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Nutrients as Efficient Immunosuppressants in Patients with Autoimmune Diseases

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A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (28 February 2019) | Viewed by 81106

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Prof. Dr. Dimitrios P. Bogdanos

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Guest Editor

Department of Internal Medicine and Autoimmune Rheumatic Diseases, School of Medicine, University of Thessaly, Larissa, Greece
Interests: autoimmunity; autoimmune diseases; diet; immunosuppression; immunoregulation; microbiome; nutrition; rheumatic diseases
Special Issues, Collections and Topics in MDPI journals

Dr. Carlo Perricone

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Guest Editor

Rheumatology, Department of Medicine and Surgery, University of Perugia, p.le Menghini 1, 06129 Perugia, Italy
Interests: inflammatory arthritis; connective tissue diseases; systemic lupus erythematosus; Sjogren's syndrome; rare diseases in rheumatology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

More than 80 autoimmune diseases currently exist, and approx 20% of the general population in developed countries suffer from at least one autoimmune disease. Efficient treatment of these diseases include steroids and other immunosuppressants, such as biologic treatments. These treatments increase susceptibility to infections. Long-term use of steroids may induce late diabetes, hypertension and osteoporosis and has a prolonged impact on the quality of life of these patients.

Various nutrients and diet supplements possess anti-oxidant and anti-inflammatory properties and as such have been used in the treatment of chronic diseases, including autoimmune diseases. Others may indeed have harmful effects unmasking autoimmune phenomena. The immunosuppressive action of various nutrients and dietary supplements has been the focus of intense investigation in human and experimental autoimmune diseases. Of great interest is the action of those nutrients which may act as immunosuppressants without sacrificing the host's ability to fight microbes.

This Special Issue will focus on the thorough discussion of these immunoregulatory nutrients or diet habits which may act in isolation or in concert with conventional immunosuppressants to prevent from the induction of autoimmune disease or to inhibit pro-inflammatory responses and/or accelerate immunoregulatory actions.

These nutrients may serve as cost-effective, safe and efficient supplements in standard clinical practice and management of patients with organ-specific and non-organ specific autoimmune diseases.

Prof. Dr. Dimitrios P. Bogdanos
Dr. Carlo Perricone
Guest Editors

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Keywords

diet
autoimmunity
immunosupressants
regulation
supplements

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Published Papers (7 papers)

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Research

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12 pages, 254 KiB

Open AccessCommunication

Dietary Habits Bursting into the Complex Pathogenesis of Autoimmune Diseases: The Emerging Role of Salt from Experimental and Clinical Studies

by Rossana Scrivo, Carlo Perricone, Alessio Altobelli, Chiara Castellani, Lorenzo Tinti, Fabrizio Conti and Guido Valesini

Nutrients 2019, 11(5), 1013; https://doi.org/10.3390/nu11051013 - 5 May 2019

Cited by 24 | Viewed by 5878

Abstract

The incidence and prevalence of autoimmune diseases have increased in Western countries over the last years. The pathogenesis of these disorders is multifactorial, with a combination of genetic and environmental factors involved. Since the epidemiological changes cannot be related to genetic background, which did not change significantly in that time, the role of environmental factors has been reconsidered. Among these, dietary habits, and especially an excessive salt, typical of processed foods, has been implicated in the development of autoimmune diseases. In this review, we summarize current evidence, deriving both from experimental models and clinical studies, on the capability of excessive salt intake to exacerbate proinflammatory responses affecting the pathogenesis of immune-mediated diseases. Data on several diseases are presented, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and Crohn’s disease, with many of them supporting a proinflammatory effect of salt. Likewise, a hypertonic microenvironment showed similar effects in experimental models both in vivo and in vitro. However, murine models of spontaneous autoimmune polyneuropathy exposed to high salt diet suggest opposite outcomes. These results dictate the need to further analyse the role of cooking salt in the treatment and prevention of autoimmune diseases, trying to shape a fine tuning between the possible advantages of a restricted salt intake and the changes in circulating metabolites, mediators, and hormones which come along salt consumption and could in turn influence autoimmunity. Full article

(This article belongs to the Special Issue Nutrients as Efficient Immunosuppressants in Patients with Autoimmune Diseases)

9 pages, 265 KiB

Open AccessArticle

The Prognostic Nutritional Index and Nutritional Risk Index Are Associated with Disease Activity in Patients with Systemic Lupus Erythematosus

by María Correa-Rodríguez, Gabriela Pocovi-Gerardino, José-Luis Callejas-Rubio, Raquel Ríos Fernández, María Martín-Amada, María-Gracia Cruz-Caparros, Norberto Ortego-Centeno and Blanca Rueda-Medina

Nutrients 2019, 11(3), 638; https://doi.org/10.3390/nu11030638 - 16 Mar 2019

Cited by 33 | Viewed by 4383

Abstract

The prognostic nutritional index (PNI), controlling nutritional status (CONUT) score and nutritional risk index (NRI) have been described as useful screening tools for patient prognosis in several diseases. The aim of this study was to examine the relationship between PNI, CONUT and NRI with clinical disease activity and damage in 173 patients with systemic lupus erythematous (SLE). Disease activity was assessed with the SLE disease activity index (SLEDAI-2K), and disease-related organ damage was assessed using the SLICC/ACR damage index (SDI) damage index. PNI and NRI were significantly lower in active SLE patients than in inactive SLE patients (p < 0.001 and p = 0.012, respectively). PNI was inversely correlated with the SLEDAI score (p < 0.001) and NRI positively correlated with SLEDAI and SDI scores (p = 0.027 and p < 0.001). Linear regression analysis adjusting for age, sex and medications showed that PNI was inversely correlated with SLEDAI (β (95% CI) = −0.176 (−0.254, −0.098), p < 0.001) and NRI positively correlated with SLEDAI (β (95% CI) = 0.056 (0.019, 0.093), p = 0.003) and SDI (β (95% CI) = 0.047 (0.031, 0.063), p < 0.001). PNI (odds ratio (OR) 0.884, 95% confidence interval (CI) 0.809–0.967, p = 0.007) and NRI ((OR) 1.067, 95% CI 1.028–1.108, p = 0.001) were independent predictors of active SLE. These findings suggest that PNI and NRI may be useful markers to identify active SLE in clinical practice. Full article

(This article belongs to the Special Issue Nutrients as Efficient Immunosuppressants in Patients with Autoimmune Diseases)

11 pages, 1949 KiB

Open AccessArticle

The Impact of Intermittent Fasting (Ramadan Fasting) on Psoriatic Arthritis Disease Activity, Enthesitis, and Dactylitis: A Multicentre Study

by Mohammad Adawi, Giovanni Damiani, Nicola Luigi Bragazzi, Charlie Bridgewood, Alessia Pacifico, Rosalynn R. Z. Conic, Aldo Morrone, Piergiorgio Malagoli, Paolo Daniele Maria Pigatto, Howard Amital, Dennis McGonagle and Abdulla Watad

Nutrients 2019, 11(3), 601; https://doi.org/10.3390/nu11030601 - 12 Mar 2019

Cited by 68 | Viewed by 15643

Abstract

Intermittent circadian fasting, namely Ramadan, is a common worldwide practice. Such fasting has a positive impact on psoriasis, but no data exist on its role in psoriatic arthritis (PsA)—a disease that is clearly linked to body mass index. We enrolled 37 patients (23 females and 14 males) with a mean age 43.32 ± 7.81 and they fasted for 17 h for one month in 2016. The baseline PsA characteristics were collected and 12 (32.4%) patients had peripheral arthritis, 13 (35.1%) had axial involvement, 24 (64.9%) had enthesitis, and 13 (35.1%) had dactylitis. Three patients (8.1%) were treated with methotrexate, 28 (75.7%) with TNF-α blockers, and 6 (16.2%) with IL-17 blockers. After a month of intermittent fasting, C-reactive protein (CRP) levels decreased from 14.08 ± 4.65 to 12.16 ± 4.46 (p < 0.0001), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 2.83 ± 1.03 to 2.08 ± 0.67 (p = 0.0078), Psoriasis Area Severity Index (PASI) decreased from 7.46 ± 2.43 to 5.86 ± 2.37 (p < 0.0001), and Disease Activity index for PSoriatic Arthritis (DAPSA) decreased from 28.11 ± 4.51 to 25.76 ± 4.48 (p < 0.0001). Similarly, enthesitis improved after fasting, with Leeds Enthesitis Index (LEI) decreasing from 2.25 ± 1.11 to 1.71 ± 0.86 (p < 0.0001) and dactylitis severity score (DSS) decreasing from 9.92 ± 2.93 to 8.54 ± 2.79 (p = 0.0001). Fasting was found to be a predictor of a decrease in PsA disease activity scores (DAPSA, BASDAI, LEI, DSS) even after adjustment for weight loss. IL-17 therapy was found to be an independent predictor of decreases in LEI after fasting. These preliminary data may support the use of chronomedicine in the context of rheumatic diseases, namely PsA. Further studies are needed to support our findings. Full article

(This article belongs to the Special Issue Nutrients as Efficient Immunosuppressants in Patients with Autoimmune Diseases)

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10 pages, 739 KiB

Open AccessArticle

The Impact of Ramadan Fasting on the Reduction of PASI Score, in Moderate-To-Severe Psoriatic Patients: A Real-Life Multicenter Study

by Giovanni Damiani, Abdulla Watad, Charlie Bridgewood, Paolo Daniele Maria Pigatto, Alessia Pacifico, Piergiorgio Malagoli, Nicola Luigi Bragazzi and Mohammad Adawi

Nutrients 2019, 11(2), 277; https://doi.org/10.3390/nu11020277 - 27 Jan 2019

Cited by 68 | Viewed by 7623

Abstract

Fasting during the month of Ramadan consists of alternate abstinence and re-feeding periods (circadian or intermittent fasting). Nothing is currently known on the impact of this kind of fasting on psoriasis. A sample of 108 moderate-to-severe plaque psoriasis patients (aged 42.84 ± 13.61 years, 62 males, 46 females) volunteered to take part in the study. A significant decrease in the “Psoriasis Area and Severity Index” (PASI) score after the Ramadan fasting (mean difference = −0.89 ± 1.21, p < 0.0001) was found. At the multivariate regression, the use of cyclosporine (p = 0.0003), interleukin-17 or IL-17 blockers (p < 0.0001), and tumor necrosis factor or TNF blockers (p = 0.0107) was independently associated with a low PASI score, while the use of apremilast (p = 0.0009), and phototherapy (p = 0.0015) was associated with a high PASI score before the Ramadan fasting. Similarly, the consumption of cyclosporine (p < 0.0001), IL-17 blockers (p < 0.0001), mammalian target of rapamycin or mTOR inhibitors (p = 0.0081), and TNF blockers (p = 0.0017) predicted a low PASI score after the Ramadan fasting. By contrast, narrow band ultraviolet light B or NB-UVB (p = 0.0015) was associated with a high PASI score after Ramadan fasting. Disease duration (p = 0.0078), use of apremilast (p = 0.0005), and of mTOR inhibitors (p = 0.0034) were independent predictors of the reduction in the PASI score after the Ramadan fasting. These findings reflect the influence of dieting strategy, the biological clock, and circadian rhythm on the treatment of plaque psoriasis. Full article

(This article belongs to the Special Issue Nutrients as Efficient Immunosuppressants in Patients with Autoimmune Diseases)

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Review

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15 pages, 1337 KiB

Open AccessReview

Fasting and Its Impact on Skin Anatomy, Physiology, and Physiopathology: A Comprehensive Review of the Literature

by Nicola Luigi Bragazzi, Maha Sellami, Iman Salem, Rosalynn Conic, Mark Kimak, Paolo Daniele Maria Pigatto and Giovanni Damiani

Nutrients 2019, 11(2), 249; https://doi.org/10.3390/nu11020249 - 23 Jan 2019

Cited by 51 | Viewed by 29373

Abstract

Skin serves as the first protective line and barrier of the body. Like many other organs, skin can be affected by several disorders in response to external factors such as pathogens, ultraviolet light, and pollution, as well as endogenous alterations related to aging and/or oxidative stress disturbance. Researchers have reported new insights into how skin cells are altered in response to caloric restriction diets in mammals. One of the most well-known caloric restriction diets is the Ramadan intermittent fasting, which is a radical change in the diet plan of practitioners for the period of one lunar month. Ramadan fasting represents the fourth of the five pillars of the Islamic creed. Even though infirm individuals are waived to take part in this religious duty, patients with various health problems, including those with different skin disorders, might choose to share this event with peers and family members. No standardized protocols or guidelines exist, however, to advise their physicians on the proper management of their patients’ condition during fasting. With an increasing Muslim population living in Western countries, this topic has started to draw substantial attention, not only of Middle-Eastern physicians, but also of clinicians in the West. For this purpose, we carried out a comprehensive overview on the topic. Our main findings are that: (1) there is a strong need for evidence-based suggestions and guidance. Literature on the impact of the Ramadan fasting, as well as of other kinds of fasting, on skin diseases is scarce and of poor quality, as well as the information available from the Internet; (2) patients willing to fast should be advised about the importance of taking proper treatments or consider alternative options including administration of trans-dermal/topical drugs, as they are permitted during daylight hours. Further, non-compliance has important, clinical and economic implications for an effective patient management. Full article

(This article belongs to the Special Issue Nutrients as Efficient Immunosuppressants in Patients with Autoimmune Diseases)

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13 pages, 1107 KiB

Open AccessReview

Oral Adjuvant Curcumin Therapy for Attaining Clinical Remission in Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Maria G. Grammatikopoulou, Konstantinos Gkiouras, Xenophon Theodoridis, Eleni Asteriou, Alastair Forbes and Dimitrios P. Bogdanos

Nutrients 2018, 10(11), 1737; https://doi.org/10.3390/nu10111737 - 12 Nov 2018

Cited by 35 | Viewed by 7933

Abstract

Curcumin has demonstrated anti-inflammatory properties and has been investigated as an adjuvant therapy of ulcerative colitis (UC). The scope of this study was to systematically review and meta-analyze the efficacy of oral curcumin administration as an adjuvant therapy of UC. MEDLINE, Cochrane/CENTRAL, ClinicalTrials.gov, WHO-ICT Registry, EMBASE and grey literature were searched for relevant randomized controlled trials (RCTs). The primary outcome was clinical remission (attainment) and the secondary outcome was clinical response (maintenance/failure). Risk of bias was assessed with the Cochrane tool. Odds ratios (OR) were calculated with a Mantel-Haenszel (M-H) random effects model and with a beta-binomial (B-B) random effects model when zero events/cells occurred. Four RCTs met the criteria, but one was removed from the analyses due to inconsistency in protocol details. With the M-H method, treatment with curcumin was significantly superior to placebo in attaining remission in the per-protocol (PP) analysis (OR = 5.83, 95%CI = 1.24–27.43), but not in the intention-to-treat (ITT) analysis (OR = 4.33, 95%CI = 0.78–24.00). However, with the more accurate B-B method, both analyses were insignificant (for PP OR = 4.26, 95%CI = 0.59–31.00, for ITT OR = 3.80, 95%CI = 0.55–26.28). Based on the current available evidence, oral curcumin administration does not seem superior to placebo in attaining remission in patients with UC. Future RCTs should be planned more cautiously with sufficient size and adhere to the ITT analysis in all outcomes. Full article

(This article belongs to the Special Issue Nutrients as Efficient Immunosuppressants in Patients with Autoimmune Diseases)

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17 pages, 640 KiB

Open AccessFeature PaperReview

Curcumin for the Management of Periodontitis and Early ACPA-Positive Rheumatoid Arthritis: Killing Two Birds with One Stone

by Eleni Asteriou, Athanasios Gkoutzourelas, Athanasios Mavropoulos, Christina Katsiari, Lazaros I. Sakkas and Dimitrios P. Bogdanos

Nutrients 2018, 10(7), 908; https://doi.org/10.3390/nu10070908 - 16 Jul 2018

Cited by 48 | Viewed by 8853

Abstract

We propose curcumin as a preventive measure to avoid/manage periodontitis (PD), and as a natural immunosuppressant for rheumatoid arthritis (RA). PD, mainly caused by Porphyromonas gingivalis forming biofilm and leading to tooth decay, is a major public health issue and a risk factor for the development of RA in humans. P. gingivalis is able to trigger experimental autoimmune arthritis in animal models and in humans can induce citrullinated peptides, which not only are a source of anti-citrullinated antibodies (ACPAs), but also participate in autoreactive responses and disease development. Curcumin appears to have efficient anti-bacterial activity against P. gingivalis infection and biofilm formation. In addition to antibacterial, anti-oxidant, and anti-inflammatory action, curcumin exerts unique immunosuppressant properties via the inhibition of Th17 pro-inflammatory responses and promotion of regulatory T cells, thus suppressing autoimmunity. We introduce curcumin as a natural product for the management of both PD and RA-related autoreactivity, possibly also as a preventive measure in early RA or individuals at high risk to develop RA. Full article

(This article belongs to the Special Issue Nutrients as Efficient Immunosuppressants in Patients with Autoimmune Diseases)

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