Vitamin B6 is a water-soluble vitamin known as pyridoxine. The active coenzyme forms of vitamin B6 are called pyridoxal-5-phosphate (PLP) and pyridoxamine 5 phosphate (PMP). Vitamin B6 performs a wide variety of functions throughout the body in these active coenzyme forms. It is involved in over 100 enzymatic reactions, many of which are a component of protein metabolism and to a lesser degree in carbohydrate and fat metabolism. Vitamin B6 is necessary for hemoglobin formation, immune health, nucleic acid production, homocysteine and glucose regulation, and energy production.
Vitamin B6 (pyridoxine), primarily in its active form pyridoxal-5-phosphate (P5P), is a crucial coenzyme in the biosynthesis of several key neurotransmitters, including serotonin, dopamine, norepinephrine, epinephrine, GABA, and glycine. It functions in decarboxylation and transamination reactions necessary for neurotransmitter conversion from amino acid precursors. For example, B6-dependent aromatic L-amino acid decarboxylase converts 5-HTP to serotonin and L-DOPA to dopamine. Glutamate decarboxylase, also B6-dependent, is required for the conversion of glutamate to GABA. These pathways are integral to mood regulation, attention, executive function, stress response, and seizure threshold, making vitamin B6 a central nutrient in neuropsychiatric health.
Vitamin B6 is also an important cofactor in the kynurenine pathway, which metabolizes tryptophan into various bioactive metabolites. One of PLP’s key roles is in the conversion of kynurenine into kynurenic acid via kynurenine aminotransferases (KATs), a process that helps balance neuroprotective and neurotoxic metabolites. B6 deficiency leads to accumulation of upstream metabolites (e.g., 3-hydroxykynurenine) and a shift toward increased production of quinolinic acid, which is implicated in neurotoxicity and the pathophysiology of depression. Meta-analyses and reviews indicate that in major depressive disorder, there is a shift in the kynurenine pathway favoring neurotoxic quinolinic acid over neuroprotective kynurenic acid, and B6 status may modulate this balance.
The complexities of the kynurenine pathway are beyond the scope of this article, but it should be noted that many naturopathic doctors do evaluate kynurenine pathway metabolites in their patients with depression, autism and ADHD. These pathway metabolites can be seen in many functional organic acid tests.
The RDA (Recommended Daily Allowance) for vitamin B6 is as follows:
| Age | Male | Female | Pregnancy | Lactation |
| Birth to 6 months | 0.1 mg* | 0.1 mg* | ||
| 7 – 12 month | 0.3 mg* | 0.3 mg* | ||
| 1 – 3 years | 0.5 mg | 0.5 mg | ||
| 4 – 8 years | 0.6 mg | 0.6 mg | ||
| 9 – 13 years | 1.0 mg | 1.0 mg | ||
| 14 – 18 years | 1.3 mg | 1.2 mg | 1.9 mg | 2.0 mg |
| 19 – 50 years | 1.3 mg | 1.3 mg | 1.9 mg | 2.0 mg |
| 51+ years | 1.7 mg | 1.5 mg |
Vitamin B6 can be found in many foods of both plant and animal origin. Pyridoxine is the form found exclusively in plant foods and comes from whole grains, potatoes, bananas, nuts and seeds. Pyridoxal is mostly found in animal products and comes from beef, fish, chicken and pork. The vitamin B6 found in plant foods is slightly less bioavailable than the vitamin B6 consumed from animal products. Some rich sources of vitamin B6 are:
A vitamin B6 deficiency on its own is quite rare, but may occur with a general B-complex deficiency. The symptoms associated with a vitamin B6 deficiency include microcytic anemia, dry, cracked and scaly lips and corners of the mouth, swollen tongue (glossitis), fatigue, and rash on the face, neck and shoulders. More severe symptoms like depression, confusion, poor immune function, and peripheral neuropathy may occur after a prolonged deficiency. It can take months for a mild B6 deficiency to result in symptoms. Infants with a vitamin B6 deficiency may show signs of irritability, poor hearing, or in rare instances, seizure activity. Since vitamin B6 is water soluble, conditions associated with fluid balance like renal disease or alcoholism can contribute to a vitamin B6 deficiency. Malabsorption conditions like Inflammatory Bowel Disease and celiac disease reduce the absorption of vitamin B6 and can lead to a deficiency. In addition, antiepileptic drugs lead to a vitamin B6 deficiency over time and children on these medications should be supplementing appropriately under the care of a physician.
This article focuses largely on the neurological effects of vitamin B6. Even suboptimal levels of vitamin B6 may cause neurological complications in certain susceptible individuals. These neurological signs may include:
It’s worth noting that these neurological effects can be caused by other conditions or deficiencies as well, and low vitamin B6 is just one of the possible causes. It’s important to see a healthcare professional to rule out other causes and to confirm a diagnosis of deficiency.
Vitamin B6 toxicity from food sources has not been reported. However, prolonged supplementation with high doses (more than 200 mg daily) can cause severe sensory neuropathy that results in a progressive loss of body control. Usually, these symptoms disappear once supplementation is stopped. Other symptoms of vitamin B6 toxicity are skin lesions, headaches, sensitivity to light, and gastrointestinal symptoms like nausea and heartburn. There has been some concern regarding vitamin B6 supplementation during pregnancy, but a recent large study found no association between supplementation and congenital defects in the offspring. Individuals with Parkinson’s who are taking L-dopa should not take supplemental vitamin B6.
Due to the risk of sensory neuropathy, the upper limits for food and supplemental intakes are as follows:
| Age | Male | Female | Pregnancy | Lactation |
| Birth to 6 months | Not possible to establish* | Not possible to establish* | ||
| 7 – 12 months | Not possible to establish* | Not possible to establish* | ||
| 1 – 3 years | 30 mg | 30 mg | ||
| 4 – 8 years | 40 mg | 40 mg | ||
| 9 – 13 years | 60 mg | 60 mg | ||
| 14 – 18 years | 80 mg | 80 mg | 80 mg | 80 mg |
| 19+ years | 100 mg | 100 mg | 100 mg | 100 mg |
Some studies show vitamin B6 supplements to be effective at reducing the symptoms associated with premenstrual syndrome (PMS). An older systematic review of randomized controlled trials found that vitamin B6 at doses up to 100 mg/day was associated with a greater likelihood of symptom improvement compared to placebo, with an odds ratio of 2.32 (95% CI: 1.95–2.54) for overall symptoms and 1.69 (1.39–2.06) for depressive symptoms. However, the quality of the included trials was generally low, limiting the strength of conclusions. The most significant effect was on reducing anxiety, likely due to the role of vitamin B6 in neurotransmitter synthesis. In adolescents, vitamin B6 may be beneficial in easing symptoms associated with PMS following menarche. Although there is some evidence supporting supplementation of vitamin B6 for PMS, more studies would be useful for determining the appropriate dose and duration.
Multiple systematic reviews and randomized controlled trials have evaluated vitamin B6, often in combination with magnesium, for the treatment of core autism spectrum disorder (ASD) symptoms. The most rigorous evidence, including a Cochrane review, found no significant benefit of vitamin B6 (with or without magnesium) on social interaction, communication, or behavioral outcomes in children with ASD, and the available studies were limited by small sample sizes and methodological weaknesses.
As a comment on this, I would like to note that this Cochrane review is now over 20 years old, and was limited by the evidence available at the time, which were small studies with no differentiation between children with vitamin B6 deficiencies, and children with no deficiencies. As a naturopathic physician I do find vitamin B6, often combined with magnesium, to be clinically helpful in treatment of some children with ASD, anxiety, ADHD (see below), and agitation. But I only attempt supplementation in children who have laboratory evidence of vitamin B6 deficiencies. Elevated xanthurenic acid is strongly specific for B6 deficiencies. Likewise, elevated HVA/VMA ratios (e.g., high HVA with low VMA) may reflect altered catecholamine metabolism due to B6 deficiency. Even still, in my clinical opinion, only some of these children respond well to vitamin B6 supplementation. But those that do seem to have significant improvement, especially in sensory sensitivities and agitation/anxiety.
A newer study in Scientific Reports in 2018 attempted to identify whether a subgroup of individuals with autism spectrum disorder (ASD) might respond positively to vitamin B6 treatment, and whether machine learning could be used to identify these responders based on phenotype variables and biomarkers. The researchers analyzed data from a small intervention trial involving 17 children and adolescents with ASD, most of whom had expressive verbal disorders. They focused on clinical signs such as hypersensitivity to sound and clumsiness, as well as plasma levels of amino acids—particularly glutamine.
Three participants were classified as “possible responders” to a 4-week high-dose vitamin B6 intervention, based on improvements in the Clinical Global Impression-Improvement (CGI-I) scale. All three exhibited both hypersensitivity to sound and clumsiness, and had significantly lower plasma glutamine levels compared to the non-responders (P = 0.004). These variables, along with autism severity scores (PARS), were used in two machine learning clustering methods—affinity propagation and k-medoids. Both algorithms reliably grouped the vitamin B6 responders into a distinct cluster, suggesting that these features may help predict B6 responsiveness.
The findings support the hypothesis that a subset of individuals with ASD may share overlapping etiologies with pyridoxine-dependent epilepsy and may benefit from vitamin B6 supplementation. However, the sample size was extremely small, and this is an area of research that should be further explored.
Though the sample size was small and the generalizability limited, the use of machine learning demonstrated a novel method to stratify treatment responders within a heterogeneous ASD population. The study recommends further validation with larger and more diverse cohorts and suggests incorporating glutamine levels and neurological signs into future clinical assessment protocols for ASD.
In several studies, vitamin B6 and magnesium have been shown to reduce some of the symptoms of ADHD. Symptoms of hyperexcitability such as physical aggression, attention at school, anxiety, and hypermobility seem to be the most significantly impacted. Interestingly, when the vitamin B6-magnesium supplement was stopped, the clinical symptoms of ADHD that had subsided reappeared within a few weeks.
Furthermore, children with ADHD tend to have a greater risk of vitamin B6 and magnesium deficiencies which may contribute to ADHD symptoms. Without adequate vitamin B6, the brain cannot make enough neurotransmitters like dopamine, norepinephrine, serotonin, and GABA. All of these neurotransmitters affect how brain cells communicate and impact mood regulation and behavior. Vitamin B6 works synergistically with magnesium, and studies have shown that magnesium improves focus, anxiety, and sleep. In short, children with ADHD tend to have low levels of both vitamin B6 and magnesium which may contribute to their symptoms. Correcting these deficiencies may help improve mood regulation and behavior.
Vitamin B6 deficiency is associated with an increased risk of depressive symptoms, but evidence for the efficacy of vitamin B6 supplementation in treating depression is limited and inconsistent. Multiple studies demonstrate that lower plasma pyridoxal-5-phosphate (PLP, the active form of vitamin B6) or lower dietary intake of vitamin B6 correlates with higher depressive symptomatology, though mostly in elderly patients. Meta-analyses of observational studies suggest an inverse association between dietary vitamin B6 intake and depression risk, with a stronger effect observed in females. Studies in adolescents have found that higher dietary vitamin B6 intake is associated with a lower prevalence of depressive symptoms, independent of other factors. These associations are observed in both boys and girls, and are consistent with findings that low B6 intake is linked to higher internalizing (including depressive) and externalizing behavior scores in adolescents. However, these studies are observational and this is an area with a serious lack of research.
However, randomized controlled trials do not show consistent benefit for use of B6 to reduce depressive symptoms in patients. A meta-analysis of B vitamin supplementation (including B6) found no significant benefit for depressive symptoms compared to placebo, though some benefit was observed in individuals at risk due to poor nutrient or mood status. Most of the research has been completed on adults, especially elderly adults, which limits our understanding of the use of B6 in children.
Considering the association between vitamin B6, mood, and mental function previously discussed, it’s easy to see how a connection may be drawn to improving overall cognitive function. Vitamin B6 also impacts the brain by managing homocysteine levels. A deficiency in vitamin B6 can result in elevations of homocysteine, a known risk factor for cerebrovascular disease that may have toxic effects on the neurons of the central nervous system8.
Considering the relationship between vitamin B6 and the brain, some studies have examined the effect vitamin B6 supplementation has on cognition. Most of the studies have been conducted on older adults and the results are inconclusive8. Little research on vitamin B6 supplementation has been done on children, but due to its vast roles throughout the body, particularly the brain, prioritizing vitamin B6 rich foods is a good way to ensure healthy growth and development in young children.
There are several forms of vitamin B6 available for supplementation, including pyridoxine hydrochloride, pyridoxal-5-phosphate (P5P), and pyridoxine alpha-ketoglutarate (PAK).
Pyridoxine hydrochloride is the most common form of vitamin B6 found in supplements and is the form of vitamin B6 used in most research studies. It is considered safe and effective when taken at recommended doses.
Pyridoxal-5-phosphate (P5P) is the active form of vitamin B6 and is already in its metabolically active form, thus it doesn’t require any further conversion by the body, it may be more effective than pyridoxine hydrochloride for some people with certain genetic variations or other metabolic factors that affect the body’s ability to convert pyridoxine to P5P.
Pyridoxine alpha-ketoglutarate (PAK) is a form of vitamin B6 that is bound to alpha-ketoglutarate, which is a molecule involved in energy production. It may enhance the absorption and effectiveness of vitamin B6.
It’s worth noting that more research is needed to determine the optimal form of vitamin B6 for supplementation, and the best form may vary depending on the individual’s needs. It’s always a good idea to consult a healthcare professional before starting any supplement regimen.
It is important to note that antiepileptic medications deplete vitamin B6, while nonsteroidal anti-inflammatory drugs, oral contraceptives, and anti-parkinson’s drugs interfere with its metabolism. People taking these medications should supplement appropriately to avoid dangerous depletions. Supplemental doses should be determined by the individual’s primary care provider or a qualified nutrition
In conclusion, vitamin B6 is an important nutrient with a role in energy production, nutrient metabolism, neurotransmitter synthesis, and more than 100 enzymatic reactions. It can be found in both animal and plant foods such as poultry, chickpeas, potatoes, bananas, and fortified grains. A deficiency is quite rare, but may occur in the presence of numerous nutrient deficiencies or malabsorptive diseases. Toxicity is also rare, but can occur with prolonged supplementation. Toxicity can lead to sensory neuropathy and thus supplementation should be considered under the supervision of a qualified medical provider. Vitamin B6 supplementation is essential for children taking anti-epileptic medication and may be beneficial in easing PMS symptoms, Autism Spectrum Disorder, ADHD, anxiety and depression. There is mixed evidence supporting its overall efficacy at improving cognition, but while further studies are conducted, consuming plenty of vitamin B6 rich foods is the best way to support a healthy brain and body!
