Effects of EnXtra® (Alpinia galanga Extract) and EnXtra® + Caffeine Combination on Mental Alertness and Fatigue in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Study

Purpose: To evaluate the efficacy and safety of EnXtra ® ( Alpinia galanga extract) alone, caffeine and its combination with caffeine on mental alertness and fatigue in healthy sleep-restricted adults through acute single-dose and sub-acute 28-day supplementation protocols. Patients and Methods: This randomized, double-blind, placebo-controlled study consisted of two stages: an acute crossover design (n=128) and a sub-acute 28-day parallel design (n=127). In both the stages, participants aged 18– 40 years with habitual caffeine intake received one of the following interventions: A. galanga extract (300 mg), caffeine (200 mg), A. galanga extract (300 mg) + caffeine (200 mg), or placebo (300 mg). The primary outcome was mental alertness evaluated using the Jin Fan Attention Network Test (ANT). Secondary outcomes included fatigue (Samn-Perelli Fatigue Scale (SPS)), psychomotor performance (Nine-Hole Peg Test), sustained attention (Continuous Performance Test), and safety parameters. Cognitive assessments were performed at 0, 1, 3, and 5 hours post-dose in controlled environments on each scheduled visit (Days 0, 5, 10, 15, 20, and 48). Results: In both acute and sub-acute phases, A. galanga extract showed statistically significant improvements in alertness compared with placebo at selected time points. The combination group demonstrated greater improvements in alertness compared with placebo in several assessments. Improvements in fatigue scores were also observed with A. galanga extract alone and in combination with caffeine, with statistically significant reductions compared with placebo at certain time points. Trends toward improvements in psychomotor performance (NHPT) and sustained attention (CPT) were observed with A. galanga extract, although these changes were not consistently statistically significant. In the sub-acute phase, caffeine showed improvements in alertness and fatigue primarily at 1 hour post-dose, with limited effects at later time points. Conclusion: Alpinia galanga extract, alone or combined with caffeine, significantly improved mental alertness and reduced fatigue without caffeine-associated rebound effects, with both interventions showing good safety profiles in healthy adults.