G Morris, BK Puri, A Carvalho, M Maes, M Berk, A Ruusunen and L Olive,
The international journal of neuropsychopharmacology, Feb 2020 08
Induced ketosis (or ketone body ingestion) can ameliorate several changes associated with neuroprogressive disorders including schizophrenia, bipolar disorder and major depressive disorder. Thus, the effects of glucose hypometabolism can be bypassed through the entry of beta-hydroxybutyrate, providing an alternative source of energy to glucose. The weight of evidence suggests that induced ketosis reduces levels of oxidative stress, mitochondrial dysfunction and inflammation - core features of the above disorders. There is also data to suggest that induced ketosis may be able to target other molecules and signalling pathways whose levels and or activity are also known to be abnormal in at least some patients suffering from these illnesses such as peroxisome proliferator-activated receptors (PPARs), increased activity of the Kelch-like ECH-associated protein (KEAP)/nuclear factor erythroid 2-related factor 2 (NRF-2),Sirtuin-1(SIRT-1) nuclear factor (NF)-κB p65 and NAD This review explains the mechanisms by which induced ketosis might reduce mitochondrial dysfunction, inflammation and oxidative stress in neuropsychiatric disorders and ameliorate abnormal levels of molecules and signalling pathways which also appear to contribute to the pathophysiology of these illnesses. This review also examines safety data relating to induced ketosis over the long term and discusses the design of future studies.