Vitamin B6

What is vitamin B6 and what does it do?

Vitamin B6 is not a single substance. It is the common name for six compounds consisting of pyridoxine (an alcohol), pyridoxal (an aldehyde), pyridoxamine (an amine) and their 5′-phosphate esters. The active coenzyme form is pyridoxal 5′-phosphate (PLP). NIH reports that pyridoxine hydrochloride is the most common form in supplements, that PLP is also found in some products, and that absorption from supplements is similar to that from foods, with no marked difference between supplement forms. ^[1]

According to EFSA, PLP and pyridoxamine phosphate are cofactors of more than 100 enzymes, mostly in amino acid metabolism; they also take part in one-carbon reactions, glycogenolysis and gluconeogenesis, heme synthesis, niacin formation, lipid metabolism, neurotransmitter synthesis and hormone action. NIH also lists immune function and hemoglobin formation. ^{[2] [1]}

A vitamin being needed by enzymes and extra supplementation improving these processes in a person without a deficiency are different claims. On this page, the evidence for the second is given separately for each individual claim.

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How much B6 is needed per day?

Reference values differ somewhat by agency, because each defines adequacy by a different blood-level criterion. NIH reports that the US Food and Nutrition Board (FNB) largely used a plasma PLP level of 20 nmol/L as the criterion in calculating adult RDAs and that a PLP above 30 nmol/L is traditionally considered adequate. EFSA, on the other hand, took the population mean of 30 nmol/L as an indicator of adequate B6 status and derived the average requirements (AR) and population reference intakes (PRI). ^{[1] [2]}

The NIH/IOM values are taken from the RDA table on the NIH fact sheets and the EFSA values from the 2016 opinion. EFSA sets an AR of 1.3 mg and a PRI of 1.6 mg for women, and an AR of 1.5 mg and a PRI of 1.7 mg for men; for pregnancy and breastfeeding it takes the additional requirement into account. ^{[1] [2]}

What is intake like in Türkiye?

In the analysis in TÜBER (Türkiye Dietary Guidelines) 2022 based on Türkiye Nutrition and Health Survey (TBSA) 2017 data, 69.2% of individuals aged 15 and over were found to be below the estimated average requirement (EAR) for B6 intake: 65.6% of men and 72.8% of women. At ages 75 and over, this proportion is 82.6% in men and 84.7% in women. This is an intake distribution based on a dietary survey; it is not a blood level measurement and cannot be read as a “deficiency rate.” ^[4]

Which foods contain vitamin B6?

NIH lists as the richest sources fish, beef liver and other organ meats, potatoes and other starchy vegetables, and fruits other than citrus; most of the B6 US adults get from food comes from fortified breakfast cereals, beef, poultry, starchy vegetables and some fruits (cereal fortification is common in the US). ^[1] For Türkiye, the standard serving table in TÜBER 2022 gives the following values (rounded to one decimal):

These values are taken from the TÜBER table; they vary with brand and cooking method. ^[4]

Who gets B6 deficiency?

NIH reports that B6 deficiency alone is not common and that inadequate B6 status is usually seen together with low levels of other B vitamins such as B12 and folic acid. Plasma PLP tends to be found low in people with alcohol dependence, people with obesity, pregnant women (especially with preeclampsia or eclampsia) and malabsorption disorders such as celiac disease, Crohn’s disease and ulcerative colitis. NIH also counts people with impaired kidney function (end-stage kidney disease and chronic kidney failure; PLP is also found low in those on regular dialysis and kidney transplant recipients) and people with autoimmune disease (for example rheumatoid arthritis) among the groups at highest risk of inadequacy. ^[1]

The symptoms (microcytic anemia, dermatitis, scaling of the lips and cracks at the corners of the mouth, swelling of the tongue, depression, confusion; irritability and seizures in infants), the plasma PLP thresholds and the question of whether a neuropathy stems from deficiency or excess are covered on a separate page.

Detailed guideVitamin B6 deficiency symptoms: who gets it, what does the PLP test say?→

Is excess B6 harmful? Why is the upper limit 100 mg and 12 mg?

NIH reports that high B6 intake from food has not been reported to cause side effects; the problem arises with supplements. ^[1] The critical effect is sensory peripheral neuropathy. The symptoms reported in the Dalton and Dalton study were paresthesia (tingling), bone pain, hypersensitivity, muscle weakness, muscle twitching and numbness. EFSA describes the association between excess B6 intake and peripheral neuropathy as “well established”; the most severe picture was seen in the first case series of seven people taking 2–6 g/day of B6 (four became unable to walk). ^[3]

Why are there two different upper limits?

The upper limit (UL) is the highest daily total amount that can be taken regularly with no adverse effects expected. As EFSA notes, the difference between the two numbers arises mainly from the agencies basing their assessments on different studies: ^[3]

• US IOM/FNB (1998; the 100 mg cited by NIH): According to NIH, the FNB judged that sensory neuropathy has been reported at doses below 500 mg/day but that this effect was not seen in patients treated with an average of 200 mg/day of B6 for up to 5 years; because long-term use data are limited, it halved this dose and set the adult UL at 100 mg/day. EFSA 2023, in turn, summarizes the IOM’s basis as studies in people with diabetic neuropathy or carpal tunnel in which neuropathy did not worsen at an intake of 100–300 mg/day (in EFSA’s summary, the NOAEL appears as 100 mg/day and the uncertainty factor as none; the two sources’ accounts differ on this detail). The IOM did not use a case-control study (Dalton and Dalton 1987) because the doses given were not sufficiently reliable. ^{[1] [3]}
• EU Scientific Committee on Food (SCF, 2000): It took as its basis the mean intake of the same case-control study, about 100 mg, and applied a 2 × 2 uncertainty factor; the result was 25 mg/day for adults, including pregnant and breastfeeding women. ^[3]
• EFSA NDA Panel (2023): The lowest observed adverse effect level (LOAEL) could not be determined from human data. The Panel set a reference point of 50 mg/day from the same case-control study together with case reports and nutrivigilance data and, applying an uncertainty factor of 4, calculated 12.5 mg/day. From a dog study (LOAEL 50 mg/kg/day, factor 300), 11.7 mg/day was calculated. Taking the midpoint of the two and rounding down, 12 mg/day was set for adults (including pregnant and breastfeeding women). ^[3]

In the Dalton and Dalton (1987) study on which EFSA relies, of 172 women who presented to a clinic for premenstrual syndrome, 103 (60%) reported neurological symptoms. The mean intake is reported as 117 mg/day in cases and 116 mg/day in controls; cases had used the supplement for a mean of 2.9 years and controls 1.6 years. Of 43 women taking under 50 mg a day (lower bound not reported), 48% had symptoms. After the supplement was stopped, 55% of the women improved partly or fully in 3 months, and by 6 months all had improved. The Panel judged that the study shows not only a mean intake–duration relationship but also a dose-dependent increase in symptoms at intakes below 50 mg/day with use longer than 6 months. The IOM, however, did not use the same study because the doses given were not sufficiently reliable. ^[3]

EFSA also cites a case who developed symptoms after 2 years while taking 75 mg/day and recovered within 3 months when it was stopped; in the case reports evaluated by the SCF, neuropathy was seen at 100–6,000 mg/day with delays varying between 1 and 72 months. Neuropathy has been reported in a man taking about 31 mg/day of B6 from energy drinks; this is a single case, and the duration of intake and the product’s other ingredients were not reported. Photosensitive skin reactions have also been mentioned in case reports. ^[3] The mechanism is not yet fully understood; a review proposes that excess pyridoxine causes preferential damage to sensory neurons and that inhibition of the pyridoxal kinase enzyme may have played a role. ^[3]

According to EFSA, the population in Europe is not expected to exceed the UL; the exception is people who regularly use supplements with high amounts of B6. The two values should be read as answers to different questions: the NIH/IOM value was derived from treatment doses at which no worsening was seen in neuropathy patients (half of the mean 200 mg/day, according to NIH), and the EFSA 2023 value from a case-control study, case reports and nutrivigilance data with a factor of 4. A person’s current intake and symptoms are evaluated together with a physician. ^[3]

Detailed guideB6 neuropathy: from deficiency or from excess?→

With which medicines does vitamin B6 interact?

• Levodopa: According to the carbidopa-levodopa product label, even oral pyridoxine doses of 10–25 mg can reverse the effects of levodopa by accelerating aromatic amino acid decarboxylation; carbidopa blocks this effect, so according to the label carbidopa-levodopa can be given to patients taking pyridoxine supplements. There is no such assurance for levodopa without carbidopa. ^[5]
• Isoniazid: The isoniazid label states that pyridoxine deficiency is occasionally seen in adults at high doses and that this may be due to isoniazid competing with pyridoxal phosphate. ^[6]
• Cycloserine and antiepileptics: In NIH’s drug interactions section, the tuberculosis medicine cycloserine (urinary pyridoxine loss associated with PLP) and some antiepileptics, including valproic acid, are mentioned. ^[1]

These interactions show that people using prescription medicines need to evaluate products containing B6 together with their drug treatment; a personal plan is made with a physician and pharmacist.

Is the benefit of B6 supplementation evidenced?

The summary below shows, for each claim, the population and the limit; details are on the benefits page.

For nausea in pregnancy, the ACOG 2018 guideline states that mild cases may improve with dietary and lifestyle changes; in drug treatment it considers pyridoxine (alone or with doxylamine) safe and effective. This is a guideline recommendation; use and amount are the physician’s decision. ^[7]

The Cochrane 2017 review combined 15 randomized trials (71,422 participants); the intervention is B6, B9 or B12 given singly or together, that is, the effect of B6 was not separated. There was no difference in heart attack (RR 1.02; 0.95–1.10) and all-cause death (RR 1.01; 0.96–1.06); a small reduction was reported in stroke (RR 0.90; 0.82–0.99). ^[10]

Detailed guideVitamin B6 benefits: which effects are supported and which are not?→

How does this guide relate to the other B vitamins?

B6, B12 and folic acid take part together in homocysteine metabolism; for this reason they are often given together in studies and the effects cannot be separated. The separate guides cover vitamin B12, folic acid and vitamin B1 (thiamin); the combination products of these vitamins and their upper limits are summarized together in the B complex guide.

Common misunderstandings about vitamin B6

• “Because it is water-soluble, the excess is excreted in urine and is harmless.” B6 is water-soluble; however, EFSA considers the relationship between long-term high intake and peripheral neuropathy well established. ^[3]
• “Since the upper limit is 100 mg, up to 100 mg is safe.” EFSA 2023 judged that, in a case-control study, symptoms were also seen at intakes below 50 mg/day and set the adult UL at 12 mg/day. ^[3]
• “PLP, the active form, is more effective.” NIH reports that there is no marked difference in absorption between supplement forms. ^[1]
• “Tingling means B6 deficiency.” Both deficiency and excess intake can cause neuropathy; telling them apart requires clinical evaluation.

This guide does not recommend a personal dose. If more than one product containing B6 is used, total intake needs to be calculated from the labels, and if there are symptoms, a health professional needs to be consulted with the product labels.