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I have a lot of BHMT and AHCY mutations, among others. Can you advise me?

Discussion in 'Genetic Testing and SNPs' started by Tom_Nightingale, Feb 19, 2013.

  1. juniemarie

    juniemarie Senior Member

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    LaurieL What brand of niacinamide do you take? Does it also have niacin and inositol hexanicotinate in it?
    Do you divide the dose throughout the day? juniemarie
  2. LaurieL

    LaurieL Senior Member

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    No Niacin. Eeeeck......did not respond well at all to that. Horrible stuff for me, made me want to claw off my own skin, sick to my stomach, and I would stay red for many hours.

    I have used Swanson's and also Vitamin Shoppe. I like Swansons the best. No, I do not divide the dose. I take 1500 mg in the morning when I wake. I stay even throughout the day. I do not seem to respond well to inositol either.

    I started taking niacinamide after learning about it and ACAT.

    LaurieL
  3. Bluebell

    Bluebell More % Neanderthal than Adreno but less hairy :-D

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    LaurieL,

    Would you mind describing what you learned about niacinamide and ACAT?

    After reading your comment, I searched the PhoenixRising forum for these two words and didn't come up with anything --
    then I searched the internet, but only came up with articles about niacinamide and veterinary issues! :cat: ha ha

    I recently bought some regular niacin and am now wondering if this is the wrong form for me to take.

    I have a +/+ ACAT and am only just learning about these issues.

    Do you have any thoughts about what I should be aware of, regarding the homozygous ACAT?

    I notice that you asked StarAnise above for her full genetic results - mine are not in my signature below, but they are listed in the first post of the following thread: http://forums.phoenixrising.me/inde...-i-would-be-grateful-for-some-guidance.23975/

    -Thank you-
  4. LaurieL

    LaurieL Senior Member

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    Blue-bell, I am not finding your genetics in that thread, perhaps I need to stop multi-tasking. Do you have a post number?

    ACAT connection to niacinamide is through the acetyl Co-A enzyme, as NAD is converted from niacinamide, NAD then onto NADH, in other reactions. The connection to MAO is through tryptophan, in which is needed to generate niacinamide. But what I found is that direct supplementation of tryptophan made me cycle too much. Niacinamide prevents the breakdown of tryptophan, of which we loose anyways as we age, or infections steal it, so tryptophan by several ways isn't making it to niacinamide in me.
  5. Bluebell

    Bluebell More % Neanderthal than Adreno but less hairy :-D

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    Sorry about that -- my first post there is quite long, and my 23andme results are buried in the middle! They are:

    reds
    ACAT1-02 AA +/+
    BHMT 02 TT +/+
    BHMT 04 CC +/+
    BHMT 08 TT +/+
    MAO A TT +/+
    VDR Taq AA +/+ [it's a +/+ in Dr. Yasko's notation, although AA is the majority allele in the population]
    yellows
    AHCY rs13043752 AG +/-
    CBS A360A (C1080T) AG +/-
    COMT H62H CT +/-
    COMT V158M AG +/-
    MTHFR A1298C (E429A) GT +/-
    MTHFR C677T (A222V) AG +/-
    MTRR A66G (A919G) AG +/-
    MTRR A664A AG +/-
  6. LaurieL

    LaurieL Senior Member

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    VDRtaq.

    This variation is not meant to be looked at alone. I know most of the population has this allele variant, but it is my understanding from reading Dr. Yasko's stuff these past few years, that it is meant to be combined and looked at as a set with COMT status. So even though the VDRtaq is a common variant, the combination with the COMT status will really determine what if any "effect" it might have, as variations in COMT don't meet the allele prevalence in the population criteria at this moment in time. The taq variation can affect dopamine levels, which when looked at combined with COMT, depending on the variation of COMT, may have then have some influence on dopamine levels. Atleast this is what I thought, but I defer in light of new info?

    LaurieL
  7. LaurieL

    LaurieL Senior Member

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    Additionally, the MTRR/MTR variations are also supposed to be combined. MTRR recycles B12 for use by MTR. It is through this reaction, that Hcy is then recycled to methionine. You have BHMT variations, so your backdoor may not be working like it should to take pressure off of the MTRR. So you may have high Hcy levels, if you don't have enough B12 to help MTRR.

    I have the CBS 360, but I do not have COMT, nor AHCY, and I have not found mine to be a problem or better said, expressed. Your situation may be a little different in that AHCY converts SAH into Hcy. If this isn't occuring at the rate it should, you very well could be producing high levels of adenosine, once you start supplementing the methylation cycle. As it stands now, with MTRR, low B12, AHCY, and CBS 360, your Hcy could be low due to the AHCY, your backdoor isn't converting Hcy to methionine, but it isn't being fed by SAH, and if low in B12, the long way isn't working either.

    AHCY is a confusing variation that it can have several effects, all conflicting. It isn't a straightforward variation.

    So if you were to supplement B12, you would want to beware of the AHCY and BHMT and watch your Hcy levels.
  8. Bluebell

    Bluebell More % Neanderthal than Adreno but less hairy :-D

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    Much obliged, LaurieL, for your thoughts on my results!

    I did a blood test for homocysteine 2 weeks ago, and I was surprised when it came back in the normal range, because I feel that I have a problem with B12 and/or Folate (due to optic neuritis, cheilitis, nail deformities, MTHFR compound heterozygosity, high MCV, etc.)

    As you pointed out, it may well be that some things are making homocysteine high, some things are making it low, and amidst all this dysfunction, the end result appears "normal" on a test result, but that might be nothing to be relaxed about.

    I do not understand biochemistry, so I'm in the dark about this entire topic. I have looked at the guides by the "heartfixer" doctor and Dr. Yasko, but the subject matter isn't intuitive to me and I am well aware that a lot of people here can picture these interlocking systems actually moving dynamically in time, with shortages being produced, doors being shut, other things feeding into it, etc. - I can do this with some other topics, but this one eludes me. All I see in those methylation diagrams is a basket of yarn that a kitten has gotten into, and then spilled a box of alphabet-letters pasta on top of. :D
    Sea and LaurieL like this.
  9. LaurieL

    LaurieL Senior Member

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    If you can do this with other things, then give yourself some time with this. Its not easy, and I just didn't pick this up in a split second. I don't have it down pat like some on here either.

    With your variations, and what you are planning to do with methylation, you are very wise not to be complacent with your current Hcy levels. When you start bringing up your methylation, I heavily suspect these test results to change.

    BTW, what a great analogy and visualization!!
  10. greenshots

    greenshots Senior Member

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    I think you should be very careful about the methyl donors you pick and take it VERY slowly with the BHMT since this increases adrenalin. This is probably the reason you felt so edgy and nervous because I would too! Your COMT isn't a big deal because the VDR Taq is ++ should mean you tolerate methyls more. The trouble is, our bodies are a wasteland of toxins so every time you add in a methyl you start a natural clean up process. One practitioner I know says this is like the Exon Valdeez oil spill where you have massive toxic waste on the surface but also all over the body where its not as obvious to the naked eye. Its the same when your sick with mental health problems or CFS. Its neuro diseaese plain and simple.

    People with full AHCYs usually need more nucleotides but Yasko's brand has folate in it so I didn't use it but I only have partials. Were supposed to be more likely to have gut problems cuz we don't have enough nucleotides for cell turnover in the gut and were also supposed to have more strep. I used the SHMT spray for a while cuz it had a little nucleotides and other stuff that got me thru the early days even tho I don't have an SHMT. That one is easy to dilute down into little doses so your not hitting your system hard and having a harder detox. I felt anxious on methyls and depressed on other ones during detox so I would take it slow so you don't make t extra hard on yourself.

    So to me, start on one methyl in teensy doses and take it slow. When one path opens, another may start flooding in chemicals like neurotransmitters. i remember when I did PS Complex I had an out of body sorta experience and felt like everything around me was fake or dreamy. This went away when I dropped it and went to only one at a time in littler doses but it showed me how close we all are to the brink when we mess with these chemicals.
  11. caledonia

    caledonia

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    I know this is from a couple of months ago, but I would just like to comment that blood tests for metals will only show recent exposures and not metals that are already stored away in the body. The best way to detect these is to do a urine toxic metals test like the one from Doctors Data. It's a urine test, with a captomer to cause a metal dump so you can see what's stored.
  12. juniemarie

    juniemarie Senior Member

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    LaurieL Been working on CBS and ran into some problems I could not figure out which I posted here http://forums.phoenixrising.me/inde...ements-suddenly-hit-a-wall.24289/#post-371807
    Doing a search on niacinamide brought me to this thread. This morning still feeling foggy in the head and fragile in my body, loosing my balance treading carefully like I was walking on eggs and decided to try 250 mg of niacinamide and with in 30 mins my head started clearing and things became so much sharper then my energy began to return.
    I still do not know how to interpret either the wall I hit or the positive results from the niacinamide.
    Laurie I know are SNP's are not exactly the same but we do have a couple in common. If you can shed any light on this I would appreciate it. I am glad I feel better but it would be good to know what about my particular SNP's would respond to niacinamide jm
  13. LaurieL

    LaurieL Senior Member

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    I am not sure about the wall you hit, but I have some time off this week, I could take a look see, don't know if I can be of assistance there.

    I can however help with some information on niacinamide. I think its the MAO-A mutation in which we have in common, of which niacinamide is helpful. Here is a link to Dr, Myhill and her thoughts on niacinamide.

    http://www.drmyhill.co.uk/wiki/Niacinamide

    It isn't too long, or too complicated, and it will be helpful in explaining why you derived energy and mood stabilization.
  14. juniemarie

    juniemarie Senior Member

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    LaurieL That was a very interesting article....I did not know niacinamide was important for all those functions. I see I am on an extremely low dose which is how I always start anything new. I may try taking 250mg 2x a day and see what that does. Is niacinamide one of those supplements that can potentially raise sulphur levels? I am trying to get that down so I can move on out of CBS to the next SNP My energy is holding up and the sleepiness has not returned so I hope its a case of if you feel better you are better!
  15. triffid113

    triffid113 Day of the Square Peg

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    Ok, I will jump in here with a very few points:

    I don't remember which VDR affects Vitamin D metabolism but if that's the one that does it means you CANNOT hang on to Vitamin D and need to have it tested and a supplementation dosage calibrated (I take 10,000 /day for 5 days a week). Vitamin D status does affect methylation.

    How do you know that your homocysteine is normal? The lab range is not based on science. Normal is 6.3. So get copies of your labs and check them out online at www.lef.org (Life Extension). If you get a mosquito bite, how long does it itch? Days or weeks? Or only for 10 minutes? Because if you are close to adequately methylated, the itch will go away in 10 minutes.

    When you supplement with methyls are you taking into account how to ferry them away? I believe you need to supplement with those things that lower homocysteine or else your homocysteine may rise upon supplementation and that is a problem (dunno if you can feel it, maybe so, but I have never done it because I would not think it wise). Thus I would take P5P and TMG when increasing methylation. I take 50mg P5P and 1-2g/day of TMG (2g for perfect homocysteine). TMG is very important because there is only 1 chemical reaction to get rid of homocysteine along that path whereas every other path requires 2 chemical reactions and thus is slower. TMG is critical to keeping homocysteine down, especially after meals.

    The way to measure copper is via hair analysis. Cheapest way through a reliable lab is via www.evenbetternow.com (they order from www.tracelements.com, which you cannot order from directly). Cost is $100

    I would not care to mix methylation and mood altering drugs as most of them say right on them something to the effect of not increasing methylation (I mean if they prevent you breaking down serotonin and you undertake a protocol to raise serotonin, then you can have too much serotonin). Theoretically. I however always have too little serotonin and too little dopamine despite methylation or anything else (even in spite of COMT +/+). Still drugs are serious business...
  16. triffid113

    triffid113 Day of the Square Peg

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    I have read that the CBS mutations that Yasko check for have only a 2% effect on homocysteine levels in adults. It may have significance in children but not adults in other words. Don't worry about CBS...just keep your eye on homocysteine levels and make sure they are normal. fyi I have posted references on this elsewhere but most recently Valentijn posted the same thing here:http://www.phoenixrising.me/forums/...table-joints-i-have-18-of-30-mutations.24324/
  17. triffid113

    triffid113 Day of the Square Peg

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    Forgive me but to me this sounds like grasping at straws - what is our proof that you even have high dopamine? Have you ever been tested? I think too much is made of Yasko's reports and most of the time I have tested her directions for me and found them to be wrong. I am greatly indebted to her for showing we non-biochemists how the methyl cycle works and for suggesting potential problems but I believe we should then test for these problems and not just assume she's right. She is often wrong! For instance CBS even +/+ like I have has very little effect on adults (2%) and I have tests to prove it's simply ROT! I have all the genes which she says are supposed to make me sensitive to methyls (even COMT +/+) and I am not. I have the genes which she says require me to take charcoal, yucca, levulose to excrete ammonia and yet two blood tests show I have no difficulty excreting ammonia o a normal (80g) of protein diet. Yada, yada. I don't see much point in worrying about ACHY or BHMT despite having many broken parts of these genes because I can get my homocysteine a perfect 6.3 despite them. Yada, yada. I read your note above paying attention to things that seem to me to be minor and I think there is a simpler way. Did you have these problems when you were younger (say under 30?) If not, twhy not ry DHEA (which peaks at age 30). It takes care of panic in 15 minutes. Bam! Your ability to tolerate stress is governed by your DHEA:cortisol ratio. If you have more cortisol (and coffee is liquid cortisol - 2 c. raise cortisol 33%) than you have DHEA to support it, the result is a panic attack. Since DHEA peaks at age 30, you can tolerate less and less stress. And inadequate nutrition is itself a big stress. Potentially inadequate nutrition can be caused by genetic mutations which prevent the enzymes they govern from working correctly - often causing them to lose their cofactors such that they cannot adequately do their job. Anyway, DHEA not only allows you to tolerate more cortisol but it is converted to hormones which themselves affect gene expression. Anyway, I'd look at restoring youthful hormone levels before I started worrying about things I don't think have the kind of impact you seem to ascribe to them.
  18. triffid113

    triffid113 Day of the Square Peg

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    Lauriel I am interested in your info on niacinamide. I cast back and could not find where you cited an article others found informative? Can you let me know where that was? I used to take niacinamide when I was a kid for about 10 years or more but gradually stopped taking it as my supplement load grew and I expended with nice-to-have's. I had read that niacinamide was helpful for diabetics and diabetes runs in my family. I also had experienced after taking a high dose of it that my skin felt more touchable - it felt sensual, like touch was the most exquisite sense. not just nice but exquisite. I actually had forgotton that I used to take it. I have always felt that it was good for me.
  19. triffid113

    triffid113 Day of the Square Peg

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    Just some studies on top in a search just now. These are by no means the Seminole or crucial studies proving this, but just a bit to get you interested in having a look yourself:

    Dehydroepiandrosterone (DHEA) treatment of depression

    Biological Psychiatry; Volume 41, Issue 3, 1 February 1997, Pages 311–318

    Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basal plasma DHEA and/or DHEA-S levels were openly administered DHEA (30–90 mg/d × 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months; her depression ratings improved 48–72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients.

    Altered salivary dehydroepiandrosterone levels in major depression in adults

    A Michael, A Jenaway, ES Paykel, J Herbert - Biological Psychiatry, 2000 - Elsevier
    ... Figure 1. Depression is associated with lowered dehydroepiandrosterone (DHEA), raised salivary
    cortisol, and elevated cortisol/DHEA ratios.

    Severity of depression in abstinent alcoholics is associated with monoamine metabolites and dehydroepiandrosterone-sulfate concentrations


    Psychiatry Research; Volume 89, Issue 2, 20 December 1999, Pages 97–106

    Depressed mood increases the relapse risk of abstinent alcoholics; its neurobiological correlates may include reduced serotonin and norepinephrine turnover rates and increased cortisol concentrations during detoxification stress. Neurosteroids such as dehydroepiandrosterone and its sulfate (DHEA and DHEA-S) may antagonize cortisol action and may have mood-elevating effects on their own. We measured severity of depression with Beck’s Depression Inventory (BDI) and Hamilton’s Depression Rating Scale (HDRS), plasma concentrations of cortisol, DHEA and DHEA-S, and CSF concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and the dopamine metabolite homovanillic acid (HVA) in 21 abstinent alcoholics after 4 weeks of abstinence and in 11 age-matched healthy control subjects. Only CSF MHPG concentrations were reduced in alcoholics compared to control subjects (41.4±6.6 vs. 53.3±8.6 pmol/ml). Self-rated depression was significantly correlated with CSF MHPG (Spearman’s R=+0.57, P<0.01), CSF 5-HIAA (R=+0.51, P<0.05) and plasma cortisol concentrations (R=+0.50, P<0.05). Negative correlations were found between DHEA-S concentrations and both self-rated depression (R=−0.45, P<0.05) and observer-rated depression (R=−0.55, P<0.05). The ratio of DHEA-S to cortisol serum concentrations was also negatively correlated with depression (BDI: R=−0.55, P<0.01; HDRS: R=−0.63, P<0.005). Anxiety (Spielberger’s State Anxiety Scale) was only associated with CSF MHPG concentrations (R=+0.58, P<0.01). Our findings point to the importance of noradrenergic dysfunction in the pathogenesis of depression among abstinent alcoholics and indicate that their mood states may also be modulated by a low DHEA-S to cortisol ratio, hypothetically indicative of low stress protection capacities.

    A paper on resilience (ability to tolerate stress): http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181630/ in the body says studies show low DHEA:cortisol ratio correlates with inability to tolerate stress. Another paper on resilience says the same: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080591/



    ---

    Brown had the studies that defined the ratio but everyone references him so if I use his name in the search string it does not narrow the search AT ALL...
  20. triffid113

    triffid113 Day of the Square Peg

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    Age-dependent and -independent associations between depression, anxiety, DHEAS, and cortisol: From the MIPH Industrial Cohort Studies (MICS)

    PsychoneuroendocrinologyVolume 37, Issue 7, July 2012, Pages 929–93
    There is a well-established link between dysphoric mood and endocrine dysregulation, but the strength of this association may vary with age. In order to investigate this possibility we assessed anxiety and depression with overnight urinary cortisol and plasma dehydroepiandrosterone-sulphate (DHEAS) in 608 factory employees ranging between 21 and 62 years. As expected, DHEAS declined with age (r = −0.54, P < 0.001) while there was a modest age-related increase in nocturnal cortisol (r = 0.17, P < 0.001). Depressive symptoms were associated with higher nocturnal cortisol (β = 0.19, P < 0.001), independent of age. While the association between anxiety and cortisol (age by anxiety interaction: β = 0.11, P < 0.05) became stronger with age, there was a similar decline in the DHEAS/cortisol ratio in high-anxious middle-aged adults (β = −0.10, P = 0.018). The current findings suggest that dysphoric mood, and in particular anxiety, may exacerbate the effects of aging on cortisol release. Prospective studies are needed to determine the causal relations between dysphoric mood, cortisol and DHEAS across the lifespan.

    Here is what Life EXtension has to say about the cognitive effects of DHEA:










    Depression. DHEA has been extensively studied in depression. DHEA levels are reduced in major depressive disorders in both adolescents and adults, and an elevated cortisol/DHEA ratio predicts a delay in recovery (Herbert J 1998; Ferrari E et al. 2004).

    Women lacking detectable DHEA have an increased occurrence of depression (Yaffe K et al. 1998).








    DHEA has also been a useful remedy for depression (van Broekhoven F et al 2003). A well-conducted study by the National

    Institute of Mental Health found DHEA to be quite effective in treating midlife long-lasting, mild depression (dysthymia). The

    symptoms that improved most significantly were inability to gain pleasure from normally pleasurable experiences (anhedonia),

    loss of energy, lack of motivation, emotional “numbness,” sadness, inability to cope, and worrying (Bloch M et al 1999). In

    another study, 3 months of DHEA supplementation improved self-reported physical and psychological well-being in ageadvanced

    individuals (Morales AJ et al 1994). These results were supported


    by a recent study that showed DHEA therapy

    improved depression among middle-aged people (Schmidt PJ et al 2005).


    I cannot find the studies I read long ago that were on my memory stick that got stolen. The irritating search rules now keep returning the same damn studies no matter what I search for. I HATE that they use history and anything other than what I specifically asked for in their searches now.

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