Folate level
Serum folate reflects recent folate intake. WHO puts deficiency below 3 ng/mL by anemia risk and below 4 ng/mL by homocysteine, and sets no serum threshold for preventing neural tube defects. Folic acid around conception cut neural tube defects about 70% in trials. Pooled trials found no significant change in cancer incidence, and stroke results were mixed.
Checked 2026-11-13
- Status
- A blood test ordered by a clinician and also sold direct to consumers by some US laboratories. FDA classifies folic acid test systems, used in the diagnosis and treatment of megaloblastic anemia, as class II devices [1].
- Measures
- The concentration of folate in serum or plasma, which WHO describes as an indicator of recent folate intake [2].
- Also called
- serum folate, folate serum, plasma folate, folic acid level, folic acid test, folate test, vitamin B9 level, vitamin B12 and folate panel
- Tested for
- folate deficiency, anemia workup, fatigue, planning a pregnancy, poor diet, heavy alcohol use, checking a folic acid supplement
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Linked in research2
- ModerateShown in trials: folic acid around conception cut neural tube defects about 70%. Risk fell as red cell folate rose, and WHO sets no serum folate threshold.
- LimitedLimited evidence: one US survey linked high serum folate together with low B12 status to more anemia and cognitive impairment in older adults.
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in ng/mL. Also reported in nmol/L. Where sources differ, each is shown.
World Health Organization, 1968 thresholds restated in 2015, macrocytic anemia as the indicator
All age groups · [2]
| Range | What the source calls it |
|---|---|
| below 3 ng/mL | "deficiency" |
| 3 to 5.9 ng/mL | "possible deficiency" |
| 6 to 20 ng/mL | "normal range" |
| above 20 ng/mL | "elevated" |
Values indicative of deficiency were based on the concentrations at which macrocytic anemia is more likely to appear, measured by a microbiological assay. WHO states that the "elevated" band was based on the assay's upper limit without dilution and not on biological implications for health. The same table sets red blood cell folate deficiency at below 100 ng/mL, which is a different test with its own scale, so a serum result cannot be placed against it [2].
World Health Organization, 2005 consultation restated in 2015, homocysteine as the indicator
All age groups · [2]
| Range | What the source calls it |
|---|---|
| below 4 ng/mL | "folate deficiency" |
| 4 or above ng/mL | No name given |
The cut-off is the folate concentration below which homocysteine starts to rise, taken from US survey data on men and women aged 30 and older. WHO prints it as 4 ng/mL (below 10 nmol/L), measured by radioimmunoassay, and notes that those measurements need adjustment to be comparable with the microbiological assay. It states that the values may not be appropriate in pregnancy, when folate concentrations typically decline, and are not adequate thresholds for preventing neural tube defects. The matching red blood cell folate cut-off is below 151 ng/mL, on a different scale [2].
US National Library of Medicine, MedlinePlus Medical Encyclopedia, reviewed 2025
People having the test, as an example of a laboratory normal range · [3]
| Range | What the source calls it |
|---|---|
| below 2.7 ng/mL | "lower-than-normal" |
| 2.7 to 17 ng/mL | "normal range" |
| above 17 ng/mL | No name given |
An encyclopedia entry licensed to the National Library of Medicine, not a guideline. It states that normal value ranges may vary slightly among laboratories and that some laboratories use different measurements or test different specimens. It gives no term for results above its normal range [3].
What has been shown to move it
Shown to raise it1
Cancer
Cancer was about as common as on placebo across 13 trials over about 5 years. The upper limit allows up to a 13% increase.
In people with a past adenoma, adenoma recurrence on folic acid was RR 1.05 (95% CI 0.86 to 1.29, high quality), and high blood folate was linked to advanced-stage tumors (OR 1.95, 95% CI 1.18 to 3.22, very low quality).
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Across 13 trials with 49,621 participants, folic acid quadrupled blood folic acid and did not significantly change cancer incidence (1,904 against 1,809 cancers, RR 1.06, 95% CI 0.99 to 1.13) over a weighted average of 5.2 years. No specific site differed [21]. A 2025 umbrella review found folic acid supplement use linked to lower colorectal cancer risk in observational data (RR 0.83, 95% CI 0.77 to 0.90, low quality). In people with a past adenoma, adenoma recurrence on folic acid was RR 1.05 (95% CI 0.86 to 1.29, high quality), and high blood folate was linked to advanced-stage tumors (OR 1.95, 95% CI 1.18 to 3.22, very low quality) [22].
- Population
- Participants in 10 cardiovascular prevention trials and 3 colorectal adenoma trials [21]; meta-analyses of trials and observational studies [22].
- Sources
- [21], [22]
- Caveats
- Covers the treatment period only. The upper confidence limit allows up to a 13% increase.
How it compares with the reference method
Matched the reference method1
Serum folate against red cell folate
Limited evidence: two reviews judged serum folate to give information equivalent to red cell folate for detecting deficiency.
The numbers and sources
- Compared with
- Red blood cell folate
- Effect
- WHO describes serum folate as an indicator of recent intake, so a single measurement cannot separate a passing fall in intake from chronic deficiency. Red cells take up folate only while they are being formed and live about 120 days, so red cell folate reflects longer-term status [2]. A review of laboratory practice in the United Kingdom concluded from the literature that serum folate provides equivalent information to red cell folate in determining whether deficiency is present [16]. A later review found that neither marker was clearly superior in characterizing deficiency, that serum folate more often showed the higher correlation with homocysteine, and that red cell folate results varied with sample pretreatment, oxygen saturation of hemoglobin and hematocrit [17]. WHO's red cell folate cut-offs are below 100 ng/mL by anemia risk, below 151 ng/mL by homocysteine, and above 400 ng/mL for women of reproductive age at the population level [2].
- Population
- Narrative reviews of published studies, one with benchmarking data from United Kingdom hematology laboratories [16][17].
- Sources
- [2], [16], [17]
- Caveats
- Neither review pooled data. Red cell folate is reported on a different scale, so its cut-offs do not apply to a serum result [2].
Mixed results1
Week to week variation in one person
One small study found serum folate varied about 11% from week to week within the same person over five weeks.
The numbers and sources
- Compared with
- The same person's results on 5 weekly draws
- Effect
- Within-person variation was 10.7% (95% CI 9.2 to 12.7), variation between people was 19.4% and analytical variation was 4.0%. The authors calculated that two results in one person need to differ by 31.7% to exceed expected variation [18].
- Population
- 22 apparently healthy volunteers aged 18 to 55 in Turkey, sampled once a week for five weeks [18].
- Sources
- [18]
- Caveats
- Twenty-two people and one laboratory. The study states no threshold for agreement, so the result is given as numbers only [18].
Did not match the reference method1
Agreement between assay types
Limited evidence: WHO reports that one protein-binding assay read about 30% lower than the microbiological assay and mass spectrometry.
The numbers and sources
- Compared with
- Microbiological assay and liquid chromatography-tandem mass spectrometry
- Effect
- WHO reports that protein-binding assays were found to be less accurate, with one measuring about 30% lower serum and red cell folate than the microbiological assay and liquid chromatography-tandem mass spectrometry, which it attributes to under-recovery of the main folate form in blood. It also reports that microbiological assays in three laboratories gave different results depending on the calibrator or microorganism used [2].
- Population
- Method comparison studies summarized by WHO [2].
- Sources
- [2]
- Caveats
- WHO summarizes the comparisons without giving sample sizes. Its 2005 cut-off was set on radioimmunoassay results, which it says need adjustment to compare with the microbiological assay [2].
What studies tie it to
Linked in research2
Neural tube defects in pregnancy
Shown in trials: folic acid around conception cut neural tube defects about 70%. Risk fell as red cell folate rose, and WHO sets no serum folate threshold.
The numbers and sources
- Effect
- In a Cochrane review, daily folic acid around conception lowered neural tube defects compared with no intervention, placebo or other micronutrients without folic acid (RR 0.31, 95% CI 0.17 to 0.58, 5 studies, 6,708 births) [4]. In a trial in women with a previous affected pregnancy, 6 of the 27 affected pregnancies were in the folic acid groups and 21 in the other groups (RR 0.28, 95% CI 0.12 to 0.71) [5]. The evidence tying a blood level to risk is for red blood cell folate. In an Irish case-control study, risk fell with early pregnancy red cell folate in a continuous dose-response relationship [6]. A model built on Chinese data estimated 25.4 defects per 10,000 births at a red cell folate of 500 nmol/L and 6 per 10,000 at 1,180 nmol/L [7]. WHO sets red cell folate above 400 ng/mL (906 nmol/L) as the population threshold for women of reproductive age and recommends no serum threshold [2]. One trial analysis estimated that this red cell threshold corresponds to a plasma folate of 25.5 nmol/L (about 11.3 ng/mL), higher in women with low vitamin B12 [8].
- Population
- 5 trials with 6,708 births [4]. 1,817 women with a previous affected pregnancy at 33 centers in 7 countries, 1,195 completed pregnancies [5]. 247,831 participants in a Chinese community intervention and 1,194 in a randomized trial [7]. 1,673 women of reproductive age in northern China [8].
- Sources
- [4], [5], [6], [7], [2], [8]
- Caveats
- WHO states that its red cell threshold is for populations and is not to be used to predict an individual's risk, since low folate is not responsible for all neural tube defects [2]. The plasma figure comes from one trial population, was published in nmol/L and is converted here [8].
Anemia and cognitive impairment when folate is high and vitamin B12 is low
Limited evidence: one US survey linked high serum folate together with low B12 status to more anemia and cognitive impairment in older adults.
The numbers and sources
- Effect
- Among seniors with low vitamin B12 status, serum folate above 59 nmol/L (about 26 ng/mL, the 80th percentile) was associated with anemia (OR 3.1, 95% CI 1.5 to 6.6) and cognitive impairment (OR 2.6, 95% CI 1.1 to 6.1), compared with folate at or below that level. Among those with normal B12 status, high folate was associated with less cognitive impairment (OR 0.4, 95% CI 0.2 to 0.9) [15].
- Population
- 1,459 seniors in the 1999 to 2002 US National Health and Nutrition Examination Survey, after folic acid fortification began [15].
- Sources
- [15]
- Caveats
- One cross-sectional survey, so it cannot show cause or order. The ng/mL figure is converted here from the study's nmol/L [15].
Mixed results1
Stroke in trials of folic acid
Mixed results: folic acid cut first stroke 21% in Chinese adults with hypertension, while a pooled analysis of 8 other trials found no significant effect.
The numbers and sources
- Effect
- In a Chinese trial, enalapril with folic acid 0.8 mg lowered first stroke compared with enalapril alone (2.7% against 3.4%, HR 0.79, 95% CI 0.68 to 0.93) over a median 4.5 years. Heart attack (HR 1.04, 95% CI 0.60 to 1.82) and death from any cause (HR 0.94, 95% CI 0.81 to 1.10) did not differ [9]. In a meta-analysis of 8 trials of folic acid in people at raised cardiovascular risk, the rate ratio for stroke was 0.96 (95% CI 0.87 to 1.06) and for major vascular events 1.01 (95% CI 0.97 to 1.05) [10]. A Cochrane review of B vitamin trials found a small reduction in stroke against placebo (RR 0.90, 95% CI 0.82 to 0.99, 10 trials) and no difference in heart attack (RR 1.02, 95% CI 0.95 to 1.10) [11].
- Population
- 20,702 adults with hypertension and no history of stroke or heart attack [9]. 37,485 participants in 8 trials, median follow-up 5 years [10]. 71,422 participants in 15 trials [11].
- Sources
- [9], [10], [11]
- Caveats
- These trials assigned folic acid, alone or with other B vitamins, and report outcomes by assigned treatment, not by the folate level reached. The Cochrane authors note that the stroke evidence for folic acid with enalapril came from one very large trial [11].
Checked, no link found2
Cancer in trials of folic acid
Not shown to change cancer incidence in trials: folic acid quadrupled plasma folate and cancer rates did not differ significantly over 5 years.
The numbers and sources
- Effect
- Across 13 trials, allocation to folic acid raised plasma folate to 57.3 nmol/L against 13.5 nmol/L on placebo (about 25.3 against 6.0 ng/mL). Overall cancer incidence did not differ significantly (1,904 cancers against 1,809, RR 1.06, 95% CI 0.99 to 1.13), with no trend toward a greater effect with longer treatment and no significant effect on cancer of the large intestine, prostate, lung, breast or any other site [12].
- Population
- 49,621 participants in 13 trials, weighted average treatment 5.2 years [12].
- Sources
- [12]
- Caveats
- The trials used doses higher than those from fortification and ran for about 5 years, so they say little about longer exposure [12]. The ng/mL figures are converted here from the study's nmol/L.
Cognitive decline in older adults
Not shown to track cognitive decline: folate did not predict decline in one cohort, and trials of B vitamins containing folic acid found no cognitive effect.
The numbers and sources
- Effect
- In an Oxford cohort followed for 10 years, markers of vitamin B12 status and homocysteine predicted cognitive decline and serum folate did not [13]. In a meta-analysis of 11 trials, B vitamins lowered homocysteine by 26% to 28% and had no significant effect on global cognitive function (z score difference -0.01, 95% CI -0.03 to 0.02) [14].
- Population
- 1,648 older adults in Oxford, United Kingdom [13]. 22,000 participants in 11 trials [14].
- Sources
- [13], [14]
- Caveats
- The cohort finding is observational. The trials tested B vitamins given to lower homocysteine and were not trials of treating folate deficiency [14].
Sources
- US Food and Drug Administration. 21 CFR 862.1295, Folic acid test system. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-862.1295
- World Health Organization. Serum and red blood cell folate concentrations for assessing folate status in populations. Vitamin and Mineral Nutrition Information System. Geneva: World Health Organization, 2015. WHO/NMH/NHD/EPG/15.01. https://iris.who.int/handle/10665/162114
- US National Library of Medicine. Folic acid, test. MedlinePlus Medical Encyclopedia, review date February 3, 2025. https://medlineplus.gov/ency/article/003686.htm
- De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC, Rayco-Solon P. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database of Systematic Reviews. 2015. https://doi.org/10.1002/14651858.CD007950.pub3
- MRC Vitamin Study Research Group. Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. The Lancet. 1991. https://doi.org/10.1016/0140-6736(91)90133-A
- Daly LE, Kirke PN, Molloy A, Weir DG, Scott JM. Folate Levels and Neural Tube Defects: Implications for Prevention. JAMA. 1995. https://doi.org/10.1001/jama.1995.03530210052030
- Crider KS, Devine O, Hao L, et al. Population red blood cell folate concentrations for prevention of neural tube defects: Bayesian model. BMJ. 2014. https://doi.org/10.1136/bmj.g4554
- Chen MY, Rose CE, Qi YP, et al. Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation. The American Journal of Clinical Nutrition. 2019. https://doi.org/10.1093/ajcn/nqz027
- Huo Y, Li J, Qin X, et al. Efficacy of Folic Acid Therapy in Primary Prevention of Stroke Among Adults With Hypertension in China: The CSPPT Randomized Clinical Trial. JAMA. 2015. https://doi.org/10.1001/jama.2015.2274
- Clarke R, Halsey J, Lewington S, et al. Effects of Lowering Homocysteine Levels With B Vitamins on Cardiovascular Disease, Cancer, and Cause-Specific Mortality: Meta-analysis of 8 Randomized Trials Involving 37 485 Individuals. Archives of Internal Medicine. 2010. https://doi.org/10.1001/archinternmed.2010.348
- Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database of Systematic Reviews. 2017. https://doi.org/10.1002/14651858.CD006612.pub5
- Vollset SE, Clarke R, Lewington S, et al. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals. The Lancet. 2013. https://doi.org/10.1016/S0140-6736(12)62001-7
- Clarke R, Birks J, Nexo E, et al. Low vitamin B-12 status and risk of cognitive decline in older adults. The American Journal of Clinical Nutrition. 2007. https://doi.org/10.1093/ajcn/86.5.1384
- Clarke R, Bennett D, Parish S, et al. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. The American Journal of Clinical Nutrition. 2014. https://doi.org/10.3945/ajcn.113.076349
- Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. The American Journal of Clinical Nutrition. 2007. https://doi.org/10.1093/ajcn/85.1.193
- Galloway M, Rushworth L. Red cell or serum folate? Results from the National Pathology Alliance benchmarking review. Journal of Clinical Pathology. 2003. https://doi.org/10.1136/jcp.56.12.924
- Farrell CJ, Kirsch SH, Herrmann M. Red cell or serum folate: what to do in clinical practice? Clinical Chemistry and Laboratory Medicine. 2013. https://doi.org/10.1515/cclm-2012-0639
- Ozkanay H, Arslan FD, Narin F, Koseoglu MH. Biological variation of plasma 25-Hydroxyvitamin D3, serum vitamin B12, folate and ferritin in Turkish healthy subject. Scandinavian Journal of Clinical and Laboratory Investigation. 2023. https://doi.org/10.1080/00365513.2023.2278537