Thursday, July 17, 2008

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!
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:

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):

Great reference for Vitamin D:
By Alex Vasquez, DC, ND, Gilbert Manso, MD, John Cannell, MD


Peter said...

Hi g,

I find it fascinating that nephrologists are so far ahead of cardiologist, certain individuals excepted, in assessing vascular disease. There are pockets of such excellence within the medical profession, why do they get ignored???

The concept of phosphate binding is well established in vet work, calcium restriction and normalisation of D3 are interesting potential adjuncts. It's a pity that 25(OH) D3 assay needs shipping to the States and is expensive for us here in the UK. There are reports of marked benefits of high protein diets in renal disease in cats, even before phosphate binders were introduced. This has not penetrated the specialist diet market. My current advice to owners of cats in renal failure is that feeding what the cat will eat is better than having unpalatable food rejected. If this increases protein intake and we can control blood phosphate levels, so much the better!


Dr. B G said...

Hey Peter,

Yes nephrologists may be ahead (and less busy 'signing death certificates' these days) but so are VETS (like you)! In America, the 'low protein'/low fat/INSULINOGENIC CKD/DOQI diet is still the fastest way to dialysis however. *sigh*

Is there a way to appease our 'inner' feline/?fish/?animal?


Anonymous said...

G: I am hearing from research people that D3 is wonderful, but problems arise from simultaneously supplementing calcium -- increased uptake happens. I would be grateful for your comments. -Rich

Dr. B G said...

Hi Rich,
What kind of uptake are they noticing?

Definitely studies show supplementing calcium alone increases serum vitamin D. Funny huh? Just as taking a statin increases serum vitamin D. Why is that? I think somehow the body thinks... hey I think I need vitamin D now --- for growth, reproduction, hormone-genesis, anti-proliferative functions, ie...SHRINKAGE... *ha haa* remember my Shrinkage 101 post?

A funny thing that I've been noticing lately --- when serum vit D goes up -- serum Magnesium goes down. Magnesium is very tightly monitored in the human body (hardly ever goes out of normal range < 1.7), just as calcium is. PTH, vit D, Mg and Ca++ PO4 all are intimately connected and fluctuate together dynamically.

Magnesium is crucial for about 275 enzymatic and mitochondrial reactions every minute of the day. Mg-ATPase is one major one.

Being both divalent cations an metals, magnesium and calcium compete for binding sites and perhaps elsewhere in the body.

Dr.Davis has already been suggesting Magnesium supplementation for years at TYP. He's brilliant! We certainly need Magnesium as we're building our bone with vit D repletion (moving calcium from plaque to more appropriate our bones).

When Mag doesn't get repleted, then Hypoparathyroidism can occur, and many other metabolic derangements in fact hypertension and even insulin resistance (maybe these are the people who report weight gain with vitamin D3?)

I strongly believe we get sufficient calcium 800-1200mg/day from a balanced Paleolithic diet (and my triple latte from Peets doesn't hurt).

Any extra from a supplement imo will probably continue calcification of tissues, pineal glands, organs, gallbladders, pancreas, etc... and the coronary blood vessels.

What are your thoughts on this?


Drs. Cynthia and David said...

I would like to find dietary sources of vitamin D3 rather than having to take pills. What do you suggest? Is it time to buy cod liver oil? (not exactly dietary) What about fish and non-fish sources- liver, eggs, etc?


Dr. B G said...

Hi Cynthia & David,

To maintain acceptable serum 25(OH)D to levels where disease and prevention of diseases occur 60-70 ng/ml, I'm not sure if food alone will cut it. Like an Inuit or trad'l diet Alaskan, you'd have to consume salmon, seal and whale at every meal!

Did you know that high quality Vitamin D3 supplements are purified from whole foods, like fish liver?

My nutritionist prefers to get his D3 from high potency Blue Ice -- he gets the vit A and sufficient EPA+DHA also (but I think he hasn't checked the 25(OH)D yet!).

Here is a LIST OF FOOD SOURCES from Weston A Price... Hope that helps.