This document summarizes research on the physiological properties and potential health benefits and risks of exogenous melatonin supplementation. It discusses melatonin's role as an antioxidant and its potential anticancer, circadian rhythm regulating, and neuroprotective effects. However, it also notes that early morning melatonin administration may impair psychomotor performance and vigilance. More research is still needed to fully understand melatonin's long-term impacts and benefits, especially regarding cancer treatments and effects on memory.

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

2. What Is Melatonin???
• Endocrine hormone
• Synthesized from Tryptophan amino acid
Precursor
• Released by
Pineal Gland
Extrapineal Tissues
Released into the blood stream (endocrine)
• Modulator (Central and Peripheral)
• Regulator (Seasonal and Circadian cycles)

3. Melatonin Physiological Properties
• Amphiphilic (fat and water loving)
• Binds to
Cellular Membrane receptors
Cytosolic receptors
Nuclear receptors
• MT1 and MT2
• Some effects are receptor independent

4. Potential Benefits of Exogenous
Melatonin
• Antioxidant properties (neural protective)
Scavenges oxygen and nitrogen free radicals
Decreases radical formation
Activates 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 activity
• Able to attenuate age related changes in Globus Pallidus of
mouse brain

5. 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.

6. 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 lines
• CCAR2 (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

8. Reduced Hepatotoxicity of EGCG
compound
• EGCG weight loss properties
Reduce Visceral adipose tissue
accumulation
Lowers fasting blood glucose
and insulin levels
Enhances glucose resistance
Resolves insulin resistance.
• High conc. Leads to
hepatic toxicity of the liver.

9. Reduced Hepatotoxicity of EGCG
compound
• Wang 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 alone
• Melatonin did not affect any weight loss genes
EGCG is effecting

11. Resynchronization of Circadian Rhythm
as Result of Physical Activity
• Leonardo, 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.

12. Leonardo, M, R., et al. (2015)
Results
• Melatonin 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 WT
• WT correlates with vasculature dilation and
relaxation (parasympathetic)
• Only slight difference in activity/body position

14. Reduction of Aging Effects
• Certain proteins and their activity increase
with age and facilitate the aging process
GFAP (increase)
NF-kB (increase)
• Melatonin calcifies with age
• Zhou, J., et al. (2013)
• Melatonin administration to the rats greatly
reduced NF-kB and GFAP protein levels
within the Globus Pallidus

15. Reduction of Aging Effects

17. Early Morning Melatonin
Administration Impairs Psychomotor
Vigilance
• Graw, 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.

18. Graw, P., et al.
(2001)

19. Visio-Spatial Impairment and
Inhibition of Neocortical LTP
• Moyano, 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
reward
• Amplitude of action potentials were increase
after tetanic train stimulation for controls but
no change for melatonin group.

21. Possibly Conflicting Research
• However 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.

22. Future Research
• More work needs to be done in regards of the
effect of melatonin on certain types of
memory in both humans and other mammals
• More 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.

23. References
• Graw, 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.12134
• Mendonca, 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:
10.3109/07420528.2015.1069830
• Moyano, 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.2006.09.009
• Wang, 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.12281
• Zhou, 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