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Why You Need Folate and Not Folic Acid


March 22, 2017 by Joel Fuhrman, MD

Pregnancy isn’t the only time in life to focus on folate. Although this vitamin has gotten the most attention for its importance to a developing fetus, folate plays an essential role throughout our lives. For example, folate is a crucial nutrient for synthesizing DNA, and therefore for cell division.1 Any biological process that involves rapid growth (fetal development, childhood growth, immune function, and cancer) has the potential to be affected by your folate status.

Insufficient folate can have devastating effects on a pregnancy, leading to birth defects. Even before a woman typically discovers she is pregnant, folate already is at work, making it most important to enter into a pregnancy with an adequate folate level.

During the initial four weeks of pregnancy, folate plays an important role in the folding of the neural tube which is the precursor to the brain and central nervous system. In a folate-deficient fetus, the tube may not close completely during folding, causing a neural tube defect. After the folding of the neural tube, folate continues to play an important role in the development of the brain and nervous system. This role is strongly suggested by studies that link low folate status during pregnancy to hyperactivity and other behavior problems in children, and higher folate intake with greater academic achievement in teens.2, 3 Consuming folate-rich foods before and during pregnancy may also offer protection against cardiac birth defects, childhood respiratory illnesses, and childhood cancers.4-8

Folate is also necessary beyond pregnancy and childhood, as this vitamin plays a critical role in supporting our health as adults. Folate is one of the many nutrients necessary for red blood cells to transport oxygen properly, and it also supports the functioning of our nervous and cardiovascular systems. Adequate amounts of B vitamins including folate are important for maintaining good cognitive function throughout life.9-11

Folic Acid is Not Folate

Folate is often called a double-edged sword. Folate deficiency, of course, is harmful. But excess in the form of folic acid has its own dangers. Just to be clear: folic acid is not the same as natural folate. Natural folate is beneficial when provided by whole foods, but may be harmful in supplement form as folic acid. Folate is abundant in green vegetables, beans and other whole plant foods. Synthetic folic acid, which is chemically different than folate, is found in supplements and fortified foods and is twice as absorbable by the human body compared to natural folate.12

While the body converts some synthetic folic acid to folate, it has a limited capacity to do so. Much of the remaining folic acid that is not converted circulates in the blood and tissues unmodified. It is unknown exactly what unmodified folic acid does in the human body. But it has the potential to disrupt normal folate metabolism and there is substantial evidence that it can even promote cancer growth.

In addition, synthetic folic acid can disrupt the actions of natural folate as it has a greater capability to bind to folate receptors on our cells. This, in turn, could result in folic acid being preferentially transported into normal healthy cells instead of natural folate. Once inside the cell, folic acid could then compete with natural folates for other binding sites, preventing them from functioning properly and potentially causing changes in normal gene expression or cell growth rates.

Harmful Effects of Too Much Folic Acid

Since folic acid is more absorbable than natural folate, we run the risk of excess when we ingest the synthetic form. It would be impossible to get excessive folate from natural foods. There is evidence that higher levels of circulating (unmetabolized) folic acid may reduce the protective functions of certain immune cells.13 High folic acid consumption can also mask the symptoms of — and exacerbate — vitamin B12 deficiency, which could be a problem especially for the elderly.14

However, the most significant concern of excess folic acid is cancer development. Since folate is involved in DNA synthesis which is crucial for cell growth and cancer cells have more folate receptors on their surfaces and produce more folate-dependent enzymes than normal cells, excess circulating folic acid could feed into this process and allow cancer cells to proliferate.15 Excess folic acid may also lead to cancer development by producing changes in gene expression.

The idea that folic acid could promote cancer is not new. In the 1940s, high doses of folic acid were given as an experimental treatment to leukemia patients and the rate of proliferation of cancer cells increased. This finding was the origin of the use of anti-folate drugs for cancer chemotherapy today.15

Natural Folate is Ideal

There are studies that suggest that synthetic folic acid from multivitamins is cancer promoting, whereas folate from food is protective.16,17 Other studies have cautioned against supplemental folic acid: A 2011 meta-analysis of six folic acid supplementation trials found that the incidence of cancers was 21 percent higher in the folic acid supplementation groups than control groups.18 Studies on multivitamin use and breast cancer have produced inconsistent findings overall, however several have reported an increase in risk, and have hypothesized that folic acid is the culprit.16,19

Since folic acid can be harmful in supplement form, the formulation for my Women’s and Men’s Daily Formula multivitamins and my Gentle Prenatal do not contain folic acid or other potentially damaging ingredients like beta-carotene, vitamins A and E, or the minerals iron and copper.

Luckily we don’t need to get folic acid from vitamins because folate is plentiful in green vegetables and other whole plant foods. When we get folate from a healthful diet it comes naturally packaged in balance with hundreds of other cancer protective micronutrients.

The recommendation for folate for healthy adults is 400 mcg/day and 600 mcg/day for pregnant women. This quantity can easily be met by eating green vegetables, beans and other whole plant foods.

Learn more about food folate, synthetic folic acid, and their different effects on our health in my Folate Position Paper.

 
References
  1. Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nutr 2008, 87:517-533.
  2. Schlotz W, Jones A, Phillips DI, et al. Lower maternal folate status in early pregnancy is associated with childhood hyperactivity and peer problems in offspring. J Child Psychol Psychiatry 2010, 51:594-602.
  3. Nilsson TK, Yngve A, Bottiger AK, et al. High folate intake is related to better academic achievement in Swedish adolescents. Pediatrics 2011, 128:e358-365.
  4. Metayer C, Dahl G, Wiemels J, Miller M. Childhood Leukemia: A Preventable Disease. Pediatrics 2016, 138:S45-S55.
  5. Haberg SE, London SJ, Stigum H, et al. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis Child 2009, 94:180-184.
  6. Whitrow MJ, Moore VM, Rumbold AR, Davies MJ. Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study. Am J Epidemiol 2009, 170:1486-1493.
  7. Haberg SE, London SJ, Nafstad P, et al. Maternal folate levels in pregnancy and asthma in children at age 3 years. J Allergy Clin Immunol 2011, 127:262-264, 264 e261.
  8. Kallen B. Congenital malformations in infants whose mothers reported the use of folic acid in early pregnancy in Sweden. A prospective population study. Congenit Anom (Kyoto) 2007, 47:119-124.
  9. Voutilainen S, Rissanen TH, Virtanen J, et al. Low dietary folate intake is associated with an excess incidence of acute coronary events: The Kuopio Ischemic Heart Disease Risk Factor Study. Circulation 2001, 103:2674-2680.
  10. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy-A Review. Nutrients 2016, 8.
  11. Higdon J: Folic Acid. In An Evidence-Based Approach to Vitamins and Minerals. 2003: 6-14
  12. Pitkin RM. Folate and neural tube defects. Am J Clin Nutr 2007, 85:285S-288S.
  13. Troen AM, Mitchell B, Sorensen B, et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 2006, 136:189-194.
  14. Johnson MA. If high folic acid aggravates vitamin B12 deficiency what should be done about it? Nutr Rev 2007, 65:451-458.
  15. Mason JB, Dickstein A, Jacques PF, et al. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev 2007, 16:1325-1329.
  16. Stolzenberg-Solomon RZ, Chang SC, Leitzmann MF, et al. Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr 2006, 83:895-904.
  17. Sanjoaquin MA, Allen N, Couto E, et al. Folate intake and colorectal cancer risk: a meta-analytical approach. Int J Cancer 2005, 113:825-828.
  18. Baggott JE, Oster RA, Tamura T. Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiol 2011.
  19. Larsson SC, Akesson A, Bergkvist L, Wolk A. Multivitamin use and breast cancer incidence in a prospective cohort of Swedish women. Am J Clin Nutr 2010, 91:1268-1272.

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cjb678

04/03/2017 10:49 AM

Hi, I have just read the end of diabetes book and have decided to change my lifestyle. I have not been diagnosed with diabetes but at my last dr appt was told that my sugar was high and I should watch what I eat, I'm guessing basically I was prediabetic, I know I am prone to it and have a history of it in my family. One thing I'm curious is, can I oven roast vegetables? The recipes and everything I've read, are either steamed, sautéed, or in a soup. Hopefully I can get some answers here?