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Human fasting modulates macrophage function and upregulates multiple bioactive metabolites that extend lifespan in Caenorhabditis elegans: a pilot clinical study

Christopher H Rhodes, Chenghao Zhu, Joanne Agus, Xinyu Tang, Qianyan Li, JoAnne Engebrecht, Angela M Zivkovic. Am J Clin Nutr. 2023 Feb;117(2):286-297.

Open-label, no control groupHumansOther animals

Design
Open-label, no control group
Subjects
20 young men and women in a 3-day protocol; isolated human macrophages; Caenorhabditis elegans worms
Dose used in the study
No palmitoylethanolamide was given to people; PEA and other metabolites were applied to macrophages and worms at doses not stated in the abstract
Duration
3-day protocol including a 36-hour fast
What was measured
Clinical and experimental markers of immune and metabolic health across four metabolic states; plasma metabolomics; effects of candidate metabolites on human macrophages and on worm lifespan

What the authors reported

A 36-hour fast changed the plasma metabolome and had immunomodulatory effects on macrophages. Four metabolites raised by fasting (spermidine, 1-methylnicotinamide, palmitoylethanolamide and oleoylethanolamide) reproduced these effects in macrophages, and alone or combined extended median C. elegans lifespan by up to 96%.

Limits of this study

A small pilot in 20 people; the PEA effects were in isolated cells and worms and cannot show effect in people. The disclosure attached to the record names a patent application and NIH funding, but its initials do not match this paper's authors.

Source

PubMed 36811567 · doi:10.1016/j.ajcnut.2022.10.015

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.