P5P is pyridoxal 5’-phosphate (also written PLP), the active coenzyme form of vitamin B6. Inside the body it is the coenzyme for more than 150 enzymatic reactions in amino acid, carbohydrate and lipid metabolism, and it is needed to make several neurotransmitters (TGA, 2026). As a supplement it is sold as an alternative to the cheaper, more common pyridoxine, and in bodybuilding circles it is promoted as a way to lower prolactin.
The single most important fact is about safety, not benefit. High intakes of vitamin B6 cause sensory peripheral neuropathy (nerve damage felt as tingling, burning or numbness in the hands and feet). Regulators in Australia and the Netherlands have acted on large numbers of adverse event reports, the European Food Safety Authority (EFSA) cut its safe upper limit to 12 mg/day in 2023, and Australia’s regulator names P5P among the B6 forms its safety warnings cover. The prolactin claim rests mostly on old, conflicting studies of pyridoxine, not P5P.
This page summarizes what the dietary reference reports, regulators and clinical studies report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Water-soluble vitamin; the active coenzyme form of vitamin B6 |
| Chemistry | C₈H₁₀NO₆P, 247.14 g/mol (PubChem CID 1051) |
| Route | Oral tablet or capsule (supplement) |
| US RDA, adults | 1.3 mg/day (ages 19–50); 1.7 mg/day men and 1.5 mg/day women over 50; 1.9 mg/day in pregnancy; 2.0 mg/day in lactation |
| US upper limit (UL) | 100 mg/day for adults, set in 1998, expressed as pyridoxine |
| EU upper limit (UL) | 12 mg/day for adults, including pregnancy and lactation (EFSA, 2023) |
| Main risk | Sensory peripheral neuropathy from long-term high intake |
| Half-life | Not well characterized for oral P5P; plasma PLP stays raised long after high-dose supplementation stops |
| Regulatory | Authorized B6 form in EU food supplements; named by Australia’s TGA among B6 forms facing rescheduling from 1 June 2027 |
| WADA status | Not on the 2026 Prohibited List |
What it is
“Vitamin B6” is a family of six related compounds, called vitamers: pyridoxine (PN), pyridoxal (PL) and pyridoxamine (PM), plus their phosphate esters, including pyridoxal 5’-phosphate (EFSA, 2023). Humans cannot make any of them, so all B6 comes from food or supplements. Chemically, P5P is the phosphate ester of pyridoxal: (4-formyl-5-hydroxy-6-methyl-3-pyridinyl)methyl dihydrogen phosphate (PubChem).
Every vitamer ends up as PLP inside cells. The liver converts pyridoxine, pyridoxal and pyridoxamine to their phosphates with the enzyme pyridoxal kinase, and then oxidizes them to PLP with pyridoxine-5’-phosphate oxidase (PNPO) (IOM, 1998). PLP is the major form of B6 in plasma, carried bound to albumin.
The forms differ in where they come from and how they are sold:
| Form | Where it is found | Notes |
|---|---|---|
| Pyridoxine (PN), usually as the hydrochloride | Plant foods; most supplements and fortified foods | The form used in almost all safety and dosing studies |
| Pyridoxal 5’-phosphate (P5P, PLP) | Animal foods (main form with PMP); some supplements | Authorized B6 form for EU food supplements |
| Pyridoxamine (PM) | Animal foods | Less common as a supplement |
In the EU, the authorized forms of B6 for food supplements are pyridoxine hydrochloride, pyridoxine 5’-phosphate and pyridoxal 5’-phosphate (EFSA, 2023). In Australia, the three B6 forms in self-selected low-risk products are pyridoxine hydrochloride, pyridoxal 5-phosphate and pyridoxal 5-phosphate monohydrate (TGA, 2026).
P5P is also used in medicine for rare genetic conditions. In PNPO deficiency, an inherited epilepsy in which the body cannot make PLP from other forms, a 2025 systematic review of 49 PLP-treated patients found that most responded only to PLP, not to pyridoxine (Stolwijk et al., J Inherit Metab Dis 2025). The same review notes that pyridoxine is authorized as a medicinal product but PLP is not, so these patients rely on less-regulated food supplements. In two families with a pyridoxal kinase (PDXK) gene defect that caused axonal polyneuropathy, PLP supplementation restored PLP levels and was associated with clinical improvement in one family (Chelban et al., Ann Neurol 2019).
How it works in the body
P5P is not absorbed intact. The gut first removes the phosphate group with phosphatase enzymes, and the nonphosphorylated form (pyridoxal) is then absorbed by passive diffusion; even very large doses are well absorbed (IOM, 1998). In other words, oral P5P enters the body as pyridoxal and is rebuilt into PLP in the liver and other tissues.
| Finding | Source |
|---|---|
| About 70% of a 50 mg dose of pyridoxal, or an equivalent dose of PLP, appears in urine within 24 h, showing that PLP is hydrolyzed and absorbed | IOM, 1998 |
| About 40% of an equivalent dose of pyridoxine appears in urine, but at high doses pyridoxine raises plasma PLP and is retained better than pyridoxal | IOM, 1998 |
| B6 in a mixed diet is about 75% bioavailable | IOM, 1998 |
| At normal intakes PLP makes up 70–90% of plasma B6; at high intakes pyridoxal becomes the main vitamer, because only limited PLP can bind protein | EFSA, 2023 |
| Plasma PLP levels off at high doses: about 600 nmol/L after 10–800 mg/day pyridoxine for 1 week, vs about 70 nmol/L without supplements | EFSA, 2023 |
In a randomized placebo-controlled study of 90 patients, three days of 40 mg/day oral B6 raised plasma PLP about 10-fold, 4-pyridoxic acid (the main urinary breakdown product) about 50-fold and pyridoxal about 100-fold, with no further rise over 84 days (Bor et al., Clin Chem 2003).
Elimination is almost entirely through urine. In a balance study of four volunteers given intravenous pyridoxine for 4 weeks, urinary B6 output fell back within 5 days of stopping, but plasma PLP fell more slowly and stayed well above its starting level for the rest of the study (Lui et al., J Lab Clin Med 1985). We found no human study that reports a plasma half-life for oral P5P supplements specifically.
Is P5P “safer” than pyridoxine? Supplement marketing often says so. In cell culture, pyridoxine killed neuronal cells and inhibited PLP-dependent enzymes, while pyridoxal, pyridoxamine, PLP and pyridoxamine-5’-phosphate did not (Vrolijk et al., Toxicol In Vitro 2017). This is laboratory data, not a human comparison. Humans also have pyridoxal reductase activity that converts pyridoxal back into pyridoxine: patients treated with PLP showed strong pyridoxine accumulation in their cerebrospinal fluid (Ramos et al., BBA 2019). EFSA notes that free pyridoxine may appear in some people after PLP supplementation. Regulators set their limits for vitamin B6 as a whole, and Australia’s safety update names P5P among the forms it covers.
Intake recommendations and upper limits
The US Institute of Medicine (IOM, now the National Academies) set the current US Dietary Reference Intakes in 1998. The RDA is based on keeping plasma PLP at or above 20 nmol/L (IOM, 1998).
| Life stage | RDA (mg/day) | UL (mg/day, as pyridoxine) |
|---|---|---|
| Children 1–3 y | 0.5 | 30 |
| Children 4–8 y | 0.6 | 40 |
| 9–13 y | 1.0 | 60 |
| Boys 14–18 y | 1.3 | 80 |
| Girls 14–18 y | 1.2 | 80 |
| Adults 19–50 y | 1.3 | 100 |
| Men over 50 | 1.7 | 100 |
| Women over 50 | 1.5 | 100 |
| Pregnancy | 1.9 | 80 (14–18 y); 100 (19 y and older) |
| Lactation | 2.0 | 80 (14–18 y); 100 (19 y and older) |
The IOM reported median US food intakes of about 2 mg/day for men and 1.4 mg/day for women, so most people meet the RDA from food. Australia’s regulator likewise notes that the recommended intake (1.3–1.7 mg/day for adults) is easily met through diet and that clinical deficiency is rare (TGA, 2026).
The upper limits differ several-fold between agencies, because they weigh the same weak human data differently:
| Agency | Adult UL | How it was set |
|---|---|---|
| US IOM (1998) | 100 mg/day | NOAEL (no-observed-adverse-effect level) of 200 mg/day from two clinical series, divided by an uncertainty factor of 2 |
| EU SCF (2000) | 25 mg/day | Earlier EU limit, based on the Dalton and Dalton case-control study |
| EFSA (2023) | 12 mg/day | Reference point of 50 mg/day from the same case-control study, with an uncertainty factor of 4; supported by a dog study and vigilance data |
The IOM rejected the Dalton data as unreliable on doses, while EFSA used them, noting that 48% of women who had taken under 50 mg/day for more than 6 months reported neuropathy symptoms in that study (EFSA, 2023). EFSA’s limit for children ranges from 2.2–2.5 mg/day (4–11 months) to 6.1–10.7 mg/day (7–17 years).
What the research shows
Prolactin
The claim that B6 lowers prolactin (the pituitary hormone that drives milk production) dates to the 1970s, when high-dose pyridoxine was tried to stop breast milk after delivery. No controlled human trial has tested P5P itself on prolactin. The human evidence is for pyridoxine, and it is mixed:
| Study | Population | B6 dose | Result |
|---|---|---|---|
| Tolis et al., JCEM 1977 | 9 people with galactorrhea, 5 with high prolactin | Pyridoxine, acute and for 2 months | No change in prolactin or growth hormone; no fall in milk secretion; bromocriptine worked |
| Canales et al., BJOG 1976 | 14 postpartum women | Pyridoxine | Did not stop milk secretion or appear to suppress prolactin |
| de Waal et al., S Afr Med J 1978 | Postpartum women; patients with chlorpromazine-induced high prolactin | Pyridoxine | No reduction in prolactin; no suppression of milk |
| Brambilla et al., J Endocrinol Invest 1979 | 18 patients with antipsychotic-induced high prolactin | 300–1,200 mg oral or IV, single or 7 days | No decrease in prolactin |
| Andon et al., Pediatrics 1985 | 20 lactating women | 0.5 vs 4.0 mg/day | Plasma PLP rose; prolactin unchanged |
| Zhuo et al., Front Psychiatry 2021 | 200 men with treatment-resistant schizophrenia and antipsychotic-induced high prolactin | 300 mg every 12 h for 16 weeks, vs aripiprazole 10 mg/day | Prolactin fell 68.1% on B6 vs 37.4% on aripiprazole |
Two systematic reviews summarize the rest:
- Stopping lactation. A 2017 review of 7 studies (1,155 women, 471 given pyridoxine at 450–600 mg/day for 5–7 days) found that two trials reported lactation suppressed in about 95% of women, while all the others found no effect on clinical signs or prolactin. The authors judged the evidence inconsistent and insufficient to support this use (AlSaad et al., J Clin Pharm Ther 2017).
- Antipsychotic-induced high prolactin. A 2022 network meta-analysis of 31 studies (1,999 participants) found that adjunctive high-dose B6 lowered prolactin by a mean of 91.84 ng/mL (95% CI 17.74–165.31) vs placebo in patients starting above 50 ng/mL. No strategy beat placebo in patients starting below 50 ng/mL (Lu et al., Transl Psychiatry 2022). The B6 estimate came from a single trial (Zhuo 2021), which compared B6 with aripiprazole rather than placebo, so the placebo comparison is indirect.
In cell culture, PLP at 10–1,000 µM (micromolar) reduced the growth of rat pituitary tumor cells and cut their prolactin secretion by about 70% (Ren and Melmed, Endocrinology 2006). These are laboratory concentrations in rat and mouse cell lines, not human results.
In practice, the only positive human data use about 600 mg/day of pyridoxine, in patients with very high, drug-induced prolactin. That dose is six times the US UL and 50 times the EFSA UL. No study has tested P5P at typical supplement doses for prolactin in men using anabolic steroids such as nandrolone or trenbolone. The established prolactin-lowering drugs are dopamine agonists such as bromocriptine, which worked where pyridoxine failed in the 1977 study, and cabergoline.
Heart surgery (MC-1)
PLP was developed as a drug, called MC-1, to protect the heart during bypass surgery. The phase 3 MEND-CABG II trial randomized 3,023 patients to PLP 250 mg/day or placebo, starting before surgery and continuing for 30 days (MEND-CABG II, JAMA 2008):
| Outcome | PLP (MC-1) | Placebo |
|---|---|---|
| Cardiovascular death or nonfatal heart attack by day 30 | 9.3% | 9.0% |
| All-cause death at day 4 | 1.0% | 0.3% (p = 0.03) |
| All-cause death at day 30 | 1.9% | 1.5% (not significant) |
The trial found no benefit (risk ratio 1.04, 95% CI 0.83–1.30).
Side effects and risks
Peripheral neuropathy
Sensory neuropathy is the critical adverse effect on which every agency bases its upper limit. Key findings from the IOM review (IOM, 1998):
- The first human report described seven patients with severe sensory neuropathy after 2,000–6,000 mg/day of pyridoxine for 2–40 months; four could not walk. All improved after stopping.
- A woman who took 200 mg/day for 2 years without problems developed neuropathy after raising her dose to 500 mg/day, which the IOM used as the lowest dose with an observed effect.
- Seventy patients took 100–150 mg/day, some for up to 5 years, without detectable neuropathy.
Newer vigilance data show cases at much lower doses:
- Netherlands, 2018. A case series of 90 reports to the Dutch pharmacovigilance center Lareb involved products with 1.4–100 mg B6 per tablet. Serum B6, known in 36 cases, ranged from 88 to 4,338 nmol/L, with no correlation between dose and blood level. The authors concluded that B6 plausibly caused the neuropathy, especially at higher doses and longer use, and that a role for doses under 50 mg/day could not be ruled out (van Hunsel et al., Drug Saf 2018).
- Netherlands, 2024. Lareb had received 238 reports of nerve pain in people using B6 products. Of these, 79 involved a daily dose of 12 mg or less, and about a third of people recovered after stopping (Lareb, 2024).
- Other EU states. France’s nutrivigilance system reported eight neuropathy cases, all below the old 25 mg/day limit, though the products contained other ingredients too (EFSA, 2023).
- Australia. As of 31 October 2025, the TGA’s adverse event database held 250 reports of peripheral neuropathy or related terms for B6 products, and 162 more with less specific terms such as tingling or burning (TGA, 2026).
The TGA warns that the main symptoms of B6 toxicity resemble those of B6 deficiency, so people may take more B6 for symptoms the B6 is causing. It also notes that delayed diagnosis and continued exposure can let the disease progress, and that hidden B6 in multivitamins, B-complex, magnesium and zinc products adds up.
The mechanism is not settled. A leading hypothesis is that high pyridoxine levels inhibit pyridoxal kinase in peripheral nerves, lowering active PLP and disrupting GABA signaling in sensory neurons (Hadtstein and Vrolijk, Adv Nutr 2021). Most human toxicity data involve pyridoxine; there are no controlled studies of neuropathy risk with P5P specifically.
Regulatory actions
| Jurisdiction | Action |
|---|---|
| Netherlands | Since 1 October 2018, supplements may not provide more than 21 mg B6 per day, with lower limits for children (Lareb, 2018). In 2024 the health ministry said it intends to align the limit with EFSA’s 12 mg/day. |
| EU (EFSA) | Adult UL lowered from 25 mg/day to 12 mg/day in 2023, at the European Commission’s request, to inform maximum amounts in supplements |
| Australia (TGA) | Since 1 March 2022, products with more than 10 mg/day must carry a warning to stop if tingling, burning or numbness occurs (previously only above 50 mg/day) |
| Australia (TGA) | From 1 June 2027, oral products providing more than 50 mg but not more than 200 mg per day become pharmacist-only; above 200 mg/day remains prescription-only; 50 mg/day or less stays on general sale |
The TGA states that neuropathy risk is greatest at higher intakes but cannot be ruled out below 50 mg/day. After the Dutch dose cap, reports involving high doses fell, but cases at lower doses were still reported (van Hunsel et al., Pharmacoepidemiol Drug Saf 2025).
Liver toxicity with long-term high-dose PLP
In the PNPO-deficiency review, liver toxicity was the most common adverse event, in 10 of 49 PLP-treated patients (20.4%), and may be linked to high-dose PLP. The authors recommend regular liver screening during PLP therapy (Stolwijk et al., J Inherit Metab Dis 2025). Hepatocellular carcinoma (liver cancer) has been reported in two unrelated patients with PNPO deficiency on long-term PLP; whether PLP caused it is unknown (De Liso et al., Eur J Paediatr Neurol 2025). These patients take PLP for years at doses far above supplement use, so the findings may not apply to typical supplement users.
Interactions and other effects
- Drugs that bind PLP. Isoniazid (a tuberculosis drug) and levodopa (L-DOPA) have been reported to lower plasma PLP (IOM, 1998).
- Breastfeeding. EFSA notes an indication that about 600 mg/day may suppress lactation, far above the UL.
- Skin lesions. Painful skin lesions were reported with 2–4 g/day of pyridoxine for over a year, without a clear dose-response relationship (IOM, 1998).
- Hip fracture. EFSA found some evidence linking 35–40 mg/day of B6 to a higher hip fracture risk, but judged it insufficient to show cause and effect.
Key takeaways
- P5P is the active form of vitamin B6. It is dephosphorylated in the gut, absorbed as pyridoxal and rebuilt into PLP in the body.
- Requirements are small. The US RDA is 1.3–1.7 mg/day for adults, and most people get this from food.
- Upper limits disagree, and the trend is downward. The US UL is 100 mg/day (1998); EFSA cut the EU limit to 12 mg/day in 2023.
- Neuropathy is the main risk. Australia and the Netherlands have hundreds of reports between them, including some at low daily doses, and Australia’s safety warnings name P5P as well as pyridoxine.
- The prolactin evidence is weak. No human trial has tested P5P on prolactin. Pyridoxine studies are conflicting, and the positive results used about 600 mg/day in patients with drug-induced high prolactin.
Sources
- Institute of Medicine. Vitamin B6. In: Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press; 1998. NAP.
- EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, Bohn T, Castenmiller J, et al. Scientific opinion on the tolerable upper intake level for vitamin B6. EFSA J. 2023;21(5):e08006. PubMed.
- Therapeutic Goods Administration. Medicines containing vitamin B6 (pyridoxine, pyridoxal or pyridoxamine). Medicine Safety Update. Published February 19, 2026; updated April 7, 2026. TGA (archived).
- Netherlands Pharmacovigilance Centre Lareb. Maximum daily dose of vitamin B6 in dietary supplements has now been legally established in the Netherlands. October 18, 2018. Lareb.
- Netherlands Pharmacovigilance Centre Lareb. Nerve damage due to the use of nutritional supplements with vitamin B6. November 13, 2024. Lareb.
- van Hunsel F, van de Koppel S, van Puijenbroek E, Kant A. Vitamin B6 in health supplements and neuropathy: case series assessment of spontaneously reported cases. Drug Saf. 2018;41(9):859–869. PubMed.
- van Hunsel F, Scholl J, Vrolijk M, Ekhart C. Impact of regulatory action on dose maximalization for vitamin B6 dietary supplements on the reporting pattern for neuropathy. Pharmacoepidemiol Drug Saf. 2025;34(2):e70108. PubMed.
- Hadtstein F, Vrolijk M. Vitamin B-6-induced neuropathy: exploring the mechanisms of pyridoxine toxicity. Adv Nutr. 2021;12(5):1911–1929. PubMed.
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- Zhuo C, Xu Y, Wang H, et al. Safety and efficacy of high-dose vitamin B6 as an adjunctive treatment for antipsychotic-induced hyperprolactinemia in male patients with treatment-resistant schizophrenia. Front Psychiatry. 2021;12:681418. PubMed.
- Lu Z, Sun Y, Zhang Y, et al. Pharmacological treatment strategies for antipsychotic-induced hyperprolactinemia: a systematic review and network meta-analysis. Transl Psychiatry. 2022;12(1):267. PubMed.
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- MEND-CABG II Investigators; Alexander JH, Emery RW Jr, Carrier M, et al. Efficacy and safety of pyridoxal 5’-phosphate (MC-1) in high-risk patients undergoing coronary artery bypass graft surgery: the MEND-CABG II randomized clinical trial. JAMA. 2008;299(15):1777–1787. PubMed.
- Stolwijk NN, van Dussen L, Reijnhout ND, et al. Effectiveness of pyridoxal-5’-phosphate in PNPO deficiency: a systematic review. J Inherit Metab Dis. 2025;48(5):e70074. PubMed.
- De Liso P, Webster R, Plecko B, Vigevano F. Hepatocellular carcinoma in two unrelated patients with PNPO deficiency epilepsy: a risk of long-term pyridoxal-5’-phosphate therapy? Eur J Paediatr Neurol. 2025;56:104–106. PubMed.
- Chelban V, Wilson MP, Warman Chardon J, et al. PDXK mutations cause polyneuropathy responsive to pyridoxal 5’-phosphate supplementation. Ann Neurol. 2019;86(2):225–240. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA.