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Methylation And Homocysteine Disorders

Discussion in 'Ask For Help or Advice' started by Highserotonin90, Dec 13, 2018.

  1. Highserotonin90

    Highserotonin90 Member

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    Hi everyone,

    The last few years for me were really painful and heavy from the health point of view.

    I state that I have no genetic test to highlight any mutations such as the MTHFR gene.

    I'd like to know if there's anyone in the Forum who understands methylation and homocysteine.

    I have discovered that I have elevated it (15) and according to the studies, those who have 12 above suffer from schizophrenia. I have many related symptoms but very often I confuse them with those of autism because I tend to avert the looks of other people.

    I also often have symptoms of chronic fatigue so definitely not recycling homocysteine I struggle to produce glutathione and SAM-e. I have difficulty with language and find the right words. Little empathy and emotions. Very often anedonia.

    What does Ray Peat suggest in these cases? hypothesizing that you have MTHFR and are struggling to recycle the homocysteine.

    My other blood tests are regular including thyroid, cortisol, testosterone, insulin, PCR, Vit. D.

    In the last two months I have done numerous "tests" with B12 and methylfolate. The first few weeks have been surprising but then I have accused big side effects like B12 induced Potassium deficiency and few folates available. I also experienced a methylation block that I do not wish for anyone.

    Today I want to disconnect all the supplements.

    I thank all those who can help me.
     
  2. marcar72

    marcar72 Member

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    I've recently tested my dna with 23andme.com and ran the raw data through strategene.com. I tested positive for two MTHFR heterozygous polymorphisms that reduce the activity of that enzyme by 50% and tested positive for a homozygous polymorphism of the MTRR gene. The season is right for anyone wanting to do these tests since the kits are on holiday sale.

    In my case, it boils down to me supplementing methylfolate for the MTHFR polymorphism, methylcobalamin for the MTRR polymorphism, and some TMG (betaine) for a CBS heterozygous polymorphism. All of this to convert the homocysteine back into methionine. I've been testing out some SAMe supplementation as well. 23andme.com didn't test the MAT1A gene so I'm not sure if there's any polymorphism there that may hinder SAMe production. Supposedly those polymorphisms are more rare.

    So the bottem line for me is that Stress pretty easily can eat me up because of the several polymorphisms that I have. I've known this all my life but now I know the why and the how of it. Supplementing the correct supplements is turning things around for me. I'd strongly urge to anyone that can to get the dna test or atleast experiment with the supplements if they're having issues with stress. :2cents:
     
  3. OP
    Highserotonin90

    Highserotonin90 Member

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    [QUOTE = "marcar72, post: 393496, membro: 784"] Ho recentemente testato il mio DNA con 23andme.com e ho eseguito i dati grezzi attraverso strategene.com. Sono risultato positivo per due polimorfismi eterozigoti MTHFR che riducono l'attività di quell'enzima del 50% e sono risultati positivi per un polimorfismo omozigote del gene MTRR . La stagione è giusta per chiunque desideri fare questi test poiché i kit sono in vendita natalizia.

    Nel mio caso, si riduce a me integrando metilfolato per il polimorfismo MTHFR , metilcobalamina per il polimorfismo MTRR e alcuni TMG (betaina) per un polimorfismo eterozigote CBS . Tutto questo per riconvertire l'omocisteina in metionina. Ho provato anche alcuni integratori SAMe. 23andme.com non ha testato il gene MAT1A quindi non sono sicuro se ci sia qualche polimorfismo che potrebbe ostacolare la produzione di SAMe. Presumibilmente quei polimorfismi sono più rari.

    Quindi la linea per me è che lo stress abbastanza facilmente può divorarmi a causa dei diversi polimorfismi che ho. L'ho conosciuto per tutta la vita ma ora conosco il perché e il come. Integrare i supplementi corretti sta cambiando le cose per me. Esorto caldamente a chiunque sia in grado di fare il test del dna o almeno di sperimentare con gli integratori se hanno problemi di stress. : 2Cents:[/CITAZIONE]

    Thanks for your Experience
     
  4. marcar72

    marcar72 Member

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    I meant to say MTR heterozygous polymorphism, my CBS gene is just fine.

    According to Dr Amy Yasko's protocol one needs to supplement lithium as well when supplementing with higher b12 doses. Lithium helps b12 get into the cells. This is probably the reason why several people who up their b12 intake do well in the first couple weeks then crash out after that. The higher b12 causing a lithium deficiency a couple weeks into it. I've been supplementing 5 mg/day lithium orotate and noticed that it indeed helps since I had the crash right off the bat as well. :2cents:
     
  5. alywest

    alywest Member

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    If you order the test, do they point you in the direction of the correct supplements to take? Or are you on your own?
     
  6. marcar72

    marcar72 Member

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    One is kind of on their own depending on the uniquely different polymorphisms one could have and how they interact with one another. It's not that hard to figure out, though and is actually quite fun learning about it all. I like Dr. Ben Lynch and his strategene.org analysis because from what I can tell he's pretty much the leading pioneer in optimizing methylation and other pathways. geneticgenie.org gives a free analysis when you upload the raw data. There are several others I guess like selfdecode.com and promethease.com that are little to no cost. Some of them offer specific supplementation protocols from what I've read. You can even pay extra for the "health" option of 23andme.com and ancestry.com for their anaylsis. gnc.com ads have even been popping up in my facebook feed for their kits and they offer specific nutrient recommendations. There is a lot of options out there.

    If I had to do it again, I'd let ancestry.com test my dna since they test more genes than 23andme.com does that are specific to the strategene.org analysis. $59 for their holiday kit and $45 for the strategene.org analysis so about $110 in all. You can upload the raw data to other sites that run analysis as well. Ancestry.com tests MAT1A (SAMe) and MAOA/MAOB (serotonin) genes that 23andme.com didn't. I'm actually thinking of doing the ancestry.com kit as well for this very reason. Watching to see if the price drops any further between now and 12/24 sale end.
     
  7. marcar72

    marcar72 Member

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    Can't edit my first post, it's strategene.org guys!! Sorry for the typo. :)
     
  8. Mito

    Mito Member

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    The majority of people have some degree of MTHFR polymorphisms the 23andMe test helps to understand how severe it might be but you already know you have elevated homocysteine so you can try these ideas to lower it.

    ChrisMasterjohn explains the details and gives plenty of ideas here: https://chrismasterjohnphd.com/2017/08/12/living-with-mthfr/

    Question to Ray Peat: “Is there a safe way to lower the Homocysteine level in the blood?”
    Ray’s answer: “A diet rich in folic acid, B12, B6, and good thyroid function. Milk, eggs, orange juice are helpful foods.”
     
  9. OP
    Highserotonin90

    Highserotonin90 Member

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    Thanks. I several sides effects with Folic Acid and not with Methylfolate. My thyroid function is very good at the moment and consume more milk, eggs.


    If I have strong negative effects when I take NAC, Whey Protein and ricotta is a signal that I have difficulty producing glutathione and methylation is low? Could I have benefits with SAM-e? very often I have symptoms of the autism spectrum. With B12 and methylfolate I have had mixed effects and probably also blockage of methylation.
     
  10. mostlylurking

    mostlylurking Member

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    Hi all, I have elevated homocysteine and low glutathione. There is a possibility that my elevated homocysteine is caused by lead toxicity; I tested positive for high lead in 2014, underwent 11 out of the 20 prescribed EDTA chelation IV treatments, got sick with rheumatoid arthritis, and stopped the treatment. Recently another doctor strongly recommended genetic testing, maximizing my methylation system, and taking glutathione supplements. I declined and the doctor fired me. Because of my concern over the elevated homocysteine numbers, I wrote to Dr. Peat and asked for his advice about using NAC (N-acetylcysteine) to lower the homocysteine (see here: Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in l... - PubMed - NCBI ). I was trying to decide which would be safer, the NAC treatment or additional EDTA chelation, or if there was something else he could suggest.

    Here is Dr. Peat's response:
    "I think it would be safe to take a supplement of vitamins B6 (10 mg) and B12 (maybe 100 mcg) for a while; I don't think it's safe to supplement methyl donors or glutathione. A high waking temperature that declines after eating suggests that cortisol is very high during the night, and that can account for low TSH combined with low thyroid function. Milk, coffee, and orange juice help to safely and slowly eliminate heavy metals."​

    I'm going to follow Dr. Peat's suggestion and increase my coffee (milk and OJ are pretty high already). I feel much more comfortable following this conservative approach.
     
  11. OP
    Highserotonin90

    Highserotonin90 Member

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    Very interesting.

    From an emotional point of view, have you noticed any changes with such a high homocysteine? do you think your methylation is insufficient and you struggle to recycle methionine?

    Watch out for the B12. By exaggerating with the dosage you can incur strong potassium deficiencies with symptoms that are anything but pleasant.

    I quit a week ago with methylfolate and B12 but I could reinsert it at low dosage to see what happens.

    If the theory of low methylation and high histamine is correct then I am waiting with the NAC. Being a precursor of glutathione you can have more side effects than benefits. It also increases the histamine response so it is to be evaluated based on how you react.

    We stay in touch;) let me know.
     
  12. mostlylurking

    mostlylurking Member

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    Reporting back and correcting the post made on 12/20/18: After further review of my blood work, internet sleuthing to better understand my test results, and leaving my doctor out of the equation, I have determined that I do NOT have elevated homocysteine. My homocysteine is optimal at a 7, my glutathione is a little low too. But after reading up on this it is my understanding that if I'm taking proper care of myself with diet, etc. and my stress is low, my glutathione would naturally be lower and if my stress becomes elevated my glutathione would rise with it. I think the doctor just wanted to sell me expensive supplements to "optimize" my glutathione level and my methylation system. It appears that "optimizing" methylation systems are very popular right now; by "optimizing" they always seem to mean cranking it up, they don't seem to ever be interested in minimizing methylation. I've decided to just rely on the once a week liver and forget about the B-12 supplementation.

    I recently read that elevated homocysteine is linked somehow with elevated TSH. For whatever reason, my TSH is around .012, almost zero. I am hypothyroid and take 180 mg of desiccated thyroid supplement, which has been a life saver for me. After over 35 years of being diagnosed as being hypothyroid I finally found an endocrinologist willing to treat me for my symptoms instead of relying on the stupid TSH test. Unfortunately, he thinks progesterone is carcinogenic, so I changed doctors, only to find that the new one is on a mission to "optimize" all her patients' methylation systems and prescribe something to elevate glutathione in everybody. She added a poster in her entry that says something like, "get your glutathione supplements here!". I declined the treatment and the doctor fired me.This doctor thing is really hard. If I didn't need the prescription for the thyroid medication I'd just not go to one.

    Dr. Peat suggested that a very low TSH can be the result of high cortisol, which I have suffered from in the past. Maybe I should take another saliva cortisol test to know if that's still an issue. I feel fine and am sleeping well. I don't know what else could be causing the very low TSH or if this is something to even be concerned about. Does anyone know of other factors that might be at play regarding super low TSH?
     
  13. Jon

    Jon Member

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    @Highserotonin90 Ironically, I happened upon this study as I was researching what clinical markers they use to study if coffee does in fact deplete B vitamins:

    Coffee consumption and circulating B-vitamins in healthy middle-aged men and women. - PubMed - NCBI

    "Coffee consumption has been associated with several risk factors for coronary heart disease, including increased cholesterol, increased blood pressure, and increased plasma total homocysteine (tHcy). tHcy is determined by several B-vitamins."

    So then I was like hmmm Homocysteine is associated with CVD risk which led me to this study:

    Homocysteine, B-vitamins and CVD. - PubMed - NCBI

    "The most important genetic determinant of tHcy in the general population is the common C677T variant in methylenetetrahydrofolate reductase (MTHFR) that results in higher tHcy."

    "Plasma tHcy is very responsive to intervention with the B-vitamins required for its metabolism, in particular folic acid, and to a lesser extent vitamins B12 and B6. Thus, although primarily aimed at reducing neural-tube defects, folic acid fortification may have an important role in the primary prevention of CVD via tHcy lowering"

    Imho I think with the things we in this forum tend to partake in (drinking coffee, being in a stressed state, eating refined carbs, wrongfully avoiding NO production) depleted the hell out of our B vitamins. I wouldn't be surprised if most of us have heightened homocysteine levels related to folate depletion. I think you're totally normal, probably just marginally depleted in b vitamins and perhaps minerals like magnesium and potassium.
     
  14. mostlylurking

    mostlylurking Member

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    The issue I experienced was not so much a health problem but rather a doctor problem, who, over the past year has completely lost my trust. So I'm going to try to find a new doctor who is a better fit.
     
  15. OP
    Highserotonin90

    Highserotonin90 Member

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    Hello Jon!

    Unfortunately I had forgotten about this thread that I had opened so I'll answer you only now:

    If I really had a deficiency of B12 and folate my MCV (like that of any deficient person) would be high (above 92-93 is already a signal).

    It actually pushes down, which is a sign of an insufficient B6 or P5P .... so the last part of methylation. The name of the precise process escapes me, but it is the transfusion path where homocysteine is directed to glutathione.

    If it is not present in quantity due to a genetic mutation or exhaustion (even the intense exercise itself) the homocysteine will go to accumulate.

    Regardless of whether you have a MTHFR defect or not, please note this.

    I'm trying the B6 of Now Foods classic 100mg and after a few days the benefits are there. I wait a month for a concrete counter test by blood tests.

    I have also ordered the P5P form to understand if there are differences in the two forms. The latter should be better.

    I do not think Ray's diet can have a lot to do. I think the cycling of the various approaches is the key to obtaining the benefits and not accustoming the body to the usual foods.

    PS: Congratulations on the physical form, I opened a new discussion on this theme. I would like your thought;)

    See you soon
     
  16. jb116

    jb116 Member

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    Thyroxine can also suppress TSH while keeping you hypothyroid especially with high rt3. Ensure adequate selenium.
     
  17. mostlylurking

    mostlylurking Member

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    Thank you for your response. My rt3 is low, not elevated. I'm eating shellfish once or twice a week; oysters, shrimp, scallops. I tested low for selenium 4 years ago and have been careful to include the shellfish regularly since then, but I have not been retested for the selenium. I don't know if a very low TSH is even something to be concerned about so long as I feel pretty good and my thyroid test is good (low TSH, T3 high normal, rT3 low, T4 midrange). I haven't been tested for cortisol level in a while; it was a saliva test. I'm wondering which cortisol test I should request that might better reveal elevated cortisol.
     
  18. OP
    Highserotonin90

    Highserotonin90 Member

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    Tu pensi:

    Sto assumendo 100 mg di B6 per drenare l'omocisteina.

    Sostituendolo con il modulo P5P, il dosaggio dovrebbe essere lo stesso o è possibile ridurlo?
     
  19. Kartoffel

    Kartoffel Member

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    Most of the studies showing an increase of homocysteine with coffee consumption use very large amounts of coffee (70g of beans/1 liter per day), and most people will probably have some sort of stress reaction to such a large increase in coffee consumption. Nevertheless, moderate coffee consumption is not associated with increased homocysteine, and actually protects agains hyperhomocysteinemia, and there is no negative association with b-vitamin levels.

    Nutrients. 2017 Mar 14;9(3). pii: E276. doi: 10.3390/nu9030276.
    Association between Coffee Consumption and Its Polyphenols with Cardiovascular Risk Factors: A Population-Based Study.
    Miranda AM1, Steluti J2, Fisberg RM3, Marchioni DM4.

    Epidemiological studies have examined the effect of coffee intake on cardiovascular disease, but the benefits and risks for the cardiovascular system remain controversial. Our objective was to evaluate the association between coffee consumption and its polyphenols on cardiovascular risk factors. Data came from the “Health Survey of São Paulo (ISA-Capital)” among 557 individuals, in São Paulo, Brazil. Diet was assessed by two 24-h dietary recalls. Coffee consumption was categorized into <1, 1–3, and ≥3 cups/day. Polyphenol intake was calculated by matching food consumption data with the Phenol-Explorer database. Multiple logistic regression models were used to assess the associations between cardiovascular risk factors (blood pressure, total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides, fasting glucose, and homocysteine) and usual coffee intake. The odds were lower among individuals who drank 1–3 cups of coffee/day to elevated systolic blood pressure (SBP) (Odds Ratio (OR) = 0.45; 95% Confidence Interval (95% CI): 0.26, 0.78), elevated diastolic blood pressure (DBP) (OR = 0.44; 95% CI: 0.20, 0.98), and hyperhomocysteinemia (OR = 0.32; 95% CI: 0.11, 0.93). Furthermore, significant inverse associations were also observed between moderate intake of coffee polyphenols and elevated SBP (OR = 0.46; 95% CI: 0.24, 0.87), elevated DBP (OR = 0.51; 95% CI: 0.26, 0.98), and hyperhomocysteinemia (OR = 0.29; 95% CI: 0.11, 0.78). In conclusion, coffee intake of 1–3 cups/day and its polyphenols were associated with lower odds of elevated SBP, DBP, and hyperhomocysteinemia. Thus, the moderate consumption of coffee, a polyphenol-rich beverage, could exert a protective effect against some cardiovascular risk factors.

    Am J Clin Nutr. 2000 Nov;72(5):1107-10.
    Heavy coffee consumption and plasma homocysteine: a randomized controlled trial in healthy volunteers.
    Urgert R1, van Vliet T, Zock PL, Katan MB.

    BACKGROUND:
    An elevated plasma concentration of total homocysteine is considered to be a strong risk factor for cardiovascular disease. Heavy coffee drinking has been related to high homocysteine concentrations in epidemiologic studies and in one experiment in which healthy subjects drank unfiltered, boiled coffee.
    OBJECTIVE:
    Our goal was to determine whether daily consumption of paper-filtered coffee raises plasma concentrations of total homocysteine in healthy subjects.
    DESIGN:
    Twenty-six volunteers (18-53 y of age) consumed 1 L/d of paper-filtered coffee brewed with 70 g regular ground beans or no coffee for 4 wk each in a randomized, crossover design.
    RESULTS:
    The mean (+/-SD) plasma concentration of total homocysteine in fasting blood was 8.1 +/- 1.8 micromol/L after abstention from coffee and 9.6 +/- 2.9 micromol/L after 3-4 wk of coffee drinking, a difference of 1.5 micromol/L (95% CI: 0.9, 2.1 micromol/L) or 18% (P: < 0.001). Coffee increased homocysteine concentrations in 24 of 26 individuals. Circulating concentrations of vitamin B-6, vitamin B-12, and folate were unaffected.
    CONCLUSION:
    Drinking large quantities of paper-filtered coffee raises fasting plasma concentrations of total homocysteine in healthy individuals.

    upload_2019-2-9_13-30-34.png
     
  20. Jon

    Jon Member

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    Wow all very interesting! Thanks for sharing :) your obviously much more educated on your situation parameters than I lol. I'm glad that you may have found a solution! Please let us know how that goes!

    I'll be sure to check out your new thread :)

    Well I stand corrected thy good sir :) coffee just gets better and better the more I learn about it Thanks for enlightening me!
     
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