r/MTHFR

C667T. Anyone have experiences or advice with lowering cholesterol and improving kidney diagnosis? LDL, triglycerides, eGFR, and creatinine are panel issues. General health is good with no noticeable symptoms or problems. Prefer dietary or supplementation measures over meds. Homocysteine levels are 9.5. Wondering if there is an MTHFR-specific that I’m missing? Thanks.

If you have tried any peptides, what were your results? Did you have any side effects? Looking for experiences from folks who have an MTHFR variant. I’m learning about peptides and curious if you’ve tried such as BPC-157, TB-500, GHKCU, AOD-9604 or any others.

A1298C Heterozygous

I’m looking for some advice on my current lab results and how to proceed.

My Genetics & Background:

• MTHFR: A1298C Heterozygous

• Gilbert’s Syndrome

• Update on COMT: I just submitted my DNA for an Ancestry test. I personally suspect I have a FAST COMT because I have mild ADHD-like symptoms (racing thoughts, talking fast, constantly dropping things). However, some people say reacting poorly to methyl-vitamins points to a SLOW COMT. I'm very confused by this paradox.

My Recent Lab Results (mid-April):

• Homocysteine: 21.0 µmol/l (Reference: <10)

• Active B12 (Holo-TC): 89.8 pmol/l (Reference: 37.5 - 188)

Supplements & Medications:

• I took a comprehensive Multivitamin complex (Eqology Nordic Energy Booster) throughout February and March. I stopped taking them exactly 1 week before my blood test. Daily doses: B12 (10 mcg), Folate (200 mcg as active Quatrefolic), B6 (2.8 mg).

• I take 5 mg Cialis (Tadalafil) daily.

My Lifestyle:

• I smoke about 4 cigarettes, 3 times a week.

• I drink about 2 liters of beer once a week (mostly on Fridays).

• High daily caffeine intake.

The Problem:

I don't get massive panic attacks from active methyl-B vitamins, but I definitely have the slight feeling that I feel better and more balanced without them. They just make me feel a bit restless or mildly jittery.

My Questions:

1. Could my Holo-TC (89.8) still be high from the supplements even after a 7-day break?

2. With only A1298C Hetero, is 21.0 Homocysteine likely driven more by my lifestyle (smoking/alcohol/caffeine) depleting my nutrients?

3. What is the gentlest way to lower homocysteine without methyl-donors? (Currently focusing on Choline/Eggs).

4. Does anyone else experience this mix of fast COMT (ADHD traits) but feeling slightly "off" on methyls?

5. Can I take Glutathione or NAC? I currently have the ones from KeKo Naturals. Would this help my liver (Gilbert's) and the oxidative stress from smoking without messing with my methyl-cycle?

Thanks for your help!

Do any of you get extreme anger/rage as a symptom of over methylation?

Like everything irritates you and is overwhelming at the same time

I tried 200mcg of methylfolate, which made me feel anxious on the 3rd day. I took an antihistamine, which helped

Also 600mcg of methyl b12. Do I need to take iron supplements as well

My dna test says take b2 but it gave me anxiety why?

Looking for brand recommendations with links please.

While egg yolks initially made a huge difference for me (very high likelihood of choline deficiency), they also contribute to my sulfur backup symptoms. I’m looking for PC recommendations that are easy on the liver and stomach, and don’t have any filler ingredients. Thanks!

Hearing many conflicting answers on this.

Hi everyone,

Are there people here who have lipomas and also know they have elevated homocysteine levels (e.g., due to MTHFR mutations)?

I came across a very interesting biochemical connection: High homocysteine has been shown to downregulate or inhibit the PTEN gene, which is a crucial tumor suppressor. PTEN normally acts as a brake on cell division and growth. If this brake is blocked by excess homocysteine, fat cells might grow unregulated, leading to the formation of lipomas.

Has anyone here looked into this specific pathway (Homocysteine -> PTEN inhibition -> Lipomas)? Even better, has anyone noticed their lipomas stopping to grow or shrinking after successfully lowering their homocysteine levels (via methylation support etc.)?

Would love to hear your experiences and thoughts on this!

I feel better when I drink a lot of nettle leaf and ginger tea but that could be just the antihistamine effect? Either way, I believe herbal teas are underrated and can potentially benefit a lot of us greatly even if just for the anti-inflammatory and antihistamine properties + a bunch of added nutrients.

Has anyone tried any of the following herbal teas? These should all be fairly safe for slow COMT:

- Lemongrass

- Fennel

- Holy basil (tulsi)

- Thyme

- Rooibos

- Rose hip

- Peppermint

- Dandelion

I have had issues with canola oil ever since it became popular in restaurants. Initially I had no idea why everytime I ate out I would get sick, but never at home where I only use olive oil to cook and avacado oil for extremely high heat, vegetable oil for baking. Then a friend with a restaurant told me about canola oil. I started paying attention to boxed foods that also made me rush to the bathroom. I was shocked how many contained it. Cereal has oil?! Veggie burgers. Wheat thins. It’s everywhere. As time went on like all food sensitivities it’s gotten much worse so I have to be extremely careful and it’s really limiting. I’m just now wondering if it is related to MTHFR.

Title is self explanatory. I had a severe, bad reaction to methylfolate on Easter (you can read my last post to this sub for more info.)

to put it simply, my blood pressure is now through the roof, with daily, constant heart palpitations and chest pain. Im being tested for things medically as ive ended up in the hospital twice in the past week for extremely elevated blood pressure.

is this a one off experience? or has anyone else gone through similar? It seems im alone at the moment, I cant find any similar accounts.

Hi everyone,

I hope someone here can help me out.

I recently started taking a multivitamin supplement (Nordic Energy Booster), but I've noticed that I often feel quite restless, jittery, and just overall "bad" after taking it. It feels like some kind of overmethylation or like my nervous system is getting way too wired.

Briefly about my genetics: I am only heterozygous for MTHFR A1298C (C677T is normal). I actually thought I wouldn't have major issues with this mild mutation.

Could this be due to the specific forms of B vitamins in this supplement (Methylcobalamin, Quatrefolic, P5P)? Or do you see anything else in the ingredient list that could trigger this inner restlessness or discomfort?

Here are the ingredients and dosage (Recommended daily dose = 4 tablets, but I feel the side effects even at a lower dose):

Ingredients:

Natural magnesium hydroxide from seawater (Aquamin™), esterified vitamin C as calcium ascorbate (Ester-C®), magnesium bisglycinate chelate (Pharmagnesia®), magnesium malate, bulking agents (microcrystalline cellulose, croscarmellose sodium), blueberry extract (Vaccinium myrtillus), zinc bisglycinate chelate (Core Chelate®), anti-caking agents (vegetable magnesium stearate, silicon dioxide), selenomethionine (Lynside® Forte Se+). Organic Ascophyllum nodosum natural iodine (PureSea® Natural), niacinamide, calcium D-pantothenate, pyridoxal-5-phosphate (B6), riboflavin (B2), thiamin (B1), copper sulfate, chromium picolinate, (6S)-5-methyltetrahydrofolate glucosamine salt (Quatrefolic®), glazing agents (hypromellose, vegetable glycerin), color (blueberry), D-biotin, methylcobalamin (B12).

Nutritional values per daily dose:

• Vitamin C (esterified): 400 mg

• Magnesium: 230 mg

• Niacin (Vitamin B3): 16 mg

• Pantothenic acid (Vitamin B5): 6 mg

• Zinc: 5 mg

• Vitamin B6 (P5P): 2.8 mg

• Riboflavin (Vitamin B2): 2.8 mg

• Thiamin (Vitamin B1): 2.2 mg

• Copper: 392 mcg

• Folate (Vitamin B9 as Quatrefolic): 200 mcg

• Iodine: 132 mcg

• Selenium: 100 mcg

• Chromium: 60 mcg

• Biotin (Vitamin B7): 50 mcg

• Vitamin B12 (Methylcobalamin): 10 mcg

• Blueberry extract: 25 mg

Has anyone with heterozygous A1298C had similar experiences with these ingredients? Should I switch to unmethylated forms of folate and B12 instead?

Thanks for your input!

My results of a recent genesight test shows I am homozygous for the C667T allele of the MTHRF gene as well as val/val for COMT.

I am looking for a really good doctor who specializes in these epigenetic fields. I have been doing a lot of research on my own and already supplementing to fill in the gaps. It’s becoming a little overwhelming. Would like to get some professional advice and work with a practitioner that can guide me.

I live in SF. Does anyone have a good recommendation for me?

I'm compound heterozygous for MTHFR, slow COMT. I also suspect a mild histamine sensitivity. I seem to have no issues eating some high histamine foods but when I eat a lot I get a constant runny nose and worse brain fog. No other symptoms though.

I have been addicted to Monster energy drinks for 10 years and was finally able to quit 6 months ago. I noticed that my brain fog still remains worse than before.

1 can of Monster has:

- Riboflavin B2: 3.4 mg (200%)

- Niacin B3: 40 mg (200%)

- Vitamin B6: 4mg (200%)

- Vitamin B12: 12 mcg (200%)

- Taurine: 2000 mg

- Parax Ginseng: 400mg

- L-carnitine (unknown amount)

I'm definitely not going to supplement all of these separately. I'm only supplementing B12 and I've added a lot of foods with B vitamins to my diet. This has helped but my brain fog is still significantly worse than before.

I also had a folate deficiency but I react poorly to all forms. I've tried folic acid, methylfolate and folinic acid. 200mcg methylfolate works best for me and I eat more folate rich food.

I was thinking of adding a vitamin B complex but I can't find any without folic acid/folate.

I've tried adding a lot of vegetables to my diet but found out I'm slightly sensitive to high histamine food. I regularly eat carrots, green peas, asparagus, brussels sprouts, bananas, apples which give me no trouble.

I also consume milk and eggs daily which add more B vitamins and some folate. I'm pretty sure I'm not sensitive to those foods since I've already tried cutting them out and it made no difference.

I prefer to get as much as possible from food and maybe add 2 or 3 supplements. I don't feel like going back to energy drinks or adding a dozen supplements. My current supplements are vitamin B12, methylfolate (200mcg), vitamin D, magnesium bisglycinate, L-theanine and fish oil.

Hello! Recently found out I have 2 MTHFR variants. I have had 2 previous pregnancy losses, 1 at 12 weeks (which we assumed was just genetic issues at the time) and 1 just before 4 weeks, which is what led to the diagnosis.

My OB is really pushing me to get on blood thinners for my next pregnancy, but they also haven’t done anything to see if blood clotting is the actual issue or if I just need to increase my folic acid.

I’m curious to hear from others what the success rate is without them or what alternatives you were given! I’ve tried to discuss with my doctor but she is very pushy and I haven’t found a new office yet.

Can't stress this enough. Supplementing with folate and b12 does use up a lot potassium. That's why in natural foods such nutrients are always combined with potassium. When someone eats a low potassium diet, high salt, high calcium, low magnesium then this would lead to big problems. Folate and b12 in natural foods are never so high like in supplements, so when taking high doses folate and b12 one needs to up potassium intake. And i mean by upping that one will probably need huge amounts of potassium to balance things out.

I've just discovered this topic because since supplementing folinic acid with hydroxo b12 i've encountered blood sugar problems and i know from the past if potassium is low then i'll get blood sugar crashes. Combined with 2-3 days high salt intake (sodium is a potassium antagonist), low potassium and on top supplementing D3 which increases calcium uptake this lead to my actual problems!

Low potassium leads to salt and carb intolerance. Probably many don't actually overmethylate but run low in potassium. The pattern is often the same: One starts supplementing folate+b12 and initially feels good (potassium levels are adequate) but over time potassium runs low because creating new blood cells consumes a lot potassium resulting in fatigue, exercise intolerance, racing heart, heavy feeling, anxiety, blood sugar crashes etc.

https://preview.redd.it/wmaw6wppmsvg1.png?width=789&format=png&auto=webp&s=94b03ac7cccb1dc2bde58b8ea12eb5c8e795901a

Hi guys! (First time posting here I am so sorry if I am asking for too much!)

I am one of those people who were misdiagnosed from an early age, all my problems were blamed solely on Major Depression (which later became treatment resistant) and GAD, instead of AuDHD and Autistic Burnout. I have never experienced any positive effects from SSRIs only side effects which after 22 years of on and off SSRI treatment (I have been threatened with non-compliance and being labeled a difficult patient, or told I just haven't had the "right" combination and they "persuade me" (which means ignoring everything that I say) so I always give in) has left me fat, sweaty, brain zappy a boat load of negative side effects etc.

I have CPTSD from a vicious series of traumatic events, I am recovering from dissociative amnesia I am also still in Autistic burnout. I can't take my ADHD medication without some form of anxiety suppression as my meds can trigger my CPTSD. I am so fcking tired of having doctors medically gaslight me and being medically neglected and traumatized. I want to recover, I am too young to be stuck in this cycle which leaves me unable to work or take proper care of myself and home. Which is why I need help understanding this and what I should do next as my brain is fried from burnout and CPTSD.

I am also poor AF.

As you can see I have the hetero MTHFR C677T gene mutation and as I am reading more about this methylation panel it seems these other gene mutations play a strong role in how my body processes (or doesn't) neurotransmitters, vitamins etc. I have an appointment with a psychiatrist on Monday, I am mildly hopeful as he is a recent graduate but I don't know of which medical school (some are more biased than others) and I want him to actually help me instead of just throwing random meds at me.

What takeaways should I take from this panel? If you can, explain it to me like I'm 12 so I can explain this to the psychiatrist. What do I need to do to help make myself healthier, as specifically as you can if at all possible. I have read the info section below the panel but keeping track of how the mutations interact with each other and what that ultimately means is way too much for my fried brain to handle.

If this is way too much of an ask, please let me know. If there is a website that better explains my results, again please let me know.

I am adding that info below:

CBS

CBS (cystathionine beta synthase) catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine. CBS defects are actually an upregulation of the CBS enzyme. 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 CBS upregulation has been clinically observed to result in sulfur intolerance in some patients. It has also been observed that 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).

Note: While some physicians think the CBS mutation is one of the most important mutations to address, there is very little medical research to support these claims and some doctors in the field disagree. In normal populations, studies have shown CBS upregulations to be protective against high homocysteine. However, CBS upregulations have shown to be harmful in Down Syndrome. Medical research has not determined if CBS upregulations are harmful in those with syndromes or disorders leading to impaired methylation.

MTHFR C677T

One function of MTHFR (Methylenetetrahydrofolate reductase) is to help convert homocysteine to methionine. A MTHFR C677T mutation means that the MTHFR enzyme may have trouble performing its task leading to high levels of homocysteine. According to Dr. Ben Lynch, impaired function of the enzyme can cause or contribute to conditions such as Autism, Chronic Fatigue Syndrome, Fibromyalgia, Miscarriages, IBS, many birth defects, Multiple Sclerosis, Alzheimer's, Bipolar Disorder, blood clots, Stroke, Chemical Sensitivity, and many other conditions.

MTHFR C677T can also lead to high homocysteine. High levels of homocysteine can be related to MTHFR C677T mutations. While homozygous (+/+) or heterozygous (+/-) mutations indicates reduced activity of this enzyme, it does not necessarily mean there will be high homocysteine levels in a clinical setting. The gene is compromised about 70% in MTHFR C677T (+/+) individuals, and about 30% in people with a heterozygous (+/-) mutation.

As S-adenosylhomocysteine (SAH) accumulates, the COMT enzyme may become impaired. Inhibitiion of COMT can increase dopamine levels in COMT V158M (-/-), but for those with COMT V158M (+/+), the high level of SAH can lead to behavior problems and mood swings according to Dr. Amy Yasko.

MTHFR A1298C

MTHFR A1298C is involved in converting 5-methylfolate (5MTHF) to tetrahydrofolate (THF). This reaction helps generate BH4. BH4 is important for the detoxification of ammonia. Unlike MTHFR C677T, A1298C does not lead to elevated homocysteine levels unless paired with a MTHFR C677T mutation (i.e. compound heterozygous).

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. BH4 is also a cofactor in the production of nitric oxide. A dysfunctional BH4 enzyme may lead to mental/emotional and/or physical symptoms. Mercury, lead, and aluminum may act as a drain on BH4.

COMT

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, it has been clinically observed by physicians that people may have trouble with methyl donors. This can lead to irritability, hyperactivity, or abnormal behavior. They may also be more sensitive to pain.

VDR

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 Tak and VDR Bsm are usually inverse from eachother. So if there is a (+/+) VDR Tak, there would be a (-/-) VDR Bsm. However, this is not always the case.

It has been clinically observed that the body may have trouble tolerating methyl donors with a COMT V158M + and a VDR Taq + status. VDR Taq (-/-) individuals may already have higher levels of dopamine, and 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.

Note: Some have pointed out that VDR Taq is reported backwards since majority of medical journals report a different risk allele or use different notation. These arguments are well-founded, but Genetic Genie reports this way so results are compatible with existing methylation nutrigenomics literature. Many claims about VDR and methylation are clinical observations. There are no medical studies to support some of the observations.

MAO-A

MAO-A (Monoamine oxidase A) is a critical enzyme involved in breaking down important neurotransmitters such as serotonin, norepinephrine, and dopamine. Males only have one allele since the gene is inherited through from their mother since it is located on the X chromosome. Only females can be heterozygous (+/-) for this mutation. When a (+/+) MAO-A mutation is combined with a (+/+) or (+/-) COMT V158M mutation, imbalances in neurotransmitters may be more severe. These imbalances can potentially lead to neuropsychiatric conditions and symptoms such as Obsessive Compulsive Disorder (OCD), mood swings, and aggressive and/or violent behavior.

Note: Genetic Genie reports the wild type as the defective variant as doctors have clinically observed that patients with methylation problems (especially those of Autism) often have trouble breaking down neurotransmitters. The high activity version of MAO-A (which is represented as -/-) can contribute to major depressive disorder. The significance of this SNP should be interpreted with caution.

ACAT/SHMT

ACAT1-02 (acetyl coenzyme A acetyltransferase) plays a role lipid metabolism and energy generation. It can also deplete B12.

MTR

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 not very common (<1% of CEU population). 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.

BHMT

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.

AHCY

AHCY (S-adenosylhomocysteine hydrolase) is involved in breaking down the amino acid methionine. It controls the step that converts S-adenosylhomocysteine hydrolase to adenosine and homocysteine. Adenosine plays an important role in energy transfer as ATP and ADP. It helps promote sleep and suppress arousal. Dysfunction of this enzyme can affect levels of homocysteine and ammonia. Some physicians claim AHCY mutations may actually take the strain off the CBS enzyme and may even prevent taurine from becoming very elevated.