High-dose vitamin B6 and risk of peripheral neuropathy

Vitamin B6 is a water-soluble vitamin that comprises different related compounds (vitamers) such as pyridoxine, pyridoxal, pyridoxamine and pyridoxal 5’-phosphate (PLP). The majority of vitamin B6 supplements contain the biologically inactive form, pyridoxine, which is converted by the body into the biologically active form, PLP. PLP functions as an important co-enzyme in various metabolic processes and neurotransmitter synthesis.¹

Locally, vitamin B6 is present in both health supplements and therapeutic products, with the latter generally indicated for vitamin deficiency prevention, and treatment of nerve pain and neuropathies. The maximum allowable daily limit for vitamin B6 in health supplements is 100mg/day based on data from several long-term studies.^2,3 This limit is aligned with the upper limit set by ASEAN, Canada and the US for vitamin B6.

Peripheral neuropathy has been reported following chronic high-dose (>100mg/day) consumption of vitamin B6. Healthcare professionals may consider reviewing the dose and duration of vitamin B6 intake (including over-the-counter health supplements) by patients who present with symptoms of peripheral neuropathy.

Vitamin B6-induced peripheral neuropathy

While peripheral neuropathy is a known safety concern with vitamin B6, the exact mechanism of this adverse event has not been fully elucidated. Postulated mechanisms include the saturation of enzymes leading to accumulation of free pyridoxine and subsequent neurotoxicity, aldehyde toxicity through elevated PLP concentration, the formation of reactive intermediates and competitive inhibition of PLP-dependent enzymes.^1,4

The precise-dose response relationship of vitamin B6 causing peripheral neuropathy and the threshold for duration of use have also not been clearly established. Evidence from literature on vitamin B6-related neuropathy is largely based on case reports, case series and small clinical studies, where the vitamin B6 dosage and duration of use ranged from <50mg to >10g, and three days to ten years, respectively.⁵ However, limitations were noted in some studies, such as the absence of a physician’s assessment or clinical neurological assessment, and potential confounding by the patient’s susceptibility to develop neuropathies (e.g., drug, alcohol and nutritional status).

Local situation

To date, HSA has received one local adverse event report in 2020 regarding non-serious severe neuralgia in a 65-year-old Chinese male who took a vitamin B6-containing product. There were no further details on the dose and duration of vitamin B6 consumption in the report. The local package inserts of therapeutic products that provide a vitamin B6 daily dose exceeding 100mg are in the process of being strengthened to include warnings on peripheral neuropathy.

HSA’s advisory

While the effect of peripheral neuropathy usually occurs when vitamin B6 is consumed in high doses and/or over long duration, the mechanism of the adverse event, precise dose-response relationship, and threshold for duration of use have not been clearly established. Healthcare professionals may consider reviewing the dose and duration of vitamin B6 intake (including over-the-counter health supplements) by patients who present with symptoms of peripheral neuropathy.

References

1. PharmaNutrition 2020; 12: 100188
2. https://www.hsa.gov.sg/health-supplements/overview
3. National Academies Press 1998: 150-195
4. Adv Nutri. 2021; 12: 1911-1929
5. Drug Saf 2018; 41: 859-869

Published: 15 May 2023

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