Methylation

Question 1

Methylation

Answer 1

Process of adding a methyl group (CH3) to a substrate:

• It is involved in almost every metabolic process in the body and contributes to crucial functions, including:

– Gene regulation (turning genes on and off)

– DNA RNA synthesis (e.g., growth, repair, cancer prevention.

– Detoxification (e.g., hormones such as oestrogen).

– Energy production (CoQ10, carnitine and ATP).

– Myelination and neurotransmitter production (e.g., dopamine and serotonin  melatonin).

– Immune function (e.g., immune cell synthesis, inflammation)

Question 2

Dietary co-factors for methylation

Answer 2

Folate, B12, B6, B2, choline, betaine (TMG) and zinc

Question 3

The ‘methyl’ (CH3) group

Answer 3

CH3 is provided to the body bythe methyl donor known as SAMe (S-adenosylmethionine).

• SAMe is formed from the amino acid methionine.
• The system that produces SAMe is reliant on the active form of folate ― methylfolate

Question 4

Methylation disruptors

Answer 4

• Insufficient substrates (folate, methionine).
• Lack of essential co-factors (B2, B12, B6, zinc) / malabsorption.
• SNPs affecting enzyme activity (involved in methylation).
• Specific nutrients depleting methyl groups (niacin).
• Drugs (e.g., contraceptive pill, metformin = ↓ B vits).
• Increased demand on processes described previously e.g., stress, imbalanced hormones, inflammation, need for repair etc.
• Toxin exposure ― aflatoxin (fungi on crops), air pollution, BPA (e.g., food packaging), phthalates (e.g., beauty products), heavy metals etc.

Question 5

Impaired methylation can contribute to

Answer 5

• Cardiovascular disease.
• Cancer (e.g., breast cancer).
• Infertility and unexplained miscarriages.
• Chronic fatigue and mood disorders.
• Neurological disease (e.g., MS, Alzheimer’s)

Question 6

How to assess for indicators of poor methylation

Answer 6

• Genetic testing ― for methylation SNPs.
• Homocysteine testing ― if methylation is poor, homocysteine levels generally rise. Ideal levels: 5–8 µmol / L. SAMe / SAH ratio in some tests may be more accurate.

Question 7

Methylation cycle

Answer 7

Question 8

Methylation cycle 2

Answer 8

Question 9

Folate cycle (MTHFR):
Gene

Answer 9

MTHFR codes for the enzyme ‘methylenetetrahydrofolate reductase’ ― converting folate into a methylated form

Question 10

Folate cycle (MTHFR)
SNPs

Answer 10

The C667T (cytosine replaced by thymine) SNP at rs1801133 is associated with reduced activity of MTHFR

Question 11

Folate cycle (MTHFR)
Recommendations

Answer 11

‒ Optimise dietary folate.

‒ Consider a methylated folate supplement.

‒ Optimise vitamin B2 (riboflavin) ― supporting the MTHFR gene.

‒ Note: The drug methotrexate is a folate antagonist.

Question 12

Methionine cycle (MTR / MTRR):
Genes

Answer 12

MTR / MTRR = code for the enzyme methionine synthase (MS), which ↑ the conversion of homocysteine to methionine

Question 13

Methionine cycle (MTR / MTRR):
SNP

Answer 13

The A allele of rs1805087 in the MTR gene is associated with decreased MS activity

The A66G SNP at rs1801394 = ↓ conversion of vitamin B12 to its methylated form

Question 14

Methionine cycle (MTR / MTRR):
Recommendations

Answer 14

Vitamin B12 and folate foods are co-factors in the conversion of homocysteine to methionine. Consider supplementation of their methylated forms.

• Ensure no mercury / lead toxicity ― these can hinder the process