Each review contains information about the ingredient’s clinical applications, formulations, dosing & administration, adverse effects, and pharmacokinetics. Learn more about our critical appraisal research or contact us for initial guidance and more information.

Vitamin B6

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

Formulations

Formulation	Characteristics
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

Antioxidative capacity
General outcomes from A-level evidence	No data currently available.
Dosing & administration	50 mg per day for 12 weeks to Px with hepatocellular carcinoma who had undergone tumor resection
Outcomes	↑ total antioxidative capacity by reducing homocysteine (11)
Class of evidence	C

Breast pain
General outcomes from A-level evidence	No data currently available.
Dosing & administration	40 mg per day for two months to women with cyclic mastalgia
Outcomes	↓ pain severity (69%) compared to baseline with improvement starting by the end of the first month Note: provided similar efficacy to 200 IU of vitamin E (52)
Class of evidence	C

Cognitive decline
General outcomes from A-level evidence	Overall, it appears there is no evidence of a preventative effect for age-related decline in cognition or mood (6)(8)(19)(33)
Dosing & administration	20 mg (as pyridoxine HCl) per day for eight weeks to elderly healthy men
Outcomes	Modestly improved long-term memory scores compared to placebo (14)
Class of evidence	C

Cardiac surgery
General outcomes from A-level evidence	No data currently available.
Dosing & administration	250 mg (as P5P) per day starting prior to surgery and for one month post-surgery to Px undergoing coronary artery bypass graft surgery
Outcomes	↓ perioperative myocardial infarctions (with creatinine kinase-myocardial bands >100 ng/ml) by 47% compared to placebo (56)
Class of evidence	B
Dosing & administration	100 mg per day for 10 weeks post-cardiac transplant
Outcomes	Improved endothelial function measured by flow-mediated dilation by 138% compared to baseline while placebo worsened (39)
Class of evidence	C

Dental decay (in pregnancy)
General outcomes from A-level evidence	No data currently available.
Dosing & administration	20 mg (as capsules) or 6.67 mg (as lozenges) three times per day to pregnant women (>16 weeks gestation) until delivery
Outcomes	↓ dental decay score & risk by 16% with capsules or 32% with lozenges (22)(47)
Class of evidence	C

Epilepsy or recurrent seizures
General outcomes from A-level evidence	↓ proportion of patients (72%) with neuropsychiatric adverse events induced by the antiepileptic levetiracetam and improved symptoms (44)
Dosing & administration	30-50 mg/kg (intravenously) per day to infants and children with recurrent seizures caused by acute infectious diseases
Outcomes	↓ response rate by 29% & resolved seizures 1.3 days earlier compared to control (24)
Class of evidence	B
Dosing & administration	7 mg/kg per day (max dose of 350 mg) for 12 months to children with epilepsy using levetiracetam
Outcomes	↓ children’s depression inventory (confusion, depression and irritability) & 68% fewer Px discontinued levetiracetam treatment due to behavioral adverse events compared to use of levetiracetam alone (35)
Class of evidence	C

Hemodialysis
General outcomes from A-level evidence	↓ likelihood of B6 deficiency caused by hemodialysis (13)
Dosing & administration	10-50 mg per day to Px undergoing hemodialysis
Outcomes	↓ likelihood of deficiency caused by hemodialysis (13)
Class of evidence	A
Dosing & administration	60 mg per day for four weeks to Px undergoing hemodialysis, many of which had peripheral polyneuropathy
Outcomes	↓ peripheral polyneuropathy symptoms (42)
Class of evidence	C

Hypertension
General outcomes from A-level evidence	No data currently available.
Dosing & administration	5 mg/kg of bodyweight per day for four weeks to Px with essential hypertension
Outcomes	↓ SBP, DBP, epinephrine, & norepinephrine (5)
Class of evidence	C

Hypertriglyceridemia
General outcomes from A-level evidence	No data currently available.
Dosing & administration	50 mg per day for 12 weeks to Px with hypertriglyceridemia
Outcomes	↓ total cholesterol & HDL-C (~10%) with effects starting by six weeks compared to placebo (23)
Class of evidence	C

Migraine headaches
General outcomes from A-level evidence	May improve migraine prophylaxis alone or in combination with B12 and/or folate (32)
Dosing & administration	40 mg twice per day for 12 weeks to Px with migraine with aura
Outcomes	↓ headache severity (31%), duration (35%), & duration/frequency (40%) compared to placebo (45)
Class of evidence	B

Nausea and vomiting (in pregnancy)
General outcomes from A-level evidence	No data currently available.
Dosing & administration	25 mg three times per day for three days to pregnant women experiencing nausea and vomiting
Outcomes	↓ nausea severity score (58%) compared to placebo for Px with severe nausea & reduced number of Px with any vomiting by ~53%, whereas vomiting frequency worsened with placebo (46)
Class of evidence	B
Dosing & administration	40 mg twice per day for four days to pregnant women experiencing mild to moderate nausea and vomiting
Outcomes	↓ total Rhodes score (severity of nausea & vomiting) by 27% compared to placebo, and with similar efficacy to 500 mg twice daily of ginger (51)
Class of evidence	B
Dosing & administration	10-25 mg three times per day for three to four days and up to three weeks to pregnant women experiencing nausea and vomiting
Outcomes	↓ nausea score (31-35%), vomiting frequency (29-31%), & number of self-reported feelings of improvement with similar efficacy to 350-500 mg of ginger, but with less efficacy than 650 mg (12)(53)(54)
Class of evidence	C

Neuroleptic-induced tardive dyskinesia (TD) or akathisia
General outcomes from A-level evidence	↑ likelihood of greater than 40% improvement in TD symptoms induced by neuroleptics (2)(4)
Dosing & administration	600 mg twice per day for five days to Px with schizophrenia using neuroleptics
Outcomes	↓ Barnes Akathisia scale (56%), brief psychiatric rating score (6%), & subjective restlessness and distress scores (~64%) within 3-5 days compared to baseline and with similar efficacy to 15 mg of mianserin, while placebo did not change More Px (50%) improved on the Barnes Akathisia Scale by at least two points than placebo (29)(41)
Class of evidence	B
Dosing & administration	Up to 400 mg twice per day over one month to Px with schizophrenia using neuroleptics
Outcomes	↓ dyskinetic (33-69%) & parkinsonism (52-57%) subscores from the extrapyramidal symptom rating scale (31)(40)
Class of evidence	B
Dosing & administration	1,200 mg per day for 12 weeks to Px with schizophrenia
Outcomes	↑ extrapyramidal symptom rating scale & improved parkinsonism and dyskinesia subscales compared to placebo (30)
Class of evidence	B
Dosing & administration	300-600 mg twice per day for five days to Px with schizophrenia using antipsychotics
Outcomes	↓ Barnes akathisia rating scale to a similar extent, regardless of dose, and with equal efficacy to 40 mg of propranolol (50)
Class of evidence	C

Oral contraceptive side effects
General outcomes from A-level evidence	No data currently available.
Dosing & administration	25 mg (as pyridoxine HCl) per day for six months to women using oral contraceptives in nutritionally vulnerable populations
Outcomes	↓ side effects for nausea/no appetite (21%), headaches (9.9%), & depression (8%) with reduced numbers of side effects beginning within one month (58)
Class of evidence	C

Premenstrual syndrome (PMS)
General outcomes from A-level evidence	↑ odds of improvement in PMS symptoms ~2.3 fold & depressive symptoms ~1.7 fold versus placebo (62)
Dosing & administration	50-100 mg per day to women with PMS
Outcomes	↑ odds of improvement in PMS symptoms ~2.3 fold & depressive symptoms ~1.7 fold versus placebo (62)
Class of evidence	A
Dosing & administration	40-50 mg per day for two to three months to women experiencing moderate to severe PMS
Outcomes	↓ autonomic (dizziness or vomiting) or behavioral symptom severity (26) ↓ emotional scores (depression, irritability, tiredness) by ~52% compared to placebo (16) ↓ physical symptoms (11%) & combined physical and psychological symptoms (8%) compared to placebo Note: placebo also reduced symptoms compared to baseline, but not as much as with B6 (34)
Class of evidence	B
Dosing & administration	80 mg per day for two months to women experiencing PMS
Outcomes	↓ psychological symptom severity and total PMS scores with approx. double the efficacy of placebo Note: placebo groups also experience reductions in scores from baseline, but with lower magnitude (25)
Class of evidence	B
Dosing & administration	250 mg per day for four months to women with PMS
Outcomes	↓ PMS symptoms (cravings, depression, water retention, anxiety, and somatic changes) score by 37% compared to baseline & 16% compared to placebo Note: placebo group also reduced significantly from baseline, but not as effectively as B6 (17)
Class of evidence	B
Dosing & administration	40 mg twice per day for two months to women
Outcomes	↓ general symptom severity score (28%) & psychological symptom severity score (23%) compared to baseline, but not as effectively as combination with calcium (37)
Class of evidence	C
Dosing & administration	50-100 mg (as pyridoxine HCl) per day for three cycles to women with PMS
Outcomes	↓ premenstrual tension syndrome scale (48%) compared to baseline, but was considered less efficacious than Vitex agnus-castus (28)
Class of evidence	C

Tuberculosis (neonatal)
General outcomes from A-level evidence	May be used as adjunct therapy to reduce risk of peripheral neuropathy from isoniazid (15)
Dosing & administration	1 mg/kg per day to breastfed newborns being treated with isoniazid
Outcomes	↓ risk of peripheral neuropathy induced by pharmacotherapy (15)
Class of evidence	A

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)

Pharmacokinetics

Absorption

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)

Distribution

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)

Metabolism

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

Excretion

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)