Vitamin D supplementation is effective for olanzapine-induced dyslipidemia
Zhou Z, Nagashima T, Toda C, Kobayashi M, Suzuki T, Nagayasu K, Shirakawa H, Asai S, Kaneko S (2023) Front Pharmacol 14 1135516. doi: 10.3389/fphar.2023.1135516. eCollection 2023.
Abstract:
Olanzapine is an atypical antipsychotic drug that is clinically applied in patients with schizophrenia. It increases the risk of dyslipidemia, a disturbance of lipid metabolic homeostasis, usually characterized by increased low-density lipoprotein (LDL) cholesterol and triglycerides, and accompanied by decreased high-density lipoprotein (HDL) in the serum.In this study, analyzing the FDA Adverse Event Reporting System, JMDC insurance claims, and electronic medical records from Nihon University School of Medicine revealed that a co-treated drug, vitamin D, can reduce the incidence of olanzapine-induced dyslipidemia.
In the following experimental validations of this hypothesis, short-term oral olanzapine administration in mice caused a simultaneous increase and decrease in the levels of LDL and HDL cholesterol, respectively, while the triglyceride level remained unaffected.
Cholecalciferol supplementation attenuated these deteriorations in blood lipid profiles.
RNA-seq analysis was conducted on three cell types that are closely related to maintaining cholesterol metabolic balance (hepatocytes, adipocytes, and C2C12) to verify the direct effects of olanzapine and the functional metabolites of cholecalciferol (calcifediol and calcitriol).
Consequently, the expression of cholesterol-biosynthesis-related genes was reduced in calcifediol- and calcitriol-treated C2C12 cells, which was likely to be mediated by activating the vitamin D receptor that subsequently inhibited the cholesterol biosynthesis process via insulin-induced gene 2 regulation.
This clinical big-data-based drug repurposing approach is effective in finding a novel treatment with high clinical predictability and a well-defined molecular mechanism.
FAB RESEARCH COMMENT:
Antipsychotic medications play an important role in the management of schizophrenia. However, their side-effects can include impairment of blood sugar regulation and/or lipid metabolism, and associated increased risks for obesity, metabolic syndrome, Type 2 diabetes and cardiovascular disease.
These side-effects are not trivial, as in addition to reducing treatment compliance, they add to the already-elevated risks for both Type 2 diabetes and cardiovascular disease in patients with schizophrenia, which impose a high cost burden on health services, and are a major cause of the signifiicant reductions in health and life expectancy associated with this condition.
A previous study, using data mining techniques to explore a large data base of adverse drug effects, found that Vitamin D supplementation reduced the risk of hyerglycaemia casued by the atypical antipsychotic quetiapine.
The researchers went on to uncover - via animal studies - the precise mechanisms by which this drug causes insulin resistance, and how Vitamin D suppementation mitigates this. See:
These findings have major clinical importance, as they show that Vitamin D supplementation can mitigate this well-known side-effect of this commonly used medication.
Vitamin D deficiency is extremely common in patients with schizophrenia and other forms of psychosis, and although supplementation to correct this is merited in any case for its general health benefits, these new findings make an important addition to the case for doing this in order both to reduce such costly adverse side-effects, and to enhance the likelihood of medication compliance.
For more information on Vitamin D and schizophrenia, please see these article lists, which are updated as new research is forthcoming:
And for more information on the importance of Vitamin D for mental and physical health, please see the following article lists:
(NB further lists on specific conditions can be found from FAB comments on many articles there)
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