Cannabidiol (CBD) is widely available and marketed as having therapeutic properties. Over-the-counter CBD is unregulated, many of the therapeutic claims lack scientific support, and controversy exists as to the safety of CBD-liver interaction. The study aims were to compare the pharmacokinetics of commercial CBD and CBD metabolites following the ingestion of five different CBD formulations, determine the influence of CBD on food induced thermogenesis, determine the influence of food on CBD pharmacokinetics, and determine the influence of CBD on markers of liver function. Fourteen males (body mass index ≥ 25 kg/m²) were studied in a placebo-controlled, randomized, crossover design. On five occasions, different CBD formulations were ingested (one per visit). On two additional occasions, CBD or placebo was ingested following a meal. CBD servings were standardized to 30 mg. Considerable pharmacokinetic variability existed between formulations; this pharmacokinetic variability transferred to several of the metabolites. CBD did not influence food induced thermogenesis but did favorably modify early insulin and triglyceride responses. Food appreciably altered the pharmacokinetics of CBD. Finally, CBD did not evoke physiologically relevant changes in markers of liver function. Collectively, these data suggest that consumers should be aware of the appreciable pharmacokinetic differences between commercial CBD formulations, CBD is unlikely to influence the caloric cost of eating but may prove to be of some benefit to initial metabolic responses, consuming CBD with food alters the dynamics of CBD metabolism and increases systemic availability, and low-dose CBD probably does not represent a risk to normal liver function.

Data supporting the physiological effects of cannabidiol (CBD) ingestion in humans are conflicting. Differences between CBD preparations and bioavailability may contribute to these discrepancies. Further, an influence of body composition on CBD bioavailability is feasible, but currently undocumented. The aims of this study were to: (1) compare the pharmacokinetics of five oral CBD preparations over 4 h; (2) examine the relationship between body composition and CBD pharmacokinetics; and, (3) explore the influence of CBD on heart rate variability. In total, five preparations of CBD, standardized to 30 mg, were orally administered to 15 healthy men and women (21–62 years) in a randomized, crossover design. Prior to and 60 min following CBD ingestion, heart rate variability was determined. Body composition was assessed using dual energy X-ray absorptiometry. Peak circulating CBD concentration, time to peak concentration, and area under the curve was superior in a preparation comprising 5% CBD concentration liquid. Fat free mass was a significant predictor (R² = 0.365, p = 0.017) of time to peak concentration for this preparation. Several heart rate variability parameters, including peak frequency of the high frequency band, were favorably, but modestly modified following CBD ingestion. These data confirm an influence of CBD preparation and body composition on CBD bioavailability, and suggest that acute CBD ingestion may have a modest influence on autonomic regulation of heart rate.

The purpose of the study was to describe and compare the pharmacokinetics of five commercial edible marijuana products, determine the influence of body composition on pharmacokinetics, and, in light of epidemiology suggesting marijuana may offer diabetes protection, explore the influence of edible marijuana on glucose tolerance. Seven regular users of marijuana self-administered five edible products in a randomized crossover design; each product contained 10 mg of delta-9-tetrahydrocannabinol (THC). Thirty minutes following marijuana ingestion, participants imbibed a 75 g glucose beverage. Time-to-peak plasma THC concentration ranged between 35 and 90 min; maximal plasma THC concentration (C_max) ranged between 3.2 and 5.5 ng/mL. Differences between products in plasma THC concentration during the first 20–30 min were detected (p = 0.019). Relations were identified between body composition and pharmacokinetic parameters for some products; however, none of these body composition characteristics were consistently related to pharmacokinetics across all five of the products. Edible marijuana had no effect on oral glucose tolerance compared with a marijuana-free control (Matsuda Index; p > 0.395). Commercially available edible marijuana products evoke different plasma THC concentrations shortly after ingestion, but do not appear to influence acute glucose regulation. These data may allow recreational marijuana users to make informed decisions pertaining to rates of edible marijuana ingestion and avoid overdose.

Sedentary obesity is associated with increased risk of many cardio-metabolic diseases, including type 2 diabetes. Weight loss is therefore a desirable goal for sedentary adults with obesity. Weight loss is also a well-documented side effect of sodium glucose co-transporter 2 (SGLT2) inhibition, a pharmaceutical strategy for diabetes treatment. We hypothesized that, compared with placebo, SGLT2 inhibition as an adjunct to out-patient dietary counselling for weight loss would lead to more favorable modification of body mass and composition, and greater improvement in glucose regulation and lipid profile. Using a randomized, double-blind, repeated measures parallel design, 50 sedentary men and women (body mass index: 33.4 ± 4.7 kg/m²; mean ± SD) were assigned to 12 weeks of dietary counselling, supplemented with daily ingestion of either a placebo or SGLT2 inhibitor (dapagliflozin: up to 10 mg/day). Dietary counselling favorably modified body mass, body fat, glucose regulation, and fasting concentrations of triglyceride and very low-density lipoprotein cholesterol (main effects of counselling: p < 0.05); SGLT2 inhibition did not influence any of these adaptations (counselling × medication interactions: p > 0.05). However, SGLT2 inhibition when combined with dietary counselling led to greater loss of fat-free mass (counselling × medication interaction: p = 0.047) and attenuated the rise in high-density lipoprotein cholesterol (counselling × medication interaction: p = 0.028). In light of these data and the health implications of decreased fat-free mass, we recommend careful consideration before implementing SGLT2 inhibition as an adjunct to dietary counselling for weight loss in sedentary adults with obesity.

The purpose of this study was to investigate the potential ergogenic effects of an oral lactate supplement. For this double-blind, randomized, placebo-controlled crossover design, fifteen recreational exercisers (nine males, six females) ingested a placebo or a commercially available lactate supplement prior to cycle ergometer exercise. Primary outcomes included peak oxygen uptake (VO_2peak; via indirect calorimetry), VO₂ at the ventilatory threshold, and work rate at the lactate threshold (arterialized venous blood from a heated hand) determined during incremental exercise to fatigue, and power output during a 20-min cycling time trial. Compared with placebo, the oral lactate supplement (19 ± 1 mg/kg body mass) did not influence VO_2peak (placebo: 44.3 ± 7.8 vs. oral lactate: 44.3 ± 7.1 mL/kg/min (mean ± SD); p = 0.87), VO₂ at the ventilatory threshold (placebo: 1.63 ± 0.25 vs. oral lactate: 1.65 ± 0.23 L/min; p = 0.82), or work rate at the lactate threshold (placebo: 179 ± 69 vs. oral lactate: 179 ± 59 W; p = 0.41). Throughout the 20-min time trial, the work rate was slightly greater (4%) with oral lactate (204 ± 41 W) compared with placebo (197 ± 41 W; main effect of treatment p = 0.02). Collectively, these data suggest that this commercially available lactate supplement did not acutely influence the physiological responses to incremental cycle ergometer exercise but elicited a modest ergogenic effect during the short-duration time trial.

Background/Objectives: Although the importance of magnesium for overall health and physiological function is well established, its influence on exercise performance is less clear. The primary study objective was to determine the influence of short-term magnesium supplementation on cycle ergometer exercise performance. The hypothesis was that magnesium would elicit an ergogenic effect. Methods: A randomized, double-blind, placebo-controlled, two-period crossover design was used to study men and women who were regular exercisers. Fifteen participants ingested either a placebo or magnesium chloride (MgCl₂ 300 mg) twice per day, for 9 days, separated by a 3-week washout. During days 8 and 9, participants completed a battery of cycle ergometer exercise tests, and whole blood, vastus lateralis, and stools were sampled. The primary outcomes were the maximal oxygen uptake (VO_2max), a simulated 10 km time trial, and the sprint exercise performance. Additional outcomes included skeletal muscle mitochondrial respiration, and, on account of the known laxative effects of magnesium, the gut microbiota diversity. Results: Compared with a placebo, MgCl₂ supplementation increased the circulating ionized Mg concentration (p < 0.03), decreased the VO_2max (44.4 ± 7.7 vs. 41.3 ± 8.0 mL/kg/min; p = 0.005), and decreased the mean power output during a 30 s sprint (439 ± 88 vs. 415 ± 88 W; p = 0.03). The 10 km time trial was unaffected (1282 ± 126 vs. 1281 ± 97 s; p = 0.89). In skeletal muscle, MgCl₂ decreased mitochondrial respiration in the presence of fatty acids at complex II (p = 0.04). There were no significant impacts on the gut microbiota richness (CHAO1; p = 0.68), Shannon’s Diversity (p = 0.23), or the beta-diversity (Bray–Curtis distances; p = 0.74). Conclusions: In summary, magnesium supplementation had modest ergolytic effects on cycle ergometer exercise performance and mitochondrial respiration. We recommend that regular exercisers, free from hypomagnesemia, should not supplement their diet with magnesium.