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Folate

Complete Testing & Optimization Guide

Optimal ranges, provider comparison, and strategies to improve your Folate levels

5/10
Providers Include It
VITAMINS &
Test Category
2-4x
Annual Testing
✓ Evidence-Based Information✓ Provider Comparison✓ Optimization Strategies✓ Clinical References

⚠️ Limited Availability

Only 5 providers include this test

📊 Test Category

Vitamins &Nutrients

🎯 Reference Range

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

Why Folate Testing Matters

⚠️ What Can Go Wrong

Abnormal Folate levels can indicate underlying health issues that may go undetected without proper testing. Regular monitoring helps catch problems early when they're most treatable.

✓ Benefits of Testing

Understanding your Folate levels enables targeted interventions, tracks treatment effectiveness, and helps optimize your overall health and performance.

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.

Bottom line: TSH and Free T4 alone miss people with conversion problems. Free T3 is the only way to know if you have enough active thyroid hormone at the tissue level.

Optimal vs Standard Reference Ranges

Range TypeLevelClinical Significance
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).

Note: Address Elevated Homocysteine

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.

Note: Fatigue, weakness|Shortness of breath, palpitations (megaloblastic anemia)|Pale or jaundiced skin|Glossitis (sore, red, smooth tongue)|Mouth ulcers, sores|Depression, low mood, irritability|Cognitive decline, memory problems, brain fog|Elevated homocysteine (>10 mcmol/L)|Increased CVD risk (via homocysteine)|Neural tube defects in pregnancy (spina bifida, anencephaly)|Premature graying of hair (rare)

Causes of Abnormal Folate

Low Folate:

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

High Folate:

  • 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

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 standard panel
✓ Blueprint
Included in standard panel
✓ Mito Health
Included in standard panel
✓ Function
Included in standard panel
✓ Marek Health
Included in standard panel
5 out of 10 providers include this test in their standard panels.

Compare Providers

ProviderIncludes TestAnnual CostTotal Biomarkers
Superpower logoSuperpower$199100+
WHOOP Advanced Labs logoWHOOP Advanced Labs$34965
Labcorp OnDemand logoLabcorp OnDemand$39830+
Life Extension logoLife Extension$48640+
Everlywell logoEverlywell$46883
Mito Health logoMito Health$798100+
InsideTracker logoInsideTracker$68048
Function Health logoFunction Health$499100+
Marek Health logoMarek Health$90070+
Blueprint Advanced logoBlueprint Advanced$1150110
Quest Health logoQuest Health$Varies75+

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Frequently Asked Questions About Folate

What does Folate test for?

Folate is a vitamins &nutrients biomarker that B vitamin important for cell division and DNA synthesis The normal reference range is >3.0 ng/mL, Optimal:7-15 ng/mL. Regular testing helps track changes and identify potential health issues early.

Which blood test providers include Folate?

5 out of 10 major blood testing providers include Folate in their standard panels. These include Superpower, Blueprint, Mito Health and others.

How often should I test Folate?

For most people, testing Folate 2-4 times per year is recommended to establish baseline levels and track trends. If you have abnormal results or are actively working to optimize this biomarker, more frequent testing (quarterly) may be beneficial. Always consult with your healthcare provider for personalized testing frequency recommendations.

What is the optimal range for Folate?

The standard laboratory reference range for Folate is >3.0 ng/mL, Optimal:7-15 ng/mL. However, many functional medicine practitioners recommend tighter "optimal" ranges for peak health and performance. Your ideal range may vary based on your age, sex, health goals, and other individual factors. Work with a healthcare provider familiar with optimal ranges to determine your target levels.

Do I need a doctor's order to test Folate?

Most direct-to-consumer blood testing services that include Folate provide the physician order as part of their service. However, some states have restrictions on direct-to-consumer testing. Check with your chosen provider about availability in your state and whether they provide the necessary physician authorization.

Why is Folate important for my health?

Essential for DNA synthesis and red blood cell formation. Critical in pregnancy to prevent neural tube defects. Deficiency causes anemia.

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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 and before making decisions about blood testing.