Vitamin B6 (Pyridoxal-5-Phosphate)

Vitamin B6 (Pyridoxal-5-Phosphate) Common Name

Vitamin B6 | Pyridoxal-5-Phosphate | Pyridoxal Phosphate | P-5-P | P5P | PLP

Top Benefits of Pyridoxal 5'-phosphate 

  • Supports energy metabolism*
  • Supports brain function*
  • Supports general immune health*

What is Pyridoxal 5'-phosphate?

Pyridoxal 5'-phosphate (P5P) is the active form of (vitamin B6), which is part of the B complex—a group of water-soluble vitamins that play important roles in cellular metabolism and energy production. The term vitamin B6 refers to six forms—pyridoxal, pyridoxamine, pyridoxine, and their phosphorylated forms. The P5P form is the bioactive form of vitamin B6: it requires less metabolic “work” to be used as coenzyme in vitamin B6-dependent enzyme reactions. The more common form of vitamin B6 used in dietary supplements, pyridoxine, must undergo metabolic transformation and requires ATP to be converted into P5P. P5P is a cofactor involved in over 4% of all enzymatic activities, including many metabolic pathways important for cellular energy generation.[1] Major functions of P5P include (1) metabolism of fats, sugars, and proteins, (2) neurotransmitter synthesis, (3) synthesis of the hemoglobin used in red blood cells, and  (4) increasing and decreasing the expression of certain genes.  

Neurohacker’s Pyridoxal 5'-phosphate Sourcing

Pyridoxal 5'-phosphate (P5P) is our preferred form of vitamin B6, because it’s the active (i.e, coenzyme) form of the vitamin. The pyridoxine form requires ATP to be “activated.” In general, we think it’s a good idea to conserve ATP for more important uses in our cells and tissues.

Pyridoxal 5'-phosphate sourcing is focused on identifying and purchasing from a reputable supplier and ensuring it’s NON-GMO, gluten-free and vegan.

Pyridoxal 5'-phosphate Dosing Principles and Rationale

Vitamin B6, no matter the form, is subject to a dosing threshold (see Neurohacker Dosing Principles), which means, while more might be better within a low to moderate range, very high amounts would be unlikely to add significant additional nutritional or functional benefits for most people but could increase the risk of unwanted responses. Our goal in formulating products is to make sure that vitamin B6 amounts will be comfortably below the levels where risk for unwanted responses exists, even if several of our products with vitamin B6 are used together. In general, we tend to dose vitamin B6 at higher amounts in formulations where it would be used to support neurotransmitter production, and lower levels when we are using it to compliment a full B complex stack. The main role of vitamin B6 in the body is as a coenzyme for metabolic reactions. It is important to have sufficient amounts of vitamin B6 in the diet to allow proper functioning of these enzymes.

Pyridoxal 5'-phosphate Key Mechanisms

Energy metabolism

  • Pyridoxal 5'-phosphate (P5P) is a cofactor in about 100 essential enzyme reactions, including enzymes of glucose, fatty acid, and amino acid metabolism[2]
  • P5P is a cofactor in the kynurenine pathway; it is required for the synthesis of NAD+ from tryptophan[3]

Hemoglobin synthesis

  • P5P is required as a cofactor in the synthesis of heme, an iron-containing molecule found in hemoglobin[4]

Brain/neurotransmitter function

  • Cofactor for the enzyme aromatic L-amino acid decarboxylase, which catalyzes the synthesis of serotonin from 5-hydroxytryptophan (5-HTP) and dopamine from L-3,4-dihydroxyphenylalanine (L-DOPA) [5–9]
  • Since dopamine is a precursor for noradrenaline, P5P is required for its synthesis [8]
  • Since serotonin is a precursor for melatonin, P5P is required for its synthesis [9]
  • Supports glutamate decarboxylase (GAD) enzyme - GAD catalyzes the synthesis of gamma-aminobutyric acid (GABA) from glutamate [10–15]
  • Supports gamma aminobutyric acid transaminase (GABA-T) enzyme - GABA-T catalyzes the breakdown of gamma-aminobutyric acid (GABA) [10,12]
  • Participates in the metabolism of the neurotransmitters glycine, D-serine, and histamine [16]
  • Supports the synthesis of neurotransmitters involved in memory, executive function, mood regulation, focus, motivation, and sleep regulation [17]
  • May support aspects of dream recall (studies have been at doses ≥100 mg) [18,19]

Immune system

  • Supports adaptive immunity [20–26]
  • Supports immune system communication [27]


  • With vitamin B12 and folic acid (vitamin B9) for cardiovascular support and homocysteine metabolism [28–30], brain support [31], mood [32], and for general well-being [33]
  • With L-tryptophan and melatonin for sleep support [34–38]
  • With magnesium, other B-complex vitamins, and melatonin supplementation for sleep support [39]


[1]J.M. Berg, J.L. Tymoczko, G.J. Gatto, L. Stryer, eds., Biochemistry, 8th ed, W.H. Freeman and Company, 2015.

[2]Linus Pauling Institute Oregon State University, (n.d.).

[3]A.A.-B. Badawy, Int. J. Tryptophan Res. 10 (2017) 1178646917691938.

[4]G.A. Hunter, G.C. Ferreira, Biochim. Biophys. Acta 1814 (2011) 1467–1473.

[5]G. Delitala, A. Masala, S. Alagna, L. Devilla, J. Clin. Endocrinol. Metab. 42 (1976) 603–606.

[6]D.G. Mappouras, J. Stiakakis, E.G. Fragoulis, Mol. Cell. Biochem. 94 (1990) 147–156.

[7]G.F.G. Allen, V. Neergheen, M. Oppenheim, J.C. Fitzgerald, E. Footitt, K. Hyland, P.T. Clayton, J.M. Land, S.J.R. Heales, J. Neurochem. 114 (2010) 87–96.

[8]M.E. Gnegy, in: S.T. Brady, G.J. Siegel, R.W. Albers, D.L. Price (Eds.), Basic Neurochemistry (Eighth Edition), Academic Press, New York, 2012, pp. 283–299.

[9]J.G. Hensler, in: S.T. Brady, G.J. Siegel, R.W. Albers, D.L. Price (Eds.), Basic Neurochemistry (Eighth Edition), Academic Press, New York, 2012, pp. 300–322.

[10]T.S. Rajeswari, E. Radha, Exp. Gerontol. 19 (1984) 87–93.

[11]M. Díaz-Muñoz, R. Tapia, J. Neurosci. Res. 20 (1988) 376–382.

[12]V.V. Tsybul’skiĭ, E.R. Nagiev, Radiobiologiia 31 (1991) 201–208.

[13]O.A.C. Petroff, Neuroscientist 8 (2002) 562–573.

[14]D.Y. Yoo, W. Kim, D.W. Kim, K.-Y. Yoo, J.Y. Chung, H.Y. Youn, Y.S. Yoon, S.Y. Choi, M.-H. Won, I.K. Hwang, Neurochem. Res. 36 (2011) 713–721.

[15]Y. Huang, L. Su, J. Wu, PLoS One 11 (2016) e0157466.

[16]P.T. Clayton, J. Inherit. Metab. Dis. 29 (2006) 317–326.

[17]M. Ebadi, Neurochem. Int. 3 (1981) 181–205.

[18]M. Ebben, A. Lequerica, A. Spielman, Percept. Mot. Skills 94 (2002) 135–140.

[19]D.J. Aspy, N.A. Madden, P. Delfabbro, Percept. Mot. Skills 125 (2018) 451–462.

[20]M.C. Talbott, L.T. Miller, N.I. Kerkvliet, Am. J. Clin. Nutr. 46 (1987) 659–664.

[21]S.N. Meydani, J.D. Ribaya-Mercado, American Journal of … (1991).

[22]K. Folkers, M. Morita, J. McRee Jr, Biochem. Biophys. Res. Commun. 193 (1993) 88–92.

[23]S. Doke, N. Inagaki, T. Hayakawa, H. Tsuge, Biosci. Biotechnol. Biochem. 61 (1997) 1331–1336.

[24]H.-K. Kwak, C.M. Hansen, J.E. Leklem, K. Hardin, T.D. Shultz, J. Nutr. 132 (2002) 3308–3313.

[25]C.-H. Cheng, S.-J. Chang, B.-J. Lee, K.-L. Lin, Y.-C. Huang, Eur. J. Clin. Nutr. 60 (2006) 1207–1213.

[26]C. Kobayashi, K. Kurohane, Y. Imai, Biol. Pharm. Bull. 35 (2012) 532–538.

[27]S.-C. Huang, J.C.-C. Wei, D.J. Wu, Y.-C. Huang, Eur. J. Clin. Nutr. 64 (2010) 1007–1013.

[28]J. Selhub, Annu. Rev. Nutr. 19 (1999) 217–246.

[29]E. Lonn, S. Yusuf, M.J. Arnold, P. Sheridan, J. Pogue, M. Micks, M.J. McQueen, J. Probstfield, G. Fodor, C. Held, J. Genest Jr, Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators, N. Engl. J. Med. 354 (2006) 1567–1577.

[30]D. Serapinas, E. Boreikaite, A. Bartkeviciute, R. Bandzeviciene, M. Silkunas, D. Bartkeviciene, Reprod. Toxicol. 72 (2017) 159–163.

[31]G. Douaud, H. Refsum, C.A. de Jager, R. Jacoby, T.E. Nichols, S.M. Smith, A.D. Smith, Proc. Natl. Acad. Sci. U. S. A. 110 (2013) 9523–9528.

[32]O.P. Almeida, K. Marsh, H. Alfonso, L. Flicker, T.M.E. Davis, G.J. Hankey, Ann. Neurol. 68 (2010) 503–510.

[33]C. Hallert, M. Svensson, J. Tholstrup, B. Hultberg, Aliment. Pharmacol. Ther. 29 (2009) 811–816.

[34]A.D. Volpe, A.D. Lucia, C. Pirozzi, V. Pastore, J Int Adv Otol 13 (2017) 69–73.

[35]A. Della Volpe, L. Dipietro, G. Ricci, V. Pastore, M. Paccone, C. Pirozzi, A. Di Stadio, Int. J. Pediatr. Otorhinolaryngol. 115 (2018) 171–174.

[36]S. Picone, P. Ariganello, V. Mondì, F. Di Palma, L. Martini, S. Marziali, G. Fariello, P. Paolillo, Ital. J. Pediatr. 45 (2019) 122.

[37]P. Lemoine, J.-C. Bablon, C. Da Silva, Complement. Ther. Med. 45 (2019) 104–108.

[38]C. Bravaccio, G. Terrone, R. Rizzo, M. Gulisano, M. Tosi, P. Curatolo, L. Emberti Gialloreti, Minerva Pediatr. 72 (2020) 30–36.

[39]G. Djokic, P. Vojvodic, D. Korcok, A. Agic, A. Rankovic, V. Djordjevic, A. Vojvodic, T. Vlaskovic-Jovicevic, Z. Peric-Hajzler, J. Vojvodic, D. Matovic, G. Sijan, U. Wollina, M. Tirant, V.T. Nguyen, M. Fioranelli, Torello, Open Access Macedonian Journal of Medical Sciences 7 (2019).