Medical Forum / General / Nutrition / September 2004
Study backs folic acid as means to cut birth defects
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tcomeau - 27 Sep 2004 19:44 GMT http://www.cbc.ca/story/science/national/2004/09/27/folic_acid040927.html
OTTAWA - Fortifying grain products with folic acid has led to a dramatic decline in the rate of birth defects such as spina bifida, a new study by Health Canada shows.
FROM AUG. 6, 2002: Folic acid in cereal cuts birth defects by half, studies find
Dark green, leafy vegetables are high in folate. The proportion of babies born with neural tube defects in Newfoundland and Labrador dropped by 78 per cent after the federal government required folic acid to be added to flour, cornmeal and pasta, researchers found.
Folic acid is the synthetic form of folate, also called vitamin B-9, which is found in citrus fruits, nuts, liver and dark green, leafy vegetables.
The vitamin has many important functions in the body, but it was in the mid-1960s that scientists discovered that folate deficiency might be the cause of neural tube defects, in which the central nervous system fails to develop fully in the fetus.
Neural tube defects can lead to spina bifida, a defect of the spinal cord and back bones, and less common defects of the brain such as anencephaly, when the brain doesn't develop fully.
Scientists don't know how folic acid reduces the risk of neural tube defects in developing babies.
Since 1992, many medical authorities have told women of child-bearing age to take folic acid supplements.
The Canadian government introduced mandatory fortification of some foods with folic acid in 1998.
Continue to fortify food, scientists say
Dr. Catherine McCourt, with Health Canada's population and public health branch in Ottawa, and her colleagues studied the effects of folic acid fortification in women aged 19 to 44 and in seniors in Newfoundland and Labrador.
The study looked at women in St. John's, Nfld. and the rural area of Clarenville, Port Blandford in the Random Island area.
Historically, the province has had one of the highest rates of neural tube defects in North America, the researchers said in the Sept. 27 issue of BMC Pregnancy and Childbirth.
McCourt's team found the fortification boosted dietary intake of folic acid by 70 micrograms per day, on average.
The incidence of neural tube defects in the province fell by 78 per cent, from an average of 4.36 defects per 1,000 births between 1991 and 1997, prior to fortification, to an average of 0.96 defects per 1,000 births between 1998 and 2001.
"Based on these findings, mandatory food fortification in Canada should continue at the current levels," the researchers concluded.
There is no way to tease out the contributions of food fortification and supplement use on the decline of neural tube defects, the researchers noted.
"Public education regarding folic acid supplement use by women of childbearing age should also continue," the study's authors added.
***********
So a diet high in cereal grains that are NOT enriched with folic acid leads to folic acid deficiency. Has it not occurred to them that a diet high in cereal grains will also lead to other vitamin deficiencies? Cereal grains contain little or no Vitamin C and B12 as well as others.
There are two options here. Fortify all cereal grains with all vitamins that it is deficient in. Or cut back on consuming these nutrient deficient cereal grains and eat other more complete nutrient-rich foods.
Cereal crains are for the birds, literally.
TC
Jan - 27 Sep 2004 21:35 GMT > *********** > [quoted text clipped - 10 lines] > > Cereal crains are for the birds, literally. Just look at this data, which shows that even unfortified cereal grains are much higher in folate than meat:
FOLATE PER 100 g: Millet 85 mcg Rye 60 mcg Rice, white 58 mcg Oats 56 mcg ... Beef 13 mcg Pork 6 mcg
(Source: NutritionData) So, meat is the bad guy, not cereal grains.
Jan
Matti Narkia - 27 Sep 2004 22:27 GMT 27 Sep 2004 13:35:32 -0700 in article <1096317332.144573.227440@k26g2000oda.googlegroups.com> "Jan" <shantigiri@luukku.com> wrote:
>> *********** >> [quoted text clipped - 25 lines] >(Source: NutritionData) >So, meat is the bad guy, not cereal grains. Meat may be the bad guy, but not because of your data, which just shows that unfortified grains are not so hot sources of folate and meats are even worse. Fishes are also poor sources of folate, but they are not regarded as the bad guys. Compare your data with the following data, which shows that liver products are the best sources of folate:
Folate, µg/100g:
Roast liver 1461.1 Pork liver 1391.2 Baking yeast 1250.0 Liver average 1226.0 Wheat germ 520.0 Basil 448.0 Soy meal, white 410.0 Soya flour low-fat 410.0 Bean brown/white 394.0 Soya beans 353.1 Kidney 353.1 Wheat bran 195.0 Asparagus 175.0 Chick pea in unsalted water 172.0 Parsley 170.0 Onion 166.0 Egg yolk 158.9 Red beet/beetroot 150.0 Bean white, cooked 149.7 Green bean/ broad bean 145.0 Carrot 143.0 Kale 120.0 Broccoli 113.1 Lentils green/ brown 110.0 Peanut 110.0
For more comprehensive lists see
Folate (HPLC), All food classes, µg/100g <URL:http://www.fineli.fi/topfoods.php?compid=2273&fuclass=all&specdiet=none&items=50 0&from=top&portion=100g&lang=en>
Folate (HPLC) in fish, µg/100g <URL:http://www.fineli.fi/topfoods.php?compid=2273&fuclass=fish&specdiet=none&items=5 00&from=top&portion=100g&lang=en>
 Signature Matti Narkia
Wolfbrother - 28 Sep 2004 06:58 GMT > 27 Sep 2004 13:35:32 -0700 in article > <1096317332.144573.227440@k26g2000oda.googlegroups.com> "Jan" [quoted text clipped - 74 lines] > Folate (HPLC) in fish, µg/100g > <URL:http://www.fineli.fi/topfoods.php?compid=2273&fuclass=fish&specdiet=none&items=5 00&from=top&portion=100g&lang=en> Yes liver is one of the ultimate sources of high quality nutrients. No plant source even comes close. All traditional meat eating cultures relished and prized such organs above all else. Her generalization of "meat" is ignorant and narrow minded. Our ancestors did not consider "meat" in the limited fashion that most people do today in our modern society and they understood its superiority over plant foods to support optimal human health. This knowledge was universal from one end of the earth to the other and in the most remote isolated regions despite total lack of communication between cultures. That is a powerful testament to the undeniable truth of such knowledge gained by so many cultures on their own over thousands of years.
Jan - 28 Sep 2004 07:00 GMT > Folate, µg/100g: > > Roast liver 1461.1 > Pork liver 1391.2 > Baking yeast 1250.0 > Liver average 1226.0 As you know there are other reasons why organ meats should not be favored as a source of folate.
http://www.nutritiondata.com/foods-000073000000000000000-w.html
Liver also collects toxic substances. It is healthier to rely on vegetarian sources of folate.
Jan
Matti Narkia - 28 Sep 2004 13:23 GMT 27 Sep 2004 23:00:01 -0700 in article <1096351201.554770.33500@h37g2000oda.googlegroups.com> "Jan" <shantigiri@luukku.com> wrote:
>> Folate, µg/100g: >> [quoted text clipped - 7 lines] > >http://www.nutritiondata.com/foods-000073000000000000000-w.html Compared with trans-fats and saturated fats, cholesterol in food is a minor issue. I've eaten 80 grams of cooked pork brain (brain foods are most cholesterol containing food items) and raw egg yolks daily for 10 years with no problems whatsoever, my serum lipid profile has in fact improved. But then I try to avoid trans- and saturated fats and eat my fatty fish and veggies, too, with extra virgin olive oil of course :-).
>Liver also collects toxic substances. It is healthier to rely on >vegetarian sources of folate. The safest bet is to use folic acid supplements (or eat foods fortified with folic acid, if they are reasonably unprocessed and healthy).
 Signature Matti Narkia
Wolfbrother - 28 Sep 2004 21:06 GMT > > Folate, g/100g: > > [quoted text clipped - 12 lines] > > Jan LOL! Cholesterol is your "other reason"?? Oh my god what a joke. You are so pathetic. Dietary cholesterol is just another reason why they are GOOD. Stop spouting your baseless garbage and fear mongering against healthy foods. You are doing a huge disservice to people and should be ashamed.
Robert - 29 Sep 2004 21:49 GMT > > > Folate, g/100g: > > > [quoted text clipped - 18 lines] > against healthy foods. You are doing a huge disservice to people and > should be ashamed. You are right. Eat anything you want and if your cholesterol is high then take statins. Eat whatever you want but the bottom line is your cholesterol level. I agree.
Matti Narkia - 30 Sep 2004 00:16 GMT 27 Sep 2004 23:00:01 -0700 in article <1096351201.554770.33500@h37g2000oda.googlegroups.com> "Jan" <shantigiri@luukku.com> wrote:
>> Folate, µg/100g: >> [quoted text clipped - 10 lines] >Liver also collects toxic substances. It is healthier to rely on >vegetarian sources of folate. I don't eat liver mainly for fear of toxic substances. But when I tried to search for information about this, I ended up almost empty handed. Seems that vegetables and fish have more environmental pollutants than liver, or for some reason liver's contamination is under reported.
Liver is loaded with nutrients, and liver-carrot juice was used Gerson's metabolic diet cancer therapy for decades until they stopped it due to difficulties getting sufficiently safe (not contaminated by toxic substances or hormones) calf livers. That may be problem in USA (or Mexico), but what's the situation Europe?
At least some people still seem to think that calf's liver is a health food:
<URL:http://www.whfoods.com/genpage.php?tname=foodspice&dbid=129>
Also Nutritiondata seems to appreciate liver and other organ meats:
343 Lamb, Veal, and Game Products With the highest ND Ratings <URL:http://www.nutritiondata.com/foods-017998000000000000000.html>
719 Beef Products With the highest ND Ratings <URL:http://www.nutritiondata.com/foods-013998000000000000000.html>
222 Pork Products With the highest ND Ratings <URL:http://www.nutritiondata.com/foods-010998000000000000000.html>
346 Poultry Products With the highest ND Ratings <URL:http://www.nutritiondata.com/foods-005998000000000000000.html>
Cholesterol is of course high, but that is a minor issue, if the diet is low in trans and saturated fatty acids and contains a lot of vegetables and monounsaturated and omega-3 fatty acids. Besides, who would want to eat liver daily?
So how about liver as an occasional health food? ;-). Perhaps once or twice in a month?
 Signature Matti Narkia
Jan - 30 Sep 2004 09:56 GMT > 27 Sep 2004 23:00:01 -0700 in article > <1096351201.554770.33500@h37g2000oda.googlegroups.com> "Jan" > <shantigiri@luukku.com> wrote:
> >Liver also collects toxic substances. It is healthier to rely on > >vegetarian sources of folate. [quoted text clipped - 8 lines] > difficulties getting sufficiently safe (not contaminated by toxic substances > or hormones) calf livers. Gerson was assured about the health benefits of natural enzymes and that was the basis of his raw juice cancer therapy. As far as I know the main reason for Gerson to use calf-liver juice were the living enzymes it contained, not so much the other nutrients. Another holistic health practioner, Paul Pitchford, estimates that it is difficult to get liver that would be safe enough and so he recommends sprouts, cereal-grass products and raw sauerkraut instead of liver as rich sources of natural food enzymes.
Jan
N-H-P - 28 Sep 2004 23:37 GMT > Compare your data with the following data, which shows that > liver products are the best sources of folate: May I suggest eating a raw salad?
Geesh!!! Folate from liver??? I mean really.
Folate requires vitamin B-12 to convert it into folic acid. B-12 is a limiting factor which comes from meat sources.
smn seems to be regressing. :( -- John Gohde
Matti Narkia - 29 Sep 2004 02:03 GMT 28 Sep 2004 15:37:26 -0700 in article <16a9b594.0409281437.3f0ffe1e@posting.google.com>
>> Compare your data with the following data, which shows that >> liver products are the best sources of folate: > >May I suggest eating a raw salad? Well, I do ;-). So? How much folate you expect to get from it into your circulation?
See
Folate Deficiency Widespread Worldwide <URL:http://www.sph.emory.edu/PAMM/folicacid.htm>
"... Recent research has shown that almost all people who do not consume supplemental folic acid are folate deficient. ..."
Remember, that folate from the food is absorbed less efficiently by our bodies than folic acid from supplements or fortified food:
<URL:http://www.ext.colostate.edu/pubs/columnnn/nn000829.html>
"... It is important to note that cooking and storing food can destroy some natural folate. The amount of the vitamin available to the body varies widely among foods and the condition of the food when it is eaten. On the other hand, the body can absorb nearly 100 percent of the synthetic form of folic acid. This has led the Institute of Medicine, the Centers for Disease Control and Prevention and the March of Dimes to recommend that all women of reproductive age take 400 micrograms of synthetic folic acid daily either through fortified breakfast cereals or a multi-vitamin. ..."
<URL:http://www.cce.cornell.edu/food/expfiles/topics/stover/folicqanda.html>
"Q. What's the difference between the terms folic acid and folate? A.In cells, folic acid exists in many chemical forms with respect to its oxidation state, one-carbon substitutions and number of glutamate residues. In general, the term folates, when used in the generic sense, refers to all chemical forms of folic acid. The term folic acid refers to the oxidized, monoglutamate form of folate otherwise known as pteroylglutamic acid. Q. Is there a difference in bioavailability between folic acid in foods versus supplements? A. The bioavailability of food folate is difficult to predict. In general, the oxidized, monoglutamate form of folate, the form found in supplements and the form used to fortify foods, has a much greater bioavailability than food folate which tends to be in a chemically reduced and in a polyglutamated form. The absorption of supplement folate during fasting is near 100%. Prior to absorption, folate polyglutamates must be enzymatically converted to folate monoglutamates, and the efficiency of this reaction varies depending upon the food source of folate. Therefore, while all sources are important, more folate is absorbed from fortified foods and supplements. Folic acid supplements are even more bioavailable if taken between meals."
<URL:http://users.umassmed.edu/martin.marinus/Mph200/FolicAcidMetabolism.pdf>
"DHF and THF from natural sources are polyglutamated and need to be enzymatically converted to the monoglutamate for absorption from the small intestine." (DHF=dihydrofolic acid; THF=tetrahydrofolic acid)
<URL:http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/fol_0110.shtml> "PHARMACOKINETICS
Folic acid or pteroylglutamic acid (PGA) is the form of folate used in food fortification and the principal form of folate found in nutritional supplements. Natural food folates are pteroylpolyglutamate derivatives. Pteroylpolyglutamate derivatives are hydrolyzed to pteroylmonoglutamate forms prior to absorption from the small intestine. The enzyme that catalyzes the cleavage is called folate conjugase or gamma-glutamylhydrolase. The monoglutamate forms of folate, including folic acid, are transported across the proximal small intestine via a saturable pH-dependent process. Higher doses of the pteroylmonoglutamates, including folic acid, are absorbed via a nonsaturable passive diffusion process. The efficiency of absorption of the pteroylmonoglutamates is greater than that of the pteroylpolyglutamates.
Because of the difference in absorption efficiency between natural food folate and folic acid, the concept of dietary folate equivalents (DFEs) has been introduced. Folic acid taken on an empty stomach is twice as available as food folate. Folic acid taken with food is 1.7 times as available as food folate. For example, 400 micrograms of folic acid taken on an empty stomach is equivalent to 470 micrograms of folic acid taken with food and is equivalent to 800 micrograms of food folate. DFEs can be calculated as follows:
1 microgram of DFEs = 1 microgram of food folate = 0.5 micrograms of folic acid taken on an empty stomach = 0.6 micrograms of folic acid taken with meals.
Following absorption of physiological amounts of folic acid into the enterocytes, a certain percentage undergoes reduction. Reduced folate is transported to the liver via the portal circulation. Much of a pharmacological dose of folic acid is transported to the liver as such, without first undergoing metabolism in the enterocytes. The various natural pteroylmonoglutamate forms undergo some metabolism in the enterocytes to pteroylpolyglutamate forms, but for the most part are also transported as their unmetabolized forms via the portal circulation to the liver. The folates are taken up by the liver and metabolized to polyglutamate derivatives (principally pteroylpentaglutamates), via the action of folylpolyglutamate synthase. Folates are stored in tissue in their polyglutamate forms. Folate is metabolized to its various metabolic forms in the liver. The various pteroylpolyglutamate forms are the active cellular cofactor forms of folate. Folate polyglutamates are released from the liver to the systemic circulation and to the bile. When released from the liver into the circulation, the polyglutamate forms are hydrolyzed by gamma- glutamylhydrolase and reconverted to the monoglutamate forms.
The principal folate in the plasma is 5- methyltetrahydrofolate in its monoglutate form. 5- Methyltetrahydrofolate circulates in erythrocytes in its polyglutamate form. Approximately two-thirds of folate in plasma is protein bound. All tissue forms of folate are polyglutamates, while circulating forms of folate are monoglutamates. When pharmacological doses of folic acid are administered, a significant amount of unchanged folic acid is found in the plasma. The liver contains approximately 50% of the body stores of folate, or about 6 to 14 milligrams. The total body store of folate is about 12 to 28 milligrams.
Folate is excreted in the urine as folate cleavage products. Intact folate enters the glomerulus and is reabsorbed into the proximal renal tubule. Very little intact folate is excreted in the urine. Folate is excreted in the bile and much of it is reabsorbed via the enterohepatic circulation."
>Geesh!!! Folate from liver??? I mean really. The fact remains that liver products are the richest sources of folate. Live with it. No recommendations were given.
>Folate requires vitamin B-12 to convert it into folic acid. Perhaps not exactly so. B12 is needed to convert circulating 5- methyltetrahydrofolate (5-methyl THFA), omce inside the cell, to THFA, the active form participating in folate-dependent enzymatic reactions. In the absence of B12, folate is "trapped" as 5-methyl THFA.
But, dietary folate is either monoglutamate or polyglutamate. Most is polyglutamate and it can not be absorbed at all. All supplement folic acid is monoglutamate and it is absorbed very well. The human gut has a peptidase that hydrolyzes all of the glutamate off the polyglutamate to give the monoglutamate form. Now, if I remember corrctly, this enzyme will not work without B12. Low B12 will cause a folate deficiency unless a folic acid supplement is used. The page
<URL:http://www.feinberg.northwestern.edu/nutrition/factsheets/folate.html>
seems to agree with me:
"... Only about half of the folate consumed from food sources has acceptable bioavailability. Folate occurs naturally attached to multiple glutamic acid molecules which must be removed by hydrolysis prior to absorption by a vitamin B12-dependent enzyme to form pteroylmonoglutamate. In general, foods with high proportions of the monoglutamate form have higher folate bioavailability irrespective of the total amount. ..."
So B12 is needed both for the absorption of dietary folate and for the folate metabolism inside the cell.
See also
<URL:http://www.emedicine.com/MED/topic802.htm>:
"Folic acid is composed of a pterin ring connected to p- aminobenzoic acid (PABA) and conjugated with one or more glutamate residues. It is distributed widely in green leafy vegetables, citrus fruits, and animal products. Humans do not generate folate endogenously because they cannot synthesize PABA, nor can they conjugate the first glutamate. Folates are present in natural foods and tissues as polyglutamates because these forms serve to keep the folates within cells. In plasma and urine, they are found as monoglutamates because this is the only form that can be transported across membranes. Enzymes in the lumen of the small intestine convert the polyglutamate form to the monoglutamate form of the folate, which is absorbed in the proximal jejunum via both active and passive transport. Within the plasma, folate is present, mostly in the 5- methyltetrahydrofolate (5-methyl THFA) form, and is loosely associated with plasma albumin in circulation. The 5-methyl THFA enters the cell via a diverse range of folate transporters with differing affinities and mechanisms (ie, adenosine triphosphate [ATP]dependent H+ cotransporter or anion exchanger). Once inside, 5-methyl THFA may be demethylated to THFA, the active form participating in folate-dependent enzymatic reactions. Cobalamin (B-12) is required in this conversion, and in its absence, folate is "trapped" as 5-methyl THFA. From then on, folate no longer is able to participate in its metabolic pathways, and megaloblastic anemia results. Large doses of supplemental folate can bypass the folate trap, and megaloblastic anemia will not occur. However, the neurologic/psychiatric abnormalities associated with B-12 deficiency ensue progressively. The biologically active form of folic acid is tetrahydrofolic acid (THFA), which is derived by the 2-step reduction of folate involving dihydrofolate reductase. THFA plays a key role in the transfer of 1-carbon units (such as methyl, methylene, and formyl groups) to the essential substrates involved in the synthesis of DNA, RNA, and proteins. More specifically, THFA is involved with the enzymatic reactions necessary to synthesis of purine, thymidine, and amino acid. Manifestations of folate deficiency thereafter, not surprisingly, would involve impairment of cell division, accumulation of possibly toxic metabolites such as homocysteine, and impairment of methylation reactions involved in the regulation of gene expression, thus increasing neoplastic risks."
>B-12 is a >limiting factor which comes from meat sources. And how much B12 is in raw salad? ;-).
See also
<URL:http://users.umassmed.edu/martin.marinus/Mph200/FolicAcidMetabolism.pdf>
"* Increased excretion/loss: Increased excretion of folate can occur subsequent to vitamin B-12 deficiency. During the course of vitamin B-12 deficiency, methylene THFA is known to accumulate in the serum, which is known as the folate trap phenomenon. In turn, large amounts of folate filter through the glomerulus, and urine excretion occurs. Another mechanism of excess excretion occurs in people with chronic alcoholism who can have increased excretion of folate into the bile. Patients undergoing hemodialysis also have been known to have excess folate loss during procedures."
 Signature Matti Narkia
Matti Narkia - 29 Sep 2004 16:50 GMT Wed, 29 Sep 2004 04:03:28 +0300 in article <5iqjl05gb60vlk2sjlcng0doq9vfkffmdh@4ax.com> Matti Narkia <mnng1_REMOVE_THIS@despammed.com> wrote:
><URL:http://www.cce.cornell.edu/food/expfiles/topics/stover/folicqanda.html> > [quoted text clipped - 9 lines] > pteroylglutamic acid. > See also
<URL:http://europa.eu.int/comm/food/fs/sc/scf/out80e_en.pdf>:
"Folate is the generic name for a number of compounds having a similar activity as folic acid (pteroylglutamic acid, PGA), i.e. being involved in single carbon (C1-) transfer reactions. Folic acid (PGA) is a synthetic folate compound used in food supplements and in food fortification because of its stability, and becomes biologically active after reduction. Natural (dietary) folates are mostly reduced folates, i.e. derivatives of tetrahydrofolate (THF), such as 5-methyl- THF (5-MTHF), 5- formyl-THF and 5,10-methylene- THF, and exist mainly as pteroylpolyglutamates, with up to nine additional glutamate molecules attached to the pteridine ring."
and
Folate (Folic acid): Implications for health and disease <URL:http://www.teknoscienze.com/agro/pdf/may_june03/folate.PDF>:
"Folate, a member of the B vitamin family, is the generic name for a number of chemical forms, which are structurally related and that have similar biological activity (1). Folate received its name from the Latin word folium, which means foliage, because it is found in high concentrations in green leafy vegetables like spinach, kale, beet greens, and chard. Other good sources of folate include legumes, whole grains, oranges, broccoli and cabbage (2).
The naturally occurring forms of folate include 5- methyltetrahydrofolate (5-MTHF), 5-formyltetrahydrofolate (5-formyl-THF), 5,10-methylenetetrahydrofolate (5,10- methylene-THF) and five other chemicals, most of which are considered pteroylpolyglutamates because of their chemical structure. Common among these folates are two to seven glutamates joined in peptide linkages to the gamma-carboxyl of glutamate (1).
One of the natural folates, folinic acid, is used as a pharmaceutical agent. Also known as 5-formyl-THF, folinic acid is used as rescue therapy following high dose methotrexate regimens (1). It is also used in the treatment of megaloblastic anemia due to folate deficiency and its combination with 5-fluorouracil has until recently been standard therapy for colorectal cancer.
Folic acid is the synthetic form of folate, which is used for nutritional supplements and food fortification. Folic acid or pterolyglutamic acid is the most oxidized and stable form of folate and is comprised of para-aminobenzoic acid linked at one end to a pteridine ring and at the other end to glutamic acid (1,3) see Figure 1 for chemical structure of folic acid).
>>Folate requires vitamin B-12 to convert it into folic acid. > [quoted text clipped - 26 lines] >So B12 is needed both for the absorption of dietary folate and for the >folate metabolism inside the cell. See also
<URL:http://europa.eu.int/comm/food/fs/sc/scf/out80e_en.pdf>:
"Food folates, mainly present as polyglutamates, have to be hydrolysed by a (brush border associated) deconjugase enzyme in the gut before absorption can occur. Folate absorption from natural food is generally lower than synthetic forms (e.g. folic acid) contained in supplements, due to matrix effects and the presence of inhibitors of the conjugase enzyme in some foods. Folic acid (PGA) enters the folate cycle after reduction by a (dihydro-)folate reductase. This enzyme is present in the intestinal mucosal cell, but also in other tissues, such as liver and kidney. Reduction of PGA may be a slow process in some subjects and at higher intake levels (> ca 260 µg) PGA may appear unchanged in the circulation (i.e. in the postprandial state after supplement use (Kelly et al., 1997). Under normal conditions 5-MTHF (as monoglutamate) is the only form present in plasma, mainly protein-bound. Tissue uptake is carrier-mediated and/or through folate binding proteins. In tissues folates are retained as polyglutamates and the folate coenzymes can be interconverted in numerous (de-)methylation reactions, such as in DNA synthesis (formation of thymidilate from deoxyuridine), amino acid interconversions, such as the remethylation of homocysteine to methionine. In this latter methionine synthase (MS) reaction vitamin B12 is also involved as a cofactor. About 50% of the folate body store, estimated to be 13-28 mg, is considered to be present in the liver (for review see Report of the Standing Committee on the scientific evaluation of dietary reference intakes (DRIs) and its panel on folate and other B-vitamins and choline. Food and Nutrition Board, Institute of Medicine, 1998)."
and
Folate (Folic acid): Implications for health and disease <URL:http://www.teknoscienze.com/agro/pdf/may_june03/folate.PDF>:
"Natural food folates, or pteroylpolyglutamates are hydrolyzed to pteroylmonoglutamate forms prior to absorption in the small intestine. The monoglutamate forms of folate, including folic acid, are transported across the proximal small intestine via a saturable pH-dependent process. Higher doses of folic acid are absorbed via a nonsaturable passive diffusion process (1,3).
The bioavailability of ingested folate monoglutamates is significantly greater than that of folate polyglutamates presumably because of the requirement for hydrolysis of the latter (3). The enzyme responsible for hydrolysis (i.e. folate conjugase) of folate polyglutamates may be specifically inhibited by food factors in yeast and beans and may be nonspecifically impaired at acid pH (3). The absorption efficiency of natural folates is approximately 50 percent that of synthetic folic acid (1-3). Folic acid taken on an empty stomach is twice as available as food folate, and folic acid taken with food is 1.7 times as available as food folate. For instance, 400 µg of folic acid taken on an empty stomach is equivalent to 470 µg of folic acid taken with food and is equivalent to 800 µg of food folate (1)."
Additional reading:
Chapter 4. Folate and folic acid <URL:http://www.fao.org/DOCREP/004/Y2809E/y2809e0a.htm> (in Human Vitamin and Mineral Requirements Report of a joint FAO/WHO expert consultation Bangkok, Thailand <URL:http://www.fao.org/DOCREP/004/Y2809E/y2809e00.htm>)
Folate Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (1998) Institute of Medicine (IOM) <URL:http://books.nap.edu/books/0309065542/html/196.html>
4. Absorption of Vitamins and Minerals <URL:http://gastroresource.com/GITextbook/En/Chapter7/7-4.htm> (in First Principles of Gastroenterology <URL:http://gastroresource.com/GITextbook/en/Default.htm>)
Bailey LB, Gregory JF 3rd. Folate metabolism and requirements. J Nutr. 1999 Apr;129(4):779-82. Review. <URL:http://www.nutrition.org/cgi/content/full/129/4/779>
Jacob RA. Folate, DNA methylation, and gene expression: factors of nature and nurture. Am J Clin Nutr. 2000 Oct;72(4):903-4. <URL:http://www.ajcn.org/cgi/content/full/72/4/903>
Duthie SJ, Narayanan S, Brand GM, Pirie L, Grant G. Impact of folate deficiency on DNA stability. J Nutr. 2002 Aug;132(8 Suppl):2444S-2449S. <URL:http://www.nutrition.org/cgi/content/full/132/8/2444S>
Choi SW, Mason JB. Folate status: effects on pathways of colorectal carcinogenesis. J Nutr. 2002 Aug;132(8 Suppl):2413S-2418S. Review. <URL:http://www.nutrition.org/cgi/content/full/132/8/2413S>
 Signature Matti Narkia
Matti Narkia - 30 Sep 2004 02:01 GMT Tue, 28 Sep 2004 00:27:32 +0300 in article <prvgl09grdeebt23n2qal51qu4ikkd30ei@4ax.com> Matti Narkia <mnng1_REMOVE_THIS@despammed.com> wrote:
>27 Sep 2004 13:35:32 -0700 in article ><1096317332.144573.227440@k26g2000oda.googlegroups.com> "Jan" [quoted text clipped - 71 lines] >Folate (HPLC), All food classes, µg/100g ><URL:http://www.fineli.fi/topfoods.php?compid=2273&fuclass=all&specdiet=none&items=50 0&from=top&portion=100g&lang=en> The list above was from the Finnish National Health Institute's database. The U.S. list provided by Nutritiondata expectedly looks different, it's dominated by fortified cereals, but I didn't expect it to show so different values for liver products:
999 Foods Highest in Folate (based on levels per 100 grams) <URL:http://www.nutritiondata.com/foods-000112000000000000000-w.html>
Do the domestic animals feeding program differ so much in different countries, and even if they do, could they explain such vast differences?
 Signature Matti Narkia
Matti Narkia - 29 Sep 2004 16:57 GMT 27 Sep 2004 11:44:18 -0700 in article <b550f406.0409271044.5e03886e@posting.google.com> tunderbar@hotmail.com
>http://www.cbc.ca/story/science/national/2004/09/27/folic_acid040927.html > >OTTAWA - Fortifying grain products with folic acid has led to a >dramatic decline in the rate of birth defects such as spina bifida, a >new study by Health Canada shows. The reference is
Liu S, West R, Randell E, Longerich L, O'Connor KS, Scott H, Crowley M, Lam A, Prabhakaran V, McCourt C. A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects. BMC Pregnancy Childbirth. 2004 Sep 27 [Epub ahead of print] PMID: 15450123 [PubMed - as supplied by publisher] <URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra ct&list_uids=15450123>
Abstract:
"BACKGROUND: Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD). In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention. METHODS: This study was carried out in women aged 19-44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I) Determination of rates of NTDs; II) Dietary assessment; III) Blood analysis; IV) Assessment of knowledge and use of folic acid supplements. RESULTS: The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991-93 and 1994-97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76-1.34). The rates of NTDs fell by 78% (95% CI 65%-86%) after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991-1997 to 0.96 per 1,000 births during 1998-2001 (RR 0.22, 95% CI 0.14-0.35). The average dietary intake of folic acid due to fortification was 70 ug/day in women aged 19-44 years and 74 ug/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B12 deficiencies, and no evidence of improved folate status masking hematological manifestations of vitamin B12 deficiency. The proportion of women aged 19-44 years taking a vitamin supplement containing folic acid increased from 17% to 28%. CONCLUSIONS: Based on these findings, mandatory food fortification in Canada should continue at the current levels. Public education regarding folic acid supplement use by women of childbearing age should also continue."
 Signature Matti Narkia
Matti Narkia - 29 Sep 2004 17:38 GMT Some people with genetic or metabolic abnormalities or diseases may have higher than normal requirements for folate (or other vitamins or nutrients). A large part, 5-15% of general population have a genetic abnormality which causes folate deficiency even if they are meeting the current dietary reference intake, see the study
Molloy AM, Daly S, Mills JL, Kirke PN, Whitehead AS, Ramsbottom D, Conley MR, Weir DG, Scott JM. Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: implications for folate intake recommendations. Lancet. 1997 May 31;349(9065):1591-3. PMID: 9174561 [PubMed - indexed for MEDLINE] <URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9 174561&dopt=Abstract>
Abstract:
"BACKGROUND: The dietary reference values for folate, as for other nutrients, are targeted to the general and supposedly normal population, not people with special needs, such as those with genetic or metabolic abnormalities or diseases. However, 5-15% of general populations are homozygous for a thermolabile variant of 5,10-methylenetetrahydrofolate reductase (C677T) which causes mild hyperhomocysteinaemia and is positively associated with the development of vascular disease and the risk of neural-tube defects. If tissue-folate status is compromised in large sectors of the population by this or other genetic variants, the present dietary reference values may need to be changed. METHODS: We identified the C677T genotype and measured red-cell folate concentrations in two groups of healthy women (pregnant, 242, not pregnant, 318). We then analysed the effect of genotype on red-cell folates, which are a reliable marker for tissue folate stores. FINDINGS: In the pregnant group there were 20 TT homozygotes, 114 wild-type CC homozygotes, and 108 CT heterozygotes. In the non-pregnant group, the numbers were 41, 148, and 129. In both pregnant and non- pregnant groups, red-cell folate was significantly lower among TT homozygous than CC homozygous women (mean 252 [95% CI 202-317] vs 347 [321-372] micrograms/L, p = 0.002 for pregnant women; 284 [250-327] vs 347 [342-372] micrograms/L, p = 0.01 for non-pregnant women). Plasma folate was also significantly lower in TT homozygous than in CC homozygous women in the pregnant group (p = 0.009) but not in the non- pregnant group. INTERPRETATION: These results suggest that a substantial minority of people in general populations may have increased folate needs. Future studies may show the presence of other common genetic variants that interact with particular nutrients and place doubts on the validity of assuming "normality" for nutrient requirements in any general population."
Comments in the "Talking Points" section in the same issue of the Lancet:
Rethinking nutrient recommendations Lancet. 1997 May 31;349(9065) <URL:http://www.thelancet.com/journal/vol349/iss9065/full/llan.349.9065.talking_point s.8590.1>
"The dietary reference-value system lists recommendations for the daily intake of nutrients based on the average need of the general population. However, Molloy and colleagues argue that for groups with genetic or metabolic abnormalities or diseases, these recommendations may not be appropriate. Pregnant and non-pregnant women were genotyped for the thermolabile variant of the 5,10- methylenetetrahydrofolate reductase enzyme (C677T). Women with the thermolabile variant are at risk of neural-tube defects developing in their babies. 8·3% of pregnant women were homozygous for the thermolabile variant and had significantly lower red-cell folate concentrations. This finding, the authors conclude, means that a substantial minority of the population is at a disadvantage because of current recommendations for folate intake, and the reference-value system should take this into account."
This study was at the time of it's publication also commented in a Yahoo's news article, from which I've saved a few excerpts:
"As many as 15% of people may have a genetic variation causing a deficiency in the vitamin folic acid, even if they are meeting nutritional guidelines for the vitamin, according to results of a new study.
"These results suggest that a substantial minority of people in general populations may have increased folate needs," write the team of Irish and America researchers. "
[...]
"If this genetic variation is as common as the study results indicate, and if there are similar genetic variations affecting other important nutrients, current dietary guidelines may lose their relevance, say the authors of a study published in this week's issue of The Lancet.
"Future studies may show the presence of other common genetic variants that interact with particular nutrients and place doubts on the validity of assuming 'normality' for nutrient requirements in any general population," write the study authors. "
[...]
A few years ago, a research team led by Dr. Anne Molloy, of Trinity College, Dublin, identified a mutation in the gene for a particular enzyme, called 5,10 methylenetetrahydrofolate reductase. The enzyme activates folate within the cells, and a mutation in the gene makes the enzyme much less effective.
People with two copies of the abnormal gene had a higher risk of having a neural tube defect, compared with people who had two normal genes or just one copy of the abnormal gene.
About 5% to 15% of people have two copies of the abnormal gene, a figure that varies with the population being studied.
The researchers went on to look for the mutation in blood samples from Irish women, a population in which there is a relatively high rate of neural tube defects. Twenty of 242 pregnant women and 41 of 318 non-pregnant women tested had two copies of the abnormal gene.
Women with two copies of the abnormal gene also had lower levels of folate in their red blood cells than other women. This suggests, but does not prove, that the women with two abnormal genes have a higher folate requirement than the rest of the population, the authors say.
[...]
The study "challenges the assumption underlying the recommended daily allowance (RDA) -- that virtually everyone can take the same amount of a vitamin and do fine," Mills stated in a press release from the NICHD.
The current RDA for folate is 400 micrograms per day for pregnant women, 180 micrograms for other adult women, and 200 micrograms for adult men.
The RDA was created to reflect the dietary requirements for an average person. "If genetic variants that cause altered nutrient status are common, as this study suggests, there may be no such thing as a 'normal' population with respect to nutrient requirements," the researchers concluded."
Related studies:
Nair KG, Nair SR, Ashavaid TF, Dalal JJ, Eghlim FF. Methylenetetrahydrofolate reductase gene mutation and hyperhomocysteinemia as a risk factor for coronary heart disease in the Indian population. J Assoc Physicians India. 2002 May;50 Suppl:9-15. PMID: 12186157 [PubMed - indexed for MEDLINE] <URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra ct&list_uids=12186157>
de Franchis R, Botto LD, Sebastio G, Ricci R, Iolascon A, Capra V, Andria G, Mastroiacovo P. Spina bifida and folate-related genes: a study of gene-gene interactions. Genet Med. 2002 May-Jun;4(3):126-30. PMID: 12180146 [PubMed - indexed for MEDLINE] <URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra ct&list_uids=12180146>
Schwahn B, Rozen R. Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences. Am J Pharmacogenomics. 2001;1(3):189-201. Review. PMID: 12083967 [PubMed - indexed for MEDLINE] <URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra ct&list_uids=12083967>
Friso S, Choi SW, Girelli D, Mason JB, Dolnikowski GG, Bagley PJ, Olivieri O, Jacques PF, Rosenberg IH, Corrocher R, Selhub J. A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5606-11. Epub 2002 Apr 02. PMID: 11929966 [PubMed - indexed for MEDLINE] <URL:http://www.pnas.org/cgi/content/full/99/8/5606>
Garcia-Fragoso L, Garcia-Garcia I, de L, Renta J, Cadilla CL. Presence of the 5,10-methylenetetrahydrofolate reductase C677T mutation in Puerto Rican patients with neural tube defects. J Child Neurol. 2002 Jan;17(1):30-2. PMID: 11913566 [PubMed - indexed for MEDLINE] <URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra ct&list_uids=11913566>
Quere I, Perneger TV, Zittoun J, Bellet H, Gris JC, Daures JP, Schved JF, Mercier E, Laroche JP, Dauzat M, Bounameaux H, Janbon C, de Moerloose P. Red blood cell methylfolate and plasma homocysteine as risk factors for venous thromboembolism: a matched case-control study. Lancet. 2002 Mar 2;359(9308):747-52. PMID: 11888585 [PubMed - indexed for MEDLINE] <URL:http://www.thelancet.com/journal/vol359/iss9308/full/llan.359.9308.original_rese arch.20160.1>
Fujimura H, Kawasaki T, Sakata T, Ariyoshi H, Kato H, Monden M, Miyata T. Common C677T polymorphism in the methylenetetrahydrofolate reductase gene increases the risk for deep vein thrombosis in patients with predisposition of thrombophilia. Thromb Res. 2000 Apr 1;98(1):1-8. PMID: 10706928 [PubMed - indexed for MEDLINE] <URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra ct&list_uids=10706928>
Lalouschek W, Aull S, Serles W, Wolfsberger M, Deecke L, Pabinger-Fasching I, Mannhalter C. The relation between erythrocyte volume and folate levels is influenced by a common mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T). J Investig Med. 2000 Jan;48(1):14-20. PMID: 10695265 [PubMed - indexed for MEDLINE] <URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra ct&list_uids=10695265>
Bjorke-Monsen AL, Ueland PM, Schneede J, Vollset SE, Refsum H. Elevated plasma total homocysteine and C677T mutation of the methylenetetrahydrofolate reductase gene in patients with spina bifida. QJM. 1997 Sep;90(9):593-6. PMID: 9349452 [PubMed - indexed for MEDLINE] <URL:http://qjmed.oupjournals.org/cgi/reprint/90/9/593>
 Signature Matti Narkia
Matti Narkia - 29 Sep 2004 21:14 GMT Additional articles of interest:
Halsted CH. The intestinal absorption of folates. Am J Clin Nutr. 1979 Apr;32(4):846-55. Review. <URL:http://www.ajcn.org/cgi/content/abstract/32/4/846>
Antony AC The biological chemistry of folate receptors. Blood. 1992 Jun 1;79(11):2807-20. Review. <URL:http://www.bloodjournal.org/cgi/reprint/79/11/2807>
Reynolds E. Fortification of flour with folic acid. Fortification has several potential risks. BMJ. 2002 Apr 13;324(7342):918. <URL:http://bmj.bmjjournals.com/cgi/content/full/324/7342/918>
Oakley GP. Delaying folic acid fortification of flour. BMJ. 2002 Jun 8;324(7350):1348-9. <URL:http://bmj.bmjjournals.com/cgi/content/full/324/7350/1348>
Lucock M. Is folic acid the ultimate functional food component for disease prevention? BMJ. 2004 Jan 24;328(7433):211-4. Review. <URL:http://bmj.bmjjournals.com/cgi/content/full/328/7433/211>
Smith R "Let food be thy medicine..." BMJ. 2004 Jan 24;328(7433) Editorial <URL:http://bmj.bmjjournals.com/cgi/content/full/328/7433/0-g>
Dickinson CJ. Does folic acid harm people with vitamin B12 deficiency? QJM. 1995 May;88(5):357-64. Review. <URL:http://qjmed.oupjournals.org/cgi/content/abstract/88/5/357>
Carmel R, Green R, Rosenblatt DS, Watkins D. Update on cobalamin, folate, and homocysteine. Hematology (Am Soc Hematol Educ Program). 2003;:62-81. Review. <URL:http://www.asheducationbook.org/cgi/content/full/2003/1/62>
Verhaar MC, Stroes E, Rabelink TJ. Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2002 Jan;22(1):6-13. Review. <URL:http://atvb.ahajournals.org/cgi/content/full/22/1/6>
Tice JA, Ross E, Coxson PG, Rosenberg I, Weinstein MC, Hunink MG, Goldman PA, Williams L, Goldman L. Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the prevention of coronary heart disease: effect of grain fortification and beyond. JAMA. 2001 Aug 22-29;286(8):936-43. <URL:http://jama.ama-assn.org/cgi/content/full/286/8/936>
Brattstrom L, Wilcken DE. Homocysteine and cardiovascular disease: cause or effect? Am J Clin Nutr. 2000 Aug;72(2):315-23. Review. <URL:http://www.ajcn.org/cgi/content/full/72/2/315>
Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002 Nov 23;325(7374):1202. <URL:http://bmj.bmjjournals.com/cgi/content/full/325/7374/1202>
Brown AA, Hu FB. Dietary modulation of endothelial function: implications for cardiovascular disease. Am J Clin Nutr. 2001 Apr;73(4):673-86. Review. <URL:http://www.ajcn.org/cgi/content/full/73/4/673>
van der Put NM, van Straaten HW, Trijbels FJ, Blom HJ. Folate, homocysteine and neural tube defects: an overview. Exp Biol Med (Maywood). 2001 Apr;226(4):243-70. Review. <URL:http://www.ebmonline.org/cgi/content/full/226/4/243>
Brent RL, Oakley GP Jr, Mattison DR. The unnecessary epidemic of folic acid-preventable spina bifida and anencephaly. Pediatrics. 2000 Oct;106(4):825-7. <URL:http://pediatrics.aappublications.org/cgi/content/full/106/4/825>
Reynolds EH. Benefits and risks of folic acid to the nervous system. J Neurol Neurosurg Psychiatry. 2002 May;72(5):567-71. Review. <URL:http://jnnp.bmjjournals.com/cgi/content/full/72/5/567>
Reynolds EH. Folic acid, ageing, depression, and dementia. BMJ. 2002 Jun 22;324(7352):1512-5. Review. <URL:http://bmj.bmjjournals.com/cgi/content/full/324/7352/1512>
Sculthorpe NF, Davies B, Ashton T, Allison S, McGuire DN, Malhi JS. Commercially available folic acid supplements and their compliance with the British Pharmacopoeia test for dissolution. J Public Health Med. 2001 Sep;23(3):195-7. <URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=1 1585191&dopt=Abstract>
Bjelland I, Tell GS, Vollset SE, Refsum H, Ueland PM. Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry. 2003 Jun;60(6):618-26. <URL:http://archpsyc.ama-assn.org/cgi/content/abstract/60/6/618>
Ramos MI, Allen LH, Haan MN, Green R, Miller JW. Plasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification. Am J Clin Nutr. 2004 Oct;80(4):1024-8. <URL:http://www.ajcn.org/cgi/content/abstract/80/4/1024>
Stover PJ, Garza C. Bringing individuality to public health recommendations. J Nutr. 2002 Aug;132(8 Suppl):2476S-2480S. Review. <URL:http://www.nutrition.org/cgi/content/full/132/8/2476S>
Ames BN, Elson-Schwab I, Silver EA. High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms. Am J Clin Nutr. 2002 Apr;75(4):616-58. Review. <URL:http://www.ajcn.org/cgi/content/full/75/4/616>
Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG; MTHFR Studies Collaboration Group. MTHFR 677C-->T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA. 2002 Oct 23-30;288(16):2023-31. <URL:http://jama.ama-assn.org/cgi/content/full/288/16/2023>
de Bree A, Verschuren WM, Bjorke-Monsen AL, van der Put NM, Heil SG, Trijbels FJ, Blom HJ. Effect of the methylenetetrahydrofolate reductase 677C-->T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample. Am J Clin Nutr. 2003 Mar;77(3):687-93. <URL:http://www.ajcn.org/cgi/content/full/77/3/687>
Ashfield-Watt PA, Pullin CH, Whiting JM, Clark ZE, Moat SJ, Newcombe RG, Burr ML, Lewis MJ, Powers HJ, McDowell IF. Methylenetetrahydrofolate reductase 677C-->T genotype modulates homocysteine responses to a folate-rich diet or a low-dose folic acid supplement: a randomized controlled trial. Am J Clin Nutr. 2002 Jul;76(1):180-6. <URL:http://www.ajcn.org/cgi/content/full/76/1/180>
Allen RH, Stabler SP, Savage DG, Lindenbaum J. Metabolic abnormalities in cobalamin (vitamin B12) and folate deficiency. FASEB J. 1993 Nov;7(14):1344-53. Review. <URL:http://www.fasebj.org/cgi/content/abstract/7/14/1344>
Fairfield KM, Fletcher RH. Vitamins for chronic disease prevention in adults: scientific review. JAMA. 2002 Jun 19;287(23):3116-26. Review. Erratum in: JAMA 2002 Oct 9;288(14):1720. <URL:http://jama.ama-assn.org/cgi/content/full/287/23/3116>
Fletcher RH, Fairfield KM. Vitamins for chronic disease prevention in adults: clinical applications. JAMA. 2002 Jun 19;287(23):3127-9. <URL:http://jama.ama-assn.org/cgi/content/full/287/23/3127>
 Signature Matti Narkia
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