Vitamin B6
Encyclopedia
Vitamin
A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate (PLP) is the active form and is a cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
in many reactions of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
metabolism, including transamination, deamination, and decarboxylation. PLP also is necessary for the enzymatic reaction governing the release of glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
from glycogen
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...
.
History
Vitamin B6 is a water-soluble compound that was discovered in the 1930s during nutrition studies on rats. In 1934, a Hungarian physician, Paul György discovered a substance that was able to cure a skin disease in rats (dermititis acrodynia), this substance he named vitamin B6. In 1938, Samuel Lepkovsky isolated vitamin B6 from rice bran. Harris and Folkers in 1939 determined the structure of pyridoxine, and, in 1945, Snell was able to show that there are two forms of vitamin B6, pyridoxal and pyridoxamine. Vitamin B6 was named pyridoxine to indicate its structural homology to pyridinePyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...
. All three forms of vitamin B6 are precursors of an activated compound known as pyridoxal 5'-phosphate
Pyridoxal-phosphate
Pyridoxal-phosphate is a prosthetic group of some enzymes. It is the active form of vitamin B6, which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine.-Role as a coenzyme:...
(PLP), which plays a vital role as the co-factor of a large number of essential enzymes in the human body.
Enzymes dependent on PLP focus a wide variety of chemical reactions mainly involving amino acids. The reactions carried out by the PLP-dependent enzymes that act on amino acids include transfer of the amino group, decarboxylation, racemization, and beta- or gamma-elimination or replacement. Such versatility arises from the ability of PLP to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby stabilizing different types of carbanionic reaction intermediates.
Overall, the Enzyme Commission has catalogued more than 140 PLP-dependent activities, corresponding to ~4% of all classified activities.
Forms
- PyridoxinePyridoxinePyridoxine is one of the compounds that can be called vitamin B6, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the '4' position. It is often used as 'pyridoxine hydrochloride'.-Chemistry:...
(PN), the form that is most commonly given as vitamin B6 supplement - Pyridoxine 5'-phosphate (PNP)
- PyridoxalPyridoxalPyridoxal is one of the three natural forms of vitamin B6, along with pyridoxamine and pyridoxine . All of these forms are converted in the human body into a single biologically active form, pyridoxal 5-phosphate. All three forms of vitamin B6 are heterocyclic organic compounds...
(PL) - Pyridoxal 5'-phosphate (PLP), the metabolically active form (sold as 'P-5-P' vitamin supplement)
- PyridoxaminePyridoxaminePyridoxamine is a vitamer in the vitamin B6 family, which includes pyridoxal and pyridoxine. Pyridoxamine is converted to the biologically active form of vitamin B6, pyridoxal 5-phosphate, via the vitamin B6 salvage pathway. Vitamin B6 acts as an enzyme cofactor in a variety of metabolic processes...
(PM) - Pyridoxamine 5'-phosphate (PMP)
- 4-Pyridoxic acid (PA), the cataboliteCatabolismCatabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...
which is excreted in the urine
All forms except PA can be interconverted.
Functions
Pyridoxal phosphate, the metabolically active form of vitamin B6, is involved in many aspects of macronutrient metabolism, neurotransmitterNeurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
synthesis, histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
synthesis, hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
synthesis and function and gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
. Pyridoxal phosphate generally serves as a coenzyme for many reactions and can help facilitate decarboxylation, transamination, racemization, elimination, replacement and beta-group interconversion reactions. The liver is the site for vitamin B6 metabolism.
Amino acid metabolism
Pyridoxal phosphate (PLP) is a cofactor in transaminases that can catabolize amino acids. PLP is also an essential component of two enzymes that converts methionineMethionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
to cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
via two reactions. Low vitamin B6 status will result in decreased activity of these enzymes. PLP is also an essential cofactor for enzymes involved in the metabolism of selenomethionine
Selenomethionine
Selenomethionine is an amino acid containing selenium. The L-enantiomer of selenomethionine, known as Se-met and Sem, is a common natural food source of selenium. In vivo, selenomethionine is randomly incorporated instead of methionine and is readily oxidized. Its antioxidant activity arises from...
to selenohomocysteine and then from selenohomocysteine to hydrogen selenide
Hydrogen selenide
Hydrogen selenide is the inorganic compound with the formula H2Se. It is the simplest and virtually the only hydride of selenium. H2Se is a colorless, flammable gas under standard conditions. It is the most toxic selenium compound with an exposure limit: 0.05 ppm over an 8 hour period...
. Vitamin B6 is also required for the conversion of tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
to niacin
Niacin
"Niacin" redirects here. For the neo-fusion band, see Niacin .Niacin is an organic compound with the formula and, depending on the definition used, one of the forty to eighty essential human nutrients.Niacin is one of five vitamins associated with a pandemic deficiency disease: niacin deficiency...
and low vitamin B6 status will impair this conversion. PLP is also used to create physiologically active amines by decarboxylation of amino acids. Some notable examples of this include: histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
to histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
, tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
to serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, glutamate to gamma-aminobutyric acid
Gamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
(GABA), and dihydroxyphenylalanine
Dihydroxyphenylalanine
Dihydroxyphenylalanine may refer to either of two chemical compounds:* D-DOPA, -3,4-dihydroxyphenylalanine* L-DOPA, -3,4-dihydroxyphenylalanine, a precursor of a neurotransmitter...
to dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
.
Gluconeogenesis
Vitamin B6 also plays a role in gluconeogenesisGluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
. Pyridoxal phosphate can catalyze transamination reactions that are essential for the providing amino acids as a substrate for gluconeogenesis. Also, vitamin B6 is a required coenzyme of glycogen phosphorylase, the enzyme that is necessary for glycogenolysis to occur.
Lipid metabolism
Vitamin B6 is an essential component of enzymes that facilitate the biosynthesis of sphingolipids. Particularly, the synthesis of ceramideCeramide
Ceramides are a family of lipid molecules. A ceramide is composed of sphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of cells. They are one of the component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer...
requires PLP. In this reaction serine is decarboxylated and combined with palmitoyl-CoA to form sphinganine which is combined with a fatty acyl CoA to form dihydroceramide. Dihydroceramide is then further desaturated to form ceramide. In addition, the breakdown of sphingolipids is also dependent on vitamin B6 since S1P lyase, the enzyme responsible for breaking down sphingosine-1-phosphate, is also PLP dependent.
Metabolic functions
The primary role of vitamin B6 is to act as a coenzyme to many other enzymes in the body that are involved predominantly in metabolism. This role is performed by the active form, pyridoxal phosphate. This active form is converted from the two other natural forms founds in food: pyridoxal, pyridoxine and pyridoxamine .Vitamin B6 is involved in the following metabolic processes:
- amino acid, glucose and lipid metabolism
- neurotransmitter synthesis
- histamine synthesis
- hemoglobin synthesis and function
- gene expression
Amino acid metabolism
Pyridoxal phosphate is involved in almost all amino acid metabolism, from synthesis to breakdown.1. Transamination: transaminase enzymes needed to break down amino acids are dependent on the presence of pyridoxal phosphate. The proper activity of these enzymes are crucial for the process of moving amine groups from one amino acid to another.
2. Transsulfuration: Pyridoxal phosphate is a coenzyme needed for the proper function of the enzymes cystathionine synthase and cystathionase. These enzymes work to transform methionine into cysteine.
3. Selenoamino acid metabolism: Selenomethionine is the primary dietary form of selenium. Pyridoxal phosphate is needed as a cofactor for the enzymes that allow selenium to be used from the dietary form. Pyridoxal phosphate also plays a cofactor role in releasing selenium from selenohomocysteine to produce hydrogen selenide. This hydrogen selenide can then be used to incorporate selenium into selenoproteins.
4. Vitamin B6 is also required for the conversion of tryptophan to niacin and low vitamin B6 status will impair this conversion.
Neurotransmitter synthesis
Pyridoxal phosphate-dependent enzymes play a role in the biosynthesis of four important neurotransmitters: serotoninSerotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
and gamma-aminobutyric acid
Gamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
. Serine racemase, which synthesizes the neuromodulator D-serine, is also a pyridoxal phosphate-dependent enzyme.
Hemoglobin synthesis and function
Pyridoxal phosphate aids in the synthesis of heme, by serving as a coenzyme for the enzyme ALA synthase. It also binds to two sites on hemoglobin to enhance the oxygen binding of hemoglobin.Gene expression
It transforms homocysteine into cistation then into cysteine. Pyridoxal phosphate has been implicated in increasing or decreasing the expression of certain genes. Increased intracellular levels of the vitamin will lead to a decrease in the transcription of glucocorticoid hormones. Also, vitamin B6 deficiency will lead to the increased expression of albumin mRNA. Also, pyridoxal phosphate will influence gene expression of glycoprotein IIb by interacting with various transcription factors. The result is inhibition of platelet aggregation.Dietary reference intakes
| Life Stage Group | RDA/AI* | UL |
|---|---|---|
| Infants 0–6 months 7–12 months |
(mg/day) 0.1* 0.3* |
(mg/day) ND ND |
| Children 1-3 yrs 4-8 yrs |
0.5 0.6 |
30 40 |
| Males 9-13 yrs 14-18 yrs 19-50 yrs 50- >70 yrs |
1.0 1.3 1.3 1.7 |
60 80 100 100 |
| Females 9-13 yrs 13-18 yrs 19-50 yrs 50- >70 yrs |
1.0 1.2 1.3 1.5 |
60 80 100 100 |
| Pregnancy <18 yrs 19-50 yrs |
1.9 1.9 |
80 100 |
| Lactation <18 yrs 19-50 yrs |
2.0 2.0 |
80 100 |
The Institute of Medicine notes that "No adverse effects associated with vitamin B6 from food have been reported. This does not mean that there is no potential for adverse effects resulting from high intakes. Because data on the adverse effects of vitamin B6 are limited, caution may be warranted. Sensory neuropathy has occurred from high intakes of supplemental forms." See the full Dietary Reference Intake Table http://www.iom.edu/~/media/Files/Activity%20Files/Nutrition/DRIs/DRI_Vitamins.ashx from the Institute of Medicine.
Food sources
Vitamin B6 is widely distributed in foods in both its free and bound forms. Good sources include meatMeat
Meat is animal flesh that is used as food. Most often, this means the skeletal muscle and associated fat and other tissues, but it may also describe other edible tissues such as organs and offal...
s, whole grain products, vegetable
Vegetable
The noun vegetable usually means an edible plant or part of a plant other than a sweet fruit or seed. This typically means the leaf, stem, or root of a plant....
s, nuts
Nut (fruit)
A nut is a hard-shelled fruit of some plants having an indehiscent seed. While a wide variety of dried seeds and fruits are called nuts in English, only a certain number of them are considered by biologists to be true nuts...
and banana
Banana
Banana is the common name for herbaceous plants of the genus Musa and for the fruit they produce. Bananas come in a variety of sizes and colors when ripe, including yellow, purple, and red....
s. Cooking, storage and processing losses of vitamin B6 vary and in some foods may be more than 50%, depending on the form of vitamin present in the food. Plant foods lose the least during processing as they contain mostly pyridoxine which is far more stable than the pyridoxal or pyridoxamine found in animal foods. For example, milk can lose 30-70% of its vitamin B6 content when dried. Vitamin B6 is found in the germ
Cereal germ
The germ of a cereal is the reproductive part that germinates to grow into a plant; it is the embryo of the seed. Along with bran, germ is often a by-product of the milling that produces refined grain products. Cereal grains and their components, such as wheat germ, rice bran, and maize may be used...
and aleurone
Aleurone
Aleurone is a protein found in protein granules of maturing seeds and tubers. The term is also used for the outermost cell layer of the endosperm, the aleurone layer.-Aleurone protein:...
layer of grains and milling results to the reduction of this vitamin in white flour. Freezing and canning are other food processing methods that results in the loss of vitamin B6 in foods.
Absorption and excretion
Vitamin B6 is absorbed in the jejunumJejunum
The jejunum is the middle section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms middle intestine or mid-gut may be used instead of jejunum.The jejunum lies between the duodenum...
and ileum
Ileum
The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
via passive diffusion. With the capacity for absorption being so great, animals are able to absorb quantities much greater than what is needed for physiological demands. The absorption of pyridoxal phosphate and pyridoxamine phosphate involves their dephosphorylation catalyzed by a membrane-bound alkaline phosphatase
Alkaline phosphatase
Alkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation...
. Those products and non-phosphorylated vitamers in the digestive tract are absorbed by diffusion, which is driven by trapping of the vitamin as 5'-phosphates through the action of phosphorylation (by a pyridoxal kinase) in the jejunal mucosa. The trapped pyridoxine and pyridoxamine are oxidized to pyridoxal phosphate in the tissue.
The products of vitamin B6 metabolism are excreted in the urine; the major product of which is 4-pyridoxic acid. It has been estimated that 40-60% of ingested vitamin B6 is oxidized to 4-pyridoxic acid. Several studies have shown that 4-pyridoxic acid is undetectable in the urine of vitamin B6 deficient subjects, making it a useful clinical marker to assess the vitamin B6 status of an individual. Other products of vitamin B6 metabolism that are excreted in the urine when high doses of the vitamin have been given include pyridoxal, pyridoxamine, and pyridoxine and their phosphates. A small amount of vitamin B6 is also excreted in the feces.
Deficiencies
The classic clinical syndrome for B6 deficiencyPyridoxine deficiency
Pyridoxine deficiency is a paediatric disease due to a lack of pyridoxine . It usually becomes noticeable within the first 12 months of life in infants with a lack of pyridoxine, a coenzyme responsible for numerous essential metabolic reactions in humans...
is a seborrhoeic dermatitis
Seborrhoeic dermatitis
Seborrhoeic dermatitis is an inflammatory skin disorder affecting the scalp, face, and torso. Typically, seborrheic dermatitis presents with scaly, flaky, itchy, and red skin. It particularly affects the sebaceous-gland-rich areas of skin...
-like eruption, atrophic glossitis with ulceration
Mouth ulcer
A mouth or oral ulcer is an open sore in the mouth, or rarely a break in the mucous membrane or the epithelium on the lips or surrounding the mouth. The types of mouth ulcers are diverse, with a multitude of associated causes including: physical abrasion, acidic fruit, infection, other medical...
, angular cheilitis
Angular cheilitis
Angular cheilitis is an inflammatory lesion at the labial commissure, or corner of the mouth, and often occurs bilaterally. The condition manifests as deep cracks or splits...
, conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...
, intertrigo
Intertrigo
An intertrigo is an inflammation of the body folds .An intertrigo sometimes refers to a bacterial, fungal, or viral infection that has developed at the site of broken skin due to such inflammation...
, and neurologic symptoms of somnolence
Somnolence
Somnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...
, confusion, and neuropathy.
While severe vitamin B6 deficiency results in dermatologic and neurologic changes, less severe cases present with metabolic lesions associated with insufficient activities of the coenzyme pyridoxal phosphate. The most prominent of the lesions is due to impaired tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
-niacin
Niacin
"Niacin" redirects here. For the neo-fusion band, see Niacin .Niacin is an organic compound with the formula and, depending on the definition used, one of the forty to eighty essential human nutrients.Niacin is one of five vitamins associated with a pandemic deficiency disease: niacin deficiency...
conversion. This can be detected based on urinary excretion of xanthurenic acid
Xanthurenic acid
Xanthurenic acid is a chemical shown to induce gametogenesis of Plasmodium falciparum, the parasite that causes malaria. It is found in the gut of the Anopheles mosquito....
after an oral tryptophan load. Vitamin B6 deficiency can also result from impaired transsulfuration of methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
to cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
. The pyridoxal phosphate-dependent transaminase
Transaminase
In biochemistry, a transaminase or an aminotransferase is an enzyme that catalyzes a type of reaction between an amino acid and an α-keto acid. To be specific, this reaction involves removing the amino group from the amino acid, leaving behind an α-keto acid, and transferring it to the...
s and glycogen phosphorylase
Glycogen phosphorylase
Glycogen phosphorylase is one of the phosphorylase enzymes . Glycogen phosphorylase catalyzes the rate-limiting step in the degradation of glycogen in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond...
provide the vitamin with its role in gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
, so deprivation of vitamin B6 results in impaired glucose tolerance.
A deficiency of vitamin B6 alone is relatively uncommon and often occurs in association with other vitamins of the B complex. The elderly and alcoholics have an increased risk of vitamin B6 deficiency, as well as other micronutrient deficiencies. Renal patients undergoing dialysis may experience vitamin B6 deficiency. Also, patients with liver disease, rheumatoid arthritis and those infected with HIV also appear to be at risk, despite adequate dietary intakes. The availability of vitamin B6 to the body can be affected by certain drugs such as anticonvulsants and corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s. The drug isoniazid (used in the treatment of tuberculosis), and cycloserine, penicillamine, and hydrocortisone all interfere with vitamin B6 metabolism. These drugs may form a complex with vitamin B6 that is inhibitory for pyridoxal kinase, or they may positively displace PLP from binding sites.
Clinical assessment of vitamin B6
The biochemical assessment of vitamin B6 status is essential, as the clinical signs and symptoms of vitamin B6 deficiency are very nonspecific. The three biochemical tests most widely used are the activation coefficient for the erythrocyte enzyme aspartate aminotransferase, plasma pyridoxal phosphate (PLP) concentrations, and the urinary excretion of vitamin B6 degradation products, specifically urinary pyridoxic acid. Of these, plasma PLP is probably the best single measure because it reflects tissue stores. When plasma pyridoxal phosphate is less than 10nmol/L, it is indicative of vitamin B6 deficiency. Urinary 4-pyridoxic acid is also an indicator of vitamin B6 deficiency. Urinary 4-pyridoxic of less than 3.0 mmol/day is suggestive of vitamin B6 deficiency.Toxicity
Adverse effects have only been documented from vitamin B6 supplements and never from food sources. This article only discusses the safety of the common supplemental form of vitamin B6 pyridoxinePyridoxine
Pyridoxine is one of the compounds that can be called vitamin B6, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the '4' position. It is often used as 'pyridoxine hydrochloride'.-Chemistry:...
(for a full discussion please see pyridoxine
Pyridoxine
Pyridoxine is one of the compounds that can be called vitamin B6, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the '4' position. It is often used as 'pyridoxine hydrochloride'.-Chemistry:...
). Toxicologic animal studies identify specific destruction of the dorsal root ganglia which is documented in human cases of overdosage of pyridoxine. Although vitamin B6 is a water-soluble vitamin and is excreted in the urine, doses of pyridoxine in excess of the RDI over long periods of time thus result in painful and ultimately irreversible neurological problems.
The primary symptoms are pain and numbness of the extremities, and in severe cases difficulty walking. Sensory neuropathy typically develops at doses of pyridoxine in excess of 1,000 mg per day. However, there have been a few case reports of individuals who developed sensory neuropathies at doses of less than 500 mg daily over a period of months. None of the studies, in which an objective neurological examination was performed, found evidence of sensory nerve damage at intakes of pyridoxine below 200 mg/day.
This condition is usually reversible when supplementation is stopped.
Existing authorisations and valuations vary considerably worldwide. In 1993 the European Community Scientific Committee on Food defines intakes of 50 mg vitamin B6 per day as harmful and established tolerable upper intake level of 25 mg/day for adults in 2000.
The Expert Group on Vitamins and Minerals of the Food Standard Agency UK (UK EVM) derived a safe upper level (SUL) of 10 mg/day for a 60 kg adult in 2003.
The tolerable upper limit has been set by the US FDA at 100 mg/day in 2000.
The nutrient reference values in Australia and New Zealand recommend an upper limit of 50 mg a day in adults. "The same figure was set for pregnancy and lactation as there is no evidence of teratogenicity at this level. The UL was set based on metabolic body size and growth considerations for all other ages and life stages except infancy. It was not possible to set a UL for infants, so intake is recommended in the form of food, milk or formula." "The ULs were set using results of studies involving long-term oral administration of pyridoxine at doses of less than 1g/day (Berger & Schaumburg 1984, Bernstein & Lobitz 1988, Dalton 1985, Dalton & Dalton 1987, Del Tredici et al 1985, FNB:IOM 1998, Parry & Bredesen 1985). A NOAEL of 200 mg/day was identified from the studies of Bernstein & Lobitz (1988) and Del Tredici et al (1985). These studies involved subjects who had generally been on the supplements for 5 to 6 months or less. The study of Dalton and Dalton (1987), however, suggested that symptoms might take substantially longer than this to appear. In this latter retrospective survey, subjects who reported symptoms had been on supplements for 2.9 years on average. Those reporting no symptoms had taken supplements for 1.9 years."
Because there have been no placebo-controlled studies showing therapeutic benefits of high doses of pyridoxine, and the well documented occurrence of significant toxic effects there is little reason to exceed the RDI using supplements unless under medical supervision e.g. in treatment of primary hyperoxaluria
Hyperoxaluria
Hyperoxaluria is an excessive urinary excretion of oxalate. Individuals with hyperoxaluria often have calcium oxalate kidney stones. Sometimes called Bird's disease, after Golding Bird who was first to describe the condition.-Causes:...
.
Oncology
Vitamin B6 intake is inversely associated with the risk of colorectal cancer.Preventive roles and therapeutic uses
Vitamin B6 has been used to treat nausea and vomiting in early pregnancyMorning sickness
Morning sickness, also called nausea gravidarum, nausea, vomiting of pregnancy , or pregnancy sickness is a condition that affects more than half of all pregnant women. Related to increased oestrogen levels, a similar form of nausea is also seen in some women who use hormonal contraception or...
for decades, commonly in conjunction with other medications such as metoclopramide or doxylamine. Alone, it has been found safe and effective, though any woman's prenatal caregiver must help guide treatment for these symptoms.
At least one preliminary study has found that this vitamin may increase dream
Dream
Dreams are successions of images, ideas, emotions, and sensations that occur involuntarily in the mind during certain stages of sleep. The content and purpose of dreams are not definitively understood, though they have been a topic of scientific speculation, philosophical intrigue and religious...
vividness or the ability to recall dreams. It is thought that this effect may be due to the role this vitamin plays in the conversion of tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
to serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
. There is anecdotal evidence suggesting supplemental Vitamin B6 may be associated with lucid dreaming
Lucid dreaming
A lucid dream is a dream in which one is aware that one is dreaming. The term was coined by the Dutch psychiatrist and writer Frederik van Eeden . In a lucid dream, the dreamer can actively participate in and manipulate imaginary experiences in the dream environment. Lucid dreams can seem real and...
.
The intake of vitamin B6, from either diet or supplements, could cut the risk of Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
by half according to a prospective study from the Netherlands. "Stratified analyses showed that this association was restricted to smokers," wrote the authors.
Pyridoxine has a role in preventing heart disease. Without enough pyridoxine, a compound called homocysteine builds up in the body. Homocysteine damages blood vessel linings, setting the stage for plaque buildup when the body tries to heal the damage. Vitamin B6 prevents this buildup, thereby reducing the risk of heart attack. Pyridoxine lowers blood pressure and blood cholesterol levels and keeps blood platelets from sticking together. All of these properties work to keep heart disease at bay.
Nutritional supplementation with high dose vitamin B6 and magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
is one of the most popular alternative medicine
Alternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....
choices for autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
but randomised control trials have had mixed results and small sample sizes mean that no conclusions can be drawn as to the efficacy of this treatment.
Some studies suggest that the vitamin B6-magnesium combination can also help attention deficit disorder, citing improvements in hyperactivity, hyperemotivity/aggressiveness and improved school attention.
A lack of the vitamin may play a role in sensitivity to monosodium glutamate
Monosodium glutamate
Monosodium glutamate, also known as sodium glutamate or MSG, is the sodium salt of glutamic acid, one of the most abundant naturally occurring non-essential amino acids....
(MSG), a flavor enhancer. This sensitivity can cause headaches, pain and tingling of the upper extremities, nausea, and vomiting. In both of these syndromes, supplementation of pyridoxine alleviates symptoms only when people were deficient in the vitamin to begin with.
If people are marginally deficient in vitamin B6, they may be more susceptible to carpal tunnel syndrome
Carpal tunnel syndrome
Carpal Tunnel Syndrome is an entrapment idiopathic median neuropathy, causing paresthesia, pain, and other symptoms in the distribution of the median nerve due to its compression at the wrist in the carpal tunnel. The pathophysiology is not completely understood but can be considered compression...
. Carpal tunnel syndrome is characterized by pain and tingling in the wrists after performing repetitive movements or otherwise straining the wrist on a regular basis. Vitamin B6 has been shown in at least two small-scale clinical studies to have a beneficial effect on carpal tunnel syndrome, particularly in cases where no trauma or overuse etiology for the CTS is known.
Vitamin B6 has long been publicized as a cure for premenstrual syndrome (PMS). Study results conflict as to which symptoms are eased, but most of the studies confirm that women who take B6 supplements have reductions in bloating, breast pain, and premenstrual acne flare, a condition in which pimples break out about a week before a woman's period begins.There is strong evidence that pyridoxine supplementation, starting ten days before the menstrual period, prevents most pimples from forming. This effect is due to the vitamin's role in hormone and prostaglandin regulation. Skin blemishes are typically caused by a hormone imbalance, which vitamin B6 helps to regulate.
Mental depression is another condition which may result from low vitamin B6 intake. Because of pyridoxine's role in serotonin and other neurotransmitter production, supplementation often helps depressed people feel better, and their mood improves significantly. It may also help improve memory in older adults. However, the effectiveness as treatment for PMS, PMDD, and clinical depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
is debatable.
It is also suggested that ingestion of vitamin B6 can alleviate some of the many symptoms of an alcoholic hangover
Hangover
A hangover describes the sum of unpleasant physiological effects following heavy consumption of alcoholic beverages. The most commonly reported characteristics of a hangover include headache, nausea, sensitivity to light and noise, lethargy, dysphoria, diarrhea and thirst, typically after the...
and morning sickness
Morning sickness
Morning sickness, also called nausea gravidarum, nausea, vomiting of pregnancy , or pregnancy sickness is a condition that affects more than half of all pregnant women. Related to increased oestrogen levels, a similar form of nausea is also seen in some women who use hormonal contraception or...
from pregnancy. This might be due to B6's mild diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
effect. Though the mechanism is not known, results show that pyridoxamine has therapeutic effects in clinical trials for diabetic nephropathy.
Larsson et al. have shown that vitamin B6 intake and pyridoxal phosphate (PLP) levels are inversely related to the risk of colon cancer. While in their study the correlation with B6 intake was moderate, it was quite dramatic with PLP levels where the risk of colon cancer was nearly decreased in half.
Vitamin B6 is also known to increase the metabolism of Parkinson's medication such as levodopa, and should be used cautiously.
External links
- Facts about Vitamin B6 from Office of Dietary Supplements at National Institutes of HealthNational Institutes of HealthThe National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
- The B6 database A database of B6-dependent enzymes at University of ParmaUniversity of ParmaThe University of Parma is one of the oldest universities in the world, founded in the 11th century. It is organised in twelve faculties. The University of Parma has currently about 30,000 students.-History:...
- COT statement on vitamin B6 (pyridoxine) toxicity (June 1997) (Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT))