Wilhelm Brünings' forgotten contribution to the metabolic treatment of cancer utilizing hypoglycemia and a very low carbohydrate (ketogenic) diet

Abstract

The growing interest in the alterations of tumor cell metabolism and their possible therapeutic exploitation also spurred new complementary and integrative approaches such as treating patients with a ketogenic diet (KD). KDs aim at inhibiting glycolytic tumor metabolism and growth, and have therefore been proposed as adjuncts not only to standard-of-care, but also to other therapies targeting tumor metabolism. Here I describe the life and forgotten work of one of the earliest researchers who realized the importance of altered tumor cell metabolism and its possible exploitation through metabolic modifications: Wilhelm Brünings. Brünings was a German natural scientist and physician famous for his innovative contributions to the fields of physiology and otorhinolaryngology. Based on the findings of Otto Warburg and his physiological reasoning he started to experiment with insulin administration and KDs in his patients with head and neck cancers, aiming to maximally lower blood glucose concentrations. He obtained encouraging short-term results, although most tumors became refractory to treatment after several weeks. His pioneering work is worth revisiting, especially for an international readership that may be unaware of his efforts, as hypoglycemic treatments, including the use of insulin injections and KDs, are currently being re-investigated as complementary and integrative cancer treatments.

Keywords: Cancer; Hypoglycemia; Insulin; Ketogenic diet; Low carbohydrate diet.

Graphical abstract

Fig. 1

Wilhelm Brünings as shown in a laudatory article by A. Greifenstein on the occasion of his 60th birthday celebration which was published in the journal Archiv für Ohren-, Nasen-und Kehlkopfheilkunde (now the European Archives of Oto-Rhino-Laryngology).

Fig. 2

An excerpt from Brünings’ first report.

Fig. 3

Timeline of studies using ketogenic diets to treat cancer patients. The early studies are labeled with author names and the year of publication.