Home Ingredients P-5-P (Pyridoxal-5-Phosphate / Active B6)
Women's Health

P-5-P (Pyridoxal-5-Phosphate / Active B6)

Evidence Level
Moderate
2 Clinical Trials
5 Documented Benefits
3/5 Evidence Score

P-5-P (pyridoxal 5'-phosphate, PLP) is the coenzyme form of vitamin B6, which takes part in more than 100 enzyme reactions, mostly in protein and amino acid metabolism. Swallowed P-5-P is not absorbed intact: the gut removes the phosphate group, the free vitamin is absorbed, and cells add the phosphate back. Plain pyridoxine ends up in the same active form, so the choice between them is mostly price and preference. The human trials behind vitamin B6's best-known uses, premenstrual mood symptoms and nausea in early pregnancy, used pyridoxine, not P-5-P. Adults need about 1.3 to 1.7 mg of B6 a day. The US upper limit is 100 mg a day because long-term high doses can damage sensory nerves, and in 2023 the European Food Safety Authority set a lower adult limit of 12 mg a day. P-5-P is distinct from pyridoxine HCl (the most common supplement form) and pyridoxamine.

Studied Dose PMS: pyridoxine 50 mg/day in one trial and 80 mg/day in another; a systematic review suggested up to 100 mg/day. Pregnancy nausea: 30 mg/day pyridoxine; ACOG suggests 10 to 25 mg three or four times a day under a doctor's care. Upper limit: 100 mg/day (US), 12 mg/day (EFSA).
Active Compound Pyridoxal-5-Phosphate (PLP / P-5-P).

Benefits

Bioactive Coenzyme Form

P-5-P is the coenzyme form of B6. When swallowed, it is dephosphorylated in the gut and absorbed as free vitamin B6, so it does not skip the body's own phosphorylation step. Healthy adults turn pyridoxine into the same active form. An advantage for people with impaired B6 conversion, such as some liver conditions or genetic variants, is a hypothesis rather than a trial finding.

Supported by Trial 1, Trial 2

Neurotransmitter Synthesis

As PLP, vitamin B6 is the cofactor for the enzymes that make serotonin (from 5-HTP), dopamine (from L-DOPA), GABA (from glutamate) and histamine (from histidine). This explains why B6 deficiency can affect mood and nerve function. It does not show that extra B6 lifts mood in people who already get enough.

Supported by Trial 1

Premenstrual symptoms (PMS)

In a systematic review of nine placebo-controlled trials (940 women), vitamin B6 at up to 100 mg/day was more likely than placebo to ease overall premenstrual symptoms and premenstrual low mood, but most were small trials of low quality. In one crossover trial, 50 mg/day helped emotional symptoms only. These trials used pyridoxine, not P-5-P.

Supported by Trial 1, Trial 2

Morning sickness in early pregnancy

In a 342-woman placebo-controlled trial, 30 mg/day pyridoxine for five days eased nausea in early pregnancy, though the drop in vomiting was not statistically significant. Trials of B6 alone have had mixed results, and a systematic review rated the evidence as low quality. ACOG suggests B6 as a first step under a doctor's care. The trials used pyridoxine, not P-5-P.

Supported by Trial 2, Trial 1

Homocysteine Lowering

As PLP, B6 is the cofactor for cystathionine beta-synthase, which clears homocysteine. Adequate B6, folate and B12 help keep homocysteine in the normal range. Lowering this marker is not the same as fewer heart events: a review of 15 randomized trials of B-vitamin homocysteine lowering found no effect on heart attacks or deaths and a small drop in stroke.

Supported by Trial 1

Mechanism of action

1

Coenzyme for more than 100 enzyme reactions

PLP is the cofactor for amino acid transaminases (including ALT and AST, measured in liver blood tests), amino acid decarboxylases (neurotransmitter synthesis), glycogen phosphorylase (glycogen breakdown), delta-aminolevulinate synthase (heme synthesis), cystathionine beta-synthase (homocysteine metabolism) and kynureninase (tryptophan breakdown).

2

Absorption and activation

Phosphorylated B6 forms, including P-5-P, are dephosphorylated in the gut and absorbed as free vitamin by passive diffusion. Cells then use pyridoxal kinase to add the phosphate back, so swallowed P-5-P and pyridoxine end up as the same active coenzyme.

3

Neurotransmitter Decarboxylase Cofactor

Needed to turn 5-HTP into serotonin, L-DOPA into dopamine, glutamate into GABA and histidine into histamine. B6 deficiency can impair these pathways together.

4

Heme Synthesis

PLP is the cofactor for delta-aminolevulinate synthase, the first and rate-limiting step of heme synthesis, which helps explain why B6 deficiency is linked to small-red-cell (microcytic) anemia.

Clinical trials

1
Vitamin B6 for premenstrual symptoms
PubMed

Randomized, double-blind, placebo-controlled crossover trial of pyridoxine 50 mg/day, three months on each treatment (Doll et al. 1989, J R Coll Gen Pract)

63 women aged 18 to 49 with moderate to severe premenstrual symptoms; 32 completed all seven months.

Pyridoxine significantly eased emotional symptoms (depression, irritability and tiredness) compared with placebo. It had no significant effect on physical or menstrual-type symptoms, and a strong placebo response complicated the results. The trial used pyridoxine, not P-5-P.

2
Pyridoxine for nausea in early pregnancy
PubMed

Randomized, double-blind, placebo-controlled trial of pyridoxine hydrochloride 30 mg/day for 5 days (Vutyavanich et al. 1995, Am J Obstet Gynecol)

342 women at 17 weeks of pregnancy or earlier at a university antenatal clinic in Thailand.

Nausea scores fell significantly more with pyridoxine than with placebo (p = 0.0008). Vomiting episodes also fell more, but the difference was not statistically significant (p = 0.0552). The trial used pyridoxine, not P-5-P.

Side effects and drug interactions

Common Potential side effects

Sensory nerve damage (neuropathy) with loss of coordination has been reported with long-term use of 1 to 6 g/day of pyridoxine, and some reports describe it below 500 mg/day; symptoms usually ease if the supplement is stopped early. The US adult upper limit is 100 mg/day, and the European Food Safety Authority set 12 mg/day in 2023.
Skin lesions and sensitivity to sunlight with excessive intakes.
Digestive upset, such as nausea and heartburn, with excessive intakes.

Important Drug interactions

Levodopa: pyridoxine can reduce how well levodopa works; check with your prescriber before taking B6.
Phenytoin and phenobarbital: 200 mg/day of pyridoxine has lowered blood levels of these drugs; phenytoin, carbamazepine and valproate can also lower B6 status.
Isoniazid: long-term use can cause nerve damage that pyridoxine helps prevent, so B6 is often given alongside it.
Cycloserine: increases urinary loss of B6; pyridoxine can help limit its nerve side effects.
Theophylline: people taking it often have low PLP levels.
Oral contraceptives: these steroid hormones can interfere with vitamin B6 metabolism.

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Frequently asked questions about P-5-P (Pyridoxal-5-Phosphate / Active B6)

What is P-5-P (pyridoxal-5-phosphate)?

P-5-P is the coenzyme form of vitamin B6. When swallowed, it is broken down to free B6 in the gut and turned back into P-5-P inside cells, the same end point as regular pyridoxine.

Is P-5-P better than regular vitamin B6?

For most people no clear difference has been shown. Both forms become the same active coenzyme in the body. Pyridoxine is cheaper and is the form used in the PMS and pregnancy nausea trials. Some people simply prefer P-5-P.

How much P-5-P should I take?

Adults need about 1.3 to 1.7 mg of B6 a day (1.9 mg in pregnancy), and supplements usually provide much more. Long-term high doses can damage nerves, whatever the form. The US adult upper limit is 100 mg a day, and European regulators set a lower limit of 12 mg a day in 2023; ask a doctor before going higher.

What is P-5-P used for?

Like vitamin B6 in general, it supports amino acid metabolism, neurotransmitter production and hemoglobin formation. Controlled trials of pyridoxine support its use for premenstrual mood symptoms and nausea in early pregnancy. Claims about mood in general rest on its role in brain chemistry rather than on mood trials.

What is P-5-P?

P-5-P (pyridoxal 5'-phosphate, PLP) is the coenzyme form of vitamin B6, which takes part in more than 100 enzyme reactions, mostly in protein and amino acid metabolism. Swallowed P-5-P is not absorbed intact: the gut removes the phosphate group, the free vitamin is absorbed, and cells add the phosphate back.

Is P-5-P safe, and does it have side effects?

Side effects and cautions reported for P-5-P include: Sensory nerve damage (neuropathy) with loss of coordination has been reported with long-term use of 1 to 6 g/day of pyridoxine, and some reports describe it below 500 mg/day; symptoms usually ease if the supplement is stopped early. It may also interact with some medications. P-5-P is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does P-5-P interact with any medications?

Possible interactions include: Levodopa: pyridoxine can reduce how well levodopa works; check with your prescriber before taking B6. Phenytoin and phenobarbital: 200 mg/day of pyridoxine has lowered blood levels of these drugs; phenytoin, carbamazepine and valproate can also lower B6 status. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for P-5-P?

NutraSmarts rates the evidence for P-5-P as Moderate (3 out of 5). It is backed by 2 study summaries and 10 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(10 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Doll H, Brown S, Thurston A, Vessey M. Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial. J R Coll Gen Pract. 1989;39(326):364-8..PubMedUsed to support: Randomized double-blind crossover trial in 63 women (32 completed): 50 mg/day pyridoxine significantly eased emotional premenstrual symptoms (depression, irritability, tiredness) versus placebo but not physical or menstrual symptoms. Used pyridoxine, not P-5-P.
  2. Kashanian M, Mazinani R, Jalalmanesh S, Babayanzad Ahari S. Pyridoxine (vitamin B6) therapy for premenstrual syndrome. Int J Gynaecol Obstet. 2007;96(1):43-4. doi: 10.1016/j.ijgo.2006.09.014.PubMedUsed to support: Randomized controlled trial of pyridoxine for premenstrual syndrome; PubMed lists no abstract. As summarized by the NIH Office of Dietary Supplements, 80 mg/day for three cycles in 94 women significantly reduced a range of PMS symptoms, especially anxiety. Used pyridoxine, not P-5-P.
  3. Kwan I, Onwude JL. Premenstrual syndrome. BMJ Clin Evid. 2007;2007:0806..PubMedUsed to support: BMJ Clinical Evidence systematic review of premenstrual syndrome treatments (52 studies, GRADE-rated) whose list of interventions includes pyridoxine. Context only.
  4. Vutyavanich T, Wongtra-ngan S, Ruangsri R. Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol. 1995;173(3 Pt 1):881-4. doi: 10.1016/0002-9378(95)90359-3.PubMedUsed to support: Randomized double-blind trial in 342 women at 17 weeks of pregnancy or earlier: 30 mg/day pyridoxine for 5 days reduced nausea scores more than placebo (p = 0.0008); the reduction in vomiting was not statistically significant (p = 0.0552).
  5. McParlin C, O'Donnell A, Robson SC, Beyer F, Moloney E, Bryant A, Bradley J, Muirhead CR, Nelson-Piercy C, Newbury-Birch D, Norman J, Shaw C, Simpson E, Swallow B, Yates L, Vale L. Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A Systematic Review. JAMA. 2016;316(13):1392-1401. doi: 10.1001/jama.2016.14337.PubMedUsed to support: JAMA systematic review of 78 studies: for mild nausea and vomiting of pregnancy, pyridoxine (vitamin B6) was associated with greater benefit than placebo; the authors rated the overall quality of evidence as low.
  6. Wyatt KM, Dimmock PW, Jones PW, Shaughn O'Brien PM. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. BMJ. 1999;318(7195):1375-81. doi: 10.1136/bmj.318.7195.1375.PubMedUsed to support: Systematic review of nine published placebo-controlled trials (940 women): vitamin B6 improved overall premenstrual symptoms (odds ratio 2.32) and premenstrual depressive symptoms (odds ratio 1.69, four trials) more than placebo. The authors noted that most trials were of low quality.
  7. Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2017;8(8):CD006612. doi: 10.1002/14651858.CD006612.pub5.PubMedUsed to support: Pooled analysis of 15 randomized trials (71,422 participants) of B-vitamin homocysteine lowering: no effect on heart attack (RR 1.02) or death from any cause (RR 1.01), and a small reduction in stroke (RR 0.90, 95% CI 0.82 to 0.99).
  8. Ebadi M, Gessert CF, Al-Sayegh A. Drug-pyridoxal phosphate interactions. Q Rev Drug Metab Drug Interact. 1982;4(4):289-331. doi: 10.1515/dmdi.1982.4.4.289.PubMedUsed to support: Review of drug and vitamin B6 interactions: pyridoxine can reduce the effect of levodopa, and pyridoxine prevents the peripheral neuropathy caused by long-term isoniazid.
  9. Bhagavan HN, Brin M. Drug--vitamin B6 interaction. Curr Concepts Nutr. 1983;12:1-12..PubMedUsed to support: Review: several drug types interfere with vitamin B6 metabolism, most by binding PLP; steroid hormones such as oral contraceptives act by stimulating B6-dependent pathways and competing with PLP.
  10. Office of Dietary Supplements, National Institutes of Health. Vitamin B6: Fact Sheet for Health Professionals. NIH Office of Dietary Supplements. 2023;Updated June 16, 2023. Not PubMed-indexed..SourceUsed to support: Not PubMed-indexed. NIH fact sheet: B6 coenzymes take part in more than 100 enzyme reactions; phosphorylated forms are dephosphorylated before absorption; adult RDA 1.3 to 1.7 mg (1.9 mg in pregnancy) and US upper limit 100 mg/day, with EFSA's 2023 adult upper limit of 12 mg/day also noted; neuropathy with long-term 1 to 6 g/day; ACOG recommends 10 to 25 mg three or four times a day for nausea and vomiting of pregnancy, while B6-alone trials have had mixed results; summarizes the 94-woman 80 mg/day PMS trial; HOPE 2 lowered stroke risk about 25%; interactions with cycloserine, antiepileptic drugs and theophylline.