Folic Acid (5-MTHF) Explained Simply

1. What Is Folate (5-MTHF)?

Folate is a group of water-soluble vitamins from the B group. An important form of it is 5-MTHF, which circulates in the blood. Naturally, folate occurs in green leafy vegetables, legumes and citrus fruits. The synthetically produced form is called folic acid. One can eat folate-rich foods, use fortified foods or take preparations.

2. Where Is It Found, and What Is It Made From?

Folate is found in green leafy vegetables, legumes, citrus fruits and liver. 5-MTHF is the predominant form in the blood. Fortified flours and cereal products can be an additional source. Folic acid is produced synthetically and added to preparations and fortified foods.

3. What Does Folate (5-MTHF) Do? What Research Shows

Homocysteine Metabolism

In adults with chronic kidney disease, a folate-based administration lowered the homocysteine level 6. In type 2 diabetes, a review also found a reduction 9. In direct comparison, 5-MTHF and folic acid lowered homocysteine to a similar extent 2125. The findings mainly concern laboratory values; whether a clinical benefit follows from this is open.

Heart and Circulation

Two reviews found a lower stroke risk under folic acid 13. In a large study, enalapril plus folic acid lowered the risk of a first stroke more than enalapril alone 16. For vascular function and blood pressure, the results are mixed 242627. It remains open whether the stroke advantages also exist with grain fortification and in people who are already ill.

Cognition and Memory

In a study, folic acid improved some test scores in older people with mild cognitive impairment 20. A review on folic acid plus vitamin B12 in Alzheimer's found a better MMSE score, but no difference in other tests 13. It remains open whether the improvements are confirmed in larger studies.

Pregnancy and Neural Tube Development

A review found overall fewer neural tube defects under folic acid, alone or with other vitamins and minerals 7. An earlier version of this review came to the same result 8. It remains open whether 5-MTHF is equivalent to folic acid in protection against neural tube defects.

Blood Formation and Anaemia

A study with synthetic folic acid found an increase in red blood cell folate compared with placebo (sham) 31. Another study with 5-MTHF found no difference from folic acid 21. For hemoglobin, two reviews showed no difference 1014. The evidence is low; it remains open whether this results in advantages in anemia.

Fertility

In men with unexplained infertility, a study with folic acid, selenium and vitamin E showed no change in semen parameters compared with a sham 23. Another study with folic acid and zinc found no differences in sperm DNA methylation 29. In both studies, folic acid was given only together with other substances. The evidence is overall unclear.

Other Investigations

Folic acid lowered the first occurrence of colorectal adenomas in a study in older adults without prior findings 30. In children with autism, high-dose folinic acid improved social reciprocity 22. In Rett syndrome, 5-MTHF in the cerebrospinal fluid increased under folinic acid, but a clinical improvement did not occur 28. It remains open which form and dose are most suitable for which population group.

4. How Was Folate (5-MTHF) Taken in the Studies?

The studies predominantly used folic acid and 5-MTHF as a tablet or capsule. Partly, folinic acid or dietary folate was also tested as part of a green Mediterranean diet. Some of the investigations tested folic acid or 5-MTHF in mixed preparations with vitamin B12, vitamin B6, omega-3 fatty acids or other micronutrients.

5. Is Folate (5-MTHF) Safe? Side Effects in the Studies

In a study with high-dose folinic acid in children with autism, no significant side effects occurred 22. A review reports no indications of short-term side effects 8. In a study, prostate cancer was diagnosed more frequently under folic acid than under placebo 19. Several studies tested folic acid only together with other substances, so the effect cannot be reliably attributed to folate alone.

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