Tag Archives: folate

Treating Malaria with Diet

Reductions in Blood Concentrations of p-aminobenzoic acid (PABA) and Folate are Therapeutic for Malaria Patients

Malaria is one of the most deadly diseases on the planet. It is a life-threatening infection caused by parasites that are transmitted to people through the bites of infected mosquitoes. The disease is responsible for more than 627, 000 deaths worldwide in 2012. Of the estimated deaths, most occur in sub-Saharan Africa (90%) and in children under 5 years of age (77%).

Strategies for the treatment, prevention and control of malaria typically involve pharmaceuticals, insecticides and nettings. Vaccines to prevent this disease have had little or no success to date. Rarely has diet been considered as an effective therapy to prevent or attenuate malarial morbidity (disease incidence) and mortality (disease death rate). Yet, virtually unknown to almost all malaria researchers is the notion that diets maintaining low concentrations of ρ-aminobenzoic acid (PABA) and folate represent an untapped tactic to thwart malarial infection.

How Diet Impacts Malarial Infection

Shikimate Pathway | The Paleo DietAn Achilles heel in the lifecycle of Plasmodia species (the bacteria which causes malaria) is its reliance upon the availability of folate, an essential nutrient for these rapidly growing parasites. Pharmaceuticals such as pyrimethamine and sulfa drugs are somewhat effective anti-malarials because they interfere with the conversion of PABA to folate (depicted in the Shikimate pathway to the left). In vitro (test-tube) experiments indicate that Plasmodia species have the ability to synthesize limited amounts of folate endogenously, however further experiments show that these parasites cannot synthesize sufficient quantities of folate to survive in living animals (in vivo).1 Hence, without adequate supplemental stores of PABA and folate from their host’s tissues, Plasmodia species have no capacity to cause lethal malarial infections. In support of this scenario is an extensive, but older literature reviewed in references2, 3 showing that exclusive milk diets suppress malarial infections in birds, rodents, and primates. Milk contains very little PABA and yields low concentrations of folate (60-90 µg/1000 kcal; ~ 20 % of the DRI for a 3 yr old child). The suppression of malarial symptoms is abrogated when supplemental PABA is added to all milk diets of infected animals.2, 3 Further, rodent models of malaria demonstrate that dietary PABA and folate reduce the efficacy of sulfa drugs,4 and in humans, high blood concentrations of folate also impair the efficacy of pyrimethamine and sulfa drugs.5 An experimental study of 20 West African infants, up to 2 years of age who were naturally infected with Plasmodia falciparum demonstrated that exclusive milk diets reduced parasite density and decreased disease symptoms within a few days in a manner similar to those (n=12) serving as controls and treated with chloroquine therapy.2

The pastoralist Fulani of West and Central Africa exhibit a well established resistance to malaria compared to other non-milk drinking African sympatric ethnic groups that is unexplained by known genetic resistance factors,6 but rather by enhanced immunity.7 Displacement of PABA and folate rich foods by milk in this population may attenuate malaria infection while allowing immune exposure, serving to prevent serious disease sequelae and facilitate the establishment of protective immunity. In support of this concept are data showing a high prevalence of adult lactase persistence (~68 % of the population)8 in the Fulani which may represent a previously unrecognized genetic factor that indirectly reduces malarial mortality. Accordingly, in high malarial regions where adult lactase persistence is widespread, reduced dietary PABA and folate intake caused by high milk consumption may disrupt the life cycle of Plasmodia species by impairing folate metabolism, thereby reducing childhood malaria fatalities and overall morbidity within adults.

Except for a single modern study,1 research involving the efficacy of PABA deficient diets in preventing or attenuating malaria symptoms effectively stopped in the early 1970s with the widespread use of insecticides, nettings and pharmaceuticals.9 One of the major shortcomings in all of these early experiments was the failure to report milk PABA concentrations2, 3 which conceivably could have been quite variable – perhaps caused by various fodders fed to the cows or by different milk processing procedures. Additionally, because PABA is not an essential human nutrient, no tables of the PABA concentrations in common foods have ever been published. To my knowledge only a single study has reported the PABA concentrations in any food items (five vegetables: carrots, spinach, brussel sprouts, endive, and lettuce),10 whereas extensive USDA tables exist showing the folate concentrations in foods. Consequently, a crucial need exists to determine the PABA content of foods so that anti-malarial diets can be formulated and eventually tested.

The formulation of PABA deficient diets for humans will have no adverse health consequences as PABA is not required in human nutrition. Because about 80% of all deaths attributed to malaria occur in sub-Saharan Africa, mainly among children less than 5 years of age,2 the greatest risk to their lives comes not from inadequate folate intake, but rather from malaria.5 At a meeting hosted by the World Health Organization in 2006, five expert reports concluded that reducing folic acid supplementation in sub-Saharan African children may reduce fatal malarial infections.11

Conclusions

PABA deficient diets have virtually no adverse health effects in humans (both children and adults) because PABA is not required for human nutrition. Yet within the confines of the bacteria, Plasmodia species which cause malaria, deficiencies of this compound in their host’s bloodstream may have devastating effects upon the bacteria’s own metabolism and ability to reproduce and elicit lethal infections in humans. Unfortunately, no tables of PABA concentrations in everyday foodstuffs currently exist. Accordingly, we have no idea how to formulate PABA deficient diets in humans to thwart lethal malarial infections.

A good starting point would be descriptive in nature with the goal of characterizing the PABA content of a wide variety of foodstuffs, including sub-Saharan African ethnic foods. This PABA database along with pre-existing folate databases could be employed to formulate low PABA and folate diets that will be nutritionally adequate in all other respects. Further, it may be possible to formulate low PABA and folate diets without the use of milk which is contraindicated in many sub-Saharan African populations because of their inability to digest the milk sugar lactose without gastric upset.

Cordially,

Loren Cordain, Ph.D., Professor Emeritus

References

1. Kicska GA, Ting LM, Schramm VL, Kim K. Effect of dietary p-aminobenzoic acid on murine Plasmodium yoelii infection. J Infect Dis. 2003 Dec 1;188(11):1776-81

2. Kretschmar W, Voller A. Suppression of Plasmodium falciparum malaria in Aotus monkeys by milk diet. Z Tropenmed Parasitol. 1973 Mar;24(1):51-9.

3. Nowell F. The effect of a milk diet upon Plasmodium berghei, Nuttallia (=Babesia) rodhaini and Trypanosoma brucei infections in mice. Parasitology. 1970 Dec;61(3):425-33.

4. Jacobs RL Role of p-aminobenzoic acid in Plasmodium berghei infection in the mouse.
Exp Parasitol. 1964 Jun;15:213-25

5. Carter JY, Loolpapit MP, Lema OE, Tome JL, Nagelkerke NJ, Watkins WM Reduction of the efficacy of antifolate antimalarial therapy by folic acid supplementation. Am J Trop Med Hyg. 2005 Jul;73(1):166-70.

6. Modiano D, Petrarca V, Sirima BS, Nebié I, Diallo D, Esposito F, Coluzzi M. Different response to Plasmodium falciparum malaria in west African sympatric ethnic groups. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13206-11

7. Bereczky S, Dolo A, Maiga B, Hayano M, Granath F, Montgomery SM, Daou M, Arama C, Troye-Blomberg M, Doumbo OK, Färnert A. Spleen enlargement and genetic diversity of Plasmodium falciparum infection in two ethnic groups with different malaria susceptibility in Mali, West Africa. Trans R Soc Trop Med Hyg. 2006 Mar;100(3):248-57

8. Swallow DM. Genetics of lactase persistence and lactose intolerance. Annu Rev Genet. 2003;37:197-219

9. Walther B, Walther M. What does it take to control malaria? Ann Trop Med Parasitol. 2007 Dec;101(8):657-72

10. Zhang GF, Mortier KA, Storozhenko S, Van De Steene J, Van Der Straeten D, Lambert WE. Free and total para-aminobenzoic acid analysis in plants with high-performance liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2005; 19(8): 963-9.

11. Oppenheimer S. Comments on background papers related to iron, folic acid, malaria and other infections. Food Nutr Bull. 2007 Dec;28(4 Suppl):S550-9

Oven Roasted Brussels Sprouts

We know what you’re thinking: Grayish-green, mushy, mini cabbages our parents forced us to eat as kids at the dinner table? Not so! Once underestimated, Brussels sprouts have gained popularity and earned a spot on menus at restaurants nationwide.1 Trust us, once you master this foolproof way to enhance the natural flavor profile of Brussels sprouts, you will want to serve them on a regular basis.

Many home chefs routinely resort to steaming or boiling Brussels sprouts, which quickly breaks down the cell walls, whereas other cooking methods cause them to release sulfur compounds, and in part, an unappetizing smell and texture.2 Roasting cruciferous vegetables not only improves taste, but also preserves antioxidants, water soluble vitamins, like vitamin C, and glucosinolates, water soluble compounds linked to reduced risk for cancer.3, 4 The National Cancer Institute recommends the consumption of 5 – 9 servings (2 1/2 – 4 1/2 cups) of fruits and vegetables daily,5 specific recommendations for cruciferous vegetables have not been established yet. However, many studies suggest aiming for weekly servings of cruciferous vegetables would be beneficial for improving health.6, 11, 12

Brussels sprouts are part of the Brassicaceae family, which includes cabbage, cauliflower, broccoli, kale, and collard greens. All are excellent sources of vitamin C, vitamin K, vitamin A and ­folate, as well as fiber, potassium, iron, vitamin B6, manganese, magnesium, and thiamin.7 Brussels sprouts are high in sulforaphane, a chemical linked to anticancer properties,8 and were recently reported to improve the behavioral challenges associated with autism.9

This versatile roasted Brussels sprout recipe will teach you the foundation of how to properly roast them, and achieve their delicious flavor profile. However, as you experiment with different variations, consider topping the finished side dish with chopped, fresh parsley or rosemary, freshly ground black pepper, lemon zest, toasted pine nuts or sliced almonds.

Serve roasted Brussels sprouts underneath poached eggs for breakfast, or as a hearty side dish to accompany a roasted turkey breast for your family’s Paleo meal. As richly dense vegetables, they also make for a satisfying snack all by themselves.10

INGREDIENTS

Serves 2-3

  • 3/4 lbs Brussels sprouts (small to medium sized)
  • 1 tsp of olive oil

DIRECTIONS

brusselsbowlolive (1)
Preheat oven to 375°F. Trim the ends and remove any old outer leaves from the Brussels sprouts.
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references

1. Available at: //www.thepacker.com/fruit-vegetable-news/marketing-profiles/Brussels-sprouts-enjoy-newfound-popularity-199591491.html. Accessed on October 14, 2014.

2. Available at: //montanahomesteader.com/cooking-brassicas/. Accessed on October 14, 2014.

3. Ismail A, Lee WY. Influence of cooking practice on antioxidant properties and phenolic content of selected vegetables. Asia Pacific J. Clinical Nutrition, 13(Suppl.), 2004: S162.

4. McNaughton SA, Marks GC. Development of a food composition database for the estimation of dietary intakes of glucosinolates, the biologically active constituents of cruciferous vegetables. British Journal of Nutrition. 2003;90:687-97.

5. Available at: //www.nlm.nih.gov/medlineplus/ency/patientinstructions/000725.htm Accessed on October 14, 2014.

6. Michaud DS, Spiegelman D, Clinton SK, Rimm EB, Willett WC, Giovannucci EL. Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort. J Natl Cancer Inst.1999;91:60513. [PubMed]

7. Available at: //www.freshvegetablesontario.com/index.php?action=display&cat=3&v=8. Accessed on October 14, 2014.

8. Available at: //lpi.oregonstate.edu/ss06/vegetables.html. Accessed on October 14, 2014.

9.Available at: //www.cbsnews.com/news/broccoli-compound-shows-promise-for-treating-autism/. Accessed on October 14, 2014.

10. Available at: //www.nlm.nih.gov/medlineplus/ency/patientinstructions/000725.htm. Accessed on October 14, 2014.

11. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of cruciferous vegetables and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2003;12:14 03- 9. [PubMed]

12. Feskanich D, Ziegler RG, Michaud DS, Giovannucci EL, Speizer FE, Willett WC, et al. Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women. J Natl Cancer Inst. 2000;92:18 12-23. [PubMed]

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

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.

Folic Acid | The Paleo Diet

Dr. Cordain,

I just heard a study reported on NPR that reported that women who took folic acid supplements during early pregnancy reduced autism in their children. This conflicts directly with the info in your latest book, The Paleo Answer, about recommendations for folic acid supplements. Where do you stand on this? My wife and I are trying to have a baby I am unsure what to do with this new info.

Dr. Cordain’s Response:

I stand by the more comprehensive data (and not a single study reported in NPR) I have compiled in my most recent book, with a myriad of references (check those, and decide for yourself!). 

Folic acid is not necessarily equivalent in vivo to folate as they are two separate compounds. Folic acid from supplements must be converted into folate in the liver. Women need adequate folate stores to prevent neural tube defects (spina bifida in particular). Folate compromised women (which is a common situation among women who consume a typical western diet low in leafy greens, fruits and organ meats) can increase their body concentrations of folate by consuming artificial folic acid found in vitamins or fortified cereals.

Nevertheless, but there are metabolic and physiologic problems associated with folic acid supplementation which I fully describe in The Paleo Answer.  My suggestion to couples contemplating pregnancy and producing healthy children free of neural tube defects would be to reduce or eliminate processed foods which contain little folate and replace them with leafy greens, fruits, organ meats and other naturally occurring foods rich in folate.

Cordially,

Loren Cordain, Ph.D., Professor Emeritus

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