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Ingredient review

Vitamin B6


What is it?

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin. It acts as a coenzyme in more than 140 biochemical reactions involving carbohydrates, lipids, proteins, and amino acids, and it helps to produce neurotransmitters, glycogen, and glucose. Its three natural forms,  pyridoxine, pyridoxal, and pyridoxamine, are converted to the active coenzyme pyridoxal-5-phosphate (PLP or P5P) when consumed. (1)(43) Each of the natural forms have a 5-phosphate form. (36) Pyridoxal-5-phosphate is the main active metabolite that is often measured to determine whether an individual’s vitamin B6 levels are suboptimal (20-30 nmol/L) or deficient (<20 nmol/L). Low levels of B6 are correlated with various chronic diseases, including cardiovascular disease, stroke, diabetes, or cancer. In supplemental forms, vitamin B6 is regularly combined with other B vitamins such as vitamin B12 (cobalamin) and vitamin B9 (folic acid) to improve efficacy. (55)

It is important to note that while vitamin B6 has been widely studied in combination with other B vitamins, only the studies that show its efficacy as an isolated ingredient are provided in this review.

Main uses

Nausea and vomiting
Neurological function
Premenstrual syndrome


Pyridoxine hydrochloride (HCl)
Most widely used form in dietary supplements and clinical trials
Pyridoxal-5- phosphate (P5P)
Commonly used in supplements as it is the active form of vitamin B6
Though P5P is the bioactive form, intestinal absorption requires orally ingested P5P to be dephosphorylated, which likely reduces bioavailability relative to its non-phosphorylated forms (i.e., pyridoxine, pyridoxal, or pyridoxamine). (18)
Supplementation with intravenous P5P may be required to raise P5P in patients with liver dysfunction since it does not require hepatocytes to metabolize B6 vitamers to P5P. (27)
Similar applications as above may be required for individuals with disorders that limit B6 metabolism. For example, genetic mutations can reduce the production of intracellular P5P by inhibiting enzymatic conversion of B6 vitamers (i.e., pyridoxine, pyridoxal, or pyridoxamine) to P5P, causing B6 deficiency. Deficiencies may manifest as clinical features including seizures as observed in PLP-dependent epilepsy. (60)
Pyridoxamine dihydrochloride (2HCl)
A B6 therapy which was particularly studied to reduce advanced glycation end products (AGEs) in diabetic nephropathy
However, since the FDA accepted pyridoxamine as the active ingredient in an investigational pharmaceutical product in 2009, it has not been legally classified to meet the definition of a dietary supplement. (57)

Dosing & administration

Adverse effects

According to cohort studies and randomized controlled trials, vitamin B6 does not appear to increase the prevalence of adverse events compared to control groups within dose ranges up to 230 mg per day. Case series and case reports indicate that high doses may cause numbness or peripheral neuropathy. (10) More than 1,000 mg per day may be required to cause neuropathy; however, some cases have been reported after taking up to 500 mg per day for several months. (21)

Overall, there is little evidence of the induction neuropathy when used at doses lower than 100 mg for up to 30 weeks, though other possible adverse effects include indigestion and nausea, light sensitivity, and breast tenderness. (1) Other side effects may include the inhibition of platelet aggregation, (49) as well as the impairment of semen quality parameters (as shown in rodents), but this needs to be confirmed in humans. (7) It may be noted that vitamin B6 intake of more than 50 mg per day may be more likely to result in clinically significant drug interactions, such as with levodopa. (48

Some in vitro evidence suggests that long-term high dosing with pyridoxine may not be as safe as P5P or other forms since pyridoxine may competitively inhibit enzymatic conversion of B6 vitamers to P5P. Bioaccumulation of pyridoxine may thereby lead (contradictorily) to polyneuropathy (an adverse event observed in B6 deficiency) induced by cellular death, an observation not recorded with other B6 forms. (59)



  • Vitamin B6 is absorbed in the upper intestinal tract by passive diffusion, though in vitro evidence for selective transporter proteins for B6 vitamers is emerging. (3)
  • Phosphorylated B6 vitamers must be dephosphorylated prior to intestinal absorption and their release to the hepatic portal system for further metabolism to P5P. (3)


  • Once absorbed, B6 is metabolized to P5P and is widely circulated throughout the body bound to albumin. (63)
  • To be absorbed into cells, P5P is dephosphorylated to pyridoxal before being re-phosphorylated back into its active coenzyme form intracellularly. (3)


  • Vitamin B6 forms are converted to the active coenzyme (P5P) and 4-pyridoxic acid (4-PA) in the liver. (3)(38)


  • B6 derivatives are excreted in the urine, primarily as 4-PA. (3)(9)(61)(63)
  • The approximate half-lives of orally administered pyridoxine and P5P is 1.3 hours and 2.3 hours, respectively. (63)


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