Citicoline is chemically identical to CPD-choline, a compound naturally produced by the body as a precursor to critical plasma membrane phospholipids. Citicoline also serves as a choline donor for the synthesis of the key parasympathetic neurotransmitter acetylcholine. Scientific research has proven the compound to have neuroprotective properties, supporting neuroplasticity and encouraging endogenous neurorepair (Grieb, 2014).* Administered clinically, Citicoline is proven to be efficacious at helping with memory loss, encouraging recovery in stroke patients and improving vision in individuals with glaucoma (Quareshi and Endres, 2010).* As a nootropic agent, Citicoline has been utilised in healthy adults to improve focus and attention; randomised placebo-controlled trials have shown it to improve cognitive inhibition, attentional performance, accuracy and impulsivity (McGlade et al., 2015; Cook et al., 2018).*

Citicoline is a rich choline source. Our bodies synthesise acetylcholine from choline. There are three supplements for obtaining choline; namely, choline bitartrate, Alpha GPC and citicoline. Choline bitartrate is a cheap form of choline that doesn’t effectively cross the blood-brain barrier. Alpha GPC is a good choline source that can cross it. Finally, citicoline is the most expensive because it’s more than just a choline source. It supplies both choline and another compound called cytidine. Cytidine is the precursor to the nootropic compound uridine. Uridine itself is another standalone ingredient in Zenergize, ensuring you obtain it from two different sources.

Citicoline reaches peak plasma concentration within an hour. It has a long half-life of 71 hours, so if you’re taking it daily, very little goes a long way. Taking too much can be overly mentally stimulating and counterproductive. Therefore, 50 milligrams per day is the optimal amount we selected to include in each capsule. It can be taken daily at that level for more extended periods without building up too much in your system over time.*

Uridine is one of the five standard nucleosides that make up nucleic acids – biopolymers that form all of human life (Wurtman et al., 2006). Pyrimidine nucleosides such as uridine are paramount for mitochondrial function, catecholamine synthesis, and glutamatergic transmission in the brain (Kondo et al., 2011), thus evidencing the importance of uridine for cognitive development health.* Uridine also acts as a precursor to brain phosphatidylcholine, a major choline source for acetylcholine production (Wurtman et al., 2006). Several studies have seen Uridine supplementation improve memory function and learning ability (Kuś, 2020), as well as having beneficial effects on mood and well-being (Kuś, 2020; Kondo et al., 2011).* In addition, there is some evidence suggesting supplementation with uridine can slow brain atrophy and improve measures of cognition (Baumel et al., 2021).*

DL-phenylalanine (DLPA) is a racemic mixture of the essential amino acid L-phenylalanine and its pharmacologically active enantiomer, D-phenylalanine. Although L-phenylalanine cannot be produced by the body, it is a critical amino acid. Supplementation with DLPA has been used to treat depression, ADHD, chronic non-malignant pain.* It has been shown to decrease stress and improve energy levels (Russel and McCarthy, 2000).* In the human body, phenylalanine hydroxylase converts phenylalanine to tyrosine, a precursor for the critical neurotransmitters adrenaline, noradrenaline and dopamine (Akram et al., 2020). DLPA has been administered to improve mood in individuals with low noradrenaline (Meyers, 2000).* Supplementation has also shown phenylalanine to contribute to cognitive improvement, though the mechanism is not entirely understood in humans (Pranav, 2013). Utilising phenylalanine as a nootropic has been shown to improve concentration, focus and motivation, alongside improving mood and relieving anxiety (Schulz et al., 2004).*

Caffeine works by binding to adenosine, a compound that is thought to regulate the sleep cycle. Studies have found that caffeine may support cognitive function and feelings of mental alertness, mood, and arousal (Lagarde et al., 2000, De Valck and Cluydts, 2001, Goldstein et al., 2010, Nehlig, 2010).* Caffeine may also help maintain vigilance and choice reaction time (Patat et al., 2000, Lieberman et al., 2002, Mclellan et al., 2005).* Caffeine reaches peak plasma levels at 3 hours following ingestion (Gonzalez et al., 2015). Wells et al. (2014) found that 28 consecutive days of ingestion was safe and well-tolerated.

L-Tyrosine is a non-essential amino acid that is metabolised to make dopamine. Dopamine is associated with motivation, reward and pleasurable feelings (Schultz, 2007, Berke, 2018).* It also appears to play a role in motor coordination of bodily movements, meaning it may potentially also be associated with physical performance (Kawashima et al., 2018).* In a study of 50 Olympic athletes and 100 nonprofessional athletes, Filonzi et al. (2015) suggested a “strong role of dopamine neurotransmitter in determining sports success, highlighting the role of emotional control and psychological management to reach high-level performances.” Dopamine is also a precursor for norepinephrine and adrenaline (Joh and Hwang, 1987).* Some evidence suggests that supplementing with tyrosine may support neurotransmitter function and cognitive performance in cases where the neurotransmitter supply is depleted due to challenging circumstances (Jongkees et al., 2015).* Increasing tyrosine levels means more of the amino acid available to be recruited for dopamine synthesis when required (Jongkees et al., 2015).* 

L-theanine is a compound found abundantly in green tea, black tea, and certain species of mushroom (Dietz and Dekker, 2017).* Some studies suggest it may support calmness and potentially help mitigate caffeine-induced physical arousal (Dietz and Dekker, 2017, Hidese et al., 2019).* It has also been suggested that it may also support verbal fluency and executive function (Hidese et al., 2019).* L-theanine has a chemical structure very similar to glutamate, a naturally occurring amino acid in the body that helps transmit nerve impulses (Adhikary and Mandal, 2017). L-theanine is metabolised into glutamate (Adhikary and Mandal, 2017). L-theanine supports dopamine and serotonin production and may also support relaxation by enhancing alpha brainwave activity (Nathan et al., 2006, Adhikary and Mandal, 2017).* It is thought to promote relaxation by supporting GABAergic neural pathways (Nathan et al., 2006).*

Panax ginseng is a root native to the mountains of Eastern Asia. It has been traditionally used for promoting energy and supporting resistance to stress for millennia (Rokot et al., 2016).* Classified as an adaptogen (Rokot et al., 2016), Panax ginseng may play a role in helping to support the regulation of hormones such as adrenaline, noradrenaline and dopamine, as well as to support calmness during heightened stress response (Kim et al., 2010, Lee and Rhee, 2017, Tian et al., 2020, Hou et al., 2020).* It is thought to support endurance and stress resistance by mildly stimulating the central nervous system (Barman et al., 2019, Hou et al., 2020).* Ginsenosides and other constituents from ginseng may also support cognition and help to maintain healthy memory (Kim, 2012, Yeo et al., 2012, Rokot et al., 2016, Lho, Kim and Kwak, 2018, Hou et al., 2020).*

Rhodiola rosea, hailing from cold mountainous regions throughout the Northern Hemisphere, has been classified as an adaptogen (Panossian et al., 2007).* It is thought to support resistance to stress by mediating the release of cortisol while simultaneously helping to maintain concentration and alertness (Panossian et al., 2007, Jówko et al., 2018).* Rhodiola may also support physical performance, but evidence of this has been mixed (Walker, 2006, Duncan and Clarke, 2012, Jówko et al., 2018, Ballmann et al., 2019).* Additionally, it may be beneficial for supporting against stress and fatigue (Spasov et al., 2000, Olsson, 2009, Jówko et al., 2018).* The USSR classified Rhodiola as a viable performance-enhancing supplement for their astronauts (Panossian and Wikman, 2010).*

Guarana is a caffeine-rich fruit resembling an eyeball that is indigenous to the Amazon basin. Native tribes have reportedly used it to support wakefulness and as an aphrodisiac (Konstantinos and Heun, 2019).* It has been suggested that guarana may work in synergy with caffeine and as such may be more effective than caffeine alone, but the evidence in support of this claim is lacking (Moustakas et al., 2015, Pomportes et al., 2019, Konstantinos and Heun, 2019).* It is, however, the richest known source of natural caffeine in existence (Konstantinos and Heun, 2019). Additionally, guarana contains tannins and catechins, which may help maintain memory and support cognition (Peixoto et al., 2017, Santana and Macedo, 2018, Konstantinos and Heun, 2019).*

Adhikary, R. and Mandal, V. 2017. Asian Pacific J of T Bio, 7(9), 842-848.

Akram, M., Daniyal, M., Ali, A., Zainab, R., Shah, S.M.A., Munir, N. and Tahir, I.M., 2020. In Synucleins-Biochemistry. IntechOpen.

Ballmann, C. G., Maze, S. B., Wells, A. C., Marshall, M. M. & Rogers, R. R. 2019. J Sports Sci, 37, 998-1003.

Barman, S., Majumder, M., Bagchi, A., Raha, A., Mukherjee, P. and Pal, M. 2019. TPI, 8(5), 420-422.

Baumel, B.S., Doraiswamy, P.M., Sabbagh, M. and Wurtman, R., 2021. Neurology and therapy, 10(1), pp.43-60.

Bello, M.L., Walker, A.J., McFadden, B.A., Sanders, D.J, & Arent, S.M. 2019. J Int Soc Sports Nutr 16, 20.

Berke, J.D. 2018. Nat Neurosci 21, 787–793.

Betendorf‭, ‬J.F.‭ 1909. Revista‭ ‬do‭ ‬Instituto‭ ‬Historico‬ e‭ ‬Geographico‭ ‬Brazileiro‭, 72, 1–682.‬‬

Cook, S., 2018 NMJ, Impact Health Media, Inc.

Daubner, S. C., Le, T., & Wang, S. 2011. Archives of biochemistry and biophysics, 508(1), 1–12.

Davis, M. P. & Behm, B. 2019. Am J HPC, 36, 630-659.

De Valck, E. & Cluydts, R. 2001. Journal of Sleep Research, 10, 203-209.

Dietz, C. & Dekker, M. 2017. Curr P Des, 23, 2876-2905.

Duncan, M. J. & Clarke, N. D. 2014. J Sports M (Hindawi Publ Corp), 2014, 563043.

Edwards, H. G. M., Farwell, D. W., De Oliveira, L. F. C., Alia, J., Le Hyaric, M. & De Ameida, M. V. 2005. Analytica Chimica Acta, 532, 177-186.

Goldstein, E. R., Ziegenfuss, T., Kalman, D., Kreider, R., Campbell, B., Wilborn, C., Taylor, L., Willoughby, D., Stout, J., Graves, B. S., Wildman, R., Ivy, J. L., Spano, M., Smith, A. E., & Antonio, J. 2010. Journal of the International Society of Sports Nutrition, 7(1), 5.

Gonzalez, A. M., Hoffman, J. R., Wells, A. J., Mangine, G. T., Townsend, J. R., Jajtner, A. R., Wang, R., Miramonti, A. A., Pruna, G. J., LaMonica, M. B., Bohner, J. D., Hoffman, M. W., Oliveira, L. P., Fukuda, D. H., Fragala, M. S., & Stout, J. R. 2015. Jour of Sports Sci & M, 14(2), 322–332.

He, H., Ma, D., Crone, L. B., Butawan, M., Meibohm, B., Bloomer, R. J., & Yates, C. R. 2017. Journal of caffeine research, 7(3), 95–102.

Hidese, S., Ogawa, S., Ota, M., Ishida, I., Yasukawa, Z., Ozeki, M. & Kunugi, H. 2019. Nutrients, 11.

Hou, W., Wang, Y., Zheng, P., & Cui, R. 2020. Frontiers in cellular neuroscience, 14, 55.

Joh, T. & Hwang, O. 1987. Annals of the New York Academy of Sciences, 493(1), 342-350.

Jongkees, B. J., Hommel, B., Kuhn, S. & Colzato, L. S. 2015. J P Res, 70, 50-7.

Jówko, E., Sadowski, J., Długołęcka, B., Gierczuk, D., Opaszowski, B. and Cieśliński, I. 2018. Journal of Sport and Health Science, 7(4), 473-480.

Kawashima, S., Ueki, Y., Kato, T., Ito, K., & Matsukawa, N. 2018. PloS one, 13(5), e0196661.

Kim, H. J., Jung, S. W., Kim, S. Y., Cho, I. H., Kim, H. C., Rhim, H., Kim, M. & Nah, S. Y. 2018. J Ginseng Res, 42, 401-411.

Kim, J. H. 2012. J Ginseng Res, 36, 16-26.

Kim, Y., Choi, E. H., Doo, M., Kim, J. Y., Kim, C. J., Kim, C. T., & Kim, I. H. 2010. Nutrition research and practice, 4(4), 270–275.

Kondo, D.G., Sung, Y.H., Hellem, T.L., Delmastro, K.K., Jeong, E.K., Kim, N., Shi, X. and Renshaw, P.F., 2011. Journal of child and adolescent psychopharmacology, 21(2), pp.171-175.

Konstantinos, F. and Heun, R. 2019. Global Ps, 2(2), 171-182

Kuhman, D. J., Joyner, K. J., & Bloomer, R. J. 2015. Nutrients, 7(11), 9618–9632.

Kuś, P.M., 2020. Molecules, 25(4), p.847.

Lagarde, D., Batéjat, D., Sicard, B., Trocherie, S., Chassard, D., Enslen, M. and Chauffard, F. 2000. Sleep, 23(5), 1-11.

Lee, S. & Rhee, D. K. 2017. J Ginseng Res, 41, 589-594.

Lho, S. K., Kim, T. H., Kwak, K. P., Kim, K., Kim, B. J., Kim, S. G., Kim, J. L., Kim, T. H., Moon, S. W., Park, J. Y., Park, J. H., Byun, S., Suh, S. W., Seo, J. Y., So, Y., Ryu, S. H., Youn, J. C., Lee, K. H., Lee, D. Y., Lee, D. W., Lee, S. B., Lee, J. J., Lee, J. R., Jeong, H., Jeong, H. G., Jhoo, J. H., Han, K., Hong, J. W., Han, J. W. & Kim, K. W. 2018. Al Res T, 10, 50.

Lieberman, H. R., Tharion, W. J., Shukitt-Hale, B., Speckman, K. L., & Tulley, R. 2002. Psyph, 164(3), 250–261.

Marques, L. L. M., Ferreira, E. D. F., De Paula, M. N., Klein, T. & De Mello, J. C. P. 2019. Revista Brasileira de Far, 29, 77-110.

McGlade E, Agoston AM, DiMuzio J et al. J Atten Disord. 2015.

McGlade E, Locatelli A, Hardy J et al. Food and Nutr Sci. 2012(3), 769-733.

McLellan, T. M., Kamimori, G. H., Voss, D. M., Bell, D. G., Cole, K. G., & Johnson, D. 2005. Aviation, space, and EM, 76(7), 647–654.

Meyers, S., 2000. Alt M Review, 5(1), pp.64-71

Moustakas, D., Mezzio, M., Rodriguez, B. R., Constable, M. A., Mulligan, M. E. & Voura, E. B. 2015. PLoS One, 10, e0123310.

Nathan, P. J., Lu, K., Gray, M., & Oliver, C. 2006. Journal of herbal ph, 6(2), 21–30.

Nehlig A. 2010. Journal of AD : JAD, 20 Suppl 1, S85–S94.

Olsson, E. M., von Schéele, B., & Panossian, A. G. 2009. Planta M, 75(2), 105–112.

Panossian, A., Hambardzumyan, M., Hovhanissyan, A. & Wikman, G. 2007. DT Insights, 2, 39-54.

Panossian, A. & Wikman, G. 2010. Ph (Basel), 3, 188-224.

Patat, A., Rosenzweig, P., Enslen, M., Trocherie, S., Miget, N., Bozon, M. C., Allain, H. & Gandon, J. M. 2000. Hum P: C&E, 15, 153-170

Peixoto, H., Roxo, M., Rohrig, T., Richling, E., Wang, X. & Wink, M. 2017. M (Basel), 4.

Pomportes, L., Brisswalter, J., Hays, A., & Davranche, K. 2019. Int Jour of Sports Physiology and Performance 14, 5, 576-582.

Quereshi, I., John.,E., 2010. Natural M Journal, 2(6)

Rokot, N. T., Kairupan, T. S., Cheng, K. C., Runtuwene, J., Kapantow, N. H., Amitani, M., Morinaga, A., Amitani, H., Asakawa, A., & Inui, A. 2016. eCAM, 2016, 2614742.

Santana, Á. and Macedo, G. 2018. Journal of Functional Foods, 47, 457-468.

Scholey, A. & Haskell, C. 2008. D, 33, 869.

Schulz, C., Eisenhofer, G. and Lehnert, H., 2004. Frontiers of hormone research, 31, pp.1-25.

Schultz, W. 2007. Trends in Neurosciences, 30(5), 203-210.

Spasov, A. A., Wikman, G. K., Mandrikov, V. B., Mironova, I. A. & Neumoin, V. V. 2000. Phytom, 7, 85-9.

Taylor, L., Mumford, P., Roberts, M., Hayward, S., Mullins, J., Urbina, S., & Wilborn, C. 2016. Journal of the International Society of Sports Nutrition, 13, 2.

Tian, M., Li, L., Zheng, R., Yang, L. and Wang, Z. 2020. CJONM, 18(7), 526-535.

Walker, T. B., & Robergs, R. A. 2006. International journal of sport nutrition and exercise metabolism, 16(3), 305–315.

Wells, A.J., Hoffman, J.R., Gonzalez, A.M., Beyer, K.S., Jajtner, A.R., Townsend, J.R., Olivera, L.P., Fukuda, D.H., Fragala, M.S., & Stout, J.R. 2014. J Int Soc Sports Nutr, 11, 59.

Yeo, H. B., Yoon, H. K., Lee, H. J., Kang, S. G., Jung, K. Y. & Kim, L. 2012. J Ginseng Res, 36, 190-7.

Yunusa, I. & Ahmad, I. M. 2011. Bayero J Pure and Applied Sciences, 4, 186–191.

Ziegenfuss, T. N., Habowski, S. M., Sandrock, J. E., Kedia, A. W., Kerksick, C. M. & Lopez, H. L. 2017. J Diet Suppl, 14, 9-24.