The inhibition of malignant cell growth by ketone bodies

The effect of ketone bodies on the growth, in culture, of transformed lymphoblasts (Raji cells) was investigated. Cell growth was inhibited and this effect was reversible, non-toxic, and proportional to the concentration of D-beta-hydroxybutyrate up to 20mM. The total glucose utilisation and the total lactate production were reduced in proportion to the inhibition of cell proliferation. D-beta-hydroxybutyrate was not metabolised by the cells. Other glycolytic inhibitors and chemical analogues of D-beta-hydroxybutyrate either did not inhibit or proved to be too toxic for cell growth. D-beta-hydroxybutyrate also inhibited the growth of rabbit kidney (RK13), HeLa, mouse melanoma (B16), fibroblast and trypsin-dispersed human thyroid and beef testis cells. Moreover, in vivo dietary-induced ketosis reduced the number of B16 melanoma deposits in the lungs of C57BL/6 mice by two-thirds. The significance of these results in the clinical management of cancer cachexia is discussed.