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The "CLOCK" gene and short term mega dosing melatonin

Discussion in 'Adrenal Dysfunction' started by drob31, Aug 5, 2014.

  1. drob31

    drob31 Senior Member

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    The following is a theory of mine that I have been thinking about for a little while now.

    Adrenal dysfunction seems to be such a tough nut to crack, and there's no doubt everyone may have a different cause such as underlying infection, methylation, toxicity or deficiency, however there often seems to be a pattern that fits a circadian rhythm mismatch. The body appears to forget when to produce cortisol during the right time, and this leads to some lows during the day. Cortisol and melatonin have an inverse relationship:

    http://s1v2.kjhosting.com/~judithk/wp-content/uploads/2012/09/cortisol-melatonin-graph.jpg

    It makes sense then that cortisol would suppress melatonin and melatonin would suppress cortisol. It has been seen however, that large doses of melatonin could potentially suppress morning cortisol, the opposite of what we want. However, the most important step is resetting our circadian rhythm which must be achieved by going to bed the same time every night and waking up at the same time every morning for a sufficient period of time, >30 days. However, while doing this we may need to trick the body into resetting the hormonal balance as well, and perhaps mega dosing melatonin 5-20 mg's for a short period of time, maybe 1 week on, and 1 week off, could jump start this process. This is similar to therapies used to restore circadian ryhthms for other sleep disorders, but I'm not seeing much about adrenal dysfunction.

    Futhermore, I have a hetereozygous mutation on the CLOCK gene. According to SNPedia:

    rs1801260, a SNP in the CLOCK gene known as 3111 T/C, has been reported to influence sleep and activity patterns in patients affected by bipolar depression. [PMID 17221848]
    From this article's abstract:

    "Compared to T/T homozygotes, carriers of the C allele had a similar degree of severity of depression, but showed higher activity levels in the evening, a delayed sleep onset (mean 79 min later), and a reduced amount of sleep during the night (mean 75 min less)."


    Could it be that many AF'ers have CLOCK gene mutations? I've always had "sleep" issues even when I was "well." The CLOCK gene is considered part of your HPA axis and endocrine system. So if your genetically predisposed to less sleep, and a hindered circadian rhythm, could this cause your cortisol rhythm to become out of whack? Your levels go high at night, so by the morning you are depleted, and then experience adrenal fatigue during the day. But if they were lower at night, you may have enough reserves for the day, and if you could restore the rhythm, it would release the proper amount at the proper time.
     
  2. Valentijn

    Valentijn Activity Level: 3

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    50% of Europeans are heterozygous for rs1801260. I doubt it's having a sizable impact, especially if you're not a "bipolar depressed" patient such as those who were in the (very small) study :p
     
  3. drob31

    drob31 Senior Member

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    What do you think about short term mega dosing melatonin?
     
  4. Valentijn

    Valentijn Activity Level: 3

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    No idea. But I doubt it's a genotype which needs to be "treated".
     
  5. adreno

    adreno Learned helplessness

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    I don't think it will work, as melatonin likely suppresses cortisol centrally, i.e. it suppresses ACTH. You need to suppress cortisol peripherally in order to raise ACTH.
     
  6. ukxmrv

    ukxmrv Senior Member

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    It didn't work for me. I am a natural night owl from a family of night owls. Having ME on top of that and low morning cortisol (blood and saliva tests) makes it much worse.

    I tried increasing melatonin and using both normal and time release versions. Currently I take 3-5mg of Melatonin each night. Sometimes mixed release. This, after my experimentation, seems to be the dose, that helps me sleep earlier and doesn't add to my morning problems too much. I'm not hyper at nights just the closest to "normal".

    What I tried was to "reset my body clock" so I could fall asleep earlier. It works at doses of 10-15mg (the most I tried) for a couple of days and then wears off for me. Sometimes sleep will occur at any early hour but then waking at nights feeling my normal happy self. The morning grogginess is pretty bad.

    I only tried this for a month. Then weeks on and off. Tried different amounts of normal release and delayed release.

    I'm still experimenting with the dose. My gut feeling is that the more I sleep AM the better my quality of life and functioning is. I'm going to cut the dose again and see what happens. Keeping an activity diary.
     
  7. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Just thought I'd break the 'good' news for UK melatonin users. Amazon will no longer ship it to the UK. I tried both Amazon UK and the international/US site. The UK one doesn't even sell it any more. Then I tried Now Foods direct (having bought it from them before). Went through all the ordering process again, only to find that they won't ship to the UK any more either.

    I have managed to get some now, but forgot to try ebay first - looks as though they may still ship to UK but can't be sure without trying.

    We clearly can't be trusted with such dangerous drugs...
     
  8. Gondwanaland

    Gondwanaland Senior Member

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    CLOCK 56301369 rs1801260 A or G (I am GG and DH is AA :confused: )

    I think the GG is the good version, since I fixed my circadian rhythm with electrolytes and vit A.
     
  9. nandixon

    nandixon Senior Member

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    G is supposed to be the risk allele with respect to circadian rhythm and sleep disorders. I'm homozygous GG for that one, too. (Edit: And I do have significant sleep problems.) GG is found in about 5% of the general population (from OpenSNP).

    There's another thread on CLOCK here:
    http://forums.phoenixrising.me/index.php?threads/clock-gene-and-sleep-disturbance.24568/

    And @Valentijn started another one for analysis here:
    http://forums.phoenixrising.me/index.php?threads/clock-snps-in-me-cfs-patients.27297/
     
    Last edited: Jan 30, 2015

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