Does the Time of Day Play a Role in the Acute Effect of p-Synephrine on Fat Oxidation Rate during Exercise in Women? A Randomized, Crossover and Double-Blind Study

p-Synephrine is deemed a safe and effective substance to increase fat utilization during exercise of low-to-moderate intensity in men but not in women. Additionally, the existence of a diurnal variation in substrate utilization has been documented during exercise with enhanced fat oxidation in the evening compared with early morning. However, it remains unknown whether there is an interaction between the effect of p-synephrine and the time of the day on fat oxidation during exercise. This study aimed to evaluate the effect of the acute ingestion of 3 milligram of p-synephrine per kilogram of body mass (mg/kg) on fat oxidation during exercise of increasing intensity when the exercise is performed in the morning vs. the evening. Using a randomized, double-blind, placebo-controlled experimental design, 16 healthy and active women performed four identical exercise trials after the ingestion of 3 mg/kg of p-synephrine and 3 mg/kg of a placebo (cellulose) both in the morning (8-10 am) and in the evening (5-7 pm). In the exercise trials, the substances were ingested 60 min before an incremental test on a cycle ergometer with 3 min stages at workloads from 30 to 80% of maximal oxygen uptake (VO(2)max). Substrate oxidation rates were measured by indirect calorimetry. In each trial, the maximum rate of fat oxidation (MFO) and the intensity that elicited MFO (Fatmax) were measured. A two-way analysis of variance (time-of-the day x substance) was used to detect differences among the trials. With the placebo, MFO was 0.25 +/- 0.11 g/min in the morning and 0.24 +/- 0.07 g/min in the evening. With p-synephrine, MFO was 0.26 +/- 0.09 g/min in the morning and 0.21 +/- 0.07 g/min in the evening. There was no main effect of substance (p = 0.349), time of day (p = 0.186) and the substance x time of day (p = 0.365) on MFO. Additionally, Fatmax was reached at a similar exercise intensity with the placebo (41.33 +/- 8.34% VO(2)max in the morning and 44.38 +/- 7.37% VO(2)max in the evening) and with p-synephrine (43.33 +/- 7.24% VO(2)max in the morning and 45.00 +/- 7.43% VO(2)max in the evening), irrespective of the time of day with no main effect of substance (p = 0.633), time of day (p = 0.191), or interaction (p = 0.580). In summary, the acute intake of 3 mg/kg of p-synephrine before exercise did not increase MFO and Fatmax, independently of the time of day, in female athletes. This indicates that the time of day is not a factor explaining the lack of effectiveness of this substance to enhance fat oxidation during aerobic exercise in women.