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Flour Fortification with Folic Acid: Good Idea or Bad Idea

Flour Fortification with Folic Acid: Good Idea or Bad Idea

Folic Acid Supplementation and Fortification

In 1947 scientists at Lederle Labs synthesized a compound called folic acid that had never previously existed on our planet. No human prior to 1947 had ever ingested this artificial substance. Exactly 51 years later in 1998, The Food and Drug Agency (FDA) mandatorily legislated that the entire U.S population would now be required to ingest this substance.4, 5, 20, 23, 24 As a democratic nation, we never were allowed to vote upon this decision. It simply happened overnight. One day folic acid was not part of our regular food supply, and the next day every man, woman and child in the U.S. (except celiac patients and Paleo Dieters) were forced to ingest folic acid whether they wanted to or not. As I will show you, this unilateral decision has turned into one of the worst health fiasco’s in the history of our country. In the 16 years since its inception, this mandatory legislation has resulted in untold numbers of morbidity (disease incidence) mortality (death) and disability.7-11, 15-17, 20, 23, 24, 26, 27-29

If you are currently a Paleo Dieter, you probably don’t have to worry about ingesting folic acid providing you are not taking any vitamin supplements containing this compound. In 1998 the FDA mandated that all enriched wheat flour was to be fortified with folic acid. Because most commercial wheat products (breakfast cereals, bread, cookies, cakes, crackers, doughnuts, pizza crust, hamburger and hotdog buns, wheat tortillas etc.) are made with enriched wheat flour, essentially the entire U.S. population began to consume folic acid in 1998. At the time, this national mandate seemed like a pretty good idea because convincing data existed to show that low folate status caused neural tube birth defects such as spina bifida. I have bolded and underlined the word folate to emphasize that it is an entirely different compound than folic acid.

In our bodies, folate and folic acid are metabolized in different ways. Folate is a natural vitamin found in leafy green vegetables and organ meats. Folic acid is not a vitamin, but rather a manmade substance that can be converted to folate in the liver. The problem is that folic acid is not rapidly converted to folate, thereby causing an excess pool of both folic acid and folate to build up in our bodies. And herein lies the problem.

I would be the first person to congratulate the FDA for mandating a national policy that could reduce or eliminate birth defects such as spina bifida.4, 5 Unfortunately, their shotgun approach to curing neural tube birth defects puts the entire U.S population at risk for death and disability from other serious diseases and nutritional deficiencies.20 In the six year period (1990-1996) before mandatory folic acid fortification, the average number of neural tube defects per year in the U.S was 1,582. In the first year (1998-1999) following fortification neural tube defects dropped to 1,337 thereby preventing 245 cases of these diseases.12 Unless you’ve experienced a neural tube defect in your immediate family, you probably know very little about these diseases.

Neural tube defects come in two basic forms: 1) spina bifida, and 2) anencephaly. Most cases of spina bifida are rarely fatal and in many people produce no visible symptoms. Anencephaly is almost always fatal at birth or shortly thereafter. However, the number of cases of anencephaly is about half that for spina bifida. Hence, the total number of lives saved by the mandatory folic acid fortification program following the first year after its introduction would have been 83. I truly have compassion for the parents and family of children born with neural tube defects, but to put the entire U.S. population at risk for additional life threatening diseases to save the lives of 83 infants makes little sense, particularly when other worldwide studies show folic acid supplementation to have little or no effect upon birth outcome6 or even to prevent cardiovascular disease.18 A much better strategy would be to selectively supplement expecting women with folate – not folic acid. The entire U.S. population is not at risk for neural tube defects – only pregnant women.

Folic Acid Fortification/Supplementation and Breast, Prostate and Colorectal Cancers

In the past decade an accumulating body of scientific evidence now makes it absolutely clear that the FDA’s mandatory folic acid fortification program represents one of the worst blunders in the history of U.S. public health. An alarming number of human clinical trials, animal experiments and epidemiological studies show that excess folate via folic acid fortification has resulted in population wide increases in the risk for breast, prostate and colorectal cancers.7-11, 15-17, 20, 23, 24, 26, 27-29

Let’s start off with prostate cancer. A recent (2010) meta analysis (compilation of many population studies) carried out at Bristol University in the UK demonstrated that high levels of blood folate were associated with increased prostate cancer risk.9 Even more convincing evidence comes from a clinical trial by Dr. Figueiredo and colleagues at the University of Southern California.11 In this experiment 643 men were randomly assigned to either a folic acid supplementation group or a placebo (dummy pill) group. After nearly 11 years, the percentage of men developing prostate cancer in the folic acid treatment group was 9.7 %, whereas only 3.3 % of the men in the placebo group were diagnosed with prostate cancer. Higher blood concentrations of folate from folic acid supplementation also cause a faster progression of this sometimes fatal disease. Although scientists aren’t completely sure how excess folate and folic acid promote cancer, animal experiments indicate that these compounds induce a cancer causing reaction called hypermethylation in the DNA of cancer cells.24, 29, 30

A disturbing number of recent epidemiological (population) studies have suggested that high folate intake, largely from folic acid in supplements and fortified foods may increase breast cancer risk. In a study of 70,656 postmenopausal women who were followed from 1992 until 2005, dietary folate intake (from both folic acid and folate) was positively associated with breast cancer risk.26

I’d like to make it clear once again that folate and folic acid are not one in the same compounds. Folate is the natural, healthful B vitamin that is found in leafy green veggies, organ meats and some nuts. Folic acid is an artificial chemical that can be converted to folate in the liver. Because folic acid builds up and forms pools of this manmade chemical in our bodies at doses as low as 200 mcg (half the DRI), it is known to disrupt normal folate metabolism. To summarize, dietary folate from natural food sources does not produce harmful health effects, whereas folic acid does.

To continue with our discussion of folic acid and breast cancer risk, a recent animal experiment by Dr. Ly and co-workers at the University of Toronto demonstrated that folic acid supplementation led to an increased risk of mammary cancer in rats.29 It is notable that the equivalent (~800 mcg) dietary levels of folic acid necessary to produce breast cancer in the rats could easily be achieved in humans by eating fortified foods and taking folic acid supplements.

The situation with colorectal cancers and folic acid supplementation/fortification is nearly identical to which I have described for breast and prostate cancer. Animal, tissue, epidemiological and human dietary trials all reveal that folic acid increases the risk for colorectal cancers. The most powerful type of research design in human supplementation experiments is called a “double blind, placebo controlled randomized trial.” With these types of experiments, scientists can be relatively sure that a certain treatment causes a certain outcome. In just such a study of 1021 men and women carried out over a 10 year period, I quote the authors of this study, “Folic acid was associated with higher risks of having 3 or more adenomas [cancers] and of noncolorectal cancers.”7 A similar double blind, placebo controlled randomized trial from Norway came up with similar conclusions, “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.”10 The folic acid fortification/cancer story certainly makes Paracelsus’s word’s ring true, “dose makes the poison.” Indeed, many European nations, including the U.K. have taken a more cautious approach and have decided not to fortify their food supply with folic acid.

Folic Acid Fortification/Supplementation and Autism

Before we leave this topic, a disturbing development involving folic acid fortification/supplementation has arisen in the past five years or so. A number of scientists now believe that excessive folic acid may play an important role in the Autism Spectrum Disorder (ASD) which includes autism, Asperger disorder and other developmental problems.1, 3, 4, 13, 14, 19, 22 Recent epidemiological studies of autism show the increasing prevalence of ASD in the U.S. coincides with the same time period mandatory folic acid fortification began.2, 3, 21 Additionally, it is known that excessive folic acid during the embryonic period may adversely affect normal brain development. Unlike the folic acid/cancer story, the data for ASD is still preliminary. Large population studies will be required to determine if the mandatory folic acid fortification program is responsible for the disturbing increase in ASD over the past 15 years.

 

Cordially,

Loren Cordain, Ph.D., Professor Emeritus

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REFERENCES

1. Adams M, Lucock M, Stuart J, Fardell S, Baker K, Ng X. Preliminary evidence for involvement of the folate gene polymorphism 19bp deletion-DHFR in occurrence of autism. Neurosci Lett. 2007 Jul 5;422(1):24-9.

2. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2006 Principal Investigators; Centers for Disease Control and Prevention (CDC). Prevalence of autism spectrum disorders – Autism and Developmental Disabilities Monitoring Network, United States, 2006. MMWR Surveill Summ. 2009 Dec 18;58(10):1-20

3. Beard CM, Panser LA, Katusic SK. Is excess folic acid supplementation a risk factor for autism? Med Hypotheses. 2011 Mar 29

4. Beaudet AL, Goin-Kochel RP. Some, but not complete, reassurance on the safety of folic acid fortification. Am J Clin Nutr. 2010 Dec;92(6):1287-8.

5. Boulet SL, Gambrell D, Shin M, et al. Racial/ethnic differences in the birth prevalence of spina bifida-United States, 1995–2005. MMWR 2009;57:1409–1413.

6. Chiaffarino F, Ascone GB, Bortolus R, Mastroia-Covo P, Ricci E, Cipriani S, Parazzini F. [Effects of folic acid supplementation on pregnancy outcomes: a review of randomized clinical trials]. Minerva Ginecol. 2010 Aug;62(4):293-301

7. Cole BF, Baron JA, Sandler RS, Haile RW et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007 Jun 6;297(21):2351-9.

8. Collin SM, Metcalfe C, Refsum H, Lewis SJ, Smith GD et al. Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer. Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2833-8

9. Collin SM, Metcalfe C, Refsum H, Lewis SJ et al. Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010 Jun;19(6):1632-42.

10. Ebbing M, Bønaa KH, Nygård O, Arnesen E, Ueland PM et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA. 2009 Nov 18;302(19):2119-26.

11. Figueiredo JC, Grau MV, Haile RW, Sandler RS, Summers RW, Bresalier RS, Burke CA, McKeown-Eyssen GE, Baron JA. Folic acid and risk of prostate cancer: results from a randomized clinical trial. J Natl Cancer Inst. 2009 Mar 18;101(6):432-5

12. Honein MA, Paulozzi LJ, Mathews TJ, Erickson JD, Wong LY. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA. 2001 Jun 20;285(23):2981-6.

13. King CR. A novel embryological theory of autism causation involving endogenous biochemicals capable of initiating cellular gene transcription: A possible link between twelve autism risk factors and the autism ‘epidemic’ Med Hypotheses. 2011 Mar 7. [Epub ahead of print]

14. Leeming RJ, Lucock M. Autism: Is there a folate connection? J Inherit Metab Dis. 2009 Jun;32(3):400-2.

15. Levine AJ, Figueiredo JC, Lee W, Conti DV, Kennedy K, Duggan DJ, Poynter JN, Campbell PT, Newcomb P, Martinez ME, Hopper JL, Le Marchand L, Baron JA, Limburg PJ, Ulrich CM, Haile RW. A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2010 Jul;19(7):1812-21

16. Lin J, Lee IM, Cook NR, Selhub J, Manson JE, Buring JE, Zhang SM. Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women. Am J Clin Nutr. 2008 Mar;87(3):734-43.

17. Lindzon GM, Medline A, Sohn KJ, Depeint F, Croxford R, Kim YI. Effect of folic acid supplementation on the progression of colorectal aberrant crypt foci. Carcinogenesis. 2009 Sep;30(9):1536-43

18. Løland KH, Bleie O, Blix AJ, Strand E, Ueland PM, Refsum H, Ebbing M, Nordrehaug JE, Nygård O. Effect of homocysteine-lowering B vitamin treatment on angiographic progression of coronary artery disease: a Western Norway B Vitamin Intervention Trial (WENBIT) substudy. Am J Cardiol. 2010 Jun 1;105(11):1577-84.

19. Main PA, Angley MT, Thomas P, O’Doherty CE, Fenech M. Folate and methionine metabolism in autism: a systematic review. Am J Clin Nutr. 2010 Jun;91(6):1598-620.

20. Refsum H, Smith AD. Are we ready for mandatory fortification with vitamin B-12? Am J Clin Nutr. 2008 Aug;88(2):253-4.

21. Rice C, Nicholas J, Baio J, Pettygrove S, Lee LC et al. Changes in autism spectrum disorder prevalence in 4 areas of the United States. Disabil Health J. 2010 Jul;3(3):186-201

22. Rogers EJ. Has enhanced folate status during pregnancy altered natural selection and possibly Autism prevalence? A closer look at a possible link. Med Hypotheses. 2008Sep;71(3):406-10. Sauer J, Mason JB, Choi SW. Too much folate: a risk factor for cancer and cardiovascular disease? Curr Opin Clin Nutr Metab Care. 2009 Jan;12(1):30-6

23. Rosenberg IH. Science-based micronutrient fortification: which nutrients, how much, and how to know? Am J Clin Nutr. 2005 Aug;82(2):279-8026. Soni MG, Thurmond TS, Miller ER 3rd, Spriggs T, Bendich A, Omaye ST. Safety of vitamins and minerals: controversies and perspective. Toxicol Sci. 2010 Dec;118(2):348-55.

24. Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nutr. 2008 Mar;87(3):517-33.

25. Smulders YM, Blom HJ. The homocysteine controversy. J Inherit Metab Dis. 2011 Feb;34(1):93-9

26. Stevens VL, McCullough ML, Sun J, Gapstur SM. Folate and other one-carbon metabolism-related nutrients and risk of postmenopausal breast cancer in the Cancer Prevention Study II Nutrition Cohort. Am J Clin Nutr. 2010 Jun;91(6):1708-15

27. Stolzenberg-Solomon RZ, Chang SC, Leitzmann MF, Johnson KA, Johnson C, Buys SS, Hoover RN, Ziegler RG. 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.

28. Ulrich CM, Potter JD. Folate and cancer–timing is everything. JAMA. 2007 Jun 6;297(21):2408-9

29. Ly A1, Lee H, Chen J, Sie KK, Renlund R, Medline A, Sohn KJ, Croxford R, Thompson LU, Kim YI. Effect of maternal and postweaning folic acid supplementation on mammary tumor risk in the offspring. Cancer Res. 2011 Feb 1;71(3):988-97.

30. Collin SM. Folate and B12 in prostate cancer. Adv Clin Chem. 2013;60:1-63.

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11 Comments on "Flour Fortification with Folic Acid: Good Idea or Bad Idea"

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  1. Doug Riexinger says:

    Let me preface the following statements with the fact that I was a chemist in the pharmaceutical industry for 36 years.

    Your statements “In 1947 scientists at Lederle Labs synthesized a compound called folic acid that had never previously existed on our planet.” and “I’d like to make it clear once again that folate and folic acid are not one in the same compounds. Folate is the natural, healthful B vitamin that is found in leafy green veggies, organ meats and some nuts. Folic acid is an artificial chemical that can be converted to folate in the liver.” are categorically false.

    While your article contains many valid points and arguments, these misstatements cannot be ignored.

    Did you take a course in organic chemistry in college? Folic acid is the protonated form of folate. They are one in the same. They exist in an equilibrium in the body which favors the folate form.

    That being said, chemically synthesized folic acid may contain (and probably does) chemical impurities if not purified properly. This is true for any chemically synthesized vitamin. If there are problems with chemically synthesized folic acid supplementation it is due either to any impurities contained in the folic acid or over consumption of folic acid.

    Your body has no way to distinguish “naturally produced” from “chemically synthesized” folic acid.

    I do not take any vitamin supplements with the exception of D3 during the winter months(I live in NJ). If you eat a well balanced diet there is no need to.

  2. John says:

    Don’t forget, iron fortification of foods happened at the same time, and high body iron levels are even more dangerous than folic acid levels.

  3. Colleen says:

    To prevent 83 deaths but cause a rise in autism seems idiotic. If we had excellent prenatal care in the US(excellent health care in general), expectant mothers could be counseled to add more greens to their diet and not have a better chance of having an autistic child caused by folic acid and not cause an increased breast cancer risk to the entire rest of the population of the United States. I wonder how governments in Europe are handling these birth defects? Oh, wait, they probably just give good advice on diet for expectant mothers.

  4. Cecile says:

    I am a senior citizen and am gluten sensitive, so I have absorption issues and take vitamin and mineral supplements, all of which contain lots of folic acid. I follow the Paleo Diet pretty closely but notice that my energy level drops without my supplements. Are there supplements without folic acid that contain the other nutrients my body doesn’t absorb from my food?

    • Markus says:

      Hi Cecile,

      myself I’m taking a Multi from Life Extension. The “two per day” are a great Multi that is quite complete and inexpensive. The minerals and vitamins contained are all in good forms, like cheleated Zinc or folate. Just make sure you have enough Magnesium, Fish, liver, proteins and greens in your diet and your system should be filled very well. Taking just one tablet per day could already bbe sufficient so you perhaps will give it a try.

    • Grama Gracie says:

      The ‘Garden of Life’ brand has ‘Vitamin Code’. the Raw B-Complex bottle lists folate on the label. Very popular brand from Jordan Rubin. Find at your favorite health food store (or ask). to my understanding they don’t use any synthetics only food based products.
      All synthetics are harmful, Why didn’t we know this years ago? The label can say ‘natural/organic’ and only have one small ingredients that is and all the rest be synthetic. How sad.
      40 plus years ago I started taking ‘natural vitamins’ not knowing that they were all petroleum based. I had hypoglycemic/chronic fatigue/fibromyalgia/lupus/depression before anyone even knew the words. I’m thinking that was actually one of the causes… If I had only known then how to change my diet I would have avoided the years of misery while I was raising our six children.
      Look other places for your ‘energy’ solutions. Synthetics give a boost because its using up your bodies own reserves to process the synthetics and make them ‘work’. When your bodies’ reserves are exhausted, then what? Then you’re really down on the concrete, draggin’ your tail… I been there oh so many times!
      Food, pure, unadulerated food, is the answer. Another one of the hardly talked about as yet challenges is hybridization. Our Wheat supply, grains,etc. Our milk cows, our bodies need A2,A2 genetics. What about chickens? fruits? vegs? nuts? etc.etc. Organic isn’t enough anymore.

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