' Death ' Bands: Subfraction LDL-IVb Strongest Predictor of CAD

Modified and Courtesy of a FDA.gov website

Let's review some subfractionation techniques. On the market 3 main methods exist. They all work. Dr. Davis prefers NMR. Superko and Krauss are affiliated with Berkeley HeartLab which uses GGE. Density gradient ultracentrifugation is also very popular (VAP-II). Recently, Krauss also appears to be introducing a new technology based on ion-mobility.

Basically, the denser the particle, the faster and mobile (like sp*rm *haa*) the particle moves through a gel (GGE). The denser the particle, the smaller the diameter (Angstroms or nanometers) as determined via electromagnetic resonance (NMR) or absorbance via density ultracentrifugation (VAP, which are indirectly compared to known sizes).

Pattern 'A' is good (all nice large buoyant fluffy particles).

Pattern 'B' is clearly BAD. Dense small stupid cr*ppy stuff. Guess what causes it? Excessive dietary carbs and/or fruit. Lack of omega-3 fats. Excessive omega-6 refined veggie oxidized refined fats not meant for human or animal consumption. Lack of saturated fatty acids. Lack of antioxidants. Lack of hormones.

The medical literature is rife with studies demonstrating that the conversion of small dense LDL to buoyant LDL is associated with regression of coronary artery disease.



Measuring LDL-Cholesterol Alone is Faulty and a Farce

Why is subfractionation via NMR/gel electrophoresis/UC of lipoproteins the most accurate way to assess cholesterol ? In doing so, the density and particle counts can be determined.

Only the marketing ploy of the statin/fibrate/zetia industries want to measure LDL-C alone without particle sizing. Yes. It is not cheap -- $99 via different labs. Some insurances cover it. Most don't at this time.

LDL-C alone tells nothing. It is like looking at someone's debt. Is it good debt (student loans, low fixed interest)? Or is it all bad debt (variable ARM, no down, several high interest boat/car/house loans)??!? Or No Debt? Or a mix (no debt on car boat house but low good student + low fixed vacation house debt)?

Do you have a good accountant? Do you have a good investor (eg, YOU)? Would you trust your money with a loser? With someone who has no money in the bank? With your statinator cardio-idiot? How many coronary events did he/she avert? Using 'tracking' EBCT/MDCT technology and targeted strategies to raise HDL2 and lower small dense LDL and Lp(a), both Drs. Davis and Blanchett (in Colorado, our colleague) have ancedotally seen single-digit events in their practices that span almost 10 years. HeartHawk likes to refer to this phenomenon as 'no event, no matter what score.' Even if the coronary calcification score is 4-digit, literally no events are seen. The failures they do see are related to noncompliance with the program and calcification scores consistently increasing 10+% or 20+%, respectively.

Well, when you trust your local neighborhood statinator, eg local General Practitioner, internal med LDL-centric drug-rep-pimped-up doc, cardiologist with lipidology credentials and certifications, what do they have in the bank? You must ask them. If they don't provide a good enough answer, seek new advice I would heartily suggest.

What do I look for?

No debt. High safe investments. High money in the B A N K . Demonstrated portofolio performance.

...EBCT regression or no EBCT score at all.

Personally I believe non-physician individuals like Richard Nikoley or Dr. Stephan Guyenet PhD or Dr. Dr. Petro Dobromylskyj (vet) or elite athlete Mark Sisson or Robb Wolf MS (Paleo/Xfit protege) know far more than your local GP statinator ninnyhead who are only focused on NCEPIII-LDL-centric guidelines. Quality of lipoproteins trumps quantity alone. Holds true for economic debt too. Does your statinator know that?!?




Lowering LDL-C Alone Does Not Reverse Heart Disease

Remember Cardio Controversies and Dr. Superko? LDL-C reduction alone was no better than placebo. Event rates barely were improved when Superko look at the whole picture comparing statin trials v. niacin trials. Yes, he made a variety of inferences. Yes, Niacin trumps all statin trials. Niacin in alone or in combo trumps ALL STATIN TRIALS in all-cause mortality, cardiac-death, and cardiac events. Superko makes educated, non-biased, medical-literature-based inferences.

So what? He is correct.

Statins raise %-sdLDL. sdLDL is oxLDL. See below. Statins create and sustain Pattern B which is predominance of small dense LDL. On statin therapy, often the LDL are 50-100% all small dense particles. sdLDL cr*p. OxLDL. On our TYP forum, the same phenomenon does appear to occur. Statins appear to prevent regression. What?? I think Superko is super-right.

On statins, the EBCT progression fails to halt despite niacin, omega-3 fish oil ULTRA high dose, 10-20+ lb fat loss, body recomposition, Lp(a) reduction, HDL2 increases... despite all TYP-directed efforts... EBCT scores increase 10-25+% annualized. Why?

Statins s*ck.

They maintain a high oxLDL concentration which the body cannot escape. It is not unlike bad revolving debt.

This is worse in those with Lp(a) -- anything greater than 3 mg/dl.

Yes. It doesn't matter how much Lp(a) one exhibits. Any amount jacks up the picture. Dr. Hecht, Superko's partner in cardio controversies, has shown that. Hecht, like Drs. Davis and Blanchett, is one of the earliest, most vocal proponents of using CT technology for screening of subclinical coronary atherosclerosis. I'll be going over later how he thrashes the retarded Heart Protection Study which marketing ploys by statin companies attempted to lower the LDL-C health standards. *urrg*

It is a good thing at TrackYourPlaque that we no longer rely on this useless drug class. (BTW fibrates s*ck. BTW zetia s*cks too.)



Niacin and n-3 fatty acids trump them all.

Statins Increase OxLDL
For oxLDL to 'transform' to Large fluffy healthy LDL, CETP needs to deposit cholesterol esters into the particles. How can it if statins block cholesterol synthesis? Or if worse Zetia blocks dietary cholesterol uptake from the gut. Frankly the lipoproteins are f*cked. They never seem to attain the large, fluffy particle size associated with regressive Pattern A in the niacin regression trials (70% converted to Pattern A compared with Placebo, HATS trial NEJM 2001).



Statins Raise %-sdLDL, Lp(a) OxLDL (or OxLDL/apoB)

Mechanism? Lp(a) 'tracks' inversely with analogously with growing and increasing Large LDL and HDL2. Statins s*ck. Statins lower all LDL species, including the good stuff, the buoyant LDL which are necessary for regression. A new marker is the oxLDL/apoB ratio and several trials found an increase in oxLDL proportions related to apoB. Yet another adverse finding was an increase in oxPL (oxidized phospholipids) which bind Lp(a). Does oxPL increase toxicity of Lp(a)? I don't know but it probably does not help and likely explains many of the increases in EBCT scores in statinators. How long are these effects in place? I wish I knew.

Increases in Lp(a) were found with every statin tested.

--COMPELL
--PROVE-IT
--lipitor and zocor
--MIRACL
--REVERSAL



Krauss and Superko: Only the Densiest Particles Predict CAD

Superko and Krauss found evidence in 2001 that the small dense LDL-III a+b subspecies tracked the best with CAD. However more recently Krauss made note that the smallest, densest fraction out of 7 subspecies actually tracked the most predictable with progression of subclinical and clinical coronary artery disease. I call this band on gel electrophoresis the 'death band'. No, I'm not talking about a rock 'n roll band. The LDL-IVb fraction is the 'death band'. The goal at Berkeley Heartlab is to achieve < 2.5% based on one trial (when angiogram stenosis > 30%). However, this goal is not low enough. We see EBCT and MDCT progression even at > 1.5%. Likely stenosis is < 30% as the trials demonstrate continued progression.

Other researchers have found similar correlations with small dense LDL being superior in predicting CAD (Koba S et al. J Atherothromb 2008).

Berkeley Heart Lab in fact advise for Pattern B a 'high 40% fat diet.' That is pretty progressive! But they fail to specify the components of the fat: monounsaturated, polyunsaturated, n-3 v. n-6 and saturated. Are they afraid of liability? Are they afraid of success? Are they afraid of regression? I dunno.

They do fail to address the carb intake therefore it probably would be fair to say that they can not broach diet unless carbohydrate intake is fairly accurately laid out.



























Only two studies exist that I can find that implicate Large LDL in coronary artery disease risk. Krauss wrote the first one in 1995, then re-clarified oh just last month. I briefly discussed HERE. In the clarification, he and other researchers retrospectively analyzed 3 large seminal trials and found no independent correlation between Large LDL and coronary atherosclerosis. One trial included in the review was the Quebec Cardiovascular trial.








TITLE: Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Québec Cardiovascular Study.
Lamarche B et al. Arterioscler Thromb Vasc Biol. 2005 Mar;25(3):553-9.

CONCLUSIONS: These results indicated that estimated cholesterol levels in the large LDL subfraction were not associated with an increased risk of IHD in men and that the cardiovascular risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles.
PMID: 15618542

Low Carb Paleo: Nothing's Impossible

Low Carb Paleo

Why is low carb Paleo the way to go for not just heart disease reversal, but also for maximum vitality, lifespan and longevity?

What is Paleo?
--no grains
--no legumes
--no sugar, candy
--(if strict: no dairy, no A1 casein (goat milk is A2 and generally acceptable)

The above are the greatest sources of carbohydrates which drive insulin and thus inflammation and elevated, toxic blood glucoses and dense small LDL. Fruit -- fruit is high carb and most of us on the 'bandwagon' are low carb and minimize ALL FRUIT because Paleolithically it rarely existed.

Saturated Fat -- even Dr. Loren Cordain is getting into saturated fatty acids...! Yes really.

Robb Wolf, his Paleo protege at our Crossfit network, mentioned it indirectly a few months ago and I alluded to it on our TYP forum. It is true. Read HERE with choice quotes from Don Metasz at his wonderful blog Primal Wisdom. Neither dietary cholesterol nor saturated fat are implicated in heart disease when the authors re-examined the literature. AAAAhhh... that is right on. Recall, Dr. Mozaffarian only found heart disease regression in the highest quintile of saturated fat intake > 12.0 %? And reduced progression in the quintile of the lowest carbohydrate intake?

Consensus. I like that.

Concordance among the critical thinkers... *haa* THINCers...

Here is a quote from Cordain et al...PDF click HERE Curr Treat Options Cardiovasc Med; 2009;11:289-301.




Low Carb, Mod-High Saturated Fat Paleo establishes all the metabolic parameters that Drs. Hecht and Davis support for optimum heart health:
--Lipoproteins dominated by buoyant large LDL particles, known as Pattern 'A' (versus 'B', for BBBBBAD)
--Regression of coronary calcification EBCT score with decrease in LDL-III (dense small LDL)
--Lowest Lp(a) values


Recall that Dr. Hecht (post: Cardio Controversies) compared a variety of lipoprotein factors with percentile rank of calcium scores. Again, total LDL made no difference at all. However if we look for patterns, one can observe a concentrated portion of high coronary calcifications around 140-160s and from his analyses, we know that the great majority of these are Pattern 'B' which are dominated with dense LDL. In the CAD patients, > 40-100% are typically dense small LDL particles. Our goal at TrackYourPlaque is to achieve < 10% or lower. We do see regression though even at < 30% so this is acceptable for some individuals who can improve the buoyant HDL2b substantially (like REALLY substantially).

Heart Disease LDL example (sdLDL = ~84 mg/dl):
Let's say that someone's LDL is 140 mg/dl.
Let's say it's solidly Pattern 'B' with 60% dense and small LDL. This is not unlike some of our subclinical atherosclerosis members (no event, no revascularization, no stent, no bypass graft). These are individuals with no symptoms who made the right decision to evaluate the coronary calcification status by having an EBCT or MDCT done. Easy -- 30 seconds -- hold the breath -- don't move. Low low radiation. DONE.

OK so how much is dense LDL? 60% of 140 is about 84 mg/dl. So on the graph above -- the L-sided red line is the actually dense small LDL. The R-sided red line is the 'total LDL'. The total LDL again does not mean a thing. The proportion of small v. large LDL is what matters and the context of HOW MUCH CORONARY CALCIFICATIONS exist to determine aggressiveness of treatment strategies (or not... since it is all controllable and reversible).

What about dense LDL created by eating low carb mod-high sat fat Paleo?

From several examples among my buddies on the blogosphere and at TYP and the seminal research on high sat fat diets of Krauss RM and Volek RS, we know that dense LDL can be controlled to... ZERO on NMR

Zero...'zero' LDL-3 on NMR, as reported by several Paleo folks at TrackYourPlaque on low carb mod-high fat Paleo, some in only 4 - 6 wks of diet implementation.

Or at most 5% (but who cares? it's less then Dr. Davis' ultimate goal 10%). Jimmy Moore's is 3%. (And, zero calcium in the coronaries -- Congrats again Jimmy! *wink* of course!)

So the 'paleo' dense LDL is orange on the graph.

Do you see it? On the FAR FAR FAR left side?


Paleo LDL example (sdLDL=~0 - 5 mg/dl):
Compared with 'non-low carb Paleo' 84 mg/dl dense small LDL. That's improvement of... infinity-times.

84 to zero.

What can be achieved by low carb, high sat Paleo?



Regression perchance...?

Complete ANNIHILATION and ERADICATION of coronary plaque...?!?


Seriously... other than avoidance of all AUTOIMMUNE diseases, congestive heart failure, DIABETES, DEMENTIA, cancer...
What can be achieved by low carb, high sat Paleo?

NOTHING IS IMPOSSIBLE (the bad*ss, brown-haired, beautOfaul broad-wide dental arches, Australian Merriweather, Last Skeptik remix, and losing his v-cherries at the V-Festival again)





Low Carb Paleo Controls Trigs and Raises HDLs

Other parameters also make a difference though these metabolic measures had less statistically related coefficients compared to Pattern B (particle size), Lp(a) and regression of coronary calcifications with reduction of LDL-III (dense LDL).

(a) Low Triglyerides (TG -- a reflection of our carb intake and insulin)

(b) High Total HDLs


Again... Paleo thrashes these metabolic parameters of heart disease. Without synthetic drugs. No statins. No fibrates. No zetia. No pletal.


Yes... again it controls Lp(a) as well. All Lp(a) is DANGEROUS when the 'death band' and low HDLs are present. Do you recall... butter and coconut oil beat the cr*pola out of canola oil and olive oil for reducing and controlling Lp(a)?


See prior animal pharm post for our wonderful TYP hall of famers and Paleo examples of PERFECT lipoproteins for PERFECT regression.



Low Carb Mod-High Sat Fat Paleo Raises HDLs OUT OF THE ROOF
In addition to all of the above metabolic parameters for control of atherosclerosis, HDLs are most stunningly and astoundingly improved. No drug can reach the height of these simple diet changes. Statins: -5 to 5% (this explains the utter lack of outcomes compared with regression trials with omega-3, niacin or vitamin D recall Cardio Controversies: Dr. Superko and his sumarai quote?). Fibrates: 5% (but they raise dense HDL-3 mostly). Zetia: 0-2% (again mostly HDL-3 and explains why all outcomes are negative and even worse than statin outcomes). Pletal: 0-3% (again HDL-3).

Our goal at TYP for HDLs is 60 mg/dl but obviously higher is not harmful if it is all the buoyant HDL-2 type which is associated with reductions in Trigs (see above) and dense LDL (see first diagram).

Never in my 10+ years pharmacological career have I ever heard of diet manipulations that substantially raise the heart- and cancer-protective HDLs until I found Paleo. *overwhelmed sigh* Yes -- sure niacin 30-50% (shift to 'A'). Yeahhh -- sure liquid GOLD that I treasure...fish oil 5-10% (generous shifting to 'A' and massive immeasurable immunomodulating anti-inflammatory benefits).

Low carb high sat fat Paleo: INCREASE BY 100-200%.

My HDLs nearly doubled (60s to 105 mg/dl with TYP + high fat Paleo, and probably higher now)

Most others report doubled or tripled total HDL values from baseline. See below examples and from the post: Part II Benefits of High-Saturated Fat Diets.

Is it really that easy?
--raise HDLs
--lower dense small LDL
--shift to Pattern A from BBBBAD
--feel more energetic, vibrant, younger with maximum vitality



N-O-T-H-I-N-G is impossible.



Summary of my favorite low carb high fat Paleo stories:

Dr. Richard Bernstein MD, Type 1 DM, 70-ish years old, no diabetic complications, low carb, high saturated fat lacto-Paleo: Triglycerides–50; LDL–53; HDL–118; and LDL subparticles - Type A.

Mr. Jimmy Moore (ultimate low carb high sat fat lacto-Paleo): Pattern A, small dense LDL 3%, HDL 60s, EBCT calcium score ZERO (percentile rank, big PHAT Z-E-R-O). Family heart disease risk: HIGH.

Mr. Richard Nikoley, the low carb high sat fat Paleo King: TC 223 (6/2008: 219) TG (57) HDL 133 (106) Real LDL 66 Calc LDL (104)

Mr. Stephan Guyenet (high sat fat semi-Paleo) TC 252 TG 49 HDL 111 Calc LDL-131 (wrong, but who cares)

Mr. Scott Miller (BF 9% -- low carb high sat fat Paleo TC 223 TG 51 HDL 98 (baseline: HDL 38-ish and BF 26%) Calc-LDL 125 Lp(a) 2

Ms. Anne (Paleo and grain-free) TC 255 TG 36 HDL 93 Calc-LDL 154

Mrs. Anna (Against the Grain blog GRRRLL! ) TC 230 (2007, still transitioning to sat fat/grain-free) TG 59 HDL 72 (from 60's) Calc LDL 146
EBCT calcium score ZERO (percentile rank, big PHAT Z-E-R-O)

My Labs (on coconut oil, low carb mod-high sat fat Paleo, [25OHD]=50 ng/ml) TC 249 TG 68 (TGs 30s when no drug adverse effects) HDL 105 Real LDL 125 Calc-LDL 130 Lp(a) 2



Dr. Bernstein: Why the Low Carb Diet is Best

Dr. Bernstein is a wonderful educator, researcher, and physician. My respect for him and his brilliant work could never be overstated. His lipoproteins also R-O-C-K.

Why the Low Carb Diet is Best (click HERE link)

Part 4 of a 5 part feature

Richard Bernstein, MD, FACE, FACN, FCCWS Apr 24, 2007

Dr. Bernstein's latest book, Diabetes Solution, 3rd Edition, was published in March 2007 by Hachette Book Group, USA. His prior book, Diabetes Diet, was published in 2005 by Little Brown and Co.

When I developed diabetes in 1946, physicians thought that the high illness and death rate of diabetics was due to dietary fat and the supposedly resultant elevation of serum cholesterol. Since the DCCT trial, the scientific literature overwhelmingly supports the role of elevated blood sugar in all long-term diabetic complications.

Yet even today, many physicians ignore the need for normal blood sugars and focus on dietary fat. The 2006 Clinical Practice Recommendations (1) of the ADA advocate large amounts of dietary carbohydrate (45 - 65% of total calories) and small amounts of protein and fat. This recommendation is preceded by the statement that "dietary carbohydrate is the major contributor to postprandial (after meal) glucose concentration."

The high carbohydrate load is justified by the claim that "the brain and central nervous system have an absolute requirement for glucose as an energy source." This statement, while only partially correct (ketones from stored fat keep the brain alive during starvation), ignores the fact that in the absence of dietary carbohydrate, the liver, intestines, and kidneys convert dietary protein into as much glucose as the brain requires.

Virtually the entire evolution of mankind occurred when our ancestors were hunter-gatherers, well before the inventions of agriculture and animal husbandry. (2) These people had scarcely any access to dietary carbohydrate and certainly no access to animal milk, cereal grains, whole-grain and refined breads, refined sugars, and sweet fruits. They ate almost exclusively lean meat and fish, plus small amounts of leafy and other low carbohydrate vegetables. Some humans, such as Eskimos, consumed only fat and protein. Our pre-agriculture ancestors frequently had violent deaths, but no coronary, kidney, or arterial disease, no tooth decay, and no diabetes.

By 1969, when I first began to measure my own blood sugars, I was already suffering from about 15 major and minor long-term complications of diabetes, thanks to the low fat, high carbohydrate diet I had been following for 23 years. By about this time, scientific studies of animals had demonstrated the prevention and even reversal of many diabetic complications by blood sugar normalization.

I soon discovered that even multiple daily insulin injections (basal/bolus dosing) would not achieve anything close to steady normal blood sugars. It was not until I lowered my carbohydrate consumption to a daily total of 30 grams (mostly from leafy and cruciferous vegetables) that things fell into place. Today my A1c is 4.5% (normal is 4.2-4.6%), and my target blood sugar is 83 mg/dl (about mid-normal for young non-diabetic adults).
Most of my long-term complications, including advanced kidney disease and severe gastroparesis, have normalized. Those that involved irreversible muscle loss (droopy eyelids, intrinsic minus feet (diabetic foot)) have not gotten worse. My lipid profile, which had been grossly abnormal, now shows: Triglycerides–50; LDL–53; HDL–118; and LDL subparticles - Type A. I see similar results in others who follow a prehistoric diet like my own (except for some type 1's with severe gastroparesis).

Until very recently, researchers were not comparing the effects of low carbohydrate diets to the ADA low fat/low protein diet. Recent results consistently support low carbohydrate, high protein¬ diets–not only for blood sugar control, but also with regard to weight loss and cardiac risk. Many of these studies are posted on the Web site of the Nutrition and Metabolism Society, at nutritionandmetabolism.com.

I am not alone. Thousands of type 1 and type 2 diabetics are following very low carbohydrate diets. Many observe that both fat and protein bring about satiety, while carbohydrate leaves them hungry and craving more carbohydrate. Other studies have focused on the importance of dietary protein for prevention of bone loss (4) and for preventing blood pressure elevation (5).

Richard K. Bernstein, M.D.,F.A.C.E., F.A.C.N., F.C.C.W.S. Mamaroneck, NY 10543

References:
1. Amer Diabetes Assoc Clinical Practice Recommendations, Diabetes Care, Vol 29 Suppl 1, Jan 2006, p. 513.
2. Cordain et al, Origins and Evolution of the Western Diet: Health Implications for the 21st Century, Amer J Clin Nutr; 81:341-54, 2005.
3. Science, 307:840, Feb 2005.
4. Bonjour J-P, Dietary Protein: An Essential Nutrient Factor for Bone Health, Jnl. Amer. Coll. Nutrition 24:6, 5265-5365, 2005.
5. Obarzanek et al, Dietary Protein and Blood Pressure, JAMA 275:20, 1598-1603, May 1996.

Case: 45 yo Female, Perfect Framingham, Perfect Cholesterol, Perfect PLAQUE PROGRESSION

When I see a female with Peripheral Vascular Disease (plaque in the legs) or angina/CAD (heart disease: plaque in the coronary arteries) or Chronic Kidney Disease (plaque in the kidney arteries)... invariably Lp(a) and low HDL2b are the PRIME factors for plaque buildup.

Another factor is a positive family history of a coronary event in the father prior to age 60 yo.



Review: Goals for Regression

Dr. Hecht has ten case studies which I will review one by one here. Earlier (Cardio Controversies: Dr. Hecht) we reviewed the success case study of the the young male with strong family CAD history, high Lp(a) and 15% EBCT regression after only 15 months on niacin 4000mg daily (and low low dose weak statin). This gentleman had regression after doubling the HDL2b from 12% to 24% and the small LDL shifted to buoyant Pattern 'A' LDL subspecies. Most notably, his Trigs started in the 200s then reduced to only 30s. O-u-t-s-t-a-n-d-i-n-g. Drugs alone? No. He must have lost weight, changed the diet, gained some body recomposition and started a good exercise program. Drugs alone cannot lower to Final Trigs 30s from the 200s. TYP goal for Trigs is 60 mg/dl however this is typically exceeded by most members especially those who are able to shift to Pattern 'A' and reach the other TYP goals. Trigs are an expression of our carbohydrates in our diet (starchy and sweet foods/beverages), saturated fats, and omega-3 fatty acids (ALA flaxseed; EPA DHA fish oil). As Trigs drop, buoyancy goes to the particles, both LDL and the HDLs. HDL-2b, the regression particle is the most buoyant, largest HDL subspecies. HDL-2b is associated with extreme longevity in centenarians, cancer-protection in remission cases and vascular regression of plaque in heart trials and at TYP.

HDL-2b are like good, loyal friends who watch out for you and your family.

Can you ever have too much?




Case Study: Perfect Scores, Perfect P L A Q U E

Dr. Hecht presents a case of a young female, no symptoms, with perfect plaque progression. She has a double-digit coronary calcification score of 95 which takes her to the top 98th percent for her age for plaque. Normal heart disease stratification at this time in conventional medicine uses the Framingham score. With her perfect baseline lipids, her score is quite good.
The Framingham 10-year risk is calculated to be < 1%.

Translation: 0-10% = 'low risk'. (10-20%=mod; >20%=high)

Her risk, in fact, is estimated to be insignificant, negligible risk.

No worries???

Yes, worry.

Alarmingly, she has the highest heart calcifications and the 'real age' of a 98 year old female.



Real Age, Real Baloney: Coronary Calcification Tells Age

Some experts Dr. Hecht discusses want to use EBCT or MDCT percentile scores as the 'real age'. This makes sense to me. It is the internal metabolic milieu, chaos and entropy which reflect our longevity and status.

Just as well, the internal metabolic calm reflect our regression and control of lifespan.



Advanced Metabolic Testing
Her results for the metabolic testing show perfect CRP (C-reactive protein). CRP is bunk. It could be elevated if you sneeze. If it is chronically elevated, then you have issues but it is no more telling of plaque than the traditional, conventional lipid panel.

On further examination, the metabolic testing which is identical to what we look at TYP program shows:
--elevated apoB (goal < 60-70)
--mildly elevated homocysteine (goal < 8.0)

Both of these indicators are related to inflammation and high carbohydrate intake. Inflammation may stem from excessive omega-6 and/or fructose, deficiencies (n-3 omegas, vitamins ADEK, B-vitamins B3 B6 B1 folate B12, minerals Magnesium Selenium Zinc Chromium Iodine Iodine, vitamin C, vitamin "O" optimism *haa*, carotenoids, mitochondrial components Carnosine CoQ10 ALCAR Carnitine; hormones adiponectin T E2 E2 P preg DHEA, etc), food allergies (wheat, gluten, A1 casein, nuts, etc), heavy metal and environmental toxicity (mercury from seafood, estrogenic pesticides, etc).





Ultimate Testing Lipoprotein Subfractionation:


The 'death band' is evident.

Recall according to Krauss, goal LDL IVb is less than zero. Just kidding, the goal is to get this subfraction which is the most dense, most lethal to as low as possible. In patients with large amounts of plaque where stenosis was > 30%, Krauss found < 2.5% of LDL-IVb was highly statistically significant for regression on angiogram. For those with 'less' plaque (read: less stable), LDL-IVb of 2.5% was still too high for regression to occur. What is good? I believe as low as possible. We see at TYP even when LDL-IVb is 1.5%, EBCT progression still occurs at 10-25%.

I don't find this acceptable.

The death band should be as low as possible. Or none.

Ultimate goal: Shift the LDL from dense to buoyant (known as LDL1 + LDL2a+b on BHL) and annihilate the 'death band'. Stop stuffing the face with fructose (fruit). Cut back olive oil and replace with some saturated fats.




Major Risk Factors for CAD: Low HDL2b, Lp(a)



Diagnosis: This young lady has extensive 98th-percentile plaque. Dense LDL, the death band LDLIVb, low HDL2b, and Lp(a).

Conventional Prognosis: No action on her doctor's part until she comes in with throbbing, painful legs or shortness of breath, back ache, jaw pain, heartburn (extensive plaque leads to vague, non-specific anginal symptoms in females). Worse case scenarios: tries to run a half-marathon or marathon and has a coronary event and is resuscitated with brain damage. Or SCD (sudden coronary death) where the first sign of heart disease is silent and fatal.
Unconventional TYP Prognosis: Longevity and shifting 98th-percentile calcifications to 15-50th-percentile less each year. Shortly... her real age will be 17 years old.

Yes, shaving YEARS off of her real age, coronary calcification percentile rank.


Hecht-Treatment: Hecht discusses niacin 4 grams per day and some statin (why? I dunno why because he contradicts himself when it comes to bashing LDL and LDL-goals; I sense some 'cognitive dissonance' on his part). Most cardiologists and physicians don't know a lick about diet, nutrition, what organs/hearts require, and basic micro- macronutrients. Didn't the father of medicine, once say 'let food be thy medicine'? We in the Paleo/Primal and TYP communities already know food can be poison (e.g. gluten, wheat, grains, legumes).

Is Hecht's therapeutic strategies enough? No. Some cases are 'treatment failures' which we'll later breakdown why.




Optimal Longevity Treatment To Reverse Vascular Dysfunction:

(1) Statin-less (statins increase Lp(a), OxLDL, OxLDL/apoB, %-dense LDL and prevent shifting from pattern B to A+++; causes autoimmunity and auto-antibodies, cellular level mitochondrial and myocyte damage, depletes antioxidants ubiquinols and coenzyme Q10; Crestor is associated with higher incidences of diabetes and kidney problems (proteinuria) in clinical trials)

(2) Niacin

(3) Omega-3 fish oil 6000++ mg EPA DHA daily for Lp(a), low HDL2b, high dense LDL, shift to pattern A, optimize n-6:3 ratio (goal ~1.5-2.0 per Dr. Barry Sears PhD and medical literature involving CKD patients)

(4) Correct Vitamin D deficiency (goal [25OHD] 60-80 ng/ml)

(5) Correct Saturated Fatty Acid Deficiency: Stop the AHA-low-fat-low-cholesterol-diet. Obtain Saturated Fats 15-20+% daily to increase HDL-2b, lower the death band LDLIVb, shift to Pattern 'A', and lower the atherogenicity of Lp(a)

(6) Correct Vitamin K2 deficiency (Sources: fermented cod liver oil, casein-free butter, hard cheeses if not allergic, natto, vitamin K2 100mcg daily MK7)

(7) Correct thyroid and adrenals by initially supporting (egg yolks, vitamins ADEK K2 Bs C; tocopherols, tocotrienols, minerals: Magnesium Selenium Zinc Chromium Iodine Iodide; saturated fatty acids, omega-3 fats ALA EPA DHA, carotenoids, avoidance of n-6 PUFAs) and if not sufficient then thyroid replacement (Armour +/- T4) and adrenal support (read HERE and HERE) to achieve optimal metabolism and stable core body temperatures 98.2 - 98.6 degrees F.

(8) Correct insulin disparities (exercise, C-A-R-B RESTRICTION, stress reduction, SLEEP, yoga, resistance train, weight loss, ketosis (diet, intermittent fasting), insulin-sensitizers: R-alpha lipoic acid, L-carnitine, Chromium, Leucine, Taurine, Glutamine, whey protein, flaxseed and fish oil, bittermelon, celery, pycnogenol, krill oil, astaxanthin, other antioxidants and proanthocyanidins, etc)

(9) Correct other calcified organ dysfunction: pineal (melatonin), hypothalamus (yoga, relaxation, breathing ex, etc), thyroid (see above), pancreas (see insulin above + digestive enzymes), gallbladder (digestive enzymes), colon (probiotics)

(10) No w-o-r-r-i-e-s ! *winky*



What about 4 grams per day of vitamin B3, niacin?

Does overdosing on niacin aid the above? Unfortunately 'no'. The mechanism of action is that niacin mimics all of the above (increases hGH, testosterone, steroids, ketosis, fasting and exercise). Adverse effects of niacin include: gout, diabetes and liver test elevations. Again I like niacin b/c it works but I don't love it. It doesn't appear to work on everyone in the year 2008-2009 and likely the future. Numerous nutritional and environmental toxicities apparently have shifted the cardiology and endocrinology playing field since the niacin trials were published, including the HATS 2001 NEJM publication by BG Brown et al.



Dr. Davis' Nutritional Wisdom and Recent TYP Topics (Members) to Reverse Vascular Dysfunction:

o Fructose: Dangerous at Any Level?
o Anthocyanidins: Eat Purple
o S-L-E-E-P -- Quality and Quantity
o Iodine Deficiency -- Importance for Heart Health
o Thermoregulation -- Thyroid and Adrenal Dysfunction
o TYP Part 3 Diet: 40% Fat Diet for Lp(a) and read more HERE

Cardio Controversies: Lp(a) Dangerous at ANY Value

What the heck...?

Can Lp(a) create more damage than we previously thought?

Dr. Hecht has apparently showed it with his examination of lipoprotein, cardiac and metabolic parameter comparisons with the real measure of heart disease risk: EBCT-determined plaque burden. Lp(a) was 3rd after HDL and LDL particle diameter in being highly associated with coronary calcifications. See below. Free PDF HERE. Normally at TrackYourPlaque we consider Lp(a) greater than 20 mg/dl as a high contributor toward accelerated plaque burden. When I look at Dr. Hecht's graphs, what I notice is that indeed this may not be true.

It appears to my observations that at ANY Lp(a) value, plaque burden is quite high reaching even 97th, 98th or 99th calcium percentile for CAD risk (of population norms) at severely low Lp(a) levels of 5 mg/dl or 10 mg/dl.



OK...what the heck?

I can make the same observations for my CAD (heart), PVD (peripheral), or CVD (stroke) patients and individuals with extensive diabetic complications. At any Lp(a), the extent of disease can still be quite pronounced.



What other factors are correlated to vascular damage?

1. Low HDL2b

2. High small dense LDL.

These THREE factors determine almost entirely the extent of disease. Both visionaries Dr. Davis and Dr. Hecht focus on these predominantly to control and halt the progression of calcifications.


How are these 3 metabolic parameters created in the first place?
--low fat SAD AHA low cholesterol low saturated fat diet
--saturated fat deficiency
--excessive carbs (>10 g/d, >20 g/d, >50 g/d, >100 g/d -- depending on a person's insulin and insulin sensitivity and pancreas/adipose/hormone status)
--inflammation (excessive omega-6 oils)


Not... necessarily... a Slo-niacin or Niaspan deficiency...




Saturated Fats Like Butter Beat the Cr*pola Out of Canola in Lowering Lp(a)

We've discussed Dr. Mozaffarian earlier in Part IV Benefits of High-Saturated Fat Diets where he showed higher sat fat (> 12.0%), lower n-6 PUFA and lower carb were associated with less coronary artery stenosis; in fact in the quartile of the highest sat fat dietary intake, regression of coronary artery stenosis was signficantly observed. No other parameter was correlated to regression. Right...! ONLY higher dietary saturated fat consumption... (this quartile also was found to smoke more and took less pharmaceuticals).

Is Krauss in the house?? OK, Dr. Mozaffarian at Harvard has come through again (sort of). He did the right study again (though... 'wrong' conclusions). In his most recent publication Mozaffarian showed that after switching human subjects off of various concentrations of dietary trans fats to different fats (saturated and n-6), dramatic changes in cardiac parameters were noticed (Mozaffarian D, Clarke R. Eur J Clin Nutr. 2009 May;63 Suppl 2:S22-33. Free PDF HERE. ) Butter and other saturated fats were shown to lower the baseline Lp(a) to greater degrees than n-6 PUFAs like soybean, cottonseed, or canola oil.

Butter, palm oil and lard beat canola and other n-6 PUFA oils by 3-4-fold.






Mechanism of Action of: B U T T E R

Butter is comprised of part monounsaturated fats and part saturated fatty acids with one of the predominant acids being BUTYRIC ACID, a 4-carbon chain entity. It turns out that ALL the saturated fatty acids behave much like the omega-3 PUFAs that we enjoy for their plaque-regression, lipoprotein improving, immunomodulating and anti-inflammatory properties. Omega-3 PUFAS bind the whole-pan-PPAR receptor family to shift to LDL larger particles and increase HDL2b. Saturated fats bind most strongly to PPAR-gamma which raises HDLs and and lowers both Lp(a) and Small Dense LDL (particularly LDL-IVb, the 'death band'). They bind weakly to PPAR-delta but sufficiently to paradoxically and P-O-T-E-N-T-L-Y lower inflammation (NFkB, TNF-alpha).

Recall: PPAR-Delta is the Dagger in the Heart of CAD


Saturated fatty acids in fact behave like hormones and bind like steroid nuclear hormones to the PPAR family of receptors (like vitamin-D-to-VDR, carotenoids-to-RXR, vitamin-A-to-RAR, thyroid-to-TR, estrogen-to-ER, etc). This research was done many years ago by Glaxo researchers Eric Xu and others (Molecular Cell, Vol. 3, 397–403, March, 1999). See below. Other researchers defined further the benefits of butyric acid (butyrate) by elucidating its binding activity of PPAR convincingly.


Our b*tt is made out of saturated fats and we eat saturated fats (almonds, coconuts, olives, fatty fish, grassfed beef, free-range eggs/fowl, wild duck, etc). Our body creates, metabolizes and burns saturated fats all day (recall: palmitic acid) esp when we are between meals, intermittent fasting, carb restricting, ketotic, exercising or starving.

Do we make butyrate??



Make Butter (Butyrate) In Your B*TT

Just kidding... North of the rectum (e.g. b*tt), in the colon , short-chain fatty acids like butyric acid (butyrate) one of the fatty acids found in butter, cream and cheeses is produced via anaerobic fermentation of dietary fiber. Our friendly happy gut flora actually produces butyrate (not us). We either consume it or we absorb it from our intestines from bacterial production.

Yes... *haaa* make BUTTER in your colon from vegetable fibers...



Butyrate Protects Against Colon Cancer by Lowering NFkB by Binding PPAR

Furthermore, butyrate has been shown in trials to be anti-inflammatory and immune-modulating. Deficiencies in luminal butyrate synthesis are associated with chronic bowel inflammation. Schwab M et al state:

"Previously, we have demonstrated that the nuclear hormone erceptors Peroxisome-Proliferator-Activated-Receptor (PPAR) and the vitamin D receptor (VDR), transcription factors with anti-inflammatory capacities, are up-regulated and activated by butyrate (Gaschott and Stein, 2003; Gaschott et al., 2001; Schwab et al., 2006;Wachtershauser et al., 2000). PPAR and VDR are highly expressed in the colonic epithelium indicating that both receptors are important agents in the physiology of the human colon (Desvergne and Wahli, 1999; Nagpal et al., 2005). Ligands for both receptors have been shown to interfere with the activity of NFkB and to influence the ability of olonocytes to express immune-modulatory cytokines (Segain et al., 2000; Sun et al., 2006)."

Independently in two labs in 2007, butyrate was found to control NFkB, one of the most potent pro-inflammatory cytokines of our immune system implicated in ALL chronic and acute diseases known to man, including colon cancer and coronary artery disease (Schwab M et al. Molecular Immunology 2007;44: 3625–3632.; Usame M et al. Nutr Res 2008;28:321–328. See end.) The anti-inflammatory power of lauric acid from coconut and palm oil and butyric acid from butter originates from their ability to bind and activiate PPAR-gamma as shown by these studies. PPAR, like the vitamin D receptor (VDR), is one of the master controllers of inflammation. Schwab shows in several publications that butyrate does in fact configure, bind, and activate PPAR receptors. Butyrate is like a DRUG. It binds the most potent receptor for energy balance, immunomodulation, control of lipids (Lp(a), HDL2b, sdLDL), and inflammation! End result... it knocks out NFkB. For the heart, this translates to kicking the cr*pola out of canola in terms of shifting to Pattern 'A', increasing HDL-2b, annihilating small dense LDL and Lp(a) and eradication of vascular atherosclersis.

See Prior Posts:
PPAR






Trying to Target Butter-Receptors: How About Grassfed GHEE??

"There is increasing evidence that the expression and activity of PPARg and VDR are under the control of butyrate implying that the receptors may participate in butyrate-mediated suppression of NFB activation (Gaschott and Stein, 2003; Gaschott et al., 2001; Schwab et al., 2006; Wachtershauser et al., 2000). PPARg and VDR are both ligand-activated transcription factors that belong to the nuclear hormone receptor family and participate in a variety of immune processes (Tirona and Kim, 2005). VDR is widely expressed in epithelial tissues, cells of the immune system and several cancer cell lines including colorectal cancer cells (Giuliano et al., 1991; Segaert and Bouillon, 1998). PPARg is activated by natural ligands such as fatty acids and eicosanoids and is highly expressed in colonic epithelium, indicating an important role of the receptor in the physiology of the human colon (Desvergne and Wahli, 1999). All these characteristics make both receptors potential targets in butyrate-mediated inhibition of NFkB signalling."

In Vivo (Live Humans) High Intake of Butter Associated with Reduced Colon Cancer

Of course Swedish researchers examined their nutrition data registry for the Swedish Mammagraphy Cohort and lo and behold found distinct correlations between high dairy intake and low colon cancer (Am J Clin Nutr. 2005 Oct;82(4):894-900.) Those in the upper 2 quartiles of CLA consumption and > 4 servings daily of high-fat dairy was highly associated with reduced colon cancer risk. The author's conclusions were: These prospective data suggest that high intakes of high-fat dairy foods and CLA may reduce the risk of colorectal cancer.



Diary Fat Potential Anti-Carcinogenic Agents

Parodi reviews the literature and reports that... "About one third of all milk triacylglycerols contain one molecule of butyric acid, a potent inhibitor of proliferation and inducer of differentiation and apoptosis in a wide range of neoplastic cell lines. Although butyrate produced by colonic fermentation is considered important for colon cancer protection, an animal study suggests dietary butyrate may inhibit mammary tumorigenesis. The dairy cow also has the ability to extract other potential anticarcinogenic agents such as beta-carotene, beta-ionone and gossypol from its feed and transfer them to milk (J Nutr. 1997 Jun;127(6):1055-60. Free PDF HERE). Grassfed cheese, cultured milk, yogurt, ghee, and butter also contain CLA. Parodi discusses that, "Recent research shows that milk fat contains a number of potential anticarcinogenic components including conjugated linoleic acid, sphingomyelin, butyric acid and ether lipids. Conjugated linoleic acid inhibited proliferation of human malignant melanoma, colorectal, breast and lung cancer cell lines. In animals, it reduced the incidence of chemically induced mouse epidermal tumors, mouse forestomach neoplasia and aberrant crypt foci in the rat colon. In a number of studies, conjugated linoleic acid, at near-physiological concentrations, inhibited mammary tumorigenesis independently of the amount and type of fat in the diet."




Beef Tallow SYNERGISTICALLY Beats the Cr*pola Out of Corn Oil (n-6 PUFA)

In another interesting animal study (mice), beef tallow (25% palmitic acid; 50% oleic acid) increased the potency of CLA in decreasing mouse mammary tumor metastasis. (J Nutr. 2006 Jan;136(1):88-93.) "Linoleic, oleic, stearic, and palmitic acids, either did not change or enhanced the cytolytic effects of CLA isomers on mouse mammary tumor cells in culture." The authors found that oleic + palmitic enhanced cytolytic CLA-derived tumor cell death, whereas n-6 PUFAs (linoleic acid) were associated with dose-dependent increases in tumorigenesis and blocking CLA-benefits.

See Prior Post:
Happy Cows and CLA (CLA is found in grassfed beef, dairy, lamb, pastured pork)




Rat Study: ONLY Olive Oil and n-6 PUFAs Associated with Cancer Model in High-Fat Diets

Rats are not humans but they have no gall bladders... so they are not unlike 80% of the individuals that I see who fail to have functioning gallbladders. Anyhow in this one study 4 high fat diets (corn, lard, beef tallow and coconut oil) and 1 low fat corn oil were used in 5 rat groups (Chan PC et al. Cancer Res. 1983 Mar;43(3):1079-83.). Mammary tumors were induced with N-nitrosomethylurea. Incidence of tumors in the high-fat groups was the lowest in the coconut oil group. Upon further analyses (these researchers were GOOD), they concluded, " the total oleic and linoleic acid intake in the five groups of rats correlated positively (r = 0.95) with mammary tumor incidence."




Role of Oliv-ola (Canola+Olive oil) Induced Colon Carcinogenesis:
Coconut Oil Beats the Cr*pola Out of OLIVOLA

Nair J et al in Germany have been conducting research in DNA damage associated with oils (Nair J et al. Mutat Res. 2007 Nov 1;624(1-2):71-9.) They tested LA (linoleic acid, n-6 PUFA), oleic acid and coconut oil in rats by lavaging them for 30day, sacrificing, then measuring etheno-DNA adducts in the organs. Etheno-DNA adducts are associated with j*cked up gene expression, mutations and carcinogenesis. They are produced by oxidative stress and lipid peroxidation. Their research showed that n-6 PUFAs have gender-specific toxicity and other surprising results. Not unlike the Israeli 'Paradox' (see below), female LA-treated rats showed increases in etheno-DNA adducts in the DNA of their circulating immune cells, the all important WBC (white blood cells). For both genders, colon was the target for stress-derived DNA-adducts in omega-6-PUFA treated rats, which supports the role for omega-6 induced colon cancer, the authors concluded.

'Unexpectedly, olive oil treatment enhanced entheno-adduct levels in prostate 3-9-fold' the researchers observed.

What... the... H E C K ?

So... olive oil (n-9 monounsaturated) is highly implicated in TWO studies with cancer: mammary and prostate. Is this only seen in certain situations?

Lame-o retard-o dietary fat composition?

Saturated fatty acid deficiencies?

Omega-3 deficiencies?

Most lab rats are vitamin D deficient as well...



Here is other provocative (ok, not really) research showing the same thing in more in vivo animal cancer model studies:
--coconut oil beats the cr*pola out of n-6 PUFAs
--MCT oil (50% of coconut oil) beats the cr*pola out of n-6 PUFAs
--the lower the rat cholesterol, the higher the incidence of mammary tumorogenesis... in other words (switch around), the larger the LDL particles induced by saturated fatty acids which results in a higher total cholesterol, the lower the risk of breast cancer in rats. Applies to humans too.

Dietary fat and mammary cancer. II. Modulation of serum and tumor lipid composition and tumor prostaglandins by different dietary fats: association with tumor incidence patterns.
Cohen LA, Thompson DO, Choi K, Karmali RA, Rose DP.
J Natl Cancer Inst. 1986 Jul;77(1):43-51.

Dietary fat and mammary cancer. I. Promoting effects of different dietary fats on N-nitrosomethylurea-induced rat mammary tumorigenesis.
Cohen LA, Thompson DO, Maeura Y, Choi K, Blank ME, Rose DP.
J Natl Cancer Inst. 1986 Jul;77(1):33-42.

Influence of dietary medium-chain triglycerides on the development of N-methylnitrosourea-induced rat mammary tumors.
Cohen LA, Thompson DO, Maeura Y, Weisburger JH.
Cancer Res. 1984 Nov;44(11):5023-8.
Medium chain triglycerides (MCT) in aging and arteriosclerosis.
Kaunitz H.
J Environ Pathol Toxicol Oncol. 1986 Mar-Apr;6(3-4):115-21.



So I've digressed... let's get back to the heart of the matter...


n-6 PUFAs Shrink LDL-Particles... To Pattern B (BAD)

Shrinkage... Not. Good. The rest of the Mozaffarian and Clarke's conclusions are not so justified by the medical literature. They further try to discuss the cardiac benefits of the n-6 vegetable oils without acknowledging the metabolic parameters that Drs. Hecht, Krauss, Superko and Davis support as the factors that are most highly correlated to plaque burden: LDL particle size, HDL2b and Lp(a). Unfortunately I find their so-called cardiac assertions kinda b-u-n-k-y. They employ parameters (TC/HDL ratio, apoB/AI ratio, CRP) that are not borne out to be associated with coronary calcium plaque burden or serial plaque progression according to Hecht's 2003 publication.

n-6 PUFA and olive oil are necessarily heart healthy?? No. In a study with rapeseed, olive oil or sunflower oil, LDL particles significantly (p=0.012) shifted to smaller, dense particles with all the oils tested, after a switch from a two-week saturated fat diet. BUNKY!!! See below.

Dietary mono- and polyunsaturated fatty acids similarly affect LDL size in healthy men and women.

Kratz M, et al. J Nutr. 2002 Apr;132(4):715-8.

The goal of this study was to investigate the effect of the dietary fat composition on LDL peak particle diameter. Therefore, we measured LDL size by gradient gel electrophoresis in 56 (30 men, 26 women) healthy participants in a controlled dietary study. First, all participants received a baseline diet rich in saturated fat for 2 wk; they were then randomly assigned to one of three dietary treatments, which contained refined olive oil [rich in monounsaturated fatty acids (MUFA), n = 18], rapeseed oil [rich in MUFA and (n-3)-polyunsaturated fatty acids (PUFA), n = 18], or sunflower oil [rich in (n-6)-PUFA, n = 20] as the principal source of fat for 4 wk. Repeated-measures ANOVA revealed a small, but significant reduction in LDL size during the oil diet phase (-0.36 nm, P = 0.012), which did not differ significantly among the three groups (P = 0.384). Furthermore, affiliation with one of the three diet groups did not contribute significantly to the observed variation in LDL size (P = 0.690). In conclusion, our data indicate that dietary unsaturated fat similarly R E D U C E S LDL size relative to saturated fat. However, the small magnitude of this reduction also suggests that the composition of dietary fat is not a major factor affecting LDL size.
PMID: 11925466

n-6 PUFAs Cause Inflammation and Cancer: Israeli Experience

Shapiri discusses how changing from traditional oils (saturated fats like schmaltz (rendered goose or chicken fat w/onions) or beef tallow) to a high consumption of n-6 PUFA oil is postulated to have lead to the astronomic rise in cancer in Israeli Jewish women (Eur J Cancer Prev. 2007 Oct;16(5):486-94.)

It is discussed HERE as well.


Wanna CUPPA of CANCER? Increase your n-6 PUFAs, reduce your saturated fatty acids.





Small Dense LDL, OxLDL and Lp(a) SYNERGISTICALLY Grow Plaque

Why is Lp(a) so extremely toxic and an accelerant for all damage whether it is diabetic complications (microvascular: eyes - kidney - nerves - penile - brain (e.g. Type 3.0 Diabetes)) or atherosclerotic disease (macrovascular: heart, carotid, peripheral)? Apparently Lp(a) binds oxidized phospholipids of apoB 100 which is attached to all LDL, including Lp(a). What is Lp(a)? It is just LDL + apo(a) combined. Large LDL are rarely oxidized -- they are protected by size, buoyancy, high cholesterol content (yes, cholesterol is an 'antioxidant') and a high content of vitamins and fat-soluble antioxidants (ubiquinols, carotenoids, menaquinones (vitamin K2s), tocopherols, tocotrienols) and apo E (carriers of minerals and other vital micronutrients).

A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma.

Bergmark C, et al. J Lipid Res. 2008 Oct;49(10):2230-9. Free PDF HERE.

Oxidized phospholipids (OxPLs) on apolipoprotein B-100 (apoB-100) particles are strongly associated with lipoprotein [a] (Lp[a]). In this study, we evaluated whether Lp[a] is preferentially the carrier of OxPL in human plasma. The content of OxPL on apoB-100 particles was measured with monoclonal antibody E06, which recognizes the phosphocholine (PC) headgroup of oxidized but not native phospholipids. To assess whether OxPLs were preferentially bound by Lp[a] as opposed to other lipoproteins, immunoprecipitation and ultracentrifugation experiments, in vitro transfer studies, and chemiluminescent ELISAs were performed. Immunoprecipitation of Lp[a] from human plasma with an apolipoprotein [a] (apo[a])-specific antibody demonstrated that more than 85% of E06 reactivity (i.e., OxPL) coimmunoprecipitated with Lp[a]. Ultracentrifugation experiments showed that nearly all OxPLs were found in fractions containing apo[a], as opposed to other apolipoproteins. In vitro transfer studies showed that oxidized LDL preferentially donates OxPLs to Lp[a], as opposed to LDL, in a time- and temperature-dependent manner, even in aqueous buffer. Approximately 50% of E06 immunoreactivity could be extracted from isolated Lp[a] following exposure of plasma to various lipid solvents. These data demonstrate that Lp[a] is the preferential carrier of PC-containing OxPL in human plasma. This unique property of Lp[a] suggests novel insights into its physiological function and mechanisms of atherogenicity.

Butyrate NFkB References

Involvement of different nuclear hormone receptors in butyrate-mediated inhibition of inducible NF kappa B signalling.
Schwab M, Reynders V, Loitsch S, Steinhilber D, Stein J, Schröder O.
Mol Immunol. 2007 Jul;44(15):3625-32. Epub 2007 May 22.

Role of nuclear hormone receptors in butyrate-mediated up-regulation of the antimicrobial peptide cathelicidin in epithelial colorectal cells.
Schwab M, Reynders V, Shastri Y, Loitsch S, Stein J, Schröder O.
Mol Immunol. 2007 Mar;44(8):2107-14. Epub 2006 Oct 19.

PPARgamma is a key target of butyrate-induced caspase-3 activation in the colorectal cancer cell line Caco-2.
Schwab M, Reynders V, Ulrich S, Zahn N, Stein J, Schröder O.
Apoptosis. 2006 Oct;11(10):1801-11.

Cardio Controversies: Dr. Harvey Hecht MD

Figure 1: Correlation of metabolic factors and calcium percentile

in asymptomatic patients with EBT showed calcified plaque

(Hecht HS. Prog Cardiovasc Dis. 2003 Sep-Oct;46(2):149-70.)

Dr. Davis has known for years that assessing and treating based on the LDL-Cholesterol alone is bunk. Just as simply visually inspecting someone's physical appearance to determine their heart status is bunk. The healthiest appearing athletes may in fact have the most profound coronary artery obstructions. Similarly an asymptomatic menopausal female with exceptionally 'high' HDLs, 'low' LDL and low Trigs may also have the highest Lp(a) and peripheral vascular obstructions in the lower extremities. Heart disease is still the #1 killer of Americans and across the globe in adults. Is it a wonder why? We are not even correctly identifying asymptomatic heart disease in moderate risk individuals ((+) family history of atherosclerosis disease (heart, kidney, peripheral, cerebral, aneurysm), Lp(a), low HDL, high Trigs, Metabolic Syndrome, high fasting or post-prandial insulin, etc).

The current protocol that physicians use to score heart disease risk is called 10-year Framingham risk scoring. Recent observational studies are elucidating the complete lack of correlation between this scoring method and detection of moderate to very severe asymptomatic subclinical disease.

Framingham scoring for low or moderate risk indivuals is bunk (Nasir et al. Int J Cardiol. 2006 Mar 22;108(1):68-75.)

Complete. Utter. BUNK.

According to Nasir et al asymptomatic Brazilian men (avg age=47) who were considered low or moderate risk according to Framingham scoring, moderate to very high risk coronary calcifications were found on an EBCT scan. "...Nearly half of individuals with CACS > or = 100 (45%) and CACS > or = 75th percentile (48%) missed eligibility..." for aggressive therapy for risk reduction. CACS = coronary artery calcium scoring.




Cardio Controversies: Dr. Harvey Hecht MD

Dr. Hecht was one of the cardiologists who has worked closely with Superko and Krauss over the last 10-20 yrs on statin trials, subfractionation of lipoproteins and more recently interventional radiology involving EBCT and MDCT. Like Callister (recall, Cardio Controversies HERE), Hecht originally saw a decline in EBTC coronary calcifications with statin monotherapy in one single study, however he could not be replicated the results at later dates. Like Krauss and Callister, he has questioned why this is the case. In a 2003 publication, he reviews the importance of many concepts that characterize our TYP program (Hecht HS. Prog Cardiovasc Dis. 2003 Sep-Oct;46(2):149-70. Free PDF HERE). Obviously, our TYP program embraces a program that is far and beyond conventional statin+niacin-centric therapy: diet, lifestyles, exercise, nutraceuticals, and no pharmaceuticals (excluding niacin and fish oil). Hecht's approach is basically mega doses of niacin niacin and more niacin (+low dose weak statin), which is quite fine but not very targeted or tolerable to most and fails to address the metabolic origins of heart disease, obesity, MetSyn, diabetes and inflammation.



LDL-Cholesterol Alone Tells Nothing

One of Dr. Hecht's first assertions is that LDL-C is completely, fully, unrelated to subclinical and clinical coronary calcifications. See above diagram, Figure 1. The R correlation quotient between LDL-C and positive coronary calcification was 0.0006 (p=0.90). To quote my favorite THINCer, Peter, 'count the ZEROES.' *ha*

Utterly. Unrelated.



Metabolic Parameters Matter

The highest correlations between overall plaque burden and measurable lipoprotein parameters were LDL peak particle diameter in angstroms, R = 0.14, P = .02 and high-density lipoprotein cholesterol, R = 0.11, P = .02). Of course these R values are not great since optimal statistically is 0.80 but this is the closest relationship determined from countless EBCT scans and patient datasets. In other words, Pattern 'A' versus Pattern 'B' makes a big difference, even a little more than how much HDL there is.

Figure 8. Correlation of annualized progression
of calcium score and change in metabolic factors.

C h a n g e in Plaque Burden Correlates Best With Small Dense LDL Changes

Hecht continued to examine how changes in the metabolic parameters related to change in coronary calcifications as visualized and quantitified by EBCT. The best relationship was found between percent change in Small Dense LDL (IIIa+b subfractions). Not HDL improvements (he apparently didn't look at HDL2b). Not Trig improvements. Definitely not LDL-C improvements (again, don't forget to count the zeroes,
R = 0.009, P=0.91). Not even the TC/HDL ratio improvements.

Regression or progression in coronary calcifications was highly associated with changes in sd-LDL out of ALL the parameters tested (R=0.46, p=0.71). See above. We see these correlations at TYP as well. Regression is highly associated with
--control of sd-LDL to < 10-30%
--annihilation of the 'death band' LDL-IVb from > 5% to as low as possible < 1-2 %
--solid Pattern 'A'
--increasing HDL-2b to as high as possible 60-200%


Our members do regression with DIET. LIFESTYLES. Supplements (omega-3, phosphatidylcholine, vitamin D, etc). LOW DOSE niacin 1-2 grams per day. STATIN-LESS... or on the way to statin-less.





High-Saturated Fat Diet Improves ALL Metabolic Metrics

These metabolic metrics -- sdLDL and HDL2b -- according to Krauss' research on lipoproteins are related mostly to (1) dietary saturated fatty acid intake (2) dietary carb loads.

Let's summarize Dr. Krauss' high fat study once more and then see how it compares in the context of CACS regression in an extremely high risk CAD patient whose father had an MI at age 46 (Case study #8; Figure 16). The carb intake again in Krauss' study is considered high by many standards at 39% and not as effective in lower small dense LDL or raising HDL-2b as lower carb or very low carb (VLCD) diets in insulin resistant individuals. Interesting comparisons can still be made.

Summary of Heart-Healthy Improvements with a High-Saturated Fat (18%) Diet in only Six Weeks:

(1) Increased total HDL-Cholesterol 18% (baseline 42 mg/dl)
(2) Increased Regression subspecies HDL-2 of 50%(3) Reduced Triglyercides by 30% (baseline 141 mg/dl)
(4) Increased total LDL-Cholesterol by 13% (good thing b/c LDL-diameter incr)
(4) Decreased LDL-IIIa+b from 27% to 18%(5) Decrease LDL-IV from 6.0% to 3.4%

Figure 16. Case 8. Metabolic data and EBT images

before and after 14 months of statin and niacin

combination therapy in a 47-year-old man with a

baseline calcium score of 442 in the 97th percentile.

Regression Case Study in a High CAD RISK Individual:
EBCT CAC Reduction 15% Annualized

This 47 yo patient's (see above) therapy included ultra high dose niacin (equivalent to 8 tablets of OTC Slo-Niacin 500mg) which was a dose similarly used in the HATS regression trial, plus low dose weak potency statin. His CAC score put him at the highest 97-percentile of extremely high coronary risk. His father had suffered an acute myocardial infarction at age 46.

What is quite notable with this regression case is the rapid changes in multiple metabolic parameters esp Lp(a) with niacin. Niacin is one of the few therapies that successfully lowers Lp(a). In the HATS trial ~20% of men and ~30% of women had elevations of Lp(a). High dose niacin worked for this gentleman with the tremendous plaque burden. In the EBCT scan, the reduction in LAD was obvious the author stated. See above.

Recall what does niacin mimic? Niacin binds the ketone body receptors which are activated during many of the strategies employed by TrackYourPlaque members:
--intermittent fasting ('fastest way to control plaque')
--carbohydrate restriction
--mod-high protein diet (Primal, Protein Power, phases 1-2 of South Beach)
--mod-high fat diet (TYP Diet Part 3, Primal, Protein Power, low carb high fat Paleo)









Metabolic Parameters Improved

Can we achieve similar multiple metabolic parameter improvements with diet + lifestyles alone?

Faster?

Without drug or ultra high dose niacin side effects?

How would ultra high dose 15 months of Niacin 4000 mg + statin daily in a 47 yo asymptomatic male compare with 6 weeks DR. Krauss' high fat diet in n=103 healthy men (46% fat, 18% sat fat when compared with AHA-Walter-Willet-low fat 8% sat fat)? Granted it is hard to make comparisons between Krauss' healthy study participants and this asymptomatic CAD Case Study, the baseline values for lipoproteins were not that significantly dissimilar from this Case Study (Low HDL, higher TG).

Very similar endpoints in fact can be achieved V E R Y rapidly!

The primary parameters to compare are:

High Fat x 1.5 months:
** Increased Regression subspecies HDL-2 of 50%
** Decreased LDL-IIIa+b from 27% to 18%
** Pattern 'A' to 'A+++' (LDL diameter from 25.9 to 26.5nm)

Pharmacotherapy x 15 months:
** Increased Regression subspecies HDL-2b of 71%** Decreased LDL-IIIa+b from 34.1% to 18.6%
** Pattern 'B' to 'A+++' (LDL diameter from 24.9 to 26.6nm)

Lp(a) Reduced By Saturated Fatty Acids and Raised by Low-Sat-Fat Diets
Benefits of Krauss high-saturated fat diet cannot be overstated. Saturated fats control CETP and thus control the amount of Lp(a) individuals produce. In fact, when an experiment group was put on a low fat, high veggie diet, Lp(a) increased significantly by as much as 9% (Silaste ML et al Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):498-503. Free PDF HERE .)

Additionally, the low fat diet produced HIGHER oxidized LDL (OxLDL) by 27%. Recall the small dense LDL are less resistant to oxidation than buoyant large LDL and transform to OxLDL rapidly.

Not good.

For. Plaque. Burden.

OxLDL causes fatty/calcified organs: arteries (atherosclerosis); endothelium (hypertension); liver (NASH); pancreas (diabetes, MetSyn); thyroid (Hashimoto's), visceral fat (obesity); etc.


Saturated fat lowers and controls Lp(a) and coconut oil is one great example (Muller H et al . J Nutr. 2003 Nov;133(11):3422-7. Free PDF HERE). In this study by Muller et al women with elevated Lp(a) in the 30s mg/dl were provided a coconut oil-rich diet (22.7% sat fat; 3.9% PUFA) was compared with a high PUFA-diet (15.6% PUFA !!yikes). Lp(a) was reduced 5.1% compared to baseline habitual diets with the high saturated fat diet whereas in the high PUFA diet, Lp(a) increased a whooping 7.5%. The difference between Lp(a) on the high sat fat compared to the high PUFA diet was 13.3%.

[Coconut oil is great unless one is allergic. I am aware of a friend allergic to both olives + oil and coconuts + oil. Dr. Hyman discusses food allergies and how to determine what they are via an elimination diet HERE to control inflammation and reduce autoimmunity.]



References

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Santos RD, Nasir K, Tufail K, Meneghelo RS, Carvalho JA, Blumenthal RS. Metabolic syndrome is associated with coronary artery calcium in asymptomatic white Brazilian men considered low-risk by Framingham risk score. Prev Cardiol. 2007 Summer;10(3):141-6.

Campbell CY, Nasir K, Carvalho JA, Blumenthal RS, Santos RD. The metabolic syndrome adds incremental value to the Framingham risk score in identifying asymptomatic individuals with higher degrees of inflammation. J Cardiometab Syndr. 2008 Winter;3(1):7-11.

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Hecht HS, Superko HR, Smith LK, McColgan BP. Relation of coronary artery calcium identified by electron beam tomography to serum lipoprotein levels and implications for treatment. Am J Cardiol. 2001 Feb 15;87(4):406-12.

Anand DV, Lim E, Raval U, Lipkin D, Lahiri A. Prevalence of silent myocardial ischemia in asymptomatic individuals with subclinical atherosclerosis detected by electron beam tomography. J Nucl Cardiol. 2004 Jul-Aug;11(4):450-7.

Rumberger JA. Cost effectiveness of coronary calcification scanning using electron beam tomography in intermediate and high risk asymptomatic individuals. J Cardiovasc Risk. 2000 Apr;7(2):113-9. Review.

Coylewright M, Blumenthal RS, Post W. Placing COURAGE in context: review of the recent literature on managing stable coronary artery disease. Mayo Clin Proc. 2008 Jul;83(7):799-805.

Grundy SM. Coronary calcium as a risk factor: role in global risk assessment. J Am Coll Cardiol. 2001 May;37(6):1512-5. Review.

Hoff JA, Daviglus ML, Chomka EV, Krainik AJ, Sevrukov A, Kondos GT. Conventional coronary artery disease risk factors and coronary artery calcium detected by electron beam tomography in 30,908 healthy individuals. Ann Epidemiol. 2003 Mar;13(3):163-9.

Budoff MJ, Gul KM. Expert review on coronary calcium. Vasc Health Risk Manag. 2008;4(2):315-24.