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Vitamin B12

From Wikipedia, the free encyclopedia
 
 
Vitamin B12
Cobalamin.png
Clinical data
AHFS/Drugs.com Monograph
Routes of
administration
oral, IV, IM, intranasal
ATC code B03BA01 (WHO)
Legal status
Legal status
  • UK: POM (Prescription only)
  • US: OTC
Pharmacokinetic data
Bioavailability Readily absorbed in distal half of the ileum
Protein binding Very high to specific transcobalamins plasma proteins
Binding of hydroxocobalamin is slightly higher than cyanocobalamin.
Metabolism hepatic
Biological half-life Approximately 6 days
(400 days in the liver)
Excretion Renal
Identifiers
CAS Number 68-19-9 Yes
PubChem CID 5479203
DrugBank DB00115 
ChemSpider 10469504 Yes
KEGG D00166 Yes
ChEMBL CHEMBL2110563 
Chemical and physical data
Systematic (IUPAC) name: α-(5,6-dimethylbenzimidazolyl)cobamidcyanide
3D model (Jmol) Interactive image
Formula C63H88CoN14O14P
Molar mass 1355.37 g/mol
 Yes (what is this?)  (verify)
 
Methylcobalamin (shown) is a form of vitamin B12. Physically it resembles the other forms of vitamin B12, occurring as dark red crystals that freely form cherry-colored transparent solutions in water.

Vitamin B12vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin that has a key role in the normal functioning of the brain and nervous system, and the formation of red blood cells. It is one of eight B vitamins. It is involved in the metabolism of every cell of the human body, especially affecting DNAsynthesis, fatty acid and amino acid metabolism.[1] No fungi, plants, nor animals (including humans) are capable of producing vitamin B12. Only bacteria and archaea have the enzymes needed for its synthesis. Proved sources of B12 are animal products (meat, fish, dairy products) and supplements. Some research states that certain non-animal products possibly can be a natural source of B12 because of bacterial symbiosis. B12 is the largest and most structurally complicated vitamin and can be produced industrially only through a bacterial fermentation-synthesis. This synthetic B12 is used to fortify foods and sold as a dietary supplement.

Vitamin B12 consists of a class of chemically related compounds (vitamers), all of which show pharmacological activity. It contains the biochemically rare element cobalt (chemical symbol Co) positioned in the center of a planar tetra-pyrrole ring called a corrin ring. The vitamer is produced by bacteria as hydroxocobalamin, but conversion between different forms of the vitamin occurs in the body after consumption.

Vitamin B12 was discovered from[clarification needed] its relationship to the disease pernicious anemia, an autoimmune disease in which parietal cells of the stomach responsible for secreting intrinsic factor are destroyed; these cells are also responsible for secreting acid in the stomach. Because intrinsic factor is crucial for the normal absorption of B12, its lack in the presence of pernicious anemia causes a vitamin B12deficiency. Many other subtler kinds of vitamin B12 deficiency and their biochemical effects have since been elucidated.[2]

Medical uses

Vitamin B12 is used to treat vitamin B12 deficiencycyanide poisoning, and hereditary deficiency of transcobalamin II.[3] It is given as part of the Schilling test for detecting pernicious anemia.[3]

For cyanide poisoning, a large amount of hydroxocobalamin may be given intravenously and sometimes in combination with sodium thiosulfate.[4] The mechanism of action is straightforward: the hydroxycobalamin hydroxide ligand is displaced by the toxic cyanide ion, and the resulting harmless B12complex is excreted in urine. In the United States, the Food and Drug Administration approved (in 2006) the use of hydroxocobalamin for acute treatment of cyanide poisoning.[5]

Dietary Reference Intake

The Food and Nutrition Board of the U.S. Institute of Medicine updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for vitamin B12 in 1998. The current EAR for vitamin B12 for women and men ages 14 and up is 2.0 μg/day; the RDA is 2.4 μg/day. RDAs are higher than EARs so as to identify amounts that will cover people with higher than average requirements. RDA for pregnancy equals 2.6 μg/day. RDA for lactation equals 2.8 μg/day. For infants up to 12 months the Adequate Intake (AI) is 0.4-0.5 μg/day. and for children ages 1–13 years the RDA increases with age from 0.9 to 1.8 μg/day. Because 10 to 30 percent of older people may be unable to effectively absorb vitamin B12 naturally occurring in foods, it is advisable for those older than 50 years to meet their RDA mainly by consuming foods fortified with vitamin B12 or a supplement containing vitamin B12.

As for safety, the Food and Nutrition Board of the U.S. Institute of Medicine sets Tolerable Upper Intake Levels (known as ULs) for vitamins and minerals when evidence is sufficient. In the case of vitamin B12there is no UL, as there is no human data for adverse effects from high doses. The European Food Safety Authority reviewed the same safety question and also reached the conclusion that there was not sufficient evidence to set a UL for vitamin B12.[6] Collectively the EARs, RDAs and ULs are referred to as Dietary Reference Intakes.[7]

For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For vitamin B12 labeling purposes 100% of the Daily Value was 6.0 μg, but as of May 2016 it has been revised downward to 2.4 μg. A table of the pre-change adult Daily Values is provided at Reference Daily Intake. Food and supplement companies have until July 2018 to comply with the change.

Controversial sources in algae

The UK Vegan Society, the Vegetarian Resource Group, and the Physicians Committee for Responsible Medicine, among others, recommend that vegans either consistently eat B12-fortified foods or take a daily or weekly B12 supplement to meet the recommended intake.[8][9][10]

It is important for vegans, whose food provides few sources of B12, and anyone else wishing to obtain B12 from food sources other than animals, to consume foods that contain little or no pseudovitamin-B12 and are high in biologically active B12.

So-called pseudovitamin-B12 refers to B12-like analogues that are biologically inactive in humans and yet found to be present alongside B12 in humans,[11]many food sources (including animals[12]), and possibly supplements and fortified foods.[13] In most cyanobacteria, including Spirulina, and some algae, such as dried Asakusa-nori (Porphyra tenera), pseudovitamin-B12 is found to predominate.[14]

There have been no significant human trials of sufficient size to demonstrate enzymatic activity of B12 from nonbacterial sources, such as Chlorella and edible sea algae (seaweeds, such as lavers), although chemically some of these sources have been reported to contain B12 that seems chemically similar to the active vitamin.[15]

Deficiency

Main article: Vitamin B12 deficiency

Vitamin B12 deficiency can potentially cause severe and irreversible damage, especially to the brain and nervous system.[16] At levels only slightly lower than normal, a range of symptoms such as fatiguedepression, and poor memory may be experienced.[2] Vitamin B12 deficiency can also cause symptoms of mania and psychosis.[17][18]

Vitamin B12 deficiency is most commonly caused by low intakes, but can also result from malabsorption, certain intestinal disorders, low presence of binding proteins, and use of certain medications. Vitamin B12 is rare from plant sources, so vegetarians are most likely to suffer from vitamin B12 deficiency. Infants are at a higher risk of vitamin B12 deficiency if they were born to vegetarian mothers. The elderly who have diets with limited meat or animal products are vulnerable populations as well.[19]

Vitamin B12 deficiency can manifest itself as anemia. In some cases, deficiency can cause permanent neurological damage. Recent studies show depression is associated with vitamin B12 deficiency; sufficient vitamin B12 levels are independently associated with a decreased risk of depression and better cognitive performance adjusted for confounders.[citation needed]

Vitamin B12 is a co-substrate of various cell reactions involved in methylation synthesis of nucleic acid and neurotransmitters. Synthesis of the trimonoamine neurotransmitters can enhance the effects of a traditional antidepressant.[20] The intracellular concentrations of vitamin B12 can be inferred through the total plasma concentration of homocysteine, which can be converted to methionine through an enzymatic reaction that uses 5-methyltetrahydrofolate as the methyl donor group. Consequently, the plasma concentration of homocysteine falls as the intracellular concentration of vitamin B12 rises. The active metabolite of vitamin B12 is required for the methylation of homocysteine in the production of methionine, which is involved in a number of biochemical processes including the monoamine neurotransmitters metabolism. Thus, a deficiency in vitamin B12 may impact the production and function of those neurotransmitters.[21]

Sources

Animal sources

Vitamin B12 is found in most animal-derived foods, including fish and shellfish, meat (especially liver), poultry, eggs, milk, and milk products.[2] The bioavailability from eggs is less than 9%, compared to 40% to 60% from fish, fowl and meat.[22] An NIH fact sheet lists a variety of animal food sources of B12.[2]

Fortified foods

Foods fortified with B12 are also dietary sources of the vitamin. Foods for which B12-fortified versions are widely available include breakfast cerealssoyproducts, energy bars, and nutritional yeast. The UK Vegan Society, the Vegetarian Resource Group, and the Physicians Committee for Responsible Medicine, among others, recommend that every vegan who is not consuming adequate B12 from fortified foods takes supplements.[23][9][10] Reputable manufacturers of fortified foods and dietary supplements include an overage (excess) in their formulas so that the products still contain the labeled amounts at the end of shelf life.[citation needed]

Supplements

 
Hydroxocobalamin injection USP (1000 µg/mL) is a clear red liquid solution of hydroxocobalamin which is available in a 30 mL brown glass multidose vial packaged in a paper box. Shown is 500 µg B12 (as 1/2 cc) drawn up in a 1/2 cc U-100 27 gauge x 1/2" insulin syringe, as prepared for subcutaneous injection.

Vitamin B12 is an ingredient in multi-vitamin pills and in some countries used to enrich grain-based foods such as bread and pasta. In the U.S. non-prescription products can be purchased providing up to 5000 µg/serving, and it is a common ingredient in energy drinks and energy shots, usually at many times the recommended dietary allowance of B12. The vitamin can also be a prescription product via injection or other means.

The sublingual route, in which B12 is presumably or supposedly taken in more directly under the tongue, has not proven to be necessary or helpful, even though a number of lozenges, pills, and even a lollipop designed for sublingual absorption are being marketed. A 2003 study found no significant difference in absorption for serum levels from oral versus sublingual delivery of 0.5 mg of cobalamin.[24] Sublingual methods of replacement are effective only because of the typically high doses (0.5 mg), which are swallowed, not because of placement of the tablet. As noted below, such very high doses of oral B12 may be effective as treatments, even if gastro-intestinal tract absorption is impaired by gastric atrophy (pernicious anemia).

Injection and patches are sometimes used if digestive absorption is impaired, but there is evidence that this course of action may not be necessary with modern high-potency oral supplements (such as 0.5–1 mg or more). Even pernicious anemia can be treated entirely by the oral route.[25][26][27] These supplements carry such large doses of the vitamin that 1% to 5% of high oral doses of free crystalline B12 is absorbed along the entire intestine by passive diffusion.

If the patient has inborn errors in the methyltransfer pathway (cobalamin C disease, combined methylmalonic aciduria and homocystinuria), treatment with intravenous, intramuscular hydroxocobalamin or transdermal B12 is needed.[28][29][30][31][32]

Non-cyanide forms as supplements

Recently sublingual methylcobalamin has become available in 5 mg tablets. The metabolic fate and biological distribution of methylcobalamin are expected to be similar to that of other sources of vitamin B12 in the diet.[33] No cyanide is released with methylcobalamin. The amount of cyanide (20 µg cyanide in a 1,000 µg cyanocobalamin tablet) is less than daily consumption from food. Safety of all forms of the vitamin is well established.[33]

Controversial sources

Besides certain fermented foods,[34][35] there are few known plant, fungus or algae sources of biologically active B12 and none of these have been subjected to human trials.

Spirulina and dried Asakusa-nori (Porphyra tenera) have been found to contain mostly pseudovitamin-B12 (see Controversial sources in algae section) instead of biologically active B12.[14][36]

Elevated plasma B12 (cobalamin) levels

Elevated levels of serum B12 or cobalamin (above about 600 pmol/L) in the absence of supplementation may be a diagnostic sign of serious disease. In such cases B12 is thought to be only a marker for disease, and not a causal agent.

One cause of elevated plasma B12 (cobalamin) is general liver disease, since hepatic cytolysis releases B12, and the affected liver shows decreased cobalamin clearance. Thus, acute hepatitiscirrhosishepatocellular carcinoma and metastatic liver disease can also be accompanied by an increase in circulating cobalamin. Elevated B12 levels have been suggested as a predictor of ICU mortality risk, but a recent study of this found that "[e]levated B12levels are not a significant predictor of mortality after ICU admission when liver function is controlled for, and may instead be a proxy for poor liver function." [37]

A second group of non-supplemented patients with high cobalamin levels have them due to enhanced production of the plasma B12 transporters haptocorrin and transcobalamin II [38] This happens in hematologic disorders like chronic myelogeneous leukemiapromyelocytic leukemiapolycythemia vera and also the hypereosinophilic syndrome. Increased cobalamin levels are one of the diagnostic criteria for the latter two diseases.

A third group of non-supplemented patients with high cobalamin levels (> 600 pmol/L) may be at immediate (mostly within one year of testing) higher risk for new diagnosis of certain smoking and alcohol-related cancers which are non-hematologic. In a study of 333,000 persons in Denmark, those with elevated B12 had a three to six times higher standard incidence ratio, with respect to those with normal B12 levels, for later development of certain types of cancer.[39]

Thus, one review states: "Altogether it can be concluded that an observed elevation of cobalamin in blood merits a full diagnostic work up to assess the presence of disease." [40]

Interactions

Vitamin B12 may interact with prescription drugs.[2]

Examples

  • H2-receptor antagonists: include cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac). Reduced secretion of gastric acidand pepsin produced by H2 blockers can reduce absorption of protein-bound (dietary) vitamin B12, but not of supplemental vitamin B12. Gastric acid is needed to release vitamin B12 from protein for absorption. Clinically significant vitamin B12 deficiency and megaloblastic anemia are unlikely, unless H2blocker therapy is prolonged (2 years or more), or the person's diet is poor. It is also more likely if the person is rendered achlorhydric(with complete absence of gastric acid secretion), which occurs more frequently with proton pump inhibitors than H2 blockers. Vitamin B12 levels should be monitored in people taking high doses of H2 blockers for prolonged periods.
  • Metformin (Glucophage): Metformin may reduce serum folic acid and vitamin B12 levels. Long-term use of metformin substantially increases the risk of B12 deficiency and (in those patients who become deficient) hyperhomocysteinemia, which is "an independent risk factor for cardiovascular disease, especially among individuals with type 2 diabetes".[41] There are also rare reports of megaloblastic anemia in people who have taken metformin for five years or more. Reduced serum levels of vitamin B12 occur in up to 30% of people taking metformin chronically.[42][43] Clinically significant deficiency is not likely to develop if dietary intake of vitamin B12 is adequate. Deficiency can be corrected with vitamin B12 supplements even if metformin is continued. The metformin-induced malabsorption of vitamin B12 is reversible by oral calcium supplementation.[44] The general clinical significance of metformin upon B12 levels is as yet unknown.[45]
  • Proton pump inhibitors (PPIs): The PPIs include omeprazole (Prilosec, Losec), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix, Pantoloc), and esomeprazole (Nexium). The reduced secretion of gastric acid and pepsin produced by PPIs can reduce absorption of protein-bound (dietary) vitamin B12, but not supplemental vitamin B12. Gastric acid is needed to release vitamin B12 from protein for absorption. Reduced vitamin B12levels may be more common with PPIs than with H2-blockers, because they are more likely to produce achlorhydria (complete absence of gastric acid secretion). Clinically significant vitamin B12 deficiency is unlikely, unless PPI therapy is prolonged (2 years or more) or dietary vitamin intake is low. Vitamin B12 levels should be monitored in people taking high doses of PPIs for prolonged periods.

Structure

B12 is the most chemically complex of all the vitamins. The structure of B12 is based on a corrin ring, which is similar to the porphyrin ring found in hemechlorophyll, and cytochrome. The central metal ion is cobalt. Four of the six coordination sites are provided by the corrin ring, and a fifth by a dimethylbenzimidazole group. The sixth coordination site, the center of reactivity, is variable, being a cyano group (-CN), a hydroxyl group (-OH), a methylgroup (-CH3) or a 5'-deoxyadenosyl group (here the C5' atom of the deoxyribose forms the covalent bond with Co), respectively, to yield the four B12 forms mentioned below. Historically, the covalent C-Co bond is one of the first examples of carbon-metal bonds to be discovered in biology. The hydrogenasesand, by necessity, enzymes associated with cobalt utilization, involve metal-carbon bonds.[46]

Vitamin B12 is a generic descriptor name referring to a collection of cobalt and corrin ring molecules which are defined by their particular vitamin function in the body. All of the substrate cobalt-corrin molecules from which B12 is made, must be synthesized by bacteria. After this synthesis is complete, except in rare cases, the human body has the ability to convert any form of B12 to an active form, by means of enzymatically removing certain prosthetic chemical groups from the cobalt atom, and replacing them with others.

The four forms (vitamers) of B12 are all deeply red colored crystals and water solutions, due to the color of the cobalt-corrin complex.

Cyanocobalamin is one such form, i.e. "vitamer", of B12 because it can be metabolized in the body to an active coenzyme form. The cyanocobalamin form of B12 does not occur in nature normally, but is a byproduct of the fact that other forms of B12 are avid binders of cyanide (-CN) which they pick up in the process of activated charcoal purification of the vitamin after it is made by bacteria in the commercial process. Since the cyanocobalamin form of B12 is easy to crystallize and is not sensitive to air-oxidation, it is typically used as a form of B12 for food additives and in many common multivitamins. Pure cyanocobalamin possesses the deep pink color associated with most octahedral cobalt(II) complexes and the crystals are well formed and easily grown up to millimeter size.

Hydroxocobalamin is another form of B12 commonly encountered in pharmacology, but which is not normally present in the human body. Hydroxocobalamin is sometimes denoted B12a. This form of B12 is the form produced by bacteria, and is what is converted to cyanocobalmin in the commercial charcoal filtration step of production. Hydroxocobalamin has an avid affinity for cyanide ions and has been used as an antidote to cyanide poisoning. It is supplied typically in water solution for injection. Hydroxocobalamin is thought to be converted to the active enzymic forms of B12 more easily than cyanocobalamin, and since it is little more expensive than cyanocobalamin, and has longer retention times in the body, has been used for vitamin replacement in situations where added reassurance of activity is desired. Intramuscular administration of hydroxocobalamin is also the preferred treatment for pediatric patients with intrinsic cobalamin metabolic diseases, for vitamin B12 deficient patients with tobacco amblyopia (which is thought to perhaps have a component of cyanide poisoning from cyanide in cigarette smoke); and for treatment of patients with pernicious anemia who have optic neuropathy.

Adenosylcobalamin (adoB12) and methylcobalamin (MeB12) are the two enzymatically active cofactor forms of B12 that naturally occur in the body. Most of the body's reserves are stored as adoB12 in the liver. These are converted to the other methylcobalamin form as needed.

Synthesis and industrial production

Neither plants nor animals are independently capable of constructing vitamin B12.[47] Only bacteria and archaea[48] have the enzymes required for its biosynthesis. The total synthesis of B12 was reported by Robert Burns Woodward[49] and Albert Eschenmoser in 1972,[50][51] and remains one of the classic feats of organic synthesis. Species from the following genera are known to synthesize B12AcetobacteriumAerobacterAgrobacteriumAlcaligenesAzotobacterBacillusClostridiumCorynebacteriumFlavobacteriumLactobacillusMicromonosporaMycobacteriumNocardiaPropionibacteriumProtaminobacterProteusPseudomonasRhizobiumSalmonellaSerratiaStreptomycesStreptococcus and Xanthomonas.

Industrial production of B12 is achieved through fermentation of selected microorganisms.[52] Streptomyces griseus, a bacterium once thought to be a yeast, was the commercial source of vitamin B12 for many years.[53][54] The species Pseudomonas denitrificans and Propionibacterium freudenreichii subsp. shermanii are more commonly used today.[55] These are frequently grown under special conditions to enhance yield, and at least one company, Rhône-Poulenc of France, which has merged into Sanofi-Aventis, used genetically engineered versions of one or both of these species.[citation needed] Since a number of species of Propionibacterium produce no exotoxins or endotoxins and are generally regarded asafe (have been granted GRAS status) by the Food and Drug Administration of the United States, they are presently the FDA-preferred bacterial fermentation organisms for vitamin B12production.[56]

The total world production of vitamin B12, by four companies (the French Sanofi-Aventis and three Chinese companies) is said to have been 35 tonnes in 2008.[57]

See cyanocobalamin for discussion of the chemical preparation of reduced-cobalt vitamin analogs and preparation of physiological forms of the vitamin such as adenosylcobalamin and methylcobalamin.

Mechanism of action

 
Metabolism of folic acid. The role of Vitamin B12 is seen at bottom-left.

Vitamin B12 functions as a coenzyme, meaning that its presence is required for enzyme-catalyzed reactions.[58][59] Three types of enzymes:

  1. Isomerases
    Rearrangements in which a hydrogen atom is directly transferred between two adjacent atoms with concomitant exchange of the second substituent, X, which may be a carbon atom with substituents, an oxygen atom of an alcohol, or an amine. These use the adoB12(adenosylcobalamin) form of the vitamin.
  2. Methyltransferases
    Methyl (-CH3) group transfers between two molecules. These use MeB12(methylcobalamin) form of the vitamin.
  3. Dehalogenases
    Reactions in which a halogen atom is removed from an organic molecule. Enzymes in this class have not been identified in humans.

In humans, two major coenzyme B12-dependent enzyme families corresponding to the first two reaction types, are known. These are typified by the following two enzymes:

  1. MUT is an isomerase which uses the AdoB12 form and reaction type 1 to catalyze a carbon skeleton rearrangement (the X group is -COSCoA). MUT's reaction converts MMl-CoA to Su-CoA, an important step in the extraction of energy from proteins and fats (for more see MUT's reaction mechanism). This functionality is lost in vitamin B12 deficiency, and can be measured clinically as an increased methylmalonic acid (MMA) level. Unfortunately, an elevated MMA, though sensitive to B12 deficiency, is probably overly sensitive, and not all who have it actually have B12deficiency. For example, MMA is elevated in 90–98% of patients with B12 deficiency; 20–25% of patients over the age of 70 have elevated levels of MMA, yet 25–33% of them do not have B12 deficiency. For this reason, assessment of MMA levels is not routinely recommended in the elderly. There is no "gold standard" test for B12 deficiency because as a B12 deficiency occurs, serum values may be maintained while tissue B12 stores become depleted. Therefore, serum B12 values above the cut-off point of deficiency do not necessarily indicate adequate B12 status. The MUT function is necessary for proper myelin synthesis (see mechanism below) and is not affected by folate supplementation.
  2. MTR, also known as methionine synthase, is a methyltransferase enzyme, which uses the MeB12 and reaction type 2 to transfer a methyl group from 5-methyltetrahydrofolate to homocysteine, thereby generating tetrahydrofolate (THF) and methionine (for more see MTR's reaction mechanism).[60] This functionality is lost in vitamin B12 deficiency, resulting in an increased homocysteine level and the trapping of folate as 5-methyl-tetrahydrofolate, from which THF (the active form of folate) cannot be recovered. THF plays an important role in DNA synthesis so reduced availability of THF results in ineffective production of cells with rapid turnover, in particular red blood cells, and also intestinal wall cells which are responsible for absorption. THF may be regenerated via MTR or may be obtained from fresh folate in the diet. Thus all of the DNA synthetic effects of B12 deficiency, including the megaloblastic anemia of pernicious anemia, resolve if sufficient dietary folate is present. Thus the best-known "function" of B12 (that which is involved with DNA synthesis, cell-division, and anemia) is actually a facultative function which is mediated by B12-conservation of an active form of folate which is needed for efficient DNA production.[61] Other cobalamin-requiring methyltransferase enzymes are also known in bacteria, such as Me-H4-MPT, coenzyme M methyl transferase.

Enzyme function

If folate is present in quantity, then of the two absolutely vitamin B12-dependent enzyme-family reactions in humans, the MUT-family reactions show the most direct and characteristic secondary effects, focusing on the nervous system (see below). This is because the MTR (methyltransferase-type) reactions are involved in regenerating folate, and thus are less evident when folate is in good supply.

Since the late 1990s, folic acid has begun to be added to fortify flour in many countries, so folate deficiency is now more rare. At the same time, since DNA synthetic-sensitive tests for anemia and erythrocyte size are routinely done in even simple medical test clinics (so that these folate-mediated biochemical effects are more often directly detected), the MTR-dependent effects of B12 deficiency are becoming apparent not as anemia due to DNA-synthetic problems (as they were classically), but now mainly as a simple and less obvious elevation of homocysteine in the blood and urine (homocysteinuria). This condition may result in long term damage to arteries and in clotting (stroke and heart attack), but this effect is difficult to separate from other common processes associated with atherosclerosis and aging.

The specific myelin damage resulting from B12 deficiency, even in the presence of adequate folate and methionine, is more specifically and clearly a vitamin deficiency problem. It has been connected to B12 most directly by reactions related to MUT, which is absolutely required to convert methylmalonyl coenzyme A into succinyl coenzyme A. Failure of this second reaction to occur results in elevated levels of MMA, a myelin destabilizer. Excessive MMA will prevent normal fatty acid synthesis, or it will be incorporated into fatty acid itself rather than normal malonic acid. If this abnormal fatty acid subsequently is incorporated into myelin, the resulting myelin will be too fragile, and demyelination will occur. Although the precise mechanism(s) are not known with certainty, the result is subacute combined degeneration of central nervous system and spinal cord.[62] Whatever the cause, it is known that B12 deficiency causes neuropathies, even if folic acid is present in good supply, and therefore anemia is not present.

Vitamin B12-dependent MTR reactions may also have neurological effects, through an indirect mechanism. Adequate methionine (which, like folate, must otherwise be obtained in the diet, if it is not regenerated from homocysteine by a B12 dependent reaction) is needed to make S-adenosyl-methionine (SAMe), which is in turn necessary for methylation of myelin sheath phospholipids. Although production of SAMe is not B12 dependent, help in recycling for provision of one adequate substrate for it (the essential amino acid methionine) is assisted by B12. In addition, SAMe is involved in the manufacture of certain neurotransmitterscatecholamines and in brain metabolism. These neurotransmitters are important for maintaining mood, possibly explaining why depression is associated with B12 deficiency. Methylation of the myelin sheath phospholipids may also depend on adequate folate, which in turn is dependent on MTR recycling, unless ingested in relatively high amounts.

Absorption and distribution

Methyl-B12 is absorbed by two processes. The first is an intestinal mechanism using intrinsic factor through which 1-2 micrograms can be absorbed every few hours. The second is a diffusion process by which approximately 1% of the remainder is absorbed.[63] The human physiology of vitamin B12 is complex, and therefore is prone to mishaps leading to vitamin B12 deficiency. Protein-bound vitamin B12 must be released from the proteins by the action of digestive proteases in both the stomach and small intestine.[64] Gastric acid releases the vitamin from food particles; therefore antacid and acid-blocking medications (especially proton-pump inhibitors) may inhibit absorption of B12. In addition some elderly people produce less stomach acid as they age thereby increasing their probability of B12 deficiencies.[65]

B12 taken in a low-solubility, non-chewable supplement pill form may bypass the mouth and stomach and not mix with gastric acids, but acids are not necessary for the absorption of free B12 not bound to protein; acid is necessary only to recover naturally-occurring vitamin B12 from foods.

R-protein (also known as haptocorrin and cobalophilin) is a B12 binding protein that is produced in the salivary glands. It must wait to bind food-B12 until B12 has been freed from proteins in food by pepsin in the stomach. B12 then binds to the R-protein to avoid degradation of it in the acidic environment of the stomach.[66]

This pattern of B12 transfer to a special binding protein secreted in a previous digestive step, is repeated once more before absorption. The next binding protein for B12 is intrinsic factor (IF), a protein synthesized by gastric parietal cells that is secreted in response to histaminegastrin and pentagastrin, as well as the presence of food. In the duodenumproteases digest R-proteins and release their bound B12, which then binds to IF, to form a complex (IF/B12). B12 must be attached to IF for it to be efficiently absorbed, as receptors on the enterocytes in the terminal ileum of the small bowel only recognize the B12-IF complex; in addition, intrinsic factor protects the vitamin from catabolism by intestinal bacteria.

Absorption of food vitamin B12 thus requires an intact and functioning stomachexocrine pancreas, intrinsic factor, and small bowel. Problems with any one of these organs makes a vitamin B12 deficiency possible. Individuals who lack intrinsic factor have a decreased ability to absorb B12. In pernicious anemia, there is a lack of IF due to autoimmune atrophic gastritis, in which antibodies form against parietal cells. Antibodies may alternately form against and bind to IF, inhibiting it from carrying out its B12 protective function. Due to the complexity of B12 absorption, geriatric patients, many of whom are hypoacidic due to reduced parietal cell function, have an increased risk of B12 deficiency.[67] This results in 80–100% excretion of oral doses in the feces versus 30–60% excretion in feces as seen in individuals with adequate IF.[67]

Once the IF/B12 complex is recognized by specialized ileal receptors, it is transported into the portal circulation. The vitamin is then transferred to transcobalamin II (TC-II/B12), which serves as the plasma transporter. Hereditary defects in production of the transcobalamins and their receptors may produce functional deficiencies in B12 and infantile megaloblastic anemia, and abnormal B12 related biochemistry, even in some cases with normal blood B12 levels. For the vitamin to serve inside cells, the TC-II/B12 complex must bind to a cell receptor, and be endocytosed. The transcobalamin-II is degraded within a lysosome, and free B12 is finally released into the cytoplasm, where it may be transformed into the proper coenzyme, by certain cellular enzymes (see above).

Investigations into the intestinal absorption of B12 point out that the upper limit of absorption per single oral dose, under normal conditions, is about 1.5 µg: "Studies in normal persons indicated that about 1.5 µg is assimilated when a single dose varying from 5 to 50 µg is administered by mouth. In a similar study Swendseid et al. stated that the average maximum absorption was 1.6 µg [...]" [68] The bulk diffusion process of B12 absorption noted in the first paragraph above, may overwhelm the complex R-factor and IGF-factor dependent absorption, when oral doses of B12 are very large (a thousand or more µg per dose) as commonly happens in dedicated-pill oral B12 supplementation. It is this last fact which allows pernicious anemia and certain other defects in B12 absorption to be treated with oral megadoses of B12, even without any correction of the underlying absorption defects.[69] See the section on supplements above.

The total amount of vitamin B12 stored in body is about 2–5 mg in adults. Around 50% of this is stored in the liver. Approximately 0.1% of this is lost per day by secretions into the gut, as not all these secretions are reabsorbed. Bile is the main form of B12 excretion; most of the B12 secreted in the bile is recycled via enterohepatic circulation. Excess B12 beyond the blood's binding capacity is typically excreted in urine. Owing to the extremely efficient enterohepatic circulation of B12, the liver can store 3 to 5 years’ worth of vitamin B12;[70] therefore, nutritional deficiency of this vitamin is rare. How fast B12 levels change depends on the balance between how much B12 is obtained from the diet, how much is secreted and how much is absorbed. B12 deficiency may arise in a year if initial stores are low and genetic factors unfavourable, or may not appear for decades. In infants, B12 deficiency can appear much more quickly.[71]

History

B12 deficiency is the cause of pernicious anemia, an anemic disease that was usually fatal and had unknown etiology when it was first described in medicine. The cure, and B12, were discovered by accident. George Whipple had been doing experiments in which he induced anemia in dogs by bleeding them, and then fed them various foods to observe which diets allowed them fastest recovery from the anemia produced. In the process, he discovered that ingesting large amounts of liver seemed to most rapidly cure the anemia of blood loss. Thus, he hypothesized that liver ingestion might treat pernicious anemia. He tried this and reported some signs of success in 1920.

After a series of clinical studies, George Richards Minot and William Murphy set out to partly isolate the substance in liver which cured anemia in dogs, and found that it was iron. They also found that an entirely different liver substance cured pernicious anemia in humans, that had no effect on dogs under the conditions used. The specific factor treatment for pernicious anemia, found in liver juice, had been found by this coincidence. Minot and Murphy reported these experiments in 1926. This was the first real progress with this disease. Despite this discovery, for several years patients were still required to eat large amounts of raw liver or to drink considerable amounts of liver juice.

In 1928, the chemist Edwin Cohn prepared a liver extract that was 50 to 100 times more potent than the natural liver products. The extract was the first workable treatment for the disease. For their initial work in pointing the way to a working treatment, Whipple, Minot, and Murphy shared the 1934 Nobel Prize in Physiology or Medicine.

These events led to discovery of the soluble vitamin, called vitamin B12, from bacterial broths. In 1947, while working for the Poultry Science Department at the University of Maryland, Mary Shaw Shorb (in a collaborative project with Karl Folkers from Merck.) was provided with a $400 grant to develop the so-called "LLD assay" for B12. LLD stood for Lactobacillus lactis Dorner,[72] a strain of bacterium which required "LLD factor" for growth, which was eventually identified as B12. Shorb and colleagues used the LLD assay to rapidly extract the anti-pernicious anemia factor from liver extracts, and pure B12 was isolated in this way by 1948, with the contributions of chemists Shorb,[73] Karl A. Folkers of the United States and Alexander R. Todd of Great Britain. For this discovery, in 1949 Mary Shorb and Karl Folkers received the Mead Johnson Award from the American Society of Nutritional Sciences.[73]

The chemical structure of the molecule was determined by Dorothy Crowfoot Hodgkin and her team in 1956, based on crystallographic data.[74] Eventually, methods of producing the vitamin in large quantities from bacteria cultures were developed in the 1950s, and these led to the modern form of treatment for the disease.

See also

References

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External links

Source: https://en.wikipedia.org/wiki/Vitamin_B12

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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.

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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

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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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