Cytotoxicity of Exogenous Acetoacetate in Lithium Salt Form Is Mediated by Lithium and Not Acetoacetate

Anticancer Res. 2020 Jul;40(7):3831-3837. doi: 10.21873/anticanres.14372.


Background/aim: The ketogenic diet has recently gained interest as potential adjuvant therapy for cancer. Many researchers have endeavored to support this claim in vitro. One common model utilizes treatment with exogenous acetoacetate in lithium salt form (LiAcAc). We aimed to determine whether the effects of treatment with LiAcAc on cell viability, as reported in the literature, accurately reflect the influence of acetoacetate.

Materials and methods: Breast cancer and normal cell lines were treated with acetoacetate, in lithium and sodium salt forms, and cell viability was assessed.

Results: The effect of LiAcAc on cells was mediated by Li ions. Our results showed that the cytotoxic effects of LiAcAc treatment were significantly similar to those caused by LiCl, and also treatment with NaAcAc did not cause any significant cytotoxic effect.

Conclusion: Treatment of cells with LiAcAc is not a convincing in vitro model for studying ketogenic diet. These findings are highly important for interpreting previously published results, and for designing new experiments to study the ketogenic diet in vitro.

Keywords: Ketogenic diet; acetoacetate; breast cancer; ketone bodies; lithium.

MeSH terms

  • Acetoacetates / chemistry
  • Acetoacetates / pharmacology*
  • Adenosine Triphosphate / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cations, Monovalent / chemistry
  • Cations, Monovalent / pharmacology
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Humans
  • Lithium / chemistry
  • Lithium / pharmacology*
  • Lithium Chloride / chemistry
  • Lithium Chloride / pharmacology
  • Lithium Compounds / chemistry
  • Lithium Compounds / pharmacology*
  • MCF-7 Cells


  • Acetoacetates
  • Cations, Monovalent
  • Lithium Compounds
  • Adenosine Triphosphate
  • Lithium
  • Lithium Chloride