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Pyridoxal 5-Phosphate (P5P)

Practitioners Information

Vitamin B6 comprises six compounds; pyridoxal, pyridoxine, pyridoxamine and their respective 5-phosphates.

As a supplement pyridoxal 5-phosphate (P5P) supplies the activated form of vitamin B6. Standard vitamin B6 supplements such as pyridoxine hydrochloride must be converted to P5P by the liver in order to be effective. In contrast, supplementing with P5P ensures the most bioactive form of vitamin B6 is supplied.

Vitamin B6 is a versatile water-soluble nutrient that supports a wide variety of functions in the body.1

  • B6 functions as a coenzyme in many reactions that are involved in amino acid, carbohydrates and lipid metabolism.2
  • Everyday stress is a part of modern life and has a major influence on mood. Within the central nervous system vitamin B6 assists synthesis of neurotransmitters.3 This includes the formation of serotonin, dopamine, norepinephrine, and gamma‐aminobutyric acid (GABA).4 Due to the central role in neurotransmitter synthesis P5P helps maintain nervous system function. P5P may support emotional wellbeing, and relief of symptoms of stress and mild anxiety.5
  • Vitamin B6 is involved in red blood cell production, and may assist haemoglobin synthesis.6 Haemoglobin is the protein inside red blood cells that carries oxygen from the lungs to tissues and organs in the body, and carries carbon dioxide back to the lungs. Testing for haemoglobin is used to check for conditions such as anaemia.7
  • P5P helps reduce homocysteine levels. Homocysteine is an amino acid produced via demethylation of dietary methionine, which is abundant in animal protein.8 In the presence of sufficient methionine, homocysteine is converted to cysteine through the sequential action of two P5P-dependent enzymes known as cystathionine beta synthase (CBS) and cystathionine gamma-lyase (CSE).9 Studies show raised blood levels of homocysteine is an independent risk factor for cardiovascular disease.10
  • Nausea and vomiting are common problems in early pregnancy. Although often called ‘morning sickness’, nausea and vomiting can occur at any time of day and may persist throughout the day.11 Studies suggest vitamin B6 may relieve morning sickness.12,13
  • Vitamin B6 may significantly relieve the symptoms of premenstrual symptom associated with emotional wellbeing such as low mood, irritability and fatigue.14,15
  • The upper level of intake is based on adverse effects caused by high doses of supplemental vitamin B6 as pyridoxine.16 Recent studies indicate that the neuropathy observed after taking relatively high doses of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal 5-phosphate.17 Consequently, given the recent findings the active P5P form of B6 is likely more effective than pyridoxine when taken as suggested.

References

1 Australian National Health and Medical Research Council (NHMRC) and the New Zealand Ministry of Health (MoH). Nutrient Reference Values for Australia and New Zealand. Vitamin B6. Page Updated: 31-01-2018.

2 Eliot AC, Kirsch JF. Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations. Annu Rev Biochem. 2004;73:383-415.

3 Parra M, Stahl S, Hellmann H. Vitamin B₆ and Its Role in Cell Metabolism and Physiology. Cells. 2018;7(7):84. Published 2018 Jul 22.

4 Stover PJ, Field MS. Vitamin B-6. Advances in Nutrition. 2015;6(1):132-133.

5 Malouf R, Grimley Evans J. The effect of vitamin B6 on cognition. Cochrane Database Syst Rev. 2003;(4):CD004393.

6 Stover PJ, Field MS. Vitamin B-6. Adv Nutr. 2015;6(1):132-3. Published 2015 Jan 7.

7 PubMed Health. Health A-Z. Hemoglobin. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0022015/

8 Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015;14:6. Published 2015 Jan 10.

9 Ueland PM, McCann A, Midttun O, et al. Inflammation, vitamin B6 and related pathways. Mol Aspects Med 2017;53:10-27.

10 Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide, 3rd ed. Folate Monograph. Sydney: Churchill Livingstone Elsevier. 2010.

11 Festin M. Nausea and vomiting in early pregnancy. BMJ Clin Evid. 2014;2014:1405. Published 2014 Mar 19.

12 Shrim A, Boskovic R, Maltepe C, et al. Pregnancy outcome following use of large doses of vitamin B6 in the first trimester. J Obstet Gynaecol. 2006 Nov;26(8):749-51.

13 Matok I, Clark S, Caritis S, et al. Studying the antiemetic effect of vitamin B6 for morning sickness: pyridoxine and pyridoxal are prodrugs. J Clin Pharmacol. 2014 Dec;54(12):1429-33.

14 Doll H, Brown S, Thurston A, Vessy M. Pyridoxine (Vitamin B6) and the premenstrual syndrome: a randomized crossover trial. JRCGP. 1989; 39:364-368.

15 Wyatt K, Dimmock P, Jones P, O’Brien P. Efficacy of Vitamin B-6 in the treatment of premenstrual syndrome: systematic review. BMJ. 1999; 318:1375–81.

16 Australian National Health and Medical Research Council (NHMRC) and the New Zealand Ministry of Health (MoH). Nutrient Reference Values for Australia and New Zealand. Vitamin B6. Page Updated: 31-01-2018.

17 Vrolijk MF, Opperhuizen A, Jansen EHJM, et al. The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function. Toxicol In Vitro. 2017 Oct;44:206-212.

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