Can folic acid (Vitamin B9) and methyl folate supplementation mask a Vitamin B12 deficiency?

From the Guidelines

Yes, folic acid (Vitamin B9) and methyl folate supplementation can mask a Vitamin B12 deficiency, which is a potentially dangerous situation. When a person takes high doses of folic acid while being deficient in B12, the folic acid can correct the anemia that would otherwise serve as a warning sign of B12 deficiency, while allowing the neurological damage from B12 deficiency to progress undetected 1. This occurs because both vitamins are involved in DNA synthesis, and folic acid can compensate for B12's role in red blood cell production but not its role in maintaining nerve health.

The typical masking dose is above 1000 mcg (1 mg) of folic acid daily. For this reason, it's recommended that anyone with unexplained neurological symptoms, especially older adults or those with risk factors for B12 deficiency (strict vegetarians/vegans, those with pernicious anemia, or taking certain medications like metformin or proton pump inhibitors), should have their B12 levels checked before starting high-dose folic acid or methyl folate supplements 1. If supplementing with both, the typical recommendation is to ensure adequate B12 intake (recommended daily allowance is 2.4 mcg for adults) alongside folate to prevent this masking effect.

Some key points to consider:

• Folic acid supplementation may mask severe vitamin B12 depletion, and it is essential to treat vitamin B12 deficiency immediately before initiating additional folic acid 1.
• The Upper Limit (UL) for folic acid was established at 1 mg/day to avoid a delayed diagnosis of vitamin B12 deficiency and minimize the risk of neurological complications in vitamin B12-deficient individuals 1.
• Increased folate consumption is not without potential hazards, including the masking of megaloblastic anemia caused by vitamin B12 deficiency, and increased risk of certain cancers in the presence of high folate levels 1.

Overall, it is crucial to prioritize checking B12 levels before starting high-dose folic acid or methyl folate supplements, especially in individuals with risk factors for B12 deficiency, to prevent the masking effect and potential neurological damage.

From the FDA Drug Label

Folic acid, when administered in daily doses above 0. 1mg, may obscure the detection of B12 deficiency (specifically, the administration of folic acid may reverse the hematological manifestations of B12 deficiency, including pernicious anemia, while not addressing the neurological manifestations). L-METHYLFOLATE CALCIUM Tablets may be less likely than folic acid to mask vitamin B12 deficiency. Administration of folic acid alone is improper therapy for pernicious anemia and other megaloblastic anemias in which vitamin B12 is deficient.

Both folic acid and methyl folate can mask a Vitamin B12 deficiency, but methyl folate may be less likely to do so 2. Folic acid can reverse the hematological manifestations of B12 deficiency, but not the neurological manifestations, making it improper therapy for pernicious anemia and other megaloblastic anemias in which vitamin B12 is deficient 3. Key points to consider:

• Folic acid can obscure the detection of B12 deficiency.
• Methyl folate may be less likely to mask B12 deficiency.
• Folic acid is not a proper treatment for pernicious anemia or other megaloblastic anemias with B12 deficiency.

From the Research

Folic Acid and Methyl Folate Supplementation

• Folic acid supplementation can mask a Vitamin B12 deficiency, as it can correct the megaloblastic anemia associated with B12 deficiency without addressing the underlying neurological damage 4.
• High-dose folic acid supplements (>5 mg/d) have been shown to exacerbate B12 deficiency, possibly by depleting serum holotranscobalamin 4.
• There is evidence to suggest that methyl folate may be less likely to mask B12 deficiency compared to folic acid, although more research is needed to confirm this 5.
• Vitamin B12 deficiency can have serious health consequences, including irreversible neurological damage, if left untreated 6, 7.

Diagnosis and Treatment of Vitamin B12 Deficiency

• Screening for Vitamin B12 deficiency is not recommended for average-risk adults, but may be warranted in patients with certain risk factors, such as gastric or small intestine resections, inflammatory bowel disease, or vegan/strict vegetarian diets 6.
• Initial laboratory assessment for Vitamin B12 deficiency should include a complete blood count and serum Vitamin B12 level, with measurement of serum methylmalonic acid used to confirm deficiency in asymptomatic high-risk patients with low-normal levels of Vitamin B12 6.
• Oral administration of high-dose Vitamin B12 (1 to 2 mg daily) is as effective as intramuscular administration for correcting anemia and neurologic symptoms, although intramuscular therapy may lead to more rapid improvement in patients with severe deficiency or severe neurologic symptoms 6.