The randomized controlled trial found that daily supplementation with 100 mg of vitamin B6 as pyridoxine significantly reduced DASS-depression scores compared to placebo and an active control (vitamin B12) over 30-40 days.
The study is the first randomized double-blind study to demonstrate the potential of vitamin B6 as a standalone or adjunctive approach to managing depressive symptoms. However, while the study authors reported no adverse effects during the study period, they highlighted that very high doses of pyridoxine over long periods can cause peripheral neuropathy (a form of nerve damage).
Despite the promising results, the researchers from the University of Reading therefore recommend that such interventions must be supervised by medical professionals.
“We have shown that high‐dose vitamin B6 has therapeutic potential for depression,” they wrote. “Large‐scale clinical trials with patients should now be conducted to determine whether these findings from our mostly female sample generalize to males, to quantify the dose–response relationship, and to evaluate its potential as an adjunct to existing treatments versus monotherapy.”
Study details
Vitamin B6 is an essential nutrient involved in haemoglobin production, energy metabolism, immune function and hormone regulation. It also plays a key role in the production of neurotransmitters, leading the researchers to hypothesize that supplementation could help manage depressive symptoms.
Specifically, pyridoxal-5′-phosphate (PLP), the active form of vitamin B6, acts as a cofactor for enzymes involved in the synthesis of neurotransmitters such as GABA, serotonin and dopamine, which are central to mood regulation and emotional wellbeing.
However, while several animal studies and longitudinal general population studies have demonstrated this link, until now, no randomized controlled trials had directly studied the effects of vitamin B6 supplementation on depression.
To test this, the researchers recruited 268 participants and randomized them into three intervention groups: placebo (lactose tablets), active control (100 mg of vitamin B12) and treatment (100 mg of vitamin B6).
Compared to both placebo and high‐dose vitamin B12, vitamin B6 produced a large improvement in depression symptoms, with the most significant effects evident in participants who had mild or more severe depression at baseline. There was no significant effect on anxiety or stress.
Despite these promising results, the researchers said several limitations will need to be addressed in follow-up studies. This includes the use of blood samples to confirm participant compliance, more male participants to ensure generalizability, and accounting for other medications such as anti-depressants. They also warned about the risks of toxicity when consuming vitamin B6 at high doses.
“It is also important to note that very high doses of vitamin B6 taken in the pyridoxine form for long periods can cause peripheral neuropathy,” they wrote. “More recently, it has been reported that in a small proportion of individuals differences in the metabolic processes converting pyridoxine to PLP may cause peripheral neuropathy at much lower doses. Therefore, taking high‐dose vitamin B6 as an intervention should be supervised by medical professionals.”
Vitamin B6 and peripheral neuropathy: What does the science say?
There are several clinical and observational studies linking vitamin B6 to peripheral neuropathy. The issue was first described in 1983 after a study by Schaumburg et al. identified several cases at very high doses of around 2 to 6 grams a day.
But perhaps the most well-known piece of research in the field is a 1987 study by Dalton and Dalton which found symptoms consistent with sensory nerve damage were present in humans at much lower doses of around 50 mg per day.
While the Dalton and Dalton study has been criticized on methodological grounds, primarily because it relied on self-reported data and lacked objective neurological testing, this study has been used by many regulatory bodies to inform upper limit (UL) recommendations and guidance.
For example, the UK’s Committee on Toxicity has recommended a maximum daily intake of 10 mg per day of vitamin B6 from supplements, while the European Food Safety Authority (EFSA) recently cut the upper limit from 25 mg to 12 mg per day.
A rising number of vitamin B6 toxicity reports have also led several regulatory bodies to implement tighter restrictions. For example, Australia’s database of Adverse Event Notifications (DAEN) linked 250 reports of neuropathy to vitamin B6 products between 2023 and 2025. This led the Australian Therapeutic Goods Administration (TGA) to require warning on products containing more than 10 mg of vitamin B6 and license products containing between 50 mg and 200 mg of vitamin B6 as pharmacist-only products.
However, industry bodies have raised concerns about these new restrictions, warning that setting the limit too low could pose a risk to consumers. The Council for Responsible Nutrition (CRN), for example, has recommended an upper limit of 100 mg per day, in line with the study’s dose.
“Evidence from credible, well-designed human studies consistently shows that neuropathy associated with vitamin B6 supplementation only occurs at substantially higher intake levels—typically above 200 mg per day, and often much higher,” said Andrea Wong, CRN’s senior vice president and chief science officer.
“When ULs are set excessively low relative to the available evidence, there is a risk that products formulated to address legitimate nutritional needs could become unavailable or reformulated to levels that may be less effective. That could create unintended public health consequences, particularly for individuals who may benefit from higher supplemental intakes under appropriate guidance.”
Emerging evidence also suggests that the form, or ‘vitamer’, of B6 may influence the development of neuropathy. Pyridoxine has been linked to adverse events, and some researchers have proposed that supplements containing pyridoxal-phosphate (the active form) may be less likely to cause peripheral neuropathy than those containing pyridoxine.
The authors of the study said this needs to be explored further in future clinical research, but caution is required until this is confirmed.
Source: Depression and Anxiety, 2026. doi: 10.1155/da/8926512. “High Dose Vitamin B6 Reduces Depression Symptoms.” Authors: D. Field, et al.
