Fuel as therapy

Three supplements didn't make the Five, and all for the same reason: they are fuel. Glutamine is the primary energy substrate for enterocytes, the cells lining the small intestine. Butyrate, a short-chain fatty acid produced when gut bacteria ferment fiber, is the primary energy substrate for colonocytes, the cells lining the colon. The two cell populations most affected in Crohn's disease and ulcerative colitis respectively run on two different fuels. Creatine is the third: a universal cellular energy buffer that operates in both. All three are inexpensive and widely available, which is part of why they come up so often. Full entries are in the barrier section.

Calling them fuel is accurate physiology, not a dismissal; fuel is therapy, just a different kind. A cell that is repairing itself under inflammatory stress has a higher energy budget than a resting one, and there is good evidence that the epithelium in active IBD is energy-starved, butyrate oxidation is impaired in inflamed colonic tissue, and the creatine-kinase system that buffers ATP in the gut lining is downregulated in active disease. Supplying substrate is a reasonable thing to do. It is just a different kind of thing from turning down NF-κB or restoring a missing bacterial species, and a guide that lumped them together would blur its own framework. A physiological role is not a proven supplement benefit; the Section F cards say where the human trials landed.

Where they live in this guide. Section F, Barrier Repair, opens with all three, each with a full product card; the butyrate card explains why form matters more for butyrate than for almost anything else here.