Researchers found a concerning pattern in four children with rare seizure disorders who were treated with high doses of vitamin B6 (pyridoxal phosphate). Three of the four children developed liver cancer after years of treatment, and one had severe liver damage that eventually improved. While vitamin B6 is normally considered safe, this study suggests that very high doses given for long periods might damage the liver in ways we don’t fully understand yet. The findings highlight the need for better quality vitamin B6 products and closer monitoring of liver health in children receiving this treatment.

The Quick Take

  • What they studied: Whether long-term, high-dose vitamin B6 treatment for rare seizure disorders might cause liver damage or liver cancer
  • Who participated: Four children with rare genetic seizure disorders (PNPO deficiency or ALDH7A1 deficiency) who all received high-dose vitamin B6 pills for several years
  • Key finding: Three out of four children developed liver cancer after receiving high-dose vitamin B6 treatment for years. One child had severe but reversible liver damage. This pattern suggests the vitamin B6 itself, not just the underlying disease, may be causing the liver problems.
  • What it means for you: If you or a child in your care takes high-dose vitamin B6 for seizures, regular liver check-ups become very important. Talk with your doctor about whether the dose can be safely reduced or if there are alternative treatments. Do not stop treatment without medical guidance, as the seizure control is also critical.

The Research Details

This study describes four individual cases of children with rare seizure disorders who all received long-term, high-dose vitamin B6 treatment. Two children had a confirmed genetic condition called PNPO deficiency, while two had a different genetic condition called ALDH7A1 deficiency. All four children took vitamin B6 pills by mouth, and the doses were changed frequently because different brands and formulations were used depending on what was available. The researchers tracked what happened to these children over time and looked for patterns in their health outcomes, particularly focusing on liver health and function.

This approach is important because it identifies a potential safety problem that might not show up in typical studies. By carefully documenting what happened to these specific children and looking for common patterns, the researchers were able to spot a concerning trend—liver cancer developing in children on the same treatment. This type of detailed case reporting can alert doctors to problems that need further investigation.

This is a small study of only four children, so the findings need to be confirmed with larger research. However, the fact that three out of four children developed the same serious complication is striking and suggests a real pattern worth investigating. The study is limited because it cannot prove that vitamin B6 caused the liver cancer—it only shows that the children were exposed to vitamin B6 and then developed liver problems. More research is needed to understand exactly how vitamin B6 might damage the liver and to identify which children are at highest risk.

What the Results Show

Three of the four children developed liver cancer (hepatocellular carcinoma) after receiving high-dose vitamin B6 treatment for several years. The fourth child developed severe liver damage that was reversible—meaning it improved when treatment was adjusted. All four children had been taking very high doses of vitamin B6 by mouth, and all had experienced frequent changes in which brand or type of vitamin B6 they were using due to availability problems. The timing of liver problems appearing after years of treatment in children with different underlying genetic conditions suggests that the vitamin B6 itself, rather than the genetic disease alone, may be responsible for the liver damage. In two of the children, doctors were able to reduce the vitamin B6 dose by more than 30% by giving it more frequently throughout the day, and importantly, the children’s seizures remained controlled even with the lower total dose.

The researchers identified three possible ways that high-dose vitamin B6 might damage the liver: by disrupting how cells produce energy (mitochondrial dysfunction), by chemically modifying proteins in harmful ways (Schiff base-mediated protein modification), and by allowing toxic breakdown products of vitamin B6 to build up in the body. The fact that two children could have their doses reduced without losing seizure control suggests that some children may be receiving more vitamin B6 than they actually need, which could reduce their risk of liver damage.

Vitamin B6 has long been considered a safe vitamin, even at higher doses, because it is water-soluble and excess amounts are normally excreted in urine. However, this case series suggests that when doses are extremely high and given for many years, safety concerns may emerge that weren’t previously recognized. This finding challenges the assumption that vitamin B6 is completely safe at any dose and suggests that the pharmaceutical industry and medical community need to reconsider safety guidelines for long-term, high-dose use.

This study describes only four children, which is a very small number. We cannot be certain that vitamin B6 caused the liver cancer based on this evidence alone—it’s possible other factors were involved. The children received different brands and formulations of vitamin B6 due to availability issues, so it’s unclear whether the problem is with vitamin B6 itself or with impurities or differences in how various products are made. The study cannot tell us how common this problem is—we don’t know if liver cancer develops in most children on high-dose vitamin B6 or if these four cases are exceptionally rare. Larger, longer-term studies are needed to understand the true risks.

The Bottom Line

Children receiving long-term, high-dose vitamin B6 for seizure disorders should have regular liver function tests (blood tests that check how well the liver is working). Doctors should consider whether doses can be safely reduced or given more frequently to lower total daily exposure. Only pharmaceutical-grade, high-quality vitamin B6 products should be used. Parents and patients should discuss with their neurologist whether alternative treatments might be available. Do not stop vitamin B6 treatment without medical guidance, as seizure control is critical. (Confidence level: Moderate—based on a small case series, but the pattern is concerning enough to warrant precaution.)

This research is most relevant to children with rare genetic seizure disorders (PNPO deficiency or ALDH7A1 deficiency) who are being treated with high-dose vitamin B6. Their parents, neurologists, and other healthcare providers should be aware of these findings. People taking normal doses of vitamin B6 as a supplement do not need to be concerned based on this study. However, anyone taking very high doses of vitamin B6 for any reason should discuss this research with their doctor.

In the cases described, liver problems developed after several years of high-dose vitamin B6 treatment. This suggests that liver damage from vitamin B6 is not immediate but develops gradually over time. Regular monitoring should begin as soon as high-dose vitamin B6 treatment starts, rather than waiting for symptoms to appear.

Want to Apply This Research?

  • If taking high-dose vitamin B6, track liver function test results (AST, ALT, and bilirubin levels) every 3-6 months. Record the date of test, the specific values, and any changes in vitamin B6 dose or formulation. Note any symptoms like yellowing of skin or eyes, dark urine, pale stools, or abdominal pain.
  • Work with your doctor to establish a regular liver monitoring schedule. Use the app to set reminders for scheduled blood tests and doctor appointments. Document which brand and formulation of vitamin B6 you’re using, and note any changes. Keep a log of seizure control to help your doctor determine if dose reductions are safe.
  • Create a long-term tracking dashboard showing liver function test trends over months and years. Set alerts if test results fall outside normal ranges. Track the relationship between vitamin B6 dose changes and both seizure control and liver function. Share this data with your healthcare provider at each visit to support informed decision-making about treatment adjustments.

This research describes a small number of cases and cannot definitively prove that vitamin B6 caused liver cancer in these children. If you or a child in your care is taking high-dose vitamin B6 for seizures, do not stop treatment without consulting your doctor, as seizure control is critical. Instead, discuss these findings with your healthcare provider to determine whether additional liver monitoring is appropriate and whether dose adjustments might be possible. This information is for educational purposes and should not replace professional medical advice. Always consult with a qualified healthcare provider before making any changes to treatment.