What are the guidelines for folate supplementation?

Folate Supplementation Guidelines

All women of childbearing age should take 400 μg (0.4 mg) of folic acid daily throughout their reproductive years to prevent neural tube defects, with higher doses recommended for high-risk women. 1

General Recommendations for Folate Supplementation

For Women of Reproductive Age:

• Women capable of becoming pregnant should consume 400-800 μg (0.4-0.8 mg) of folic acid daily throughout their reproductive years 1
• Supplementation should begin at least 4 weeks prior to planned conception and continue through at least the first trimester of pregnancy 1
• Folic acid can be obtained through supplements, multivitamins, fortified foods, or a combination of these sources 1
• Since neural tube defects develop within the first 28 days after conception (often before pregnancy recognition) and many pregnancies are unplanned, continuous supplementation is recommended for all women of reproductive age 1

For High-Risk Women:

• Women with a prior pregnancy affected by neural tube defects should take 4 mg (4000 μg) of folic acid daily 1
• This higher dose is also recommended for women who:
  • Have a personal history of neural tube defects 1
  • Have a first or second-degree relative with neural tube defects 1
  • Have diabetes mellitus type 1 1
  • Are taking medications that interfere with folate metabolism (e.g., antiepileptic drugs like valproic acid or carbamazepine, methotrexate) 1
• The 4 mg dose should begin at least 1-3 months before conception and continue through the first trimester 1

Special Considerations

After Bariatric Surgery:

• Women planning pregnancy after bariatric surgery should optimize nutritional supplementation 3-6 months prior to conception 1
• A higher folic acid dose of 5 mg daily is recommended during the periconception period for these women 1
• Regular monitoring of folate levels (every 3 months) is recommended for women planning pregnancy after bariatric surgery 1

For Inflammatory Bowel Disease (IBD) Patients:

• Patients with IBD, especially those treated with sulphasalazine or methotrexate, should receive folic acid supplementation 1
• For IBD patients on methotrexate: 5 mg once weekly 24-72 hours after methotrexate, or 1 mg daily for 5 days per week 1
• Pregnant women with IBD should have iron status and folate levels monitored regularly throughout pregnancy 1

Safety Considerations:

• Total daily intake of folic acid should not exceed 1000 μg (1.0 mg) unless prescribed by a physician, to avoid potential masking of vitamin B12 deficiency 1
• However, recent evidence suggests that food fortification has not led to a major increase in masking of vitamin B12 deficiency 1
• Folic acid supplementation is often given as part of a multivitamin that includes B12, further reducing this risk 1

Benefits Beyond Neural Tube Defects

• Folate supplementation may provide protection against other adverse birth outcomes:
  • Congenital heart defects 2
  • Low birth weight 2, 3
  • Preterm birth 2, 3
• Some evidence suggests a protective effect of folic acid supplementation on colorectal cancer development in IBD patients 1
• The bioactive form (6S)5-methyltetrahydrofolate may be preferred over folic acid in women with MTHFR polymorphisms that affect folic acid metabolism 4

Common Pitfalls and Caveats

• Inadequate folate intake is common during pregnancy, with studies showing up to 65% of women have intake below recommendations 3
• Risk factors for inadequate folate intake include:
  • Smoking 3
  • Following dietary restrictions 3
  • Low adherence to Mediterranean diet 3
  • Low educational level 3
• The retinol form of vitamin A should be avoided during pregnancy due to teratogenicity risk 1
• Women should be advised that dietary folate alone is usually insufficient to meet requirements during pregnancy, as folates from food are not as well absorbed as synthetic folic acid 1, 5
• Despite supplementation, some neural tube defects have multifactorial or monogenic etiology and cannot be completely prevented 1

By following these guidelines for folate supplementation, the risk of neural tube defects and potentially other adverse pregnancy outcomes can be significantly reduced.