Melatonin in Health and Disease – Effects of Fluoride

1. Melatonin in Health and Disease – Effects of Fluoride Ray Kearney Email:ray.kearney@sydney.edu.au

2. Inter-dependency of species in LCBP Fungi gnat eggs Hygrocybe erythrocala Mossis essential for the survival of most fungal species (biotrophs = parasitic) in the family Hygrophoraceae

3. Pterostylis nutans & fungi gnats – flow-on effects Viscidium (glue) Pollinium Gnat pollination H. griseoramosa

4. Cause of effect and ‘flow-on’ effects Fungus Gnat Orchid Moss = = = Anti-moss chemical

5. Cause of effect and ‘flow-on’ effects Fungus Gnat Orchid Moss = = = Anti-moss chemical Fertilizers Trampling Petroleum products Etc.

6. Cause of effect and ‘flow-on’ effects Fungus Gnat Orchid Moss = = = Melatonin (analogy) Anti-moss chemical (analogy) Fluoride Roundup Beta-blockers EMF

7. Melatonin - maintains the body's circadian rhythm NEJM (1997) v 336, p186-195

8. Extra-pineal tissues and organs synthesize melatonin • These include: • retina, • ciliary body (inside eye), • lens, • Harderian gland (outside eye), • brain, • thymus, • airway epithelium, • bone marrow, • gut (400x higher than in pineal gland), • ovary, • testicle, • placenta, • lymphocytes, • skin • Note: • Extra-pineal melatonin synthesis is not subject to light/dark regulation. • 2. Locally generated melatonin is consumed by the tissues in which it is • produced as a protective mechanism of oxidative stress. Journal of Pineal Research (2007), Vol. 42 p 28-42

9. *Decline prevented by calorie restriction with adequate nutrition Note: 1pg = one trillionth of a gram *The Journal of Clinical Endocrinology & Metabolism (2001) vol. 86 p. 3292-3295

10. (Melatonin is highly lipophilic and remains 20-90 minutes in bloodstream)

11. MELATONIN Biological properties e.g., • capacity to scavenge free radicals, especially the hydroxyl radical (e.g., neuron & heart damage) • prevents DNA damage by free radicals • protects against cancer initiation; anti-cancer • binds calmodulin and blocks activation of oestrogen receptor-alpha • down-regulates glucocorticoid receptors Journal of Pineal Research (2012) Vol. 52 p. 1-11

12. Mitochondrial dysfunction and cell death outer mitochondrial membrane Mitochondrion Phospholipid bi-layer Cytochrome C (bound to Inner membrane) Superoxidase Dismutase Melatonin Ischaemia- reperfusion, degenerative disease & ageing (multi-factorial) Cardiolipin (CL) CLOOH Promotes detachment of Cytochrome C Journal of Pineal Research (2010) Vol. 48, p.297-310

13. MELATONIN Activates: • bone marrow cells • natural killer (NK) cells • antibody response e.g., anti-bacterial/viral (Th1) responses and suppresses allergic (Th2) responses • antibody-dependent cell cytotoxicity • T-cell proliferation (& increases size of thymus gland) • monocytes, neutrophils and cytokine release (e.g., IL-1, IL-6 and TNF ) http://linkinghub.elsevier.com/retrieve/pii/S1529104904000509?via=sd

14. Melatonin Augments Antibody Responses • Inhibition of melatonin production results in severe suppression of immune responses including production of antibodies • Immune responsiveness is restored by melatonin NOTE: Relatively high doses of melatonin can exacerbate autoimmunity e.g., rheumatoid arthritis. http://linkinghub.elsevier.com/retrieve/pii/S1529104904000509?via=sd

15. MELATONIN • Melatonin inhibits LDL receptor activity and synthesis of cholesterol Biochem Biophys Res Commun. (1994) Vol. 203:416-21 • Decreases blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index Int J Exp Pathol. (2007) Vol. 88:19-29.

16. Melatonin helps control weight gain It stimulates the appearance of ‘beige fat’ which burns calories instead of storing them. http://www.sciencedaily.com/releases/2013/09/130925091745.htm http://genesdev.cshlp.org/content/27/3/234.full

17. MELATONIN • Anti-tumour effects with human tumours • e.g., • melanoma • osteosarcoma • breast carcinoma • prostate carcinoma • cervical carcinoma • glioblastoma • endometrial cancer e.g., Journal of Pineal Research (2005) vol. 39(4) p 360-366.

18. Journal of Pineal Research (2011) Vol. 51 p. 259-269

19. R. Kearney

20. 1 mm tumour with blood supply R. Kearney

21. Tumour - Cell Growth and Death Normal cell Carcinogen e.g., DMBA in diesel Initiation and transformation Tumour Tumour cell ( early growth) Dormancy death rate = division rate Apoptosis ( cell suicide) Acceleration of Tumour growth • Inflammation • Lipopolysaccharide • Low melatonin PROMOTERS e.g., - Diet - Age - Obesity

22. R. Kearney

24. MELATONIN • Confers protection against carcinogenic effects of environmental toxins (Qi, Reiter et al., 2000) • Confers protection against potential carcinogenic hormones e.g., oestrogen (Karbownik, Lewinski et al., 2001)

25. Melatonin and Cancer • Breast cancer growth isaccelerated by dietary linoleic acid (LA). • Melatonin interacts with breast cancer cells to down-regulate the effect of LA. • Melatonin blocks fatty acid transport andstimulates apoptosis. • Melatoninslowsbreast-cancer growth by70%, at night. • Constant exposure to lightaccelerates cancer growth 7-foldand consumes LA. • Circadian disruption of the nocturnal melatonin signalactivates human breast cancer growth. D.E. Blask (2003) American Association for Cancer Research 94th Annual Meeting, Washington,D.C., July 11-14. http://cancerres.aacrjournals.org/content/59/18/4693.short Endocrine (2005) Vol. 27(2), p.179-188 Journal of Pineal Research (2011) Vol. 51, p.259-269

26. Longitudinal human studies of low night melatonin and breast cancer • There is increasingly strong long-termevidence that low melatonin production is a risk factor for at least post-menopausal breast cancer. http://www.bioinitiative.org/table-of-contents/

27. Fluoride accumulates to high levels in the pineal gland • In the 1990s, a British scientist, Jennifer Luke, discovered that fluoride accumulates to strikingly high levels in the pineal gland. (Luke 2001). • National Research Council has stated that “fluoride is likely to cause decreased melatonin production and to have other effects on normal pineal function, which in turn could contribute to a variety of effects in humans” (NRC, 2006, p. 256).

28. Pineal Gland and Sodium/Calcium Fluoride • High levels of Sodium Fluoride accumulate in the • pineal gland and causes its calcification and inhibits • melatonin • The human pineal gland contains the highest • concentration of fluoride in the body > bone and teeth • See references in bibliographies: • http://fluoridealert.org/researchers/health_database/ • http://meridianenergies.net/the-effect-of-fluoride-on-the-physiology-of-the-pineal-gland/ • http://www.globalresearch.ca/harvard-study-fluoride-lowers-childrens-intelligence-by-7-iq-points/5368216 • http://www.fluorideresearch.org/463/files/FJ2013_v46_n3_p104-117_sfs.pdf • Caries Res (2001); Vol. 35:125-128

29. http://thehigherlearning.com/2014/03/07/flouride-the-greatest-case-of-scientific-fraud-in-history-guest-piece/http://thehigherlearning.com/2014/03/07/flouride-the-greatest-case-of-scientific-fraud-in-history-guest-piece/

30. World Health Organization Data (2004) - Tooth Decay Trends (12 year olds) in Fluoridated vs. Unfluoridated Countries: 

31. Risk for Melatonin Deficiency • Most medications prescribed to lower blood pressure may reduce serum melatonin levels e.g., beta-blockers e.g., propranolol calcium channel blockers, calcium antagonists • An estimated 40% of individuals who take beta-blockers have sleep disorders • Melatonin should be combined with statins to reduce the free-radical-mediated side effects of these cholesterol-lowering drugs. Int. J. Clin. Prac. 2007, vol. 61 (5) p. 835-845. http://onlinelibrary.wiley.com/doi/10.1111/j.1600-079X.2009.00697.x/full

32. Retino-hypothalamic (RH) Suprachiasmatic nucleus (SCN) Paraventricular nucleus (PVN) Darkness Superior Cervical Ganglion (SCG) (Noradrenaline) Serotonin Darkness Reviews of Reproduction (1998) 3, 13-22

33. Midnight

35. Does fluoride lower IQ? • Harvard University Studies (2012): “ Fluoride lowers IQ by 7 IQ points and causes other health problems” http://www.ncbi.nlm.nih.gov/pmc/?term=10.1289/ehp.1104912 • Dunedin (NZ) Multidisciplinary Study (2014): “Our analysis showed no significant differences in IQ by fluoride exposure” http://www.medicalnewstoday.com/articles/277240.php

36. Duty of care • According to the USA EPA, fluoride is a chemical "with substantial evidence of developmental neurotoxicity". • Why subject our children to this ongoing fluoridation experiment to satisfy the political agenda of special-interest groups? Even if fluoridation reduced cavities,is brain health more important than tooth health?

37. Periodontitis Inflammation - response to tissue injury e.g., infection There are different types, or classes, of periodontitise.g., chronic and invasive

38. PERIODONTAL CHANGES IN FLUOROSED AND NON-FLUOROSED TEETH • A strong association of periodontal disease with high fluoride water. • No effort appears to have been reported in the literature to account for increased periodontal disease in high fluoride areas. http://www.fluorideresearch.org/402/files/FJ2007_v40_n2_p128-133.pdf

39. Beware of illogical co-relations! • More and more people drink milk • More and more people get cancer Therefore, milk causes cancer! • coronary heart disease is more common in wealthier countries than in poorer Therefore, wealth causes heart disease!

40. Melatonin expression in periodontal disease • Patients with periodontal disease had significantly (p < 0.001) lower plasma (9.46 +/- 3.18 pg/mL) and saliva (2.55 +/- 0.99 pg/mL) melatonin levels than healthy control patients (14.33 +/- 4.05 and 4.22 +/- 0.87 pg/mL, respectively). J Periodontal Res. 2007 Dec;42(6):536-40. http://www.ncbi.nlm.nih.gov/pubmed/17956466

41. Evaluation of melatonin levels in saliva in periodontal health and disease • Periodontitis sufferers had a significantly lower melatonin level than the healthy subjects. • The reduction in the saliva production with higher age and the decreased melatonin production in older adults reflected in low salivary melatonin levels predispose these individuals to an increased risk of developing oral and periodontal disease. J Int Clin Dent Res Organ 2010; 2:119-25

42. Periodontitis Inflammation - response to tissue injury e.g., infection (Mel moderates inflammation) There are different types, or classes, of periodontitise.g., chronic and invasive S-IgA antibody is anti-inflammatory (Mel augments S-IgA levels)

43. IgA levels in the saliva in patients with periodontal disease • Average value of IgA in saliva of periodontitis patients (30) was 0.30 g/l and it is significantly lower than in the control (30) group (p < 0.001). Med Pregl. 1997 Jan-Feb;50(1-2):9-11. http://www.ncbi.nlm.nih.gov/pubmed/9132555

44. Melatonin and Periodontal Disease • Melatonin, activates several elements of the immune system that reduce tissue destruction during the inflammatory response: • Either directly by scavenging free radical, reactive oxygen species and reactive nitrogen species or, • Indirectly by modulating the action of agents such as cytokines and adhesion molecules, which contribute to the advance of cell damage. J Int Clin Dent Res Organ 2010;2:119-25

45. ‘Roundup’ blocks tryptophan synthesis • Dopamine, serotonin, melatonin and norepinephrine are all derived from the aromatic amino acids (e.g., tryptophan) whose synthesis is blocked by glyphosate (Roundup). http://www.westonaprice.org/health-topics/roundup-the-nontoxic-chemical-that-may-be-destroying-our-health/

46. ELF Magnetic Field EXPOSURE and MELATONIN Conclusion: • Eleven (11) of the 13 published epidemiologic residential and occupational studies are considered to provide (positive) evidence that high ELF MF exposurecan result in decreased melatonin production. http://www.bioinitiative.org/table-of-contents/ http://www.smh.com.au/tv/documentary/resonance-beings-of-frequency-4321309.html http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130204/ http://www.ncbi.nlm.nih.gov/pubmed/16059923

47. Sulphate insufficiency is a critical factor in neurological disease • Melatonin is transported within the ventricles as melatonin sulphate • Both oxidative stress and impaired clearance of cellular debris are implicated in neurological diseases. http://dx.doi.org/10.4236/as.2015.61005

48. Third Ventricle and Pineal Gland The third ventricle is depleted in heparan sulphate in association with autism in both humans and mice*,** Heparan sulphate depleted Heparan sulphate in the lysosomes is critical for recycling cellular debris ** * Melatonin-sulphate Pineal Gland ** Stephanie Seneff International Symposium on Vaccines Nice, France Mar. 26, 2014 H. Tricoire et al., Endocrinology 2002, 143(1):84–90 * *B.L. Pearson et al., Behav Brain Res. 2013, Apr 15;243:138-45. **F Mercie et al., Neurosci Lett. 2012,506: 208-213.

49. National Research Council of the National Academies of Science (2006) • NRC identified a range of health effects that can be associated with fluoride exposure, including damage to the brain, disruption of the endocrine system (thyroid gland, pineal gland, and glucose metabolism), and bone cancer. http://www.nap.edu/catalog/11571/fluoride-in-drinking-water-a-scientific-review-of-epas-standards

50. Cause of effect and ‘flow-on’ effects Fungus Gnat Orchid Moss = = = Melatonin (analogy) Anti-moss chemical (analogy) Fluoride Roundup Beta-blockers EMF