DISCLAIMER: This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.

 

Overview of Product(s)

Vitamin B6, also known as pyridoxine, is a water-soluble essential nutrient naturally present in many foods and commonly included in dietary supplements and vitamins. It functions as a coenzyme in various enzymatic reactions involved in protein, carbohydrate, and lipid metabolism and is critical for neurotransmitter synthesis, haemoglobin formation, and the immune system.^1,2

In Malaysia, vitamin B6 is classified into two categories: health supplements and over-the-counter (OTC) medicines.³ Health supplements are permitted to contain a maximum daily dose of 100 mg, and are commonly included in multivitamins, B-complex combinations, and single-ingredient preparations available in tablet, capsule, or liquid forms. In contrast, OTC formulations contain daily doses exceeding 100 mg and are generally indicated for the management of neurological and other disorders related to disturbances of metabolic functions influenced by the vitamin B complex.⁴

 

Overview of Safety Concerns

Peripheral neuropathy refers to damage affecting the peripheral sensory, motor, or autonomic nerves to varying degrees.⁵ Clinical manifestations typically include tingling, burning sensations, or numbness, most commonly affecting the hands and feet.

Vitamin B6 from supplemental intake has been associated with the development of peripheral neuropathy.² This condition is generally observed with high-dose or long-term use of vitamin B6-containing supplements, particularly when individuals consume multiple products containing pyridoxine. Notably, the symptoms of vitamin B6 toxicity often resemble those of vitamin B6 deficiency.⁶

 

Source of Safety Concern

The National Pharmaceutical Regulatory Agency (NPRA) became aware of a news article published on an Australian website in July 2025 describing a consumer who developed severe peripheral neuropathy following excessive intake of vitamin B6.⁷ Previously in November 2022, the Therapeutic Goods Administration (TGA) of Australia issued a safety advisory on health supplements containing vitamin B6, noting that beyond the known risks from high or prolonged vitamin B6 intake, peripheral neuropathy may also occur at low doses without a clear minimum threshold.⁸ The TGA subsequently required warning labels on products containing even low doses of vitamin B6.

 

Background of the Safety Issue

While vitamin B6 deficiency is associated with the development of neurological disorders such as peripheral neuropathy, excessive and prolonged intake of vitamin B6 has paradoxically also been linked to polyneuropathy as an adverse effect.^1,9,10 Although the precise mechanism is not fully understood, several pathways have been proposed, including potential accumulation of free pyridoxine or alterations in vitamin B6 metabolism that may impair nerve function. The minimum dose and treatment duration needed to elicit neuropathy have also not been firmly established.^1,11

Most of the pyridoxine-induced neuropathy cases reported in the literature involved high doses, typically exceeding 2 g per day taken over many months to years.¹¹ Recovery durations varied widely, ranging from 3 months up to 3 years after discontinuation of vitamin B6, depending on the dose administered and treatment duration.^11,12

 

Local Adverse Drug Reaction Reports¹³

As of 29 October 2025, the NPRA has received a total of 1,156 reports following the use of health supplements or OTC products containing vitamin B6. The most frequently reported adverse events include vomiting, nausea, dizziness, pruritus, and rash.

To date, no local ADR reports of neuropathy or peripheral neuropathy have been received following the use of health supplements or OTC products containing vitamin B6. However, related adverse events, such as tingling (1 report), numbness (4), and muscle cramp (1) were reported with Vitamin B1/B6/B12 products. The time to onset ranged from 1 hour to 3 days after product use, and all events resolved upon product discontinuation. In two (2) cases, the reported intake of vitamin B6 was 200mg per day, and in another case, the same adverse events recurred following re-administration of the suspected product, indicating a positive rechallenge.  

Although international evidence shows that neuropathy may occur even at low doses, local data have not identified confirmed cases linked solely to vitamin B6, as the suspected products contained additional active ingredients and underlying conditions may have contributed to the reactions.      

 

Advice for Healthcare Professionals

• Be aware that neurological adverse events have been associated with the administration of vitamin B6, including at low doses.
• Although the risk is rare and often reversible upon early discontinuation, routinely review patients’ vitamin intake to allow prompt identification and management of potential adverse effects.
• For patients taking one or more health supplements, advise them to check the vitamin B6 content in each product and to be mindful of their total daily intake.
• Advise patients to stop taking vitamin B6 and consult a doctor if they experience symptoms of peripheral neuropathy, such as tingling, burning sensation, or numbness of the hands and feet.
• Report all suspected adverse events associated with vitamin B6-containing products to the NPRA.

 

References:

1. Muhamad, R.; Akrivaki, A.; Papagiannopoulou, G.; Zavridis, P.; Zis, P. The Role of Vitamin B6 in Peripheral Neuropathy: A Systematic Review. Nutrients 2023, 15, 2823. Available from: https://doi.org/10.3390/nu15132823
2. Australia Therapeutic Goods Administration (TGA). Consultation: Proposed amendments to the Poisons Standard - ACMS #46 and joint ACMS-ACCS #38 meetings, November 2024. [Internet] 2024 Sep 23 [cited 2025 Oct 28]. Available from: https://consultations.tga.gov.au/tga/scheduling-pre-meeting-november-2024/user_uploads/final---pre-meeting-public-notice---acms-46--accs-40--joint-38---november-2024---pdf.pdf
3. Drug Registration Guidance Document. [Internet] 2025. Available from: https://www.npra.gov.my/index.php/en/component/sppagebuilder/925-drug-registration-guidance-document-drgd.html
4. National Pharmaceutical Regulatory Agency (NPRA). QUEST3+ Product Search [Internet]. 2025 [cited 2025 Oct 29). Available from: https://www.npra.gov.my
5. Overview: Peripheral neuropathy. [Internet] 2022 Oct 10 [cited 2025 Oct 28]. Available from: https://www.nhs.uk/conditions/peripheral-neuropathy
6. Hemminger A, Wills BK. Vitamin B6 Toxicity. [Updated 2023 Feb 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554500/
7. Hayley Taylor. Class action looms over Blackmores after vitamin B6 toxicity causes ‘tragic’ injuries to expecting father. Available from: https://7news.com.au/news/excruciating-class-action-looms-over-blackmores-after-vitamin-b6-toxicity-causes-tragic-injuries-to-expecting-father-c-19413643
8. Australian Therapeutic Goods Administration (TGA). Safety Alert: Health supplements containing vitamin B6 can cause peripheral neuropathy. 10 November 2022. Available from: https://www.tga.gov.au/safety-and-shortages/safety-monitoring-and-information/safety-alerts/health-supplements-containing-vitamin-b6-can-cause-peripheral-neuropathy
9. van Hunsel, F., Scholl, J., Vrolijk, M. and Ekhart, C. (2025), Impact of Regulatory Action on Dose Maximalization for Vitamin B6 Dietary Supplements on the Reporting Pattern for Neuropathy. Pharmacoepidemiol Drug Saf, 34: e70108. Available from: https://doi.org/10.1002/pds.70108
10. Staff NP, Windebank AJ. Peripheral neuropathy due to vitamin deficiency, toxins, and medications. Continuum (Minneap Minn). 2014 Oct;20(5 Peripheral Nervous System Disorders):1293-306. doi: 10.1212/01.CON.0000455880.06675.5a. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC4208100/
11. Hadtstein F, Vrolijk M. Vitamin B-6-Induced Neuropathy: Exploring the Mechanisms of Pyridoxine Toxicity. Adv Nutr. 2021 Oct 1;12(5):1911-1929. doi: 10.1093/advances/nmab033. PMID: 33912895; PMCID: PMC8483950. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8483950/
12. Schellack N, Yotsombut K, Sabet A, Nafach J, Hiew FL, Kulkantrakorn K. Expert Consensus on Vitamin B6 Therapeutic Use for Patients: Guidance on Safe Dosage, Duration and Clinical Management. Drug Health Patient Saf. 2025 Apr 7;17:97-108. doi: 10.2147/DHPS.S499941. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12090844/
13. National Pharmaceutical Regulatory Agency (NPRA). The Malaysian National ADR Database (QUEST) [Internet]. 2025 [cited 2025 Jul 22]. Available from: https://www.npra.gov.my (access restricted)

 

Written by: Azura Abdullah, Wang Khee Ing

Reviewed/Edited by: Lim Sze Gee, Dr Rema Panickar, Noor'ain Shamsuddin, Norleen Mohamed Ali