The active form of vitamin B6, pyridoxal-5-phosphate (P5P), serves as a cofactor for more than 150 enzymes in the body, including transsulfuration and decarboxylation reactions. These reactions catalyse the synthesis of dopamine, serotonin, gamma-aminobutyric acid (GABA) and histamine, and the metabolism of homocysteine and tryptophan.
In the plasma 70-80% of vitamin B6 occurs as P5P with adequate levels inversely associated with inflammatory markers. Research shows that inflammation increases the uptake of P5P into the tissues markedly reducing available plasma and liver levels.
Low plasma levels are also seen in numerous diseases, including cardiovascular disease, cancer, rheumatoid arthritis, inflammatory bowel disease and diabetes.
A 2017 prospective study showed sufficient plasma P5P levels were clearly associated with a reduced risk of colorectal cancer. Additionally, stress will also increase the need for P5P, as the effects of cortisol increase the cellular demand for this active form.
P5P is necessary for the function of two enzymes, cystathione ß-synthase (CBS) and cystathione γ-lyase (CSE) in the transsulfuration of homocysteine to cysteine, reducing homocysteine accumulation. This is also crucial for detoxification as 20-50% of the cysteine produced through this pathway is used for glutathione synthesis. Therefore, those with genetic variations (SNPs) that slow down CBS activity, or those with increased homocysteine levels, may require additional P5P.
In the metabolism of tryptophan, through the kynurenine pathway, various reactions require P5P to maintain the correct levels of the neuroactive and immunomodulatory compounds produced during this process. Inflammation upregulates this pathway increasing P5P requirement.
As humans are unable to synthesise P5P de novo, a regular intake is required. Meat, dairy, nuts, potatoes and several fruits and vegetables supply P5P, although it is not the main form in plant-derived foods. It has always been known that the liver regulates P5P metabolism; however, research has also revealed that intestinal cells play a substantial role, with all enzymes involved in vitamin B6 metabolism present in intestinal samples. One of these enzymes is the zinc-dependant alkaline phosphatase (ALP).
The health of the liver and intestinal environment is key for adequate P5P availability. One study reported that supplementation with P5P rather than pyridoxine hydrochloride was necessary in subjects with decompensated cirrhosis, because of the liver’s difficulty in phosphorylating pyridoxine to P5P.
Therefore, in cases of liver disease, zinc deficiency, inflammatory and/or malabsorption syndromes, or some genetic variations, P5P supplementation may be necessary.
- Ueland PM, McCann A, Midttun O, et al. Inflammation, vitamin B6 and related pathways. Mol Aspects Med 2017;53:10-27. [Full Text]
- Paiardini A, Giardina G, Rossignoli G, et al. New insights emerging from recent investigations on human group II pyridoxal 5’-phosphate decarboxylases. Curr Med Chem. 2017;24(3):226-44. [Abstract]
- Gylling B, Myte R, Schneede J, et al. Vitamin B-6 and colorectal cancer risk: A prospective population-based study using 3 distinct plasma marker of vitamin b-6 status. Am J Clin Nutr. 2017;105(4):897-904. [Full Text]
- Albersen M, Bosma M, Knoers NV, et al. The intestine plays a substantial role in human vitamin B6 metabolism: A Caco-2 cell model. PLoS One 2013;8(1):e54113. [Full text]
- Labadarios D, Rossouw JE, McConnell JB, et al. Vitamin B6 deficiency in chronic liver disease--evidence for increased degradation of pyridoxal-5’-phosphate. Gut 1977;18(1):23-27. [Full text]