Enhanced bioavailability and relative distribution of free (unconjugated) curcuminoids following the oral administration of a food-grade formulation with fenugreek dietary fibre: A randomised double-blind crossover study

•Enhanced free curcuminoids oral bioavailability (>45×) with improved pharmacokinetics.•Randomised double-blinded crossover study on largest number of subjects (n = 50).•Relative distribution of free curcuminoids over conjugated metabolites in plasma.•CGM provided >70% of the absorbed curcuminoids in unconjugated form.•Formulation of curcumin with fenugreek galactomannans as curcumagalactomannosides (CGM). Despite the various reports on enhanced bioavailable formulations of curcumin, systemic oral bioavailability of unconjugated curcuminoids remains a challenge. Considering the differences in plasma bioactivity and membrane permeability of free curcuminoids over conjugated metabolites, herein we report a randomised double-blinded crossover study (n = 50) to investigate the relative bioavailability and pharmacokinetics of free curcuminoids following the oral administration of high (1000 mg) and low (250 mg) doses of a food-grade formulation of curcumin with fenugreek dietary fibre as curcumagalactomannosides (CGM), which was reported to exhibit improved blood-brain – barrier permeability in rats. CGM administration provided over 45.5-fold enhancement in free curcuminoids bioavailability with improved pharmacokinetics when compared to unformulated standard curcumin. Further investigations with and without enzymatic hydrolysis of plasma collected over 5 h post-administration of CGM at 1000 mg dose revealed higher free curcuminoids in plasma (74 ± 8%) as compared to conjugated curcuminoids (26 ± 12%) indicating a significant distribution of free curcuminoids over conjugated curcumin metabolites.