Animal Pharm

Modern Wheat: Staff of Life or... Staff of Cancer? Death?

2008-07-24T21:33:00.000-07:00

Admittedly, stopping wheat was the last part of TYP regimen that I embraced. It's also perhaps the H-A-R-D-E-S-T (yeah, harder than quitting cigars and cigarettes). Wheat is ubiquitious as a convenient and yummy food component. Don't we need wheat for life? Well, after nearly one month now of complete wheat cessation (cheated with 1-2 chocolate croissants -- oh yeah -- a few beers, bread puddings and slices of Ezekiel), I have to say, there is life after wheat, honey. No one died. No one had seizures or delirium tremens. No one even puked.

Now my kids are a different story -- they whine when they don't get their pizza, PB&J or penne pasta from Pasta Pomodoro, our favorite (former) restaurant. It turns out that potential replacements do exist (on earth)! Whole Foods Market (aka 'Whole WALLET' $$) does have a gluten-free pizza shell in the frozen gluten-free area that is purportedly tasty. Pasta and bread...!! we're still figuring that out... any thoughts are welcome!

Why is Wheat so filthy and abominable in the Track Your Plaque plan for plaque stabilization and regression? Sounds so blasphemous doesn't it? Like cursing food of the gods? Wheat helped potentially grow the Roman empire (by supplying their soldier-class with a convenient portable energy source). In modern times, why does it represent disease? Wheat is currently linked to all the below chronic conditions. Acute sudden death does not generally occur (nor does anaphylaxis or other fatal reactions like scurvy or beri beri) however the death is chronic, slow, mildly painful, taking decades.
--celiac sprue
--'silent' celiac sprue
--autoimmune diseases -- most arthritis syndromes (?even OA/DJD), Type 1, MS, Hashimoto's, Grave's, ?asthma
--infertility
--PCOS
--NASH/NAFLD
--primary biliary
--lymphoma
--colon cancer
--pancreatic cancer, other cancers
--eczema, acne, psoriasis
--systemic inflammation
--et cetera

I'm more of a true believer now for complete wheat cessation after witnessing not only amazing stories that Dr. Davis has frequently blogged about at HEARTSCANBLOG but some amazing stories from people who have stopped wheat completely in their lives.

elimination of 30-50 units insulin daily
complete reduction in pain from arthritis
decrease or cessation of pain and arithritis medications
improvement in vitality, energy and youthfulness
acne resolution
skin showing glowing clarity and smoothness, eczema-free

Many parts of the TYP plan promote heart health as well as cancer prevention. Wheat cessation is just one part of this ultimate optimum health guarantee. Other critical components which clinical studies have shown to promote cancer prevention and regression include:
--fish oil omega-3 PUFAs EPA + DHA (high dose and ultra high dose)
--elimination of pro-inflammatory omega-6 polyunsaturated fatty acids
--excessive fructose
--elimination of trans fats and fructose/high-fructose-corn-syrup
--normalization and optimization of steroid hormones: vitamins ADEK2, B-complex, C, micronutrients (Zn, MAGNESIUM, Se, Cu, etc), Estrogen, Progesterone, Testosterone, DHEA, et cetera

Wheat, the staff of death... and cancer. Stop wheat products now for elite health and fitness. Try it for 1-2 wks -- you will be surprised by the results just as I was!

Hearts of Stone, Arteries of Glass

2008-07-17T19:21:00.000-07:00

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 a 21% reduction in Agatston CAC score (from 968 to 756; see Figure 2). 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
Http://www.chineseherbacademy.org/Vitamin_D.pdf

TYPs: Success To Regress

2008-07-14T06:13:00.000-07:00

Sometimes it does not hurt to hear the fundamentals repeated because we can be bogged down by advanced discussions on treatment, sophisticated lab testing or diagnostics.

Boiled down Track-Your-Plaque tips for success:

1. BMI -- achieve normal BMI. Advantages -- loss of toxic belly fat and increased metabolism. May take 3-6mos depending on degree of toxic belly fat.

2. Vitamin D3 -- obtain blood 25(OH)D to 60-70 ng/ml -- and Vitamin B3 Niacin (Slo-Niacin or NIASPAN) to raise HDLs. Clinical event reduction and plaque regression with these 2 powerful 'vitamins' cannot be overemphasized. The importance of raising HDL is reviewed here: TYP HDL Report. And we reviewed already here (at the end of the post).

3. Eliminate wheat, cornstarch and grains; Paleo diet RULES

4. Exercise/play/move -- increases metabolism, reduces inflammation, reduces mental stress, and prevents diastolic heart failure -- very common in people with NASH/NALFD and insulin resistance (like Metabolic Syndrome) and Type 2 Diabetes.

5. Do you exhibit elevated Lp(a) (or ultra low HDL)? If so, consider ultra high dose fish oil 8.5 g EPA+DHA daily (studies show only works when combined with moderate exercise/weight loss). Use high potency caps or liquid.

6. Strength training + Intermittent Fasting -- accelerates loss of toxic belly fat.
(However, if you have diabetic retinopathy, please avoid and discuss with your doctor. Extra cerebral pressures (like straining, Valsava, heavy weight lifting) can increase risk of retinal tears and subsequent vision changes/loss.)

7. For the first 1-2yrs of the TYP program, consider L-arginine. Benefits incl increasing NO in the vasculature which lower BP (goal < 110/75), allows better perfusion, improves immunity, reverses ED, and improves circulation.

8. Mental stress -- this is often overlooked but may be the MOST IMPORTANT KEY. Control stress, you'll control plaque growth. Stress can overrule the immune system. Sleep deprivation is one of the hardest to control factors in modern society -- leads to high cortisol, toxic belly fat and sleep apnea. You need the healthiest immune system to combat inflammation, insulin, Lp(a) and other plaque growth factors (ie oxLDL, low HDL).

I believe the great majority of individuals meet TYP goals 60-60-60-60 in 2-3 mos with a few painless, simple changes as listed above. The HDL and Lp(a) may take 3-6mos if focus is placed on the each of the 8 steps above. They all work together simultaneously and synergistically to help you attain SUCCESS TO REGRESS.

Have you seen the most awesome summer thriller 'Wanted' yet (WSJ Joe Morgenstern's movie review 7/11/2008)? Do you need a trainer? As Wesley bluntly puts it at the end...after his 6 week-long life transformation toward purposeful, elite living... 'so wtf have you done lately...?'

-BG

Atheroma Regression 101 -- Focus on HDL

2008-07-08T06:51:00.000-07:00

Dr. Steve Nissen certainly deserves some respect. Not only does (a) he stick his neck out for the heart protection of Americans and (b) endorses CAC scoring/EBT for plaque/atheroma validation, he supports regression data in alignment with the Track Your Plaque goals for regression 60-60-60-60 already established by Dr. William Davis MD FACC. In a recent post-hoc analysis he reviewed data pooled from 4 major trials (ASTEROID, CAMELOT, REVERSAL, ACTIVATE) where plaque was diagnosed with angiography and tracked via IVUS over ~18 months (n=1455). The plaque volume % (PAV) decrements tracked well with i-n-c-r-e-a-s-i-n-g HDLs. And even more substantial reductions in total atheroma volume (TAV) were seen with more dramatic increases in HDLs.

The average 'regression' lead to an average 0.5 increase in PAV (2% increase and wide SD=15.7%) and a total atheroma volume reduction of 2.4 mm3 (only -0.2%; wide SD=17.4%). The authors note that in the ACTIVATE trial nearly 90% of patients were already on a statin and in fact their LDLs were less than 100 at baseline. Benefits for plaque stabilization and regression may have already been reaped prior to initiation for this sub-group which makes up 1/4 of the study. The duration of statin therapy was unknown.

These changes (avg plaque change: + 0.5)) were observed with the combination:
(1) LDL reduction (study avg=87.5 mg/dl final)
(2) increased HDL changes (the 'higher the better' with avg change=7.5% --the greatest regression was associated with HDL increases of 40% and HIGHER)
(3) lower LDL/HDL ratio (study ratio=2.1)

Average apo B was also significantly reduced from 131 mg/dl to 95 mg/dl (36% reduction) which was statistically correlated to changes in both PAV and total atheroma volume (p less than 0.001). The regression graph (see Figure and graph areas where PAV change is less than zero) lines up with TYP standard goals 60-60 for LDL and HDL.

TYP Goals (standard):
-LDL-C =60 mg/ml (see above arrow)
-HDL-C = 40% increase to 60 mg/ml (study baseline avg = ~43 mg/dl; sorry--arrow wrong!)
-LDL/HDL ratio = 60/60 = 1.0

This regression data certainly emulates TYP to me!! The results truly seem to demonstrate the '60/60' vision...of a regressionist!! Like our beloved Dr. Davis :)

Often Dr. D achieves lipoproteins even beyond his standard goals. Many who follow TYP obtain LDLs lower than 60 and HDLs far higher than 60. Of course TGs fall far lower than 60 as well (often 40s) and of course apo B naturally drop as well (I'd conjecture less than 60).

So perhaps standard goals may be revised for those with 'stubborn' plaque.... based on this new information.

Who might benefit? The analysis showed that independent predictors of change in PAV were baseline PAV, the presence of diabetes and/or hypertension. For total atheroma volume, independent predictors of change were baseline TAV and BMI.

Refer to the L-sided endpoints of each graph in the Figure. The regression data certainly supports substantial size reductions of plaque occur with further improvements in LDL and HDL. HHHhhhhmmm..... Therefore, based on reported values of TYP'ers who experience regression/stabilization, the below standards may apply. At TYP, we are not LDL-centric. Small-LDLp centric extremely so, but never accuse us of LDL-mania...

Ultimate TYP (hypothetical) for Ultimate Regression:

-LDL-C = 60 mg/dl
-HDL-C = 60-80s mg/dl
-TG = 40-50 mg/dl
-TG/HDL ratio = ~50/83 = 48/80 = ~40/67 = 0.60
-LDL/HDL ratio = 60/80 = 0.75

-(? 60-60-60-0.60 ===> LDL-25(OH)D-apoB-TG/HDL-ratio)

The most significant contribution that Nissen made I believe was actually not mentioned in his comments or conclusions. In fact his conclusions from the data differed from mine regarding reduction of clinical events at 18 months and less than 18months after starting a Statin (or for ACTIVATE subjects, statin duration prior to the study longer than the rest of the test subjects). If you review Dr. Nissen's Table 6 below, you'll notice an interesting phenomenon. The best reduction of clinical events outcomes (obstructed events or events requiring re-vasc) supports actually a higher LDL-C (calculated) v. lower LDL-C at time 18 months for the group with a 'good' healthy HDL increase and LDL surprisingly g-r-e-a-t-e-r than average LDL=87.5 mg/dl.... hhhmmm... what could be going on here...? May stabilization (which translates best to reduced revasculariazations) require a little increase in % atheroma volume (though total plaque mass show decreases)?? The data may suggest this (see below 2 duplicated Table 6's).

Dividing out the study pop into 4 subgroups compared responses related to HDLs (and apo B) which appear to exhibit the highest association with clinical events. Perhaps when LDL is less than 87.5 mg/dl, the presence of small LDL still plays a HUGE role? Perhaps those individuals who experienced the most substantial INITIAL improvement in HDLs also had the greatest shift from Pattern B to Pattern A? Perhaps this shift explains the reduction in revascularizations (p=0.07) since these occur at higher frequency 6-12 months after a previous PTCA/stent. Rates of prior percutaneous intervention were in fact high in the study groups (71%, 30%, 81%, n/a). Could the first sub-group have had some plaque shrinkage but were still in the early stages of plaque-remodelling? Perhaps the first sub-group contained two distinct stages of regression -- one early (not stabilizied yet) and one late (stabilization + regression). Of course, the unstabilized will increase clinical events, especially if the presence of small LDL has not been addressed (ie, fish oil deficiency, vitamin D3 deficiency, carb-overloading). It only takes a few events or revascularizations to affect the data. Maybe there is a period of even 'fluffiness' of plaque (surface, core/internal) right before it stabilizes and regresses... synonymous with the changes occuring in the arteries where small LDL is shifting toward buoyant, more benevolent particles? Perhaps it's a phase... and we only have part of the snapshot...

What an amazing picture to behold though... Regression t-r-a-c-k-e-d in such a large population!

Let's thinc again... Perhaps the LDL-calculated based conclusions are bunk? Is LDL-calcuated really the 'lousy' cholesterol???

It's too bad the large trials failed to VAP or NMR the lipoproteins (or at least failed to report smLDL-particles) .

Nicholls SJ, Tuzcu EM, Sipahi I, Grasso AW, Schoenhagen P, Hu T, Wolski K, Crowe T, Desai MY, Hazen SL, Kapadia SR, Nissen SE. (Full PDF here)
Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis.
JAMA. 2007 Feb 7;297(5):499-508.
PMID: 17284700

The conclusions that I draw from the data (though apparently non-statistically significant; who the heck was the statistician) is that human clinical events data support an approximately 50%+ decrease in revascularization-events in the group with higher LDL-C (read: lower small-LDLp) when compared with those with lower LDL-C (read: still high small-LDL in a subset of patients which may have contributed to higher clinical events requiring revascularization).

When plaque stabilizes, the echogenicity increases on ultrasound. Does this also contribute to mildly increased plaque volume? Perhaps? When you get a scab on a traumatic wound, does the scab appear thicker and heavier (esp if you're swimming!) before subsequently falling off after new pink epithelium grows?

Dr. Nissen notes:

"Greater percentage increases in HDL and lower levels of LDL (NOT) and LDL/HDL ratio in patients during treatment with a statin resulted in atheroma regression (BUT NOT HUMAN CLINICAL CAD/CVD EVENTS)...

...This is, to our knowledge the first time that increases in HDL levels have been shown to be an independent predictor of beneficial outcome with statin therapy."

Now Nissen is erudite.

He also looked at 'substantial' responders, meaning those with massive regression (b/c the above data otherwise makes little sense -- to statinators). And HDL-cholesterol undoubtedly must be raised for regression. Could Crestor have higher affinity for PPAR receptors or indirectly affect PPAR more?

His results when looking from a different perspective comparing Non-Responders v. Responders is even more intriguing than the above data. And holds more answers to the key to SUBSTANTIAL REGRESSION. Additionally this data is in direct compliance with TYP principles 60-60-60. Responders were assigned if significant volume/PAV% relative reduction of 5% or greater regression occurred (?about twice or more the average amount?).

Responders comprised 34% of the study population (n=370 were they all Crestor/ASTEROID??). Looking at this data (see Table 5 in the PDF), you'll notice immediately that huge increases in HDL and apo B occurred and likely lead to the dramatic PAV reductions in responders. In fact the difference between HDL improvements between Non-regression subjects and Substantial-Regression subjects was nearly 58% (6.5% v. 10.3%; wide SD 17.2%)) Remember average HDL change was 7.5%. Wow. I bet some of these individuals with massive plaque regression hit the TYP goals of 40% increase to HDL=60 mg/dl (perhaps combined with exercise/diet changes) and TG=60 mg/dl. For apo B, there was also wide variation apparently among the subjects, but also apo B dropped substantially by 40.9 mg/dl to an average of 90.1 mg/dl in the Regression group (almost close to TYP less than 60-70 mg/dl goals!). The median change was 34.8% (SD wide 25.0%) whereas the Non-regression median apoB change was only 25.7% (SD 24.8%).

Wouldn't it have been interesting to see if the Responders had reduced clinical events? Instead of just breaking down LDL-subsets?

Does Nissen know that Statins substantially affect PPAR???! And the regression benefits for regression may be attributed more strongly to PPAR than LDL? Evidently not... though he mentions VA-HIT and Helsinki Heart (he forgot DAIS) which are primary and secondary prevention trials that demonstrated reduced mortality and events with fibrates (PPAR-alpha agonists) especially in the diabetes subsets (ie, high insulin).

We discussed how statins both bind and indirectly affect plaque-mac PPAR earlier here.

The many pleiotropic benefits of statins are related to reduction in inflammation via Macrophage's PPAR activation at the plaque level in damaged endothelium:
--reduction in CRP
--plaque stabilization
--reduced oxLDL in plaque
--atheroma regression

Does this suggest that PPARs regress plaque...?

I do believe so

How do statins causes lipoprotein benefits via activation of Mac PPAR a and PPAR g ?

Nissen saw no significant contribution of statins on TGs on changes in PAV but TGs were statistically associated with improvement. The regression was attributed most strongly to vast HDL increases he reports (and to dramatic apoB and small-LDLp reductions which he didn't really address in the text) .

PPAR activation leads to these lipoprotein benefits:
--reduction in small-LDLp
--reduction in apoB
--reduction in TGs
--INCREASES IN HDL-C

So statins are like PPAR agonists? So statins work like food and food sensors?

What food item works the best as a PPAR agonist? What's my favorite supplement?

Bays et al nicely describes the benefits, MOA, and clinical implications of omega-3 fatty acids. Next to the NIACIN-king... fish oil R-O-C-K-S. Fish oil raises HDLs by an impressive 11-14% in clinical trials. The benefits are dose related, the higher the dose, the higher the HDLs. The lower the baseline HDL, the higher the potential increases.

Fish oils benefits for regression are three-fold:
(a) reduced systemic inflammation via PPAR
(b) increase HDLs via PPAR
(c) reduce apoB and insulin via PPAR

Another dimension of fish oil CAD benefits is its electro-stabilizing effects on cardiac conduction and prevention of arrhythmias.

Bays HE, Tighe AP, Sadovsky R, Davidson MH.
Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications.
Expert Rev Cardiovasc Ther. 2008 Mar;6(3):391-409. Review. (Full PDF here)
PMID: 18327998

Synergistically, Statins and Fish oil can work together to stabilize and regress plaque. The authors eloquently review how both have separate mechanisms which complement and accelerate the conversion of small-LDLp to IDL than to large non-atherogenic LDL.

Synergism... I like that...

What are other mechanisms to raise and maximize HDL?

Depending on the degree of plaque, the more the below are achieved, the greater the increase in HDLs...
--stop all wheat
--stop all grains
--minimize all fruit
--stop all HFCS garbage
--consume adequate high-quality protein 1 g/kg
--consume Hg-free seafood
--consume EPA+DHA
--consume nuts/seeds
--intermittently fast
--exercise, some HIT (high intensity training -- only after medical clearance -- of course)
--get lean muscle mass
--abdominal fat loss
--decrease IR (see above)
--tobacco cessation
--maintain good sleep

-BG

Eden: Liver = Heart

2008-07-07T21:37:00.000-07:00

HOOVERPHONIC: Eden
Which Samurai with his spunky

spiky haired-side kick deftly defeats PLAQUE?

Courtesy of Youtube.com

Eating is definitely a sensory activity that starts with the brain-- have you heard that saying 'eating with your eyes'? Have you ever given your liver much thought while you consuming your meals or snacks? Ever wonder where does the food go before it hits the bloodstream?

In fact, the human liver is the largest internal organ comprising of 3 lobes and receives all the blood after a meal from the stomach and intestines via the portal vein. How does the body sense abundance in the environment?

Through the eyes? No... ye ol' LIVER...

If food (quantity and quality and composition) serves as one of the cues from our external physical environment, then the liver and the PPAR receptors located there there are the sensors of the degree of energy abundance/scarcity. What elements are essential for life outside of air? Food -- water -- light.... Similarly, what senses light? It is likely that VDR (vitamin D receptor) plays an equally important and parallel role. Abundant sunlight for most countries near the equator typically signals abundant food/energy. Vitamin D does rev up energy, productivity, and *hey* fertility! Naturally it follows that the skeletal muscles are the sensor for muscle movement and certainly the PPAR receptors in skeletal muscle do a great deal to command the balance of energy demand and supply/thermogenesis.

What might the holy trinity of human energy look like? mTOR--PPAR--VDR ? How might it have been shaped in our 'evolutionary heritage'...??? (thanks for the term Grey Whale!)

Well, we certainly know a lot of about what contribute's to this trinity's dysregulation...

Lean-muscle-and movement-deficiency
Wheat/grains consumption (including excessive fruit/FRUCTOSE too)
Vitamin D3/sunlight deficiency

Even statins improve this trinity... by activating (!!) PPAR ... This special anti-inflammatory and MMP-stabilizing effect occurs specifically at the macrophage level and for plaque, this translates directly to the surface, volume and core of plaque atheroma. The pleiotropic benefits of statins can now be attributed to a direct activation of PPAR on macrophages via the MAPK pathway.

Paumelle R, Staels B. Peroxisome proliferator-activated receptors mediate pleiotropic actions of statins.Circ Res. 2007 May 25;100(10):1394-5. No abstract available. (see Diagram: Cross-talk of statins/ PPARs in the antiatherogenic properties of statins -- PDF here) PMID: 17525375

Yano M, Matsumura T, et al. Statins activate peroxisome proliferator-activated receptor gamma through extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase-dependent cyclooxygenase-2 expression in macrophages. Circ Res. 2007 May 25;100(10):1442-51. PMID: 17463321

Paumelle R, Staels B, et al. Acute antiinflammatory properties of statins involve peroxisome proliferator-activated receptor-alpha via inhibition of the protein kinase C signaling pathway.
Circ Res. 2006 Feb 17;98(3):361-9. PMID: 16397146

Landrier JF, Thomas C, et al. Statin induction of liver fatty acid-binding protein (L-FABP) gene expression is peroxisome proliferator-activated receptor-alpha-dependent.
J Biol Chem. 2004 Oct 29;279(44):45512-8. PMID: 15337740

Verreth W, De Keyzer D, et al. Rosuvastatin (INCREASES mRNA of PPAR-GAMMA AND) restores superoxide dismutase expression and inhibits accumulation of oxidized LDL in the aortic arch of obese dyslipidemic mice. Br J Pharmacol. 2007 Jun;151(3):347-55. PMID: 17384667

Roglans N, Sanguino E, et al. Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats. J Pharmacol Exp Ther. 2002 Jul;302(1):232-9. PMID: 12065722

Sanguino E, Roglans N, et al. Atorvastatin reverses age-related reduction in rat hepatic PPARalpha and HNF-4. Br J Pharmacol. 2005 Aug;145(7):853-61. PMID: 15912134

In historical texts (ie, the Bible), the liver was actually considered 'the heart.' And, in the ancient days, harm to the liver was actually worse than to the heart. How were they so wise (without high tech ALT/AST tests or abdominal u/s) ??! For warriors, the liver was an easier, bigger target to hit than the smaller heart. We often neglect this fantastic vital organ. Interestingly, when the trinity is disrupted, this organ becomes metabolically deranged even before the heart.

Here are the liver's awesome functions and roles:

first pass effect = all blood during digestion is maximized to flow through the liver. Perhaps this is the role after meal apertifs, Greek grappe or (!!YUM)aged port have -- they relax, increase Vagal communications to the GI system to further shunt blood flow to the stomach and intestines for digestion

cytochrome P450 -- detox's, purifies everything we eat including plant toxins and exogenous chemicals like drugs (explains why oral estrogen can worsen HDLs whereas topical/transdermal estrogen improves and RAISES HDLs by bypassing the liver route)

cytochrome P450 activates and processes everything we eat including all food components and neutraceuticals (vitamin D3, essential fatty acids, protein)

energy sensor (carbs, fats, proteins, alcohol, caffeine, etc -- all my favorite food groups)

ultimate CONTROLLER in the financial as well as airtraffic sense because the liver contains the highest concentration of PPAR receptors: alpha, gamma, and D-E-L-T-A (aka beta)

producer of lipoproteins which are the energy 'traffickers' for the immune system, skeletal muscles and even brain (which relies on ketones/fatty acids when blood glucose (BG) is naturally lower)

producer of TGs -- the lipoprotein fraction where carbohydrate-energy (dietary carb +/- fat) is bundled into for transport to the rest of the body (including clogging up the heart tissues and arteries). Recall that TGs is the second RISK FACTOR most highly associated with plaque. First is... fasting insulin levels.

regulates and synthesizes cholesterol which is the template of EVERY nuclear steroid (and some aromatases, desaturases, and cyt P450 are under the control of VitaminD3) -- steroids like testosterone, estrogen, cortisol -- and composes the structural backbone/shell of every cell in our body and in particular the brain/nervous system which is comprised nearly entirely of cholesterol and fats (should pregnant moms eat 'low fat'? do pregnant moms want brain-deficient, cognitively-challenged children?)

vitally crucial for producing mannose-binding lectin (MBL) which is an activator of our host defenses in the innate broad-spectrum non-specific immune system (which fights virus, bacteria, and other foreign invaders including FRUCTOSE attached to our own cells) ; 'fruct-osylated-cells' aint good... sounds pretty bad eh? indeed VERY BAD

first organ to become unhappy when carbohydrates are excessive ('fatty liver', NAFLD, NASH, etc); see diagram above

one of the most prized organ meats and delicacy (in indigenous cultures and our household with a little soy sauce and honey) highly valued for its nutritional content of metabolically-active and heart protective Vitamins K2, D3, A, E and other essential nutrients and minerals.

In a recent Circulation article, researchers are elucidating the important role of Von Willebrand factor (VWF) in acute coronary syndromes (ACS).

"von Willebrand factor (VWF) plays a pivotal role in platelet adhesion and aggregation at sites of high shear rates (eg, in coronary arteries that have stenotic or ruptured atherosclerotic plaque lesions). Numerous studies have investigated the relationship between VWF plasma levels and thromboembolic cardiovascular events. In contrast to the rather weak association in the general population, in patients with preexisting vascular disease, VWF is significantly predictive for adverse cardiac events, including death. Likewise, VWF typically rises during the course of acute coronary syndrome, and the extent of this VWF release is an independent predictor of adverse clinical outcome in these patients. Various lines of evidence indicate that VWF is not only a marker but also actually an important effector in the pathogenesis of myocardial infarction. This central role of VWF in thrombogenesis has made it a promising target for research into new antiplatelet therapies that specifically inhibit VWF (AND BLAH BLAH BLAH... DRUGS)..."

How is VWF related to the thrombosis and clotting effects in our blood vessels? Obviously there is a healthy balance. Those with VWF deficiency have bleeding gums, mucus membranes and bleeding under the skin.

Is the liver involved? It appears the liver is involved in everything!

Platelets require the intervention of a blood protein known as Von Willebrand factor (vWF), which facilitates platelet adhesion to the sub-endothelial matrix of damaged, exposed endothelium. When the liver is aged, i.e. metabolically/oxidatively affected, a corresponding increase in vWF occurs intrahepatically (see below). Can this also occur systemically? To the coronary arteries? Or carotids? If we keep the endothelium of one of our most vital organs, the liver, happy... clear and uncongested, then endothelium elsewhere is likely to be protected as well. Prevent hardening of the liver, and you'll prevent hardening of the arteries. Reverse liver damage, and you'll reverse artery damage.

Timing as usual makes a difference. Even young-obese children are displaying NASH/NAFLD and early changes in myocardial structure such as diastolic dysfunction/heart failure.

The below changes including the increase in vWF from the endothelium in the liver blood circulation sounds a lot like instigation of arteriosclerosis of the liver...

Love your liver... and both hearts will appreciate it...

Ways to maximize liver function and productivity:
** Movement, play, movement, work, intervals of intensity, play, grow your muscles... especially with our children. 'The family that plays together, stays together...and doesn't have heart attacks together,' quoted by a member at my CF gym
** Complete Wheat/Grain avoidance and minimal fruit
** Adequate vitamin D3 (achieve: 25(OH)D 60-70 ng/ml)

Old age and the hepatic sinusoid.

Anat Rec (Hoboken). 2008 Jun;291(6):672-83. Le Couteur DG, et al.

Morphological changes in the hepatic sinusoid with old age are increasingly recognized. These include thickening and defenestration of the liver sinusoidal endothelial cell, sporadic deposition of collagen and basal lamina in the extracellular space of Disse, and increased numbers of fat engorged, nonactivated stellate cells. In addition, there is endothelial up-regulation of von Willebrand factor and ICAM-1 with reduced expression of caveolin-1. These changes have been termed age-related pseudocapillarization (SOUNDS TO ME LIKE CALCIFICATIONS AND ARTERIOSCLEROSIS). The effects of old age on Kupffer cells are inconsistent, but impaired responsiveness is likely. There are functional implications of these aging changes in the hepatic sinusoid. There is reduced sinusoidal perfusion, which will impair the hepatic clearance of highly extracted substrates. Blood clearance of a variety of waste macromolecules takes place in liver sinusoidal endothelial cells (LSECs). Previous studies indicated either that aging had no effect, or reduced the endocytic capacity of LSECs. However, a recent study in mice showed reduced endocytosis in pericentral regions of the liver lobules. Reduced endocytosis may increase systemic exposure to potential harmful waste macromolecules such as advanced glycation end products. Loss of fenestrations leads to impaired transfer of lipoproteins from blood to hepatocytes. This provides a mechanism for impaired chylomicron remnant clearance and postprandial hyperlipidemia associated with old age. Given the extensive range of substrates metabolized by the liver, age-related (I.E. METABOLIC DEREGULATION) changes in the hepatic sinusoid and microcirculation have important systemic implications for aging and age-related diseases.
PMID: 18484614

Lp(a): Running With Scissors (Part 1)

2008-06-30T22:08:00.000-07:00

I'm sure as a kid, your mother warned you over and over and over how dangerous running with sharp objects is...

Or sharp pencils... Or knives... Or chopsticks...

Or Lp(a)??! wtf??

Ben Harper and friends: THERE WILL BE LIGHT

Rome Concert Live

Courtesy of Youtube.com

I wish we could live forever...

Then melt into the sun

Melt into the sun

Time is gonna change you

Once it gets you on the run

Gets you on the run

--Chorus--

I've been running

Ever since

Ever since I was a child

Some call it free

And some call it wild

There will be
There will be
There will be a light
There will be a light
There will be
There will be
There will be a light
There will be a light

Why is Lp(a) elevated for some individuals? Why is it directly correlated with premature vascular disease (when BP is elevated)?

It's estimated there are potentially three families of factors that influence Lp(a) which affects about 17-25% of the general population:
(a) Structure and metabolism of very-low-density lipoprotein (VLDL) such as triglycerides, phospholipids, apoC-II, C-III, E, A-II and uric acid (which are of course ALL related to insulin)
(b) Thrombosis-related centering on platelets
(c) Acute phase reactions represented by 1 hr and 2 hr erythrocyte sedimentation rates (ESR) (in other words, immune system stimulation)
(I'd add a 4th factor in the formula (d) kidney dysregulation which is the site of Lp(a) catabolism and recycling/disposal in the human body)

Nakajima K, Hata Y. Intraindividual variations in lipoprotein (a) levels and factors related to these changes. J Atheroscler Thromb. 1996;2(2):96-106. PMID: 9225216

At TrackYourPlaque.com we have several reports addressing Lp(a). The challenge in controlling this one single, severe plaque-building factor can not be underestimated. It can be an unrelenting foe...

-Lp(a) Report I (2006): Lipoprotein(a): What it is, why it's important, and why you need to know if you've got it!

-Lp(a) Report II (2008): Unique Strategies for Lipoprotein(a) Reduction

-Lp(a) Lipoprotein Checklist

There appear to be distinct subpopulations affected by Lp(a) from my (anecdotal, untrained) nonscientific observations:

--high-carb consuming well known athletes (and unknown) who drop dead at endurance events of MIs (Brian Maxwell Northern Cal POWERBAR guru, Jim Fixx, and lucky survivor-Alberto Salazar)
--advanced stage chronic kidney disease (CKD)
--end-stage-renal-disease (ESRD) and dialysis patients
--individuals with kidney stones
--individuals with Metabolic Syndrome (MetSyn) with premature heart disease in the family tree (females affected before age 65; males affected before age 55)
--men with diabetes Type 2 and erectile dysfunction
--individuals with MetSyn who have survived cancer (a condition that really sets off acute phase reactions and the immune system to heal)
--youth and young children with MetSyn, esp PCOS or any other hormone derangements (ie, wheat addiction/prolactin, big-man-boobs, appear 4-mos pregnant and they are male )
--children with elevated insulin and apo B
--adults with elevated insulin and apo B (and this is much more toxic for women for some reason than men)
--women after menopause, esp if no hormone replacement occurs

Can we avoid the dangers of running with scissors (or chopsticks)?

I certainly believe so. (Heed the words of your mother)

Let's keep running... wild and free... until we melt with the sun...

Lp(a): PPAR-Delta... Dagger in the Heart of Lp(a) (Part II) coming soon...

Control Insulin (Part Two)

2008-06-23T07:03:00.000-07:00

Briefly, the history of insulin and its relationship to atherosclerosis:

Stout RW. Insulin and atheroma. 20-yr perspective. Diabetes Care. 1990 Jun;13(6):631-54. Review. PMID: 2192848 Department of Geriatric Medicine, Queen's University of Belfast, Northern Ireland.
Many clinical studies have shown an increased insulin response to oral glucose in patients with ischemia of the heart, lower limbs, or brain. Hyperinsulinemia also occurs in patients with angiographically proved atherosclerosis without ischemia and thus appears to be related to arterial disease and not to be a nonspecific response to tissue injury. Fasting insulin levels and insulin responses to intravenous stimuli, including glucose, tolbutamide, and arginine, are normal, suggesting a gastrointestinal factor may be involved in the increased insulin response to oral glucose. In patients with atherosclerosis, insulin sensitivity appears to be normal or enhanced with respect to both glucose and lipid metabolism. Five population studies have shown that insulin responses to glucose are higher in populations at greater risk of cardiovascular disease. Many of the hyperinsulinemic populations also had upper-body obesity, hypertriglyceridemia, lower high-density lipoprotein (HDL) levels, and hypertension. These prospective studies support an independent association between hyperinsulinemia and ischemic heart disease, although their results differ in detail. Hyperinsulinemia is associated with raised triglyceride and decreased HDL cholesterol levels. Total and low-density lipoprotein (LDL) cholesterol is less closely related to hyperinsulinemia. Upper-body adiposity is associated (in separate studies) with coronary heart disease, diabetes, hyperinsulinemia, and hypertriglyceridemia. Insulin and blood pressure are closely related in both normotensive and hypertensive people. Although obesity and diabetes are often found in hypertensive people, hyperinsulinemia also occurs in nonobese nondiabetic hypertensive people. Thus, hyperinsulinemia is closely associated with a cluster of cardiovascular risk factors, i.e., hypertriglyceridemia, low HDL levels, hypertension, hyperglycemia, and upper-body obesity. There is a possibility that insulin has a role in the sex differences in ischemic heart disease incidence and their absence in diabetes, but additional work is required for its clarification. Long-term treatment with insulin results in lipid-containing lesions and thickening of the arterial wall in experimental animals. Insulin also inhibits regression of diet-induced experimental atherosclerosis, and insulin deficiency inhibits the development of arterial lesions. Insulin stimulates lipid synthesis in arterial tissue; the effect of insulin is influenced by hemodynamic factors and may be localized to certain parts of the artery. In physiological concentrations, insulin stimulates proliferation and migration of cultured arterial smooth muscle cells but has no effort on endothelial cells cultured from large vessels. Insulin also stimulates cholesterol synthesis and LDL binding in both arterial smooth muscle cells and monocyte macrophages.

Despres JP et al showed in the below study how elevated fasting insulin blood levels was closely associated to the presence of ischemic heart disease. The higher the concentration of insulin, the greater the odds ratio. And additionally they found other factors compounded the risk of heart disease:

--High Triglyercides

--High Total/HDL ratio (in other words, low HDL)

--High Apolipoprotein B

Després JP, Lamarche B, Mauriège P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ.Hyperinsulinemia as an independent risk factor for ischemic heart disease.N Engl J Med. 1996 Apr 11;334(15):952-7. PMID: 8596596

Figure. Odds Ratios for Ischemic Heart Disease according to Plasma Insulin and Triglyeride Concentrations, Total:HDL Cholesterol Ratios, and Apolipoprotein B Concentrations. Insulin was measured after subjects had fasted for 12 hours. The median TG concentration (150 mg/dl [1.7mmol/L]), total:HDL ratio (6.0), and apoplipoprotein B concentration (119 mg/dl) were used to define men with either low levels (below the 50th percentile) or high levels (at or above the 50th percentile) for these variables. The results of tests of multiplicative interactions did not reach signficance at the 0.05 level for any of the combinations. P values are for comparisons with the reference group, which was assigned an addos ratio of 1.0. To convert values for insulin to picomoles per liter, multiply by 6.

The researchers Lemarche et al have done a great deal of research examining 'non-traditional risk factors '(see Table 2) and also showed the same link between insulin and associated ischemic heart disease.
Lamarche B, Tchernof A, Mauriège P, Cantin B, Dagenais GR, Lupien PJ, Després JP. Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease. JAMA. 1998 Jun 24;279(24):1955-61. (Full PDF here) PMID: 9643858

In fact, their results uncovered the fact that the largest odds ratio between traditional (LDL, TG, HDL) and nontraditional (small dense LDL, apo B and fasting insulin) fell to the Hyperinsulinemia risk factor. So high fasting insulin correlated stronger with the presence of evidence of coronary artery disease than than LDL-cholesterol. Triglyericides (TGs) even associated to a higher degree than LDL-cholesterol. HHmmmm?

Why do we always call LDL the 'bad' cholesterol? It appears that TGs is a bad character, indeed it appears TGs are the worse cholesterol out of all the traditional risk factors! Dr. Davis has pursued a lower TG goal lower than 'traditional' guidelines for many years. Current 'conventional' cardiovascular advice aims for TGs less than 150 however the Track Your Plaque program advocates an aggressive TG goal of 'normal' less than 60.

Is the 'LDL-cholesterol hypothesis' completely bunk?

Shouldn't Triglyerides be known as the 'lousy/bad' cholesterol?

Is this why statin-monotherapy fail to prevent signficant mortality and morbidity caused by plaque in heart disease and strokes?

The TYP goals for regression of ischemic heart disease are 60-60-60-60 (TG-HDL-LDL-25(OH)D). Many achieve this and beyond -- HDLs 80-90s and TGs 25-50s in the program!

And Elevated Fasting Insulin goal is not just less than 12 mU/L as discussed in the 2nd study above but at TYP the goal for regression is normal fasting insulin levels less than 5-10 mU/mL (30-60 pmol/L).

Is this why the Track Your Plaque program controls plaque comprehensively and trumps all 'conventional' cardiology programs by controlling triglycerides and insulin by a multifaceted strategy?

--Vitamin D3

--Wheat and grain cessation

--Exercise

--Weight loss to achieve normal BMI

--High/ultra-high dose fish oil EPA+DHA

--Hormone optimization (estrogen, testosterone, DHEA, etc)

--Vitamins K2/E/A

--Et cetera

Conclusions by the above authors Lamarche, et al:
'Beyond the mechanisms underlying the atherogenicity of hyperinsulinemia, hyperapobetalipoproteinemia, and small, dense LDL, and irrespective of whether these mechanisms share common paths, results of the present study suggest that the risk of IHD is increased substantially when these metabolic abnormalities cluster. The synergistic contribution of the nontraditional cluster of risk factors to IHD risk and the fact that almost 1 of every 2 IHD cases had these abnormalities simultaneously reflect the multifactorial etiology of IHD. It also emphasizes the importance of defining the risk of IHD based on more than 1 risk factor.
There are a number of critical issues that have to be considered before any decision can be made toward the measurement of these nontraditional risk factors on a routine basis. Among others, results of this prospective case-control study will have to be confirmed through larger population-based studies, as the relatively low number of IHD cases allowed only a gross assessment of risk. The relatively large CIs associated with the estimated risk in some of the subgroups reflect this phenomenon. Population reference values such as those used for LDL-C, triglycerides, and HDL-C also will be needed before critical levels of fasting insulin, apolipoprotein B levels, and LDL particle size or density at which a person becomes at greater risk for IHD are identified. Means to achieve effective treatment of the nontraditional risk factors is also a critical issue that deserves a great deal of scrutiny before decisions can be made toward use of these variables in the risk management of IHD. There are data to suggest that LDL particle size can be modulated by changes in plasma triglyceride levels.41 Studies have shown that triglyceride-lowering therapy with fibric acid derivatives can lead to a significant increase in LDL particle size.42-43 There is also a large body of evidence demonstrating that LDL particle size, apolipoprotein B level, and insulin resistance and/or hyperinsulinemia can be effectively altered by diet and exercise-induced weight loss.44-45 Thus, the ability to favorably modify the nontraditional risk factors by diet, exercise, and appropriate pharmacotherapy provides further support for the use of these risk factors in the management of IHD risk...'

Lawlor DA, Fraser A, Ebrahim S, Smith GD. Independent associations of fasting insulin, glucose, and glycated haemoglobin with stroke and coronary heart disease in older women. PLoS Med. 2007 Aug;4(8):e263. PMID: 17760500

Full PDF here:

Editor's Summary

Background: Narrowing of the vessels that take blood to the heart and brain is a common form of cardiovascular disease—i.e., a disorder of the heart and blood vessels. It is a major cause of illness and death. By starving the heart and brain of oxygen, this condition causes coronary heart disease (CHD; heart problems such as angina and heart attacks) and strokes. A major risk factor for CHD and strokes is diabetes, a common chronic disease characterized by high levels of sugar (glucose) in the blood. In people who don't have diabetes, the hormone insulin controls blood-sugar levels. Insulin, which is released by the pancreas after eating, “instructs” insulin-responsive muscle and fat cells to absorb the glucose (released from food) from the bloodstream. In the very early stages of type 2 diabetes (the commonest type of diabetes, also called “adult onset” or “noninsulin-dependent” diabetes”), muscle and fat cells become unresponsive to insulin, so blood-sugar levels increase. This is called “insulin resistance.” The pancreas responds by making more insulin. As a result, people with insulin resistance have high blood levels of both insulin (hyperinsulinemia) and glucose (hyperglycemia). Eventually, the insulin-producing cells in the pancreas start to malfunction, insulin secretion decreases, and type 2 diabetes is the result.

Conclusions:

'Our findings indicate that amongst older women without diabetes and with fasting glucose levels in the normal range, fasting insulin is a stronger predictor of CHD and stroke risk than are fasting glucose or HbA1c.'

In addition, the results demonstrated a 'positive linear association between fasting insulin and CHD and stroke events is consistent with findings from the Atherosclerosis Risk in Communities study (SEE LAST CITATION), in which there was a positive linear association with CHD events that remained after adjustment for other CHD risk factors amongst women, but not amongst men [27]. A metaregression analysis of 17 prospective studies, primarily conducted in men and younger age groups than the current study, found a pooled relative risk of CHD per 50 pmol/l of insulin of 1.18 (95% CI 1.08–1.29) [9], which is consistent with our fully adjusted association with CHD (our results equate to 1.13 [95% CI 1.01–1.27] per 50 pmol/l of insulin). Overall the evidence suggests a modest positive association between fasting insulin and CHD events in women and men. Fasting insulin may exert its effect on cardiovascular risk via a direct impact on endothelial function [28,29].'

CRACK DOWN on insulin... CRACK DOWN on plaque (and cancer)...

Hunger will disappear away as well. Part of insulin's purpose is to drive energy into cells for storage. Insulin drives hunger as well. (...and mainly the consumption of carbs drive insulin secretion)

You will realize the benefits of low blood insulin and will often 'forget' to eat without prompting from this powerful hormone. You'll hunger for other things... vitality, movement, effortless-boundless ENERGY.

Importance of controlling triglycerides and insulin:

INSULIN ==> TG/HDL ratio ==> SMALL DENSE LDL

Zavaroni I, Dall'Aglio E, Alpi O, Bruschi F, Bonora E, Pezzarossa A, Butturini U.
Evidence for an independent relationship between plasma insulin and concentration of high density lipoprotein cholesterol and triglyceride.
Atherosclerosis. 1985 Jun;55(3):259-66.
PMID: 3893447 [PubMed - indexed for MEDLINE]

Ghiselli G, Bon GB, Soldan S, Avogaro P.
Regulatory function of glucose and insulin on high-density lipoprotein cholesterol in normolipidemic subjects.
Metabolism. 1994 Nov;43(11):1332-7.
PMID: 7968586 [PubMed - indexed for MEDLINE]

Cominacini L, Garbin U, Davoli A, Campagnola M, De Santis A, Pasini C, Pastorino AM, Bosello O.
High-density lipoprotein cholesterol concentrations and postheparin hepatic and lipoprotein lipases in obesity: relationships with plasma insulin levels.
Ann Nutr Metab. 1993;37(4):175-84.
PMID: 8215234 [PubMed - indexed for MEDLINE]

Laws A, King AC, Haskell WL, Reaven GM.
Relation of fasting plasma insulin concentration to high density lipoprotein cholesterol and triglyceride concentrations in men.
Arterioscler Thromb. 1991 Nov-Dec;11(6):1636-42.
PMID: 1931867 [PubMed - indexed for MEDLINE]

Stalder M, Pometta D, Suenram A.
Relationship between plasma insulin levels and high density lipoprotein cholesterol levels in healthy men.
Diabetologia. 1981 Dec;21(6):544-8.
PMID: 7040144 [PubMed - indexed for MEDLINE]

Tchernof A, Lamarche B, Prud'Homme D, Nadeau A, Moorjani S, Labrie F, Lupien PJ, Després JP.
The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men.
Diabetes Care. 1996 Jun;19(6):629-37.
PMID: 8725863 [PubMed - indexed for MEDLINE]

Laws A, Reaven GM.
Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations.
J Intern Med. 1992 Jan;231(1):25-30.
PMID: 1732395

Katzel LI, Coon PJ, Rogus E, Krauss RM, Goldberg AP.
Persistence of low HDL-C levels after weight reduction in older men with small LDL particles.
Arterioscler Thromb Vasc Biol. 1995 Mar;15(3):299-305.
PMID: 7749838

McNamara JR, Jenner JL, Li Z, Wilson PW, Schaefer EJ. ***
Change in LDL particle size is associated with change in plasma triglyceride concentration.
Arterioscler Thromb. 1992 Nov;12(11):1284-90.
PMID: 1420088

Folsom AR, Szklo M, Stevens J, Liao F, Smith R, Eckfeldt JH. **
A prospective study of coronary heart disease in relation to fasting insulin, glucose, and diabetes. The Atherosclerosis Risk in Communities (ARIC) Study.
Diabetes Care. 1997 Jun;20(6):935-42.
PMID: 9167103

-G

Control Insulin, Control Plaque... (And Cancer)

2008-06-22T10:56:00.000-07:00

Killa Whale

By Nickatina
Advisory: lyrics NSFW

(For sensitive ears... resist... the urge... to c-l-i-c-k)
'Track, Smack, Whack Plaque' as HH
always says... extinguish plaque for an eternity.
Forge elite heart fitness...

BTW this song rocks when thrashin' at Crossfit...

Chewy boy, doobie with the buddha cess...
So read my mind, the situation's critical...
You think you know me?
Well test your luck and try me out...

Then watch that valium on your dome
I'm putting beary fairy nig*** in a state of shock (shock!)
And I'm a killa whale but nigga check my pit lock
So bust that, crush that, crush that
Cuh-crack crack!

...I'm harmon like that wolverine
Deadly like that Octagon
Fillmoe to the fu*** heart
Crooked like the Pentagon
Recka!

...So check my rep, survival tech, and hit man killa tactics
Nig*** get berry faced down on silver plastic...
The fat rat dominator, microphone terminator
Quick to break the neck of an E-40 imitator

Nig*** don't front, you know I got you open
With more Raider in me than they ever had in Oakland
To all you moth*** that juss can't tell
I'm a Pisces but I'd rather be a KILLA WHALE
POD!

Controlling insulin reaps many rewards. As the previous article suggests, insulin is an ancient hormone ubiquitous in all animals -- from worms to humans -- with classic/nonclassic responsibilities including (see Table 1). Some of these actions are beneficial like Thermogenesis, however many of the others are detrimental in the great majority of situations:
--low potassium

--raised heart rate
--increased uric acid (ie, gout)

--increased clotting

--CNS stimulation (ie, anxiety, epression, ADHD)
--prevention of fat from being liberalized for energetic uses

We require only tiny, neglible amounts of insulin for thermogenesis and shuttling of energy (glucose) into muscles and liver for storage.

In fact, increased energy expenditure is exponentially increased when insulin resistance is kept at bay. What is insulin resistance (IR)? It is like being at a rock concert (or Hannah Montana venue with screaming little girls everywhere) where temporary hearing loss is induced by inclement noise pollution. As soon as the volume returns to a low level, hearing resumes. Shut insulin down by going grain-free, carb-restricted, intermittent fasting and exercising, then inflammatory responses and processes are cut off. The same research demonstrated that men and women have blunted energy expenditure when the 'volume of insulin' is dialed exceptionally high. And for us women, we may even have a 'negative' energy output (in other words 'storage') with energy expenditure during the presence of insulin resistance... huhhh??! Talk about an exceedingly 'thrifty' gene... *urgh* Insulin-resistant gals gain weight with exercise... how exceedingly unfair. This actually is a common phenomenon and very discouraging for women trying to lose weight and fight an uphill battle as they eat per conventional medical advice 'low fat'/high-carbohydrate/insulin-inducing diets (USDA 'whole grain' pyramidal nonsense).

Degrees of IR can also be effectively cranked down by (Isharwal S, et al. Dietary nutrients and insulin resistance in urban Asian Indian adolescents and young adults.Ann Nutr Metab. 2008;52(2):145-51.):
--normal BMI achievement
--reduction of pro-inflammatory omega-6 oils
--increase of anti-inflammatory omega-3 EPA+DHA oils (ie, cod liver, fish oil, pasture-fed milk, meat, eggs, etc)

And of course...wheat avoidance, grain elimination, carb restriction, intermittent fasting and exercise.

Excessive insulin (ie, hyperinsulinemia) leads to the below changes (see below diagram):
--inflammation
--generation of TGs and small dense atherogenic LDL
--conversion from fatty streaks to plaque
--plaque growth
--increased adipose tissue mass (Obesity, Metablic Syndrome, PCOS)
--accumulation of Triglycerides in non-adipocytes
--nonalcoholic steatohepatitis (fatty liver/NAFLD)
--pancreatic beta-cell failure (fatty pancreas, insulin resistance)
--dilated cardiomyopathy (myocyte (heart cell) stiffening and diastolic dysfunction)
--arterial stiffening
--blood glucose spikes
--expansion of visceral fat (belly fat colonies)
--fatty liver, fatty pancreas, fatty gallbladder, fatty heart
--Diabetes Type 2
--strokes, heart attacks
--cancer (see end)

So... when insulin becomes rampant and uncontrolled like ex-KGB-satellites gaining prominence and power to control global McMafia-like franchises for cocaine, opioid, and crack trafficking, then world and global economies are undoubtedly affected. Whole human systemic organ functions become dominated by hyperinsulinemia, leading to all sorts of dysfunction and energy dysregulation. Why rely on primitive petrol... when nuclear power exists?

Fig 1. Lipotoxicity in humans originates from excessive release of free fatty acids from hypertrophied adipocytes in obese persons. Organ exposure to high levels of free fatty acids causes lipid droplets to accumulate within the cytosol of nonadipose tissues in proximity to mitochondria (white arrows, bottom).By-products of cytosolic triglyceride accumulation and of lipid metabolism may lead to organ dysfunction and failure. McGavock JM, Victor RG, Unger RH, Szczepaniak LS. Adiposity of the heart, revisited. (Full PDF here.) Ann Intern Med. 2006 Apr 4;144(7):517-24. Review. PMID: 16585666

The inflammation associated with insulin is akin to the oxidative damage that occurs when soft materials like rubber or plastic is left outside exposed to the elements. Over time, the rubber hardens and becomes inelastic and rigid, easily breaking with any shear force. Sort of like running a high-powered hose made out of glass, right? With the elimination of inflammatory influences, human tissues can return to their original soft, elastic, pliable states. This includes endothelium, heart blood vessels, contractile tissues like our heart and skeletal muscles... even our oral gum tissues!

Reversal occurs when insulin is shut down.

The previous review of the research eloquently illustrates the special properties that dictate this ancient 'reactive' hormone. Insulin is one of the few hormones that is controlled by consumed 'substrates'.... What is in charge of turning insulin on and off? What are substrates of insulin?

C-A-R-B-O-H-Y-D-R-A-T-E-S.

Found in our daily meals and snacks! What we consume indeed dictates what we are (biochemically speaking).

Food composition directly lowers or raises insulin concentrations. Various other factors of course determine how quick and how sustained hyperinsulinemia occurs (exercise, weight loss, skeletal muscle dominance, size and location of visceral fat colonies (ie, 'belly' is 'bad') but in essence our food controls blood insulin levels.

If what we put in our mouth dictates are insulin levels, then equally powerful is what we don't... In other words, processes like starvation, skipping meals, random eating, intermittent fasting and going low-carb or restricted-carb are ways to reduce and control insulin. Consumption of adequate protein and fats and fiber control insulin release as well.

Take powerful control over plaque and inflammatory processes by shutting insulin secretion off. At Track Your Plaque the Paleo grain-free diet produces the best plaque-busting results. Consider the complete avoidance of all wheat and grains:

--wheat

--wheat products (incl cereal, pasta, noodles, bread, crackers, pita, tortilla)

--buckwheat

--bulgur (cracked wheat)

--barley

--rye

--oat (except oat bran)

--quinoa

--rice

--corn (incl popcorn, grits, cornmeal, tortilla, chips)

--couscous

--amaranth

--millet

--sorghum

--triticale

--et cetera

Consume most of the carbohydrates from non-starchy vegetables and raw nuts/seeds and low-GI fruit like berries.

Controlling insulin not only controls CAD but also controls cancer... Is 'whole grains' just promoting 'whole C-A-N-C-E-R'? As well as 'whole CORONARY ARTERY DISEASE'?
--breast cancer
--prostate cancer
--colon cancer

--pancreatic cancer

Berstein LM. Endocrinology of the wild and mutant BRCA1 gene and types of hormonal carcinogenesis. Future Oncol. 2008 Feb;4(1):23-39. Review. PMID: 18240998
Hede K.Doctors seek to prevent breast cancer recurrence by lowering insulin levels.
J Natl Cancer Inst. 2008 Apr 16;100(8):530-2. PMID: 18398091
Barnard RJ.Prostate cancer prevention by nutritional means to alleviate metabolic syndrome. Am J Clin Nutr. 2007 Sep;86(3):s889-93. Review.PMID: 18265484
Park JH.Inhibition of colon cancer cell growth by dietary components: role of the insulin-like growth factor (IGF) system. Asia Pac J Clin Nutr. 2008;17 Suppl 1:257-60. PMID: 18296350
Tenenbaum A, et al. Does the lipid-lowering peroxisome proliferator-activated receptors ligand bezafibrate prevent colon cancer in patients with coronary artery disease? Cardiovasc Diabetol. 2008 Jun 19;7(1):18. PMID: 18565233
Pisani P. Arch Physiol Biochem. 2008 Feb;114(1):63-70. Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies.

Background: A substantial body of evidence links sex hormones, diet, excess body weight and physical activity to the risk of developing cancer at several sites common in affluent countries. The hypothesis that high circulating levels of insulin could be the underlying factor increasing cancer risk has been proposed. Epidemiological studies on markers of hyper-insulinaemia and cancer are reviewed and summarized. Methods: Studies of cancers of the colon and rectum, pancreas, breast, and endometrium examining the association with blood levels of C-peptide, insulin, glucose, glycated haemoblobin (HbA1c) were searched in PubMed. Multivariate, adjusted relative risks (RR) and their 95% confidence intervals were abstracted and summarized by meta-analyses. Results: Most of the studies identified were cohorts that relied on measurements obtained at baseline or assessed in blood stored at low temperature several years before the onset of cancer. The meta-analyses showed excess risks of colorectal and pancreatic cancers associated with higher levels of circulating C-peptide/insulin and with markers of glycaemia. Significant heterogeneity was found among four epidemiological studies of endometrial cancer and C-peptide giving a summary RR compatible with no association. Overall breast cancer risk was significantly higher in the upper categories of C-peptide/insulin, however, the excess derived entirely from retrospective studies. Conclusion: Current evidence suggests that subjects who develop colorectal and pancreatic cancers have increased pre-diagnostic blood levels of insulin and glucose. PMID: 18465360

'Wanted': Elite Heart Health NOW

2008-06-15T23:27:00.000-07:00

There is a new summer blockbuster I'm looking forward to...(!!) 'Wanted' shortly will be released. Angelina Jolie plays a sort of 'trainer'... to a novice apprentice. All the tools to assassinate the target are provided, and he is 'invited' to lead a new life. Do we all have opportunities to transcend and create extraordinary goals? ...And achieve what we never dreamed? Would you know unless the first steps are taken? Do you need a trainer?

Shift time... Shift your destiny... and make every minute count.

Live like you mean it

Don't accept a 'normal' standard heart life (ie, 'conventional cardiovascular care')
Don't expect mediocrity
Don't wait for an AED defibrillator to be mandated for each home for a home myocardial infarction
Don't play with fire...

Protect a life, yours, and protect others, those who depend on you

Learn all the weapons to l-i-v-e... super-vital, plaque-free, extra-extended lives

Forge elite heart health and fitness now

'This is your destiny. Join us...' Morgan Freeman

Choose your destiny

Choose elite heart health now...And change your life forever...

Track Your Plaque (TYP 2.0):
--controls plaque
--controls weight and body fat
--controls TGs ('bad cholesterol') and small dense bullet-like LDL
--controls blood pressure
--controls inflammation and insulin
--controls glucoses
--controls heart rhythms
(These interventions also controls the same factors which cause strokes, ED, and most cancers.)

Do you need a trainer?

-G