' Endoplasmic reticulum (ER) stress has been suggested to be associated with some human neurological diseases, such as PD and AD. Melatonin, a neuroendocrine hormone mainly synthesized in the pineal gland, is involved in pleiotropically biological functions, including the control of the circadian rhythm, immune enhancement, and antioxidant, anti-aging, and anti-tumor effects. Although there are many papers on the prevention or suppression of diseases by melatonin, there are very few papers about the effects of melatonin on ER stress in neurons and neurodegenerative diseases. This paper aims to summarize and present the effects of melatonin reported so far, focusing on its effects on neurons and neurodegenerative diseases related to ER stress. Studies have shown that the primary target molecule of ER stress for melatonin is CHOP, and PERK and GRP78/BiP are the secondary target molecules. Therefore, melatonin is crucial in protecting neurons and treating neurodegeneration against ER stress. '
Art
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Give it another try. When hubby was first diagnosed, Melatonin caused him confusion and fatigue. He now takes 5mg Melatonin every night along with Serotrex and Pharma Gaba and he sleeps through out the night.
Art, I currently take 40mg of melatonin at night and I’m thinking of increasing. A Dr. Told me it may contribute to insulin resistance/diabetes. I see opinions and studies that say it does, and it doesn’t. Could you break this down for us, or if you’ve already done so, point me to the right thread? Can’t find one.
From what I have read to date, the problem is related to dose timing in relation to food intake. Food taken while melatonin level is high can create problems with insulin resistance and that is part of the reason I take my melatonin just before bedtime. On the other hand, a person working the nightshift would likely be eating at a time when melatonin levels would normally be higher and this may create a problem in terms of insulin resistance and ability to properly utilize glucose.
There are still unanswered questions in this area of research. My general understanding is that keeping melatonin higher when it is supposed to be higher during the night, is appropriate, but taking midnight snacks or consuming food when your melatonin level is high can be problematic.
Generally I avoid supplemented melatonin during the day, with a few exceptions, such as when I have Covid-19 or if I had a severe health issue such as cancer. In those cases I would try to time my meals accordingly when possible and still take melatonin around the clock.
Melatonin taken at the appropriate time and away from food is likely to have the opposite effect, improving insulin resistance and glucose intolerance.
' Circadian system may be a tractable target for decreasing the prevalence of hyperglycemia and insulin resistance. The loss of glycemic control and substantial elevations of fasting glucose are complications that arise from type 2 diabetes and typically result from progressive loss of pancreatic beta-cell function and decline in insulin. Different animal studies suggest that melatonin supplementation may have beneficial effects on glucose homeostasis and body weight regulation under certain circumstances, which should encourage clinical trials in humans to evaluate the therapeutic potential of this hormone in diabetes. Diabetes is a prevalent disease in middle-aged and older adults and maintenance of optimal levels of blood sugar in diabetes patients is a major clinical issue. The present evidence that melatonin induces insulin secretion by IP3- signaling pathway and can improve β-cell function, so melatonin supplementation may have beneficial effects on glucose homeostasis. It would advance the current therapeutic strategy to overcome the diabetes effects which is currently prescribed for sleep and circadian rhythm. '
The beta cell protective effects of melatonin are very important in diabetes.
Additionally, Berberine is likely to be additive to the beneficial effects of melatonin because it increases insulin sensitivity while decreasing insulin resistance and this would be important in multiple disease states where insulin resistance is known to be a problem such as diabetes, AD or PD among others.
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Multiple mechanisms to clear a-synuclein with natural substances (in mice).
DO YOUR RESEARCH. Cure yourself. 
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