MTHFR Mutated Genes & Undermethylation

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MTHFR Symptoms / Undermethylation - Suffering from Chronic Fatigue?


MTHFR is a common genetic mutation, affecting 1 in 2. This can lead to a loss of methylation function, causing big problems such as Undermethylation. If you exhibit chronic fatigue/ low energy with symptoms of anxiety & depression, chances are you’re an undermethylating. 


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Suspect you may be carrying MTHFR Mutated Genes? You SHOULD! 

Especially if you’re feeling low energy with symptoms of anxiety and depression! Read this to discover about UNDERMETHYLATION & what to do about it?

How Common is MTHFR Genetic Mutations

1 in 2 or up to 50% of all people experience from this MTHFR Gene defects, inherited from parent to child.

What’s MTHFR mutation

MTHFR actuallys stands for Methylenetetrahydrofolate Reductase, a type of enzyme to turn folic acid into methylfolate (aka usable form of folate) which is used constantly in each “methylation cycle”.

MTHFR Gene Mutations affect our body’s ability to convert folic acid into folate, impacting the body’s ability to carry out methylation function effectively.

MTHFR and Methylation Functions 

Methylation is a process by which methyl groups are either removed (“de-methylation”) or added (“re-methylation”) from other molecules, transforming these methyl groups into various compounds. Note: a Methyl group is made of 1 carbon & 3 hydrogen molecules.

Methylation regulates gene expression, activates MTHFR genes on & off through different metabolic processes. Methylation occurs at a rate of 12 million times per second.

This influences your enzymes, hormones, and neurotransmitters, and so many things!

Table: Basics of Methylation Cycle 

Methylation Cycles ProcessesCrucial For
Make new cells (e.g. red blood cells)Recovery. Every single organs of our body regenerates new cells all the time
Neurotransmitters production

Serotonin, dopamine or norepinephrine

Brain health: healthy neurotransmitter activity is responsible for emotional stability.

Psychological & psychiatric wellbeing.

Histamine pathwayNutrients conversion & distribution and bioavailability.

Regulating histamine load, bodily response’s to allergies

Homocysteine to Methionine Amino acidHealthy heart function : keeping cholesterol levels balanced so it doesn’t clog up our arteries & organs. This is important to maintain low level of LDL/ Bad cholesterol, preventing fatty liver disease, high blood pressure,  etc.
Mitochondrial functionCritical for cellular energy production/
DetoxificationHelp the body to detoxify heavy metals and toxins
SAM / S-adenosylmethionineHomocysteine comes together with folate and methyl-B12 to make something called SAM or S-adenosylmethionine (in supplements, it is called SAMe). Without enough SAM, our metabolic processes, including detoxification in the liver, breakdown of adrenaline, and energy production in the mitochondria, come to a standstill.
Nitric oxideExercise & physical performance
Immune systemhe nervous system communicates with immune cells, so a faulty methylation process can lead to immune imbalances, which can turn a simple cold or flu into pneumonia or and auto-immune disease.

Methylation cycles impact pretty much every single biological processes in our body. Our systems are interconnected.

When you don’t have enough methyl group, you will be undermethylating. When you have too much methyl groups, you will be overmethylating.

Undermethylation and Overmethylation influence our physical & mental health quite significantly!


Do you identify with this list of MTHFR mutation symptoms?

SymptomsBowel dysfunction

Cognitive decline symptoms (e.g. poor concentration, brain fog)

Poor detoxification

Susceptible to anxiety & depression due to abnormally low serotonin

Women – fertility problems, painful menstrual cycles, period moodswing,, fibromyalgia, ovarian issues

Low pain tolerance

Seasonal allergies

Highly activated neurotransmitters, so often think outside of the box

Difficulty slowing down

Low libido

When experiencing depression, this can be life-consuming. These individuals are more susceptible to suicidal thoughts, behaviors.

High pain tolerance

CharacteristicsCompetitive, ambitious, driven & passionate to succeed, control freak

E.g. doctors, teachers, sales people or other high-pressure type roles

Creative – artists, musicians, poets, actors 

Typical Nutrients Deficiencies for Undermethylators vs Overmethylators

High histamineLow histamine
Low zincHigh zinc
Low copperHigh copper
High basophil countLow basophil count
High homocysteine levelLow homocysteine level
High heavy metalsLow heavy metals

MTHFR/ Undermethylation – Link to Chronic Fatigue!

Prolonged undermethylation can lead to severe health symptoms.

When you’re an undermethylator, inadequate conversion of folic acid strips methyl group at the DNA level. DNA is where all the instructions are made to your genes.

Undermethylation has already been linked to these health problems:

  • Autism
  • ADHD
  • Alzheimer’s
  • Atherosclerosis
  • Autoimmune disorders

Researchers & Scientists are increasingly studying the links between MTHFR-mutated genes to various health concerns and medical conditions.

So much is going on this field, Which is highly exciting! Hopefully, we will learn more in the not too distant of future.

When this happens, our medical doctors are becoming more educated on the topic, and able to transition to more holistic health care practise rather than viewing the symptoms in isolation.

Currently, diagnosis of anxiety & depression is highly premature, and to prescribe antidepressants in actually premature & dangerous!

Severity Varies for the Different MTHFR Mutation

The most commonly studied MTHFR genes mutation are:  c677t & a1298c alleles.

Since we inherit 2 allele copies of MTHFR genes (1 gene SNP from our mom + 1 gene SNP from our dad).

Table: Homozygous, Heterozygous and Compound Heterozygous MTHFR Mutated Genes

MTHFR c677t SNPMTHFR a1298c SNPMTHFR Mutated GenesLoss of Methylation Function
2 copiesxHomozygous-70%
1 copy1 copyCompound Heterozygous-50%
1 copyxHeterozygous-40%
x1 copyHeterozygous-30%

MTHFR Symptoms List 

MTHFR Symptoms include:

ImpactIllness/ ManifestationCommon Symptoms
BrainAnxiety and DepressionCognitive decline (brain fog)

Low mood, Low motivation, Low levels of serotonin

Lack of interest in sex

Problems with sleep (chronic insomnia)

Attention deficit problem (ADHD)

Neurotransmitter levels

Gut HealthIrritable Bowel Syndrome (“Leaky Gut Syndrome”)Issues with digestive health/ symptoms of irritable bowel syndrome

Poor nutrients absorption

Struggle to keep inflammation levels under control (allergies to foods ingredients, chemicals, preservatives)

Recurring yeast infection/ candida

Neurotransmitter levels

Hormone levels.

Endocrine / Hormone productionChronic Fatigue Syndrome & FibromyalgiaInability to deal with stress


Hormone levels

Autoimmune disorders

Thyroid disorders (especially hypothyroid)

LiverOxidative Stress / Immune system issues such as Autoimmune conditionDetoxification

Eliminate Toxins & Heavy metals

Glutathione production


Chronic Pain disorders

Heart / CardiovascularHigh CholesterolHigh/ Elevated homocystine levels
Ask Your Naturopathic / Integrative Medicine Doctor About MTHFR 
  • Mayo clinic
  • Naturopathic doctor (with a doctorate degree from a federally-accredited program) Doctors near you

If you suspect you may be suffering from MTHFR genetic defect, speak to your medical doctor who will be able to organize some testing for yo. There is a good chance that your insurance won’t cover MTHFR gene testing – this can cause an arm & a leg.

MTHFR Mutation Blood Test & Diagnosis  
  1. 23andme
  2. Gene genie
  3. Cheapest option: order a Simple Blood Histamine Test
  • Not a fool-proof test but it’s probably a cheap option if you just want to confirm UNDER-METHYLATION VS OVER-METHYLATION. Ask your doctor to interpret the results.
  • There’s an indirect relationship between histamine and methylation. So we see individuals who are, for example, high in histamine. they tend to be low in methyl. And when they are high in methyl, they tend to be low in histamine. So we can actually measure indirectly concentrations of methyl.

How to treat Undermethylation

Watch out for Toxic Negative Effects of Pharmaceutical Medication!

Undermethylators often don’t do well when taking pharmaceutical medications due to limited detoxing capability.

Watch out especially when you’re taking these commonly prescribed medications:

  • Birth Control Pills
    • Birth control pills are synthetic estrogens to regulate your hormone & menstrual cycles. The byproduct of these pills must be processed. If you have a C677T MTHFR mutation, you are less able to eliminate this out of your symptoms.
  • Anti-depressant pills
    • Negative side-effects, which are mostly depression or even suicidal or homicidal behaviors.
  • Anti-anxiety medication

So what is can you do to treat undermethylation? Our recommendation is to take a targeted nutritional approach/ nutrients therapy. But the answer is not as simple as: taking copper. In fact, there are dangers of copper toxicity and taking copper supplement can actually do more harm than good. Discover how Fatigue No More can support you in your healing journey.