Pharmacokinetic profile of a novel sustained-release caffeine with extended benefits on alertness and mood: A randomized, double-blind, single-dose, active-controlled, crossover study

Oral consumption of caffeine typically leads to its instant release and subsequent rapid absorption, high plasma caffeine levels followed by a quick steep decline reducing its beneficial effects which is frequently referred to as “caffeine crash”. To overcome this limitation, we developed a new slow and sustained-release caffeine (SRC) formulation, Xtenergy™. The primary objective was to compare the plasma pharmacokinetic profile of SRC with immediate-release caffeine (IRC). Secondary objectives included the use of caffeine research visual analogue scales (Caff - VAS) to evaluate some of the nootropic benefits of SRC and safety assessments. This was a randomized, double-blind, single-dose, active-controlled, crossover study. Twenty-six subjects were randomized to receive 200 mg caffeine from SRC and IRC in a crossover fashion as per the randomization schedule. Blood samples were collected at -4, 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, and 24 h in each period. Plasma caffeine levels were analyzed by a validated LC-MS/MS method. The changes in Caff-VAS relaxed, alert, jittery, tired, tense, headache, overall mood from baseline i.e., 0 to 1, 2, 4, 6, 8, 10, and 12 h were evaluated. Twenty-four male subjects with mean age 32.71±6.18 years completed the study. The median Tmax was 325.53% higher (p < 0.05) for SRC as compared to IRC (4.00 vs. 0.94 h) and mean t1/2 was 21.34% higher (p < 0.05) for SRC as compared to IRC (9.± 4.56 vs. 7.61± 3.98 h). SRC demonstrated similar total exposure as IRC based on the 90% CI of 84.63% - 114.45% for ln-transformed AUC0–24. AUC4–8 and AUC6–12 were 6.80% and 22.84% higher for SRC as compared to IRC, respectively. Compared to IRC, SRC showed significant beneficial effects (p < 0.05) on feelings of being more alert, less tired, better overall mood, less jittery and less tense at several of the study time points. No safety concerns were observed. SRC showed a slow absorption and sustained plasma caffeine levels. Compared to IRC, we saw significant benefits of SRC at several of the time points on alertness, tiredness, overall mood, jitteriness and tenseness without any safety concerns.