Calculator

Methylation Load Estimator

Compare your daily methyl-donor intake (folate, B12, choline, betaine) and cofactors against reference targets, with MTHFR status factored in.

Read this first. This is an educational intake estimator, not a diagnostic tool. It cannot measure your methylation status; that requires blood work (homocysteine, serum folate, B12, methylmalonic acid) ordered by a clinician. The American College of Medical Genetics and Genomics recommends against MTHFR polymorphism testing in routine clinical care because genotype alone rarely changes management (Hickey et al., reaffirmed 2020). If you already have a genotype result from a consumer test, this tool puts it in context; it is not a reason to get tested.

MTHFR genotype (if known)

In vitro enzyme activity relative to normal: C677T heterozygous roughly 30 to 40 percent reduced, C677T homozygous roughly 70 percent reduced, A1298C variants smaller effects. If untested, leave as Unknown.

Sex (sets the choline adequate intake)

Dietary folate sources (servings per day)

Leafy greens

1 cup raw or 1/2 cup cooked; ~100 mcg DFE each

Legumes

1/2 cup cooked lentils, beans, chickpeas; ~140 mcg DFE each

Fortified grains

Enriched bread, pasta, cereal; ~60 mcg folic acid each

Supplements

Folate form

Folate dose (mcg)

Enter mcg of the compound itself, not "mcg DFE" from the label

B12 form

B12 dose (mcg)

Vitamin B6 (mg/day)

From supplements only; US UL is 100 mg

Riboflavin, B2 (mg/day)

MTHFR cofactor; the Ward/McNulty trials used 1.6 mg/day

Supplemental choline (mg/day)

Choline bitartrate is ~41% choline by weight; enter elemental choline if the label states it

Whole eggs per day

~147 mg choline each

Betaine / TMG (mg/day)

Vegan or mostly plant-based (no reliable dietary B12)

Current symptoms (optional)

These do not diagnose anything. They only adjust which lab conversations the results suggest raising with your clinician. Every symptom below has many common causes unrelated to methylation.

Persistent fatigue Low mood or brain fog Tingling or numbness in hands/feet Clinician told me my homocysteine is elevated Anxiety, irritability, or insomnia that started after B-vitamin supplements

Flags and notes

How this works

MTHFR (methylenetetrahydrofolate reductase) converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the methyl donor that B12-dependent methionine synthase uses to remethylate homocysteine to methionine, which feeds S-adenosylmethionine synthesis. MTHFR requires FAD, made from riboflavin, as its cofactor. The common C677T variant produces a thermolabile enzyme with roughly 70 percent reduced in vitro activity in TT homozygotes and 30 to 40 percent reduced in CT heterozygotes; A1298C has smaller effects. A parallel liver and kidney pathway remethylates homocysteine using betaine, which the body also makes by oxidizing choline; this is why choline and betaine count as methyl donors here.

The calculator sums folate intake in dietary folate equivalents (DFE): food folate counts 1:1, and folic acid from fortified food or supplements counts at 1.7x per the Institute of Medicine conversion (methylfolate and folinic acid are treated the same way as an approximation). Serving estimates come from USDA averages: about 100 mcg DFE per leafy-green serving, 140 mcg per half cup of cooked legumes, and 60 mcg folic acid (102 DFE) per fortified grain serving, plus a 110 mcg DFE baseline for a mixed diet. Totals are compared against the 400 mcg DFE RDA, the 1,000 mcg upper limit for synthetic folic acid, and choline adequate intakes of 550 mg (men) or 425 mg (women). Absorbed B12 is estimated as a saturable intrinsic-factor pathway of about 1.5 mcg per dose plus roughly 1.2 percent passive diffusion, which is why a 500 mcg tablet yields only about 7 mcg absorbed.

Two honest points about the evidence. First, the best-replicated genotype-specific intervention is not high-dose folate; it is riboflavin. In randomized trials from the Ward and McNulty group at Ulster University, 1.6 mg/day riboflavin for 16 weeks lowered systolic blood pressure by roughly 6 to 9 mmHg in people with the 677TT genotype, with no effect in CC or CT. That is a blood-pressure finding, not a general "methylation fix". Second, "overmethylation" symptom lists and the claim that niacin relieves them come from case reports and practitioner anecdote, not controlled trials; this tool flags high methylfolate doses because doses above about 1,000 mcg have no established benefit for healthy people, not because overmethylation is a validated syndrome.

Evidence grades used in results: RCT (randomized trial evidence), Guideline (reference intakes or professional-society guidance), Observational (association studies only), and Anecdotal (case reports and practitioner claims without controlled trials). Where a flag rests on weak evidence, it says so.

References

Wilson CP, et al. Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial. Hypertension. 2013;61(6):1302-1308.

McNulty H, et al. Evidence of a Role for One-Carbon Metabolism in Blood Pressure: Can B Vitamin Intervention Address the Genetic Risk of Hypertension Owing to a Common Folate Polymorphism? Curr Dev Nutr. 2020;4(1):nzz102.

Maruvada P, et al. Knowledge gaps in understanding the metabolic and clinical effects of excess folates/folic acid: a summary, and perspectives, from an NIH workshop. Am J Clin Nutr. 2020;112(5):1390-1403.

Hickey SE, et al. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013;15(2):153-156. Addendum: Genet Med. 2020;22(12):2125.