Lubiprostone (Constipation Drug) Stops Kidney Decline

This truly is amazing. It may be applicable to various mitochondrial dysfunction disorders. This drug, lubiprostone, increases spermidine levels! Obviously, this is phase 2, so early days, but work is underway.

Lubiprostone in chronic kidney disease: Insights into mitochondrial function and polyamines from a randomized phase 2 clinical trial

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

“Chronic kidney disease (CKD) is a life-threatening condition, and constipation is a progressive risk factor. We evaluated changes in uremic toxins, renal function, and the safety of lubiprostone, a selective chloride channel activator, in patients with CKD. In this phase 2, randomized, double-blind, placebo-controlled trial across nine centers in Japan, 150 patients with stage IIIb–IV CKD received lubiprostone (8 or 16 micrograms) or placebo for 24 weeks. The primary end point was change in indoxyl sulfate levels. Secondary end points included other uremic toxins and renal function markers. Lubiprostone did not alter uremic toxin levels but improved or preserved estimated glomerular filtration rate and its slope in the 16-microgram group. Mild-to-moderate gastrointestinal events occurred in the placebo and 16-microgram groups. Multiomics analysis revealed that lubiprostone modulated the gut microbial agmatine pathway and increased spermidine levels, thereby improving renal mitochondrial function. Lubiprostone is a previously unknown and safe therapeutic option to mitigate renal decline in CKD.”

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It may not hurt to try a little spermidine supplementation.

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Very interesting, thanks for the post

My understanding is that lubiprostone lowers agmatine levels (by increasing its synthesis along the pathway to polyamines).

Agmatine has a direct beneficial affect on the microglia and has other neuroprotective properties. I wonder if supplementation with agmatine sulfate or even its precursor arginine would be sensible during the lubiprostone treatment.

Long-Term (5 Years), High Daily Dosage of Dietary Agmatine—Evidence of Safety: A Case Report

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