also would like to attract your attention to the paper on vit. D in the latest posts. The paper described that people with depression did better if they were located in the side of the hospital with sun exposure as well as people recovering from surgery. I assume that the exposure is mostly sunlight filtered by windows so in theory no UVB exposure. Light itself stimulates the pituitary gland resulting in hormone secretions and that could explain quicker recovery from depression as opposed to people kept in darker rooms. Perhaps light itself plays a role in addition to vit D. from UVB exposure. I guess my understanding is that UVB are filtered by glass. Am I right on this? What do you think Jimmylegs?
Med Hypotheses. 2000 Sep;55(3):239-41.
The possible role of gradual accumulation of copper, cadmium, lead and iron and gradual depletion of zinc, magnesium, selenium, vitamins B2, B6, D, and E and essential fatty acids in multiple sclerosis.
Multiple sclerosis (MS) has a much higher incidence among caucasians that in any other race. Furthermore: females are much more susceptible than males and white females living in colder, wetter areas are much more susceptible than those living in warmer areas. On the other hand, menstruating women have increased copper (Cu) absorption and half-life, so they tend to accumulate more Cu than males. Moreover, rapidly growing girls have an increased demand for zinc (Zn), but their rapidly decreasing production of melatonin results in impaired Zn absorption, which is exacerbated by the high Cu levels. The low Zn levels result in deficient CuZnSuperoxide dismutase (CuZnSOD), which in turn leads to increased levels of superoxide. Menstruating females also often present with low magnesium (Mg) and vitamin B6 levels. Vitamin B6 moderates intracellular nitric oxide (NO) production and extracellular Mg is required for NO release from the cell, so that a deficiency of these nutrients results in increased NO production in the cell and reduced release from the cell. The trapped NO combines with superoxide to form peroxinitrite, an extremely powerful free radical that leads to the myelin damage of MS. Iron (Fe), molybdenum (Mo) and cadmium (Cd) accumulation also increase superoxide production. Which explains MS in males, who tend to accumulate Fe much faster and Cu much less rapidly than females. Since vitamin D is paramount for Mg absorption, the much reduced exposure to sunlight in the higher latitudes may account for the higher incidence in these areas. Moreover, vitamin B2 is a cofactor for xanthine oxidase, and its deficiency exacerbates the low levels of uric acid caused by high Cu levels, resulting in myelin degeneration. Finally Selenium (Se) and vitamin E prevent lipid peroxidation and EPA and DHA upregulate CuZnSOD. Therefore, supplementation with 100 mg MG, 25 mg vit B6, 10 mg vit B2, 15 mg Zn and 400 IU vit D and E, 100 microg Se, 180 mg EPA and 120 mg DHA per day between 14 and 16 years of age may prevent MS.
Melatonin: Where It Comes From
Melatonin is a naturally occuring hormone that is synthesized from the neurotransmitter serotonin which in turn is synthesized from the amino acid tryptophan. This synthesis or production occurs primarily in a gland located at the center of the brain called the pineal gland. The pineal gland is light-activated, i.e., it is controlled by the amount of light seen by the eyes each day. This light activation gives rise to the belief that the pineal gland functions as the body's internal clock, regulating functions that are time-related such as sleep and the ageing process. Melatonin production via serotonin synthesis occurs at its peak during the dark hours around 2:00 a.m. Inversely, during daylight hours, melatonin production is low. It is for this reason that melatonin is believed to aid in regulating our sleep cycle and help stimulate sleep. Also, evidence exists that the pineal gland not only controls our 24 hour clock but our "life clock", meaning that it appears to be a major controller regarding our ageig process. As we age, several things happen to our pineal gland that result in it producing less melatonin. Since the pineal gland is derived from nerve tissue, the gland's cells do not replicate when damaged or lost. This loss of pineal gland cells may result from chemical or biological injury to the gland, or for a myriad of other reasons. Therefore, as we age, the pineal gland literally decreases in size or atrophies which has a direct effect on the amount of melatonin it is capable of synthesizing. Additionally, the gland itself is susceptible to the ageing processes that occur, such as calcium deposits and a decreased blood supply due to atherosclerosis. These in conjunction with other ageing processes interfere with the pineal gland’s melatonin-producing activities.
The interaction of melatonin and its precursors with aluminium, cadmium, copper, iron, lead, and zinc : An adsorptive voltammetric study
Auteur(s) / Author(s)
LIMSON J. (1) ; NYOKONG T. (1) ; DAYA S. (2) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Department of Chemistry, Rhodes University, Grahamstown 6140, AFRIQUE DU SUD
(2) Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, AFRIQUE DU SUD
Résumé / Abstract
Melatonin, a pineal secretory product, and its precursors, tryptophan and serotonin, were examined for their metal binding affinities for both essential and toxic metals: aluminium, cadmium, copper, iron, lead, and zinc. An electrochemical technique, adsorptive stripping voltammetry, showed the varying abilities of melatonin and its precursors to bind the metals in situ. The results show that the following metal complexes were formed: aluminium with melatonin, tryptophan, and serotonin; cadmium with melatonin and tryptophan; copper with melatonin and serotonin; iron(III) with melatonin and serotonin; lead with melatonin, tryptophan, and serotonin; and zinc with melatonin and tryptophan. Iron(II) showed the formation of an in situ complex with tryptophan only. These studies suggest a further role for melatonin in the reduction of free radical generation and metal detoxification, and they may explain the accumulation of aluminium in Alzheimer's disease.
Revue / Journal Title
Journal of pineal research (J. pineal res.) ISSN 0742-3098 CODEN JPRSE9
Source / Source
1998, vol. 24, no1, pp. 15-21 (25 ref.)
Located in the third ventricle of the brain, the pineal gland secretes melatonin, a potent antioxidant and modulatory hormone that mediates the body's response to light/dark cycles, immune dysfunction, stress, and a variety of other physiological and emotional factors. Recently, pineal gland dysfunction has been strongly implicated in the pathogenesis and clinical course of MS. Interestingly, independent research has cited both abnormally high and abnormally low levels as possible triggers for the disease.
MS is more prevalent in northern regions of the globe. One possible explanation is that reduced exposure to sunlight in higher latitudes results in chronic oversecretion of melatonin by the pineal gland. This in turn promotes hypertrophy of the thymus, eventually resulting in the inability of the thymus to entrain T-lymphocytes to distinguish between foreign antigens and cells normally found in the body. Indeed, experimental models show that constant darkness exacerbates the symptoms of autoimmune disease. Based on these findings, one researcher proposed that "intercurrent virus infection and higher melatonin levels in winter could be interactive or synergistic risk factors for the development of MS."1
Another model for the etiology of MS focuses on the potential immune vulnerability posed by a melatonin deficiency. MS rarely strikes an individual before age 15--and one researcher has suggested that this age of onset corresponds with rapidly declining levels of melatonin just before puberty--producing heightened immunological susceptibility. A small study of MS patients with onset of the disease immediately before or after puberty revealed significantly lowered nocturnal levels of melatonin.2
Hokkaido Igaku Zasshi. 1994 Jan;69(1):46-64.Links
[Regulation mechanism of melatonin rhythm in the pineal gland by light: experimental studies by in vivo microdialysis][Article in Japanese]
Department of Physiology, Hokkaido University School of Medicine, Sapporo, Japan.
Light has dual effects on the pineal melatonin; one is the entrainment of the circadian rhythm and the other is suppression of the melatonin synthesis. It is not known whether the entraining and suppressing effects of light are mediated by the same pathway or not. To elucidate the mechanism of the dual effects of light, (1) the sensitivity of the retina, (2) effects of acetylcholine agonist and, (3) the arrhythmicity induced by longterm continuous light, were studied by measuring melatonin continuously from a single rat by means of in vivo microdialysis. Pineal melatonin was suppressed by light more strongly at the late dark phase than at midnight, and by green light (520nm) than by red light (660nm). Pineal melatonin measured by microdialysis was decreased rapidly by a short light exposure and the melatonin rhythm was shifted on the following days. Microinjection of cholinergic agonist, carbachol, into the suprachiasmatic nucleus neither suppressed nor entrained the pineal melatonin rhythm. Immediately after the blinding, rats showed the circadian rhythm in pineal melatonin which had been abolished under long-term continuous light. While, it took several days for the locomotor rhythm to reappear. It is concluded that, (1) suppression of the pineal melatonin by light depends on the circadian phase and on the wavelength of light, (2) the threshold for light suppression is lower than that for phase-shift, (3) the melatonin rhythm starts to phase-shift on the following day of light pulse. (4) Acetylcholine is unlikely to be involved in the photic transmission both to the circadian clock and to the pineal, (5) arrhythmicity induced by long-term continuous light seems to be due to masking for the melatonin rhythm, and to uncoupling from the clock for the locomotor rhythm.
In higher animals melatonin is produced by pinealocytes in the pineal gland (located in the brain) and also by the retina, lens and GI tract. It is naturally synthesized from the amino acid tryptophan (via synthesis of serotonin) by the enzyme 5-hydroxyindole-O-methyltransferase.
Production of melatonin by the pineal gland is under the influence of the suprachiasmatic nucleus of the hypothalamus (SCN) which receives information from the retina about the daily pattern of light and darkness.
Melatonin is also synthesized by various plants, such as rice, and ingested melatonin has been shown to be capable of reaching and binding to melatonin binding sites in the brains of mammals.
The trigger for melatonin secretion each evening is decreased light exposure; at the end of the day, when our sunlight exposure decreases, melatonin begins to switch on.
Melatonin and the Immune System
It is thought that much repair of the immune system occurs at night, therefore interacting with melatonin. When people are exposed to frequent artificial light and they do not get enough sleep melatonin levels are suppressed. Some forms of cancer are thought to be related to melatonin levels. ôMelatonin levels of breast and prostate patients are reduced to half the normal levels.ö (http://www.liberty.com/home/appaloosa/mel.htm). In two cases of sarcoidosis, which were not responding to long term treatments, melatonin was used. In between four to five months of being treated with 20mg daily, the symptoms were alleviated
Up until the 1990s, no research had ever been conducted to determine the impact of fluoride on the pineal gland - a small gland located between the two hemispheres of the brain that regulates the production of the hormone melatonin. Melatonin is a hormone that helps regulate the onset of puberty and helps protect the body from cell damage caused by free radicals.
It is now known - thanks to the meticulous research of Dr. Jennifer Luke from the University of Surrey in England - that the pineal gland is the primary target of fluoride accumulation within the body.
The soft tissue of the adult pineal gland contains more fluoride than any other soft tissue in the body - a level of fluoride (~300 ppm) capable of inhibiting enzymes.
The pineal gland also contains hard tissue (hyroxyapatite crystals), and this hard tissue accumulates more fluoride (up to 21,000 ppm) than any other hard tissue in the body (e.g. teeth and bone).
After finding that the pineal gland is a major target for fluoride accumulation in humans, Dr. Luke conducted animal experiments to determine if the accumulated fluoride could impact the functioning of the gland - particulalry the gland's regulation of melatonin.
Luke found that animals treated with fluoride had lower levels of circulating melatonin, as reflected by reduced levels of melatonin metabolites in the animals' urine. This reduced level of circulating melatonin was accompanied - as might be expected - by an earlier onset of puberty in the fluoride-treated female animals.
Luke summarized her human and animal findings as follows:
"In conclusion, the human pineal gland contains the highest concentration of fluoride in the body. Fluoride is associated with depressed pineal melatonin synthesis by prepubertal gerbils and an accelerated onset of sexual maturation in the female gerbil. The results strengthen the hypothesis that the pineal has a role in the timing of the onset of puberty. Whether or not fluoride interferes with pineal function in humans requires further investigation."
Comp Biochem Physiol A Mol Integr Physiol. 1998 Feb;119(2):593-8. Related Articles, Links
Vitamin A deficiency reduces the responsiveness of pineal gland to light in Japanese quail (Coturnix japonica).
Fu Z, Kato H, Sugahara K, Kubo T.
Faculty of Agriculture, Utsunomiya University, Japan.
Synthesis of melatonin in pineal gland is under the control of light environment. The recent finding of the presence of rhodopsin-like photopigment (pinopsin) and retinal in the avian pinealocytes has led to a hypothesis that vitamin A is involved in photoresponses of the pineal gland. We have thus analyzed the effect of vitamin A deficiency on the regulatory system of melatonin synthesis in the pineal gland of Japanese quail. Depletion of vitamin A from Japanese quails was attained by feeding them with a vitamin A-free diet supplemented with retinoic acid. In the vitamin A-deficient birds, diurnal rhythm in melatonin production persisted such that the phase of the wave was similar to that seen in the control birds. However, the amplitude of the nighttime surge of pineal melatonin was damped by vitamin A deficiency. When the control birds were briefly exposed to light at night, pineal melatonin dropped to the daytime level. In contrast, only slight decrease was observed in the vitamin A-deficient quails. The light responsiveness was restored after feeding the vitamin A-deficient quails with the control diet for 1 week. These results indicate that vitamin A plays essential roles in maintaining sufficient responsiveness of the avian pineal gland to photic input.
Vol. 95, Issue 11, 6097-6102, May 26, 1998
Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the photoactive pigments for setting the circadian clock in mammals
(cryptochromes / retina / suprachiasmatic nucleus)
Yasuhide Miyamoto and Aziz Sancar*
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599
Communicated by Johann Deisenhofer, University of Texas Southwestern Medical Center, Dallas, TX, April 1, 1998 (received for review March 9, 1998)
In mammals the retina contains photoactive molecules responsible for both vision and circadian photoresponse systems. Opsins, which are located in rods and cones, are the pigments for vision but it is not known whether they play a role in circadian regulation. A subset of retinal ganglion cells with direct projections to the suprachiasmatic nucleus (SCN) are at the origin of the retinohypothalamic tract that transmits the light signal to the master circadian clock in the SCN. However, the ganglion cells are not known to contain rhodopsin or other opsins that may function as photoreceptors. We have found that the two blue-light photoreceptors, cryptochromes 1 and 2 (CRY1 and CRY2), recently discovered in mammals are specifically expressed in the ganglion cell and inner nuclear layers of the mouse retina. In addition, CRY1 is expressed at high level in the SCN and oscillates in this tissue in a circadian manner. These data, in conjunction with the established role of CRY2 in photoperiodism in plants, lead us to propose that mammals have a vitamin A-based photopigment (opsin) for vision and a vitamin B2-based pigment (cryptochrome) for entrainment of the circadian clock.
Vitamin D3 enhances mood in healthy subjects during winter
Allen T. G. Lansdowne1, S. C. Provost1
Mood changes synchronised to the seasons exist on a continuum between individuals, with anxiety and depression increasing during the winter months. An extreme form of seasonality is manifested as the clinical syndrome of seasonal affective disorder (SAD) with carbohydrate craving, hypersomnia, lethargy, and changes in circadian rhythms also evident. It has been suggested that seasonality and the symptoms of SAD may be due to changing levels of vitamin D3, the hormone of sunlight, leading to changes in brain serotonin. Forty-four healthy subjects were given 400rIU, 800rIU, or no vitamin D3 for 5 days during late winter in a random double-blind study. Results on a self-report measure showed that vitamin D3 significantly enhanced positive affect and there was some evidence of a reduction in negative affect. Results are discussed in terms of their implications for seasonality, SAD, serotonin, food preference, sleep, and circadian rhythms.
...He had hypothesized that nighttime illumination, by interrupting the body's mainly nocturnal production of the hormone melatonin, might increase the risk of breast cancer. Animal experiments and surveys of people over the past 2 decades supported that hypothesis without proving it, says Stevens, currently at the University of Connecticut Health Center in Farmington.
"Now, a watershed study has provided the first strong experimental support," Stevens says.
A woman's blood provides better sustenance for breast cancer just after she's been exposed to bright light than when she's been in steady darkness, researchers led by David E. Blask of the Bassett Research Institute in Cooperstown, N.Y., report.
"Light at night is now clearly a risk factor for breast cancer," Blask says. "Breast tumors are awake during the day, and melatonin puts them to sleep at night." Add artificial light to the night environment, and "cancer cells become insomniacs," he says.
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