Abstract
Resveratrol provides multiple physiologic benefits which promote healthspan in various model species and clinical trials support continued exploration of resveratrol treatment in humans. However, there remains concern regarding low bioavailability and wide inter-individual differences in absorption and metabolism in humans, which suggests a great need to develop novel methods for resveratrol delivery. We hypothesized that oral transmucosal delivery, using a lozenge composed of a resveratrol-excipient matrix, would allow resveratrol to be absorbed rapidly into the bloodstream. We pursued proof of concept through two experiments. In the first experiment, the solubility of trans-resveratrol (tRES) in water and 2.0 M solutions of dextrose, fructose, ribose, sucrose, and xylitol was determined using HPLC. Independent t-tests with a Bonferroni correction were used to compare the solubility of tRES in each of the solutions to that in water. tRES was significantly more soluble in the ribose solution (p = 0.0013) than in the other four solutions. Given the enhanced solubility of tRES in a ribose solution, a resveratrol-ribose matrix was developed into a lozenge suitable for human consumption. Lozenges were prepared, each containing 146±5.5 mg tRES per 2000 mg of lozenge mass. Two healthy human participants consumed one of the prepared lozenges following an overnight fast. Venipuncture was performed immediately before and 15, 30, 45, and 60 minutes following lozenge administration. Maximal plasma concentrations (C max) for tRES alone (i.e., resveratrol metabolites not included) were 325 and 332 ng⋅mL−1 for the two participants at 15 minute post-administration for both individuals. These results suggest a resveratrol-ribose matrix lozenge can achieve greater C max and enter the bloodstream faster than previously reported dosage forms for gastrointestinal absorption. While this study is limited by small sample size and only one method of resveratrol delivery, it does provide proof of concept to support further exploration of novel delivery methods for resveratrol administration.
Highlights
Resveratrol is a stilbene polyphenol found in grapes and other plant products which has received considerable attention in the past decade for its potential to improve health and combat agerelated diseases [1]
The solubility of tRES was significantly enhanced in the 2.0M ribose solution (p = 0.0013), but not in fructose (p = 0.0950), dextrose (p = 0.2284), sucrose (p = 0.5824), or xylitol (p = 0.3330)
The results of this study demonstrate that ribose increases the aqueous solubility of tRES compared to its solubility in water alone
Summary
Resveratrol is a stilbene polyphenol found in grapes and other plant products which has received considerable attention in the past decade for its potential to improve health and combat agerelated diseases [1]. The dose and concentration of tRES in blood in human trials are often below the doses used in animal and cell culture studies [5,6,7,8], even with multiple daily oral doses [9]. A 5,000 mg daily dose of a proprietary tRES formulation has been associated with renal failure in multiple myeloma patients [13], where existing renal dysfunction may have been exacerbated by a large quantity of resveratrol metabolites. These side effects have limited the oral dose in most human trials to 1,000 mg or lower [14]. Most commercially available supplements contain #500 mg tRES [15]
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