Vitamin B6 – Pyridoxine

Vitamin B6, also known as pyridoxine, is a water-soluble B vitamin that comes in several forms, all of which the body converts into a single active coenzyme: pyridoxal 5′-phosphate (PLP). PLP is a cofactor in more than 100 enzyme reactions, most of them in amino acid metabolism, neurotransmitter production, and releasing glucose from storage. That range makes vitamin B6 one of the more consequential B vitamins for both mental and physical performance — and it’s also one of the few water-soluble vitamins where too much from supplements causes a well-documented toxicity, nerve damage, which happens at lower doses than once thought.

Key Mechanisms

Pyridoxal 5′-phosphate (PLP) — the active form: all forms of vitamin B6 must be converted to PLP before they can work. PLP acts mainly as a coenzyme for aminotransferases (enzymes that move amino groups between molecules) and decarboxylases (enzymes that remove a carboxyl group to produce active compounds such as neurotransmitters). Both are essential for processing amino acids and for making neurotransmitters, heme, and glucose.

Neurotransmitter production: one of vitamin B6’s most important roles. PLP is needed for key steps in making several major neurotransmitters:

• Serotonin: tryptophan → 5-HTP → serotonin (the second step needs PLP). Serotonin helps regulate mood, sleep, appetite, and impulse control.
• Dopamine: tyrosine → L-DOPA → dopamine (the second step needs PLP). Dopamine drives motivation, reward, focus, and movement control.
• Noradrenaline: made from dopamine, so it depends on PLP indirectly — the final step itself uses copper and vitamin C rather than B6. Noradrenaline regulates arousal, attention, and the stress response.
• GABA: glutamate → GABA (needs PLP). GABA is the brain’s main calming neurotransmitter, reducing nerve activity.
• Histamine: histidine → histamine (needs PLP). Histamine acts as both a neurotransmitter and an immune signal.
• Melatonin: made from serotonin, so it depends on PLP indirectly — PLP is needed for the serotonin step upstream.

This helps explain why vitamin B6 deficiency can cause depression, irritability, confusion, and poor sleep — and why, in infants, severe deficiency can cause seizures, since GABA production falls.

Haemoglobin and heme production: PLP is the cofactor for aminolevulinic acid synthase (ALAS) — the first and rate-limiting enzyme in making heme, the iron-containing part of haemoglobin and myoglobin. Without enough PLP, heme production falls, and vitamin B6 deficiency can cause a distinctive anemia — microcytic and sideroblastic — in which iron builds up but can’t be properly built into haemoglobin.

Glycogen phosphorylase: PLP is a cofactor for glycogen phosphorylase — the enzyme that breaks down glycogen (stored glucose) in muscle and liver during exercise and fasting. In fact, most of the body’s vitamin B6 is stored in muscle, largely bound to this enzyme. That gives vitamin B6 a direct connection to exercise metabolism — though there’s no evidence that extra B6 speeds up glycogen use or improves performance in people who already get enough.

Homocysteine clearance: PLP is needed for the transsulfuration pathway, which converts homocysteine into cysteine. Without enough vitamin B6, homocysteine can build up in the blood. High homocysteine is linked with cardiovascular disease, stroke, and cognitive decline, and vitamin B6, along with B12 and folate, is one of three B vitamins that control homocysteine levels. (Large trials of B vitamins to lower homocysteine have generally not reduced heart attacks, though.)

Gluconeogenesis: during fasting or prolonged exercise, when glycogen runs low, PLP-dependent enzymes help convert amino acids (particularly alanine) into glucose, helping maintain blood sugar.

Vitamin B6 RDA (Recommended Dietary Allowance)

* Adequate Intake (AI) for infants. Source: US National Academies, via the NIH Office of Dietary Supplements. The daily value used on food labels is 1.7mg.

Note the increase after age 50 — unusual for a water-soluble vitamin. Blood levels of PLP tend to fall with age, so older adults need a higher intake to maintain the same vitamin B6 status.

ODA (Optimal Daily Allowance)

Meet the RDA — 1.3–1.7mg a day for adults — mainly from food. There’s no good evidence that higher intakes improve health, and with vitamin B6, more can do harm: nerve damage has been reported in some people taking 50mg a day or less over long periods. If you take a supplement long-term, keep your total supplemental vitamin B6 modest — Europe’s upper limit is 12mg a day, from all supplements combined. Higher doses for specific purposes, such as morning sickness or PMS, are covered below and are best used short-term, with medical guidance.

Found In (per 100g)

* Value from USDA’s SR Legacy data, where the Foundation Foods entry doesn’t include it.

Poultry, meat, and fish are the most reliable everyday sources of vitamin B6, and pistachios and sunflower seeds stand out among plant foods. Bananas and potatoes are often cited as sources — they provide moderate amounts, but are eaten often enough to contribute meaningfully. Some of the vitamin B6 in plant foods is bound in a form (pyridoxine glucoside) that the body absorbs only about half as well, so B6 from animal foods is generally more available.

Vitamin B6 Helps With

• Making serotonin, dopamine, GABA, and histamine — and, indirectly, noradrenaline and melatonin
• Protein and amino acid metabolism
• Haemoglobin production and oxygen transport
• Releasing stored glycogen for fuel, through glycogen phosphorylase
• Keeping homocysteine in check
• Making glucose from amino acids during fasting and prolonged exercise
• Immune function — low vitamin B6 status is linked with weaker immune cell responses
• Morning sickness in pregnancy — a first-line treatment recommended by obstetric guidelines
• PMS symptoms — some evidence of modest benefit, particularly for mood symptoms
• Brain development during pregnancy and early childhood

Vitamin B6 for Athletes and Active People

Vitamin B6’s role in glycogen breakdown sets it apart from most B vitamins for athletes — it’s directly involved in fueling exercise, not just general metabolism. As with the other B vitamins, though, adequate intake is what matters; extra hasn’t been shown to help.

Glycogen use: every time muscles break down glycogen to fuel hard efforts — sprints, heavy sets, intervals, team sports — glycogen phosphorylase is at work, with PLP as its cofactor. Low B6 status may impair this, but in well-nourished athletes there’s no evidence that extra B6 improves it. In some studies, high-dose B6 before exercise actually increased glycogen use and reduced fat use — not necessarily what an endurance athlete wants.

Protein metabolism: processing amino acids draws on PLP, so vitamin B6 needs rise somewhat with protein intake. Helpfully, the main high-protein foods — poultry, meat, and fish — are also among the best B6 sources, so a high-protein diet built on whole foods usually supplies more B6 as well.

Neurotransmitters during hard training: dopamine supports motivation, GABA has a calming effect, serotonin influences mood, and melatonin governs sleep — all depend on PLP directly or indirectly. Adequate vitamin B6 keeps these systems supplied during demanding training blocks, when motivation, mood, and sleep quality matter for performance.

Haemoglobin and oxygen delivery: since PLP is needed to make heme, adequate vitamin B6 is part of the nutritional foundation for haemoglobin production — a smaller factor than iron, but relevant to oxygen-carrying capacity.

Watch for hidden B6: vitamin B6 is added to many sports and wellness products — magnesium supplements, energy drinks, pre-workouts, and B-complexes. Athletes taking several of these can easily exceed safe long-term intakes without realizing it, which is the main way people develop B6 toxicity.

Vitamin B6 Deficiency

Deficiency risk is higher in:

• People with chronic heavy alcohol use — alcohol speeds up the breakdown of PLP; one of the most common causes of low B6 in high-income countries
• People with kidney disease, especially those on dialysis
• People taking certain medications:
  • Isoniazid (tuberculosis treatment): binds to vitamin B6 and inactivates it. Vitamin B6 is routinely prescribed alongside isoniazid for this reason.
  • Hydralazine (blood pressure): a similar mechanism to isoniazid
  • Penicillamine (rheumatoid arthritis, Wilson’s disease): binds and inactivates vitamin B6
  • Some anti-seizure medicines (such as phenytoin, carbamazepine, and valproate): can lower vitamin B6 levels
  • Oral contraceptives: linked with lower B6 levels, though the effect varies
• People with rheumatoid arthritis and other inflammatory conditions — inflammation lowers blood PLP levels
• Older adults — the higher RDA after 50 reflects this
• People with malabsorption conditions — such as Crohn’s disease, celiac disease, or after some types of weight-loss surgery
• Pregnant women — whose needs are higher

Symptoms of vitamin B6 deficiency:

• Depression, irritability, and confusion — linked to reduced neurotransmitter production
• Poor sleep
• Fatigue and weakness
• Microcytic, sideroblastic anemia — iron builds up but can’t be properly built into haemoglobin
• Cracks and sores at the corners of the mouth (angular cheilitis) and on the lips
• An inflamed, sore tongue (glossitis)
• Scaly, itchy skin rashes (seborrheic dermatitis)
• Tingling or numbness in the hands and feet (peripheral neuropathy) — which, confusingly, is also the main sign of B6 toxicity
• Weaker immune responses
• Seizures, particularly in infants

Because the symptoms of B6 deficiency and B6 toxicity overlap — especially tingling and numbness — anyone with these symptoms who takes supplements should tell their doctor exactly what they take. Raising your B6 intake to treat symptoms that are actually caused by too much B6 makes them worse.

Morning sickness and PMS: for nausea and vomiting in pregnancy, the American College of Obstetricians and Gynecologists recommends pyridoxine — typically 10–25mg three or four times a day, alone or combined with the antihistamine doxylamine — as a first-line treatment, one of the few nutritional treatments with this level of clinical endorsement. For PMS, doses of 50–100mg a day have been studied, with some evidence of modest benefit, mostly for mood symptoms, though the trials were generally small and of low quality. Given the nerve damage reports at doses of 50mg a day or less, PMS use is best short-term and discussed with a doctor.

Excessive Doses of Vitamin B6

Upper limit (UL): in the US, 100mg a day for adults, set in 1998. Limits are lower for children:

Source: US National Academies, via the NIH Office of Dietary Supplements.

Other countries have become far more cautious. In 2023, the European Food Safety Authority (EFSA) lowered its upper limit for adults — including during pregnancy and breastfeeding — to 12mg a day, from 25mg, with lower limits for children (about 3–11mg a day, depending on age). In Australia, after hundreds of reports of nerve damage linked to vitamin B6 products, the Therapeutic Goods Administration (TGA) has decided that higher-dose vitamin B6 supplements will become pharmacist-only from June 2027, and it already requires a nerve damage warning on products providing more than 10mg a day.

Vitamin B6 is one of the few water-soluble vitamins with well-documented toxicity from supplements. Taken in excess over time, it causes sensory neuropathy — damage to the nerves that carry sensation:

• Most reported cases involve high doses — often above 500mg a day — but cases have been reported at much lower doses, and Australia’s regulator concluded that nerve damage can’t be ruled out at 50mg a day or less
• Symptoms: tingling, burning, or numbness in the hands and feet; difficulty walking; loss of balance and coordination; and in severe cases, pain or loss of normal sensation
• Symptoms usually improve after stopping the supplement, but recovery can take months, and some people are left with lasting damage
• Sensitivity varies a lot between people, and risk rises with both dose and duration
• The most common route to toxicity is stacking several products — a multivitamin, a magnesium supplement with B6, an energy drink — without realizing how much B6 they add up to

Why too much B6 damages nerves: the mechanism isn’t fully understood. One leading explanation from laboratory research is that high levels of pyridoxine compete with active PLP and block PLP-dependent enzymes — effectively causing a functional B6 deficiency in nerves, which would explain why toxicity and deficiency produce such similar symptoms. Some practitioners consider the P5P form lower-risk at high doses, but this hasn’t been proven, and EFSA’s upper limit applies to all forms of vitamin B6.

At the doses in a typical multivitamin, vitamin B6 is safe for the vast majority of people.

Types of Vitamin B6

• Pyridoxine (pyridoxine hydrochloride): the most common supplement form — stable, inexpensive, and well researched. It’s converted to PLP in the body, mainly in the liver. The standard form used in multivitamins and for morning sickness.
• Pyridoxal 5′-phosphate (PLP / P5P): the active coenzyme form, which needs no conversion. Often suggested for people whose conversion may be impaired, such as older adults or people with liver disease, though it’s mostly broken down and rebuilt during absorption. More expensive than pyridoxine. Sometimes described as carrying less risk of nerve damage at high doses, but that hasn’t been established.
• Pyridoxamine: a natural form found mainly in animal foods, also converted to PLP. Rarely used in supplements. It has been studied as a drug for diabetic kidney disease, because it can block the formation of advanced glycation end products (AGEs), but trials haven’t shown a clear benefit.

Which form for your goal:

How to Take Vitamin B6

Vitamin B6 can be taken with or without food; taking it with a meal can reduce stomach upset. It works alongside other B vitamins: it needs riboflavin (B2) to be activated, and it works with B12 and folate to keep homocysteine in check.

General needs: most people get enough from food. Multivitamins and B-complexes typically contain about 2–10mg — enough to cover needs without approaching the limits.

Higher doses: doses of 25–100mg a day are used for morning sickness and PMS, and many standalone B6 supplements contain doses in this range. Given the nerve damage reports, these are best used for a specific purpose, for a limited time, and ideally with medical guidance — not as a long-term daily habit.

Check everything you take: add up the vitamin B6 in all your supplements and fortified drinks — magnesium products, energy drinks, pre-workouts, and “stress” or “sleep” formulas often contain it. If you develop tingling, burning, or numbness in your hands or feet, stop the supplements and see a doctor.

Timing: there’s no good evidence that timing matters. Evening dosing is sometimes suggested for sleep, through the serotonin–melatonin pathway, but there’s no strong evidence that it works better than morning dosing.

Levodopa: vitamin B6 speeds up the breakdown of levodopa (a Parkinson’s disease medicine) outside the brain, reducing its effect — but this applies mainly to levodopa taken on its own. Most levodopa today is combined with carbidopa, which largely prevents the interaction. Anyone taking levodopa should still check with their doctor before taking B6 supplements.

Interactions

Isoniazid, hydralazine, and penicillamine inactivate vitamin B6 — vitamin B6 is routinely prescribed alongside isoniazid. Some anti-seizure medicines lower vitamin B6 levels, while high doses of vitamin B6 (around 200mg a day) can lower blood levels of phenytoin and phenobarbital, making them less effective — important for people with epilepsy. Oral contraceptives may modestly lower vitamin B6 levels. Alcohol speeds up the breakdown of PLP. High-dose B6 interferes with levodopa taken without carbidopa (see above).

Synergy

• Works with B12 and folate to clear homocysteine — a shortage of any one of the three can raise homocysteine.
• Often combined with magnesium — the pairing has been studied for stress and PMS, with some modest positive results. Check the B6 dose in combined products, since they’re a common source of hidden B6.
• Needs riboflavin (B2) for its own activation — the enzyme that makes PLP depends on a B2-derived coenzyme.
• Supports tryptophan metabolism, both for making serotonin and melatonin and for making niacin (vitamin B3) — two pathways that draw on the same tryptophan supply.
• Works with iron to make haemoglobin — PLP is needed to build heme, and iron sits at its center.

Antagonistic Interactions

Too much pyridoxine causes sensory nerve damage — the opposite of its normal role in supporting the nervous system.

Alcohol speeds up the breakdown of PLP — one of the most common causes of depletion.

Isoniazid, hydralazine, and penicillamine inactivate vitamin B6 directly.

High-dose vitamin B6 can reduce the effectiveness of some anti-seizure medicines, and of levodopa taken without carbidopa.

Food values: USDA FoodData Central — pistachios, raw (Foundation Foods, FDC ID 2515379, vitamin B6 from SR Legacy); sunflower seeds, raw (Foundation Foods, 2515381, vitamin B6 from SR Legacy); chicken breast, braised (Foundation Foods, 331960); turkey breast, roasted (SR Legacy, 174516); venison loin, cooked (SR Legacy, 172604); pork top loin chops, broiled (SR Legacy, 167841); Atlantic salmon, farmed, cooked (SR Legacy, 175168); lamb liver, braised (SR Legacy, 172532); ground beef, cooked (SR Legacy, 171797); light tuna, canned in water (Foundation Foods, 334194); potato, baked, flesh (SR Legacy, 170112); spinach, boiled (SR Legacy, 168463); banana, ripe (Foundation Foods, 1105314); brown rice, cooked (SR Legacy, 169704). RDA and US upper limits from the US National Academies, via the NIH Office of Dietary Supplements. % Daily Values use the FDA’s current Daily Value of 1.7mg.