Interpretation of methylation genetic results (23andme)

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    Dear all, I would highly appreciate it if you could help me with interpretation of my 23andme results.
    I have already tried to interpret them myself by reading information on the website, but I am having a hard time coming up with exact actions to take based on analysis

    To be perfectly honest, I am getting very confused on whether I am under or over methylated.

    I am currenty taking a multivitamin that contains 600-800 mg of Folate (as Metafolin®, L-5-MTHF) and 666-1000 of methylcobalamin (B12) – depending on whether I take 4 or 6 caps. Name of the product: Nutrient 950 with vitamin K or Ultranutrient by Pure Encapsulations.

    For complete list of ingredients, please, click on the links.

    I have been taking it for over a year. But recently I started to suspect that it might be the cause of brain fog / fatigue I have been experiencing for last couple of months.

    I also take Carlson D3, usually about 4 000 IU daily and magnesium citrate.
    I also cycle creatine and sometimes L-glutamine & Whey. Several of months ago I also started experimenting with L-Carntinine / Acetyl L-Carnitine and CoQ10.

    1. Is multivitamin really problematic, should I stop taking it / reduce dosage / increase dosage?
    2. Will TMG be beneficial or dangerous for me? What is the good dosage to start at? (haven’t tried it yet)
    3. Will SAM-e be beneficial or dangerous for me? What is the good dosage to start at? (haven’t tried it yet)
    4. Will additional NIacin be beneficial or dangerous for me? What is the good dosage to start at? (hard to judge by effects)
    5. Will additional Acetyl L-Carnitine be beneficial or dangerous for me? What is the good dosage to start at? (hard to judge by effects)
    6. Will n-acetylcysteine be beneficial or dangerous for me? What is the good dosage to start at? (hard to judge by effects)
    7. Will liposomal gluthaionine be beneficial or dangerous for me? What is the good dosage to start at? (hard to judge by effects)
    8. Will L-Citrulline be beneficial or dangerous for me? What is the good dosage to start at? (hard to judge by effects)
    9. Are there any other dietary / lifestyle changes I might want to consider?
    10. Are there any other supplements changes I might want to consider?
    11. Am I missing anything important?

    ! My homocysteine levels are fine (currently 12 vs. max. 15).
    My CRP levels are perfect (0.1 when last measured).

    Also, I don’t know if it’s relevant, but I think it’s better to share it:
    I have done 23andme testing and found out that I have a relatively rare mutation in APOE (Apolipoprotein E) gene. Practically, it means that I have 6 times higher risk to get Alzheimer (which gets me to 40% chance). Basically, I hit both risk alleles. And I hit both twice. A little more information on APOE:

    Overall, I have a very active lifestyle. I have a demanding full-time job in a multinational corporation, run my own entrepreneurial projects, on the side and train hard (weightlifting) about twice a week, do yoga about once a week / once a couple of weeks.
    I sleep about 8.5 hours on average (it’s not time in bed, but the actual sleep I get, measured by Zeo): about 7-8 on weekdays and about 9-10 on weekends. Yes, I need a lot
    Basically, I enjoy having an active lifestyle and want to be able to maintain it. I usually feel the greatest after a very tough workout or exhausting yoga session (Ashtanga yoga).
    I eat a kind of high-carb version of Paleo diet (lots of meat, fish, veggies, fruits, berries, potatoes, rice, etc).
    All my bloodwork is fine. Not only typical things (blood sugar, etc), but also hormones (Testo, free testo, estradiolm progesterone, SHBG, T3, free T3, T4, free T4, insulin, adreanaline, nor-adrenaline, cortisol, serotonin, growth hormone).

    I have used to generate automatic report and here is what it says:

    Gene & Variation rsID Alleles Result
    COMT V158M rs4680 AG +/-
    COMT H62H rs4633 CT +/-
    COMT P199P rs769224 GG -/-
    VDR Bsm rs1544410 CT +/-
    VDR Taq rs731236 AG +/-
    VDR Fok-I not found n/a n/a
    MAO A R297R rs6323 G –
    ACAT1-02 rs3741049 GG -/-
    MTHFR C677T rs1801133 GG -/-
    MTHFR 03 P39P rs2066470 GG -/-
    MTHFR A1298C rs1801131 GT +/-
    MTR A2756G rs1805087 AA -/-
    MTRR A66G rs1801394 GG +/+
    MTRR H595Y rs10380 CC -/-
    MTRR K350A rs162036 AA -/-
    MTRR R415T rs2287780 CC -/-
    MTRR S257T not found n/a n/a
    MTRR A664A rs1802059 GG -/-
    BHMT-01 not found n/a n/a
    BHMT-02 rs567754 CT +/-
    BHMT-04 rs617219 AC +/-
    BHMT-08 rs651852 CC -/-
    AHCY-01 rs819147 TT -/-
    AHCY-02 rs819134 AA -/-
    AHCY-19 rs819171 TT -/-
    CBS C699T rs234706 GG -/-
    CBS A360A rs1801181 AG +/-
    CBS N212N rs2298758 GG -/-
    SUOX S370S not found n/a n/a
    NOS3 D298E not found n/a n/a
    SHMT1 C1420T rs1979277 GG -/-
    Before getting started: Understanding the basics

    We have two copies of most of the genes we are born with – one from our mother and one from our father. Genetic Genie uses the SNPs (Single Nucleotide Polymorphisms) generated from your unique DNA sequence to determine if one or both copies of your genes have a mutation at a specific location in a specific gene. If there are no mutations present, your result will be displayed as (-/-). If one gene is mutated, the result will read (+/-). If both copies have a mutation, the result is (+/+). Along with the (+/-) symbols, the colors on the table also denote the type of mutation for visual comprehension. The color red indicates a homozygous (+/+) mutation, the color yellow indicates a (+/-) heterozygous mutation and the color green (-/-) indicates that you don’t carry the specific mutation.

    The terms heterozygous and homozygous are used by geneticists to denote whether one or both copies of a gene are mutated. Heterozygous mutations (+/-) may differ from homozygous mutations (+/+) in associated disease risk since a person with a heterozygous mutation will often still have one fully functioning copy of the gene. It is also important to understand that having a gene with a SNP mutation does not mean that the gene is defective or nonfunctioning, only that it is working with an altered efficiency. Sometimes this means that it is working at a decreased level, but it could also mean that it is functioning at a higher than normal efficiency, or that the gene is lacking regulatory mechanisms normally involved in its expression.

    Although mutations can occur at any time during our lifetime, it is most likely that we are born with these mutations and will have them throughout our life. These inherited mutations have been passed down to us from previous generations (our parents and grandparents) and may be passed to future generations (our children). This may provide an explanation as to why certain traits or diseases “run in the family”.

    Although we cannot change our genetic code, we can change how our genes are expressed. Research has revealed that our gene expression is not determined solely by hereditary factors, but it is also influenced by our diet, nutritional status, toxic load and environmental influences or stressors. This phenomenon has been termed “epigenetics”. Researchers in the growing field of epigenetics have demonstrated that certain genes can be over- or under-expressed with certain disease processes. Researchers in this field hope that by understanding of how these genes are regulated and what is influencing them, we may be able to change their expression. Using epigenetic concepts along with a good understanding of the methylation cycle, researchers have begun to make recommendations to optimize genetic expression and help to restore health.

    Disclaimer: The information on this website is for educational purposes only and should not be used a substitute for a consultation with a healthcare provider. You, the reader, are instructed to consult with a qualified healthcare provider prior to acting on any suggestions presented on this website. This information is not intended for the diagnosis, treatment or cure of disease.

    MTHFR Mutations

    First we’ll look at a few of your MTHFR mutations. According to research, these mutations are important and can be implicated in various disease states.

    You have 1 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 A1298C
    Now let’s move on to discuss what these MTHFR mutation(s) mean.
    MTHFR A1298C
    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 1 homozygous (+/+) mutations and 7 heterozygous (+/-) mutations.

    Here are your homozygous mutations as indicated in your SNP gene table above (not including MTHFR):

    MTRR A66G
    Here are your heterozygous mutations as indicated in your SNP gene table above (not including MTHFR):

    COMT V158M
    COMT H62H
    VDR Bsm
    VDR Taq
    CBS A360A
    CBS Mutations
    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.

    MTR/MTRR Mutations
    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.

    COMT Mutations
    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 Mutations
    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 mutations
    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 methylationis 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.

    If you have a BHMT 01, BHMT 02, or BHMT 04 mutation and don't have a CBS mutation, information about CBS was not included in your report. If you have these mutations, you can find our info about addressing the CBS upregulation at

    More information

    For more comprehensive information, you can look at these sources:

    Autism: Pathways to Recovery (ESP) Book, Workbook & DVD Methyl Cycle NutriGenomics

    #376722 Reply

    Julie P

    Hi incogg,

    It looks like your email includes a long question AND a long reply. Was the question yours? Was the reply from Dr. Ben??

    Just curious.


    #376723 Reply

    Julie P

    Oops! I just figured out that the second half of your email was quoted from Genetic Genie. Sorry!


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