Pyridoxal phosphate or P-5-P is the active form of vitamin B6 that drives over 100 enzyme reactions in your body, especially when you’re under stress. As a supplement, P-5-P promises to deliver greater benefits with fewer side effects. Read on to learn if pyridoxal phosphate is for you.

What is Pyridoxal Phosphate (P-5-P)?

One Vitamin, Many Roles

Pyridoxal-5’-phosphate (PLP, P-5-P) is an active form of vitamin B6. This all-around vitamin enables the metabolism of amino acids, carbs, and lipids in your body. It’s involved in [1, 2]:

  • Supporting the immune system
  • Controlling blood glucose
  • Creating hemoglobin
  • Enhancing antioxidant defense

Along with vitamin B12 and folate, vitamin B6 also helps break down homocysteine and thus protects your heart, brain, and reproductive health [3, 4, 5].

Vitamin B6 has a profound effect on cognition and mental health. Low vitamin B6 status can lower your brain’s production of serotonin and GABA – two neurotransmitters that control mood, pain perception, and anxiety. For this reason, it’s essential if you’re under stress [6, 7].

A variety of foods, such as meat, fish, nuts, grains, and vegetables contain vitamin B6. You can get enough of it from food, but supplements will provide much higher doses when you need them [8].

Your body converts vitamin B6 (pyridoxine) from food and supplements into active pyridoxal phosphate in the liver.

Supplements with active P-5-P are supposed to be more efficient as they don’t require conversion, but the available research is limited.

Vitamin B6 supports your heart, immunity, mental health, and cognition. Pyridoxal phosphate (P-5-P) is a popular supplement that contains an active form of this vitamin.

Snapshot

PROs

  • Doesn’t require metabolic conversion
  • May be safer and more efficient than pyridoxine
  • Better for infantile seizures and sideroblastic anemia
  • May cut the risk of a heart attack

CONs

  • Not well studied in humans
  • Causes digestive issues in some patients
  • May suppress the pituitary gland
  • Not suitable for pregnant women

Metabolism

“Vitamin B6” refers to six compounds with similar roles and structures. The first three are [9]:

  • Pyridoxine (PN)
  • Pyridoxal (PL)
  • Pyridoxamine (PM)

Their 5′-phosphates make up the remaining three:

  • Pyridoxine-5′-phosphate (PNP)
  • Pyridoxal-5′-phosphate (PLP or P-5-P)
  • Pyridoxamine-5′-phosphate (PMP)

These are so-called pyridoxine vitamers. They all play unique roles, and your body can switch between them as needed. That said, only pyridoxal phosphate is an active coenzyme that drives over 140 enzyme reactions [10, 11].

The active form is responsible for the health benefits, and its blood levels are the best lab marker of vitamin B6 status [12].

The two liver enzymes that shift other forms into pyridoxal phosphate are pyridoxal (PL) kinase and pyridoxine-5’-phosphate (PNP) oxidase [13, 14].

Genetic defects in these enzymes reduce pyridoxal phosphate levels and may have a detrimental impact on your health. PLP supplementation is vital in such cases, and we’ll discuss them later in this text.

Vitamin B6 exists in six different forms, of which only pyridoxal phosphate (P5P) is active. Your body converts other forms into PLP, but certain genetic defects can hinder this process.

P-5-P Benefits

For the most part, pyridoxal phosphate has the same benefits as other vitamin B6 supplements with pyridoxine hydrochloride (HCl).

What Lowers Your Levels?

Low blood levels of pyridoxal phosphate are present in numerous chronic diseases such as:

Optimal vitamin B6 intake from food and supplements (including P-5-P) restores the levels and may lower the risk of these conditions.

Role in Anxiety & Sleep

Older studies reported low blood levels in people with anxiety, but newer studies debunked them. People with depression have low B6 levels, and this might explain why supplementing with vitamin B6 also reduces anxiety in people with depression [37, 38].

P5P is needed for the production of melatonin, also known as the sleep hormone. Research hasn’t found a direct link between P-5-P levels and insomnia, but taking vitamin B6 before bed increased melatonin release from the pineal gland in children [39, 40, 41].

Impact on Brain Cells

P-5-P drives the activity of over 100 enzymes in your body. It’s especially important for brain health. Enzymes that create the following neurotransmitters need P-5-P to work [42]:

Whether or not supplemental P-5-P reaches the brain and affects these neurotransmitters in humans is still unknown.

Effects on Prolactin

Once vitamin B6 is converted to P-5-P, it increases dopamine in the brain. The rise in dopamine lowers prolactin [46].

Bodybuilders report benefits from P-5-P during or after cycles. Anecdotally, it helps them with gynecomastia by lowering prolactin levels. Some prefer it over taking L-DOPA.

One small pilot study suggests they might be right. In six healthy people, vitamin B6 infusions before exercise increased growth hormone levels and decreased prolactin levels, compared with placebo [46].

However, this study was conducted back in 1982. It used vitamin B6, not P-5-P and no newer research has replicated its findings. In a recent study on mice cells, P-5-P lowered both prolactin and growth hormone. It’s hard to say how these cell-based findings translate to humans [47].

With this in mind, you may want to look into better-researched natural supplements for lowering prolactin levels.

Until more studies are out, it’s hard to say whether using P-5-P (or vitamin B6) to lower prolactin works or not.

Reasons to Supplement

Different conditions may deplete your vitamin B6, triggering nerve damage and other deficiency symptoms. Experts suggest preventive supplementation in people with digestive disorders (celiac disease and IBD), malnutrition, alcohol dependence, and kidney failure [48, 49, 50, 51, 27].

According to clinical trials, vitamin B6 supplementation may also help with:

  • Nausea and vomiting during pregnancy [52]
  • Diabetes [53, 54]
  • Breast pain and migraines (usually PMS-related) [55, 56, 57]
  • Premenstrual syndrome* [58, 59, 60]
  • Nerve disorders (pain, numbness, tingling) [61, 62]
  • Atherosclerosis [63]
  • Some symptoms of brain damage in autism* [37, 64, 65]
  • Sideroblastic anemia [66, 67]
    *combined with magnesium

Additionally, animal studies suggest it improves coping with high stress. Plus, the whole group of B vitamins lowered work-related stress and burnout in a clinical trial of 200 people [6, 68].

Vitamin B6 supplements such as P-5-P may also prevent deficiency caused by the following drugs [69, 1, 70, 71]:

  • NSAIDs
  • Antiepileptics (seizure medications)
  • Antibiotics (penicillamine)
  • Drugs for tuberculosis (isoniazid, cycloserine)
Vitamin B6 supplements such as P-5-P may help with migraines, diabetes, nerve disorders, and premenstrual syndrome. They can also prevent deficiency caused by some drugs and diseases.

P-5-P Advantages Over Vitamin B6

1) Doesn’t Require Conversion

Pyridoxal phosphate supplements provide the active form of vitamin B6, which doesn’t require conversion in your liver. Some people have a reduced conversion rate and don’t get expected results from standard vitamin B6 supplements (pyridoxine HCl).

The following may inhibit the enzymes that convert other forms into active P-5-P [8, 72, 73]:

  • Genetic mutations
  • Antiseizure drugs
  • Drugs for asthma (xanthines)
  • Liver disease

In 17 patients with liver disease, treatment with pyridoxal phosphate increased plasma P-5-P levels better than an equal amount of pyridoxine HCl. The study had a tiny sample and used intravenous therapy, so we can’t draw definite conclusions [74].

Drugs, genetic defects, and liver disease hinder the conversion of vitamin B6 into active P-5-P. Liver disease patients may get better results from P-5-P, but the evidence is scarce.

2) Protects the Heart

Sudden changes in blood flow can trigger oxidative stress and calcium overload, resulting in heart damage. Pyridoxal phosphate was able to prevent heart injury in animals [75, 76].

In 900 patients undergoing bypass surgery, P-5-P cut the risk of a heart attack by 30-40%. However, it didn’t reduce mortality and the risk of stroke [77].

The same clinical trial included over 3K patients in the next phase and failed to confirm the benefits of pyridoxal phosphate [78].

Pyridoxal phosphate may prevent heart injury and cut the risk of a heart attack, but a large clinical trial failed to confirm this.

3) Better for Vitamin B6-Dependent Seizures

The lack of vitamin B6 can cause severe neurological damage right after birth; it usually results in seizures, known as vitamin B6-dependent epilepsy [79, 72, 80].

A rare type of this disorder is so-called PLP-dependent epilepsy. It occurs due to mutations in the pyridoxine-5’-phosphate oxidase (PNPO) gene. These patients require large doses of PLP as the liver can’t produce it from pyridoxine [81, 82].

Prompt treatment with PLP can prevent permanent brain damage and death [83, 82, 84].

Some authors have successfully treated other types of seizures with vitamin B6, and they have reported better results with PLP compared with pyridoxine [80, 85].

Pyridoxal phosphate (PLP) is the only effective treatment for rare PLP-dependent seizures in newborns. It may also give better results than pyridoxine for other types of seizures.

4) May Be Better for Sideroblastic Anemia

In sideroblastic anemia, the bone marrow produces defective cells with iron rings (sideroblasts) instead of healthy red blood cells, causing a drop in hemoglobin levels. It can be acquired (due to vitamin B6 deficiency or alcoholism) or inborn [86].

Treatment with vitamin B6 is successful only in 40-80% of cases. In general, acquired cases respond better [87, 88].

Some of these patients don’t convert pyridoxine to P-5-P well, which may explain the partial response to pyridoxine supplementation.

One older woman with sideroblastic anemia experienced rapid improvement from P-5-P supplementation, even though she previously failed to respond to pyridoxine [89].

One patient with pyridoxine-responsive anemia improved better with 50 mg of P-5-P than with 300 mg of pyridoxine. According to the authors, some patients with this condition lack pyridoxal-kinase, an enzyme that converts pyridoxal into active P-5-P [90].

That said, we can’t draw reliable conclusions from individual case reports. Well-designed clinical trials should verify the benefits of P-5-P for sideroblastic anemia.

Vitamin B6 helps with sideroblastic anemia, but some patients can’t convert it to active pyridoxal phosphate. P-5-P might give better results, though the research is far from conclusive.

5) May Be Safer Than Pyridoxine

High doses of pyridoxine from supplements inhibit the enzymes that convert it to P-5-P, which may drop P-5-P levels and lead to nerve damage. Pyridoxal phosphate didn’t show this effect in test tubes [91].

As the active form, P-5-P may achieve the same effects in much lower doses compared with pyridoxine, but the evidence for this is limited [90].

P-5-P Side Effects & Toxicity

Prolonged supplementation with high doses of pyridoxine can result in [1, 8, 72]:

  • Nerve damage
  • Movement disorders
  • Skin lesions

High vitamin B6 doses may tell the body it has too much of this vitamin. In turn, enzymes that convert vitamin B6 to P-5-P are blocked, reducing P-5-P levels [91].

The conversion step is bypassed with P-5-P, but its long-term safety remains unknown [91].

Additionally, P-5-P may cause digestive side effects such as [92, 78, 77]:

  • Vomiting
  • Diarrhea
  • Stomach cramps

Doctors had to withdraw P-5-P in some newborns with severe digestive issues. It also increased liver enzymes in newborns with no apparent symptoms [92].

Pyridoxine inhibited the pituitary gland and caused a slight drop in prolactin in 2 smaller clinical trials. In a study on mice cells, pyridoxal phosphate suppressed [93, 94, 47]:

The safe upper limit for pyridoxine is 100 mg daily while there’s no established limit for P-5-P. Pregnant women should avoid P-5-P until we know more about its safety [95].

Pyridoxal phosphate may cause vomiting, diarrhea, and stomach pain.

P-5-P Dosage & Supplements

How Much Should You Take?

In the largest clinical trial to date, pyridoxal phosphate dosage of 250 mg/day (for 30 days) was safe, but it had limited efficacy. A higher dosage (750 mg/day) provided no further benefits [78, 77].

Lower doses (50 mg) may be sufficient for sideroblastic anemia. That said, you should seek medical attention ASAP if you suspect a vitamin B6-dependent disorder; most of them require strict medical supervision [90, 83, 92].

Supplements

Supplements usually contain pills with 25-100 mg of P-5-P. Bulk powders are also available.

Some manufacturers suggest dissolving the pills in water and consuming the liquid. The P-5-P content and stability of the liquid may vary, depending on the manufacturer. Make sure to choose reliable brands and follow your product’s instructions carefully [96].

User Experiences

People use pyridoxal phosphate to combat breast pain due to PMS (cyclical mastalgia), nerve disorders, fatigue, and anxiety. Most of them have reported positive experiences.

Just like pyridoxine, P-5-P seems to make dreams more real and vivid.

Some users complain of dizziness, insomnia, and upset stomach from P-5-P supplements.

Supplements contain pills with 25-100 mg of P-5-P. People use them for nerve disorders, fatigue, and anxiety.

Is P5P Right For You?

If you’re unsure about which vitamins and minerals you need more or less of, check out our Vitamin and Mineral DNA Wellness reports. These reports tell you if you’re genetically more or less predisposed to have a vitamin or mineral deficiency. We also give personalized recommendations to fix these deficiencies when they occur.

If you’re interested in natural and more targeted ways of improving your mood, we at SelfHacked recommend checking out this mood DNA wellness report. It gives genetic-based diet, lifestyle and supplement tips that can help improve your mood. The recommendations are personalized based on your genes.

SelfDecode is a sister company of SelfHacked.

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Takeaway

Pyridoxal phosphate (P-5-P or PLP) is an active form of vitamin B6, which supports your immune system, heart and brain health, blood sugar control, hemoglobin formation, and more.

P-5-P drives the activity of over 100 enzymes in your body, including those that make key neurotransmitters in your brain.

Vitamin B6 may help in times of high stress and fatigue. It is also beneficial for nausea during pregnancy, migraines, diabetes, nerve disorders, and premenstrual syndrome.

Taking P-5-P delivers the active B6 form to your body. People with liver disease and genetic mutations can’t convert vitamin B6 into the active form, and they may need P-5-P supplements.

Other people may benefit from P-5-P as well, but the research is limited. P-5-P side effects are mild and typically include digestive issues.

About the Author

Aleksa Ristic, MSc (Pharmacy)

MS (Pharmacy)

Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.

 

Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

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