DISCUSSION
hypothermia, daytime sleepiness, dizziness, morning grogginess, headache
MUSCLE RELAXATION
Despite significant research efforts for sleep and mental health management, to date, available intervention options from natural sources are very limited. In particular, the sleep aid market is significantly saturated by high doses of synthetic melatonin or cocktails of melatonin and other botanical extracts with minimal to no clinical evidence to support their meaningful clinical usage. Higher dosages of synthetic melatonin supplements could also produce side effects such as morning grogginess, daytime sleepiness, headache, dizziness, and hypothermia.Supplementation of a standardized corn leaf extract, UP165, improved sleep quality of clinical study participants by increasing the deep sleep stage of sleep approximately by half an hour. The total deep sleep times at the start of the study period for the 250 mg/day, 500 mg/day, and placebo were 64, 68, and 58 minutes, respectively, indicating neither the supplement nor the placebo group was to the level considered good-quality sleep per night. Following the 4-week supplementation, the deep sleep times were found to be increased to 92, 94, and 62 minutes for the 250 mg/day, 500 mg/day, and placebo group, respectively. Such increase of deep sleep time for high-dose Maizinol group was statistically significant at week 2 and 4 with Due to small number of subjects in each group of this pilot study, both low- and high-dose Maizinol group showed statistically strong trend of increased deep sleep time with The increase in the deep sleep time observed in the UP165-supplemented group was possibly a direct reflection of the fourfold higher affinity of UP165 to the MT2 receptor, which is known to induce deep sleep when activated. The improved sleep quality findings from the sleep tracker were also verified by the PSQI questionnaire with participants showing a 10-fold increase in quality and efficiency of sleep improvement as a result of 250 mg/day of UP165, compared to that of participants who were supplemented with the placebo.Again, substantiating the objective measures from the individual sleep tracker, when participants were asked about their mental health status using the POMS questionnaire, they provided statistically significant improvements in mood state and well-being compared to their baseline (37–58% improvement at 250 mg/day and 36–42% improvement at 500 mg/day), whereas the improvements for the placebo group were very minimal (9–15% improvement) and statistically nonsignificant.The clinical superiority in performance observed for the UP165-supplemented participants compared to the placebo was closely correlated to the level of salivary cortisol during the course of the study. It has been known that high cortisol level is strongly linked to premature nocturnal awakening, decrease in deep sleep, and hence poor sleep quality.It has been well documented that sleep displays a close and inverse relationship with increased level of cortisol and HPA axis regulation.These clinical study results support the fact that participants who were supplemented with a standardized corn leaf extract, UP165, had significantly reduced cortisol levels (up to 36%) and increased slow-wave deep sleep time (up to 30 minutes), which translated to better sleep quality when compared to the placebo group. These clinical findings also added additional dimension to the mechanism of action of UP165, in that, by reducing cortisol level, there is a possibility that UP165 could correct a dysregulated HPA axis, leading to normal homeostasis of vital physiological functions, including sleep. This clinical evidence in association with the ability of UP165 to induce the body to synthesize endogenous melatonin, directly binding to MT1 and MT2 receptors, being structurally similar to melatonin, and having a muscle relaxation property, could produce a potential additive and/or synergistic effect that will lead to enhanced induction and maintenance of sleep.Collectively, UP165 showed a statistically significant (1) dose-correlated reduction in salivary cortisol level compared to placebo; (2) improved deep sleep time in a dose-correlated manner; (3) increased total sleep time compared to baseline; (4) improved sleep quality and efficiency as measured by PSQI; and (5) improved overall well-being as measured by POMS scale. Therefore, UP165 could be used as a safe nutritional supplement for a 24-hour support for a better quality and efficiency of sleep at night and for improved mood state and overall well-being by day. These data suggest the possibility of the standardized, natural, hormone-free, corn leaf extract, UP165, to be considered a natural alternative to a synthetic melatonin.