Patient’s with Hypophosphatasia (HPP) typically have high levels of Vitamin B6 in their blood. The level is not just high, it can be 5 to 6 times higher than the upper limit and because this is very common in HPP patients it is often used as a tool to help when diagnosing HPP. The reason the Vitamin B6 levels are so high is because the enzyme Alkaline Phosphatase (ALP) is responsible for regulating vitamin B6 intracellularly in the blood. In HPP patients our bodies do not make enough ALP, and therefore we cannot regulate Vitamin B6 in our blood like a normal person which leads to these high levels. Here is a photo of my lab work showing how high my level was.
As a general into to B6, Vitamin B6 is one of eight B vitamins, where B vitamins are important for proper cell function. It is water-soluble, so they aren’t stored in the body normally, and we are supposed to get our vitamin B6 through what we eat. Vitamin B6 specifically is involved in immune function, brain development and more. You can also find vitamin B6 in many tissues and organs including the Blood, liver, intestines, muscles, bones, kidney, brains and more. So, it truly is an essential vitamin.
Often times the assumption is that because the vitamin B6 levels in the blood are so high that HPP patients experience vitamin B6 toxicity.
One of the questions I was asked to look into in terms of research was “Do we (HPPers) actually have B6 toxicity or do we have b6 deficiency because we don’t break down the B6 into pyridoxine.”
Basically, do we really have B6 toxicity (too high) or deficiency? The answer was actually fascinating!
I came across several research papers, the first titled “Perinatal Hypophosphatasia: Tissue Levels of Vitamin B6 Are Unremarkable Despite Markedly Increased Circulating Concentrations of Pyridoxal-5’-Phosphate.” What they did was collect tissue samples from multiple areas of the body of Hypophosphatasia patients, including the Plasma, Vertebra, Liver, Kidney, Muscle, and Brain and measured the Vitamin B6 directly in those tissues.
The reason they wanted to do this type of testing was this: “Of interest, except for the occasional occurrence of seizures or nephrocalcinosis in the severe forms, we noted that manifestations of B6 deficiency or intoxication are generally absent in Hypophosphatasia.” We do not usually show signs of actual B6 toxicity even though our plasma levels are usually very high.
The plasma PLP was high as expected but surprisingly the B6 in all the tissue samples were normal. They determined that Alkaline Phosphatase is what is called an Ectoenzyme, which just means that ALP works to regulate B6 intracellularly. This means ALP is regulating B6 within the blood, but it does not regulate B6 elsewhere in the body. Some other enzyme is regulating the B6 levels within the tissues. This is why the tissue samples showed normal levels of B6 and why HPP patients who have high B6 levels do not show actual symptoms of B6 toxicity or actually have B6 toxicity. I want to be clear that this is not simple or cut and dry and there can be times when this may not be the case.
So, the answer to the question “Are HPP patients truly B6 deficient of toxic” is in most cases we are neither. The instances where vitamin B6 related seizures happen is sort of an outlier and I have not dug into more in-depth research on that yet. There are other tests that can be performed to see if you are vitamin B6 deficient/toxic, but usually these aren’t warranted unless there are some symptoms that could be due to B6 toxicity of deficiency.
My next post is about a new paper out where a newborn had severe life-threatening perinatal HPP but when they checked his B6 levels they were normal, it’s a fascinating case study. I really hope this helps in some way and makes sense, if not, please feel free to ask questions or for clarity. I am looking forward to posting more and shedding as much insight as I can.
I just wanted to say thank you to my friends at SoftBones for allowing me to do this and for providing me with additional research papers. It truly is a collective effort to make a difference for patients, and I am very grateful for their help.