Ketone Therapy as a New Approach to Infectious Disease

The World Health Organization recently estimated that sepsis accounts for almost 20% of all global causes of death, with almost half of the cases occurring in children under the age of five. Simply put, sepsis is the body’s extreme reaction to an infection, be it bacterial, fungal, parasitic or viral. Sepsis often causes lasting organ injury due to the inflammation and oxidative stress that occurs while an individual is infected. Although antibiotics may ultimately treat the infection, the pathogen remains active and continues to cause inflammation while it is alive. Most notably, there is currently no effective treatment to prevent this inflammation-mediated damage. Interestingly, blood ketone levels increase during sepsis and may an adaptive defense mechanism. Ketones, mainly β-hydroxybutyrate, are classically known to function as an additional source of fuel in low energy conditions, such as fasting and prolonged exercise. In addition to being a metabolic fuel, ketones also have non-metabolic signalling properties such as reducing inflammation and oxidative stress. Since inflammation and oxidative stress and two key processes that mediate septic organ injury, increasing ketone levels during sepsis may help protect against the inflammation-mediated organ damage. Thus, we elevated blood ketone levels using a new and safe ketone ester drink in a mouse model of sepsis (lipopolysaccharide infection). Compared to the vehicle, mice that received the ketone treatment had significantly lower inflammation in the circulation, heart, kidney, and liver as observed with protein and gene expression of >20 pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, interferon-γ. We also expect reduced organ damage as will be observed by immunohistological analysis and functional assays. Altogether, “ketone therapy” may serve as a cheap and effective treatment option for sepsis and other acute inflammation-mediated diseases and may subsequently reduce the complications that come from organ damage after recovering from septic infection.