Pyridoxine toxicity from over‑the-counter supplements

Case 1

A man aged in his late 60s, with multiple sclerosis (MS) and migraine, reported increasing burning bilateral, symmetrical paraesthesia in his feet over several months. He had put this down to MS, but his symptoms had otherwise been stable over a period of years, and MRI showed no new central nervous system lesions. Vitamin B12, lead and blood sugar levels were all normal. His vitamin B6 level was elevated at 2610 nmol/L pyridoxal-5-phosphate (normal range 20–190 nmol/L). On review, he reported taking ‘BLACKMORES EXECUTIVE B STRESS FORMULA’ (Blackmores Ltd, Melbourne, Vic, Australia), one tablet daily, since the time of his MS diagnosis roughly 25 years ago. This contains 20.6 mg pyridoxine equivalent per tablet; 12-fold the recommend daily intake (RDI) for a man of his age per tablet.¹ His symptoms were improving one year after cessation of this supplement, and his vitamin B6 levels had normalised.

Case 2

A woman aged in her early 70s with Hashimoto hypothyroidism, urogenital changes of menopause, osteoarthritis, osteopaenia and mitral valve prolapse presented with restlessness and numbness in the feet, progressing over months to bilateral burning paraesthesia and hyperalgesia of the legs extending up the anterior thigh to the hip. Vitamin B12, lead and blood sugar levels were normal. Her vitamin B6 level was found to be 850 nmol/L (normal range 29–190 nmol/L). On review of her supplements, she reported taking ‘SUPER B 50’ (Australian Naturalcare Products Pty Ltd, Sydney, NSW). She recounted being told this would be helpful for her mood at a time when she felt under stress, and she had been taking it for over one year. This formulation contains 41.1 mg pyridoxine equivalent; 27.4-fold the RDI of vitamin B6 for a woman of her age per tablet.¹ The supplement was stopped, her vitamin B6 levels declined, and her symptoms were almost resolved by 4.5 months.

Question 1

What is the recommended daily intake of vitamin B6?

Question 2

What are the symptoms of vitamin B6 deficiency and vitamin B6 toxicity?

Question 3

What sorts of supplements can lead to vitamin B6 toxicity?

Question 4

How much vitamin B6 is in products available in Australian pharmacies?

Answer 1

Vitamin B6 is used to describe pyridoxine, pyridoxamine, pyridoxal and their phosphorylated derivatives.¹ Australian RDI for vitamin B6 (pyridoxine equivalent) ranges from 0.1 mg/day for children aged 0–6 years to 1.7 mg/day for men aged over 50 years, and as high as 1.9 mg/day during pregnancy and 2.0 mg/day during breastfeeding (Table 1).

The Australian recommendation for the upper daily limit of vitamin B6 for age 19+ years is 50 mg/day, based primarily on studies from the 1980s.¹ Data from that time period primarily relate to very high doses that might have skewed the analysis.² The 2023 recommendation regarding recommended upper limits from the European Food Safety Authority Panel on Nutrition, Novel Foods and Food Allergens is substantially lower at 12 mg/day for adults.²

Answer 2

Vitamin B6 is found in a wide range of food types including meats, cereals, vegetables and fruits, and it has high bioavailability, so deficiency is considered rare.¹ There is a lack of agreement regarding what cut-offs indicate a deficiency state.¹ Symptoms of vitamin B6 deficiency can include seborrhoeic dermatitis, convulsions, microcytic anaemia, depression and confusion.¹

Signs and symptoms of toxicity include paraesthesia, hyperaesthesia, weakness, atrophy, reduced reflexes, fasciculation, numbness and pain.^1,3 The Therapeutic Goods Administration (TGA) requires all vitamin B6-containing listed medications with a recommended daily dose >10 mg to include a paraesthesia warning.

Answer 3

Vitamin B6 toxicity has been reported in people taking daily pyridoxine supplementation at a range of doses,^2–5 a single large dose supplementation with pyridoxine,⁶ daily mixed B-group vitamin supplements⁷ and daily multivitamin supplements,^8–10 as well as in the newborn of a person taking vitamin supplements during pregnancy and breastfeeding.¹¹ Elevated plasma levels of pyridoxine have also been reported in the context of regular intake of energy drinks and multivitamins.¹²

A 2024 survey of vitamin B6-containing products available from Chemist Warehouse¹³ found that over one-quarter of products identified were named in a way that implied that they were supplements for non-B vitamins and minerals, and another quarter indicated that they were to be taken for specified health conditions.

Answer 4

Vitamin B6 doses in products available in Australia vary widely (a searchable index of all listed medications registered with the TGA is available at https://compliance.health.gov.au/artg). Doses in products available for online purchase from Chemist Warehouse in July 2024 ranged from 0.3 to 263 mg daily.¹³ Doses exceeding the current Australian recommended pyridoxine equivalent upper daily limit (UDL)¹ and European UDL are found in B-group vitamins, multivitamins, non-B vitamins/minerals, health products and sports supplements (Tables 2 and 3). Patients taking multiple vitamins, supplements and sports products, or taking supplements for prolonged periods, might also be at risk of toxicity.

Key points

• Excessive pyridoxine causes neurological injury.
• Over-the-counter vitamins and supplements contain vitamin B6 levels sufficient to cause toxicity when taken as directed.
• Vitamins and supplements not labelled as B vitamins can contain high levels of vitamin B6.

AI declaration: The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript.