Vitamin B6

[1][2][3][4] The term essential nutrient refers to a group of six chemically similar compounds, i.e., "vitamers", which can be interconverted in biological systems.

Its active form, pyridoxal 5′-phosphate, serves as a coenzyme in more than 140 enzyme reactions in amino acid, glucose, and lipid metabolism.

[1][2][3] Plants synthesize pyridoxine as a means of protection from the UV-B radiation found in sunlight[5] and for the role it plays in the synthesis of chlorophyll.

Beef, pork, fowl and fish are generally good sources; dairy, eggs, mollusks and crustaceans also contain vitamin B6, but at lower levels.

At present, while the industry mainly utilizes the oxazole method, there is research exploring means of using less toxic and dangerous reagents in the process.

PLP generally serves as a coenzyme (cofactor) for many reactions including decarboxylation, transamination, racemization, elimination, replacement, and beta-group interconversion.

[6] PLP also catalyzes transamination reactions that are essential for providing amino acids as a substrate for gluconeogenesis, the biosynthesis of glucose.

Also, PLP influences expression of glycoprotein IIb by interacting with various transcription factors; the result is inhibition of platelet aggregation.

Ultraviolet-B radiation (UV-B) from sunlight stimulates plant growth, but in high amounts can increase production of tissue-damaging reactive oxygen species (ROS), i.e., oxidants.

Using Arabidopsis thaliana (common name: thale cress), researchers demonstrated that UV-B exposure increased pyridoxine biosynthesis, but in a mutant variety, pyridoxine biosynthesis capacity was not inducible, and as a consequence, ROS levels, lipid peroxidation, and cell proteins associated with tissue damage were all elevated.

The European Food Safety Authority (EFSA) adult UL for vitamin B6 is set at 12 mg/day[22] versus 100 mg/day for the United States.

[23] 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.

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.

Sensory neuropathy typically develops at doses of pyridoxine in excess of 1,000 mg per day, but adverse effects can occur with much less, so intakes over 200 mg/day are not considered safe.

This was divided by two to allow for people who might be extra sensitive to the vitamin, referred to as an "uncertainty factor", resulting in the aforementioned adult UL of 100 mg/day set for the United States.

[22] While Australia has set an upper limit of 50 mg/day, the Therapeutic Goods Administration requires a label warning about peripheral neuropathy if the daily dose is predicted to exceed 10 mg/day.

[34][35] 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.

Total body stores, the majority in muscle, with a lesser amount in liver, have been estimated to be in the range of 61 to 167 mg.[4] Enzymatic processes utilize PLP as a phosphate-donating cofactor.

PLP is restored via a salvage pathway that requires three key enzymes, pyridoxal kinase, pyridoxine 5'-phosphate oxidase, and phosphatases.

[4] The classic clinical syndrome for vitamin B6 deficiency is a seborrheic dermatitis-like eruption, atrophic glossitis with ulceration, angular cheilitis, conjunctivitis, intertrigo, abnormal electroencephalograms, microcytic anemia (due to impaired heme synthesis), and neurological symptoms of somnolence, confusion, depression, and neuropathy (due to impaired sphingosine synthesis).

[1] Less severe cases present with metabolic disease associated with insufficient activity of the coenzyme pyridoxal 5' phosphate (PLP).

[42] 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.

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.

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.

[46][47] Use of oral contraceptives and treatment with certain anticonvulsants, isoniazid, cycloserine, penicillamine, and hydrocortisone negatively impact vitamin B6 status.

[54] In 1934, the Hungarian physician Paul György discovered a substance that was able to cure a skin disease in rats (dermatitis acrodynia).

[62][63][64] 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.

[65] 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.

[66] For coronary heart disease, a meta-analysis reported lower relative risk for a 0.5 mg/day increment in dietary vitamin B6 intake.

In reviews of observational and intervention trials, neither higher vitamin B6 concentrations[68] nor treatment[69] showed any significant benefit on cognition and dementia risk.

Pyridoxine (PN)
Pyridoxamine (PM)
Pyridoxal (PL)