Vitamin B6

What it is

Vitamin B6 is not one molecule but six: pyridoxal, pyridoxine and pyridoxamine, and their 5'-phosphates.^[1] Animal foods carry mostly the pyridoxal and pyridoxamine forms; plant foods carry mostly pyridoxine, sometimes bound to a sugar.^[1] The body converts them to pyridoxal 5'-phosphate (PLP), the coenzyme that does the work.

PLP is involved in a long list of reactions. It is the coenzyme for the first committed step in making heme, the iron-carrying part of hemoglobin, and for decarboxylases that make neurotransmitters.^[1] It also runs two of the enzymes that clear homocysteine through the transsulfuration pathway, which links it to folate and vitamin B12.^[1] The classic signs of deficiency follow from those roles: a scaly skin rash (seborrheic dermatitis), small-cell anemia, convulsions, and depression and confusion.^[1]

In the US diet, the main sources are fortified ready-to-eat cereals, mixed dishes built on meat, fish or poultry, white potatoes and other starchy vegetables, and noncitrus fruits. Organ meats and fortified cereals are especially rich.^[1] The DRI committee assumed that about 75 percent of the B6 in a mixed diet is bioavailable.^[1]

Supplements commonly use pyridoxine hydrochloride, a stable salt; some use PLP directly. Replenish uses pyridoxine HCl.

How much adults need

Source: Institute of Medicine, Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (1998).^[1] The UL is for vitamin B6 as pyridoxine. The European Food Safety Authority set a lower adult UL of 12 mg a day in 2023.^[2] RDA = Recommended Dietary Allowance; UL = Tolerable Upper Intake Level.

Amount in Replenish: confirmed at launch

The RDA rises after 50, more for men than for women.^[1] When the 1998 report was written, median US intake from food was about 2 mg a day for men and 1.4 mg for women, so the typical woman's intake sat close to the RDA. The 95th percentile of intake from food plus supplements was 6 to 10 mg.^[1] B6 is unusual among water-soluble vitamins in that the upper limit is a real constraint: high-dose single-ingredient B6 products can reach it, and the European limit is lower still.

What the evidence says

Homocysteine and heart disease. Because B6, folate and B12 all lower homocysteine, and high homocysteine is linked with cardiovascular disease in observational studies, large trials tested whether B vitamins prevent heart attacks and strokes. In HOPE-2, 5,522 people aged 55 and older with vascular disease or diabetes took 2.5 mg folic acid, 50 mg vitamin B6 and 1 mg vitamin B12, or placebo, for an average of five years. Homocysteine fell, but the combined rate of cardiovascular death, heart attack and stroke did not change (relative risk 0.95). Strokes were fewer, and hospital admissions for unstable angina were more frequent.^[3]

NORVIT randomized 3,749 people who had just had a heart attack and included a B6-alone arm of 40 mg a day. B6 brought no significant benefit (relative risk 1.14), and the group given B6 with folic acid and B12 showed a trend toward more events (relative risk 1.22, P=0.05). The authors concluded that such treatment should not be recommended for that purpose.^[4] These are trials of doses many times the RDA in people with heart disease. They say nothing against meeting the RDA; they say high-dose B6 is not a cardiovascular treatment.

Status in alcohol use. People who drink heavily have low plasma PLP, and the DRI report attributes this partly to acetaldehyde, separate from poor diet or liver disease.^[1]

Eating less. B6 is not on the 2025 joint advisory's list of nutrients most at risk for people taking GLP-1 medications.^[5] It comes from the same foods that shrink when appetite does, though: meat, fish, poultry, potatoes and fortified cereal. Our article on vitamins on a GLP-1 covers B6 alongside folate.

Safety and interactions

Nerve damage at high doses. The critical adverse effect of too much B6 is sensory neuropathy.^[1] The first clear description, in 1983, was of seven adults with unsteady gait and severe sensory loss after taking high daily doses of pyridoxine; four were severely disabled, and all improved after stopping.^[6]

How the US limit was set. The DRI committee found no neuropathy in 70 patients given 100 to 150 mg a day, some for up to 5 years, or in 24 patients given 100 to 300 mg a day for 4 months. It took 200 mg a day as the highest dose without observed harm, divided by an uncertainty factor of 2, and set the adult UL at 100 mg a day.^[1]

Why Europe set 12 mg. In 2023 the European Food Safety Authority reviewed the evidence again, with neuropathy as the critical effect. It took 50 mg a day as a reference point from a case-control study, supported by case reports and vigilance data, and applied an uncertainty factor of 4 because symptoms appear sooner at higher doses and the data are limited. That gave 12.5 mg; a separate calculation from a dog study gave 11.7 mg. EFSA set the adult UL at 12 mg a day, including in pregnancy and lactation, and judged that people in the EU are unlikely to exceed it unless they regularly take high-dose B6 supplements.^[2] The two agencies agree on the hazard and differ on the margin. If you take more than one product, add up the B6.

Medicines. Drugs that react with carbonyl groups can interact with PLP. The DRI report notes that isoniazid, a tuberculosis medicine, and levodopa, used for Parkinson's disease, have been reported to lower plasma PLP.^[1] It also notes small falls in B6 status with the high-dose oral contraceptives of earlier decades, which carried three to five times the estrogen of current pills.^[1] If you take levodopa, ask before adding any B6 product, because dosing is specific to your regimen.

If you take prescription medicine, ask your pharmacist or prescriber before adding a supplement.

In Replenish

Replenish contains vitamin B6 as pyridoxine HCl, one of the 6 vitamins in the formula. With thiamin, folate and B12 it provides key vitamins and minerals^† for days when meals are small. The amount per serving is published with the Supplement Facts panel on the Replenish page, so you can add it to any other B6 you take and compare the total with the upper limits above.