Yet another study identifying that relying predominantly on fat as fuel is highly detrimental to cells/tissues, especially the heart. While at rest, skeletal muscles and the heart oxidize primarily lipids that preference quickly switches to glucose when the muscles/heart are under load. The cellular “fatigue” in the ailing/aging heart has been known for a long time and has been linked to excessive FAO as far back as the 1960s. As a result, drugs such as Meldonium were developed and they work by limiting the excessive FAO. However, the elevated FAO in ailing hearts has so far been thought to be just a symptom of the condition and not a cause. As such, Meldonium continues to be marketed as a symptomatic treatment for angina, CVD, and heart failure. The study below now shows that excessive FAO is perhaps the main driver of the actual heart condition (in this case heart failure) and the mechanism of action through which FAO damages the heart is by depleting the essential mitochondrial lipid cardiolipin. This finding matches the other recent post I did on supplementing phosphatidylcholilne as anti-aging therapy, given that such supplementation has been shown to restore cardiolipin levels. So, the study below effectively shows that restricting FAO is likely a “disease-modifying” (read: curative) treatment. In addition to Meldonium, aspirin and niacinamide are two other effective inhibitors of FAO and it just so happens that both have shown promise in animal models of virtually all heart conditions they have been tested on.
https://www.jci.org/articles/view/202528
https://www.utsouthwestern.edu/newsroom/articles/year-2026/june-overactive-fat-burning.html
“…When heart cells burn fat without normal metabolic controls, they can deplete a lipid needed to keep mitochondria functioning properly, according to a study by UT Southwestern Medical Center researchers. The findings, published in The Journal of Clinical Investigation, identify a mechanism linking disrupted energy metabolism to heart failure and point to potential strategies for earlier intervention. “This study challenges a long-held assumption that maximizing fat burning is beneficial for the heart,” said senior author Jay Horton, M.D., Director of the Center for Human Nutrition and Professor of Internal Medicine and Molecular Genetics at UT Southwestern. “It demonstrates that unrestrained fatty acid oxidation (FAO) paradoxically destroys the heart’s own mitochondrial architecture through depletion of cardiolipin, an essential structural lipid.” To examine what happens when the heart cannot properly regulate its fuel use, two related enzymes, acetyl-CoA carboxylase 1 and 2, were genetically removed from mouse heart muscle cells. These enzymes normally help control how many fatty acids enter mitochondria, the structures inside cells that generate energy. Without that control, the mice developed enlarged hearts and impaired blood-pumping function.”
“…The researchers also found that drugs that inhibit CPT1, a protein that helps move fatty acids into mitochondria, prevented heart failure when given early, before cardiac dysfunction developed. However, the same approach did not improve heart function once cardiomyopathy was established.
