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Is Methylation Helping or Hurting Your Health?

Why DNA Methylation is Critical

As this is a hot topic, you might wonder what the buzz is all about?

Many don’t realize how critical methylation is to optimize their health.

Methylation is a simple yet powerful biochemical process taking place in every cell of our bodies.

References: [1,2,3,4,5,6,7,8,9,10]

Conditions Linked to Methylation Issues:

While methylation is not a direct cause of these conditions, it is a contributing factor and one which can worsen the condition and block recovery.

  • Fatigue
  • Insomnia
  • Depression
  • Addictions
  • Obsessive-compulsive disorders
  • Seasonal allergies
  • Delusions
  • Low threshold for pain
  • Digestive issues
  • Frequent headaches
  • High libido
  • Self-motivation
  • Powerful Will
  • Perfectionism


Methylation Issues are Surprisingly Common

Between 30-40% of Americans may have a DNA variation called C677T.

This is to say we have genetic predispositions that can cause changes in the body.

These variations, however, don’t change our actual DNA sequence.

This is good news, meaning these changes are potentially reversible.

Four Sectors of Our DNA

Our DNA comprises four sectors; adenine, cytosine, guanine, and thymine.

Adding itself to cytosine in an enzymatic process, a methyl group, containing three hydrogen atoms, and one carbon, influences the methylation process.

How Methylation Occurs

Methyl-groups are affected by methyl-donors, each affecting the methylation process.

Primary methyl donor SAMe (S-adenosylmethionine) distributes methyl groups.

5-MTHF, our active folate, regulates SAMe production to optimize our methylation cycle.

Other methyl-donors are listed towards the bottom of the article.

Methylation Gene Variants

SNPs or defects in the MTHFR enzyme can cause too little methylation to occur.

“Under-methylation” can inhibit proper folate conversion, further affecting methyl group conversion.

This results in the accumulation of toxic waste products such as heavy metals and other chemicals.

Because of the C667T homozygous variant of the MTHFR gene, we see an elevation in homocysteine levels.

And high homocysteine levels, when not converted to methionine, are linked to many diseases such as cardiovascular disease, mental health disorders like Alzheimer’s disease, Parkinson’s disease, and depression.

Fetal neural tube defects can occur along with other obstetric issues such as recurring pregnancy loss and placental vasculopathy, as in abruption and pre-eclampsia.

Because of a “gene mutation”, or more correctly, a MTHFR gene variant, insufficient 5-MTHF leads to a poorly functioning methylation cycle.

Affected Genes

Researchers believe insufficient methylation to occur in various conditions.

Besides cardiovascular disease and cognitive disorders, we also see mood disorders and anxiety when methylation is not sufficient.

This may occur in these MTHFR variants:

A1298C, BHMT, C677T, MAT, MTR, and SAHH.

Associated conditions include:

  • Addictions
  • Delusions
  • Depression
  • Digestive issues
  • Fatigue
  • Insomnia
  • Frequent Headaches
  • High Libido
  • Low Threshold for Pain
  • Obsessive-Compulsive Disorders
  • Seasonal Allergies
  • Self-motivation
  • Strong will
  • Perfectionism



As with anything, too much of a good thing can also be too much.

Such is the case with over-methylation.

This can be because of gut health, mold, infections, viruses, low Vitamin B12, low detoxification, as this can create a cascading effect of negative conditions.

Over methylation is correlated to the following conditions and symptoms:

  • Anxiety
  • Artistic/ Musical Ability
  • Depression (typically accompanying anxiety and other mood disorders)
  • Dry Eyes and Mouth
  • Eczema
  • High Threshold to Pain
  • Hyperactivity
  • Fast Speech
  • Low Libido
  • Low Motivation
  • Obsession without compulsion
  • Pacing/ Restless Legs
  • Paranoia and Paranoid Schizophrenia
  • Self-mutilation
  • Sleep Disorders



How Methylation can be a Game Changer

Most significantly, methylation can inhibit the expression of certain genes.

This is beyond notable, as methylation can prevent a tumor-causing gene from activating itself, and thus preventing the cancer progression.

Leading to reducing the genetic risk of developing conditions, such as an array of cancers or metabolic disease or other serious conditions, we want to know what we can do to affect this.

What Causes Methylation Dysfunction?

Acute and chronic stress, chronic infections, environmental toxins, high estrogens, high histamine intake, and immune challenges all cause poor methylation.

Invariably, when we lose this methyl group, demethylation occurs.

As this is a red hot topic, researchers are working with the aim of a better understanding of the DNA methylation process.

Early evidence is telling us diet and nutrients play a role in DNA methylation.

Methyl Donors


1)Choline (Also Found in Phosphatidylcholine/ Phospholipid Lecithin-Algae-Krill Oil)


3)B9 Folate (5-MTHF) (Avoid Folic Acid)

4)B12 Methylcobalamin B12 (Avoid Cyanocobalamin)

5) B6 Pyroxidine (Look for P-5-P)

6) B2 Riboflavin

7) TMG (Betaine) (Also Increases SAMe)(Best for Homocysteine with Riboflavin)

(#’s 3 to 6 can be met with a high-quality multi-vitamin. This is the very highest quality and best value multi-vitamin I have found in 14 years of health sciences research.)

2nd Tier





(Generally: Methylated b-vitamins should be the goal, while we should avoid folic acid at all costs. Always read labels and avoid foods with added folic acid.)

Methyl Buffers





(Over 80% of SAMe, the primary methyl donor, is used in creatine and phosphatidylcholine production. Taking these two supplements spares SAMe levels and supports methylation.)

Methylation Burners







(Lysine and niacin take sizeable amounts of methylation to be processed. While they are both important and needed in slight amounts, taking larger amounts may require taking equal amounts of TMG or SAMe to offset their drag on methylation.)

(As stress is a heavy methyl burner, lowering stress is an effective method to optimize methylation.)

Methylation Blockers

Acetyl aldehyde (Yeast and Alcohol)



Enzymes Which can Have SNP’s Affecting Your Health

1)MTHFR: Methylenetetrahydrofolate Reductase (11)

Master methylation gene. Stress response, immunity, mood, inflammation, genetic expression, energy, antioxidants, brain chemistry, cellular repair, detox.

2)COMT: Catechol-O-Methyltransferase (12)

COMT is one of several catecholamine, catechol estrogen, and various drug and catechol substance metabolizing enzymes.

Mood, focus, energy.

(Fast or Slow Metabolism)


(Dopamine metabolism: Catecholamines. Dopamine-Norepinephrine-Epinephrine.)

3)DAO: Diamine oxidase (13)

The key digestive enzyme made in the kidneys, thymus, and the intestinal lining of the digestive tract, which breaks down excess histamine in the body.


(Histamine response, food allergies, and sensitivities. Mast cell disease. Auto-immunity.)

4)MAO-A: Monoamine Oxidase A (14)

One of two side by side genes encoding mitochondrial enzymes, MAO-A metabolizes amines, such as dopamine, norepinephrine, epinephrine, and serotonin.

Balances levels of dopamine-norepinephrine-epinephrine-serotonin.

(Fast or Slow Metabolism)


(Mood swings, appetite, carb cravings, addictions, energy, alertness, self-confidence, sleep.)

5)GST/GPX: Glutathione S-transferases/ Glutathione Peroxidase (15)

These two eliminate toxic body compounds such as arsenic, chlorine, formaldehyde, and hydrogen peroxide through the production of glutathione.


(Detox, DNA damage, cancers, autoimmunity.)

6)NOS3: Nitric Oxide Synthase 3 (16)

As a reactive free radical acting as a biologic mediator in an array of processes, including antimicrobial, antitumoral, and neurotransmission actions. Nitric oxide is synthesized from L-arginine through nitric oxide syntheses.


(Cardiovascular health, blood pressure, blood circulation, and blood vessel formation. Cognition, and mood.)

7)PEMT: Phosphatidylethanolamine N-methyltransferase (17)

PEMT is a transferase enzyme converting phosphatidylethanolamine to phosphatidylcholine in the liver.


(Phosphatidylcholine, cell membranes and liver, bile flow, muscle health, and brain development.)

Final Thoughts


  1. Determine whether you might be influencing too much or too little methylation.
  2. Determine if you have too much or too little methyl donors or methyl-blockers, buffers, burners, etc.
  3. Adjust lifestyle accordingly with diet, exercise, sleep, while lowering stress, alcohol, junk food, and smoking.

4. A fully active B-complex preferably in a good multi-vitamin, krill oil, creatine, and TMG is a good supplement foundation for most.


So what did you think of this review?

Perhaps, you’ll leave us a comment below?

Your Friend in Health

Mark Stein