A KETOGENIC diet (KD) may worsen osteoarthritis (OA) severity and increase pain sensitivity according to the results of a new study. Researchers utilized a destabilization of the medial meniscus (DMM) mouse model to assess the impact of KD on knee OA. Adult male mice underwent either DMM or sham surgery and were subsequently fed a KD or standard chow for eight weeks. Mechanical allodynia was evaluated biweekly, and analyses of knee joint histology, gut microbiome composition, and serum cytokine levels were conducted.
The findings revealed that mice on the KD exhibited more severe histopathologic OA post-DMM surgery, with a mean Osteoarthritis Research Society International score of 4.0 ± 0.5, compared to 2.7 ± 0.08 in the chow-fed DMM group (P = 0.02). Additionally, KD-fed mice demonstrated increased mechanical allodynia following surgery (P = 0.005). Significant alterations in the gut microbiome were observed in KD-fed mice, with 59 clades affected in the DMM group and 39 in the sham group; 36 of these clades were common to both groups, and 25 overlapped with findings from previous murine OA studies. Notably, certain clades, such as Lactobacillus, showed correlations with both histologic severity (P = 0.004) and allodynia (P = 1 × 10−4). Serum analysis indicated elevated levels of cytokines, including interleukin (IL)-1β, IL-2, IL-3, and IL-13, in the KD groups.
These results suggest that initiating a KD immediately after OA induction via DMM is associated with worsened histologic outcomes and increased pain sensitivity. The KD also induces significant gut microbiome dysbiosis, affecting clades previously linked to murine OA. This study underscores the importance of considering dietary interventions carefully in the context of OA management, as certain diets may have unintended adverse effects on disease progression and pain perception.
Reference: Dyson G et al. Ketogenic Diet-Associated Worsening of Osteoarthritis Histologic Secerity, Increased Pain Sensitivity and Gut Microbiome Dysbiosis in Mice. ACR OR. 2025;7:e11794.
Anaya Malik | AMJ
