Pharmacokinetics and safety of calcium L-threonate in healthy volunteers after single and multiple oral administrations

Abstract

Aim:To evaluate the pharmacokinetics of L-threonate after single or multiple oral administrations and its safety profile in healthy Chinese volunteers. Methods:This was an open-label, single-and multiple-dose study. The subjects were assigned to receive a single dose, 675, 2025, or 4050 mg, of calcium L-threonate (n=12) or repeated doses of 2025 mg twice daily for 4 d (n=12). Serial plasma and urine samples were analyzed with HPLC-MS/MS. Pharmacokinetic parameters of L-threonate were calculated using non-compartmental analysis with WinNonlin software. Results: In the single dose group, C max reached at 2.0 h and the mean t 1/2 was approximately 2.5 h. Area under curve (AUC) and C max increased with dose escalation, but dose proportionality was not observed over the range of 675 to 4050 mg. AUC and C max in the fasted subjects were lower compared with those in the non-fasted subjects. Cumulative urinary excretion of L-threonate over 24 h represented 5.9% of the administered dose with a mean Cl/r of 0.8 L/h. In the multiple-dose study, no accumulation appeared upon repeated doses of 2025 mg twice daily for 4 d. There were no serious adverse events that occurred during this study. Conclusion: Calcium L-threonate was well tolerated in healthy Chinese subjects, with no pattern of dose-related adverse events. Plasma exposure increased with dose escalation, but linear pharmacokinetics were not observed over the studied doses. L-threonate was absorbed rapidly, and its absorption was enhanced by food intake. No systemic accumulation appeared after repeated administrations.

Gut microbiota and metabolite alterations associated with reduced bone mineral density or bone metabolic indexes in postmenopausal osteoporosis

“…However, laboratory studies have shown that L-lysine supplements can cause bone-building cells to be more active, with enhanced collagen production [52]. The calcium salt of L-threonate has been developed for osteoporosis treatment [53]. These findings appear to be inconsistent with our results, but much of the relevant existing literature is based on rodent studies, a small number of specimens or a specific type of osteoporosis.…”

Safety of magnesium l‐threonate as a novel food pursuant to regulation (EU) 2015/2283 and bioavailability of magnesium from this source in the context of Directive 2002/46/EC

“…The Panel notes that the available information on the metabolic fate of threonic acid in the human body is very limited, and the conversion of threonic acid to oxalic acid has not been reported. In the study by Wang et al (2011), no accumulation of l-threonate in the plasma was observed after repeated doses of 2025 mg twice daily for 4 days.…”

Canine Carboxyl- and Hydroxyl-Containing Metabolites Altered after a Three-Week Supplementation of Cannabidiol (CBD)-Containing Treats in an Exploratory Study

“…Increased concentrations of an isomer of threonate, 2-hydroxy-3-oxopropanoate, nicotinate, 3-oxopropanoate, an isomer of 3-oxopropanoate, deoxyadenosine, and an isomer of deoxyadenosine may suggest an alteration of vitamin and nucleotide metabolism by CBD. Threonate is an intermediate in ascorbate metabolism that is thought to play a role in bone mineralization, prevent androgendriven balding, and improve learning and memory when combined with magnesium [97][98][99]. Nicotinate, or vitamin B3, is required for the formation of coenzymes NAD and NADP.…”