*Article* **Heme Oxygenase-1 and Blood Bilirubin Are Gradually Activated by Oral D-Glyceric Acid**

**O. Petteri Hirvonen \*, Maarit Lehti, Heikki Kyröläinen and Heikki Kainulainen**

Faculty of Sport and Health Sciences, Neuromuscular Research Center, University of Jyväskylä, 40014 Jyväskylä, Finland

**\*** Correspondence: petteri.hirvonen@replicon.fi

**Abstract:** 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-aerobiccapacity 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 unsatisfactorilymet 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.

**Keywords:** HO-1; bilirubin; HIF-1α; subclinical inflammation; ROS
