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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutritional Immunology".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 60260

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Prof. Dr. Maurizio Cutolo

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Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Specialties, University of Genova, 16132 Genova, Italy
Interests: systemic sclerosis; rheumatoid arthritis; polymialgia rheumatica; Raynaud’s phenomenon; COVID-19; capillaroscopy; sex hormones; circadian rhythms; glucocorticoids; DMARDs in rheumatoid arthritis; microcirculation; Mediterranean diet; vitamin D; neuroendocrine immunology
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Dr. Elena Nikiphorou

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Centre of Rheumatic Diseases, King's College London, London, UK
Interests: rheumatoid arthritis; spondyloarthritis; DMARDs; biologics; inflammation; patient care; comorbidities; nutrition in RMDs; epidemiology
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

The impact of food on a person’s health, body and mind, has been known since the Hippocratic era. Since then, major advances in our understanding of the role of nutrition in health and disease have taken place; more recently, also in the field of rheumatic diseases. Rheumatoid arthritis (RA) is an autoimmune, chronic disease, greatly influenced by lifestyle factors including dietary habits and nutrition. Increasingly RA patients (and MD and GP) are enquiring about the role of nutrition in their disease progression and management; a subject that once used to be poorly addressed (if addressed at all) in routine clinical practice. In this Special Issue of Nutrients, we hope to throw more light and improve understanding into the role of diet in RA . We hope to achieve this through a series of manuscripts that address topics ranging from the role of important and negletted nutrients in mechanistic processes triggering inflammation, through to practical tips on how to ‘use’ diet to improve disease course and outcomes in rheumatoid arthritis.

Prof. Maurizio Cutolo
Dr. Elena Nikiphorou
Guest Editors

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Keywords

Rheumatoid arthritis
Connective tissue diseases
Nutrients in RDs
Mediterranean diet
Vitamin D
Circadian rhythms
Metallomics
Microbiome

Published Papers (12 papers)

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Editorial

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4 pages, 203 KiB

Open AccessEditorial

Nutrition and Diet in Rheumatoid Arthritis

by Maurizio Cutolo and Elena Nikiphorou

Nutrients 2022, 14(4), 888; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14040888 - 19 Feb 2022

Cited by 6 | Viewed by 5119

Abstract

Rheumatic and musculoskeletal diseases (RMDs) are chronic systemic immune/inflammatory conditions characterized by the interaction between gene predisposition, autoimmunity and environmental factors [...] Full article

(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)

Research

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13 pages, 652 KiB

Open AccessArticle

Metabolic Profile and Bone Status in Post-Menopausal Women with Rheumatoid Arthritis: A Monocentric Retrospective Survey

by Sabrina Paolino, Elvis Hysa, Sabrina Atena Stoian, Emanuele Gotelli, Andrea Casabella, Paolo Vittoriano Clini, Greta Pacini, Carmen Pizzorni, Alberto Sulli, Elena Nikiphorou, Vanessa Smith and Maurizio Cutolo

Nutrients 2021, 13(9), 3168; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13093168 - 11 Sep 2021

Cited by 7 | Viewed by 2287

Abstract

Background: Rheumatoid arthritis (RA) and metabolic syndrome (MetS) are chronic conditions that share common inflammatory mechanisms. Both diseases can lead to an impairment of the bone microarchitecture. The aims of our study were to evaluate clinical, metabolic, and bone parameters in RA patients with or without MetS (MetS+, MetS−) and potential correlations between the glico-lipidic profile, RA disease activity, and bone status. Methods: A total of thirty-nine RA female post-menopausal patients were recruited (median age 66.6 ± 10.4, disease duration 3 ± 2.7). Anthropometric data, medical history, and current treatment were recorded along with basal blood tests, bone, and lipid metabolism biomarkers. RA disease activity and insulin resistance were evaluated through standard scores. Quantitative assessment of the bone (bone mineral density—BMD) was performed by dual-energy-X ray absorption (DXA), whereas bone quality was quantified with the trabecular bone score (TBS). Results: No statistically significant differences concerning both BMD and TBS were detected between the MetS+ and MetS− RA patients. However, the MetS+ RA patients exhibited significantly higher disease activity and lower serum 25-hydroxyvitamin D [25(OH)D] concentrations (respectively, p = 0.04 and p = 0.01). In all RA patients, a significant negative correlation emerged between the BMD of the femoral trochanter with plasmatic triglycerides (TG) concentrations (r = −0.38, p = 0.01), whereas the lumbar BMD was positively correlated with the abdominal waist (AW) and fasting glucose (FG) concentrations. On the other hand, the TBS was negatively correlated with insulin concentrations, FG, and RA disease activity (respectively, r = −0.45, p = 0.01, r = −0.40, p = 0.03, r = −0.37, p = 0.04), the last one was further negatively correlated with 25-OHD serum concentrations (r = −0.6, p = 0.0006) and insulin-resistance (r = 0.3, p = 0.04). Conclusions: Bone quantity (BMD) and quality (TBS) do not seem significantly changed among MetS+ and MetS− RA patients; however, among MetS+ patients, both significantly higher disease activity and lower vitamin D serum concentrations were observed. In addition, the significant negative correlations between the alterations of metabolic parameters limited to the TBS in all RA patients might suggest that qualitative bone microarchitecture impairments (TBS) might manifest despite unchanged BMD values. Full article

(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)

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11 pages, 1793 KiB

Open AccessCommunication

Dietary Derived Propionate Regulates Pathogenic Fibroblast Function and Ameliorates Experimental Arthritis and Inflammatory Tissue Priming

by Jasna Friščić, Kerstin Dürholz, Xi Chen, Cecilia Engdahl, Lisa Möller, Georg Schett, Mario M. Zaiss and Markus H. Hoffmann

Nutrients 2021, 13(5), 1643; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13051643 - 13 May 2021

Cited by 12 | Viewed by 2657

Abstract

Short-chain fatty acids are gut-bacteria-derived metabolites that execute important regulatory functions on adaptive immune responses, yet their influence on inflammation driven by innate immunity remains understudied. Here, we show that propionate treatment in drinking water or upon local application into the joint reduced experimental arthritis and lowered inflammatory tissue priming mediated by synovial fibroblasts. On a cellular level, incubation of synovial fibroblasts with propionate or a physiological mixture of short-chain fatty acids interfered with production of inflammatory mediators and migration and induced immune-regulatory fibroblast senescence. Our study suggests that propionate mediates its alleviating effect on arthritis by direct abrogation of local arthritogenic fibroblast function. Full article

(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)

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22 pages, 342 KiB

Open AccessFeature PaperArticle

A Posteriori Dietary Patterns and Rheumatoid Arthritis Disease Activity: A Beneficial Role of Vegetable and Animal Unsaturated Fatty Acids

by Valeria Edefonti, Maria Parpinel, Monica Ferraroni, Patrizia Boracchi, Tommaso Schioppo, Isabella Scotti, Tania Ubiali, Walter Currenti, Orazio De Lucia, Maurizio Cutolo, Roberto Caporali and Francesca Ingegnoli

Nutrients 2020, 12(12), 3856; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12123856 - 17 Dec 2020

Cited by 11 | Viewed by 3050

Abstract

To our knowledge, no studies have investigated the relationship between a posteriori dietary patterns (DPs)—representing current dietary behavior—and disease activity in patients with rheumatoid arthritis (RA). We analyzed data from a recent Italian cross-sectional study including 365 RA patients (median age: 58.46 years, 78.63% females). Prevalent DPs were identified through principal component factor analysis on 33 nutrients. RA activity was measured according to the Disease Activity Score on 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI). Single DPs were related to disease activity through linear and logistic regression models, adjusted for the remaining DPs and confounders. We identified five DPs (~80% variance explained). Among them, Vegetable unsaturated fatty acids (VUFA) and Animal unsaturated fatty acids (AUFA) DPs were inversely related to DAS28 in the overall analysis, and in the more severe or long-standing RA subgroups; the highest score reductions (VUFA: 0.81, AUFA: 0.71) were reached for the long-standing RA. The SDAI was inversely related with these DPs in subgroups only. This Italian study shows that scoring high on DPs based on unsaturated fats from either source provides independent beneficial effects of clinical relevance on RA disease activity, thus strengthening evidence on the topic. Full article

(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)

10 pages, 266 KiB

Open AccessArticle

Nutritional Status and Bone Microarchitecture in a Cohort of Systemic Sclerosis Patients

by Sabrina Paolino, Greta Pacini, Carlotta Schenone, Massimo Patanè, Alberto Sulli, Samir Giuseppe Sukkar, Adriano Lercara, Carmen Pizzorni, Emanuele Gotelli, Francesco Cattelan, Federica Goegan, Vanessa Smith and Maurizio Cutolo

Nutrients 2020, 12(6), 1632; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12061632 - 01 Jun 2020

Cited by 11 | Viewed by 2570

Abstract

Systemic sclerosis (SSc) is a connective tissue disease characterized by initial microvascular damage, immune system activation and progressive fibrosis with insufficiency of internal organs. Gastrointestinal (GI) involvement is characterized by atrophy of the smooth muscle and small bowel hypomotility, mainly resulting from an autonomic nerve dysfunction. These modifications significantly affect gut transit and nutrient absorption, thus leading to malnutrition deficit induced by malabsorption. Nutritional deficit induced by malabsorption might also lead to bone alterations. This study aims to evaluate the relationship between malnutrition and bone status. Thirty-six postmenopausal female patients fulfilling the ACR 2013 criteria for SSc underwent dual-energy X-ray absorptiometry scan (DXA) to detect quantitative lumbar spine bone mineral density (BMD) and trabecular bone score (TBS) analysis to detect bone quality. Data from DXA also allow to assess body composition and provide several quantitative parameters, including free fat mass index (FFMI) that identifies the patient with malnutrition (values <15 kg/m² in women and 17 kg/m² in men), according to the ESPEN criteria. Body mass index (BMI) was calculated for all SSc patients and every patient completed a diary reporting GI symptoms. Two groups of SSc patients with or without diagnosed malnutrition according to FFMI parameter were identified. Malnourished SSc patients showed significantly lower weight (p = 0.01) and BMI (p = 0.001), as well as lower serum levels of hemoglobin (p = 0.009), albumin (p = 0.002), PTH (p = 0.02) and 25OH-vitamin D (p = 0.008). DXA analysis showed significantly lower lumbar L1-L4 T-score (p = 0.009) and BMD values (p = 0.029) in malnourished SSc patients. Consistently, TBS values were significantly lower in malnourished patients (p = 0.008) and correlated with BMD (at any site) and serum albumin levels (p = 0.02). In addition, FFMI positively correlated with bone parameters as well as with symptoms of intestinal impairment in malnourished SSc patients. Finally, GI symptoms significantly correlated with BMD but not with TBS. This pilot study shows that in malnourished SSc patients (2015 ESPEN criteria: FFMI<15 kg/m²), an altered bone status significantly correlates with GI involvement, in terms of symptoms being mainly due to intestinal involvement together with the presence of selected serum biomarkers of malnutrition. Full article

(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)

Review

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13 pages, 1169 KiB

Open AccessReview

Alcohol Consumption in Rheumatoid Arthritis: A Path through the Immune System

by Vugar Azizov and Mario M. Zaiss

Nutrients 2021, 13(4), 1324; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13041324 - 16 Apr 2021

Cited by 19 | Viewed by 4843

Abstract

Benefits and harms of different components of human diet have been known for hundreds of years. Alcohol is one the highest consumed, abused, and addictive substances worldwide. Consequences of alcohol abuse are increased risks for diseases of the cardiovascular system, liver, and nervous system, as well as reduced immune system function. Paradoxically, alcohol has also been a consistent protective factor against the development of autoimmune diseases such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis (RA). Here, we focused on summarizing current findings on the effects of alcohol, as well as of its metabolites, acetaldehyde and acetate, on the immune system and RA. Heavy or moderate alcohol consumption can affect intestinal barrier integrity, as well as the microbiome, possibly contributing to RA. Additionally, systemic increase in acetate negatively affects humoral immune response, diminishing T_FH cell as well as professional antigen-presenting cell (APC) function. Hence, alcohol consumption has profound effects on the efficacy of vaccinations, but also elicits protection against autoimmune diseases. The mechanism of alcohol’s negative effects on the immune system is multivariate. Future studies addressing alcohol and its metabolite acetate’s effect on individual components of the immune system remains crucial for our understanding and development of novel therapeutic pathways. Full article

(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)

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10 pages, 295 KiB

Open AccessReview

Diet in Rheumatoid Arthritis versus Systemic Lupus Erythematosus: Any Differences?

by Alessia Alunno, Francesco Carubbi, Elena Bartoloni, Davide Grassi, Claudio Ferri and Roberto Gerli

Nutrients 2021, 13(3), 772; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13030772 - 27 Feb 2021

Cited by 7 | Viewed by 4569

Abstract

In recent years, an increasing interest in the influence of diet in rheumatic and musculoskeletal diseases (RMDs) led to the publication of several articles exploring the role of food/nutrients in both the risk of developing these conditions in normal subjects and the natural history of the disease in patients with established RMDs. Diet may be a possible facilitator of RMDs due to both the direct pro-inflammatory properties of some nutrients and the indirect action on insulin resistance, obesity and associated co-morbidities. A consistent body of research has been conducted in rheumatoid arthritis (RA), while studies in systemic lupus erythematosus (SLE) are scarce and have been conducted mainly on experimental models of the disease. This review article aims to outline similarities and differences between RA and SLE based on the existing literature. Full article

(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)

18 pages, 899 KiB

Open AccessReview

The Role of Nutritional Factors and Intestinal Microbiota in Rheumatoid Arthritis Development

by Deshiré Alpízar-Rodríguez, Axel Finckh and Benoît Gilbert

Nutrients 2021, 13(1), 96; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13010096 - 30 Dec 2020

Cited by 13 | Viewed by 6111

Abstract

Evidence about the role of nutritional factors and microbiota in autoimmune diseases, and in rheumatoid arthritis (RA) in particular, has grown in recent years, however many controversies remain. The aim of this review is to summarize the role of nutrition and of the intestinal microbiota in the development of RA. We will focus on selected dietary patterns, individual foods and beverages that have been most consistently associated with RA or with the occurrence of systemic autoimmunity associated with RA. We will also review the evidence for a role of the intestinal microbiota in RA development. We propose that diet and digestive microbiota should be considered together in research, as they interact and may both be the target for future preventive interventions in RA. Full article

(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)

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17 pages, 2380 KiB

Open AccessReview

Efficacy of Oral Vitamin Supplementation in Inflammatory Rheumatic Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Yann Nguyen, Johanna Sigaux, Jean-Guillaume Letarouilly, Pauline Sanchez, Sébastien Czernichow, René-Marc Flipo, Martin Soubrier, Luca Semerano, Raphaèle Seror, Jérémie Sellam and Claire Daïen

Nutrients 2021, 13(1), 107; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13010107 - 30 Dec 2020

Cited by 26 | Viewed by 5871

Abstract

Background: We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of oral vitamin supplementation on symptoms and disease activity in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA). Methods: A systematic literature review and meta-analysis of randomized controlled trials including patients with inflammatory rheumatic diseases were performed using MEDLINE, EMBASE and abstracts from recent international rheumatology congresses. Studies were reviewed in accordance with PRISMA guidelines. We analysed clinical outcomes according to each type of vitamin supplementation. Results. The initial search yielded 606 articles. Of these, 13 studies were included in the qualitative synthesis: eight studied vitamin D supplementation, two assessed vitamin E supplementation, two folic acid, and one vitamin K, all of them on RA patients. No studies on SpA or PsA were selected. Oral vitamin supplementations were not associated with a reduction in RA activity (DAS-28 or pain) or RA flares. Conclusions: Despite their beneficial effects, the effects of vitamin supplementation on RA activity, if any, seem to be limited. Evidence on their efficacy on SpA or PsA activity is lacking. However, folic acid supplementation should be suggested to prevent methotrexate-related side effects, and vitamin D should be given to patients with vitamin D deficiency to prevent musculo-skeletal complications. Full article

(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)

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22 pages, 395 KiB

Open AccessReview

Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis

by Theoharris Frangos and Wolfgang Maret

Nutrients 2021, 13(1), 53; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13010053 - 26 Dec 2020

Cited by 42 | Viewed by 6912

Abstract

Osteoarthritis (OA) and rheumatoid arthritis (RA) are inflammatory articular conditions with different aetiology, but both result in joint damage. The nutritionally essential metal zinc (Zn²⁺) and the non-essential metal cadmium (Cd²⁺) have roles in these arthritic diseases as effectors of the immune system, inflammation, and metabolism. Despite both metal ions being redox-inert in biology, they affect the redox balance. It has been known for decades that zinc decreases in the blood of RA patients. It is largely unknown, however, whether this change is only a manifestation of an acute phase response in inflammation or relates to altered availability of zinc in tissues and consequently requires changes of zinc in the diet. As a cofactor in over 3000 human proteins and as a signaling ion, zinc affects many pathways relevant for arthritic disease. How it affects the diseases is not just a question of zinc status, but also an issue of mutations in the many proteins that maintain cellular zinc homoeostasis, such as zinc transporters of the ZIP (Zrt-/Irt-like protein) and ZnT families and metallothioneins, and the multiple pathways that change the expression of these proteins. Cadmium interferes with zinc’s functions and there is increased uptake under zinc deficiency. Remarkably, cadmium exposure through inhalation is now recognized in the activation of macrophages to a pro-inflammatory state and suggested as a trigger of a specific form of nodular RA. Here, we discuss how these metal ions participate in the genetic, metabolic, and environmental factors that lead to joint destruction. We conclude that both metal ions should be monitored routinely in arthritic disease and that there is untapped potential for prognosis and treatment. Full article

(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)

12 pages, 1118 KiB

Open AccessFeature PaperReview

Efficacy of Spice Supplementation in Rheumatoid Arthritis: A Systematic Literature Review

by Jean-Guillaume Letarouilly, Pauline Sanchez, Yann Nguyen, Johanna Sigaux, Sébastien Czernichow, René-Marc Flipo, Jérémie Sellam and Claire Daïen

Nutrients 2020, 12(12), 3800; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12123800 - 11 Dec 2020

Cited by 18 | Viewed by 7612

Abstract

Background: Spices, i.e., curcumin, ginger, saffron, and cinnamon, have a thousand-year history of medicinal use in Asia. Modern medicine has begun to explore their therapeutic properties during the last few decades. We aimed to perform a systematic literature review (SLR) of randomized controlled trials (RCTs) assessing the effect of spice supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis, or psoriatic arthritis). Methods: An SLR of RCTs, reviews, and meta-analyses was performed, searching for articles in MEDLINE/PubMed. Abstracts from international rheumatology and nutrition congresses (2017–2020) were also scrutinized. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration’s tool and the Jadad scale. Results: Altogether, six studies, assessing the use of spice supplementation only in RA patients, were included: one on garlic supplementation, two on curcumin, one on ginger, one on cinnamon, and one on saffron supplementation. Garlic, ginger, cinnamon, or saffron supplementation was associated with a decrease in RA clinical activity. However, several points limit the external validity of these studies. No conclusion on the impact of curcumin supplementation on RA activity could be drawn due to low-quality studies. Conclusions: Garlic, ginger, cinnamon, and saffron supplementation could have a beneficial effect on RA activity, but the risk of bias of these studies is difficult to assess and data are too limited to recommend them in daily practice. Full article

(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)

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19 pages, 1222 KiB

Open AccessReview

Beverages in Rheumatoid Arthritis: What to Prefer or to Avoid

by Mrinalini Dey, Maurizio Cutolo and Elena Nikiphorou

Nutrients 2020, 12(10), 3155; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12103155 - 15 Oct 2020

Cited by 15 | Viewed by 6995

Abstract

Background: The role of nutrition in the pathogenesis of rheumatic diseases, including rheumatoid arthritis (RA), has gained increasing attention in recent years. A growing number of studies have focussed on the diverse nutritional contents of beverages, and their possible role in the development and progression of RA. Main body: We aimed to summarise the current knowledge on the role of a range of beverages in the context of RA. Beverages have a key role within the mosaic of autoimmunity in RA and potential to alter the microbiome, leading to downstream effects on inflammatory pathways. The molecular contents of beverages, including coffee, tea, and wine, have similarly been found to interfere with immune signalling pathways, some beneficial for disease progression and others less so. Finally, we consider beverages in the context of wider dietary patterns, and how this growing body of evidence may be harnessed by the multidisciplinary team in patient management. Conclusions: While there is increasing work focussing on the role of beverages in RA, integration of discussions around diet and lifestyle in our management of patients remains sparse. Nutrition in RA remains a controversial topic, but future studies, especially on the role of beverages, are likely to shed further light on this in coming years. Full article

(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)

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