What is vitamin B6?
Vitamin B6 is a group of closely related water-soluble nutrients. Seven forms of vitamin B6 are known.Advertisements
The phosphate ester derivatives of vitamin B6, pyridoxal 5'-phosphate (PLP) and pyridoxamine 5’ phosphate (PMP) are the metabolically active forms. The deficiency of PLP is known to cause several diseases. The conversion of dietary vitamin B6 into pyridoxal 5'-phosphate (PLP) is dependent on flavin mononucleotide (FMN) as a cofactor which is produced from riboflavin (B2).Forms of vitamin B6
The seven forms of this micronutrient are:- Pyridoxine (PN),
- Pyridoxine 5'-phosphate (PNP)
- Pyridoxal (PL),
- Pyridoxal 5'-phosphate (PLP),
- Pyridoxamine (PM)
- Pyridoxamine 5'-phosphate (PMP) and
- 4-Pyridoxic acid (PA).
Vitamin B6 food sources
The various vitameric forms of vitamin B6 are present in a wide variety of food sources of animal and plant origins.Plant foods contain mostly pyridoxine form whereas pyridoxal or pyridoxamine forms are found in animal foods. Drying, freezing and canning contribute to the loss of the nutrient in the foods. The Recommended Daily Allowance of vitamin B6 for adults is about 1.3 mg/day. Normally excesses in water-soluble vitamins are removed from the body by excretion in the urine.
Absorption and excretion of vitamin B6
Vitamin B6 is present in the forms of pyridoxine, pyridoxal and pyridoxamine and their phosphorylated derivatives in the foods. They are absorbed in the jejunum and ileum by passive diffusion. The phosphorylated derivatives of vitamin B6 undergo dephosphorylation for absorption.The dietary pyridoxine, pyridoxal and pyridoxamine forms of B6 are converted to PLP in the liver. Liver is the principal organ for releasing PLP into plasma. 95% of of the circulating PLP is bound to albumin and the rest is bound to various enzymes. Only a small fraction circulates in the plasma freely.
PLP cannot cross plasma membranes and is reduced to pyridoxal (PL) before entry into cells. Once inside the cells, PL is rephosphorylated to form PLP or converted to PMP to function as intracellular cofactors for several enzymatic reactions. The excess vitamin B6 is degraded to 4-pyridoxic acid mostly b liver and excreted into the urine.
Vitamin B6 functions
Pyridoxamine 5'-phosphate (PLP) is involved in amino acid and lipid metabolism. PLP form of vitamin B6 is a cofactor in the synthesis of five important neurotransmitters. It is also involved in histamine synthesis, hemoglobin synthesis and gene expression.- Transaminase enzymes activity of breaking down amino acids and moving amine groups among amino acids is PLP dependent.
- Pyridoxamine 5'-phosphate is a cofactor in the biosynthesis of serotonin, dopamine, epinephrine, norepinephrine, and gamma-aminobutyric acid (GABA).
- PLP is also involved in the synthesis of histamine.
- The biosynthesis of neuromodulator d-serine by serine racemase is PLP dependent.
- The enzymes involved in the transformation of methionine to cysteine are PLP dependent.
- The conversion of tryptophan to niacin is PLP dependent.
- Ceramides, an important family of waxy lipid molecules, require PLP form of vitamin B6 for their synthesis.
- Aminolevulinic acid (ALA) synthase is a PLP-dependent enzyme required for biosynthesis of hemes (components of hemoglobin and myoglobin) and cobalamins.
Vitamin B6 deficiency causes
As vitamin B6 is present in most of the foods of both animal and plant origin, primary dietary deficiency is rare. The secondary insufficiency of the nutrient occurs simultaneously with the inadequacy of other B-complex group of nutrients. The elderly, alcoholics and those with malabsorption diseases may have low plasma levels of B6.Certain health conditions like protein-energy malnutrition, malabsorption diseases, use of pyridoxine-inactivating anticonvulsants, corticosteroids and penicillamine, increased metabolic demand as in hyperthyroidism and genetic errors of metabolism can alter and lower the Vitamin B6 serum levels.
Vitamin B6 deficiency symptoms
Several neurologic, cardiovascular, gastrointestinal and dermal symptoms are observed in association with severe vitamin B6 deficiency. Some of the associated symptoms are:- irritability,
- depression,
- confusion,
- seizures,
- peripheral neuropathy,
- intellectual disability,
- somnolence (sleepiness),
- pellagra-like symptoms,
- intertrigo (rash of the body folds),
- seborrheic dermatitis,
- glossitis (inflammation of the tongue),
- ulcers of the mouth,
- cheilosis (ulcers of the corners of the mouth),
- conjunctivitis (inflammation of the conjunctiva),
- impaired glucose tolerance and
- sideroblastic anemia.
Diagnosis of vitamin B6 deficiency
Plasma PLP levels may reflect the nutritional status in the body. A PLP concentration greater than 20nmol/l indicates sufficiency of the nutrient in the body. Urinary 4-pyridoxic acid (PA) levels also can be taken as an indicator of vitamin B6 status. PA levels below 3.0 mmol/day is suggestive of vitamin B6 inadequacy.Vitamin B6 deficiency diseases
There are several indicative symptoms of vitamin B6 deficiency. The disease conditions include skin inflammation, mucous membrane inflammation, damage to nervous system, anemia and cardiovascular manifestations.Inflammatory diseases
People with chronic inflammation had been found to have low blood levels of PLP. As cell structures get damaged in low levels of PLP apparent symptoms appear on the skin in the form of dermatitis and other skin diseases. Cell structure and functions get affected when PLP levels are low. PLP dependent ceramides are a family of waxy lipid molecules. Ceramides and other sphingolipids found in cell membrane, apart from being structural elements, are involved in regulating differentiation, proliferation and apoptosis of cells.Neurological diseases
In the brain, as a cofactor of several dependent enzymes, PLP form of vitamin B6 is involved in the metabolism of several amino acids. It is also involved in the metabolism of amine neurotransmitters such as dopamine, serotonin, glutamate, glycine, GABA, D-serine and taurine. Vitamin B6 is also involved in the the synthesis of neuroprotective compounds such as kynurenic acid. Neuropsychiatric diseases including seizures, migraine, chronic pain and depression have been linked to vitamin B6 deficiency.Vitamin B6 is a cofactor in the tryptophan-serotonin pathway and its low levels cause depression. Hvas AM et al. reported that "a low level of plasma PLP is associated with symptoms of depression".
Adams JB et al in their study 'Abnormally high plasma levels of vitamin B6 in children with autism not taking supplements compared to controls not taking supplements' found that, "(1) pyridoxal kinase had a very low activity in children with autism and (2) pyridoxal 5 phosphate (PLP) levels are unusually low in children with autism. Thus, it appears that the low conversion of pyridoxal and pyridoxine to PLP results in low levels of PLP, which is the active cofactor for 113 known enzymatic reactions, including the formation of many key neurotransmitters."
Inborn metabolic disorders of vitamin B6
So far four genetic mutations are known to cause vitamin B6 deficiency diseases. They are hypophosphatasia, pyridoxine nonresponsive, PLP-responsive neonatal epileptic encephalopathy, hyperprolinemia type II and pyridoxine dependent epilepsy (PDE).Hypophosphatasia
Hypophosphatasia is a rare and sometimes fatal metabolic bone disease. It is caused by a molecular defect in the gene encoding tissue non-specific alkaline phosphatase (TNSALP). TNSALP deficiency affects bone mineralization, leading to rickets in children or osteomalacia in adults. PLP, the principal form of vitamin B6, must be dephosphorylated by TNSALP into pyridoxal for cross over the cell membrane for carrying out intracellular neurotransmitters biosynthesis functions. TNSALP deficiency caused Vitamin B6 deficiency in the brain, impairs synthesis of neurotransmitters, which can cause seizures.Pyridoxamine 5'-phosphate oxidase (PNPO) deficiency
pyridoxine nonresponsive, PLP-responsive neonatal epileptic encephalopathy is caused by mutation in the PNPO gene. There is reduced activity of aromatic L-amino acid decarboxylase and other PLP-dependent enzymes. Affected infants suffer from severe myoclonic epilepsy, progressive hypomyelination and global atrophy. Seizures cease with the administration of PLP form of vitamin B6.Hyperprolinemia type II
Hyperprolinemia type II results in very high proline levels in the blood. This disease is caused by a mutation in the ALDH4A1 gene, for the enzyme 1-pyrroline-5-carboxylate dehydrogenase. Hyperprolinemia type II disease sometimes appear benign but often involves seizures, convulsions, and mental retardation. The epilepsy is responsive to pyridoxine form of vitamin b6. The disease causes accumulation of pyrroline-5-carboxylic acid resulting in inactivation of PLP and finally PLP deficiency.Pyridoxine dependent epilepsy (PDE)
Pyridoxine dependent epilepsy is caused by the mutation of the aldehyde dehydrogenase (ALDH) 7A1 gene, which is located on chromosome 5q31. The activity of α-aminoadipic semialdehyde dehydrogenase is curtailed resulting in accumulation of L-Δ1-piperideine-6-carboxylate (P6C). P6C condenses with PLP making it inactive. This leads to B6 deficiency in the brain and epilepsy. Huei-Shyong Wang, et al reported that patients with PDE do not respond to anticonvulsant medications, but seizures rapidly cease with therapeutic intravenous doses of Vitamin B6 in the form of pyridoxine.Treatment of vitamin B6 deficiency diseases
Dietary deficiency can be corrected by taking a balanced diet and adding B-complex vitamin rich sources. The secondary factors responsible for the development of deficiency diseases must be treated and also vitamin B-complex supplements may taken. Doses of pyridoxine in excess of the RDA over long periods is found to cause nerve damage and neurological diseases.Advertisements
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References: 1.Hvas AM, Juul S, Bech P, Nexø E. Vitamin B6 level is associated with symptoms of depression. Psychother Psychosom. 2004 Nov-Dec;73(6):340-3. 2.Wang HS, Kuo MF. Vitamin B6 related epilepsy during childhood. Chang Gung Med J. 2007 Sep-Oct;30(5):396-401. 3.Adams JB, George F, Audhya T. Abnormally high plasma levels of vitamin B6 in children with autism not taking supplements compared to controls not taking supplements. J Altern Complement Med. 2006 Jan-Feb;12(1):59-63. 4.Malouf R, Grimley Evans J. The effect of vitamin B6 on cognition. Cochrane Database Syst Rev. 2003;(4):CD004393. |
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