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P5P

Also known as: Pyridoxal 5′-phosphate, PLP, P5P, vitamin B6 active form, Pyridoxal 5'-phosphate

Overview

Pyridoxal 5'-phosphate (P5P), also known as PLP, is the active coenzyme form of vitamin B6. It is found naturally in animal tissues and available as a dietary supplement. P5P acts as a coenzyme in over 160 enzymatic reactions related to amino acid, carbohydrate, and lipid metabolism, as well as neurotransmitter synthesis. It is used to address vitamin B6 deficiency, support metabolic functions, and has been investigated for its roles in sleep regulation, nausea during pregnancy, and cancer risk reduction. As the bioactive form, P5P bypasses the need for hepatic conversion from pyridoxine, potentially improving bioavailability. Research maturity is moderate to advanced, with systematic reviews and meta-analyses available for some health outcomes. Evidence varies by indication, with strong support for biochemical roles and cancer risk associations, and moderate support for clinical symptom relief such as nausea and sleep quality.

Benefits

P5P offers several evidence-based benefits. It can reduce nausea and vomiting during pregnancy, as supported by a systematic review and meta-analysis of randomized controlled trials, although specific data on the P5P form are less reported. Higher serum PLP concentrations are associated with reduced daytime sleepiness and abnormal sleep duration, particularly in males, according to cross-sectional data from NHANES. Furthermore, a meta-analysis of observational studies demonstrated a statistically significant inverse association between PLP levels and the risk of colorectal, pancreatic, lung, and gastrointestinal cancers, indicating a potential risk reduction of up to 44% for colorectal cancer. Potential secondary benefits include roles in neurotransmitter metabolism and immune function. These benefits are most pronounced in pregnant women for nausea, males for sleep quality, and general adult populations for cancer risk reduction.

How it works

P5P functions as a coenzyme in numerous enzymatic reactions, primarily within amino acid metabolism, including transamination and decarboxylation. It also plays a crucial role in neurotransmitter synthesis, such as serotonin, dopamine, and GABA. Additionally, P5P is involved in modulating homocysteine metabolism. These processes impact the nervous system through neurotransmitter synthesis, the immune system, and various metabolic pathways. P5P directly interacts with enzymes requiring it as a cofactor, including aminotransferases and decarboxylases. Unlike pyridoxine hydrochloride, P5P is directly bioavailable and does not require conversion, potentially leading to faster and more efficient utilization by the body.

Side effects

Vitamin B6 and its active form, P5P, are generally considered safe at recommended doses. Common side effects are rare at typical doses, but high doses exceeding 100 mg per day may lead to sensory neuropathy. Uncommon side effects, occurring in 1-5% of users, may include mild gastrointestinal discomfort. Rare side effects, affecting less than 1% of users, involve sensory neuropathy with chronic excessive dosing. P5P may interact with certain medications, such as isoniazid and hydralazine, which can affect B6 metabolism. Caution is advised for individuals with sensitivity to vitamin B6 or pre-existing neuropathy. Pregnant women can benefit from supplementation for nausea, but dosing should be carefully managed to avoid excessive intake.

Dosage

For managing nausea during pregnancy, pyridoxine doses around 10-25 mg per day are commonly used, although specific P5P dosing is less standardized. Up to 100 mg per day of vitamin B6, including P5P, is generally considered safe and effective in many studies. However, long-term use of doses above 100 mg per day may increase the risk of neuropathy. Daily dosing is recommended, and timing relative to meals may affect absorption. P5P may be preferred for individuals with impaired conversion of pyridoxine to PLP. P5P has higher bioavailability than pyridoxine. Magnesium and other B vitamins may support its metabolism.

FAQs

Is P5P more effective than pyridoxine?

P5P is the active form of vitamin B6 and may be more bioavailable, especially in individuals with impaired conversion enzymes, potentially leading to better utilization.

Can P5P help with sleep?

Observational evidence suggests that higher PLP levels correlate with better sleep quality and less daytime sleepiness, but causality has not been definitively established.

Is it safe during pregnancy?

Vitamin B6 is commonly used to reduce nausea during pregnancy, and P5P is considered safe within recommended doses, typically around 10-25mg per day.

How soon can benefits be expected?

For nausea relief, benefits may be observed within days to weeks of supplementation. However, benefits related to cancer risk reduction are long-term and require consistent intake.

Are there risks of overdose?

High doses of P5P, particularly above 100 mg per day over extended periods, may cause neuropathy. It is important to adhere to recommended dosage guidelines.

Research Sources

https://pubmed.ncbi.nlm.nih.gov/36719452/ – This systematic review and meta-analysis of randomized controlled trials found that pyridoxine supplementation reduces nausea severity and vomiting frequency during pregnancy. The study included multiple RCTs with adequate sample sizes, showing statistically significant improvements (p<0.05), but noted variability in dosing and formulations, with limited specific data on the P5P form.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9460331/ – This cross-sectional study analyzed NHANES data (n>10,000) and found significant inverse associations between serum PLP and daytime sleepiness, especially in males. The study used robust statistical models but is observational, limiting causal inference regarding the direct impact of PLP on sleep.
https://lpi.oregonstate.edu/mic/vitamins/vitamin-B6 – This resource from the Linus Pauling Institute provides a comprehensive overview of vitamin B6, including its functions, dietary sources, and potential health benefits. It highlights the importance of PLP as the active form of vitamin B6 and discusses its role in various metabolic processes.
https://academic.oup.com/jnci/article/109/3/djw230/2572054 – This meta-analysis of observational studies demonstrated significant inverse associations between PLP levels and gastrointestinal cancers, including colorectal cancer (RR ~0.5). The study included numerous observational studies with large populations, showing no heterogeneity and dose-response relationships, supporting a protective role of PLP.
https://foodandnutritionresearch.net/index.php/fnr/article/view/10259 – This scoping review for Nordic Nutrition Recommendations emphasizes PLP as the main active form of vitamin B6, highlighting biochemical markers of deficiency and recommending plasma PLP >30 nmol/L for adequacy. The review suggests that higher levels may be optimal for certain health outcomes, providing a comprehensive overview of vitamin B6 requirements.