Below is a summary of the scientific literature on each ingredient in the Zen1 formula.
Geniposide has historically been a relatively seldom studied iridoid glycoside, until relatively recently.* It is commonly extracted from the fruits of Gardenia jasminoides. Gardenia jasminoides is said to have been used as a dietary supplement in China for hundreds of years, for a variety of purposes, including mood support (Ye et al., 2018).*
Recent preliminary studies have indicated that geniposide may indeed play a role in helping to support a positive mood, although knowledge regarding the mechanism is limited and further research is needed (Cai et al., 2015, Zhao et al., 2018, Zhang et al., 2019, Sun et al., 2020, Yuan et al., 2020).* This is a research area of keen interest to certain companies and Zenstra does not wish to comment further on geniposide at this time.* Further research may possibly be found online by searching for the term "geniposide mood," or by reading any of the aforementioned studies which can be found in the below reference list.*
5-HTP (5-hydroxytryptophan) is said to be a compound that our body allegedly synthesizes from the amino acid tryptophan, which is said to be found in seeds, eggs, salmon and turkey.* Our bodies are said to use 5-HTP to make 5-hydroxytryptamine (5-HT), also known as serotonin (Weinberg-Wolf et al., 2018, Israelyan et al., 2019).* Serotonin is thought to play a role in mood, appetite and autonomic functions (Yohn, Gergues and Samuels, 2017, Heisler et al., 2006, Chang et al., 2018).*
Some evidence suggests that 5-HTP may help to support a positive mood (Kious et al., 2017, Meloni et al., 2020).* However, a 2019 meta study of 13 investigations has referred to the strength of the evidence of those 13 particular investigations as "relatively weak," calling for more placebo controlled studies to support the numerous positive findings (Javelle et al., 2019).* Indeed there have reportedly been hundreds of studies done on 5-HTP in relation to mood health, most of which have been dubbed "largely be of insufficient quality" by (Shaw, Turner, and Del Mar, 2002, Hinz, Stein and Uncini, 2012).*
Perhaps interestingly, in August 2020, the Editor-in-Chief and Publisher of the journal in which the Hinz, Stein and Uncini (2012) meta study was published, raised concerns regarding, "the alleged undisclosed competing interests of some of the authors and alleged excessive self-citation for the published article." Zenstra does not wish to comment on the alleged undisclosed competing interests of the authors, but we do always applaud bravery and integrity. It may perhaps be speculated that Editor-in-Chief Dr Roger M. Pinder and publisher Dove Press could perhaps be said to be heros, but futher evidence is needed to support such claims.
In relation to mood health, another point worth mentioning is that individuals may differ and serotonin levels may need to be adequately balanced with catecholamines such as dopamine and/or norepinephrine (Hinz, Stein and Uncini, 2012).* As the aforementioned allegedly questionable study pointed out, it has been said that long-term supplementation of 5-HTP can deplete these catecholamines, which may be another reason that it may be prudent to pay attention to dopamine in conjunction with serotonin, particularly over a longer time-horizon (Hinz, Stein and Uncini, 2012).* Another one of our products, Zenergize, contains l-tyrosine, which has been said to be effective for helping to support healthy dopamine levels, as part of a holistic approach to brain health (Hinz, Stein and Uncini, 2012).*
Other studies have suggested that 5-HTP may also potentially play a role in helping to maintain reduced sugar cravings (Ceci et al., 1989, Cangiano et al., 1998, Cangiano et al., 1991, Cangiano et al., 1992, Rondanelli et al., 2012).*
Polygala tenuifolia also known as Yuan Zhi, is a root which is said to have been traditionally consumed in Asia to support memory, calmness and sleep.*
Some evidence has suggested it may help to support healthy memory (Lee et al., 2009).* Some evidence also suggests that Polygala tenuifolia may help to support a positive mood (Lee et al., 2009, Hu et al., 2009, Yao et al., 2010, Hu et al., 2010, Hu et al., 2011).*
Other research has suggested that a saponin from polygala may interact with N-methyl-D-aspartic acid and its receptors, which may to help support a good mood (Jin et al., 2014).*
Additionally, it has been suggested that polygala tenuifolia may help to support calmness (Yao et al., 2010) and support both REM and NREM sleep (Cao et al., 2016).*
Bacopa monnieri has been said to be an adaptogenic herb. Some studies claim to have shown it may help maintain memory and support a calm mood (Rai et al., 2003, Bhattacharya and Ghosal, 1998).* Another study suggested it may help to support the regulation of cortisol (Benson et al., 2014).* Cortisol is thought to be a hormone linked to stress (Benson et al., 2014).*
One 12-week study reported to have observed that taking Bacopa monnieri daily helped to support the speed of processing visual information, learning rate, and memory (Stough et al., 2001).* Another study claimed that it supported dendritic length and branching (Vollala, Upadhya and Nayak, 2011).* Dendrites are parts of nerve cells in the brain which have been said to be closely linked to learning and memory (Vollala, Upadhya and Nayak, 2011).*
Two other studies found that taking Bacopa monnieri daily may help to support calmness and happiness scores in adults over 12 weeks (Stough et al., 2001, Calabrese et al., 2011).*
Gotu kola (Centella asiatica), which has been referred to as the “herb of longevity,” is said to have been traditionally used in Asia to support calmness, a positive mood, brain health, skin health, as well as liver and kidney health (Jana et al., 2010, Wattanathorn et al., 2008, Gray et al., 2016, Bylka et al., 2013).*
A 2013 review concluded that gotu kola may help to maintain a calm, relaxed mood (Sarris, McIntyre and Camfield, 2013).* A study conducted in 2016 found that gotu kola promoted calmness in male mice that were sleep deprived for 72 hours (Chanana and Kumar, 2016).* A separate study, looking at the cognitive effects of gotu kola on mice, suggested that it may help to support both learning and memory formation (Gray et al., 2016).*
Another 2016 study found that gotu kola Gotu Kola may perhaps help to support a healthy, positive mood.* The participants were asked to take gotu kola for 60 days. They self-reported decreased stress, improved calmness, and a positive mood (Lokanathan et al., 2016).*
A 2017 study suggested it may potentially help to support restful sleep, as well as liver and kidney health (Cauffield and Forbes, 2017).* The significance of gotu kola's benefits will only become fully apparent once further research becomes available.
Phosphatidylserine is said to be a compound similar to a dietary fat which is thought to be prevalent in human brain tissue.* It is thought to be vital for cognitive function and is thought to be synthesized naturally in our brains.*
It has been suggested that phosphatidylserine may help to support mood.* In a 2015 study of people over the age of 65, the participants took a supplement containing phosphatidylserine and the omega-3 fatty acids DHA and EPA three times daily for 12 weeks. At the study's end, scores on a mood scale were said to have markedly improved (Komori, 2015).* Further research is needed to confirm these results.
It has been suggested that phosphatidylserine may also help to support memory.* In a 2010 study, 78 elderly people were reportedly given either phosphatidylserine or a placebo for six months.* Participants with relatively low memory scores at the start of the study were found to have experienced a significant improvement in memory (Kato-Kataoka et al., 2010).* Further research is needed to confirm these results.
Schisandra chinensis (five flavour fruit) is a vine which seemingly typically bears purple-red berries described by some as apparently amalgamating all five tastes: sweet, sour, salty, bitter and spicy (Ko, 2006).* According to Ko (2006), in Chinese tradition, Schisandra is believed to beneficial to qi, the allegedly perceived life force or energy, said to be inherent in all living things (the existence of qi is not supported by science).*
Schisandra berry may be categorized as an adaptogen, as some evidence has suggested that it may help the body adapt to both physical and chemical stress (Guan et al., 2011).*
Some studies have suggested it may potentially help to support healthy energy levels by supporting neural ATP synthesis, as well as brain function, relaxation and blood circulation (Lam and Ko, 2012, Park et al., 2013, Huang et al., 2007, Tsi and Tan, 2008).*
Park et al. (2013) reported that Schisandrin C, a component of Schisandra, appears to support healthy brain function.* A compound called deoxyschizandrin, claimed to be found in Schisandra, has been claimed to support cognition and memory (Hu et al., 2012).* A double-blind, placebo-controlled, randomised study claimed to have found that Schisandra helped to maintain attention, cognition, and accuracy of people under stress (Aslanyan et al., 2010).*
Schisandra's alleged calmness and relaxation promoting properties have reportedly been shown to be beneficial for sleep by Huang et al. (2007).* It has also been suggested that schisandra may be effective for helping the body control adrenaline and serotonin changes caused by stress (Chen et al., 2011).* Some evidence seems to suggest that schisandra might afford broad spectrum support against stress (Panossian and Wikman, 2008).*
One study reported that taking a daily dose of about 130mg of Schisandra correlated with an approximately 9% improvement in blood circulation in healthy adults (Tsi and Tan, 2008).* It has also reportedly been shown to support nitric oxide production, which could perhaps lead to improvements in physical performance, although further research is needed (Panossian et al., 1999).*
Among numerous other alleged benefits, Schisandra may also potentially support the liver and provide antioxidant support (Pu et al., 2012).* In a recent study, it was reportedly found to support the production of antioxidant enzymes, particularly SOD and glutathione peroxidase (Nowak et al., 2019).* Endogenous glutathione is thought to help protect the brain against oxidative stress, which may help to support memory (Nowak et al., 2019).*
5-HTP Efficacy and Contraindications [Expression of Concern]. (2020). Neuro D&T, 16, 1059.
Aslanyan, G., Amroyan, E., Gabrielyan, E., Nylander, M., Wikman, G. & Panossian, A. 2010. Phyto, 17, 494-9.
Benson, S., Downey, L. A., Stough, C., Wetherell, M., Zangara, A. & Scholey, A. 2014. Phyto Res, 28, 551-9.
Bhattacharya, S. K. & Ghosal, S. 1998 Phyto, 5, 77-82.
Boominathan, L. 2017. [Online]. (GBMD). Available: genomediscovery org.
Bylka, W., Znajdek-Awizen, P., Studzinska-Sroka, E. & Brzezinska, M. 2013. PDA, 30, 46-9.
Cai, L., Li, R., Tang, W. J., Meng, G., Hu, X. Y., & Wu, T. N. 2015. Eur Col Neur, 25(8), 1332–1341.
Calabrese, C., Gregory, W. L., Leo, M., Kraemer, D., Bone, K. & Oken, B. 2008. JAC, 14, 707-13.
Cangiano, C., Ceci, F., Cairella, M., Cascino, A., Del Ben, M., Laviano, A., Muscaritoli, M. & Rossi Fanelli, F. 1991. In: Schwarcz R., Y. S. N., Brown R.R. (ed.) Advances in Experimental Biology. Boston, MA: Springer.
Cangiano, C., Ceci, F., Cascino, A., Del Ben, M., Laviano, A., Muscaritoli, M., Antonucci, F. & Rossi-Fanelli, F. 1992. Am J C Nutr, 56, 863-7.
Cangiano, C., Laviano, A., Del Ben, M., Preziosa, I., Angelico, F., Cascino, A. & Rossi-Fanelli, F. 1998. Int J ORMD, 22, 648-54.
Cao, Q., Jiang, Y., Cui, S. Y., Tu, P. F., Chen, Y. M., Ma, X. L., Cui, X. Y., Huang, Y. L., Ding, H., Song, J. Z., Yu, B., Sheng, Z. F., Wang, Z. J., Xu, Y. P., Yang, G., Ye, H., Hu, X. & Zhang, Y. H. 2016. Phyto, 23, 1797-1805.
Cauffield, J. S. & Forbes, H. J. 1999. Lippincotts, 3, 290-304.
Ceci, F., Cangiano, C., Cairella, M., Cascino, A., Del Ben, M., Muscaritoli, M., Sibilia, L. & Rossi Fanelli, F. 1989. J Neural Transm, 76, 109-17.
Chanana, P. & Kumar, A. 2016. Phyto Res, 30, 671-80.
Chang, W., Lee, I., Chi, M., Lin, S., Chen, K., Chen, P., Chiu, N., Yao, W. and Yang, Y. 2018. Scientific Reports, 8(1).
Chen, W. W., He, R. R., Li, Y. F., Li, S. B., Tsoi, B. & Kurihara, H. 2011. Phyto, 18, 1144-7.
Gray, N. E., Harris, C. J., Quinn, J. F. & Soumyanath, A. 2016. J Ethno, 180, 78-86.
Guan, J., Zhu, H. Y., Zhang, X. R., Zhao, Y. & Sun, D. Y. 2011. ZYC, 34, 1912-5.
Heisler, L. K., Jobst, E. E., Sutton, G. M., Zhou, L., Borok, E., Thornton-Jones, Z., Liu, H. Y., Zigman, J. M., Balthasar, N., Kishi, T., Lee, C. E., Aschkenasi, C. J., Zhang, C. Y., Yu, J., Boss, O., Mountjoy, K. G., Clifton, P. G., Lowell, B. B., Friedman, J. M., Horvath, T., Cowley, M. A. 2006. Neuron, 51(2), 239–249.
Hinz, M., Stein, A., & Uncini, T. 2012. Neuro DT, 8, 323–328.
Hu, D., Li, C., Han, N., Miao, L., Wang, D., Liu, Z., Wang, H. & Yin, J. 2012. Planta, 78, 1332-6.
Hu, Y., Liao, H. B., Liu, P., Guo, D. H. & Rahman, K. 2009. Phzie, 64, 605-8.
Hu, Y., Liu, M., Liu, P., Guo, D. H., Wei, R. B. & Rahman, K. 2011. J PP, 63, 869-74.
Hu, Y., Liu, P., Guo, D. H., Rahman, K., Wang, D. X. & Xie, T. T. 2010. P Biol, 48, 794-800.
Huang, F., Xiong, Y., Xu, L., Ma, S. & Dou, C. 2007. J Ethno, 110, 471-5.
Israelyan, N., Del Colle, A., Li, Z., Park, Y., Xing, A., Jacobsen, J., Luna, R., Jensen, D., Madra, M., Saurman, V., Rahim, R., Latorre, R., Law, K., Carson, W., Bunnett, N., Caron, M. and Margolis, K. 2019. Gastr, 157(2), 507-521.e4
Jacobsen, J., Rudder, M., Roberts, W., Royer, E., Robinson, T., Oh, A., Spasojevic, I., Sachs, B. and Caron, M. 2016. Neuro, 41(9), 2324-2334.
Jana, U., Sur, T. K., Maity, L. N., Debnath, P. K. & Bhattacharyya, D. 2010. Nepal Coll J, 12, 8-11.
Javelle, F., Lampit, A., Bloch, W., Häussermann, P., Johnson, S. and Zimmer, P. 2019. Nutrition Reviews, 78(1), 77-88.
Jin, Z. L., Gao, N., Zhang, J. R., Li, X. R., Chen, H. X., Xiong, J., Li, Y. F. & Tang, Y. 2014. Prog Neuro Biol, 53, 9-14.
Kato-Kataoka, A., Sakai, M., Ebina, R., Nonaka, C., Asano, T. & Miyamori, T. 2010. J Biochem Nutr, 47, 246-55.
Kious, B. M., Sabic, H., Sung, Y. H., Kondo, D. G., & Renshaw, P. 2017. Jour c psy, 37(5), 578–583.
Ko, K. M., & Chiu, P. Y. 2006. American JCM, 34(2), 171–176.
Komori, T. 2015. MI, 7, 5647.
Lam, P. Y. & Ko, K. M. 2012. Oxid Cell Longev, 2012, 250825.
Lee, J. Y., Kim, K. Y., Shin, K. Y., Won, B. Y., Jung, H. Y. & Suh, Y. H. 2009. Neurosci Lett, 454, 111-4.
Lokanathan, Y., Omar, N., Ahmad Puzi, N. N., Saim, A. & Hj Idrus, R. 2016. Malays J Sci, 23, 4-14.
Meloni, M., Puligheddu, M., Carta, M., Cannas, A., Figorilli, M. and Defazio, G. 2020. Eur J Neur, 27: 779-786.
Nowak, A., Zaklos-Szyda, M., Blasiak, J., Nowak, A., Zhang, Z. & Zhang, B. 2019. Nutrients, 11.
Panossian, A. & Wikman, G. 2008. J Ethno, 118, 183-212.
Panossian, A. G., Oganessian, A. S., Ambartsumian, M., Gabrielian, E. S., Wagner, H. & Wikman, G. 1999. Phyto, 6, 17-26.
Park, S. Y., Park, S. J., Park, T. G., Rajasekar, S., Lee, S. J. & Choi, Y. W. 2013. Int Imm, 17, 415-26.
Pu, H. J., Cao, Y. F., He, R. R., Zhao, Z. L., Song, J. H., Jiang, B., Huang, T., Tang, S. H., Lu, J. M. & Kurihara, H. 2012. EBCA, 2012, 161062.
Rai, D., Bhatia, G., Palit, G., Pal, R., Singh, S. & Singh, H. K. 2003. P Biochem Behav, 75, 823-30.
Rhauf, K., Subhan, F., Abbas, M. and Haq, I. 2012. AJPP, 6(39), 2767-2774.
Rondanelli, M., Opizzi, A., Faliva, M., Bucci, M. & Perna, S. 2012. EWD, 17, e22-8.
Sarris, J., Mcintyre, E. & Camfield, D. A. 2013. CNSD, 27, 301-19.
Shaw, K., Turner, J. and Del Mar, C. 2002. Australian & New Zealand JOS, 36(4), 488-491.
Stough, C., Lloyd, J., Clarke, J., Downey, L. A., Hutchison, C. W., Rodgers, T. & Nathan, P. J. 2001. Psy (Berl), 156, 481-4.
Sun, B., Jia, X., Yang, F., Ren, G. and Wu, X. 2020. Neuroscience Research.
Tsi, D. & Tan, A. 2008. Bioinformation, 2, 249-52.
Vollala, V. R., Upadhya, S. & Nayak, S. 2011. Cl (Sao Paulo), 66, 663-71.
Walsh, R. M., Shen, E. Y., Bagot, R. C., Anselmo, A., Jiang, Y., Javidfar, B., Wojtkiewicz, G. J., Cloutier, J., Chen, J. W., Sadreyev, R., Nestler, E. J., Akbarian, S. & Hochedlinger, K. 2017. Nat Commun, 8, 15142.
Wattanathorn, J., Mator, L., Muchimapura, S., Tongun, T., Pasuriwong, O., Piyawatkul, N., Yimtae, K., Sripanidkulchai, B. & Singkhoraard, J. 2008. Ethno, 116, 325-32.
Weinberg-Wolf, H., Fagan, N.A., Anderson, G.M.,Tringides, M., Dal Monte, O., & Chang, S.W.C. 2018. Neuro, 43, 1589–1598.
Yao, Y., Jia, M., Wu, J. G., Zhang, H., Sun, L. N., Chen, W. S. & Rahman, K. 2010. P Biol, 48, 801-7.
Ye, D., Zhang, L., Fan, W., Zhang, X. and Dong, E., 2018. Epigenetics, 13(3), 310-317.
Yohn, C.N., Gergues, M.M. & Samuels, B.A. 2017. Mol Brain, 10, 28.
Yuan, J., Zhang, J., Cao, J., Wang, G. and Bai, H. 2019. Cellular and Molecular Neurobiology, 40(4), 511-520.
Zhang, B., Chang, H., Hu, K., Yu, X., Li, L. and Xu, X. 2019. CJI
Zhang, H., Xue, W., Wu, R., Gong, T., Tao, W., Zhou, X., Jiang, J., Zhang, Y., Zhang, N., Cui, Y., Chen, C. & Chen, G. 2015. EBCA, 2015, 761238.
Zhang, Z., Deng, T., Wu, M., Zhu, A. and Zhu, G., 2019. CM, 14(1).