THE PRODIGY-5 MICRONUTRIENT FORMULA FOR GENERAL HEALTH: Vitamin A • Vitamin C • Vitamin D • Vitamin E • Vitamin K • Vitamin B6 • Vitamin B12 • Folate • B1 (Thiamin) • B2 (Riboflavin) • B3 (Niacin) 

MICRONUTRIENT FORMULA FOR EYE HEALTH: Lutein • Zeaxanthin • Copper • Zinc 

 

Folic acid

From Wikipedia, the free encyclopedia
  (Redirected from Folate)
 
Folic acid
Skeletal formula
Folic acid as a yellow-orange crystalline powder
Systematic (IUPAC) name
(2S)-2-[[4-[(2-Amino-4-oxo-1H-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid[1]
Clinical data
Pronunciation foe' lik
AHFS/Drugs.com Monograph
MedlinePlus a682591
Pregnancy
category
  • US: A (No risk in human studies)
Routes of
administration
By mouth, IM, IV, sub-Q
Pharmacokinetic data
Bioavailability 50-100%[2]
Metabolism Liver[2]
Excretion Urine[2]
Identifiers
CAS Number 59-30-3
ATC code B03BB01 (WHO)
PubChem CID 6037
IUPHAR/BPS 4563
DrugBank DB00158 Yes
ChemSpider 5815
UNII 935E97BOY8
KEGG C00504
ChEBI CHEBI:27470
ChEMBL CHEMBL1622
Synonyms N-(4-{[(2-amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamic acid, pteroyl-L-glutamic acid, vitamin B9,[3]vitamin Bc,[4] vitamin M,[5]folacin, pteroyl-L-glutamate
Chemical data
Formula C19H19N7O6
Molar mass 441.40 g·mol−1
3D model (Jmol) Interactive image
Physical data
Melting point 250 °C (482 °F) (decomposition)
Solubility in water 1.6 mg/L (25 °C) mg/mL (20 °C)

Folic acid, another form of which is known as folate, is one of the B vitamins.[2] It is used as a supplementduring pregnancy to prevent neural tube defects (NTDs). It is also used to treat anemia caused by folic acid deficiency.[2] More than 50 countries require fortification of certain foods with folic acid as a measure to decrease the rate of NTDs in the population.[6][7] Long term supplementation is also associated with small reductions in the risk of stroke and cardiovascular disease.[8] It may be taken by mouth or by injection.[2]

There are no common side effects. It is not known whether high doses over a long period of time are of concern.[2] There are concerns that large amounts of folic acid might hide vitamin B12 deficiency. Folate is essential for the body to make DNARNA, and metabolise amino acids which are required for cell division.[9]As humans cannot make folic acid, it is required from the diet.[10]

Not enough folate can lead to folate deficiency. This may result in a type of anemia in which low numbers of large red blood cells occur. Symptoms may include feeling tiredheart palpitationsshortness of breath, open sores on the tongue, and changes in the color of the skin or hair. Low levels in early pregnancy are believed to be the cause more than half of cases of neural tube defects in babies.[9] Deficiency in children may develop within a month of poor dietary intake.[11] In adults normal total body folate is between 10,000–30,000 micrograms (µg) with blood levels of greater than 7 nmol/L (3 ng/mL).[9]

Folic acid was discovered between 1931 and 1943.[12] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[13] The wholesale cost of supplements in the developing world is between 0.001 and 0.005 USD per dose as of 2014.[14] The term "folic" is from the Latin word folium, which means leaf.[15] Folates occur naturally in many foods especially dark green leafy vegetables and liver.[9]

Definition

Food supplement manufacturers often use the term folate for something different from "pure" folic acid: in chemistry, folate refers to the deprotonated ion, and folic acid to the neutral molecule—which both coexist in water. The International Union of Pure and Applied Chemistry and the International Union of Biochemistry and Molecular Biology state that folate and folic acid are the preferred synonyms for pteroylglutamate and pteroylglutamic acid, respectively.[16] Folate indicates a collection of "folates" that is not chemically well-characterized, including other members of the family of pteroylglutamates, or mixtures of them, having various levels of reduction of the pteridine ring, one-carbon substitutions and different numbers of glutamate residues.

Names

Other names include vitamin B9,[17] vitamin Bc,[18] vitamin M,[5] folacin, and pteroyl-L-glutamate.

Health effects

Pregnancy

Folic acid intake during pregnancy has been linked to a lessened risk of neural tube defects and some other specific kinds of birth defects.[19]

There is growing concern worldwide that prenatal high folic acid in the presence of low vitamin B12 causes epigenetic changes in the unborn predisposing them to metabolic syndromes, central adiposity and adult diseases such as Type 2 diabetes.[20]

Despite concerns, there appears to be no correlation between maternal folic acid supplementation and an increased risk for asthma in the child[21]

Fertility

Folate is necessary for fertility in both men and women. It contributes to spermatogenesis. Therefore, it is necessary to receive sufficient amounts through the diet to avoid subfertility.[22] Also, polymorphisms in genes of enzymes involved in folate metabolism could be one reason for fertility complications in some women with unexplained infertility.[23]

Heart disease

Taking folic acid over years reduced the risk of cardiovascular disease by 4%,[8] where another study found it did not affect cardiovascular disease, even while reducing homocysteine levels.[24]

Folic acid supplements consumed before and during pregnancy may reduce the risk of heart defects in infants.[25]

Stroke

Long-term supplementation with folic acid reduced the risk of stroke by 10%, which may be due to the role folate plays in regulating homocysteine concentration.[8] The reviews indicate the risk of stroke appears to be reduced only in some individuals, but a definite recommendation regarding supplementation beyond the current RDA has not been established for stroke prevention.[26] Asian populations had greater protection against stroke with folate supplementation than did European or North American subjects.[8]

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. Folic supplements are inexpensive and relatively safe to use, which is why stroke or hyperhomocysteinemia patients are encouraged to consume daily B vitamins including folic acid.[27]

Cancer

Folic acid supplementation may slightly increase the risk of some cancers such as prostate cancer.[28][29] Low levels of folate have been associated with other specific cancers.[30] However, it is not clear whether consuming recommended (or higher) amounts of folic acid—from foods or in supplements—can lower cancer risk.[31]

Antifolate chemotherapy

Folate is important for cells and tissues that rapidly divide.[32] 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). However, methotrexate can be toxic,[33][34][35] producing side effects, such as inflammation in the digestive tract that make it difficult to eat normally. Also, bone marrow depression (inducing leukopenia and thrombocytopenia), and acute kidney and liver failure have been reported.

Folinic acid, under the drug name leucovorin, a form of folate (formyl-THF), can help "rescue" or reverse the toxic effects of methotrexate.[36] Folinic acid is not the same as folic acid. Folic acid supplements have little established role in cancer chemotherapy.[37][38] 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 cells dividing less rapidly enough folate to maintain normal cell functions. The amount of folate given is depleted by rapidly dividing cells (cancer) quickly, and so does not negate the effects of methotrexate.

Psychological

Some evidence links a shortage of folate with depression.[39] Limited evidence from randomised controlled trials showed using folic acid in addition to SSRIs may have benefits.[40] Research at the University of York and Hull York Medical School has found a link between depression and low levels of folate.[41] One study by the same team involved 15,315 subjects.[42] Folic acid supplementation affects noradrenaline and serotonin receptors within the brain, which could be the cause of folic acid's possible ability to act as an antidepressant.[43][44] The exact mechanisms involved in the development of schizophrenia and depression are not entirely clear, but the bioactive folate, methyltetrahydrofolate (5-MTHF), a direct target of methyl donors like S-adenosyl methionine (SAMe), recycles the inactive dihydrobiopterin (BH2) into tetrahydrobiopterin (BH4), the necessary cofactor in various steps of monoamine synthesis, including that of dopa. BH4 serves a regulatory role in monoamine neurotransmission and is required to mediate the actions of most antidepressants. 5-MTHF also plays both direct & indirect roles in DNA methylation, NO2 synthesis, and one-carbon metabolism.[45]

Age related macular degeneration

A substudy of the Women's Antioxidant and Folic Acid Cardiovascular Study published in 2009 reported use of a nutritional supplement containing folic acid, pyridoxine, and cyanocobalamin decreased the risk of developing age-related macular degeneration by 34.7%.[46]

Folic acid, B12 and iron

There is a complex interaction between folic acid, vitamin B12 and iron. A deficiency of one may be "masked" by excess of another so the three must always be in balance.[47][48][49]

Toxicity

The risk of toxicity from folic acid is low, because folate is a water-soluble vitamin and is regularly removed from the body through urine.[50] One potential issue associated with high dosages of folic acid is that it has a masking effect on the diagnosis of pernicious anaemia (vitamin B12 deficiency),[51] and a variety of concerns[clarification needed] of potential negative impacts on health.[52]

Folate deficiency

Main article: Folate deficiency

Folate deficiency can be caused by unhealthy diets that do not include enough fruits and vegetables, diseases in which folic acid is not well absorbed in the digestive system (such as Crohn's disease or celiac disease), some genetic disorders that affect levels of folate, and certain medicines (such as phenytoin, sulfasalazine, or trimethoprim-sulfamethoxazole).[53] Folate deficiency is accelerated by alcohol consumption.[54]

Folate deficiency may lead to glossitis, diarrhea, depression, confusion, anemia, and fetal neural tube defects and brain defects (during pregnancy).[55]Other symptoms include fatigue, gray hair, mouth sores, poor growth, and swollen tongue.[53] Folate deficiency is diagnosed by analyzing CBC and plasma vitamin B12 and folate levels.[55] CBC may indicate megaloblastic anemia but this could also be a sign of vitamin B12 deficiency.[55] A serum folate of 3 μg/L or lower indicates deficiency.[55] Serum folate level reflects folate status but erythrocyte folate level better reflects tissue stores after intake.[55] Serum folate reacts more rapidly to folate intake than erythrocyte folate.[56] An erythrocyte folate level of 140 μg/L or lower indicates inadequate folate status.[55]Increased homocysteine level suggests tissue folate deficiency but homocysteine is also affected by vitamin B12 and vitamin B6, renal function, and genetics.[55]

One way to differentiate between folate deficiency from vitamin B12 deficiency is by testing for methylmalonic acid levels.[55] Normal MMA levels indicate folate deficiency and elevated MMA levels indicate vitamin B12 deficiency.[55] Folate deficiency is treated with supplemental oral folate of 400 to 1000 μg per day. This treatment is very successful in replenishing tissues, even if deficiency was caused by malabsorption.[55] Patients with megaloblastic anemia need to be tested for vitamin B12 deficiency before folate treatment, because if the patient has vitamin B12 deficiency, folate supplementation can remove the anemia, but can also worsen neurologic problems.[55] Morbidly obese patients with BMIs of greater than 50 are more likely to develop folate deficiency.[57] Patients with celiac disease have a higher chance of developing folate deficiency.[57] Cobalamin deficiency may lead to folate deficiency, which, in turn, increases homocysteine levels and may result in the development of cardiovascular disease or birth defects.[58]

Malaria

Some studies show iron–folic acid supplementation in children under 5 may result in increased mortality due to malaria; this has prompted the World Health Organization to alter their iron–folic acid supplementation policies for children in malaria-prone areas, such as India.[59]

Dietary reference intake

Because of the difference in bioavailability between supplemented folic acid and the different forms of folate found in food, the dietary folate equivalent (DFE) system was established. One DFE is defined as 1 μg of dietary folate, or 0.6 μg of folic acid supplement.

National Institutes of Health (US) nutritional requirements[60] (µg per day)
Age Infants (AI) Infants (UL) Adults (RDA) Adults (UL) Pregnant women (RDA) Pregnant women (UL) Lactating women (RDA) Lactating women (UL)
0–6 months 65 None set
7–12 months 80 None set
1–3 years 150 300
4–8 years 200 400  –
9–13 years 300 600
14–18 400 800 600 800 500 800
19+ 400 1000 600 1000 500 1000

The Dietary Reference Intakes (DRIs) were developed by the United States National Academy of Sciences to set reference values for planning and assessing nutrient intake for healthy people. DRIs incorporate four reference values: Estimated Average Requirements (EARs), Recommended Dietary Allowances (RDAs; the daily intake level that is adequate for 97–98% of the population in the United States), Adequate Intakes, for when the existing science is inadequate to set EARs and RDAs, and tolerable upper intake levels (UL, the highest level of intake considered safe). The UL for folate refers to only synthetic folic acid, as no health risks have been associated with high intake of folate from food sources.[60][61] The European Food Safety Authority reviewed the same safety question and also set the adult UL at 1000 μg.[62]

For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For folic acid labeling purposes 100% of the Daily Value was 400 μg. As of the May 2016 update it was kept unchanged at 400 μg. A table of the pre-change adult Daily Values is provided at Reference Daily Intake. Food and supplement companies have until July 28, 2018 to comply with the change.

Sources

 
Vitamins C and M as featured on a monument in front of University of Warsaw's Centre of New Technologies

Folate naturally occurs in a wide variety of foods, including vegetables (particularly dark green leafy vegetables), fruits and fruit juices, nuts, beans, peas, dairy products, poultry and meat, eggs, seafood, grains, and some beers.[9][63] Avocado,[64] beetrootspinachliveryeastasparagus, and Brussels sprouts are among the foods with the highest levels of folate.[9]

Folic acid is added to grain products in many countries, and in these countries, fortified products make up a significant source of the population's folic acid intake.[65] Because of the difference in bioavailability between supplemented folic acid and the different forms of folate found in food, the dietary folate equivalent (DFE) system was established. 1 DFE is defined as 1 μg of dietary folate, or 0.6 μg of folic acid supplement. This is reduced to 0.5 μg of folic acid if the supplement is taken on an empty stomach.[66]

Folate naturally found in food is susceptible to high heat and ultraviolet light, and is soluble in water.[67] It is heat-labile in acidic environments and may also be subject to oxidation.[67]

Some meal replacement products do not meet the folate requirements as specified by the RDAs.[68]

Folate (B9) can also be processed from the provitamin Pteroylmonoglutamic acid (Vitamin B10).

History

In the 1920s, scientists believed folate deficiency and anemia were the same condition.[69] In 1931, researcher Lucy Wills made a key observation that led to the identification of folate as the nutrient required to prevent anemia during pregnancy. Wills demonstrated that anemia could be reversed with brewer's yeast. In the late 1930s, folate was identified as the corrective substance in brewer's yeast.

It was first isolated via extraction from spinach leaves by Herschel K. MitchellEsmond E. Snell, and Roger J. Williams in 1941.[70] Bob Stokstad isolated the pure crystalline form in 1943, and was able to determine its chemical structure while working at the Lederle Laboratories of the American Cyanamid Company.[71] This historical research project, of obtaining folic acid in a pure crystalline form in 1945, was done by the team called the "folic acid boys," under the supervision and guidance of Director of Research Dr. Yellapragada Subbarow, at the Lederle Lab, Pearl River, NY.[72]

This research subsequently led to the synthesis of the antifolate aminopterin, the first-ever anticancer drug, the clinical efficacy was proven by Sidney Farber in 1948. In the 1950s and 1960s, scientists began to discover the biochemical mechanisms of action for folate.[69] In 1960, experts first linked folate deficiency to neural tube defects.[69] In the late 1990s, US scientists realized, despite the availability of folate in foods and in supplements, there was still a challenge for people to meet their daily folate requirements, which is when the US implemented the folate fortification program.[69]

Biological roles

DNA and cell division

 
A diagram of the chemical structure of folate

Folate is necessary for the production and maintenance of new cells, for DNA synthesis and RNA synthesis, and for preventing changes to DNA, and, thus, for preventing cancer.[32] It is especially important during periods of frequent cell division and growth, such as infancy and pregnancy. Folate is needed to carry one-carbon groups for methylation reactions and nucleic acid synthesis (the most notable one being thymine, but also purine bases).[73]Thus, folate deficiency hinders DNA synthesis and cell division, affecting hematopoietic cells and neoplasms the most because of their greater frequency of 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, is hindered and leads to megaloblastic anemia, which is characterized by large immature red blood cells. This pathology results from persistently thwarted attempts at normal DNA replication, DNA repair, and cell division, and produces abnormally large red cells called megaloblasts (and hypersegmented neutrophils) with abundant cytoplasm capable of RNA and protein synthesis, but with clumping and fragmentation of nuclear chromatin. Some of these large cells, although immature (reticulocytes), are released early from the marrow in an attempt to compensate for the anemia.[74] Both adults and children need folate to make normal red and white blood cells and prevent anemia.[75] Deficiency of folate in pregnant women has been implicated in neural tube defects (NTD); therefore, many developed countries have implemented mandatory folic acid fortification in cereals, etc. NTDs occur early in pregnancy (first month), therefore women must have abundant folate upon conception. Folate is required to make red blood cells and white blood cells and folate deficiency may lead to anemia, which causes fatigue, weakness and inability to concentrate.[76]

DNA and amino acid production

 
Metabolism of folic acid to recycle homocysteine into methionine

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, and so required for all dividing cells.[77]

The pathway leading to the formation of tetrahydrofolate (FH4) begins when folic acid (F) is reduced to dihydrofolate (DHF) (FH2), which is then reduced to THF. Dihydrofolate reductase catalyses the last step.[78]Vitamin B3 in the form of NADPH is a necessary cofactor for both steps of the synthesis. Thus, hydride molecules are transferred from NADPH to the C6 position of the pteridine ring to reduce folic acid to THF.[79]

Methylene-THF (CH2FH4) is formed from THF by the addition of a methylene bridge from one of three carbon donors: formateserine, or glycineMethyl tetrahydrofolate (CH3-THF, or methyl-THF) can be made from methylene-THF by reduction of the methylene group with NADPH.

Another form of THF, 10-formyl-THF, results from oxidation of methylene-THF or is formed from formate donating formyl group to THF. Also, histidine can donate a single carbon to THF to form methenyl-THF.

Vitamin B12 is the only acceptor of methyl-THF, and this reaction produces methyl-B12 (methylcobalamin). There is also only one acceptor for methyl-B12, homocysteine, in a reaction catalyzed by homocysteine methyltransferase. These reactions are important because a defect in homocysteine methyltransferase or a deficiency of B12 may lead to a so-called "methyl-trap" of THF, in which THF converts to a reservoir of methyl-THF. Thereafter, this THF has no way of being metabolized, and serves as a sink of THF that causes a subsequent deficiency in folate.[71] Thus, a deficiency in B12 can generate a large pool of methyl-THF that is unable to undergo reactions and mimics folate deficiency.

The reactions that lead to the methyl-THF reservoir can be shown in chain form:

folate → dihydrofolate → tetrahydrofolate ↔ methylene-THF → methyl-THF
 
Folate metabolism

Conversion to biologically active derivatives

All the biological functions of folic acid are performed by tetrahydrofolate and other derivatives. Their biological availability to the body depends upon dihydrofolate reductase action in the liver. This action is unusually slow in humans, being less than 2% of that in rats (and with an almost-5-fold variation in enzymatic activity), leading to the accumulation of unmetabolized folic acid.[80] It has been suggested this low activity limits the conversion of folic acid into its biologically active forms "when folic acid is consumed at levels higher than the Tolerable Upper Intake Level (1 mg/d for adults)."[80]

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 trimethoprimpyrimethamine, and methotrexate; the sulfonamides (competitive inhibitors of 4-aminobenzoic acid in the reactions of dihydropteroate synthetase).

Valproic acid, one of the most commonly prescribed anticonvulsants that is also used to treat certain psychological conditions, is a known inhibitor of folic acid, and as such, has been shown to cause neural tube defects and cases of spina bifida and cognitive impairment in the newborn. Because of this considerable risk, those mothers who must continue to use valproic acid or its derivatives during pregnancy to control their condition (as opposed to stopping the drug or switching to another drug or to a lesser dose) should take folic acid supplements under the direction and guidance of their health care providers.

The National Health and Nutrition Examination Survey (NHANES III 1988–91) and the Continuing Survey of Food Intakes by Individuals (1994–96 CSFII) indicated most adults did not consume adequate folate.[81][82] 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.[83]

Food fortification

 
In the USA many grain products are fortified with folic acid.

Folic acid fortification is a process where folic acid is added to flour with the intention of promoting public health through increasing blood folate levels in the populace. In the USA, food is fortified with folic acid, only one of the many naturally-occurring forms of folate, and a substance contributing only a minor amount to the folates in natural foods.[52]

Since the discovery of the link between insufficient folic acid and neural tube defects, governments and health organizations worldwide have made recommendations concerning folic acid supplementation for women intending to become pregnant.

Fortification is controversial, with issues having been raised concerning individual liberty,[52] as well as the health concerns described in the Toxicity section above. In the USA, there is concern that the federal government mandates fortification, but does not provide monitoring of potential undesirable effects of fortification.[52]

76 countries worldwide require mandatory folic acid fortification of at least one major cereal grain, with nearly all fortifying at least wheat flour, according to November 2013 data from the Flour Fortification Initiative.[84] These countries are:

Antigua and Barbuda, Argentina, Australia, Bahamas, Bahrain, Barbados, Belize, Benin, Bolivia (Plurinational State of), Brazil, Burkina Faso, Cameroon, Canada, Chile, Colombia, Costa Rica, Cote d'Ivoire, Cuba, Dominica, Dominican Republic, Ecuador, Egypt, El Salvador, Fiji, Ghana, Grenada, Guatemala, Guinea, Guyana, Haiti, Honduras, Indonesia, Iran (Islamic Republic of), Iraq, Jamaica, Jordan, Kazakhstan, Kenya, Kosovo, Kuwait, Kyrgyzstan, Liberia, Mali, Mauritania, Mexico, Morocco, Nepal, Nicaragua, Niger, Nigeria, Oman, Palestine (Occupied Territory), Panama, Papua New Guinea, Paraguay, Peru, Republic of Moldova, Rwanda, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Saudi Arabia, Senegal, Sierra Leone, Solomon Islands, South Africa, Suriname, Tanzania (United Republic of), Togo, Trinidad and Tobago, Turkmenistan, Uganda, United States of America, Uruguay, Uzbekistan, and Yemen.[84]

As of November 2013, no EU country has mandated folic acid fortification.[84]

Australia

There has been previous debate in Australia regarding the inclusion of folic acid in products such as bread and flour.[85]

Australia and New Zealand have jointly agreed to fortification though the Food Standards Australia New Zealand. Australia will fortify all flour from 18 September 2009.[86] Although the food standard covers both Australia and New Zealand, an Australian government official has stated it is up to New Zealand to decide whether to implement it there, and they will watch with interest.[87]

The requirement is 0.135 mg of folate per 100g of bread.

Canada

In 2003, a Hospital for Sick ChildrenUniversity of Toronto research group published findings showing the fortification of flour with folic acid in Canada has resulted in a dramatic decrease in neuroblastoma, an early and very dangerous cancer in young children.[88] In 2009, further evidence from McGill University showed a 6.2% decrease per year in the birth prevalence of severe congenital heart defects.[89]

Folic acid used in fortified foods is a synthetic form called pteroylmonoglutamate.[90] It is in its oxidized state and contains only one conjugated glutamateresidue.[90] Folic acid therefore enters via a different carrier system from naturally occurring folate, and this may have different effects on folate binding proteins and its transporters.[91] Folic acid has a higher bioavailability than natural folates and are rapidly absorbed across the intestine,[90] therefore it is important to consider the Dietary Folate Equivalent (DFE) when calculating one's intake. Natural occurring folate is equal to 1 DFE, however 0.6 µg of folic acid is equal to 1 DFE.

Folic acid food fortification became mandatory in Canada in 1998, with the fortification of 150 µg of folic acid per 100 grams of enriched flour and uncooked cereal grains.[92] The purpose of fortification was to decrease the risk of neural tube defects in newborns.[92] It is important to fortify grains because it is a widely eaten food and the neural tube closes in the first four weeks of gestation, often before many women even know they are pregnant. Canada's fortification program has been successful with a decrease of neural tube defects by 19% since its introduction.[93] A seven-province study from 1993 to 2002 showed a reduction of 46% in the overall rate of neural tube defects after folic acid fortification was introduced in Canada.[94] The fortification program was estimated to raise a person’s folic acid intake level by 70–130 µg/day, however an increase of almost double that amount was actually observed.[93]This could be from the fact that many foods are over fortified by 160–175% the predicted value.[93] In addition, much of the elder population take supplements that adds 400 µg to their daily folic acid intake. This is a concern because 70–80% of the population have detectable levels of unmetabolized folic acid in their blood and high intakes can accelerate the growth of preneoplastic lesions.[95] It is still unknown the amount of folic acid supplementation that might cause harm.[92]

Supplementation promotion

According to a Canadian survey, 58% of women said they took a folic acid containing multivitamin or a folic acid supplement as early as three months before becoming pregnant. Women in higher income households and with more years of school education are using more folic acid supplements before pregnancy. Women with planned pregnancies and who are over the age of 25 are more likely to use folic acid supplement. Canadian public health efforts are focused on promoting awareness of the importance of folic acid supplementation for all women of childbearing age and decreasing socio-economic inequalities by providing practical folic acid support to vulnerable groups of women.[94]

New Zealand

New Zealand was planning to fortify bread (excluding organic and unleavened varieties) from 18 September 2009, but has opted to wait until more research is done.[86]

The Association of Bakers [96] and the Green Party [97] have opposed mandatory fortification, describing it as "mass medication". Food Safety Minister Kate Wilkinson reviewed the decision to fortify in July 2009, citing links between overconsumption of folate with cancer .[98] The New Zealand Government is reviewing whether it will continue with the mandatory introduction of folic acid to bread.[99]

United Kingdom

There has been previous debate in the United Kingdom regarding the inclusion of folic acid in products such as bread and flour.[100] While the Food Standards Agency has recommended folic acid fortification,[101][102][103] and wheat flour is fortified with iron,[84] folic acid fortification of wheat flour is allowed voluntarily rather than required.

United States

The United States Public Health Service recommends an extra 0.4 mg/day for newly pregnant women, which they can take as a pill. However, many researchers believe this supplementation can never work effectively enough, since about half of all pregnancies in the U.S. are unplanned, and not all women comply with the recommendation. Approximately 53% of the US population uses dietary supplements and 35% uses dietary supplements that contain folic acid.[104]

Men consume more folate (in dietary folate equivalents) than women, and non-Hispanic whites have higher folate intakes than Mexican Americans and non-Hispanic blacks.[104] Twenty-nine percent of black women have inadequate intakes of folate.[104] The age group consuming the most folate and folic acid is the >50 group.[104] 5% of the population exceeds the Tolerable Upper Intake Level.[104]

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.[105][106] This ruling took effect on January 1, 1998, and was specifically targeted to reduce the risk of neural tube birth defects in newborns.[107] There are concerns that the amount of folate added is insufficient .[108] 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.[109]

As a result of the folic acid fortification program, fortified foods have become a major source of folic acid in the American diet.[9] The Centers for Disease Control and Prevention in Atlanta, Georgia used data from 23 birth defect registries covering about half of United States births, and extrapolated their findings to the rest of the country. These data indicate that, since the addition of folic acid in grain-based foods as mandated by the FDA, the rate of neural tube defects dropped by 25% in the United States.[110] Before folic acid fortification, about 4,100 pregnancies were affected by a neural tube defect each year in the United States. After fortification, this number declined to around 3,000.[111] The results of folic acid fortification on the rate of neural tube defects in Canada have also been positive, showing a 46% reduction in prevalence of NTDs;[112] the magnitude of reduction was proportional to the prefortification rate of NTDs, essentially removing geographical variations in rates of NTDs seen in Canada before fortification.

When the U.S. Food and Drug Administration set the folic acid fortification regulation in 1996, the projected increase in folic acid intake was 100 µg/d.[113]Data from a study with 1480 subjects showed that folic acid intake increased by 190 µg/d and total folate intake increased by 323 µg dietary folate equivalents (DFE)/d.[113] Folic acid intake above the upper tolerable intake level (1000 µg folic acid/d) increased only among those individuals consuming folic acid supplements as well as folic acid found in fortified grain products.[113] Taken together, folic acid fortification has led to a bigger increase in folic acid intake than first projected.[113]

See also

References

  1. Jump up^  "Folic Acid". The PubChem Project.
  2. Jump up to:a b c d e f g "Folic Acid"Drugs.com. American Society of Health-System Pharmacists. January 1, 2010. Retrieved 1 September 2016.
  3. Jump up^  Fenech, Michael (May 2012). "Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity". Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis733 (1-2): 21–33. doi:10.1016/j.mrfmmm.2011.11.003PMID 22093367.
  4. Jump up^  "Definition of vitamin Bc". Medical-dictionary.thefreedictionary.com. Retrieved 2012-09-09.
  5. Jump up to:a b Darby, William J.; Jones, Edgar (1 November 1945). "Treatment of Sprue with Synthetic L. casei Factor (Folic Acid, Vitamin M)."Experimental Biology and Medicine60 (2): 259–262. doi:10.3181/00379727-60-15154P. Retrieved 13 December 2014.
  6. Jump up^  Bailey, Lynn B. (2009). Folate in Health and Disease, Second Edition. CRC Press. p. 198. ISBN 9781420071252.
  7. Jump up^  Obeid, R; Herrmann, W (October 2012). "The emerging role of unmetabolized folic acid in human diseases: myth or reality?". Current drug metabolism13 (8): 1184–95. PMID 22746304.
  8. Jump up to:a b c d Li Y, Huang T, Zheng Y, Muka T, Troup J, Hu FB (2016). "Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials"J Am Heart Assoc5 (8). doi:10.1161/JAHA.116.003768PMC 5015297Freely accessiblePMID 27528407.
  9. Jump up to:a b c d e f g "Dietary supplement fact sheet: Folate"Health Information. Office of Dietary Supplements, US National Institutes of Health. Retrieved 1 September 2016.
  10. Jump up^  Pommerville, Glendale Community College Jeffrey C. (2009). Alcamo's Fundamentals of Microbiology: Body Systems. Jones & Bartlett Publishers. p. 511. ISBN 9780763787127.
  11. Jump up^  Marino, Bradley S.; Fine, Katie Snead (2009). Blueprints Pediatrics. Lippincott Williams & Wilkins. p. 131. ISBN 9780781782517.
  12. Jump up^  Pond, Wilson G.; Nichols, Buford L.; Brown, Dan L. (2009). Adequate Food for All: Culture, Science, and Technology of Food in the 21st Century. CRC Press. p. 148. ISBN 9781420077544.
  13. Jump up^  "WHO Model List of Essential Medicines" (PDF)World Health Organization. October 2013. Retrieved 22 April 2014.
  14. Jump up^  "Folic Acid"International Drug Price Indicator Guide. Retrieved 1 September 2016.
  15. Jump up^  Chambers Concise Dictionary. Allied Publishers. 2004. p. 451. ISBN 979-8186-06236-3.
  16. Jump up^  "Folic Acid"qmul.ac.uk.
  17. Jump up^  Fenech, Michael (May 2012). "Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity". Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis733 (1-2): 21–33. doi:10.1016/j.mrfmmm.2011.11.003PMID 22093367.
  18. Jump up^  "Definition of vitamin Bc". Medical-dictionary.thefreedictionary.com. Retrieved 2012-09-09.
  19. Jump up^  Wilson RD, Wilson RD, Audibert F, Brock JA, Carroll J, Cartier L, Gagnon A, Johnson JA, Langlois S, Murphy-Kaulbeck L, Okun N, Pastuck M, Deb-Rinker P, Dodds L, Leon JA, Lowel HL, Luo W, MacFarlane A, McMillan R, Moore A, Mundle W, O'Connor D, Ray J, Van den Hof M (2015). "Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies". J Obstet Gynaecol Can37 (6): 534–52. doi:10.1016/s1701-2163(15)30230-9PMID 26334606.
  20. Jump up^  [needs update ]Yajnik CS, Deshmukh US (September 2008). "Maternal nutrition, intrauterine programming and consequential risks in the offspring". Rev Endocr Metab Disord9 (3): 203–11. doi:10.1007/s11154-008-9087-zPMID 18661241.
  21. Jump up^  Crider KS, Cordero AM, Qi YP, Mulinare J, Dowling NF, Berry RJ (2013). "Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis". Am. J. Clin. Nutr98 (5): 1272–81. doi:10.3945/ajcn.113.065623PMID 24004895.
  22. Jump up^  Ebisch IM, Thomas CM, Peters WH, Braat DD, Steegers-Theunissen RP (2007). "The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility". Hum. Reprod. Update13 (2): 163–74. doi:10.1093/humupd/dml054PMID 17099205.
  23. Jump up^  Altmäe S, Stavreus-Evers A, Ruiz JR, et al. (June 2010). "Variations in folate pathway genes are associated with unexplained female infertility". Fertil. Steril94 (1): 130–7. doi:10.1016/j.fertnstert.2009.02.025PMID 19324355.
  24. Jump up^  Bazzano LA (August 2011). "No effect of folic acid supplementation on cardiovascular events, cancer or mortality after 5 years in people at increased cardiovascular risk, although homocysteine levels are reduced". Evid Based Med16 (4): 117–8. doi:10.1136/ebm1204PMID 21402567.
  25. Jump up^  Bazzano LA (July 2009). "Folic acid supplementation and cardiovascular disease: the state of the art". Am. J. Med. Sci338 (1): 48–9. doi:10.1097/MAJ.0b013e3181aaefd6PMID 19593104.
  26. Jump up^  "Folic acid 'reduces stroke risks'"BBC News. London. 31 May 2007.
  27. Jump up^  Terwecoren A, Steen E, Benoit D, Boon P, Hemelsoet D (September 2009). "Ischemic stroke and hyperhomocysteinemia: truth or myth?". Acta Neurol Belg109 (3): 181–8. PMID 19902811.
  28. Jump up^  Wien TN, Pike E, Wisløff T, Staff A, Smeland S, Klemp M (2012). "Cancer risk with folic acid supplements: a systematic review and meta-analysis"BMJ Open2 (1): e000653. doi:10.1136/bmjopen-2011-000653PMC 3278486Freely accessiblePMID 22240654.
  29. Jump up^  Wang, R; Zheng, Y; Huang, JY; Zhang, AQ; Zhou, YH; Wang, JN (29 December 2014). "Folate intake, serum folate levels, and prostate cancer risk: a meta-analysis of prospective studies.". BMC Public Health14 (1): 1326. doi:10.1186/1471-2458-14-1326PMID 25543518.
  30. Jump up^  Weinstein SJ, Hartman TJ, Stolzenberg-Solomon R, et al. (November 2003). "Null association between prostate cancer and serum folate, vitamin B(6), vitamin B(12), and homocysteine"Cancer Epidemiol. Biomarkers Prev12 (11 Pt 1): 1271–2. PMID 14652294.
  31. Jump up^  "Folic Acid"cancer.org.
  32. Jump up to:a b Kamen B (October 1997). "Folate and antifolate pharmacology". Semin. Oncol24 (5 Suppl 18): S18–30–S18–39. PMID 9420019.
  33. Jump up^  Rubio IT, Cao Y, Hutchins LF, Westbrook KC, Klimberg VS (May 1998). "Effect of glutamine on methotrexate efficacy and toxicity"Ann. Surg227(5): 772–8; discussion 778–80. doi:10.1097/00000658-199805000-00018PMC 1191365Freely accessiblePMID 9605669.
  34. Jump up^  Wolff JE, Hauch H, Kuhl J, Egeler RM, Jurgens H (1998). "Dexamethasone increases hepatotoxicity of MTX in children with brain tumors". Anticancer Research18 (4B): 2895–9. PMID 9713483.
  35. Jump up^  Kepka L, De Lassence A, Ribrag V, et al. (March 1998). "Successful rescue in a patient with high dose methotrexate-induced nephrotoxicity and acute renal failure". Leuk. Lymphoma29 (1–2): 205–9. doi:10.3109/10428199809058397PMID 9638991.
  36. Jump up^  Branda RF, Nigels E, Lafayette AR, Hacker M (1998). "Nutritional folate status influences the efficacy and toxicity of chemotherapy in rats". Blood92(7): 2471–6. PMID 9746787.
  37. Jump up^  Shiroky JB; Frcp(c) (November 1997). "The use of folates concomitantly with low-dose pulse methotrexate". Rheum. Dis. Clin. North Am23 (4): 969–80. doi:10.1016/S0889-857X(05)70369-0PMID 9361164.
  38. Jump up^  Keshava C, Keshava N, Whong WZ, Nath J, Ong TM (February 1998). "Inhibition of methotrexate-induced chromosomal damage by folinic acid in V79 cells". Mutat. Res397 (2): 221–8. doi:10.1016/S0027-5107(97)00216-9PMID 9541646.
  39. Jump up^  Coppen A, Bolander-Gouaille C (January 2005). "Treatment of depression: time to consider folic acid and vitamin B12". J. Psychopharmacol. (Oxford)19 (1): 59–65. doi:10.1177/0269881105048899PMID 15671130.
  40. Jump up^  Taylor MJ, Carney SM, Goodwin GM, Geddes JR (June 2004). "Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials". J. Psychopharmacol. (Oxford)18 (2): 251–6. doi:10.1177/0269881104042630PMID 15260915.
  41. Jump up^  Gilbody S, Lewis S, Lightfoot T (January 2007). "Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review". Am. J. Epidemiol165 (1): 1–13. doi:10.1093/aje/kwj347PMID 17074966.
  42. Jump up^  Gilbody S, Lightfoot T, Sheldon T (July 2007). "Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity"J Epidemiol Community Health61 (7): 631–7. doi:10.1136/jech.2006.050385PMC 2465760Freely accessiblePMID 17568057.
  43. Jump up^  Gaweesh S, Ewies AA (February 2010). "Folic acid supplementation cures hot flushes in postmenopausal women". Med. Hypotheses74 (2): 286–8. doi:10.1016/j.mehy.2009.09.010PMID 19796883.
  44. Jump up^  García-Miss Mdel R, Pérez-Mutul J, López-Canul B, et al. (May 2010). "Folate, homocysteine, interleukin-6, and tumor necrosis factor alfa levels, but not the methylenetetrahydrofolate reductase C677T polymorphism, are risk factors for schizophrenia". J Psychiatr Res44 (7): 441–6. doi:10.1016/j.jpsychires.2009.10.011PMID 19939410.
  45. Jump up^  Krebs MO, Bellon A, Mainguy G, Jay TM, Frieling H (December 2009). "One-carbon metabolism and schizophrenia: current challenges and future directions". Trends Mol Med15 (12): 562–70. doi:10.1016/j.molmed.2009.10.001PMID 19896901.
  46. Jump up^  Christen WG, Glynn RJ, Chew EY, Albert CM, Manson JE (February 2009). "Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study"Arch. Intern. Med169 (4): 335–41. doi:10.1001/archinternmed.2008.574PMC 2648137Freely accessiblePMID 19237716.
  47. Jump up^  Vreugdenhil G, Wognum AW, van Eijk HG, Swaak AJ (February 1990). "Anaemia in rheumatoid arthritis: the role of iron, vitamin B12, and folic acid deficiency, and erythropoietin responsiveness"Ann. Rheum. Dis49 (2): 93–8. doi:10.1136/ard.49.2.93PMC 1003985Freely accessiblePMID 2317122.
  48. Jump up^  Reynolds E (November 2006). "Vitamin B12, folic acid, and the nervous system". Lancet Neurol5 (11): 949–60. doi:10.1016/S1474-4422(06)70598-1PMID 17052662.
  49. Jump up^  Allen RH, Stabler SP, Savage DG, Lindenbaum J (June 1990). "Diagnosis of cobalamin deficiency I: usefulness of serum methylmalonic acid and total homocysteine concentrations". Am. J. Hematol34 (2): 90–8. doi:10.1002/ajh.2830340204PMID 2339683.
  50. Jump up^  Hathcock JN (August 1997). "Vitamins and minerals: efficacy and safety". Am. J. Clin. Nutr66 (2): 427–37. PMID 9250127.
  51. Jump up^  FAOWHO (2002), "ch. 4, Folate and Folic Acid", Human Vitamin and Mineral Requirements
  52. Jump up to:a b c d Smith AD (January 2007). "Folic acid fortification: the good, the bad, and the puzzle of vitamin B-12"Am. J. Clin. Nutr85 (1): 3–5. PMID 17209170.
  53. Jump up to:a b "Folate deficiency: MedlinePlus Medical Encyclopedia"www.nlm.nih.gov. Retrieved 2015-11-16.
  54. Jump up^  Diaz, V. H. US Patent 20080020071, Jan 24, 2008.
  55. Jump up to:a b c d e f g h i j k http://www.merck.com
  56. Jump up^  Lohner, Szimonetta; Fekete, Katalin; Berti, Cristiana; Hermoso, Maria; Cetin, Irene; Koletzko, Berthold; Decsi, Tamás (2012). "Effect of folate supplementation on folate status and health outcomes in infants, children and adolescents: A systematic review". International Journal of Food Sciences and Nutrition63 (8): 1014–20. doi:10.3109/09637486.2012.683779PMID 22574624.
  57. Jump up to:a b Malterre T (September 2009). "Digestive and nutritional considerations in celiac disease: could supplementation help?" (PDF)Altern Med Rev14(3): 247–57. PMID 19803549.[unreliable medical source?]
  58. Jump up^  Varela-Moreiras G, Murphy MM, Scott JM (May 2009). "Cobalamin, folic acid, and homocysteine". Nutr. Rev. 67 Suppl 1: S69–72. doi:10.1111/j.1753-4887.2009.00163.xPMID 19453682.
  59. Jump up^  Pasricha S, Shet A, Sachdev HP, Shet AS (October 2009). "Risks of routine iron and folic acid supplementation for young children" (PDF)Indian Pediatr46 (10): 857–66. PMID 19887691.
  60. Jump up to:a b "Dietary Supplement Fact Sheet: Folate"National Institutes of Health.
  61. Jump up^  Folate. IN: Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy Press. 2001, PP.196-305.
  62. Jump up^  Tolerable Upper Intake Levels For Vitamins And Minerals (PDF), European Food Safety Authority, 2006
  63. Jump up^  Owens, Janel E.; Clifford, Andrew J.; Bamforth, Charles W. (2007). "Folate in Beer". Journal of the Institute of Brewing113 (3): 243–248. doi:10.1002/j.2050-0416.2007.tb00283.xISSN 0046-9750.
  64. Jump up^  "USDA Nutrient Database (Table)". United States Department of Agriculture. Retrieved 2014-08-14.
  65. Jump up^  Dietrich, M; Brown, CJ; Block, G (2005). "The effect of folate fortification of cereal-grain products on blood folate status, dietary folate intake, and dietary folate sources among adult non-supplement users in the United States". J Am Coll Nutr24 (4): 266–274. doi:10.1080/07315724.2005.10719474PMID 16093404.
  66. Jump up^  Suitor, CW; Bailey, LB (2000). "Dietary folate equivalents: interpretation and application". J Am Diet Assoc100 (1): 88–94. doi:10.1016/S0002-8223(00)00027-4PMID 10646010.
  67. Jump up to:a b "Effects of Cooking on Vitamins (Table)". Beyondveg.com. Retrieved 2012-09-09.
  68. Jump up^  Cabanillas, M; Moya Chimenti, E; González Candela, C; Loria Kohen, V; Dassen, C; Lajo, T. (2009). "Usefulness of meal replacement: analysis of the principal meal replacement products commercialised in Spain". Nutr Hosp24(5): 535–42. PMID 19893863.
  69. Jump up to:a b c d Lanska, DJ. (2009). "Chapter 30 Historical aspects of the major neurological vitamin deficiency disorders: the water-soluble B vitamins". Handb Clin Neurol. Handbook of Clinical Neurology. 95: 445–76. doi:10.1016/S0072-9752(08)02130-1ISBN 978-0-444-52009-8PMID 19892133.
  70. Jump up^  Mitchell HK, Snell EE, Williams RJ (1941). "The concentration of "folic acid"". J Am Chem Soc63 (8): 2284. doi:10.1021/ja01853a512.
  71. Jump up to:a b Hoffbrand AV, Weir DG (June 2001). "The history of folic acid". Br. J. Haematol113 (3): 579–89. doi:10.1046/j.1365-2141.2001.02822.xPMID 11380441.
  72. Jump up^  Angier RB, Boothe JH, Hutchings BL, et al. (August 1945). "Synthesis of a Compound Identical with the L. Casei Factor Isolated from Liver". Science102 (2644): 227–8. Bibcode:1945Sci...102..227Adoi:10.1126/science.102.2644.227PMID 17778509.
  73. Jump up^  Figueiredo JC, Grau MV, Haile RW, et al. (March 2009). "Folic acid and risk of prostate cancer: results from a randomized clinical trial"J. Natl. Cancer Inst101 (6): 432–5. doi:10.1093/jnci/djp019PMC 2657096Freely accessiblePMID 19276452.
  74. Jump up^  Smith C, Lieberman M, Marks DB, Marks AD (2007). Marks' essential medical biochemistry. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-9340-8.[page needed ]
  75. Jump up^  Zittoun J (1993). "Anemias due to disorder of folate, vitamin B12 and transcobalamin metabolism". La Revue du praticien (in French). 43 (11): 1358–63. PMID 8235383.
  76. Jump up^  "Folate and Your Health - HealthLinkBC File #68g". Healthlinkbc.ca. Retrieved 2012-09-09.
  77. Jump up^  Goh YI, Koren G (January 2008). "Folic acid in pregnancy and fetal outcomes". J Obstet Gynaecol28 (1): 3–13. doi:10.1080/01443610701814195PMID 18259891.
  78. Jump up^  "EC 1.5.1.3". Us.expasy.org. Retrieved 2012-09-09.
  79. Jump up^  Benkovic SJ, Hammes-Schiffer S (August 2003). "A perspective on enzyme catalysis". Science301 (5637): 1196–202. Bibcode:2003Sci...301.1196Bdoi:10.1126/science.1085515PMID 12947189.
  80. Jump up to:a b Bailey SW, Ayling JE (September 2009). "The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake"Proceedings of the National Academy of Sciences of the United States of America106 (36): 15424–9. Bibcode:2009PNAS..10615424Bdoi:10.1073/pnas.0902072106PMC 2730961Freely accessiblePMID 19706381.
  81. Jump up^  Alaimo K, McDowell MA, Briefel RR, Bischof AM, Caughman CR, Loria CM, Johnson CL (1994). "Dietary intake of vitamins, minerals, and fiber of persons ages 2 months and over in the United States: Third National Health and Nutrition Examination Survey, Phase 1, 1988–91". Advance Data from Vital and Health Statistics (258): 1–28. PMID 10138938.
  82. Jump up^  Raiten DJ, Fisher KD (1995). "Assessment of folate methodology used in the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994)". The Journal of Nutrition125 (5): 1371S–1398S. PMID 7738698.
  83. Jump up^  Lewis CJ, Crane NT, Wilson DB, Yetley EA (August 1999). "Estimated folate intakes: data updated to reflect food fortification, increased bioavailability, and dietary supplement use". Am. J. Clin. Nutr70 (2): 198–207. PMID 10426695.
  84. Jump up to:a b c d "Global Progress". Flour Fortification Initiative website. Flour Fortification Initiative. November 2013.
  85. Jump up^  "Bread fortification 'not justified'". The Sydney Morning Herald. 29 July 2006.
  86. Jump up to:a b NZPA (2007-06-22). "Bread to be fortified with folic acid". NZ Herald. Retrieved 2009-07-13.
  87. Jump up^  "Bread additive call 'up to NZ'". Retrieved 2009-07-15.
  88. Jump up^  French AE, Grant R, Weitzman S, et al. (September 2003). "Folic acid food fortification is associated with a decline in neuroblastoma". Clin. Pharmacol. Ther74 (3): 288–94. doi:10.1016/S0009-9236(03)00200-5PMID 12966372.
  89. Jump up^  Ionescu-Ittu R, Marelli AJ, Mackie AS, Pilote L (2009). "Prevalence of severe congenital heart disease after folic acid fortification of grain products: time trend analysis in Quebec, Canada"BMJ338: b1673. doi:10.1136/bmj.b1673PMC 2682153Freely accessiblePMID 19436079.
  90. Jump up to:a b c Smith AD, Kim YI, Refsum H (March 2008). "Is folic acid good for everyone?". Am. J. Clin. Nutr87 (3): 517–33. PMID 18326588.
  91. Jump up^  Ulrich CM, Potter JD (February 2006). "Folate supplementation: too much of a good thing?". Cancer Epidemiol. Biomarkers Prev15 (2): 189–93. doi:10.1158/1055-9965.EPI-152COPMID 16492904.
  92. Jump up to:a b c Mason JB, Dickstein A, Jacques PF, et al. (July 2007). "A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis". Cancer Epidemiol. Biomarkers Prev16 (7): 1325–9. doi:10.1158/1055-9965.EPI-07-0329PMID 17626997.
  93. Jump up to:a b c Quinlivan EP, Gregory JF (January 2003). "Effect of food fortification on folic acid intake in the United States"Am. J. Clin. Nutr77 (1): 221–5. PMID 12499345.
  94. Jump up to:a b "Welcome to the Health Canada Web site". Hc-sc.gc.ca. Retrieved 2012-09-09.
  95. Jump up^  Chustecka, Z. (2009). "Folic-acid fortification of flour and increased rates of colon cancer". Retrieved 9 November 2009.
  96. Jump up^  "Work Starts on Wilkinson's Mass Medication Plan" (Press release). Association Of Bakers. 2009-07-08. Retrieved 2009-07-13.
  97. Jump up^  "NZ should push pause on folic fortification" (Press release). Green Party. 2009-07-09. Retrieved 2009-07-13.
  98. Jump up^  NZPA (2009-07-08). "Bakers, Govt battle over folic acid". NZ Herald. Retrieved 2009-07-13.
  99. Jump up^  "Govt reviewing folic acid policy". Stuff. Retrieved 15 July 2009.
  100. Jump up^  BBC 'Put folic acid in bread' 2000-01-13
  101. Jump up^  FSA (2007-05-17). "Board recommends mandatory fortification". Retrieved 2007-05-18.
  102. Jump up^  "Backing for folic acid in bread"BBC News. 17 May 2007. Retrieved 2007-05-18.
  103. Jump up^  BBC Experts back folic acid in flour 11 May 2007
  104. Jump up to:a b c d e Bailey RL, Dodd KW, Gahche JJ, et al. (January 2010). "Total folate and folic acid intake from foods and dietary supplements in the United States: 2003-2006"Am. J. Clin. Nutr91 (1): 231–7. doi:10.3945/ajcn.2009.28427PMC 2793110Freely accessiblePMID 19923379.
  105. Jump up^  Malinow MR, Duell PB, Hess DL, et al. (April 1998). "Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease". N. Engl. J. Med338 (15): 1009–15. doi:10.1056/NEJM199804093381501PMID 9535664.
  106. Jump up^  Daly S, Mills JL, Molloy AM, et al. (December 1997). "Minimum effective dose of folic acid for food fortification to prevent neural-tube defects". Lancet350 (9092): 1666–9. doi:10.1016/S0140-6736(97)07247-4PMID 9400511.
  107. Jump up^  Crandall BF, Corson VL, Evans MI, Goldberg JD, Knight G, Salafsky IS (July 1998). "American College of Medical Genetics statement on folic acid: fortification and supplementation". Am. J. Med. Genet78 (4): 381. doi:10.1002/(SICI)1096-8628(19980724)78:4<381::AID-AJMG16>3.0.CO;2-EPMID 9714444.
  108. Jump up^  "FDA muffed chance to reduce birth defects". Boston Globe. 6 January 2004.
  109. Jump up^  "US denies Vegemite ban". 25 October 2006. Archived from the original on 2009-03-01.
  110. Jump up^  Centers for Disease Control and Prevention (CDC) (May 2004). "Spina bifida and anencephaly before and after folic acid mandate--United States, 1995-1996 and 1999-2000"MMWR Morb. Mortal. Wkly. Rep53 (17): 362–5. PMID 15129193.
  111. Jump up^  "Birth Defects COUNT | Folic Acid | NCBDDD | CDC"www.cdc.gov. Retrieved 2015-11-16.
  112. Jump up^  De Wals P, Tairou F, Van Allen MI, et al. (July 2007). "Reduction in neural-tube defects after folic acid fortification in Canada". N. Engl. J. Med357 (2): 135–42. doi:10.1056/NEJMoa067103PMID 17625125.
  113. Jump up to:a b c d Choumenkovitch SF, Selhub J, Wilson PW, Rader JI, Rosenberg IH, Jacques PF (September 2002). "Folic acid intake from fortification in United States exceeds predictions"J. Nutr132 (9): 2792–8. PMID 12221247.

External links[edit]

Biochemistry links

Source: https://en.wikipedia.org/wiki/Folic_acid

PRODIGY-5

ALL IN ONE NUTRITIONAL WITH TRANS-ARMOR® NUTRIENT TECHNOLOGY

BREAKTHROUGH TECHNOLOGY IN PRODIGY 5.

THE FIVE UNIQUE ATTRIBUTES

A revolutionary new product featuring five unique attributes that create an all-in-one nutritional experience for everyone, every day. Take advantage of the technology and know-how, and enjoy the benefits of the phytoplankton, antioxidants, vitamins, and energy you can feel in minutes with the new ForeverGreen product: Prodigy-5.

Vitamins in Prodigy-5

We all know that vitamins and minerals are essential to our overall health, yet many of us are left not getting most of the vitamins and minerals we need through our normal eating habits. Prodigy-5 features a unique blend of vitamins and minerals that were each specifically chosen using the best peer reviewed scientific research available to support your general and eye health.  

Technology & Know-how behind Prodigy-5

​Adam Saucedo, M.D., has teamed up with the brilliant mind of Balamurali Ambati, M.D., PhD, MBA to bring you the exclusive TransArmor™ Nutrient Technology, found only in Prodigy-5. The patent-pending TransArmor™ technology increases the transit time of nutrients through the digestive system and primes the body for increased absorption of these nutrients.

Antioxidants in Prodigy-5

Prodigy-5 features natural pomegranate and raspberry for a bold flavor that also delivers powerful antioxidants! Antioxidants help to rid the body of damaging free radicals. Antioxidants become a powerful defense system to these free radicals, which if left unchallenged, can contribute to the cause of a range of health problems. Raspberries and pomegranates, Marine phytoplankton, Curcuma.

Phytoplankton in Prodigy-5

The most fundamental nutrient on the planet, phytoplankton are microscopic plant-based organisms that generate most of the world’s oxygen. Phytoplankton, found naturally in both salt and fresh water, are a viable source of vitamins, minerals, amino acids, and other micronutrients.

Energy of the Prodigy-5

Prodigy-5 features natural green tea extract, which is known to help increase energy and mental focus. It helps provide the alertness associated with caffeine without the jittery side effects! Green tea has a range of health benefits, and also contains powerful antioxidants, making it the perfect way to get a little extra boost with your daily dose of Prodigy-5.

PRODIGY-5 DEVELOPED BY MEDICAL INDUSTRY LEADERS

Prodigy-5 revolutionaly Trans-Armor™ nutrient technology, developed by medical industry leader doctors aids the body in absorbing more of the nutrition than it normally would, thereby increasing efficiencies and overall health.

In addition to this scientifically proven technology, Prodigy-5 is considered an all-in-one nutritional habit.

Dr. Ambati, child prodigy, and ForeverGreen’s own Research Scientist Adam Saucedo have partnered together and developed what is being called the check-mate in the conversation of nutrition, Prodigy-5.

DR. AMBATI

CHILD PRODIGY

Dr. Ambati started calculus at age 4, graduated high school at age 11, pre-med age 13, med-school at 14 and was announced the Guinness Book of World Records holder for youngest doctor at age 17.

DR. ADAM SAUCEDO

RESEARCH SCIENTIST

Dr. Adam Saucedo is ForeverGreen’s own Research Scientist, founder and Chief Medical Adviser of the Center for the Heart and Founder of the New Life Center; the largest eating disorder clinic in the world.

DID YOU KNOW THAT HUMAN STOMACH ACIDS ARE STRONG ENOUGH TO DISSOLVE A RAZOR BLADE?

This means that your stomach acids act like a wall, preventing supplements and nutrients from passing to your blood stream and cells; only a percentage survives. Plain English? Your body gets only a fraction of the nutrients it digests. So, this begs the question, Can it be changed?

Can we use modern science to get more out of the digestive process? The answer is a very exciting yes!

Prodigy-5 with the perfect micro-nutrient formula featuring “Trans-Armor Nutrient Technology” that can quickly deliver the nutrients you need throughout your entire body and has the ability to increase the absorption and utilization of those nutrients to maximize your results. With this ground-breaking technology and formula, Prodigy-5 is the solution to the global problem of malnutrition.

With today’s nutritionally bankrupt foods, and the bodies inability to absorb 100% of even the healthiest whole foods, malnutrition effects every singe one of us. Whether you are healthy, wealthy, poor or starving, every person on this planet needs the nutritional revolution offered in Prodigy-5. It is literally for EVERYONE, EVERY DAY.

Prodigy-5 delivers a new TransArmor™ Nutrition bio-enhancing technology.
See how it works:

Prodigy-5 revolutionaly Trans-Armor™ nutrient technology, developed by medical industry leader doctors aids the body in absorbing more of the nutrition than it normally would, thereby increasing efficiencies and overall health. In addition to this scientifically proven technology, Prodigy-5 is considered an all-in-one nutritional habit.

Prodigy 5 contains the new "Trans-Armor™" delivery technology that provides nutrition and energy at the highest level of absorption to our body's cells, including:

• a micronutrient formula for general health,
• a micronutrient formula for eye health,
• an impressive antioxidant profile,
• an impressive and new bio-enhancing absorption technology


Does not contain artificial sweetners or additives. Sweetened with Pomegranate, Raspberry, and Stevia.

PRODIGY-5 HIGHLIGHT

PHYTOPLANKTON

One of those rare products that contains almost everything you need for life (and the rebuilding of cells) is marine phytoplankton.

Marine phytoplankton are one-cell plants that are too small to be seen individually without the aid of a microscope. Because they are microscopic, the body’s cells can absorb them immediately (bioavailability) and receive all of their valuable nutrients at the same time for maximum effectiveness.

The marine phytoplankton, also known as a “Superfood”, is according to NASA and plenty of scientific researches the most important plant and food in the world as it provides the earth with over 90% of it’s oxygen. Marine phytoplankton is not only an important source of oxygen it is a critical food source for ocean life and apparently, for us too.

There are very few (foods) that provide all, or even most, of the raw materials to make new cells and sustain the existing ones. A complete super food, these amazing plants contain more than 90 nutrients vital for a healthy body.

It contains all nine amino acids that the body cannot make. The essential fatty acids are also present (Omega-3 and Omega-6). Further it contains the most important vitamins and mineral nutrients. For example vitamin C, H, B1, B2, B3, B6, B12, E, selenium, zinc, chromium, magnesium, calcium, nickel, iron and many more. (General informations about vitamins)

These valuable nutrients are essential for the production of healthy new cells. We all have, at one time or another, cellular or energy blockages, whether they be emotional or physical. And, among the functional ingredients identified from marine algae, natural pigments (NPs) have received particular attention.

Some benefits (but not all) of marine phytoplankton include:

Support Cardiovascular Health: The high level of antioxidants, amino acids, and high levels of omega-3 fatty acids are known to support a healthier cardiovascular system.

Promotes Healthy Skin: There are large amounts of bioflavonoids that can remove toxins from skin cells. Marine phytoplankton also contains riboflavin that reduces free radical attacks in skin cells.

Boost the Immune System: Alanine, beta-carotene, bioflavonoids, and vitamin E are all immune system enhancers found in this superfood.

Increase Energy: Marine phytoplankton detoxifies the body, and eliminates toxins from the cells. This will improve your energy and mood levels.

Stabilizes Blood Sugar Levels: Marine phytoplankton is really good for stabilizing blood sugar levels. Chromium helps to prevent and moderate against diabetes. Glutamic acids help to reduce alcohol and sugar cravings. Phenylalanine is a known sugar craving reducer.

Helps with Joint Health: Manganese helps to assist in joint mobility. Omega-6 fatty acids can relieve symptoms of arthritis. Pathogenic acid can reduce morning pain caused by arthritis. It will help a lot with joint mobility, and reducing pain and stiffness.

Liver Support: The arginine is found in this superfood and is known to help detoxify the liver.

Improves Brain Function: The high amount of omega-3 fatty acids improve brain function. The nucleic acids can enhance the memory. Phenylalanine improves mental clarity. Proline increases learning ability. Magnesium helps reduce mood swings.

More information about phytoplankton

PRODIGY-5 HIGHLIGHT

VITAMINS AND MINERALS

MICRONUTRIENT FORMULA FOR GENERAL HEALTH

Vitamin A • Vitamin C • Vitamin D • Vitamin E • Vitamin K • Vitamin B6 • Vitamin B12 • Folate • B1 (Thiamin) • B2 (Riboflavin) • B3 (Niacin)



MICRONUTRIENT FORMULA FOR EYE HEALTH

Lutein • Zeaxanthin • Copper • Zinc

Vitamins have specific role to play in the natural wear and tear of the body. There are many vitamin benefits that have a major impact on our overall health.
Vitamins are divided into two types: fat soluble and water soluble. Fat soluble vitamins (vitamin A, D, E and K) are stored in the fat tissues and liver. They can remain in the body up to six months. When the body requires these, they are transported to the area of requirement within the body with help of special carriers. Water soluble vitamins (B-vitamins and vitamin C) are not stored in the body like the fat soluble ones. They travel in the blood stream and need to be replenished everyday.


Below is a list of the 13 major vitamins and what each does for your body:

Prodigy-5 contains: Vitamin A (Beta-Carotene) is a natural antioxidant. It belongs to a class of pigments known as carotenoids which include the yellow, red and orange pigments that give many vegetables and plants their coloring. Vitamin A has been found to enhance immune system functions by supporting and promoting the activities of white blood cells as well as other immune related cells. It also helps to inhibit free radicals and their damaging effects which have been associated with arthritis, heart disease and the development and progression of malignant cells (cancer). Beta-carotene is a precursor for vitamin A (approximately 6 mg of ß-carotene = 1 mg vitamin A). Beta-carotene is best known for the body’s ability to convert it into retinal, which is essential for good vision and visual health, skin, and immune functions.
Natural sources of beta-carotene include carrots, pumpkin, sweet potato, spinach, kale, collard and turnip greens, and winter squash.

According to the National Institutes on Health, the average adult male should be getting 900mcg of vitamin C each day. Females should be getting 700mg a day. Individuals with special needs (women who are pregnant, smokers) may have different requirements and should consult their health professional.

Prodigy-5 contains: Vitamin B1 (Thiamin) is a water-soluble B-vitamin involved with many cellular functions including carbohydrates metabolism, break down of amino acids, production of certain neurotransmitters and multiple enzyme processes (through the coenzyme thiamin pyrophosphate, or TPP). Thiamin can be found in small amounts in a wide variety of foods. Pork, sunflower seeds, yeast, peas and wheat are a few examples. Very little thiamin is stored within the body and must be consumed on a regular basis. A deficiency may result in weakness, loss of appetite, nerve degeneration and irritability.

Prodigy-5 contains: Vitamin B2 (Riboflavin), like most B-vitamins, is involved in many cellular functions. Riboflavin is important in energy metabolism, folate synthesis, conversion of tryptophan to niacin and acts as important coenzymes (FAD/FMN) involved in many reactions. It can be found in liver, mushrooms, spinach, milk, eggs and grains. Because it is water-soluble, there is minimal storage of riboflavin within the body and when dietary intake is insufficient, deficiency can occur (usually accompanied with other vitamin deficiencies).

Prodigy-5 contains:Vitamin B3 (Niacin), also referred to as nicotinamide and nicotinic acid, is another water-soluble, B-vitamin involved with energy metabolism. The coenzymes of niacin (NAD/NADH/NADP/NADPH) are necessary for ATP synthesis (the body’s main energy source), synthesis of fatty acids and some hormones and the transport of hydrogen atoms. When niacin levels are low, the body can use L-tryptophan (an essential amino acid) to manufacture the vitamin. This process is not ideal, however, as it can rapidly deplete L-tryptophan in the body and take away from its other needs such as maintaining optimal levels of serotonin and melatonin. Niacin can be found in grains, liver, fish and chicken.

Prodigy-5 contains: Vitamin B6 is a water-soluble vitamin which plays a variety of important roles in numerous biological processes. Humans cannot produce vitamin B6 so it must be obtained from the diet. Adequate sources of B6 include meats (salmon, turkey, chicken) and whole grain products, such as spinach, nuts and bananas. There are three forms of vitamin B6: pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM). Pyridoxal-5′-phosphate (PLP) is the principal coenzyme form and has the most importance in human metabolism. It acts as a cofactor for many enzymatic reactions involving L-tryptophan, including L-tryptophan’s conversion to serotonin, an important neurotransmitter in the brain. Pyridoxal-5′-phosphate is also involved in other enzymatic reactions where other neurotransmitters, such as gamma-aminobutyric acid (GABA), are synthesized. This plays a critical role in the functions of the nervous system.
Regarding cardiovascular health, there is an association between low vitamin B6 intake with increased blood homocysteine levels and increased risk of cardiovascular diseases, which has been documented in several large observational studies. Vitamin B6, along with folic acid, vitamin B5, vitamin B12 and niacin, is involved in cell metabolism, enhances the immune system, supports the functions of the nervous system, aids in carbohydrate metabolism to produce energy and promotes cognitive health. Vitamin B6 is necessary for the conduction of nerve impulses, regulation of steroid hormones, catabolism of glycogen to glucose, heme synthesis, and the synthesis/ metabolism of amino acids and neurotransmitters.

Prodigy-5 contains: Vitamin B12 is a water-soluble vitamin essential for numerous processes in the body. The richest food sources of vitamin B12 include animal products such as meat, poultry and fish. It is not generally present in plant products with the exeption of peanuts and soybeans which absorb vitamin B12 from bacteria-filled nodules growing on the roots of these plants. Cyanocobalamin is the form most commonly used in supplements but it must be converted into methylcoblamin before it can join the metabolic pool and be properly utilized by the body. Vitamin B12 is also available as methylcobalamin, which is the methylated form, allowing it to become active quicker and be more effective. Vitamin B12 is necessary for countless processes within the body; it transfers methyl groups, plays a part in DNA synthesis and regulation, helps facilitate cell synthesis, maturation and division, helps convert homocysteine to methionine playing a role in cardiovascular protection, aids in the proper functioning of the nervous system, participates in the metabolism of carbohydrates, proteins and fats, helps produce SAMe for mood and cognitive health and also helps produce energy.

Prodigy-5 contains: Vitamin C (Ascorbic acid) is a water-soluble antioxidant essential for human health and life. It has been proven necessary for healthy immune responses, wound healing, non-heme iron absorption (coming from grains and vegetables), reduction in allergic responses, development of connective tissue components such as collagen, and for the prevention of diseases. Vitamin C has also been shown to be important for cardiovascular health, reducing free radicalproduction and free radical damage, and good cognitive health and performance.
Due to human’s inability to produce vitamin C, it is essential to ingest sources containing vitamin C on a regular, if not daily basis. Natural sources of vitamin C include oranges, guavas, peppers (green, red, yellow), kiwis, strawberries, cantaloupes, Brussels sprouts, broccoli, and many other fruits and vegetables.

Prodigy-5 contains: Vitamin D is a fat-soluble vitamin essential for normal growth and development, the formation and maintenance of healthy bones and teeth, and influences the absorption and metabolism of phosphorus and calcium. It is necessary for proper muscle functioning, bone mineralization and stability, and multiple immune functions. Primarily the vitamin D used by the body is produced in the skin after exposure to ultraviolet light from sunlight. Lack of exposure to sunlight, reduced ability to synthesize vitamin D in the skin, age, low dietary intake, or impaired intestinal vitamin D absorption can result in deficiency. Deficiency has been associated with rickets (poor bone formation), porous or weak bones (osteopenia, osteoporosis), pain and muscle weakness, increased risk for cardiovascular disease, impaired cognitive health, and the development and progression of malignant cells (cancer).
Natural food sources of vitamin D are few; these foods are eggs from hens that have been fed vitamin D or fatty fish such as herrings, mackerel, sardines and tuna. Due to low vitamin D levels, countries such as the United States and Canada have opted to fortify foods such as milk and other dairy products, margarines and butters, some natural cereal and grain products.
According to the National Institutes on Health, the average adult should be getting 600IU of vitamin D each day. Individuals with special needs (the elderly, women who are pregnant) may have different requirements and should consult their health professional.

Prodigy-5 contains: Vitamin E is one of the most powerful fat-soluble antioxidants in the body. It has been proven to help promote cardiovascular health, enhanced immune system function, aid in skin repair and to protect cell membranes from damage caused by free radicals. Vitamin E contributes to proper blood flow and clotting as well as cognitive health and function.
Natural sources of vitamin E include herbs such as cloves and oregano, whole grains, nuts and seeds, wheat germ, avocado, egg yolks, and vegetables/fruits such as dark leafy greens, peppers (red, yellow, orange, green), tomatoes, and mangos. Other sources are vegetable oils, margarines, and fortified cereals.

Prodigy-5 contains: Folic Acid is water-soluble vitamin important for many aspects of health. Sources of folic acid include dark, green leafy vegetables such as spinach or asparagus, fortified cereals, orange juice and legumes. Folic acid (folate) must go through a series of chemical conversions before it becomes metabolically active to be properly utilized within the body.
Folinic acid is the highly bioavailable, metabolically active derivative of folic acid and does not require the action of the enzyme dihydrofolinate reductase to become active, so it’s not affected by medicines and herbs that inhibit this enzyme. Adequate folate is necessary for proper DNA and RNA synthesis in regards to fetal growth and development. Due to these effects, the U.S. Public Health Service recommends all women capable of becoming pregnant consume 400 mcg of folic acid daily to prevent neural tube defects.
In addition to its clear effects on fetal growth and development, folic acid also plays an important role in cardiovascular health. By aiding in the conversion of homocysteine to methionine, it has been shown to reduce the levels of homocysteine, a sulfur containing amino acid. In the absence of adequate folic acid levels, homocysteine levels increase and high homocysteine levels are associated with atherosclerosis and the reduced circulation of oxygen and nutrients to the heart, ears and other organs. These results have been documented in countless studies. Folic acid, along with vitamin B6, vitamin B5, vitamin B12 and niacin, is involved in cell metabolism, enhances the immune system, supports the functions of the nervous system, aids in carbohydrate metabolism to produce energy and promotes cognitive health.

Prodigy-5 contains: Vitamin K, a generic term for a group of fat soluble vitamins, are involved mostly in the process of blood clotting, but also needed in metabolic pathways of bones and other tissues. The most well known are vitamin K1, also known as phylloquinone, and vitamin K2, known as menaquinone. Vitamin D and vitamin K work together in bone metabolism and development. Vitamin K works against oral anticoagulants such as 4-hidroxikumarin, and excessive vitamin K intake, either through supplementation or a change in diet, can reduce the anticoagulant effect. Vitamin K1 is mainly found in leafy green vegetables (such as spinach, swiss chard and kale), avocado and kiwi fruit; vitamin K2 can be found in meat, eggs, and dairy and is also synthesized by bacteria in the colon.

More information about vitamins

PRODIGY-5 HIGHLIGHT

ANTIOXIDANTS


WHAT ARE OXIDANTS?

Oxidants are free radicals that either our bodies produce or we get from the environment. Our bodies create oxidants as a response to stress or poor diet, or we are exposed to oxidants through environmental factors like pollution. Oxidative damage is a contributing factor to many diseases, including muscle and tissue degeneration, heart disease, diabetes, cancer, and many other health problems.


WHAT ARE FREE RADICALS?

Free radicals are atoms or groups of atoms with an odd (unpaired) number of electrons. They are like bullies that are low in energy and attack healthy cells and steal their energy to satisfy themselves. Free radicals cause damage to our blood vessels, which can lead to deposits of bad cholesterol and block arteries. Free radicals come in many shapes, sizes, and chemical configurations. What they all share is a voracious appetite for electrons, stealing them from any nearby substances that will yield them.

The human body naturally produces free radicals and the antioxidants to counteract their damaging effects. However, in most cases, free radicals far outnumber the naturally occurring antioxidants. In order to maintain the balance, a continuous supplemental source of external antioxidants are necessary in order to obtain the maximum benefits of antioxidants.


WHAT ARE ANTIOXIDANTS AND WHY DO WE NEED THEM?

Antioxidants are the nutrients’ police force! They are free radical scavengers! They get rid of the bullies! Antioxidants are like a million microscopic special ops on a mission to save your body from the inside out. The benefits of antioxidants are very important to good health, because if free radicals are left unchallenged, they can cause a wide range of illnesses and chronic diseases.

WHERE CAN WE FIND ANTIOXIDANTS?

Obtained through our foods and produced by are bodies, antioxidants are a powerful defense system.
Antioxidants can be found in flavonols (found in chocolate), resveratrol (found in wine), Ellagic acid (found in Raspberries and pomegranate), and lycopene (found in tomatoes). Other popular antioxidants include vitamins A (beta-carotene), C, E, and catechins.

GREAT SOURCES OF ANTIOXIDANTS IN PRODIGY-5

Marine phytoplankton, Raspberries, Pomegranates, Curcuma

Raspberries and pomegranates contain one of the most powerful antioxidants known, Ellagic acid. Ellagic acid is a potent natural antioxidant that can be found in raspberries and pomegranates. Ellagic acid has been shown to be an effective anti- mutagen and anti-carcinogen.

Anthocyanins (red flavonoid pigment found in plants) give pomegranates their red color and offer a strong serving of antioxidants. Punicalagins (a type of phenolic compound) specifically support cardiovascular and neurological health. Studies have shown that antioxidants 18. can play a role in reducing the cell damage of free radicals.

ANTIOXIDANTS AND AGING

Antioxidants are powerful molecules that support healthy aging in more ways than one. These potent compounds aid in an overall healthy lifestyle by supporting cellular health. Aging isn’t about your chronological age; it is more about the amount of stress in your life and the the function of your cells!

More information about antioxidants

ORDER PRODIGY-5

 
 
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PRODIGY 5 PRICES


PRODIGY-5 Single Case
(One case contains 28 serving) prices
$ 75.95
€ 69.11
Prodigy 5 Single DEF small

PRODIGY-5 Double Case 
(One case contains 28 serving) prices
$ 149.95
€ 136.45
Prodigy 5 Double DEF small

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Az eredeti Powerstrips fejlesztőjének, Dr. Minsoo Kim legújabb tapasz fejlesztésére váltottunk:
BEPIC - ALLEVI8 PRO
Nagyobb hatékonyság, jobb ár, megbízhatóbb szállítás!

www.bepic.com/shop

We have changed! More efficiency, better price, more reliable delivery!
We've switched to the latest product from the original Powerstrips developer, Dr. Minsoo Kim: BEPIC - ALLEVI8 PRO

Wir haben uns verändert! Mehr Effizienz, besserer Preis, zuverlässigere Lieferung!
Wir haben auf das neueste Produkt des ursprünglichen Entwicklers von Powerstrips, Dr. Minsoo Kim, umgestellt: BEPIC - ALLEVI8 PRO

Мы изменились! Больше эффективности, лучше цена, надежнее доставка!
Мы перешли на новейший продукт от оригинального разработчика Powerstrips, доктора Минсу Кима: BEPIC - ALLEVI8 PRO

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Siamo passati all'ultimo prodotto dello sviluppatore originale di Powerstrips, il Dr. Minsoo Kim: BEPIC - ALLEVI8 PRO

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