Melatonin

[Ski]

I know many here use this religiously, Id be curious on your thoughts with regards to this causing your own body to stop producing melatonin?

From Chris Kresser:

Melatonin is another commonly used sleep aid. But I don’t recommend it for anything more than emergency, short-term use. Why? Because melatonin is a hormone. Taking any supplemental hormone disrupts our natural regulatory mechanisms of that hormone and throws our internal production of it out of whack. This can create dependence over time and disrupt our circadian rhythm, which is crucial not only to sleep, but to overall health.

I know my endo was very much against taking testosterone therapy because of the exact same issue...negative feedback loop. Im asking as I seem to have fallen into this trap of a couple times a week waking at 4.30am and not being able to go back to sleep and considering melatonin for a bit.

[Julie G]

I've seen the same argument made against antioxidants. By supplementing, do we encourage our bodies to stop extracting them from our food?

FWIW, In the case of melatonin, Dr. Perlmutter, suggests the benefits far outweigh the risk of dependence- at least in a high risk group, like ours.

Much research shows that melatonin levels naturally decrease as we age, especially in AD patients. Some studies have even shown that ApoE ε4 carriers have the lowest levels... leading to a vicious cycle as lack of sleep greatly increases inflammation, which in turn leads to both AD and CVD. Very recent studies even demonstrate that sleep actually reverses AB plaque.

Dr. P advocates starting with 1mg for a few days/half a week, then going up in increments of 1mg (waiting a few days again to gauge effect) until you reach a therapeutic dose that enables 8 hours of restorative sleep. A typical dose usually ends up being somewhere between 3-5mg. It is very important to slowly titrate up as a high dose can be very depressive to the CNS.

Melatonin Reverses the Profibrillogenic Activity of Apolipoprotein E4 on the Alzheimer Amyloid AB Peptide
http://www.case.edu/artsci/chem/faculty ... /pub46.pdf

Significantly, the lowest levels of melatonin are found in AD patients who are homozygous for the apoE-ε4/4 allele, suggesting a more severe deficiency in this subpopulation of patients

[Ski]

Thanks.


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[circular]

This article seems to suggest the opposite, that ApoE4 would have high levels of melatonin, at least in some areas? http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract

" In conclusion, the increased melatonin level in ApoE4-C6 cells results from up-regulation of NAT expression, a key enzyme for melatonin synthesis, and down-regulation of MAOA and MAOB expression, the metabolic enzyme for its precursor serotonin."

[Julie G]

Very interesting, Circ. To top if off, strangely, many here (including me) carry the MAO defect. Trying to sort THAT out, in conjunction with the melatonin variable, is giving me a headache

[RBK]

I'm so curious about this one. The research in favor of E4s supplementing seems compelling, and my less than ideal sleep patterns aren't all against any help they can get. However, my doctor was pretty hesitant for me to start artificially messing with my hormone levels when I'm so healthy. I did not have my melatonin levels checked this time in my initial labs, but I am going to follow them going forward.

For the time being, I agreed to do other things to help my body naturally increase melatonin production:

Diet - Oats, Barley, oranges, occasional banana (high GL), tomatoes. (Things I already eat, but I'm making sure I get at least one of these each day now.)
Bought a switch sort of thing that my lamp plugs into and it slowly turns lamp up over a period of time to simulate sunrise. He said fixing circadian rhythm helps fix melatonin production.
De-stress and lower cortisol levels (I don't know that mine are actually high.) I read that to mean "get more massages." ha

I would love to know how many here are supplementing though. In large part, it seems intuitively wise to me, assuming levels are shown to be low after testing.

[Ski]

RBK I'm with you here. Whilst vitamins etc I feel are okay, I chose to leave artificially supplementing hormones alone. My endo who is a professor and noted as one of the best in the field is very much against hormone supplementation as it directly affects the bodies natural cycle of production. It's completely different than popping vitamins.

If you truly have a deficit that may be okay but I've used it for a couple of nights when I've struggled to sleep but that's it.

I saw what supplementing testosterone did to my other hormones and how it affects that cycle. I personally don't think it's a good thing.....unless you are truly in deficit. Just my ,02 cents.


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[RBK]

Skibike,

Yes, I agree for the most part. I am not willing to mess with a hormone that is going to have a domino effect on other hormones until I know that I'm severely lacking melatonin relative to normal for my age. However, I do think that the research regarding melatonin is compelling, and it's hard to argue with the growing number of anecdotal stories. My doctor is reading a package I've given him with melatonin and alcohol studies now. I'll be interested to hear how he weighs in on those two issues. All anecdotal things I've read are, of course, from those already very effected by AD, not from those of us trying to prevent it. Hard to know what's going on before the symptoms show up. I'm hoping that tracking my melatonin levels will give me some insight. Who knows… just the beginning of this for me.

[Julie G]

I've noticed we have bits and pieces about melatonin floating around in multiple threads. In an attempt to keep us organized, I've tried to compile relevant links and papers below:

From Spunky, an LEF article:
http://www.lef.org/magazine/mag2013/sep ... one_01.htm

Also from Spunky, another LEF article:
http://www.lef.org/magazine/mag2012/sep ... ors_01.htm

From Circular, a paper demonstrating melatonin's role in decreasing amyloid-beta plaque:
http://www.ncbi.nlm.nih.gov/m/pubmed/21354274/

Also, from Circular, a paper that outlines the positive effect melatonin may have especially for E4 carriers:
http://www.experts.scival.com/indiana/p ... 13&o_id=22&

From Silver, a time released melatonin recommendation:
http://www.swansonvitamins.com/swanson- ... mg-60-tabs

Also From Silver, a report about a new study that found combining exercise with melatonin provided even more benefit against dementia:
http://www.sciencedaily.com/releases/20 ... 110110.htm

Another paper from Silver- Clinical Aspects of Melatonin Intervention in Alzheimer's Disease Progression
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001215/

And, another paper from Silver-Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells
http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract

From Silver, another paper- Reduced hippocampal MT2 melatonin receptor expression in Alzheimer’s disease This one is good in that E4 is specifically examined.
http://web1.sssup.it/pubblicazioni/ugov ... 5_1472.pdf

And (drum roll please!) a final paper from Silver- Role of melatonin in Alzheimer-like neurodegeneration
http://www.melatonina.it/farma/download ... atonin.pdf

From Susan, a paper- Clinical Aspects of Melatonin Intervention in Alzheimer’s Disease Progression
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001215/

Also from Susan, another paper- Clinical Aspects of Melatonin Intervention in Alzheimer’s Disease Progression
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001215/

A caveat from Susan: I have chosen not to take melatonin - although RA patients show that their molecular machinery controlling the circadian rhythm is disturbed, melatonin does not help (and may hurt), whereas other autoimmune diseases improve.

And, a paper from Susan supporting her decision, but outlining positive effects on other autoimmune diseases- Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709754/

[circular]

Thanks for doing this Juliegee! Is there. Simple blood test for M, and does it say anything about brain levels? Anyone? Gearing up for more bloodwork.