Just a few weeks ago, I did a post on the anti-acid drug famotidine being a potent inhibitor of cellular carnitine uptake, which is the main mechanism of beneficial action of the drug Meldonium (Mildronate) as well. Blocking the cellular uptake of carnitine decreases the rate of oxidation of long-chain fatty acids and promoted the oxidation of glucose (via the Randle Cycle effect). However, the study below demonstrates that these drugs may have another, previously unknown, benefit due to decreased carnitine uptake. Namely, the study below shows that carnitine uptake into the cell via the OCTN2 carrier, synergizes with endotoxin/LPS to drive systemic inflammation through the so-called “pyrin inflammasome“, and cause muscle injury. As such, drugs that block OCTN2 (famotidine, Meldonium, etc) have a direct anti-inflammatory effect as well. This mechanism may very well explain the mysterious healing effects famotidine has on GI inflammation at doses that do not suppress gastric acid release. The study below could also partially explain why a predominantly meat-based diet may become harmful with advancing age, considering the well-known fact that chronic inflammation and muscle injury / sarcopenia are known to increase with age. Yet another reason to eat more dairy and less meat.
https://doi.org/10.1016/j.cell.2026.09.015
https://draxe.com/health/wire-j-cell-2026-09-015-d5a5e175573f/
“…A study first published October 19, 2026 in Cell found that ʟ-carnitine, an amino acid concentrated in muscle meat, switches on a specific inflammation alarm called the pyrin inflammasome in immune-primed mice and in immune cells. Researchers reported in Cell that ʟ-carnitine, an amino acid highly concentrated in skeletal muscle, triggers inflammasome activation. The work used mice exposed to a bacterial toxin called LPS to prime their immune systems, plus LPS-primed mouse and human immune cells called macrophages in lab dishes. Sample size was not reported. The authors found that extracellular ʟ-carnitine, meaning carnitine sitting outside cells, gets pulled in by a transporter called OCTN2, and that uptake represses mevalonate synthesis, a cellular process cells use to build cholesterol and related molecules. That repression triggered the pyrin inflammasome, a protein complex inside immune cells that senses danger and launches inflammation. The same pyrin-and-OCTN2 pathway was required for the inflammatory response to actual skeletal muscle injury in the mice. The authors describe immune cells as acting like sentinels that treat free-floating carnitine, whether from muscle damage or from food, as a signal of muscle injury worth reacting to with inflammation.”
“…The mechanism gives a concrete biological explanation for why diets heavy in red meat, which is especially rich in carnitine, have long been linked to inflammatory disease in population studies. The authors state this work opens the door to examining how excess dietary carnitine intake could drive inflammatory disease, rather than concluding that it does so in people.”
