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FUT2, Secretor Status, and the Methionine Cycle: What Your Genotype May Mean for Methylation and Nutrient Support

The FUT2 gene affects whether your ABO blood group antigens are present in bodily fluids like saliva and gut mucus. That secretor status can shape the gut environment, influence which bacteria thrive, and indirectly affect nutrient interactions in the digestive tract. Because vitamin B12 and folate are essential cofactors for the Methionine Cycle in the Methylation Pathway, differences in secretor status may influence methylation efficiency in some people.

How FUT2 Connects to Methylation Biology

  • FUT2 encodes an enzyme that places ABO antigens on mucosal surfaces. People who are non-secretors do not express these antigens in saliva and gut mucus.
  • Those mucosal changes can alter the gut microbiome composition, including levels of bifidobacteria, and can influence immune signaling at mucosal surfaces.
  • Some bacteria, including Helicobacter pylori, use mucosal antigens as attachment sites. H. pylori infection has been linked to reduced stomach acid and gastritis, which can impair vitamin B12 absorption.
  • Vitamin B12 is a required cofactor for methionine synthase (MTR), the enzyme that converts homocysteine to methionine. Methionine is needed to form S-adenosylmethionine (SAMe), the body’s main methyl donor.
  • Therefore, factors that reduce B12 availability or absorption can hinder methylation capacity and raise homocysteine levels for some individuals.

Practical Strategies to Support Methylation

Regardless of genotype, lifestyle and diet shape methylation health. If you are concerned about methylation or nutrient absorption, consider these general approaches and discuss them with your healthcare provider.

  • Diet: Eat a balanced diet rich in B12 sources (animal proteins, fortified foods), folate (leafy greens, legumes), choline (eggs, soy, cruciferous vegetables), and betaine (beets, spinach). Include a variety of fiber-rich plants to support a healthy microbiome.
  • Testing: Check serum B12, methylmalonic acid (MMA), red blood cell folate, homocysteine, and, when appropriate, H. pylori testing to evaluate absorption and infection status.
  • Supplement options: If absorption is a concern, consider sublingual methylcobalamin or cyanocobalamin, high-dose oral methylcobalamin, or intramuscular B12 injections under medical supervision. A folate supplement as methylfolate may be recommended if there are folate-related issues. A balanced B complex can help provide cofactors for methylation.
  • Address digestion: Support stomach acid when indicated under medical guidance. Treating H. pylori if present and optimizing digestive function can improve B12 absorption.
  • Gut health: Foster a diverse microbiome with prebiotics (fruits, vegetables, resistant starch) and fermented foods. Probiotics targeted to support bifidobacteria may be helpful for some people.
  • Lifestyle: Prioritize sleep, stress management, regular movement, and limit excessive alcohol, which can impair nutrient absorption and methylation.

Genetic Interpretation

Two effect alleles (AA) — Non-secretor

If your genotype at rs601338 is AA, you carry two copies of the effect allele, leading to loss of FUT2 function and a non-secretor status. Non-secretors do not express ABO antigens in saliva and gut mucus. This change in mucosal glycosylation is associated with shifts in gut microbiome composition, often including reduced bifidobacteria, and with altered mucosal immune interactions.

While direct evidence that non-secretor status definitively impairs vitamin B12 or folate absorption is limited, non-secretor-associated changes to the gut environment could increase susceptibility to infections or dysbiosis that indirectly reduce B12 availability. For example, an increased risk of colonization by certain bacteria or altered interactions with H. pylori could contribute to reduced stomach acid in susceptible individuals, which may compromise B12 uptake.

Practical considerations for non-secretors:

  • Monitor serum B12, methylmalonic acid, homocysteine, and red blood cell folate periodically.
  • If B12 markers are low or if there are signs of poor absorption, discuss sublingual or injectable B12 with your provider to bypass gastrointestinal uptake barriers.
  • Support gut health with prebiotic fibers and targeted probiotic strategies that encourage bifidobacteria populations.
  • Address digestive issues, including testing and treating H. pylori when clinically indicated, to protect stomach acid and intrinsic factor function.
  • Ensure adequate dietary intake of B12, folate, choline, and betaine to support the Methionine Cycle.
One effect allele (AG) — Likely secretor with possible subtle changes

If your genotype is AG at rs601338, you carry one effect allele and one non-effect allele. This genotype is generally associated with secretor status, meaning ABO antigens are usually present in bodily fluids, though expression might be somewhat reduced compared to individuals with two non-effect alleles.

The impact on the gut microbiome and immune signaling is typically less pronounced than in AA non-secretors. Evidence that AG status alters vitamin B12 or folate absorption is limited and inconclusive. Small shifts in bifidobacteria have been reported in some studies, but these shifts do not necessarily translate to clinically meaningful nutrient deficiencies for most people.

Practical considerations for AG carriers:

  • Maintain a diet adequate in B12 and folate and include foods rich in choline and betaine for methylation support.
  • Consider periodic monitoring of B12 and folate status if you have symptoms suggestive of deficiency or if other risk factors for poor absorption are present.
  • Address gastrointestinal symptoms promptly. Treating infections and improving digestive function helps protect nutrient absorption.
  • Use supplementation strategies under healthcare guidance only when testing or symptoms indicate need.
Zero effect alleles (GG) — Secretor, typical mucosal glycosylation

If your genotype is GG for rs601338, you carry two copies of the non-effect allele and are associated with typical secretor status. ABO antigens are expressed on mucosal surfaces and in bodily fluids. This status is linked to common patterns of gut mucosal glycosylation, a microbiome often richer in bifidobacteria, and normal mucosal immune signaling.

There is no strong evidence that secretor status directly impairs B12 or folate absorption. With sufficient dietary intake and normal digestive function, Methionine Cycle activity in the methylation pathway is likely to be well supported in most GG individuals.

Practical considerations for GG carriers:

  • Continue a balanced diet with reliable sources of B12 and folate.
  • Address digestive health as needed and test for deficiencies only when clinically appropriate.
  • Use supplements when testing or symptoms indicate necessity, under medical supervision.

When to Talk with Your Healthcare Provider

  • If you have symptoms of B12 deficiency such as fatigue, numbness, memory changes, or anemia.
  • If blood work shows low B12, elevated methylmalonic acid, low folate, or high homocysteine.
  • If you have persistent digestive symptoms, a history of H. pylori infection, or conditions that affect stomach acid or intrinsic factor.
  • If you are considering high-dose oral, sublingual, or injectable supplements to address suspected absorption issues.

Disclaimer: PlexusDx provides genetic education and interpretation only. This information is not medical advice. Always consult your healthcare provider before making changes to diet, supplements, or treatment based on genetic information.