Folate

B vitamin important for cell division and DNA synthesis

12/22Providers
Vitamins &NutrientsCategory
>3.0 ng/mL, Optimal:Reference

Widely Available

12 of 22 providers

Category

Vitamins &Nutrients

Reference Range

>3.0 ng/mL, Optimal:7-15 ng/mL

What is Folate?

Folate (vitamin B9) is a water-soluble vitamin essential for DNA synthesis, cell division, methylation, and red blood cell formation. The term "folate"refers to the natural form found in foods (leafy greens, legumes, citrus), while "folic acid"is the synthetic form used in supplements and fortified foods. Folate is critical during periods of rapid cell division—pregnancy, infancy, adolescence—and deficiency causes neural tube defects (spina bifida) in developing fetuses, which is why folic acid fortification of grain products has been mandatory in the US since 1998.

Here's the critical insight:not all folate is created equal. Folic acid (synthetic) must be converted to the active form, 5-methyltetrahydrofolate (5-MTHF or methylfolate), via the MTHFR enzyme. ~40% of people have MTHFR gene variants (C677T or A1298C) that reduce enzyme activity by 30-70%, impairing folic acid metabolism. These individuals may have normal serum folate but functional deficiency at the cellular level. Methylfolate supplements bypass this issue entirely and are preferred, especially for those with MTHFR variants, depression, or cardiovascular disease.

Folate works in tandem with B12 in the methylation cycle, converting homocysteine→methionine. Deficiency of either vitamin causes elevated homocysteine (>10 mcmol/L), a risk factor for cardiovascular disease, stroke, cognitive decline, and Alzheimer's. If folate is low but B12 is also low, you MUST correct B12 first—giving folate alone can mask B12 deficiency anemia while allowing irreversible neurological damage to progress.

Why Folate Matters for Longevity

  • DNA synthesis and cell division:Folate is required for synthesis of purines and pyrimidines (building blocks of DNA). Deficiency impairs rapidly dividing cells, causing megaloblastic anemia.
  • Methylation cycle:Folate (as 5-MTHF) is the methyl donor for homocysteine→methionine conversion. Adequate folate lowers homocysteine, reducing CVD and stroke risk.
  • Neural tube defect prevention:Folate is critical in first 28 days of pregnancy for neural tube closure. Deficiency causes spina bifida, anencephaly. Folic acid supplementation (400-800 mcg) reduces NTD risk by 70%.
  • Cardiovascular health:Folate lowers homocysteine, protecting against atherosclerosis, heart attack, and stroke. Low folate associated with 30-50% higher CVD risk.
  • Brain health and mood:Folate supports neurotransmitter synthesis (serotonin, dopamine). Deficiency linked to depression (especially treatment-resistant depression), cognitive decline, dementia.
  • Cancer prevention (controversial):Adequate folate may protect against colorectal cancer by supporting DNA repair and methylation. However, excessive folic acid supplementation (>1000 mcg) may promote existing cancers.

Optimal vs Standard Ranges

Range TypeLevelSignificance
Optimal (Longevity)>20 ng/mLTarget for optimal methylation, brain health, CVD prevention. Many functional medicine doctors target >15-20 ng/mL.
Adequate (Standard)>10 ng/mLMeets standard guidelines. Sufficient to prevent megaloblastic anemia but may be suboptimal for methylation and homocysteine.
Suboptimal4-10 ng/mLLow-normal. May have elevated homocysteine. Consider supplementation, especially if MTHFR variant or CVD risk factors.
Deficient<4 ng/mLFrank deficiency. Causes megaloblastic anemia, elevated homocysteine, increased NTD risk in pregnancy. Requires immediate folate supplementation.
Standard lab range: >3.0 ng/mL, Optimal:7-15 ng/mL

How to Optimize Folate

1. Very High

>20 ng/mL

2. Seen with folic acid supplementation (>400 mcg/day). Generally safe but excessive folic acid (>1000 mcg) may mask B12 deficiency or promote cancer growth (controversial).

Folate Supplementation (Dose and Form)

3. Methylfolate (5-MTHF):400-1000 mcg/day. PREFERRED form, especially if MTHFR gene variant, depression, or CVD. Bypasses MTHFR enzyme, directly provides active folate. | Folic acid:400-800 mcg/day. Synthetic form, requires conversion via MTHFR. Adequate for most people but inferior to methylfolate. Avoid doses >1000 mcg unless medically indicated. | Folinic acid (calcium folinate):400-800 mcg/day. Intermediate form, partially converted to 5-MTHF. Alternative if methylfolate not available. | Pregnancy:400-800 mcg/day folic acid or methylfolate starting before conception and throughout first trimester to prevent neural tube defects.

Dietary Sources of Folate

4. Leafy greens:Spinach, kale, collards, romaine (highest food sources, 100-300 mcg per cup cooked). | Legumes:Lentils, chickpeas, black beans (200-350 mcg per cup). | Citrus:Oranges, grapefruit (50-70 mcg per fruit). | Avocado:1 medium avocado ~160 mcg. | Fortified grains:Bread, pasta, cereal (100-400 mcg per serving, added folic acid). | Liver:Beef or chicken liver (extraordinarily high, 200-600 mcg per 3 oz, but avoid in pregnancy due to vitamin A toxicity risk).

Optimize Methylation Cofactors

5. Folate + B12 + B6 work synergistically in methylation and homocysteine metabolism. | Vitamin B12:500-1000 mcg/day (methylcobalamin preferred). MUST check B12 before supplementing folate—folate can mask B12 deficiency. | Vitamin B6:25-50 mg/day. Cofactor for homocysteine→cysteine conversion (transsulfuration pathway). | Betaine (TMG):500-2000 mg/day. Alternative methyl donor;can lower homocysteine if folate/B12 insufficient.

MTHFR Testing and Methylfolate

Symptoms of Abnormal Folate

Low Folate

  • MTHFR gene variants:C677T and A1298C reduce MTHFR enzyme activity by 30-70%. ~40% of population has one variant;~10% have two (homozygous C677T=70% reduced activity).
  • If you have MTHFR variant, elevated homocysteine, or treatment-resistant depression, use methylfolate instead of folic acid.
  • Testing:Genetic testing (23andMe, other services) or functional testing (homocysteine—if >10 mcmol/L despite adequate folate intake, suggests MTHFR issue).

High Folate

  • Elevated homocysteine (>10 mcmol/L) indicates functional folate or B12 deficiency even if serum levels appear normal.
  • Target:<7-8 mcmol/L optimal;<10 acceptable. Levels >15 increase CVD risk by 50-100%.
  • Folate + B12 + B6 supplementation lowers homocysteine by 25-30%. Use methylfolate (800-1000 mcg) + methylB12 (1000 mcg) + B6 (25-50 mg). Retest in 3 months.

Causes of Abnormal Folate

Low Levels

  • Deficiency <4 ng/mL causes megaloblastic anemia and elevated homocysteine. Levels 4-10 ng/mL may cause subclinical deficiency (check homocysteine).

High Levels

  • Excessive folic acid supplementation (>1000 mcg/day) may:
  • Mask B12 deficiency:Corrects anemia but allows neurological damage to progress (DANGEROUS).
  • Promote cancer growth (controversial):High folic acid may accelerate existing colorectal or prostate cancer. Natural folate from food does NOT have this risk.
  • Unmetabolized folic acid (UMFA):Accumulates in blood if intake exceeds conversion capacity, potentially impairing immune function.

When to Retest

  • High folate from supplementation (>20 ng/mL) is generally safe from methylfolate. High folic acid (>1000 mcg/day) has potential risks.

Scientific Evidence

Dietary insufficiency:Low intake of leafy greens, legumes, citrus, fortified grains.|Malabsorption:Celiac disease, Crohn's disease, tropical sprue, bacterial overgrowth (SIBO).|Medications:Methotrexate (chemotherapy, rheumatoid arthritis), sulfasalazine, anticonvulsants (phenytoin), metformin.|Alcohol abuse:Impairs folate absorption and increases excretion.|MTHFR gene variants:C677T or A1298C reduce folic acid conversion to active form, causing functional deficiency despite normal serum folate.|Pregnancy and lactation:Increased folate requirements (600-800 mcg/day). Deficiency increases NTD risk.|Chronic hemolytic anemia:Increased cell turnover consumes folate (sickle cell, thalassemia).

Excessive folic acid supplementation (>1000 mcg/day). Natural folate from food cannot cause toxicity.|Fortified foods + supplements:Easy to exceed 1000 mcg/day if consuming fortified grains + multivitamin + B-complex.|Rarely, kidney disease (impaired excretion).

Source:Baseline:Check serum folate if symptoms (fatigue, anemia, depression) or risk factors (low vegetable intake, malabsorption, alcohol use, MTHFR variant).|Check homocysteine:More sensitive marker of functional folate status. If homocysteine >10 mcmol/L, consider folate (and B12) deficiency even if serum folate appears normal.|After starting supplementation:Retest folate and homocysteine in 3 months. Goal:folate >15 ng/mL, homocysteine <8 mcmol/L.|Pregnancy:Baseline folate before conception. Supplement 400-800 mcg/day throughout pregnancy.|If on methotrexate:Monitor folate closely;may need leucovorin (folinic acid) rescue to prevent toxicity.

Folate and Neural Tube Defects

Folic acid supplementation (400-800 mcg/day) started before conception reduces NTD risk by 70%. US grain fortification (since 1998) reduced NTD prevalence by 25-30%. Neural tube closes by day 28 of pregnancy—before most women know they're pregnant—hence recommendation for all women of childbearing age to supplement.

Source:MRC Vitamin Study Research Group. Prevention of neural tube defects with folic acid. Lancet. 1991;338(8760):131-137.

Folate and Homocysteine/CVD

Folate supplementation lowers homocysteine by 25-30%. Meta-analyses show folic acid supplementation (800 mcg/day) reduces stroke risk by 10-20%, with greater benefit in populations without grain fortification. CVD benefit is modest in RCTs, possibly because started too late in disease process or because homocysteine is a marker, not a cause.

Source:Wang X, et al. Efficacy of folic acid supplementation in stroke prevention:a meta-analysis. Lancet. 2007;369(9576):1876-1882.

Folate and Depression

Folate deficiency is common in depression (15-40% of depressed patients have low folate). Low folate associated with poor antidepressant response. Methylfolate (15 mg/day) improves treatment-resistant depression when added to SSRIs in RCTs. Methylfolate enhances serotonin, dopamine, and norepinephrine synthesis.

Source:Papakostas GI, et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression. Am J Psychiatry. 2012;169(12):1267-1274.

Folate and Cognitive Decline

Low folate (<10 ng/mL) associated with 2-3x higher dementia risk. Folate + B12 + B6 supplementation slows cognitive decline and brain atrophy in elderly with elevated homocysteine. Benefits greatest when started early (MCI stage) before significant dementia.

Source:Durga J, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults. Lancet. 2007;369(9557):208-216.

Which Providers Test Folate?

Superpower
Included in panel
Blueprint
Included in panel
Mito Health
Included in panel
Function
Included in panel
Marek Comp.
Included in panel
Marek Complete
Included in panel
Marek Exec.
Included in panel
Empirical Health
Included in panel
SiPhox Health
Included in panel
Hims Adv.
Included in panel
Vitality Std
Included in panel
Vitality Elite
Included in panel

Full Provider Comparison

ProviderIncludesAnnual CostBiomarkers
SuperpowerSuperpower✓$199100+ (150 with ratios)
WHOOP Advanced LabsWHOOP Advanced Labs—$34965
Labcorp OnDemandLabcorp OnDemand—$39830+
Life ExtensionLife Extension—$48640+
EverlywellEverlywell—$46883
Mito HealthMito Health✓$349100+
InsideTrackerInsideTracker—$68054
Function HealthFunction Health✓$365100+
Marek Health BaseMarek Health Base—$25065
Marek Health ComprehensiveMarek Health Comprehensive✓$49570+
Marek Health CompleteMarek Health Complete✓$895100+
Marek Health ExecutiveMarek Health Executive✓$1950150+
BlueprintBlueprint—$399100+
Quest HealthQuest Health—$Varies75+
Empirical HealthEmpirical Health✓$190100+
Oura Health PanelsOura Health Panels—$9950
SiPhox HealthSiPhox Health✓$12560
Hims Labs BaseHims Labs Base—$19950
Hims Labs AdvancedHims Labs Advanced✓$499120+
HealthspanHealthspan—$418880+
Vitality Blueprint StandardVitality Blueprint Standard✓$37585
Vitality Blueprint EliteVitality Blueprint Elite✓$700129

Ready to Test Folate?

12 providers include this biomarker in their panels

View Top ProviderCompare All Providers

Frequently Asked Questions

What does Folate test for?
Folate is a vitamins &nutrients biomarker. B vitamin important for cell division and DNA synthesis The normal reference range is >3.0 ng/mL, Optimal:7-15 ng/mL.
Which providers include Folate?
12 of 22 providers include this test:Superpower, Blueprint, Mito Health, Function and others.
How often should I test Folate?
For most people, testing 2-4 times per year is recommended to establish baseline levels and track trends. Consult your healthcare provider for personalized recommendations.
What is the optimal range?
The standard reference range is >3.0 ng/mL, Optimal:7-15 ng/mL. Many functional medicine practitioners recommend tighter optimal ranges for peak health. Your ideal range may vary based on age, sex, and health goals.
Why is Folate important?
Essential for DNA synthesis and red blood cell formation. Critical in pregnancy to prevent neural tube defects. Deficiency causes anemia.

Medical Disclaimer

This information is for educational purposes only and is not medical advice. Always consult with a qualified healthcare provider about your specific health needs.