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\u2019s no clinical evidence to back this up. Read on to learn everything about pyridoxal phosphate.<\/p>\n
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Pyridoxal-5\u2019-phosphate (PLP, P-5-P)<\/b> is an active form of vitamin B6<\/a>. This all-around vitamin enables the metabolism of amino acids, carbs, and lipids in your body. It\u2019s involved in [R<\/a>, R<\/a>]:<\/p>\n Along with vitamin<\/a> B1<\/a>2<\/a> and folate<\/a>, vitamin B6 also helps break down homocysteine<\/a> and thus protects your heart, brain, and reproductive health [R<\/a>, R<\/a>, R<\/a>].<\/p>\n Vitamin B6 is a crucial nutrient for cognition and mental health<\/b>. Low vitamin B6 status can lower your brain\u2019s production of serotonin<\/a> and GABA<\/a> – two neurotransmitters that control mood, pain perception, and anxiety [R<\/a>, R<\/a>].<\/p>\n A variety of foods, such as meat, fish, nuts, grains, and vegetables<\/b> contain vitamin B6. You can get enough of it from food, but supplements will provide much higher doses when you need them [R<\/a>].<\/p>\n 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\u2019t require conversion, but the available research is limited<\/b>.<\/p>\n \u201cVitamin B6\u201d refers to six compounds with similar roles and structures. The first three are [R<\/a>]:<\/p>\n Their 5\u2032-phosphates make up the remaining three:<\/p>\n These are so-called pyridoxine vitamers<\/i>. They all play unique roles, and your body can switch between them as needed. That said, only pyridoxal phosphate is an active coenzyme <\/b>that drives over 140 enzyme reactions [R<\/a>, R<\/a>].<\/p>\n The active form is responsible for the health effects, and its blood levels are the best lab marker of vitamin B6 status [R<\/a>].<\/p>\n The two liver enzymes that shift other forms into pyridoxal phosphate are pyridoxal (PL) kinase<\/a> and pyridoxine-5\u2019-phosphate (PNP) oxidase<\/a> [R<\/a>, R<\/a>].<\/p>\n Genetic defects<\/b> 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\u2019ll discuss them later in this text.<\/p>\n Important notes<\/b>:<\/p>\n Low blood levels of pyridoxal phosphate are present in numerous chronic diseases such as:<\/p>\n Optimal vitamin B6 intake from food and supplements (including P-5-P) restores the levels and may lower the risk of these conditions.<\/p>\n 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<\/a> in people with depression in some clinical trials [R<\/a>, R<\/a>].<\/p>\n P5P is needed for the production of melatonin<\/a>, also known as the sleep hormone<\/i>. Research hasn\u2019t found a direct link between P-5-P levels and insomnia<\/a>, but taking vitamin B6 before bed increased melatonin release from the pineal gland in a study of 120 children [R<\/a>, R<\/a>, R<\/a>].<\/p>\n P-5-P drives the activity of over 100 enzymes in your body. It\u2019s especially important for brain health. Enzymes that create the following neurotransmitters need optimal levels of P-5-P to work [R<\/a>]:<\/p>\n Whether or not supplemental P-5-P reaches the brain and affects these neurotransmitters in humans is still unknown.<\/b><\/p>\n Once vitamin B6 is converted to P-5-P, it increases dopamine in the brain. The rise in dopamine lowers prolactin<\/a> [R<\/a>].<\/p>\n 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<\/a>.<\/p>\n One pilot study suggests they might be right. In six healthy people, vitamin B6 infusions before exercise increased growth hormone<\/a> levels and decreased prolactin levels, compared with placebo [R<\/a>].<\/p>\n However, this study:<\/p>\n In a recent study on mice and cells, P-5-P lowered both prolactin and growth hormone. It\u2019s hard to say how these cell-based findings translate to humans [R<\/a>].<\/p>\n Different conditions may deplete your vitamin B6, triggering nerve damage and other deficiency symptoms. Experts suggest preventive<\/i> supplementation in people with digestive disorders (celiac disease and IBD), malnutrition, alcohol dependence, and kidney failure [R<\/a>, R<\/a>, R<\/a>, R<\/a>, R<\/a>].<\/p>\n Vitamin B6 supplementation may help with:<\/p>\n It may also prevent deficiency caused by the following drugs [R<\/a>, R<\/a>, R<\/a>, R<\/a>]:<\/p>\n 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\u2019t interpret them as supportive of any health benefit.<\/i><\/p>\n 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).<\/p>\n The following may inhibit the enzymes that convert other forms into active P-5-P [R<\/a>, R<\/a>, R<\/a>]:<\/p>\n 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 [R<\/a>].<\/p>\n Since it doesn\u2019t 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.<\/p>\n 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 [R<\/a>, R<\/a>, R<\/a>].<\/p>\n A rare subtype of this disorder is so-called PLP-dependent epilepsy<\/b>. It occurs due to mutations in the pyridoxine-5\u2019-phosphate oxidase (PNPO)<\/i>. These patients require large doses of PLP as the liver can\u2019t produce it from pyridoxine [R<\/a>, R<\/a>].<\/p>\n According to multiple case reports, prompt treatment with PLP can prevent permanent brain damage and death [R<\/a>, R<\/a>, R<\/a>].<\/p>\n Some authors have successfully treated other types of seizures with vitamin B6, and they have reported better results with PLP compared with pyridoxine [R<\/a>, R<\/a>].<\/p>\n We can\u2019t make conclusions based on these case reports. Further studies should evaluate the safety and efficacy of PLP for vitamin B6-dependent seizures.<\/b><\/p>\n In sideroblastic anemia, the bone marrow produces defective cells with iron rings (sideroblasts) instead of healthy red blood cells<\/a>, causing a drop in hemoglobin levels. It can be acquired<\/b> (due to vitamin B6 deficiency or alcoholism) or inborn<\/b> [R<\/a>].<\/p>\n Vitamin B6 is an approved treatment for this condition, but, according to some stats, it\u2019s successful only in 40-80% of cases<\/b>. In general, acquired cases respond better [R<\/a>, R<\/a>].<\/p>\n Some of these patients don\u2019t convert pyridoxine to P-5-P well, which may explain the partial response to pyridoxine supplementation.<\/p>\n One older woman with sideroblastic anemia experienced rapid improvement from P-5-P supplementation, even though she previously failed to respond to pyridoxine [R<\/a>].<\/p>\n 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<\/i>, an enzyme that converts pyridoxal into active P-5-P [R<\/a>].<\/p>\n That said, we can\u2019t 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.<\/b><\/p>\n 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 <\/i>www.fda.gov\/medwatch<\/i><\/a>. In Canada, you may report side effects to Health Canada at 1-866-234-2345.<\/i><\/p>\n Pyridoxine is likely safe when taken in recommended amounts. However, prolonged supplementation with high doses (>1000 mg\/day) can result in [R<\/a>, R<\/a>, R<\/a>]:<\/p>\n High vitamin B6 doses may tell the body it has too much<\/i> of this vitamin. In turn, enzymes that convert vitamin B6 to P-5-P are blocked, reducing P-5-P levels [R<\/a>].<\/p>\n The conversion step is bypassed with P-5-P, but its long-term safety remains unknown [R<\/a>].<\/p>\n Additionally, P-5-P may cause digestive side effects<\/b> such as [R<\/a>, R<\/a>, R<\/a>]:<\/p>\n Doctors had to withdraw P-5-P in some newborns with severe digestive issues. It also increased liver enzymes<\/b> in newborns with no apparent symptoms [R<\/a>].<\/p>\n Pyridoxine inhibited the pituitary gland and caused a slight drop in prolactin<\/a> in 2 smaller clinical trials. In a study on mice cells, pyridoxal phosphate suppressed [R<\/a>, R<\/a>, R<\/a>]:<\/p>\n The safe upper limit for pyridoxine is 100 mg daily while there\u2019s no established limit for P-5-P. Pregnant women should avoid P-5-P until we know more about its safety<\/b> [R<\/a>].<\/p>\n Unlike pyridoxine, P-5-P has not been approved by the FDA for medical use. In general, regulatory bodies aren\u2019t assuring the quality, safety, and efficacy of supplements. Speak with your doctor before supplementing.<\/i><\/p>\n 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.<\/i><\/p>\n In the largest clinical trial to date, pyridoxal phosphate dosage of 250 mg\/day<\/b> (for 30 days) was safe, but it had limited efficacy. A higher dosage (750 mg\/day) provided no further benefits [R<\/a>, R<\/a>].<\/p>\n 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<\/b> [R<\/a>, R<\/a>, R<\/a>].<\/p>\n\n
Snapshot<\/b><\/span><\/h3>\n
Proponents:<\/b><\/h4>\n
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Skeptics:<\/b><\/h4>\n
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Metabolism<\/b><\/span><\/h3>\n
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P-5-P Health Effects<\/b><\/span><\/h2>\n
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What Lowers It?<\/b><\/span><\/h3>\n
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Role in Anxiety & Sleep<\/b><\/span><\/h3>\n
Impact on Brain Cells<\/b><\/span><\/h3>\n
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Effects on Prolactin<\/b><\/span><\/h3>\n
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Potential Benefits<\/b><\/span><\/h3>\n
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\n*<\/b>combined with magnesium<\/a><\/li>\n<\/ul>\n\n
P-5-P Potential Advantages Over Vitamin B6<\/b><\/span><\/h2>\n
Insufficient Evidence:<\/span><\/h3>\n
1) Doesn’t Require Conversion<\/b><\/span><\/h3>\n
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2) May Be Better for Some Forms of Vitamin B6-Dependent Seizures<\/b><\/span><\/h3>\n
3) May Be Better for Sideroblastic Anemia<\/b><\/span><\/h3>\n
P-5-P Side Effects & Toxicity<\/b><\/span><\/h2>\n
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P-5-P Dosage & Supplements<\/b><\/span><\/h2>\n
Dosage<\/b><\/span><\/h3>\n