Methylation

Question 1

Methylation

Answer 1

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

Question 2

Methylation functions

Answer 2

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).
–Myelinationand neurotransmitter production (e.g., dopamine and serotonin melatonin).
–Immunefunction (e.g., immune cell synthesis, inflammation)

Question 3

Dietary co-factors for methylation

Answer 3

Folate
B12
B6
B2
Choline
Betaine (TMG)
Zinc.

Question 4

The ‘methyl’ (CH3) group

Answer 4

• CH3 is provided to the body by the 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 5

Distruptors

Answer 5

• 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 demandon 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 6

Impaired methylation diseases

Answer 6

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

Question 7

Folate cycle (MTHFR)

Answer 7

• Gene: MTHFR codes for the enzyme ‘methylenetetrahydrofolate reductase’ ―converting folate into a methylated form.
• Key SNP: The C667T (cytosine replaced by thymine) SNP at rs1801133 is associated with reduced activity of MTHFR.
• Recommendations:
  ‒ Optimise dietary folate.
  ‒ Consider a methylated folate supplement.
  ‒ Optimise vitamin B2 (riboflavin) ― supportingthe MTHFR gene.
  ‒ Note: The drug methotrexate is a folate antagonist.

Question 8

Methionine cycle (MTR / MTRR)

Answer 8

• Genes: MTR / MTRR = code for the enzyme methionine synthase (MS), which ↑ the conversion of homocysteine to methionine.
• MTR SNP: The A allele of rs1805087 in the MTR gene is associated with decreased MS activity.
• MTRR SNP: The A66G SNP at rs1801394 =↓ conversion of vitamin B12 to its methylated form.
• Recommendations: 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.

Question 9

Transsulphuration

Answer 9

Another ‘output route’ for homocysteine that provides a substrate for glutathione synthesis and the key phase 2 detoxification processes of sulphation and glutathione conjugation.

Question 10

Transsulphuration cycle (CBS)

Answer 10

• Genes: CBS converts homocysteine to cystathionine.
• SNP: C669T SNP at rs234706 ↑ CBS activity = less homocysteine converted and potential ↓ SAMe. Faster conversion to ammonia (pressure on urea cycle) increasing the need for glutathione.
• Recommendations: Increase zinc, choline and TMG(e.g., beetroot). Neutralise the ammonia (↓ animal protein,probiotics to ↓bacterial production, supplement activated charcoal. Limit sulphur-containing foods, e.g., eggs.

Question 11

Biopterin Cycle

Answer 11

• Genes: MTHFR essential for 5-MTHF, thus biopterin and synthesis of serotonin, dopamine, adrenaline etc. SAMe-dependent COMT breaks down dopamine, adrenaline and noradrenaline. COMT also converts active oestrogen to less active oestrogen.
• SNPs: rs4680 ―the A allele is associated with ↓ COMT activity:
  ‒ AA = excessive catecholamines ―also associated ↑ oestrogen (and hence breast cancer, etc.).
  ‒ GG = fast metabolism of catecholamines.
• Recommendations: Choline, betaine, folate and B12-rich foods support the production of SAMe. Avoid exogenous oestrogens (e.g., avoid plastic, anti-perspirants, dairy products,etc.).

Question 12

Urea Cycle

Answer 12

• Genes: eNOS is responsible for generating nitric oxide from arginine, which plays a key role as a vasodilator.
• SNPs: At rs1799983 the T allele is associated with ↓ eNOS activity and nitric oxide linked to slower ammonia detoxification, ↑ free radical levels and an ↑risk of cardiovascular disease.
• Recommendations:
  – Increase antioxidants (‘rainbow of colour’).
  – Moderate intake of ammonia-generating foods (↓ animal protein).
  – Support NO production with L-arginine and beetroot juice.