Pyridoxal Phosphate (P-5-P) Benefits, Dosage & Side Effects

Pyridoxal phosphate or P-5-P is the active form of vitamin B6, a crucial nutrient for physical and mental health. As a supplement, P-5-P is promoted to deliver greater benefits with fewer side effects, but there’s no clinical evidence to back this up. Read on to learn everything about pyridoxal phosphate.

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 B1 2 and folate, vitamin B6 also helps break down homocysteine and thus protects your heart, brain, and reproductive health [3, 4, 5].

Vitamin B6 is a crucial nutrient for 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 [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 promoted 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 but poorly researched supplement that contains an active form of this vitamin.

Snapshot

Proponents:

Doesn’t require metabolic conversion
May be more efficient than pyridoxine
May be better for some types of infantile seizures
May be better for sideroblastic anemia

Skeptics:

Not well studied in humans
Causes digestive issues in some patients
May suppress prolactin and growth hormone
May not be safe 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 effects, 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 might be 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 P5P, but certain genetic defects can hinder this process.

P-5-P Health Effects

Important notes:

The proven health effects of vitamin B6 as a nutrient don’t necessarily mean that pyridoxine or P-5-P supplements would have the same benefits
Pyridoxine is the only well-researched form of vitamin B6 supplements. Its effects may or may not translate to P-5-P and other forms

What Lowers It?

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

Inflammatory and autoimmune disorders (IBD, rheumatoid arthritis) [15, 16, 17]
Heart disease [18, 19, 20]
Depression [21, 22, 23]
Dementia and cognitive impairment [24, 25]
Chronic fatigue syndrome [26]
Diabetes (type 1 and 2) [27, 28, 29]
Lung and colorectal cancer [30, 31, 32, 33]
Osteoporosis [34, 35]
Panic attacks [36]

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 B6 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 reduced anxiety in people with depression in some clinical trials [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 a study of 120 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 optimal levels of P-5-P to work [42]:

Dopamine, which controls motivation, attention, and feelings of pleasure
Norepinephrine, which improves mood and cognition function
Serotonin, the “happiness neurotransmitter”
GABA, the mind’s natural calmness signal
Acetylcholine, the driver of rest-and-digest activity that also boosts cognition

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 [43].

Bodybuilders report benefits from P-5-P during or after cycles. Anecdotally, it helps prevent gynecomastia (abnormal breast growth) by lowering prolactin levels. Some prefer it over taking L-DOPA.

One 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 [43].

However, this study:

Had a tiny sample.
Was conducted back in 1982. and no newer research has replicated its findings.
Used vitamin B6, not P-5-P.

In a recent study on mice and cells, P-5-P lowered both prolactin and growth hormone. It’s hard to say how these cell-based findings translate to humans [44].

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

Potential Benefits

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 [45, 46, 47, 48, 27].

Vitamin B6 supplementation may help with:

Nausea and vomiting during pregnancy [49]
Premenstrual syndrome* [50, 51, 52]
Atherosclerosis [53]
Sideroblastic anemia [54, 55]
Vitamin B6-dependent seizures [56, 57, 58]
*combined with magnesium

It may also prevent deficiency caused by the following drugs [59, 1, 60, 61]:

NSAIDs
Antiepileptics (seizure medications)
Antibiotics (penicillamine)
Drugs for tuberculosis (isoniazid, cycloserine)

Vitamin B6 supplements such as P-5-P may help with nausea, premenstrual syndrome, atherosclerosis, and anemia. They can also prevent deficiency caused by some drugs and diseases.

P-5-P Potential Advantages Over Vitamin B6

Insufficient Evidence:

No valid clinical evidence supports the potential P-5-P advantages in this section. Below is a summary of up-to-date animal studies, cell-based research, or low-quality clinical trials which should spark further investigation. However, you shouldn’t interpret them as supportive of any health benefit.

1) Doesn’t Require Conversion

Pyridoxal phosphate is 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, 57, 62]:

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 [63].

Since it doesn’t require metabolic activation, pyridoxal phosphate is promoted as a safer and more effective alternative to vitamin B6 supplements. However, well-designed clinical trials have yet to investigate its therapeutic value.

Drugs, genetic defects, and liver disease hinder the conversion of vitamin B6 into active P-5-P. Some people might get better results from P-5-P supplements, but the evidence is scarce.

2) May Be Better for Some Forms of 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. Intravenous pyridoxine is the treatment of choice and can be lifesaving [56, 57, 58].

A rare subtype of this disorder is so-called PLP-dependent epilepsy. It occurs due to mutations in the pyridoxine-5’-phosphate oxidase (PNPO). These patients require large doses of PLP as the liver can’t produce it from pyridoxine [64, 65].

According to multiple case reports, prompt treatment with PLP can prevent permanent brain damage and death [66, 65, 67].

Some authors have successfully treated other types of seizures with vitamin B6, and they have reported better results with PLP compared with pyridoxine [58, 68].

We can’t make conclusions based on these case reports. Further studies should evaluate the safety and efficacy of PLP for vitamin B6-dependent seizures.

Pyridoxal phosphate (PLP) seems to be the only effective treatment for rare PLP-dependent seizures in newborns. It may also give better results than pyridoxine for other types of seizures, but the available evidence is scant.

3) 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 [69].

Vitamin B6 is an approved treatment for this condition, but, according to some stats, it’s successful only in 40-80% of cases. In general, acquired cases respond better [70, 71].

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 [72].

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 [73].

That said, we can’t draw reliable conclusions from individual case reports. Well-designed clinical trials should investigate the benefits of P-5-P for sideroblastic anemia. Work with your doctor to get an optimal treatment.

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.

P-5-P Side Effects & Toxicity

This list does not cover all possible side effects. Contact your doctor or pharmacist if you notice any other side effects. In the US, you may report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.

Pyridoxine is likely safe when taken in recommended amounts. However, prolonged supplementation with high doses (>1000 mg/day) can result in [1, 8, 57]:

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 [74].

The conversion step is bypassed with P-5-P, but its long-term safety remains unknown [74].

Additionally, P-5-P may cause digestive side effects such as [75, 76, 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 [75].

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 [78, 79, 44]:

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 [80].

In rare cases, pyridoxal phosphate may cause vomiting, diarrhea, and stomach pain. There’s not enough clinical data to evaluate its long-term safety.

P-5-P Dosage & Supplements

Unlike pyridoxine, P-5-P has not been approved by the FDA for medical use. In general, regulatory bodies aren’t assuring the quality, safety, and efficacy of supplements. Speak with your doctor before supplementing.

Dosage

The below doses may not apply to you personally. If your doctor suggests using a P-5-P supplement, work with them to find the optimal dosage according to your health condition and other factors.

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 [76, 77].

Lower doses (50 mg) may be sufficient for sideroblastic anemia. That said, you should seek medical attention ASAP if you suspect any vitamin B6-dependent disorder; most of them require strict medical supervision [73, 66, 75].

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 [81].

User Experiences & Reviews

The opinions expressed in this section are solely from the users who may or may not have a medical background. Their reviews do not represent the opinions of SelfHacked. SelfHacked does not endorse any specific product, service, or treatment.

Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice from your doctor or another qualified healthcare provider because of something you have read on SelfHacked.

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.

Takeaway

Pyridoxal phosphate (P-5-P or PLP) is an active form of vitamin B6, a nutrient that supports the immune system, heart and brain health, blood sugar control, and more. P-5-P drives the activity of over 100 enzymes and helps make key neurotransmitters in the brain.

Vitamin B6 supplements may help with nausea during pregnancy, sideroblastic anemia, atherosclerosis, vitamin B6-dependent seizures, and premenstrual syndrome.

Taking P-5-P delivers the active B6 form to your body. People with liver disease and rare genetic disorders can’t convert vitamin B6 into the active form and may thus need P-5-P supplements. The therapeutic potential of P-5-P in the general population is not well researched.

P-5-P side effects are mild and typically include digestive issues. Pregnant women should avoid it just in case, while others should consult with their doctor before supplementing.