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How Betaine (Trimethylglycine) and BHMT Genetics Affect Your Methylation and Health

Betaine, also called trimethylglycine or TMG, is a small nutrient that plays an important role in the body’s methylation system. The enzyme betaine-homocysteine methyltransferase, or BHMT, uses betaine to convert homocysteine into methionine. This reaction supports production of S-adenosylmethionine, SAMe, the body’s primary methyl donor. Because BHMT works independently of the folate and vitamin B12 dependent methionine synthase pathway, it serves as a helpful backup pathway when other remethylation routes are stressed.

Variations in the BHMT pathway can change how effectively your body makes or uses betaine. One commonly reported variant is rs3733890. Depending on your genotype for this variant, your ability to convert choline into betaine and to support the BHMT remethylation route can be different. Below we explain what those differences mean for nutrition, lifestyle, and monitoring, and offer practical, consumer friendly recommendations.

Why this matters

  • Methylation supports DNA regulation, neurotransmitter balance, energy metabolism, and detoxification.
  • When BHMT or betaine availability is reduced, more demand may fall on the folate and B12 pathway to keep homocysteine low and SAMe available.
  • Dietary choices and targeted supplements can help maintain methylation balance and normal homocysteine levels.

Actionable considerations

  • Increase intake of choline-rich foods: eggs, soy, liver, quinoa, beets, spinach.
  • Eat betaine-rich foods: beets, spinach, wheat bran, quinoa.
  • Ensure adequate zinc and B vitamins through diet or a balanced multivitamin if intake is limited.
  • Discuss with your clinician whether low-dose betaine (TMG) supplementation or targeted folate/B12 support is appropriate if you have concerns or elevated homocysteine.
  • Consider periodic blood testing for homocysteine and B12/folate status if you or your clinician are monitoring methylation health.
Two effect alleles (AA) — reduced BHMT conversion

If your genotype is AA at rs3733890 you carry two copies of the effect allele. The enzyme that helps convert choline into betaine may be less efficient. That can mean your body produces less betaine from dietary choline and the BHMT backup remethylation route may be under stronger demand. When BHMT activity is lower, more reliance falls on the folate and B12 dependent remethylation pathway to keep homocysteine and SAMe balanced.

Practical steps

  • Eat more choline-rich foods: eggs, soy, liver, quinoa, beets, spinach.
  • Include betaine-rich foods: beets, spinach, quinoa, wheat bran.
  • Ensure adequate folate and B12 intake through diet or medical guidance. If folate and B12 support is strong, the body can compensate.
  • Discuss with your clinician whether a low-dose betaine (trimethylglycine) supplement is appropriate, especially if homocysteine is elevated.
  • Support cofactors: adequate zinc and a balanced B-complex or multivitamin if diet is limited.
  • Consider testing homocysteine and B12/folate status periodically if recommended by your clinician.

These steps help sustain SAMe production and methylation-dependent processes such as energy regulation, neurotransmitter balance, and detoxification.

One effect allele (AG) — slight reduction in BHMT efficiency

If your genotype is AG at rs3733890 you carry one copy of the effect allele. This is commonly associated with a mild reduction in the efficiency of converting choline-derived compounds into betaine. The BHMT subcycle may work a bit less efficiently, so your liver could rely slightly more on dietary betaine or the folate/B12 remethylation route to maintain SAMe and normal homocysteine levels.

Practical steps

  • Boost betaine-rich foods: beets, spinach, quinoa, and whole grain wheat products when appropriate.
  • Include choline sources regularly: eggs, soy, lean meats, legumes, and leafy greens.
  • Support cofactors with zinc and a B-complex or balanced multivitamin if needed.
  • If you have concerns or lab evidence of elevated homocysteine, speak with your clinician about targeted betaine supplementation or focused folate and B12 support.
  • Maintain a balanced diet, regular physical activity, and moderate alcohol use, since alcohol can affect methylation and liver function.

For most people with one effect allele, the impact is small and lifestyle and dietary measures are usually sufficient to keep methylation functioning well.

Zero effect alleles (GG) — typical BHMT activity

If your genotype is GG at rs3733890 you carry two copies of the non-effect allele and are expected to have typical BHMT activity and conversion of choline to betaine. The BHMT/betaine subcycle should normally help remethylate homocysteine alongside the folate/B12 route, so you likely do not have a bottleneck from this specific variant.

Practical steps

  • Continue a diet that includes choline and betaine sources: eggs, soy, beets, spinach, quinoa, and lean proteins.
  • Ensure basic nutrient sufficiency: zinc, folate, and vitamin B12 through diet or a multivitamin if needed.
  • Maintain healthy lifestyle habits: regular exercise, moderate alcohol intake, adequate sleep, and stress management to support liver function and methylation.
  • Routine blood testing is not usually required solely because of this genotype, but speak with your clinician about testing if you have symptoms or other risk factors.

Overall, standard healthy eating and nutrient support usually maintain methylation balance when BHMT is operating normally.

Diet, supplements, lifestyle, and testing summary

  • Diet: emphasize choline sources (eggs, soy, liver), betaine foods (beets, spinach, quinoa, wheat bran), and a variety of fruits and vegetables to supply B vitamins and zinc.
  • Supplements: consider a balanced B-complex and zinc if diet is limited. Betaine (TMG) supplements may help reduce homocysteine for some people but should be discussed with a clinician before starting.
  • Lifestyle: regular physical activity, moderate alcohol intake, good sleep, and stress management support liver function and methylation.
  • Blood tests: if concerned or if recommended by your healthcare provider, check homocysteine, serum B12, and folate to guide targeted interventions.

PlexusDx does not provide medical advice. The information above is educational and explains how a BHMT-related genetic variant can influence methylation and nutrient needs. Always consult with your healthcare provider before making changes to your diet, supplements, or medical care. Your healthcare provider can interpret genetic results in the context of your overall health, medications, and lab tests.