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Living FRIendly Summaries of the Body of Evidence using Epistemonikos (FRISBEE)
Medwave 2019;19(5):e7639 doi: 10.5867/medwave.2019.05.7639
Effects of Mediterranean diet on the treatment of rheumatoid arthritis
Maximiliano Porras, Gabriel Rada, Josefina Durán
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Key Words: Rheumatoid arthritis, mediterranean diet, Epistemonikos, GRADE

Abstract

INTRODUCTION
It has been suggested that environmental and lifestyle factors might contribute to the severity and progression of inflammation in rheumatoid arthritis. An intervention generating high interest due to its supposed anti-inflammatory properties is the Mediterranean diet.

METHODS
We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.

RESULTS AND CONCLUSIONS
We identified seven systematic reviews including four primary studies, of which only one corresponded to a randomized trial. We concluded Mediterranean diet may make little or no difference in pain or disease activity and may slightly increase weight in rheumatoid arthritis patients, but the certainty of the evidence is low. On the other hand, it was not possible to clearly establish whether Mediterranean diet has any effect on functionality, morning stiffness or quality of life as the certainty of the existing evidence has been assessed as very low.


 
Problem

Rheumatoid arthritis is a chronic autoimmune disease whose etiology is not fully known. There are important variations in its frequency, which cannot only be attributed to genetic or racial factors, so it has been suggested that environmental factors, such as tobacco use and diet might contribute to both the development and the severity of the disease [1].
Moreover, the Mediterranean diet has beneficial effects in the prevention and treatment of various health conditions, which are mediated by various mechanisms, such as increasing antioxidant levels, modifying intestinal flora, promoting an anti-inflammatory lipid profile (omega 3: omega 6 ratio) and possibly decreasing inflammation in other ways [2]. Its anti-inflammatory properties have generated a particular interest in its use as part of the treatment of rheumatoid arthritis, however, if this really translates into a relevant clinical effect is a matter of controversy.

Methods

We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others, to identify systematic reviews and their included primary studies. We extracted data from the identified reviews and reanalyzed data from primary studies included in those reviews. With this information, we generated a structured summary denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos) using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies when it is possible, a summary of findings table following the GRADE approach and a table of other considerations for decision-making. 

Key messages

  • The Mediterranean diet may make little or no difference in pain and disease activity for patients with rheumatoid arthritis (low certainty evidence). 
  • We are uncertain whether Mediterranean diet improves functionality, morning stiffness and quality of life in rheumatoid arthritis as the certainty of the evidence has been assessed as very low. 
  • Mediterranean diet may slightly increase weight among rheumatoid arthritis patients (low certainty evidence).
About the body of evidence for this question

What is the evidence.
See evidence matrix  in Epistemonikos later

We found seven systematic reviews [1], [2], [3], [4], [5], [6], [7] which included four primary studies, reported in six references [8], [9], [10], [11], [12], [13] of which only one was a randomized trial [8]. The information provided by the observational studies did not increase the level of certainty of the evidence, nor did add new relevant information. Therefore the table presented and the summary is based on the only randomized trial. 

What types of patients were included*

The trial was conducted in Sweden [8] and included 51 patients, mostly women (82.3%), with rheumatoid arthritis diagnosed by criteria ACR 1987, with at least two years from diagnosis and controlled disease according to the clinician criteria at randomization. The trial excluded patients who already had a vegetarian or Mediterranean diet, with high doses of corticosteroids, or recent adjustments in therapy.

What types of interventions were included*

The trial [8] evaluated a Mediterranean diet high in oils for 12 weeks in the intervention group, compared to Western diet in the control group.

The intervention was conducted in two stages with three weeks of education and diet in the hospital, followed by nine weeks of strict clinical follow-up where the food included in the diet was provided.

What types of outcomes
were measured

The trial [8] evaluated multiple outcomes, which were grouped by the systematic reviews as follows:

  • Pain (visual analogue scale, VAS)
  • Functionality (Health Assessment Questionnaire, HAQ)
  • Morning stiffness (minutes)
  • Activity Score (Disease Activity Score, DAS 28)
  • Vitality (SF-36)
  • Weight (kg) at week 12 of the intervention. 
  • Inflammatory parameters (C reactive protein, CRP) 

* The information about primary studies is extracted from the systematic reviews identified, unless otherwise specified.

Summary of findings 

The information on the effects of the Mediterranean diet in rheumatoid arthritis is based on one randomized trial [8] that included 51 patients for the outcomes pain, disease activity, functionality, morning stiffness, quality of life and weight. 

The summary of findings is as follows: 

  • Mediterranean diet may make little or no difference to pain in rheumatoid arthritis (low certainty of the evidence).
  • Mediterranean diet may make little or no difference to disease activity in rheumatoid arthritis (low certainty of the evidence).
  • We are uncertain whether Mediterranean diet improves functionality in rheumatoid arthritis as the certainty of the evidence has been assessed as very low. 
  • We are uncertain whether Mediterranean diet improves morning stiffness in rheumatoid arthritis as the certainty of the evidence has been assessed as very low. 
  • We are uncertain whether Mediterranean diet improves quality of life in rheumatoid arthritis as the certainty of the evidence has been assessed as very low. 
  • Mediterranean diet may slightly increase weight in rheumatoid arthritis (certainty of low evidence).

Follow the link to access the interactive version of this table (Interactive Summary of Findings – iSoF)

Other considerations for decision-making

To whom this evidence does and does not apply

  • These results are applicable to patients with rheumatoid arthritis with controlled disease. The population with uncontrolled (active) disease was explicitly excluded from the trial and it is reasonable, from the clinical point of view, to expect a different effect in these cases.
About the outcomes included in this summary
  • The outcomes selected are those considered critical for decision-making by the authors of this summary, among those reported in the analyzed trial. In the case of having had information about other relevant outcomes such as ACR 20 or ACR 70 these would have been incorporated as well.
  • It is important to emphasize that although the effect observed in some outcomes is statistically significant in favor of the Mediterranean diet, the magnitude of the benefit does not exceed the thresholds usually defined to consider the effect clinically relevant. It is not possible to establish whether the Mediterranean diet really has a small but existing effect, or if it is only a spurious finding derived from the methodological limitations of the trial.
Balance between benefits and risks, and certainty of the evidence
  • This is an intervention where the benefits on symptoms and progression of rheumatoid arthritis are uncertain in some outcomes and not clinically relevant in others. 
  • Although the adverse effects of the intervention are minimal, which translates into treatment withdrawal rates due to adverse effects that were not different from the control group [7], it is important to note that a higher final weight was reported.
Resource considerations
  • This intervention has costs associated to both food and the necessary processes to get people to incorporate it efficiently into their lives. For example, in the trial analyzed, a first stage of intensive education was carried out in an in-hospital setting, followed by an out-of-hospital follow-up managed by the health team, including the appropriate food for the study participants. The total cost of implementing an intervention with these characteristics depends to a large extent on whether there are nutritional programs that are responsible for training dietary changes or food provision for patients. 
  • None of the identified studies reported a formal cost or cost-benefit analysis.
What would patients and their doctors think about this intervention
  • When faced with the evidence presented in this summary, most patients and treating physicians should lean against its use. 
  • However, people might be inclined in favor of its use, since there is a positive perception regarding the possible benefits that the Mediterranean diet has on other diseases that are not related to rheumatoid arthritis symptoms and progression (cardiovascular effects, cancer, dementia, among others).

Differences between this summary and other sources

  • The results of this summary are in general in agreement with the reviews analyzed, in terms of the limitations of existing evidence and the associated uncertainty. 
  • Although the conclusions presented by the authors of the trial are concordant with this summary, they are in general more optimistic on interpreting the results, based on the effect on some surrogate outcomes, such as plasma markers of inflammation [8]
  • In the main clinical guidelines, such as the American College of Rheumatology 2015 [14] and the European League Against Rheumatism 2016 [15], the Mediterranean diet is not mentioned.
Could this evidence change in the future?
  • The conclusions of this summary are likely to change when new evidence is available, due to the existing uncertainty. 
  • Two relevant randomized trials were identified in the International Clinical Trials Registry Platform of the World Health Organization [16][17], but their results have not yet been published. These could shed new light on this debate.
How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Mediterranean diet for rheumatoid arthritis.

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier.

After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

This article is part of the Epistemonikos Evidence Synthesis project. It is elaborated with a pre-established methodology, following rigorous methodological standards and internal peer review process. Each of these articles corresponds to a summary, denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos), whose main objective is to synthesize the body of evidence for a specific question, with a friendly format to clinical professionals. Its main resources are based on the evidence matrix of Epistemonikos and analysis of results using GRADE methodology. Further details of the methods for developing this FRISBEE are described here (http://dx.doi.org/10.5867/medwave.2014.06.5997)

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

Potential conflicts of interest

The authors do not have relevant interests to declare.

Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

INTRODUCCIÓN
Se ha planteado que factores ambientales y relacionados con el estilo de vida pueden contribuir a la severidad y progresión de la inflamación en la artritis reumatoide. Una intervención que genera un alto interés, debido a sus supuestas propiedades antiinflamatorias es la dieta mediterránea.

MÉTODOS
Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE.

RESULTADOS Y CONCLUSIONES
Identificamos siete revisiones sistemáticas que en conjunto incluyeron cuatro estudios primarios, de los cuales sólo uno corresponde a un ensayo aleatorizado. Concluimos que la dieta mediterránea podría hacer poca o nula diferencia en el dolor articular o actividad de la enfermedad, y aumentar levemente el peso en pacientes con artritis reumatoide, pero la certeza de la evidencia es baja. Por otra parte, no es posible establecer con claridad si la dieta mediterránea tiene algún efecto sobre la funcionalidad, rigidez matinal o calidad de vida, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja.

Authors: Maximiliano Porras[1,2], Gabriel Rada[2,3], Josefina Durán[2,4]

Affiliation:
[1] Facultad de Medicina, Universidad Católica del Norte, Coquimbo, Chile
[2] Proyecto Epistemonikos, Santiago, Chile
[3] Departamento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[4] Departamento de Inmunología y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

E-mail: jgduran@uc.cl

Author address:
[1] Centro Evidencia UC
Pontificia Universidad Católica de Chile
Diagonal Paraguay 476
Santiago
Chile

Citation: Porras M, Rada G, Durán J. Effects of Mediterranean diet on the treatment of rheumatoid arthritis. Medwave 2019;19(5):e7639 doi: 10.5867/medwave.2019.05.7639

Submission date: 1/4/2019

Acceptance date: 29/4/2019

Publication date: 11/6/2019

Origin: This article is a product of the Evidence Synthesis Project of Epistemonikos Fundation, in collaboration with Medwave for its publication.

Type of review: Non-blinded peer review by members of the methodological team of Epistemonikos Evidence Synthesis Project.

PubMed record

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  1. Forsyth C, Kouvari M, D'Cunha NM, Georgousopoulou EN, Panagiotakos DB, Mellor DD, Kellett J, Naumovski N. The effects of the Mediterranean diet on rheumatoid arthritis prevention and treatment: a systematic review of human prospective studies. Rheumatol Int. 2018 May;38(5):737-747. | CrossRef | PubMed |
  2. Hagen KB, Byfuglien MG, Falzon L, Olsen SU, Smedslund G. Dietary interventions for rheumatoid arthritis. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD006400. | CrossRef | PubMed |
  3. Bloomfield HE, Koeller E, Greer N, MacDonald R, Kane R, Wilt TJ. Effects on Health Outcomes of a Mediterranean Diet With No Restriction on Fat Intake: A Systematic Review and Meta-analysis. Ann Intern Med. 2016 Oct 4;165(7):491-500. | CrossRef | PubMed |
  4. Cramp F, Hewlett S, Almeida C, Kirwan JR, Choy EH, Chalder T, Pollock J, Christensen R. Non-pharmacological interventions for fatigue in rheumatoid arthritis. Cochrane Database Syst Rev. 2013 Aug 23;(8):CD008322. | CrossRef | PubMed |
  5. González Cernadas L, Rodríguez-Romero B, Carballo-Costa L. [Importance of nutritional treatment in the inflammatory process of rheumatoid arthritis patients; a review]. Nutr Hosp. 2014 Feb 1;29(2):237-45. | CrossRef | PubMed |
  6. Serra-Majem L, Roman B, Estruch R. Scientific evidence of interventions using the Mediterranean diet: a systematic review. Nutr Rev. 2006 Feb;64(2 Pt 2):S27-47. | PubMed |
  7. Smedslund G, Byfuglien MG, Olsen SU, Hagen KB. Effectiveness and safety of dietary interventions for rheumatoid arthritis: a systematic review of randomized controlled trials. J Am Diet Assoc. 2010 May;110(5):727-35. | CrossRef | PubMed |
  8. Hagfors L, Nilsson I, Sköldstam L, Johansson G. Fat intake and composition of fatty acids in serum phospholipids in a randomized, controlled, Mediterranean dietary intervention study on patients with rheumatoid arthritis. Nutr Metab (Lond). 2005 Oct 10;2:26. | PubMed | PMC |
  9. Sköldstam L, Hagfors L, Johansson G. An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis. Ann Rheum Dis. 2003 Mar;62(3):208-14. | PubMed | PMC |
  10. Hagfors L, Leanderson P, Sköldstam L, Andersson J, Johansson G. Antioxidant intake, plasma antioxidants and oxidative stress in a randomized, controlled, parallel, Mediterranean dietary intervention study on patients with rheumatoid arthritis. Nutr J. 2003 Jul 30;2:5. | PubMed | PMC |
  11. Abendroth A, Michalsen A, Lüdtke R, Rüffer A, Musial F, Dobos GJ, Langhorst J. Changes of Intestinal Microflora in Patients with Rheumatoid Arthritis during Fasting or a Mediterranean Diet. Forsch Komplementmed. 2010;17(6):307-13. | CrossRef | PubMed |
  12. Michalsen A, Riegert M, Lüdtke R, Bäcker M, Langhorst J, Schwickert M, Dobos GJ. Mediterranean diet or extended fasting's influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: an observational study. BMC Complement Altern Med. 2005 Dec 22;5:22. | PubMed | PMC |
  13. McKellar G, Morrison E, McEntegart A, Hampson R, Tierney A, Mackle G, Scoular J, Scott JA, Capell HA. A pilot study of a Mediterranean-type diet intervention in female patients with rheumatoid arthritis living in areas of social deprivation in Glasgow. Ann Rheum Dis. 2007 Sep;66(9):1239-43. | PubMed | PMC |
  14. Singh, J. A., et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis & rheumatology, 68(1), 1-26. | CrossRef | PubMed |
  15. Smolen, J. S., et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Annals of the rheumatic diseases, 76(6), 960-977. | CrossRef | PubMed |
  16. Castillo Martínez, L. Exercise and Mediterranean Diet on Body Composition, Disease Activity and Inflammatory Markers in Rheumatoid Arthritis. clinicaltrials.gov. 2014. | Link |
  17. Harokopio University. Lifestyle Interventions Based on the Mediterranean Diet for Patients With Rheumatoid Arthritis. clinicaltrials.gov. 2009. | Link |
Forsyth C, Kouvari M, D'Cunha NM, Georgousopoulou EN, Panagiotakos DB, Mellor DD, Kellett J, Naumovski N. The effects of the Mediterranean diet on rheumatoid arthritis prevention and treatment: a systematic review of human prospective studies. Rheumatol Int. 2018 May;38(5):737-747. | CrossRef | PubMed |

Hagen KB, Byfuglien MG, Falzon L, Olsen SU, Smedslund G. Dietary interventions for rheumatoid arthritis. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD006400. | CrossRef | PubMed |

Bloomfield HE, Koeller E, Greer N, MacDonald R, Kane R, Wilt TJ. Effects on Health Outcomes of a Mediterranean Diet With No Restriction on Fat Intake: A Systematic Review and Meta-analysis. Ann Intern Med. 2016 Oct 4;165(7):491-500. | CrossRef | PubMed |

Cramp F, Hewlett S, Almeida C, Kirwan JR, Choy EH, Chalder T, Pollock J, Christensen R. Non-pharmacological interventions for fatigue in rheumatoid arthritis. Cochrane Database Syst Rev. 2013 Aug 23;(8):CD008322. | CrossRef | PubMed |

González Cernadas L, Rodríguez-Romero B, Carballo-Costa L. [Importance of nutritional treatment in the inflammatory process of rheumatoid arthritis patients; a review]. Nutr Hosp. 2014 Feb 1;29(2):237-45. | CrossRef | PubMed |

Serra-Majem L, Roman B, Estruch R. Scientific evidence of interventions using the Mediterranean diet: a systematic review. Nutr Rev. 2006 Feb;64(2 Pt 2):S27-47. | PubMed |

Smedslund G, Byfuglien MG, Olsen SU, Hagen KB. Effectiveness and safety of dietary interventions for rheumatoid arthritis: a systematic review of randomized controlled trials. J Am Diet Assoc. 2010 May;110(5):727-35. | CrossRef | PubMed |

Hagfors L, Nilsson I, Sköldstam L, Johansson G. Fat intake and composition of fatty acids in serum phospholipids in a randomized, controlled, Mediterranean dietary intervention study on patients with rheumatoid arthritis. Nutr Metab (Lond). 2005 Oct 10;2:26. | PubMed | PMC |

Sköldstam L, Hagfors L, Johansson G. An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis. Ann Rheum Dis. 2003 Mar;62(3):208-14. | PubMed | PMC |

Hagfors L, Leanderson P, Sköldstam L, Andersson J, Johansson G. Antioxidant intake, plasma antioxidants and oxidative stress in a randomized, controlled, parallel, Mediterranean dietary intervention study on patients with rheumatoid arthritis. Nutr J. 2003 Jul 30;2:5. | PubMed | PMC |

Abendroth A, Michalsen A, Lüdtke R, Rüffer A, Musial F, Dobos GJ, Langhorst J. Changes of Intestinal Microflora in Patients with Rheumatoid Arthritis during Fasting or a Mediterranean Diet. Forsch Komplementmed. 2010;17(6):307-13. | CrossRef | PubMed |

Michalsen A, Riegert M, Lüdtke R, Bäcker M, Langhorst J, Schwickert M, Dobos GJ. Mediterranean diet or extended fasting's influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: an observational study. BMC Complement Altern Med. 2005 Dec 22;5:22. | PubMed | PMC |

McKellar G, Morrison E, McEntegart A, Hampson R, Tierney A, Mackle G, Scoular J, Scott JA, Capell HA. A pilot study of a Mediterranean-type diet intervention in female patients with rheumatoid arthritis living in areas of social deprivation in Glasgow. Ann Rheum Dis. 2007 Sep;66(9):1239-43. | PubMed | PMC |

Singh, J. A., et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis & rheumatology, 68(1), 1-26. | CrossRef | PubMed |

Smolen, J. S., et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Annals of the rheumatic diseases, 76(6), 960-977. | CrossRef | PubMed |

Castillo Martínez, L. Exercise and Mediterranean Diet on Body Composition, Disease Activity and Inflammatory Markers in Rheumatoid Arthritis. clinicaltrials.gov. 2014. | Link |

Harokopio University. Lifestyle Interventions Based on the Mediterranean Diet for Patients With Rheumatoid Arthritis. clinicaltrials.gov. 2009. | Link |