One of those articles that fully corroborates Ray’s views that metabolism is central not only to “function”, but to structure as well, and also provides direct support that pro-metabolic measures can be life-saving. The wasting phenotype, most commonly seen in cancer, untreated diabetes I, and various mitochondrial pathologies has baffled medicine for a long time. Many remedies have been tried, with limited success. Anabolic steroids have so been the only somewhat reliable clinical intervention. Also, inflammation certainly plays a role and it has been shown that anti-inflammatory drugs are directly anabolic for critically ill or very old people, who all exhibit various forms of cachexia. However, the benefit is limited, showing that either inflammation is not the sole cause or that it is a downstream effect of a more general/systemic process. The study below demonstrates that cancer induces a dramatic drop in oxidative metabolism (OXPHOS), with concomitant depletion of mitochondrial NAD+. The drop in OXPHOS and NAD+ are likely driven by chronic inflammation, which again implicates PUFA and various other environmental factors. The drop in mitochondrial NAD+ is directly caused by the fact that NAD+ is regenerated from the reduced form NADH through the Krebs Cycle and electron transport chain (ETC), which combined constitute what is commonly known as OXPHOS. Cancer cells produce a lot of NAD+, but it is only in the cytosol and comes at the expense of producing a lot of lactate (by using pyruvate as emergency oxidizing agent). Without OXPHOS, which happens only in the mitochondria, cancer cells cannot regenerate NAD+ oxidatively. The study below demonstrates that the inhibition of OXPHOS and the drop in mitochondrial NAD+ are not only core symptoms of cancer, but are also the main causes of cachexia (which is the dominant cause of death in such patients). Conversely, blocking pathways that result in NAD+ consumption, it is possible to elevate mitochondrial NAD+ and block the cachexia phenotype. That means something as simple as a combination of niacinamide and an oxidizing agent such as methylene blue, CoQ10, vitamin K, emodin, etc may be sufficient to not only block the cachexia, but also reverse the cancer process altogether.
https://doi.org/10.1016/j.molmet.2020.101046
“…Cancer cachexia and muscle loss are associated with increased morbidity and mortality. In preclinical animal models, blocking activin receptor (ACVR) ligands has improved survival and prevented muscle wasting in cancer cachexia without an effect on tumour growth. However, the underlying mechanisms are poorly understood. This study aimed to identify cancer cachexia and soluble ACVR (sACVR) administration-evoked changes in muscle proteome.
