Folic acid, the form most commonly in supplements and fortified food, is a synthetic oxidized form not found naturally in food. It must be converted to tetrahydrofolate. Evidence shows that in a large majority of the human population (maybe 25%), this process may be slow and inefficient due to negative epigenetic expression, leaving us with extended exposure to unconverted folic acid. There is a belief that with this overload, a very small part of the population may be at higher risk for certain forms of cancer. Recent data has clarified this issue, which should allay any concern.
- Last week, Harvard researchers reported “no evidence for an increased risk of advanced or multiple cancerous adenomas” from folic acid, according to a double-blind, randomized trial.
- Eating plenty of folate may reduce the risk of colorectal cancer by 64% in women consuming more than 300 mcg. daily compared to those consuming less than 200 mcg. A review paper published by Joel Mason from USDA Human Nutrition Research Center on Aging at Tufts University, best addressed folate's effect on colorectal health. “Under most circumstances, adequate intake of folate appears to assume the role of a protective agent against cancer, most notably colorectal cancer,” wrote Dr Mason. A possible explanation for the contradictory results of studies with folic acid and colorectal cancer may be the difference between the synthetic and natural forms of the vitamin. “The fact that folic acid, which is not a naturally occurring form of the vitamin, is used by food and pharmaceutical industries for fortification and supplementation is potentially of importance.” On passage through the intestinal wall, folic acid is converted to 5-methyltetrahydrofolate, the naturally circulating form of folate.
Some studies have suggested that oral doses of folic acid in high doses may overwhelm this conversion pathway, leading to measurable levels of folic acid in the blood. “There has been some concern that this oxidized, non-substituted form of folate might feasibly be detrimental because it is not a naturally occurring co-enzymatic form of the vitamin,” Mason added. Bonnie - the concern only comes from excessively high doses of folate, which according to the next study, is non-existent. As the new Harvard study reported, at normal levels this is not an issue.
- Intakes of folic acid from fortified foods and supplements do not lead to excessive intakes. “At current fortification levels, US adults who do not consume supplements or who consume an average of 400 micrograms folic acid/d from supplements are unlikely to exceed the upper limit in intake for folic acid,” wrote Robert Berry from the Centers for Disease Control and Prevention. Less than 3 per cent of the study population exceeded the tolerable upper level of 1,000 micrograms a day. Because of this study and other successes seen around the world, the United Kingdom Food Standard Agency just recommended that folic acid be added to bread on a mandatory basis. A total of 51 countries now have some degree of mandatory fortification of flour with folic acid.
- Drugs that interfere with the action of folic acid produce a six-fold increase in birth defects in pregnant women.
- The Scottish Spina Bifida Association said 15 babies had been born in Scotland with the condition since January 2009 - double the normal number. It said folic acid supplements, which research suggests can prevent many cases, were often taken too late. Scotland does not have a folic acid fortification program.
- Low maternal folate levels are linked to the development of attention-deficit/hyperactivity problems in children at age seven to nine years. Researchers state that maternal nutrition contributes to an individuals' development, with potential consequences for their behavior later in life. The long term effects of poor maternal nutrition may even branch out to the child's ability to interact with peers or form social bonds.
- Low serum folate concentration is associated with an altered morphology of human bone in older adults.
- Folate may prevent premature birth and heart defects. Now pregnancy specialists are asking if it's time for the government to boost the amount being added to certain foods to help ensure mothers-to-be get enough.
Texas researchers analyzed nearly 35,000 pregnancies and found that women who reported taking folic acid supplements for at least a year before becoming pregnant cut in half their risk of having a premature baby. Their risk of having very early preemies, the babies least likely to survive, dropped even more.
Canadian researchers analyzed 1.3 million births in Quebec since 1990 to look for heart defects, the most common type of birth defect. They found the rate of serious heart defects has dropped 6 percent a year since Canada began its own food fortification in December 1998.
The U.S. Preventive Services Task Force recommend that women take a daily supplement with 400 micrograms to 800 micrograms of folic acid daily. But because only about a third of non-pregnant women take precautionary folic acid supplements, fortifying foods made with enriched flour ensures everyone gets a modest amount.
- Increased intake of folate and folic acid may reduce the risk of hearing loss in men by 20 per cent. Researchers used the most recent figures from the Health Professionals Follow-up Study cohort from years 1986 to 2004, a group consisting of 51,529 male health professionals. The study identified 3,559 cases of men with hearing loss. When the nutritional data was analyzed, men over the age of 60 with high folate intake from foods and supplements had a 20 per cent decrease in risk of developing hearing loss.
- Supplements of folic acid may improve cardiovascular health and reduce the prevalence of peripheral arterial disease (PAD). Daily doses of 400 micrograms of folic acid led to significant improvements in blood pressure and improved blood flow after 16 weeks of supplementation. Furthermore, equal doses of 5-methyltetrahydrofolate (5-MTHF), the naturally circulating form of folate, produced the same results, leading the researchers to conclude that “5-MTHF may be a safe and effective alternative to folic acid in those who have a genetic predisposition to synthesizing folic acid.”
- Do not exceed 1 gram (1000 mcg.) of supplemental folate unless supervised by a licensed health professional.
- Make sure that along with folate, you supplement with an adequate amount of vitamin B-12 and vitamin B-6 .
- Because testing for a genetic predisposition to synthesizing folic acid is prohibitively expensive, insure yourself by supplementing with all three forms of folate (folic acid, 5-methyltetrahydrofolate, 5 formyl tetrahydrofolate; available in Metagenics ActiFolate).
Nutrition Reviews, April 2009
Proceedings on the National Academy of Sciences, August 2009
European Journal of Clinical Nutrition, August 2009
British Journal of Surgery, September 2009
BBC News, 2009
American Academy of Otolaryngology-Head and Neck Surgery Foundation Annual Meeting, October 2009
British Journal of Clinical Pharmacology, October 2009
Journal of Child Psychology and Psychiatry, November 2009
American Journal of Epidemiology, November 2009
American Journal Clinical Nutrition, November 2009; December 2009