Vitamin B6

Vitamin B₆ is one of the B vitamins, and is an essential nutrient for humans. Vitamin B₆ serves as a co-factor in more than 140 cellular reactions, mostly related to amino acid biosynthesis and catabolism, but is also involved in fatty acid biosynthesis and other physiological functions. and Bacillus subtilis, respectively. Despite the disparity in the starting compounds and the different number of steps required, the two pathways possess many commonalities. The DXP-dependent pathway:

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Commercial synthesis

The starting material is either the amino acid alanine, or propionic acid converted into alanine via halogenation and amination. Then, the procedure accomplishes the conversion of the amino acid into pyridoxine through the formation of an oxazole intermediate followed by a Diels–Alder reaction, with the entire process referred to as the "oxazole method". The product used in dietary supplements and food fortification is pyridoxine hydrochloride, the chemically stable hydrochloride salt of pyridoxine. Fermentative bacterial biosynthesis methods are also being explored, but are not yet scaled up for commercial production.

Functions

PLP is involved in many aspects of macronutrient metabolism, neurotransmitter synthesis, histamine synthesis, hemoglobin synthesis and function, and gene expression. PLP generally serves as a coenzyme (cofactor) for many reactions including decarboxylation, transamination, racemization, elimination, replacement, and beta-group interconversion.

Amino acid metabolism

1. Transaminases break down amino acids with PLP as a cofactor. The proper activity of these enzymes is crucial for the process of moving amine groups from one amino acid to another. To function as a transaminase coenzyme, PLP bound to a lysine of the enzyme then binds to a free amino acid via formation of a Schiff's base. The process then dissociates the amine group from the amino acid, releasing a keto acid, then transfers the amine group to a different keto acid to create a new amino acid. Biosynthesis of chlorophyll depends on aminolevulinic acid synthase, a PLP-dependent enzyme that uses succinyl-CoA and glycine to generate aminolevulinic acid, a chlorophyll precursor. Co-treatment with vitamin B₆ alleviates the numbness.

Overconsumption of seeds from Ginkgo biloba can deplete vitamin B₆, because the ginkgotoxin is an anti-vitamin (vitamin antagonist). Symptoms include vomiting and generalized convulsions. Ginkgo seed poisoning can be treated with vitamin B₆.

Dietary recommendations

From regulatory agency to regulatory agency there is a wide range between what is considered Tolerable upper intake levels (ULs). The European Food Safety Authority (EFSA) adult UL for vitamin B₆ is set at 12 mg/day

The EFSA refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA. For women and men ages 15 and older the PRI is set at 1.6 and 1.7 mg/day, respectively; for pregnancy 1.8 mg/day, for lactation 1.7 mg/day. For children ages 1–14 years the PRIs increase with age from 0.6 to 1.4 mg/day. The EFSA also reviewed the safety question and in 2023 set an upper limit for vitamin B₆ of 12 mg/day for adults, with lower amounts ranging from 2.2 to 10.7 mg/day for infants and children, depending on age. This replaced the adult UL set in 2008 at 25 mg/day.

The Japanese Ministry of Health, Labour and Welfare updated its vitamin and mineral recommendations in 2015. The adult RDAs are at 1.2 mg/day for women 1.4 mg/day for men. The RDA for pregnancy is 1.4 mg/day, for lactation is 1.5 mg/day. For children ages 1–17 years the RDA increases with age from 0.5 to 1.5 mg/day. The adult UL was set at 40–45 mg/day for women and 50–60 mg/day for men, with the lower values in those ranges for adults over 70 years of age.

Safety

Adverse effects have been documented from vitamin B₆ dietary supplements, but never from food sources. Even though it is a water-soluble vitamin and is excreted in the urine, doses of pyridoxine in excess of the dietary upper limit (UL) over long periods cause painful and ultimately irreversible neurological problems.

Labeling

For US food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value. For vitamin B₆ labeling purposes 100% of the Daily Value was 2.0 mg, but as of May 27, 2016, it was revised to 1.7 mg to bring it into agreement with the adult RDA. A table of the old and new adult daily values is provided at Reference Daily Intake.

Sources

Bacteria residing in the large intestine are known to synthesize B-vitamins, including B₆, but the amounts are not sufficient to meet host requirements, in part because the vitamins are competitively taken up by non-synthesizing bacteria.

Vitamin B₆ is found in a wide variety of foods. In general, meat, fish and fowl are good sources, but dairy foods and eggs are not (table). Crustaceans and mollusks contain about 0.1 mg/100 grams. Fruit (apples, oranges, pears) contain less than 0.1 mg/100g.

Cooking, storage, and processing losses vary, and in some foods may be more than 50% depending on the form of vitamin present in the food. Plant foods lose less during processing, as they contain pyridoxine, which is more stable than the pyridoxal or pyridoxamine forms found in animal-sourced foods. For example, milk can lose 30–70% of its vitamin B₆ content when dried.

Dietary supplements

In the US, multi-vitamin/mineral products typically contain 2 to 4 mg of vitamin B₆ per daily serving as pyridoxine hydrochloride. However, many US dietary supplement companies also market a B₆-only dietary supplement with 100 mg per daily serving. To make a health claim based on a food's vitamin B₆ content, the amount per serving must be in the range of 0.3–25 mg. The allowed claim is: "Vitamin B₆ is a nutrient that helps produce energy from protein and helps maintain healthy skin and mucous membranes."

In 2010, the European Food Safety Authority (EFSA) published a review of proposed health claims for vitamin B₆, disallowing claims for bone, teeth, hair skin and nails, and allowing claims that the vitamin provided for normal homocysteine metabolism, normal energy-yielding metabolism, normal psychological function, reduced tiredness and fatigue, and provided for normal cysteine synthesis.

The US Food and Drug Administration (FDA) has several processes for permitting health claims on food and dietary supplement labels. There are no FDA-approved Health Claims or Qualified Health Claims for vitamin B₆. Structure/Function Claims can be made without FDA review or approval as long as there is some credible supporting science. while another source indicates half-life of vitamin B₆ is in range of 25 to 33 days. After considering the different sources, it can be concluded that the half-life of vitamin B₆ is typically measured in several weeks. The three biochemical tests most widely used are plasma PLP concentrations, the activation coefficient for the erythrocyte enzyme aspartate aminotransferase, and the urinary excretion of vitamin B₆ degradation products, specifically urinary PA. Of these, plasma PLP is probably the best single measure, because it reflects tissue stores. Plasma PLP of less than 10 nmol/L is indicative of vitamin B₆ deficiency. A PLP concentration greater than 20 nmol/L has been chosen as a level of adequacy for establishing Estimated Average Requirements and Recommended Daily Allowances in the USA.

The classic clinical symptoms for vitamin B₆ deficiency are rare, even in developing countries. A handful of cases were seen between 1952 and 1953, particularly in the United States, having occurred in a small percentage of infants who were fed a formula lacking in pyridoxine.

Causes

A deficiency of vitamin B₆ alone is relatively uncommon and often occurs in association with other vitamins of the B complex. Evidence exists for decreased levels of vitamin B₆ in women with type 1 diabetes and in patients with systemic inflammation, liver disease, rheumatoid arthritis, and those infected with HIV. Use of oral contraceptives and treatment with certain anticonvulsants, isoniazid, cycloserine, penicillamine, and hydrocortisone negatively impact vitamin B₆ status. Hemodialysis reduces vitamin B₆ plasma levels. Overconsumption of Ginkgo biloba seeds can also deplete vitamin B₆.

Genetic defects

Genetically confirmed diagnoses of diseases affecting vitamin B₆ metabolism (ALDH7A1 deficiency, pyridoxine-5'-phosphate oxidase deficiency, PLP binding protein deficiency, hyperprolinaemia type II and hypophosphatasia) can trigger vitamin B₆ deficiency-dependent epileptic seizures in infants. These are responsive to pyridoxal 5'-phosphate therapy.

History

An overview of the history was published in 2012. In 1938, Richard Kuhn was awarded the Nobel Prize in Chemistry for his work on carotenoids and vitamins, specifically B₂ and B₆. Also in 1938, Samuel Lepkovsky isolated vitamin B₆ from rice bran. A year later, Stanton A. Harris and Karl August Folkers determined the structure of pyridoxine and reported success in chemical synthesis, and then in 1942 Esmond Emerson Snell developed a microbiological growth assay that led to the characterization of pyridoxamine, the aminated product of pyridoxine, and pyridoxal, the formyl derivative of pyridoxine. vitamin B₆ is the official name for all 2-methyl,3-hydroxy,5-hydroxymethylpyridine derivatives exhibiting the biological activity of pyridoxine. Because these related compounds have the same effect, the word "pyridoxine" should not be used as a synonym for vitamin B₆.

Research

Observational studies suggested an inverse correlation between a higher intake of vitamin B₆ and all cancers, with the strongest evidence for gastrointestinal cancers. However, evidence from a review of randomized clinical trials did not support a protective effect. The authors noted that high B₆ intake may be an indicator of higher consumption of other dietary protective micronutrients. A review and two observational trials reporting lung cancer risk reported that serum vitamin B₆ was lower in people with lung cancer compared to people without lung cancer, but did not incorporate any intervention or prevention trials.

According to a prospective cohort study the long-term use of vitamin B₆ from individual supplement sources at greater than 20 mg per day, which is more than ten times the adult male RDA of 1.7 mg/day, was associated with an increased risk for lung cancer among men. Smoking further elevated this risk. However, a more recent review of this study suggested that a causal relationship between supplemental vitamin B₆ and an increased lung cancer risk cannot be confirmed yet.

For coronary heart disease, a meta-analysis reported lower relative risk for a 0.5 mg/day increment in dietary vitamin B₆ intake. As of 2021, there were no published reviews of randomized clinical trials for coronary heart disease or cardiovascular disease. In reviews of observational and intervention trials, neither higher vitamin B₆ concentrations nor treatment showed any significant benefit on cognition and dementia risk. Low dietary vitamin B₆ correlated with a higher risk of depression in women but not in men. When treatment trials were reviewed, no meaningful treatment effect for depression was reported, but a subset of trials in pre-menopausal women suggested a benefit, with a recommendation that more research was needed. The results of several trials with children diagnosed as having autism spectrum disorder (ASD) treated with high dose vitamin B₆ and magnesium did not result in treatment effect on the severity of symptoms of ASD.

References

External links

• The B₆ database A database of B₆-dependent enzymes at University of Parma