Richvank -- day vs. night symptoms (glutathione??)

Discussion in 'Fibromyalgia Main Forum' started by Scapper, Apr 27, 2011.

  1. Scapper

    Scapper New Member

    Hi Rich: I was wondering if you could give me an explanation as to why my symptoms would be so severe during the day and much less so by 7:00pm on (approximate time).

    I have been consistently sick with CFS for 16 years, mostly homebound.....I have no experience with relapse and remission.

    I attempted the simplified methylation protocol in 2007-2008 and went into a severe detox reaction. It took me a very long time to take care of the yeast, bacteria, parasites, etc., that "came up" and to regain my strength to get out of bed. However, I landed back in the same place as before I started (this has been my experience w/ every protocol I've tried).

    I'm attempting to try again though.

    I was just curious to see if you had an explanation for this bizarre day vs. night issue? I was wondering if toxins built up overnight. I awake **deathly** sick every day (my head completely fogged and in an agitated state) and only begin to feel somewhat better after 7:00pm (if that happens) by 9:00pm or so (I do not feel fogged or agitated right now, but it's like living in the movie Ground Hog Day -- tomorrow will be the same!).


    [This Message was Edited on 04/27/2011]
  2. kat0465

    kat0465 New Member

    One thing that i found was my cortisol level was virtually non existent all thru the day, then in the evenings it would come up some.

    Which is why I feel a little better at night, but in the mornings it's the same ole song and dance :(
    I tried isocort for about a year, not much difference really.

    If I'm not mistaken, The cortisol thing goes along with the methylation prob too. Rich can confirm or deny this for ya.

    The low cortisol is pretty common with us.

  3. richvank

    richvank New Member

    Hi, scapper.

    I'm with Kat on this one. I do think it's likely that your diurnal cortisol variation is wacko (a very scientific term, right!)

    This is a very common problem in ME/CFS. The normal variation of cortisol is that it rises to its high about the time people normally rise in the morning, or slightly later, and then it generally decreases during the day, hitting its minimum in the wee morning hours. It normally jumps a little after meals, or if any stress is put on the body (physical, mental, etc.)

    In ME/CFS, it appears that before onset of the disorder, cortisol is running higher than normal, probably due to the variety of stresses that eventually bring on glutathione depletion in genetically susceptible people, in my opinion. After onset of ME/CFS, cortisol is generally lower than normal. Some people develop a reversed diurnal variation, so that cortisol is higher at night than during the day, so they sleep during the day and are awake at night. Some people experience a drop in blood sugar during the night, and cortisol comes up to correct that, and wakes them up. Some people don't have enough cortisol generation to correct the blood sugar drop, and adrenaline substitutes for it, causing them to awaken with a panic attack. Some people's diurnal cortisol variation loses its synch with the biological clock in the suprachiasmic nucleus of the hypothalamus, and their day-night cycle drifts with respect to the earth's rotational day-night cycle. There are many varieties of torment involved with abnormal cortisol variation.

    If you would like to test to see what your cortisol variation looks like, you could order the Sabre Science adrenal saliva panel from without a doctor's order. This test involves sampling the saliva every four hours for a 24-hour day. Other labs offer this test, too, but Sabre Science has a 4 a.m. measurement, which the others don't have, and I think that's important.

    I think that the cortisol problems in ME/CFS result from glutathione depletion in the hypothalamus and pituitary. Lifting the partial methylation cycle block does cause glutathione to come up to normal. We have verified that with lab testing in our clinical study (Neil Nathan, M.D. and myself). I've had one report from a person who ran the saliva panel before and after 6 months of methylation treatment, and they saw improvement in their cortisol variation. Most people don't rerun tests after they are doing better, and I can understand that, but it's nice to get closure on some of these issues, to see if the hypothesis is really valid in the details of it.

    Yes, I remember that you tried the methylation treatment way back when. From what you have reported, I think it will be important for you to get your digestive system in better shape before trying it again, if you haven't already done that. Both the gut and the liver need to be working well enough that when the toxins are mobilized, they will be excreted in the stools, and not just recirculated around, making you miserable. One of the docs who is using this treatment routinely told me that he starts all his patients on it, and then if it is not tolerable, he stops it and works on the gut and the liver until they are doing better, and then restarts the methylation treatment. This seems to work well for his patients. If they are able to tolerate the methylation treatment well from the git-go, he keeps them on it. So he sort of uses it as a diagnostic to see how the gut and the liver are functioning.

    I hope this helps, and I hope that things will go better for you this time.

    Best regards,


    [This Message was Edited on 04/28/2011]
  4. Scapper

    Scapper New Member

    Kat -- yes! As soon as I read this I remembered I had my cortisol checked way back when. Non-existent during day and highest at 4:00pm -- all levels way below the norm. I remember they put me on "Cortef" and I couldn't tolerate it. We were never able to address the issue (I don't handle meds or anything stimulating well).

    Rich: Thank you SO much for helping to make sense of this for me. This is exactly what's happening w/ me!

    Lately (new for me) when I get nervous about something, I get a weak feeling in all my muscles and almost like a panic feeling, sometimes heart racing. In my brain I'm thinking "why am I feeling this way, this isn't that big of a deal" but it's as if my body's reaction is separate from my thoughts. My health has definitely deteriorated over the last several years.

    Do you think this is my adrenaline over-compensating b/c of low cortisol?

    I'm having a hard time finding a doctor in New York that is versed in the methylation cycle -- any input on this?????

    Thank you again.....I don't post much, but I read ALL of your work!

  5. Scapper

    Scapper New Member

    2 more questions:

    Why would some people feel sick from supplementing w/ Glutathione?

    My body seems to freak out from Folates -- an immediate severe headache and awful CNS feelings......overstimulated.

    If you don't know of any docs in New York, do you know of any in Connecticut who are methylation literate? I rrrreally need to find a doctor who knows what they are doing (who doesn't here :)

    Thanks again!

  6. Scapper

    Scapper New Member

    Thank you for sharing your experience w/ me!

    You're absolutely right, I need to go **extremely** slow w/ meth products. I do muscle test (have been for many many years), but my body seems to say I can handle more than I actually can.

    I have a very well educated holistic prac who does "bioenergetic" healing. I've supported my adrenals for many many years, with no result. I'm currently not on an adrenal product, but I'm going to get back on one ASAP. I tolerate adrenal products ok.

    The last 3 years my practitioner has basically focused on cleaning up the toxins, etc. released from stimulating my methylation cycle (in my wording). The "general" support of my body/endocrine system fell by the wayside with all of this crisis type work.

    I believe (and hope) that the methylation cycle is the crux of this problem. As Rich said, the lack of glutathione in my pit/hypothal create this never-ending pit of need.

    I had never heard of the Clymer Institute. Just looked it up....very interesting place!!!! They use similar and alot of the same products I've used over the past 16 years. My practitioner uses only high quality and tests everything that goes into my body.

    I have done A TON of nutritional and supplementational support since onset with ZERO results. I have to believe the methylation cycle is the issue!

    In the meantime, I'll support my adrenals in a variety of ways and prepare to begin the methylation protocol again.

    I was hoping to find an M.D. to support me this time around. My holistic practitioner cannot do the bloodwork, etc.

    Thank you again for sharing your knowledge :)

  7. richvank

    richvank New Member

    Hi, Scapper.

    This is a question that has bedeviled me for more than 10 years! We have very good evidence that glutathione is depleted in most cases of CFS. It seems that most PWCs receive a temporary benefit from boosting glutathione in various ways. However, some feel worse, as you mentioned. Why?

    I've considered several possible explanations over the past few years, but here is my current guess as to why some people with ME/CFS feel sick when they supplement glutathione: they have niacin (B3) deficiency.

    The logic here is first, several PWCs have sent me their reports from Acumen Lab in the UK, and on some of them NAD is measured, and it is often found to be low. NAD is an active form of niacin, and it is the substrate for making NADP. NADP is normally chemically reduced by the pentose phosphate shunt on the glycolysis pathway, which metabolizes glucose from carbs in the diet.

    NADPH is necessary for chemically reducing glutathione when it has become oxidized, via the glutathione reductase reaction.

    I've heard from Dr. Cheney that he has had NADPH measured in some PWCs and has found it to be low.

    PWCs are in a state of oxidative stress, with glutathione depletion. When glutathione is boosted, it rapidly becomes oxidized. If there is insufficient NADPH available, the ratio of reduced to oxidized glutathione will drop. This ratio is responsible for maintaining the redox potential of the cells. If this becomes too oxidizing, it will impact a lot of the biochemical reactions in the cells deleteriously. The cells will export the excess oxidized glutathione, but temporarily, I think this ratio will be decreased in the cells, and I think that's what accounts for the bad reaction some PWCs have if they supplement glutathione.

    This is an easity tested hypothesis, but I don't know of anyone who has tried to test it.

    In the simplified treatment approach, one of the supplements is a multi that includes niacin. This would tend to build up niacin in the body as the partial methylation cycle block is lifted and glutathione is automatically raised by lifting this block, and perhaps that's why building up glutathione in that way seems to work well for most PWCs.

    With regard to folates, do you have problems with 5L-methyltetrahydrofolate (FolaPro or Metafolin)? The others, folic acid and folinic acid, both require NADPH for conversion to 5L-methyltetrahydrofolate. "Freddd," on the PhoeixRising forums, has posted that he has trouble with glutathione, folic acid, and folinic acid, and I have suggested that this might be because all three of them require NADPH, and it might be deficient.

    With regard to physicians in New York, Dr. Derek Enlander in NYC does treat the partial methylation cycle block, using his own protocol, which is somewhat different from the one I've suggested, but does incorporate folinic acid and hydroxocobalamin, I think.

    Dr. Steven Bock in Rhinebeck, NY, is familiar with the methylation issue. I don't know if or how he treats it, though.

    I don't know of any physicians in Connecticut who treat the methylation issue. There may be some, but I'm not aware of them. I think this issue is starting to become better known, at least among the alternative and complementary physicians, those involved in functional medicine, the ILADS Lyme docs, and the environmental medicine docs. Naturopaths seem receptive to it, too. If you know of a physician who would be interested in receiving information about it. I would be happy to communicate with them.

    Best regards,

  8. Scapper

    Scapper New Member

    Thank you for taking the time to answer in-depth, I cannot tell you how much I appreciate it!

    As far as my reactions to the folates, etc., in 2007-2008 I took both Folapro and Intrinsi B12 together. My symptoms were: constipation, dizzy, yeast, prolonged ear infection, worsened insomnia; itchiness all over (especially scalp); tired but was all pretty severe.

    Fast forward to present: I took 1/4 Intrinsi B12 for 2 days several weeks ago. I got the overstimulated CNS feeling and a migraine immediately. Sleep was impossible (but this is on-going for me).

    I'm not sure if you could take a "guess" at this one, but, my scalp has remained *very* itchy and sore since 2008 methylation detox began. Could my body be "stuck" in some sort of process......seems like a very long time. It's driving me nuts. Yeast, bacteria and parasite issues have been resolved. I can't figure out why my scalp won't calm down.

    Anyway, I'm overwhelmed.....finding it difficult to treat my body when I'm so weakened to start with. I'm scared this time around that the supplements will put me back into bed.

    Perhaps I'll get my B3 level checked and supplement w/ Glutathione first......maybe build myself up before MCB work (?)

    I saw Dr. Enlander about 6 years that time, he was supplementing w/ Glutathione. I did this for a year under his care and I got worse (well, my insomnia got worse), reducing my ability to make the travel to him.

    Thanks again Rich for any insight you might have!

  9. richvank

    richvank New Member

    Hi, Scapper.

    There might be some clues to what is going on in your case from your health history prior to your onset of ME/CFS.

    If you don't mind, would you review for me what occurred during the few weeks or months prior to the onset of your illness? Were you taking any medications? What sort of stressors were you experiencing, physical, chemical, biological or emotional/psychological? What was your nutritional status like? Did you have a sudden or gradual onset? Possible exposure to tick bites or positive Lyme testing? Positive testing for other infections? Vaccinations? Exposure to toxic molds in home or workplace? Exposure to mercury or other toxic heavy metals or organic toxins? Etc.

    If you would prefer not to post this information on the board, please email it to me, and I will keep it in confidence. I think it's against the rules to post my email address, but you can probably find it by googling me or checking some earlier posts.

    Best regards,

    Rich Van Konynenburg
    [This Message was Edited on 05/02/2011]
  10. Scapper

    Scapper New Member

    I sent you my history.