What is a normal folate level?

Normal Folate Levels

Normal serum folate levels should be ≥10 nmol/L (4.4 ng/mL), while normal red blood cell folate levels should be ≥340 nmol/L (150 ng/mL) to prevent deficiency-related health complications. 1

Folate Measurement Methods and Reference Ranges

• Folate status is conventionally assessed by measuring levels in serum/plasma or red blood cells (RBC) 1
• Serum/plasma folate concentrations reflect recent dietary folate intake and are the earliest indicator of altered folate exposure 1
• RBC folate levels are a sensitive marker of long-term folate status, reflecting folate accumulation during the preceding 3 months and tissue folate stores 1
• The gold standard method for measuring folate is the microbiological assay using Lactobacillus rhamnosus 1
• Normal serum folate levels should be ≥10 nmol/L according to current guidelines 1
• Normal red blood cell folate levels should be ≥340 nmol/L 1
• Some researchers propose that normal serum folate levels should be ≥13.0 ng/mL (29.5 nmol/L) for optimal prevention of neural tube defects 2

Clinical Significance of Folate Levels

• Folate plays a critical role as a cofactor in the metabolism of nucleic acid precursors and several amino acids, as well as in methylation reactions 1
• Folate deficiency can lead to megaloblastic anemia, pancytopenia, glossitis, angular stomatitis, oral ulcers, and neuropsychiatric manifestations 1
• Serum folate levels below 8 μg/L (18 nmol/L) are associated with significant rises in homocysteine concentrations, which is a risk factor for cardiovascular disease 3
• Haematological abnormalities typically occur only with profound folate deficiency, with significant effects on red blood cell indices observed at serum folate levels under 6 μg/L (14 nmol/L) 3
• For women of reproductive age, RBC folate concentrations below 906 nmol/L (400 ng/mL) indicate folate insufficiency and suboptimal neural tube defect prevention 4
• A corresponding plasma folate threshold of approximately 25.5 nmol/L has been suggested for optimal neural tube defect prevention 4

Factors Affecting Folate Levels

• Vitamin C improves folate bioavailability by limiting the degradation of natural folate coenzymes and folic acid supplements in the stomach 1
• Folate forms are susceptible to degradation by light, temperature, pH, and oxygen, requiring pre-analytical precautions during sample collection and preparation 1
• Folate status can be affected by vitamin B12 status, as both folate and cobalamin deficiencies can result in elevated homocysteine levels 1
• The relationship between RBC and plasma folate concentrations can be modified by body mass index (BMI), methyltetrahydrofolate reductase (MTHFR) genotype, and vitamin B12 status 4
• Inflammation may affect folate metabolism, though limited evidence is available on the effects of inflammation on plasma or red blood cell folate assays 1

Dietary Intake and Supplementation

• For the general population, the Dietary Reference Intake (DRI) of Dietary Folate Equivalent (DFE) varies from 250 to 400 μg/day 1
• The European Food Safety Authority (EFSA) suggests a Population Reference Intake of 330 μg DFE 1
• For pregnant and lactating women, the needs are about twice as high (500-600 μg DFE/day) 1
• Folate intake can be obtained through careful selection of foods, with major sources including pulses, leafy green vegetables, eggs, nuts, and whole grain products 1
• Food folates have lower bioavailability than synthetic folic acid, with 1 μg DFE equaling 1 μg food folate or 0.6 μg folic acid from fortified food 1
• For women planning pregnancy, supplementation with 400 μg/day of folic acid is recommended for neural tube defect prevention 1

Monitoring and Clinical Management

• In patients with macrocytic anemia or at risk of malnutrition, folate status should be measured at baseline and repeated within 3 months after supplementation 1
• In diseases known to increase folate requirements, folate status can be measured every 3 months until stabilization, then once a year 1
• When measuring folate, it's important to also assess vitamin B12 status, as folate supplementation can mask B12 deficiency 1
• Total daily folate consumption should be kept below 1 mg per day to avoid potential complications, including masking vitamin B12 deficiency 1
• After normal folate levels are achieved, maintenance intake should be about 330 μg DFE for adults and 600 μg DFE for pregnant and lactating women per day 1