How do you make a hormone? You put her in the sunshine. The discussion of the biochemistry of vitamin D is just as convoluted and confounded as the last statement. To quote the words of Reinhold Vieth, “There is probably no other area of steroid biochemistry so burden by terminology complexity as the field of vitamin D.” This has always been painfully obvious to me as I have tried to sort through the nomenclature of vitamin D to reach an understanding of what doctors, researchers, and scientist were saying. The confusion has recently been brought to my attention again in an email conversation with a reader.
It seems that the main fall back word is vitamin D and we do not know what the person using the word is really referring to, or more clearly, what specific compound the communicator is pointing toward. In some cases and I am afraid more often than not, even the person using the word does not know what compound they are giving for reference. I have been guilty of that error myself in writing this blog. To make matters worse, it has been assumed, that various compounds of vitamin D are equal in their biochemistry. This could not be further from the reality. Now that Oxford scientist have shown that over 2700 genes can be impacted by vitamin D, the clarity of the various sterols is necessary in order to reach defining realities inside of the human body.
As an undergraduate student, I started as a major in chemistry. My first year laboratory professor was Dr. Forrest C. Hentz. Dr. Hentz’s advice to us as we approached the various curricula was to spend as much time as necessary in learning the nomenclature of each subject. He went on to describe that ninety-seven percent of learning was in the understanding of the physical realities of the words that were being used. This could not be more appropriated when related to the studies of vitamin D. Dr. Hentz also went on to say that the many intermediates in chemical reactions might not every be understood, but the importance was in the beginning and ending compounds. It is time stop playing ‘money games’ with the analogs of vitamin D, and to start looking for the many diseases from the deficiency of vitamin D as formed from UVB light incident on the skin.
The art and science of medicine will always be a slave to the definition of the words that are used to communicate physical realities. – Pandemic Survivor
Vitamin D Deficiency Survivor 
Mark, this is an incredibly interesting subject. Having studied vitamin D for around 10 years, I will attempt to shed some light on the terminology of the vitamin D “life cycle”.
Long before there is vitamin D there is a form of cholesterol in your skin, called 7-dehydrocholesterol. In the presence of UVB radiation (which only occurs midday), this version of cholesterol gets converted to what is commonly called “pre-vitamin D”. The pre-vitamin D hydroxylates in the liver to become 25-hydroxy-vitamin D, usually abbreviated as 25(OH)D. Some researchers (like Anthony Norman) abbreviate it as 25(OH)D3, but it’s the same.
25(OH)D, also known as calcidiol, is the storage form of vitamin D, that is to say, it is not yet the active form. Calcidiol circulates in the bloodstream whereupon it becomes a chemical precursor instantly available when the body signals a need. Mostly the kidney converts calcidiol into the active form of vitamin D, calcitriol, or 1,25 dihydroxy vitamin D, usually abbreviated 1,25(OH)2D. Whoever came up with the names calcidiol and calcitriol, I need to talk to them. It’s like naming twin boys Jeff and Geoff, an incredibly bad idea guaranteed to cause confusion.
Once in the active form, the vitamin D (or calcitriol) is available to occupy vitamin D receptors which are present in the nucleus of most of our cells. When the receptor is “happy” (by mating with 1,25(OH)D ) the cell functions normally. When the vitamin D receptor mates with whatever happens to be floating by (which it does when not enough vitamin D is available), all kinds of bad things happen.
Mark, you started this article with the tired old joke about hormones, which brings up a whole new opportunity for even more confusion. Is D a vitamin or a hormone? The answer depends on where in the lifecycle you are looking. If you take an oral supplement, I can build a strong case it is a vitamin. However, after the liver converts the 25(OH)D to 1,25(OH)2D it is clearly a hormone. Not just any hormone but a secosteroid hormone. And not just any secosteroid hormone, but one that acts as a biochemical switch for approximately 10% of all the genes in the human genome. And it’s not just any biochemical switch, but its specialty is to switch ON genes that promote health and longevity, and turn OFF genes that promote chronic degenerative disease. Your readers who wish to delve into this further should investigate “epigenetics”, or how food, lifestyle, mental state, etc, affect our genetic heritage as expressed in DNA.
There. The confusion is gone. Le me know when you are ready for the quiz.
Regards, Rich
Rich,
It is good to hear from you. I hope all is well. Thanks for your efforts in clarification, but you make the very point that I was talking about. In your second paragraph, you make the statement that 25(OH)D and 25(OH)D3 are “all the same”. The American Chemical Society is trying to clear up the confusion(American Chemical Society – “New Standard for vitamin D testing to assure accurate test results”, January 25, 2012. http://www.eurekalert.org/pub_releases/2012-01/acs-nsf012512.php ) to bring testing data inline for 25(OH)D. I would hope in the future that when stated as 25(OH)D that this is the total of all the types of 25(OH)D’s. You most have
watched the “chicken mesmerized” video on my post Mesmerized by
Epimerization https://pandemicsurvivor.com/2012/01/28/mesmerized-by-epimerization/ – just kidding, but it is a great video showing how our scientist are ‘mesmerized by the complexity in vitamin D nomenclature. The ACS has shown that the assays for test should pick up 3-epi-25(OH)D3, 25(OH)D3, 3-epi-25(OH)D2, and 25(OH)D2. The confusion continues because worldwide standardization should be made. I will not be willing to take the test until clarification has been made by a group representing the major countries of the world have reached agreement in nomenclature and I believe that it should either be headed by Anthony Norman or Reinhold Vieth. Until then, no papers should be accepted for publication without clarification of what the writer is discussing. I think now the greatest confusion is trying to interpret papers that just say 25(OH)D and its effect on disease states without clarifying whether it is 25(OH)D2 or 25(OH)D3 or the total. You will note in the news release that other important forms are not even mentioned like 25(OH)D sulfate. According to one paper that I referenced in the epimer post, the researchers stated that 25(OH)D3 and 25(OH)D3 sulfate occurred in almost equal amounts in serum.
Yeah, I know that I don’t have a degree in organic chemistry either, but someone needs to reach clarification.
The argument on whether a hormone, I was baiting you for my next post. Don’t be pinching anyone now!
Be well!
Mark
Okay Rich, if you just want to watch the chicken video again here it is:http://www.youtube.com/watch?v=sqZZ95L2n7o&feature=related It is a great one minute video!