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Vitamin D, as we all know, is made in the skin, or can be taken as a supplement or found sparingly in foods. From there, it travels to the liver where the liver makes “blood vitamin D” [called calcidiol, or 25(OH)D]. From there, “blood vitamin D” travels two directions to complete two functions.

The first function is the endocrine function. “Blood vitamin D” is taken to the kidney and the kidney pumps “activated vitamin D” into the blood, and this hormonal “activated vitamin D” maintains calcium in the body. “Activated vitamin D” is called calcitriol or 1,25(OH)2D.

The second function is the autocrine function. “Blood vitamin D” is taken to cells all over the body; cells in the brain, the heart, the pancreas, the lungs and more. These cells produce “activated vitamin D” inside their own cells, and this intracellular “activated vitamin D” tells cells what to do. This autocrine function is what researchers are really excited about and why you hear about new discoveries in the news all the time.

Only in rare health conditions is the body not able to complete the endocrine and/ or autocrine functions with a sufficient supply of “blood vitamin D.” One of these rare conditions is chronic kidney failure (CKD), where the body’s kidneys simply cannot produce circulating “activated vitamin D” and maintain blood calcium for endocrine function. However the autocrine function works just fine still because “blood vitamin D” goes straight to the cells for production of “activated vitamin D,” not through the kidney.

When someone has chronic kidney failure, they are sometimes prescribed Zemplar, which is “activated vitamin D,” and it allows the person with CKD to still maintain calcium. These patients still need regular vitamin D however, to make sure they still have enough “blood vitamin D” to fulfill the autocrine function.

This fundamental understanding is important when we look at study designs, particularly in studies that use vitamin D analogues (forms of “activated vitamin D”). Fairly recently, a study came out that reported there was no benefit in vitamin D therapy for heart health in patients with CKD.

Ravi Thadhani, MD,et al. Vitamin D Therapy and Cardiac Structure and Function in Patients With Chronic Kidney Disease. JAMA February 15, 2012, Vol 307, No. 7, pp 637-742

You may have seen the media cover this story; again, claiming that vitamin D does not help. This study was a randomized controlled trail that used “activated vitamin D” for one group and placebo for the other group. But neither group actually received vitamin D to boost “blood vitamin D.”

In essence, they designed the study so that the “activated vitamin D” group could carry out endocrine function but not autocrine function, while the placebo group could carry out neither endocrine function nor autocrine function. If both groups cannot boost their autocrine function, then you would not expect to see better health outcomes in your trial. This is something we could have concluded prior to the investigators even completing the study.

The authors state:

“Given our results with an active vitamin D analog, it is unlikely that nutritional vitamin D supplementation (ergocalcfierol or cholecalciferol) of similar duration modifies LVH (left ventricular hypertrophy).”

As I have explained in this post, this thought process is fundamentally incorrect. In the 80s, this was the line of thinking, where researchers were really excited about the potential for “activated vitamin D” after they saw profound effects in test tubes. We know now, however, that organs all over the body prefer to make their own “activated vitamin D” with “blood vitamin D,” and for the most part, you cannot force feed organs “activated vitamin D” and expect results.

If you really wanted to test whether vitamin D helps with cardiac function in patients with CKD, you would have to administer two things. For ethical reasons, you have to administer a drug like Zemplar to all, to make sure both groups are making up for their kidney’s inability to produce circulating “activated vitamin D.” Then you administer vitamin D to half. The two groups would look like this:

  • Vitamin D daily + Zemplar
  • Placebo daily + Zemplar

That way the kidney gets what it needs in all the patients, and half the patients get vitamin D to see if the heart improves. If you want to see if vitamin D can help the heart in kidney failure patients, this is the only way to do it. Unfortunately, this study wasn’t designed properly, and this is something the media cannot assess.

In short, this study did not use vitamin D , it used Zemplar, and it is important for the media to clarify that this was a Zemplar study, not a vitamin D study.

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