When should folic acid (Vitamin B9) be replaced?

From the Guidelines

Folic acid (Vitamin B9) should be replaced when a deficiency is diagnosed or in specific high-risk situations, such as pregnancy, to prevent neural tube defects in the developing fetus, as supported by the US Preventive Services Task Force recommendation statement 1. The standard adult dose is 400-1000 mcg daily, with higher doses of 1-5 mg daily for those with severe deficiency or increased needs.

• Pregnant women should take 600 mcg daily, ideally starting before conception and continuing throughout pregnancy to prevent neural tube defects in the developing fetus.
• People with certain medical conditions like malabsorption disorders, alcoholism, liver disease, or those taking medications such as methotrexate, phenytoin, or trimethoprim should also supplement with folic acid.
• Individuals with the MTHFR gene mutation may benefit from the active form, methylfolate, instead of standard folic acid. Replacement is important because folic acid is essential for DNA synthesis, cell division, and red blood cell formation.
• Deficiency can lead to megaloblastic anemia, fatigue, weakness, and in pregnant women, birth defects.
• Most people can get adequate folic acid through a diet rich in leafy greens, legumes, and fortified grains, but supplements are necessary when diet alone is insufficient, as indicated by studies 1. The USPSTF concludes that, for women who are planning or capable of pregnancy, there is high certainty that the net benefit is substantial, and recommends folic acid supplementation at a dose of 0.4 to 0.8 mg daily, starting at least 1 month before conception and continuing through the first 2 to 3 months of pregnancy 1.

From the FDA Drug Label

Although most patients with malabsorption cannot absorb food folates, they are able to absorb folic acid given orally. When clinical symptoms have subsided and the blood picture has become normal, a daily maintenance level should be used, i.e., 0.1 mg for infants and up to 0.3 mg for children under 4 years of age, 0.4 mg for adults and children 4 or more years of age, and 0.8 mg for pregnant and lactating women, but never less than 0. 1 mg/day.

Folic acid (Vitamin B9) should be replaced with a maintenance dose when:

• Clinical symptoms have subsided
• The blood picture has become normal The maintenance dose is:
• 0.1 mg for infants
• Up to 0.3 mg for children under 4 years of age
• 0.4 mg for adults and children 4 or more years of age
• 0.8 mg for pregnant and lactating women 2

From the Research

Replacement of Folic Acid

Folic acid, also known as Vitamin B9, is an essential micronutrient that plays a critical role in one-carbon metabolism. The replacement of folic acid with other forms of folate, such as 5-methyltetrahydrofolate (5-MTHF), is considered in certain situations.

• Advantages of 5-MTHF: Naturally occurring 5-MTHF has important advantages over synthetic folic acid, including better absorption and bioavailability, even in individuals with gastrointestinal pH alterations or metabolic defects 3.
• Prevention of Neural Tube Defects: Folic acid supplementation is essential for preventing neural tube defects, and 5-MTHF can be used as an alternative to folic acid in this context 4.
• Genetic Polymorphisms: The use of 5-MTHF instead of folic acid can overcome metabolic defects caused by methylenetetrahydrofolate reductase polymorphism, reducing the potential for masking haematological symptoms of vitamin B12 deficiency 3.
• Comparison with Folinic Acid: Folinic acid and 5-MTHF have been compared in terms of their efficacy in lowering serum total homocysteine levels, with both supplements showing significant reductions 5.

Specific Situations for Replacement

The replacement of folic acid with other forms of folate may be considered in the following situations:

• Pregnancy: Folic acid supplementation is mandatory during pregnancy to prevent neural tube defects, and 5-MTHF can be used as an alternative 4.
• Genetic Defects: Individuals with genetic defects, such as methylenetetrahydrofolate reductase polymorphism, may benefit from the use of 5-MTHF instead of folic acid 3.
• Drug Interactions: The use of 5-MTHF instead of folic acid can reduce interactions with drugs that inhibit dihydrofolate reductase 3.