Two Weeks on a Plant-Based Diet: How MicroRNAs and Rheumatoid Arthritis Symptoms Change

A plant-based plate isn’t just about fiber and vitamins. In a pilot clinical trial by Mexican scientists, just 14 days of a personalized plant-based diet in patients with rheumatoid arthritis (RA) was associated with a reduction in disease activity and changes in the level of circulating microRNAs involved in inflammation. The study was published in the journal Nutrients.

Background of the study

Rheumatoid arthritis (RA) is a chronic autoimmune inflammation in which the immune system attacks the synovial membrane of the joints and triggers cytokine cascades (TNF, IL-6, IL-1β), NF-κB/STAT activation, and pathological activation of B and T cells. Disease-modifying antirheumatic drugs (cs/bio/tsDMARDs) reduce disease activity and slow down joint destruction, but some patients continue to have symptoms, side effects, and need supportive non-drug strategies. Hence the persistent interest in diet as a “co-therapy” that can gently suppress systemic inflammation and improve metabolic status.

In recent years, evidence has accumulated that dietary patterns that emphasize plant-based foods - vegetables, fruits, whole grains, legumes, nuts, olive oil - and reduce saturated fat/ultra-processed foods are associated with lower levels of inflammatory markers and subjective improvement in well-being in RA. Possible mechanisms include: increased intake of antioxidants and polyphenols; a shift in the fatty acid profile towards mono- and polyunsaturated fatty acids; fermentable fiber that increases the production of short-chain fatty acids (butyrate, propionate) and maintains tolerance by intestinal immunity via the microbiota. However, causal inferences are limited: controlled studies are few, the duration of interventions is often short, and the molecular “bridges” between diet and immune response are incompletely characterized.

Against this backdrop, there is growing interest in microRNAs (miRNAs), small non-coding RNAs that fine-tune the expression of multiple genes simultaneously. A number of “inflammatory” miRNAs (e.g. miR-155, miR-146a, miR-125 family, miR-26a) are involved in T-cell differentiation, macrophage activation, and B-cell responses and have been repeatedly found to be elevated in patients with RA, correlating with disease activity. This makes miRNAs attractive biomarkers of rapid changes and potential mediators of dietary effects: if diet alters the levels of “key” miRNAs, it can quickly be reflected in clinical outcomes.

Therefore, a logical scientific step is to test whether a short but strictly prescribed plant-based diet, combined with stable drug therapy, can induce parallel changes in: (1) clinical indicators of disease activity (DAS28-CRP, joint tenderness/swelling) and (2) circulating miRNAs pre-selected for their role in inflammatory pathways (NF-κB, PI3K-AKT, cytokine-receptor interactions). Such a design closes two gaps at once - it tests the feasibility of a rapid dietary effect and provides molecular clues about the mechanisms linking “what’s on the plate” to immune regulation in RA.

What the researchers did

• We recruited 23 patients with RA (mild-moderate activity, stable drug therapy ≥3 months; no biologics) and 12 healthy controls for comparison of baseline miRNA levels.
• A 14-day isocaloric plant-based diet was followed: ~57% carbohydrates, 28% fat, 17% protein; 80% protein from plant sources (legumes, grains, seeds, vegetables). Animal products were limited to 20% of protein (eggs, fish, white cheeses); ultra-processed foods, sugar, and saturated fats were excluded. Adherence was monitored using diaries and 24-hour surveys.
• Before and after the intervention, DAS28-CRP, clinical and biochemical parameters, and expression of five candidate microRNAs (miR-26a-5p, miR-125a-5p, miR-125b-5p, miR-146a-5p, miR-155-5p) were measured by RT-qPCR. The microRNA set was pre-selected using bioinformatics (microarray GSE124373 + literature) followed by pathway analysis.

The bottom line is that there are two main pieces of news. First, the clinical picture and some of the biochemistry improved after just two weeks. Second, the levels of three of the five microRNAs studied, which are involved in key inflammatory cascades in RA, decreased at the same time - a potential mechanism for "how nutrition talks to immunity."

What results were achieved in 14 days

• Disease activity: the DAS28-CRP index decreased from a median of 4.04 to 3.49 (p < 0.0001); the number of painful joints decreased from 7 to 3 (p < 0.0001), and inflamed joints decreased from 5 to 3 (p = 0.005).
• Inflammation and metabolism: CRP decreased (5.61 → 4.78 mg/L; p = 0.020), total cholesterol 180 → 155 mg/dL (p = 0.004), glucose 92 → 87 mg/dL (p = 0.022). Triglycerides and HDL did not change significantly; ESR - without statistical significance.
• Anthropometry: slight decrease in weight (65.5 → 64.7 kg; p = 0.014) and BMI (29.5 → 29.2 kg/m²; p = 0.001); proportion of fat and circumference - without significant changes.
• MicroRNAs: miR-26a-5p, miR-125a-5p and miR-155-5p significantly decreased; no significant changes were observed for miR-125b-5p and miR-146a-5p. According to bioinformatics, the targets of these microRNAs lie in the PI3K-AKT, NF-κB and cytokine-receptor interactions.

Behind the scenes is some neat bioinformatics. The team first sifted through the microarray data, then compiled a list of RA-related microRNAs and narrowed it down to key candidates. The resulting pathways point not to one “magic” mechanism, but to inflammatory regulatory nodes that nutrition could theoretically “reach” via microRNAs.

Why is this important?

• RA is treated with drugs, but diet can be a companion: reducing activity and CRP within two weeks is a quick, clinically tangible signal.
• The miRNA shift in RA is a molecular signature of the potential anti-inflammatory effects of diet, consistent with the fact that levels of these miRNAs are elevated in patients and associated with disease severity.
• However, this is a pilot study: small sample, no control group, short duration, female predominance - so it is too early to make long-term generalizations. Randomized and longer trials are needed.

The question of “what exactly worked” remains open: the “vegetarian” diet itself, the rejection of sugar and saturated fats, the improvement of the fat and carbohydrate profile - or a combination of these. The authors carefully remind: the inclusion of plant products does not cancel out medications, but complements them - especially when it comes to a safe, isocaloric regimen under the supervision of a doctor.

What can be checked further?

• RCTs with controls and longer follow-up to understand whether miRNA and clinical shifts are sustained.
• Stratification: who responds better - by gender, initial activity, metabolic profile, microbiota.
• Mechanisms: To experimentally validate miRNA targets at the cellular level and link them to DAS28-CRP reduction in specific patients.

Conclusion

Two weeks of a deliberate, isocaloric plant-based diet in RA patients was associated with reduced symptoms and inflammatory markers and lower levels of “inflammatory” microRNAs—a cautious but promising argument for considering nutrition as part of comprehensive disease management.

Source: Peña-Peña M., Bermúdez-Benítez E., Sánchez-Gloria JL, et al. A 14-Day Plant-Based Dietary Intervention Modulates the Plasma Levels of Rheumatoid Arthritis-Associated MicroRNAs: A Bioinformatics-Guided Pilot Study. Nutrients. 2025;17(13):2222. doi:10.3390/nu17132222.