Join Us | Latest Articles | Contact

Journal Home

Editorial Board

Recent Articles

Submit to this journal

Special Issues

Current issue

International Journal of Pathology and Clinical Research

DOI: 10.23937/2469-5807/1510029

Micronutrients Deficiencies in Rheumatoid Arthritis Patients

Graziela Biude Silva*, Bruna Zavarize Reis and Silvia Maria Franciscato Cozzolino

Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Science, University of São Paulo, São Paulo, Brazil

*Corresponding author: Graziela Biude Silva, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, AvProf Lineu Prestes, 580, Bloco 14, 05508-000 São Paulo, SP, Brazil, Tel: +55 11 3091 3625; E-mail:
Int J Pathol Clin Res, IJPCR-2-029, (Volume 2, Issue 1), Mini Review; ISSN: 2469-5807
Received: December 24, 2015 | Accepted: February 26, 2016 | Published: February 29, 2016
Citation: Silva GB, Reis BZ, Cozzolino SMF (2016) Micronutrients Deficiencies in Rheumatoid Arthritis Patients. Int J Pathol Clin Res 2:029. 10.23937/2469-5807/1510029
Copyright: © 2016 Silva GB, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Rheumatoid arthritis (RA) is a chronic inflammatory disease that predominantly involves synovial joints and affects up to 2% of adults worldwide. Poor nutrient status in RA patients has been reported and some drug therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed to alleviate RA symptoms, may increase the requirement for some nutrients and reduce their absorption. The importance of micronutrients in this disease is related to their cofactor role in immune system functions and in different metabolic processes in articular tissues. Dietary interventions can assist with the management of disease symptoms that accompany RA, such as pain, tender swollen joints, stiffness, and associated disability and disease progression. This paper reviews the scientific evidence for the role of diet and nutrient supplementation in the management of RA, by alleviating symptoms or decreasing progression of the disease.


Micronutrients, Nutrition, Nutritional status, Rheumatoid arthritis, Selenium, Zinc, Calcium, Vitamin D


Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology characterized by a symmetrical polyarticular inflammation of synovial membrane that affects most often the joints of the hands, wrists and feet. The localized and systemic inflammation can result in a progressive joint damage causing bone and cartilage degradation, until the loss of function. The RA occurs in all ethnicities, with slight variations and has a higher rate among women than men at a ratio of 3:1 [1-3]. The diagnosis is made based on the criteria established by the American College of Rheumatology (ACR) involving clinical, laboratory and radiographic assessments [4].

In relation to the nutritional status of these patients, observational studies have been reported a low energy intake from carbohydrates, high consumption of fat and a diet low in micronutrients [5]. The reduction of calorie intake in the case of patients with RA can also be associated with disease-related symptoms such as loss of motor function, fatigue, and pain, which in turn can interfere with the purchase, preparation and consumption of food. Furthermore, adverse reactions such as nausea, dyspepsia and change in taste caused by drug therapy, may also influence the decrease in calorie intake and, consequently, vitamins and minerals [6].

Studies addressing micronutrient deficiency in patients with RA are scarce. Thus, this short review has focused particularly on four important micronutrients in this disease: zinc, selenium, calcium and vitamin D.


Although the pathophysiological basis of RA is not fully understood, studies show an important role of oxidative stress in this disease. Excessive production of reactive oxygen species (ROS) may be caused, for example, in response to an inflammatory stimulus, the presence of phagocytic leukocytes and inflammatory cytokines that stimulate the production of superoxide and hydroxyl radicals, highly reactive generated during phagocytosis by macrophages and neutrophils. Furthermore, the presence of ischemia and reperfusion during the performance of joint movement also contributes to the production of free radicals that act as mediators of tissue damage in RA [7-9]. The mineral zinc is important in human nutrition since it plays an important role as an antioxidant, by participating as a cofactor in the structure of superoxide dismutase (SOD), as well as in the inflammation, by inhibiting the activation pathway of NF-κB and reducing the production of pro-inflammatory cytokines [10,11]. In RA patients, in addition to these functions, some studies in vitro have been shown that this mineral can stimulate bone formation and inhibit osteoclastic activity [12]. The assessment of human nutritional status of zinc is made not only by evaluation of food consumption, but also through blood biomarkers.

Studies that have evaluated zinc intake in patients with RA are scarce in the literature, but they show that the dietary intake of this mineral is usually low [13,14]. The tools available for assessment of food consumption have flaws inherent to various factors that may hinder the collection of reliable data. However, the science of nutrition is improving more and more not only the question of the methodology of those instruments, but also encompassing the behavioral aspects, that is, considering the lifestyle of individuals and certain populations [15]. The lack of data on food consumption, especially of micronutrients, makes it difficult not only the investigation of the intake of these nutrients, but also the appropriate nutritional guidance to be made aiming the improvement of the nutritional status and the quality of life of these patients.

The zinc concentration in plasma is the biomarker indicated by the WHO/UNICEF/IAE/IZiNCG and the most widely used to assess the nutritional status of populations [16]. According to this parameter, RA patients have low concentrations of plasma zinc [13,17-19]. These results can be explained by the fact that inflammatory cytokines involved in the pathogenesis of RA inhibit albumin synthesis in the liver, decreasing mineral binding capacity and its distribution to other tissues. Albumin is the main zinc binding protein (90%) in plasma [20]. Animal studies showed that during the inflammatory process there is a redistribution of zinc to the liver. This mechanism appears to be associated with a high mineral pool attached to metallothionein protein that acts in the metabolic regulation of metals. In obesity, for example, the production of inflammatory cytokines stimulates zinc carriers synthesis compromising the bioavailability of this element to the needs of the body of these individuals [21,22].

Other studies have assessed the zinc status using as a biomarker the serum, and these authors also found low concentrations of this mineral [18,23,24]. The pharmacological treatment can also influence in serum zinc concentrations. Önal et al. [25] observed significantly reduced serum zinc in 32 patients with RA compared to controls. Among the medications, the use of methotrexate increased serum zinc levels, but these patients were still deficient. The treatment with corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) and chloroquine did not affect serum concentrations of this mineral.

The concentration of zinc in erythrocytes is a biomarker that reflects the long-term changes in the nutritional status of this mineral since the half-life of erythrocytes is 120 days and it is not widely used in scientific studies. The studies using this biomarker are still controversial. Tuncer et al. [18] found significantly high levels (p < 0.001) of erythrocyte zinc in patients with RA compared with a control group, whereas Mierzek et al. [26] observed low concentrations, but with no significant difference between the groups.

In relation to the SOD activity, enzyme that depends on copper and zinc atoms so that it can perform its function as an antioxidant, there are a lot of data in the literature, but also with controversies. Karatas et al. [27] observed a significantly lower activity of SOD (p < 0.005) in patients diagnosed with RA than in control group. As described above, patients with RA have a low intake of zinc, decreasing the amount of substrate so that the enzyme cannot perform its normal activity. The decrease in SOD activity may indicate a process of enzyme degradation by ROS during the detoxification process [28]. Taysi et al. [29] observed a significantly higher activity (p < 0.001) of this enzyme. The exacerbated production of ROS in inflammatory processes makes the enzyme have a higher activity, acting as a compensatory mechanism to eliminate these compounds [18].

The effects of zinc supplementation in patients with RA need to be further studied, since data in the literature are still very scarce. It is also important to evaluate the effects of this supplementation on the bioavailability of other nutrients which may be consumed also as a supplement such as calcium. From the results of these studies will be possible to evaluate the most effective form of supplementation to these patients considering all aspects of the disease and the influence of drug therapy.


Selenium is an essential micronutrient for the human health and exerts its biological functions as the amino acid selenocysteine (Sec) by means of selenoproteins. In mammalian, twenty five selenoproteins have been characterized, among which are the glutathione peroxidase (GPx), the thioredoxin reductases (TR), the iodothyronin deiodinases (IDI), the selenophosphate synthase2 (SPS2), selenoprotein P, (SePP), among others [30,31]. This mineral has several functions in human body, among them the anti-inflammatory and antioxidant. Selenium may act on the inflammatory response by inhibiting NF-κB cascade, reducing the production of inflammatory mediators, or even in immune cells, mainly in macrophages signal transduction pathways [32,33]. The antioxidant role of this micronutrient is assigned to its participation as an essential component of GPx enzyme [34].

The concentration of selenium in foods varies according to its content in soils and the plant's ability to absorb this element [35]. In consequence, the intake of this micronutrient by the population of different regions can vary widely. The scarcity of data regarding the assessment of dietary intake of selenium can be attributed to a lack of data on the concentration of this mineral in food. Because of the great variation in the concentration of this element in the soil of different regions of the world, the ideal would be that each country had its own food composition table, avoiding overestimating or underestimating the consumption of selenium by the population. The main food source of this mineral is the Brazil nut. The nutritional status of selenium can be assessed by measuring its concentration in the blood (plasma, serum and erythrocytes) or by evaluation of selenoproteins as GPx, SePP among others. Low selenium concentrations were observed in plasma, erythrocytes, leukocytes and synovial fluid of patients with RA [36-39]. Pemberton et al. [40] showed that these patients had low plasma selenium concentration when compared with the control group, and an increase of the lipid peroxidation marker (8-isoprostane), C-reactive protein (CRP), interleukin-6 (IL-6) and adhesion molecules(E-selectin and VCAM).

In case of selenium, the pharmacological treatment as the use of methotrexate, corticosteroids, NSAIDs and chloroquine do not seems to alter the concentration of this mineral [25]. Drug therapy is the main treatment of RA and with the development of new drugs, it is important that further studies be conducted to evaluate the drug-nutrient interaction. These data are essential to establish an appropriate nutritional therapy considering the bioavailability aspects of nutrients, particularly the micronutrients.

As an antioxidant mineral, the assessment of the GPx activity has been evaluated in several studies. Karatas et al. [24] observed that the GPx activity was significantly lower in patients with RA compared to controls. The same result were also found by other authors [8,28,29,41]. Staron et al. [42], in turn, did not observed significant difference in GPx activity between RA patients and the control group. Selenium regulates the activity of GPx in vivo and thus controls the intracellular levels of ROS. Increased expression of the GPx reduces ROS levels by inhibiting the phosphorylation of IκB-α, preventing the translocation of NF-κB to the nucleus. Furthermore, it was observed an increase in half-life of IκB, thereby preserving its degradation. Thus, the increasing of this micronutrient can prevent the transactivation of genes encoding inflammatory cytokines and inhibit the release of acute phase proteins [32,33,43].

The supplementation of selenium has been studied by some researchers, and present conflicting results. Some studies show that supplementation was effective in improving the nutritional status of selenium [36,44,45], while others found no change [46-48]. These differences may be explained by differences in studies design, the chemical form of the mineral that was used (selenomethionine, selenite, selenate), the time of supplementation, and pharmacological treatment. However, as in the case of zinc, more studies related to the effects of supplementation with selenium should be performed in order to evaluate the responses in different degrees of the disease, the type of supplement to be used and the interaction with the drug therapy.


Calcium (alongside other nutrients such as vitamin D) is needed to develop and maintain healthy bones and teeth. Adequate calcium intake is important for the general population and especially for patients with RA which are vulnerable to steroid-induced and disease-associated osteoporosis. In RA, vertebral bone density has been found to be 5-15% less than aged matched controls [49]. In addition, corticosteroids, used in the treatment of RA, impair intestinal calcium absorption [50]. Doses a slow as 2.5 mg prednisone per day or equivalent for longer than 3 months increase the risk of vertebral fractures [51]. It appears that bone loss occurs rapidly within the first 6-12 months of corticosteroid therapy and then slows [52].

Glucocorticoids (GC) have indirect effects on bone by inhibiting gastrointestinal calcium absorption and decreasing renal tubular reabsorption of calcium, and direct effects on bone cells. GC decrease bone remodeling and bone formation, leading to diminished bone quality and density with increased fracture risk [53-55].

Studies have examined the effect of calcium and vitamin D3 supplementation on bone mineral density (BMD) among subjects taking corticosteroids in men and women who were predominantly post-menopausal [56-58]. Calcium prophylaxis alone appears to offer only minimal protection from corticosteroid-induced spinal bone loss [58]. A 2-year randomized control trial of calcium combined with vitamin D3 in 65 RA patients taking corticosteroids demonstrated a reduction in BMD loss in both the spine and trochanter, but not the femoral neck [57].

No change in BMD with calcium and vitamin D3 supplementation has been seen in RA patients not receiving corticosteroids [57] and therefore, considering the possible side-effect of hypercalcaemia [58] there is no evidence to support calcium and vitamin D supplementation in these patients, unless they have symptoms of hypocalcaemia or decreased blood biomarkers.

Vitamin D

Vitamin D is needed to regulate calcium absorption and homeostasis. It is important for healthy bones and teeth. Low vitamin D levels have been implicated in a number of chronic diseases (such as the metabolic syndrome and diabetes etc.) including RA [59].

It can be obtained from food sources, such as cod liver oil and from other fat-rich fish (salmon, tuna, mackerel), or from endogenous cutaneous synthesis, which represents the most important source of this vitamin for the majority of human beings [60]. In the skin, the precursor is the 7-dehydrocholesterol (7-DHC). During exposure to sunlight the ultraviolet B radiation converts 7-dehydrocholesterol to previtamin D3 which in turn rapidly isomerizes to vitamin D3. Once formed, vitamin D3 is metabolized in the liver to 25-hydroxyvitamin D3 and in the kidneys to its active form 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) [61].

Vitamin D has been shown to alter the expressions of genes that affect cellular functions, such as, proliferation, differentiation, apoptosis, and angiogenesis [62]. Furthermore, vitamin D is involved in interleukin-2 inhibition, antibody production, and in lymphocyte proliferation, and, thus, is considered a regulator of the immune system [63] essential in the development and function of both T-regulatory cells [64,65] and dendritic cells [66,67].

Experimental evidence suggests that biologically active form of vitamin D (1,25-(OH)2D3) influences the process by which immune cells acquire signaling molecules that enable them to migrate to normal extra lymphoid tissue sites, as well as sites of inflammation [68]. In addition, it is known that 1,25-(OH)2D3 inhibits IFN-γ secretion and negatively regulates IL-12 production by down regulating NF-κB [69].

The expression of vitamin D receptor (VDR) constitutively or after immune stimulation, on antigen presenting cells, dendritic cells, T and B cells, further suggests an immunoregulatory role of vitamin D [70-72].

Given the immunosuppressive effects of vitamin D and the potential link between vitamin D deficiency and autoimmune diseases, vitamin D has been studied as potential player in the pathogeneses of many autoimmune diseases. Epidemiologic data indicate low vitamin D concentrations in autoimmune diseases such as RA, inflammatory bowel disease and multiple sclerosis [73-76].

However, it is unclear whether low vitamin D intake is a risk factor of RA development, and the relation between low serum vitamin D levels and increased activity in RA patients remains controversial. Little data derived from systematic approaches to the relationship between vitamin D intake and development of RA or between serum vitamin D levels and RA activity are available [77].

A meta-analysis by Song et al. [77] examined the relation between serum vitamin D levels and RA activity from published observational studies. Three cohort and eight studies (six cross-sectional and two case-control studies) on the association between serum vitamin D levels and RA activity were included. After combining the data of the three cohort studies that assessed the effect of vitamin D intake on RA risk, a significant association was found between total vitamin D intake and RA incidence (relative risk (RR) of the highest vs. the lowest group = 0.758, 95% confidence interval 0.577-0.937 (p = 0.047). Individuals in the highest group for total vitamin D intake were found to have a 24.2% lower risk of developing RA than those in the lowest group. In the other eight studies, seven of them showed that vitamin D levels are inversely associated with RA activity, such as, DAS28.

However, these findings should be interpreted with care given the small number of studies incorporated in this meta-analysis and other limitations - the study did not combine data on vitamin D levels and RA activity because the individual study designs and clinical outcomes were too heterogeneous.

Further studies are necessary to elucidate the effect of vitamin D on the development and the activity of RA to test the hypothesis that vitamin D status directly contributes to the pathogenesis of RA and to determine whether vitamin D supplementation has a beneficial effect in RA.


Studies on the nutritional status of patients with RA, particularly on the intake of macronutrients and, even more about micronutrients are still scarce and inconclusive. The etiology of this disease has not been established, and treatment goals, which is mainly pharmacological, are to prevent and control joint damage, improve and maintain functional capacity, reduce pain and get the remission of the disease. Some nutrients have important functional properties that may help in health and quality of life of these patients. The zinc and selenium, for example, due to their antioxidant and anti-inflammatory properties may help attenuate the effects of chronic inflammation from disease. RA patients are more susceptible to osteoporosis frames and so the monitoring of adequate intake of calcium and vitamin D are important. Still, it emphasizes once again the importance of further studies on the evaluation of nutritional status of micronutrient in these patients. One must consider the importance of a good design of the study, and look for to the best assessment methods, the chemical forms of supplementation when there are indications of deficiency, and the interaction of the nutrient with the drugs used in the treatment. These data will contribute significantly to the establishment of appropriate prescribing of these nutrients for these patients.


We would like to thank FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) for the financial support of our works with rheumatoid arthritis (processes numbers 2011/14801-0 and 2011/18025-4).

  1. Kahlenberg JM, Fox DA (2011) Advances in the medical treatment of rheumatoid arthritis. HandClin 27: 11-20.

  2. Harris ED Jr (1990) Rheumatoid arthritis. Pathophysiologyandimplications for therapy. N Engl J Med 322: 1277-1289.

  3. McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat RevImmunol 7: 429-442.

  4. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, et al. (1988) The American Rheumatism Association 1987 revised criteria for classification of rheumatoid arthritis. ArthritisRheum 31: 315-324.

  5. Rennie KL, Hughes J, Lang R, Jebb SA (2003) Nutritional management of rheumatoid arthritis: a review of the evidence. J Hum Nutr Diet 16: 97-109.

  6. Darlington LG, Ramsey NW (1993) Review of dietary therapy for rheumatoid arthritis. Br J Rheumatol 32: 507-514.

  7. Babior BM, Kipnes RS, Curnutte JT (1973) Biological defense mechanisms: the production of superoxide by leukocytes, a potential bactericidal agent. J. Clin. Invest 52: 741-746.

  8. Kamanli A, Naziroglu M, Aydilek N, Hacievliyagil C (2004) Plasma lipid peroxidation and antioxidant levels in patients with rheumatoid arthritis. CellBiochemFunct 22: 53-57.

  9. Oztürk HS, Cimen MY, Cimen OB, Kaçmaz M, Durak I (1999) Oxidant/antioxidant status of plasma samples from patients with rheumatoid arthritis. RheumatolInt 19:35-37.

  10. MAFRA D, Sílvia Maria Franciscato(2004) Importância do zinco na nutrição humana RevNutr 17: 79-87.

  11. Prasad AS, Bao B, Beck FW, Sarkar FH (2011) Zinc-suppressed inflammatory cytokines by induction of A20-mediated inhibition of nuclear factor-κB. Nutrition 27: 816-823.

  12. Kishi S, Yamaguchi M (1994) Inhibitory effect of zinc compounds on osteoclast-like cell formation in mouse marrow cultures. BiochemPharmacol 48: 1225-1230.

  13. Honkanen VE, Lamberg-Allardt CH, Vesterinen MK, Lehto JH, Westermarck TW, et al. (1991) Plasma zinc and copper concentrations in rheumatoid arthritis: influence of dietary factors and disease activity. Am J ClinNutr 54: 1082-1086.

  14. Stone J, Doube A, Dudson D, Wallace J (1997 ) Inadequate calcium, folic acid, vitamin E, zinc, and selenium intake in rheumatoid arthritis patients: results of a dietary survey. SeminArthritisRheum 27: 180-185.

  15. Oltersdorf U, Schlettwein-gsell D, Winkler G (1999) Assessing eating patterns-an emerging research topic in nutritional sciences: introduction to the symposium. Appetite 32: 1-7.

  16. Gibson RS, Hess SY, Hotz C, Brown KH (2008) Indicators of zinc status at the population level: a review of the evidence. Br J Nutr 99 Suppl 3: S14-23.

  17. Balogh Z, El-Ghobarey AF, Fell GS, Brown DH, Dunlop J, et al. (1980) Plasma zinc and its relationship to clinical symptoms and drug treatment in rheumatoid arthritis. Ann RheumDis 39: 329-332.

  18. Tuncer S, Kamanali L, AkÇil E, Kavas GÖ, SeÇkin B, Atay MB (1999) Element and magnesium levels and superoxide dismutase activity in rheumatoid arthritis. Biological Trace Element Research 2:137-142, 1999.

  19. Ala S, Shokrzadeh M, Pur Shoja AM, Saeedi Saravi SS (2009) Zinc and cooper plasma concentrations in rheumatoid arthritis patients from a selected population in Iran. Pak J Biol Sci 12: 1041-1044.

  20. Tapiero H, Tew KD (2003) Trace elements in human physiology and pathology: zinc and metallothioneins. Biomed Pharmacother 57: 399-411.

  21. Bury NR, Chung MJ, Sturm A, Walker PA, Hogstand C (2008) Cortisol stimulates the zinc signaling pathway and expression of metallothioneins and ZnT1 in rainbow trout gill epitelial cells. Am J Physiol Integr Comp Physiol 294: 623-629.

  22. Oliveira KDJFD, Koury JC, Donangelo CM (2007) Micronutrientes e capacidade antioxidante em adolescentes sedentários e corredores RevNutr 20: 171-179.

  23. Zoli A, Altomonte L, Caricchio R, Galossi A, Mirone L, et al. (1998) Serum zinc and copper in active rheumatoid arthritis: correlation with interleukin 1β and tumour necrosis fatorα. ClinRheumatol 17: 378-382.

  24. Li J, Liang Y, Mao H, Deng W, Zhang J (2014) Effects of B-lymphocyte dysfunction on the serum copper, selenium and zinc levels of rheumatoid arthritis patients. Pakistan J MedScienc 30: 1064.

  25. Önal S, Nazıroğlu M, Çolak M, Bulut V, Flores-Arce MF (2011) Effects of different medical treatments on serum copper, selenium and zinc levels in patients with rheumatoid arthritis. Biol Trace Elem Res 142: 447-455.

  26. Mierzecki A, Strecker D, Radomska K (2011) A pilot study on zinc levels in patients with rheumatoid arthritis. Biol Trace Elem Res 143: 854-862.

  27. Karatas F, Ozates I, Canatan H, Halifeoglu I, Karatepe M, et al. (2003) Antioxidant status & lipid peroxidation in pacients with rheumatoid arthritis. Indian. J Med Res 118: 178-118.

  28. Seven A, Güzel S, Aslan M, Hamuryudan V (2008) Lipid, protein, DNA oxidation and antioxidant status in rheumatoid arthritis. ClinBiochem 41: 538-543.

  29. Taysi S, Polat F, Gul M, Sari RA, Bakan E (2002) Lipid peroxidation, some extracellular antioxidants, and antioxidant enzymes in serum of patients with rheumatoid arthritis. RheumatolInt 21: 200-204.

  30. Papp LV, Lu J, Holmgren A, Khanna KK (2007) From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid Redox Signal 9: 775-806.

  31. Huang Z, Rose AH, Hoffmann PR (2012) The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities. Antioxidants& Redox Signaling 16: 706-733.

  32. Kretz-Remy C, Arrigo AP (2001) Selenium: a key element that controls NF-kappa B activation and I kappa B alpha half life. Biofactors 14: 117-125.

  33. Duntas LH (2009) Selenium and inflammation: underlying anti-inflammatory mechanisms. HormMetab Res 41: 443-447.

  34. Fairweather-Tait SJ, Bao Y, Broadley MR, Collings R, Ford D, et al. (2011) Selenium in human health and disease. Antioxid Redox Signal 14: 1337-1383.

  35. Combs GF Jr (2015) Biomarkers of selenium status. Nutrients 7: 2209-2236.

  36. Heinle K, Adam A, Gradl M, Wiseman M, Adam O (1997) selenium concentration in erythrocytes of patients with rheumatoid arthritis. Clinical and laboratory chemistry infection markers during administration of selenium. MedKlin 15: 29-33.

  37. Yazar M, Sarban S, Kocyigit A, Isikan UE (2005) Synovial fluid and plasma selenium, copper, zinc, and iron concentrations in patients with rheumatoid arthritis and osteoarthritis. Biol Trace Elem Res 106: 123-132.

  38. Köse K, Doğan P, Kardas Y, Saraymen R (1996) Plasma selenium levels in rheumatoid arthritis. Biol Trace Elem Res 53: 51-56.

  39. Brown KM, Pickard K, Nicol F, Beckett GJ, Duthie GG, et al. (2000) Effect of organic and inorganic selenium supplementation on selenoenzyme activity in blood lymphocytes, granulocytes, platelets and erythrocytes. Clinical Science 98: 593-599.

  40. Pemberton PW, Ahmad Y, Bodill H, Lokko D, Hider SL, et al. (2009) Biomarkers of oxidant stress, insulin sensitivity and endothelial activation in rheumatoid arthritis: a cross-sectional study of their association with accelerated atherosclerosis. BiomedicalResearch 2: 1-7.

  41. Chandankhede MS, Gupta MM (2013) Oxidative stress and antioxidant status in patients with rheumatoid arthritis. Int J BiolMed Res 4: 3088-3090.

  42. Staroń A, Mąkosa G, Koter-Michalak M (2012) Oxidative stress in erythrocytes from patients with rheumatoid arthritis. RheumatolInt 32: 331-334.

  43. Maehira F, Miyagi I, Eguchi Y (2003) Selenium regulates transcription factor NF-kappaB activation during the acute phase reaction. ClinChimActa 334: 163-17.

  44. Munthe E, Aeseth J, Jellum E (1986) Trace elements and rheumatoid arthritis (RA)- pathogenic and therapeutic aspects. Acta Pharmacologica Toxicologica, 59 (Suppl.7):1365-373.

  45. Peretz A, Neve J, Duchateau J, Famaey JP (1992) Adjuvant Treatment of Recent Onset Rheumatoid Arthritis by Selenium Supplementation: Preliminary Observations. Br J Rheumatol 31: 281-282.

  46. Peretz A, Siderova V, Nève J (2001) Selenium supplementation in rheumatoid arthritis investigated in a double blind, placebo-controlled trial. Scand J Rheumatol 30:208-12.

  47. Tarp U, Stengaard-Pedersen K, Hansen JC, Thorling EB (1992) Glutathione redox cycle enzymes and selenium in severe rheumatoid arthritis: lack of antioxidative response to selenium supplementation in polymorphonuclear leucocytes. Annalsoftherheumatic diseases 51: 1044-1049.

  48. Jantti J, Vapaatalo H, Seppala E, Ruutsalo HM, Isomaki H (1991) Treatment of rheumatoid arthritis with fish oil, selenium, vitamins A and E and placebo. Scand J Rheumatol:20:225.

  49. Adachi JD, Bell MJ, Bensen WG, Bianchi F, Cividino A, et al. (1997) Fluoride therapy in prevention of rheumatoid arthritis induced bone loss. J Rheumatol 24: 2308-2313.

  50. Reid IR, Veale AG, France JT (1994) Glucocorticoidosteoporosis. J Asthma 31: 7-18.

  51. vanStaa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2000) Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford) 39: 1383-1389.

  52. Adachi JD, Bensen WG, Cividino A (1998) Corticosteroid-induced osteoporosis. J Am Med WomensAssoc 53: 25-30, 40.

  53. Huybers S, Naber TH, Bindels RJ, Hoenderop JG (2007) Prednisolone-induced Ca2+ malabsorption is caused by diminished expression of the epithelial Ca2+ channel TRPV6. Am J Physiol Gastrointest Liver Physiol 292: G92-97.

  54. Zallone A (2006) Direct and indirect estrogen actions on osteoblasts and osteoclasts. Ann N Y AcadSci 1068: 173-179.

  55. Canalis E, Mazziotti G, Giustina A, Bilezikian JP (2007) Glucocorticoid-induced osteoporosis: pathophysiology and therapy. OsteoporosInt 18: 1319-1328.

  56. Adachi JD, Bensen WG, Bianchi F, Cividino A, Pillersdorf S, et al. (1996) Vitamin D and calcium in the prevention of corticosteroid induced osteoporosis: a 3 year followup. J Rheumatol 23: 995-1000.

  57. Buckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM (1996) Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial. Ann InternMed 125: 961-968.

  58. Adachi JD, Ioannidis G (1999) Calcium and vitamin D therapy in corticosteroid-induced bone loss: what is the evidence? CalcifTissueInt 65: 332-336.

  59. O'Connor à (2013) An overview of the role of diet in the treatment of rheumatoid arthritis. NutritionBulletin 39: 74-88.

  60. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357: 266-281.

  61. Holick MF (2011) Vitamin D: evolutionary, physiological and health perspectives. CurrDrugTargets 12: 4-18.

  62. Cantorna MT (2000) Vitamin D and autoimmunity: is vitamin D status an environmental factor affecting autoimmune disease prevalence? ProcSocExpBiolMed 223: 230-233.

  63. Maruotti N, Cantatore FP (2010) Vitamin D and the immune system. J Rheumatol 37: 491-495.

  64. Taher YA, van Esch BC, Hofman GA, Henricks PA, van Oosterhout AJ (2008) 1alpha,25-dihydroxyvitamin D3 potentiates the beneficial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-beta. J Immunol 180: 5211-5221.

  65. Xystrakis E, Kusumakar S, Boswell S, et al. (2006) Reversing the defective induction on IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. J ClinInvest 116:146-155.

  66. Adorini L, Giarratana N, Penna G (2004) Pharmacological induction of tolerogenic dendritic cells and regulatory T cells. SeminImmunol 16: 127-134.

  67. Griffin MD, Xing N, Kumar R (2004) Gene expression profiles in dendritic cells conditioned by 1alpha,25-dihydroxyvitamin D3 analog. J SteroidBiochem Mol Biol 89-90: 443-8.

  68. Weiss ST (2011) Bacterial components plus vitamin D: the ultimate solution to the asthma (autoimmune disease) epidemic? J AllergyClinImmunol 127: 1128-1130.

  69. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, et al. (2001) 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 167: 4974-4980.

  70. Arnson Y, Amital H, Shoenfeld Y (2007) Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann RheumDis 66: 1137-1142.

  71. Fritsche J, Mondal K, Ehrnsperger A, Andreesen R, Kreutz M (2003) Regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase and production of 1 alpha,25-dihydroxyvitamin D3 by human dendritic cells. Blood 102: 3314-3316.

  72. Bouillon R, Bischoff-Ferrari H, Willett W (2008) Vitamin D and health: perspectives from mice and man. J Bone Miner Res 23: 974-979.

  73. Aguado P, del Campo MT, Garces MV, Gonzalez-Casuas ML, Bernad M, et al. (2000) Low vitamin D levels in outpatient postmenopausal women from a rheumatology clinic in Madrid, Spain: their relationship with bone mineral density. OsteoporosisInt 11: 739-744

  74. Oelzner P, Muller A, Deschner F, Holler M, Abendroth K, et al. (1998) Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis. CalcifTissueInt 62:193-198.

  75. Jahnsen J, Falch JA, Mowinckel P, Aadland E (2002) Vitamin D status, parathyroid hormone and bone mineral density in patients with inflammatory bowel disease. Scand J Gastroenterol 37: 192-199.

  76. Nieves J, Cosman F, Herbert J, Shen V, Lindsay R (1994) High prevalence of vitamin D deficiency and reduced bone mass in multiple sclerosis. Neurology 44: 1687-1692.

  77. Song GG, Bae SC, Lee YH (2012) Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis. ClinRheumatol 31: 1733-1739.

International Journal of Anesthetics and Anesthesiology (ISSN: 2377-4630)
International Journal of Blood Research and Disorders   (ISSN: 2469-5696)
International Journal of Brain Disorders and Treatment (ISSN: 2469-5866)
International Journal of Cancer and Clinical Research (ISSN: 2378-3419)
International Journal of Clinical Cardiology (ISSN: 2469-5696)
Journal of Clinical Gastroenterology and Treatment (ISSN: 2469-584X)
Clinical Medical Reviews and Case Reports (ISSN: 2378-3656)
Journal of Dermatology Research and Therapy (ISSN: 2469-5750)
International Journal of Diabetes and Clinical Research (ISSN: 2377-3634)
Journal of Family Medicine and Disease Prevention (ISSN: 2469-5793)
Journal of Genetics and Genome Research (ISSN: 2378-3648)
Journal of Geriatric Medicine and Gerontology (ISSN: 2469-5858)
International Journal of Immunology and Immunotherapy (ISSN: 2378-3672)
International Journal of Medical Nano Research (ISSN: 2378-3664)
International Journal of Neurology and Neurotherapy (ISSN: 2378-3001)
International Archives of Nursing and Health Care (ISSN: 2469-5823)
International Journal of Ophthalmology and Clinical Research (ISSN: 2378-346X)
International Journal of Oral and Dental Health (ISSN: 2469-5734)
International Journal of Pathology and Clinical Research (ISSN: 2469-5807)
International Journal of Pediatric Research (ISSN: 2469-5769)
International Journal of Respiratory and Pulmonary Medicine (ISSN: 2378-3516)
Journal of Rheumatic Diseases and Treatment (ISSN: 2469-5726)
International Journal of Sports and Exercise Medicine (ISSN: 2469-5718)
International Journal of Stem Cell Research & Therapy (ISSN: 2469-570X)
International Journal of Surgery Research and Practice (ISSN: 2378-3397)
Trauma Cases and Reviews (ISSN: 2469-5777)
International Archives of Urology and Complications (ISSN: 2469-5742)
International Journal of Virology and AIDS (ISSN: 2469-567X)
More Journals

Contact Us

ClinMed International Library | Science Resource Online LLC
3511 Silverside Road, Suite 105, Wilmington, DE 19810, USA


Get Email alerts
Creative Commons License
Open Access
by ClinMed International Library is licensed under a Creative Commons Attribution 4.0 International License based on a work at
Copyright © 2017 ClinMed International Library. All Rights Reserved.