Exogenous Melatonin Hormonal Supplements and the Associated Potential Benefits and Risks

Exogenous Melatonin Hormonal Supplements and the Associated Potential Health Benefits and Risks Presented By: Kyle Viehweger

What Is Melatonin???Endocrine hormoneSynthesized from Tryptophan amino acid Precursor Released byPineal GlandExtrapineal TissuesReleased into the blood stream (endocrine)Modulator (Central and Peripheral)Regulator (Seasonal and Circadian cycles)

Melatonin Physiological PropertiesAmphiphilic (fat and water loving)Binds to Cellular Membrane receptorsCytosolic receptorsNuclear receptorsMT1 and MT2Some effects are receptor independent

Potential Benefits of Exogenous Melatonin Antioxidant properties (neural protective)Scavenges oxygen and nitrogen free radicalsDecreases radical formationActivates antioxidant enzymes (superoxide dismutase and glutathione).Anticancer effects (promote apoptosis, inhibit proliferation)Reduce hepatotoxicity effects of EGCG(compound found in green tea extracts)Synchronization of circadian patterns after extraneous physical activityAble to attenuate age related changes in Globus Pallidus of mouse brain

Anti-Cancer Oncostatic Properties (physiological conc.)Cyotoxic Properties (pharmaceutical conc.)Inhibits metastasis, proliferation, and invasiveness (melanoma, glioma, lymphoma, prostate, breast, osteosarcoma, gastrointestinal and colon)Ineffective against ER(estrogen receptor) negative cancers.

Melatonin and Conventional Anti-Cancer Treatment Team up!Kim, W., Jeong, W, J., Kim, E, J. (2014) looked at the effects of Melatonin administered with conventional treatments(UV radiaton) in ER-negative small lung cancer (NSCLC).Specifically looked at A549 and A427 linesCCAR2 (both anti and pro cancer properties)Results low level CCAR2 cell lines with Melatonin and UV radiation led to an increase in PARP-1 cleaving

Reduced Hepatotoxicity of EGCG compoundEGCG weight loss propertiesReduce Visceral adipose tissue accumulationLowers fasting blood glucose and insulin levelsEnhances glucose resistanceResolves insulin resistance.High conc. Leads to hepatic toxicity of the liver.

Reduced Hepatotoxicity of EGCG compoundWang et al (2015)Reduction in H2A.X (oxidation marker) with EGCG and melatonin administration compared with just EGCG administration.Increased survivability of mice treated with EGCG and melatonin vs EGCG aloneMelatonin did not affect any weight loss genes EGCG is effecting

Resynchronization of Circadian Rhythm as Result of Physical ActivityLeonardo, M, R., et al. (2015) conducted a study to see if melatonin would attenuate resistance trained athletes circadian rhythms in response to intense physical activity.All athletes were of good health, and consistent nutrient diet.No athlete was taking any medication.

Leonardo, M, R., et al. (2015) ResultsMelatonin regulates wrist temperature (WT) and activity/body position rhythms.Subjects who took the melatonin before sleep had a 1 hour phase shift as well as a longer duration of an increase in WTWT correlates with vasculature dilation and relaxation (parasympathetic)Only slight difference in activity/body position

Reduction of Aging EffectsCertain proteins and their activity increase with age and facilitate the aging processGFAP (increase)NF-kB (increase)Melatonin calcifies with ageZhou, J., et al. (2013)Melatonin administration to the rats greatly reduced NF-kB and GFAP protein levels within the Globus Pallidus

Reduction of Aging Effects

Early Morning Melatonin Administration Impairs Psychomotor VigilanceGraw, P., et al. (2001)Participants were administered (80-100mg) of melatonin at 0700 hours and were tested on vigilance, awareness, attention(PVT) and concentration(d2) tasks throughout the day.Found a significant decrease in awareness and vigilance up until around 12pm.Concentration remained the same as controls, and even had a slight increase as the day proceeded.

Graw, P., et al. (2001)

Visio-Spatial Impairment and Inhibition of Neocortical LTPMoyano, S, R., et al. (2006)Administration of Melatonin greatly increased the error made by the rats in the 8 arm radial maze as well as total time trying to get to food rewardAmplitude of action potentials were increase after tetanic train stimulation for controls but no change for melatonin group.

Possibly Conflicting ResearchHowever Liet, C., et al. (2015) found that acute administration of melatonin at high dosages lead to no change or effect on rats attention, executive and working memory at all.

Future ResearchMore work needs to be done in regards of the effect of melatonin on certain types of memory in both humans and other mammalsMore in depth work in regards to the potential risks of long-term use of high doses of exogonous melatonin (longitudinal studies) Look at more potential benefits and strengths of melatonin in regards to cancer research.

ReferencesGraw, P., et al. (2001). Early morning melatonin administration impairs psychomotor vigilance. Behavioural Brain Research. DOI: 10.1016/S0166-4328(01)00158-9

Kim, W., Jeong, W, J., Kim, E, J. (2014). CCAR2 deficiency augments genotoxic stress-induced apoptosis in the presence of melatonin in non-small cell lung cancer cells. Tumor Biology. DOI: 10.1007/s13277-014-2370-6

Liet, C., et al. (2006). Effects of acute administration of melatonin on attentional, executive, and working memory processes in rats. Fundamental and Clinical Pharmacology. DOI: 10.1111/fcp.12134Mendonca, L, C, R., et al. (2015). The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes. The Journal of Biological and Medical Rhythm Research. DOI: 10.3109/07420528.2015.1069830Moyano, S, R., et al. (2006). Melatonin administration impairs visuo-spatial performance and inhibits neocortical long-term potentiation in rats. Pharmacology Biochemistry and Behavior. DOI: 10.1016/j.pbb.2006.09.009Wang, D., et al. (2015). Melatonin attenuates (-)-epigallocatehin-3-gallate-triggered hepatotoxicity without compromising its down regulation of hepatic gluconeogenic and lipogenic genes in mice. Journal of Pineal Research. DOI: 10.1111/jpi.12281Zhou, J., et al. (2013). Dietary melatonin attenuates age-related changes in morphology and in levels of key proteins in globus pallidus of mouse brain. Brain Research. DOI:10.1016/j.brainres.2013.12.013