Vitamin B6 is a very safe and useful nutraceutical.

Click the picture for the story by Michelle Wisbey

Click the picture for the video of the story

The article, ‘‘I couldn’t walk’: GP’s personal story of vitamin B6 toxicity’ highlights the personal experience of Dr. Mary Buchanan, a general practitioner, who developed peripheral neuropathy attributed to vitamin B6 toxicity. She began taking magnesium tablets to manage restless leg syndrome, unaware they contained vitamin B6. Over time, she experienced progressive muscle weakness and difficulty walking. After a thorough diagnostic process, her condition was linked to prolonged use of these tablets. Although she stopped taking them, her recovery has been slow and incomplete. The article emphasises the need for awareness about B6 ‘toxicity’, noting it is often overlooked by both doctors and patients due to its presence in many products. Experts call for better labelling, patient education, and routine discussions about supplements in clinical settings.

The article’s conclusion that vitamin B6 toxicity was the sole cause of Dr. Buchanan’s neuropathy is too simplistic and overlooks several critical factors:

1. B6 Dose Not Excessive: While the article highlights B6 toxicity, the doses mentioned are not excessive by general standards. The patient was taking a daily dose of 50mg, much higher than the RDI but much lower than is sometimes used. Tens of thousands of individuals consume similar or higher doses of vitamin B6 daily for years without adverse effects. In Australia, vitamin B6 is a common ingredient in numerous health products. The Therapeutic Goods Administration (TGA) reports that there are currently more than 1,000 listed medicines containing vitamin B6. Regarding the prevalence of vitamin B6 consumption, a national survey indicated that 63% of Australians regularly use complementary medicines, which include dietary supplements. While this statistic encompasses all types of supplements, it suggests that a significant portion of the population may be consuming vitamin B6, either as a standalone supplement or as part of a multivitamin complex. Given the widespread availability and consumption of vitamin B6-containing products, it is reasonable to infer that tens of thousands of Australians take vitamin B6 daily over extended periods without experiencing adverse effects. This widespread use underscores the importance of considering individual factors, such as genetic predispositions or sensitivities, when evaluating cases of neuropathy potentially linked to vitamin B6.

2. The Form of Vitamin B6 Matters: Pyridoxine hydrochloride, a common form of B6 in supplements, can accumulate in the body and cause toxicity in sensitive individuals. The active form of vitamin B6, pyridoxal-5-phosphate (P5P), is less likely to cause issues because it is better metabolised. Interestingly, the conversion of pyridoxine hydrochloride requires a zinc dependent enzyme, insufficient zinc being a common finding. The form of B6 in the magnesium tablets was not addressed in the article. Here is the product that the patient had been taking according to the television interview and pictures provided by the RACGP article above:

BioCeuticals Ultra Muscleze® is a magnesium-based supplement designed to support muscle health and function. Each 6g dose provides 280.2 mg of magnesium from a combination of magnesium amino acid chelate (UltraMag®) and magnesium oxide. In addition to magnesium, the formula includes a range of B vitamins, such as:

• Vitamin B1 (Thiamine hydrochloride): 25 mg

• Vitamin B2 (Riboflavin): 5 mg

• Vitamin B3 (Nicotinamide): 20 mg

• Vitamin B5 (Pantothenic acid, as calcium pantothenate): 25 mg

• Vitamin B6 (Pyridoxine hydrochloride): 50 mg, equivalent to 41.1 mg of pyridoxine

• Folic acid (Vitamin B9): 150 micrograms

• Vitamin B12 (Cyanocobalamin): 18 micrograms

These B vitamins are included to support energy production and reduce tiredness and fatigue. The product also contains other ingredients like glutamine, taurine, and antioxidants to further support muscle function and recovery.

Practitioner only vitamins & supplements

It's important to note that each 6g dose contains 50 mg of pyridoxine hydrochloride (vitamin B6). Regular consumption of such doses should be monitored, especially considering that the Therapeutic Goods Administration (TGA) in Australia has strengthened labeling requirements for products containing daily doses over 10 mg of vitamin B6 due to potential risks of peripheral neuropathy.

Practitioner only vitamins & supplements

As with any supplement, it's advisable to consult with a healthcare professional before beginning use, particularly if you have underlying health conditions or are taking other medications.

As you can see, the product contained the hydrochloride form and not the pyridoxyl-5-phosphate form of B6.

3. B6 Alone Is Problematic: Vitamins in the B-complex work synergistically, and taking B6 alone can disrupt this balance, potentially exacerbating deficiencies or side effects. Dr. Buchanan’s supplement regimen should have been evaluated for completeness and balance. The inclusion of 50 mg of vitamin B6 (pyridoxine hydrochloride) in BioCeuticals Ultra Muscleze® is notable, but its balance within the broader B vitamin complex could potentially be optimised for better synergy and prevention of side effects such as neuropathy. Specifically, higher doses of vitamin B1 (thiamine), vitamin B3 (niacin), folic acid (B9), and vitamin B12 (cyanocobalamin) could provide more comprehensive support for nerve health and function.

Folic acid and vitamin B12, in particular, play critical roles in preventing neuropathies, as they are involved in the methylation cycle and the maintenance of the myelin sheath. Insufficient levels of these vitamins may leave users more susceptible to neurological side effects, especially when taking higher doses of isolated B6.

It is important to clarify that this is not intended as a criticism of the current formulation, which is clearly designed with care and attention to muscle health and energy metabolism. Rather, it is a suggestion to explore the potential benefits of a more balanced ratio within the B vitamin complex. Achieving proper balance in biochemical systems is essential for optimal performance and long-term health.

Such adjustments could further enhance the formulation's effectiveness and minimize the risk of adverse effects, providing even greater support for those who rely on it for muscle function and recovery.

4. Individual Sensitivities: The patient may have genetic or non-genetic sensitivities to vitamin B6, such as polymorphisms affecting B6 metabolism. Such factors are rarely considered in conventional assessments of toxicity. The patient in question may have specific genetic or non-genetic predispositions that affect their sensitivity to vitamin B6. Genetic polymorphisms, particularly those impacting enzymes involved in B6 metabolism, can alter the way the body processes and utilizes the vitamin. For instance there may be genetic variants in pyridoxal kinase (PDXK). PDXK is the zinc dependent enzyme responsible for converting pyridoxine (the form of B6 commonly found in supplements) into its active form, pyridoxal-5’-phosphate (PLP). Polymorphisms in the PDXK gene may impair this conversion, leading to suboptimal utilisation or accumulation of B6 in a form that could contribute to toxicity. Also there may be variations in enzymes of the homocysteine pathway. B6 plays a key role in the metabolism of homocysteine, and mutations in enzymes like CBS (cystathionine beta-synthase) or MTHFR (methylenetetrahydrofolate reductase) may interact with B6 metabolism. These interactions could lead to imbalances in metabolic pathways and increased vulnerability to low level neuropathic effects.

Non-genetic factors such as reduced liver function, chronic illness, or medication use might impair the detoxification or excretion of B6, leading to its accumulation in tissues and increasing the risk of neuropathy. Older individuals or those with underlying conditions like diabetes, renal impairment, or malabsorption syndromes may process vitamins differently, making them more prone to adverse effects.

5. Neurological Issues with Other Vitamins: Other vitamins, including folic acid and vitamin B12, have also been linked to neurological issues when taken in isolation or inappropriate doses. The focus on B6 alone may oversimplify the broader risks of unbalanced supplementation.

6. Reversibility of Neuropathy: Neuropathy caused by vitamin B6 is often reversible with timely intervention. While Dr. Buchanan’s recovery has been slow, the article could have provided more hopeful guidance based on similar cases.

Conventional assessments of vitamin toxicity often rely on population-wide dose thresholds and ignore individual metabolic differences. This one-size-fits-all approach fails to account for:

1. Subpopulations with Unique Sensitivities: These individuals may develop symptoms of toxicity at doses well below those considered "safe."

2. Cumulative Effects: Prolonged intake of small amounts of B6 from multiple sources, even when individually below toxic thresholds, could overwhelm someone with an impaired ability to process the vitamin. There may also be the phenomenon of toxic synergism with other toxins the patient is exposed to such as medications, domestic and industrial chemicals.

To improve safety, healthcare professionals should:

1. Consider genetic testing or assessments of metabolic function when unexplained symptoms arise.

2. Recognize that "normal" intake levels for the general population may be excessive for certain individuals.

3. Advocate for personalised supplementation strategies based on genetic and biochemical profiles.

A Call for Extensive and Better Training in Nutritional Medicine for all Medical Disciplines

The case underscores a critical gap in medical education. Doctors and other healthcare professionals should be trained in nutritional medicine to understand nutrient uses and interactions, recognise potential side effects (rare), and provide the best evidence-based advice on supplementation.

My deepest sympathy goes to Dr. Buchanan. Her experience is a sobering reminder of the complexities of nutritional supplementation. While her story raises important concerns, a more nuanced and evidence-based discussion could better inform both medical professionals and the public about the safe use of nutraceuticals.

In summary, understanding and addressing individual sensitivities is crucial in avoiding adverse effects from essential nutrients like vitamin B6. Further research into the genetic and metabolic factors influencing B6 metabolism could enhance clinical guidelines and ensure safer supplementation practices. It is an extremely valuable nutrient for a very wide range of patients with many conditions.

References and Sources

General Information on Vitamin B6 and Toxicity

1. Therapeutic Goods Administration (TGA)

Vitamin B6 (pyridoxine) – Potential for peripheral neuropathy.

https://www.tga.gov.au/news/safety-alerts/vitamin-b6-pyridoxine

2. Australian Prescriber.

The safety of commonly used vitamins and minerals

https://australianprescriber.tg.org.au/articles/the-safety-of-commonly-used-vitamins-and-minerals.html

Genetic Sensitivities and Metabolism of Vitamin B6

3. Clayton, P. T. (2006).

B6-responsive disorders: A model of vitamin dependency.

Journal of Inherited Metabolic Disease, 29(2–3), 317–326.

https://pubmed.ncbi.nlm.nih.gov/16763894/

4. Fowler, B. (2005).

Homocysteine: Biochemistry, molecular biology, and role in disease.

Clinical Chemistry and Laboratory Medicine, 43(7), 688–693.

https://pubmed.ncbi.nlm.nih.gov/16047261/

5. Wilson, M. P., & Plecko, B. (2018).

Vitamin B6 metabolism and its role in neurological disease

Handbook of Clinical Neurology, 147, 365–375.

https://pubmed.ncbi.nlm.nih.gov/30671974/

Role of Balance in B Vitamins

6. Kennedy, D. O. (2016).

B vitamins and the brain: Mechanisms, dose and efficacy—A review.

Nutrients, 8(2), 68.

DOI: [10.3390/nu8020068](https://doi.org/10.3390/nu8020068)

7. McCaddon, A. (2013).

B vitamin therapy for homocysteine-related cognitive decline: An update.

BioMed Research International, 2013, Article ID 472797.

- DOI: [10.1155/2013/472797](https://doi.org/10.1155/2013/472797)

Adverse Effects of Vitamin B6 and Neuropathy Reversibility

8. Parry, G. J., & Bredesen, D. E. (1985).

Sensory neuropathy with low-dose pyridoxine

Neurology, 35(10), 1466–1468.

DOI: [10.1212/WNL.35.10.1466](https://doi.org/10.1212/WNL.35.10.1466)

9. Schaumburg, H. H., Kaplan, J., & Windebank, A. J. (1983).

Sensory neuropathy from pyridoxine abuse.

New England Journal of Medicine, 309(8), 445–448.

DOI: [10.1056/NEJM198308253090802](https://doi.org/10.1056/NEJM198308253090802)

10. Guilherme, P., et al. (2017).

Reversible peripheral neuropathy induced by excessive vitamin B6: A case report.

Journal of Clinical Neurology, 13(3), 291–294.

BioCeuticals Ultra Muscleze® Formula

11. BioCeuticals.

"Ultra Muscleze®"

Product information available at:

https://www.bioceuticals.com.au/products/ultra-muscleze

Ian Brighthope