Exploring the bioavailability and bioactivity of thiamine versus allithiamine: studies in Drosophila melanogaster and mice.

OBJECTIVE

Thiamine (vitamin B1) is an essential micronutrient involved in carbohydrate metabolism and mitochondrial function. Allithiamine, a lipid-soluble thiamine derivative, has been proposed to exhibit thiamine bioactivity.

METHODS

Here, we conducted complementary studies in Drosophila melanogaster and laboratory mice to compare the bioavailability and bioactivity of thiamine and allithiamine. First Drosophila was established as a whole-organism model to assess thiamine activity. Flies were reared on a chemically defined, thiamine-free medium supplemented with thiamine, allithiamine or benfotiamine as a lipophilic reference compound. Developmental progression was monitored from egg to adult. In a subsequent mouse experiment, growing thiamine-deficient mice were supplemented with either thiamine or allithiamine up to 7 days. Thiamine status was determined by HPLC-based quantification of whole blood thiamine levels, in parallel with assessments of metabolic and enzymatic parameters.

RESULTS

In flies, thiamine deficiency caused developmental arrest at the first-instar larval stage, whereas supplementation with thiamine or allithiamine fully restored normal development. Notably, HPLC analysis revealed slightly higher tissue thiamine levels following allithiamine supplementation. In thiamine-depleted mice, supplementation with either thiamine or allithiamine resulted in similarly elevated whole blood thiamine levels and increased phosphorylated pyruvate dehydrogenase E1 subunit alpha (pPDHA1) to total PDHA1 ratios. Mitochondrial oxidative phosphorylation (OXPHOS) related protein levels remained largely unchanged, except for moderate increases in ATP synthase F1 subunit alpha (ATP5A). Likewise, only minor effects on mRNA levels of thiamine-related genes were observed following supplementation with either vitamer.

CONCLUSION

Together, these findings provide the first direct in vivo comparison of thiamine and allithiamine across two complementary animal models. Thiamine and allithiamine exhibited comparable bioavailability and biological activity under controlled experimental conditions, while revealing subtle differences in early metabolic regulation. These results establish allithiamine as a biologically active thiamine vitamer in vivo. They further highlight post-translational regulation as a key mechanism governing metabolic adaptation to thiamine repletion with implications for nutrition research and the evaluation of thiamine vitamers in dietary strategies.