Refueling the post COVID-19 brain: potential role of ketogenic medium chain triglyceride supplementation: an hypothesis

Abstract

COVID-19 infection causes cognitive changes in the acute phase, but also after apparent recovery. Over fifty post (long)-COVID symptoms are described, including cognitive dysfunction (“brain fog”) precluding return to pre-COVID level of function, with rates twice as high in females. Additionally, the predominant demographic affected by these symptoms is younger and still in the workforce. Lack of ability to work, even for six months, has significant socio-economic consequences. This cognitive dysfunction is associated with impaired cerebral glucose metabolism, assessed using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), showing brain regions that are abnormal compared to age and sex matched controls. In other cognitive conditions such as Alzheimer’s disease (AD), typical patterns of cerebral glucose hypometabolism, frontal hypometabolism and cerebellar hypermetabolism are common. Similar FDG-PET changes have also been observed in post-COVID-19, raising the possibility of a similar etiology. Ketone bodies (B-hydroxybutyrate, acetoacetate and acetone) are produced endogenously with very low carbohydrate intake or fasting. They improve brain energy metabolism in the face of cerebral glucose hypometabolism in other conditions [mild cognitive impairment (MCI) and AD]. Long-term low carbohydrate intake or prolonged fasting is not usually feasible. Medium chain triglyceride (MCT) is an exogenous route to nutritional ketosis. Research has supported their efficacy in managing intractable seizures, and cognitive impairment in MCI and AD. We hypothesize that cerebral glucose hypometabolism associated with post COVID-19 infection can be mitigated with MCT supplementation, with the prediction that cognitive function would also improve. Although there is some suggestion that post COVID-19 cognitive symptoms may diminish over time, in many individuals this may take more than six months. If MCT supplementation is able to speed the cognitive recovery, this will impact importantly on quality of life. MCT is readily available and, compared to pharmaceutical interventions, is cost-effective. Research shows general tolerability with dose titration. MCT is a component of enteral and parenteral nutrition supplements, including in pediatrics, so has a long record of safety in vulnerable populations. It is not associated with weight gain or adverse changes in lipid profiles. This hypothesis serves to encourage the development of clinical trials evaluating the impact of MCT supplementation on the duration and severity of post COVID-19 cognitive symptoms.

MCT-Induced Ketosis and Fiber in Rheumatoid Arthritis (MIKARA)—Study Protocol and Primary Endpoint Results of the Double-Blind Randomized Controlled Intervention Study Indicating Effects on Disease Activity in RA Patients

“…MCT supplementation can raise blood BHB up to 0.3 to 1.0 mmol/L because MCT degrades 5 to 8 times faster than does LCT from the gastrointestinal tract, and MCFAs are transported directly into the liver via the portal vein and rapidly metabolized to ketone bodies via conversion from acetyl CoA [15,[17][18][19][20]. Exogenous ketosis from MCT is independent of the fasting state, plasma insulin or low to moderate carbohydrate intake and MCTs offer a potential advantage of inducing nutritional ketosis without the need for a drastic change in dietary habits [21]. Besides the benefits of ketosis, MCT can improve immunity, gut microbiota, and intestinal health [22,23].…”