Folic Acid, Folate & MTHFR; Key Facts for Wellness

Navigating Misinformation in Prenatal Wellness

Medical information at its best guides evidence informed agreed consensus

At its worst, we have inconsistencies, mis-information & derailed patient care

Social media misinformation may convince you that you do not need to take your prenatal folic acid, or leave you wondering whether you are unable to absorb synthetic folic acid

Here are the Key Facts & Science That You Need to Know

1. Folate is the naturally occurring form of vitamin B9

2. Folic acid is the synthetic form of vitamin B9

3. Synthetic folic acid is the only type of folate shown to help prevent neural tube defects (NTDs) Source: CDC

4. It is difficult for most people to get the daily recommended amount of folate through food alone

5. Folate rich foods include kale, spinach, arugula and swiss chard; in pregnancy aim for 2 servings daily

6. 5-methyltetrahydrofolate (5-MTHF)or L- methylfolate is the active form of vitamin B9 i.e. the form that our body can actually use

7. To convert food folate and synthetic folic acid to the active form, relies on methylenetetrahydrofolate reductase enzyme (MTHFR)

8. Mutations in the genes that code for this enzyme can happen. These mutations result in different enzyme forms

9. Mutated forms of the enzyme work less well

10. In females, the MTHFR type C677T mutation has been associated with low folate and lower oocytes & impaired follicle development

11. In males the MTHFR is associated with low sperm counts & impaired sperm development

12. low levels of MTHFR can increase homocysteine levels, which is linked to disease

13. If you have the mutated enzyme and are taking synthetic folic acid it could build up in the blood

14. The implications of excess folic acid in the blood are unknown.

15. Taking folic acid at the recommended amounts has not been shown to cause harm.

16. Prevalence of MTHFR mutations varies by ethnicity (1):

• Caucasians: 10 - 14 %

• Hispanics 21%

• Africans 1 - 7 %

• Asians 11%.

17. MTHFR type C677T frequency is approximately 20–25% in the general population (3) and reduces the activity of the enzyme by 30%

18. There are only a few studies that address what dose of 5-MTHF is optimal for preconception and pregnancy in those with MTHFR polymorphisms.

19. The Royal College of Obstetricians and Gynaecologists (RCOG) generally does not recommend testing for MTHFR polymorphisms because evidence as a cause of miscarriage is conflicting

20. Where there is a history of recurrent miscarriage, the focus should be on assessing other established risk factors of miscarriage

21. While MTHFR gene variations exist, they are common and often don't have a significant clinical impact; there is no strong evidence of a direct link with pregnancy complications.

22. People with an MTHFR gene variant can still process all types of folate, including folic acid, just to different extents

23. MTHFR mutations have been found to have a significant association with recurrent miscarriage in only one study from China (4)

24. Other studies did not find an association and advise against testing for this mutation

25. Where there is a MTHFR mutation identified, there is no agreed consensus on the dose of 5-MTHF to use

26. If you're curious, a more accessible test can be homocysteine levels. Higher homocysteine levels may be linked with MTHFR mutations

Final Notes For Mammas

Folic acid is the only type of folate that has been proven to prevent neural tube defects

Folic acid supplementation increases blood folate concentrations, reaching the optimal red blood cell folate concentration after 3 to 6 months of supplementation, even if you have a MTHFR mutation

Ensuring that you get 400mcg daily, consistently, and for sufficient time before pregnancy, is more important in achieving adequate blood levels

If you are identified to have a 5-MTHFR mutation, you may need high dose L-methylfolate; discuss with a clinician

References

1 Botto L.D., Yang Q. 5,10-methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol. 2000;151(9):862–877

2 Morovvati S., Khaleghparast A., Noormohammadi Z. Evaluation of the association between the C677T and A1298C polymorphisms of MTHFR gene and recurrent miscarriage. J Med Council Islamic Republic of Iran. 2010;28(4):465

3. Cornet D., Cohen M., Clement A., et al. Association between the MTHFR-C677T isoform and structure of sperm DNA. J Assist Reprod Genet. 2017;34(10):1283–1288. doi: 10.1007/s10815-017-1015-2.

4 Regan L, Rai R, Saravelos S, Li T-C, on behalf of the Royal College of Obstetricians and Gynaecologists. Recurrent Miscarriage: Green-top Guideline No. 17. BJOG. 2023; 130(12): e9–e39