Folate
Folate (vitamin B9) is needed for DNA synthesis, red blood cell formation, and methylation reactions. Deficiency causes macrocytic anemia and, in pregnancy, neural tube defects, and can result from poor intake, alcohol use, malabsorption, or certain medications. Most grain products are fortified, so frank deficiency is less common today in high-income countries.
Units: ng/mL; some labs report nmol/L (nmol/L = ng/mL × 2.27). Check the units on your report before comparing to any range here.
Optimal range: who says what
Institutions, researchers and practitioners draw the line in different places. Each position is listed with who holds it and, where a document states it, a link. How we verify ranges.
- Institution or studyPlasma folate ≥25.5 nmol/L (about 11 ng/mL)Chen et al. 2019 (Am J Clin Nutr), folic acid trial in ChinaThe plasma concentration that matched the population RBC folate threshold of 906 nmol/L (400 ng/mL) for neural tube defect prevention, in 1,673 women of reproductive age
- Institution or studyDeficiency risk below 7 nmol/L serum (about 3 ng/mL) or 305 nmol/L RBCCDC NHANES analysis (Pfeiffer et al. 2016)Cutoffs for megaloblastic-anemia risk derived with the microbiologic assay; applying them to other assays misclassifies status
- Institution or studySerum above 3 ng/mL; RBC above 140 ng/mLNIH Office of Dietary Supplements fact sheetAdequacy cutoffs; serum folate follows recent intake, while RBC folate reflects longer-term status
- Lab reference interval>3.0 ng/mLWhat a lab report flags against. A lab interval is not an optimal target.
13 of 21 itemized panels
Vitamins & Nutrients
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.
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.
Interpretation bands (curated, PMID-backed)
Holder: OptimizeBiomarkers editorial synthesis of: Folate Biomarkers, Folate Intake, and Risk of Death From All Causes, Cardiovascular Disease, and Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies (Fallah et al., 2025); Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials (Li et al., 2016); Association of folate intake with cardiovascular-disease mortality and all-cause mortality among people at high risk of cardiovascular-disease (Xu et al., 2022). No single paper sets these cutoffs; for attributed targets see who says what.
Optimal (Longevity)>20 ng/mL▼
- Target for optimal methylation, brain health, CVD prevention
- Many functional medicine doctors target >15-20 ng/mL
Adequate (Standard)>10 ng/mL▼
- Meets standard guidelines
- Sufficient to prevent megaloblastic anemia but may be suboptimal for methylation and homocysteine
Suboptimal4-10 ng/mL▼
- Low-normal
- May have elevated homocysteine
- Consider supplementation, especially if MTHFR variant or CVD risk factors
Deficient<4 ng/mL▼
- Frank deficiency
- Causes megaloblastic anemia, elevated homocysteine, increased NTD risk in pregnancy
- Requires immediate folate supplementation
- Folate Biomarkers, Folate Intake, and Risk of Death From All Causes, Cardiovascular Disease, and Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.
- Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials.
- Association of folate intake with cardiovascular-disease mortality and all-cause mortality among people at high risk of cardiovascular-disease.
What raises or lowers Folate
Causes of high Folate
- 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).
Causes of low Folate
- 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).
Symptoms when Folate is high or low
When high
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.
High folate from supplementation (>20 ng/mL) is generally safe from methylfolate. High folic acid (>1000 mcg/day) has potential risks.
When low
- 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)
Deficiency <4 ng/mL causes megaloblastic anemia and elevated homocysteine. Levels 4-10 ng/mL may cause subclinical deficiency (check homocysteine).
How to move Folate
Effect sizes (how much something moves the marker) appear only where the paper cited under the item states them. Talk to your clinician before starting or changing any medication or supplement.
Folate Supplementation (Dose and Form)
- 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
- 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
- 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
- MTHFR gene variants: C677T and A1298C reduce MTHFR enzyme activity. Carrying one variant is common; two copies of C677T (homozygous) cause the larger loss of activity, and how common that is varies by ancestry.
- 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).
Address Elevated Homocysteine
- Elevated homocysteine (>10 mcmol/L) indicates functional folate or B12 deficiency even if serum levels appear normal.
- Homocysteine targets differ by source; the homocysteine page lists who says what. Levels above 15 mcmol/L are associated with higher cardiovascular risk.
- In a meta-analysis of 12 trials, folic acid (0.5-5 mg daily) lowered homocysteine by about 25%, vitamin B12 added about 7% more, and B6 added no significant effect (Homocysteine Lowering Trialists' Collaboration 1998). Use methylfolate (800-1000 mcg) + methylB12 (1000 mcg) + B6 (25-50 mg). Retest in 3 months.
When to retest
- 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. Compare folate with the positions in who says what above; homocysteine positions are on its own page.
- 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.
Scientific Evidence
Folic Acid and Neural Tube Defects
In the MRC Vitamin Study, 1,817 women with a previous affected pregnancy were randomized around conception. Folic acid prevented 72% of neural tube defects (relative risk 0.28); a mix of other vitamins had no significant effect.
Folic Acid and Stroke Prevention
A meta-analysis of 8 randomized trials found folic acid reduced stroke risk by 18% (relative risk 0.82, borderline significance). The effect was larger in trials lasting over 36 months, trials that lowered homocysteine by more than 20%, regions without full grain fortification, and people without prior stroke.
Source: Efficacy of folic acid supplementation in stroke prevention: a meta-analysis.
L-Methylfolate in SSRI-Resistant Depression
In two trials of adults whose depression had not fully responded to an SSRI, adding L-methylfolate at 7.5 mg/day showed no benefit. At 15 mg/day it improved response rates and symptom scores over placebo, with a number needed to treat of about six.
Folic Acid and Cognitive Function
In the FACIT trial, 818 adults aged 50-70 with raised homocysteine took 800 µg folic acid daily or placebo for 3 years. Homocysteine fell 26%, and memory, information processing speed, and sensorimotor speed declined less with folic acid.
Which Providers Test Folate?
Cheapest: Empirical Health at $190/year. Most comprehensive: Function Health, 160+ biomarkers for $365/year.
13 panels that include it, cheapest first
| Provider | Annual Cost | Total Biomarkers | $/Biomarker |
|---|---|---|---|
| $190 | 100+ | $1.90 | |
| $297 | 100+ | $2.97 | |
 Superpower | $349 | 100+ | $3.49 |
| $349 | 75+ | $4.65 | |
 Function Health | $365 | 160+ | $2.28 |
| $365 | 100+ | $3.65 | |
| $375 | 108 | $3.47 | |
| $495 | 80+ | $6.19 | |
| $700 | 138 | $5.07 | |
| $829 | 54 | $15.35 | |
| $895 | 100+ | $8.95 | |
| $996 | 59 | $16.88 | |
| $1950 | 130+ | $15.00 |
$/Biomarker is annual cost divided by the panel's advertised biomarker count, not the price of this one test. We track 23 blood test providers (32 plans); 21 of those plans are itemized marker by marker. Compare all of them.
8 itemized panels do not include Folate
WHOOP Advanced Labs · Labcorp OnDemand · Life Extension Elite · Everlywell · Marek Health Base · Oura Health Panels · Healthspan · Ultrahuman Blood Vision Annual
11 providers not itemized in our matrix
We have not itemized these marker by marker (some sell tests one at a time), so this page cannot say whether they offer Folate. Check with them directly.
Life Extension Standard · Quest Health · Ultrahuman Blood Vision · Lifeforce · Hundred Health · Personalabs · Walk-In Lab · HealthLabs · WHOOP Specialized Panels · Marek Health Essential · Vitality Blueprint Upload
Experts discussing Folate
Podcast episodes where clinicians and researchers cover this marker in depth. Curated by hand; an episode is listed only when the marker is a substantial topic, not a passing mention.
Frequently Asked Questions
What is the optimal range for Folate?
Published positions differ: Plasma folate ≥25.5 nmol/L (about 11 ng/mL) (Chen et al. 2019 (Am J Clin Nutr), folic acid trial in China); Deficiency risk below 7 nmol/L serum (about 3 ng/mL) or 305 nmol/L RBC (CDC NHANES analysis (Pfeiffer et al. 2016)); Serum above 3 ng/mL; RBC above 140 ng/mL (NIH Office of Dietary Supplements fact sheet). Lab reference interval: >3.0 ng/mL. That is what a lab report flags against, not an optimal target.
Which blood test providers include Folate?
13 of the 21 blood testing panels we itemize marker by marker include Folate in their panels. This biomarker is widely available across major providers.
Related: YouBoost rates lifestyle and supplement interventions by evidence.
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.
Last reviewed Sep 23, 2026 · First published Sep 30, 2025