Abstract
Background: Based on earlier studies, natural metabolite D-glyceric acid (DGA) does not seem to play any role in whole-body metabolism. Nevertheless, one ethanol oxidation-related rat study with controversial results raised our interest. According to preparatory studies for the regulatory approval of DGA, some highly conserved mechanism seems to subtly activate the cellular energy metabolism. Therefore, the present 25-days double-blind human study with placebo control was initiated. Purpose: The main target in the present study with 27 healthy 50–60-year-old human volunteers was to find out whether an “acute” 4-days and a longer 21-days exogenous DGA regimen caused moderate activation of the mitochondrial energy metabolism. The simultaneous target was to find out whether a halved dose of DGA continued to be an effective regimen. Main Findings: The results revealed the following statistically significant findings: 1) plasma concentrations of metabolites related to aerobic energy production, especially lactate, were strongly reduced, 2) systemic inflammation was lowered both in 4- and 21-days, 3) mitochondria-related mRNA expressions in circulating immune cells were noticeably modulated at Day4, 4) cellular membrane integrity seemed to be sharply enhanced, and 5) cellular NADH/NAD+ -ratio was upregulated. Conclusion: Mitochondrial metabolism was clearly upregulated at the whole-body level in both 4- and 21 days. At the same time, the effect of DGA was very well tolerated. Based on received solid results, the DGA regimen may alleviate acute and chronic energy metabolic challenges in main organs like the liver, CNS, and skeletal muscles. Enhanced membrane integrity combined with lower systemic inflammation and activated metabolic flows by the DGA regimen may be beneficial especially for the aging population.
Highlights
D-glyceric acid (DGA) is a natural organic acid present in very small amounts in vertebrates and plants
The 4- and 21-days changes of carefully selected plasma metrics and mRNA expressions from white blood cells (WBCs) were used as indirect primary markers for the activation of mitochondrial metabolism
Energy Substrate Net Inflow Into Cells Point to Mitochondrial Activation and Increased NADH/NAD+ -Ratio We found that the 4-days DGA regimen caused an extremely significant 21% average decline in plasma lactate (p 0.0009, Figure 2A)
Summary
D-glyceric acid (DGA) is a natural organic acid present in very small amounts in vertebrates and plants. In pediatric patients, the ratio of DGA concentration in cerebrospinal fluid to plasma seems to be clearly higher than that of organic acids in general (Hoffmann et al, 1993). This may indicate that the diffusion of DGA through the blood-brain barrier as well as other membranes is not totally fluent. Purpose: The main target in the present study with 27 healthy 50–60-year-old human volunteers was to find out whether an “acute” 4-days and a longer 21-days exogenous DGA regimen caused moderate activation of the mitochondrial energy metabolism. The simultaneous target was to find out whether a halved dose of DGA continued to be an effective regimen
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