Impact of Regulatory Action on Dose Maximalization for Vitamin B6 Dietary Supplements on the Reporting Pattern for Neuropathy.

Background: Vitamin B6 deficiency is linked to neurological disorders. However, supplementation with high doses of vitamin B6 has also been linked to neuropathy as an adverse drug reaction. Review of cases from the Dutch Spontaneous Reporting System (SRS) and other data led to a regulatory action to lower the maximum daily dose (DD) of vitamin B6 in supplements to 21 mg/day from October 1, 2018.

Purpose: The aim of this study was to investigate if there was an effect of the regulatory action in 2018 on maximum daily dosage for vitamin B6 on the reporting pattern of neuropathy to the SRS in the Netherlands.

Methods: We investigated trends in the number of reports received until December 31, 2023, DD mentioned in the reports, and the correlation between DD and plasma vitamin B6 levels. A change point analysis was used to get insight into the pattern of reports over time.

Results: Two hundred and twenty-four reports were included. After the regulatory action for dose maximization from October 2018, only one report mentions a dosage which is much higher than the recommended 21 mg DD. Only 15% of the variability in plasma levels mentioned in reports can be explained by the DD. Twelve statistical change points were noted, especially around some peaks in the reporting pattern for instance in 2018. However, from the second half of 2019, the number of reports on vitamin B6 and neuropathy per time period is lower and no change points were detected.

Conclusions: Although our study has limitations, we clearly see an effect of regulatory action on the doses of vitamin B6 used in neuropathy reports. However, some cases describing neuropathy related to vitamin B6 supplementation with lower doses are still reported after the regulatory action in 2018. Therefore, the association between low-dose vitamin B6 products and neuropathy should be studied further.