Highlights
- Intermittent fasting (IF) improved physical function and disease activity scores in overweight and obese postmenopausal women with rheumatoid arthritis (RA).
- No significant effects were seen on inflammatory or oxidative stress markers.
- Further research is needed to clarify IF’s role in RA management, especially regarding inflammation.
Study Background and Disease Burden
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by persistent joint inflammation, progressive disability, and increased comorbidity risk. Postmenopausal women, particularly those who are overweight or obese, face heightened disease burden due to hormonal changes and metabolic factors that can exacerbate disease activity and functional impairment. Traditional pharmacotherapy remains the mainstay of treatment, but adjunctive lifestyle interventions are increasingly recognized for their potential to improve outcomes. Among these, intermittent fasting (IF)—a dietary strategy involving periodic restriction of caloric intake—has garnered interest for its purported anti-inflammatory, metabolic, and weight-reducing effects. Despite promising data in other populations, the impact of IF on RA, particularly in postmenopausal women with increased adiposity, remains underexplored.
Study Design
This randomized controlled clinical trial by Ranjbar et al. was designed as a parallel-group, superiority study to evaluate the effects of IF in overweight and obese postmenopausal women with RA. A total of 44 women were randomized to either a 16/8 IF regimen (16 hours fasting, 8 hours feeding daily; n=22) or a usual diet control group (n=22) for 8 weeks. The primary endpoint was the Health Assessment Questionnaire-Disability Index (HAQ-DI), which assesses physical function and disability. Secondary endpoints included body mass index (BMI), morning joint stiffness (MS), and laboratory markers of inflammation (erythrocyte sedimentation rate [ESR], high-sensitivity C-reactive protein [hs-CRP], interleukin 6 [IL-6]), oxidative stress (total oxidant capacity [TOC], total antioxidant capacity [TAC], oxidative stress index [OSI]), and composite disease activity scores (Disease Activity Score-28 [DAS-28], Clinical Disease Activity Index [CDAI]). Measurements were taken at baseline and after 8 weeks.
Key Findings
The study demonstrated that IF led to statistically significant improvements in BMI, DAS-28, CDAI, and HAQ-DI scores compared to the control group. These findings suggest that IF can positively influence disease activity and functional outcomes in this population over an 8-week period. Specifically:
- BMI: The IF group experienced a greater reduction in BMI, indicating meaningful short-term weight loss.
- Disease Activity: Both DAS-28 and CDAI scores improved significantly, reflecting reduced joint inflammation and overall RA activity.
- Physical Function: HAQ-DI scores decreased (improved), suggesting better patient-reported functional status and daily living abilities.
However, the trial did not observe significant changes in morning stiffness, ESR, hs-CRP, IL-6, TOC, TAC, or OSI, indicating that the improvements in clinical measures were not paralleled by measurable biochemical changes in systemic inflammation or oxidative stress within the study timeframe.
Effects of IF on outcomes of participants using a linear mixed model to assess between-group differences in trial outcomes.
| Outcome | IF | Control | Difference between groups (CI 95 %) | P-value | P-value* | ||
|---|---|---|---|---|---|---|---|
| After | Change | After | Change | ||||
| HAQ | 16.72 (11.49, 21.96) | −3.18 (−10.58, 4.22) | 21.18 (15.61, 26.74) | 0.63 (−7.23, 8.5) | −3.82 (−5.52, −2.12) | 0.001> | 0.015 |
| BMI (Kg/m2) | 29.65 (28.29, 31.01) | −0.67 (−0.95, −0.40) | 29.26 (27.86, 30.65) | 0.12 (−0.16, 0.40) | −0.79 (−1.18, −0.41) | 0.001> | 0.009 |
| SJC | 1.77 (1.13, 2.41) | −1.00 (−1.56, −0.43) | 4.59 (3.13, 6.05) | 0.40 (−0.27, 1.08) | −1.40 (−2.26, −0.55) | 0.005 | 0.015 |
| TJC | 2.72 (1.77, 3.67) | −0.77 (−1.52, −0.02) | 5.36 (3.82, 6.90) | 0.72 (−0.36, 1.82) | −1.50 (−2.78, −0.21) | 0.024 | 0.038 |
| DAS−28 | 3.17 (2.76, 3.59) | −0.75 (−1.35, −0.17) | 3.82 (3.40, 4.24) | −0.15 (−0.40, 0.11) | −0.59 (−1.01, −0.17) | 0.007 | 0.048 |
| CDAI | 10.95 (8.27, 13.63) | −3.72 (−6.04, −1.41) | 17.90 (14.39, 21.42) | 1.68 (−3.29, 6.65) | −5.4 (−8.35, 2.45) | 0.001 | 0.022 |
| MS | 2 (1.02, 2.97) | −0.5 (−1.71, 0.71) | 2.63 (1.91, 3.35) | 0.0 (−0.01, 0.01) | −0.5 (−1.50, 0.50) | 0.298 | 0.552 |
| ESR (mm/hour) | 19.40 (10.85, 75.95) | −0.85 (−3.69, 1.98) | 16.90 (11.26, 22.55) | 2.13 (−2.40, 6.67) | −2.99 (−8.18, 2.20) | 0.301 | 0.251 |
| hs-CRP (ng/ml) | 5059.69 (2850.65, 7268.74) | −396.62 (−1550.94, 757.69) | 4655.42 (3028.06, 6282.78) | 86.70 (−1450.02, 1623.43) | −483.33 (−2348.44, 1381.77) | 0.604 | 0.503 |
| IL−6 (pg/ml) | 75.69 (62.07, 89.31) | −4.52 (−15.36, 6.32) | 64.86 (60.70, 69.02) | −3.85 (−10.94, 3.22) | −0.66 (−13.36, 12.02) | 0.916 | 0.123 |
| TAC (nmol/ml of Trolox) | 131.01 (125.18, 136.84) | −0.11 (−5.53, 5.30) | 135.57 (127.42, 143.73) | 4.52 (0.64, 8.40) | −4.62 (−11.03, 1.77) | 0.152 | 0.688 |
| TOS (nmol/ml) | 0.89 (−0.58, 1.20) | −0.34 (−1.16, 0.47) | 1.05 (0.58, 1.52) | −0.19 (−0.42, 0.04) | −0.15 (−0.98, 0.67) | 0.713 | 0.104 |
| OSI | 0.68 (0.44, 0.92) | −0.26 (−0.89, 0.36) | 0.73 (0.46, 1.00) | −0.18 (−0.35, −0.01) | −0.08 (−0.71, 0.55) | 0.795 | 0.606 |
Expert Commentary
This study adds to a growing body of literature exploring the role of dietary interventions in RA management, particularly for populations with high metabolic risk. The findings are clinically relevant, as improved BMI and functional status are associated with better long-term outcomes in RA. However, the lack of significant change in inflammatory and oxidative stress markers highlights the complex interplay between dietary patterns, metabolic health, and immune activity in RA.
Several factors may explain the dissociation between clinical improvement and biochemical markers:
- The study’s duration (8 weeks) may be insufficient for substantial changes in systemic inflammation or oxidative stress to manifest.
- Biomarker variability and the influence of background pharmacologic therapy (e.g., DMARDs, corticosteroids) could mask subtle effects of IF.
- IF may improve subjective and functional outcomes through weight loss, improved insulin sensitivity, or modulation of gut microbiota, even if traditional inflammatory markers remain unchanged in the short term.
It is also important to note the study’s limitations: small sample size, short duration, and lack of blinding. The findings may not be generalizable to men, non-obese individuals, or those with different disease durations or comorbidities. No major safety concerns or adverse events were reported, supporting the short-term feasibility of IF in this group.
Conclusion
Intermittent fasting appears to offer short-term benefits in disease activity, weight management, and functional ability for overweight and obese postmenopausal women with RA. However, its effects on systemic inflammation and oxidative stress remain uncertain. Given the rising prevalence of obesity and metabolic syndrome in RA populations, IF represents a promising adjunctive strategy, but larger and longer-term studies are required to inform clinical guidelines and clarify mechanistic pathways.
References
Ranjbar M, Shab-Bidar S, Rostamian A, Mohammadi H, Tavakoli A, Djafarian K. Effects of intermittent fasting diet in overweight and obese postmenopausal women with rheumatoid arthritis: A randomized controlled clinical trial. Complement Ther Med. 2025 Aug;91:103189. doi: 10.1016/j.ctim.2025.103189 IF: 3.5 Q1 .
Additional references on intermittent fasting and RA:
– Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev. 2017;39:46-58.
– Sparks JA. Rheumatoid Arthritis. Ann Intern Med. 2019;170(1):ITC1-ITC16.
