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葉酸(ビタミンＢ９)(Folic Acid)( B 9 )

メタフォリン葉酸 (Ｌ－メチルフォーレイト)(Metafolin Folic Acid)( L-methylfolate ) Source Naturals 800 mcg 120 タブレット
１，７９０円

葉酸1ｍｇ(Folic Acid 1 mg ) Natural Factors 1 mg 90 タブレット
６５０円

葉酸(Folic Acid) Natural Factors 400 mcg 90 タブレット
５８０円

葉酸(ビタミンＢ９)(Folic Acid)( Vitamin B 9 ) Source Naturals 800 mcg 500 タブレット.
お買い得！
１，５８０円

葉酸(ビタミンＢ９)(Folic Acid)(Vitamin B 9) Nature's Way 800 mcg 100 カプセル.
６５０円

アドバンスドビタミンＢ１２コンプレックス (メチルコバラミン＋ディベンコサイド)((T) Advanced B-12 Complex)( MethylCobalamin + Dibencozide) 5 mg Source Naturals 60 タブレット
メチルコバラミン + 葉酸
２，７６０円

葉酸・ビタミンＢ12配合（Now Foods Folic Acid with Vitamin B-12） 800 mcg 250 タブレット
７４０円

葉酸（ビタミンＢ9）（Jarrow Formulas Folic Acid） 800 mcg 100 カプセル

９３０円

葉酸（ビタミンＢ９）ハート（Nature's Plus Folic Acid Hearts） 90 タブレット

１，０２０円

フォレイトメタフォリン葉酸（ビタミンB9）（Solgar Folate Metafolin Folic Acid） 800 mcg 100 タブレット

２，８４０円

フォレイトメタフォリン葉酸（ビタミンB9）（Solgar Folate Metafolin Folic Acid） 400 mcg 100 タブレット

２，３６０円

葉酸（ビタミンB9）（Solgar Folic Acid） 800 mcg 250 ベジタブルカプセル

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葉酸（Solgar Folic Acid） 400 mcg 250 タブレット

２，９１０円

ビタミンB6 B12 プラス葉酸ラズベリー噛めるタブレット（Bluebonnet Nutrition Vitamin B-6 B-12 Plus Folic Acid Raspberry） 60 噛めるタブレット

１，６９０円

メガフォリニック（葉酸）（ビタミンB9）（Source Naturals MegaFolinic ( compare to metafolin ) 800 mcg 120 タブレット

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葉酸（ビタミンＢ9）（Carlson Labs Folic Acid） 400 mcg 300 タブレット

９７０円

葉酸（ビタミンＢ9）（Carlson Labs Folic Acid） 800 mcg 1000 タブレット

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メタフォリン葉酸（ビタミンＢ9）（Solgar Folate Metafolin Folic Acid） 800 mcg 100 タブレット

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オプティマイズドフォーレイト（Ｌメチルフォーレイト）（Life Extension Optimized Folate (L-Methylfolate)） 1000 mcg 100 ベジタブルカプセル
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葉酸（ビタミンＢ9）ナチュラルストロベリー風味（NutraLife Folic Acid Natural Strawberry Flavor） 400 mcg 360 Lozenges

１，２３０円

葉酸（ビタミンＢ9）ナチュラルストロベリー風味（NutraLife Folic Acid Natural Strawberry Flavor） 800 mcg 180 Lozenges

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葉酸（ビタミンＢ9）スプレー（Pure Advantage Folic Acid） 800 mcg Spray 1 fl oz

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葉酸（ビタミンＢ9）（Country Life Folic Acid） 800 mcg 100 タブレット

９１０円

葉酸（ビタミンＢ9）（Country Life Folic Acid） 800 mcg 250 タブレット

１，２５０円

葉酸（ビタミンＢ9）パウダー（Life Extension Folic Acid Powder） 30 g

２，３３０円

葉酸（ようさん）はビタミンM、ビタミンB9、プテロイルグルタミン酸とも呼ばれ、水溶性ビタミンに分類される生理活性物質である。プテリジンにパラアミノ安息香酸とグルタミン酸が結合した構造を持つ。1941年に乳酸菌の増殖因子としてホウレンソウの葉から発見された。ホウレンソウの葉はラテン語で folium と呼ばれることから葉酸 (folic acid) と名付けられた。葉酸は体内で還元を受け、ジヒドロ葉酸を経てテトラヒドロ葉酸に変換された後に補酵素としてはたらく。

はたらき
テトラヒドロ葉酸は、ホルミル基 (?CHO)、ホルムイムノ基 (?CHNH)、メチレン基 (>CH2)、メチル基 (?CH3) など1つの炭素原子を含む断片をドナー分子から受け取り、それをアミノ酸や核酸合成の中間体へ渡す役割を担うなど、核酸およびアミノ酸の代謝に用いられている。不足すると赤血球障害や悪性貧血などの状を生じる。

栄養
葉酸の栄養所要量は、推定平均必要量が 200 μg、推奨量が 240 μg、上限量が 1000 μg（いずれも成人男女）とされている。ただし、妊娠期および授乳期にはさらに推定平均必要量として +170 μg、+80 μgを、推奨量として +200 μg、+100 μg を付加する。また、妊娠を計画している、あるいは妊娠の可能性のある女性は、一日あたり 400μg の摂取が望ましいとされる。

葉酸を多く含む食品は、レバー、緑黄色野菜、果物である。ただし、調理や長期間保存による酸化によって葉酸は壊れるため、新鮮な生野菜や果物が良い供給源となる。大量の飲酒も葉酸の吸収および代謝を妨げる。

欠乏
妊娠や授乳による要求量の増加、の理的変化、アルコール中毒、メトトレキサートなどの薬剤投与によって引き起こされる。葉酸はアミノ酸や核酸の合成に必要となる補酵素であるため、細胞分裂の盛んな箇所において欠乏が現れやすい。また、妊娠期に葉酸が欠乏すると、管閉鎖障害が起こり、重度の場合は死に至る。

貧血に関しては、葉酸は造血作用に対しビタミンB12と協調してはたらき、いずれのビタミンの欠乏も巨赤芽球性貧血を引き起こす。

管閉鎖障害に対しては、妊娠初期が重要で、特に通常まだ妊娠に気付かない第一週が最も葉酸を必要とする期間であると考えられている。

過剰
過剰はビタミンB12の欠乏を隠すため、悪性貧血が潜在化する危険性が指摘されている。また、治療に用いられる抗葉酸剤に対して、過剰な葉酸はを低減させる。

医薬品との関係
葉酸は制酸剤やアスピリンおよびその関連物質と相互作用し、これらの薬剤は葉酸のはたらきを阻害することが知られている。また、抗けいれん薬（フェニトイン、フェノバルビタール等）や潰瘍性炎治療薬（スルファサラジン等）は葉酸の吸収を低下させる。さらに、やの治療に用いられるメトトレキサートなどの抗葉酸剤、あるいはのトリメトプリム‐スルファメトキサゾール（ST合剤）は葉酸の代謝を阻害する。したがって、これらの薬剤を頻繁に服用する人は葉酸欠乏に気を配る必要がある。

Folic acid (also known as Vitamin M and Folacin) and Folate (the anionic form) are forms of the water-soluble Vitamin B9. These occur naturally in food and can also be taken as supplements. Folate gets its name from the Latin word folium ("leaf").

Folate in foods and other sources
Leafy vegetables such as spinach, turnip greens, lettuces, dried beans and peas, fortified cereal products, sunflower seeds and certain other fruits and vegetables are rich sources of folate. Liver and liver products also contain high amounts of folate, as does bakers yeast. Some breakfast cereals (ready-to-eat and others) are fortified with 25% to 100% of the recommended dietary allowance (RDA) for folic acid. A table of selected food sources of folate and folic acid can be found at the USDA National Nutrient Database for Standard Reference.Folate is also found in Vegemite or Marmite, with an average serving (5g) containing 100μg or 2000μg per 100g. Folate is also synthesized in bacteria.

History
A key observation by researcher Lucy Wills in 1931 led to the identification of folate as the nutrient needed to prevent anemia during pregnancy. Dr. Wills demonstrated that anemia could be reversed with brewer's yeast. Folate was identified as the corrective substance in brewer's yeast in the late 1930s and was first isolated in pure form from spinach leaves by Mitchell and others in 1941 [1]. It was first synthesized in 1946 by Yellapragada Subbarao.

Biological roles of folate
 
A diagram of the chemical structure of folate.
[edit] DNA and cell division
Folate is necessary for the production and maintenance of new cells.[2] This is especially important during periods of rapid cell division and growth such as infancy and pregnancy. Folate is needed to synthesize DNA bases (most notably thymine, but also purine bases) needed for DNA replication. Thus folate deficiency hinders DNA synthesis and cell division, affecting most notably bone marrow and cancer, both of which participate in rapid cell division. RNA transcription, and subsequent protein synthesis, are less affected by folate deficiency as the mRNA can be recycled and used again (as opposed to DNA synthesis where a new genomic copy must be created). Since folate deficiency limits cell division, erythropoiesis, production of red blood cells (RBCs) is hindered and leads to megaloblastic anemia which is characterized by large immature RBCs. This pathology results from persistently thwarted attempts at normal DNA replication, DNA repair, and cell division and produces abnormally large cells (megaloblasts) with abundant cytoplasm capable of RNA and protein synthesis but with clumping and fragmentation of nuclear chromatin. Some of these large cells, although immature, are released early from the marrow in an attempt to compensate for the anemia caused by lack of RBCs. [3] Both adults and children need folate to make normal RBCs and prevent anemia.[4] Deficiency of folate in pregnant women has been implicated in neural tube defects; therefore, many cereals sold in developed countries are enriched with folate to avoid such complications.

Biochemistry of DNA base and amino acid production
In the form of a series of tetrahydrofolate (THF) compounds, folate derivatives are substrates in a number of single-carbon-transfer reactions, and also are involved in the synthesis of dTMP (2′-deoxythymidine-5′-phosphate) from dUMP (2′-deoxyuridine-5′-phosphate). It is a substrate for an important reaction that involves vitamin B12 and it is necessary for the synthesis of DNA, required for all dividing cells.

The pathway leading to the formation of tetrahydrofolate (FH4) begins when folate (F) is reduced to dihydrofolate (DHF) (FH2), which is then reduced to THF. Dihydrofolate reductase catalyses the last step.[5] Vitamin B3 in the form of NADPH is a necessary cofactor for both steps of the synthesis.

Methylene-THF (CH2FH4) is formed from THF by the addition of methylene groups from one of three carbon donors: formaldehyde, serine, or glycine. Methyl tetrahydrofolate (CH3-THF) can be made from methylene-THF by reduction of the methylene group with NADPH. It is important to note that Vitamin B12 is the only acceptor of methyl-THF. There is also only one acceptor for methyl-B12 which is homocysteine in a reaction catalyzed by homocysteine methyltransferase. This is important because a defect in homocysteine methyltransferase or a defeciency of B12 can lead to a methyl-trap of THF and a subsequent deficiency. Thus, a deficiency in B12 can generate a large pool of methyl-THF that is unable to undergo reactions and will mimic folate deficiency. Another form of THF, formyl-THF or folinic acid) results from oxidation of methylene-THF or is formed from formate donating formyl group to THF. Finally, histidine can donate a single carbon to THF to form methenyl-THF.

In other words:

F → DHF → THF → CH2-THF Formyl-THF ? Methynl-THF ? Methylene-THF → Methyl-THF

Overview of drugs that interfere with folate reactions
A number of drugs interfere with the biosynthesis of folic acid and THF. Among them are the dihydrofolate reductase inhibitors such as trimethoprim, pyrimethamine and methotrexate; the sulfonamides (competitive inhibitors of para-aminobenzoic acid in the reactions of dihydropteroate synthetase).

Recommended Daily Allowance (RDA)
1998 RDAs for Folate Men Women 
(19+) (19+) Pregnancy Breast feeding 
400 μg 400 μg 600 μg 500 μg 
1 μg of food folate = 0.6 μg folic acid from supplements and fortified foods

The National Health and Nutrition Examination Survey (NHANES III 1988?91) and the Continuing Survey of Food Intakes by Individuals (1994?96 CSFII) indicated that most adults did not consume adequate folate.[6][7] However, the folic acid fortification program in the United States has increased folic acid content of commonly eaten foods such as cereals and grains, and as a result diets of most adults now provide recommended amounts of folate equivalents.[8]

Folate deficiency
See Folate deficiency

Human reproduction
Folic acid is an important nutrient for women who may become pregnant. Adequate folate intake during the periconceptional period, the time just before and just after a woman becomes pregnant, helps protect against a number of congenital malformations including neural tube defects.[9] Neural tube defects result in malformations of the spine (spina bifida), skull, and brain (anencephaly). The risk of neural tube defects is significantly reduced when supplemental folic acid is consumed in addition to a healthy diet prior to and during the first month following conception.[10][11] Women who could become pregnant are advised to eat foods fortified with folic acid or take supplements in addition to eating folate-rich foods to reduce the risk of some serious birth defects. The most notable birth defects that occur from folate deficiency are neural tube defects. Taking 400 micrograms of synthetic folic acid daily from fortified foods and/or supplements has been suggested. The Recommended Dietary Allowance (RDA) for folate equivalents for pregnant women is 600-800 micrograms, twice the normal RDA of 400 micrograms for women who are not pregnant.[12]

Recent research has shown that it is also very important for men who are planning on fathering children, reducing chromosomal defects in their sperm.[13]

Some current issues and controversies about folate

Dietary fortification of folic acid
Since the discovery of the link between insufficient folic acid and neural tube defects (NTDs), governments and health organizations worldwide have made recommendations concerning folic acid supplementation for women intending to become pregnant. For example, the United States Public Health Service (see External links) recommends an extra 0.4 mg/day, which can be taken as a pill. However, many researchers believe that supplementation in this way can never work effectively enough since about half of all pregnancies in the U.S. are unplanned and not all women will comply with the recommendation.

This has led to the introduction in many countries of fortification, where folic acid is added to flour with the intention of everyone benefiting from the associated rise in blood folate levels. This is controversial, with issues having been raised concerning individual liberty, and the masking effect of folate fortification on pernicious anaemia (vitamin B12 deficiency). However, almost all western countries now fortify their flour, along with a number of Middle Eastern countries and Indonesia. Mongolia and a number of ex-Soviet republics are amongst those having widespread voluntary fortification; about five more countries (including Morocco, the first African country) have agreed but not yet implemented fortification. In the UK the Food Standards Agency has recommended fortification.[14][15][16] To date, no EU country has yet mandated fortification.[17] Australia and New Zealand have jointly agreed to fortification. Australia will fortify all flour, whereas New Zealand will fortify bread (excluding organic and unleavened varieties) from 18 September 2009.[18] The requirement is 0.135mg of folate per 100g of bread.

There has been previous debate in the United Kingdom[19] and Australia[20] regarding the inclusion of folic acid in products such as bread and flour.

In the USA many grain products are fortified with folic acid.In 1996, the United States Food and Drug Administration (FDA) published regulations requiring the addition of folic acid to enriched breads, cereals, flours, corn meals, pastas, rice, and other grain products.[21][22] This ruling took effect 1998-01-01, and was specifically targeted to reduce the risk of neural tube birth defects in newborns.[23] There are concerns that the amount of folate added is insufficient[3]. In October 2006, the Australian press claimed that U.S. regulations requiring fortification of grain products were being interpreted as disallowing fortification in non-grain products, specifically Vegemite (an Australian yeast extract containing folate). The FDA later said the report was inaccurate, and no ban or other action was being taken against Vegemite.[4]

Since the folic acid fortification program took effect, fortified foods have become a major source of folic acid in the American diet. The Centers for Disease Control and Prevention in Atlanta, Georgia used data from 23 birth defect registries that cover about half of United States births and extrapolated their findings to the rest of the country. This data indicates that since the addition of folic acid in grain-based foods as mandated by the Food and Drug Administration, the rate of neural tube defects dropped by 25% in the United States.[24]

Although folic acid does reduce the risk of birth defects, it is only one part of the picture and should not be considered a cure. Even women taking daily folic acid supplements have been known to have children with neural tube defects.

Heart disease
Adequate concentrations of folate, vitamin B12, or vitamin B6 may decrease the circulating level of homocysteine, an amino acid normally found in blood. There is evidence that an elevated homocysteine level is an independent risk factor for heart disease and stroke.[25] The evidence suggests that high levels of homocysteine may damage coronary arteries or make it easier for blood clotting cells called platelets to clump together and form a clot.[26] However, there is currently no evidence available to suggest that lowering homocysteine with vitamins will reduce risk of heart disease. Clinical intervention trials are needed to determine whether supplementation with folic acid, vitamin B12 or vitamin B6 can lower the risk of developing coronary heart disease. The NORVIT trial suggests that folic acid supplementation may do more harm than good.[27]

As of 2006, studies have shown that giving folic acid to reduce levels of homocysteine does not result in clinical benefit. One of these studies suggests that folic acid in combination with B12 may even increase some cardiovascular risks.[28][29][30]

However a 2005 study found that 5 mg. of folate daily over a three-week period reduced pulse pressure by 4.7 mmHg. compared with a placebo, and concluded that[31]

Folic acid is a safe and effective supplement that targets large artery stiffness and may prevent isolated systolic hypertension. 
Also, as a result of new research, "heart experts" at Johns Hopkins Medical Center reported in March 2008 [32] in favour of therapeutic folate, although they cautioned that it is premature for people to begin to self-medicate by taking high doses of folic acid."

Stroke
Folic acid appears to reduce the risk of stroke. The reviews indicate only that in some individuals the risk of stroke appears to be reduced, but a definite recommendation regarding supplementation beyond the current recommended daily allowance has not been established for stroke prevention.[33] Observed stroke reduction is consistent with the reduction in pulse pressure produced by folate supplementation of 5 mg per day, since hypertension is a key risk factor for stroke.

Antifolates
Folate is important for cells and tissues that rapidly divide.[2] Cancer cells divide rapidly, and drugs that interfere with folate metabolism are used to treat cancer. The antifolate methotrexate is a drug often used to treat cancer because it inhibits the production of the active form of THF from the inactive dihydrofolate (DHF). Unfortunately, methotrexate can be toxic,[44][45][46] producing side effects such as inflammation in the digestive tract that make it difficult to eat normally.

Folinic acid, under the drug name leucovorin, is a form of folate (formyl-THF) that can help "rescue" or reverse the toxic effects of methotrexate.[47] Folinic acid is not the same as folic acid. Folic acid supplements have little established role in cancer chemotherapy.[48][49] There have been cases of severe adverse effects of accidental substitution of folic acid for folinic acid in patients receiving methotrexate cancer chemotherapy. It is important for anyone receiving methotrexate to follow medical advice on the use of folic or folinic acid supplements. The supplement of folinic acid in patients undergoing methotrexate treatment is to give non rapidly dividing cells enough folate to maintain normal cell functions. The amount of folate given will be depleted by rapidly dividing cells (cancer) very fast and so will not negate the effects of methotrexate. Low dose methotrexate is used to treat a wide variety of non-cancerous diseases such as rheumatoid arthritis, lupus, scleroderma, psoriasis, asthma, sarcoidoisis, primary biliary cirrhosis, and inflammatory bowel disease.[50] Low doses of methotrexate can deplete folate stores and cause side effects that are similar to folate deficiency. Both high folate diets and supplemental folic acid may help reduce the toxic side effects of low dose methotrexate without decreasing its effectiveness.[51][52] Anyone taking low dose methotrexate for the health problems listed above should consult with a physician about the need for a folic acid supplement. While the role in folate as a cancer treatment is well established its long term effectiveness is diminished by cellular response. In response to decreased THF the cell begins to transcribe more DHF reductase, the enzyme that reduces DHF to THF. Because methotrexate is a competitive inhibitor of DHF reductase increased concentrations of DHF reductase can overcome the drugs inhibition.

Memory and mental agility
In a 3-year trial on 818 people over the age of 50, short-term memory, mental agility and verbal fluency were all found to be better among people who took 800 micrograms of folic acid daily ( twice the current RDA ) than those who took placebo. The study was reported in The Lancet on 19 January 2007.[56]

Fertility
Folate is necessary for fertility in both men and women. In men, it contributes to spermatogenesis. In women, on the other hand, it contributes to oocyte maturation, implantation, placentation, in addition to the general effects of folic acid and pregnancy. Therefore, it is necessary to receive sufficient amounts through the diet, in order to avoid subfertility.[57]

Folic acid supplements and masking of B12 deficiency
There has been concern about the interaction between vitamin B12 and folic acid.[58]Folic acid supplements can correct the anemia associated with vitamin B12 deficiency. Unfortunately, folic acid will not correct changes in the nervous system that result from vitamin B12 deficiency. Permanent nerve damage could theoretically occur if vitamin B12 deficiency is not treated. Therefore, intake of supplemental folic acid should not exceed 1000 micrograms (1000 μg or 1 mg) per day to prevent folic acid from masking symptoms of vitamin B12 deficiency. In fact, to date the evidence that such masking actually occurs is scarce, and there is no evidence that folic acid fortification in Canada or the US has increased the prevalence of vitamin B12 deficiency or its consequences.[59]

However one recent study has demonstrated that high folic or folate levels when combined with low B12 levels are associated with significant cognitive impairment among the elderly.[60] If the observed relationship for seniors between folic acid intake, B12 levels, and cognitive impairment is replicated and confirmed, this is likely to re-open the debate on folic acid fortification in food, even though public health policies tend generally to support the developmental needs of infants and children over slight risks to other population groups.[citation needed]

In any case, it is important for older adults to be aware of the relationship between folic acid and vitamin B12 because they are at greater risk of having a vitamin B12 deficiency. If you are 50 years of age or older, ask your physician to check your B12 status before you take a supplement that contains folic acid.[61]

Health risk of too much folic acid
The risk of toxicity from folic acid is low.[62] The Institute of Medicine has established a tolerable upper intake level (UL) for folate of 1 mg for adult men and women, and a UL of 800 μg for pregnant and lactating (breast-feeding) women less than 18 years of age. Supplemental folic acid should not exceed the UL to prevent folic acid from masking symptoms of vitamin B12 deficiency.[63]

Research suggests high levels of folic acid can interfere with some antimalarial treatments.[64]

A 10000-patient study at Tufts University in 2007 concluded that excess folic acid worsens the effects of B12 deficiency and in fact may affect the absorption of B12. [65]

Bibliography
This article contains information from the public domain resource at http://www.cc.nih.gov/ccc/supplements/folate.html 
Herbert V (1999). "Folic Acid". in Shils ME, Olson J, Shike M, Ross AC. Modern nutrition in health and disease (9th ed.). Baltimore: Williams and Wilkins. ISBN 0-683-30769-X.  
Food and Nutrition Board, Institute of Medicine (1998). Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline / a report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients. Washington, D.C.: National Academy Press. ISBN 0-309-06554-2.  
Dietary Guidelines Advisory Committee, Agricultural Research Service, United States Department of Agriculture (USDA). Report of the Dietary Guidelines Advisory Committee on the Dietary Guidelines for Americans, 2000. http://www.ars.usda.gov/dgac

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