Aims and Rationale
We aim to:
Examine the association between blood ketone levels and cognitive function in both the general population and individuals with severe mental illness (SMI), where cognitive deficits represent a major unmet therapeutic need.
Investigate the relationship between ketone levels and physical health markers-particularly lipid profiles-in both groups, to better understand the broader physiological effects of ketosis.
Research Questions
A. Are higher blood ketone levels associated with better cognitive function in individuals with and without SMI?
B. Are blood ketone levels associated with physical health markers, such as lipid levels, in these groups (excluding pathological ketosis)?
Scientific Rationale
Ketogenic diets (KDs) have been used for over a century to treat drug-resistant epilepsy, reducing seizure frequency by mimicking a fasting state. This metabolic shift lowers glucose levels and increases fatty acid use, producing ketone bodies like beta-hydroxybutyrate (BHB), which serve as an alternative energy source. In the brain, BHB may influence neurotransmission by modulating the GABA/glutamate balance via effects on the tricarboxylic acid cycle. Beyond epilepsy, KDs have been linked to improved cognitive performance and physical health outcomes-effects especially relevant in SMI, where cognitive impairment is common and often poorly treated.
However, strict dietary adherence to KDs can be difficult. Emerging evidence suggests that elevated ketone levels alone-without a full ketogenic diet-may provide cognitive benefits. Using UK Biobank data, this project will explore whether naturally occurring ketone levels are associated with cognition and physical health in the general population and in people with SMI.
Our findings could inform safer, more accessible interventions for cognitive and physical health, especially in vulnerable populations