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What causes high night-time cortisol?

Discussion in 'Sleep' started by aaron_c, Jul 8, 2014.

  1. aaron_c

    aaron_c Senior Member

    Like many people with ME/CFS, I have sleep issues. Part of these issues seem to be related to both high night time cortisol and low daytime cortisol. I have read about a number of things that might help this, but what I cannot find is what specifically causes this pattern. The closest I have come are some vague comments about how stress causes us to excrete lots of cortisol. While I agree this is part of the issue, I don't see it explaining why cortisol would be higher at night time...if anything, I imagine stress-induced cortisol output should be higher during the day, or at least day and evening cortisol would be equal. Does anyone have some insight?
  2. South

    South Senior Member

    Southeastern United States
    What does it for me is this: a day or more of a low carb diet. Experimenting with a low carb diet for unrelated reasons a few years ago, I always got high cortisol at night for the first few days of the diet. Not sure why.

    I don't use that diet anymore, for many reasons.
  3. vamah

    vamah Senior Member

    Washington , DC area
    Maybe it has to do with the fact that you experience stress throughout the day and so it gets higher. The, in the morning after you have been sleeping, it has decreased. Just conjecture on my part.
  4. place

    place Be Strong!

    Oh, I have been on this hunt too. I have noticed I will get a spike in something, not sure if it's cortisol but I have noticed what ever I think about , makes me agitated, angry. I will find something that urks me. Not rage but definately anger, when I'm not angry about anything. It so weird. But I looked up the hormone and found this:

    Rage/anger occurs when oxytocin, vasopressin, and corticotropin-releasing hormone are rapidly released from the hypothalamus. This results in the pituitary gland producing and releasing large amounts of the adrenocorticotropic hormone, which causes the adrenal cortex to release corticosteroids. This chain reaction occurs when faced with a threatening situation.[4]
    Last edited: Jul 10, 2014
  5. place

    place Be Strong!

    OK, so I found this study:
    Neuronal histamine and expression of corticotropin-releasing hormone, vasopressin and oxytocin in the hypothalamus: relative importance of H1 and H2 receptors.
    Kjaer A1, Larsen PJ, Knigge U, Jørgensen H, Warberg J.
    Author information

    Centrally administered histamine (HA) stimulates the secretion of the pro-opiomelanocortin-derived peptides ACTH and beta-endorphin as well as prolactin. The effect of HA on secretion of these adenohypophysial hormones is indirect and may involve activation of hypothalamic neurons containing corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP) or oxytocin (OT). We studied the effect of activating central HA receptors by central infusion of HA, HA agonists or antagonists on expression of CRH, AVP and OT mRNA in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Intracerebroventricular infusion of HA (270 nmol), the H1-receptor agonist 2-thiazolylethylamine or the H2-receptor agonist 4-methylhistamine increased the level of CRH mRNA in the PVN, and OT mRNA in the SON. In contrast, none of these compounds had any effect on expression of AVP mRNA in the PVN or SON. Administration of the H1-receptor antagonist mepyramine or the H2-receptor antagonist cimetidine had no effect on basal expression of CRH, AVP or OT mRNA in the PVN and/or SON except for a slight inhibitory effect of cimetidine on CRH mRNA expression in the PVN. Pretreatment with mepyramine or cimetidine before HA administration inhibited the HA-induced increase in OT mRNA levels but had no effect on the HA-induced increase in CRH mRNA levels in the PVN. We conclude that HA stimulates hypothalamic CRH and OT neurons by increasing mRNA levels, and this effect seems to be mediated via activation of both HA H1 and H2 receptors.
    aaron_c likes this.
  6. perchance dreamer

    perchance dreamer Senior Member

    I always test very high for cortisol at 4:00 a.m. My PA thinks it could be a blood sugar drop from stopping eating at 7:00 or 7:30. I have to do this because I take Xyrem, and it doesn't work for me unless I go that long without eating before bed.

    If you could eat a snack an hour or so before bed, you might try something like almonds with a few dried figs. The almonds are a long-acting protein and the figs have carbs and a little tryptophan. It would be an easy test to see if a blood sugar drop is part of the high night-time cortisol.
    Little Bluestem likes this.
  7. place

    place Be Strong!

    Ok I did some research and apparently there is a bunch of people who are taking the above meds and Singulair to drastically reduce their histomine load.

    As a side note, I really slept well with doxy. My doc said it acts as an anti inflamitory.

    So tonight I will take 2400 mg of fish oil, my normal Singulair, Zyrtec and Tagamet . My hope is that I will be able to sleep, not perfect, but without the spike I always get at 6:00am. No matter what time I go to bed. Now that I think about it, this consistent cortisol spike started when I upped my methyl folate. I am wondering if I push my 4:00 pm dose to 6:00 pm would I then wake up at 8:00am? I will try that next if this does not work.
    Last edited: Jul 10, 2014
  8. ukxmrv

    ukxmrv Senior Member

    Aaron, have you had your cortisol tested?

    My cortisol (blood and saliva tests) was low in the mornings but never went to high at night. It did raise and I feel better as it raises during the day but even at night it was never in the "high" range.

    In my family we start as larks then as we get older we turn into owls. No amount of sleep hygiene and other lifestyle workarounds makes any difference.

    I come from a family of night-birds so we are all like this to an extent. Having ME just made it much, much worse.
  9. heapsreal

    heapsreal iherb 10% discount code OPA989,

    australia (brisbane)
    PVN paraventricular nucleus is suppose to control cortisol and phosphatidylserine is suppose to improve the cortisol sensitivity of the PVN. I have had some success using doses of 500mg.

    I also don't think the cortisol levels get that high generally, but just above what's normal at that time to wreck our sleep.

    not that I have been tested for this but ammonia levels can be high in insomniacs. A friend put me on to a herb yucca for sleep. I was skeptical it would help but it worked. Definitely improved my sleep quality, although still using meds. He stated he uses this 3 nights in a row and 3 nights off. This has been my experience too.

    My sleep is far from 100% but the above has helped.

    Any cures though please share.
  10. aaron_c

    aaron_c Senior Member

    Thank you all so much for responding! I am really enjoying looking into this stuff with yall.

    This has gotten long...titles added for clarity.


    @place : Huh...I've thought about histamine before, but I haven't really found a great way to bring it down.

    Here is an interesting article saying that dehydration causes our bodies to make more histamine--which would explain at least some of the "dry" concept in chinese medicine--but it would also imply that getting enough water could help. Who knows how much...

    Here is a hypothesis, part of which is that people with ME are overtly sensitive to histamine. I don't have access to the whole thing, so I can't see why they think this. But it seems like histamine dysfunction might be part of the ME picture. And if chronic infection is part of the picture, then I can imagine that mast cells would release histamine more often.

    Here is a detailed paper on histamine and sleep regulation. Some quotes I found of particular interest:

    Histaminergic perikarya are located exclusively in the tuberomamillary nucleus and adjacent areas of the posterior hypothalamus.

    [The posterior hypothalamus] is the only brain structure so far identified, in which lesioning or inactivation using the GABA agonist muscimol results in hypersomnia in several species and restores sleep in various insomniac models in the cat (reviewed in Sakai et al., 1990; Lin, 2000)​

    So GABA and magnesium should be helpful in terms of blunting histamine release from the posterior hypothalamus...

    These quotes (from the same article) are about the H3 receptor, which is the histamine autoreceptor--the histamine receptor that regulates histamine, keeping it from going too high:

    Histamine neurons display a pacemaker firing pattern that depends on a number of intrinsic properties: dendritic Ca2+-mediated prepotentials, decisive in this process, are suppressed by H3 receptor activation. The H3 receptors also cause inhibition of release at axonal varicosities by blocking Ca2+
    channels that are essential for triggering the transmitter exocytosis.
    So once again, excess calcium means stronger histamine reaction.

    H3 receptor activation inhibits glutamate release from rat striatal synaptosomes...This action is severely compromised in an animal model of hepatic encephalopathy.​

    Assuming that H3 receptors aren't inhibiting histamine release as much as we would like, then glutamate is part of the problem too. Of course, it was probably part of the problem already. The bit about the liver is interesting to me, as I am under the impression that my liver is particularly dysfunctional, and Rich Van K has mentioned inefficient estrogen metabolism (occurring mainly in the liver, I believe) as a cause of oxidative stress, and thus a perpetuator of the ME cycle.

    Here is an article on herbal fixes for histamine. Although quercetin is mentioned, I looked into it and it is an mao-a inhibitor. Also, I believe it increases dopamine. For myself, I will try chondriotin sulfate. Exciting! Not mentioned was Reishi, which prevents mast cell degranulation. I have been taking it for five years or so, and it works wondefully. I take it an hour before bed.

    So it's pretty cool to see the link from gaba/magnesium (deficiency) to histamine (excess) to acth (excess), to cortisol (excess). However, I have some doubts if this whole cycle is happening in ME. Here is a link where Rich Van K talks about the difficulty of producing POMC (from which ACTH is snipped) without enough glutathione. And in the first of his three-part video, he says that he believes this is why people with ME tend to have flat cortisol tests. And yet cortisol dysfunction is the one cause of sleep disturbance I know about that includes the pattern where I get more energy and feel more awake in the evening.


    @ukxmrv : I didn't know that low morning cortisol rising to normal evening cortisol can interfere with sleep...very interesting. I have not had my cortisol tested recently...insurance will pay for multiple blood tests (but not saliva), but I don't think I can get one at 10:00 at night, which would be the interesting time. But I very much wonder if you are right. It would certainly fit more with Rich's theory.

    Melatonin inhibits ACTH response. So 5-htp and melatonin might help. I take 5-htp to sleep, and it certainly is helpful. Tiny amounts of melatonin knock me out, and this is probably why.

    @perchance dreamer : Eating late, particularly eating protein, has actually contributed to insomnia in the past. I think maybe we have two different patterns of insomnia--I have difficulty getting to sleep, but once I do I generally sleep to 8 or 9 am. But it is helpful to hear that for the "wake up at 4 am" insomnia, almonds and a fig are helpful.


    @heapsreal : I did not know that about ammonia and insomnia, very interesting! I have been dealing with ammonia issues for a while now. I was buying a fortune in BH4 supplements, but recently I started taking liposomal fumaric acid, which for some reason works in a way that carnitine-fumarate never did. I am definitely interested in ornithine. That's exciting, thanks!


    Just some background, because I have and will mention magnesium and calcium, but I want to fill in the context for those who are not familiar. Also, laying it out like this makes me try to fill in the gaps in my understanding:

    Gaba and glutamate are in a dynamic balance. They can, in fact, be converted into each other. When there is more of one, there is less of another. Magnesium stimulates gaba receptors and Calcium stimulates Glutamate receptors. Normally, calcium is mostly present outside of cells, while magnesium is mostly present inside of cells. Enzymes on the cell membranes that use ATP maintain these gradients. People with ME, who do not produce enough ATP, have weaker potentials--meaning that our cells have less magnesium in them, and more calcium.

    I think the body can regulate plasma electrolyte concentrations more easily than intracellular concentrations, because excess can be excreted by the kidneys. Someone please fill in if I am missing something. But I believe this is why I can take huge amounts of magnesium and no calcium in order to feel slightly more balanced.

    I thought this was all worth mentioning, because I like to know that what I am taking is bringing the body back to its natural balance.

    What I Take To Sleep

    ...in case anyone needs more ideas

    100 mg 5-htp
    Lithium Orotate 30 mg: Yasko has observed that people taking high amounts of b12 can become lithium deficient. It happens to a greater extent in some people than in others, and she thought a particular genetic mutation might be involved, but she didn't know why or how. I think it was a COMT or possibly MAO-A mutation, but I'm not sure. Anyhow, I have it. I take 14 mg of daily b12.
    Peace Pearls: You have to get them from an acupuncturist, they won't sell to the public. But they are excellent both for putting me to sleep, and for giving me good quality sleep.
    Reishi Extract 1.5 g (1 hour before bed): As mentioned above, prevents mast cell degranulation

    200 mg phosphatidylserine
    Vitamin K: I was low in it. It convinces glutamate and calcium to head towards the bones and away from the nervous system.
    Magnesium (up to bowel tolerance): I make liposomal magnesium glycinate, as that allows me to get more in my body without diarrhea. I take it throughout the day, including before bed. As with all liposomal things, they need to be taken 15-25 min away from other stuff, even water.

    CholineCDP (Citicoline) 250-500 mg: It increases glutamate uptake and glutathione synthesis, preventing glutamate excitotoxicity. Makes me sleepy, and lets me sleep more deeply.
    Raw Beef (Lunch or dinner, about 1/7 pound):
    I have no idea why this helps. To muse on this, check out this thread I started on it. If you feel concerned about the dangers, please read the discussion on the topic on the same thread first.
    Last edited: Jul 10, 2014
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  11. aaron_c

    aaron_c Senior Member

    @place : For what it's worth, I was methyl-sensitive until I began limiting my active b2 supplementation to about 35 mg per day. I do not know of anyone else who has tried it, though, so the evidence is pretty thin. Please let us know how the switch in timing worked.
  12. place

    place Be Strong!

    Aaron- anytime I have a busy mind when trying to get to sleep, I take GABA. It works great for calming things down. And from the research, it sounds like I have to much glutamate. I did try to take GABA for the 5-6am spike issue but then it just made me sleep till 12 = (.

    I take my B2 at night with my multi b vitamin. When I first started methyl a couple years ago, I was running out of my b's.

    First test: fish oil, tagement, singular and zyrtec. I also take Melatonin normally. I felt like my quality was good and I woke up with less pain. My pain has been increasing lately and I think it is due to dropping my fish oil (Which concerns me a bit). Even though my sleep was better, I still woke up at 6:00am. Tonight I took my last dose of mfolate (3200) at 6:45pm with 4mg of mb12. I will continue taking the items from my first test all this week. I'll post back tomorrow on the timing of Mfolate.
  13. aaron_c

    aaron_c Senior Member


    Any luck? Have you found things that work?

    EDIT TO EARLIER POST: I stated that I used liposomal fumaric acid to deal with ammonia. It is liposomal malic acid.

    I have been sleeping decently recently, and I attribute it to two things: The first is aloe. I am only on day two, but I am taking George's Always Active Aloe, which claims it is anthraquinone free...I believe this a big part of what can cause diarrhea with aloe. So I am hoping it is safe for long term use. We'll see!

    The second thing is that I have begun taking more selenium again, from 300 mcg / day up to 700 mcg / day. Dr Marz (author of the naturopathic textbook "Medical Nutrition from Marz") says that 800 mcg appears to be the upper safe daily limit for selenium. This is what I think is happening (mostly grabbed from another post I did):


    First, some background on selenium in the body: Selenocysteine is the "active" form of selenium, in that it is necessary to form some proteins, including most glutathione peroxidases (an enzyme that uses glutathione to protect us from oxidative damage). Because selenocysteine is fairly reactive, it is not stored as such. Wikipedia says that selenite is the storage form in the body, and to this I would add selenomethionine. Selenite and selenomethionine are storage forms of selenium akin to storing money in a checking account and a CD, respectively. Selenomethionine is a methionine molecule with selenium instead of sulfur. Unlike selenocysteine, which has uses unique from cysteine, selenomethionine is used just like methionine. The body has no way to draw on the selenium in selenomethionine, it can only wait for the proteins to degrade.

    Next, some Background on Magnesium: Magnesium helps with sleep. It is involved in propagating GABAergic pathways, much like Calcium is involved with the glutaminergic ones. It is also necessary to produce glutathione. Healthy cells spend energy to pump magnesium in and calcium out, but since we have problems producing enough atp, people with ME generally have more calcium and less magnesium than would be ideal. Calcium and magnesium levels in the blood are more tightly regulated (maybe because excess is excreted in urine?). To fix this, some doctors recommend taking high doses of magnesium. As the study in the last link indicates, the results are pretty darned good for most everyone.

    The problem is it doesn't seem to last. After some number of months using high doses of magnesium most people with ME find it becomes less and less effective. Here is one example, but I have read others (that I did not bookmark, alas!) Why is this? I think the answer is selenium.

    Magnesium deficiency impedes selenium absorption, while magnesium deficient people (measured by RBC magnesium) who failed to improve RBC magnesium with magnesium supplementation, improved when given selenium. So we need magnesium to absorb selenium, but we need selenium to get magnesium into our cells.

    Rats fed a
    selenium deficient diet but then supplemented with selenomethionine showed ten times the selenium concentration in their muscle than rats supplemented with equivalent amounts of selenite and selenocysteine--probably because the selenomethionine was being integrated into proteins just as methionine would-primarily in the muscles, whereas selenocysteine and selenite is used more readily for glutathione peroxidase.

    Magnesium deficiency causes an increase in selenium concentration in muscle tissue but lowers selenium concentration *most* other places in rats. Which sounds an awful lot like the rats fed lots of selenomethionine.

    Alltogether, this looks like magnesium deficiency causes more selenium to be integrated into selenomethionine instead of selenocysteine. Since magnesium is necessary to turn methionine into cysteine, it is not surprising that it would be necessary to to to turn selenomethionine into selenocysteine. (B6 also appears to help increase intracellular Magnesium. Perhaps the common denomonator here is Glutathione, as both magnesium and B6 are necessary to produce glutathione.) As magnesium deficiency is remedied, we produce more glutathione, convert more selenomethionine into selenocysteine, and generally become more protected from oxidative stress by glutathione peroxidases, which is why people get more energy. My hypothesis is that this does not last because after however much time, glutathione peroxidase has used up the selenium stored as selenomethionine. Basically, we have burned through our selenium savings, so our body brings less magnesium into our cells, and we are back experiencing magnesium deficiency: We produce less glutathione, we feel tired again, and we sleep worse. This would explain why medium-high doses of magnesium stop working after some number of months, and also, I think, why daily magnesium IV's would stop working much more quickly--it won't use up your selenomethionine stores, but it will quickly use up everything else.

    Personally, I have tried taking fairly high doses of selenium (up to 2 mg per day, I believe), but did not experience an increased benefit after a certain point. But there was enough else going on, that I am not totally sure. And I was taking liposomal magnesium, not IV's, so maybe with higher magnesium, more selenium? However amounts over 800 mcg per day *might* be dangerous, although some physicians do prescribe larger doses for some cancers.

    In any case, I hope you have found something that works.

    Very best wishes,

    Aaron C
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  14. A zombie

    A zombie Senior Member

    is CholineCDP the same as phophatidyl choline?

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