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Understanding Your Vitamin B12 Genetics and Why It Matters

Vitamin B12, also called cobalamin, is a key nutrient your body uses to support methylation. Methylation helps produce SAMe, the universal methyl donor used in DNA maintenance, neurotransmitter production, lipid metabolism, and detoxification. B12 is required by the enzyme methionine synthase to convert homocysteine back into methionine. When B12 is low, or when related enzymes are less active, remethylation becomes less efficient and backup pathways step in. Those backups can help but are not as efficient, so keeping B12 in a healthy range supports energy, cognition, blood health, and detox pathways.

What this genetic result tells you

Your genotype at rs526934 is linked to differences in circulating vitamin B12. This variant influences how your body absorbs, transports, and maintains B12 in the blood. Depending on whether you carry zero, one, or two copies of the effect allele, your typical B12 levels may be unchanged, slightly lower, or lower enough to merit monitoring and intervention.

Two effect alleles (GG) — higher likelihood of lower B12

If your genotype is GG, you carry two copies of the effect allele associated with lower circulating vitamin B12. Lower B12 can reduce methionine synthase efficiency and slow the remethylation process that regenerates SAMe. When remethylation is impaired, your body may rely more on the betaine/BHMT pathway to keep methionine and SAMe supplied. This backup route helps but is less complete and can lead to mildly elevated homocysteine or metabolic strain over time.

Potential practical implications include increased risk for fatigue, poor concentration, or mild anemia if B12 becomes insufficient. Because B12 supports brain function, energy production, and detoxification, maintaining adequate levels is especially important for people with this genotype.

Actionable steps

  • Test: Talk to your clinician about checking serum B12 and a functional marker such as methylmalonic acid (MMA) or holo-transcobalamin for a clearer picture.
  • Diet: Increase B12-rich foods — eggs, fish, shellfish, red meat, poultry, dairy, and fortified foods.
  • Supplement: Consider a daily B12 supplement such as methylcobalamin 500–1,000 mcg or hydroxocobalamin as advised by your provider until levels are confirmed optimal.
  • Lifestyle: If you take acid-suppressing medications or have GI disorders that affect absorption, discuss alternative B12 routes (sublingual, subcutaneous, or high-dose oral) with your clinician.
One effect allele (AG) — slightly lower B12 tendency

If your genotype is AG, you carry one copy of the effect allele associated with a modest tendency toward lower blood B12. This can slightly reduce B12 availability for methionine synthase and may modestly affect the methionine–folate part of the methylation cycle. The consequence may be small for many people, but it could matter more when combined with low dietary B12, absorption issues, or other genetic factors that stress methylation.

Actionable steps

  • Test: Consider basic screening with serum B12; if results are borderline, ask about MMA or holo-transcobalamin.
  • Diet: Include reliable B12 sources such as fortified cereals, dairy, eggs, fish, and lean meats. For vegetarians and vegans, fortified foods and supplements are important.
  • Supplement: If testing shows low or borderline levels, a clinician-guided B12 supplement (methylcobalamin or hydroxocobalamin) can restore normalcy.
  • Monitor: Recheck levels if you start a supplement, change medications that affect absorption, or experience symptoms such as fatigue or cognitive changes.
No effect alleles (AA) — typical B12 levels expected

If your genotype is AA, your genetic signal is associated with typical circulating B12 levels. This means there is no clear genetic reason to expect lower B12 based on rs526934 alone. Normal B12 still remains essential for methylation, energy, brain health, and maintaining healthy homocysteine.

Actionable steps

  • Diet: Maintain a balanced intake of B12 through fish, poultry, meat, dairy, eggs, or fortified products.
  • Life stage considerations: If you are over 60, vegetarian, vegan, pregnant, or breastfeeding, consider periodic testing or routine supplementation, because absorption and dietary exposure can change needs.
  • Test if concerned: If you have unexplained fatigue, neuropathy, or macrocytic anemia, speak with your clinician about testing serum B12 and MMA.

Diet, supplements and lifestyle recommendations

Regardless of genotype, these practical steps support healthy B12 status and overall methylation balance.

  • Food sources: Prioritize animal-based sources such as beef, lamb, chicken, fish (salmon, trout, tuna), shellfish (clams, mussels), eggs, and dairy. Fortified plant foods include nutritional yeast and fortified cereals.
  • Supplement forms: Methylcobalamin and hydroxocobalamin are bioavailable options. Cyanocobalamin is widely used and effective for many people. Typical supplemental ranges for repletion or maintenance vary by individual and clinical guidance; common daily supplemental doses range from 50 to 1,000 mcg depending on need.
  • Absorption issues: Conditions like pernicious anemia, atrophic gastritis, celiac disease, Crohn disease, prior gastric surgery, or long-term use of proton pump inhibitors can impair B12 absorption. In such cases, higher-dose oral supplements or injectable B12 may be needed under medical supervision.
  • Functional support: Adequate folate (preferably as 5-MTHF when recommended), adequate B6, and dietary betaine help connected pathways. Avoid unnecessary high-dose folic acid without addressing B12, because imbalanced folate can mask B12 deficiency symptoms.
  • Lifestyle: Maintain a balanced diet, manage alcohol intake, and address gut health to support nutrient absorption. Regular checkups help catch changes in B12 status early.

Recommended blood tests to consider with your clinician

  • Serum B12
  • Methylmalonic acid (MMA) for more sensitive detection of deficiency
  • Holo-transcobalamin (active B12) when available
  • Complete blood count if anemia is suspected
  • Serum homocysteine when assessing methylation status

When to talk to a healthcare provider

  • If you have symptoms such as persistent fatigue, numbness or tingling in hands or feet, memory trouble, or signs of anemia
  • If you use medications that can reduce B12 absorption or have GI conditions that affect nutrient uptake
  • If blood tests show low or borderline B12, or elevated MMA or homocysteine
  • Before starting any new supplement regimen, especially at higher doses or if you are pregnant, breastfeeding, or have chronic health conditions

PlexusDx provides educational information about genetic results and potential implications but does not provide medical advice. Always consult your healthcare provider to interpret test results, order appropriate labs, and design personalized diet or supplement plans. Your clinician can integrate genetic information, lab results, medical history, and medications to create the safest and most effective approach for your health.