Ernährung gegen Rheuma: ein unterschätztes Thema

Buchkapitel

Ernährungspyramide S. 1106 entspricht nicht konsequent den gewonnenen Erkenntnissen, sondern bringt v.a. eine Abschwächung der schädlichen Faktoren.

Omega-3 fatty acids are immunoregulatory. Vitamin D has multiple immunosuppressive effects. Antioxidants can be acquired through the diet. Adipose tissue is metabolically active and has effects on the inflammatory response.

Importance of the Balance of n-3 and n-6 Fatty Acids in the Inflammatory Process The balance of AA and EPA can be altered through dietary fatty acid intake.

Production of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, are part of the normal immune response. Acting through transcription factors such as NF-κB, ROS increase production of proinflammatory eicosanoids and cytokines, including PGE2, TNF, and IL-1β. Thus unchecked production of ROS may cause inflammation and tissue damage. Antioxidant enzymes such as superoxide dismutase and glutathione peroxidase remove superoxide, thereby providing protection from oxidative damage. Vitamin C (ascorbic acid), vitamin E (α-tocopherol), and β-carotene are acquired through the diet and can act as ROS scavengers.

Obesity might affect disease activity and outcomes in RA. Increased BMI predisposes to gout. Obesity is associated with knee osteoarthritis (OA). Direct biomechanical effects of obesity contribute to OA. Increased leptin provides another link between obesity and OA.

Trotzdem ist das Fazit verhalten: Omega-3 fatty acids modestly reduce disease activity and NSAID requirements. There is no evidence for the benefit of antioxidants in the management of RA. Fasting, vegetarian/vegan, and elimination diets are difficult to sustain, and it is difficult to predict which patients may respond

DOI: 10.1016/B978-0-323-31696-5.00068-1

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Systematisches Review und Meta-Analyse

Most dietary exposures were assessed by relatively few studies. Exposures that have been assessed by multiple, well conducted studies (eg, OA: vitamin D, chondroitin, glucosamine; RA: omega-3) were classified as moderate evidence of small effects on disease progression.

Conclusion The current literature suggests that there is moderate evidence for a small benefit for certain dietary components. High-level evidence of clinically meaningful effect sizes from individual dietary exposures on outcomes in RMDs is missing.

DOI: 10.1136/rmdopen-2021-002167

Study: strong evidence

Prospektive Beobachtungsstudie

For biologic-naïve patients with disease duration < 5 years, 6-month LUNDEX-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 22%, 28%, 33%, and 42%, respectively. Corresponding rates for patients with disease duration > 10 years were 27%, 32%, 41%, and 43%, respectively. Remission rates were 33%, 40%, 45%, and 56% for men and 17%, 23%, 24%, and 32% for women, respectively. For patients aged < 45 years at diagnosis, 6-month LUNDEX-adjusted remission rate for pain was 29% vs 18% for patients ≥ 45 years.

DOI: 10.3899/jrheum.2023-0764

Study: moderate evidence

Beobachtungskohortenstudie

13 752 of 21 904 (62.8%) individuals with RA had data on DAS28 at 3 months after initial rheumatology assessment, of whom 4764 (34.6%) achieved remission. National remission rates were stable from 2018 to 2024; however, wide geographical variation was observed, ranging from 28.4% (London) to 40.3% (East of England). Threefold differences in remission rates were seen between individual hospitals within regions. Younger age, female sex, Black ethnicity, higher baseline DAS28, delayed DMARD initiation and longer symptom duration were independently associated with reduced odds of remission. Delays between symptom onset and referral have increased since the COVID-19 pandemic.

Conclusion

While national remission rates for early RA have remained stable in England and Wales since 2018, there is marked regional and hospital-level variation, highlighting ongoing inequities in service delivery. Addressing factors beyond referral-to-treatment time—particularly delayed presentation to primary care—is required to improve remission rates.

DOI: 10.1093/rheumatology/keaf233

Study: moderate evidence

Narratives Review

Traditionally considered an episodic crystal-induced arthritis, gout is now increasingly recognized as a disease with underlying dysregulation of innate immune memory mechanisms. Growing evidence supports the central hypothesis of this review: that trained immunity, defined as persistent epigenetic and metabolic reprogramming of innate immune cells, plays a critical role in gout pathogenesis and progression, contributing to heightened inflammatory responsiveness even in the presence of urate-lowering therapy (ULT). Understanding these mechanisms opens new therapeutic opportunities by directly targeting the maladaptive immune memory that sustains chronic inflammation [10].

Up to this date, observational studies have demonstrated that innate immune cells can undergo epigenetic, transcriptional, and metabolic reprogramming resulting in a heightened and sustained response to future triggers/stimuli [14–16]. Metabolism and epigenetics serve as fundamental pillars of trained immunity, engaging in a dynamic and reciprocal interplay [17]. Altered metabolic pathways not only provide the energy and biosynthetic precursors for immune activation but also generate key metabolites, such as acetyl-CoA and fumarate, which directly modify the epigenetic landscape by influencing histone acetylation and methylation, thereby regulating pro-inflammatory gene expression [18]. Consequently, recent research increasingly implicates these interconnected pathways in gout and related rheumatic diseases [10].

Despite the growing interest in trained immunity and immune modulation, it is important to emphasize that hyperuricemia remains the essential upstream driver of gout. The innate immune cascade cannot be activated in the absence of elevated uric acid levels, as no MSU crystals form in normouricemic conditions. Therefore, ULT remains the cornerstone of gout management. In parallel with therapies targeting immune pathways, ongoing research into novel agents that modulate uric acid synthesis, renal excretion, and metabolism, including xanthine oxidase inhibitors, uricosurics, recombinant uricase, and newer dual-mechanism agents, offers additional opportunities for comprehensive disease control.

DOI: 10.37349/emd.2025.1007103

Study: weak evidence

Narratives Review

The gut microbiota plays a crucial role in chronic inflammation associated with HUA. Dysbiosis increases intestinal permeability, which promotes the translocation of bacteria or their products, such as lipopolysaccharide (LPS), into the bloodstream[8]. High serum levels of LPS induce chronic inflammation, thus increasing the risk of HUA[19]. This information on the underlying mechanisms can provide insights into the complexity of HUA and the potential for targeted interventions[20].

Singh AK, Durairajan SSK, Iyaswamy A, Williams LL. Elucidating the role of gut microbiota dysbiosis in hyperuricemia and gout: Insights and therapeutic strategies. World J Gastroenterol 2024; 30(40): 4404-4410 [PMID: 39494101 DOI: 10.3748/wjg.v30.i40.4404]

Gout treatment is complex, with the main challenges related to low rates of urate-lowering therapy initiation and continuation, along with the side effects of traditional drugs. These side effects include gastrointestinal toxicity, tolerance, allopurinol hypersensitivity syndrome, nephrotoxicity, and contraindications in patients with other prevalent comorbid conditions[34-36]. About 40% of gout patients are affected by chronic kidney disease and a decrease in glomerular filtration rate[37]. Even the use of NSAIDs, colchicine, and uricosuric medications has limitations[38]. Therefore, safer treatment methods that can effectively intervene in gout development are urgently needed.

Singh AK, Durairajan SSK, Iyaswamy A, Williams LL. Elucidating the role of gut microbiota dysbiosis in hyperuricemia and gout: Insights and therapeutic strategies. World J Gastroenterol 2024; 30(40): 4404-4410 [PMID: 39494101 DOI: 10.3748/wjg.v30.i40.4404]

Several important directions for future research and development have emerged. A well-designed human clinical trial is needed to evaluate the efficacy of microbiome-targeted interventions for treating gout with respect to their effect on clinically relevant endpoints, UA, and inflammation. Personalized treatment strategies for gout based on the makeup of the microbiome of each person should be developed using the capabilities of high-throughput sequencing and machine-learning tools for deducing microbial signatures associated with susceptibility to gout or response to treatment. Future research should focus on elucidating the complex relationships between the gut microbiome and gout pathogenesis, particularly examining specific metabolites and signaling pathways involved in microbiota-host interactions related to UA metabolism and inflammation. Microbiome studies offer promising avenues for developing novel therapeutic agents, including designer probiotics, UA degradation methods, and targeted prebiotics that selectively promote beneficial bacteria growth. In the future, microbiome data analysis and other omics technologies need to be combined to gain deeper insights into the systemic effects of gut microbiota dysbiosis in gout patients.

Singh AK, Durairajan SSK, Iyaswamy A, Williams LL. Elucidating the role of gut microbiota dysbiosis in hyperuricemia and gout: Insights and therapeutic strategies. World J Gastroenterol 2024; 30(40): 4404-4410 [PMID: 39494101 DOI: 10.3748/wjg.v30.i40.4404]

DOI: 10.3748/wjg.v30.i40.4404

Study: weak evidence

Querschnittsstudie (cross-sectional study)

Camilla et al. highlighted that WHO projections suggest that gout mortality may increase by 55% by 2060.

Hyperuricemia represents the primary risk factor for gout. However, epidemiological studies indicate that the majority of individuals with hyperuricemia remain asymptomatic throughout their lifetime; only approximately 10% progress to clinically evident gout (14). One-third of patients have normal SUA levels during acute flares of gouty arthritis. Interestingly, the proportion of MSU deposits in patients with early clinical gout (one or two joint flares) seems similar to that in asymptomatic hyperuricemic patients according to ultrasound scans (15). Thus, it is difficult to predict gout attack by monitoring the uric acid level or deposits of MSU crystals, and more factors that have not yet been studied should be considered.

An increasing number of studies have shown that the gut microbiota may modulate local immune responses in mice and that the human gut microbiota is linked to inflammatory cytokine production (20, 21). However, few studies have examined the association between the gut microbiota and hyperuricemia in humans.

DOI: 10.3389/fendo.2025.1643566

Study: moderate evidence

Kohortenstudie mit zusätzlicher Modellierungsstudie

Methods: We analysed the prevalence, incidence, mortality, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) of RA across 953 locations worldwide, as well as their inequalities and ideal frontiers. A deep-learning pipeline was developed to forecast long-term burdens with scenario simulations.

Results

In 2021, RA affected 17.9 million people globally, with a 13.2% increase in incidence rate from 1990-2021, trending younger and broader. The age-standardised death rate fell 32.7% from 1980 to 2021, but global DALYs nearly doubled from 1990 to 2021. In 2021, among 652 subnational regions, West Berkshire in the UK had the highest age-standardised incidence rate (35.1; 95% uncertainty interval [UI]: 30.8-39.8). Zacatecas in Mexico had the highest age-standardised DALY rate (112.6; 95% UI: 87.2-142.7). Regions with a high sociodemographic index (SDI) bore the heaviest burden, with regional inequalities aggravating from 1990 to 2021. Over 90% of areas lagged in RA frontiers of multiple indicators. Japan uniquely showed declining trends (1990-2021), exemplified by Tokyo’s age-standardised DALY rate dropping by 22.4% since 1990, unlike that in other high SDI regions. Implementing smoking control policies is forecasted to reduce RA-related deaths by 16.8% and DALYs by 20.6% among male patients in high-smoking regions like China.

DOI: 10.1016/j.ard.2025.04.009

Study: moderate evidence

Die Autor:innen weisen darauf hin, dass die vorliegenden Quellen durchaus unsicher sind. Fast alle Studien beruhen auf Routinedaten, die allein Abrechnungsdiagnosen und nicht den aktuellen Krankheitsstatus umfassen. „Wir wissen um die Schwächen dieser Schätzungen, aber da es in Deutschland kein Bevölkerungsregister zur Erfassung der entzündlich-rheumatischen Erkrankungen gibt, sind systematische Analysen verfügbarer Studien mit Routinedaten und Surveys die wichtigste Datengrundlage“, sagt Dr. med. Katinka Albrecht, Erstautorin der Studie. Auch erschwerten fehlerhafte und überlappende Krankheitskodierungen eine zuverlässige Bestimmung. Für validere Zahlen seien mehrstufige Bevölkerungsstudien erforderlich, an denen es jedoch mangele.

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Narratives Review

Siehe Tabelle S. 4: Although findings are inconsistent, some studies suggest that fish or fish oil intake decreases the risk of RA, mostly due to long-chain n-3 polyunsaturated fatty acids (PUFAs) content [102–104]. Especially long-term intake of more than 0.21 g/day long-chain n-3 PUFAs was associated with a decreased risk of developing RA [105]. As the estimated dietary intake of n-3 PUFAs may not correlate with their plasma levels, the percentage of long-chain n-3 PUFAs in erythrocyte membranes may serve as a surrogate measure [106]. Higher erythrocyte membrane content of n-3 PUFAs was associated with a lower prevalence of anti-CCP antibodies and RF in subjects at risk for RA and a lower risk of transition from anti-CCP positivity to inflammatory arthritis [107–109]. However, in a large prospective cohort study, no association between n-3 PUFAs, but a significant inverse association with n-6 PUFA linoleic acid levels and risk of RA was described [110]. Other foods are considered in association with the risk of RA, although findings are inconsistent as well. Moderate alcohol intake [111,112], fruit and vitamin C [113], olive oil, cooked vegetables [114], mushrooms, beans, poultry, and dairy products [115] are considered protective in RA. The protective effect of alcohol intake was included in the risk calculation formula of RA development [116]. Interestingly, an inverse relationship between the presence of RA and the consumption of alcohol at or before disease onset was predominantly confined to ACPApositive RA, while a non-significant association was observed for ACPAnegative RA [117]. The possible mechanisms for the protective effect of alcohol are via attenuation of the innate inflammatory response shown in vitro and in vivo or via intrinsic corticosteroid production [112,118–120].

DOI: 10.1016/j.autrev.2021.102797

Study: weak evidence

Mendelian Randomisation (MR) Studie

A recent observational study suggested that excessive SFA intake might trigger inflammation and muscle degradation in patients with RA, possibly leading to sarcopenia and inflammatory processes. The American College of Rheumatology dietary guidelines for RA recommend a Mediterranean diet with limited SFA intake. Nevertheless, given the extant controversies and inherent biases in observational research methodologies, it is imperative to rigorously assess the causative implications of SFAs for RA.

DOI: 10.3389/fnut.2024.1337256

Study: moderate evidence

Beobachtungsstudie (Querschnittsstudie)

Results: A total of 1,388 participants (mean age 61.3 years, 57.4% women) were included in the study, of whom 72 had symptomatic hand OA (prevalence of symptomatic hand OA 5.2%). Beta-diversity of the gut microbiome, but not α-diversity, was significantly associated with the presence of symptomatic hand OA (P = 0.003). Higher relative abundance of the genera Bilophila and Desulfovibrio as well as lower relative abundance of the genus Roseburia was associated with symptomatic hand OA. Most functional pathways (i.e., those annotated in the KEGG Ortholog hierarchy) that were observed to be altered in participants with symptomatic hand OA belonged to the amino acid, carbohydrate, and lipid metabolic pathways.

Conclusion: This large, population-based study provides the first evidence that alterations in the composition of the gut microbiome were observed among study participants who had symptomatic hand OA, and a low relative abundance of Roseburia but high relative abundance of Bilophila and Desulfovibrio at the genus level were associated with prevalent symptomatic hand OA. These findings may help investigators understand the role of the microbiome in the development of symptomatic hand OA and could contribute to potential translational opportunities.

DOI: 10.1002/art.41729

Study: moderate evidence

Narratives Review

Modern genetic technologies combined with large, well-characterised clinical cohorts have advanced our understanding of the genetics of the disease.

Therapeutic approaches Disease-modifying antirheumatic drugs (DMARDs) target infl ammation and by defi nition must reduce structural damage progression. Non-steroidal anti-infl ammatory drugs (NSAIDs), while reducing pain and stiff ness and improving physical function, do not interfere with joint damage and are thus not disease modifying. Glucocorticoids off er rapid symptomatic and disease-modifying eff ects,111 but are associated with serious long-term side-eff ects. There are two major classes of DMARDs: synthetic and biological. Synthetic DMARDs are further defi ned as conventional synthetic or targeted synthetic.112 The use of conventional synthetic DMARDs has evolved empirically and their modes of action are still largely unknown. By contrast, targeted synthetic DMARDs have been developed to modulate a particular target implicated in the generation of infl ammation. Key examples include janus kinase (JAK) inhibitors, such as tofacitinib or baricitinib (Eli Lilly, Indianapolis, IN, USA).

According to EULAR recommendations,89 treatment should be initiated with a conventional synthetic DMARD, ideally methotrexate, plus low-dose glucocorticoids (fi gure 4). There is compelling evidence that this is the optimal approach.

The biological agents and the targeted synthetic DMARDs induce more adverse events than do conventional synthetic DMARDs. In particular, the incidence of serious infections is increased, although it decreases over time.5,151

Second, we cannot predict optimal responses or toxic risk for a given treatment;

Early diagnosis and initiation of DMARD therapy are pivotal to prevent damage from occurring or becoming clinically signifi cant.164

DOI: 10.1016/S0140-6736(16)30173-8

Study: weak evidence

Prospektive Kohortenstudie

her population samples. In this prospective observational study, we have found no strong evidence to suggest that increased dietary intake of antioxidant nutrients protects against the incidence of knee OA. Knee OA progression, however, and the development of knee pain, appears to be reduced in people with high intakes of vitamin C and possibly other antioxidants. The possibility that dietary modification might contribute to the secondary prevention of this public health problem requires further investigation.

DOI: 10.1002/art.1780390417

Study: moderate evidence

Narratives Review

Lifestyle factors such as cigarette smoking, excess weight, dietary intake, physical activity, and dental hygiene may play important roles in RA pathogenesis. While the mechanisms and associations of cigarette smoking and RA development are the best established, further work is needed to identify and quantify associations of excess weight, dietary intake, physical activity, and dental hygiene on RA risk. The current research is epidemiologic in nature and thus have intrinsic pitfalls including selection bias, recall bias, small sample size, limited follow-up, potential for unmeasured confounding, and reliance on surrogate outcomes that may not always accurately predict progression to RA. These restrictions make it difficult to establish a causal pathway between risk factors and RA incidence. Based on these current limitations, randomized trials of lifestyle interventions are needed to establish a causal relationship with RA, and to make it possible for providers to recommend lifestyle changes to high risk individuals.

Thus, measuring the impact of healthy lifestyle on RA progression is difficult because of barriers to effectively implementing behavior change as well as intrinsic challenges in isolating individual behaviors. RA prevention trials for weight loss, increasing physical activity, optimizing dietary intake, and improving dental hygiene are all relatively feasible and could yield important results elucidating the biologic mechanisms for RA pathogenesis. The results of this research could help researchers to better understand RA development, and motivate at-risk individuals to adopt healthier behaviors. Therefore, it is essential to invest time and funding to lifestyle modification trials, for an ounce of prevention is worth a pound of cure.

DOI: 10.1016/j.clinthera.2019.04.021

Study: weak evidence

Narratives Review

High fat consumption can cause excessive accumulation of triglycerides, inducing increased fat mass and obesity. It has been reported that overweight/obesity was connected with 60% of hyperuricemia cases in a clinical trial of 14,624 adults [70], possibly due to lipid metabolic disorder promoting purine metabolism by elevating XO activity [71].

Sugar-sweetened beverages containing high-fructose corn syrup and sucrose or almost equal amounts of fructose and glucose, which account for approximately one-third of added sugar consumption in the diets of American adults [80], have been thought to be closely connected with a high prevalence of hyperuricemia in Western countries [81]. Long-term high sugar consumption has been found to accelerate the accumulation of uric acid and promote MSU deposition in fly renal tubules, suggesting that a similar problem may occur in human excretory systems under dietary challenges [82]. In a follow-up study of 650 participants, the results confirmed that a high-sugar diet participates in kidney dysfunction and uric acid metabolism disorders [82].

For example, the plasma concentrations of vitamin C saturation ranges daily from 200 to 400 mg, implying that exceeding the recommended supplemental dose has little effect on the consequences [120]. More importantly, taking high-dose and long-term supplements of vitamin C may be associated with adverse effects, and the resulting excessive uric acid excretion could elevate the risk of kidney stones in gouty patients [121,122].

The typical dietary patterns include a DASH and Mediterranean diet, both of which are comprised of fruits, vegetables, and low-fat dairy products with reductions in total and saturated fats. Increasing evidence supports that consuming a DASH diet can continuously attenuate SUA in hyperuricemia patients and reduce the incidence of gout in participants [34,45]. Similar SUA-lowering effects have been observed in a research investigations of the Mediterranean diet [58]. Moreover, intervention with the DASH diet combined with adequate sodium and plant-derived protein shows more beneficial functions in reducing SUA levels [33,37].

Therefore, our recommendation is for individuals to follow a healthy diet for prevention purposes, and for patients with mild gout, we recommend the DASH and Mediterranean diet, which focus on plant-based components. Additionally, we recommend a reduction in the consumption of high-fat foods (fast food and cream products), especially foods with trans fatty acids (such as margarine and butter), and for individuals to pay attention to the amount of nutrient supplements consumed. For patients with severe gout, dietary modification and medication should be combined, and health care providers should remind patients of food–drug interactions to achieve synergistic effects.

DOI: 10.3390/nu14173525

Study: weak evidence

Narratives Review

Excessive consumption of products with high fructose content can cause hyperuricemia and gout. In addition, the increase in uric acid resulting from excessive consumption of fructose, and overall and sustained high serum uric acid levels have been shown to cause various disorders that will give rise to metabolic syndrome. In this review, the interwoven relationships between hyperuricemia—an increase in serum uric acid levels—and the resulting gout, as well as metabolic syndrome, and the role excessive fructose consumption plays in these, have been investigated.

Alcohol, fructose-sweetened foods and beverages, and purine-rich foods are dietary factors that cause an increase in uric acid levels.

Metabolic syndrome is a condition related to type 2 diabetes, hypertension, dyslipidemia, and abdominal obesity. Cardiovascular diseases and NAFLD are also associated with metabolic syndrome. It is stated that the prevalence of gout and metabolic syndrome increases in parallel with each other.40

DOI: 10.5152/cjm.2024.24001

Study: weak evidence

Narratives Review

Consumption, and Metabolic Syndrome Metabolic syndrome is a condition related to type 2 diabetes, hypertension, dyslipidemia, and abdominal obesity. Cardiovascular diseases and NAFLD are also associated with metabolic syndrome. It is stated that the prevalence of gout and metabolic syndrome increases in parallel with each other.40

DOI: 10.1016/j.autrev.2018.05.009

Study: weak evidence

Mendelian Randomisation (MR) Studie

Although many studies have found an association between other factors such as vitamin supplementation, appropriate coffee citation, and improvement in IA disease activity, the fact that our study did not find a causal association cannot be excluded from being related to the insufficient sample size for the inclusion of several exposure factors of interest in the study, suggesting that the sample size should be continued to be expanded in the future to obtain more stable results.

It also identifies causal relationships between several dietary modalities and different types of IA. These findings have significant implications for the prevention and management of IA through dietary modification.

Unhealthy diets, such as those high in sugar, salt, trans fats, and ultra-processed foods, can lead to imbalances in the gut microbiota, increased oxidative stress, and activation of inflammatory genes. In addition, vitamin and mineral deficiencies and insufficient intake of omega-3 fatty acids have also been linked to inflammation. Healthy eating habits, such as increased intake of fruits, vegetables, and fiber-rich foods, may help to reduce inflammation (41) and may also assist in regulating gut microbiota diversity and stability to prevent disease (42).

IA, a major disease characterized by a long-term chronic inflammatory state, has become increasingly prevalent in recent years, and the identification of modifiable risk factors (e.g., dietary factors) is an achievable way to halt the onset and progression of this type of disease. To overcome the problem of the low inclusion of dietary factors and the homogeneity of the diseases studied in previous studies, we conducted this comprehensive study to assess the causal relationship between several dietary factors (cereals, bread, vegetables and fruits, meat and fish, beverages, dairy products, salt, vitamins, minerals) and IA.

DOI: 10.3389/fnut.2024.1426125

Study: moderate evidence

Narratives Review

Developed societies, although having successfully reduced the burden of infectious disease, constitute an environment where metabolic, cardiovascular, and autoimmune diseases thrive. Living in westernized countries has not fundamentally changed the genetic basis on which these diseases emerge, but has strong impact on lifestyle and pathogen exposure. In particular, nutritional patterns collectively termed the “Western diet”, including high-fat and cholesterol, high-protein, high-sugar, and excess salt intake, as well as frequent consumption of processed and ‘fast foods’, promote obesity, metabolic syndrome, and cardiovascular disease. These factors have also gained high interest as possible promoters of autoimmune diseases. Underlying metabolic and immunologic mechanisms are currently being intensively explored. This review discusses the current knowledge relative to the association of “Western diet” with autoimmunity, and highlights the role of T cells as central players linking dietary influences to autoimmune pathology.

DOI: 10.1007/s11882-013-0404-6

Study: weak evidence

narratives Review mit strukturierter Literaturrecherche

In conclusion, the MD appears to be a promising complementary tool for managing rheumatic and thyroid autoimmune diseases by potentially reducing disease activity, improving autoimmunity-related outcomes and promoting weight loss. Its beneficial nutritional profile helps enhance immune system performance, maintain a healthy gut microbiota and preserve redox balance, thanks to its antioxidant, anti-inflammatory and immunomodulatory properties.

Changing the dietary habits of patients could, therefore, have a positive effect on the inflammatory state associated with the disease [49]. Several studies have investigated the efficacy of different dietary patterns, including the MD, in the treatment of RA patients (Table 2).

DOI: 10.3390/nu17081383

Study: weak evidence

Systematisches Review

Risk of IBD among immigrants approximates that in hosts over subsequent generations.

UC incidence changes prior to CD incidence in immigrants.

Based on our systematic review, the epidemiology of IMIDs among immigrants varies according to native and host countries, immigrant generation, and IMID type. The rapid evolution suggests a role for non-genetic factors and gene-environment interactions.

Vangay et al. demonstrated that migration from Thailand to the US was associated with an immediate loss of gut microbiome diversity, compounded in subsequent generations [82].

DOI: 10.1016/j.jaut.2019.07.002

Study: strong evidence

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Protein, ever since its discovery in 1839, has been considered by many people to be an exceptionally important nutrient, often assuming that the more we consume the better.

We now know, however, that this importance is exaggerated, to mythical proportions. For a starter, protein is not exclusive to animal-based foods. In the late 1800s protein was also found to be present in plant foods. Yet the myth of its being tightly or even exclusively linked to animal-based foods still lingers. 

The problem with this proposition is that high quality does not necessarily mean better health. Increasing body growth may be useful for farm animal production and growing children faster, but it also means growing cancer cells faster, improving conditions for heart disease and speeding up aging—each of which has been documented. Growing young girls more rapidly means earlier sexual maturation, higher circulating levels of estrogen and, eventually, elevated breast cancer risk.

Plant based proteins tend not to promote these events, not at least when fed at levels typically found in the whole foods, plant based (WFPB) diet. These findings beg the next important question of what is the proper amount and kind of protein for individuals to consume for optimum health.

To round it off for convenience, a diet of 10% protein (the RDA) easily represents enough protein for good health. 

But because we revere protein in general, especially animal-based protein, an average American diet contains about 17% dietary protein—not the RDA of 10%. The key question then is what kind of diet provides this RDA of 10% protein? A whole food plant based diet easily provides the 10% protein (even the low protein potato has 8% protein) while also including the countless other nutrients required for good health. But 90-95% of us consume substantially more protein than the RDA. Almost all of the protein in excess of this RDA comes from animal-based foods which brings with it two types of adverse health consequences, including 1) the adverse effects of the protein itself and 2) the displacement of the health benefits of the nutrients of plant-based foods.

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In summarizing the mechanisms by which polyphenols targeting the UPS to ameliorate metabolic disorders, the four possible pathways are proposed: lipid metabolism, inflammation, insulin resistance, and oxidative stress. Hence, the relationship between UPS and these four metabolic pathways is comprehensively summarized.

Polyphenols interact the UPS activity. Polyphenolic compounds such as EGCG, curcumin, quercetin, and resveratrol modulate UPS function by either promoting the degradation of proteins indirectly through UPS interactions or directly regulating intracellular proteasome levels.

EGCG modulates the UPS process to regulate lipid metabolism

EGCG modulates the UPS process to exert antioxidative and anti-inflammatory effect

Curcumin modulates the UPS process to improve lipid metabolism and insulin resistance

Curcumin regulates the UPS process to exert anti-inflammatory effects

Quercetin modulates the UPS process to improve lipid metabolism

Quercetin regulates the UPS process to exert anti-inflammatory effects

Resveratrol modulates the UPS process to improve lipid metabolism

Resveratrol regulates the UPS process to show anti-inflammatory and antioxidative effects

Other polyphenols modulates UPS process to protect metabolic disorders

DOI: 10.3389/fnut.2024.1445080

Study: weak evidence

Empfehlungen (Guidelines)

This is in part because available evidence has not been sufficiently collated and synthesised, and in part because there has not been a coherent public health strategy for promoting musculoskeletal health in primary, secondary or tertiary healthcare sectors. Furthermore, there is heterogeneity in information materials on lifestyle factors across countries and often these materials are not evidence based, are very generic, and may be limited to certain lifestyle domains. Individual socioeconomic factors (including health literacy) may further determine the access to and understanding of information people with RMDs receive, possibly limiting changes in lifestyle behaviour.

The World Health Organisation (WHO) states that all adults should aim for a healthy, balanced diet containing fruits, vegetables, nuts and whole grains, and limited free sugar, fat and salt6; 

whereas many of the studies on diet were rated as having a high risk of bias (including potential conflicts of interest of study sponsors and incomplete descriptions of the randomisation and blinding processes).

Diet 1: A healthy, balanced diet is integral to lifestyle improvement for people with RMDs

Diet 2: People with RMDs should be informed that consuming specific food types is unlikely to have large benefits for RMD outcomes

DOI: 10.1136/annrheumdis-2021-222020

Study: weak evidence

The dietary changes do not reverse joint deformities, but the pain diminishes because the improved diet helps reduce the inflammation in the joints.

At the TrueNorth Health Center, we see many people experience a decrease in their osteoarthritis after changing their diets.

The incidence of arthritis is lower, and the ability to manage it is higher, in places where people consume smaller quantities of animal fat and animal protein than we do in the US. For instance, vegetarian and vegan diets have been shown to decrease arthritis pain and inflammation; even the more moderate Mediterranean diet, characterized by lower consumption of animal products, is associated with a lower risk of rheumatoid arthritis.^[7][8]

A study published in the Lancet supports the contention that diet plays a role in controlling numerous arthritis symptoms.^[9] Compared to a control group, individuals randomized to fast before transitioning to vegan and vegetarian diets for a year showed significant improvement in several measures, including pain score, duration of morning stiffness, health assessment questionnaire, and strength.

If a person suffering from rheumatoid arthritis wants to identify their food sensitivities, the best method is to undertake a period of fasting (ingesting only pure water), followed by a period of rotational feeding. Many arthritis patients have fasted at the TrueNorth Health Center. During the fasting period, it is common for joint pain and swelling to totally disappear.

This pain-free period provides welcome relief, but proper refeeding after the fast is crucial. In fact, there is no point in undertaking a fast if your intention is to revert to your previous way of eating because this behavior is part of the problem (possibly the major part).

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The microbiome isn’t just about digesting food—it’s a master conductor in the orchestra of human health. Trillions of microbes communicate with our immune system, shape our metabolism, and even influence how we think and feel. Far from being passive passengers, these microscopic partners generate metabolites that regulate inflammation, signal through the vagus nerve to the brain, and produce neurotransmitters like serotonin, which governs mood, appetite, and sleep. Increasingly, scientists describe the microbiome as an endocrine organ in its own right through which imbalances can ripple across the body, affecting everything from chronic disease risk to mental well-being.

Immune Modulation
Microbes educate both our innate and adaptive immune systems, helping distinguish harmful pathogens from benign or beneficial ones. This training is foundational to maintaining immune balance and preventing overreactions.

 Studies show that dietary diversity is a strong predictor of microbial diversity, a quality linked to lower rates of inflammation, obesity, and metabolic disease. A diet rich in vegetables, fruits, legumes, whole grains, nuts, and seeds supplies hundreds of distinct phytochemicals and fibers that together shape a more balanced, adaptive microbial community.

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Es ist wahrscheinlich, dass die Quellen nachträglich hinzugefügt wurden, da der Text keine hochgestellten Quellennummern enthält. Somit ist der Bezug zwischen Text und Literaturverzeichnis lose.

Systematische Kommentare über die Rolle der Ernährung und konkret umsetzbare Tipps haben wir im Quellenverzeichnis keine gefunden. Die anwendbarsten Tipps beschränken sich auf eine Auflistung von schädlichen und förderlichen Inhaltsstoffen - oder aber auf die mediterrane Diät, was wir so nicht vollkommen unterstützen können, siehe Text.

Quellen 18 und 22 beleuchten wichtige Zusammenhänge im Detail, geht aber auch nicht in die Praxis der Ernährung. (Quelle 21 ist ein Doppel zu 18)

Quelle 1 informiert über Einzelfakten, Ernährungsfaktoren und Einflüsse auf die Krankheit, ist aber risikenfokussiert und nicht besonders lösungsorientiert.

Quelle 3 zeigt zwar das Problem des leaky guts, diskutiert aber keine konkreten Ernährungsmassnahmen dagegen (streift aber Fecal microbiota transplantation und live biotherapeutics)

Quellen 9 und 17 erwähnen Ernährungsstrategien am Rand, zweitere etwas genauer.

Quelle 14 ist sehr allgemein gehalten und informiert über Ernährung und Entzündungen. Auch Quelle 16 ist sehr allgemein.

Quelle 15 ist leider theoretisch und nicht menschbezogen: In addition, several dietary manipulations can alter the course of SLE, which may be partly mediated by effects on the gut microbiota as hypothesized above. Studies have shown that caloric restriction prevents the progression of lupuslike disease in NZB and (NZB NZW)F1 mice41,42 as well as the SLE-associated antiphospholipid syndrome (APS) in (NZW BXSB)F1 mice.43 Other dietary interventions or factors, such as polyunsaturated fatty acids, vitamins A, D, and E, and phytoestrogens also lead to improved outcome in animal models of SLE, mostly via reduction in proteinuria and glomerulonephritis.44 Furthermore, using two isocaloric diets that differed in their fat composition, Reifen et al. showed that enrichment with n-3 polyunsaturated fatty acids prevents fetal loss and other clinical manifestations of lupus-associated APS.45

Quelle 23 schlussfolgert immerhin: In particular, widespread evidence highlighted the importance of a diet rich in vitamins (mainly A, B₆, C, D and E) and MUFA/PUFA (particularly n-3 PUFA and MUFA) with an adequate fibre intake, protein and Na restriction and moderate energy consumption in reducing co-morbidities and preventing SLE flares, thus minimising unnecessary burden in patients with SLE. It is also remarkable the promising role of dietary polyphenols included in the diet through vegetables, fruits, cereals, legumes and drinks such as tea and wine in the management of SLE. Likewise, it is important to encourage patients to stop smoking, avoid being overweight and optimise their blood pressure, lipid profile, and control of disease activity to decrease cardiovascular morbidity. Den Hinweis auf Wein unterstützen wir nicht.

Quelle 26 zeigt klar positive Effekte von roh-veganer Ernährung, aber an 2 (!) PatientInnen.

Quelle 31 ist seriös recherchiert, deckt sich aber mit unserer Quelle 1 neueren Datums.

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When you are trying to heal your body, all foods that increase inflammation must be avoided. The following three steps focus on three such food groups.

Step 1: Eliminate Animal Products - Details dort

Step 2: Eliminate Added Oils - Details dort

Step 3: Eliminate Processed Foods - Details dort

When I teach this information to my clients, their first question is “how do I get calcium?” They fear that they will weaken their bones without dairy products. Research has shown that dairy products actually cause bone loss; countries that have the highest rates of dairy consumption, like the USA, Canada, Norway, Sweden, Australia, and New Zealand, also have the highest rates of osteoporosis.^[10][11] The lowest rates are among people who eat the fewest animal-derived foods, like natives of rural Asia and rural Africa.^[10][11] These people also have lower overall calcium intake than dairy-consuming cultures do. Calcium is abundant and easy to absorb from green leafy vegetables like kale and broccoli, which come without the risks accompanying dairy products.

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There’s no single known cause for the immune dysregulation associated with more than 80 different autoimmune diseases, but possible triggers include:^[6]

• Poor gut health or leaky gut.
• Excess of stressors from diet, environment, and/or physical and emotional burdens.

For example, elevated levels of immune cells specific to a particular protein in cow’s milk have been discovered in people with type 1 diabetes.^[9] The molecular mimicry theory suggests these proteins are similar to proteins in the pancreas, which causes an immune reaction that targets not only the milk proteins but also pancreatic “self” cells.

Other dietary triggers may be related to foods’ effects on gut health. According to one study, additives in highly processed foods may increase intestinal permeability. This can allow antigens and pathogens to pass out of the gut and into the bloodstream, where immune cells subsequently target and attack them.^[10] Many of these same foods also affect short-chain fatty acid production in the gut, further contributing to permeability and potentially preventing T-reg cells from maturing properly.^[11]

High-sodium diets may also play a role. Salt appears to increase levels of immune cells involved in inflammation and autoimmunity, which makes another case for avoiding highly processed foods.^[12] Eating other proinflammatory foods^[13] like meat, dairy, and processed vegetable oils puts additional stress on the immune system and may make autoimmune diseases worse.

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A whole food, plant-based (WFPB) diet in particular may be beneficial in several key areas associated with autoimmunity.

Eliminating the Biggest Offenders

Lowering Inflammation

Healing the Gut

Supporting Immune Health

Specific plant foods contain nutrients and antioxidants to modulate the immune system^[10][11] and support healthy immune responses:

• Carotenoids and flavonoids: brightly-colored vegetables and fruits, especially berries^[12]
• B Vitamins: grains, nuts, seeds, leafy greens, root vegetables, and nutritional yeast
• Vitamin C: bell peppers, oranges, papayas, broccoli, tomatoes^[13]
• General immune support: leafy greens, mushrooms, ginger, garlic, and onions^[14]

Supplementing with high-quality plant-based vitamin D may provide additional support if vitamin D levels are low.

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Randomisierte kontrollierte Studie RCT

Dietary manipulation is commonly used among rheumatoid arthritis (RA) patients despite the relative lack of data from controlled studies of these regimens.

This is the first controlled study to demonstrate a long-term (1 yr) effect of a vegan diet free of gluten on signs and symptoms of RA. In addition, a decrease in serum levels of IgG antibodies to gliadin and b-lactoglobulin was selectively recorded in the group of patients who responded positively to the vegan diet.

DOI: 10.1093/rheumatology/40.10.1175

Study: strong evidence

Narrative Review

Flaxseed, hempseed and canola oil are the main sources of ALA.  Nuts and seeds are important sources of ALA and other micronutrients. As for the ALA content of nuts and seeds, 28 g of hempseed or walnuts exceeds the adequate intake for ALA, which is ideally set at 1.1 g/day for women and 1.6 g/day for men. 

Humans evolved on a diet with an omega-6/omega-3 ratio of about 1, while Westerners (e.g., those on Western diets) have a ratio of 15/1–16/1. These diets are deficient in omega-3 fatty acids and contain excessive amounts of omega-6 fatty acids. Excessive amounts of omega-6, including LA, or a very high unbalanced omega-6/omega-3 ratio, promote the pathogenesis of many diseases, including cardiovascular, cancer and inflammatory/autoimmune diseases.

DOI: 10.3390/ijms241814319

Study: weak evidence

randomisierte kontrollierte klinische Studie (RCT)

The beneficial effect of a 1-yr vegetarian diet in RA has recently been demonstrated in a clinical trial. We have analysed stool samples of the 53 RA patients by using direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. Based on repeated clinical assessments disease improvement indices were constructed for the patients At each time point during the intervention period the patients in the diet group were then assigned either to a group with a high improvement index (HI) or a group with a low improvement index (LI). Significant alteration in the intestinal flora was observed when the patients changed from omnivorous to vegan diet. There was also a significant difference between the periods with vegan and lactovegetarian diets. The faecal flora from patients with HI and LI differed significantly from each other at 1 and 13 months during the diet. This finding of an association between intestinal flora and disease activity may have implications for our understanding of how diet can affect RA

Briefly, the study was a 13-month prospective, single-blind, randomized trial. Fifty-three patients (45 women and eight men) with active RA were enrolled in the study. Twenty-seven patients were randomized to a diet group and 26 to a control group. The patients in the diet group spent the first month at a health farm, while the patients in the control group were sent to a convalescent home. For the test group the dietary intervention began with a fast of 7-10 days. The vegan diet period lasted 3.5 months and the lactovegetarian period 9 months. The vegan diet contained no meat, fish, eggs, dairy products, refined sugar, added salt, preservatives, tea, coffee, alcoholic beverages or strong spices. In addition, gluten and citrus fruits were excluded. After the fast a 'new' food item was added to the diet every second day, and if any increase in RA symptoms was observed within 48 h it was omitted for 7 days. If the reintroduction of the food item after 7 days re-exacerbated the symptoms, it was excluded from the diet for the remaining study period (individual adjustment of diet).

Alterations in the intestinal flora will change the antigenic challenge and in turn, this may be of importance for the disease activity in RA. A clinically important change in the faecal flora is not necessarily due to changes of a single or a few bacterial species. It may be due to a combination of changes in a large number of different species, as a response to an environmental factor such as diet. The GLC method readily detects changes, differences or similarities between the fatty acid profiles of the stool samples.

The finding that significant differences in the faecal flora were observed between the HI group and the LI group suggests strongly an association between intestinal bacteria and clinical improvement of RA. Based on this, it is tempting to speculate whether antimicrobials, which usually change faecal flora, might be of use in controlling the disease activity in RA. Further studies within this field are warranted, since, at least, clotrimazole [27, 28], metronidazole [29] and minocyclin [30-32] have been claimed to have some effect in RA.

The early appearance (at 1 month) of the difference in faecal flora between HI and LI groups suggests that the primary change would be in the faecal flora rather than in disease improvement This gives support to the idea that changes in faecal flora may be one of the mechanisms through which certain diets and other factors affect disease activity in RA patients.

DOI: 10.1093/rheumatology/33.7.638

Study: strong evidence

Systematisches Review

Fasting/vegetarian/vegan diet

Exclusion diet

DOI: 10.2147/NDS.S6922

Study: strong evidence

Experimentelle Studie mit Tiermodell (Collagen-Induced Arthritis, CIA, in Ratten)

The correlation between food allergy and RA: Recent studies have recognized that intestinal immune reactions might be associated with the articular inflammation. Taking into consideration the fact that IgG is the most important antibody playing a role in the pathogenesis of RA, in the present study we measured IgG antibody activities against the “big eight” food antigens using ELISA. As shown in Figure 6i, the results indicated that occurrence of RA is more related to egg- or milk-specific IgG. Furthermore, egg- or milk-specific IgE was determined by RAST and significant elevated concentrations of specific IgE (sIgE) were observed in CIA rats.

DOI: 10.4103/1947-2714.175206

Study: weak evidence

Narratives Review

Hormonal factors such as those associated with long-term stress, or dietary factors, either through increased consumption of foods with a high density of food additives or through the high consumption of gliadin-rich cereals pose threats to the integrity of cell-binding complexes (70). Increased permeability of body barriers is associated with a high risk of endotoxemia, chronic inflammation and insulin resistance (71). In a recent systematic review, most of the included studies showed a higher concentration of lipopolysaccharides (LPS) in diabetic patients than in healthy subjects (72).

A meta-analysis has measured the efficacy of using supplements rich in omega-3 fatty acids and their analgesic effect on inflammatory joint pain, highlighting how eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation reduces the intensity of joint pain, morning stiffness and non-steroidal anti-inflammatory drugs (NSAID) consumption (105).

DOI: 10.3389/fmed.2021.663703

Study: weak evidence

Expertenmeinung

Among many consequences, obesity begets more type 2 diabetes, raises blood pressure, promotes systemic inflammation, has haemodynamic impacts that can accelerate progression to chronic kidney disease (CKD) or heart failure (HF), has biomechanical impacts, one of which is to make activity harder [4], or more painful (by accelerating osteoarthritis) and impacts mental health in multiple ways. Obesity is also associated with more infections [3], a finding not well appreciated but important given infection risks inherent in several inflammatory RMDs and attendant therapeutics. It would be important to establish whether obesity impacts infection rates for those on disease-modifying anti-rheumatic drug (DMARDs) and, if so, whether intentional weight loss helps reduce infections in patients with RMDs, allowing more patients to stay on their medications without adverse effects.

Weight also impacts liver fat levels.

Summary of the potential impact of weight loss in RMDs

Likely benefits of intentional weight loss in rheumatological diseasesReduced incidence of RMDs (particularly those with a dominant metabolic component)Reduced disease severity and better outcomesImproved response and persistence of response to disease modifying therapies meaning more likely to remain on such therapies, reducing a need to switch and/or escalate treatment thereby reducing the need for clinic appointmentsReduced adverse effects from current RMD treatments, including possible reduced infections based on data from recent trials in other disease areasImprovement in activities of daily living with potentially reduced pain, fatigue and improvements in mental health, allowing more people to stay in work and remain productive. Potential health economic benefits in some with RMDs?Reduced comorbidities (especially CVD, MASLD, hypertension, and type 2 diabetes)

DOI: 10.1016/j.ard.2025.02.013

Study: weak evidence

Systematisches Review mit bibliometrischer Auswertung

Microbial research in SLE primarily focused on changes in microbial composition, particularly gut microbiota, as well as the mechanisms and practical applications in SLE. Recent trends emphasize “metabolites,” “metabolomics,” “fatty acids,” “T cells,” “lactobacillus,” and “dietary supplementation,” indicating a growing emphasis on microbial metabolism and interventions in SLE.

Zhang et al. (2014) beobachteten eine signifikante Reduktion der Laktobazillen und eine erhöhte Häufigkeit von Lachnospiraceae in der Darmflora von MRL/lpr-Mäusen. Die Häufigkeit von Lachnospiraceae korrelierte eng mit dem Krankheitsverlauf, während die Besiedlung des Darms mit Laktobazillen negativ mit der Lupusaktivität war. Diese Ergebnisse legen nahe, dass die Darmmikrobiota in gewissem Masse an der Entwicklung von SLE beteiligt ist.

DOI: 10.3389/fmicb.2024.1319654

Study: strong evidence

Narratives Review

Effects of Dietary Cholesterol and Egg Intake on Lipoprotein Metabolism and Immune Inflammation

Diets rich in cholesterol appear to have the capacity to regulate immune function through modulation of cellular cholesterol levels and lipoprotein metabolism . The effects of dietary cholesterol and cholesterol-rich foods, specifically eggs, on plasma lipids have been reviewed by Blesso and Fernandez ; thus, the following sections focus on the effects of dietary cholesterol on immunomodulatory lipid pathways. In interpreting these findings, it is important to note that human studies evaluating the effects of dietary cholesterol often use whole eggs as the intervention treatment. Eggs are considered to be a rich source of dietary cholesterol, providing approximately 186 mg of cholesterol per large egg.

DOI: 10.3390/nu10060764

Study: weak evidence

Narratives Review

Effects of Dietary Cholesterol from Egg Intake on LDL-C, HDL-C, and the LDL-C/HDL-C Ratio

Berger et al. [29] examined the serum lipid responses to dietary cholesterol across 19 intervention trials. Dietary cholesterol intake, which came mostly from eggs, was shown to significantly increase both serum LDL-C (6.7 mg/dL net change) and HDL-C (3.2 mg/dL net change), resulting in only a marginal increase in the LDL-C/HDL-C ratio (0.17 net change) [29]. Using the LDL-C/HDL-C ratio may provide an estimate of how much cholesterol is delivered to plaques via LDL, as well as potentially how much is being removed by HDL [47]. An LDL-C/HDL-C ratio <2.5 is considered optimal based on individual lipoprotein recommendations, while evidence suggests there is an increase in the risk for cardiovascular events above this level in some populations . Table 1 summarizes results from clinical studies examining the effects of added dietary cholesterol via egg intake on serum lipids during weight maintenance in healthy and hyperlipidemic populations. In children and adults with normal cholesterol levels, consumption of 2–4 eggs per day vs. yolk-free egg substitute significantly increased both LDL-C and HDL-C in most studies, with no change in the LDL-C/HDL-C ratio . Healthy men who were classified as hyper-responders (15 out of 40 participants) did show a significant increase in the LDL-C/HDL-C ratio with the consumption of three eggs per day for 30 days, however, the mean ratio (2.33 ± 0.80) was still within the optimal range of <2.5 [45]. Similar responses were observed in hyperlipidemic adults; consuming two eggs per day resulted in elevated HDL-C without a change in LDL-C in hypercholesterolemic adults, while there was an increase in both LDL-C and HDL-C in combined hyperlipidemics (elevated serum cholesterol and triglycerides) [49]. In older adults taking statins, consuming either two or four eggs per day did not significantly increase LDL-C, whereas HDL-C was increased with both doses of eggs.

DOI: 10.3390/nu10040426

Study: weak evidence

Prospektive Kohortenanalyse

Importance  Cholesterol is a common nutrient in the human diet and eggs are a major source of dietary cholesterol. Whether dietary cholesterol or egg consumption is associated with cardiovascular disease (CVD) and mortality remains controversial.

Objective  To determine the associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality.

Design, Setting, and Participants  Individual participant data were pooled from 6 prospective US cohorts using data collected between March 25, 1985, and August 31, 2016. Self-reported diet data were harmonized using a standardized protocol.

Exposures  Dietary cholesterol (mg/day) or egg consumption (number/day).

Main Outcomes and Measures  Hazard ratio (HR) and absolute risk difference (ARD) over the entire follow-up for incident CVD (composite of fatal and nonfatal coronary heart disease, stroke, heart failure, and other CVD deaths) and all-cause mortality, adjusting for demographic, socioeconomic, and behavioral factors.

Results  This analysis included 29 615 participants (mean [SD] age, 51.6 [13.5] years at baseline) of whom 13 299 (44.9%) were men and 9204 (31.1%) were black. During a median follow-up of 17.5 years (interquartile range, 13.0-21.7; maximum, 31.3), there were 5400 incident CVD events and 6132 all-cause deaths. The associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality were monotonic (all P values for nonlinear terms, .19-.83). Each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.17 [95% CI, 1.09-1.26]; adjusted ARD, 3.24% [95% CI, 1.39%-5.08%]) and all-cause mortality (adjusted HR, 1.18 [95% CI, 1.10-1.26]; adjusted ARD, 4.43% [95% CI, 2.51%-6.36%]). Each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06 [95% CI, 1.03-1.10]; adjusted ARD, 1.11% [95% CI, 0.32%-1.89%]) and all-cause mortality (adjusted HR, 1.08 [95% CI, 1.04-1.11]; adjusted ARD, 1.93% [95% CI, 1.10%-2.76%]). The associations between egg consumption and incident CVD (adjusted HR, 0.99 [95% CI, 0.93-1.05]; adjusted ARD, −0.47% [95% CI, −1.83% to 0.88%]) and all-cause mortality (adjusted HR, 1.03 [95% CI, 0.97-1.09]; adjusted ARD, 0.71% [95% CI, −0.85% to 2.28%]) were no longer significant after adjusting for dietary cholesterol consumption.

Conclusions and Relevance  Among US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner. These results should be considered in the development of dietary guidelines and updates.

DOI: 10.1001/jama.2019.1572

Study: moderate evidence

Primär-, Sekundär-, Tertiärprävention

Die Arten der Prävention in dieser Einteilung folgen dem Zeitpunkt des Einsetzens und der Zielrichtung der Massnahmen. Sie ist vorwiegend medizinisch orientiert.

Primärprävention

Die Primärprävention setzt vor der Entstehung eines Problems an und richtet sich an die allgemeine Bevölkerung oder auch an spezielle Personengruppen, die keine Risikogruppen darstellen.

Sekundärprävention

Die Sekundärprävention wendet sich an definierte Risikogruppen (d.h. Gruppen der Bevölkerung, die gefährdeter erscheinen, süchtig zu werden), aber auch an Personen, die sich bereits im Anfangsstadium einer Suchterkrankung befinden.

Tertiärprävention

Die Tertiärprävention richtet sich an Personen, die bereits an einer Abhängigkeitserkrankung leiden.

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Narratives Review

Although synovitis is the pathological hallmark of rheumatoid arthritis (RA), many extra-articular manifestations (EMs) and comorbidities likely occur due to the complex, chronic, inflammatory, and autoimmune features of RA. Cardiovascular (CV) disease is the most common cause of death in patients with RA. Compared to the general population, patients with RA have twice the risk of myocardial infarction and up to 50% increased CV mortality risk. Severe and prolonged disease activity, genetics, and inflammation (e.g. CRP, ACPA, cytokines, matrix-degrading enzymes) play important roles in CV disease and atheroscleroticdamage. The second major cause of death in patients with RA is respiratory disease, which occurs in 30–40% of patients. RA may affect the lung interstitium, airways, and pleurae, while pulmonary vascular involvement is less frequent.

DOI: 10.1016/j.autrev.2021.102776

Study: weak evidence

Narratives Review

Today, gout and hyperuricemia are recognized as systemic metabolic disorders associated with a range of comorbidities, including cardiovascular diseases, chronic kidney disease, metabolic syndrome, and hepatic steatosis. These associated conditions, if left unaddressed, can significantly impact the patient quality of life and long-term health outcomes. Thus, the effective management of gout necessitates a comprehensive approach that considers the underlying metabolic disturbances and comorbid conditions, rather than focusing solely on joint pain management.

...and discuss the clinical implications for optimizing patient care. In doing so, we highlighted the need for a holistic approach that addresses both gout itself and its broader health impacts.

Hyperuricemia does not necessarily lead to gout. It has been reported that only up to 36% of hyperuricemic individuals develop gout attacks [22].

Many pharmacologic agents influence SUA levels. The drugs that increase SUA levels include diuretics (particularly thiazide diuretics), low-dose aspirin, nicotinic acid, testosterone, xylitol, the anti-tubercular drugs pyrazinamide and ethambutol, and some immunosuppressants, such as ciclosporin, tacrolimus, and mizoribine [80]. Cytotoxic chemotherapy may induce tumor lysis syndrome, which leads to an increase in SUA levels due to the massive breakdown of tumor cells [81]. Tumor lysis syndrome has also been reported following treatment with dexamethasone, zoledronic acid, thalidomide, bortezomib, rituximab, and ibrutinib [82].

Several drugs prescribed for indications other than treating hyperuricemia decrease the SUA levels. These include losartan, calcium channel blockers, high-dose aspirin, leflunomide, statins, fenofibrates, sodium glucose co-transport 2 (SGLT2) inhibitors, and estrogen [83].

Dietary modifications should also be considered. Patients with gout and hyperuricemia should be advised to limit purine-rich foods, such as red meats, seafood, and legumes, and to avoid sugar-sweetened drinks and foods rich in fructose. Alcohol avoidance should be encouraged as well.

DOI: 10.3390/jcm13247616

Study: weak evidence

Klinische Querschnittsstudie

Results: This cohort included 211 RA patients: D2TRA-PIRRA (n=32), DT2RA-NIRRA (n=34), non-D2TRA (n=145). At least one EULAR comorbidity was present in 46% of patients (range 0 to 4). The most represented EULAR comorbidities were cardiovascular diseases (29.5%), osteoporosis (19.5%) and gastrointestinal diseases (8.0%). The number of EULAR comorbidities was similar across groups (p=0.581 by Kruskal-Wallis test), and it was moderately correlated with age at RA onset (r=0.439, p<0.0001). When separately analyzing each comorbidity, there were no significant differences yet a numerical increase in the prevalence of gastrointestinal diseases (15.6% vs 7.3% vs 0.0%, p=0.162) and serious infections (12.5% vs 6.0% vs 5.9%, p=0.328) in D2TRA-PIRRA compared to D2TRA-NIRRA and non-D2TRA patients (Figure 1A). With regard to comorbidities not encompassed in the EULAR domains, fibromyalgia was highly prevalent among D2TRA-NIRRA (23.5%) compared to DT2-RAPIRRA (3.1%) and non-D2TRA (2.7%) patients (p<0.0001; Figure 1A). Extra-articular manifestations were recorded in 27.2% of non-DT2RA, 25.0% of DT2RA-PIRRA and 17.62% of DT2RA-NIRRA (p=0.787), without significant differences in single manifestations. DT2RA-PIRRA patients had numerically more serositis, inflammatory eye disease, and interstitial lung disease than non-D2TRA, while D2TRA-NIRRA patients only showed features of serositis and Sjogren's syndrome (Figure 1B).

DOI: 10.1136/annrheumdis-2023-eular.1864

Study: moderate evidence

prospektive Beobachtungsstudie mit Querschnittsanalysen aus einer grossen Patientendatenbank

Results. CC were most common in FM, followed by SLE. FM comorbidity was dominated by depression, mental illness, and symptom-type comorbidity (e.g., gastrointestinal and genitourinary disorders). In SLE, there were substantial increases in hypertension, depression, cataract, fractures, and cardiovascular and cerebrovascular, neurologic, lung, gall bladder and endocrine disorders compared with RA. Any current CC reduced the EQ-5D utility by 0.08 to 0.16 units. The lowest EQ-5D score was noted for current psychiatric illness (0.55) and current depression (0.60). Conclusion. Four patterns of comorbidity emerged: that associated with aging; that associated with aging but enhanced by the index condition, as in SLE and cardiovascular disease; comorbidity that is part of the symptoms complex of the index condition; and CC that represent lifetime traits or manifestations of the underlying illness. Depression was the most strongly associated correlate of EQ-5D quality of life, and current depression was present in about 15% of patients with RA or NIRD and 34% to 39% of those with SLE and FM. (First Release January 15 2010; J Rheumatol 2010; 37:305–15; doi:10.3899/jrheum.090781).

DOI: 10.3899/jrheum.090781

Study: moderate evidence

Narratives Review

Rheumatoid arthritis (RA) is typically diagnosed in clinical care based on the presence of symptoms and signs of active joint inflammation (ie, a swollen joint on physical examination consistent with synovitis), as well as biomarkers such as autoantibodies and imaging findings that can demonstrate joint inflammation and/or damage. This diagnosis can be termed “clinical RA.” In addition, there are established classification criteria for RA, which include the 1987 American College of Rheumatology (ACR) criteria and the 2010 ACR/European Alliance of Associations for Rheumatology (EULAR) criteria. There are also 2 categories of clinical RA termed “seropositive” and “seronegative,” defined as the presence or absence, respectively, of serum elevations of autoantibodies, which currently include rheumatoid factor (RF) and/or anticitrullinated protein antibodies (ACPA). After a diagnosis is made, treatment is typically initiated with disease-modifying antirheumatic drug (DMARD) therapies that have been established as effective in treating the primary disease manifestation of inflammatory arthritis (IA) in controlled clinical trials.For the majority of individuals who are diagnosed with clinical RA, DMARD therapy results in improved well-being and function as well as reduced joint damage, with a subset of individuals reaching disease remission and an even smaller subset reaching DMARD-free remission.However, for the majority of individuals who develop clinical RA, it is a disease that will require lifelong therapy, with ongoing adverse effects on their well-being and finances, and sustained remission is infrequent (< 50% of patients in some studies). As such, ultimately, the prevention of RA may result in substantially less impact on personal and public health.

DOI: 10.3899/jrheum.2023-0334

Study: weak evidence

Expertenmeinung

In contrast, well over half of patients diagnosed with RA in the modern era can now achieve disease remission through a combination of early diagnosis, treat-to-target drug escalation and a pathogenesis-driven introduction of novel therapeutics.1 With disease remission now an achievable treatment target in RA, can—and should—we aim higher to achieve disease cure?

Remission versus cure: what is the difference?

The concept of disease cure has been established for centuries, even featuring in the Latin lexicon as restitutio ad integrum, meaning ‘restoration to original condition’. In contrast, remission as a medical term is a relatively modern concept with origins in the field of oncology. Following eradication of detectable malignancy through surgery, radiotherapy and/or chemotherapy/immunotherapy, a patient is said to be ‘in remission’. Following a period in remission without relapse of malignancy, a patient is then said to be ‘cured’—the time period differs for different malignancies, but many studies focus on 5-year survival rates as analogous to cure. These concepts are relatively straightforward to formulate for conditions caused by clearly defined ‘foreign’ agent, such as a malignancy composed of transformed cancer cells, or an infection driven by an exogenous pathogen. However, despite being frequently discussed in the context of RMDs, the concepts of remission and cure are more difficult to define in the dynamic dysregulation of endogenous immunity that underpins RMD pathogenesis.

In the context of RMDs, remission refers to the absence (or near-absence) of symptoms and signs of the disease. Thus, a patient in remission still has disease, but the symptoms have been controlled or eliminated for a period of time. Remission is usually achieved through the use of immunomodulatory drugs, and usually most patients require ongoing treatment to keep the disease under control (ie, on-drug remission). After a prolonged period of remission, some patients may choose to taper and potentially stop treatment, achieving drug-free remission. Transition between these states is dynamic, such that an individual patient may move bidirectionally between active disease, on-drug remission and drug-free remission throughout their disease course (figure 1). In contrast, cure refers to a specific subset of patients in drug-free remission who have regained a state of enduring immune tolerance, such that they are no longer at increased risk of disease relapse compared with the healthy population. In essence, transition to cure is thus unidirectional, that is, once cure is achieved, there is no (or at least negligible) risk of transition back to a disease state.

DOI: 10.1136/ard-2024-226772

Study: weak evidence

Narratives Review

The most important bioactive chemical constituents of turmeric are curcuminoids, including curcumin, demethoxycurcumin and bis-demethoxycurcumin, which are extracted from the rhizome of the herb Curcuma longa which belongs to the Zingiberaceae family. The best known, curcumin, is a hydrophobic polyphenol which, thanks to its antioxidant and anti-inflammatory properties, seems to be effective in the prevention of various pathologies, including autoimmune and inflammatory ones, going to interact with numerous molecular targets.

Curcumin, in particular, has shown an interesting preventive effect, proving effective in the prevention of RA. In vitro, curcumin showed antiproliferative and anti-inflammatory action in fibroblast-like synoviocytes in rheumatoid arthritis (RA-FLS) inducing apoptosis and causing inhibition of COX-2 pathways leading to the production of prostaglandin E2 (PGE2). Furthermore, the exposure of RA-FLS to curcumin led to the decrease of cytokines and growth factors, such as Interleukin-6 (IL-6) and the growth factor of the vascular endothelium and the deactivation of the nuclear factor kB (NF-kB). The influence of curcumin on specific signal transduction pathways is therefore an interesting point, because the activation of these pathways can alter the threshold for immune activation in rheumatoid arthritis. In animal model studies, curcumin has been shown to increase anti-inflammatory cytokines, reduce pro-inflammatory cytokines and activate the antioxidant defense system.

DOI: 10.1016/j.clnu.2020.08.020

Study: weak evidence

Narratives Review

Stand der Therapie heute, Interdisziplinäre Behandlung, Nichtsteroidale Antirheumatika, Glukokortikoide, Basismedikamente, Kombinationstherapien, Prophylaxe und Therapie von Begleiterkrankungen.

Study: weak evidence

Narratives Review

One of the challenges in studying OA and RA, and rheumatic diseases in general, is deriving epidemiological data that can be used to understand better the factors that contribute to the initiation and progression of these diseases. Only with such an understanding can significant progress be made in the diagnosis, treatment and management of patients.

However, the heterogeneity of the two most common rheumatic diseases, RA and OA, and the lack f any clear clinical correlation with pathology make an exact estimate of incidence and prevalence difficult, although risk factors have been identified. The lack of standardized clinical criteria, especially in OA, may also affect our ability to evaluate outcomes in clinical trials adequately, which are often of short duration in selected populations and have surrogate or biological endpoints for determination of both efficacy and safety, rather than patient-orientated endpoints.

The economic and social burden of these diseases is great. Their impact on both individuals and society results from a decreased quality of life, lost productivity and increased costs of health care. Without appropriate approaches to patient management and control of these diseases, this impact can be expected to increase as the population ages. 

DOI: 10.1093/rheumatology/39.suppl_2.3

Study: weak evidence

Systematisches Review

Basierend auf dieser Art der Falldefinition, schätzen wir, dass die Prävalenz der RA in der erwachsenen Bevölkerung in einem Bereich zwischen 0,8 % und 1,2 % liegt.

DOI: 10.1007/s00393-022-01305-2

Study: strong evidence

Klinische Querschnittsstudie

They can be difficult to diagnose, therefore understanding the expected clinical appearance is essential.¹

In general, there is no specific test to diagnose rheumatic diseases; however, the signs and symptoms lead to tests that confirm the diagnosis.⁷ Many untrained physicians may misdiagnose a patient with rheumatoid arthritis due to the finding of a positive rheumatoid factor, even though the clinical presentation was not suggestive of this diagnosis, whereas it may be found positive in many other rheumatic and nonrheumatic diseases, such as hypothyroidism.^7,8 

Thus, the field of rheumatology faces difficulties in diagnosing many patients with vague symptoms, and clinics are overwhelmed with unnecessary referrals because asymptomatic patients are referred for a positive serology ordered as “screening tests”.

In some cases, nonspecialist physicians (who are frequently the first physicians consulted by patients) may fail to recognize the symptoms and signs of rheumatic diseases. This may be due to a lack of training in rheumatology, the belief that the patient’s symptoms are caused by another condition, or the patient’s failure to provide a complete medical history.¹¹ Systemic factors can also contribute to the delayed diagnosis of rheumatic diseases. This may be due to lengthy wait times for appointments, a lack of access to specialists, high health care costs, and a lack of medical insurance coverage.^9,11

DOI: 10.2147/PPA.S448999

Study: moderate evidence

Epidemiologischer Überblick / Review

Im Bereich der muskuloskeletalen Erkrankungen wird teilweise mit sehr unterschiedlichen Zahlen argumentiert. Dies lässt sich einerseits mit unterschiedlichen Definitionen rheumatischer und muskuloskeletaler Erkrankungen, andererseits mit zeitlich oder räumlich differenten Stichproben erklären.

Eine Verständigung auf Häufigkeitsannahmen für Deutschland auf Basis der verfügbaren Evidenz soll dazu beitragen, in derÖffentlichkeit undinDiskussionen mit Politikern und Leistungsträgern „mit einer Stimme“ zu sprechen, d. h. von einheitlichen Annahmen zu Inzidenz und Prävalenz und damit auch zum Versorgungsbedarf der einzelnen Krankheitsbilder auszugehen. Die uns gestellte Aufgabe ist nicht ganz einfach, weil es keine „absolut richtigen“ Zahlen zu Prävalenz und Inzidenz muskuloskeletaler Erkrankungen gibt. Die verfügbaren Daten beziehen sich auf empirische Studien, die sich hinsichtlich der methodischen Herangehensweisen, der Falldefinitionen undStichproben, der Zeitpunkte der Erhebungen und der untersuchten Populationen unterscheiden. Allein aufgrund genetischer Differenzen ist mit einer erheblichen Bandbreite von Prävalenzschätzungen zu rechnen. Sich ausschliesslich auf Zahlen aus Deutschland zu beziehen verbietet sich wegen der wenigen vorliegenden Studien.

DOI: 10.1007/s00393-016-0094-2

Study: weak evidence

Narrative Review

The latest findings, including 7 publications this year, highlight key insights. The main publication focuses on the most recent data of the GBD 2021 (incorporating data up to 2020), revealing that OA affected 7.6% of the global population in 2020 (equivalent to 595 million individuals). OA prevalence was higher in women than men, with a 2020 global age-standardized prevalence of 8058.9 per 100,000 (95% uncertainty intervals (UI) 7251.9–8867.9) for women and 5780.1 per 100,000 (95% UI 5217.8–6341.2) for men. 

The prevalence increased by 132.2% over 30 years and is projected to rise by 60 to 100% by 2050.

DOI: 10.1016/j.joca.2024.07.014

Study: weak evidence

Expertenmeinung

However, limited understanding of the burden of RMDs amongst public health professionals and policy-makers means that these diseases are often not considered a public health priority.

DOI: 10.1007/s10067-014-2841-6

Study: weak evidence

Expertenmeinung

In addition, although rheumatic conditions in total are among the most common of all medical problems, many of the individual diseases are uncommon or even rare. This situation results in an ever-present dilemma for the field. Most of the public and policymakers around the world do not know about many of the rheumatic and musculoskeletal diseases (RMDs) and even if they have heard of them, there is broad lack of awareness about the complexity and enormous importance of this area of medicine.

To further public awareness and support policies directed towards lessening the impact of these diseases on patients and society, a working group from the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR), consisting of practising and academic rheumatologists, a patient representative and a rheumatology health professional, has developed a formal description of these conditions. The goal of this effort was to create a succinct general statement describing RMDs in adults and children in language that can be used in conversations with the general population with and without RMDs; media; healthcare providers; policymakers at local, national and international levels; health insurance companies; charities; employers and other stakeholders.

DOI: 10.1136/annrheumdis-2017-212565

Study: weak evidence

Narrative Review

As current treatment options in OA are very limited, OA patients would benefit greatly from some ability to self-manage their condition. Since diet may potentially affect OA, we reviewed the literature on the relationship between nutrition and OA risk or progression, aiming to provide guidance for clinicians. For overweight/obese patients, weight reduction, ideally incorporating exercise, is paramount. The association between metabolic syndrome, type-2 diabetes and OA risk or progression may partly explain the apparent benefit of dietary-lipid modification resulting from increased consumption of long-chain omega-3 fatty-acids from oily fish/fish oil supplements. A strong association between OA and raised serum cholesterol together with clinical effects in statin users suggests a potential benefit of reduction of cholesterol by dietary means. Patients should ensure that they meet the recommended intakes for micronutrients such as vitamin K, which has a role in bone/cartilage mineralization. Evidence for a role of vitamin D supplementation in OA is unconvincing.

DOI: 10.1093/rheumatology/key011

Study: weak evidence

Narratives Review

Despite gout being one of only a few ‘curable’ rheumatic diseases (through the use of pharmacological urate-lowering therapies (ULTs)), management of the disease is inadequate in many parts of the world, owing to low uptake of ULT and patient adherence to these medications.

It is difficult to estimate the global occurrence of gout accurately owing to a lack of data for many countries and the highly variable prevalence estimates across different geographical regions and populations that are obtained using different disease definitions (Fig. 1; Table 1). A gout diagnosis should ideally be based on classification criteria or the demonstration of monosodium urate crystals in aspirated joint fluid or tophi, but most studies rely on self-reported diagnosis or identification of diagnostic codes or prescription of gout-specific medication in medical registries, which are prone to recall or misclassification bias. Underascertainment is possible due to long intercritical periods between flares, individuals not consulting for flares that they self-manage, or when prevalence and/or incidence are measured in Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors Mats Dehlin1, Lennart Jacobsson 1 and Edward Roddy 2,3 ✉ Abstract | Gout is the most common inflammatory arthritis and occurs when hyperuricaemia, sustained elevation of serum urate levels resulting in supersaturation of body tissues with urate, leads to the formation and deposition of monosodium urate crystals in and around the joints. Recent reports of the prevalence and incidence of gout vary widely according to the population studied and methods employed but range from a prevalence of <1% to 6.8% and an incidence of 0.58–2.89 per 1,000 person-years. Gout is more prevalent in men than in women, with increasing age, and in some ethnic groups. Despite rising prevalence and incidence, suboptimal management of gout continues in many countries. Typically, only a third to half of patients with gout receive urate-lowering therapy, which is a definitive, curative treatment, and fewer than a half of patients adhere to treatment. Many gout risk factors exist, including obesity, dietary factors and comorbid conditions. As well as a firmly established increased risk of cardiovascular disease and chronic kidney disease in those with gout, novel associations of gout with other comorbidities have been reported, including erectile dysfunction, atrial fibrillation, obstructive sleep apnoea, osteoporosis and venous thromboembolism. Discrete patterns of comorbidity clustering in individuals with gout have been described. Increasing prevalence and incidence of obesity and comorbidities are likely to contribute substantially to the rising burden of gout. 1Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 2Primary Care Centre Versus Arthritis, School of Primary, Community and Social Care, Keele University, Keele, UK. 3Haywood Academic Rheumatology Centre, Haywood Hospital, Midlands Partnership NHS Foundation Trust, Stoke-on-Trent, UK. ✉e-mail: e.roddy@keele.ac.uk https://doi.org/10.1038/ s41584-020-0441-1 REVIEWS Nature Reviews | Rheumatology secondary or tertiary care registries rather than primary care where most patients with gout are managed. A 2015 meta-analysis of 71 studies of gout prevalence published between 1962 and 2012 found a pooled global prevalence of 0.6% (95% CI 0.4–0.7%), although there was marked statistical heterogeneity among the included estimates2 .

The importance of hyperuricaemia as a risk factor for the development of gout has been confirmed in recent studies.

As a result, hyperuricaemia alone is insufficient to enable a diagnosis of gout without the presence of typical clinical features or evidence from joint aspiration. Obesity and dietary factors Obesity is an important risk factor for gout and is thought to be a major contributor to the rising prevalence and incidence of gout. 

Although the role of dietary factors in the pathogenesis of gout has been suspected for centuries, supporting epidemiological evidence has only emerged over the past 15 years. Consumption of red meat, seafood and shellfish, fructose, sugar-sweetened soft drinks and alcoholic drinks (particularly beer) increase the risk of incident gout...

Most studies have investigated epidemiological associations between gout and single comorbidities, whereas multiple comorbidities commonly coexist. However, little is known about the associations between these multiple comorbidities. Metabolic syndrome is a constellation of interrelated conditions, including obesity, dyslipidaemia, hypertension and insulin resistance, and is associated with increased risk of atherosclerosis. The prevalence of metabolic syndrome in individuals with gout in a Korean university hospital86 and the US NHANES-III (ref.87) was 51% and 63%, respectively, and the NHANES-III patients with gout had three times the odds of having metabolic syndrome than age-matched and sex-matched controls without gout.

DOI: 10.1038/s41584-020-0441-1

Study: weak evidence

Randomisierte, kontrollierte klinische Studie (RCT)

Nonsteroidal antiinflammatory drugs (NSAIDs) were introduced in the 1960s and became the most widely prescribed class of drugs in the world, with more than 100 million prescriptions issued annually in the United States alone. NSAIDs inhibit cyclooxygenase (COX), which reduces pain and inflammation through the inhibition of prostaglandins. However, the COX enzyme is also present in gastric mucosa, where it stimulates gastroprotective prostaglandins. The identification of two isoforms, COX-1 and COX-2, and the recognition that antiinflammatory and analgesic effects are mediated through COX-2 inhibition — whereas the gastrointestinal toxic effects are linked to COX-1 inhibition — resulted in the development of selective COX-2 inhibitors that offered the potential to retain efficacy while reducing gastrointestinal adverse effects.

Evidence of adverse cardiovascular outcomes in a placebo-controlled trial resulted in the withdrawal of the selective COX-2 inhibitor rofecoxib in 2004. On the basis of a small number of events, the results of another trial suggested that cardiovascular harm may result from the use of higher-than-approved doses of celecoxib.

DOI: 10.1056/NEJMoa1611593

Study: strong evidence

Lehrbuchkapitel / Übersichtsartikel

Die Glucocorticoide gehören zusammen mit den Mineralocorticoiden zu den sog. Corticosteroiden, die in der Nebennierenrinde gebildet werden. Cortisol ist das Hauptglucocorticoid der Nebennierenrinde. Darüber hinaus sind eine Reihe synthetischer Glucocorticoide entwickelt worden, die in der Pharmakotherapie von Bedeutung sind. Glucocorticoide werden zum einen zur Substitution bei Mangel an endogenen Glucocorticoiden eingesetzt. Zum anderen spielen insbesondere die antiinflammatorischen und immunsuppressiven Effekte der körpereigenen und synthetischen Glucocorticoide eine wichtige Rolle bei der Behandlung zahlreicher Erkrankungen.

DOI: 10.1007/978-3-662-58304-3_49

Book

Klinische Fallserie mit prospektivem, interventionellem Design

Periarthritis of the shoulder is a condition characterized by painful and global restriction of active and passive glenohumeral range of motion in at least two directions most notably shoulder abduction and external rotation.[¹] Periarthritis of the shoulder has an incidence of 3%–5% in the general population and up to 20% in those with diabetes.[²] It has prevalence rate of 2%–5%.[³] It is more common in females, peaks in 40–60 years of age group and 10 times more in diabetic patients. 

Inflammation is an important event that leads to stiffness, pain, and capsular fibrosis.[⁴] Inflammatory cytokines such as (tumor necrosis factor)-alpha, interleukin (IL)-1 alpha, IL-1 beta, and IL-6 are known to appear both in the glenohumeral and subacromial bursa.[⁵] Fibroblast/myofibroblast with abundant type-3 collagen deposition is seen on the coracohumeral ligament and rotator interval capsule. The absence of multiplication is seen at the superficial synovial layers.

Therapeutic options for the management of periarthritis of shoulder are as follows: NSAIDs, intra-articular steroid injections, suprascapular nerve block (SSNB), platelet-rich plasma (PRP) injection, manipulation under general anesthesia, or arthroscopic capsular release.[^6,7,8,9,10] PRP is an emerging treatment option, and its efficacy needs to be examined.

Several fundamental protein growth factors that are actively secreted by platelets initiate wound healing process. Blood activation causes the granules present in platelets to fuse to its cell membrane and release their growth factors (degranulation). The secretory proteins (e.g., platelet-derived growth factor and transforming growth factor-β) are then transformed into their bioactive state by the addition of histones and carbohydrate side chains.[¹¹] The active proteins then bind to the transmembrane receptors of target cells, which include mesenchymal stem cells, osteoblasts, fibroblasts, endothelial cells, and epidermal cells.

 The suprascapular nerve supplies sensory fibers to about 70% of the shoulder joint, including the superior and posterosuperior regions of the shoulder joint, capsule, and acromioclavicular joint. Nerve blockage increases patient's pain tolerability.

DOI: 10.4103/jotr.jotr_38_19

Study: moderate evidence

Narratives Review

Rheumatoid arthritis (RA) is a chronic immune-driven inflammatory disease characterised by joint swelling, joint tenderness, destruction of synovial joints and systemic inflammation, ultimately causing severe disability and premature mortality. Early mortality has been largely attributed to an increased rate of cardiovascular (CV) events that is independent of traditional CV risk factors and associated with increased systemic inflammation.

SCFAs are an energy source for gut epithelial cells, having an indirect anti-inflammatory effect by improving the assembly of tight junctions and enhancing intestinal barrier function.

DOI: 10.3390/nu12113504

Study: weak evidence

Prospektive Kohortenstudie mit serologischen Analysen

Objective: Autoantibodies have been demonstrated in single serum samples from healthy subjects up to 10 years before they developed rheumatoid arthritis (RA). However, the time course for the development of antibodies before onset of clinical RA is unknown, nor is it known which antibody, or combinations of antibodies, might be most sensitive or specific for predicting future development of the disease. The present study was undertaken to investigate this.

Methods: Patients with RA who had been blood donors before the onset of disease symptoms were enrolled. Frozen serum samples from each donor were retrieved, together with 2 serum samples from controls matched for age, sex, and date of donation. All samples were tested for IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies.

Results: Seventy-nine patients with RA (62% female; mean age at onset of symptoms 51 years) were included. A median of 13 samples (range 1-51) per patient were available; the earliest samples had been collected a median of 7.5 years (range 0.1-14.5) before the onset of symptoms. Thirty-nine patients (49%) were positive for IgM-RF and/or anti-CCP on at least one occasion before the development of RA symptoms, a median of 4.5 years (range 0.1-13.8) before symptom onset. Of the 2,138 control samples, 1.1% were positive for IgM-RF, and 0.6% were positive for anti-CCP.

Conclusion: Approximately half of patients with RA have specific serologic abnormalities several years before the onset of symptoms. A finding of an elevated serum level of IgM-RF or anti-CCP in a healthy individual implies a high risk for the development of RA. We conclude that IgM-RF and anti-CCP testing with appropriately high specificity may assist in the early detection of RA in high-risk populations.

DOI: 10.1002/art.20018

Study: moderate evidence

Expertenmeinung

The Study Group for Risk Factors for Rheumatoid Arthritis was established by the EULAR Standing Committee on Investigative Rheumatology to facilitate research into the preclinical and earliest clinically apparent phases of rheumatoid arthritis (RA). This report describes the recommendation for terminology to be used to define specific subgroups during different phases of disease, and defines the priorities for research in this area. Terminology was discussed by way of a three-stage structured process: A provisional list of descriptors for each of the possible phases preceding the diagnosis of RA were circulated to members of the study group for review and feedback. Anonymised comments from the members on this list were fed back to participants before a 2-day meeting. 18 participants met to discuss these data, agree terminologies and prioritise important research questions. The study group recommended that, in prospective studies, individuals without RA are described as having: genetic risk factors for RA; environmental risk factors for RA; systemic autoimmunity associated with RA; symptoms without clinical arthritis; unclassified arthritis; which may be used in a combinatorial manner. It was recommended that the prefix ‘pre-RA with:’ could be used before any/any combination of the five points above but only to describe retrospectively a phase that an individual had progressed through once it was known that they have developed RA. An approach to dating disease onset was recommended. In addition, important areas for research were proposed, including research of other tissues in which an adaptive immune response may be initiated, and the identification of additional risk factors and biomarkers for the development of RA, its progression and the development of extra-articular features. These recommendations provide guidance on approaches to describe phases before the development of RA that will facilitate communication between researchers and comparisons between studies. A number of research questions have been defined, requiring new cohorts to be established and new techniques to be developed to image and collect material from different sites.

DOI: 10.1136/annrheumdis-2011-200990

Study: weak evidence

Website

Narratives Review

From the immunological point of view, RA is caused by a complex interplay of the innate (macrophages, neutrophils, pro-inflammatory cytokines, complement factors, etc.) and adaptive (T and B lymphocytes, Th1/2/17 cytokines, autoantibodies, etc.) immune mechanisms, and in the sequence of immunological events, the loss of tolerance due to perturbed immune regulation is of special importance [3]. RA is a polygenic disease with a special “constellation” of genetic components [4,5] that determine disease susceptibility and severity, modified by environmental factors [1,3,6], for example smoking (which promotes citrullination of self-proteins) [7], the composition of the oral and intestinal microbiome [8,9,10], and obesity [11]. Despite extensive studies, the triggering and/or causative factors of the disease are unknown; therefore, no causative treatment is available to date.

Overall, in the last two decades, there has been significant progress in the therapeutic possibilities in RA that led to slower disease progression and improved life quality of the patients; however, none of these offer a complete remission, and the termination of treatment almost certainly leads to the flare-up of the symptoms. 

Since RA is a chronic and progressive disease, it usually needs long-term therapy after the diagnosis. The ideal therapy would prevent the progression of the disease and create a symptom-free state for a long time by inhibiting the molecular mechanisms involved in the development of RA while not affecting the physiological functions of normal cells. Such a treatment does not exist so far. All currently available treatments have serious side effects, and some patients develop resistance against them. Therefore, it is necessary to search for new therapeutic agents.

DOI: 10.3390/ijms26072943

Study: weak evidence

Narratives Review

Rheumatoid arthritis (RA) is a progressive autoimmune disease that leads to severe functional impairment and a significantly reduced quality of life. Recent estimations suggest that the global prevalence of RA is approximately 0.5%. This condition typically manifests as painful and swelling small joints of the hands and feet. The pathogenesis of RA is complex and involves interactions between articular and immune cells. Fibroblast-like synoviocytes (FLSs) are considered to be the major drivers of the development of RA. T cells, which are categorised into several subtypes, among which Th17 cells are highly implicated in the progression of the disease.

DOI: 10.3390/nu16183215

Study: weak evidence

Narratives Review

Rheumatic and musculoskeletal diseases (RMDs) are chronic systemic immune/inflammatory conditions characterized by the interaction between gene predisposition, autoimmunity and environmental factors. A growing scientific interest has focused on the role of nutrition in RMDs, suggesting its significant contribution to the pathogenesis and prognosis of these diseases. The diet can directly modulate the immune response by providing a wide range of nutrients, which interfere with multiple pathways at both the gastro-intestinal and systemic level. Moreover, diet critically shapes the human gut microbiota, which is recognized to have a central role in the modulation of the immune response and in RMD pathogenesis, such as in rheumatoid arthritis (RA). Choosing the ‘right’ diet is therefore crucial and a form of self-management ‘intervention’ that could impact on disease expression, course and outcome.

DOI: 10.3390/nu14040888

Study: weak evidence

Optimize the Gut Microbiome
The most unique, diverse, and robust microbiomes develop from daily intake of fiber-rich, whole foods.
• Eat fiber-rich foods at each meal (leafy greens and vegetables, berries and whole fruit, nuts and seeds, whole grains, beans, and lentils)
• Foods rich in polyphenols – berries, green tea, flax seed, black olives, capers, and red onion. Spices with polyphenols – cloves, rosemary, oregano, turmeric
• Eat 2 to 3 forkfuls of fermented foods daily (if tolerated) such as sauerkraut, kimchi, kefir, and unsweetened yogurt
• Minimize added sugar and artificial sweeteners
• Keep food and symptom journals to identify potential food sensitivities
• Minimizing stress supports the microbiome. Eat in a calm, relaxed place and sit down while you eat. Chew food well and eat slowly. Try not to eat on the run.

Support the Body’s Natural Detoxification Process
• Include foods high in fiber and rich in antioxidants at every meal (vegetables, berries and whole fruits, nuts and seeds, whole grains, beans and lentils, herbs, and spices)
• Eat cruciferous vegetables daily (arugula, bok choy, Brussel sprouts, broccoli, cabbages, cauliflower, collard greens, daikon, radishes, kale, kohlrabi, and turnips)
• Keep yourself hydrated with water and herbal or green tea
• Avoid artificial sweeteners – especially aspartame, acesulfame K, saccharin, and sucralose

Avoid Nutritional Deficiencies
Deficiencies in certain nutrients may increase muscle pain. Ensure you’re eating foods rich in the following nutrients.
• Vitamin D: Best obtained from safe sun exposure or a supplement
• Folate: Dark leafy greens, asparagus, Brussel sprouts, nuts, beans, and peas Nutrition and Food Services (04/2023) www.nutrition.va.gov Page 2
• Selenium: Brazil nuts (limit to 1 to 2 Brazil nuts per day to avoid selenium toxicity), yellowfin tuna, turkey, and chicken
• Magnesium: Dark leafy greens, pumpkin seeds, sesame seeds, halibut, pollock, avocados, bananas, berries, whole grain, seaweed
• Zinc: Oysters, beef, pork chop, chicken especially dark meat, pumpkin seeds, cashews, chickpeas
• Omega-3: Flax seed or flax seed oil, chia seed, salmon, herring, anchovies, mackerel, sardines, oysters, canola oil, and English and black walnuts
• Lean protein: Eggs, poultry, seafood, grass-fed beef, beans, lentils, nuts, and seeds.

Nutritional Considerations for Worsening Symptoms
The below foods may need to be modified or restricted. Talk to your nutrition provider to determine if this is right for you.
• Red meat: Limiting portions, selecting lower fat cuts, and choosing grass-fed beef may reduce the impact of red meat on inflammation and pain
• Dairy products: Trial non-dairy alternatives. If you choose to consume dairy, fermented dairy (yogurt, kefir) may be better tolerated
• Gluten: Found in wheat, rye, and barley and might contribute to higher levels of pain in some individuals. Talk to your nutrition provider about assessing for a gluten sensitivity.
• Excess added sugar and alternative sweeteners
• Food additives: Including monosodium glutamate (MSG), hydrolyzed protein, protein isolates/concentrates, yeast extract, and aspartame.

Other Lifestyle Factors
• Mind-body practices: Yoga, Tai Chi, meditation, and Qi Gong.
• Exercise: Stress relief and muscle strength.

Website

Narratives Review

The treatment of FS remains a challenging and complex endeavor due to the multifactorial nature of the disease, involving both metabolic and inflammatory components. Current therapeutic approaches range from non-surgical interventions, such as physical therapy, corticosteroid injections, and manual mobilization, to more invasive procedures, like arthroscopic capsular release and hydrodilation [3]. However, these methods primarily focus on symptom relief and improving shoulder mobility, with limited effectiveness in addressing the underlying inflammatory and fibrotic processes [104].

In addition, dietary modifications, such as time-restricted feeding or intermittent fasting, have been found to modulate leptin levels, offering a potential avenue for metabolic correction in FS patients [105]. However, while restoring leptin sensitivity could theoretically ameliorate fibrosis and inflammation, potential risks remain. Excessive leptin modulation could impact systemic metabolism, potentially influencing appetite regulation, insulin sensitivity, and immune function [113]. Further research is required to determine the optimal balance between therapeutic benefits and metabolic stability in FS treatment.

Emerging research highlights the role of gut microbiota in regulating systemic metabolism, particularly energy balance, glucose homeostasis, and low-grade inflammation associated with obesity [74,75,76]. Alterations in the gut microbiota, such as those caused by a high-fat diet, have been linked to a reduction in beneficial bacterial populations, like Bifidobacterium spp., Lactobacillus spp., and Roseburia spp. [77,78,79]. The interaction between gut microbiota and the immune system is mediated by pattern recognition receptors like Toll-like receptors (TLRs), which detect microbial components such as LPS. Fatty acids can stimulate innate immunity by interacting with the TLR4/CD14 complex, further promoting inflammatory responses [80]. Alterations in the gut microbiota have been implicated in the development of obesity and its related metabolic disorders, with evidence suggesting that modulating the gut microbiota can influence leptin sensitivity and metabolic outcomes [81,82,83].

Interestingly, the gut microbiota also appears to regulate leptin action, with studies showing that dietary interventions, like prebiotics, can improve leptin sensitivity in obese and diabetic mice [84]. This suggests that gut microbiota modulation may offer a novel therapeutic strategy for restoring leptin sensitivity and addressing metabolic dysregulation in FS.

Recent studies have highlighted the role of the gut microbiota in regulating systemic inflammation and metabolic health, including leptin sensitivity [116]. Alterations in gut microbiota composition, often observed in obesity and metabolic syndrome, can exacerbate leptin resistance and inflammatory processes via bacterial translocation and LPS-mediated activation of the JAK-STAT pathway [117]. Probiotic and prebiotic interventions may offer a novel therapeutic strategy to improve metabolic and immune regulation in FS patients, potentially reducing the chronic inflammation and fibrosis associated with the condition [8,118]. However, the precise role of microbiota-driven inflammation in FS remains to be fully elucidated, warranting further clinical investigation.

DOI: 10.3390/jcm14051780

Study: weak evidence

Klinische Konsequenz ist eine rechtzeitige Behandlung der Hyperurikämie. Deren Wirksamkeit konnte sowohl klinisch (Gichtschübe) wie im MR (Synovitis) gezeigt werden (Dalbeth N. Arthritis Rheumatology 2017;69:2386–95; Koto R. Ann Rheum Dis 2021;annrheumdis-2021-220439).

Problematische Aussagen wie folgende diskutieren wir unter "Rheuma - was bedeutet das?":

• Eckpfeiler der Betreuung ist die Motivation und Compliance der Patientinnen und Patienten für die regelmässige und lebenslängliche Medikamenteneinnahme, während den Ernährungsempfehlungen nur geringe Bedeutung zukommt.
• Die Laienpresse hält nach wie vor das Bild des schuldigen Patienten aufrecht, welcher die Gicht-Diät nicht befolgt. Die Forschung beschäftigt sich mit Genetik. Das Potenzial für Ernährung betrug in einer Studie 0.3%, der Einfluss der Genetik jedoch 23.9% (Chiu THT. Clin Nutrition 2020;39:837). 13 Varianten von Urat-Transportern und metabolischen Genen, nicht aber entzündlichen Genen, korrelierten mit dem Übergang von Hyperurikämie zu Gicht (Sandoval-Plata G. Ann Rheum Dis 2021;annrheumdis-2020-219796).

Damit sei nicht bestritten, dass eine geringe Wirkung mit Diät, beispielsweise mit einer DASH-Diät (Juraschek SP. Arthritis Rheum 2021;73:1014), erreicht werden kann. Wichtig ist die motivierende Betreuung der Patientinnen und Patienten, wie dies eine Studie mit spezialisierten Pflegefachpersonen gezeigt hat (Doherty M. Lancet 2018;392:1403–8).

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Systematic Review

RA may cause progressive joint damage and disability. Risk factors for RA are genetic and non-genetic, including smoking, changes in the microbiota, female sex, Western diet, and ethnic factors.

Nutritional therapy for RA aims to attenuate inflammation by altering the ratio of ω-6 to ω-3 fatty acids and increasing antioxidants. The reduction of arachidonic acid (AA), an ω-6 fatty acid, is particularly relevant. AA is the precursor of eicosanoids, which are involved in a variety of cellular functions and reactions. Eicosanoids are also mediators of inflammation, and the amount of AA released from the cell membrane determines the intensity of inflammation. When less AA is present in the cell membrane, less AA is released, and fewer eicosanoids are formed.

The impact of dietary fibers on the composition and metabolic activity of the gut microbiome further contributes to the anti-inflammatory effect of vegetarian, vegan or Mediterranean diets. In RA patients, a high-fiber diet increases anti-inflammatory short-chain fatty acids, decreases pro-inflammatory cytokines, and favorably alters the gut microbiome composition.

Vegetarian diets contain less AA than diets with meat, whereas vegan diets contain virtually no AA. There is evidence from population studies that nutrients of animal origin, as consumed in high amounts in the Western diet, correlate with the occurrence of RA. Therefore, vegetarian and vegan diets may favorably influence inflammation.

The ketogenic diet may reduce eicosanoid formation through the lower generation of reactive oxygen species (ROS) of the ketone metabolism compared to the glucose metabolism. ROS activate phospholipase A2 in the cell membrane of immune cells, which exclusively cleaves AA from phospholipids of the cell membrane. ROS also serve as substrates for the oxidation of AA and lead to excessive eicosanoid formation. In addition, the ketogenic diet increases adenosine, which may alleviate pain and have an anti-inflammatory effect.

DOI: 10.3390/nu13124221

Study: strong evidence

Narratives Review

While it primarily affects young and middle-aged women, FM can affect individuals of any gender or age who chronically suffer from widespread pain in the fibromuscular tissue, tendons, ligaments, and other areas.

Challenges associated with identifying whether vitamin D supplementation has a beneficial effect in RCTs to date include inter-study heterogeneity and relatively small sample numbers for a meta-analysis, with only 5 RCTs included, thus emphasising the need for larger RCTs in different subsets of RA patients to fully elucidate the role, if any, for vitamin D supplementation in the management of RA. In addition, there may be differences in vitamin D-binding protein levels, and other genetic variants, which influence the efficacy of vitamin D supplementation [135]. Vitamin D supplementation in low/moderate doses is not thought to be harmful to patients, has wider health benefits, is relatively inexpensive and has fewer side effects/interactions compared with many other commonly used treatments for RA, such as non-steroidal anti-inflammatory drugs (NSAIDs), or conventional synthetic or biological disease-modifying anti-rheumatic drugs (DMARDs). Evidence is also emerging that vitamin D may augment certain therapies in RA. In one in vitro study, vitamin D 1,25-(OH)₂D3 was shown to act synergistically with the biologic drug abatacept to inhibit T cell activation driven by anti-CD3 cross-linking, and promote a pro-regulatory CD28 phenotype [136]. The potential for enhancing the effects of biologics with simple, low-risk addition of 1,25-(OH)₂D3 is interesting, and further work is required to validate this initial in vitro finding.

DOI: 10.3390/nu17030530

Study: weak evidence

Narratives Review

Red meat, eggs and dairy products are the main sources of trimethylamine-N-oxide (TMAO), a pro-inflammatory metabolite deriving from choline and carnitine metabolism [43,44]. Choline and related metabolites, including TMAO, mainly deriving from diet, have been associated with cardiovascular inflammation. These metabolites have been identified in blood samples, synovial fluid and tissue of mice models of arthritis as well as in human studies on CV risk, but their role in RA has not been fully investigated [45].

DOI: 10.3390/nu12051456

Study: weak evidence

Narratives Review

We have performed an umbrella review to understand the impact of food on the development of RA. As described in current clinical guidelines [8], it is true that not all RA patients benefit from dietary intervention; however, following consideration of the research data, a sub-set of RA patients appear to respond favourably to dietary changes. The dietary interventions providing the most significant effect are fasting, gluten-free vegan diets, and/or a customised dietary reintroduction protocol. Although the studies are heterogeneous with regards to the fasting protocol, the time of fast and inclusion criteria for medication use, fasting appears to show the most consistent improvements in both subjective [11–13] and objective [13–19] outcomes measures. At the end of a 1 week fast, significant improvements in objective measures, such as ESR, CRP, and IL-6, have been documented [13, 18–20]. This aligns with significant improvements in disease activity scores [13, 18–22], suggesting that dietary factors may be a source of inflammation in RA. In support of this body of research, a recent study has shown that removal of the gut microbiota with bowel cleansing followed by a 7-day fasting protocol in RA patients, led to a significant decline in DAS-28 scores, and markers of inflammation and mucosal barrier disruption [23].

DOI: 10.1007/s00296-024-05541-4

Study: weak evidence