Analysis of Safety from a Human Clinical Trial with Pterostilbene

Objectives. The purpose of this trial was to evaluate the safety of long-term pterostilbene administration in humans. Methodology. The trial was a prospective, randomized, double-blind placebo-controlled intervention trial enrolling patients with hypercholesterolemia (defined as a baseline total cholesterol ≥200？mg/dL and/or baseline low-density lipoprotein cholesterol ≥100？mg/dL). Eighty subjects were divided equally into one of four groups: (1) pterostilbene 125？mg twice daily, (2) pterostilbene 50？mg twice daily, (3) pterostilbene 50？mg + grape extract (GE) 100？mg twice daily, and (4) matching placebo twice daily for 6–8 weeks. Safety markers included biochemical and subjective measures. Linear mixed models were used to estimate primary safety measure treatment effects. Results. The majority of patients completed the trial (91.3%). The average age was 54 years. The majority of patients were females (71%) and Caucasians (70%). There were no adverse drug reactions (ADRs) on hepatic, renal, or glucose markers based on biochemical analysis. There were no statistically significant self-reported or major ADRs. Conclusion. Pterostilbene is generally safe for use in humans up to 250？mg/day. 1. Introduction Pterostilbene is a phenol that is chemically related to resveratrol, a possible contributor to the “French Paradox” which associates red wine consumption and lower coronary heart disease [1, 2]. Naturally found in blueberries and grapes, pterostilbene is a phytoalexin, a class of compounds naturally synthesized by plants during pathogen infection. The primary structural difference between pterostilbene and resveratrol is that pterostilbene contains two methoxy groups and one hydroxyl group while resveratrol has three hydroxyl groups. The two methoxy groups cause pterostilbene to be more lipophilic, which increases oral absorption and gives pterostilbene a higher potential for cellular uptake [3]. Pterostilbene has a longer half-life (105 minutes versus 14 minutes) and higher oral bioavailability (80% versus 20%) compared to resveratrol [4–7]. Pterostilbene also has low total body clearance and subsequent Vss which suggests extensive tissue distribution [4]. There has been extensive animal research examining both the safety and efficacy of pterostilbene. Animal studies have demonstrated efficacy in cardiometabolics (e.g., cholesterol and blood glucose), as well as cancer and cognition mediators [8–10]. Substances that are generally recognized as safe (GRAS) are exempt from premarket Food and Drug Administration (FDA) review and may be intentionally added to