HSA | FSA CARDS ARE NOW ACCEPTED

ALDH1L1 and One-Carbon Metabolism: What Your Genotype Means

The ALDH1L1 gene encodes the enzyme 10-formyltetrahydrofolate dehydrogenase, a central regulator of formate metabolism and the body’s one-carbon pool. This enzyme converts 10-formyl-THF into tetrahydrofolate (THF) and carbon dioxide. In practical terms, ALDH1L1 helps decide whether one-carbon units are used for nucleotide synthesis (DNA and RNA) or are conserved for methyl donor production via 5-methyltetrahydrofolate (5-MTHF) and the methionine cycle. That decision affects production of S-adenosylmethionine (SAMe), an essential methyl donor for DNA methylation, neurotransmitter balance, and detoxification reactions.

Variants that reduce ALDH1L1 activity can shift one-carbon flow, potentially causing accumulation of 10-formyl-THF, altered nucleotide synthesis, and reduced methylation efficiency. Optimal function depends on adequate folate, vitamin B12, choline, serine and glycine availability, and healthy mitochondrial and antioxidant systems that rely on NADPH. The sections below explain how different rs1127717 genotypes may influence ALDH1L1 function and offer actionable lifestyle, dietary, supplement, and testing considerations to support balanced one-carbon metabolism.

Genetic Interpretation

2 effect alleles — CC (higher likelihood of altered ALDH1L1 function)

What this means: Carrying two copies of the effect allele (CC) is associated with altered ALDH1L1 function or expression. This may shift the enzyme’s activity toward clearing 10-formyl-THF to CO2 and can change the availability of one-carbon units and cellular NADPH production.

Potential implications:

  • Less efficient conservation of one-carbon units for methylation under some conditions
  • Possible shifts in nucleotide synthesis balance
  • Greater reliance on adequate folate, B12, choline, serine, and glycine to maintain methylation capacity
  • Increased importance of antioxidant and NADPH-supporting strategies to protect redox balance

Actionable considerations:

  • Ensure consistent dietary folate from leafy greens and folate-rich foods; consider 5-MTHF supplementation if recommended by a clinician
  • Optimize B12 status (especially methylcobalamin forms if needed) to support remethylation of homocysteine
  • Include choline-rich foods (eggs, soy, cruciferous vegetables) to support methyl group supply and membrane health
  • Support serine and glycine intake through protein-rich foods, legumes, and certain vegetables
  • Support antioxidant defenses and NADPH generation with dietary antioxidants (vitamin C, vitamin E, polyphenol-rich foods) and lifestyle measures that reduce oxidative stress
  • Monitor labs (homocysteine, serum folate, B12, methylmalonic acid) with a healthcare provider to tailor interventions
1 effect allele — CT (moderate impact on ALDH1L1)

What this means: Carrying one effect allele (CT) is associated with a moderate impact on ALDH1L1-mediated oxidation of 10-formyl-THF and NADPH generation. Under everyday conditions function may be near typical, but stressors can reveal limitations.

Potential implications:

  • Moderate sensitivity to folate and methyl donor availability when demands increase (illness, stress, rapid cell growth)
  • Possible transient reductions in methylation efficiency under oxidative or anabolic stress

Actionable considerations:

  • Maintain a balanced diet with regular sources of folate, B12, choline, and quality protein to supply serine and glycine
  • Consider periodic lab checks (homocysteine, folate, B12) if planning pregnancy, when recovering from illness, or when under chronic stress
  • Support mitochondrial and antioxidant health through aerobic exercise, sleep, and foods high in antioxidants
0 effect alleles — TT (typical ALDH1L1 function)

What this means: Carrying two copies of the non-effect allele (TT) is associated with typical ALDH1L1 function. The enzyme is expected to facilitate physiological oxidation of 10-formyl-THF to support NADPH production while allowing appropriate one-carbon turnover.

Potential implications:

  • Normal balance of one-carbon flux between nucleotide synthesis and methylation under usual conditions
  • Standard recommendations for supporting folate and methyl donor status generally apply

Actionable considerations:

  • Follow a balanced, nutrient-dense diet with adequate folate, B12, choline, and protein
  • Encourage lifestyle habits that support mitochondrial and redox health
  • Screen labs as part of routine care or if clinical concerns arise

Dietary Recommendations

  • Prioritize natural folate: spinach, kale, asparagus, Brussels sprouts, lentils, and beans. If supplementation is recommended by your clinician, consider active folate (5-MTHF) forms for efficient use.
  • Optimize B12: animal proteins, fish, dairy, fortified foods, or clinician-directed supplementation when levels are low. Monitor methylmalonic acid to confirm functional B12 status.
  • Boost choline intake: eggs, soy, liver, cruciferous vegetables, and certain nuts and seeds to support methylation and membrane synthesis.
  • Include serine/glycine precursors: quality proteins (poultry, fish, legumes), soy, and some vegetables help maintain one-carbon precursor pools.
  • Eat antioxidant-rich foods: berries, dark leafy greens, nuts, seeds, and colorful vegetables to support NADPH-dependent antioxidant defenses.

Supplement Suggestions (Discuss with Your Clinician)

  • Active folate (5-MTHF) if low folate status or if advised by your clinician
  • Methylcobalamin or appropriate B12 formulation when deficiency is suspected
  • Choline (dietary or supplemental) if dietary intake is low or increased demand exists
  • Antioxidant support such as vitamin C, vitamin E, and targeted polyphenols when indicated
  • Consider a balanced B-complex if multiple B vitamin inputs are low or if higher metabolic demand is present

Lifestyle and Health Monitoring

  • Avoid excessive alcohol intake. Alcohol can interfere with folate utilization and methylation processes.
  • Prioritize good sleep and stress management. Chronic stress increases demand on one-carbon metabolism for repair and detoxification.
  • Include regular aerobic exercise and strength training to support mitochondrial function and overall metabolic health.
  • Maintain a balanced diet focusing on whole foods rather than isolated nutrients whenever possible.
  • Work with your healthcare provider to monitor labs such as homocysteine, serum folate, serum B12, methylmalonic acid, and basic metabolic panels when making changes or if symptoms arise.

When to Talk with Your Healthcare Provider

  • Before beginning any supplement regimen or making significant dietary changes
  • If you are pregnant, planning pregnancy, or breastfeeding
  • If you have unexplained fatigue, cognitive changes, or lab abnormalities related to folate or B12 status
  • If you are receiving treatments that increase one-carbon demand, such as certain medications or intensive physical training

PlexusDx provides educational information about genetic predispositions only. This content is not medical advice. Always consult with your healthcare provider before making medical, dietary, or lifestyle changes based on genetic results.