Melatonin info. for Marie

A forum for the discussion of antibiotics as a potential therapy for MS

Melatonin info. for Marie

Postby SarahLonglands » Tue Oct 04, 2005 9:43 am

Melatonin

Sleep disorders are common in MS, with a flattening of the normal circadian sleeping/waking rhythm, leading to wakefulness at night and somnolence during the day [Fleming WE, Pollak CP. Sleep disorders in multiple sclerosis. Semin Neurol. 2005 Mar;25(1):64-8. Review.] One cause of this may be decreased nocturnal biosynthesis of melatonin [Wu YH et al., Molecular changes underlying reduced pineal melatonin levels in Alzheimer disease: alterations in preclinical and clinical stages. J Clin Endocrinol Metab. 2003 Dec;88(12):5898-906.] Decreased melatonin biosynthesis is associated with pineal calcification [Kunz D et al., A new concept for melatonin deficit: on pineal calcification and melatonin excretion. Neuropsychopharmacology. 1999 Dec;21(6):765-72.] Pineal calcification is common in MS [Sandyk R, Awerbuch GI. The pineal gland in multiple sclerosis. Int J Neurosci. 1991 Nov;61(1-2):61-7.] Indeed, nocturnal melatonin levels were found to be lower than daytime levels in 11 of 25 patients with MS. [Sandyk R, Awerbuch GI. Nocturnal plasma melatonin and alpha-melanocyte stimulating hormone levels during exacerbation of multiple sclerosis.] Melatonin is a major antioxidant in the brain. [Reiter RJ et al., Reactive oxygen intermediates, molecular damage, and aging. Relation to melatonin. Ann N Y Acad Sci. 1998 Nov 20;854:410-24. Review.] These authors observe: 'Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger and indirect antioxidant. In terms of its scavenging activity, melatonin has been shown to quench the hydroxyl radical, superoxide anion radical, singlet oxygen, peroxyl radical, and the peroxynitrite anion. Additionally, melatonin's antioxidant actions probably derive from its stimulatory effect on superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase and its inhibitory action on nitric oxide synthase. Finally, melatonin acts to stabilize cell membranes, thereby making them more resistant to oxidative attack. Melatonin is devoid of prooxidant actions. In models of oxidative stress, melatonin has been shown to resist lipid peroxidation induced by paraquat, lipopolysaccharide, ischemia-reperfusion, L-cysteine, potassium cyanide, cadmium chloride, glutathione depletion, alloxan, and alcohol ingestion. Likewise, free radical damage to DNA induced by ionizing radiation, the chemical carcinogen safrole, lipopolysaccharide, and kainic acid are inhibited by melatonin. These findings illustrate that melatonin, due to its high lipid solubility and modest aqueous solubility, is able to protect macromolecules in all parts of the cell from oxidative damage. Melatonin also prevents the inhibitory action of ruthenium red at the level of the mitochondria, thereby promoting ATP production. In humans, the total antioxidative capacity of serum is related to melatonin levels. Thus, the reduction in melatonin with age may be a factor in increased oxidative damage.'

Sleep well!

Sarah :)
An Itinerary in Light and Shadow Completed Dr Charles Stratton / Dr David Wheldon abx regime for aggressive secondary progressive MS in June 2007, after four years. Still improving with no relapses since starting. Can't run but can paint all day.
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Postby bromley » Tue Oct 04, 2005 10:50 am

Thanks Sarah,

Does anyone know if one can boost melatonin to make up for the deficit e.g. supplements?

Is it possible to de-calcify a calcified pineal gland?

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Postby mrhodes40 » Tue Oct 04, 2005 3:23 pm

Melatonin is available over the counter in the US. I have been using it for some time actually. I stopped taking LDN for a few days that seems to have cleared up my sleeping trouble. It's common for people to have sleep problems with LDN and to need to take a few off every once in a while, but that's never happened to me...til now! Boy, it is a pharmacopia of stuff to keep track of and pay attention to is it not? Goodness. Thank you for the info...
BLessings
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Postby SarahLonglands » Wed Oct 05, 2005 3:40 am

Hello Bromley,

You can boost melatonin by taking supplemnts. As with most things, I import it from the States:
http://store.yahoo.com/iherb/melatonin11.html
It will make you very drowsy, so only take it at night. If you find one is too much, split open the capsiule and take it over a couple of nights. I find that if I take a whole capsule, I fall asleep immediately.

You will find this at the bottom of David's latest new page on mitochondrial stress:

http://www.davidwheldon.co.uk/supplement_rationale.html

Melatonin
Melatonin was originally described as a hormone biosynthesized from L-tryptophan within the pineal gland in the brain; it was found to regulate sleep patterns. Since its discovery, this remarkable molecule has been found to be a potent antioxidant, protecting mitochondria from oxidative stress [reviewed by Leon J, Acuna-Castroviejo D, Sainz RM, Mayo JC, Tan DX, Reiter RJ. Melatonin and mitochondrial function. Life Sci. 2004 Jul 2;75(7):765-90.] It may also act directly on the electron transport chain, increasing ATP synthesis while preventing the oxidative damage associated with such an increase. [Acuna-Castroviejo D, Escames G, Leon J, Carazo A, Khaldy H. Mitochondrial regulation by melatonin and its metabolites. Adv Exp Med Biol. 2003;527:549-57.] These authors also found that melatonin restored levels of the important antioxidant glutathione.

Melatonin is a remarkably mobile molecule and is able to pass into any tissue, cell or cell compartment with ease. [reviewed by Hardeland R, Pandi-Perumal SR. Melatonin, a potent agent in antioxidative defense: Actions as a natural food constituent, gastrointestinal factor, drug and prodrug. Nutr Metab (Lond). 2005 Sep 10;2(1):22.] These authors observe that, unusually for a hormone, melatonin is a normal dietary constituent, and is found in yeasts and plants; walnuts are a particularly rich source. Dietary melatonin can markedly influence blood-levels. [Reiter RJ, Manchester LC, Tan DX.Melatonin in walnuts: Influence on levels of melatonin and total antioxidant capacity of blood. Nutrition. 2005 Sep;21(9):920-4.] The fact that melatonin is found in the diet removes some of the hesitation which one may have in using it for supplementation.

Melatonin protects against endotoxin-induced lipid peroxidation. [Sewerynek E, Melchiorri D, Chen L, Reiter RJ. Melatonin reduces both basal and bacterial lipopolysaccharide-induced lipid peroxidation in vitro. Free Radic Biol Med. 1995 Dec;19(6):903-9.] This is very important in the CNS, where key lipids are relatively unprotected by other antioxidants.

Reiter and colleagues, in a comprehensive review, observe: 'Melatonin reduces oxidative stress by several means. Thus, the indole [melatonin] is an effective scavenger of both the highly toxic hydroxyl radical, produced by the 3 electron reduction of oxygen, and the peroxyl radical, which is generated during the oxidation of unsaturated lipids and which is sufficiently toxic to propagate lipid peroxidation. Additionally, melatonin may stimulate some important antioxidative enzymes, i.e., superoxide dismutase, glutathione peroxidase and glutathione reductase. In in vivo tests, melatonin in pharmacological doses has been found effective in reducing macromolecular damage that is a consequence of a variety of toxic agents, xenobiotics and experimental paradigms which induce free radical generation. In these studies, melatonin was found to significantly inhibit oxidative damage that is a consequence of paraquat toxicity, potassium cyanide administration, lipopolysaccharide treatment, kainic acid injection, carcinogen administration, carbon tetrachloride poisoning, etc., as well as reducing the oxidation of macromolecules that occurs during strenuous exercise or ischemia-reperfusion. In experimental models which are used to study neurodegenerative changes associated with Alzheimer's and Parkinson disease, melatonin was found to be effective in reducing neuronal damage. Its lack of toxicity and the ease with which melatonin crosses morphophysiological barriers and enters subcellular compartments are essential features of this antioxidant.' [Reiter RJ, Carneiro RC, Oh CS. Melatonin in relation to cellular antioxidative defense mechanisms. Horm Metab Res. 1997 Aug;29(8):363-72.]

Melatonin was found to inhibit the production of endotoxin-induced Tumour Necrosis Factor [Sacco S et al., Mechanism of the inhibitory effect of melatonin on tumor necrosis factor production in vivo and in vitro. Eur J Pharmacol. 1998 Feb 19;343(2-3):249-55.] and in an animal model was found to exert immunoregulatory effects via T-helper 2 (Th2) cell products. Th2 products may modulate the secretion and/or action of inflammatory cytokines, which play an important role in the development of septic shock associated with endotoxemia. [Maestroni GJ. Melatonin as a therapeutic agent in experimental endotoxic shock. J Pineal Res. 1996 Mar;20(2):84-9.]

Post-mortem studies showed diminished levels of melatonin in the ventricular CSF of those who had died with Alzheimer's disease compared with age-matched controls. The same authors found that CSF levels of melatonin in the elderly were much lower than in younger persons. However, melatonin levels were uniformly low in those who had died with presenile and senile dementia. [Liu RY, Zhou JN, van Heerikhuize J, Hofman MA, Swaab DF. Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer's disease, and apolipoprotein E-epsilon4/4 genotype. J Clin Endocrinol Metab. 1999 Jan;84(1):323-7.] Melatonin depletion was found to be an early event in the development of Alzheimer's disease. [Zhou JN, Liu RY, Kamphorst W, Hofman MA, Swaab DF. Early neuropathological Alzheimer's changes in aged individuals are accompanied by decreased cerebrospinal fluid melatonin levels. J Pineal Res. 2003 Sep;35(2):125-30.] A loss of the diurnal rhythm of melatonin levels may precede clinical signs of the disease. [Wu YH, Feenstra MG, Zhou JN, Liu RY, Torano JS, Van Kan HJ, Fischer DF, Ravid R, Swaab DF. Molecular changes underlying reduced pineal melatonin levels in Alzheimer disease: alterations in preclinical and clinical stages. J Clin Endocrinol Metab. 2003 Dec;88(12): 5898-906.]

Sleep disorders are common in MS, with a flattening of the normal circadian sleeping/waking rhythm, leading to wakefulness at night and a tendency to somnolence during the day. [Fleming WE, Pollak CP. Sleep disorders in multiple sclerosis. Semin Neurol. 2005 Mar;25(1):64-8. Review.] One cause of this may be decreased nocturnal biosynthesis of melatonin. [Wu YH et al., Molecular changes underlying reduced pineal melatonin levels in Alzheimer disease: alterations in preclinical and clinical stages. J Clin Endocrinol Metab. 2003 Dec;88(12):5898-906.] Decreased melatonin biosynthesis is associated with pineal calcification. [Kunz D et al., A new concept for melatonin deficit: on pineal calcification and melatonin excretion. Neuropsychopharmacology. 1999 Dec;21(6):765-72.] Pineal calcification is common in MS. [Sandyk R, Awerbuch GI. The pineal gland in multiple sclerosis. Int J Neurosci. 1991 Nov;61(1-2):61-7.] Indeed, nocturnal melatonin levels were found to be lower than daytime levels in 11 of 25 patients with MS. [Sandyk R, Awerbuch GI. Nocturnal plasma melatonin and alpha-melanocyte stimulating hormone levels during exacerbation of multiple sclerosis. Int J Neurosci. 1992 Nov-Dec;67(1-4):173-86. Review] Melatonin is a major antioxidant in the brain, and chronic depletion would be expected to allow widespread oxidative damage in the CNS. [Reiter RJ et al., Reactive oxygen intermediates, molecular damage, and aging. Relation to melatonin. Ann N Y Acad Sci. 1998 Nov 20;854:410-24. Review.]

Melatonin would thus seem a valuable supplement in disease forms characterized by oxidative stress.


If you like walnuts, you are in luck! :wink:

Sarah
An Itinerary in Light and Shadow Completed Dr Charles Stratton / Dr David Wheldon abx regime for aggressive secondary progressive MS in June 2007, after four years. Still improving with no relapses since starting. Can't run but can paint all day.
SarahLonglands
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Posts: 2110
Joined: Thu Jun 17, 2004 3:00 pm
Location: Bedfordshire UK


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