gms | German Medical Science

Introduction: Certain gut-associated metabolites including medium-chain fatty acids (MCFAs) and short-chain fatty acids (SCFAs), which are ketogenic, may play a role in bone-related diseases such as RA. Many preclinical studies have confirmed that butyrate could ameliorate the damage in RA. However, the role of MCTs has not been investigated in human RA studies to date. The potential for a ketogenic diet to reduce inflammation has gained greater awareness in recent years. Beta-hydroxybutyrate (BHB) is the most abundant circulating ketone and recent evidence indicates that BHB may be able to act as a direct signal to inhibit cellular pathways involved in inflammation. BHB can also be increased independent of whatever else is eaten by supplementation with MCFAs allowing for induction of ketosis without requiring additional metabolic adaptations.

Methods: Our aim was to investigate the effect of supplementation of regular diet with medium-chain triglycerides with and without fiber on disease activity as measured by SDAI (Simplified Disease Activity Index) in RA patients. A total of 61 patients with RA on stable drug treatment were randomly assigned to a twice-daily control regime or to a twice-daily regime of a dietary supplement, containing medium-chain triglycerides (MCTs) 30 g/day, for 8 weeks followed by a second twice-daily regimen of combining MCTs (30 g/day) plus fiber (30 g/day) for an additional 8 weeks. At baseline (t0), week 8 (t2) and week 16 (t4), clinical assessment, routine laboratory, gut microbiota composition, and immunologic parameters were measured. The primary outcome was a change in Simple Disease Activity Index (SDAI) from baseline to week 16. Secondary endpoint measures included the change in BHB levels from baseline to t2 and t4. The study was conducted from August 2021 to October 2022.

Results: There was a significant decrease in the SDAI in the test group compared to the control group between t0 and t4 was seen (p=0.008) using Wilcoxon’s Signed Rank test. Descriptive results of BHB levels are summarized in Figure 1 [Fig. 1].

Conclusion: Our preliminary results showed a significant reduction in disease activity as measured by SDAI in RA patients through supplementation of the regular diet with medium-chain triglycerides in combination with fiber compared to consuming a control supplement. The results of this study showed a significant increase in BHB levels (t4–t0) through supplementation of the regular diet with medium-chain triglycerides alone that was sustained when MCTs were combined with fiber compared to consuming a control supplement of long chain triglycerides (LCTs) with and without fiber. We are currently investigating our hypothesis that the mechanism by which MCTs could further reduce disease activity is through microbiota-mediated host effects on gut-barrier function and autoimmunity.