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Ernährung bei Rheumatoider Arthritis: Ihr Einfluss auf Erkrankungsrisiko und Krankheitsverlauf
Abstract
Zusammenfassung
Die Art der Ernährung trägt nach den Daten großer Kohortenstudien als ätiologischer Faktor zur Entstehung einer rheumatoiden Arthritis (RA) bei. Die Bedeutung einzelner Nahrungskomponenten ist am besten belegt für den protektiven Effekt von geringen Alkoholmengen und die risikosteigernde Wirkung eines hohen Konsums an rotem Fleisch. Relativ gut untersucht ist die Rolle einer Adipositas, die Schweregrad-abhängig das Erkrankungsrisiko für die RA erhöht. Zusätzlich wird diskutiert, ob vor allem eine abdominelle Adipositas die Entstehung entzündlicher Gelenkerkrankungen begünstigt. Interventionsstudien, welche den Nutzen einzelner Kostformen bei etablierter RA untersuchen sollten, sind in ihrer Qualität und Aussagekraft beschränkt. Eine an den Prinzipien der Mittelmeerkost ausgerichtete Ernährung ist wahrscheinlich von Nutzen für RA-Patienten, auch wenn die positiven Auswirkungen am ehesten die Reduktion des kardiovaskulären Risikos betreffen. Es existieren nur wenige valide Daten zum sinnvollen Einsatz von Nahrungsergänzungsmitteln bei etablierter RA. Einige positive Effekte lassen sich für Fischölkapseln in ausreichend hoher Dosierung von Omega-3-Fettsäuren ableiten. Die Zufuhr von Eisenpräparaten und Vitamin D sollte an objektiven Kriterien und aktuellen Leitlinien ausgerichtet sein.
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Objective
To evaluate Safety and efficacy of probiotic supplementation in inflammatory arthritis.
Methods
The literature on the treatment of inflammatory arthritis with probiotics has been collected in databases such as CNKI, Pubmed, Cochrane library, Embase, etc. The search time is for them to build the database until May 2022. The included literatures are randomized controlled trials (RCTs) of probiotics in the treatment of hyperuricemia and gout. The Cochrane risk assessment tool was used for quality evaluation, and the Rev Man5.3 software was used for meta-analysis.
Results
A total of 37 records were finally included, involving 34 RCTs and 8 types of autoimmune disease (Hyperuricemia and gout, Inflammatory bowel disease arthritis, juvenile idiopathic arthritis [JIA], Osteoarthritis [OA], Osteoporosis and Osteopenia, Psoriasis, rheumatoid arthritis (RA), Spondyloarthritis). RA involved 10 RCTs (632 participants) whose results showed that probiotic intervention reduced CRP. Psoriasis involved 4 RCTs (214 participants) whose results showed that probiotic intervention could reduce PASI scores. Spondyloarthritis involved 2 RCTs (197 participants) whose results showed that probiotic intervention improved symptoms in patients. Osteoporosis and Ostepenia involving 10 RCTs (1156 participants) showed that probiotic intervention improved bone mineral density in patients. Hyperuricemia and gout involving 4 RCTs (294 participants) showed that probiotic intervention improved serum uric acid in patients. OA involving 1 RCTs (433 participants) showed that probiotic intervention improved symptoms in patients. JIA involving 2 RCTs (72 participants) showed that probiotic intervention improved symptoms in patients. Inflammatory bowel disease arthritis involving 1 RCTs (120 participants) showed that probiotic intervention improved symptoms in patients. All of the above RCTs showed that probiotics did not increase the incidence of adverse events.
Conclusion
Probiotic supplements may improve Hyperuricemia and gout, Inflammatory bowel disease arthritis, JIA, OA, Osteoporosis and Osteopenia, Psoriasis, RA, Spondyloarthritis. However, more randomized controlled trials are needed in the future to determine the efficacy and optimal dosing design of probiotics.
Systematic Review Registration
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021286425, identifier CRD42021286425.
Rheumatoid arthritis (RA) is associated with both local and systemic inflammatory processes via the aberrant regulation of inflammatory pathways and imbalances in several mediators of inflammation. Cytokines, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1B, IL-6, IL-17, IL-18, rheumatoid factor, anti-cyclic citrullinated protein, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) have been used in diagnosing and tracking the progression of RA. The primary objective of this review is to identify and summarize which specific dietary patterns and nutritional interventions go beyond symptom management to improve the response to known inflammatory cytokines and possibly decrease markers of inflammation in the RA disease process. Analysis of the 41 identified publications demonstrated that certain dietary patterns, the consumption of specific macronutrients, and supplementation with herbals or other compounds have shown some effect on improving cytokine profiles in patients with RA. This review illustrates the importance of proper patient education on the anti-inflammatory and potential protective impacts substantial dietary change may have on the disease progression and symptoms of RA. Identifying nutritional interventions and dietary patterns that improve the inflammatory cytokine profile, and therefore disease progression and inflammatory comorbidities of RA will help further focus research on treatments that may provide a better overall improvement in quality of life for RA patients by focusing on the root cause inflammatory processes that affect not only joint destruction but also depression-rated disability. This review further notes that while depression is commonly found in patients who suffer from chronic illnesses, it is especially prevalent in the RA population. The pathology of depression is associated with systemic inflammation, which is a known outcome of RA and may explain this strong association. Cytokines IL-6, IL-1, and TNF-α, known mediators involved in the progression of RA, are strongly associated with stress-related disorders including depression and anxiety. The presence of these cytokines is also correlated with the severity and duration of depression. This may signal a potential use of cytokines in diagnosing and following the progression of depression not only in patients with RA but also others. Given the statistics presented on depression and suicide in patients with RA, and the shared inflammatory pathway between the two diseases, depression and suicide screening scales should be included along with analysis of inflammatory markers and disease activity scores (DAS) in any future RA study.
Background
Modern pharmacological research found that the chemical components of Curcuma longa L. are mainly curcumin and turmeric volatile oil. Several recent randomized controlled trials (RCT) have shown that curcumin improves symptoms and inflammation in patients with arthritis.
Methods
Pubmed, Cochran Library, CNKI, and other databases were searched to collect the randomized controlled trials (RCTs). Then, the risk of bias of RCTs were assessed and data of RCTs were extracted. Finally, RevMan 5.3 was utilized for meta-analysis.
Results
Twenty-nine (29) RCTs involving 2396 participants and 5 types of arthritis were included. The arthritis included Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Osteoarthritis (OA), Juvenile idiopathic arthritis (JIA) and gout/hyperuricemia. Curcumin and Curcuma longa Extract were administered in doses ranging from 120 mg to 1500 mg for a duration of 4-36 weeks. In general, Curcumin and Curcuma longa Extract showed safety in all studies and improved the severity of inflammation and pain levels in these arthritis patients. However, more RCTs are needed in the future to elucidate the effect of Curcumin and Curcuma longa Extract supplementation in patients with arthritis, including RA, OA, AS and JIA.
Conclusion
Curcumin and Curcuma longa Extract may improve symptoms and inflammation levels in people with arthritis. However, due to the low quality and small quantity of RCTs, the conclusions need to be interpreted carefully.
Plant-derived nutraceuticals are proposed as new key instruments to represent a profound “back to basics” shift in medical treatment. Data accumulated over the past ten years suggest that curcumin, the major active compound of the turmeric plant, has anti-inflammatory properties. It has yet to be determined whether the anti-inflammatory profile of curcumin is potent enough to justify the application of this substance as a nutritional supplement for patients with rheumatic diseases. To address this question, the most relevant in vitro studies that investigate the mechanism of action of curcumin were reviewed in this article. In addition, a total of 18 animal and human trials were evaluated. The pleiotropic, anti-inflammatory and immunomodulatory effects of curcumin were observed in animal studies. In addition, human trials demonstrated promising findings. In these studies, curcumin was able to reduce the expression of proinflammatory cytokines, lower the level of the C-reactive protein and improve clinical parameters. A limiting factor of the application of curcumin is the inconsistent bioavailability of the substance. Therefore, new formulations have been developed to improve the pharmacodynamic profile of curcumin. The future acceptance of the substance is dependent on new controlled clinical trials with a standardised formulation of curcumin administered as well as standard of care.
Background
Rheumatoid arthritis (RA) is a disease characterized by a chronic inflammatory state. High pro-inflammatory cytokine levels are associated with disease activity. Exercise and the Mediterranean diet (MD) exert anti-inflammatory effects; however, their impacts on inflammation in RA patients remains unknown. This study aimed to compare the effects of six-months of dynamic exercise program (DEP) vs. MD on pro- and anti-inflammatory cytokine serum concentrations.
Methods
Secondary analysis of a randomized clinical trial in which 90 women with RA were randomly assigned to the DEP (n = 30), MD (n = 30), or control group (n = 30). All patients received pharmacological treatment. Serum concentrations of pro-inflammatory (TNF-α, TNF-β, IL-1β, IL-6 pg/mL) and anti-inflammatory (IL-10, IL-Ra pg/mL) cytokines were measured at baseline and after 6 months using the Luminex technique.
Results
After 6 months of follow-up, we found an improvement of the median percentages changes concentrations of TNF-α (DEP, −12.3; MD, −13.3; control, 73.2; p = 0.01), TNF-β (DEP, −67.4; MD, −54.9; control, 0; p = 0.04), and IL-6 (DEP, −19.9; MD, −37.7; control, 45.5; p = 0.04) in the DEP and MED groups in comparison with control group. IL-1Ra concentrations increased only in the MD group (13.8) compared to levels in the control group (−31.7), p = 0.04. There were no statistically significant differences between DEP and MD groups. Only n = 27 participants in the DEP group, n = 26 in the MD group, and n = 21 in the control group completed the follow-up.
Conclusion
The DEP and the MD have potential effects in the concentrations of pro-inflammatory cytokines compared with those in a control group. Only the MD elevated the concentration of IL-Ra.
Clinical Trial Registration
[ClinicalTrials.gov], identifier [NCT02900898].
Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the joints. The multifactorial etiopathogenesis of RA has been heavily investigated, but is still only partially understood. Diet can represent both a risk factor and a protective factor, based on some evidence that suggests specific properties of certain foods and their ability to increase/reduce inflammation. To date, the studies done on this topic provide discordant results and are heterogeneous in terms of design and cohort size. In this work, we investigated for the first time the relationship between nutrition and the risk of RA onset using a sample size of about half a million subjects from one of the largest publicly available biobanks that is the UK biobank. Results showed that oily fish, alcohol, coffee and breakfast cereals have protective roles in RA; whereas, tea can increase the risk of RA. In conclusion, the obtained results confirm that diet plays key roles in RA, either by promoting or by preventing RA onset and development. Future research should focus on unravelling the effects of dietary habits on immune-mediated diseases to establish better preventive strategies.
Fish consumption has been thought to reduce the risk of rheumatoid arthritis (RA), but the reported data are conflicting. We aimed to assess the association between fish consumption (overall, lean fish, and oily fish) and the risk of RA. The E3N Study is a French prospective cohort study including 98,995 women since 1990. Dietary data were collected via a validated food frequency questionnaire in 1993. Cox proportional hazards models were used to calculate HRs and 95% CIs for incident RA. Models were adjusted for age and for the main potential confounders including cigarette smoking. Among 62,629 women, 480 incident cases of RA were identified. In the overall population, we did not find a linear association between overall fish consumption and RA risk (p for trend 0.65), but a moderate consumption of fish was associated with a decreased risk of RA (HR 0.74; 95% CI 0.59–0.94 for tertile 2 compared with tertile 1), especially among current or former smokers (HR 0.61; 95% CI 0.44–0.85). Although not statistically significant, a trend towards an inverse association was only found with oily fish consumption (HR 0.81; 95% CI 0.65–1.02), but not with lean fish. Our results suggest that moderate fish consumption could reduce the risk or RA and potentially counterbalance the increased risk of RA induced by smoking. This inverse association might be explained by the omega-3 fatty acid content of oily fish.
Background:
We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of probiotics supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis (SpA), or psoriatic arthritis).
Methods:
A systematic literature review and meta-analysis from RA and SpA randomized controlled trials were conducted searching for articles in MEDLINE/PubMed and abstracts from recent international rheumatology meetings. The control group was a placebo or another dietary intervention. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration tool and the Jadad scale.
Results:
The initial search yielded 173 articles. Of these, 13 studies were included in the qualitative synthesis, 8 concerning a total of 344 RA patients and 2 concerning a total of 197 SpA patients. Three meta-analyses were also analyzed. Probiotic strains and quantities used were different among trials (5 studies using Lactobacillus sp., 1 trial Bacillus coagulans and the others a mix of different probiotic strains). Time to assess response ranged from 8 weeks to one year. Two studies associated probiotic supplementation with a dietary intervention. Meta-analysis showed a statistically significant decrease of C-reactive protein (CRP) concentration (mean difference (MD)) -3.04 (95% CI -4.47, -1.62) mg/L, p < 0.001; I2 = 20%, n patients = 209) with probiotics in RA. However, after excluding high-risk-of-bias trials of meta-analysis, there was no difference between probiotics and placebo on DAS28 (standard MD -0.54; 95% CI -1.94 to 0.85, p = 0.45, I2 93%, n patients = 143). The two studies on SpA patients showed no efficacy of probiotics.
Conclusions:
Probiotic supplementation might decrease RA activity with a moderate decrease effect on CRP, but lack of evidence and studies' heterogeneity do not allow us to propose them to patients with inflammatory arthritis to control their disease. Further RCTs are required in the future to determinate the efficacy of probiotics and the optimal administration design.
This article presents the 1st set of dietary recommendations of the French Society for Rheumatology for patients suffering from chronic inflammatory rheumatic diseases (IRD) made by a working group consisting of 12 rheumatology experts, 3 physician nutrition specialists, 1 internal medicine specialist, 1 registered dietician and 3 representatives from patient associations. This group relied on a systematic literature review and on expert opinions, while taking into consideration not only the joint effects of diet in IRD but also the extra-articular ones. Eight general principles and nine recommendations were established. The general principles emphasize that nutritional advice is not a substitute for pharmacological treatment of IRD and that it is an integral part of the patients’ overall care, which could help the patient actively participate in their care. The recommendations propose supporting weight loss in subjects who are overweight or obese, a Mediterranean-type diet and supplementation in polyunsaturated fatty acids, mainly omega-3. Conversely, gluten-free diets (in the absence of celiac disease), vegetarian/vegan diets, fasting and elimination of dairy products should not be proposed. Supplementation with vitamins or trace elements is not indicated for controlling chronic IRD activity, while the use of probiotics or spices is not recommended given the limited or disparate data.
Rheumatoid arthritis (RA) is the most common systemic inflammatory rheumatic disease. It is associated with significant burden at the patient and societal level. Extensive efforts have been devoted to identifying a potential cause for the development of RA. Epidemiological studies have thoroughly investigated the association of several factors with the risk and course of RA. Although a precise etiology remains elusive, the current understanding is that RA is a multifactorial disease, wherein complex interactions between host and environmental factors determine the overall risk of disease susceptibility, persistence and severity. Risk factors related to the host that have been associated with RA development may be divided into genetic; epigenetic; hormonal, reproductive and neuroendocrine; and comorbid host factors. In turn, environmental risk factors include smoking and other airborne exposures; microbiota and infectious agents; diet; and socioeconomic factors. In the present narrative review, aimed at clinicians and researchers in the field of RA, we provide a state-of-the-art overview of the current knowledge on this topic, focusing on recent progresses that have improved our comprehension of disease risk and development.
Introduction:
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease affecting the synovial joints and causing severe disability. Environmental and lifestyle factors, including diet, have been proposed to play a role in the onset and severity of RA. Dietary manipulation may help to manage the symptoms of RA by lowering inflammation and potentially decreasing pain.
Methods:
In 40 patients with long-standing RA with stable symptoms and treated with conventional (c-) and biological (b-) disease modifying anti-rheumatic drugs (DMARDs), the effect of a 3-month diet avoiding meat, gluten, and lactose (and all dairy products; privative diet) was evaluated in comparison with a control balanced diet including those foods. Both diets were designed to reduce weight since all patients were overweight or obese. Patients were randomly assigned to one of the diets, and RA was clinically assessed at Time 0 (T0), through the Visual Analogue Scale (VAS), for pain, and the Disease Activity Score of 28 joints (DAS 28) for RA activity. Patients were also administered the Short Form Health survey (SF-36) and the Health Assessment Questionnaire (HAQ). At T0, a blood sample was collected for laboratory tests and adipokines measurements, and anthropometric measurements were compared. These evaluations were repeated at the end of the 3 months' dietary regimens.
Results:
A significant decrease in VAS and the improvement of the overall state of physical and mental health, assessed through SF-36, was observed in patients assigned to the privative diet. Both dietary regimens resulted in the improvement of quality of life compared to baseline values; however, the change was significant only for the privative diet. With either diet, patients showed significant decreases in body weight and body mass index, with a reduction in waist and hips circumference and lower basal glucose and circulating leptin levels. A privative diet was also able to significantly reduce systolic (p = 0.003) and diastolic (p = 0.025) arterial pressure. The number of circulating leukocytes and neutrophils, and the level of hs-C-Reactive Protein also decreased after 3 months of the meat-, lactose-, and gluten-free diet.
Conclusions:
Our results suggest that a privative diet can result in a better control of inflammation in RA patients under stable optimized drug treatment.
Chronic inflammation plays a central role in the pathophysiology of various non-communicable diseases. Dietary interventions can reduce inflammation, in part due to their effect on the gut microbiome. This systematic review aims to determine the effect of dietary interventions, specifically fiber intake, on chronic inflammatory diseases and the microbiome. It aims to form hypotheses on the potential mediating effects of the microbiome on disease outcomes after dietary changes. Included were clinical trials which performed a dietary intervention with a whole diet change or fiber supplement (>5 g/day) and investigated the gut microbiome in patients diagnosed with chronic inflammatory diseases such as cardiovascular disease (CVD), type 2 diabetes (T2DM), and autoimmune diseases (e.g., rheumatoid arthritis (RA), inflammatory bowel disease (IBD)). The 30 articles which met the inclusion criteria had an overall moderate to high risk of bias and were too heterogeneous to perform a meta-analysis. Dietary interventions were stratified based on fiber intake: low fiber, high fiber, and supplemental fiber. Overall, but most pronounced in patients with T2DM, high-fiber plant-based dietary interventions were consistently more effective at reducing disease-specific outcomes and pathogenic bacteria, as well as increasing microbiome alpha diversity and short-chain fatty acid (SCFA)-producing bacteria, compared to other diets and fiber supplements.
Background:
We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of oral vitamin supplementation on symptoms and disease activity in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA).
Methods:
A systematic literature review and meta-analysis of randomized controlled trials including patients with inflammatory rheumatic diseases were performed using MEDLINE, EMBASE and abstracts from recent international rheumatology congresses. Studies were reviewed in accordance with PRISMA guidelines. We analysed clinical outcomes according to each type of vitamin supplementation.
Results:
The initial search yielded 606 articles. Of these, 13 studies were included in the qualitative synthesis: eight studied vitamin D supplementation, two assessed vitamin E supplementation, two folic acid, and one vitamin K, all of them on RA patients. No studies on SpA or PsA were selected. Oral vitamin supplementations were not associated with a reduction in RA activity (DAS-28 or pain) or RA flares.
Conclusions:
Despite their beneficial effects, the effects of vitamin supplementation on RA activity, if any, seem to be limited. Evidence on their efficacy on SpA or PsA activity is lacking. However, folic acid supplementation should be suggested to prevent methotrexate-related side effects, and vitamin D should be given to patients with vitamin D deficiency to prevent musculo-skeletal complications.
Osteoarthritis (OA) and rheumatoid arthritis (RA) are inflammatory articular conditions with different aetiology, but both result in joint damage. The nutritionally essential metal zinc (Zn2+) and the non-essential metal cadmium (Cd2+) have roles in these arthritic diseases as effectors of the immune system, inflammation, and metabolism. Despite both metal ions being redox-inert in biology, they affect the redox balance. It has been known for decades that zinc decreases in the blood of RA patients. It is largely unknown, however, whether this change is only a manifestation of an acute phase response in inflammation or relates to altered availability of zinc in tissues and consequently requires changes of zinc in the diet. As a cofactor in over 3000 human proteins and as a signaling ion, zinc affects many pathways relevant for arthritic disease. How it affects the diseases is not just a question of zinc status, but also an issue of mutations in the many proteins that maintain cellular zinc homoeostasis, such as zinc transporters of the ZIP (Zrt-/Irt-like protein) and ZnT families and metallothioneins, and the multiple pathways that change the expression of these proteins. Cadmium interferes with zinc’s functions and there is increased uptake under zinc deficiency. Remarkably, cadmium exposure through inhalation is now recognized in the activation of macrophages to a pro-inflammatory state and suggested as a trigger of a specific form of nodular RA. Here, we discuss how these metal ions participate in the genetic, metabolic, and environmental factors that lead to joint destruction. We conclude that both metal ions should be monitored routinely in arthritic disease and that there is untapped potential for prognosis and treatment.
Background:
Spices, i.e., curcumin, ginger, saffron, and cinnamon, have a thousand-year history of medicinal use in Asia. Modern medicine has begun to explore their therapeutic properties during the last few decades. We aimed to perform a systematic literature review (SLR) of randomized controlled trials (RCTs) assessing the effect of spice supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis, or psoriatic arthritis).
Methods:
An SLR of RCTs, reviews, and meta-analyses was performed, searching for articles in MEDLINE/PubMed. Abstracts from international rheumatology and nutrition congresses (2017-2020) were also scrutinized. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration's tool and the Jadad scale.
Results:
Altogether, six studies, assessing the use of spice supplementation only in RA patients, were included: one on garlic supplementation, two on curcumin, one on ginger, one on cinnamon, and one on saffron supplementation. Garlic, ginger, cinnamon, or saffron supplementation was associated with a decrease in RA clinical activity. However, several points limit the external validity of these studies. No conclusion on the impact of curcumin supplementation on RA activity could be drawn due to low-quality studies.
Conclusions:
Garlic, ginger, cinnamon, and saffron supplementation could have a beneficial effect on RA activity, but the risk of bias of these studies is difficult to assess and data are too limited to recommend them in daily practice.
The aim was to compile the evidence from Randomized Controlled Trials (RCTs) of diet or dietary supplements used to reduce disease activity in adults with Rheumatoid Arthritis (RA). Searches were performed in the databases PubMed, Scopus and Cochrane. Only RCT studies of diets, foods or dietary supplements, looking at effects on the Disease Activity Score in 28 joints (DAS28) among adults with RA, published in peer-reviewed journals, were included. A total of 27 articles were included—three of whole diets (Mediterranean diet, raw food and anti-inflammatory diet), five of food items, five of n-3 fatty acids, five of single micronutrient supplements, four of single antioxidant supplements and five of pre-, pro- or synbiotics. Studies that showed moderate strength evidence for positive effects on disease activity in RA included interventions with a Mediterranean diet, spices (ginger powder, cinnamon powder, saffron), antioxidants (quercetin and ubiquinone), and probiotics containing Lactobacillus Casei. Other diets or supplements had either no effects or low to very low strength of evidence. In conclusion, RCT studies on diet or dietary supplements are limited in patients with RA, but based on the results in this review there is evidence that some interventions might have positive effects on DAS28.
Objective Observational studies have shown that vitamin D levels are inversely related to rheumatoid arthritis activity, yet evidence from population interventions remains inconsistent.
Methods: The PubMed, Cochrane Library, Embase, CNKI, VIP, and Wanfang databases were searched for studies published before June 2020. Information was collected about the pain visual analog scale (VAS), Disease Activity Score 28 (DAS28), serum vitamin D level, tender joint count (TJC), swollen joint count (SJC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and parathyroid hormone (PTH) research data.
Results: Six studies (n = 438) were included in the meta-analysis. Vitamin D supplementation resulted in a significant improvement in the DAS28 (weighted mean difference (WMD) = −0.41, 95% CI (−0.59, −0.23), P < 0.001), ESR (WMD = −3.40, 95% CI (−6.62, −0.18), P = 0.04) and TJC (WMD = −1.44, 95% CI (−2.74, −0.14), P = 0.03) but not in other outcomes. According to the subgroup analyses, VAS and serum vitamin D were improved in the European ethnic subgroups. TJC and serum vitamin D were improved in the Asian ethnic subgroups. TJC and serum vitamin D were improved in the duration ≤ 12 w subgroups, and the VAS and DAS28 in the duration > 12 w subgroup were different from those of the control group. With a vitamin D dose ≤50,000 IU, only serum vitamin D and TJC improved, and with a vitamin D dose> 50,000 IU, the VAS and DAS28 improved.
Conclusions: Compared with placebo control interventions, vitamin D supplementation seemed to be an effective intervention for patients with rheumatoid arthritis. Different doses of vitamin D and durations of intervention produce different effects.
The aim is to systematically assess the health impact of a low-inflammatory diet intervention (full-diet or supplement), compared to usual diet or other dietary interventions, on weight change, inflammatory biomarkers, joint symptoms, and quality of life in adults with osteoarthritis, rheumatoid arthritis or seronegative arthropathy (psoriatic, reactive, ankylosing spondylitis or IBD-related), on outcomes assessed in prospective studies within 6 months of intervention commencement (PROSPERO CRD42019136567). Search of multiple electronic library databases from inception to July 2019, supplemented by grey literature searches, for randomised and prospective trials assessing the above objective. After exclusion of 446 ineligible studies, five randomised and two prospective trials involving 468 participants with either osteoarthritis or rheumatoid arthritis were included. GRADE assessment for all outcomes was very low. Meta-analyses produced the following standardised mean differences (SMD) and 95 % confidence interval (CI) 2–4 months following commencement of the diets favouring the low-inflammatory diet: weight SMD −0⋅45 (CI −0⋅71, −0⋅18); inflammatory biomarkers SMD −2⋅33 (CI −3⋅82, −0⋅84). No significant effects were found for physical function (SMD −0⋅62; CI −1⋅39, 0⋅14), general health (SMD 0⋅89; CI −0⋅39, 2⋅16) and joint pain (SMD −0⋅98; CI −2⋅90, 0⋅93). In most studies, the quality of dietary intervention (dietitian input, use of validated dietary compliance tool) could not be gauged. In conclusion, very low-level evidence suggests that low-inflammatory diets or supplements compared to usual diets are associated with greater weight loss and improvement in inflammatory biomarkers. More high-quality trials are needed to assess the health effects of a low-inflammatory diet more comprehensively and conclusively in arthritic conditions.
Background:
Many patients with rheumatoid arthritis (RA) report symptom relief from certain foods. Earlier research indicates positive effects of food and food components on clinical outcomes in RA, but insufficient evidence exists to provide specific dietary advice. Food components may interact but studies evaluating combined effects are lacking.
Objectives:
We aimed to investigate if an anti-inflammatory diet reduces disease activity in patients with RA.
Methods:
In this single-blinded crossover trial, 50 patients with RA were randomly assigned to an intervention diet containing a portfolio of suggested anti-inflammatory foods, or a control diet similar to the general dietary intake in Sweden, for 10 wk. After a 4-mo washout period the participants switched diet. Food equivalent to ∼50% of energy requirements was delivered weekly to their homes. For the remaining meals, they were encouraged to consume the same type of foods as the ones provided during each diet. Primary outcome was change in Disease Activity Score in 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR). Secondary outcomes were changes in the components of DAS28-ESR (tender and swollen joints, ESR, and visual analog scale for general health) and DAS28-C-reactive protein.
Results:
In the main analysis, a linear mixed ANCOVA model including the 47 participants completing ≥1 diet period, there was no significant difference in DAS28-ESR between the intervention and control periods (P = 0.116). However, in unadjusted analyses, DAS28-ESR significantly decreased during the intervention period and was significantly lower after the intervention than after the control period in the participants who completed both periods (n = 44; median: 3.05; IQR: 2.41, 3.79 compared with median: 3.27; IQR: 2.69, 4.28; P = 0.04, Wilcoxon's Signed Rank test). No significant differences in the components were observed.
Conclusions:
This trial indicates positive effects of a proposed anti-inflammatory diet on disease activity in patients with RA. Additional studies are required to determine if this diet can cause clinically relevant improvements.This trial was registered at clinicaltrials.gov as NCT02941055.
Background:
Extensive studies have been carried out to investigate the association between obesity and the risk of rheumatoid arthritis (RA); however, the results of the current reported original studies remain inconsistent. This study aimed to clarify the relationship between body mass index and rheumatoid arthritis by conducting an updated overall and dose-response meta-analysis.
Methods:
The relevant literature was searched using the PubMed and Embase databases (through 20 September 2018) to identify all eligible published studies. Random-effect models and dose-response meta-analyses were used to estimate the pooled risk ratio (RR) with a 95% confidence interval (CI). Subgroup analyses were also conducted based on the characteristics of the participants. Sensitivity analyses and publication bias tests were also performed to explore potential heterogeneity and bias in the meta-analysis.
Results:
Sixteen studies that included a total of 406,584 participants were included in the meta-analysis. Compared to participants with normal weight, the pooled RRs of rheumatoid arthritis were 1.12 (95% CI, 1.04-1.20) in overweight and 1.23 (95% CI, 1.09-1.39) in obese participants. There was evidence of a nonlinear relationship between body mass index (BMI) and RA (P for nonlinearity less than 0.001 in the overall meta-analysis, P for nonlinearity=0.025 in the case-control studies, P for nonlinearity=0.0029 in the cohort studies). No significant heterogeneity was found among studies (I2=10.9% for overweight and I2=45.5% for obesity).
Conclusion:
The overall and dose-response meta-analysis showed that increased BMI was associated with an increased risk for rheumatoid arthritis, which might present a prevention strategy for the prevention or control of rheumatoid arthritis. The nonlinear relationship between BMI and RA might present a personal prevention strategy for RA.
Introduction:
It has been suggested that environmental and lifestyle factors might contribute to the severity and progression of inflammation in rheumatoid arthritis. An intervention generating high interest due to its supposed anti-inflammatory properties is the Mediterranean diet.
Methods:
We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.
Results and conclusions:
We identified seven systematic reviews including four primary studies, of which only one corresponded to a randomized trial. We concluded Mediterranean diet may make little or no difference in pain or disease activity and may slightly increase weight in rheumatoid arthritis patients, but the certainty of the evidence is low. On the other hand, it was not possible to clearly establish whether Mediterranean diet has any effect on functionality, morning stiffness or quality of life as the certainty of the existing evidence has been assessed as very low.
Background
Obesity is over-represented in patients with psoriatic arthritis (PsA) and associated with higher disease activity, poorer effect of treatment and increased cardiovascular morbidity. Studies on the effects of weight loss are however needed. This study aimed to prospectively study the effects of weight loss treatment with very low energy diet (VLED) on disease activity in patients with PsA (CASPAR criteria) and obesity (body mass index BMI ≥ 33 kg/m²).
Methods
VLED (640 kcal/day) was taken during 12–16 weeks, depending on pre-treatment BMI. Afterwards, an energy-restricted diet was gradually reintroduced. Weight loss treatment was given within a structured framework for support and medical follow-up.
Treatment with conventional synthetic and/or biologic disease-modifying anti-rheumatic drugs was held constant from 3 months before, until 6 months after baseline.
Patients were assessed with BMI, 66/68 joints count, Leeds enthesitis index, psoriasis body surface area (BSA), questionnaires and CRP at baseline, 3 and 6 months. Primary outcome was the percentage of patients reaching minimal disease activity (MDA) and secondary outcomes were reaching Psoriatic Arthritis Response Criteria (PsARC) and American College of Rheumatology (ACR) response criteria.
Results
Totally 41/46 patients completed the study, 63% women, median age 54 years (IQR 48–62). At baseline increased BMI was associated with higher disease activity and poorer function.
The median weight loss was 18.7 kg (IQR 14.6–26.5) or 18.6% (IQR 14.7–26.3) of the baseline weight. A majority of the disease activity parameters improved significantly after weight loss, including 68/66 tender/swollen joints count, CRP, BSA, Leeds enthesitis index, HAQ and patient VAS for global health, pain and fatigue. A larger weight loss resulted in more improvement in a dose-response manner. The percentage of patients with MDA increased from 29 to 54%, (p = 0.002). PsARC was reached by 46.3%. The ACR 20, 50 and 70 responses were 51.2%, 34.1% and 7.3% respectively.
Conclusions
Short-term weight loss treatment with VLED was associated with significant positive effects on disease activity in joints, entheses and skin in patients with PsA and obesity. The study supports the hypothesis of obesity as a promotor of disease activity in PsA.
Trial registration
ClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016—retrospectively registered
Electronic supplementary material
The online version of this article (10.1186/s13075-019-1810-5) contains supplementary material, which is available to authorized users.
The present meta-analysis aimed to evaluate the relationship between body mass index (BMI) and rheumatoid arthritis (RA). A systematic search of the Cochrane, Pubmed, and Embase databases was conducted to identify relevant studies published before September 2017 using terms related to BMI and RA. Fixed or random-effect models were used to estimate the pooled relative risk (RR) with 95 % confidence interval (CI). Subgroup analyses by sex were performed to investigate the association between BMI and RA in male and female subgroups. A total of 14 eligible studies containing 353,948 patients were included in the analysis. The pooled results suggested that the odds ratios (ORs) of RA were 1.08 (95 % CI: 1.00~1.15) for overweight, and 1.32 (95 % CI: 1.11~1.54) for obesity, respectively, suggesting that a higher BMI increases the risk of RA compared to normal weight. Further subgroup analyses showed a positive association between BMI and RA risk but only in females, with a RR of 1.11 (95 % CI: 1.00~1.22) for overweight and 1.40 (95 % CI: 1.24~1.57) for obesity. In conclusion, an increased BMI may lead to a higher risk for RA development. Furthermore, the positive association between BMI and RA risk may be stronger in female populations than in males. However, additional analyses are needed. © 2018, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.
Microbial communities inhabiting the human body, collectively called the microbiome, are critical modulators of immunity. This notion is underpinned by associations between changes in the microbiome and particular autoimmune disorders. Specifically, in rheumatoid arthritis, one of the most frequently occurring autoimmune disorders worldwide, changes in the oral and gut microbiomes have been implicated in the loss of tolerance against self-antigens and in increased inflammatory events promoting the damage of joints. In the present review, we highlight recently gained insights in the roles of microbes in the etiology of rheumatoid arthritis. In addition, we address important immunomodulatory processes, including biofilm formation and neutrophil function, which have been implicated in host-microbe interactions relevant for rheumatoid arthritis. Lastly, we present recent advances in the development and evaluation of emerging microbiome-based therapeutic approaches. Altogether, we conclude that the key to uncovering the etiopathogenesis of rheumatoid arthritis will lie in the immunomodulatory functions of the oral and gut microbiomes.
Our objective was to investigate whether a dietary pattern derived using inflammatory biomarkers is associated with rheumatoid arthritis (RA) risk. We prospectively followed 79,988 women in the Nurses’ Health Study (NHS, 1984–2014) and 93,572 women in the NHSII (1991–2013); incident RA was confirmed by medical records. Food frequency questionnaires (FFQ) were completed at baseline and approximately every 4 years. Inflammatory dietary pattern was assessed from FFQ data using the Empirical Dietary Inflammatory Pattern (EDIP), including 18 anti-/pro-inflammatory food/beverage groups weighted by correlations with plasma inflammatory biomarkers (interleukin-6, C-reactive protein, and tumor necrosis factor-α receptor 2). We investigated associations between EDIP and RA using Cox regression. We identified 1185 incident RA cases over 4,425,434 person-years. EDIP was not associated with overall RA risk (p trend = 0.21 across EDIP quartiles). Among women ≤ 55 years, increasing EDIP was associated with increased overall RA risk; HRs (95% CIs) across EDIP quartiles were 1.00 (reference), 1.14 (0.86–1.51), 1.35 (1.03–1.77), and 1.38 (1.05–1.83; p for trend = 0.01). Adjusting for BMI attenuated this association. Increasing EDIP was associated with increased seropositive RA risk among women ≤ 55 years (p for trend = 0.04). There was no association between EDIP and RA among women > 55 years (EDIP-age interaction, p = 0.03). An inflammatory dietary pattern was associated with increased seropositive RA risk with onset ≤ 55 years old, and this association may be partially mediated through BMI.
Background:
The Mediterranean diet has been associated with lower mortality and lower risk of cardiovascular diseases and cancer. Although its components have been analysed in several studies, only one study has specifically investigated the association between Mediterranean diet and risk of rheumatoid arthritis (RA), and reported no association.
Methods:
Data on 1721 patients with incident RA (cases) and 3667 controls, matched on age, gender and residential area, from the Swedish epidemiological investigation of RA (EIRA), a population-based case-control study, were analysed using conditional logistic regression. The Mediterranean diet score, ranging from 0 to 9, was calculated from a 124-item food frequency questionnaire.
Results:
In the EIRA study (median age of participants 53 years), 24.1% of the patients and 28.2% of the controls had high adherence to the Mediterranean diet (a score between 6 and 9). After adjustments for body mass index, educational level, physical activity, use of dietary supplements, energy intake, and smoking, high adherence reduced the odds of developing RA by 21% (OR 0.79; 95% CI 0.65-0.96) as compared to low adherence (a score between 0 and 2). The OR was even lower among men (OR 0.49; 95% CI 0.33-0.73), but no significant association was found among women (OR 0.94; 95% CI 0.74-1.18). An association between high diet score and low risk of RA was observed in rheumatoid factor (RF)-positive (OR 0.69; 95% CI 0.54-0.88), but not RF-negative RA (OR 0.96; 95% CI 0.68-1.34), and in RA characterised by presence of antibodies to citrullinated peptides (ACPA), but not in ACPA-negative RA.
Conclusions:
In this large population-based case-control study, the Mediterranean diet score was inversely associated with risk of RA. However, an association was only found among men and only in seropositive RA.
Background
Observational cohort studies and a secondary prevention trial have shown inverse associations between adherence to the Mediterranean diet and cardiovascular risk.
Methods
In a multicenter trial in Spain, we assigned 7447 participants (55 to 80 years of age, 57% women) who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was a major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes). After a median follow-up of 4.8 years, the trial was stopped on the basis of a prespecified interim analysis. In 2013, we reported the results for the primary end point in the Journal. We subsequently identified protocol deviations, including enrollment of household members without randomization, assignment to a study group without randomization of some participants at 1 of 11 study sites, and apparent inconsistent use of randomization tables at another site. We have withdrawn our previously published report and now report revised effect estimates based on analyses that do not rely exclusively on the assumption that all the participants were randomly assigned.
Results
A primary end-point event occurred in 288 participants; there were 96 events in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). In the intention-to-treat analysis including all the participants and adjusting for baseline characteristics and propensity scores, the hazard ratio was 0.69 (95% confidence interval [CI], 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.72 (95% CI, 0.54 to 0.95) for a Mediterranean diet with nuts, as compared with the control diet. Results were similar after the omission of 1588 participants whose study-group assignments were known or suspected to have departed from the protocol.
Conclusions
In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. (Funded by Instituto de Salud Carlos III, Spanish Ministry of Health, and others; Current Controlled Trials number, ISRCTN35739639.)
Probiotics are considered as -immunomodulatory agents; their efficacy as an adjunct therapy option for rheumatoid arthritis (RA), however, remains controversial. The main aim of the present meta-analysis, therefore, was to compare available data from the published randomized, controlled trials (RCTs) recruiting adults with RA which compared probiotics with placebo. The English literature search was performed using Ovid version of Medline, EmBase, Web of Science, and the Central Cochrane library through October 2016 and supplemented by hand searching reference lists. Among 240 citations identified, 4 RCTs (153 participants; 89% female) were included. All data were pooled using a standardized mean difference (SMD) with a 95% CI. Compared to the placebo, probiotics did not change the inflammatory parameters (erythrocyte sedimentation rate, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, IL-10, and IL-12) and oxidative stress indices (total antioxidant capacity and malondialdehyde) significantly. The borderline significant reduction as a result of probiotic administration was only determined in C-reactive protein [SDM − 0.32 (95% CI − 0.65 to 0.00)]. Among disease activity indices (disease activity score [DAS], tender joint count, and swollen joint count), DAS showed a significant improvement following probiotic treatment with a SMD (95% CI) of − 0.58 (− 0.97 to − 0.19). The number of trials was too small to determine if a strain-, dose-, or duration-response effect was present. Probiotics seem to be less effective in RA; however, to reach a firm conclusion, we need further evidence.
Rheumatoid arthritis is a progressive autoimmune disease characterised by severely swollen and painful joints. To compliment pharmacotherapy, people living with rheumatoid arthritis often turn to dietary interventions such as the Mediterranean diet. The aim of the present systematic review is to discuss the effects of the Mediterranean diet on the management and prevention of rheumatoid arthritis in human prospective studies. Four studies met the inclusion criteria, including two intervention studies reporting improvement in the pain visual analogue scale (p < 0.05) and a decrease in the health assessment questionnaire for rheumatoid arthritis score (p < 0.05) in the Mediterranean diet groups. Only one study reported a reduction in the 28 joint count disease activity score for rheumatoid arthritis for the Mediterranean diet group (p < 0.05). This review has identified beneficial effects of the Mediterranean diet in reducing pain and increasing physical function in people living with rheumatoid arthritis. However, there is currently insufficient evidence to support widespread recommendation of the Mediterranean diet for prevention of rheumatoid arthritis.
Objectives:
To evaluate the association between long-term dietary quality, measured by the 2010 Alternative Healthy Eating Index, and risk of rheumatoid arthritis (RA) in women.
Methods:
We prospectively followed 76 597 women in the Nurses' Health Study aged 30-55 years and 93 392 women in the Nurses' Health Study II aged 25-42 years at baseline and free from RA or other connective tissue diseases. The lifestyle, environmental exposure and anthropometric information were collected at baseline and updated biennially. Cumulative follow-up rates were more than 90% for both cohorts. The primary outcome was RA alone with two subtypes of the disease: seropositive and seronegative RA.
Results:
During 3 678 104 person-years, 1007 RA cases were confirmed. In the multivariable-adjusted model, long-term adherence to healthy eating patterns was marginally associated with reduced RA risk. To assess potential effect modification by age at diagnosis, we stratified by age. Among women aged ≤55 years, better quality diet was associated with lower RA risk (HRQ4 vs Q1: 0.67; 95% CI 0.51 to 0.88; p trend: 0.002), but no significant association was found for women aged >55 years (p interaction: 0.005). When stratifying by serostatus, the inverse association among those aged ≤55 years was strongest for seropositive RA (HRQ4 vs Q1: 0.60; 95% CI 0.42 to 0.86; p trend: 0.003).
Conclusions:
A healthier diet was associated with a reduced risk of RA occurring at 55 years of age or younger, particularly seropositive RA.
Background:
Knowledge on specific biological pathways mediating disease occurrence (e.g., inflammation) may be utilized to construct hypotheses-driven dietary patterns that take advantage of current evidence on disease-related hypotheses and the statistical methods of a posteriori patterns.
Objective:
We developed and validated an empirical dietary inflammatory index (EDII) based on food groups.
Methods:
We entered 39 pre-defined food groups in reduced rank regression models followed by stepwise linear regression analyses in the Nurses' Health Study (NHS, n = 5230) to identify a dietary pattern most predictive of 3 plasma inflammatory markers: interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor α receptor 2 (TNFαR2). We evaluated the construct validity of the EDII in 2 independent samples from NHS-II (n = 1002) and Health Professionals Follow-up Study (HPFS, n = 2632) using multivariable-adjusted linear regression models to examine how well the EDII predicted concentrations of IL-6, CRP, TNFαR2, adiponectin, and an overall inflammatory marker score combining all biomarkers.
Results:
The EDII is the weighted sum of 18 food groups; 9 are anti-inflammatory and 9 proinflammatory. In NHS-II and HPFS, the EDII significantly predicted concentrations of all biomarkers. For example, the relative concentrations comparing extreme EDII quintiles in NHS-II were: adiponectin, 0.88 (95% CI, 0.80, 0.96), P-trend = 0.003; and CRP, 1.52 (95% CI, 1.18, 1.97), P-trend = 0.002. Corresponding associations in HPFS were: 0.87 (95% CI, 0.82, 0.92), P-trend < 0.0001; and 1.23 (95% CI, 1.09, 1.40), P-trend = 0.002.
Conclusion:
The EDII represents, to our knowledge, a novel, hypothesis-driven, empirically derived dietary pattern that assesses diet quality based on its inflammatory potential. Its strong construct validity in independent samples of women and men indicates its usefulness in assessing the inflammatory potential of whole diets. Additionally, the EDII may be calculated in a standardized and reproducible manner across different populations thus circumventing a major limitation of dietary patterns derived from the same study in which they are applied.
There are conflicting reports on the correlation between serum selenium (Se) levels with rheumatoid arthritis (RA). Through a meta-analysis approach, the aim of the present study is to clarify the relationship between serum Se levels with RA. We searched literatures that met our predefined criteria in PubMed, ScienceDirect, and OVID published as of September 2015. Ten eligible articles with 14 case-control studies involving 716 subjects were identified. Overall, pooled analysis indicated that subjects with RA had lower serum levels of Se than the healthy controls (standardized mean difference (SMD) = -1.347, 95 % confidence interval (CI) = [-1.872, -0.823], p < 0.001). Further subgroup analysis indicated that subjects with RA had lower serum Se levels than healthy controls in Europe (SMD = -1.063, 95 % CI = [-1.571, -0.556], p < 0.001) and Asia (SMD = -3.254, 95 % CI = [-4.687, -1.821], p < 0.001) but not in USA (SMD = -0.322, 95 % CI = [-0.657, 0.012], p = 0.059). The serum Se levels were lower in RA than healthy controls measured by graphite furnace atom absorption spectrometry (GFAAS) (SMD = -1.026, 95 % CI = [-1.522, -0.530], p < 0.001), electrothermal absorption spectrometry (EAS) (SMD = -1.197, 95 % CI = [-2.373, -0.020], p < 0.05), flame atomic absorption spectrophotometry (FAAS) (SMD = -0.681, 95 % CI = [-1.049, -0.313], p < 0.001), and inductively coupled plasma-mass spectrophotometer (ICP-MS) (SMD = -11.707, 95 % CI = [-15.189, -8.224], p < 0.001) but not by neutron activation analysis (NAA) (SMD = -0.674, 95 % CI = [-1.350, 0.003], p = 0.051). In conclusion, this meta-analysis supports a significant association between low serum Se concentration with RA. However, this finding needs further confirmation by a trans-regional multicenter study to obtain better understanding of causal relationship between serum Se with RA of different human races or regions.
The evidence from published studies on the association between obesity and rheumatoid arthritis (RA) has been contradictory. To clarify the association between obesity and RA, we conducted a systematic review and dose-response meta-analysis to assess the relationship between body mass index (BMI) and RA risk.
A systematic literature search of Pubmed and Embase (up to July 12, 2014) was performed to identify all eligible published reports. The pooled relative risk (RR) results with corresponding 95% confidence intervals (CIs) of RA development were estimated using a random effects model.
Eleven eligible related citations fulfilled the inclusion criteria and were included in the study. Compared with individuals with BMI < 30, obese individuals showed an association with a significantly increased risk of RA (RR = 1.25, 95%CI 1.07-1.45, Pheterogeneity < 0.01, I(2) = 63%). Compared to normal weight subjects, the pooled RRs for RA were 1.31 (1.12-1.53) and 1.15 (1.03-1.29) for the categories of obese and overweight, respectively. In the dose-response analysis, there was evidence of a nonlinear association (Pnon-linear =0.005) and the estimated summary RR for a 5-unit increment was 1.03 (95%CI 1.01-1.05, Pheterogeneity = 0.001, I(2) = 70.0%).
An increase in BMI can contribute to a higher risk for RA development. However, the finding also highlights the need for research on the association between BMI and RA risk with adjustment for more confounding factors.
IntroductionThe association between fish consumption and rheumatoid arthritis (RA) is unclear. The aim of this paper was to summarize the available evidence on the association between fish consumption and risk of RA using a dose-response meta-analysis.Methods
Relevant studies were identified by a search of MEDLINE and EMBASE through December 2013, with no restrictions. A random-effects dose-response meta-analysis was conducted to combine study specific relative risks. Potential non-linear relation was investigated using restricted cubic splines. A stratified analysis was conducted by study design.ResultsSeven studies (four case-controls and three prospective cohorts) involving a total of 174 701 participants and 3346 cases were included in the meta-analysis. For each one serving per week increment in fish consumption, the relative risk (RR) of RA was 0.96 (95% confidence interval (CI) 0.91 to 1.01). Results did not change when stratifying by study design. No heterogeneity or publication bias was observed. When fish consumption was modeled using restricted cubic splines, the risk of RA was 20 to 24% lower for 1 up to 3 servings per week of fish (RR¿=¿0.76, 95% CI: 0.57 to 1.02) as compared to never consumption.Conclusions
Results from this dose-response meta-analysis showed a non-statistically significant inverse association between fish consumption and RA.
Daily food intake plays an important role in the pathogenesis of arthritis. However, an association between arthritis, food intake, and cardiovascular disease (CVD) risk remains unclear. We hypothesized that higher intakes of nutrients, fruits, and vegetables are associated with a lower risk of arthritis, osteoarthritis (OA), and rheumatoid arthritis (RA) in the Korean population with various comorbidities. This study aims to identify the association between arthritis, OA, RA, food intake, and CVD risk among the elderly population. We conducted a cross-sectional study of 33,966 eligible subjects aged over 50 years who completed the 2009–2019 Korea National Health and Nutrition Examination Survey. Logistic regression was used to identify associations between the presence of arthritis, OA, and RA and risk factors and to predict risks of arthritis, OA, and RA based on marginal effects. The prevalence of arthritis (OR 1.26, 95%CI, 1.15-1.37) and OA (OR 1.24, 95%CI, 1.14-1.36) were significantly higher among individuals with a high risk of CVDs compared with those with low risk. A two-fold increase in daily vitamin B1, B2, PUFA, and n-3 fatty acid consumption is associated with a significantly lower risk of arthritis and OA development. The odds ratios (ORs) for high-consumption of fruit were 0.72 (0.54 ̶ 0.95) in arthritis, and 0.70 (0.52 ̶ 0.94) in OA, in comparison with the low-consumption group. Furthermore, the OR for high consumption of green vegetables was 0.74 (0.55 ̶ 0.98) in arthritis. Of note, people who have arthritis, or OA, have a significantly increased CVD risk. In conclusion, high consumption of nutrients, fruits, and vegetables was found to be associated with the presence of arthritis and OA. More research is needed to explore whether interactions between intake of nutrients, fruits, and vegetables impact the presence of arthritis, OA, and CVDs.
Objective
To examine the association of long-term weight change with rheumatoid arthritis (RA) risk in a large prospective cohort study.
Methods
The Nurses’ Health Study (NHS) II started in 1989 (baseline); after exclusions, we studied 108,505 women 25-42 years old without RA. Incident RA was reported by participant and confirmed by medical record review. Body weight was reported biennially through 2015. We investigated two time-varying exposures: weight changes from baseline and from age 18; change was divided into 5 categories. We used a marginal structural model (MSM) approach to account for time-varying weight change and covariates.
Results
Over 2,583,266 person-years, with a median follow-up time of 25.3 years, 541 women developed RA. Compared to women with stable weight from baseline, weight change was significantly associated with increased RA risk [weight gain 2-<10 kg: RR = 1.98 (95% CI 1.38, 2.85); 10-<20 kg: RR = 3.28 (95% CI 2.20, 4.89); ≥20 kg: RR = 3.81 (95% CI 2.39, 6.07); and weight loss >2 kg: RR = 2.05 (95% CI 1.28, 3.28)]. Weight gain of 10 kg or more from age 18 compared with stable weight was also associated with increased RA risk [10-< 20 kg: RR = 2.12 (95% CI 1.37, 3.27), ≥20 kg: RR = 2.31 (95% CI 1.50, 3.56)]. Consistent findings were observed for seropositive and seronegative RA.
Conclusion
Long-term weight gain was strongly associated with increased RA risk in women, with weight gain of ≥ 20 kg associated with more than a three-fold increased RA risk. Maintenance of healthy weight may be a strategy to prevent or delay RA.
Objective
Being overweight or obese increases rheumatoid arthritis (RA) risk among women, particularly among those diagnosed at younger age. Abdominal obesity may contribute to systemic inflammation more than general obesity, thus we investigated whether abdominal obesity, compared with general obesity, predicted RA risk in 2 prospective cohorts, the Nurses’ Health Study (NHS) and NHS II.
Methods
We followed 50,682 women (1986-2014) in NHS and 47,597 women (1993-2015) in NHS II, without RA at baseline. Waist circumference (WC), body mass index (BMI), health outcomes and covariate data were collected through biennial questionnaires. Incident RA cases and serologic status were identified by chart review. We examined the associations of WC and BMI with RA risk using time-varying Cox proportional hazards models. We repeated analyses restricted to age ≤55 years.
Results
During 28 years of follow-up, we identified 844 incident RA cases (527 NHS, 317 NHS II). Women with WC >35 inches (88 cm) had increased RA risk (HR 1.22, 95% CI 1.06-1.41). A similar association was observed for seropositive RA, which was stronger among young and middle-aged women. Further adjustment for BMI attenuated the association to null. In contrast, BMI was associated with RA (HRBMI ≥30vs<25 1.33, 95% CI 1.05-1.68) and seropositive RA, even after adjusting for WC, and, as in WC analyses, this association was stronger among young and middle-aged women.
Conclusion
Abdominal obesity was associated with increased RA risk, particularly for seropositive RA, among young and middle-aged women, however, it did not independently contribute to RA risk beyond general obesity.
Objective
To systematically identify and appraise evidence of the formulation specific effects and population specific responses of probiotics in inflammatory arthritis.
Methods
MEDLINE (PubMed), CINAHL, EMBASE, and SCOPUS databases were searched for studies utilising probiotics in populations with inflammatory arthritis. The Joanna Briggs Institute (JBI) method was used to conduct the systematic review. A single reviewer undertook screening and data extraction. Two independent reviewers assessed the quality of evidence using JBI tools.
Results
The search identified 8158 articles, with 154 potentially relevant full text articles retrieved. Twelve studies met the inclusion criteria and were included in the review, of which ten (83%) were randomised control trials (RCT) and two (17%) were quasi-experimental studies. Four studies included a variety of spondyloarthopathies (SpAs) and eight studies focused on rheumatoid arthritis (RA). Probiotics were supplied for a median of 60 days and mode of 56 days across all included studies (range 7–365 days). Overall, 17 different probiotics were supplied in colony forming units (CFU) per 24 h s ranging from 1 × 10⁸ to 2.25 × 10¹¹. The order of probiotics supplied to the most participants and across the most studies was Lactobacillales.
There was no statistical difference in the relative risk (RR) of minor adverse events between probiotic and control groups (RR 1.02, 95% CI 0.69 to 1.51) when including nil event studies. Meta-analysis identified a statistically significant benefit of probiotics on quality of life with a standard mean difference (SMD) of −0.37 (95% CI -0.59,-0.15) with subgroup analysis favouring Lactobacillales-only formulations. Small but statistically significant reductions in pain were identified, with a mean difference (MD) of −8.97 (95% CI-15.38, −2.56), independent of formulation. Meta-analysis confirmed the known statistically significant benefit of probiotics on the inflammatory marker C-reactive protein (CRP) MD -2.3 (95% CI -4.26, −0.41), with subgroup analysis demonstrating a greater effect in RA and from combined Bifidobacteriales and Lactobacillales formulations.
Conclusion
This review indicates there may be differential benefits to combined formulations of Bifidobacteriales and Lactobacillales compared to purely Lactobacillales formulations, with respect to reducing pain, lowering C-reactive protein and improving quality of life. It also suggests variable benefits associated with the type of Inflammatory arthritis. Relatively less benefit for lowering CRP was attributed to individuals with SpA compared to individuals with RA.
Generalisability of results to clinical practice is limited by the dominant demographic of older individuals with established disease beyond the ‘therapeutic window of intervention’. Small but statistically significant benefits require confirmation in clinical studies with greater consideration to confounding factors of age, gender, diet and individual microbial signature.
Context:
The impact of various dietary interventions on rheumatoid arthritis (RA), characterized by immune-inflammatory response, has been subject to increased attention.
Objective:
A systematic review was conducted to update the current knowledge on the effects of nutritional, dietary supplement, and fasting interventions on RA outcomes.
Data sources:
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with prespecification of all methods, Medline and Embase were systematically searched for relevant articles.
Data extraction:
Data were extracted by 2 independent reviewers.
Results:
A total of 70 human studies were identified. Administration of omega-3 polyunsaturated fatty acids at high doses resulted in a reduction in RA disease activity and a lower failure rate of pharmacotherapy. Vitamin D supplementation and dietary sodium restriction were beneficial on some RA outcomes. Fasting resulted in significant but transient subjective improvements. While the Mediterranean diet demonstrated improvements in some RA disease activity measures, outcomes from vegetarian, elimination, peptide, or elemental diets suggested that responses are very individualized.
Conclusion:
Some dietary approaches may improve RA symptoms and thus it is recommended that nutrition should be routinely addressed.
Objectives:
To determine the independent association of central adiposity, assessed by waist circumference, with odds of psoriasis, PsA and RA prevalence after controlling for general adiposity (BMI).
Methods:
A cross-sectional study of UK Biobank participants aged 40-70 years was performed. Logistic regression was used to calculate the odds of psoriasis, PsA and RA occurrence compared with controls without these conditions by waist circumference, adjusting for covariates: age, sex, smoking status, socioeconomic deprivation and self-reported physical activity (Model 1), followed additionally by BMI (Model 2).
Results:
A total of 502 417 participants were included; 5074 with psoriasis (1.02%), 905 with PsA (0.18%), 5532 with RA (1.11%) and 490 906 controls without these conditions. Adjusted odds ratios (ORs) (Model 1) for psoriasis, PsA and RA, per s.d. (13.5 cm) higher waist circumference were 1.20 (95% CI 1.16, 1.23), 1.30 (95% CI 1.21, 1.39) and 1.21 (95% CI 1.17, 1.24), respectively (all P < 0.001). These ORs remained significant after further adjustment for BMI (Model 2) in psoriasis [OR 1.19 (95% CI 1.12, 1.27), P < 0.001] and RA [OR 1.19 (95% CI 1.12, 1.26), P < 0.001], but not in PsA [OR 1.11 (95% CI 0.95, 1.29), P = 0.127].
Conclusion:
Central adiposity as measured by waist circumference is associated with greater odds of psoriasis and RA prevalence after adjustment for confounders and for BMI. Our findings add support for central adiposity as a long-term clinically relevant component of these conditions.
Background:
The efficacy of vitamin D supplementation in patients with systemic lupus erythematosus (SLE) remains uncertain. This meta-analysis aimed to systematically evaluate the efficacy and safety of vitamin D supplementation in patients with SLE.
Materials and methods:
Randomized controlled trials (RCTs) were searched in PubMed, Embase, Cochrane CENTRAL and Web of Science databases. The retrieved studies were subjected to meta-analysis using the fixed-effect or random-effect model.
Results:
Five eligible RCTs enrolling 490 participants were included. Compared to the placebo treatment, vitamin D supplementation significantly increased the level of serum 25-hydroxyvitamin D (25(OH)D) (5 trials, 490 participants: standard mean difference (SMD) = 2.072, 95% CI: 1.078-3.066, P < 0.001). The pooled result from 2 RCTs showed that vitamin D supplementation decreased the fatigue severity scale scores in patients with SLE (2 trials, 79 participants: SMD = -1.179, 95% CI: -1.897 to -0.460, P = 0.001). The SLE disease activity index scores and positivity of anti-double-stranded DNA antibodies (anti-dsDNA) did not differ significantly (4 trials, 223 participants: SMD = -0.507, 95% CI: -1.055-0.041, P = 0.070; 3 trials, 361 participants: Risk ratio = 0.880, 95% CI: 0.734-1.054, P = 0.165) between the vitamin D supplementation group and the placebo treatment group. None of the included studies reported severe adverse events associated with vitamin D supplementation.
Conclusions:
This meta-analysis suggested that vitamin D supplementation is effective in increasing the serum 25(OH)D levels, may improve fatigue, and is well-tolerated in patients with SLE, however, it does not seem to have significant effects in decreasing the positivity of anti-dsDNA and disease activity.
Objectives
Findings relating to dietary intake of n-3 polyunsaturated fatty acids (PUFA) and risk of rheumatoid arthritis (RA) are mixed. Erythrocyte membrane PUFA is an accurate objective biomarker of PUFA status; however, there are little data on erythrocyte membrane PUFA and risk of RA. The objective was therefore to compare erythrocyte membrane PUFA between pre-RA individuals and matched controls from a population-based sample, and specifically to test the hypothesis that higher levels of longer chain n-3 PUFA are associated with lower risk of RA.
Methods
The European Prospective Investigation into Cancer and Nutrition (EPIC) is a large European prospective cohort study of apparently healthy populations. We undertook a nested case–control study by identifying RA cases with onset after enrolment (pre-RA) in four EPIC cohorts in Italy and Spain. Confirmed pre-RA cases were matched with controls by age, sex, centre, and date, time and fasting status at blood collection. Conditional logistic regression analysis was used to estimate associations of PUFA with the development of RA, adjusting for potential confounders including body mass index, waist circumference, education level, physical activity, smoking status and alcohol intake.
Results
The study analysed samples from 96 pre-RA subjects and 258 matched controls. In this analysis, the median time to diagnosis (defined as time between date of blood sample and date of diagnosis) was 6.71 years (range 0.8–15). A significant inverse association was observed with n-6 PUFA linoleic acid (LA) levels and pre-RA in the fully adjusted model (highest tertile: OR 0.29; 95% CI 0.12 to 0.75; P for trend 0.01). No association was observed with any individual n-3 PUFA, total n-3 PUFA or total n-3:n-6 ratio.
Conclusions
Erythrocyte levels of the n-6 PUFA LA were inversely associated with risk of RA, whereas no associations were observed for other n-6 or n-3 PUFA. Further work is warranted to replicate these findings and to investigate if lower LA levels are a bystander or contributor to the process of RA development.
Objectives:
Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease of multiple joints that puts the patient at high risk for developing cardiovascular diseases (CVDs). The aim of the present study was to conduct an up-to-date systematic review and meta-analysis of published randomized controlled trials (RCTs) to assess potential changes in RA disease activity, inflammation, and CVD risk after oral intake of ω-3 polyunsaturated fatty acids.
Methods:
Publications up to July 31, 2016 were examined using the PubMed, SCOPUS, and EMBASE databases.
Inclusion criteria:
English language; human subjects; both sexes; RCTs; oral intake of ω-3 fatty acids; minimum duration of 3 mo; and no medication change throughout intervention. The Cochrane Risk of Bias tool was used to assess quality of trials. We included 20 RCTs, involving 717 patients with RA in the intervention group and 535 RA patients in the control group.
Results:
Despite the evidence of overall low quality of trials, consumption of ω-3 fatty acids was found to significantly improve eight disease-activity-related markers. Regarding inflammation, only leukotriene B4 was reduced (five trials, standardized mean difference [SMD], -0.440; 95% confidence interval [CI], -0.676 to -0.205; I(2) = 46.5%; P < 0.001). A significant amelioration was found for blood triacylglycerol levels (three trials, SMD, -0.316; 95% CI, -0.561 to -0.070; I(2) = 0.0%; P = 0.012).
Conclusion:
The beneficial properties of ω-3 polyunsaturated fatty acids on RA disease activity confirm the results of previous meta-analyses. Among five proinflammatory markers evaluated, only leukotriene B4 was found to be reduced. However, a positive effect on blood lipid profile of patients with RA was evident, perhaps for the first time.
Objectives Previously, we found that omega-3 fatty acids (n-3 FAs) were inversely associated with anti-cyclic citrullinated peptide (anti-CCP) positivity in participants at risk for future rheumatoid arthritis (RA). We investigated whether n-3 FAs were also associated with rheumatoid factor (RF) positivity and whether these associations were modified by shared epitope (SE) positivity.
Methods The Studies of the Etiology of RA (SERA) cohort includes RA-free participants who are at increased risk for RA. We conducted a nested case–control study (n=136) to determine the association between RF and anti-CCP2 positivity and n-3 FA percentage in erythrocyte membranes (n-3 FA% in red blood cells (RBCs)). Additionally, in the baseline visit of the SERA cohort (n=2166), we evaluated the association between reported n-3 FA supplement use and prevalence of RF and anti-CCP2. We assessed SE positivity as an effect modifier.
Results In the case–control study, increasing n-3 FA% in RBCs was inversely associated with RF positivity in SE-positive participants (OR 0.27, 95% CI 0.10 to 0.79), but not SE-negative participants. Similar associations were seen with anti-CCP positivity in SE-positive participants (OR 0.42, 95% CI 0.20 to 0.89), but not SE-negative participants. In the SERA cohort at baseline, n-3 FA supplement use was associated with a lower prevalence of RF positivity in SE-positive participants (OR 0.32, 95% CI 0.12 to 0.82), but not SE-negative participants; similar but non-significant trends were observed with anti-CCP2.
Conclusions The potential protective effect of n-3 FAs on RA-related autoimmunity may be most pronounced in those who exhibit HLA class II genetic susceptibility to RA.
Objective:
To summarize the relationship between obesity and remission (primary objective), other measures of treatment response, and mortality (secondary objectives) in rheumatoid arthritis (RA).
Methods:
Medline and EMBASE searches were performed (March 2016) using relevant MeSH and keyword terms for obesity and RA. Articles were selected if they reported estimates for achieving remission in obese subjects relative to other BMI categories, or changes in composite or individual disease activity measures or patient-reported outcomes during therapy, or mortality rates, in relationship to BMI category or on a continuous scale. Remission outcomes were conducive to meta-analysis and all other outcomes were summarized.
Results:
A total of 3,368 records were screened; we included 8 reporting remission rates, 9 reporting disease activity measures or patient-reported outcomes, and 3 examining mortality by obesity status or BMI. Obese patients had reduced frequency of obtaining remission compared to non-obese and/or normal weight patients. In adjusted models, obese patients demonstrated lower odds of achieving remission (pooled OR 0.57, 95%CI 0.45 to 0.72) and sustained remission (pooled OR 0.49, 95%CI 0.32 to 0.74) relative to non-obese categories. Most studies found obese patients to have worse DAS28 or DAS, tender joint counts, inflammatory markers, patient global evaluation, pain and physical function scores during follow-up, but not swollen joint counts. Obesity was not associated with increased mortality.
Conclusions:
Obesity decreases the odds of achieving remission in RA, and negatively impacts disease activity and patient-reported outcomes during therapy. Interventions to reduce BMI should be investigated for the ability to improve disease outcomes. This article is protected by copyright. All rights reserved.
Objective:
We investigated the effect of weight loss after bariatric surgery among patients with rheumatoid arthritis (RA).
Methods:
We conducted a retrospective cohort study of RA patients who underwent bariatric surgery (Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, or sleeve gastrectomy) at two medical centers. We obtained anthropometrics, laboratory values, RA disease activity, and medication use at baseline (prior to surgery), at six and twelve months post-surgery, and at most recent follow-up visits. RA disease activity was determined by clinical or validated measures. At each post-surgical visit, characteristics were compared to baseline.
Results:
We identified 53 RA patients who underwent bariatric surgery. At baseline prior to surgery, mean body mass index was 47.8 kg/m(2) (SD 7.7), mean weight was 128.2 kg (SD 24.1), and 57% had moderate/high RA disease activity. Twelve months post-surgery, subjects lost a mean of 41.0 kg (SD 17.3), 70% (SD 24) of excess weight (P<0.001). RA disease activity significantly improved at post-surgical visits (P<0.001). At 12 months post-surgery, 6% had moderate/high disease activity compared to 57% at baseline (P<0.001). At most recent follow-up (mean 5.8 years [SD 3.2] after surgery), 74% were in remission compared to 26% at baseline (P<0.001). Subjects had significantly lower erythrocyte sedimentation rate, C-reactive protein, and RA-related medication use at follow-up visits compared to baseline (P<0.05).
Conclusion:
After substantial weight loss from bariatric surgery, RA patients had lower disease activity, decreased serum inflammatory markers, and less RA-related medication usage. Weight loss may be an important non-pharmacologic strategy to reduce RA disease activity. However, other factors, such as improved efficacy of medications, improved physical activity, and metabolic changes, may also have contributed to these post-surgical improvements. This article is protected by copyright. All rights reserved.
Background:
Sugar-sweetened soda consumption is consistently associated with an increased risk of several chronic inflammatory diseases such as type 2 diabetes and cardiovascular diseases. Whether it plays a role in the development of rheumatoid arthritis (RA), a common autoimmune inflammatory disease, remains unclear.
Objective:
The aim was to evaluate the association between sugar-sweetened soda consumption and risk of RA in US women.
Design:
We prospectively followed 79,570 women from the Nurses' Health Study (NHS; 1980-2008) and 107,330 women from the NHS II (1991-2009). Information on sugar-sweetened soda consumption (including regular cola, caffeine-free cola, and other sugar-sweetened carbonated soda) was obtained from a validated food-frequency questionnaire at baseline and approximately every 4 y during follow-up. Incident RA cases were validated by medical record review. Time-varying Cox proportional hazards regression models were used to calculate HRs after adjustment for confounders. Results from both cohorts were pooled by an inverse-variance-weighted, fixed-effects model.
Results:
During 3,381,268 person-years of follow-up, 857 incident cases of RA were documented in the 2 cohorts. In the multivariable pooled analyses, we found that women who consumed ≥1 serving of sugar-sweetened soda/d had a 63% (HR: 1.63; 95% CI: 1.15, 2.30; P-trend = 0.004) increased risk of developing seropositive RA compared with those who consumed no sugar-sweetened soda or who consumed <1 serving/mo. When we restricted analyses to those with later RA onset (after age 55 y) in the NHS, the association appeared to be stronger (HR: 2.64; 95% CI: 1.56, 4.46; P-trend < 0.0001). No significant association was found for sugar-sweetened soda and seronegative RA. Diet soda consumption was not significantly associated with risk of RA in the 2 cohorts.
Conclusion:
Regular consumption of sugar-sweetened soda, but not diet soda, is associated with increased risk of seropositive RA in women, independent of other dietary and lifestyle factors.