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.
Over the past 50 years, intentional genetic selection within the broiler industry has led to major improvements in both body weight gain (BWG) and feed conversion efficiency. Next to its economic advantages, enhancing BWG can increase the risk for metabolic and skeletal disorders. The aim of this study was to examine whether higher BWG is a predisposing factor for broiler necrotic enteritis. In this study, 300 broilers were challenged with Clostridium perfringens using a well-established, previously described challenge model. It was found that birds with a higher body weight (BW) and BWG before challenge were predisposed to develop more severe necrotic enteritis lesions. After challenge, the average BWG of the birds developing mild to severe lesions dropped significantly, negatively affecting animal welfare and performance. These results show a significant interplay between BWG and the development of necrotic enteritis lesions. This raises the question whether there is a limit to broiler performance with respect to maintaining intestinal health, and whether decreasing BWG (at certain stages of the growth cycle) can be part of a plan to prevent intestinal pathology. Research highlights Higher body weight is a predisposing factor to necrotic enteritis in broilers.
It has been shown that small doses of oral D-glyceric acid (DGA) activate mitochondrial metabolism and reduce inflammation among 50–60-year-old healthy volunteers. The present results with the same small doses reveal that after a 4-day DGA regimen, a dose of DGA activated the HO-1 pathway acutely, while enhanced inflammatory status after the 4-day DGA regimen seemed to be able to downregulate the HO-1 pathway in non-acute measurement. Blood bilirubin was strongly upregulated towards the end of the altogether 21-day study period with positive associations towards improved inflammation and reduced blood triglycerides. After the 4-day DGA regimen, hepatic inflow of blood bilirubin with albumin as the carrier was clearly upregulated in the lower-aerobic-capacity persons. At the same time also, blood triglycerides were down, pointing possibly to the activation of liver fatty acid oxidation. The combination of activated aerobic energy metabolism with transient HO-1 pathway activation and the upregulation of blood bilirubin may reduce the risks of chronic diseases, especially in aging. Furthermore, there exist certain diseases with unsatisfactorily-met medical needs, such as fatty and cholestatic liver diseases, and Parkinson’s disease, that can be possibly ameliorated with the whole-body mechanism of the action of the DGA regimen.
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
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