Methylation, autoimmune issues, low T, oh my!
- 03-23-2013, 07:11 PM
- 03-23-2013, 07:52 PM
03-23-2013, 11:15 PM
03-24-2013, 12:11 AM
03-24-2013, 12:13 AM
I did read that in a group of 7 similar genotypes I have the highest homecysteine levels and lowest B-12.
03-24-2013, 12:55 AM
03-24-2013, 12:57 AM
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.MTHFR 03 P39P
There is currently not enough research or data to draw conclusions from this SNP.
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.
All of Your Other Mutations
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
- MTRR A66G
Addressing ACAT and SHMT SNPs
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.
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.
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.
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.
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 (-/-).
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.
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.
03-24-2013, 03:08 AM
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
03-24-2013, 09:01 AM
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?
03-24-2013, 10:32 AM
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
03-24-2013, 11:36 AM
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
03-24-2013, 11:59 AM
03-24-2013, 12:05 PM
You got 23andme pm.me
04-01-2013, 01:21 PM
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.
04-01-2013, 11:36 PM
04-02-2013, 12:26 AM
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
04-07-2013, 07:03 AM
Thanks for all the valuable info Matthersby! I will keep checking in with ya on this thread. Best of luck on your journey bro!
04-18-2013, 10:55 AM
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
04-18-2013, 10:40 PM
adrenal saliva and neuro panel
if you can not find the answer.in here then practitioner needs to find another job lol
04-21-2013, 09:28 PM
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.
04-22-2013, 09:33 PM
04-24-2013, 11:37 PM
04-24-2013, 11:44 PM
Im not going ti.spend over 2 hours.looking each one of the 300.genes up. She can do.it.in 20 minutes Lol
I have better use of.my.time which is extremely.limited these days due to.consults with clients and medical professional as well as research and speaking.
Not.enough time in the day and.even night
05-04-2013, 12:43 PM
I now see what you mean. Sterling did a fantastic job spread sheeting my 23&Me analysis and explaining every SNP. A lot of problems I have make more sense now.
05-04-2013, 01:26 PM
If only now people would listen. I had one guy other week 100 different Dr could not figure out why he had dysautononia. I suggest 23and me with him then contact sterling. Once I got the report back saw it was starting right at us. He finally got his answers why his heart rate was all over the place especially when he would eat certain foods which drop dopamine up with Major COMT. It was hard to pin point because he had alot of IGG vs IGA. Why I am one of the best in the field when it comes to these issues..Sterling will testify. This is the future of medicine bro. I will be traveling around the world in upcoming months to teach it MD, DO, ND's. I have well repected PH.D, MD, DO, ND name's associated with paper to be peer reviewed with in the next year associated with proposals I have made for areas of studies. One of them will be on Genetics and cellular energy in relationship to treatment in mitochondrion dysfunction. Amazing what happens when people give you an opportunity to prove your self. With in the next year, my career is going to be whole new level. My credentials will not be questioned when there are peer review articles with your name published on them..
05-09-2013, 10:44 AM
05-09-2013, 12:14 PM
05-12-2013, 06:20 PM
05-15-2013, 12:02 AM
Changing awareness one Dr at a time ...Actually its much faster now as i work with clients, but have their open mind Dr shadowing what i am doing may help his other cases..
05-24-2013, 04:48 PM
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