AIM: The aim of this exploratory study is to estimate the relationship between vitamin D (vit D) deficiency and active rheumatoid arthritis (RA), and the role of supplementation in improving disease activity.
METHOD: A randomized recruitment, consent screening, open-label interventional study was conducted in patients who fulfilled American College of Rheumatology/European League Against Rheumatism 2010 criteria for diagnosing RA and on stable disease-modifying anti-rheumatic drugs (DMARDs) for 3 months. Serum vit D levels and Disease Activity Score of 28 joints/C-reactive protein (DAS28-CRP) disease activity status were estimated at the first visit. Subjects with low vit D levels and DAS28-CRP > 2.6 were supplemented with vit D for 12 weeks, and were assessed for improvement in disease activity and serum vit D levels.
RESULTS: One hundred and fifty RA patients of mean age 49 ± 12.1 years, mean duration of illness 78 ± 63 months, and on treatment with DMARDs for 44 ± 39 months were recruited for the study. Of these, 73 (49%) subjects were found to have DAS28-CRP > 2.6 and serum vit D below 20 ng/mL. The patients received vit D supplement of 60 000 IU/week for 6 weeks, followed by 60 000 IU/month for a total duration of 3 months. Disease activity and vit D status were assessed for 59 (80.8%) patients who reported at the end of 12 weeks of treatment. Mean DAS28-CRP of these patients showed a statistically significant improvement from 3.68 ± 0.93 at baseline to 3.08 ± 1.11 after supplementation (P = 0.002). Serum vit D levels improved from 10.05 ± 5.18 to 57.21 ± 24.77 ng/mL (P < 0.001) during the period.
CONCLUSION: Supplementation of vit D in RA patients with persisting disease activity and vit D deficiency contributed to significant improvement in disease activity within a short duration.
(1) BACKGROUND: Marine n-3 polyunsaturated fatty acids (PUFA) and ɤ-linolenic acid (GLA) are well-known anti-inflammatory agents that may help in the treatment of inflammatory disorders. Their effects were examined in patients with rheumatoid arthritis; (2) METHODS: Sixty patients with active rheumatoid arthritis were involved in a prospective, randomized trial of a 12 week supplementation with fish oil (group I), fish oil with primrose evening oil (group II), or with no supplementation (group III). Clinical and laboratory evaluations were done at the beginning and at the end of the study; (3) RESULTS: The Disease Activity Score 28 (DAS 28 score), number of tender joints and visual analogue scale (VAS) score decreased notably after supplementation in groups I and II (p < 0.001). In plasma phospholipids the n-6/n-3 fatty acids ratio declined from 15.47 ± 5.51 to 10.62 ± 5.07 (p = 0.005), and from 18.15 ± 5.04 to 13.50 ± 4.81 (p = 0.005) in groups I and II respectively. The combination of n-3 PUFA and GLA (group II) increased ɤ-linolenic acid (0.00 ± 0.00 to 0.13 ± 0.11, p < 0.001), which was undetectable in all groups before the treatments; (4) CONCLUSION: Daily supplementation with n-3 fatty acids alone or in combination with GLA exerted significant clinical benefits and certain changes in disease activity.
The aim of this study was to evaluate differences in T helper cell sub-types and osteoclast (OCs) precursors in peripheral blood between patients affected by early rheumatoid arthritis (eRA) and healthy controls. The effect of administration of cholecalcipherol on clinical and laboratory parameters was subsequently evaluated, by a parallel, randomized double blind, placebo controlled trial. Thirty nine eRA patients and 31 age-matched controls were enrolled and compared for levels of 25OH vitamin D, T helper cell sub-types, OCs precursors including both classical and non-classical and pro-inflammatory cytokines at baseline. Eligible patients were female ≥18 years of age with a diagnosis of RA, as defined by the American College of Rheumatology 2010 criteria for <6 months prior to inclusion in the study. Patients with auto-immune or inflammatory diseases other than RA were excluded. Patients treated with glucocorticoids (GCs), disease modifying activity drugs and biologic agents within the past 6 months were also excluded. In the second phase of the study, eRA patients were randomly assigned to standard treatment with methotrexate (MTX) and GCs with (21) or without (18) cholecalcipherol (300,000 IU) and followed for 3 months; the randomization was done by computer generated tables to allocate treatments. Three patients didn't come back to the follow up visit for personal reasons. None of the patients experienced adverse events. The main outcome measures were T cells phenotypes, OCs precursors and inflammatory cytokines. Secondary outcome measure were clinical parameters. In eRA, 25OH vitamin D levels were significantly lower. CD4+/IFNγ+,CD4+/IL4+, CD4+/IL17A+ and CD4+IL17A+IFNγ+, cells were increased in eRA as well as non-classical OCs precursors, whereas T regulatory cells were not altered. TNFα, TGFβ1, RANKL, IL-23 and IL-6 were increased in eRA. Non-classical OCs, IL-23 and IL-6 correlated with disease severity and activity. Standard treatment with MTX and GC ameliorated clinical symptoms and reduced IL-23, whereas it did not affect CD4+ cells sub-sets nor OCs precursors. After 3 months, the combined use of cholecalcipherol significantly ameliorated the effect of treatment on global health. In eRA, a significant imbalance in T CD4+ sub-types accompanied by increased levels of non-classical OCs precursors and pro-inflammatory cytokines was observed. A single dose of cholecalcipherol (300,000 IU) combined with standard treatment significantly ameliorates patients general health.
We aimed at investigating whether the frequency and function of T helper 17 (Th17) and regulatory T cells (Treg) are affected by a restriction of dietary sodium intake in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We enrolled RA and SLE patients not receiving drugs known to increase urinary sodium excretion. Patients underwent a dietary regimen starting with a restricted daily sodium intake followed by a normal-sodium daily intake. The timepoints were identified at baseline (T0), after 3 weeks of low-sodium dietary regimen (T3), after 2 weeks of normal-sodium dietary regimen (T5). On these visits, we measured the 24-hour urinary sodium excretion, the frequency and function of Th17 and Treg cells in the peripheral blood, the serum levels of cytokines. Analysis of urinary sodium excretion confirmed adherence to the dietary regimen. In RA patients, a trend toward a reduction in the frequencies of Th17 cells over the low-sodium dietary regimen followed by an increase at T5 was observed, while Treg cells exhibited the opposite trend. SLE patients showed a progressive reduction in the percentage of Th17 cells that reached a significance at T5 compared to T0 (p = 0.01) and an increase in the percentage of Treg cells following the low-sodium dietary regimen at both T1 and T3 compared to T0 (p = 0.04 and p = 0.02, respectively). No significant apoptosis or proliferation modulation was found. In RA patients, we found a reduction at T5 compared to T0 in serum levels of both TGFβ (p = 0.0016) and IL-9 (p = 0.0007); serum IL-9 levels were also reduced in SLE patients at T5 with respect to T0 (p = 0.03). This is the first study investigating the effects of dietary sodium intake on adaptive immunity. Based on the results, we hypothesize that a restricted sodium dietary intake may dampen the inflammatory response in RA and SLE patients.
<b>OBJECTIVES: </b>Rheumatoid arthritis (RA) is an autoimmune disease characterized by an increase in some autoantibodies and proteolytic enzymes, leading to joint destruction. Although recent investigations have considered vitamin K as an anti-inflammatory nutrient with an important role in bone metabolism, there is currently limited information on its efficacy in RA. We aimed to examine the effects of vitamin K1 (phylloquinone) on the biomarker of joint destruction and autoantibody in patients with RA.<b>MATERIALS AND METHODS: </b>This was a randomized clinical trial in which 64 women with RA who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Vitamin K1 or placebo was administered to the participants for 8 weeks. Baseline characteristics and anthropometric measures were obtained. Clinical status using disease activity score in 28 joints (DAS-28), serum levels of matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF) were assessed before and after the intervention.<b>RESULTS: </b>The serum level of MMP-3 compared with the baseline values did not change significantly in the groups. However, the serum concentration of RF decreased significantly in the vitamin K1 group (p = 0.041). Intergroup comparison showed no significant change in RF serum level after adjusting for relevant confounders (p > 0.05).<b>CONCLUSIONS: </b>Vitamin K1 supplementation at 10 mg/day for 8 weeks did not alter joint destruction and immune status in the patients with RA compared with the controls.
BACKGROUND: Rheumatoid arthritis is a symmetric peripheral polyarthritis of unknown etiology that, untreated or if unresponsive the therapy, typically leads to deformity and destruction of joints due to erosion of cartilage and bone. Omega-3 fatty acids have been shown to reduce morning stiffness, the number of tender joints and swollen joints in patients with rheumatoid arthritis. This study is designed for evaluation of omega-3 effects on disease activity and remission of rheumatoid arthritis in DMARDs treated patients and on weight changes and reduction of analgesic drugs consumption versus placebo.
METHODS: Sixty patients with active rheumatoid arthritis (49 female and 11 male) underwent rheumatologist examination and disease activity score were calculated. Then patients were enrolled in this 12 week, double blind, randomized, placebo- controlled study. The patients in both groups continued their pre study standard treatment. The patients were visited every 4 weeks, 4 times and data were recorded.
RESULTS: Significant improvement in the patient's global evaluation and in the physician's assessment of disease was observed in those taking omega-3. The proportions of patients who improved and of those who were able to reduce their concomitant analgesic medication were significantly greater with omega-3 consumption. There were no weight changes.
CONCLUSION: Daily supplementation with omega-3 results has significant clinical benefit and may reduce the need for concomitant analgesic consumption without weight changes.
ANTECEDENTES: Los efectos del aceite de pescado (AP) en la artritis reumatoide (AR), no han sido examinados en el contexto del tratamiento contemporáneo de la AR temprana. Este estudio examinó los efectos de la alta versus dosis baja FO en la AR temprana empleando un protocolo 'tratar-to-target' de una combinación de medicamentos antirreumáticos modificadores de la enfermedad (DMARD).
MÉTODOS: Los pacientes con AR <12 meses de duración y que eran DMARD naïve fueron inscritos y aleatorizados 2: 1 a FO a una dosis alta o baja dosis (para el enmascaramiento). Estos grupos, designados FO y control, recibieron 5,5 ó 0,4 g / día, respectivamente, de las grasas omega-3, ácido eicosapentaenoico + ácido docosahexaenoico. Todos los pacientes recibieron metotrexato (MTX), sulfasalazina e hidroxicloroquina, y dosis DMARD se ajustaron de acuerdo con un algoritmo teniendo actividad de la enfermedad y la toxicidad en cuenta. Velocidad de sedimentación globular-DAS28, modificado Health Assessment Questionnaire (mHAQ) y remisión fueron evaluados cada tres meses. La medida de resultado primario fue el fracaso de la terapia triple DMARD.
RESULTADOS: En el grupo de FO, el fracaso de la terapia triple DMARD fue menor (IC HR = 0,28 (95%: 0,12 a 0,63; p = 0,002) sin ajustar y 0,24 (IC 95% 0,10 a 0,54; p = 0,0006) después de ajustar por los antecedentes de tabaquismo , epítopo compartido y anti-citrullinated péptido cíclico línea de base. La tasa de primera Colegio Americano de Reumatología (ACR) remisión fue significativamente mayor en el FO en comparación con el grupo control (IC HR = 2,17 (95%: 1,07 a 4,42; p = 0,03) no ajustada y 2,09 (IC 95% 1.2 a 4.30; p = 0,04) ajustado). No hubo diferencias entre los grupos en la dosis de MTX, DAS28 o puntuaciones MHAQ, o eventos adversos.
CONCLUSIONES: FO se asoció con beneficios adicionales a los obtenidos por la combinación con DMARD uso MTX similares 'tratar para objetivo'. Estos incluyen el fracaso DMARD triples reducida y una mayor tasa de remisión ACR.
A randomised controlled trial (RCT) of high-dose v. low-dose fish oil in recent-onset rheumatoid arthritis (RA) demonstrated that the group allocated to high-dose fish oil had increased remission and decreased failure of disease-modifying anti-rheumatic drug (DMARD) therapy. This study examines the relationships between plasma phospholipid levels of the n-3 fatty acids in fish oil, EPA and DHA, and remission and DMARD use in recent-onset RA. EPA and DHA were measured in blood samples from both groups of the RCT. The data were analysed as a single cohort, and Cox proportional hazards models were used to examine relationships between plasma phospholipid (PL) EPA and DHA and various outcome measures. When analysed as a single cohort, plasma PL EPA was related to time to remission, with a one unit increase in EPA (1 % total fatty acids) associated with a 12 % increase in the probability of remission at any time during the study period (hazard ratio (HR)=1·12; 95 % CI 1·02, 1·23; P=0·02). Adjustment for smoking, anti-cyclic citrullinated peptide antibodies and ‘shared epitope’ HLA-DR allele status did not change the HR. Plasma PL EPA, adjusted for the same variables, was negatively related to time to DMARD failure (HR=0·85; 95 % CI 0·72, 0·99; P=0·047). The HR for DHA and time to remission or DMARD failure were similar in magnitude to those for EPA, but not statistically significant. Biomarkers of n-3 status, such as plasma PL EPA, have the potential to predict clinical outcomes relevant to standard drug treatment of RA patients.
OBJECTIVE: Although many studies have considered alpha-lipoic acid (ALA) as a potent antioxidant with anti-inflammatory functions in oxidative stress-associated inflammatory diseases, few studies have evaluated its efficacy in rheumatoid arthritis (RA). Therefore, we aimed to examine the effects of ALA on serum biomarkers of joint damage and inflammation in women with RA.
METHODS: We performed a randomized, double-blind, placebo-controlled clinical trial in which RA patients (n = 70) aged 20-50 years were randomly assigned 1:1 to receive either ALA (1200 mg/day) or placebo for 8 weeks. Fasting blood samples were taken before and after the study to analyze inflammatory biomarkers including serum high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and serum matrix metalloproteinase-3 (MMP-3) as a marker of joint erosion. Moreover, 3-day dietary records, the International Physical Activity Questionnaire (IPAQ), and the Spielberger State-Trait anxiety inventory form Y (STAI-Y) were assessed before and after the intervention.
RESULTS: Sixty-five RA patients completed the trial. No statistically significant differences were observed in serum levels of hs-CRP, TNF-α, IL-6, and MMP-3 within and between the ALA and placebo groups (p > 0.05). There were no statistically significant differences in dietary intakes, physical activity, and anxiety levels between groups at baseline and they remained statistically unchanged during the study period (p > 0.05).
CONCLUSION: Although in theory ALA supplementation could serve as a beneficial nutraceutical in RA patients, in the present study serum inflammatory biomarkers and MMP-3 were not significantly affected by 8 weeks of ALA supplementation.
OBJETIVO: activador del receptor soluble de ligando del factor kappa B nuclear (sRANKL) al cociente de la osteoprotegerina se designa como una ecuación de metabolismo óseo en muchos trastornos reumatológicos y sería modificado con aceite de pescado (FO) suplementación.
DISEÑO Y MÉTODOS: Ochenta y tres mujeres con artritis reumatoide fueron divididos al azar a 40 y de 43 pacientes tratados con (1 g / día) o sin FO durante 3 meses, acompañados con los fármacos convencionales, respectivamente. La osteoprotegerina, sRANKL, factor de necrosis tumoral alfa (TNF-alfa) niveles séricos se midieron antes y después del tratamiento.
RESULTADOS: Los niveles séricos de osteoprotegerina aumentaron, aunque sRANKL, TNF y la relación sRANKL / osteoprotegerina disminuyeron con el tratamiento FO. Se observó una correlación positiva significativa entre sRANKL relación / osteoprotegerina y niveles TNFalfa (r = 0,327, p = 0,040) en el grupo tratado con FO.
CONCLUSIONES: FO podrían disminuir la respuesta inflamatoria mediante la reducción de los niveles séricos TNFalfa y relación / osteoprotegerina sRANKL.
The aim of this exploratory study is to estimate the relationship between vitamin D (vit D) deficiency and active rheumatoid arthritis (RA), and the role of supplementation in improving disease activity.
METHOD:
A randomized recruitment, consent screening, open-label interventional study was conducted in patients who fulfilled American College of Rheumatology/European League Against Rheumatism 2010 criteria for diagnosing RA and on stable disease-modifying anti-rheumatic drugs (DMARDs) for 3 months. Serum vit D levels and Disease Activity Score of 28 joints/C-reactive protein (DAS28-CRP) disease activity status were estimated at the first visit. Subjects with low vit D levels and DAS28-CRP > 2.6 were supplemented with vit D for 12 weeks, and were assessed for improvement in disease activity and serum vit D levels.
RESULTS:
One hundred and fifty RA patients of mean age 49 ± 12.1 years, mean duration of illness 78 ± 63 months, and on treatment with DMARDs for 44 ± 39 months were recruited for the study. Of these, 73 (49%) subjects were found to have DAS28-CRP > 2.6 and serum vit D below 20 ng/mL. The patients received vit D supplement of 60 000 IU/week for 6 weeks, followed by 60 000 IU/month for a total duration of 3 months. Disease activity and vit D status were assessed for 59 (80.8%) patients who reported at the end of 12 weeks of treatment. Mean DAS28-CRP of these patients showed a statistically significant improvement from 3.68 ± 0.93 at baseline to 3.08 ± 1.11 after supplementation (P = 0.002). Serum vit D levels improved from 10.05 ± 5.18 to 57.21 ± 24.77 ng/mL (P < 0.001) during the period.
CONCLUSION:
Supplementation of vit D in RA patients with persisting disease activity and vit D deficiency contributed to significant improvement in disease activity within a short duration.
