- 01Same blood picture, different danger
Low folate and low B12 both make red cells large and few, and a blood count cannot tell them apart. Only B12 deficiency damages nerves, and folic acid can fix the blood count while that damage continues, so B12 is always checked before low folate is treated.
Most people meet folate deficiency through a blood count that came back with large red cells, or a folate result flagged low. The cause is usually ordinary: a diet light on greens and beans, heavy drinking, a gut that absorbs poorly, a pregnancy, or a medicine that blocks folate 1. Folate and vitamin B12 deficiency look identical on a blood count, and only B12 deficiency damages nerves, so the two are always read together 2.
Symptoms of folate deficiency
Folate deficiency causes symptoms because cells cannot copy their DNA fast enough to divide on schedule. Bone marrow keeps making red cells, but they come out oversized and fewer in number, a pattern called megaloblastic anemia. The lining of the mouth and gut, which renews every few days, is hit by the same slowdown 2.
- Blood (from anemia): tiredness, breathlessness on exertion, pale skin, a pounding or fast heartbeat, headaches.
- Mouth and gut: a sore, smooth, red tongue (glossitis), mouth ulcers, cracks at the corners of the mouth, poor appetite and weight loss.
- Mind: low mood, irritability and poor concentration.
Early folate deficiency often causes no symptoms at all, and is found only because a routine blood count shows large red cells. Tiredness from low folate is easy to confuse with the many other causes covered in our guide to <a href="/symptoms/fatigue">fatigue</a>. Numbness, pins and needles in the feet, or an unsteady walk point more toward <a href="/conditions/b12-deficiency">vitamin B12 deficiency</a> than toward low folate (see <a href="/symptoms/tingling-hands-and-feet">tingling hands and feet</a>).
What causes low folate
Folate deficiency comes from taking in too little, absorbing too little, needing more than usual, or a medicine that blocks folate. In the US, enriched grain has been fortified with folic acid since 1998 8, so a purely dietary deficiency is less common than it was, and drinking, gut disease and medicines account for a bigger share 1.
| Cause | Why it lowers folate | Who it affects |
|---|---|---|
| Low intake | Few leafy greens, beans, citrus or fortified grains; folate is also lost in long cooking | Older adults eating little, restrictive or grain-free diets |
| Alcohol | Less folate eaten, less absorbed, more lost in urine | Heavy and long-term drinkers; one of the most common causes 1 |
| Malabsorption | The upper small intestine, where folate is absorbed, is damaged or bypassed | Celiac disease, Crohn's disease, after gastric bypass |
| Higher demand | Faster cell turnover uses folate up | Pregnancy, breastfeeding, hemolytic anemia (red cells breaking down early), severe psoriasis, dialysis |
| Medicines | Block folate absorption or its conversion to the active form | Methotrexate, trimethoprim, sulfasalazine, phenytoin and other anticonvulsants 1 |
Who is most at risk
- Anyone pregnant, breastfeeding or planning a pregnancy (see <a href="/for/fertility">fertility</a>).
- People who drink heavily.
- People with <a href="/conditions/celiac-disease">celiac disease</a>, Crohn's disease, or a past gastric bypass.
- Older adults with a poor appetite or limited diet.
- People taking methotrexate, trimethoprim, sulfasalazine or anti-seizure medicines.
- People with ongoing hemolysis or on dialysis.
How folate deficiency shows up in your blood test
Folate deficiency develops in a set order. In Victor Herbert's 1962 experiment, in which he ate a folate-free diet himself, serum folate fell by about week 3, neutrophils with too many nuclear lobes (hypersegmented neutrophils) appeared around week 7, large oval red cells around week 18, and megaloblastic anemia after about four to five months 4. A low serum folate with a normal blood count is therefore an early stage, and a high MCV with anemia is a late one.
Serum folate and red blood cell folate answer different questions. Serum folate reflects the last few days to weeks of intake and can jump after a single folate-rich meal or supplement. Red blood cell folate reflects stores laid down over the roughly 120-day life of a red cell, so it is the better guide to long-term status 1.
On a full blood count, the folate pattern is a high MCV and MCH, a high RDW and a low hemoglobin. Our <a href="/biomarkers/mcv/high">high MCV</a> page notes that alcohol and most mild causes keep MCV below about 110 fL, while "an MCV above about 115 fL, or a high MCV with other low counts or nerve symptoms, points toward B12 or folate deficiency or a marrow problem." Our <a href="/biomarkers/rdw-cv/high">high RDW</a> page adds that "the MCV on the same report is the quickest way to tell these apart." For folate, the point is that the marrow makes all three cell lines, so a severe deficiency can also lower white cells and platelets (see <a href="/biomarkers/wbc/low">low white blood cell count</a>). Our <a href="/learn/cbc-explained">CBC guide</a> explains each line.
The blood-count side of low folate
Normal and low folate levels
Serum folate: an example resultng/mL
| Test | Deficient | Borderline | Normal |
|---|---|---|---|
| Serum folate 1 7 | Below 3 ng/mL (below 6.8 nmol/L) | 3 to 5.9 ng/mL (6.8 to 13.4 nmol/L) | 6 to 20 ng/mL (13.6 to 45.3 nmol/L) |
| Red blood cell folate 1 3 | Below 140 ng/mL (below 305 nmol/L) | Lab-dependent | 400 ng/mL or more (906 nmol/L) is the WHO target before pregnancy |
Labs set their own ranges, so the flag on a report may differ slightly from these cutoffs; our guide to <a href="/learn/how-to-read-any-lab-result">reading any lab result</a> explains why. Claims of an "optimal" serum folate well above the normal band are not backed by NIH or WHO thresholds 1 7. Three things can skew a folate result 2:
- A recent meal or supplement raises serum folate.
- A hemolyzed sample (red cells burst in the tube) raises it, because red cells hold far more folate than plasma.
- B12 deficiency can trap folate in the blood, so serum folate looks normal while red cell folate falls.
The <a href="/biomarkers/folate-serum">serum folate page</a> covers the test itself.
If your folate came back low
- 1Ask for B12 alongside itAsk your clinician to check vitamin B12 before any folic acid is started, and to add methylmalonic acid (MMA) if B12 is borderline.
- 2Look for the causeGo through diet, alcohol and medicines (methotrexate, trimethoprim, anti-seizure drugs) together. If there is no clear reason, ask about a celiac blood test (<a href="/biomarkers/ttg-iga">tTG-IgA</a>).
- 3RetestExpect a repeat blood count about 8 to 12 weeks into treatment to confirm the MCV and hemoglobin are recovering.
Folate or B12? Telling them apart
Folate deficiency and B12 deficiency produce the same oversized red cells, and the blood count alone cannot tell them apart. Two extra markers help. Homocysteine rises in both deficiencies, while methylmalonic acid (MMA) rises when B12 is short but not when folate is 2. MMA can also rise with reduced kidney function, so it is read alongside kidney tests 2.
| Pattern | Serum folate | Vitamin B12 | MMA | Homocysteine | MCV | Nerve symptoms |
|---|---|---|---|---|---|---|
| Low folate | Low | Normal | Normal | High | High | Uncommon |
| Low B12 | Normal or high | Low or borderline | High | High | High | Common: numbness, unsteady walk |
| Both low | Low | Low | High | High | High | Possible |
| Low folate plus low iron | Low | Normal | Normal | High | Can look normal | Uncommon; RDW is wide |
| Alcohol, liver or thyroid | Often normal | Normal | Normal | Normal or high | Mildly high | Depends on cause |
A mixed picture is common. When iron and folate are both low, the small iron-deficient cells and large folate-deficient cells average out, so the MCV can look normal while the RDW is wide (see <a href="/conditions/iron-deficiency">iron deficiency</a>; <a href="/learn/iron-studies-explained">iron studies explained</a> shows how to read the iron side). A high MCV with a normal folate and B12 usually points elsewhere: alcohol, <a href="/conditions/fatty-liver">liver disease</a>, an <a href="/conditions/hypothyroidism">underactive thyroid</a> or some medicines. Our <a href="/conditions/anemia">anemia guide</a> sorts the types.
The tests that separate folate from B12
Treatment: how low folate is corrected
Folate deficiency is treated with folic acid and by dealing with whatever caused it. British guidelines describe a prescribed daily folic acid course for four months, continued longer if the cause persists, such as ongoing hemolysis or a medicine that cannot be stopped 2. The dose and length are set by the clinician treating you. Treating the cause matters as much: cutting down alcohol, testing for <a href="/conditions/celiac-disease">celiac disease</a> (a <a href="/biomarkers/ttg-iga">tTG-IgA</a> blood test) when the deficiency is unexplained, or reviewing a folate-blocking medicine.
- 1Within about a weekYoung red cells (<a href="/biomarkers/reticulocyte-absolute">reticulocytes</a>) usually climb as the marrow restarts normal production 2.
- 2Over the next few weeksHemoglobin usually rises and tiredness and breathlessness ease; a sore tongue usually settles.
- 3Around 8 to 12 weeksMCV usually returns toward normal, and a repeat blood count shows whether the course is working.
Food keeps folate up once stores are restored. Good sources are leafy greens such as spinach, beans and lentils, asparagus, Brussels sprouts, oranges and fortified breakfast cereals. Folate is destroyed by long boiling, so steaming or eating some greens raw keeps more of it. Liver is rich in folate but is avoided in pregnancy because of its vitamin A content.
Daily needs are set as a recommended dietary allowance (RDA) in dietary folate equivalents (DFE), a unit that counts 1 mcg of folic acid taken with food as about 1.7 mcg DFE, because folic acid is absorbed better than food folate 1.
| Who | Daily amount 1 |
|---|---|
| Adults | 400 mcg DFE |
| Pregnancy | 600 mcg DFE |
| Breastfeeding | 500 mcg DFE |
| Upper limit, folic acid from supplements and fortified food | 1,000 mcg (natural food folate has no upper limit) |
Folate is the vitamin found naturally in food; folic acid is the synthetic form used in supplements and fortified flour. Methylfolate is the already-active form. The <a href="/compounds/folate">folate guide</a> compares the three.
Supplements used once B12 has been checked
Folate deficiency in pregnancy
Folate matters most in the weeks around conception. The neural tube, which becomes the brain and spinal cord, closes within about 28 days of conception, often before a pregnancy is known 1. In the MRC Vitamin Study, women who had a previous pregnancy affected by a neural tube defect and took 4 mg folic acid daily before conception and in early pregnancy had about 72% fewer repeat defects 5. WHO recommends a red blood cell folate of at least 400 ng/mL (906 nmol/L) in women of reproductive age for the fullest protection 3.
The USPSTF recommends that all persons planning to or who could become pregnant take a daily supplement containing 0.4 to 0.8 mg (400 to 800 µg) of folic acid.US Preventive Services Task Force, JAMA (2023) 6
Fortification works at population scale too. Since US enriched grain was fortified in 1998, neural tube defects (spina bifida and anencephaly) have fallen by about 28%, roughly 1,300 fewer affected births a year 8.
A higher, prescribed dose is used for people at higher risk, such as a previous pregnancy with a neural tube defect 5, and is often considered with <a href="/conditions/diabetes">diabetes</a> or some anti-seizure medicines; that decision belongs with an obstetric clinician. Our <a href="/for/fertility">fertility page</a> covers the other markers worth reading before pregnancy.
Can low folate be a sign of something serious?
Low folate is usually explained by diet, alcohol, gut absorption, pregnancy or a medicine. It is not used as a test for cancer. Fast-growing tumors and some blood disorders use folate up faster, but in those conditions other signs are usually present. A folate deficiency that has no clear cause, or that returns after treatment, is a reason to look for celiac disease or another absorption problem 2. A high homocysteine that comes with low folate is a sign of the deficiency, and our <a href="/biomarkers/homocysteine">homocysteine page</a> covers what else raises it.
Free, no accountRead your blood testGot a blood test with a large MCV or a low folate flag? See it read beside your B12, MCV and RDW.Read my results
Do not start folic acid on your own to treat a low result: vitamin B12 needs to be checked first, because folic acid can correct the blood count while B12 nerve damage gets worse. Get same-day care for chest pain, breathlessness at rest, fainting, black or bloody stools, or new numbness, weakness or unsteady walking.
Citations
- NIH Office of Dietary Supplements. Folate: Fact Sheet for Health Professionals (2022)
- Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. British Society for Haematology. Br J Haematol (2014)
- WHO. Guideline: optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects (2015)
- Herbert V. Experimental nutritional folate deficiency in man. Trans Assoc Am Physicians (1962);75:307-20
- MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet (1991)
- US Preventive Services Task Force. Folic acid supplementation to prevent neural tube defects: recommendation statement. JAMA (2023)
- WHO Vitamin and Mineral Nutrition Information System. Serum and red blood cell folate concentrations for assessing folate status in populations (2012)
- Williams J, Mai CT, Mulinare J, et al. Updated estimates of neural tube defects prevented by mandatory folic acid fortification, United States, 1995-2011. MMWR (2015)
Educational context only, not medical advice or a diagnosis. Always discuss your results with a clinician.
