointestinal symptoms in patients with ankylosing spondylitis. Clin Rheumatol. 2011;30:71–6.
  25. Sundström B, Johansson G, Kokkonen H, Cederholm T, Wallberg-Jonsson S. Plasma phospholipid fatty acid content is related to disease activity in ankylosing spondylitis. J Rheumatol. 2012;39:327–33.
  26. Ebringer A, Wilson C. The use of a low starch diet in the treatment of patients suffering from ankylosing spondylitis. Clin Rheumatol. 1996;15(Suppl1):62–6.
  27. Appelboom T, Durez P. Effect of milk product deprivation on spondyloarthropathy. Ann Rheum Dis 1994;53:481–2.
  28. Azzini M, Girelli D, Olivieri O, Guarini P, Stanzial AM, Frigo A, et al. Fatty acids and antioxidant micronutrients in psoriatic arthritis. J Rheumatol. 1995;22:103–8.
  29. Barter MJ, Bui C, Young DA. Epigenetic mechanisms in cartilage and osteoarthritis: DNA methylation, histone modifications and microRNAs. Osteoarthritis Cartilage. 2012;20:339–49.
  30. McKay JA, Mathers JC. Diet induced epigenetic changes and their implications for health. Acta Physiol (Oxf). 2011;202:103–18.
  31. Oliviero F, Sfriso P, Scanu A, Fiocco U, Spinella P, Punzi L. Epigallocatechin-3-gallate reduces inflammation induced by calcium pyrophosphate crystals in vitro. Front Pharmacol. 2013;4:51.
  32. Prasad P, Krishnan E. Filipino gout: a review. Arthritis Care Res (Hoboken). 2014;66:337–43.
  33. Torralba KD, De Jesus E, Rachabattula S. The interplay between diet, urate transporters and the risk for gout and hyperuricemia: current and future directions. Int J Rheum Dis. 2012;15:499–506.
  34. Choi JW, Ford ES, Gao X, Choi HK. Sugar-sweetened soft drinks, diet soft drinks, and serum uric acid level: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2008;59:109–16.
  35. Juraschek SP, Miller ER 3rd, Gelber AC. Effect of oral vitamin C supplementation on serum uric acid: a meta-analysis of randomized controlled trials. Arthritis Care Res (Hoboken). 2011;63:1295–306
  36. Andrés M, Sivera F, Falzon L, Buchbinder R, Carmona L. Dietary supplements for chronic gout. Cochrane Database Syst Rev. 2014;10:CD010156
  37. Kontogianni MD, Chrysohoou C, Panagiotakos DB, Tsetsekou E, Zeimbekis A, Pitsavos C, et al. Adherence to the Mediterranean diet and serum uric acid: the ATTICA Study. Scand J Rheumatol. 2012;41:442–9.
  38. Vallverdú-Queralt A, Regueiro J, Martínez-Huélamo M, Rinaldi Alvarenga JF, Leal LN, Lamuela-Raventos RM. A comprehensive study on the phenolic profile of widely used culinary herbs and spices: Rosemary, thyme, oregano, cinnamon, cumin and bay. Food Chem. 2014;154:299–307.
  39. Serra-Majem L, Ngo de la Cruz J, Ribas L, Tur JA. Olive oil and the Mediterranean diet: beyond the rhetoric. Eur J Clin Nutr. 2003;57(Suppl 1):S2–7.
  40. Pérez-Jiménez F, Ruano J, Perez-Martinez P, Lopez-Segura F, Lopez-Miranda J. The influence of olive oil on human health: Not a question of fat alone. Mol Nutr Food Res. 2007;51:1199–208.
  41. Oliviero F, Punzi L, Spinella P. Mediterranean Food Pattern in Rheumatoid Arthritis. Current Rheumatology Rev. 2009;5:233–40.
  42. Ferretti A, Nelson GJ, Schmidt PC, Kelley DS, Bartolini G, Flanagan VP. Increased dietary arachidonic acid enhances the synthesis of vasoactive eicosanoids in humans. Lipids. 1997;32:435–9.
  43. Li B, Birdwell C, Whelan J. Antithetic relationship of dietary arachidonic acid and eicosapentaenoic acid on eicosanoid production in vivo. J Lipid Res. 1994;35:1869–77.
  44. Magdalon J, Vinolo MA, Rodrigues HG, Paschoal VA, Torres RP, Mancini-Filho J, et al. Oral administration of oleic or linoleic acids modulates the production of inflammatory mediators by rat macrophages. Lipids. 2012;47:803–12.
  45. Musumeci G, Trovato FM, Pichler K, Weinberg AM, Loreto C, Castrogiovanni P. Extra-virgin olive oil diet and mild physical activity prevent cartilage degeneration in an osteoarthritis model: an in vivo and in vitro study on lubricin expression. J Nutr Biochem. 2013;24:2064–75.
  46. Volker DH, Fitzgerald PE, Garg ML. The eicosapentaenoic to docosahexaenoic acid ratio of diets affects the pathogenesis of arthritis in Lew/SSN Rats. J Nutr. 2000;130:559–65.
  47. Carluccio MA, Siculella L, Ancora MA, Massaro M, Scoditti E, Storelli C, et al. Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: antiatherogenic properties of Mediterranean diet phytochemicals. Arterioscler Thromb Vasc Biol. 2003;23:622–9.
  48. Scoditti E, Calabriso N, Massaro M, Pellegrino M, Storelli C, Martines G, et al. Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and COX-2 inhibition in human vascular endothelial cells: a potentially protective mechanism in atherosclerotic vascular disease and cancer. Arch Biochem Biophys. 2012;527:81–9.
  49. Silva S, Sepodes B, Rocha J, Direito R, Fernandes A, Brites D, et al. Protective effects of hydroxytyrosol-supplemented refined olive oil in animal models of acute inflammation and rheumatoid arthritis. J Nutr Biochem. 2015;26:360–8.
  50. Scotece M, Gómez R, Conde J, Lopez V, Gómez-Reino JJ, Lago F, et al. Further evidence for the anti-inflammatory activity of oleocanthal: inhibition of MIP-1α and IL-6 in J774 macrophages and in ATDC5 chondrocytes. Life Sci. 2012;91:1229–35.
  51. Impellizzeri D, Esposito E, Mazzon E, Paterniti I, Di Paola R, Morittu VM, et al. Oleuropein aglycone, an olive oil compound, ameliorates development of arthritis caused by injection of collagen type II in mice. J Pharmacol Exp Ther. 2011;339:859–69.
  52. Rosillo MA, Alcaraz MJ, Sánchez-Hidalgo M, Fernández-Bolaños JG, Alarcón-de-la-Lastra C, Ferrándiz ML. Anti-inflammatory and joint protective effects of extra-virgin olive-oil polyphenol extract in experimental arthritis. J Nutr Biochem. 2014;25:1275–81.
  53. Johnson JJ. Carnosol: a promising anti-cancer and anti-inflammatory agent. Cancer Lett. 2011;305:1–7.
  54. Calder PC, Yaqoob P, Thies F, Wallace FA, Miles EA. Fatty acids and lymphocyte functions. Br J Nutr. 2002;87Suppl1:S31–48.
  55. Jaudszus A, Gruen M, Watzl B, Ness C, Roth A, Lochner A, et al. Evaluation of suppressive and pro-resolving effects of EPA and DHA in human primary monocytes and T-helper cells. J Lipid Res. 2013;54:923–35.
  56. Yessoufou A, Ple A, Moutairou K, Hichami A, Khan NA. Docosahexainoic acid HA reduces suppressive and migratory functions of CD4+CD25+ regulatory T-cells. J Lipid Res. 2009;50:2377–88.
  57. Kremer JM, Lawrence DA, Jubiz W, DiGiacomo R, Rynes R, Bartholomew LE, et al. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects. Arthritis Rheum. 1990;33:810–20.
  58. Jaudszus A, Gruen M, Watzl B, Ness C, Roth A, Lochner A, et al. Evaluation of suppressive and pro-resolving effects of EPA and DHA in human primary monocytes and T-helper cells. J Lipid Res. 2013;54:923–35.
  59. Teague H, Rockett BD, Harris M, Brown DA, Shaikh SR. Dendritic cell activation, phagocytosis and CD69 expression on cognate T cells are suppressed by n-3 long-chain polyunsaturated fatty acids. Immunology. 2013;139:386–9.
  60. Rockett BD, Melton M, Harris M, Bridges LC, Shaikh SR. Fish oil disrupts MHC class II lateral organization on the B-cell side of the immunological synapse independent of B-T cell adhesion. J Nutr Biochem. 2013;24:1810–6.
  61. Palmerini CA, Carlini E, Saccardi C, Servili M, Montedoro G, Arienti G. Activity of olive oil phenols on lymphomonocyte cytosolic calcium. J Nutr Biochem. 2005,16:109–13.
  62. Montemurno E, Cosola C, Dalfino G, Daidone G, De Angelis M, Gobbetti M, et al. What would you like to eat, Mr CKD Microbiota? A Mediterranean Diet, please! Kidney Blood Press Res. 2014;39:114–23.
  63. Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature. 2011;474:327–36.
  64. Rogier R, Koenders MI, Abdollahi-Roodsaz S. Toll-like receptor mediated modulation of T cell response by commensal intestinal microbiota as a trigger for autoimmune arthritis. J Immunol Res. 2015;2015:527696
  65. Lima SCS, Ribeiro Pinto LF, Herceg Z. The Effects of Diet on Epigenetic Processes. Handbook of Epigenetics. The New Molecular and Medical Genetics. Edited by: Trygve Tollefsbol
  66. Di Francesco A, Falconi A, Di Germanio C, Micioni Di Bonaventura MV, Costa A, Caramuta S, et al. Extravirgin olive oil up-regulates CB1 tumor suppressor gene in human colon cancer cells and in rat colon via epigenetic mechanisms. J Nutr Biochem. 2015;26:250–58.
  67. Martín-Núñez GM, Cabrera-Mulero R, Rubio-Martín E, Rojo-Martínez G, Olveira G, Valdés S, et al. Methylation levels of the SCD1 gene promoter and LINE-1 repeat region are associated with weight change: an intervention study. Mol Nutr Food Res. 2014;58:1528–36.
  68. Sköldstam L, Hagfors L, Johansson G. An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis. Ann Rheum Dis. 2003;62:208–14.
  69. Michalsen A, Riegert M, Lüdtke R, Bäcker M, Langhorst J, Schwickert M, et al. Mediterranean diet or extended fasting’s influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: an observational study. BMC Complement Altern Med. 2005;5:22.
  70. Abendroth A, Michalsen A, Lüdtke R, Rüffer A, Musial F, Dobos GJ, et al. Changes of Intestinal Microflora in Patients with Rheumatoid Arthritis during Fasting or a Mediterranean Diet. Forsch Komplementmed. 2010;17:307–13.
  71. McKellar G, Morrison E, McEntegart A, Hampson R, Tierney A, Mackle G, et al. 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. 2007:66;1239–43.