Failing Heart and Starving Brain
Ketone Bodies to the Rescue
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One of my favorite quotes in literature comes from the biochemist-turned-writer Isaac Asimov (1920–1992), who wrote, “The saddest aspect of life right now is that science gathers knowledge faster than society gathers wisdom.”1 Two recent articles2,3 published back to back in Circulation seem to challenge this notion by exposing results of strategic value. Both studies analyzed and sorted vast amounts of metabolites, proteins, and gene transcripts in failing human heart muscle,2,3 and both came independently to the same conclusions: Of all of the energy-providing substrates for the heart, the enzymes regulating ketone body metabolism are upregulated while those regulating glucose and fatty acid metabolism are downregulated. In other words, a strong signal emerged from a mountain of data. What does this mean? Here are my thoughts.
When I am in congenial company, and especially over a glass of wine, I like to reflect on the story of metabolism, which is actually the story of people. It has been said that I am the only practicing cardiologist with a living connection to the Krebs cycle. Krebs often referred to metabolism as “biochemistry with a purpose”. More specifically, contraction and metabolism in the heart are inextricably linked and obey the First Law of Thermodynamics (energy in=energy …