Ingredient review —Vitamin B6
What is it?
Description
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
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.
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
Class of evidence
c
Neuroleptic-induced tardive dyskinesia (TD) or akathisia
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
Class of evidence
b
Dosing & administration
Up to 400 mg twice per day over one month to Px with schizophrenia using neuroleptics
Outcomes
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
Metabolism
References
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