Ketogenic diet does not promote triple-negative and luminal mammary tumor growth and metastasis in experimental mice

Vol.:(0123456789)1 3Clinical & Experimental Metastasis
https://doi.org/10.1007/s10585-023-10249-z
RESEARCH PAPER
Ketogenic diet does not promote triple-negative and luminal
mammary tumor growth and metastasis in experimental mice
Meret Grube1 · Arno Dimmler2 · Anja Schmaus1 · Rafael Saup1 · Tabea Wagner 1 · Boyan K. Garvalov 1 ·
Jonathan P. Sleeman1,3 · Wilko Thiele 1
Received: 17 October 2023 / Accepted: 21 November 2023
© The Author(s) 2023
Abstract
Ketogenic diets (KDs) can improve the well-being and quality of life of breast cancer patients. However, data on the effects
of KDs on mammary tumors are inconclusive, and the influence of KDs on metastasis in general remains to be investigated.
We therefore assessed the impact of a KD on growth and metastasis of triple negative murine 4T1 mammary tumors, and
on the progression of luminal breast tumors in an autochthonous MMTV-PyMT mouse model. We found that KD did not
influence the metastasis of 4T1 and MMTV-PyMT mammary tumors, but impaired 4T1 tumor cell proliferation in vivo, and
also temporarily reduced 4T1 primary tumor growth. Notably, the ketogenic ratio (the mass of dietary fat in relation to the
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mass of dietary carbohydrates and protein) that is needed to induce robust ketosis was twice as high in mice as compared to
humans. Surprisingly, only female but not male mice responded to KD with a sustained increase in blood β-hydroxybutyrate
levels. Together, our data show that ketosis does not foster primary tumor growth and metastasis, suggesting that KDs can
be safely applied in the context of luminal breast cancer, and may even be advantageous for patients with triple negative
tumors. Furthermore, our data indicate that when performing experiments with KDs in mice, the ketogenic ratio needed to
induce ketosis must be verified, and the sex of the mice should also be taken into account.