Most people don't realize the difference between folic acid and folate, since they believe they are both 'the same vitamin.'
If you look up the folic acid cycle, you'll see that folic acid (synthetic, in supplements) needs to be converted to 5-methyltetrahydrofolate (5-MTHF, aka methyl folate) in order to be used in the methyl cycle (a primary use of folate in humans). This conversion involves a number of enzymes, including MTHFR. In a significant portion of the population (ballpark of 40-50%), the MTHFR enzyme isn't as efficient as in the rest of the population, and as a result, their methyl folate levels tend to be lower. That means their methylation may be impaired, and they're at risk for a long list of diseases.
Folic acid is absorbed better in the digestive tract than food folate (5-MTHF and folinic acid are the food forms). As a result, taking folic acid can mean you're not absorbing as much food folate. There's a limit (diminishing returns) to how much folic acid your body can metabolize. It drops off around 260 mcg, and pretty much plateaus at 400mcg. I *think* those numbers are general population numbers not taking into account MTHFR. As you start supping more than you can process, you get unmetabolized, unusable folic acid floating around in your body and it competes for transport with the good stuff. Nobody really knows what effect the unmetabolized stuff has, but based on what we've learned, it doesn't look great.
I don't think anybody is saying anything good about being deficient in folate. What the latest research is starting to show is that the form of folate that you get really does matter. I think we'd all agree that food sources of nutrients are best whenever possible, and this is providing an explanation of *why* that's true for this vitamin in particular.
(originally posted by Shannon)
This thread has more information. http://www.mothering.com/discussions/showthread.php?t=1184692&h...
Here is more about MTHFR: http://www.detoxpuzzle.com/mthfr.php
1. Stolzenberg-Solomon RZ 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 Apr;83(4):895-904.
Conclusions: Our results do no t support the hypothesis that high folate intake reduces breast cancer risk; instead, they suggest that a high intake, generally attributable to supplemental folic acid, may increase the risk in postmenopausal women.
2. Kim YI. Does a high folate intake increase the risk of breast cancer? Nut Rev; 2006; 64(10PT1) 468-75.
Furthermore, although food folate intake was not significantly related to breast cancer risk, total folate intake, mainly from folic acid supplementation, significantly increased breast cancer risk by 32%.
3. Figueiredo JC et al. Folic acid and risk of prostate cancer: results from a randomized clinical trial. J Natl Cancer Inst. 2009 Mar 18;101(6):432-5. Epub 2009 Mar 10.
Folic acid supplementation was associated with increased risk of prostate cancer. By contrast, baseline dietary folate was inversely associated with prostate cancer risk.
http://jnci.oxfordjournals .org/cgi/c...hort/101/6/43 2
4. Fife, J et al. Folic Acid Supplementation and Colorectal Cancer Risk; A Meta-analysis. Colorectal Dis. 2009 Oct 27.
In fact, a 2009 meta-analysis of studies of folic acid supplementation showed that those receiving supplements for over three years had an increased risk of pre-cancerous bowel adenomas and bowel cancer.
http://info.cancerresearch uk.org/can...r-risk-factor s
5. Whitrow MJ. Effect of Supplemental Folic Acid in Pregnancy on Childhood Asthma: A Prospective Birth Cohort Study. Am J Epidemiol. 2009 Oct 30.
Asthma was reported in 11.6% of children at 3.5 years (n = 57) and in 11.8% of children at 5.5 years (n = 50). Folic acid taken in supplement form in late pregnancy was associated with an increased risk of childhood asthma at 3.5 years (relative risk (RR) = 1.26, 95% confidence interval (CI): 1.08, 1.43) and with persistent asthma (RR = 1.32, 95% CI: 1.03, 1.69).
6. Haberg SE, London SJ, Stigum H, Nafstad P, Nystad W. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis Child. 2009 Mar;94(3):180-4.
CONCLUSIONS: Folic acid supplements in pregnancy were associated with a slightly increased risk of wheeze and lower respiratory tract infections up to 18 months of age. The results suggest that methyl donors in the maternal diet during pregnancy may influence respiratory health in children consistent with epigenetic mechanisms.
7. Ebbing M et al. Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12. JAMA. 2009;302(19):2119-2126.
Conclusion Treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.
http://jama.ama-assn.org/c gi/content/short/302/19/21 19
8. Charles D et al. Taking folate in pregnancy and risk of maternal breast cancer. BMJ 2004;329:1375–6
In women randomised to high doses of supplemental folate, all cause mortality was about a fifth greater, and the risk of deaths attributable to breast cancer was twice as great.
9. Harvard School of Public Health; The Nutrition Source: Keep the Multi, Skip the Heavily Fortified Foods; www.hsph.harvard.edu/nutri tionsource/what-should-you -eat/folicacid/ Date accessed: 8/29/08.
http://www.hsph.harvard.ed u/nutritio...cid/index.htm l
10. Hirsch S et al. Colon cancer in Chile before and after the start of the flour fortification program with folic acid. Eur J Gastroenterol Hepatol. 2009 Apr;21(4):436-9.
Conclusion: Our data provide new evidence that a folate fortification program could be associated with an additional risk of colon cancer.
http://journals.lww.com/eu rojgh/Abst...e_start.7.asp x
11. http://www.medscape.com/vi ewarticle/591111
In an interview with Medscape Oncology, Dr. Mason said that the new data from Chile "contribute to this concern that the total amount of folic acid present in the food stream can potentially contribute to an increase in certain types of cancer."
It is not just a question of folic-acid fortification of food, however; there is also the issue of folic-acid supplementation, such as in multivitamin pills. Dr. Mason noted that recent data from the US Centers for Disease Control suggest that 70% to 80% of the general adult population has detectable levels of folic acid in the blood, but "under more natural conditions, folic acid would not even be present in the blood."
12. Kwan ML et al. Maternal diet and risk of childhood acute lymphoblastic leukemia. Public Health Rep. 2009 Jul-Aug;124(4):503-14.
CONCLUSIONS: These data suggest that it may be prudent for women to consume a diet rich in vegetables and adequate in protein prior to and during pregnancy as a possible means of reducing childhood ALL risk in their offspring.
Tower RL et al. The epidemiology of childhood leukemia with a focus on birth weight and diet. Crit Rev Clin Lab Sci. 2007;44(3):203-42.
Increased intake of fruits and vegetables has been associated with decreased leukemia risk and, relatedly, lack of maternal folate supplementation has been associated with increased childhood leukemia risk, possibly by causing DNA hypomethylation and increased DNA strand breaks. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms modify this risk.
http://informahealthcare.c om/doi/abs...ournalCode=la b
Petridou E et al. Maternal diet and acute lymphoblastic leukemia in young children.Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):1935-9.
Thompson et al. (45) reported that offspring of women who during their pregnancies received supplements with folate (naturally found in several leafy vegetables) had lower risk of ALL. Additionally, Jensen et al. (46) have found that increased maternal intake immediately before the index pregnancy (and inferentially, during that pregnancy) of vegetables and fruits was associated with decreased risk of ALL.
Pogoda JM et al. An international case-control study of maternal diet during pregnancy and childhood brain tumor risk: a histology-specific analysis by food group. Ann Epidemiol. 2009 Mar;19(3):148-60.
14. Sellers TA et al. Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology. 2001 Jul;12(4):420-8.
15. Kim YI. Folic acid fortification and supplementation--good for some but not so good for others. Nutr Rev. 2007 Nov;65(11):504-11.
However, recent human studies have suggested that FA supplementation and fortification may promote the progression of already existing, undiagnosed, preneoplastic and neoplastic lesions, thereby corroborating earlier observations from animal and in vitro studies.
http://www.cancer.gov/clin icaltrials...inal-CARET120 4
Researchers exploring the notion that certain nutrients might protect against pancreatic cancer found that lean individuals who got most of these nutrients from food were protected against developing cancer. The study also sugges...ts this protective effect does not hold true if the nutrients come from vitamin supplements.
The researchers also say that they uncovered another interesting trend that some people who received these nutrients from multivitamin pills had an increased risk of developing the disease. According to the researchers, individuals who said they used multivitamins, and whose blood showed traces of these nutrients, had a 139 percent increased relative risk of developing pancreatic cancer.
http://www.huliq.com/23341 /dietary-vitamin-b6-b12-fo late-to-decre...
http://cancerres.aacrjourn als.org/content/67/11/5553 .abstract
Another separate study of 81,922 women and men, specific to folate from food sources.
CONCLUSION: Our results suggest that increased intake of folate from food sources, but not from supplements, may be associated with a reduced risk of pancr...eatic cancer.
"The methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism is associated with a reduced risk of some forms of cancer. The protective effect of this folate-related polymorphism is dependent on adequate folate status. Cancer risk ma...y be increased in individuals with the homozygous genotype for the MTHFR 677CT polymorphism who have low status of methyl-related nutrients including folate. Intake recommendations to potentially reduce cancer risk include substitution of low folate foods with folate-dense fruits and vegetables."
http://jn.nutrition.org/co ntent/133/11/3748S.abstrac t
"Compared with 677CC individuals with high folate intake, elevation of breast cancer risk was most pronounced among 677TT women who consumed the lowest levels of dietary folate (OR, 1.83; 95% CI, 1.13-2.96) or total folate intake."
http://cancerres.aacrjourn als.org/content/65/4/1606. full
"In this study we investigated how one particular form of the MTHFR gene polymorphism, 1298A>C, effects cancer risk and how it may convey its effect through either the coexistence of the second known polymorphism, 677C>T, or from a different mechanism."
"Over the past two decades evidence has been mounting for folate being an important nutrient in the prevention of cancer. Methyl-deplete diet and status, in particular, low folate intake and status has been positively associated with a number of cancers, including that colorectal, esophageal, breast, stomach, and cervical with colorectal cancer being the most extensively studied. Low folate in combination with low methionine and high alcohol intake, as well as low vitamin B12 and B6 and cigarette smoking are factors that may contribute to a methyl-deplete status."
"Inadequate availability of nutrients involved in one-carbon metabolism may contribute to carcinogenesis via imbalances in the methylation and uracil incorporation in DNA that may manifest as aberrant gene expression and diminished chromosomal integrity."
"We have observed protective associations for pancreatic cancer with greater dietary folate intake and serum folate and vitamin B6"
"Our results support the hypothesis that folate and vitamin B12, cofactors for their respective enzyme products, may play a role in the carcinogenesis of these cancers."
I found all of this research in PubMed in March 2009 when searching for information for my mom related to her new diagnosis of pancreatic cancer.
I'm astounded that universal folic acid fortification occurs still. (However, its taken us 50 ...years to consider removing fluoride from the water, and we're just going to "decrease it".) Other countries do not allow folic acid fortification. Concurrently, we've had a rise in autism rates which are related to methylation detoxification impairments in the same period since folic acid fortification began on January 1, 1998.
The MTHFR gene polymorphism was just identified around 1998, variants in 2001 and 2003. 35-50% of Americans are affected with this gene polymorphism and consequential methylation impairment (specifically of processing folic acid).
"High FA intake early in pregnancy also has been linked to an increase in the frequency of the methylenetetrahydrofolate reductase (MTHFR) 677T-allele in the fetus [30,31]. Carrying this genetic variant has been associated with chronic conditions including depression, schizophrenia, bipolar disorder, asthma, and wheezing later in life [32-35]."