A Randomized Double-Blind Placebo-Controlled Trial of a Purported Dietary Supplement Cognitive Enhancer in Healthy Teenage Subjects Original Research

Main Article Content

Jaime Tartar
Marc Astacio
Minh Chau
Lois Lin
Ashley LeMoire
Jonathan Banks


Supplement, alpha-GPC, Cognition, Nootropics, Phosphatidylserine


Introduction: The prevalence of using dietary supplements among teenagers is rising. In particular, the use of nutritional supplements to improve cognitive performance is becoming more commonplace. Given the prevalence of use, it is important to empirically assess the effects of nutritional supplements on cognitive performance. The current study sought to test the effects of an existing cognition supplement, Brain Doctors’ Formula® (BDF) Mega Brain Boost® (MBB), across different cognitive domains in a healthy teenage population.

Methods: We carried out a 6-week randomized, placebo-controlled, double-blind study. The study lasted approximately 42 days (6 weeks) for each participant. Study visits included screening and baseline testing, week 3 interim and week 6 end of study visit. Cognition outcomes were measured by the National Institutes of Health (NIH) Toolbox Cognitive Battery of Testing (Dimensional Change, Flanker, and Pattern Comparison) and a Symmetry Span Task at baseline, interim, and final visits. Another efficacy outcome was the self-assessment of mind wandering, which was captured in a study daily diary from baseline to the end of study visit. There were two study groups, including one MBB group and one placebo group. Twenty-four participants were screened and randomized to include 12 participants in each group.

Results: The change from baseline to interim (Week 3) and from baseline to the final visit (Week 6) did not show a significant between-group difference on any measure of cognition (all p-values >0.05) except one. There was a significant between-group difference with a large effect size at Week 3 showing that the MBB group performed significantly better than the placebo group on the Dimensional Change Card Sort Task.

Conclusions: This study suggests that MBB potentially improves executive cognitive processes (as assessed by the Dimensional Change Card Sort Task) in healthy teenagers. However, this effect was only significant at the interim visit. Therefore, it is uncertain if there are any lasting beneficial effects. Further research should be conducted in a larger group of participants and focus on broader measures of executive function.

Abstract 683 | PDF Downloads 233


1. Alsulaimani RA, Quinn TJ. The efficacy and safety of animal-derived nootropics in cognitive disorders: systematic review and meta-analysis. Cerebral Circulation-Cognition and Behavior 2021;2:100012
2. Dresler M, Sandberg A, Bublitz C, et al. Hacking the brain: dimensions of cognitive enhancement. ACS chemical neuroscience 2018;10(3):1137-48
3. Roe AL, Venkataraman A. The Safety and Efficacy of Botanicals with Nootropic Effects. Current Neuropharmacology 2021;19(9):1442
4. Stierman B, Mishra S, Gahche JJ, Potischman N, Hales CM. Dietary supplement use in children and adolescents aged≤ 19 years—United States, 2017–2018. Morbidity and Mortality Weekly Report 2020;69(43):1557
5. Herbold NH, Vazquez IM, Goodman E, Emans SJ. Vitamin, mineral, herbal, and other supplement use by adolescents. Topics in Clinical Nutrition 2004;19(4):266-72
6. Hirayama S, Terasawa K, Rabeler R, et al. The effect of phosphatidylserine administration on memory and symptoms of attention‐deficit hyperactivity disorder: A randomised, double‐blind, placebo‐controlled clinical trial. Journal of human nutrition and dietetics 2014;27:284-91
7. Zhang Y, Jia X, Chen X, et al. L-theanine and Neumentix mixture improves sleep quality and modulates brain neurotransmitter levels in mice. Ann Palliat Med 2021;10(4):4572-81 doi: 10.21037/apm-21-663[published Online First: Epub Date]|.
8. Falcone PH, Nieman KM, Tribby AC, et al. The attention-enhancing effects of spearmint extract supplementation in healthy men and women: a randomized, double-blind, placebo-controlled, parallel trial. Nutr Res 2019;64:24-38 doi: 10.1016/j.nutres.2018.11.012[published Online First: Epub Date]|.
9. Glade MJ, Smith K. Phosphatidylserine and the human brain. Nutrition 2015;31(6):781-6 doi: 10.1016/j.nut.2014.10.014[published Online First: Epub Date]|.
10. Moré MI, Freitas U, Rutenberg D. Positive effects of soy lecithin-derived phosphatidylserine plus phosphatidic acid on memory, cognition, daily functioning, and mood in elderly patients with Alzheimer's disease and dementia. Adv Ther 2014;31(12):1247-62 doi: 10.1007/s12325-014-0165-1[published Online First: Epub Date]|.
11. Lee SH, Choi BY, Kim JH, et al. Late treatment with choline alfoscerate (l-alpha glycerylphosphorylcholine, α-GPC) increases hippocampal neurogenesis and provides protection against seizure-induced neuronal death and cognitive impairment. Brain Res 2017;1654(Pt A):66-76 doi: 10.1016/j.brainres.2016.10.011[published Online First: Epub Date]|.
12. Kim J, Song Y, Lee SJ, et al. Enzymatic preparation of food-grade l-α-glycerylphosphorylcholine from soy phosphatidylcholine or fractionated soy lecithin. Biotechnol Prog 2020;36(1):e2910 doi: 10.1002/btpr.2910[published Online First: Epub Date]|.
13. Yamada Y, Nishii K, Kuwata K, et al. Effects of pyrroloquinoline quinone and imidazole pyrroloquinoline on biological activities and neural functions. Heliyon 2020;6(1):e03240 doi: 10.1016/j.heliyon.2020.e03240[published Online First: Epub Date]|.
14. Taylor BK, Frenzel MR, Eastman JA, et al. Reliability of the NIH toolbox cognitive battery in children and adolescents: a 3-year longitudinal examination. Psychological Medicine 2020:1-10 doi: 10.1017/S0033291720003487[published Online First: Epub Date]|.
15. Weintraub S, Dikmen SS, Heaton RK, et al. Cognition assessment using the NIH Toolbox. Neurology 2013;80(11 Suppl 3):S54-64 doi: 10.1212/WNL.0b013e3182872ded[published Online First: Epub Date]|.
16. Foster JL, Shipstead Z, Harrison TL, Hicks KL, Redick TS, Engle RW. Shortened complex span tasks can reliably measure working memory capacity. Mem Cognit 2015;43(2):226-36 doi: 10.3758/s13421-014-0461-7[published Online First: Epub Date]|.
17. Walfish S. A review of statistical outlier methods. Pharmaceutical technology 2006;30(11):82
18. Miyake A, Friedman NP, Emerson MJ, Witzki AH, Howerter A, Wager TD. The unity and diversity of executive functions and their contributions to complex “frontal lobe” tasks: A latent variable analysis. Cognitive psychology 2000;41(1):49-100
19. Richter Y, Herzog Y, Lifshitz Y, Hayun R, Zchut S. The effect of soybean-derived phosphatidylserine on cognitive performance in elderly with subjective memory complaints: a pilot study. Clinical interventions in aging 2013;8:557
20. Shiojima Y, Takahashi M, Takahashi R, et al. Effect of dietary pyrroloquinoline quinone disodium salt on cognitive function in healthy volunteers: A randomized, double-blind, placebo-controlled, parallel-group study. Journal of the American College of Nutrition 2021:1-14
21. Ostfeld I, Ben-Moshe Y, Hoffman MW, Shalev H, Hoffman JR. Effect of Spearmint Extract Containing Rosmarinic Acid on Physical and Executive Functioning After a Tactical Operation. Journal of Special Operations Medicine: a Peer Reviewed Journal for SOF Medical Professionals 2018;18(4):92-96
22. Parnetti L, Mignini F, Tomassoni D, Traini E, Amenta F. Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation? Journal of the neurological sciences 2007;257(1-2):264-69
23. Luciana M, Conklin HM, Hooper CJ, Yarger RS. The development of nonverbal working memory and executive control processes in adolescents. Child development 2005;76(3):697-712

Most read articles by the same author(s)