Tuesday, September 3, 2013

Why Would My Intracellular Calcium Be Elevated?

I recently received a question from someone reading this blog asking me why his/her intracellular calcium would be elevated. Intracellular Calcium is not something that is typically measured, but I would suspect that it is elevated in most ME patients. Why? Because it takes energy (ATP) to pump Calcium out of cells. Energy (ATP) is not something we have a whole lot of, or at least are able to utilize normally. On most cells there are a couple different ways to keep Calcium ions on the outside of the cell so that a gradient is present and the Ca++ ions can rush back into the cell to cause some sort of event - this is important for cell signaling, nerve action potentials, muscle contraction, and a host of other physiologic events.

Check out these graphics that show what happens to nerve cells in the brain during/after a stroke. I believe this is very much analogous to what is happening all the time to all cells in ME patients, just not to the same extreme, or lethal, degree. ME patients show signs of being functionally hypoxic, meaning they are not actually hypoxic (have normal O2 levels), but look very similar to people who are hypoxic - see previous post and look at how normal people in the Everest III study (simulated high altitude) look exactly the same as ME patients on ECHO. Getting into why we look functionally hypoxic is a big topic that I am too weak to write about now, but hopefully sometime soon.

While we are discussing Calcium it would be a shame not to mention vitamin D. Vitamin D, its regulation, and its many effects are often misunderstood or at least over-simplified by physicians into, high vitamin D = good, low vitamin D = bad. The whole vitamin D axis is extremely complex and even those who know it the best, I am sure do not know everything as it is highly unlikely that we have discovered all of its effects at this time.

That being said, it is important to note that ME patients often have strange, often widely varying levels of the "regular" form of vitamin D that is typically tested: 25-hydroxyvitamin D (25-D).  It is also important to know that 25-D has little to no correlation to the bioactive form that our bodies primarily use: 1,25-dihydroxyvitamin D, also named Calcitriol.  If you are a ME patient and your doctor is suggesting you take vitamin D based off the "regular" 25-D vitamin D test, I would look into getting the bioactive form tested before taking any action.

Why?  Because 1,25-dihydroxyvitamin D, (aka Calcitriol or 1,25-D) is the bio-active form of vitamin D. It is the form of vitamin D that actually causes the important physiological changes of calcium metabolism and immune system regulation.

In healthy people, or those without chronic inflammatory diseases, 25-hydroxyvitamin D (25-D) is an excellent test because it indicates the vitamin D stored in a patient's body and consequently is the typical vitamin D lab ordered.

Calcitriol in healthy people is rarely abnormal as it is normally very tightly regulated. However, in patients with ME and similar chronic inflammatory diseases, the vitamin D axis can become dysregulated and any correlation between 25-D and Calcitriol no longer exists and cannot be assumed. For example, in patients with ME, Calcitriol levels may be extremely high, while 25-D remains normal or even low.