PYRIDOXAL 5`-PHOSPHATE iSOTROPE

Pyridoxal 5`-Phosphate (P5P): Highly Bioavailable Vitamin B6

Pyridoxal 5’-Phosphate is the active form of Vitamin B6 that drives approximately 168 vital enzyme processes in our body. Among these vital roles, P5P facilitates a process known as deamination—which is responsible for converting essential amino acids into non-essential ones. P5P also helps shuttle certain nutrients—such as magnesium—across cellular membranes which helps increase absorption rates. Pyridoxal 5’-Phosphate is a compound vital to our health, yet often found in short supply. Learning more about what it is, where you can get it, and how our bodies use it may help you maintain a better overall nutritional balance.

What Is Pyridoxal 5’Phosphate

Pyridoxal 5’-phosphate (P5P) is the active coenzyme form of Vitamin B6 which can be directly utilized by the body without conversion. There are several compounds that are commonly referred to as B6 including Pyridoxine, Pyridoxal, Pyridoxamine, and their respective 5`-phosphate forms. These are considered Pyridoxine vitamers, and our body is capable of interconverting between them. That is to say, pyridoxine can be converted to pyridoxal 5`-phosphate, and then back into pyridoxine later. Each of these compounds plays unique roles in our body, but only P5P has an active coenzyme role. Pyridoxal 5’-phosphate controls the metabolism of amino acids, aids in the production of neurotransmitters, and is a cofactor for more than 150 enzymes in our body [1].

Bioavailable Vitamin B6

The most common active ingredient found in most Vitamin B6 supplements is Pyridoxine Hydrochloride. This compound can be used by the body to help drive the many enzymatic processes attributed to P5P, but it must first be converted. This conversion takes place in the liver almost immediately, and releases the several pyridoxine metabolites into our bloodstream, with Pyridoxal 5-phosphate being the most preferred [2]. Very limited research on this conversion process suggests that 30 minutes after oral ingestion of pyridoxine, as much as 40% has been diffused into the bloodstream as various metabolites. This illustrates how efficient this conversion process is already in our body. There have been very limited amounts of research done on the differences of the efficacy of pyridoxal 5`-phosphate vs pyridoxine compounds such as pyridoxine hydrochloride. Some limited data suggests that those suffering from impaired liver function may benefit from taking the active form. One study found that plasma levels of pyridoxal 5`-phosphate were increased nearly 60% after administration of the active P5P form compared to the administration of pyridoxine hydrochloride [3].

Benefits Of Pyridoxal 5`-Phosphate

When considering the benefits of pyridoxal 5`-phosphate, it’s best to broadly consider the benefits of all the B6 vitamers. While many health professionals believe P5P to be the superior form, there still isn’t a lot of research to support that notion. P5P is simply a more efficient form of pyridoxine and avoids the hepatic conversion processes needed to create the active enzyme form. This would likely be beneficial for those with impaired liver function. Ultimately, the case for P5P comes down to it being a bio-optimized form of Vitamin B6 that our body can put to work immediately. Below you’ll find some of the many benefits of pyridoxal 5`-phosphate.

Reduces Inflammation

Pyridoxal 5`-phosphate levels are inversely correlated to inflammatory markers such as Tumor Necrosis Factor Alpha (TNF-α) Interleukin 6 (IL-6) and Interferon Gamma (INF-γ). These markers are commonly used to accurately gauge the level of inflammation in response to certain medical conditions such as IBS, Cancer, Cardiovascular Disease, and Arthritis. Any treatment that effectively lowers these markers likely exhibits an anti-inflammatory action on a cellular level. One study found that levels of these compounds were significantly (p=0.01) lower in Rheumatoid Arthritis patients after being given 100mg/day of Vitamin B6. These levels were measured to be inversely correlated with measured serum levels of P5P [4].

Boosts Immune System

One Taiwanese study considered 50 patients in the Taichung Veteran’s General Hospital. These patients were separated into three groups; those receiving no B6 supplementation, those receiving 50mg/day B6, and those receiving 100mg/day B6 [5]. After 14 days of treatment, researchers measured a wide array of serum Vitamin B vitamer markers and immune function markers. Both the 50mg/day group and 100mg/day group showed significant increases in serum P5P and immune cell counts such as total lymphocyte count (TLC) and CD3, CD4, CD8, and CD19 cells. This research suggests that Vitamin B6 is an effective treatment for generalized immune improvement.

Helps Support Positive Mood & Relaxation

Some of the more significant research on Vitamin B and its role in anxiety and hypertension has been conducted with a focus on premenstrual women.  One such study investigated the impact of supplementation with magnesium and Vitamin B6 on several mood factors of 126 women. Among those given a magnesium/vitamin B6 supplement, there was a significant decrease in symptoms of depression, water retention, and anxiety [6]. Another such study found supporting results and noted that the reduction in PMS symptoms was slightly more significant in the group given a magnesium/Vitamin b6 compound than a magnesium compound alone [6].

Lower Risk Of Lung Cancer

Cancer is generally regarded as being a disease seeded by inflammation. Vitamin B6’s demonstrated ability to reduce pro-inflammatory markers makes it a likely candidate in nutritional for the prevention of cancer. One study found that among 1770 participants having donated blood, of which 899 later developed lung cancer, there was a significant inverse correlation between serum levels of Vitamin B6 and those with cancer. Simply put, lower levels of Vitamin B6 equate to higher chances of lung cancer—the lower the level, the higher the chance [7].

Cases For Pyridoxal 5`-Phosphate

There isn’t much research that provides data contrasting the efficacy of different types of Vitamin B6. Many suggest that using the activated pyridoxal 5`-phosphate form may likely provide more accessible nutritive value compared to more common forms like Pyridoxine Hydrochloride. There have been a few limited studies which investigate this notion, and below you’ll find a brief overview of their results

Better At Controlling Seizures

Certain types of epilepsy are known to be centric to the genetic mutations preventing a person from producing enough Vitamin B6. One such disorder named Pyridoxal 5`-phosphate-dependant epilepsy begins to cause disturbances immediately after birth [8]. Babies experiencing this type of seizure are unresponsive to normal seizure medications and are given large doses of P5P to control seizure activity. This type of genetic dysfunction can be traced to the Pyridoxine 5`-Phosphate Oxidate (PNPO) gene [9]. This condition is very rare, and only practically illustrative in potential roles of Vitamin B6 in healthy neural function. One study investigating the role of Vitamin B6 supplementation on children with active forms of epilepsy divided their test groups into those receiving Pyridoxine and others receiving Pyridoxal Phosphate. This research found that PLP was often more effective in limiting seizure events, particularly in those cases where infantile spasms were noted. This study also found that many patients unresponsive to Pyridoxine were responsive to Pyridoxal Phosphate, particularly in the long-term analysis [10].

Healthy Red Blood Cell Formation

Part of the process our body undergoes to produce healthy erythrocytes (red blood cells) starts in our bone marrow. Sometimes these immature red blood cells enter the bloodstream in en masse—characterized by abnormal rings of iron about the mitochondria. This condition is known as sideroblastic anemia and is almost always found in concurrence with low levels of pyridoxine. Treatment with pyridoxine supplementation for this condition was known to be successful, but only in about 50% of cases. It is also found that megadoses of pyridoxine are often required to generate the desired response in these patients. One potential explanation of this phenomenon is that an underlying issue with the natural conversion process of pyridoxine to pyridoxal `5-phosphate may be at play. In one single case study, a 72-year-old woman with such sideroblastic anemia had been unresponsive to treatments with pyridoxine but saw immediate and significant improvement with given pyridoxal `5-phosphate [11]. In another case of pyridoxine responsive anemia, researchers found that pyridoxal 5`-phosphate was able to prompt a greater positive effect in measurable markers in lesser amounts the pyridoxine alone. In this single-patient study of pyridoxine-dependent anemia, researchers found that a 25mg/day dose of P5P was much more effective than a 300mg/day dose of pyridoxine [12]. Much more research is needed to confirm the notion that P5P is able to be more fully utilized compared to other B6 vitamers.

Pyridoxal 5`-Phosphate Deficiency

According to the SIB ExPASy Bioinformatics Resources Panel (ExPASy), Pyridoxal 5`-Phosphate is a cofactor of 168 unique enzymes [1]. To get some perspective; Magnesium is recorded by ExPASy as being a cofactor for 208 unique enzymes. This paints a picture of P5P being an essential nutrient used by our body for a wide range of processes. With such broad-reaching involvement, it’s almost redundant to describe symptoms of a Pyridoxal 5`-phosphate deficiency since they could like be a great many—similar to magnesium. Among clinically-studied incidences of patients suffering low levels of P5P, there seems to be a strong relationship between seizures, anemia, irritability, auditory sensitivity, depression, skin issues, and weakened overall immune function [13]. A Vitamin B deficiency is generally regarded as being rare in the isolated incidence of other vitamin b deficiencies. This type of deficiency is likely to be present for years without being symptomatic.

Pyridoxal 5`-Phosphate & Magnesium

Vitamin B6 has been observed as being particularly synergistic in combination with magnesium. It is thought that pyridoxal 5`-phosphate is responsible for facilitating intercellular transportation of magnesium.  While there has been a significant amount of research to investigate this hypothesis, much of that research has failed to specify which type of B6 compound was being used or to investigate the efficacy of contrasting B6 vitamers. As we continue, we are making the assumption that Pyridoxal 5`-phosphate is in many cases a superior form of Vitamin B6.

Increases Plasma Magnesium

One study of premenstrual women found that those given 100mg of Vitamin B6 per day for a period of one month were found to measure higher levels of plasma magnesium [14]. Researchers noted RBC levels of magnesium doubling after a period of 4 weeks. They regarded these results as supportive evidence that Vitamin B6 is actively involved in the transportation of minerals such as magnesium across cellular membranes. In another study, researchers found that only the administration of large doses of Vitamin B6 (>1000mg) was able to show a marked increase of cellular magnesium [6]. They note that considering neurological damages have been observed in doses of 2000mg and higher, this type of therapy isn’t advisable.

Reduces Pms Symptoms

Another study with premenstrual women found that in a combination of Vitamin B6 and magnesium was able to lower PMS symptoms, as defined by the American Psychiatry Association. Researchers found that Magnesium and Vitamin B6 in combination was more effective in reducing PMS symptoms than magnesium alone—though both were significantly more effective than placebo [15]. In another study, researchers separated 44 premenstrual women into groups receiving magnesium, vitamin B6, magnesium and vitamin B6, or placebo. Researchers concluded that there was a small synergistic effect noted in the absorption of magnesium among those given the Vitamin B6 + Magnesium combination therapy [16]. It’s worth noting that researchers opted to use magnesium oxide as the test compound in this study. This type of magnesium is noted as being very poorly absorbed, and not recommended for treatments designed to increase overall magnesium levels.

Final Considerations

Pyridoxal 5`phosphate is a vital compound that drives approximately 168 unique enzymatic reactions in our body. This wide array of interactivity likely cascades into nearly every aspect of our health, to some extent. P5P is one of 6 Vitamin B6 vitamers, including pyridoxine, pyridoxamine, pyridoxal, and their respective phosphorylated forms. Vitamin B6 supplements are most commonly made of the Pyridoxine Hydrochloride compound. Some limited research suggests that in many cases direct supplementation with P5P can affect serum levels when Pyridoxine may not. Pyridoxal 5`-phosphate is regarded as having a synergistic relationship with magnesium. Limited research supports this notion; suggesting that P5P facilitates the transport of minerals across cellular membranes. This action suggests that the combination of Pyridoxal 5`-Phosphate and supplements such as magnesium malate or magnesium glycinate may increase the overall effective dosage. Serum levels of P5P have been shown to be accurate predictors of many types of disease including cancer, diabetes, cardiovascular, and certain blood diseases.  Ensuring you maintain a healthy level of Vitamin B6 can help fortify your health and promote longevity.

References

  1. “ENZYME.” ENZYME Cofactor Pyridoxal 5′-Phosphate, ExPASy, enzyme.expasy.org/cgi-bin/enzyme/enzyme-search-cf?Pyridoxal_5%27-phosphate. Accessed 3/2017
    http://enzyme.expasy.org/cgi-bin/enzyme/enzyme-search-cf?Pyridoxal_5%27-phosphate
  2. Lumeng, L, et al. “Plasma Content of B6 Vitamers and Its Relationship to Hepatic Vitamin B6 Metabolism.” Journal of Clinical Investigation, U.S. National Library of Medicine, Oct. 1980, www.ncbi.nlm.nih.gov/pmc/articles/PMC371643/.
  3. Rossouw, J E, et al. “Vitamin B6 and Aspartate Aminotransferase Activity in Chronic Liver Disease.” South African Medical Journal = Suid-Afrikaanse Tydskrif Vir Geneeskunde., U.S. National Library of Medicine, 25 Mar. 1978, www.ncbi.nlm.nih.gov/pubmed/675385.
  4. Huang, S C, et al. “Vitamin B(6) Supplementation Improves pro-Inflammatory Responses in Patients with Rheumatoid Arthritis.” European Journal of Clinical Nutrition., U.S. National Library of Medicine, Sept. 2010, www.ncbi.nlm.nih.gov/pubmed/20571496.
  5. Cheng, C H, et al. “Vitamin B6 Supplementation Increases Immune Responses in Critically Ill Patients.” European Journal of Clinical Nutrition., U.S. National Library of Medicine, Oct. 2006, www.ncbi.nlm.nih.gov/pubmed/16670691.
  6. Ebrahimi, Elham, et al. “Effects of Magnesium and Vitamin B6 on the Severity of Premenstrual Syndrome Symptoms.” Journal of Caring Sciences, Tabriz University of Medical Sciences, Dec. 2012, www.ncbi.nlm.nih.gov/pmc/articles/PMC4161081/.
  7. Johansson, Mattias. “Serum B Vitamin Levels and Risk of Lung Cancer.” JAMA, American Medical Association, 16 June 2010, jamanetwork.com/journals/jama/fullarticle/186079.
  8. National Institutes of Health. “Pyridoxal 5′-Phosphate-Dependent Epilepsy.” Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, 23 Sept. 2013, rarediseases.info.nih.gov/diseases/10730/pyridoxal-5-phosphate-dependent-epilepsy.
  9. Genetics Home Reference. “PNPO Gene.” U.S. National Library of Medicine, National Institutes of Health, June 2008, ghr.nlm.nih.gov/gene/PNPO.
  10. Wang, H, et al. “Pyridoxal Phosphate Is Better than Pyridoxine for Controlling Idiopathic Intractable Epilepsy.” Archives of Disease in Childhood, U.S. National Library of Medicine, May 2005, www.ncbi.nlm.nih.gov/pmc/articles/PMC1720393/.
  11. Mason, D. Y., and Pauline M. Emerson. “Primary Acquired Sideroblastic Anaemia: Response to Treatment with Pyridoxal-5-Phosphate.” British Medical Journal, U.S. National Library of Medicine, 17 Feb. 1973, www.ncbi.nlm.nih.gov/pmc/articles/PMC1588335/.
  12. Gehrmann, G. “Pyridoxine Responsive Anaemias.” British Journal of Haematology, Wiley/Blackwell (10.1111), 7 July 2008, onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.1965.tb00087.x/full.
  13. National Institutes of Health – Office of Dietary Supplements. “Dietary Supplement Fact Sheet: Vitamin B6.” NIH Office of Dietary Supplements, U.S. Department of Health and Human Services, ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/#h5.
  14. Abraham, G E, et al. “Effect of Vitamin B-6 on Plasma and Red Blood Cell Magnesium Levels in Premenopausal Women.” Annals of Clinical and Laboratory Science., U.S. National Library of Medicine, July 1981, www.ncbi.nlm.nih.gov/pubmed/7271227.
  15. Eisinger, J, and J Dagorn. “Vitamin B6 and Magnesium.” Magnesium., U.S. National Library of Medicine, Jan. 1986, www.ncbi.nlm.nih.gov/pubmed/3959594.
  16. De, M C, et al. “A Synergistic Effect of a Daily Supplement for 1 Month of 200 Mg Magnesium plus 50 Mg Vitamin B6 for the Relief of Anxiety-Related Premenstrual Symptoms: a Randomized, Double-Blind, Crossover Study.” Journal of Women’s Health & Gender-Based Medicine., U.S. National Library of Medicine, Mar. 2000, www.ncbi.nlm.nih.gov/pubmed/10746516.