In a paper critical of higher levels of vitamin D for allegedly increasing a marker of inflammation, c-reactive protein (CRP), Drs. Muhammad Amer and Rehan Qayyum of the Johns Hopkins School of Medicine, began their paper by saying:
“The cardiovascular protection offered by vitamin D and its analogues is probably mediated by modulation of inflammatory cytokines.”
Amer M, Qayyum R. Relation Between Serum 25-Hydroxyvitamin D and C-Reactive Protein in Asymptomatic Adults (From the Continuous National Health and Nutrition Examination Survey 2001 to 2006). Am J Cardiol. 2011 Oct 12.
If you will notice, both physicians know that vitamin D offers “cardiovascular protection.” However, they are concerned 25(OH)D levels higher than 20 ng/ml will increase inflammation as measured by CRP and thus worsen cardiovascular protection. CRP is a protein in the blood which tends to rise in response to inflammation or injury. Its physiologic role is to take part in the “complement system.”
The authors arrived at this conclusion by adjusting their data for up to 9 variables and finding that a 25(OH)D of 20 ng/ml is associated with a CRP (range 0-5) of approximately 1.7 while a 25(OH)D of 50 ng/ml is associated with a CRP of 1.9. Their raw findings contradict their adjusted data in that the raw data showed what we have known for some time and that is that in the lower ranges of 25(OH)D, vitamin D reduces CRP. As with most biomarkers of vitamin D, the big improvement is in people who get their 25(OH)D up from 5 ng/ml up to 20 ng/ml. We know that in most cases, the biggest bang for the buck is in treating severe deficiency in people with such low levels.
So if you have natural levels of vitamin D, say a 25(OH)D of 50 ng/ml, and you want to decrease your CRP by 0.2, then stop your vitamin D and stay out of the sun, get your levels to 20 ng/ml, and see if all the corrections and adjustments the doctors performed were correct. I certainly am not going to do such a silly thing.
Dozens of studies now exist showing supplemental vitamin D3 reduces mortality rates, in part due to its cardiovascular protection. The majority of these studies show that improvement in mortality continues through 30 ng/ml and even up to 40 ng/ml. Not enough people have levels of 50 ng/ml for scientists to see if such levels offer further protection. However, cardiovascular disease is rare in native peoples around the equator where vitamin D levels of 50 ng/ml are not uncommon.
The takeaway message from this paper is that scientists will need to recalculate lots of different “normals,” using vitamin D sufficient subjects. It’s not just that normal CRP may be a bit higher in vitamin D sufficient people, their red blood count and the protein albumin may be a bit lower, for example. The point is that pathologists and epidemiologists will need to redo much of their work. We don’t know the normal range of CRP in 65-year-old men; we know the range of CRP in 65-year-old vitamin D deficient men. Likewise, we don’t know the incidence of heart disease in 65-year-old men; we know the incidence of heart disease in vitamin D deficient 65 year-old men. We have lots of work to do.