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Choline, PEMT Genetics, and Your Methylation Health

Choline is an essential nutrient that supports many body systems. One of its key roles is as a precursor to betaine, an alternative methyl donor used by the betaine-homocysteine methyltransferase (BHMT) pathway to remethylate homocysteine back to methionine. This choline-to-betaine route works independently of folate and vitamin B12 and acts as a critical backup when folate/B12-dependent methylation is strained. By helping keep homocysteine low and supporting S-adenosylmethionine (SAMe) levels, choline helps sustain DNA methylation, neurotransmitter production, and healthy lipid metabolism.

PEMT (phosphatidylethanolamine N-methyltransferase) is a liver enzyme that makes phosphatidylcholine, an internally produced form of choline that supports cell membranes, fat transport, and methyl donor balance. A common genetic variant near the PEMT gene (rs12325817) affects how much phosphatidylcholine your liver can make. Depending on your genotype, your reliance on dietary choline and the choline→betaine BHMT pathway will differ, which can influence liver health, methylation capacity, and nutrient needs.

How to read this page

Below are practical interpretations for each genotype at rs12325817. Expand the section that matches your genetic result for personalized considerations and actionable steps. Remember that genetics is one piece of the puzzle. Diet, lifestyle, life stage, and health conditions also affect choline needs.

Two effect alleles (GG) — higher choline need

If your genotype is GG, you carry two copies of the effect allele associated with reduced PEMT activity. That means your liver likely makes less phosphatidylcholine and produces fewer choline-derived methyl donors. The choline→betaine backup pathway that feeds BHMT may be diminished, increasing reliance on dietary folate and vitamin B12 for remethylation.

What this may mean for you

  • Higher dietary requirement for choline to maintain methylation and normal liver fat handling
  • Greater risk of choline insufficiency if your diet is low in choline-rich foods
  • Potential impact on lipid transport and fat-soluble nutrient delivery when choline is low
  • If pregnant or planning pregnancy, heightened importance of meeting choline needs for fetal development

Practical steps

  • Increase choline-rich foods: eggs (especially yolks), liver, soy products (tofu, tempeh), legumes, fish, and lean meats
  • Consider a choline-containing supplement or betaine supplement only after discussing with your healthcare provider
  • Ensure adequate folate and vitamin B12 from diet or supplements to support the folate-dependent remethylation pathway
  • Avoid excessive alcohol intake which can impair liver function and increase choline demand
  • For women who are pregnant or breastfeeding, discuss choline targets with your provider — needs increase during these life stages

Suggested tests to discuss with your provider

  • Plasma homocysteine to assess methylation status
  • Routine liver function tests (ALT, AST) if concerned about liver health
  • Nutrient status checks for B12 and folate if you are not supplementing

Always talk with your healthcare provider before starting supplements, especially if you have medical conditions or take medications.

One effect allele (CG) — modestly increased choline need

If your genotype is CG, you carry one copy of the effect allele and may have moderately reduced PEMT activity. Your liver’s ability to make phosphatidylcholine is likely slightly lower than average, which modestly increases reliance on dietary choline and the choline→betaine BHMT pathway.

What this may mean for you

  • Small increase in dietary choline requirements compared with people without the effect allele
  • Modest risk of choline shortfall when intake is low, potentially affecting methylation and liver fat handling
  • In pregnancy, even a modest reduction in internal choline synthesis can mean higher dietary needs

Practical steps

  • Include choline-rich foods regularly: eggs, fish, soy, legumes, and occasional liver if acceptable
  • Support the methylation system by ensuring adequate folate and vitamin B12 through diet or a multivitamin
  • Limit heavy alcohol use and manage excess weight to reduce liver stress
  • Consider discussing targeted supplementation with your provider if your diet is restricted (vegan, low-protein) or you are pregnant

Suggested tests to discuss with your provider

  • Homocysteine levels, especially if you have other reasons to suspect impaired methylation
  • Screening for B12 and folate status when dietary intake may be inadequate

Consult your healthcare provider before making changes to supplements or if you have specific health concerns.

No effect alleles (CC) — typical PEMT function

If your genotype is CC, you carry two copies of the non-effect allele and are likely to have normal PEMT activity. Your liver should produce phosphatidylcholine at typical levels, contributing to internal choline supply and helping balance methyl donor demand.

What this may mean for you

  • Standard dietary choline needs usually apply
  • PEMT-mediated choline production helps spare folate/B12 pathways under normal conditions
  • Life stages and behaviors can still increase choline demand, including pregnancy, breastfeeding, high alcohol use, or certain liver conditions

Practical steps

  • Consume choline-containing foods regularly: eggs, lean liver occasionally, soy, fish, and legumes
  • Keep folate and vitamin B12 adequate through a balanced diet or a routine multivitamin if needed
  • Maintain healthy body weight, moderate alcohol, and follow a liver-supportive lifestyle

Suggested tests to discuss with your provider

  • Routine preventive labs as recommended by your clinician
  • Consider homocysteine measurement if you have other risk factors for impaired methylation

If you are pregnant, breastfeeding, or have liver disease, discuss specific choline intake targets with your healthcare provider.

Diet, supplements, and lifestyle — practical guidance

General steps to support choline and methylation health regardless of genotype:

  • Eat whole-food sources of choline regularly: one large egg contains about 125 mg of choline; organ meats like liver are very concentrated; soy, beans, and fish are good plant and animal sources
  • Keep folate and vitamin B12 adequate to support the primary remethylation pathways — consider a prenatal or standard multivitamin if diet is limited
  • Limit alcohol and address excess weight to reduce liver stress and choline demand
  • Discuss supplements only with your healthcare provider. Options they may consider include choline (citicoline, phosphatidylcholine), betaine (trimethylglycine), or B-complex vitamins if indicated
  • If pregnant or nursing, plan choline intake proactively because needs increase during these life stages

Important note and disclaimer

PlexusDx provides educational information about genetic predispositions only. This report is not medical advice and does not replace consultation with a qualified healthcare provider. Always review genetic results and any planned dietary, supplement, or medical changes with your healthcare provider, especially if you have existing health conditions, are taking medications, or are pregnant or breastfeeding.