Methylation, autoimmune issues, low T, oh my!

Matthersby

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Lately, I've noticed a lot of threads, myself included where healthy, young men (from mid thirties all the way down to early twenties) are having a ton of health problems. The Matrix has graciously been patiently and tediously offering his help to almost everyone of these guys. I have recently had several health problems and have had a lot of doctor visits(endocrinologist, primary care, urologist) and have had a lot of labs and tests done. My results have been alarming(low test, high bp, high blood sugar, hyperthyroidism, anxiety and depression followed by normal levels weeks later, then back to out of whack levels again.) What's even more alarming is the common response from most of these traditional Medical Doctors. "Let's treat your symptoms with meds that cause even more symptoms and have you make more appointments and get more labs done monthly, and basically wait for you to get worse to treat you medically" Not one was even curious why a healthy active 34 year old would have all of these issues. This has caused me to do ALOT of research of my own. I'm not even going to get started on food allergies including gluten and the massive host of problems they cause. This thread is to start to understand Methylation and how critical it is to balance it. Below is a copy and paste from multiple sources online. I am willing to edit anything that is false or misleading but its just a start to get some basic info and discussion going.
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Some Methylation Facts:
Methylation is the passing of a chemical fragment called a methyl group (a carbon atom linked to three hydrogen atoms) from one molecule to another. It is most easily understood by thinking of methylation as a repair process.
o The amount of homocysteine (Poor methylation leads to higher amounts)is a good indicator of how "biologically old" a person is (as opposed to chronological age). High homocysteine levels are especially indicated in:
o Heart disease and stroke (by encouraging clumping together of platelets
o Higher levels of oxidized LDL cholesterol
o Dementia and Alzheimer's
o Destruction of telomeres
o Liver Disease
o Birth Defects
o Depression
o It has been shown in studies where methylation of DNA was limited or prevented that mouse embryos would not develop and the process of life just stops (Li, et al., 1992).
o Low DNA methylation of blood cells is believed to be a cause of autoimmune disease(Yung et al. 1995).
o Low methylation in humans is also highly related to Alzheimer's disease and thedevelopment of cataracts.
o Low methylation results in liver cancer, vascular disease and shorter life span in animals (Salmon and Copeland -1946).
o Methylation is essential in the making of melatonin (the "sleep" hormone), adrenaline (the fight-or-flight hormone), acetylcholine (a neurotransmitter), creatine (for muscle energy metabolism), carnitine (involved in fat burning in mitochondria), and choline (fat mobilization and cell membrane fluidity).
 
Matthersby

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Faulty Methylation*
Methlylation is what occurs when your body takes one substance and turns it into another, so it is detoxified and can be excreted from the body.
Methylation is a process that occurs one billion times per second, it takes place in the liver during phase two detoxification. *A methyl group is a carbon atom with three hydrogen atoms attached to it. *Methylation occurs when SAMe (S-adenosine methionine) donates a methyl group, which is then attached to the molecule that is being detoxified. *SAMe then becomes homocysteine. *Vitamin B6, B12, and folic acid are necessary to reduce homocysteine and keep the methylation process occurring.
Faulty methylation has been linked to heart disease, stroke, neural tube defects, Alzheimer's disease, colon cancer, reproductive cancers, kidney infarct, cervical dysplasia, faulty detoxification and impaired DNA repair. When you have poor methylation your body's levels of homocysteine will elevate. *Homocysteine is a amino acid that is toxic to the body. *Dr. Kilmer McCulley (author of "The Homocysteine Revolution"), discovered that high levels of homocysteine caused heart disease and stroke in animal studies. *He then found that B vitamins decreased the homocysteine levels, and therefore stopped the heart disease process. *Our society has the mindframe that cholesterol is the biggest factor to heart disease, but only 40% of people who have heart attacks have any of the standard risk factors. *Could the cause be homocysteine?
*According to the "Lancet" 1980 poor methylation will cause neural tube defects. *It was found that mothers who had children with neural tube defects from a previous birth, who took a multivitamin had a 1:178 incident of repeated neural tube defects, where the control group with no multivitamin had a 5:260 incident of neural tube defects. *In 1991 the "Lancet" reported that folic acid was the nutrient that prevented neural tube defects. *In the "Journal of the American Medical Association" 1992 it was found that low folic acid levels increased the incidence of cervical dysplasia. *It was also discovered that folic acid supplementation could stop the process and even reverse it. *The "Journal of Nutrition" year 2000, reported that the lower the levels of folic acid and vitamin B12 the more severe the cervical dysplasia. *In 1988, the "New England Journal of Medicine" stated that lower levels of folic acid and vitamin B12 increased the incidence of Alzheimer's. *This is because folic acid and vitamin B12 are needed for phospholipid synthesis in the brain.
Methylation is also used in DNA. *Every cell in your body has the DNA for every other cell, but your liver cell doesn't make a heart cell. *This is because methyl groups turn off the DNA we don't want our bodies to read. *If you have poor methylation your body will start to take the methyl groups off of your genes to use for other purposes. *Now if that methyl group was removed from a cancer gene, it may begin to express cancer. *This is how methylation turns off your oncogenes and your metastatic promoter genes. *The "Journal of Nutrition and Cancer" year 2000, stated that cancer cells have lower levels of folic acid and vitamin B12 and therefore lower levels of methylation. *"Journal of Carcinogenesis" year 2000, states that methylation is needed to mask DNA as well as repair DNA.
Approximately one trillion molecules of oxygen passes through every single cell in our body in a 24-hour period. *This equals approximately 100,000 free radical hits on our cellular DNA. *99 to 99.9 percent is repaired by methylation. *Approximately one-third of people have the 677 C to T polymorphism (which can be tested through genomics). *This doesn't allow them to convert folic acid to the activated form of 5 methyl tetrahydrofolate or 5-MTHF, which is needed to make the enzyme 5 methylene tetrahydrofolate reductase, appropriately named 5-MTHFR. *This is the enzyme that is needed to remove homocysteine. Individuals who have this genetic polymorphism will have an increased risk of the above mentioned diseases.
*
CFS - The Methylation Cycle

Chronic Fatigue Syndrome is a symptom, not a diagnosis, and the name of the game is to identify the underlying causes. In fatigue syndromes we don't see macro-pathology, we see micro-pathology - that is to say the problems are bio-chemical and occur at the molecular level.
There are several cycles, which I now know to be centrally important in causing fatigue. All these cycles interlink with each other like Olympic rings and getting one cycle going will drive another. The important cycles which I know to be major players include blood sugar wobbles, allergy problems, sleep cycles, mitochondrial function, anti-oxidant status, the NO/OONO cycle, thyroid and adrenal hormones cycles and de-toxification. I am greatly indebted to Rich van Konynenburg for updating me on a new player which interlinks with many of the above, namely the methylation cycle.
The Methylation Cycle
Rich van Konynenburg's idea is ineffective methylation is a major cause of fatigue. There are many possible reasons but those that he's identified for which methylation is essential to are:
? To produce vital molecules such as Co Q-10 and carnitine.
? To switch on DNA and switch off DNA. This is achieved by activating and deactivating genes by methylation. This is essential for gene expression and protein synthesis. Proteins of course make up the hormones, neurotransmitters, enzymes, immune factors and are fundamental to good health. When viruses attack our bodies, they take over our own DNA in order to replicate themselves. If we can't switch DNA/RNA replication off then we will become more susceptible to viral infection.
? To produce myelin for the brain and nervous system.
? To determine the rate of synthesis of glutathione which is essential for detoxification.
? To determine the rate of synthesis of glutathione which is an essential anti-oxidant as glutathione-peroxidase. Furthermore oxidative stress blocks glutathione synthesis - yet another vicious cycle!
? To control sulphur metabolism of the body, not just glutathione but also cysteine, taurine and sulphate. This is an important process for detoxification.
? As part of folic acid metabolism. This also switches on synthesis of new DNA and RNA.
? For normal immune function. The methylation cycle is essential for cell mediated immune function and blockages here will mean that infections will not be adequately dealt with. I know this clinically because many patients tell me that once they get on to their B12 injections (an essential co-factor for methylation) this seems to protect them from getting infections.
The overall effect here is that if the methylation cycle doesn't work, the immune system mal-functions, the detoxification system mal-functions, our ability to heal and repair is reduced and the anti-oxidant system mal-functions.
The Bio-chemistry
(You can ignore this bit if you like because it's not essential to know but it's interesting.)
There are four cornerstones to the methylation cycle and on each cornerstone sit four molecules namely homocysteine, methionine, S-adenosylmethionine (SAMe) and S-adenosylhomocysteine. Each of these molecules leads into the next one by means of enzymes. The important co-factors that allow this to happen are the B vitamins such as folic acid, vitamin B12 and vitamin B6. In converting from S-adenosyl methionine into S-adenosyl homocysteine, a methyl group is given up and this can be used to stick on to other molecules - hence the name, the methylation cycle.
However, there is a particular bio-chemical glitch here. In order for the methylation cycle to work these B vitamins have to be in their activated form, namely methylcobalamin, folinic acid and pyridoxyl-5-phosphate. In order to get cobalamin into methylcobalamin, the methylation cycle has to be working. So if this cycle has crashed completely, the body can't make methyl cobalamin in order to get it up and running again. Since this cycle is so fundamental to other biochemical cycles including trans-sulphuration and folate metabolism, it can't change the vitamin B6, folic acid and cobalamin into the active forms necessary for the methylation cycles to work.
This means that in order to get this cycle up and running initially we have to prime the pump with the activated vitamins, but hopefully once the methylation cycle is up and running, it can function on the vitamins in their normal states.
Testing for how well the methylation works
We don't have a simple test to see how well the methylation cycle works. What we can do is measure levels of homocysteine and SAMe. If these were raised this would show a blockage in one part of the pathway. Indeed, a raised homocysteine we know to be a major risk factor for arterial disease, almost certainly because this represents blockages in the methylation cycle. However, one could have a normal homocysteine and normal SAMe but blockages elsewhere in the system, which would still impair the ability to methylate. So there is no simple test.

One can also measure urinary MMAs (test for methylated B12) and FIGLu (test for methylated folate) but these can only be done as part of an Organic acids present in urine (Metabolic Analysis Profile).
How do we go about treating this?
Rich van XXXXxxx has identified a package of micronutrients specifically to support the methylation cycle. He recommends the activated form of vitamins. These are more expensive than the basic forms, but I think that the idea here is that they are necessary in the short term to get the cycle working and in the longer term they can be dropped off. In addition to the basic three B vitamins Rich van XXXXxxx has one or two other additions which you may also like to choose to use, but my initial suggestions would be as follows.
The Methylation Cycle - which supplements to take to support
This is the package of supplements to support the methylation cycle. It needs to be taken in addition to everything else, i.e. the standard nutritional package (multivits, multiminerals, EFAs, vits C + D) and the mitochondrial rescue package (D-ribose, acetyl-L-carnitine, CoQ10, etc.)! But the methylation package will change with time because as the methylation cycle starts to work again, it will start to stand on its own feet. Everyone"s package will be a bit different depending on how poorly their cycle is working. One day we will have the biochemical tests to tailor make each package for each person, but until then I suggest the following regime for those sufferers who have been takingvitamin B12 in oral form (as either hydroxocobalamin or cyanocobalamin):
For two months a daily dose of
? Methylcobalamin 1 mg sublingually
? Methyltetrahydrofolate 800mcg (ActiFolate)
? Pyridoxal-5-phosphate 100mgs (50mgs twice daily)
? Glutathione 250mgs daily
? Phosphatidyl Serine 200mgs (100mgs twice daily) - BioCare
If you are better - fine! If you are worse - it may be the reaction to the methylation package because it may cause an acute detox reaction (see below). Slow down the regime - take smaller amounts of the supplements and build up slowly. If you are unchanged - swap the sublingual B12 for injected B12 ie:
? Daily subcutaneous injections methylcobalamin 0.5mgs (this is a bit more expensive than cyanocobalamin). Some CFSs will not respond clincially until 5mgs daily is injected. B12 is very safe with no known toxicity- as a collegue commented - the only way you could kill yourself with B12 would be to drown in the stuff!
? Methyltetrahydrofolate 800mcg (ActiFolate)
? Pyridoxal-5- phosphate 100mgs (50mgs twice daily)
? Glutathione 250mgs daily
? Phosphatidyl Serine 200mgs (100mgs twice daily) - BioCare
If you are better - fine! If you are worse - it may be the reaction. If you are unchanged, add in:
? Tri-methylglycine (also known as betaine hydrochloride, also used to increase stomach acid so take at meal times and be mindful that it may cause symptoms of acidity. (See Heartburn.)
? Lecithin (phosphatidyl choline) and Phosphatidyl Ethanolamine.
? S-adenosyl methionine (SAMe) directly as a supplement 400mgs daily
For those sufferers who have already tried B12 by injection as either hydroxocobalamin or cyanocobalamin before starting the methylation cycle protocol, go straight on to injections of methylcobalamin.
Once you are substantially better
Then the regime can be relaxed. Once you are a good methylator, then methyl B12, ActiFolate and glutathione could be tailed off. Injections could be swapped for oral supplements. However, do this slowly - some people need a small supplement long term in order to stay well.
? Methyltetrahydrofolate 800mcg (ActiFolate).
? Hydroxocobalamin 5000mcgms sublingually (or cyanocobalamin sublingually as Shot-0-B12). It may be necessary for some people to continue with B12 by injection to get the best effect (easy to self inject 0.5 - 5mg daily - once you have improved on methylcobalamin, then switch to the less expensive cyanocobalamin). Then the injections can be spaced out and the frequency adjusted according to clinical response.
? Pyridoxyl-5-phosphate 50mgs (this is present in the BioCare multivitamin)
? Phosphatidyl Serine 200mgs (100mgs twice daily) - BioCare
These should be taken in addition to my basic package of supplements, namely multivitamins, Mineral Mix, essential fatty acids, vitamins C and D - these are the supplements I like all people to take on a regular basis. See Nutritional Supplements - what everybody should be taking all the time even if nothing is wrong
Problems with starting this package of treatment
Rich van XXXXxx has been in contact with patient and support groups and about 60 so far have gone through this regime. He seems to see two categories of effect - firstly sometimes a quite rapid and profound improvement in some of the common symptoms, or secondly symptoms worsening or new symptoms arise because in getting the methylation cycle going one suddenly starts to get detox and die off symptoms. The reason for this is that when the methylation cycle was not working the body was unable to detox properly and unable to produce cell mediated immune responses to get rid of chronic infections. Once the methylation cycle is up and running, suddenly the body can swing into action with respect to detox and cell mediated immune responses and this can make the person much worse. The reasons for this are fairly obvious - as soon as one starts to detox one mobilises chemicals and toxins into the blood stream, this makes people ill. Secondly remember that it is not viruses and chronic infections that make one ill, it is the immune reason against them. Cell medicated immune responses make you feel sick! So it is really important to go into this regime gently, be mindful that it may make things worse initially but see this as a good sign.
Rich tells me that the following symptoms of CFS have been reported to have been corrected and so I have taken his list and repeated it at length so you can see the sort of things to expect. PWC means People With Chronic fatigue.
"The following symptoms of CFS have been reported to have been corrected by various PWCs on this treatment. Note that these are gathered from reports from many PWCs, so that not all have been reported by a single person.
? Improvement in sleep (though a few have reported increased difficulty in sleeping initially).
? Ending of the need for and intolerance of continued thyroid hormone supplementation.
? Termination of excessive urination and night-time urination.
? Restoration of normal body temperature from lower values.
? Restoration of normal blood pressure from lower values.
? Initiation of attack by immune system on longstanding infections.
? Increased energy and ability to carry on higher levels of activity without post-exertional fatigue or malaise. Termination of "crashing."
? Lifting of brain fog, increase in cognitive ability, return of memory.
? Relief from hypoglycaemia symptoms.
? Improvement in alcohol tolerance
? Decrease in pain (though some have experienced increases in pain temporarily, as well as increased headaches, presumably as a result of detoxing).
? Notice of and remarking by friends and therapists on improvements in the PWC's condition.
? Return of ability to read and retain what has been read.
Improved tolerance for heat.
? Feeling unusually calm.
? Feeling "more normal and part of the world."
? Ability to stop steroid hormone support without experiencing problems from doing it.
? Lowered sensation of being under stress.
? Loss of excess weight.
The following reported symptoms, also gathered from various PWCs trying this simplified treatment approach, are those that I suspect result from die-off and detox:
? Headaches, "heavy head," "heavy-feeling headaches"
? Alternated periods of mental "fuzziness" and greater mental clarity.
? Feeling "muggy-headed" or "blah" or sick in the morning.
? Transient malaise, flu-like symptoms.
? Transiently increased fatigue, waxing and waning fatigue, feeling more tired and sluggish, weakness.
? Dizziness.
? Irritability.
? Sensation of "brain firing: bing, bong, bing, bong," "brain moving very fast".
? Depression, feeling overwhelmed, strong emotions.
? Greater need for "healing naps."
? Swollen or painful lymph nodes.
? Mild fevers
? Runny nose, low grade "sniffles," sneezing, coughing.
? Sore throat.
? Rashes.
? Itching.
? Increased perspiration, unusual smelling perspiration.
? "Metallic" taste in mouth.
? Transient nausea, "sick to stomach"
? Abdominal cramping/pain.
? Increased bowel movements.
? Diarrhoea, loose stools, urgency.
? Unusual colour of stools, e.g. green.
? Temporarily increased urination
? Transiently increased thirst.
? Clear urine.
? Unusual smelling urine
? Transient increased muscle pain.
What to do if you're not getting better
If you are still struggling then there must be another cause of fatigue that has not been addressed. Remember, fatigue is just a symptom! This work has been pioneered by Dr Xxxxxx N.D., Ph.D. in
 
RecompMan

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Insane thread. Subbed


Reading later. Super interested
 
Matthersby

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Good to hear. I'm sure most of us have a lot to learn on this matter and I'm anxious to see Matrix chime in
 
The Matrix

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I have been trying to.educate people on this for.almost a decade. Now i am educating. few select medical.professionals in this new field of medicine. imo will be future of.medicine. There are only.a small.handfull of.health professional in the world who truly.know this. I have contacts who are working with me on this on every continent around the world. I have been keeping this under the covers for almost past year. In younger guys balancing out this cycle.helping them.to.come.off trt, help actually get to source of their hidden adrenal and stress related.Neurological imbalances are being helped resulting in.reducing med for.depression and anxiety ..this is just the beginning as i do.more research into.mastering this genetic modulation.
 
The Matrix

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There will be.huge transition on how cancer prevention will.be approached in very near.future. Do not want to say.much because if I am correct it will have a dramatic impact potential Changing medicine in its views..I have shared it with a few close medical professionals i trust. They agreed it not fiction, but a reality. Since I am genetically Aspergers it allows.thinking on a more abstract plan. I have been lucky to be surrounded by a group of incredible medical professionals who are supportive ...I will say this "the wings of change are on the horizons "..watch what unfolds in the next 6 months ...
 
The Matrix

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I.knew Rich for many years. One of the most passionate people.one could know. He died doing what he loved educating people. Recommendations from in some genetic expressions could be problematic. I help Drs around the world in helping with complex cases where altered genetic expressions are the missing part of the puzzle from lyme,autism, neurological disorder, unresolved gi issues. One need to know what they are doing or they could.be putting them selves in potential.harms way. People just do not understand the full power of how just a few supplements in right combination could change a persons life..I see it on a weekly basis from cases i work on with medical professionals..
 
Matthersby

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Matrix: how do you feel about that generic non-tailored dosing protocol laid out here for someone that seems to be convinced they are an undermethylater?

For two months a daily dose of
? Methylcobalamin 1 mg sublingually
? Methyltetrahydrofolate 800mcg (ActiFolate)
? Pyridoxal-5-phosphate 100mgs (50mgs twice daily)
? Glutathione 250mgs daily
? Phosphatidyl Serine 200mgs (100mgs twice daily)

Should everyone just get fully tested first, pay a ton of $, and get a tailored dosing schedule or could one just do a trial run with the above low doses and see what improvements are noticed?
 
The Matrix

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Have several people who tried it and got worse..they did not understand the complex chemistry involved which was causing them major neurological issues..

$99 is not a ton of.money lol
 
Matthersby

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Good point. 3 copays plus the 5 medications I take JUST to manage my hyperthyroid SYMPTOMS cost almost twice that every 90 days. Really hoping some guys get in here and start learning. I am 100% completely sold that genetic mutations, methylation imbalances, omega 3 and B vitamin deficiencies(inability to convert to active), and a generation raised on processed food is the plague of my generation. I barely know anyone my age (27-37) that aren't on an antidepressant, have celiac, thyroid, adrenal issues or struggle with addiction or alcoholism. I truly don't believe 300 years ago, 28 year old farmer/hunter Joe was just like "fu¢k it... I just don't feel like providing for my family today, my fibromyalgia's acting up, I'm depressed and my T is super low. :( "
 
The Matrix

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It does not happen over night, but accumulated since the time we were brought into this world. When you are a slow detoxifer genetically then have.mouth mercury from age.of.9. Guess what the half life of.mercury is 30.years. Do the math. Do not forget about the vaccination blasted in you as a child on top compounding the issue. These vaccination can effect us later in life. People with mouthful of.mercury, loaded with vaccination, then spending many years in smoke filled night clubs all on top of being a slow detoxifer...Something had to give eventually our.genetic expression weakening the immune system. Now these genes are being passes on to the child and are being expressed at birth. Autism is one in 88 children no **** why!! Poor children are.potential being.condemned at birth unknowingly. This is a lot.to take in but if we do not act now we as a nation will be in a major health crisis.with big pharma in control. Why I have been working with practitioners around the world to.help educate them to look at the very top of the cascade ..our genetics instead of.looking down stream chasing symptoms. The biggest impact has been neurological issues dramatically improving as well as cfs and fibro. CFS is diagnosis for chronically full of sh*t...
 
Matthersby

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[QUOTE="The Marix; Why I have been working with practitioners around the world to.help educate them to look at the very top of the cascade ..our genetics instead of.looking down stream chasing symptoms. The biggest impact has been neurological issues dramatically improving as well as cfs and fibro. CFS is diagnosis for chronically full of sh*t...[/QUOTE]

^ this stuff needs to be stickied ^
 
The Matrix

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^ this stuff needs to be stickied ^
Note: I am not here to advise or "fish for clients", but to share my years of clinical experience and what I have found when dealing with complex cases in order to prevent people from being lead on wild goose chase. Majority of the time the solution to the most complex cases is common sense which is the most powerful tool heavily over looked today. There will be people out there who may disagree with me or medical professionals who try to debunk me because I do not have letters after my name. To each is their own and they are entitled to their own views.
 
Matthersby

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Just thought I'd share a little bit about my journey thus far from being a totally clueless healthcare worker that believed in traditional medicine until I developed hyperthyroidism and was told my treatment plan would be TREAT SYMPTOMS and wait for my condition to worsen, which it inevitably will. Resulting in an intentional destruction of my thyroid so i can then take synthetic thyroid for the next 50 years. No proactive preventative approach of any kind was even mentioned to me... I was lucky enough to see an urgent care doctor in October who pointed me in the right direction and was semi-naturopathic in her testing and suggestions. Since then I have simply cut out gluten, abstained from alcohol completely, and blindly added methylfolate (not recommended) at a low dose just until I get fully tested for genetic issues and methylation imbalances. Since then, I have had some detoxing effects but the anti depressant and anxiety effects are quite noticeable. Such that I have cut my Zoloft dose in half and asked my doctor to LOWER my valium dosage.(very impressive coming from an alcoholic/addict if you ask me). My goal is in 6 months to have normal testosterone levels, thyroid levels and to be off my 5 medications. This will be 6 months after I get my required testing done and have followed Matrix's supplement treatment plan. Hope this gets more traffic because I believe in what this guy and his predecessors are and have been doing!
 
The Matrix

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I have been in contact with.majority of the medical professionals involved with this for many years. Have meeting with US largest alternative cancer center next months. When i present the information, it will be interesting to.see their reaction. I presented to just a few medical professional I trust, they agreed on the.logic and how a complex issue has a potential simple solution..
 
Matthersby

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23 & me genetic test ordered and will have results posted in a month or so.
 
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Matthersby

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Matrix, you have not wrote a shred of info that I have researched and found to be untrue. QUITE disturbing information. I will be asking you to tailor my undermethylator supplement regiment (pending 23&Me results) for all to see on this forum and I will update daily on my progress. I am excited to see results and will be honest with my problems, symptoms and improvements.
 
The Matrix

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Matrix, you have not wrote a shred of info that I have researched and found to be untrue. QUITE disturbing information. I will be asking you to tailor my undermethylator supplement regiment (pending 23&Me results) for all to see on this forum and I will update daily on my progress. I am excited to see results and will be honest with my problems, symptoms and improvements.
One thing I have learned is information presented is not only on my own experiences but from thousands of hours researching in pubmed and gov't data bases many years. I would not recommend posted your recommendation. This is not like dealing with hormones where too much and you become a crying baby, but rather it can be potential end up causing suicide, and pushing people into schizophrenia as well as other neurological disorders. It has taken years to understand these enzymatic and genetic pathways how they are interelated with hormones, adrenals, GI, neurological, environmental imbalances. Playing with methylation cycle is playing russian roulette with your brain which can be simple changed for good or bad by the wrong combination of OTC supplements. I see this alot from clients who have gone to uninformed Drs who have the best intent of helping people. They just do not know the complexity of how things interact at the genetic level. This changes the ball game when it comes to HRT and people actuallly starting to optimize when HRT has not helped them..Protocols listed above are out dated and potentially dangerous in the wrong genetic profile..
 

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Most of what is posted above sounds like me. MTHFR and numerous other genetic mutations, mid thirties and chronic fatigue. 23andme results and protocol will be given to me tomorrow afternoon. I have alot of faith in The Matrix
 
Matthersby

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I would not recommend posted your recommendation..
I didn't understand this part.

Let me be clear with what I'm trying to accomplish here.
1. I am following your advice.
2. I am educating myself on reasons WHY I have thyroid problems, blood pressure problems, blood sugar problems, folic acid deficiencies, addictions and compulsiveness, severe anxiety, depression, and fatigue. So far, methylation and mercury(and awful genetics) do seem like some of the culprits so I am trusting Matrix and taking the first step and getting genetic testing done.
3. I am trying to help others by keeping this whole journey documented and shed some light on why us 30+ are having so many health problems out of nowhere.
4. I am hoping that I can be pointed in the right direction based on my genetic test results on how to reverse, treat or cure my ailments.
 
Matthersby

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Most of what is posted above sounds like me. MTHFR and numerous other genetic mutations, mid thirties and chronic fatigue. 23andme results and protocol will be given to me tomorrow afternoon. I have alot of faith in The Matrix
Me too. Hoping my results can help him or someone who knows what they're doing get me on a supplement and diet that will help me out...
 

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Sounds identical to my troubles, looking forward to seeing what you can find
 
The Matrix

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I didn't understand this part.

Let me be clear with what I'm trying to accomplish here.
1. I am following your advice.
2. I am educating myself on reasons WHY I have thyroid problems, blood pressure problems, blood sugar problems, folic acid deficiencies, addictions and compulsiveness, severe anxiety, depression, and fatigue. So far, methylation and mercury(and awful genetics) do seem like some of the culprits so I am trusting Matrix and taking the first step and getting genetic testing done.
3. I am trying to help others by keeping this whole journey documented and shed some light on why us 30+ are having so many health problems out of nowhere.
4. I am hoping that I can be pointed in the right direction based on my genetic test results on how to reverse, treat or cure my ailments.
Number one rule people can do chelation which in wrong genetic profile.ended.up.damaging a few clients. Chelation is a huge bandaid. A better approach is to.look at the genetic pathways which are not working properly correct them so the body can detox naturally. Factor in these.mutations it changes.how.you approach a persons health.
 
Matthersby

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I think I understand what you're saying.
The article I posted was simply posted to show the potential damage mercury and other metals can cause. I should have copied and pasted just that part. I am not endorsing their treatment plan as I am just begining to learn all of this. I left the Army in 2005 as a medic and since then my career has 100% old school traditional healthcare thinking-Find the problem-fix it.... I never worried about what I put in my body or what I've been exposed to because I always knew that medicine would be there to "fix it"..... I never realized how ineffective this was until I started getting sick. Losing your quality of life and chasing a symptom, which causes another ailment or symptom and then chasing that is no way to live as a healthy 30 year old. I would have laughed if you told me 6-7 years ago I would be on 5 medications and taking cialis because of my high blood pressure medication (making the total 6 actually)at 34 years old. And just 6 months after the biggest, strongest and most fit I've ever been. I am dedicated to fixing this and enjoying my middle age years. So until then, you have to realize I am impressionable and literally have to Google 2 or 3 of the words you use in your posts. But I have not run into anyone that I'm going to trust with a treatment plan once my genetic testing comes back so its getting posted up here for you, Mr. Matrix
 
Matthersby

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I know I'm not alone here... 3 more weeks till genetic results!
 
The Matrix

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I know I'm not alone here... 3 more weeks till genetic results!
Goggle Mthfr support click on blog talk radio then scroll down to last 2 interviews at the bottomNext 2-3 months I will not have a chance to even breath, 23andme expects to have 1-2 million people in the next 2 years doing the test. All those people are going to want to have test evaluated then interpreted. As of now there are only aboutThere is no more greater satisfaction to be able to help people around the world who have been dealing with neurological or biological conditions for years even decades to start to have ability to function as normal humans again. Medicine has a huge learning curve so people can make mistakes in the past which I will have admit too as any other person.Vast majority of cases are physician referred and supervised due to the nature and complexity of the case.Would a MD risk putting potentially their license or reputation on the line for a quack...I have learned over the years smart and successful Doctors do not discriminate they want to learn and expand their knowledge.
 
Matthersby

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Got my 23andme results back and i thought I was given a genotype and I can't find it. MATRIX where you at?
 
Matthersby

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OK on the ancestry portion I got this:
H1n
R1b1b2a1a2f2
 
The Matrix

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Did you dowload the data to geneticgenie.org???
Misses to.many.important polymorphisms. We have started a platform of around 300 different genes which will be just a starting point for an on going project..
 

Mr.TT

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Misses to.many.important polymorphisms. We have started a platform of around 300 different genes which will be just a starting point for an on going project..
I agree, GENETICGENIE only covers some of the Methylation haplotypes, but what do you have to offer that scans for anything????
 
Matthersby

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OK on the ancestry portion I got this:
H1n
R1b1b2a1a2f2
I'm a smart guy. I do a lot of research. That being said, I have no effing clue what this means. I don't really want to be on 5 medications or get on TRT prematurely. I'm also not superpsyched about having hyperthyroidism. What's the next step is all I'm asking...?????
 
Matthersby

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I did read that in a group of 7 similar genotypes I have the highest homecysteine levels and lowest B-12.
 
Matthersby

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You have 2 heterozygous (yellow) mutation(s). These are generally not as bad as red homozygous mutation, but they may still worth paying attention to. They include:

  • MTHFR 03 P39P
  • MTHFR A1298C
Now let's move on to discuss what these MTHFR mutation(s) mean.[h=4]MTHFR 03 P39P[/h]There is currently not enough research or data to draw conclusions from this SNP.
[h=4]MTHFR A1298C[/h]MTHFR A1298C is involved in converting 5-methylfolate (5MTHF) to tetrahydrofolate (THF). Unlike MTHFR C677T, the A1298C mutation does not lead to elevated homocysteine levels. This reaction helps generate BH4. BH4 is important in the detoxification of ammonia. The gene is compromised about 70% in MTHFR A1298C (+/+) individuals, and about 30% in people with a heterozygous (+/-) mutations.
BH4 acts as a rate limiting factor for the production of neurotransmitters and catecholamines including serotonin, melatonin, dopamine, norepinephrine, and epinephrine. A MTHFR A1298C + status may cause a decrease in any of these neurotransmitters or catecholamines. It's also a cofactor in the production of nitric oxide. If your BH4 cycle is not working effectively, you may experience mental/emotional and/or physical symptoms. Mercury, lead, and aluminum may act as a drain on BH4.
Adressing MTHFR A1298C
L-methylfolate supplementation may be implicated. One should start with low doses of L-methylfolate, and in the case of adverse reaction time-released niacin and/or potassium may help.
Metal detoxification (especially aluminum) can help address dysfunctions associated with MTHFR A1298C and BH4 deficiency, and can help many other biochemical abnormalities as well. Aluminum toxicity can hinder one's ability to fight infection, so addressing the gut and treating chronic bacterial infection may be important. Since the A1298C mutation can lead to excess ammonia, one can address these elevated levels with things like charcoal/magnesium flushes, Yucca Root, and L-Ornithine. Keeping ammonia low helps preserve BH4 levels.
Low doses of BH4 may be helpful after one's methylation cycle is fully supported.
[h=3]All of Your Other Mutations[/h]
Now we are going to look at all of your mutations. You do not necessarily need to worry about all of these mutations, but certain mutations may cause problems in certain individuals. Genetic Genie does not look at the expression of your genes, it only looks at specific gene SNPs. Keep in mind that even if you are homozygous or heterozygous for a certain mutations, it doesn't necessarily mean there is a problem with the functioning of that gene. You have 4 homozygous (+/+) mutations and 7 heterozygous (+/-) mutations.Here are your homozygous mutations as indicated in your SNP gene table above (not including MTHFR):

  • COMT V158M
  • COMT H62H
  • MAO-A R297R
  • CBS A360A
Here are your heterozygous mutations as indicated in your SNP gene table above (not including MTHFR):

  • VDR Bsm
  • VDR Taq
  • ACAT1-02
  • MTRR A66G
  • BHMT-02
  • BHMT-04
  • BHMT-08
[h=4]Addressing ACAT and SHMT SNPs[/h]ACAT1-02 (acetyl coenzyme A acetyltransferase) plays a role lipid metabolism and energy generation. It can also deplete B12. As with CBS, Dr. Yasko views this as a first priority mutation. Going by Yasko's clinical experience, she says to address them first if you have elevated iron on a UEE, elevated iron on a UEE test, Short Chain Fatty Acid (SCFA) imbalances on a CSA test, suberic acid, beta hydroxyl methylglutaric acid, or other ketone and fatty acid metabolites imbalances on a MAP or OAT test; or if there are severe gut issues or muscle weakness (which can be related to aluminum retention)". She says people with ACAT or SHMT are more likely to experience gut dysbiosis. Because of disrupted flora, microbes may have an affinity for and retain toxic metals. Stabilizing the gut environment is very important.
More info to come as Genetic Genie continues to research these SNPs.
[h=4]CBS Mutations[/h]CBS (cystathionine beta synthase) catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine. Dr. Yasko considers addressing CBS mutations as first priority aside from addressing the gut. CBS defects are actually upregulations. This means the enzyme works too fast. In these patients, it's common to see low levels of cystathionine and homocysteine since there is a rapid conversion to taurine. This leads to high levels of taurine and ammonia. The NOS mutation can exacerbate ammonia issues. Furthermore, addressing CBS can help lower excessive levels of taurine and help detoxify ammonia. Dr. Yasko recommends that one supports their CBS enzyme for at least 6 weeks before starting methylation supplements. When one tries to take nutrients to support their methylation cycle before addressing the CBS upregulation, all the nutrients basically lead to nowhere. Instead of generating glutathione, the supplements may deplete the rest of the cycle.
Addressing the CBS Mutation
Before one starts adding supplements, it may be a good idea to get a baseline UAA from a doctor. This will determine one's Taurine levels. After about 4-6 weeks of following the CBS protocol (outlined in the book Autism: Pathways to Recovery), one should retest their UAA. Once one's UAA is at 50% or below, one can add the methylation supplements. It's important to regularly use UAA testing as taurine should remain at 50% or less. If taurine climbs one may need to address ammonia. Yucca Root and Charcoal/Magnesium flushes can help address high ammonia levels. High doses of L-Ornithine may be effective as well according to medical studies.
The CBS mutation not only leads to excess taurine, but can also lead to excess sulfur groups. For this reason, it may be a good idea to limit sulfur intake. Excess sulfur intake can trigger a stress response or chronic stress. Sulfur is normally bound to amino acids, but the CBS upregulation can instead release the sulfur groups to sulfites in the body. There are many things one may need to avoid with a CBS upregulation. Some of the items include garlic, broccoli, eggs, onions, legumes, meat, Epsom salt baths, alpha lipoic acid, glutathione, chelating agents such as DMPS, NAC, Milk Thistle, various other supplements, and much more. Please look to other sources for foods and supplements that are high in sulfur.
Supplementing with molybdenum may help as excess sulfites deplete it. Manganese is also important in ammonia detoxification. A Low protein diet can help as the body will have less ammonia to detoxify. It's important to measure molybdenum and manganese with a minerals test before supplementing.
BH4 can also become depleted with a CBS upregulation. BH4 helps regulate neurotransmitters and mood. Other mutations, such as MTHFR A1298C, Chronic bacterial infections, and aluminum can also lead to low BH4 levels. Lack of BH4 can lead to mast cell degranulation and possibly mast cell activation disorder (MCAD). While difficult to obtain, BH4 supplementation may help in the presence of BH4 deficiency.
Other supplements that may help are Slippery elm bark for the gut. And according to Dr. Yasko Molybdenum, EDTA, carnosine, and zinc may help balance the copper/zinc ratio.
The CBS Upregulation is a complicated subject and for more info, I suggest purchasing or finding the book Autism: Pathways to Recovery. Searching for other websites or online support groups talking about the subject may be of help as well.
[h=4]MTR/MTRR Mutations[/h]MTRR (Methionine synthase reductase) helps recycle B12. The combination of MTR and MTRR mutations can deplete methyl B12. MTR A2756G, MTRR A66G, MTRR H595Y, MTRR K350A, MTRR R415T, MTRR S257T, and MTRR A664A all work together to convert homocysteine to methionine.
MTR (5-methyltetrahydrofolate-homocysteine methyltransferase) provides instructions for making the enzyme methionine synthase. Methionine synthase helps convert the amino acid homocysteine to methionine. To work properly, methionine synthase requires B12 (specifically in the form of methylcobalamin). An MTR A2756G mutation increases the activity of the MTR gene causing a greater need for B12 since the enzyme causes B12 to deplete since it is using it up at a faster rate. Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency. Megaloblastic anemia can occur as a consequence of reduce methionine synthase activity.
A homozygous mutation of MTR A2756G is relatively rare (<1%). Some studies have demonstrated that people with a combination of MTHFR C677T and MTR A2756G have persistently high homocysteine levels unless they are treated with both B12 and folate.
Nutritional support of MTR/MTRR
According to Dr. Yasko's clinical experience, one should first take into account COMT V158M and VDR Taq status. She finds that those with COMT V158M + and VDR Taq - mutations often don't tolerate methyl donors well. She says that those with these mutations should carefully balance their ratio of Hydroxyl B12 and Methyl B12. She often suggests low dose cyano B12, adenosyl B12, and vitamin E succinate. High dose methylcobalamin (5 mg per day and above) may be implicated and necessary with this mutation - especially if one is homozygous and/or has MTRR + mutations. The level of B12 one needs depends often depends on the number and combination of these mutations. Like everything else, one should slowly build up doses of both methylcobalamin and/or hydroxocobalamin to avoid adverse effects.
DMG and the supplement TMG also stimulate the BHMT pathway to convert homocysteine to methionine, but one should take caution if they are sensitive to methyl donors.
Patients with MTR/MTRR may also benefit from the combination of GABA and L-Theanine. L-Theanine is a methyl donor. They may also benefit from taurine, Pycnogenol® pine bark extract, and grape seed extract.
[h=4]MAO-A R297R[/h]MAO-A (Monoamine oxidase A) is a critical enzyme involved in breaking down important neurotransmitters such as serotonin, norepinephrine, and dopamine. While a homozygous (+/+) mutation is very common, prolonged periods of stress, violence, or trauma can lead to epigenetic changes that further decrease enzyme activity. On the table above, males only have one allele since the gene is inherited through from their mother since it is located on the X chromosome. Males are more likely to have this mutation, represented on the table as homozygous (+). Only females can be heterozygous (+/-) for this mutation. When a (+/+) MAO-A mutation is combined with a (+/+) or (+/-) COMT V158M mutation, one may be more prone to develop Obsessive Compulsive Disorder (OCD), mood swings, aggressive and/or violent behavior, and personality disorders. Chronic infection can deplete tryptophan stores, and this can be tested with an organic acid test (OAT) and urine amino acid tests (UAA) according to Dr. Yasko. This test may indicate high levels of 5HIAA (5-hydroxy indole acetic acid).
Nutritional support of MAO-A R297R
Dr. Yasko says that her Mood S RNA formula and 5HTP may help balance serotonin. Furthermore, she satiates that BH4 deficiency (often caused by aluminum toxicity), increased levels of ammonia, and MTHFR A1298C are all factors that can negatively impact serotonin levels.
There is not a whole lot of information out there on how to increase the activity of the enzyme. And while not nutritional, there is a product called Respen-A developed for Autism with intention of increasing MAO-A activity. Respen-A can only be obtained from a few compounding pharmacies and requires a prescription.
[h=4]COMT Mutations[/h]COMT (catechol-O-methyltransferase) helps break down certain neurotransmitters and catecholamines. These include dopamine, epinephrine, and norepinephrine. Catechol-O-methyltransferase is important to the areas of the pre-frontal cortex. This area of the brain is involved with personality, inhibition of behaviors, short-term memory, planning, abstract thinking, and emotion. COMT is also involved with metabolizing estrogens.
COMT (-/-) individuals can usually break down these neurotransmitters efficiently, but COMT (+/+) individuals may have trouble breaking these chemicals down from impaired function of the enzyme. With a COMT + status, people may have trouble with methyl donors. This can lead to irritability, hyperactivity, or abnormal behavior. They also may be more sensitive to pain.
Nutritional support of COMT mutations
Since COMT + individuals often have trouble tolerating methyl donors, they tend to do better on a combination of hydroxy B12, adenosyl B12, and/or cyano B12. Methyl B12 is usually much easier to tolerate for those that are COMT (-/-).
[h=4]VDR Mutations[/h]VDR (Vitamin D Receptor) encodes the nuclear hormone receptor for vitamin D3. Low or low normal vitamin D values are often seen in those with chronic illness and even the general population. Low vitamin D is related to a lot of neurological and immunological conditions. Vitamin D stimulates enzymes that create dopamine.
VDR Fok has been associated with blood sugar issues and poor pancreatic activity.
With COMT V158M + and a VDR Taq + status, the body may have further trouble tolerating methyl donors. VDR Taq (-/-) individuals may already have higher levels of dopamine, and it's worth noting that combinations of variations COMT and VDR Taq can lead to a wide range of dopamine levels. Those that are VDR Taq (+/+) and COMT (-/-) may have lowest dopamine levels.
Nutritional support of VDR Mutations
Dr. Yasko advises patients to rotate methyl-containing supplements (instead of using them all daily) for those with COMT V158M + and VDR Taq (-/-).
Ginkgo biloba may increase dopamine uptake. Small doses of Mucuna Pruriens contains natural dopamine, and can be helpful for those with low dopamine.
VDR Fok + can impact vitamin D levels. Research shows that supplementing vitamin D may be beneficial. Sage and rosemary support vitamin D receptors. It may be necessary to support the pancreas when having a VDR Fok + mutation using vitamin and digestive/pancreatic enzymes.
[h=4]BHMT mutations[/h]BHMT (betaine homocysteine methyltransferase) acts as a shortcut through the methylation cycle helping convert homocysteine to methionine. The activity of the enzyme can be negatively influenced by stress. The Information on this enzyme related to methylation is mostly based on Dr. Amy Yasko's clinical experience and research.
According to Dr. Yasko, a homozygous mutation of BHMT 01, BHMT 02, BHMT 04, can produce results similar to one with a CBS upregulation even if you don't have a CBS upregulation. In her book, Autism: Pathways to Recovery, She also states that a BHMT 08 mutation may "increase MHPG levels relative to dopamine breakdown (HVA)". This can result in attention type symptoms. It is common to see elevated glycine in someone with a homozygous BHMT 08 mutation.
Addressing the BHMT mutations
According to Dr. Yasko, limiting taurine for BHMT 01, 02, and 04 may be helpful, and supplementing NADH, SAMe, and DMG may help with BHMT 08 + status. According to the Heartfixer Analysis, one may bypass the dysfunctional enzymes by stimulating the BHMT pathway to convert homocysteine to methionine in several other ways. Phosphatidylcholine or phosphatidylserine can stimulate the BHMT pathway. A good quality lecithin is a good source of phosphatidylcholine (it usually comes from soy, eggs, or sunflower seed). Egg yolks are a good source of lecithin as well. TMG is also an option, but one should take caution if they are sensitive to methyl donors.
 
The Matrix

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Not bad information..Things have grown byleaps and bounds when it comes to genetics. I do about 20 or.more of these profiles a week for doctors. Where have I.been.Been slammed with doing 23andme prepping for lectures, networking with medical professionals. contact mthfr support and.sterling hill
 

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I share your CBS and BHMT mutations. 500mg of TMG, 300mcg Molybdenum, and 7mg Manganese really helped.
There is a debate about the amount of P5P you are taking.
Next week I am blood testing my Homocysteine and ammonia levels.

Are you on phoenixrising site, the methylation forum?

Where are your D3 blood levels?
 
Matthersby

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Here's the labs from November that were pretty bad. But I was drinking heavily then. Things have changed a lot since then. Time for some specific labs. My B-12 and folate were fine but unless I've read wrong that may not mean anything if my body is unable to break down and absorb propely

ForumRunner_20130324_072956.png
 
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Im part of mthfr support worlds largest researched base methylation group . Vitamin d.levels are probably ly low do.to another reason magnesium deficiency. folate and b12 serum are.not accurate measurement
 
Matthersby

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folate and b12 serum are.not accurate measurement
Exactly. I am almost positive based on studies of my genotype and symptoms, these two are low, homocysteine is high. Time for more labs.
 
The Matrix

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You got 23andme pm.me
 

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How to tell if one is Undermethylation or over if Histamine levels are normal? I'm waiting for other tests to come back and to see what my homocysteine is but I keep hearing histamine can tell if over or under.
 
Matthersby

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How to tell if one is Undermethylation or over if Histamine levels are normal? I'm waiting for other tests to come back and to see what my homocysteine is but I keep hearing histamine can tell if over or under.
homocysteine's way better indication of issues. I thought histamine levels change too much but I don't know much on this one..
 
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How to tell if one is Undermethylation or over if Histamine levels are normal? I'm waiting for other tests to come back and to see what my homocysteine is but I keep hearing histamine can tell if over or under.
you are hearing mis information from people.who.are probably been chasing their tale for a long time..See it on a daily basis. Have to cut through the bs to see the clinical out come

majority of population is.undermethylated not.over. If wrong pathways are not.working right then.one can over.methylate easier then others. Its not that simple as it looks
 
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Thanks for all the valuable info Matthersby! I will keep checking in with ya on this thread. Best of luck on your journey bro!
 

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Do I need to get anymore tests to tell why I have been feeling like crap.
Testosterone coming up but still feel anxious, depressed and fatigue and do have the MTHFR mutation.

Neurotransmitter test with 4 cortisol test
23 and me test
Amino acid test
Organic acid test
 
The Matrix

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Nutreval
adrenal saliva and neuro panel
23andme
blood.work comprehensive

if you can not find the answer.in here then practitioner needs to find another job lol
 
Matthersby

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Sterling has analyzed my 23andMe and is doing a one hour consult with me on Tuesday. I am then supposed to take her information to someone that understands methylation and snp's and can recommend what supplements to take.
 

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