Double Blinded Clinical Study on D-Glyceric Acid, a Potential Novel Energy Metabolic Signaling Metabolite

Abstract

\n Based on earlier few studies natural metabolite D-glyceric acid does not seem to play any major role in cellular metabolism. Nevertheless, one study that concentrated on ethanol oxidation in the liver increased our curiosity. Therefore, research leading to the present 25 days lasting double blinded human study with placebo control was initiated. Main targets in the present study were: 1) to find out whether acute and long-term exogenous D-glyceric acid (DGA) regimen will cause activation related to energy metabolism in healthy 50-60-year old humans, and 2) to find out whether elevated levels of endogenous DGA can be found in the plasma after 30 min of a strenuous cycling exercise. Additional target was to find out whether certain effects of exogenous DGA regimen resemble the effects of physical exercises, and whether lowered halved dose of DGA regimen during a 14-day follow-up period continues to be effective. The main results revealed that: I) there was an acute effect on plasma glucose maintenance from DGA regimen, II) plasma metabolites and gene expressions related to aerobic energy production were strongly modulated, and subclinical inflammation was lowered already after the 4-day DGA regimen, and III) cycling with increasing load towards exhaustion increased endogenous levels of DGA in human plasma (p=0.013). Because the amounts of administered DGA were exceedingly small and cannot directly have caused observed substantial changes, we hypothesise that an increase in tissue DGA concentration causes an endogenous signal or a cascade of intracellular signals: “ more ATP is needed immediately ”. At the whole body level, the signal causes metabolic activation cascade that resembles initiation of physical exercises but without literally no signs of exhaustion. Tested exogenous DGA regimen possessed an effect even on circulating immune cells. Based on obtained results, the DGA regimen may facilitate in resolving energy metabolic challenges in main organs, like fatty liver, and simultaneously it seemed to lower systemic inflammation. The DGA regimen can possibly alleviate chronic diseases and disorders related to energy metabolism and/or elevated subclinical inflammation.Trial registration number (18th of Jan 2021), ClinicalTrials.gov Identifier: NCT04713319