You may, or may not, have heard about Vitamin B6 toxicity and its side effects. There is a lot of hype surrounding this essential B-vitamin along with much mis-information. It is always best to get vitamins from whole foods, but should supplementation be required always consult a qualified health professional. It is also important to be aware of supplements that contain a complex of nutrients – check all supplements you are taking to ensure you aren’t getting more of one, especially B6.
Here are some facts:
From homocysteine regulation to mood and immune function, vitamin B6 is a foundational nutrient that underpins diverse bodily functions. But like many nutrients, balance is essential. Deficiency can lead to fatigue and nerve pain, while excess may result in peripheral neuropathy with burning, numbness or tingling as hallmark signs.1 With rising media coverage of ‘B6 poisoning’ cases, its use is now under intense scrutiny, leaving healthcare practitioners and patients increasingly uncertain about its safety.
Most people metabolise vitamin B6 without issue and adverse events remain rare. According to the Therapeutic Goods Administration’s (TGA) Database of Adverse Events, 174 reports of neuropathies have been documented in Australia, mostly since January 2023. The TGA’s interim decision report also notes that while intake greater than 200 mg/day for extended periods were previously linked to these events, some European cases now involve low to moderate doses.2
It’s important to recognise that these reports do not necessarily indicate true toxicity. Elevated test results and symptoms can be misleading as they do not always equate to clinical toxicity and may even result from deficiency.
This raises an important question: Why does vitamin B6 pose a risk for some but not others and how can we identify those who may be more susceptible to adverse effects?
The issue isn’t just about dosage, it’s also about how individuals metabolise B6, which can vary based on genetic factors, overall nutrient intake and other confounding variables. Although the activated form pyridoxal 5′-phosphate (PLP/P5P) is considered the safest, the growing number of adverse events suggests that all forms of B6 carry some level of risk. This reinforces the importance of practitioner-only dispensing and individualised dosing, with regular monitoring to ensure ongoing suitability.
Peripheral neuropathy: differential diagnosis
Aside from vitamin B6 imbalances, it’s important to recognise that peripheral neuropathy can be caused by various conditions including diabetes, hypothyroidism and chronic liver disease, as well as factors such as toxic exposures, medications, infections and hereditary disorders.3 These should always be considered as part of a patient’s assessment.
Under Review: The Regulatory Response to Vitamin B6 Safety
The TGA’s recent interim decision limits listed medicines to a maximum of 50mg of vitamin B6 in any form. Supplements exceeding this threshold will be reclassified as Schedule 3, requiring a prescription from a registered practitioner, pharmacist or doctor. This means the TGA currently considers doses below 50mg to be low risk in the general population.
How can you measure your levels:
- Plasma PLP is the most common and clinically significant marker used to assess vitamin B6 status as it reflects liver concentrations and is minimally influenced by dietary fluctuations. However, PLP can also be measured in serum, urine and erythrocytes.
- Vitamin B6 levels correlate strongly with intake, increasing up to tenfold with supplementation and adjusting within 1–2 weeks in response to changes in status.
However, because Vitamin B6 is involved in numerous enzymatic reactions in our body, we can also get an idea of levels by testing the following:
Erythrocyte AST and ALT tests
Excess: Normal or unchanged activity: enzymes are saturated with PLP
Deficiency: Higher activity in PLP-supplemented assays reflects low B6 status (enzymes are inactive without PLP)
Kynurenine pathway metabolites
Excess: Increased HAA:HK ratio reflecting enhanced PLP-dependent conversion
Deficiency: Decreased HAA:HK ratio indicating poor PLP-dependent enzyme activity
Plasma amino acids
Excess: Decreased glycine and serine due to enhanced enzymatic breakdown
Deficiency: Increased glycine and serine due to reduced activity of glycine decarboxylase and SHMT
One-carbon metabolism
Excess: Increased methylation and amino acid conversion
Deficiency: Impaired conversion of serine to glycine and reduced methylation capacity
Transsulfuration and homocysteine
Excess: Decreased cystathionine and homocysteine due to inefficient conversion to cysteine
Deficiency: Increased cystathionine due to impaired cystathione γ-lyase activity. Potentially high homocysteine due to reduced transsulfuration
Pathology results can show high variability, often influenced by confounding factors that may account for 30–40% of the variance in plasma PLP levels. These factors should also be considered for accurate evaluation:
- Chronic inflammation
- Alkaline phosphatase (ALP) activity
- Low serum albumin concentration
- Renal function
- Liver function
- Inorganic phosphate consumption (common sources include food additives/preservatives in processed foods, canned and bottled foods and beverages) These are highly absorbable (>90%).
- Other considerations: pregnancy, menopause, alcohol intake, some medications and total B6 intake (supplemental and dietary sources)
Clinical Note: Plasma PLP levels drop within hours of glucose or high carbohydrate intake and are inversely associated with fasting glucose and HbA1c. These findings emphasise the importance of using fasting samples for accurate assessment and considering elevated glucose levels in diabetic patients.4
What range is considered high?
Plasma PLP concentrations in the 100 – 200nmol/L are often considered moderately elevated,5 although reference ranges vary by laboratory and assay method. Importantly, high PLP does not necessarily indicate toxicity, as individual tolerance also varies. Symptoms of B6 toxicity, such as peripheral neuropathy, are more commonly associated with plasma levels exceeding 190nmol/L.6 Toxicity risk is influenced by dose, duration, form of supplementation and individual factors such as genetics, hepatic and renal clearance and cofactor status (e.g., zinc, magnesium, and riboflavin). Given this complexity, B6 toxicity is typically diagnosed clinically and testing is often reserved for cases with a suggestive history and symptoms.
Understanding elevations in children
Consider the overuse of supplementation, genetic variants or increased intake of fortified foods such as breads, cereals, energy drinks or snacks. Total B6 is also abnormally high in autism, due to low conversion of pyridoxine to PLP.7
The pyridoxine paradox8
High plasma PLP can also coexist with low intracellular B6 activity, leading to deficiency-like symptoms. At high doses, pyridoxine competes with PLP, inhibiting PLP-dependent enzymes and disrupting key pathways. Essentially, excess pyridoxine can ‘overwhelm the system’, creating a functional bottleneck that mimics deficiency – despite elevated levels. This phenomenon is known as the ‘B6 paradox’.
Solving the puzzle: why responses vary9
Similar to MTHFR gene variants that impair folic acid metabolism, certain genetic polymorphisms can disrupt the conversion of B6, particularly in its pyridoxine form. In such cases, pyridoxine may not efficiently convert to its active form, causing a buildup of unmetabolised B6 and the onset of neurotoxic effects. This highlights the importance of selecting the appropriate form of B6 based on the patient’s metabolic profile, rather than avoiding supplementation, especially when aiming for specific health or treatment goals.
Gene variants influencing B6 metabolism
Functional testing for these variants can provide valuable insights into an individual’s vitamin B6 metabolism and help guide appropriate supplementation and treatment strategies.
In light of the above information I hope that you now have a better understanding of why it is important to consult a qualified naturopath for your supplemental needs and to definitely avoid the temptation of self-prescribing or buying inferior products on-line.
References:
1. Office of Dietary Supplements, National Institutes of Health. Vitamin B6 – Fact Sheet for Health Professionals. 2023. Accessed August 15, 2025. https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/#h18
2. Therapeutic Goods Administration. Notice of Interim Decision to Amend (or Not Amend) the Current Poisons Standard in Relation to Pyridoxine, Pyridoxal or Pyridoxamine (Vitamin B6).; 2025. https://anta.informz.net/ANTA/data/images/TGA%20Report%20-%20B6%20Update.pdf
3. Azhary H, Farooq MU, Bhanushali M, Majid A, Kassab MY. Peripheral Neuropathy: Differential Diagnosis and Management. Peripheral Neuropathy.
4. Ueland PM, Ulvik A, Rios-Avila L, Midttun Ø, Gregory JF. Direct and Functional Biomarkers of Vitamin B6 Status. Annu Rev Nutr. 2015;35(1):33-70. doi:10.1146/annurev-nutr-071714-034330
5. Stewart SL, Thomas S, Höke E, Simpson D, Singleton JR, Höke A. Vitamin B6 levels do not correlate with severity of neuropathy in chronic idiopathic axonal polyneuropathy. J Peripheral Nervous Sys. 2022;27(1):31-37. doi:10.1111/jns.12480
6. Sherley M. Pyridoxine toxicity from over‑the-counter supplements. The Royal Australian College of General Practitioners. 2025;54(8).
7. Adams JB, George F, Audhya T. Abnormally High Plasma Levels of Vitamin B6 in Children with Autism Not Taking Supplements Compared to Controls Not Taking Supplements. The Journal of Alternative and Complementary Medicine. 2006;12(1):59-63. doi:10.1089/acm.2006.12.59
8. Vrolijk MF, Opperhuizen A, Jansen EHJM, Hageman GJ, Bast A, Haenen GRMM. The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function. Toxicol In Vitro. 2017;44:206-212. doi:10.1016/j.tiv.2017.07.009