Pre-clinical and clinical studies have investigated the role of a dysregulated metabolism
in the sustainability of tumor initiation and progression. One of the most familiar
metabolic alterations encountered in several types of cancers is the upregulation of glycolysis,
which is also maintained in conditions of normal oxygen tension (aerobic glycolysis, Warburg
effect) while oxidative phosphorylation is apparently reduced. As a result, cancer cells convert
most incoming glucose to lactate. Although more rapid, adenosine triphosphate (ATP)
production by glycolysis is less efficient in terms of ATP generated per unit of glucose consumed
than oxidative phosphorylation. The consequence is that tumor cells require an abnormally
higher rate of glucose compared to the normal counterpart. New evidence shows that
other metabolic substrates such as glutamine may also have an important role in cancer metabolism.
Ketogenic diet (KD) replaces all but non-starchy vegetable carbohydrates with low
to moderate amounts of proteins and high amounts of monounsaturated and polyunsaturated
fats. The rationale of KD is valid both because it lowers carbohydrate uptake possibly leading
to cancer cell starvation and apoptosis and, at the same time, increases the levels of ketone
bodies available for energy production in normal cells but not in cancer cells which have an
allegedly downregulated oxidative phosphorylation. For this reason, several authors speculate
on the possibility to evaluate KD as a novel approach in the treatment of cancer. In this review
we will assess the data supporting the use of such alimentary regimen and its impact on
tumor development and progression.
Keywords: Cancer, ketogenic diet, low-carbohydrate diet, carbohydrate restricted, aerobic glycolysis, calorie restriction.
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