Lithocholic acid (CR mimetic)
Lithocholic acid (LCA) — a calorie-restriction mimetic. Aging itself. Reviewed Oct 2026.
Two Nature papers show a bile acid reproducing calorie-restriction effects in mice, worms and flies. There is no human data, and the same molecule is a standard way to induce liver injury in rodents.
What it is
A secondary bile acid. Your liver makes primary bile acids from cholesterol; gut bacteria carrying 7α-dehydroxylase convert the fraction that escapes reabsorption into LCA in the colon. Two Nature papers in 2025 reported that LCA accumulates in calorie-restricted mice and that giving LCA alone reproduces several effects of calorie restriction — without cutting food. The proposed route is a TULP3–sirtuin–v-ATPase–AMPK pathway, i.e. LCA binds TULP3, sirtuins deacetylate the v-ATPase V1E1 subunit, and AMPK switches on.
The evidence
Qu et al., Nature 2025 (doi 10.1038/s41586-024-08329-5): LCA activated AMPK, improved muscle regeneration and restored grip strength and running capacity in mice, and extended lifespan and healthspan in C. elegans and Drosophila. AMPK knockout abolished every effect. Companion paper (doi 10.1038/s41586-024-08348-2) mapped the TULP3 mechanism. What is missing matters more: no human trial, no human dosing, and in mice LCA extended healthspan without a reported lifespan extension — the lifespan results are in worms and flies, which cannot even synthesise LCA. Against it: LCA is the most hepatotoxic of the bile acids and is routinely used to induce cholestatic liver injury in rodents (Mol Med Rep 2020, PMID 32626965), and secondary bile acids are implicated in colon pathology (Acta Cir Bras 2015, PMID 26465107). A longevity molecule that is also a standard liver-toxicity model is not a supplement candidate yet. Also unproven: the popular claim that intermittent fasting, cyclic ketosis or “liver support” measurably raise your own LCA and thereby deliver calorie-restriction benefits. No human study has shown that chain. Note on route: the animal effects came from administered LCA at controlled doses, not from coaxing the gut microbiome into making more of it. Those are different interventions and only the first one was tested.
What you can do today
Not available for this use, and years away if it arrives at all. Anything sold today with this claim is not backed by human evidence for it.
Sources
- Primary sourcenature.com
Change history
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