Category Archives: Methylation


Are You Methylating Properly?

The methylation pathways in the body is critical to good health. There are various functions of methylation within the body:

  • detoxification of carcinogens and other toxins
  • repair damage DNA
  • the formation of new cells
  • the manufacture of certain hormones

One of the indicators that the body is not methylating properly is a high homocysteine serum level.

Methylation is the transfer of a methyl group, which is what happened with carbon attached to three atoms of hydrogen, from one molecule to another.

Methylation is composed of two components:

1. Methyl donors-methyl donors are compounds that supply the methyl groups needed for methylation.

2. Methylating factors-methylating factors are nutrients that assist with the methylation process by providing enzymes that detach the methyl groups from the methyl donors and reattach them to other molecules.

Methyl donors consists of the following:

  • Methionine
  • Choline
  • Trimethylglycine (TMG)
  • Dimethylglycine (DMG)
  • S-Adenosyl methionine (SAMe)

Methylating factors consist of the following:

  • Vitamin B12
    • Three active forms:
      • Methylcobalamin
      • Hydroxocobalamin
      • Adenosylcobalamin
      • Never consume Cynocobalamin
  • Vitamin B6  (as P-5-P (Pyridoxal 5-Phosphate))
  • Folate
    • Two active forms:
      • L-5-MTHF as (6S)-5-methyltetrahydrofolate
      • L-5-FTHF  (5-formyltetrahydrofolate) as folinic acid calcium salt) (folinic acid)
  • Zinc

When the body is deficient in both methyl donors or methylating factors detoxification and repair functions of the body are compromised.

Methylation is the enzymatically-catalyzed process of adding a methyl group to proteins, DNA and RNA. This process is involved in RNA metabolism and the regulation of gene expression and protein function. While it does not change the sequence of the genome, methylation determines which genes are expressed and are responsible for changes in gene expression.

In general, methylation is a normal process that occurs in humans. DNA methylation has been found to play an important role in embryonic development, genomic imprinting, X-chromosome inactivation in females and cases where individuals possess two X-chromosomes, and chromosome stability.

Studies have found that embryos lacking the enzyme that catalyzes the transfer of a methyl group to DNA die during the differentiation stage. The methylation of histones, proteins involved in the packaging and ordering of DNA into structural units, regulates processes such as gene transcription and DNA repair.

Given the importance of methylation, errors in the process can result in devastating genetic disorders and human diseases. For instance, a loss of methylation results in the genomic instability present in the tumor cells of an individual with cancer.

On the other hand, if methylation is present in cells that are normally unmethylated and cause the process of transcribing DNA into RNA to be silenced, tumors can develop that in turn can lead to cancer (i.e., colon cancer).

Aside from cancer, errors in DNA methylation are also responsible for:

  • Immunodeficiency-centromeric instability-facial anomalies syndrome (ICF syndrome)
  • Prader-Willi syndrome
  • Angelman’s syndrome
  • Beckwith-Wiedemann syndrome 


You can ask your doctor to test your Methylation Pathway in order to determine the effectiveness of the functions and levels of its various biochemical pathways and to determine if there are any single nucleotide polymorphisms (SNPSs) in the Methylation Pathway.

Two labs that can test the Methylation Pathway:

Doctor’s Data, Inc.

Methylation Profile; plasma

    Sample Report of Methylation Profile; plasma

DNA Methylation Blood Spot

Identification of SNPs that influence health and disease risk may improve clinical success and allow patients to optimize health and wellness.

    Sample Report of DNA Methylation Blood Spot

Health Diagnostics and Research Institute

The Methylation Pathway

Cover photo credit: Dr. Amy Yasko

High Homocysteine Levels Can Damage Your Brain

It’s well established that at high levels, homocysteine, an amino acid metabolite, can damage the arteries feeding your heart.

However, new research shows it can also do some damage to your brain, resulting in poor memory, cognition and worsening hand-eye coordination.

Dr. Mike will discuss the latest research and offer safe and effective solutions for lowering homocysteine.

Listen to this excellent radio show from Healthy Talk w/ Dr. Michael Smith at

High Homocysteine Can Damage Your Brain (Original Air Date September 05, 2013)

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B Vitamins: Lowers Homocysteine resulting in slower acceleration of Brain Atrophy

A study from 2010 entitled Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial, PLoS One. 2010; 5(9): e12244. Published online 2010 Sep 8. doi:  10.1371/journal.pone.0012244, determined whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial.

The tissue and plasma concentrations of homocysteine are largely determined by the body’s status of certain B vitamins (folate, B6 and B12), which are cofactors or substrates for enzymes involved in homocysteine metabolism.  Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. There is a wide body of scientific evidence that plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.

The 2010 study was a single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study.

Participants were randomly assigned to two groups of equal size, one treated with:

  • folic acid (0.8 mg/d)
  • vitamin B6 (20 mg/d)
  • vitamin B12 (0.5 mg/d)

the other with placebo; treatment was for 24 months.

A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores.

The conclusion of the study was that the accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins.


Folic Acid (as L-Methylfolate)

Vitamin B6 (as Pyridoxal 5’-phosphate)

Vitamin B12 (as Methylcobalamin)

Whole Food Vitamin B Complex

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The Relationship between Neurotransmitter Synthesis and Homocysteine

Methylation relies on B-vitamin cofactors:

  • Vitamin B6
  • Vitamin B12
  • Folate

for the proper synthesis of the neurotransmitters that play an important role in mood regulation.

The methylation cycle becomes impaired, due to an decline in the B-vitamin cofactors which then leads to a concurrent increase in homocysteine levels. The end result is a disruption in neurotransmitter synthesis.

There is a close relationship between neurotransmitter synthesis and homocysteine formation, and that levels of homocysteine are an effective marker for B-vitamin status, and that changes in homocysteine levels correlate with changes in mood.

A target blood level of less than 7 – 8 µmol/L of homocysteine helps to ensure proper neurotransmitter metabolism and may balance mood during times of stress, depression and anxiety.


Coppen A et al. Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol. 2005 Jan;19(1):59-65.

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