Blueberry Improves the Therapeutic Effect of Etanercept on Patients with Juvenile Idiopathic Arthritis: Phase III Study

Abstract

Juvenile idiopathic arthritis (JIA) is the most common arthritis in the adolescents under the age of 16. Etanercept, an inhibitor of tumor necrosis factor, is often used to treat JIA despite its significant side effects. Homeopathic remedies, such as blueberries, have anti-inflammatory properties with fewer unwanted effects and should be considered as a primary treatment. We aimed to explore the efficacy and safety of combination therapy of blueberry and etanercept for JIA. Two hundred and one JIA patients were selected, and randomly and evenly assigned to three groups: ETA (50 mg of etanercept twice weekly), ETABJ (matched etanercept and 50 ml blueberry juice daily) and ETAPJ (matched etanercept and placebo juice). The severity of JIA was measured using American College of Rheumatology scales (ACR) 20, 50 and 70. The levels of pro-inflammatory cytokines, interleukin-1 (IL1) alpha and IL1 beta, and interleukin-1 receptor antagonist (IL1RA) were measured by qRT-PCR and ELISA. After a 6-month follow-up, the ACR20, ACR50 and ACR70 in an ETABJ group were higher than those in other two groups (P < 0.05), suggesting clinically meaningful improvement in JIA. Meanwhile, the symptoms and side effects were reduced significantly or absent in an ETABJ group, including mental diseases, retrobulbar optic neuritis, gaining weight, infection, cutaneous vasculitis, diarrhea, uveitis and pancytopenia. Blueberries reduced the levels of IL1 alpha and beta, and increased the level of IL1RA. Thus, a combination therapy of blueberry and etanercept can reduce the severity of JIA and should be developed as a new method for JIA therapy.

Health promoting properties of blueberries: a review

“…300 mg kg À1 d À1 ) by rats resulted in a positive anti-inflammatory effect, as it led to a reduction in paw edema, myeloperoxidase activity (a maker for neutrophil infiltration) and formation of granulomatous tissue. Figueira et al (2016) reported that a blueberry extract caused a reduction in joint degradation in a mice model for rheumatoid arthritis in mice, results that support the observations of Zhong et al (2015) who found that blueberry juice consumption by adolescents suffering from Juvenile idiopathic arthritis (thought to be inflammatory in nature) led not only to a considerable improvement of the activity of etanercept (a known remedy) but also an amelioration of the drugs secondary effects. Ebenezer et al 2016described that the supplementation of the diet with 2% of freeze-dried blueberry powders, led to a decrease in inflammation in a post-traumatic stress disorder rat model.…”

Diet and Rheumatoid Arthritis Symptoms: Survey Results From a Rheumatoid Arthritis Registry

“…Our study did not test whether specific foods affect RA disease activity, and we did not find a cross‐sectional association between RA disease activity scores and self‐reported change in RA symptoms from food. It is possible that certain foods on our survey do have antiinflammatory effects in RA; for example, a recent randomized trial in juvenile idiopathic arthritis tested the effect of etanercept, etanercept plus daily blueberry juice, and etanercept plus placebo juice on disease activity and circulating interleukin‐1 (IL‐1) levels . At 6 months, the etanercept plus blueberry juice group had reduced IL‐1 levels, and a significantly higher percentage of subjects achieved ACR criteria for 20%, 50%, and 70% improvement compared to the other 2 groups.…”

Effect of resveratrol and pterostilbene on aging and longevity

“…A randomized controlled trial demonstrated that blueberry consumption decreases serum TNF‐α concentrations in postmenopausal women with pre‐ and stage 1‐hypertension . Blueberries also reduced the IL‐1α and β production and increased the level of IL‐1 antagonist in patients with juvenile idiopathic arthritis in a phase III study . Overall, pterostilbene may be a potential inflammatory suppressor as indicated by in vitro and in vivo studies.…”