Hearts of Stone, Arteries of Glass

A recent Wall Street Journal article "Defending Against Disease -- With Vitamin D New Studies Suggest It Isn't Just Bones That Might Benefit" by the wonderful Melinda Beck highlights benefits of Vitamin D3. In TYP, we've known the benefits for years :) but it's nice to see the rest of the world catching up.

The benefits of Vitamin D3 are potent, powerful immunomodulation -- to the point where autoimmune diseases, viral and bacterial infections and cancer are effectively reduced. What is the value for heart disease and diabetes prevention? In hemodialysis patients, great lessons are can be learned. Nephrologists often describe patients with severe (stage 5) chronic kidney disease (CKD) patients on hemodialysis as having 'hearts of stone, blood vessels of glass.' Unfortunately over 70% of chronic hemodialysis patients have coronary artery disease (and Lp(a)). What medical science shows is that Agatston coronary calcification scores can be dramatically reduced when vitamin D is replenished and calcium is restricted. Sevelamer (Renagel) is a calcium-free, metal-free polymer phosphate binder. In 52-weeks, calcium restriction, a phosphate-binder and vitamin D resulted in one individual in a 21% reduction in Agatston CAC score (from 968 to 756; see Figure 2).

Average reduction in CAC at 6-mos in the Sevalamer group was 8% CAC score reduction/regression, whereas the Calcium-binder group exhibited an increase of CAC score of 10%. Interestingly, the study protocol encouraged discontinuation of Vitamin D once PTH was 150 therefore regression does not appear to be achieved further in the Sevelamer group between the 6-12 month period.

With chronic kidney disease, impaired activation of Vitamin D occurs which leads to degeneration of bones (renal osteodystrophy) and subsequent release of calcium and phosphate into the blood stream (ie, the building blocks of bone). To normalize phosphate and prevent precipitation of bony matrix in soft tissues (including the heart), phosphate binders are used. In the past, calcium carbonate was used -- cheap and effective. The problem was that calcium added to the mix created higher CAC scores and vascular calcification. Higher rates of mortality secondary to coronary artery disease, peripheral vascular disease and strokes were witnessed in the past. However now with newer calcium-free phosphate binders and Vitamin D (real and fake) as standard of medical care, vascular calcifications, aortic, valvular and coronary calcifications can be halted. In fact... even dramatically REDUCED. Wow... Dr. Davis, you R-O-C-K !

He's right about wheat toxicity... and he's right about the powers of vitamin D!

• Chertow GM, Burke SK, Raggi P; Treat to Goal Working Group. (Vitamin D !! and) Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002 Jul;62(1):245-52. PMID: 12081584
• Nunes JP. The case for dietary calcium restriction in patients with atherosclerosis.
  Med Hypotheses. 2005;65(3):521-4. Review.
  PMID: 15905041
• Wonderful review article from the Kidney.org (see above and below diagrams)
  Clinical Outcomes. in CKD Stage 5: The Impact of Mineral. and Bone Disorders

Why did these UCSF and Tulane researchers use EBT calcium scanning to 'track plaque'? There reasoning was 'The purpose of EBT imaging in our study was to investigate whether the treatments would contribute differently to calcium deposition in the arterial wall. Since the Agatston score is very sensitive to density, and is directly related to the calcium content of the plaque, this was considered the primary EBT end-point. The volumetric scoring method does not apply a scalar density factor but rather estimates the bulk of atherosclerosis [16], and was calculated for completeness. The median inter-scan variability is 8 to 10% for the Agatston score [17, 18] and 6 to 8% for the volume score [16].' Kidney specialists have known the value of EBT scanning (non-invasive, cheap, low-radiation) for YEARS because diagnostic tests which utilize iodine contrast dyes are harmful to kidneys. EBT requires no dyes and therefore maintains protection against kidneys. Additionally, clinical events track well with EBT and vascular calcifications.





Vitamin D used in the trial was one of the below per the investigator:

• 1,25-dihydroxy vitamin D3
• Synthetic analog, IV
• Synthetic analog, PO

EBT scoring measures up and predicts events in coronary disease patients with CKD:
Huybrechts KF, Caro JJ, London GM.
Modeling the implications of changes in vascular calcification in patients on hemodialysis.
Kidney Int. 2005 Apr;67(4):1532-8. PMID: 15780108

METHODS: Data on 179 patients on hemodialysis treated at one center in France included biochemical values during the year prior to study entry, patient characteristics, and cardiovascular events over an average of 4 years. As arterial calcification was evaluated ultrasonographically and quantified using a 0 to 4 score, an equation relating this to the electron-beam tomography (EBT)-based calcification score used in the trial was developed and applied to all patients. The estimated scores were then used in survival and Cox proportional hazards analyses of cardiovascular events in relation to the degree of calcification, controlling for other characteristics.

RESULTS: Mean age at inclusion was 54 years, dialysis vintage 70 months, average follow-up 49 months; 32% suffered an event. The calcification score, diabetes, C-reactive protein (CRP), diastolic blood pressure, gender, smoking and hypertension are independent predictors of cardiovascular risk. The resulting equation indicates that, relative to a calcification score below 400, the risk of an initial event increases 44% for a score of 600, and more than doubles for a score of 1000.




Heart protection has been demonstrated with Vitamin D in this CAD hemodialysis subgroup. Reduced clinical events and mortality are demonstrated and discussed below:

• Wolf M, Shah A, Gutierrez O, Ankers E, Monroy M, Tamez H, Steele D, Chang Y, Camargo CA Jr, Tonelli M, Thadhani R.
  Vitamin D levels and early mortality among incident hemodialysis patients.
  Kidney Int. 2007 Oct;72(8):1004-13.
  PMID: 17687259
• Teng M, Wolf M, Ofsthun MN, Lazarus JM, Hernán MA, Camargo CA Jr, Thadhani R.
  Activated injectable vitamin D and hemodialysis survival: a historical cohort study.
  J Am Soc Nephrol. 2005 Apr;16(4):1115-25.
  PMID: 15728786
• Cheng S, Coyne D.
  Vitamin D and outcomes in chronic kidney disease.
  Curr Opin Nephrol Hypertens. 2007 Mar;16(2):77-82. Review.
  PMID: 17293681
• Levin A, Li YC.
  Vitamin D and its analogues: do they protect against cardiovascular disease in patients with kidney disease?
  Kidney Int. 2005 Nov;68(5):1973-81. Review.
  PMID: 16221197
• Wu-Wong JR, Melnick J.
  Vascular calcification in chronic kidney failure: role of vitamin D receptor.
  Curr Opin Investig Drugs. 2007 Mar;8(3):237-47. Review.
  PMID: 17408120
• Gesek FA, Desmond JS.
  Improved patient outcomes in chronic kidney disease: optimizing vitamin D therapy.
  Nephrol Nurs J. 2008 Mar-Apr;35(2 Suppl):5S-22S; quiz 23S. Review.
  PMID: 18505229

We also know that Vitamin D in just a single dose (100,000 IU D2... which is dose-equivalent to 33,333 IU natural D3) administered to elderly Scotland residents with Type 2 Diabetes significantly improves endothelial function with testing flow-mediated vasodilatation (FMD):

• Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD.
  Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels.
  Diabet Med. 2008 Mar;25(3):320-5.
  PMID: 18279409

Great reference for Vitamin D:
THE CLINICAL IMPORTANCE OF VITAMIN D (CHOLECALCIFEROL): A PARADIGM SHIFT WITH IMPLICATIONS FOR ALL HEALTHCARE PROVIDERS (CME)
By Alex Vasquez, DC, ND, Gilbert Manso, MD, John Cannell, MD