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Pyridoxine Paradox: The Type of Vitamin B6 that Causes Vitamin B6 Deficiency

Vitamin B6 includes the family of compounds including pyridoxine, pyridoxal, pyridoxal 5`-phosphate and a few others. Recent research suggests that consuming high levels of the inactive form, pyridoxine, can lead to negative side effects that are oddly similar to B6 deficiency.

In their paper, The Vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin b6 function, Misha et. al shed light on mysterious phenomena in which people reported cognitive issues associated with B6 supplementation. Oddly enough, B6 is regarded largely for its benefits for cognitive health.

Pyridoxine Paradox

This in-vitro study detailed two very important findings. First, researchers demonstrated pyridoxine toxicity to neuronal cells. Second, and this was the kicker; researchers showed that high levels of pyridoxine ultimately limits the amount of pyridoxal 5`-phosphate (P5P, PLP).

The research team concluded this dynamic of pyridoxine may help explain cases where supplementation Vitamin B6 ultimately results in symptoms of Vitamin B6 deficiency.

Bioavailability

Pyridoxine doesn’t have a direct role in human health other than to be converted into pyridoxal. Pyridoxine is found in high amounts in many plant sources as well as supplements.  Supplements containing pyridoxine are often labeled as Vitamin B6. Knowing which form is in a supplement requires some label reading.

As Chris Masterjohn, Ph.D. notes, plant-based sources of Vitamin B6 should, perhaps, not be regarded as offering bioavailable equivalents as animal-based sources. Dr. Masterjohn had this to say in a recent Tweet:

Plant foods exclusively have pyridoxine, which is useless unless converted to pyridoxal, mainly in the liver, using an enzyme that requires riboflavin and is subject to polymorphisms that lower its activity.

Worse, pyridoxine is often bound to sugars within plants, lowering its bioavailability. These have lower absorption and even what is absorbed is often never freed, and can pass into mother’s milk and antagonize B6 status in her infant.

It is egregious for any source to use the terms “vitamin B6” and “pyridoxine” synonymously. This is in every way equivalent to calling “vitamin A” “beta-carotene.”

Masterjohn concluded by noting supplementation with the pyridoxine form, or excess consumption of plant-based sources could inhibit the conversion to active forms. In other words: taking the wrong kind of Vitamin B6 could cause symptoms of Vitamin B6 deficiency.

For those wanting to learn more about Vitamin B6, as well as other nutritional “gotchas,” Dr. Masterjohn has a free 30-day online course that covers many nutrients, their role in the body, and why they’re important.

Vitamin B6 Supplements

One major highlight of this research is that taking the wrong kind of Vitamin B6 can be disastrous. Quality supplements brands rarely use the pyridoxine form—at least in my experience. That said, I’ve still seen brands that I know and love offer Pyridoxine forms. Always check your labels.

Given the recent EFSA reduction in upper limits for B6 and this recent (2017) research, it seems that negative symptoms associated with Vitamin B6 supplementation are likely attributable to the form taken—not the amount.

Researchers in this study concluded as such:

Perhaps it might be better to replace pyridoxine by pyridoxal or pyridoxal-phosphate as vitamin B6 supplements, which are much less toxic. In this way, the vitamin B6 paradox may potentially be prevented.

Types of Vitamin B6

The term Vitamin B6 is used to describe several different compounds. Several of these may be the only—or one of several—active ingredient in Vitamin B6 supplements.

I’ve seen many P5P supplements labeled as such but I suggest you always check the label. The following are the vitamer forms commonly referred to as Vitamin B6:

  • Pyridoxal (PL)
  • Pyridoxine (PN)
  • Pyridoxamine (PM)

Additionally, the following compounds may also be called Vitamin B6:

  • Pyridoxal 5′-phosphate (PLP)
  • Pyridoxine 5′-phosphate (PNP)
  • Pyridoxamine 5′-phosphate (PMP)

From these second forms, I’ve only ever seen Pyridoxal 5′-phosphate (PLP) for sale as a supplement. As noted by researchers in this study, pyridoxine is likely the worst choice for a Vitamin B6 supplement while P5P would be a better option.

Vitamin B6 Deficiency

Common causes of Vitamin B6 deficiency include dietary restrictions, digestive issues, or medications that decrease the liver’s ability to convert B6 to the active P5P form. The symptoms of B6 deficiency are as follows:

  • Weakness
  • Numbness and/or pain in extreme ties
  • Depression
  • Confusion
  • Seizures

Vitamin B6 Dosage

The European Food Safety Authority (EFSA) originally held that the Tolerable Upper Intake Level (UL) for Vitamin B6 to be 100mg/day but later revised that number to 25mg/day. The United States currently maintains the 100mg/day number (R) with an RDA for adults being between 1.3-1.7mg/day. The European Population Reference Intake (PRI) (Comparable to US RDA) is 1.6-1.7mg/day for adults (R).

I won’t argue the merit of either stance but this recent research suggests the issue is more with the form of B6 being consumed rather than the amount. That’s to say: a 25mg/day UL is probably better suited when pyridoxine is the form taken but may not be necessary for other forms.

I think one huge takeaway is that symptoms of Vitamin B6 deficiency should be carefully re-assessed in cases where pyridoxine-fortified foods or pyridoxine-based B6 supplementation is involved.

Review

Nutrition is, at the best of times, a very personal subject. One person’s nutrition state isn’t likely to ever be the same as another. Of course, there are broad similarities between us all. One is the requirement of Vitamin B6 to help support our bodies’.