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under methylation,over methylation, and precursers (laymans version)

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by markmc20001, Jan 16, 2010.

  1. richvank

    richvank Senior Member

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    Hi, Ross.

    Intolerance of meds and problems with tolerating sulfur-containing supplements like SAMe are very common in people who have the partial methylation cycle block. I think the former is due to the fact that the detox system is very dependent on metabolites within the sulfur metabolism, including cysteine, glutathione, taurine and sulfate, and hte levels of all of these can be abnormal when there is a partial methylation cycle block. Glutathione depletion also impacts the operation of the Phase I cytochrome P450 enzymes that metabolize many of the meds, because oxidizing free radicals are produced by them, and glutathione is the basis for the cell's antioxidant enzyme system.

    The sensitivity to sulfur-containing substances may be caused by their conversion to forms such as hydrogen sulfide and sulfite, which are toxic at sufficient levels. Sometimes supplementing with molybdenum can help with this problem, because it forms a cofactor for the enzyme sulfite oxidase, which converts sulfite to sulfate for excretion.

    With regard to Dr. Richard Kunin, it's true that he has been interested in methylation for many years. He and his son supply a supplement called Ola Loa that is intended to address methylation issues. He has also spoken several times at the Orthomolecular Health Medicine Society, of which he is the president. He has been very encouraging to me in working on methylation-related issues. He invited me to speak at the Society's meeting two years ago, which I did, and he invited Dr. Neil Nathan to speak on our clinical study of methylation block treatment in CFS at the most recent meeting of this Society last weekend, which he did. So yes, I have learned a lot from Dr. Kunin, and he is very aware of what we are doing. He hasn't actually written much on the methylation topic, so I haven't had anything written by him to quote, but we are friends.

    Best regards,

    Rich
     
    Lotus97 likes this.
  2. dannybex

    dannybex Senior Member

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    SAM-e intolerance...

    Hi Rich,

    Just wondering...what are typical symptoms of intolerance to SAM-e?

    I think I tolerate it okay...in fact it seems to be one of few supps that will help bring me out of 'dips'...but at the same time if I take more than say 600mgs a day, then I tend to get a little hyper or have this kind of false 'giddiness' (is that a word)?

    Thanks in advance,

    Dan
     
  3. Wayne

    Wayne Senior Member

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    600 mg SAM-e

    Hi Dan,

    I just started taking SAM-e regularly in the past few months, and I've noticed that it seems to help me a lot. I did notice way more in the beginning than I currently do, but my overall health is up as well, I believe at least in part because I'm taking the SAM-e.

    When I first started taking it, I was taking a full 200 mg tablet per day. I felt a "bubbling" up of energy, and after a few days this bubbling started to be a little too intense. So I backed off to half a 200 mg tablet, and then backed off further to a 1/4 200 mg tablet.

    I began to wonder if I would be able to continue to take it. But I soon noticed my body seemed to want more than the 1/4 tablet. So I went back up to a 1/2. I now try to gauge every day the optimal amount I should take (sort of like my low-dose hydrocortisone), and usually take a 1/2 or a full 200 mg tablet.

    I was surprised to hear you take as much as 600 mg. I can certainly understand how it could make you experience some "giddiness". And yes, giddiness is a word. :Retro smile:

    Wayne
     
  4. Cloud

    Cloud Guest

    Thanks Rich, great info that makes a lot of sense to me, especially......

    "Glutathione depletion also impacts the operation of the Phase I cytochrome P450 enzymes that metabolize many of the meds, because oxidizing free radicals are produced by them, and glutathione is the basis for the cell's antioxidant enzyme system".

    Most of this physiology is over my head, but from what I do understand, it seems to explain a lot of why I have these reactions. I can take truckloads of certain meds (metabolized in the liver) with no problem at all....yet others will put me in bed within 2-3 days. This leaves me with the question of whether a methylation block could cause malfunction of some, but not all of the P450 isozymes. It will sure be nice if this is just a downstream problem of blocked methylation.
    I haven't really noticed reactions to sulphur containing drugs/supplements more than anything else, but then I haven't watched that too closely. Also, my reactions are the opposite of "giddy".....I feel poisoned, and decreasing the dose will do no good at all. The only remedy is to stop the med, SAMe, or whatever it is I'm taking that's causing the reaction.

    Yea, many of my family members had seen Dr Kunin over the years and had the greatest respect for him.....it was only recently that I stumbled upon his pioneering work on Methyaltion and was just curious about his involvement. So, thanks for that info as well.
     
  5. Freddd

    Freddd Senior Member

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    Hi Wayne,

    SAM-e turned out to be one of those things that helped me a lot. Just like Mb12, adb12, l-carnitine-fumarate there was an "energized intensity" to the SAM-e. I started with 400mg and it was just like the first hour taking methylb12. And like methylb12 but more quickly, perhaps 2 weeks, the effects of the SAM-e faded. Later after adding TMG and methylfolate I tried some other doses and 600 mg did nothing more at all. So I tried 200mg, and changed once a week to 400mg a few times and established that 200mg was all that I now needed. I stopped for a week and it had "energizing" startup all over again but not as intense as the first time. This less intense one is repeatable. Just like with the mb12 after a while taking the SAM-e the energized feeling faded away with my body at a new higher energy steady state.

    Just like with the mb12 if a person avoids the energized feeling, the thermastat overshoot effect, then the body doesn't appear to adapt to the revized nutrient state and get rid of the fatigue that is so prominent, both the "body" fatigue and the "mental" fatigue.

    All I have to do to have mb12 startup responses each time I take a sublingual is reduce myself to 1000mcg sublingual daily. That is not a dose for me that can maintain erquilibrium.

    So be careful in avoiding being "energized" and a dozen other ways to describe the effects because that appears to avoid certain parts of recovering. I honestly don't know how to recover from deep down in the pit of CFS/FMS without having the sensations associated the high acceleration and speed elevator. When the nervous system changes we can feel the effects of change, slowly or quickly. I feel it every day and using those feelings I can tell what is working. Often it is possible to feel change but not be able to tell direction for a while longer. With the vitamins and supplements generally and mb12, adb12, SAM-e, TMG, methylfolate, l-carnitine fumarate and zinc specifically all had moderate to very substantial startup and every single one faded into homeostasis but with a different setpoint over time.

    Giddiness might even be a prettry good indicator that the setpoint is being changed.
     
  6. Freddd

    Freddd Senior Member

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    Hi Rich,

    Ola Loa is a brand of supplements. Is there a specific product mentioned? I would be interested in seeing what is in it.

    So that might explain why so many people deficient of mb12 had hypersensitivity to medications, foods, chemicals and all that and why it can clear up with the supplements as things normalize.
     
  7. Wayne

    Wayne Senior Member

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    SAM-e - B12 Protocol

    Hi Fredd,

    Thank you very much for your reply. I've not been able to keep up very well at all with your long thread on B-12, etc. I've long felt I would need to get on top of my life in many ways, and then at some point take several days or weeks to try to determine what's all in your main thread, and how it might be able to help me.

    Your description in your reply to me today has been very helpful. I can now see more clearly how much of what I may be experimenting with, based on your voluminous information and suggestions, may be very similar to my own experience with SAM-e.

    In fact, your reply today may very well be a catalyst to allow me to think I can now start delving into this whole subject area, without necessarily having to wait until I'm "on top of" many other areas of my life.

    This is all feeling very heartening to me. And you can't put a price tag on feeling heartened. :Retro smile: Thanks again!

    Wayne
     
  8. Cloud

    Cloud Guest

    I am amazed that some of you were able to take SAMe for prolonged periods of time early on in treating blocked methylation. I cannot do that, but wish I could. Regardless, it seems the right thing for me is to move forward with treating a possible methylation block. If I don't do something that will allow me to tolerate these abx (antibiotics), I will slide right back into the (deeper) abyss. My response to abx has convinced me that infection is a major player (probably cause) in this illness. But I can't take the effective abx more than a week without becoming toxic. We have tried one parenteral med attempting to bypass this detox problem, and it does work very well in that respect.....but it has minimal effectiveness on the infection and it's related symptoms. Another symptom I get with the toxicity is right upper abdominal and flank pain that will fluctuate with the levels of "toxicty". I have had extensive liver and gallbladder tests that show nothing remarkable. Anyone know how common this right flank pain may be with a methylation block?

    Thanks everyone
     
  9. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Hi Ross,

    I know from following all the discussion around Rich's Simplified Protocol that probably the majority of patients with a partial methylation block had trouble with SAMe. It was originally in the protocol, but made optional later when it was clear that it gave a lot of people trouble.

    I am one of those who have done fine with it. I started with only 50 mg, and slowly increased to 400 mg. then dropped back when my second methylation panel showed normal SAMe levels. It may have to do with genetics and whether or not you have a SNP in the CBS gene--or maybe something else!

    I haven't been following this thread, so sorry if I am repeating.

    Wish you the best with it,
    Sushi
     
  10. susan

    susan Senior Member

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    I have not been following this thread

    Do you any of you take TMG with SAMe....I thought TMG converted to SAMe anyway.
     
  11. Freddd

    Freddd Senior Member

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    Hi Susan,

    SAM-e and TMG are entirely different things. SAM-e (S-Adenosyl Methionine) is an intermediate substance in the homocystein > methionine cycle. SAM-e is considered the body's "universal methyl doner". When methylb12 is taken SAM-e is increased. When hydroxyb12/cyanob12 are taken they take a methyl group from the SAM-e. Methylfolate/folate can also donate or receive methyl groups within this process.

    Choline is tetra methyl glycine. Remove one methyl group and you have TriMethylGlycine and remove one more methyl and you have DiMethylGlycine. While these methyl groups from TMG can be donated for use to other things the glycine always remains glycine and does not turn into homocysteine or methionine or SAM-e.
     
  12. Freddd

    Freddd Senior Member

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    I have taken that list of under and over methylators (sounds like some kind of rifle-shotgun combo) symptoms and categorized them as to type of b12 deficiency(s) by color and grouping them based on what symptoms I used to have.

    I have included the characteristics as listed on several sites of under and over methylators. They BOTH include depression which seems contradictory to me. Color red means mb12 deficiency symptom. Color pink means frequent mb12 deficiency co-correlate. Color red-brown means adb12 deficiency symptom. There are no hydroxyb12 deficiency symptoms or co-correlates because they don't exist as such because hydroxyb12 has no direct usage except to be converted to adb12 and/or mb12. Be aware that virtually all b12 deficiency symptoms, taken one at a time, may have multiple other causes. Does anybody actually have only one set ot the other of these symptoms/charcteristics?


    UNDER METHYLATORS


    My remaining symptoms and characteristics after b12 & cofactors

    2 - Poor tolerance of heat
    9 - Excess perspiration
    16 - Perfectionism
    17 - Competitiveness
    19 - Vasomotor rhinitis
    27 - Good tolerance of cold

    My symptoms before taking b12 and cofactors


    1 - Depression - Depression
    2 - Poor tolerance of heat
    3 - Unexplained nausea
    4 - Frequent colds and flu
    5 - Poor pain tolerance
    6 - Joint pain
    7 - Joint swelling
    8 - Joint stiffness
    9 - Excess perspiration
    10 - Insomnia
    11 - Muscle pains - Muscle pains
    12 - Seasonal depression
    13 - Inhalant allergies
    14 - Oppositional –defiant -so my mother said but she was highly disturbed and psychotic and it was only her I was opposing and defying when she was irrational
    15 - Frequent headaches - Frequent headaches

    16 - Perfectionism
    17 - Competitiveness
    18 - Asthma
    19 - Vasomotor rhinitis
    20 - Allergic skin disorders
    21 - Pruritis
    22 - Sparse body hair - increased a lot to normal after mb12 and cofactors, especially on slick legs
    23 - Fatigue
    24 - Respond well to SAM-e and methylfolate and TMG and inositol and mb12 and adb12

    25 - Anorexia/bulimia - physical, not psychological, no body distortion, no motivation to be anorexic except for b12 containing foods in some people
    26 - Prone to hives
    27 - Good tolerance of cold

    Not my symptoms/chraracteristics

    High salivary flow
    High tear flow
    Never dry eyes
    Hyperactivity
    Phobias
    Highly motivated
    Hard driving personality
    Addictive tendencies
    bipolar disorder
    OCD
    Schizophrenia
    Abundant or excess saliva in mouth
    Obsessive compulsive
    Slenderness
    Do worse on b12 and folates (4)
    Shopping/gambling disorders
    Excess stomach acid
    High libido
    Elevated absolute basophils
    Extreme internal anxiety despite outwardly calm
    Delusion thinking rather than hallucinations
    Respond well to SAM-e, methionine, avoid folic acid (1)
    Low serotonin
    Low dopamine
    Low norepinephrine
    Psychosis
    26 Total



    OVER METHYLATORS


    My remaining symptoms and characteristics after b12 & cofactors

    1- High religiosity - if you include high spirituality instead of religiosity, I am anti-religiosity as such.
    2 - High artistic/musical ability
    4 - Absence of seasonal inhalant allergies - my seasonal inhalant allergies nave gone away with methylb12/methylfolate almost entirely
    19 - Intolerance to SSRI drugs
    21 - Low motivation





    My symptoms before taking b12 and cofactors, except where noted


    1- High religiosity - if you include high spirituality instead of religiosity, I am anti-religiosity as such.
    2 - High artistic/musical ability
    3 - Auditory hallucinations
    4 - Absence of seasonal inhalant allergies - my seasonal inhalant allergies nave gone away with methylb12/methylfolate
    5 - Frequent dry eyes
    6 - Multitude of chemical sensitivities
    7 - Multitude of food sensitivities
    8 - Low libido - Low libido
    9 - Auditory hallucinations
    10 - Underachievement as child - so my mother would say
    11 - Nervous legs - Nervous legs
    12 - Depression - Depression
    13 - Despair
    14 - Respond well to mb12 and SAM-e and TMG and methylfolate and inositol and and adb12

    15 - Upper body pain
    16 - Head pain
    17 - Low salivary
    18 - Low tears
    19 - Intolerance to SSRI drugs
    20 - Treatment revolves around folic acid, niacin, B12, and a high protein diet. (2)
    21 - Low motivation


    Not my symptoms/chraracteristics

    Elevated serotonin
    Elevated dopamine
    Elevated norepinephrine
    Self injury
    High anxiety evident to all
    Obsessions but not compulsions
    Paranoia
    Heavy body hair
    Hyperactivity
    Grandiosity
    Respond well to b12 but avoid SAM-e, inositol, methionine TMG and DMG (1)
    Panic attacks
    Nervous
    High pain tolerance
    “space cadet”
    Learning disabilities
    Low perspiration
    17 Total

    Once again, what remains after b12 and cofactors is approximately equal and down to 5 or 6 items in each category. Nothing distinguishing.
     
  13. aquariusgirl

    aquariusgirl Senior Member

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    I have a question for Fredd.
    My mother has some pretty funky B12 readings and I would like your take on it.
    She is 63 and has cirrhosis and very little liver function left, which I assume throws things off.
    Her most recent blood B12 reading is 18532 pg/mL (183-883) (Yes, they double checked that figure.)
    Previous reading was over 6,000 (anything under 1,000 was normal)
    Folic Acid is 14.6 ng/mL (2.3-17.6)
    Red cell folic acid 1010 ug/L (180-750 )
    MCV 100.2 fL (80-100)
    MCH 30.5 pg (27-32)
    MCHC 30.4 g/dL (31-35)

    MMA was 3.2 on a Metabolic Acid profile mid 2009
    Figlu was dl

    So is she B12 deficient or not. I'm not clear on what is going on here.
    Her doctor thinks she's fine, with respect to b12.

    Thanks for any input.
     
  14. Freddd

    Freddd Senior Member

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    Hi Aquariusgirl,

    First a clarifying question, is that 3.2 serum or urine MMA. It imay be high for serum and just below top of range for urine depending upon whaty units are being used.

    Her MCV is high at 100.2 but the MCH is not as corespondingly high.

    The serum b12 of 18,532 pg/ml in the absence of high b12 supplementation rates indicates liver damage which you do indicate. The problem with looking just at that number is it doesn't actually tell us anything about the quality of the cobalamins present. The liver appears to have lost the functionality of clearing the blood of cobalamins and accumulating it for excretion in the bile. These cobalamins the liver collects are mainly methylb12, the normally main cirulating cobalamin, inactive cobalamins resulting from detox such as cyanocoblamin, misc inactive circulating cobalamins such as aqeouscoblamin, glutathionylcoblamin and the many various inacitve plant (junk) cobalamins that normally are present in only small amounts as they are swept up into the liver and excreted. So this number alone can't tell the story.

    So a further question is about kidney function. There are two kinds of tubules in the kidneys, only one kind of which gathers cobalamins. Normally the kidneys serve to keep the cobalamins well below that level. A specific test of that one kind of tubule is to inject maybe 20mg of b12 and check the urine over the next few hours for a visible output.

    MCV can also be affected by liver function but I am not clear on how. The new test on bound active b12 could be very useful here to determine what might actually be going on here. Also, perhaps kidney function tests and serum homocystein levels. If that is the serum MMA you show that high could be indicating a shortage of adb12. She could actually be short on both adb12 and mb12. There is a blood test that uses special opaque tubes and syringes for collecting blood for a type of cobalamin test so it is not changed by exposure to light. It is expensive and rarely done and requires a special collection kit.

    It may also be possible that she has a CNS/CSF cobalamin deficiency, especially if most of the cobalamins in circulation or inactive.

    She appears to have good folate levels but that might not be a an indicator of sufficient active folates if it is actually measuring folic acid. The devil is in the details.

    Does she have a bunch of symptoms indicative of b12 deficiency?

    Some additional testing may throw some light upon this.

    My serum cobalamin level is at an estimated 200,000pg/ml so it is not anywhere near as high as somebody injecting substantial amounts daily.

    I don't know the ramifications of various supplements with somebody with serious liver problems like this.
    Good luck.
     
  15. susan

    susan Senior Member

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    Hi Fredd,
    Thanks for your response. I tried following you early in the piece but lost confidence in my ability to understand the scientific facts. So I found a Dr. now a naturopath who has been healing Autism/CFS for 15 yrs thru methylation. I did the Metametrix test which he said was abominable, only 40 % o of me working....Krebs cycle almost at standstill. My B12 was not too low but the folic acid was very low. He made me a formula containing Methyl b12 folinic acid with minerals that I was short. He then only told me to take 2000mg of TMG. He says I am an Undermethylator but I cant relate to many of the above symptoms. Nausea and loud burping is sometimes extreme......usually begins early morn and leaves about midday.

    I have extremely high neurotransmitters, scary level so i dont have depression. I am nearly 3 mths now on this program and feeling some improvement. Of course after so many years sick and not being young any more, I want to get better faster. Should I take SAMe along with TMG....will this hasten methylation..... yrs ago I tested extremely low homocystine. My Dr is very ill and I might not be able to continue on and in this country I dont have much other choice. What do you think about the SAMe with TMG
     
  16. aquariusgirl

    aquariusgirl Senior Member

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    Fredd
    The MMA was urine. The range is anything under 19.
    What is the bound B12 test you refer to? Where could I order it?
    thanks
    aq
     
  17. Freddd

    Freddd Senior Member

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    Hi Aquariusgirl,

    Axis-Shield's Active-B12. This runs on health care major Abbott Laboratories' AxSYM automated immunoassay system, which is used in thousands of hospitals and clinical laboratories worldwide.

    This is all I found on it. Through your doc who would do the blood draw. It measures holotranscobalamin.
     
  18. knackers323

    knackers323 Senior Member

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    hi Susan, can I ask what is wrong with your doc? is he thinking of finishing up working soon? have you seen enough improvement to continue his treatment? thanks
     
  19. susan

    susan Senior Member

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    HI Knackered,
    He has the Big C....2nd time it has emerged. Working from home a bit now while undergoing treatment and going to their new office a few times a week. Does most of his work by email as he goes primarily on Metametrix tests and treats accordingly. Yes I have noticed an improvement...more energy especailly when I bend down I dont feel I need an oxygen machine. I am gardening a little bit too.......walking first time in 2yrs......doing mercury detox too which is chlorella based. He said I did not have to do that but I want to.
     
  20. richvank

    richvank Senior Member

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    Overdriving the methylation cycle, elevated sarcosine and prostate cancer

    Hi, all.

    I just learned something that I think I should pass on to you.

    As you know, I have expressed concern in the past about the possibility that high dosages of 5-methyl THF together with high dosages of methyl B12 could overdrive the methylation cycle in people with CFS.

    I have now received plasma amino acids test results from two people who have been on this type of protocol for some time (names withheld because of patient privacy rights), and this is the pattern they have both shown:

    1. MethionineHigh

    2. HomocystineBelow detection limit

    3. Methionine sulfoxide--Detectable to elevated

    3. SarcosineVery high

    4. Serine/Glycine ratio--Low

    5. CystathionineBelow detection limit

    6. TaurineLow-normal


    This is how I interpret this pattern:

    The high methionine level is unusual in CFS, as it is usually low. This suggests that it is being recycled rapidly from homocysteine, unless it is being supplemented.

    The undetectable homocystine, which is the oxidized form of homocysteine, suggests that homocysteine is also very low. This inference can be made because the presence of methionine sulfoxide gives evidence of a state of oxidative stress, which suggests that if homocysteine were present in significant amounts, homocystine would also be detected.

    The combination of inferred low homocysteine and high methionine suggests that the conversion of homocysteine to methionine is rapid, thus inferring that the methylation cycle is running faster than normal.

    The very high sarcosine confirms that the methylation cycle is running faster than normal. The formation of sarcosine from glycine by the enzyme glycine N-methyl transferase serves as sort of a pressure relief valve for the methyation cycle, dissipating methylation capacity by forming sarcosine when the ratio of S-adenosylmethionine to S-adenosylhomocysteine is tending to become too high.

    The low ratio of serine to glycine suggests that the serine hydroxymethyltransferase (SHMT) reaction is running faster than normal, which suggests that tetrahydrofolate is higher than normal, which in turn suggests that the methionine synthase reaction is running faster than normal.

    If the methionine synthase reaction is running faster than normal, the cystathionine beta synthase reaction would not be expected to be able to compete as well as normal for homocysteine, and thus the flow down the transsulfuration pathway would be expected to be lower than normal. Evidence that this true is the undetectable level of cystathionine.

    Additional support for low flow down the transsulfuration pathway comes from the low-normal level of taurine.


    What would be the consequences of overdriving the methylation cycle?

    I think that one would be that the sulfur metabolism, including cysteine, glutathione and taurine would not be able to recover as rapidly as they would if the methylation cycle was not running so fast. This could slow the overall recovery, I think. It would leave the person in a state of oxidative stress longer, and would slow the recovery of the detox system and the immune system, as well as maintaining the symptoms caused by low glutathione for a longer time.

    The other consequence is that sarcosine remains high in an effort to control the SAMe to SAH ratio, which is being pushed higher than normal. Does this matter?
    It looks as though it might, from a paper published last year, abstracted below (the full paper is available from PubMed, by entering the PMID number in their search box, and then clicking on the colored box at the upper right of the abstract page.) Note especially the paragraph that begins with the word "sarcosine":


    Nature. 2009 Feb 12;457(7231):910-4.
    Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression.

    Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM.

    The Michigan Center for Translational Pathology, Ann Arbor, USA.

    Comment in:

    * Nature. 2009 Feb 12;457(7231):799-800.

    Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer (42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease.

    Sarcosine, an N-methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non-invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells.

    Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.

    PMID: 19212411 [PubMed - indexed for MEDLINE]


    I think this is something to be concerned about. In particular, I think it would be wise for any men who have been on this protocol for an extended time to have a digital rectal exam and a PSA test to check for prostate cancer. If prostate cancer is present, I think it would be wise to lower these dosages to allow sarcosine to come down.

    Beyond that, I continue to have doubts about the advisability of use of this high dosage protocol. If sarcosine stimulates prostate cancer, it might stimulate other types of cancer as well. I continue to believe that people should proceed more slowly with treatment, and should monitor the status of their methylation cycle by lab testing during the treatment, aiming to restore it to normal status, rather than to overdriven status.


    Best regards,

    Rich
     

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