Long COVID-19 Syndrome Lifestyle Intervention Study

Hyperglycemia, obesity, and diabetes are recognized risk factors for worse outcomes in acute COVID-19. Several studies have proposed that a change in the host metabolic state from a carbohydrate-dependent glycolytic to a fat-dependent ketogenic state is expected to be beneficial in acute Covid-19. The benefits may involve several mechanisms including inhibition of inflammatory cytokine secretion, inhibition of the NLRP3 inflammasome, anti-inflammatory effects on specific T cell populations, altered viral replication, increased resistance to mitochondrial stress, an improvement in antioxidant defenses, augmented autophagy, and DNA repair.

Many of the proposed beneficial mechanisms are thought to be mediated by the main ketone body produced in the ketogenic state, beta-hydroxybutyrate (BHB). Besides its role as a metabolic energy carrier, BHB also has pleiotropic signaling functions and potent anti-inflammatory effects. Numerous studies indicate that the ketogenic state is tissue- and organ-protective 12-15 such as in acute kidney injury, and cardiac and liver injury.

The ketogenic state can be induced by dietary interventions such as intermittent fasting, time-restricted feeding, and high-fat, low-carbohydrate ketogenic diets. All of these interventions led to the lowering of blood glucose and insulin levels and increased BHB levels. Since the 1920s, ketogenic diets have been used to treat epilepsy in children. They are effective in blood glucose control and lead to effective fat weight loss in obese individuals. Ketogenic diets are increasingly used and studied to rapidly reverse nonalcoholic fatty liver disease and insulin resistance, polycystic kidney disease (PKD), and in the management of severe obesity, metabolic diseases, migraine, cancer, and numerous other conditions.

Recent research indicates that the hyper-inflammatory responses seen in acute COVID-19 are also a feature of long-COVID. Long-COVID is characterized by a varying range of long-standing, often disabling symptoms that are persisting or appearing after the initial infection and recovery from acute COVID-19. Common symptoms include fatigue, brain fog, muscle and chest pain, migraines, shortness of breath, anosmia, muscle weakness, and cognitive dysfunction. Interestingly, a study found that 35% of long-COVID patients reported having decreased kidney function at 6 months post-discharge, and 13% of patients with normal kidney function during the acute phase presented with decreased eGFR at follow-up 28. Furthermore, patients with long-COVID and mast cell activation syndrome (MCAS) tend to experience virtually identical symptoms. As a result, the induction of ketosis by fasting, or the administration of exogenous BHB, has been shown to ameliorate hypersensitivity and mast cell degranulation in a rat model of (mast cell activation syndrome) MCAS.

In this study, we will evaluate the effects of nutritional management for patients with long-COVID. Nutritional management is aimed at lowering blood glucose levels and raising blood BHB levels. The dietary plan will recommend a low-carbohydrate diet, including avoiding foods containing sugars and starch, while simultaneously increasing the consumption of healthy fats and protein sources. The dietary intervention is supported by the consumption of a medical food, KetoCitra®, that delivers exogenous BHB in order to raise blood BHB levels without the necessity of adhering to a strict ketogenic diet which would be difficult to implement and typically requires strict medical supervision.