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Dr. Bredesen incorporates melatonin into his protocol, which makes good sense. But it's not that simple.

Normal melatonin blood levels increase an hour or longer before bedtime and they are sustained throughout the night. So far, so good.

Exogenous melatonin often creates unpredictable blood levels. There are several things to consider regarding this.

1. Unlike in the EU, melatonin is considered a nutritional supplement in the US and is not regulated. The dose on the bottle doesn't necessarily reflect what's in the tablet. The New York Times did a series of articles on OTC supplements revealing that some had no active ingredient. And this is not new. With melatonin in particular, the concentration actually in the pill often is very discordant from the label.
http://www.nytimes.com/2015/02/06/opini ... ments.html

2. Most melatonin does not survive gastric acid and the first pass through the liver. The subsequent blood levels are a bit hard to predict when you take the intended dose of the real thing.

3. Regular immediate release melatonin is cleared from the blood pretty quickly, in about 4 hours. This falls way short of covering the entire sleep cycle, particularly when it is often taken a while before bedtime.

So what to do? If you are in a country where prescription Circadin is available, that's an option. It's time released and reliably pure. But if you can't access that, you can settle for the crude immediate release melatonin that is cheap and everywhere. Or you can get slow release melatonin. The trick there is to find a brand that you believe in. Note what the University of Michigan says about contaminants.

http://www.uofmhealth.org/health-library/d04058a1

Mayo Clinic

http://www.mayoclinic.org/drugs-supplem ... b-20059770

Here's another concern:

Arsenic concerns and improper levels
Two of the top 30 melatonin brands that were tested were shown to have arsenic content that exceeded California's Prop 65 proposed limit for inorganic arsenic. According to the proposal, inorganic arsenic levels should not exceed 0.1 mcg/day.

Additionally, 16 out of 30 products contained less melatonin than what their labels promise. Ubervita Ubersleep was the worst performer, measuring only 0.01 mg/serving of its 6 mg/serving claim.

On the opposite end of the spectrum, some melatonin products contained much more melatonin than necessary -- and more does not equal better.

“The key is to find an effective low dose,” explains Benita Lee, MPH, research associate at LabDoor. “Taking a lot of melatonin does not mean it’s more effective. If too much is taken, peak and normalizing times can be delayed which can disrupt sleep for the next night.

Natrol Melatonin 5 mg (Time Release) exceeded its label claim by 47.4%, the most by all products tested. It measured 7.37 mg/serving compared to its claim of 5 mg/serving. Twelve tested brands recorded melatonin content above their label claims, with five products exceeding their claims by at least 20%.



In our sleep center we've usually relied on this product. It seems as good as most and the company has a good reputation. The extended release formula should be at least double what you'd expect in the standard preparation.



I hope all this helps. But there are no guarantees that melatonin will help you, that it's not contaminated, and that the dose is what you think it is. Sorry.

Oh dear.....I'll stop complaining about melatonin being prescription only and regulated by our Medicines Control Board in my country. We have Circadin...so its really good? I cam try it and let everyone know.

consumerlab.com goes some distant to help identify supplement brands that pass some independent testing (by supplement). In the case of melatonin they checked for lead contamination and that the supplement has the amount it claims. Also that it disintegrated properly. A good number of brands passed at least that much testing.

Throughout most of my 2 years of low carb experimenting, good sleep was even harder to come by than it is now. I've always been an early riser but it seems my body responds to depleted glycogen and hunger with even higher cortisol. Cortisol is no friend to good sleep. I would wake after 5-6 hours, eyes wide open -not a single yawn.

Marty, is my "low glycogen -> higher cortisol -> less sleep" theory plausible ?

We assayed Melatonin and it was normal but this is a good two months into a more balanced diet. I wish I had assayed cortisol in the midst of my worse insomnia. I wonder how much is known about how these hormones are influenced by diet?



Would there be any reason to supplement melatonin if an assay shows normal levels? By default, I'm highly skeptical of exogenous hormone supplementation.

Hep, your theory is exactly the one I have about my own sleep problems, and I did have early morning cortisol tested three times over the last few years when I was on more severe, daily CR than I am now: through the roof high.

CR when I was younger didn't cause this problem, so something changed a few years ago in my late 40s: either I became more susceptible to the anti-sleep effects of the cortisol, or the cortisol got higher. I suspect it's the former, but don't know because I don't have pre–sleep disaster cortisol test results.

My crazy temporary solution is to pig out at dinner for two days (high-fat or low-fat: doesn't matter -- I sleep pretty well), then, on the third day, quasi-fast and take a Z drug. Current strategy: zaleplon in the middle of the night -- very short half-life, so helps, though not much... with the early waking prob.; though zopiclone at bedtime carries me through six or so hours usually, which is enough if I can get in a power nap later. Zolpidem has the middle-ish half-life which makes timing impossible. I really want to try suvorexant though. As it is, I seem stuck with a choice, if I want to get half-decent (though still not great) sleep: pig out less, and suffer the greater risk of more frequent Z drug usage, or pig out more, and suffer the greater risk of not being on any significant version of CR. Nothing else has helped. I've tried everything that isn't unsafe aside from Suvorexant -- which, of course, is new, and might in fact not not be safe.... NOne of the putative cortisol-lowering supplements help at all. (And stress-reduction is pointless: the cortisol rise has notghing to do with stress.)

Wait, just checked my long list of things to try for sleep. Aside from suv., one other thing I haven't tried is trazodone. Would that be risky? Haven't found studies correlating long-term use iwth dementia.

Melatonin

I use Solgar's liquid melatonin, which has passed a couple assays. ≈500 mcg at bedtime (I have zero problems falling asleep at bedtime, ergo no need to take it earlier), and again at one of my 2-4 mid-night peeings.

Much higher doses of melatonin have been trialed in lab animal models of AD with some success. Possibly human trials as well, but I've not dug into the literature lately. The higher dose probably isn't needed for sleep, though (except for circadian resyncing).

Gilgamesh wrote:
Wait, just checked my long list of things to try for sleep. Aside from suv., one other thing I haven't tried is trazodone. Would that be risky?

Most drugs used on- or off-label for sleep have the potential to be detrimental to cognition. Trazodone is "possibly" anticholinergic per this link:

http://www.agingbraincare.org/uploads/p ... l_size.pdf

Here is a link from Harvard concerning drug classes to avoid due to higher risk of dementia. (Note many insomnia meds)

http://www.health.harvard.edu/mind-and- ... your-brain

Another drug to consider is gabapentin (off label). I don't see it listed as an anticholinergic drug in the first above link. Its original FDA indication was for seizures, and is currently used for other "neurological" purposes such as restless leg syndrome and neuropathic pain. If lack of sleep is your greatest issue, then it may be worth a try.

Why do you think your AM cortisol level is high?

PS. My husband has intermittent insomnia, where he will wake up early in the morning (2-3 am) and is unable to return to sleep. What worked best for him was a combination of loose dried herbs made into a tea: hops, skullcap, passion flower, wild lettuce, and lemon balm.

PPS. You may enjoy reading an interesting and entertaining memoir on insomnia, written by journalist Patricia Morrisroe. She tried EVERYTHING, turning it into grist for the mill of her book. Spoiler alert: meditation was the only thing that worked for her, and imperfectly.

Be aware that calming herbs can also be anticholinergic.

Does anyone wake with a headache after taking melatonin 1mg?

My guess is that's a clue your level may be too high. FWIW, I think Dr. Bredesen only recommends 0.5 mg. I've settled on 3 mg of the immediate release. I tried the extended release, but was so hungover the next day- bleh. I may try Marty's brand...

I'll try 0.25mg tonight and see.