StudyRepo

Describes the concept of "substrate competition" in the mitochondria, where competing substrates (glucose, fatty acids, amino acids) lead to "indecision" in which of the fuels to burn. Speculates that substrate competition is the root cause of "insulin resistance," that the reason is "too much mixed food all the time," and that restricting at least one macro (e.g. doing keto) might alleviate this issue.

The article reviews the literature about the Randle cycle and mitochondrial inertia, and develops a model to explain how lipids and BCAAs play together to promote insulin resistance. A literature review shows that BCAAs are associated with insulin resistance and diabetes more than any other metabolite studied. Yet the negative effects of BCAAs only seem to show up in "high-fat" diets. The authors therefore believe that BCAAs can "clog up" the TCA cycle similarly to lipids, possibly competing for similar pathways. This can then lead to glucose intolerance.