Methylliberine (Dynamine; DYM) and theacrine (Teacrine; TCR) are purine alkaloids. Previous research on TCR reported increases in feelings of energy, focus, and concentration, and decreases in fatigue. Currently, there are no published human safety data on DYM. PURPOSE: The purpose of this study was to examine the effect of four weeks of DYM supplementation with and without TCR on blood biomarkers. METHODS: One-hundred twenty-five men (n = 60) and women (n = 65) were assigned to one of five groups: low dose DYM (100 mg), high dose DYM (150 mg), low dose DYM with TCR (100 mg + 50 mg), high dose DYM with TCR (150 mg + 25 mg) , and 125 mg maltodextrin. Participants visited the laboratory fasted on two occasions (week 0 and week 4), separated by four weeks of supplementation, for a blood draw. Blood was analyzed by an independent third-party (i.e. LabCorp). RESULTS: Three-way repeated measures analyses of variance were performed for all blood biomarkers. Group × sex × time interactions (p < 0.05) with post-hoc analyses revealed differences for mean corpuscular hemoglobin (MCH) concentration with MCH being higher in men consuming the placebo than women consuming low dose DYM (p = 0.028) and high dose DYM with TCR (p = 0.011) at week 4. Group × time interactions (p < 0.05) revealed differences for platelets, blood urea nitrogen, total globulins, alanine transaminase, total proteins, triglycerides, and high-density lipoproteins. However, post-hoc analyses showed specific increases for blood urea nitrogen in groups consuming low dose DYM with TCR compared to low dose DYM participants, and an increase in high-density lipoproteins in the group consuming high dose DYM. Significant main effects for time were observed. Specifically, increases in mean corpuscular volume, MCH, basophils, absolute eosinophils, creatinine, and high-density lipoproteins from week 0 to week 4, while decreases in glomerular filtration rate, chloride, carbon dioxide, bilirubin, and alanine transaminase were seen. CONCLUSIONS: While small changes were found in some biomarkers, in all cases values remained within normal clinical limits. This suggests that DYM alone or in combination with TCR consumed at the dosages used in this study does not appear to negatively impact blood biomarkers associated with health. Compound Solutions, Inc. grant