As the study below demonstrates, the constipation drug lubiprostone significantly slowed the decline of kidney function (eGFR) in patients with moderate CKD over 24 weeks. The higher dose (16 mcg) outperformed the lower dose (8 mcg), which outperformed placebo. The researchers observed changes in gut bacteria and increased levels of spermidine, which they attribute to mitochondrial protection.

However, from the bioenergetic perspective, the primary mechanism is almost certainly endotoxin reduction. Constipation increases gut transit time, which allows Gram-negative bacteria to proliferate and release large quantities of lipopolysaccharide (LPS). LPS absorbed from the gut circulates to the kidneys, where it triggers inflammation, oxidative stress, fibrosis, and mitochondrial dysfunction. By relieving constipation, lubiprostone reduces LPS load, thereby lowering the inflammatory burden on the kidneys. The observed increase in spermidine may be a secondary or parallel effect — but the core intervention is simply keeping the gut moving.

This explains why Ray Peat recommended carrot salad (fiber that binds endotoxin) and other pro-motility agents for kidney protection. The drug industry has now accidentally validated what Peat has said for decades: treat constipation, lower endotoxin, protect the kidneys. The human-equivalent doses are already provided in the article as the clinical doses used (8 mcg and 16 mcg daily), since this was a human trial — no animal-to-human conversion is needed.

Once again, a simple intervention targeting gut motility outperforms complex pharmaceutical approaches by addressing the root issue: endotoxin-driven inflammation.

https://doi.org/10.1126/sciadv.adw3934

https://www.earth.com/news/common-constipation-drug-lubiprostone-may-also-protect-failing-kidneys/

“Some received a placebo. Others took 8 micrograms or 16 micrograms of lubiprostone daily for 24 weeks… The primary measure was estimated glomerular filtration rate (eGFR). In moderate kidney disease, that number falls year over year.”

“Patients on placebo did what the research predicted. Their eGFR drifted downward over the six-month window. The lubiprostone groups did not – or did so more slowly. Higher doses held kidney function steadier. The 16 microgram group outperformed the 8 microgram group, which in turn outperformed placebo.”

“When the gut microbiome falls out of balance, inflammation tends to rise and bacterial byproducts that should leave the body start to build up instead.”

“The mechanism is where the work gets strange… the drug had reshaped which bacteria were thriving in patients’ guts… Spermidine has drawn attention in aging research for its effects on mitochondria – the tiny structures inside cells that turn nutrients into usable energy. Kidney cells… are particularly sensitive to mitochondrial decline.”

“Going in, the researchers had a different prediction. They expected lubiprostone to lower uremic toxins… That is not what happened. Uremic toxin levels held roughly steady throughout. The kidney benefit traveled through a different route entirely: gut bacteria changes and mitochondrial support, not detoxification.”

Via: https://haidut.me/?p=3022