Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements

In the paper

“Phytomelatonin was found to have 646% stronger COX-2 inhibition (see Figure 3), 267–470% more potent free-radical scavenging ability (see Figure 4), and 100% greater efficacy in reducing cellular ROS in a human skin cell line (see Figure 5) when compared to synthetic melatonin”

What the sources say

• Not checked yetcites [34] Kukula-Koch, W., Szwajgier, D., Gaweł-Bęben, K., Strzępek-Gomółka, M., Głowniak, K., and Meissner, H.O. (2021). Is Phytomelatonin Complex Better Than Synthetic Melatonin? The Assessment of the Antiradical and Anti-Inflammatory Properties. Molecules, 26. source

In the paper

“Phytomelatonin was found to have 646% stronger COX-2 inhibition (see Figure 3), 267–470% more potent free-radical scavenging ability (see Figure 4), and 100% greater efficacy in reducing cellular ROS in a human skin cell line (see Figure 5) when compared to synthetic melatonin”

What the sources say

• Not checked yetcites [34] Kukula-Koch, W., Szwajgier, D., Gaweł-Bęben, K., Strzępek-Gomółka, M., Głowniak, K., and Meissner, H.O. (2021). Is Phytomelatonin Complex Better Than Synthetic Melatonin? The Assessment of the Antiradical and Anti-Inflammatory Properties. Molecules, 26. source

In the paper

“Phytomelatonin was found to have 646% stronger COX-2 inhibition (see Figure 3), 267–470% more potent free-radical scavenging ability (see Figure 4), and 100% greater efficacy in reducing cellular ROS in a human skin cell line (see Figure 5) when compared to synthetic melatonin”

What the sources say

• Not checked yetcites [34] Kukula-Koch, W., Szwajgier, D., Gaweł-Bęben, K., Strzępek-Gomółka, M., Głowniak, K., and Meissner, H.O. (2021). Is Phytomelatonin Complex Better Than Synthetic Melatonin? The Assessment of the Antiradical and Anti-Inflammatory Properties. Molecules, 26. source

In the paper

“In one of the studies, Akkermansia muciniphila and Lactobacilli species were increased in the melatonin-treated animals [46].”

What the sources say

• Not checked yetcites [46] Park, 2020, Melatonin in the colon modulates intestinal microbiota in response to stress and sleep deprivation, Intest Res. source

In the paper

“Both doses of melatonin taken in the morning, approximately 6 h after the sleep midpoint, will cause a phase delay.”

In the paper

“For instance, 0.5 mg and 3.0 mg of melatonin taken eleven hours before the sleep midpoint will cause a phase advance, so the individual feels sleepy earlier and awakens earlier.”

In the paper

“Trials that used higher doses of melatonin and conducted over a longer duration demonstrated even greater effects on these two sleep issues, and overall sleep quality was also significantly improved in melatonin users [1,91].”

What the sources say

• Not checked yetcites [1] Wunsch, N.-G. (2022, July 31). Sales of Melatonin 2020. Available online: https://www.statista.com/statistics/1267421/sales-of-melatonin-in-the-united-states/.
• Not checked yetcites [91] Qawasmi, 2018, Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders, Focus source

In the paper

“Both doses improved sleep efficiency, but the higher dose impacted the biological day and night sleep patterns, the duration of non-REM sleep, and awakening time [93].”

What the sources say

• Not checked yetcites [93] Duffy, 2022, High dose melatonin increases sleep duration during nighttime and daytime sleep episodes in older adults, J. Pineal Res. source

In the paper

“A meta-analysis of melatonin for the treatment of primary sleep disorders analyzed nineteen studies involving 1683 individuals.”

What the sources say

• Not checked yetcites [1] Wunsch, N.-G. (2022, July 31). Sales of Melatonin 2020. Available online: https://www.statista.com/statistics/1267421/sales-of-melatonin-in-the-united-states/.
• Not checked yetcites [91] Qawasmi, 2018, Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders, Focus source

In the paper

“In 2022, researchers at Harvard Medical School and Brigham and Women’s Hospital explored low (0.3 mg) and high (5 mg) dose melatonin in a relatively small sample of healthy older adults.”

What the sources say

• Not checked yetcites [93] Duffy, 2022, High dose melatonin increases sleep duration during nighttime and daytime sleep episodes in older adults, J. Pineal Res. source

In the paper

“In one study, six months of low-dose 2 mg melatonin supplementation taken at the same clock time (between 10–11 pm, personalized to the individual’s chronotype) resulted in a decrease in iRBD symptom severity over the first four weeks of treatment.”

What the sources say

• Not checked yetcites [94] Kunz, 2021, Treatment of isolated REM sleep behavior disorder using melatonin as a chronobiotic, J. Pineal Res. source

In the paper

“This improvement was maintained over the follow-up period of 4.2 ± 3.1 years [94].”

What the sources say

• Not checked yetcites [94] Kunz, 2021, Treatment of isolated REM sleep behavior disorder using melatonin as a chronobiotic, J. Pineal Res. source

In the paper

“Trials that used higher doses of melatonin and conducted over a longer duration demonstrated even greater effects on these two sleep issues, and overall sleep quality was also significantly improved in melatonin users [1,91].”

What the sources say

• Not checked yetcites [1] Wunsch, N.-G. (2022, July 31). Sales of Melatonin 2020. Available online: https://www.statista.com/statistics/1267421/sales-of-melatonin-in-the-united-states/.
• Not checked yetcites [91] Qawasmi, 2018, Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders, Focus source

In the paper

“Sleep quality was also significantly improved during and after the study [110,111].”

What the sources say

• Not checked yetcites [110] Gelfand, 2016, The Role of Melatonin in the Treatment of Primary Headache Disorders, Headache source
• Not checked yetcites [111] Danilov, 2020, Safety and Efficacy of Melatonin in Chronic Tension-Type Headache: A Post-Marketing Real-World Surveillance Program, Pain Ther. source

In the paper

“Melatonin was superior to amitriptyline in the percentage of patients with a greater than 50% reduction in migraine frequency, and melatonin was better tolerated than amitriptyline.”

What the sources say

• Not checked yetcites [109] Ribeiro, 2016, Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention, J. Neurol. Neurosurg. Psychiatry source

In the paper

“A more extensive, longer-term study found that patients with mild cognitive impairment scored better on the Mini-Mental Status Exam and the Sleep Disorders Index when taking melatonin [106].”

What the sources say

• Not checked yetcites [106] Furio, 2007, Possible therapeutic value of melatonin in mild cognitive impairment: A retrospective study, J. Pineal Res. source

In the paper

“Melatonin was superior to amitriptyline in the percentage of patients with a greater than 50% reduction in migraine frequency, and melatonin was better tolerated than amitriptyline.”

What the sources say

• Not checked yetcites [109] Ribeiro, 2016, Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention, J. Neurol. Neurosurg. Psychiatry source

In the paper

“Overall, significant decreases in pain and tension headache-associated symptoms were observed after melatonin use.”

What the sources say

• Not checked yetcites [110] Gelfand, 2016, The Role of Melatonin in the Treatment of Primary Headache Disorders, Headache source
• Not checked yetcites [111] Danilov, 2020, Safety and Efficacy of Melatonin in Chronic Tension-Type Headache: A Post-Marketing Real-World Surveillance Program, Pain Ther. source

In the paper

“A randomized, multi-center, parallel-group design was conducted in which melatonin was compared with amitriptyline and placebo for twelve weeks. A 3 mg dose of melatonin reduced migraine frequency, demonstrating the same effectiveness as amitriptyline in the primary endpoint of the frequency of migraine headaches per month [109].”

What the sources say

• Not checked yetcites [109] Ribeiro, 2016, Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention, J. Neurol. Neurosurg. Psychiatry source

In the paper

“There are distinct similarities between melatonin and vitamin D in the depth and breadth of their impact on health.”

In the paper

“most likely resulting in the more than doubling of melatonin dietary supplement sales in the U.S. to USD 821 million in 2020 compared with 2017 [1].”

What the sources say

• Not checked yetcites [1] Wunsch, N.-G. (2022, July 31). Sales of Melatonin 2020. Available online: https://www.statista.com/statistics/1267421/sales-of-melatonin-in-the-united-states/.

In the paper

“Aside from aging, production of melatonin can be influenced by illness [12], diet [4], environmental factors like bright light at night [13], medication use [14], and lifestyle [15].”

What the sources say

• Not checked yetcites [12] Maas, 2020, Factors Disrupting Melatonin Secretion Rhythms During Critical Illness, Crit. Care Med. source
• Not checked yetcites [4] Srinivasan, 2006, Melatonin: Nature’s most versatile biological signal?, Febs. J. source
• Not checked yetcites [13] Kubota, 2002, Effects of nocturnal bright light on saliva melatonin, core body temperature and sleep propensity rhythms in human subjects, Neurosci. Res. source

In the paper

“Even though the pineal gland receives much attention for its melatonin production, there is 400 times more melatonin in the gut mucosa [5].”

What the sources say

• Not checked yetcites [5] Chen, 2011, Distribution, function and physiological role of melatonin in the lower gut, World J. Gastroenterol. source

In the paper

“Production gradually declines as people age, starting in the late twenties to the fifties, with production leveling at approximately 30 pg/mL [4,11] (see Figure 1).”

What the sources say

• Not checked yetcites [4] Srinivasan, 2006, Melatonin: Nature’s most versatile biological signal?, Febs. J. source
• Not checked yetcites [11] Karasek, 2006, Melatonin in humans, J. Physiol. Pharmacol.

In the paper

“Children typically produce more melatonin than adults, which may infer that their need for dietary supplementation may require further scrutiny and be limited to specific disease states [4,11].”

What the sources say

• Not checked yetcites [4] Srinivasan, 2006, Melatonin: Nature’s most versatile biological signal?, Febs. J. source
• Not checked yetcites [11] Karasek, 2006, Melatonin in humans, J. Physiol. Pharmacol.

In the paper

“suggesting that dietary supplementation with exogenous melatonin in later years may be an effective therapeutic intervention for such age-related conditions [33].”

What the sources say

• Not checked yetcites [33] Hardeland, R. (2019). Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks. Int. J. Mol. Sci., 20. source

In the paper

“In addition, melatonin has the dual capability of targeting receptor-independent and receptor-dependent processes.”

In the paper

“Overall, age-related decreases in endogenous melatonin production are correlated with disease and dysfunction.”

In the paper

“It is present in nearly all bodily fluids: cerebrospinal fluid, saliva, bile, synovial fluid, amniotic fluid, urine, feces, semen, and breast milk [16,19,20].”

What the sources say

• Not checked yetcites [16] Tan, D.X., Xu, B., Zhou, X., and Reiter, R.J. (2018). Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland. Molecules, 23. source
• Not checked yetcites [19] Meng, X., Li, Y., Li, S., Zhou, Y., Gan, R.Y., Xu, D.P., and Li, H.B. (2017). Dietary Sources and Bioactivities of Melatonin. Nutrients, 9. source
• Not checked yetcites [20] Sharbatoghli, 2015, The Relationship between Seminal Melatonin with Sperm Parameters, DNA Fragmentation and Nuclear Maturity in Intra-Cytoplasmic Sperm Injection Candidates, Cell J.

In the paper

“In vitro and in vivo studies demonstrate melatonin’s protective ability against mitochondria-mediated injury with hypertension and obesity, suggesting that dietary supplementation with exogenous melatonin in later years may be an effective therapeutic intervention for such age-related conditions [33].”

What the sources say

• Not checked yetcites [33] Hardeland, R. (2019). Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks. Int. J. Mol. Sci., 20. source

In the paper

“Notably, as stated above, it is a highly efficient antioxidant as one molecule of melatonin can scavenge multiple (~10) reactive oxygen and nitrogen species through a cascading mechanism related to its secondary, tertiary, and even quaternary metabolites [24,31].”

What the sources say

• Not checked yetcites [24] Tan, 2007, One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species?, J. Pineal Res. source
• Not checked yetcites [31] Ighodaro, 2018, First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid, Alex. J. Med.

In the paper

“Most relevant for the discussion of this paper is that it can bind the vitamin D receptor (VDR), resulting in an enhancement of vitamin D’s signaling effects and subsequent cellular activities [18].”

What the sources say

• Not checked yetcites [18] Fang, 2020, Identification of a novel melatonin-binding nuclear receptor: Vitamin D receptor, J. Pineal Res. source

In the paper

“most likely due to the other constituents found in phytomelatonin such as chlorophyll, beta-carotene, lutein, and other protective, antioxidant phytonutrients [values derived from the original data presented in [34].”

What the sources say

• Not checked yetcites [34] Kukula-Koch, W., Szwajgier, D., Gaweł-Bęben, K., Strzępek-Gomółka, M., Głowniak, K., and Meissner, H.O. (2021). Is Phytomelatonin Complex Better Than Synthetic Melatonin? The Assessment of the Antiradical and Anti-Inflammatory Properties. Molecules, 26. source

In the paper

“Melatonin is colloquially referred to as the “hormone of darkness” since it is produced in response to darkness, as perceived by the eye’s retina [4].”

What the sources say

• Not checked yetcites [4] Srinivasan, 2006, Melatonin: Nature’s most versatile biological signal?, Febs. J. source

In the paper

“From a practical and even clinical perspective, vitamin D and melatonin may act as biochemical sensors to meet requirements for both light and darkness, respectively.”

In the paper

“In fact, it has been suggested to be one of the most potent antioxidants because of its ability to scavenge up to 10 reactive oxygen (ROS) and nitrogen species (RNS) with its metabolites compared with most antioxidants, which may only be able to quench a few ROS [16,23,24].”

What the sources say

• Not checked yetcites [16] Tan, D.X., Xu, B., Zhou, X., and Reiter, R.J. (2018). Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland. Molecules, 23. source
• Not checked yetcites [23] Gitto, 2001, Individual and synergistic antioxidative actions of melatonin: Studies with vitamin E, vitamin C, glutathione and desferrioxamine (desferoxamine) in rat liver homogenates, J. Pharm. Pharmacol. source
• Not checked yetcites [24] Tan, 2007, One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species?, J. Pineal Res. source

In the paper

“At the same time, melatonin is an antioxidant in the skin to ward off the damaging effects of UV light.”

In the paper

“Melatonin has been found in many tissues other than the pineal gland and gut mucosa, including the brain, retina, lens, cochlea, trachea, skin, liver, kidney, thyroid, pancreas, thymus, spleen, and reproductive tissues [6].”

What the sources say

• Not checked yetcites [6] Mahmood, 2019, Pleiotropic Effects of Melatonin, Drug Res. source

In the paper

“For example, it has been demonstrated that melatonin can bind several target proteins, including enzymes, receptors, pores, and transporters [17].”

What the sources say

• Not checked yetcites [17] Liu, 2019, Melatonin Target Proteins: Too Many or Not Enough?, Front. Endocrinol. source

In the paper

“Rather than respond to the signals of the light/dark cycle or the pineal gland, the mitochondria can induce the production of melatonin based on intracellular need.”

In the paper

“It is estimated that the enterochromaffin cells within the gut contain upwards of 400 times the amount of melatonin than what is produced by pinealocytes.”

In the paper

“An investigation into gut microbiota has identified microbial influences on the serotonergic and melatonergic systems [25].”

What the sources say

• Not checked yetcites [25] Tan, 2015, Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism, Molecules source

In the paper

“Both serotonergic and melatonergic systems are also prone to immune and inflammatory responses, adding to the complexities of the gut-brain axis [44].”

What the sources say

• Not checked yetcites [44] Bantounou, M., Plascevic, J., and Galley, H.F. (2022). Melatonin and Related Compounds: Antioxidant and Anti-Inflammatory Actions. Antioxidants, 11. source

In the paper

“There may be the ability to offset some of the decline accompanying the aging process through physiological regeneration with supplemental melatonin, as has been documented in animal and human studies [36].”

What the sources say

• Not checked yetcites [36] Reiter, R.J., Tan, D.X., Rosales-Corral, S., Galano, A., Zhou, X.J., and Xu, B. (2018). Mitochondria: Central Organelles for Melatonin’s Antioxidant and Anti-Aging Actions. Molecules, 23. source

In the paper

“In addition to these functions, melatonin facilitates mitochondrial function by encouraging healthy endogenous levels of antioxidant defense enzymes like superoxide dismutase.”

In the paper

“Further, melatonin has anti-excitatory properties in the gut.”

In the paper

“Levels of gut melatonin can be anywhere from 10 to 100 times greater than melatonin in blood serum levels [37,38].”

What the sources say

• Not checked yetcites [37] Zhang, 2022, Gut Microbiota Dysbiosis Induced by Decreasing Endogenous Melatonin Mediates the Pathogenesis of Alzheimer’s Disease and Obesity, Front. Immunol. source
• Not checked yetcites [38] Laborda-Illanes, A., Sánchez-Alcoholado, L., Boutriq, S., Plaza-Andrades, I., Peralta-Linero, J., Alba, E., González-González, A., and Queipo-Ortuño, M.I. (2021). A New Paradigm in the Relationship between Melatonin and Breast Cancer: Gut Microbiota Identified as a Potential Regulatory Agent. Cancers, 13. source

In the paper

“With the increased production of gastrin, melatonin has also been attributed to increasing the tone of the lower esophageal sphincter [42].”

What the sources say

• Not checked yetcites [42] Majka, J., Wierdak, M., Brzozowska, I., Magierowski, M., Szlachcic, A., Wojcik, D., Kwiecien, S., Magierowska, K., Zagajewski, J., and Brzozowski, T. (2018). Melatonin in Prevention of the Sequence from Reflux Esophagitis to Barrett’s Esophagus and Esophageal Adenocarcinoma: Experimental and Clinical Perspectives. Int. J. Mol. Sci., 19. source

In the paper

“While low serotonin levels are known to be consistent with clinical depression, low melatonin levels also appear to have a significant connection.”

In the paper

“The broader picture of mental health, specifically depression, has been correlated with melatonin levels.”

In the paper

“Preliminary animal research indicates a relationship between gut dysbiosis, endogenous melatonin production, and pathological changes associated with Alzheimer’s disease [37].”

What the sources say

• Not checked yetcites [37] Zhang, 2022, Gut Microbiota Dysbiosis Induced by Decreasing Endogenous Melatonin Mediates the Pathogenesis of Alzheimer’s Disease and Obesity, Front. Immunol. source

In the paper

“Along these lines of research, melatonin administration in animals helped reduce dysbiosis due to sleep restriction [45,46].”

What the sources say

• Not checked yetcites [45] Wang, 2022, Melatonin prevents the dysbiosis of intestinal microbiota in sleep-restricted mice by improving oxidative stress and inhibiting inflammation, Saudi J. Gastroenterol. source
• Not checked yetcites [46] Park, 2020, Melatonin in the colon modulates intestinal microbiota in response to stress and sleep deprivation, Intest Res. source

In the paper

“Newer data indicate that the mitochondria are pivotal for several aspects of melatonin: its production, metabolism, and activity through receptors [35].”

What the sources say

• Not checked yetcites [35] Tan, 2019, Mitochondria: The birth place, battle ground and the site of melatonin metabolism in cells, Melatonin Res. source

In the paper

“Mitochondrial dysfunction is one of the mechanisms related to diseases of aging [36].”

What the sources say

• Not checked yetcites [36] Reiter, R.J., Tan, D.X., Rosales-Corral, S., Galano, A., Zhou, X.J., and Xu, B. (2018). Mitochondria: Central Organelles for Melatonin’s Antioxidant and Anti-Aging Actions. Molecules, 23. source

In the paper

“There are initial indications that the antioxidant and anti-inflammatory actions of melatonin may work together with select polyphenols (e.g., resveratrol, epigallocatechin 3-gallate) for therapeutic indications [48,49,50,51,52,53,54].”

What the sources say

• Not checked yetcites [48] Tascioglu Aliyev, A., Panieri, E., Stepanić, V., Gurer-Orhan, H., and Saso, L. (2021). Involvement of NRF2 in Breast Cancer and Possible Therapeutical Role of Polyphenols and Melatonin. Molecules, 26. source
• Not checked yetcites [49] Labban, 2021, Effects of melatonin and resveratrol on recognition memory and passive avoidance performance in a mouse model of Alzheimer’s disease, Behav. Brain Res. source
• Not checked yetcites [50] Aguiar, 2019, Evaluation of the therapeutic activity of melatonin and resveratrol in Inflammatory Bowel Disease: A longitudinal PET/CT study in an animal model, Int. J. Pharm. source
• Not checked yetcites [51] Marhuenda, 2017, Effect of the dietary intake of melatonin- and hydroxytyrosol-rich wines by healthy female volunteers on the systemic lipidomic-related oxylipins, Food Funct. source
• Not checked yetcites [52] Elbe, 2015, Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats, Hum. Exp. Toxicol. source
• Not checked yetcites [53] Zhang, L., He, Y., Wu, X., Zhao, G., Zhang, K., Yang, C.S., Reiter, R.J., and Zhang, J. (2019). Melatonin and (-)-Epigallocatechin-3-Gallate: Partners in Fighting Cancer. Cells, 8. source
• Not checked yetcites [54] Chattree, V., Singh, K., Singh, K., Goel, A., Maity, A., and Lone, A. (2022). A comprehensive review on modulation of SIRT1 signaling pathways in the immune system of COVID-19 patients by phytotherapeutic melatonin and epigallocatechin-3-gallate. J. Food Biochem., e14259. source

In the paper

“When AhR is triggered, overall endogenous pineal melatonin production is suppressed [32,55,56,57,58].”

What the sources say

• Not checked yetcites [32] Chitimus, D.M., Popescu, M.R., Voiculescu, S.E., Panaitescu, A.M., Pavel, B., Zagrean, L., and Zagrean, A.M. (2020). Melatonin’s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease. Biomolecules, 10. source
• Not checked yetcites [55] Ferlazzo, N., Andolina, G., Cannata, A., Costanzo, M.G., Rizzo, V., Currò, M., Ientile, R., and Caccamo, D. (2020). Is Melatonin the Cornucopia of the 21st Century?. Antioxidants, 9. source
• Not checked yetcites [56] Maffei, M.E. (2020). 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology. Int. J. Mol. Sci., 22. source
• Not checked yetcites [57] Reiter, 2010, Neurotoxins: Free radical mechanisms and melatonin protection, Curr. Neuropharmacol. source
• Not checked yetcites [58] Brinkmann, 2019, The Aryl Hydrocarbon Receptor (AhR) in the Aging Process: Another Puzzling Role for This Highly Conserved Transcription Factor, Front. Physiol. source

In the paper

“Neurodegenerative conditions share mitochondrial dysfunction in their pathogenesis.”

In the paper

“The melatonin phase response curve specifies how exogenous melatonin will shift the individuals’ body clock when given at various times in relation to their sleep midpoint [65].”

What the sources say

• Not checked yetcites [65] Burgess, 2010, Human phase response curves to three days of daily melatonin: 0.5 mg versus 3.0 mg, J. Clin. Endocrinol. Metab. source

In the paper

“High concentration levels of kynurenine in the brain are present in instances of depression [32,55].”

What the sources say

• Not checked yetcites [32] Chitimus, D.M., Popescu, M.R., Voiculescu, S.E., Panaitescu, A.M., Pavel, B., Zagrean, L., and Zagrean, A.M. (2020). Melatonin’s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease. Biomolecules, 10. source
• Not checked yetcites [55] Ferlazzo, N., Andolina, G., Cannata, A., Costanzo, M.G., Rizzo, V., Currò, M., Ientile, R., and Caccamo, D. (2020). Is Melatonin the Cornucopia of the 21st Century?. Antioxidants, 9. source

In the paper

“Exercise has been found to increase the throughput in the serotonin-melatonin pathway, eventually increasing both serotonin and melatonin levels and impacting mood and cognition [55].”

What the sources say

• Not checked yetcites [55] Ferlazzo, N., Andolina, G., Cannata, A., Costanzo, M.G., Rizzo, V., Currò, M., Ientile, R., and Caccamo, D. (2020). Is Melatonin the Cornucopia of the 21st Century?. Antioxidants, 9. source

In the paper

“Preliminary research also indicates that it may be an active component in the glymphatic fluid, assisting in removing metabolic waste such as amyloid buildup [61].”

What the sources say

• Not checked yetcites [61] Reiter, 2022, Melatonin in ventricular and subarachnoid cerebrospinal fluid: Its function in the neural glymphatic network and biological significance for neurocognitive health, Biochem. Biophys. Res. Commun. source

In the paper

“Melatonin supplementation can also modulate the circadian rhythm by causing an advance or delay, depending on the administration time.”

In the paper

“Mitochondrial membranes selectively take up melatonin, a function not shared by other antioxidants [63].”

What the sources say

• Not checked yetcites [63] Srinivasan, 2011, Melatonin in mitochondrial dysfunction and related disorders, Int. J. Alzheimers Dis. source

In the paper

“Human circadian rhythms are entrained to the environmental day primarily by light exposure, particularly at dawn and dusk [64].”

What the sources say

• Not checked yetcites [64] Ashton, A., Foster, R.G., and Jagannath, A. (2022). Photic Entrainment of the Circadian System. Int. J. Mol. Sci., 23. source

In the paper

“Conversely, acute or chronic inflammation and stress have been found to increase the throughput of the kynurenine pathway, leading to an increase in tryptophan’s conversion to kynurenine [32,55].”

What the sources say

• Not checked yetcites [32] Chitimus, D.M., Popescu, M.R., Voiculescu, S.E., Panaitescu, A.M., Pavel, B., Zagrean, L., and Zagrean, A.M. (2020). Melatonin’s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease. Biomolecules, 10. source
• Not checked yetcites [55] Ferlazzo, N., Andolina, G., Cannata, A., Costanzo, M.G., Rizzo, V., Currò, M., Ientile, R., and Caccamo, D. (2020). Is Melatonin the Cornucopia of the 21st Century?. Antioxidants, 9. source

In the paper

“In addition to the kynurenine pathway, Fila et al. [59] reported that the GI tract is also a major site for tryptophan metabolism.”

What the sources say

• Not checked yetcites [59] Fila, M., Chojnacki, J., Pawlowska, E., Szczepanska, J., Chojnacki, C., and Blasiak, J. (2021). Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal Disorders. Int. J. Mol. Sci., 22. source

In the paper

“Lifestyle factors can result in extrinsic circadian rhythm disorders such as shift work disorder or jet lag disorder [66].”

What the sources say

• Not checked yetcites [66] Sateia, M.J. (2014). Disorders. International. Classification of Sleep Disorders, American Academy of Sleep Medicine. [3rd ed.]. source

In the paper

“Multiple studies, opinions, and guidelines have suggested melatonin as primary therapy for improved health and sleep of shift workers [69,70,71].”

What the sources say

• Not checked yetcites [69] Knutsson, 2003, Health disorders of shift workers, Occup. Med. source
• Not checked yetcites [70] Zee, 2010, Treatment of shift work disorder and jet lag, Curr. Treat. Options. Neurol. source
• Not checked yetcites [71] Morgenthaler, 2007, Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report, Sleep source

In the paper

“Melatonin supplementation has shown promise in a rare sleep disorder, idiopathic REM Behavior Disorder (iRBD).”

What the sources say

• Not checked yetcites [94] Kunz, 2021, Treatment of isolated REM sleep behavior disorder using melatonin as a chronobiotic, J. Pineal Res. source

In the paper

“A decrease in core body temperature is soporific [90].”

What the sources say

• Not checked yetcites [90] Reid, 1996, Day-time melatonin administration: Effects on core temperature and sleep onset latency, J. Sleep Res. source

In the paper

“In fact, individuals who are blind tend to have increased abnormalities in circadian rhythm compared with those who have sight [95].”

What the sources say

• Not checked yetcites [95] Aubin, 2017, Melatonin and cortisol profiles in the absence of light perception, Behav. Brain Res. source

In the paper

“In this way, exogenous melatonin can have a direct effect on sleep.”

In the paper

“Melatonin has a hypothermic action.”

In the paper

“Of particular mention, one of Lissoni’s studies indicated that melatonin supplementation (20 mg daily, starting seven days before chemotherapy) was helpful in chemotherapy response rate in fifty metastatic non-small cell lung cancer patients [185].”

What the sources say

• Not checked yetcites [185] Messina, 2010, Enhancement of the efficacy of cancer chemotherapy by the pineal hormone melatonin and its relation with the psychospiritual status of cancer patients, J. Res. Med. Sci.

In the paper

“The melatonin content of the 31 over-the-counter melatonin products was found to be −83% to +478% of that listed on the label. [257]”

What the sources say

• Not checked yetcites [257] Erland, 2017, Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content, J. Clin. Sleep Med. source

In the paper

“A recent meta-analysis and systematic review by researchers at The Chinese University in Hong Kong concluded that a controlled-release oral melatonin supplement reduced asleep systolic blood pressure by 3.57 mm Hg [120].”

What the sources say

• Not checked yetcites [120] Lee, 2022, Controlled-release oral melatonin supplementation for Hypertension and nocturnal Hypertension: A systematic review and meta-analysis, J. Clin. Hypertens. source

In the paper

“A randomized double-blinded placebo-controlled clinical trial with two parallel arms using either placebo or oral 10 mg melatonin supplementation per day for twenty-four weeks in patients with heart failure and reduced ejection fraction observed improvements in endothelial function in those who did not also have diabetes [125].”

What the sources say

• Not checked yetcites [125] Hoseini, 2021, Effect of melatonin supplementation on endothelial function in heart failure with reduced ejection fraction: A randomized, double-blinded clinical trial, Clin. Cardiol. source

In the paper

“A recent, relatively small, placebo-controlled study in male diabetics showed reduced insulin sensitivity by 12% after 10 mg of melatonin for three months [126].”

What the sources say

• Not checked yetcites [126] Lauritzen, 2022, Three months of melatonin treatment reduces insulin sensitivity in patients with type 2 diabetes-A randomized placebo-controlled crossover trial, J. Pineal Res. source

In the paper

“Genetic results suggest a melatonin-signaling deficiency in ADHD [113].”

What the sources say

• Not checked yetcites [113] Checa-Ros, A., Jeréz-Calero, A., Molina-Carballo, A., Campoy, C., and Muñoz-Hoyos, A. (2021). Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications. Nutrients, 13. source

In the paper

“Depleted gut melatonin may be involved in migraine occurrence because of the relative increase in N-acetylserotonin to melatonin ratios, resulting in hyperactive glutamatergic excitatory transmission in migraines.”

In the paper

“It has also been reported as an effective treatment for primary headache disorders [109].”

What the sources say

• Not checked yetcites [109] Ribeiro, 2016, Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention, J. Neurol. Neurosurg. Psychiatry source

In the paper

“One study observed a significantly greater decrease in tinnitus scores on an audiometric test and self-rated tinnitus after treatment with melatonin compared to placebo [112].”

What the sources say

• Not checked yetcites [112] Hurtuk, 2011, Melatonin: Can it stop the ringing?, Ann. Otol. Rhinol. Laryngol. source

In the paper

“Migraines have a solid correlation to altered gut microbiota involving amines and indoles.”

In the paper

“A recent study [219] in healthy adults found that Montmorency tart cherries as either juice (2 × 240 mL per day) or as a supplement (two capsules containing 500 mg freeze-dried tart cherry powder) for thirty days did not affect serum melatonin (although it was measured in the morning when levels tend to be low), or sleep time or quality compared with placebo.”

What the sources say

• Not checked yetcites [219] Hillman, A.R., Trickett, O., Brodsky, C., and Chrismas, B. (2022). Montmorency tart cherry supplementation does not impact sleep, body composition, cellular health, or blood pressure in healthy adults. Nutr. Health, 2601060221111230. source

In the paper

“Improvements in LDL cholesterol and blood pressure have been shown in as few as two months of melatonin use (5 mg/day, two hours before bedtime) in thirty patients with documented metabolic syndrome who had not responded to a three-month intervention of therapeutic lifestyle modifications [119].”

What the sources say

• Not checked yetcites [119] Poliwczak, 2011, Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome, J. Pineal Res. source

In the paper

“Cai et al. [124] correlated low levels of endogenous melatonin to decreased long-term survival in patients with pulmonary hypertension.”

What the sources say

• Not checked yetcites [124] Cai, Z., Klein, T., Geenen, L.W., Tu, L., Tian, S., van den Bosch, A.E., de Rijke, Y.B., Reiss, I.K.M., Boersma, E., and Duncker, D.J. (2020). Lower Plasma Melatonin Levels Predict Worse Long-Term Survival in Pulmonary Arterial Hypertension. J. Clin. Med., 9. source

In the paper

“Most research on the use of melatonin for jet lag is from 10–20 years ago or longer.”

In the paper

“Higher oral doses (50 mg daily) were given in a subsequent study with immunotherapy to 14 patients with advanced hepatocellular carcinoma [280].”

What the sources say

• Not checked yetcites [280] Aldeghi, 1994, Low-dose interleukin-2 subcutaneous immunotherapy in association with the pineal hormone melatonin as a first-line therapy in locally advanced or metastatic hepatocellular carcinoma, Eur. J. Cancer source

In the paper

“A particular proprietary form of phytomelatonin made from alfalfa (Medicago sativa), chlorella powder (Chlorella vulgaris), and rice (Oryza sativa) powders have been shown to contain other phytonutrients in addition to phytomelatonin such as chlorophyll, beta-carotene, isoflavones, phytates, and saponins, all of which are naturally occurring in the plant matrix concentrate [34]”

What the sources say

• Not checked yetcites [34] Kukula-Koch, W., Szwajgier, D., Gaweł-Bęben, K., Strzępek-Gomółka, M., Głowniak, K., and Meissner, H.O. (2021). Is Phytomelatonin Complex Better Than Synthetic Melatonin? The Assessment of the Antiradical and Anti-Inflammatory Properties. Molecules, 26. source

In the paper

“Older clinical studies with smaller subject numbers found no difference [286,287] or modest differences [288] in sleep outcomes compared with placebo.”

What the sources say

• Not checked yetcites [286] Wright, 1998, Randomized clinical trial of melatonin after night-shift work: Efficacy and neuropsychologic effects, Ann. Emerg. Med. source
• Not checked yetcites [287] James, 1998, Can melatonin improve adaptation to night shift?, Am. J. Emerg. Med. source
• Not checked yetcites [288] Jorgensen, 1998, Does exogenous melatonin improve day sleep or night alertness in emergency physicians working night shifts?, Ann. Emerg. Med. source

In the paper

“Since the average human adult produces between 0.1 mg and 0.9 mg of melatonin daily [277], this range is known as physiological doses.”

What the sources say

• Not checked yetcites [277] Scholtens, 2016, Physiological melatonin levels in healthy older people: A systematic review, J. Psychosom. Res. source

In the paper

“The low dose in the study did not raise melatonin levels into the normal range.”

What the sources say

• Not checked yetcites [278] Zhdanova, 2001, Melatonin treatment for age-related insomnia, J. Clin. Endocrinol. Metab. source

In the paper

“Controlled-release formulations have been discouraged in older adults due to the possibility of prolonged melatonin levels and unknown implications thereof [273].”

What the sources say

• Not checked yetcites [273] Vural, 2014, Optimal dosages for melatonin supplementation therapy in older adults: A systematic review of current literature, Drugs Aging source

In the paper

“Those with certain genotypes, such as polymorphisms in the melatonin receptor 1B (MTNR1B) gene, may require monitoring of hemoglobin A1C if they take supplemental melatonin [275,276].”

What the sources say

• Not checked yetcites [275] Benedict, 2022, Melatonin’s Potential Side Effects: It May Be in Your Genes, Mayo Clin. Proc. source
• Not checked yetcites [276] Bonnefond, 2009, A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk, Nat. Genet. source

In the paper

“A recent systematic review and meta-analysis of safety studies on high-dose melatonin (≥10 mg/day) in adults concluded that there are limited studies from which to draw any solid conclusion about its safety profile [274].”

What the sources say

• Not checked yetcites [274] Phillips, 2022, Safety of higher doses of melatonin in adults: A systematic review and meta-analysis, J. Pineal Res. source

In the paper

“Other studies since these pivotal publications have used this dose as a reference [181,182,183,184].”

What the sources say

• Not checked yetcites [181] Elsabagh, 2020, Efficacy of Melatonin in prevention of radiation-induced oral mucositis: A randomized clinical trial, Oral. Dis. source
• Not checked yetcites [182] Johnston, 2019, Phase I dose-finding study for melatonin in pediatric oncology patients with relapsed solid tumors, Pediatr. Blood Cancer source
• Not checked yetcites [183] Petersen, 2015, Effects of melatonin on physical fatigue and other symptoms in patients with advanced cancer receiving palliative care: A double-blind placebo-controlled crossover trial, Cancer source
• Not checked yetcites [184] Sookprasert, 2014, Melatonin in patients with cancer receiving chemotherapy: A randomized, double-blind, placebo-controlled trial, Anticancer Res

In the paper

“They found the best objective data at 0.3 mg of melatonin.”

What the sources say

• Not checked yetcites [278] Zhdanova, 2001, Melatonin treatment for age-related insomnia, J. Clin. Endocrinol. Metab. source

In the paper

“In one study, the fast-release formula was more effective than the slow-release preparation [283].”

What the sources say

• Not checked yetcites [283] Suhner, 1998, Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag, Chronobiol. Int. source

In the paper

“In 2002, Lewy et al. found that physiological doses (0.5 mg) may offer benefits that pharmacologic doses (20 mg) do not [281,282].”

What the sources say

• Not checked yetcites [281] Lewy, 2002, Low, but not high, doses of melatonin entrained a free-running blind person with a long circadian period, Chronobiol. Int. source
• Not checked yetcites [282] Sack, 2000, Entrainment of free-running circadian rhythms by melatonin in blind people, N. Engl. J. Med. source

In the paper

“In fact, those additional constituents may completely or partially explain why this phytomelatonin outperformed synthetic melatonin in cellular assays for inflammation (using COX-2 inhibition) and free radical scavenging [34]”

What the sources say

• Not checked yetcites [34] Kukula-Koch, W., Szwajgier, D., Gaweł-Bęben, K., Strzępek-Gomółka, M., Głowniak, K., and Meissner, H.O. (2021). Is Phytomelatonin Complex Better Than Synthetic Melatonin? The Assessment of the Antiradical and Anti-Inflammatory Properties. Molecules, 26. source

In the paper

“Common contaminants of synthetically produced melatonin, which may or may not be in the final product, include the following compounds [210]:”

What the sources say

• Not checked yetcites [210] Arnao, M.B., and Hernández-Ruiz, J. (2018). The Potential of Phytomelatonin as a Nutraceutical. Molecules, 23. source

In the paper

“In fact, those additional constituents may completely or partially explain why this phytomelatonin outperformed synthetic melatonin in cellular assays for inflammation (using COX-2 inhibition) and free radical scavenging [34]”

What the sources say

• Not checked yetcites [34] Kukula-Koch, W., Szwajgier, D., Gaweł-Bęben, K., Strzępek-Gomółka, M., Głowniak, K., and Meissner, H.O. (2021). Is Phytomelatonin Complex Better Than Synthetic Melatonin? The Assessment of the Antiradical and Anti-Inflammatory Properties. Molecules, 26. source

In the paper

“Finally, to underscore the discussion of dosing in both pediatrics and adults, it is important to understand that melatonin is metabolized via the liver primarily by the enzyme CYP1A2 [292].”

What the sources say

• Not checked yetcites [292] Ma, 2005, Metabolism of melatonin by human cytochromes p450, Drug Metab. Dispos. source

In the paper

“While there are many reasons to be concerned about interactions, there may also be a role for melatonin to offset the toxicity of certain drugs through its antioxidant activity [307,308].”

What the sources say

• Not checked yetcites [307] Raza, 2020, Melatonin ameliorates the drug induced nephrotoxicity: Molecular insights, Nefrologia source
• Not checked yetcites [308] Shaki, 2016, Melatonin can attenuate ciprofloxacin induced nephrotoxicity: Involvement of nitric oxide and TNF-α, Biomed. Pharmacother. source

In the paper

“In a cell assay, vitamin C and phytomelatonin have been shown to demonstrate significant increases in free radical scavenging activity compared to either by themselves [34]; however, those results need to be tested in a clinical trial to be able to extrapolate those findings to humans.”

What the sources say

• Not checked yetcites [34] Kukula-Koch, W., Szwajgier, D., Gaweł-Bęben, K., Strzępek-Gomółka, M., Głowniak, K., and Meissner, H.O. (2021). Is Phytomelatonin Complex Better Than Synthetic Melatonin? The Assessment of the Antiradical and Anti-Inflammatory Properties. Molecules, 26. source

In the paper

“A meta-analysis [289] found essentially no benefit from melatonin.”

What the sources say

• Not checked yetcites [289] Buscemi, 2006, Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: Meta-analysis, Br. Med. J. source

In the paper

“Importantly, melatonin metabolism and activity can be potentially impacted by many dietary, supplemental, and pharmaceutical agents, all of which add to the fact that there is variability in an individual’s personalized response to this compound based on their dietary and medical context.”

What the sources say

• Not checked yetcites [306] Therapeutic Research (2022, July 31). Melatonin. Available online: https://naturalmedicines.therapeuticresearch.com/.

In the paper

“Currently, there is a lack of significant data to make therapeutic suggestions about combinations.”

In the paper

“Caution should be exercised when melatonin is taken with one or more medications; otherwise, adverse side effects (like extreme sedation) can result [303].”

What the sources say

• Not checked yetcites [303] Foster, 2015, Melatonin Interaction Resulting in Severe Sedation, J. Pharm. Pharm. Sci. source

In the paper

“Oral melatonin is mostly perceived as safe based on published reports, even in higher doses [300]; however, there can be specific instances that may necessitate further diligence and clinical oversight.”

What the sources say

• Not checked yetcites [300] Foley, 2019, Adverse events associated with oral administration of melatonin: A critical systematic review of clinical evidence, Complement. Ther. Med. source

In the paper

“Therefore, loss of response after several weeks may suggest a patient’s tolerance of melatonin and necessary dose reduction.”

What the sources say

• Not checked yetcites [293] Braam, 2010, Loss of response to melatonin treatment is associated with slow melatonin metabolism, J. Intellect. Disabil. Res. source

In the paper

“Therefore, medications that affect these enzymatic pathways will influence melatonin metabolism.”

What the sources say

• Not checked yetcites [292] Ma, 2005, Metabolism of melatonin by human cytochromes p450, Drug Metab. Dispos. source
• Not checked yetcites [302] Huuhka, 2006, The effect of CYP2C19 substrate on the metabolism of melatonin in the elderly: A randomized, double-blind, placebo-controlled study, Methods Find Exp. Clin. Pharmacol. source

In the paper

“Earlier research has identified that the majority of melatonin is metabolized through cytochrome (CYP) 1A2 [292,301], with lesser metabolic activity through CYP1A1, CYP1B1, and CYP2C19 [292,302].”

What the sources say

• Not checked yetcites [292] Ma, 2005, Metabolism of melatonin by human cytochromes p450, Drug Metab. Dispos. source
• Not checked yetcites [301] Hidestrand, 2001, Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes, Eur. J. Clin. Pharmacol. source
• Not checked yetcites [302] Huuhka, 2006, The effect of CYP2C19 substrate on the metabolism of melatonin in the elderly: A randomized, double-blind, placebo-controlled study, Methods Find Exp. Clin. Pharmacol. source

In the paper

“Diet: There is still insufficient data about how dietary (exogenous) and gut/pineal (endogenous) sources of melatonin interact and how measurements could be implicated by potential cross-talk among the melatonin inputs.”

In the paper

“Promising clinical data indicates that melatonin may help enhance oocytes’ quality.”

What the sources say

• Not checked yetcites [312] Rizzo, 2010, Effect of the treatment with myo-inositol plus folic acid plus melatonin in comparison with a treatment with myo-inositol plus folic acid on oocyte quality and pregnancy outcome in IVF cycles. A prospective, clinical trial, Eur. Rev. Med. Pharmacol. Sci.
• Not checked yetcites [313] Pacchiarotti, 2016, Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome, Gynecol. Endocrinol. source
• Not checked yetcites [314] Wdowiak, 2020, The effect of myo-inositol, vitamin D3 and melatonin on the oocyte quality and pregnancy in in vitro fertilization: A randomized prospective controlled trial, Eur. Rev. Med. Pharmacol. Sci.

In the paper

“Moreover, since people are not likely to adopt the lifestyle of being in such low evening light, the utility of such a test seems limited unless the practitioner wants to verify that the patient’s pineal gland can make melatonin when they are in dim light conditions.”

In the paper

“Parsanathan and Jain [316] have demonstrated the effects of glutathione deficiency in high-fat-fed mice with observed epigenetic changes in genes responsible for vitamin D metabolism.”

What the sources say

• Not checked yetcites [316] Parsanathan, 2019, Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice, Sci. Rep. source

In the paper

“Combining myo-inositol and folic acid with added melatonin increased oocyte quality in women with PCOS compared with only using myo-inositol and folic acid or folic acid by itself [313].”

What the sources say

• Not checked yetcites [313] Pacchiarotti, 2016, Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome, Gynecol. Endocrinol. source

In the paper

“In summary, there are many variables to consider with a laboratory assessment that may lead to inaccuracies.”

In the paper

“Blue-light-blocking glasses can protect from the melatonin suppressing effects of light [319].”

What the sources say

• Not checked yetcites [319] Hester, 2021, Evening wear of blue-blocking glasses for sleep and mood disorders: A systematic review, Chronobiol. Int. source

In the paper

“One study found that adding melatonin to a supplemental protocol of myo-inositol and folic acid may help increase oocyte viability in women undergoing IVF [312].”

What the sources say

• Not checked yetcites [312] Rizzo, 2010, Effect of the treatment with myo-inositol plus folic acid plus melatonin in comparison with a treatment with myo-inositol plus folic acid on oocyte quality and pregnancy outcome in IVF cycles. A prospective, clinical trial, Eur. Rev. Med. Pharmacol. Sci.

In the paper

“Even light of five to ten lux while sleeping with eyes closed will impact the circadian system [318].”

What the sources say

• Not checked yetcites [318] Partonen, 2019, Systematic review of light exposure impact on human circadian rhythm, Chronobiol. Int. source

In the paper

“Finally, when added to a regimen with vitamin D3, melatonin and myo-inositol were beneficial in oocyte quality, fertilization, and pregnancy outcomes in women undergoing an intracytoplasmic sperm injection [314].”

What the sources say

• Not checked yetcites [314] Wdowiak, 2020, The effect of myo-inositol, vitamin D3 and melatonin on the oocyte quality and pregnancy in in vitro fertilization: A randomized prospective controlled trial, Eur. Rev. Med. Pharmacol. Sci.