Objective: Although Alpinia galanga has been reported to improve cognitive performance in animals, it has not been thoroughly studied for its potential psychostimulant effect in humans. A randomized, double-dummy, double-blind, placebo-controlled cross-over study was conducted to determine the effect of A galanga on mental alertness and sustained attention in comparison with caffeine and placebo in participants with a habitual caffeine intake.
Methods: Fifty-nine participants (18–40 years and body mass index of min 18.5 and max 25.00 kg/m2) with moderate caffeine consumption were enrolled. The participants had a Generalized Anxiety Disorder-7 score max 7, Patient Health Questionnaire-9 score max 14 and a Jin Fan’s Attention Network Test alertness score of 50 § 20 ms. The interventional product (placebo, A galanga proprietary extract [E-AG-01], caffeine, and a combination of E-AG-01 with caffeine) was administered to the participants, followed by sequential administration of the remaining interventions on the consecutive study visits; the effects on mental alertness, sustained attention, and sleep architecture, along with safety and tolerability, were analyzed by validated methods.
Results: In the E-AG-01 group, the alertness score was increased by 11.65 ± 23.94, 12.50 ± 19.73, and 12.62 ± 0.68 ms from baseline at 1, 3 (p = 0.042), and 5 hours, respectively, indicating its efficacy to enhance mental alertness and the increase in alertness score as compared to placebo. In the composite group (E-AG- 01 with caffeine), mean response time was significantly reduced, by 15.55 ms (p = 0.026) at 3 hours.
Conclusions: A galanga (E-AG-01) induces a beneficial effect in mental alertness and the combination of A galanga with caffeine impedes the caffeine crash and improves sustained attention at 3 hours. Thus, these stimulant effects might yield a new usage for A galanga as a key ingredient in energy drinks or similar products.
Effect of Alpinia galanga on Mental Alertness and Sustained Attention With or Without Caffeine: A Randomized Placebo-Controlled Study. Shalini Srivastava, Mark Mennemeier, and Surekha Pimple, 2017 American College of Nutrition. Study for enXtra

Abstract : Dopamine is a neurotransmitter responsible for sending signals from the central nervous system. It allows human beings to stay attentive and focused.
Caffeine, the most widely consumed psychoactive substance in the world, is known to improve alertness by enhancing dopamine signaling in the brain.
EnXtra®, an Alpinia galanga extract has been clinically proven to promote alertness however the mechanism for such action required elucidation. The current study was designed to explore the mechanism for the neurocognitive enhancing property of EnXtra® by the in-silico interaction of its potential compounds with various targets involved in such process namely Dopamine and Acetyl cholinesterase (AchE). As evident by the outcomes of the study, active compounds of EnXtra® can block the dopamine reuptake thereby increasing the dopamine levels which further can enhance the visuospatial performance and mental clarity, leading to improved mental alertness. At the same time, its strong effect on Acetylcholinesterase target protein is indicative of its nootropic potential.
Keyword : EnXtra®, Caffeine, Dopamine, Enovate Biolife, Energy Drink, Cognitive, In-Silico
Molecular Docking Studies of Alpinia galanga Phytoconstituents for Psychostimulant Activity - Santhy Sivanandan, Surekha Pimple - Advances in Biological Chemistry, 2018, 8, 69-80

Rationale : The market focus is being diverted to caffeine-free natural psychostimulants with an onset and duration of action comparable to the caffeine but devoid of its crash effect. In an attempt to develop an efficient alternative or adjuvant, we designed a randomized, placebo- controlled study wherein we evaluated the effect of C. flexuosus (LG), A. galanga (AG1, AG2), and G. glabra (GG1, GG2) extracts in comparison with caffeine and placebo on the different aspects of attention along with the safety profile.
Methods : In this study, 70 caffeine-habituated subjects were assessed to determine the express effect on the mean response time (MRT), alertness, orientation and execution functions by Attention Network Test over a span of 5 hours on day 1 followed by a safety assessment on day 7.
Results : Among the studied groups, LG, AG2 and GG1 were unable to exhibit a beneficial effect in any of the outcome measures; caffeine reduced MRT at 3 hours by 3.94 % (p = 0.07) as compared to the baseline and placebo; AG1 exhibited a statistically significant and stable increase in alertness score compared to the baseline until 5 hours [107.31 % at 1 hour (p = 0.07); 119.27 % at 3 hours and 103.99 % at 5 hours]; GG2 also produced a positive effect on the alertness until 3 hours (33.79 %).
Conclusion : In summary, caffeine, AG1 and GG2 demonstrated an improvement in the separate aspects of the attention network. All the interventions were safe to use as no serious adverse event occurred throughout the study. These findings necessitate the profound assessment of the AG1 (Galanga water-soluble extract) as a potential psychostimulant.
Keywords: Alertness; Attention; Caffeine Crash; Dietary Supplement; Energy Drink; Mean Response Time (MRT).
Effects of Cymbopogon Flexuosus, Alpinia Galanga, and Glycyrrhiza Glabra on Attention: A Randomized Double-Blind, Placebo-Controlled Pilot Study - Shalini Srivastava and Surekha Pimple (Enovate Biolife), BAOJ Nutrition 2017 3: 1

The purpose of the secondary analysis of the data from the clinical trial “A Study to Evaluate Efficacy of IP on Alertness and Mental Fatigue” (ClinicalTrials.gov NCT02816827) was to investigate the effect of the Alpinia galanga proprietary extract E-AG-01 (EnXtra) on focused attention, in comparison with caffeine and placebo in moderate caffeine habitués. Participants and methods: A total of 59 caffeine-habituated healthy young adults (aged 18–40 years) with body-mass index of 18.5–25.0 kg/m2 were crossed over in four interventional groups: placebo, E-AG-01, caffeine, and a combination of caffeine and E-AG-01. All participants completed the attention-network test, which measures the accuracy and speed factors of the alerting, orienting, and executive-control networks. Results: The results of accuracy parameters in terms of percentage-error rate showed a remarkable difference between E-AG-01 and the other treatment groups, wherein the error rate dropped by 1.63% (1 hour), 1.32% (3 hours), and 0.78% (5 hours) from baseline. The caffeine group demonstrated a decrease of 0.37% (1 hour) and 0.44% (3 hours), followed by an increase of 0.2% (5 hours), whereas the error rate of subjects in the caffeine + E-AG-01 group decreased by 0.24% (1 hour) and 0.26% (3 hours), followed by an increase of 0.2% at 5 hours. The placebo group exhibited an increase of 0.14% (3 hours) and 0.77% (5 hours). Conclusion: These results show that E-AG-01 exhibited selectively enhanced focused attention to a higher extent in comparison with caffeine and placebo. Keywords: accuracy, ANT, dietary supplement, error rate, energy drink, EnXtra, clinical trial
Selective enhancement of focused attention by Alpinia galanga in subjects with moderate caffeine consumption, Shalini Srivastava, Journal of Clinical Trials 2018

ABSTRACT
Objective: The present randomized, placebo-controlled study aimed to assess the long-term safety and perceivable mental acuity benefits of EnXtra in healthy individuals.
Methods: Study participants were administered EnXtra with or without caffeine for a period of 12 weeks. The cardiovascular safety was evaluated by assessing change in QT interval, blood pressure and heart rate. Further, other efficacy variables evaluated were change in perceived alertness and calmness by Bond and Lader mood scales, Sleep disturbance by Pittsburgh sleep quality Index and daytime sleepiness by Epworth sleepiness scale.
Results: None of the study group showed any significant change in the ECG or haemodynamic parameters as compared to baseline (p min 0.05). Post consumption, alertness and calmness scores were significantly increased in the EnXtra , and EnXtra plus caffeine group (p max 0.001) as compared to placebo. Daytime sleep scores decreased in the EnXtra group however change was not significant. Sleep quality remained undisturbed in all three arms.
Conclusion: The findings demonstrated the psychostimulant efficacy of EnXtraVR with no safety concerns on long-term usage.
Abbreviation: HRV: Heart rate variability; GCP: Good Clinical Practices; GAD: Generalized Anxiety Disorder; PHQ: Patient Health Questionnaire; ECG: Electrocardiogram; BP: Blood pressure; HR: Heart rate; ESS: Epworth Sleepiness Scale; PSQI: Pittsburgh Sleep Quality Index
A Randomized Placebo Controlled Clinical Trial Demonstrating Safety and Efficacy of EnXtra in Healthy Adults - Shalini Srivastava, Mark Mennemeier and Jayesh Anand Chaudhary - Journal Of The American College Of Nutrition

Background: Nootropics are products that improve cognitive function and offer consumers solutions to optimise performance at work and play. Alpinia galanga Extract (AGE) has been shown to increase mental alertness in clinical settings.
Aim: We evaluated the acute effect of AGE on mental alertness, accuracy, and fatigue through a randomized, double-blind, placebo-controlled, cross-over clinical study in healthy human subjects.
Methods: Sixty-two adults were randomized to receive either 300mg of AGE or placebo 30 minutes after lunch on Day 1 followed by cross-over treatments on Day 7. The primary objective was to evaluate the effect of AGE on mental alertness and accuracy, as assessed by Symbol Digit Coding test, Shifting Attention test, Stroop Test and Alertness Rating Scale of CNS Vital Signs at baseline, 0.5, 1-, 2- and 5-hours post dose. Further, fatigue and energy levels were measured by Visual Analogue Scale and daytime sleepiness by Epworth Sleepiness Scale as secondary outcomes. Adverse events were monitored for safety assessment.
Results: AGE supplementation showed significant improvements in alertness, reaction time, correct responses, and reduction in errors at several time points over placebo. Further, AGE consumption demonstrated significant increase in subjective feelings of energy and decreased fatigue levels over placebo.
Conclusion: AGE supplementation improves alertness, accuracy, reaction time, and reduces errors in individuals, and may be a reasonable alternative to caffeine for those seeking same-day effects to increase alertness and energy levels.
The study provides strong support for the acute effect of enXtra on improved alertness, accuracy, and attention as early as 30 minutes after supplementation and lasting for up to five hours. This evidence strengthens the findings of previous studies in this area. We believe that AGE could be a viable alternative to caffeine for individuals seeking to increase their alertness, accuracy, and energy levels.
Keywords: Alpinia galanga; Cognitive impairment; Energy; Mental alertness; Mental fatigue; Nootropics
Acute Effects of Alpinia galanga Extract on Mental Alertness, Accuracy and Fatigue in Human Subjects: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study - Mohan Muttanahally Eraiah, Mamatha Kundapur, Lincy Joshua and Jestin V Thomas - Advances in Complementary / Alternative Medicine 18/05/2023