Scientists and Bumble Bee Watchers

This is a bumble bee watchers’ article [click here to learn what that means]. It is based on clinical observations that have not been fully proven in the laboratory. It is primarily educational and should be discussed with your doctor.

Folate and Cervical Dysplasia: What the Studies Say

This is something I learned at a seminar presented by Dr. Jonathan Wright more than 30 years ago. He talked about folate being necessary for cells that rapidly turn over—like those in the cervix and that some cases of cervical dysplasia may be due to a folate deficiency. He cited a study done in 1982 where women with mild/moderate cervical dysplasia who were taking oral contraceptives received 10 mg folic acid/day or placebo for three months. Cytology and biopsy scores improved significantly with folate [1]. Ten milligrams of folate is an extremely high dose; it is 25 times the RDA. The authors proposed that in some women a localized disturbance of folate metabolism might actually be mistaken for cervical dysplasia [1].

Other studies have supported the idea of giving folate to women with cervical dysplasia. One study found that folate status appeared to influence the relationship between HPV-16 and cervical dysplasia. The adjusted odds ratio associated with HPV-16 was 1.1 in women with higher red-blood-cell folate levels, compared with 5.1 in women with lower folate levels [2]. A later randomized double-blind trial gave women with CIN1 5 mg folate/day for six months. CIN1 regressed 83.3% of the folate group versus 52.0% of placebo [3].

Is There a Problem with Taking a High Dose of Folate?

In the 1980s, when the study was done, the FDA did not allow folate supplements to be more than 400 mcg. The reason given was that too much folate may mask a vitamin B12 deficiency. At one point, the FDA banned folate supplements containing more than 400 mcg.

Because high-dose folic acid can mask the anemia caused by vitamin B12 deficiency while neurological damage continues, I routinely gave B12 along with folate. I used 2 mg (2,000 mcg) of B12 orally. At high doses, enough B12 can be absorbed by passive diffusion even when normal B12 absorption is impaired. Research has found that 1–2 mg of oral B12 can be effective even in patients being treated for B12 deficiency [4,5].

Bottom Line:

This is a “Bumble Bee Watchers” article. That means the therapy was put together by clinicians who pieced together clinical observations, small studies, and knowledge of physiology rather than being proven by a large double-blind clinical trial. However, “not proven” does not mean “doesn’t work”. Still, you should discuss this with your doctor. Here is what the “Bumble Bee Watchers” may come away with:

  • High doses of folate may help reverse cervical dysplasia in some patients.
  • Low folate status may increase the association between HPV-16 infection and cervical dysplasia.
  • High folate dosage may help regress CIN1, possibly lowering chances of cervical cancer.
  • When taking high doses of folate, it is a good idea to take 2 mg/day of B12.

This material really is for education only and self-treatment is discouraged. This is, however, interesting information that you can share with your doctor. Folate is water-soluble and generally well tolerated, but the doses discussed in this article are much higher than ordinary nutritional doses and should be used with professional guidance.

 Selected References:

  1. Am J Clin Nutr. 1982 Jan;35(1):73-82. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives
  2. 1992 Jan;267(4):528-33. Folate deficiency and cervical dysplasia
  3. Nutrition Volume 32, Issue 6, June 2016, Pages 681-686 Effects of long-term folate supplementation on metabolic status and regression of cervical intraepithelial neoplasia: A randomized, double-blind, placebo-controlled trial
  4. 2022 Dec 28;28(1):240. Vitamin B12 in Foods, Food Supplements, and Medicines—A Review of Its Role and Properties with a Focus on Its Stability
  5. Wang H, Li L, Qin LL, Song Y, Vidal-Alaball J, Liu TH. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database of Systematic Reviews 2018, Issue 3. Art. No.: CD004655.