Current opinion on the regulation of small intestinal magnesium absorption Original paper

This mini-review updated how clinicians should think about magnesium absorption in the small intestine, moving beyond the older idea that absorption is mostly passive and unregulated. It explained that the duodenum, jejunum, and ileum absorb magnesium through both transcellular routes (through TRPM6, TRPM7, and TRPM6/7 channels with basolateral export mechanisms) and paracellular routes (through tight junction pores influenced by claudins). It also emphasized that small-intestinal magnesium uptake changes quickly in response to hormones, luminal acidity, pH-sensing channels and receptors, and medications like proton pump inhibitors, which means absorption is more regulated and more clinically “tunable” than many clinicians assume.

Who was reviewed?

Because this was a review, it did not enroll patients; it synthesized evidence from human and animal intestinal tissues, epithelial models, and mechanistic transport studies. The reviewed work included experiments that measured segmental transport in the duodenum, jejunum, and ileum using epithelial preparations and Ussing chamber approaches, plus cell models such as Caco-2 monolayers that clarified pH sensing and transporter regulation. It also reviewed clinical observations around proton pump inhibitor–associated hypomagnesemia, integrating them with mechanistic animal and cell findings to explain why long-term acid suppression can lower magnesium absorption in the small intestine.

What were the most important findings?

The review argued that small-intestinal magnesium handling is a regulated system with identifiable control points that can explain real-world magnesium deficiency patterns. It described transcellular uptake through TRPM6/TRPM7 family channels in small-intestinal epithelium and noted that heteromeric TRPM6/7 may allow more continuous uptake than TRPM6 alone in some contexts. It also described paracellular movement as a major contributor, but it emphasized that tight junction composition can change permeability and therefore change magnesium flux. Hormones mattered: parathyroid hormone and FGF-23 directly suppressed transcellular magnesium absorption in multiple small-intestinal segments through signaling that reduces membrane-associated TRPM6 expression. Luminal pH also mattered: acidity improves magnesium solubility and supports absorption, while bicarbonate secretion and pH elevation can precipitate magnesium and reduce free ion availability. Proton-sensing pathways created a practical bridge between acid suppression and magnesium loss, because ASIC1a, OGR1/GPR68, and P2Y2-linked signaling can shift bicarbonate secretion and thereby alter soluble magnesium.

What are the greatest implications of this review?

Clinicians should treat hypomagnesemia risk as a gut-absorption problem as often as a renal-loss problem, especially in patients using proton pump inhibitors or with symptoms of malabsorption, small intestinal bacterial overgrowth, or chronic inflammation. The review supports a practical mindset: when magnesium is low, raising luminal magnesium intake alone may not correct the problem if acid suppression, bicarbonate secretion, tight junction changes, or transporter dysfunction is limiting absorption. It also strengthens microbiome-informed care logic, because luminal acidity, fermentation patterns, and barrier integrity can all change magnesium bioavailability; in other words, dysbiosis and magnesium deficiency can reinforce each other through pH, inflammation, and epithelial function.