Shifting to Pattern ' A ' for Longevity

Increasing Saturated Fat Intake Shifts to Pattern 'A'

Krauss has shown that increasing saturated fat intake and reducing carbohydrates lowers sd-LDL and shifts to Pattern 'A' (Influence of dietary carbohydrate and fat on LDL and HDL particle distributions. Siri PW, Krauss RM. Curr Atheroscler Rep. 2005 Nov;7(6):455-9.).

Undeniably Pattern A with a dominance of Large-LDL is desired for regression, longevity and cancer protection. Again, Krauss has spelled out in seminal articles that Large-LDL-Particles are not associated independently with atherosclerosis (JAMA rebuttal: Is the size of low-density lipoprotein particles related to the risk of coronary heart disease? Krauss RM. JAMA. 2002 Feb 13;287(6):712-3.; Ion Mobility Analysis of Lipoprotein Subfractions Identifies Three Independent Axes of Cardiovascular Risk. Krauss RM et al. ATVB. 2009 Sep 3.)




What is independently associated with CAD???

(1) Small Dense LDL, particularly the 'death band' LDL-IVb produced by dietary deficiencies of saturated fatty acid and/or ketones and/or excessive dietary carb loads

(2) Low HDL-2 (ditto)


No individual at TYP with subclinical or post-CAD event fails to demonstrate the above two characteristics. Without a doubt, these 2 metabolic parameters describes all atherosclerotic processes that lead to obstructive disease, clinical events, morbidity and mortality. Some individuals with 2-4 stents or bypasses, exhibit zero HDL-2 at the start of our program and 100% sd-LDL.

No joke.

Of course it immediately changes on the TrackYourPlaque program (faster when it is STATIN-LESS).



Krauss and Pattern 'A'
Of all the literature I have reviewed on Pattern A, Krauss has performed nearly all the seminal, landmark research. He has explored a variety of manners to shift to Pattern 'A' (sans statins, sans niacin).

Lots of Fat. 46% minimum.

Saturated Fat. 18% saturated minimum.

Carb restriction. See first diagram, at top.



Can we obtain zero% Pattern B:100% Pattern A in individuals? Minimal and near-zero 'death bands' of LDL-IVb? It sure would be nice.

When the line breaks 'zero' fat intake is ~ 65% and carb intake 20%. Is 20% still too high for some inviduals? I believe so.

I consume about 20-50 grams daily when I am insulin resistant (around my mense when my body thinks I'm getting ready for a baby; during the year of synthetic hormone h*ll). How do I know when carbs are excessive for me (eg, eating a whole dark chocolate candy carb = 30-40grams)?? I ck my blood glucose on a meter 10-20min afterwards (because I peak fast on high GI foods) and it may be > 110-120 g/dl. After rice/sushi, the BG may peak to 180 g/dl for like... 5 min. I can tell the damaging high glucoses are followed by damaging high insulin (and a reduction in adiponectin, the hormone related to body fat loss) because I may have heart palpitations, rapid/racing heart rate, a little anxious (?? or is it the I.V. Caffeine), not relaxed, (HUNGER for 24-72hrs afterwards) and basically feel like... CR*P.

I weigh about 125 lbs now and consume about 1-2 g per kilo of protein daily (somedays more with more exercise, somedays less with IF) which is approx 45-56 grams daily (= approx 2 chicken breasts) which makes up about ~15% of energy (or more).

If I estimate I obtain about 1000-1600 cal/day and calculate 20% would be allocated to carbs as an example, then that would be equivalent to ~50-80 grams of carbs daily. WOW. That is a lot more than my current consumption and my experience is that I would gain weight on that dietary intake (esp during insulin resistant periods), even if I consumed 65% fat and 15% protein (or even 50% fat and 30% protein).

Perhaps if carbs were restricted further, more individuals would have achieved Pattern 'A'?

10% Carbs?

5% Carbs?

See below, same graph, I've extrapolated into Pattern A territory by extending the Fat%/Carb% x-axis.



Saturated Fat Intake Lowers LDL-IVa+b

In a trial in n=103 men, low-fat versus high-fat diet were compared. Krauss yet demonstrates again that increased dietary fat and specifically the saturated fat portion are statistically related with reducing small dense LDLs LDL-III and LDL-IV and shifting lipoproteins toward Pattern A. (Change in dietary saturated fat intake is correlated with change in mass of large low-density-lipoprotein particles in men. Dreon DM, Krauss RM et al. Am J Clin Nutr. 1998 May;67(5):828-36.)

In summary, the present study showed that changes in dietary saturated fat are associated with changes in LDL subclasses in healthy men. An increase in saturated fat, and in particular, myristic acid, was associated with increases in larger LDL particles (and decreases in smaller LDL particles). LDL particle diameter and peak flotation rate were also positively associated with saturated fat, indicating shifts in LDL-particle distribution toward larger, cholesterol-enriched LDL. This study also showed that increases in dietary saturated fat were associated with decreases in HL activity. This finding, together with our previous cross-sectional analyses that revealed significant inverse relations of HL activity with LDL peak flotation rate (15), suggests an inverse association of HL activity with concentrations of buoyant LDL particles.

Diet Compositions

Low fat diet:
--24% of energy as fat (6% saturated, 12% monounsaturated, and 4% polyunsaturated)
--59% as carbohydrate, with equal amounts of simple and complex
carbohydrates.

High fat diet:
--46% of energy as fat (18% saturated, 13% monounsaturated, and 12% polyunsaturated)
--39% as carbohydrate. TOO HIGH!!

The main fat as described by the authors was "Palmitic acid (16:0) ... the primary dietary saturated fatty acid in both diets, followed bystearic (18:0) and myristic (14:0) acids, which are representative of the major saturated fatty acids in most human diets (3)." The carbohydrates would be considered high and associated with a higher incidence of Pattern B according to the first Krauss trial described earlier in the post. Nonetheless the results were quite fascinating. Only saturated fatty acids corresponded statistically with improvements in shifting to Pattern A, increased LDL diameter size and to reductions in small dense LDL (both LDL-III and LDL-IV). Please see below stats.




Reduction of LDL-IV by 39% With Increased Saturated Fat
The amount of dietary saturated fat tripled up from 6% to 18% of total energy. This change statistically correlated to reductions in LDL-IV by a total of 39%. The 'death band' which would have corresponded to LDL-IVb was not determined in this trial but definitely some proportion was significantly decreased. Between LDL-IVa and LDL-IVb, we do not know the precise proportional changes.



3X Increase in Saturated Fat Increased HDL-2 by 50%

Recall in the HATS regression trial (NEJM, 2001) where 90% reduction in death and events were observed, the niacin arm was associated with a 70% shift to large buoyant LDL and HDL-2 increase of 60%. With an increase in saturated fats of from 6% to 18% daily, the HDL-2 subfraction increased 50%.


'Death Band': Percent-LDL-IV Changed from 6.0% to Only 3.4%
Examing the relative amount of the 'death band' LDL-IV, Percent of LDL-IV changed from 6.0% in the low-fat group to only 3.4% in the high-fat group. Recall in the previous post Krauss observed that regression (where stenosis is > 30%) was highly associated with quartiles of LDL-IVb less than 2.5%.




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

(1) Increased total HDL-Cholesterol 18% and the improvements were in vast increases of the regression subspecies HDL-2 of 50%

(2) Reduced Triglyercides by 30%

(3) Increased total LDL-Cholesterol by 13% which is a good indicator that large buoyant LDL are starting to prevail because this change is accompanied by increases in HDL-Cholesterol. An increase in LDL-C is a good thing and associated with regression when the HDL-C is increasing concomitantly. This is not the case in Metabolic Syndrome. Increasing LDL-C in MetSyn are ONLY associated with higher small dense LDL-C which translates to Pattern B (for extremely BBBBAAADD).

(4) Decreased small dense LDL (LDL-III) from 27% on the low fat diet to 18% on high saturated fat. Not bad. The TYP is goal is < 10-30%. For our TYP members who restrict dietary carbohydrates (eg, grains, fruit/berries, etc) and add significant amounts of saturated fat, in 4-6wks they observe basically eradication of small dense LDL to ZERO. These members may have struggled with dense LDL of even 70-80% for years.

(5) Decrease in the deadliest, smallest LDL (LDL-IV) from 6.0% to 3.4% with high saturated fat intakes.




Longevity: Small Dense LDL and HDL-2
We learn so many lessons from the regression trials with niacin, vitamin D (Dr. Davis publication, CKD hemodialysis patients HERE) and the omega-3 trials. The longevity observations in centenarians fascinate me to no end. I enjoy reading them since they conceptualize the same principal components that Krauss, Superko, Callister, Davis and other forward-thinking, visionary cardiologists and physicians advocate for heart health:
(a) achieve low small dense LDL
(b) bank on high HDL-2

The centenarian study that we reviewed earlier HERE is worth another mention at this time (Unique lipoprotein phenotype and genotype associated with exceptional longevity. Barzilai N et al. JAMA. 2003 Oct 15;290(15):2030-40.).




Centenarians Exhibit Pattern 'A+' With sd-LDL << 10%

The Ashkenazi Jewish study compared centenarians, their offspring and population controls (both short-living Ashkenzi Jewish as well as Framingham). Corollaries exist between the long-living (probrand) centenarians and the CAD regression pattern in the trials that we have reviewed here. The long-living typically have resistance against hypertension, diabetes, cancer and coronary artery disease. Uncannily, these centenarians have Pattern A and an extremely low percentage of small dense LDL subparticles, not unlike our Paleo (low carb, high fat) friends and Paleo/ TYP members who achieve all of Dr. Davis TYP goals.



Figure 1. Frequency Distribution of Lipoprotein Properties in Female Probands, Offspring, and Controls. The frequency distribution of plasma high-density lipoprotein (HDL) oncentration levels and particle sizes, and low-density lipoprotein (LDL) particle sizes in female probands, their offspring, and an Ashkenazi control population. [To convert HDL oncentration to mmol/L, multiply by 0.0259. The solid lines represent the mean and the dotted lines represent 1 SD of control.]


What strikes me is that the centenarians (probrands) exhibit generous quantities of large buoyant LDL (60-70+%), only < 10% sd-LDL, Pattern 'A' lipoproteins and an inordinate amount of large-sized HDL-2. Even with modern eating (refined processed foods), their children also similarly exhibit a prevalence of high HDL-2 and high buoyant LDLs. Like good wine, the centenarians' HDL-2 and buoyant LDL appear to have gotten better with age!



Maximize Genetic Expression
Burst your genetic ceilings and boundaries! With the appropriate diet low in carbohydrates, wheat/gluten-free, containing sufficient saturated fatty acids, we can achieve similar longevity-associated lipoproteins. Many are doing it and it's not that hard. Clinical studies support the validity of the benefits of high-saturated fat diets for achieving regression, shifting to Pattern ' A ', controlling small dense LDL, and raising HDL-2.

'Death Band' = sdLDL on Lipoprotein Subfractionation

Diagrams #1, 2

Modified and Courtesy of some FDA.gov website

Subfractionation of Lipoproteins 101

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

Basically, the denser the particle, the faster and more mobile 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 = Large LDL-C Predominance

Pattern 'A' is good (all nice large buoyant fluffy particles). LDL particles are not perfectly spherical; they can appear even flat like red blood cells. Large LDL however fit 'perfectly' into LDL receptors on cholesterol-requiring tissues like our sex organs (which produce testosterone and estrogen from cholesterol) and the all-important adrenal glands, tiny triangularlike-walnuts sitting on the kidneys which regulate our blood pressure, tension in the endothelium/smooth vasculature, and minute-to-minute brain functions by issuing cortisol, another cholesterol-based derivative that is mandatory for life.

Pattern 'A' is desirable and highly asscociated with regressive patterns for calcification in the vasculature whether the plaque build up (scar-tissue) is in the renal (kidney) arteries, carotid (neck) arteries, peripheral (legs), coronary (heart), or inner lining of the entire arterial tree (hypertension).

Hypertension? This is just extensive calcium deposition occurring at the smooth muscle, endothelium and vessel wall fibroblast level in the vascular tree. HERE and HERE discuss the role of oxLDL on increasing MMP-9 and arterial stiffening.



What is easier to regress? Dr. D and I agree that the carotids are the easiest (plaque there comes and goes based on full moons or voodoo medicine... no joke, it's so easy). Since the brain is the most important organ... (again, yes, debatable...arguably it might be the... liver...*haa*) the carotids provide blood flow to this GINORMOUS organ. Consequently these arteries are 7-8mm, titanic-sized bilateral highways.

Distribution of blood flow at rest and during flight-fight-fright correlates well with artery lumen sizes IMHO (courtesy of a Rutgers anatomy phys student w/concise pictures HERE).

At rest:a. Brain: 13% (7-8mm)b. Heart 4% (2mm distal LAD; 3-4mm LAD; 4-5mm RCA) (Brown BG et al. Circulation 1992;86;232-246.)
c. Kidney: 20% (5-6mm)d. Abdominal organs (incl liver): 24% (5-6mm)

During exercise:
a. Skin, muscles and heart increase
b. Remaining tissues either remain same or decrease

Renal is the hardest. I think Dr. T at Nephropal will agree. These are relatively narrow yet receive the greatest majority of tissue perfusion, and have less possibility of collateral growths/angiogenesis than other arterial vasculature. Renal stents notoriously ALL 100% fail. Bypasses are currently unconceivable. Peripheral is not good either (but again, also reversible).

No matter where the plaque is, however, it is ALL potentially reversible.

A L L .

A good 'indicator' of regression is blood pressure normalization < 110/70. Everyone at TYP on the program who maximizes expression of Pattern 'A' with sdLDL as low as possible and HDL2b as high as possible (200-400% increases) notice dramatic reductions in blood pressure. Of course !

In the HATS trial, again where events were prevented by 90% and angiographic regression observed, reductions in blood pressure occurred. We see this in ALL of our successful TYP members as well. Pattern A for A+++ (blood pressure, Large-LDL, HDL2b and sexy hot elastic unstiffened unobstructed vasculature).




Pattern B = Small Dense LDL-C Predominance

Pattern 'B' is clearly BAD.

Dense small stupid cr*ppy stuff.

Small dense LDL quickly and rapidly become oxidized LDL (OxLDL) which do NOT fit into traditional LDL Receptors. They instead are attracted to many non-LDL receptor surfaces and tissues (Galeano NF et al, J Lipid Res. 1998;39:1263-1273). These sites include the endothelium to initiate 'stiffened'/calcified arteries (eg, hypertension), atherosclerosis (plaque burden: CAD ED CVD PVD RAS) or liver to initiate NASH/fatty liver or even our pancreatic islet cells that are highly related to hastening T2DM pathogenesis (Cnop M et al. Endocrinology. 2002 Sep;143(9):3449-53.).

Yes.

sdLDL is sad news. Especially if one has 50 to 100% sdLDL. Yeah, that is kinda f*cked up and highly associated with prevention of regression. This explains the sad results and outcomes from all statin trials compared with the niacin trials (HATS, FATS, CDP, etc). Recall: Cardio Controversies and Dr. Superko. Pattern ' B ' perpetrated by statins also explains the lack of regression in nearly all EBCT and MDCT clinical trials. Ten out of about 12 to 13 trials that I have reviewed for statins and CT coronary calcifications show no difference between statin and placebo arms.... Or.... even worsening (one lipitor study). Why?
Statins s*ck. (And zetia is worse, eg SEAS, ENHANCE trials... more %-sdLDL... more HDL-3... more cancer... more plaque progression)



Small dense LDL and OxLDL penetrate deeply through several tissue layers.

Tissues involved: any tissue. You name it.






CAD is Autoimmune
OxLDL attract auto-antibodies.

Auto-antibodies are like the 'cleaners' (you know... in Mob terms). Auto-antibodies can go CRAZY.

O-U-T-T-A . . . C-O-N-T-R-O-L . . . (Baby Bash Feat. PITBULL OOOhh... Yeah).

Yes, CAD is an autoimmune process not unlike Hashimoto's/thyroid-insufficiency or NASH/calcified-liver or T1DM or T2DM/pancreatic-insufficiency or Addison's/adrenal-insufficiency







What Promotes Pattern ' B ' ?

Guess what?

Silent and overt celiac disease (gluten intolerances: wheat barley rye) and other food allergies (A1-casein, egg whites, nightshades, nuts, etc)

Excessive dietary carbs (grains, potatoes, peas, corn and fruit). Candy/sweets. Artificial sweetners. Lack of omega-3 fats. Excessive omega-6 refined veggie oxidized refined fats not meant for human or animal consumption.

Lack of s a t u r a t e d fatty acids.

Lack of antioxidants.

Lack of hormones (thyroid, estrogen, testosterone, adiponectin, vitamin D, melatonin, etc).

Synthetic vitamins, hormones or drugs (Lurotin/fake-beta-carotene (used in the HATS AO-arm; ATBC: 7% higher death rate; CARET: 28% higher cancer+mortality); levonorgestrel, Provera/medroxy-progesterone, Premarin/horsey-hormones, oral contraceptives).

Zetia.

S-T-A-T-I-N-S . . . and thus statins +/- Zetia s*ck...





Role of Large LDL in Pattern 'A'

LDL-5 (on VAP) and LDL-6 (on VAPII) are the densest smallest LDL subspecies (devoid of cholesterol content). See below diagram #2. These subparticles oxidize to OxLDL in the metabolic pathway of lipoproteins quickly in the bloodstream, studies show. LDL1 and LDL2 are the Large LDL subspecies which are rich in cholesterol content and extremely resistant to oxidation. Additionally, these magnificently-sized particles are the carriers of antioxidants which provide protection from oxidation, ROS and free radicals, to peripheral tissues after digestion from food. Large LDL transport the great majority of our important fat-soluble antioxidants: coenzyme Q10 (idebenone, etc), carotenoids, vitamin E (tocopherols, tocotrienols), vitamin K1 K2 (menaquinones 4 - 9 chain lengths), et cetera.








Conversion of Pattern 'B' to Pattern 'A' Associated with Regression

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. In the HATS trial where 90% of cardiac death and events were COMPLETELY AVERTED after 3 yrs of niacin ultra-high-dose of 3-4 grams daily (and low low dose of weak-statin 10-40mg/d), conversion to Pattern A occurred in an astounding 70% of the treatment arm. Even niacin alone produces similar outcomes of 60-70% relative risk reduction, compared with statins 17-25%. In other words, niacin alone or in combo is 300-400% better than statins relatively speaking.

What mimics niacin? What binds 'niacin'-receptors?

Ketone bodies.

Generated from intermittent fasting, physical prolonged exercise (low intensity) or... a ketotic diet, eg high protein or high fat and no carbs.





Large LDL Not Associated with Heart Disease

Only 2 studies show Large LDL are remotely associated with heart disease (that I can find) and definitive CAD progression. In each case, the presence of the 'death band', a high peak of LDL-IVb and LDL-IIIa+b (sdLDLs) and an absence of the 'regression peak' HDL-2 occurred (Campos H, Krauss RM, et al. 1995 ATVB. 15;1043-1048.; Campos H et al. 2001 JAMA 286:1468-1474). In 1995, only 3 LDL subspecies were determined. The more infinitely denser, heaveir sub-species -- LDL-IIIb, LDL-IVa, LDL-IVb -- hadn't yet been 'discovered'. 'LDL-III' from Campos/Krauss' article is actually LDL-IIIa.




The 'Death Band' = sdLDL Highly Associated With CAD

See below. LDL-III is considered dense particles. Dense like bullets. In the below graph the 'densest' of the LDL-III is circled. This is not a rock band... I refer to it as the 'death band' since it is associated with coronary events. Peaks corresponding the heaviest, smallest of the LDL-III particles (far left 2 lines at ~1.4%; red) in the CAD group was significantly higher than the control ones (1 line at ~0.5%; pink). If I do some retardo-calculus, then the 'circled' tiny death-band peak is ~2.8% versus ~0.5%. 5.6 times greater in area under the curve.

So, this 'circled' sd-LDL subfraction contained 560% more of the smallest densest 'death-band' particles in the CAD group than compared to control (no CAD).

HDL2 in the CAD group was statistically lower at 10 mg/dl (out of 38 mg/dl, 26%) whereas the control was 50% higher, 15 mg/dl (out of 42 mg/dl, 36%).

Controls (no CAD)... had HDL-2 fifty-percent HIGHER. (Recall, HDL2 increased 60% in the HATS trial in the niacin arm).

In a 'response' to the second Campos study, Krauss wrote an articulate rebuttal to Campos et al discussing the relevance of high sdLDL-Particles and low HDL2-Particles in CAD progression, not Large-LDL-Particles. HERE (sorry, not free yet).





The Denser, The More D A N G E R O U S

How dense is Campos?? How deep do LDL-centric-zealot-statinator-idiots dig?





The Densest Bullet of Them All: LDL-IVb

The bands I circled above were dense. Even denser LDL subparticles exist. These smaller, more atherogenic particles contain even less antioxidants, less transportable-cholesterol and are tremendously prone to oxidation. On NMR these are identified as subclass LDL-IVb and on VAP LDL-5 (VAP-II, LDL-6).

Eight years later after these newer LDL subparticles were identified, Superko and Krauss demonstrated that the mere presence of the SMALLEST, DENSEST LDL sub-species (IV-b) was MOST associated with fastest plaque progression (Superko, Krauss et al. ATVB 2003 Feb 1;23(2):314-21.) Japanese researchers have arrived at the same conclusions as well (Koba S et al. J Atheroscl Thromb 2008,15(5):250-260. Free PDF HERE)

As to be expected, Superko and Krauss, also showed that reduction of the SMALLEST, DENSEST LDL sub-species (IV-b) was highly associated with fastest plaque regression. Therefore, when sdLDL were controlled and reduced to the point where the smallest denset LDL (IVb) were less than 2.5%, a decrease in plaque burden and regression of atherosclerosis was observed. However this observation did not hold true for those with less extensive angiographic plaques where stenosis < 30% (?soft plaque still progressing? yet lower appears better). Diagram from Superko and Krauss 2003.




What Ultimately Lowers 'Death Bands' LDL-IVb The Best?

Saturated fatty acids (all of them: short-chain, medium-chain, long-chain) (Noakes M et al. Nutr Metab Cardiovasc Dis. 2009 Aug 17.; Krauss RM et al. Curr Atheroscler Rep. 2005 Nov;7(6):455-9.; Noakes M et al. Am J Clin Nutr. 2009 Jul;90(1):23-32.)

High-protein, Low Carb Diets (Clifton P, Krauss RM, et al. Am J Clin Nutr. 2008 May;87(5):1571S-1575S.)

Carb restriction (Volek JS et al. J Nutr. 2009 Sep;139(9):1667-76.)

Ketotic Diets (Clifton P et al. Obes Rev. 2006 Feb;7(1):49-58.)

Paleo Diets (Frasetto LA et al. Eur J Clin Nutr. 2009 Aug;63(8):947-55. Hays JH, Editorial 2004. )

Niacin (ultra high dose) (HATS trial, NEJM 2001)

Omega-3 PUFAs: DHA EPA ALA (Schaefer EJ et al. Atherosclerosis. 2008 Mar;197(1):12-24.; Mozzafarian D. J Cardiovasc Med (Hagerstown). 2007 Sep;8 Suppl 1:S23-6.)






What Lowers Blood Pressures Concomitantly Whilst Annihilating 'Death Bands' and Raising HDL2b?

ALL THE ABOVE (see above citations)

(Except for Niacin, A-L-L the above are additionally associated with weight control, body fat loss, improvement in Metabolic Syndrome, T1DM, T2DM, insulin control, hyperinsulinemia)





What Does Not:
--olive oil (monounsaturated fatty acid)
--omega-6 veg/seed/bean oils
--mercury, cadium, heavy metal toxicity; selenium-deficiency (Houston MC. Altern Ther Health Med. 2007 Mar-Apr;13(2):S128-33.)
--low fat/high carb AHA diet
--low fat diets
--low cholesterol diets
--low saturated fat diets
--statins
--zetia

Palmitic Acid+ CARBS = Mouse Skeletal Muscle IR

Peter at Hyperlipid and Stephan at Whole Health have dispelled yet again myths regarding the indictment of the 16:0 long-chained saturated fatty acid Palmitic Acid as the prime instigator of insulin resistance (IR). Researchers are always wrong -- it's... HIGH CARBS PLUS Palmitic acid.

Their brilliant posts discuss below:
--Sportzaid (FRUCTOSE) + Palmitate = IR RETARDNESS
--High Carb Lab Chow + Palmitate = IR in the brain

Yes. Such inferences applied to low carbers (LCers) is pure ridiculousness. Non-applicable.

Low/no carb + Palmitic Acid = GOOD THING. All the low-carb/high saturated fat (palmitic acid) and ketosis trials by Hays JH, Volek JS, and Krauss RM have shown reductions in blood insulin, blood glucoses (BG) and peripheral tissue insulin resistance (IR). Directly contrary to the high carb animal or human studies.



Palmitic Acid (16:0 SFA)

Palmitic acid has a special evolutionary, adaptive role in mammalian metabolism. Stephan showed that it likely 'fills in' when blood glucose starts to decline.

G E N I U S ! !

Our mammalian *sses are full of palmitic acid. We release palmitic acid into our blood streams during b*tt-burning long low-intensity cardio, physical exercise, ketosis, starvation, and intermittent fasting.

What is the most important organ in the body? (Some males may argue otherwise. Hey, get your mind outta the gutter for a second -- and I apologize gentlereader if the last post had anything to do with it.) The organ of the most vital importance is understandably controversial but in reading Stephan's post and given that he is a neurobiologist, let's say for a moment... it's the B R A I N. The brain like other vital organs (nerves, retina, kidneys) have unregulated glucose access because glucose is the valued currency of energy. Few GLUT transporters (or none) exist in these tissues. Whatever is in the bloodstream, is in the tissue. These also are the first organs to be damaged by high, unremitting, toxic blood glucose concentrations. We tell individuals with diabetes on hypoglycemic medications, if the BG goes below 60 g/dl, they are in a lot of trouble. Consciousness, rational thoughts, driving (yes, DUIs can be cited), physical movements SHUT DOWN. Comas occur at below BG 40 g/dl, including fatal ones. Of course this rarely happens to those not taking pharmaceuticals because the liver and other tissues have the ability to make ANYTHING into glucose. Protein, fatty acids, glycogen via gluconeogenesis turns into blood glucose for the brain and other vital tissues (eyes, kidneys/adrenals, peripheral/central nervous system). So after a good 8-hour sleep, your blood glucose continues churning on at 70s-83 g/dl (non-diabetic, normal range) when the sun glows on your happy shining face every morning.

When protein, carbs and fat (eg, FOOD) become scarce, by default, ketones become the currency of brain-energy. Our brains are hard-wired to run well on two different types of fuel depending on the energy 'environment'. Ketones can be generated from ANYTHING with prefential production from fatty acids. Proteins from muscles are protected as long as possible. Muscle-wasting was NOT an evolutionary advantage for survival. This is why with intermittent fasting, I rarely notice any degradation of my hard-earned HIIT, Crossfit and jogging muscles! Atrophy occurs when I sit on my b*tt all day.




IR at the Skeletal Muscle Level

From the skeletal muscle point of view, a bunch of the same inaccurate inferences have been made by researchers de Wilde et al (Physiol Genomics. 2008 Feb 19;32(3):360-9. Free PDF HERE). They looked at the induction of genes and glucose/insulin levels in mice on high-HIGH-carb, 10%-Palmitate v. HIGH-carb, 45%-Palmitate diets in skeletal muscle. Mice were sacrificed at Day 3 v. Day 28 and their quadricep genetic and fatty acid profiles were compared (quads are a mixture of Type 1 Slow and predominant Type II Fast twitch muscles). At the skeletal muscle level, with both diets, both glucose and insulin increased over time. The researchers have concluded that insulin resistance has occurred to a higher extent however in the high-fat group. This makes sense if evolution-wise, little carbs existed and Paleo man intermittently hunted and ate gamey-meat. In this experiment, high carbs enter into the picture and sets off another metabolic pathway. Insulin (?and IR) appears to have spiked exponentially in the high-fat +carb group; blood glucose actually declined by Day 28 in this group.









Bizarre Love Triangle

In nature, paleotologically speaking, 3 things never rarely occurred together at one time as they do in research trials such as the ones that Stephan, Peter or the one highlighted here.

These are indeed BIZARRO COMBINATIONS:
--high carb + high SFA ('large kill') + no omega-3 DHA
--high carb + low SFA ('small kill')+ no omega-3 DHA
--high carb + no SFA (no kill) + no omega-3 DHA

Palmitic acid is always consumed with DHA if one is eating grassfed meat/fowl or wild seafood. Or if I ate these study mice. :) J/k. And . . . in a 'paleo' environment... with scarce dietary carbohydrates.

So paleolithically speaking, high carb was not an environmental norm and therefore no genetic norm was ever established. Studies show human metabolic machinery is mainly set up for intermittent/daily consumption of fats and proteins (Huss, Kelly. Circ Res. 2004). However... the machinery for carbs does exist and for survival, these ancestral pathways seem to override and take precedence above all else. The ability to store fat for the purpose of reproduction, growth, and surviving harsh winters may have been key in determining that genetic material would be passed along in certain geographic niches. Anabolism of adipose is the metabolic pathway chosen when environmental 'carbohydrates' became readily available, eg fruit harvest at the end of summer (+/- big game 'kills'). Ingested carbs become post-prandial triglycerides, then small LDL and oxLDL, then into adipose eventually. Dr. T discusses a role for small LDL in evolutionary terms. It makes sense. Some research suggests a role for small LDL in delivering triglyerides to non-LDL-receptor sites perhaps for the same reason ultimately, fat storage for winter, a winter that never comes.

You can see inherently in mice (despite eating lab chow), in the muscle fat breakdown of the experimental mice -- DHA is about 10% of the total fatty acids in the quad muscles. Palmitic about 25-30%. DHA is an omega-3 PUFA associated with longevity and reduced cancer and coronary artery disease. Consuming more saturated fat and less carbohydrates, these mice had a noticable increase in DHA content and lower content of toxic omega-6 in their muscle-meat in the high-palmitate group (see below).



High-carb scenarios did not exist as humans evolved over 200,000 years.
-- Fruit didn't grow on acres of groves. Honey and ripe fruit were available for only a very short weeks at the end of summer.
-- Tubers, potatoes and yams didn't grow in 50 lb bushels at Costco
-- Grains and legumes were pre-ag


High carb actually has little bearing for those who are LC and semi-Paleo. After a 'kill', Paleo man was glycogen-depleted and running on ketones (if not already earlier). His BGs had already flat-lined at 70-80s g/dl for who knows how many days the tribe had been tracking and following herds of game. Gluconeogenesis and ketotic processes were in full force to keep Slow twitch Type I fibers on the go (walking muscles Gastronemius/ Gluts, Heart, lower back Trapezius, Psoas ('filet mignon' like other dark meats). Below table courtesy of Drobson. Type I Slow Twitch muscles require less glycogen (stored carbohydrates) than Fast Twitch. Conversion to Type I Slow Twitch musculature makes some evolutionary sense to prepare for certain physical tasks and energy demands when one considers the nature of how food was scarce and how it was intermittently obtained (hunting v. foraging v. fishing).







Insulin Resistance Increases with HIGH CARBS

Naturally IR increases with HIGHER Palmitic Acid/HIGH-carb digestion MORE than with the high-HIGH-carb, lower Palmitic Acid mouse diet. The mouse metabolic system was utterly CONFUSED -- two energetic systems were switched on concurrently:
(1) HIGH CARB/ Metabolic Syndrome (MetSyn), related to fat storage
(2) HIGH Palmitic Acid/Ketotic Efficiency, related to fat burning


Dr. T talks about MetSyn as 'evolutionary suicide' in some recent wonderful, concise and explicit posts (Part I and Part II). PPAR-gamma, the nuclear steroid involved with carbohydrate metabolism and energy balance, are normally whacked out and completely degraded in those with obesity and diabetes. In these mice, on the other hand, both groups exhibit expression of PPAR-gamma. This is not expected. Both 10% and 45% saturated Palmitate did it. (that's because Palmitate like omega-3 EPA DHA are agonists and activate the PPARs gamma and delta).

In fact, PPAR-gamma is turned ON in similar fashions with diabetic drugs (Avandia Actos which are PPAR-agonists), life-extending Resveratrol, ketosis, niacin and omega-3 PUFAs (fish oil EPA DHA). How PPAR-gamma is related are in prior animal pharm posts HERE.













Authors Conclusions Are Correct Except...

The authors are in fact correct -- insulin resistance occurs as Stephan and Peter agree as well and it is a good thing under certain circumstances. Low carb. Under high carb circumstances, it appears that MetSyn consequences are unavoidable and perhaps even hastened by Palmitic acid (perhaps via two ancient metabolic pathways both being induced simultaneously). When food sources are low and we need to continue walking/moving/hunting/foraging/carrying carcasses etc, we want to turn on the ox phos in the Type I slow twitch muscles as these authors discovered so that we can obtain more ATP which requires phosphorylation. We want morphogenesis -- change more muscles to Type 1 slow twitch as we are going to keep physically exerting ourselves after consuming a nice tasty high fat/protein-containing meal or in preparation for the next physical demand. If carbs are very scarce, we want some insulin resistance to continue to shunt any available glucose to the brain and eyes and nerve endings to the ears to see/listen for predators. We want decreased protein and carb catabolism (save all the stores in the muscles). We want increased fat catabolism.

Repeat... increased fatty acid (FA) catabolism. Easy release of the palmitate OFF of our cheeky b*tts.

They are CORRECT in the genetic analysis... Except... The authors surmise (see above Figure 3) that the entry of saturated fats like palmitate into the cellular membranes is associated with poor benefits including reduction in detox and immune function. How did they get that?!? They also extrapolated to the membranes of mitochondria. I think that these researchers have failed to take into account that again humans never consumed palmitate alone, always with omega-3 PUFAs DHA and EPA, and paleolithically always low carb. Palmitate and n-3 PUFAs balance the fatty acids and cholesterol of the cell membranes, providing structure and rigidity and important hormone signalling (see Hulbert below). The authors appear to also have forgotten or failed to reconcile the evidence for Palmitic acid in IMPROVING immune function (see last 2 citations below). Additionally the authors fail to recognize the role of high dietary carbohydrates, its downstream increase of LA omega-6 content in muscles, high dietary omega-6 intake or the role of dietary omega-3 PUFA deficiencies in instigating Metabolic Syndrome.

• The fructose-fed rat: a review on the mechanisms of fructose-induced insulin resistance and hypertension.
  Tran LT, Yuen VG, McNeill JH.
  Mol Cell Biochem. 2009 Jun 18.
• High fructose consumption combined with low dietary magnesium intake may increase the incidence of the metabolic syndrome by inducing inflammation.
  Rayssiguier Y, Gueux E, Nowacki W, Rock E, Mazur A.
  Magnes Res. 2006 Dec;19(4):237-43.
• Temporal changes in dietary fats: role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity.
  Ailhaud G, Massiera F, Weill P, Legrand P, Alessandri JM, Guesnet P.
  Prog Lipid Res. 2006 May;45(3):203-36.
• Omega-3 and omega-6 fatty acids in the insulin resistance syndrome. Lipid and lipoprotein metabolism and atherosclerosis. Rustan AC, Nenseter MS, Drevon CA. Ann N Y Acad Sci. 1997 Sep 20;827:310-26.
• An emerging risk factor for obesity: does disequilibrium of polyunsaturated fatty acid metabolism contribute to excessive adipose tissue development?
  Ailhaud G, Guesnet P, Cunnane SC.
  Br J Nutr. 2008 Sep;100(3):461-70.
• Dietary fats and membrane function: implications for metabolism and disease.
  Hulbert AJ, Turner N, Storlien LH, Else PL.
  Biol Rev Camb Philos Soc. 2005 Feb;80(1):155-69.
• Membrane fatty acids as pacemakers of animal metabolism.
  Hulbert AJ.
  Lipids. 2007 Sep;42(9):811-9.
• Effects [beneficial] of palm oil on cardiovascular risk.
  Chong YH, Ng TK.
  Med J Malaysia. 1991 Mar;46(1):41-50.
• Dietary palmitic acid influences LDL-mediated lymphocyte proliferation differently to other mono- and polyunsaturated fatty acids in rats.
  Tinahones FJ, Gómez-Zumaquero JM, Monzón A, Rojo-Martínez G, Pareja A, Morcillo S, Cardona F, Olveira G, Soriguer F.
  Diabetes Nutr Metab. 2004 Oct;17(5):250-8.
• Dietary palmitic acid modulates intestinal re-growth after massive small bowel resection in a rat.
  Sukhotnik I, Hayari L, Bashenko Y, Chemodanov E, Mogilner J, Shamir R, Bar Yosef F, Shaoul R, Coran AG.
  Pediatr Surg Int. 2008 Dec;24(12):1313-21.

Hot Paleo Cave Girls

Thanks Dr. T my NephroPal.

Cavegirl company... is good company.






Viva la hunter-gatherers and FUR. Raquel Welch . . . One Million Years B.C. and neolithically... unforgettable.





My personal faves are historically captured on celluoid... female hunter-gatherers who are oh so talented and good with their weapons and swords....




Crossfit babe?

Maybe...







Ursula Andress, quintessional #1 Bond Girl, catwoman, and H-G babe. (she's Swiss -- they're pretty much as Paleo as Europeans eat, drink, handstand, hike, live, get sunshine). WOW. EXCELLENT handstand... any Crossfitter would be impressed. Still working on mine...


This blogger wonders where are all the hawwwt Paleo cavewomen?


They are at . . . C R O S S F I T .

DCF rules

Xfit Princess Melissa Byer's Health/F*ckoff FOOD SCALE (a must-read)

Hard Exercises: Pistols

From ZenPharoah
Demo of the Single-Leg Squats/Pistol
On an inverted Bosu... with dumbbells... (don't get dizzy with that lame camera)
Instability + Multiple Joints + Weights = Explosive Power + HOTNESS
http://www.youtube.com/watch?v=R-N-lBbTtYw

If I tried this, I'd get explosive knees...





Working on a couple of things this year...Gotta a feeling...!
--basic pistols
--handstands
--kipping (can do a 100 w/bands but that's bunk, need to do REAL ones)



Courtesy of sexy Steve Maxwell -- check out his new updated Strength and Conditioning coaching site! This gal is STRONG. What a trooper... My max is 4 pistols each side right now (without any pre-exhaustion bridge work). At our Crossfit gymnastics workshop I learned how to do handstands on the rings -- cool deal and very fun! Real handstands on the other hand are tough...

Cardio Controversies: Tale of Two Equal LDLs and 17-fold MI Risk

Figure 2. Cox proportional hazards survival curves demonstrating
time to acute MI for patients with a yearly calcium volume
score change > 15% or < 15%. Callister et al, 2004 ATVB.

TITLE: Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy.

Free PDF click HERE. Raggi P, Callister TQ, Shaw LJ. Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1272-7.

OBJECTIVE: Statins reduce cardiovascular risk and slow progression of coronary artery calcium (CAC). We investigated whether CAC progression and low-density lipoprotein (LDL) reduction have a complementary prognostic impact.

METHODS AND RESULTS: We measured the change in CAC in 495 asymptomatic subjects submitted to sequential electron-beam tomography (EBT) scanning. Statins were started after the initial EBT scan. Myocardial infarction (MI) was recorded in 41 subjects during a follow-up of 3.2+/-0.7 years. Mean LDL level did not differ between groups (118+/-25 mg/dL versus 122+/-30 mg/dL, MI versus no MI). On average, MI subjects demonstrated a CAC change of 42%+/-23% yearly; event-free subjects showed a 17%+/-25% yearly change (P=0.0001). Relative risk of having an MI in the presence of CAC progression was 17.2-fold (95% CI: 4.1 to 71.2) higher than without CAC progression (P<0.0001). In a Cox proportional hazard model, the follow-up score (p=0.034) as well as a score change >15% per year (P<0.001) were independent predictors of time to MI.

CONCLUSIONS: Progression of CAC was significantly greater in patients receiving statins who had an MI compared with event-free subjects despite similar LDL control. Continued expansion of CAC may indicate failure of some patients to benefit from statin therapy and an increased risk of having cardiovascular events.
PMID: 15059806



Cardio Controversies: Dr. Callister MD

I think Callister is cool. First he found statins were associated with regressed EBCT scores in 1998 but then confessed up when he could not replicate it in several subsequent trials. He has even postulated why. Correctly I think!

He and his colleagues have found a dilemma in current cardiology concepts, much like Dr. Superko. Despite LDL < 120 mg/dl and treatment with statins, patients progressed to an MI when the calcium volume score via EBCT increased > 15% annualized. In fact, they summarize that "the relative risk of suffering a MI in the presence of CVS progression was 17.2-fold (95% CI4.1 to 71.2) higher than that of subjects without progression (P<0.0001)."

Our goal at TYP as designated by Dr. Davis from his extensive experience and research is for EBCT annualized progression of no more than 10% to halt all risk of long-term clinical CAD events. Naturally, some EBCT regression is desirable.



Is LDL Reduction Necessary?

For reduction in hard clinical events, is LDL reduction really necessary? Actually, I don't think so... From lipid researchers like Dr. Barry Sears PhD on omega-3 and the tremendous outcomes from the secondary prevention Lyon Heart Diet trial, we know that with a significant reduction of dietary omega-6 toxic vegetable oils and sufficient increments of dietary omega-3 (ALA, EPA, DHA), clinical CAD events can be nearly halted in very high risk group of CAD individuals. Moreover, with only minor improvements in the n-6:3 balance a reduction in all-cause mortality (cancer, suicides, accidents, etc) in addition to CAD mortality and events was observed in this landmark study. Recall, these improvements were witnessed with no improvements in total HDL (final 49 mg/dl) or LDL (final 161 mg/dl). I always have to ask why save the heart and coronary vessels yet advance to experience cancer and/or suicide and depression? One of the most tragic and saddest stories that I have come across related to the low-saturated fat debacle is that of the famous Dr. Pritikin who conquered heart disease but committed suicide after silently battling leukemia. What was he missing? Could his demise have been prevented?



Low Dietary Saturated Fat

Why may low saturated fat be dangerous for the long-term? Can a 'deficiency' in dietary saturated fat be as insiduous and quietly dangerous as cancer or subclinical atherosclerosis itself?

I see a lot of HDLs in the 20s 30s 40s (or HDL2b nonexistent to single-digit). What is wrong with these kind of numbers? For one, according to clinical trials, they are highly associated with CAC progression and early events. Of course, there are cases that are exceptions to the rule... for instance if you are . . .
(1) Nissen infusing HDL-apoAI-recombinant pieces into your arm every night (JUST KIDDING... don't get any stupid ideas)
(2) an apo A1-Milano carrier
(3) allergic to kryptonite *haa*
(4) consuming boatloads of niacin or omega-3 fish oil until gills grow


Are low HDLs a sign of dietary saturated fat deficiency? Or just high carbohydate intake? Or both? Moreno JA et al showed that with a high fat diet (40%) both high saturated fat (20% SFA) and high monounsaturated fat (22% MUFA), shifted individuals equally from pattern B to A when compared to a high carbohydrate (CHO 57%) diet (J Nutr. 2004 Oct;134(10):2517-22). PDF click HERE. However, like other saturated fat studies, only the SFA diet across every apo E type (4/3, 3/3, 3/2) raised the HDL to the highest degree. Interestingly, apo-AI was increased as well to the greatest magnitude with the high saturated fat diet and was the case for every apo E genotype. Both HDL and apo-AI are atheroprotective and associated with plaque regression. See below chart (p<0.05). FYI, these diets in healthy volunteers were still very VERY high carbohydrate at (yikes) 47% and explains why a higher majority of individuals were pattern B (predominance of small dense atherogenic LDL) to begin with, particularly in the males. Certainly, I know I would immediately be clinically T2DM with this type of diet.





Callister's Other Findings: 'Incomplete Effectiveness of Statins'

Callister et al concluded that 'statin resistance' may be responsible for the lack of efficacy for these drugs in preventing hard clinical events observed in this trial. How about...

Lack of HDLs?

Excessive carbohydrates? 47+% Carbohydrates in the AHA 'low fat' diet?

Lack of dietary saturated fatty acids?

The authors concluded that "molecular mechanisms—as yet not fully understood—could help explain the incomplete effectiveness of statins therapy. The HMG-CoA reductase enzyme is a pivotal rate-limiting enzyme in the production of intracellular cholesterol and is selectively inhibited by statins. To inhibit excess synthesis of cholesterol, the HMG-CoA reductase enzyme is degraded in the presence of high levels of intracellular mevalonate and sterols. Statin resistance at the cellular level has been described to occur via 2 mechanisms: overexpression of the gene regulating secretion of the HMGCoA reductase enzyme and loss of degrading ability of the enzyme in cell cultures exposed to high concentration of lipoproteins and lovastatin in the medium."


OK... well they were close. HMGCoA reductase is certainly controlled by several factors. Ness and Chamber discuss this 'cholesterol buffering capacity' effect of HMGCoA reductase, the enzyme that produces LDL-Cholesterol (the good lbLDL and the 'bad' sdLDL) and is mechanistically inhibited by statins. Unfortunately like all interconnected systems in biological environments, feedback control ultimately inhibits or stimulates HMGCoA reductase activity based on many factors which are regulated by needs for growth, reproduction, fasting v. fat-storage, and relaxation. Click HERE.
--dietary cholesterol downregulates (yup... cheap-egg-yolks vs. Crestor; yolks WIN)
--hyperinsulinemia turns it on (poor glycemic diabetic control, high-carbs-low-fat-idiocy, again)
--hypothyroidism turns on
--peri- and menopause (low estrogen states -- or like those induced by $*%&@# contraceptives and $*%&^! progestins)
--high cortisol (mental stress, physical stress)
--lack of bile salts (taurine deficiency)




Factors NOT Affected by Statins: Lp(a), IDL, Small LDL, Microbes

Callister and the other authors are brilliant! In addition, they concluded: "Because we did not measure hemoglobin-A1c, we were unable to verify whether the glycemic control had an effect on CVS progression and development of MI. Lipoproteins not affected—or incompletely affected by therapy with statins—such as Lp(a), small dense LDL, and other mediators of vascular damage (viruses, homocysteine, fibrinogen, Chlamydia Pneumoniae, and others) may also have played an important role that could not have been detected because of the design of our study."



What Does Lower Lp(a), IDL, Small Dense LDL and Microbial Burden?

Oh please... Gentle Readers... I hope you get this correct.

Yes?

Saturated fatty acids, my dear audience members, of course.

Synergistically with a low LOW carbohydrate diet (or no carb).

Did you know that coconut oil, grassfed ghee/butter, cream, tallow, lard (which contain short-, medium- and long-chained saturated fatty acids) control and kill yeast, parasites and other microbes like Giardia, Salmonella and Campylobacter, in vivo and in vitro?



Krauss is in the House! The Three Axes of Evil

Yes -- of course (without Superko's help) Krauss has figured it out again and confirm the theories above as well as what we already acknowledge and tackle at TrackYourPlaque. Subfraction of lipoproteins yields the 'death' bands on ion mobility analysis which are independent subsets of cardiovascular risk. (Krauss et al, Arterioscler Thromb Vasc Biol. 2009 Sep 3. Not free yet.)

(PC1) LDL-associated risk: Concentration-sdLDL, Small Dense LDL, VLDL [Lipoprotein (a)]

(PC2) Metabolic Syndrome/Hyperinsulinemia pattern of decreased large HDL, increased small/medium LDL, and increased triglycerides (eg, Pattern B)

(PC3) HDL-associated protection: large HDL subfraction ('absent' band)

Note: Krauss does not list Large LDL-P as one of the axes of coronary risk. After reviewing 3 large landmark trials, he and the other researchers concluded Large LDL are not associated independently with CAD risk. Again, the presence of small LDL-IVb (the densest of 7 subparticles) is associated with risk and progression of plaque, not a high particle count of Large LDL.

Krauss and the other authors state, "Our study demonstrated that (1) levels of small/medium LDL particles are associated with [CV disease] and (2) levels of large LDL particles are not significantly related to cardiovascular disease, is consistent with other large prospective cohort studies whose data were obtained by 2 different lipoprotein measurement techniques: the Quebec Cardiovascular Study (GGE) and the Multi-Ethnic Study of Atherosclerosis and Women's Health Study (NMR). (p. 5)"

Large-LDL are Not Associated with Increased CAD Risk

This bears redundancy. Many cardiologists and even NMR experts do not understand this concept. Repeat... Krauss and other cardiologists found no increased risk associated independently with the presence of Large LDL.

Why is Large LDL even implicated sometimes?

Are fire-fighters implicated in causing atrocious out-of-control fires?

No. That is frankly ridiculous...

The arsonist is the smallest densest LDL. (See PC1 or PC2.)
And, the co-conspirator is the lack of large HDL2. (See PC3 or PC2)


(Read: dietary saturated fat deficiency. Excessive compliance with the AHA low chol/sat fat indictment).

Genetically we are all different -- some individuals naturally produce more Large LDL (apo E4? these folks elude infectious agents better, esp coupled with Lp(a); unfortunately the CAD is concordantly worse on inappropriate diets, e.g. non-ketogenic). However, when the NMR is examined, these individuals who have both CAD and bunches of Large LDL exhibit the 'death' band. Subfraction particles of LDL-IVb will often be 10x higher than normal. Or even 20x higher. What's normal and optimal? Optimal is none to 0.60% in my opinion.




Pattern A + the tiny LDL-IVb 'death' band is not a good thing.

You only need one axis of 'evil' for heart disease and EBCT progression.

Paleo folks sometimes have very high LDL mass and stunningly enormous proportions of Large LDL. Funny... this is also observed in individuals in longevity and centenarian studies. The long-living 100-year old Ashkenazi Jewish (pro-bands) have enormous HDL and Large LDL yet the small dense LDL was minor consisting of ~6-7%. Is all that Large LDL harmful? I doubt it. Their offspring have HDLs like us mod-high fat Paleo folks of 80s-100s. Okinawan centenarians also have enormous HDL of 60s with consuming goat milk full of saturated fat (MCTs), lard, fatty pork and gamey goat sashimi. Their LDLs are high in the 100-120s mg/dl like the Ashkenazi.

Read here: Benefits of High-Saturated Fat Diets (Part II).

For the Paleo/Primal/PP folks, if the LDL is mostly (or all) large, no problem. If however there are some of the smallest densest stuff (subspecies: LDL-IVb, the black sheep) and no large HDL2, then... it... maybe a problem. LDL-IVb is eradicated within 4wks with the right diet. Low low carb, fat and protein, Paleo.

Only subfractionation of the lipoproteins will identify the culprit.





Statins Fail to Improve ALL 3 Principal Components (PC)

Do statins help with any other of the above independent axes of coronary risk: PC1, PC2, or PC3? Or other identified CAD risk factors: vitamin D deficiency? Omega-3 deficiency? Hypothyroidism? Excessive omega-6 clogging up cell membranes and raising serum insulin and inflammatory markers?

Well... statins raise vitamin D. (yeah... Sunshine/ supplement v. Crestor which raises vit D 159%? Sun+Vitamin D WIN. When my blood [25OHD] increased from 20 to 70 ng/ml (350%), my HDL increased 29%. OK... here is a vitamin D formula: every 10% vitamin D conc increase = 1% HDL increase; according to Castelli, every 1% HDL increase is equivalent to 2-3% CAD relative risk reduction)


Well...statins may raise HDL max 5-15% yet niacin raises HDL 30-200% (depending on duration and patient population).

So the action on promoting regression via HDL by Niacin is 2 to 40x more than statins.

Niacin prominently lowers Lp(a), small dense LDL/IDL, triglycerides and provokes shifts to Pattern A. In the HATS trial, recall, after 3 yrs, niacin raised HDL 30% and HDL2 60%. Niacin was associated also with reductions in blood pressure. Statins are not in any trial.

In fact, any non-synthetic, therapeutic intervention that raises HDLs also lowers Lp(a), IDL, small dense LDL/medium LDL and triglycerides. And increases nice large buoyant LDL. Indeed, these lipoprotein species all improve in parallel. Conversely, they are exacerbated in parallel. With no exception, any strategy that raises HDLs consequently affects blood pressures positively downstream (eg, carb restriction, body fat loss, lean muscle gain, yoga, omega-3, vitamin D, saturated fat intake, thyroid replenishment, hormone optimization, many antioxidants and proanthocyanidins).

Except statins. What the authors missed mentioning was that in addition to 'statin resistance', statins worsen Lp(a) and Percent-sdLDL. And they fail to shift to pattern A. What else?
Statins s*ck.



Correctly Catching the Calcification Culprit(s)

TrackYourPlaque is a self-management program. To optimize the program and control plaque, one must accurately and knowledgeably assess personal and familial risk factors that caused suboptimal lipoproteins and/or positive EBCT scores and progression. The three factors listed above comprise 99% of the most common coronary culprits.

If one is just trying to beat down the LDL-Particle Count into submission and fails to take into account the three 'axes' of coronary risk, one will invariably miss the big picture.

Is it... dangerous...??

Certainly... it is not equivalent to EBCT stabilization or regression. Targeting and ameliorating the correct coronary culprits on the other hand yields potent control on plaque and reduce EBCT calcification progression to < 10%. For regression in 9-18 months on EBCT, 'perfect' lipoproteins are not mandatory but a trend toward improvements in both reductions in small dense LDL, IDL, Lp(a) and increases in HDL2 and relative LDL-buoyancy are requirements. Control of hypertension, more vitality, loss of body fat are all extra side perks.

Do you have 'leaky gut' where microbes are flowing into the blood stream from the intestines?
Do you have low HDL?
Do you have high small-LDL?
Do you have Pattern B?
Do you have Lp(a) and/or high homocysteine?
Do you have progression or calcium score > 10% annualized?
Do you have premature CAD or stroke or peripheral vascular disease or renoarteriosclerosis in your family history?
Do you have proteinuria, dialysis or chronic kidney disease in your family?
Do you have heart failure in your family history?
Do you have 'statin resistance'?

Then... one cannot hesitate or prolong an approach that is more targeted and aggressive than the one that Callister and his colleagues discussed ('incomplete effectiveness') associated with a 17.2-fold MI-risk in 6-7 years.


Ketosis/niacin, low LOW carb Paleo diets, mod-high SFA diets, high omega-3 supplementation, dietary omega-6 elimination, hormone optimization, cardio/weights and many MANY other TrackYourPlaque strategies improve all three axes of high cardiovascular risk.



Related posts:

Egg Yolks and High SFA Diet Raise HDL2, Lower IDL VLDL triglycerides, and Increase LDL Particle Buoyancy

Benefits of High-Saturated Fat Diets (Part I): Krauss 18%-High SFA Diet Lowers sdLDL particularly LDL-IVb, Raises HDL2b and lowers IDL VLDL triglyerides

Benefits of High-Saturated Fat Diets (Part III): High SFA, Low Carb Paleo Diet annihilate sdLDL from 1000nmol/L to nearly no particles or 'None', Raises both HDL2/HDLs 200-400%, Lowers IDL VLDL triglyerides, Lowers Lp(a)

HDL2b: Quintessential Regression Particle and How to Raise It

Lp(a) and Women's Heart Risk

Umbellularia Californication: SFA kicks olive oil's *ss

Lp(a) and the Power of Fish Oil (8.5 grams/d EPA DHA)

Cardio Controversies: Dr. Superko, MD

“It is not good to settle into a set of opinions. At first
putting forth great effort to be sure that you have
grasped the basics, then practicing so that they may
come to fruition is something that will never stop for
your whole lifetime. Do not rely on following the
degree of understanding that you have discovered,
but simply think. . . This is not enough.”

Hagakure, Yamamoto Tsunetomo (a Samurai)
September 10, 1716
Quoted by Dr. Superko, MD



Often at TrackYourPlaque I've been curious as to why regression on CT isn't admittedly easy as pie... like one-two-three... ?? A-B-C...??

Routinely now I would say all the lipoproteins I've been coaching or those that refer to us from Paleo/ Primal/ Protein Power sites are being reported at goal and optimal within months of starting TYP or after only 4-5 weeks of tweaking the diet. These wonderous and spectacular results are reported by members, both new and old, with HORRIFIC family histories of premature CAD events. Lp(a) is a risk factor for 90-100% of these individuals, the toxic vascular plaque accelerant.

Yes, all are Paleo or lacto-Paleo.
Yes, all are moderate to HIGH dietary saturated fat.
Yes, all are lower carb or VLC (very low carb).

No, they do not necessarily lose weight.
No, no changes in the $200+ supplements per month. (or...even better taking virtually none)
No, it was not hard. (OK, maybe... !debatable, but hey members pay $80/yr to learn how to live the 'spartan' *ironic laugh* tasty, high fat life where you feel younger, more vital, enjoy better skin/hair and at the same time beat subclinical CAD and stroke risks!??)

Yes, some LOWERED THE DOSE OF THE STATIN by extreme measures (sometimes against the advice of their LDL-centric-fool-cardiologist... SSSSSHhhhh)
because of the, remember, low-trig-statin- i-n-t-e-r-a-c-t-i-o-n.
Yes, repeat, they lowered the stupid-statin-red-pill and obtained BETTER RESULTS.



Or... unequivocally better no statins at all.

Yes, they are not unlike the previous Paleo/semi-Paleo (statin-free) peeps I profiled earlier HERE including Doug/dcarrns regression story.




No Statins

Why do statins ruin results often? Maybe because they are actually ineffective in this world of 'whole grain happiness' and veggie oil madness? Maybe because Lp(a) is not responsive to statins and, in fact, statins raise Lp(a)? Maybe because IDL, another frequent and overlooked cause of premature and subclinical atherosclerosis, is not responsive to statins? Maybe because statins completely fail to shift lipoproteins to the desirable Pattern 'A'? Maybe because statins do not lower coronary calcifications on EBCT or MDCT in over a dozen of trials that I've reviewed? Maybe because statins block wound-healing which may not exclude plaque lesions? Maybe because statins cause muscle tissue breakdown, mitochondrial defects and coenzme Q10 depletion? Maybe because statins inhibits nerve ending re-myelination of our nervous system?

Maybe because statins prevent the formation of Large LDL which are the primary/only transport units in our circulatory system for cancer- and heart-protective antioxidants like Vitamin K2 (MK-4 through MK-9), Carotenoids (Astaxanthin, Lutein and the 200+ others), Vitamin E tocopherols tocotrienols, and cholesterol which comprises 20+% of our nervous system, integral to every cell membrane and the provides the backbone structure to ALL our vital hormones necessary for life, survival and reproduction?? (Vitamin A, another fat-soluble 'hormone-like' nutrient, on the other hand is so important it has its own transporter known as retinol binding proteins.) For regression and hard clinical event reduction, Dr. B.G. Brown showed in the landmark 3-yr HATS trial in post-CAD men and women (see below graph), the treatment group achieved a high rate of large buoyant LDL (~70% of participants) and HDL2 increased by 61% (total HDL increased 30% from baseline low-30's mg/dl). About 25-30% of participants had Lp(a).

Many cardiologists are starting to speak out about statins' frank lack of outcomes and even their dangerous side effects. Stanford doctor Dr. Mark Hlatky, MD is no exception in an NEJM editorial HERE. How scary is it that the statin industry is trying to peddle these teratogenic Category 'X' drugs to S.A.D. obese teenagers (who might have s*x and might get pregnant)? Obese children are their targets too, children who have rapidly growing brains and nervous systems which require cholesterol?

How about... Lack of regression? Marginal regression? 'Sucky' lack of clinical reduction in coronary events when comprehensively compared to niacin trials and omega-3 trials? Do cardiologists even know regression if it smacked them in the knee? Like those that sit on committees? In the AHA?




Question: Which drug/vitamin, which mimics ketosis, trumps statins in comparisons of CAD outcomes, all-cause mortality, AND angiographic-regression studies, by raising Large HDL2, lowering small dense LDL and controlling toxic Lp(a)? (Figure 1, from the below reference)


Lipid management to reduce cardiovascular risk: a new strategy is required.
Superko HR, King S 3rd.
Circulation. 2008 Jan 29;117(4):560-8; discussion 568. Free PDF




"Myopic Focus on LDL"

Soon I'll be meeting a patient of Dr. Superko's from 10yrs ago; this gentleman was on niacin and doing NMR subfractionation of cholesterol lipoproteins before it became en vogue at places like TrackYourPlaque. I find it be a quite a coincidence because I've been reading much of Dr. Superko's work the last few weeks. Dr. Superko was no longer his physician after he became busy on the lecture circuit and with Berkeley Heart Lab. It appears this eminent cardiologist, prolific researcher, and author is still pretty busy and now earnestly trying to prevent more Americans from dying from the coronary artery disease epidemic. Will it be enough?

"Although this level of success in the fight against heart disease is laudable, a great danger for our patients’ future health lies in the assumption that cholesterol reduction alone will stem the tide of coronary heart disease (CHD). It is wise and prudent to remember the words of Yamamoto Tsunetomo that “this is not enough.” The purpose of this article is to challenge healthcare workers to consider the possibility that the cholesterol-lowering program has in large part failed to stem the epidemic of CHD and that the well-meaning focus on LDL-C reduction has deflected interest in other therapeutic aspects of lipoprotein treatment that provide equal or greater benefit. This myopic focus on LDL alone is not surprising because, so far, guidelines have not adequately addressed other evidence."

"Statistical Significance Does Not Necessarily Mean Clinical Relevance"

Which strategies appear to lower CAD risk the most? It appears from Superko's provocative assertions that raising Large HDL2-cholesterol is the most critical according to current secondary prevention studies (niacin: HATS HATS-MetSyn FATS FATS-10yr CDP CDP-15yr CLAS-I CLAS-II ARBITER). With trials like the well-designed secondary trial in post-MI men and women, the Lyon Diet Heart, it was observed how mildly re-balancing the n-6:3 ratio resulted in 73% reduction in CAD events as well nearly an equally impressive 70% reduction in all-cause mortality (cancer, accidents, suicides, etc). In fact, in the Lyon Diet trial, LDL increased 1.7% and HDL decreased (yikes) 3%. Could the improvements in death rates be from increases in the Large HDL2? Subfractionation of the lipids were not done (or at least I can't find them) but that is necessary to see below the surface how omega-3 fatty acids work. Omega-3 PUFAs, like saturated fatty acids, bind PPAR and effectively lower small LDL (which are toxic) and raise Large HDL (which are regressive). Quite literally, in clinical trials, fish oil does not change total HDL-Cholesterol hardly at all but instead invokes dramatic, TECTONIC shifts in HDL2, sometimes even increasing by 150-300%. Niacin has a similar shifting effect on subfractions enlarging and enriching small particles into larger, buoyant, fluffier particles. Like omega-3 PUFAs and saturated fatty acids, niacin improves both HDL and LDL particle content and functionality.

"Statistical, or mathematical, significance is a tool useful in calculating how likely it is that the results of an experiment are due to chance alone and not really due to the intervention. Achieving statistical significance generally means that the results observed probably were not due to chance alone and probably were the result of the intervention used in the clinical trial. A value of P=0.05 indicates that there is still a 1 in 20 chance that the results were due to chance alone and not the intervention. Thus, statistical significance is a mathematical tool to test the hypothesis that the results observed were probably due to the intervention, but it does not necessarily mean the results are clinically significant or even meaningful..."

"The potential harm in the assumption that mathematical significance is equivalent to clinical significance is that many public and professional individuals have the misleading impression that if they just get their LDL-C low enough, they will be free of CHD risk. The results of 5 large statin trials show that this is a dangerous misconception in that it leaves large numbers of patients still at risk for cardiovascular events."

Statins and LDL reduction... 'This is not enough.'

Niacin . . . m a y b e .

Diet is definitely the best. Trumps them all.




At TrackYourPlaque we agree with Superko and have taken it further.





Grasp the 'Basics' for Regression (TYP Goals):
1. No statins
2. Vitamin D > 60
3. Trig < 60
4. HDL > 60
5. Small LDL less than 10% or none (LDL-IVb as low as possible and diet works well, again, very VERY well)
6. Large LDL > 60%
7. Large HDL (2b) > 50%


Regression is associated with Large HDL (Krauss RM et al, ATVB 1996).
Progression is associated with Small LDL, notably LDL-IVb (Superko HR, Krauss RM et al, ATVB 2003).


Answer: Niacin (which mimics ketotic diets, coming up in Benefits of High-Saturated Fat Diets, Parts VI and VII)