Can B6 Cause Neuropathy?

Peripheral Neuropathy (PN) affects the peripheral nervous system, causing damage to motor, sensory, or autonomic nerves. While commonly associated with factors like diabetes and excessive alcohol intake, vitamin deficiencies, particularly vitamin B6, have been identified as contributors to PN. Surprisingly, both deficiency and toxicity of vitamin B6 can lead to neurological dysfunction, emphasizing the importance of maintaining optimal levels. This article explores the various forms of vitamin B6, its crucial role in the body, the hypothesized mechanism of B6-induced neuropathy, and recent regulatory changes addressing it.

The Role and Importance of Vitamin B6

Vitamin B6 is an essential water-soluble vitamin crucial for the proper functioning of the human body. It exists in six chemically related compounds, including pyridoxine, pyridoxal, pyridoxamine, and their 5’-phosphates, with pyridoxal-phosphate (PLP) being the biologically active form. PLP plays a pivotal role in over 140 biochemical reactions, contributing to macronutrient metabolism, cellular signaling, neurotransmitter synthesis, and nerve function. While pyridoxine is excreted in urine, PLP is found in muscle tissue and the liver, with a half-life elimination of approximately 15-20 days.

Recommended Daily Intake and Potential Toxicity of Vitamin B6

The recommended daily intake (RDI) for adults ranges between 1.3-2mg/day, with an upper level (UL) set at 50mg/day. While food sources provide up to 5mg/day, supplementation can contribute up to 80% of daily intake. Exceeding the UL through supplementation, especially at or above 50mg/day, increases the risk of toxicity. Long-term daily supplementation may lead to accumulation, emphasizing the need for moderation.

Hypothesized Mechanism of Vitamin B6-Induced Neuropathy

The mechanism behind vitamin B6-induced neuropathy is not fully understood. It is hypothesized that pyridoxine inhibits pyridoxal kinase (PDXK) activity, reducing γ-aminobutyric acid (GABA) synthesis and decreasing GABA signaling within sensory neurons. As GABA is an inhibitory neurotransmitter, decreased GABA neurotransmission may damage sensory nerves, leading to symptoms such as tingling, numbness, and burning sensations.

Variance of Sensitivity to Vitamin B6 Toxicity

Individual sensitivity to vitamin B6 toxicity varies widely. The Therapeutic Goods Administration (TGA) notes that PN can occur at doses less than 50mg/day. Plasma PLP concentrations exceeding 30 nmol/L are traditionally considered indicators of adequate vitamin B6 status in adults.

Prevalence and Source of Vitamin B6

Over 1,500 medicines, including multivitamins and supplements, contain vitamin B6. PN often arises when individuals unknowingly consume multiple products containing vitamin B6. Pyridoxine, the most common form in supplements, has been linked to a cytotoxic effect on neuronal cells, influencing PN development more than the vitamin B6 dosage itself.

In March of 2022 the Therapeutic Goods Administration in Australia implemented regulatory changes to address the growing prevalence of peripheral neuropathy from elevated vitamin B6 levels.  Products containing more than 10mg of vitamin B6 per daily dose will now carry a warning label in Australia. Additionally, the maximum daily dosage of vitamin B6 in a single product for adults has been reduced from 200mg to 100mg, promoting safer supplementation practices.  Sadly, no such measures have been taken to protect the public in the United States as of the time of this writing.

Vitamin B6 is a vital micronutrient with diverse functions in the body. Neuropathy, whether due to deficiency or toxicity, highlights the delicate balance needed for optimal health. Recent regulatory changes signify a step towards ensuring the safety of vitamin B6 supplementation. Individuals should be mindful of their vitamin B6 intake, particularly when using multiple supplements, and practitioners should educate patients about potential risks. Further research is needed to understand better individual differences in sensitivity and the impact of specific vitamin forms found in supplements.