A Ketogenic Diet May Protect Against Gout

Could a low-carb, high fat diet help in treating the symptoms of gout? A new study investigates how the diet affects rodents and humans. Characterized as a rheumatic disease, gout affects more than 8 million people in the United States every year. It is caused by either an excessive production or insufficient excretion of uric acid. In gout, the uric acid crystals sediment in tissues and fluids, triggering the body's immune cells. This results in disabling pain, inflammation, and fever. These kinds of episodes of immune cell activation (known as flares) are triggered by a protein complex called the NLRP3 inflammasome. Vishnu Deep Dixit (Professor of comparative medicine and immunobiology at Yale School of Medicine in New Haven, CT) suggests that the so-called ketogenic diet may help to relieve the symptoms of gout. To be specific, a ketogenic diet is low in carbohydrates, and typically is used to lose weight. This is able to work by inducing a "physiological ketosis" in the body, which is a state where the body's glucose reserves are not sufficient for the body's central nervous system. Subsequently, because the body's central nervous system needs an alternative source of energy, it makes the liver convert fats into fatty acids and ketone bodies. The new study published in Cell Reports proposes that one of these ketone bodies, the beta-hydroxybutyrate (BHB), may relieve urate crystal-induced gout. To test this, the research team created a new model of gout flares in rodents. Discovering that the flares were triggered by the NLRP3 inflammasome with the help of neurosis (the most common type of white blood cell), NLRP3 activates the IL-1B pro-inflammatory cytokine, leading to episodes of intense pain, fever, and joint destruction. The researchers induced gout by injecting 1.25 milligrams of monosodium urate into the rat's knees. The researchers measured the thickness of the rodent's knees, and performed pathology analyses on the rat's ligaments and menisci. Keeping the rats in pathogen-free conditions, they were fed a ketogenic diet one week before the experiments commenced. The level of BHB in their blood was also measured by the scientists. Healthy, steroid-free human subjects between the ages of 18-45 years of age were also examined, as well as older adults aged 65 years and over. Those who participated were not fasting when their peripheral blood was collected. Dixit and her colleagues conducted statistical analyses and performed all of the experiments at least twice. They concluded that that a ketogenic diet raised BHB levels, which consequently helped to repress the NLRP3 inflammasome. As a consequence, the symptoms of urate crystal-induced gout were alleviated, without negatively impacting the immune system or its ability to defend against bacterial infections. BHB was also seen to block the IL-1B in the neutrophils of both mice and humans, regardless of age. "Collectively, our studies show that BHB, a known alternate metabolic fuel, is also an anti-inflammatory molecule that may serve as treatment for gout," Dixit and her colleagues concluded. Emily Goldberg, co-author on the study, associate research scientist, and clinical veterinarian in comparative medicine, explains that, "In isolated neutrophils, (BHB) completely blocked NLRP3 inflammasome activation, even when provided at low concentrations that are physiologically achievable through dietary modification." She also suggests that targeting the NLRP3 inflammasome to reduce inflammation during a flare may improve the gout patients' symptoms. However, more studies still need to be done to test this possibility.