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)

Vitamin D and Other TYP Basics

We use a lotta Vitamin D at Track Your Plaque. Everyone is deficient and everyone requires supplementation. Dr. Davis has found that Vitamin D revolutionized and accelerated coronary calcification reversal in addition to many other attributes:
--improved insulin resistance
--increase in HDL 20-30% (in 6-12mos)
--lowering of blood pressure
--energy
--increased testosterone (and I've noticed higher estrogen)
--protection from colds and infections


Vitamin D is a pro-hormone... powerful, potent, and paleo-to-the-core. Since pre-paleolithic times, Vitamin D has been produced in our skin from the UVB radiation of sunlight. The sun indeed powers nearly all life on earth. It is essential and signals reproduction, energy and longevity for not just humans but all land and marine plants, prokaryotes, and animals. The sun has been around the last ~4 Billion years and scientists estimated it will continue to burn another ~4 Billion years.

If you are taking vitamin D, then you are on 'bio-identical hormone replacement therapy' baby!

Typical Dose: 2000 to 10,000 IU daily (enough to achieve and maintain ideal blood ranges 60-70 ng/ml)

Typical Administration: Morning/Daytime

(many people report insomnia, including me, if taken in the evening *makes sense right?*)

Typical Lab Monitoring: Calcium, Magnesium, PTH, [25(OH)D] every 6 months once optimal levels are obtained

TYPical Goal: Blood [25(OH)D] = 60-70 ng/ml




Other TYP staples are:

--High to Ultra-high dose fish oil 6 to 10 g EPA + DHA daily (Depending on how much inflammation and Lp(a); low dose 3 g/day if no inflammation)

--Niacin, Vitamin B3 1-2 grams daily (we prefer Slo-Niacin which is EFFECTIVE and cheap $12.99 at Costco for #150 tabs)




Side benefits of all the above:
--diminished infections (and maybe incl HIV?)
--diminished immunosuppression
--diminished cancers, melanoma
--diminished wrinkles *twinkle*
--increases life span



Vitamin A (natural; not vitamin A precursors like beta-carotene)
Vitamin A helps all the above as well. I like Vitamin A esp because most rice-eating communities are deficient of vitamin A (Bamji MS Experientia Suppl. 1983;44:245-63.). On the Japanese diet, 20% of individuals were deficient in Vitamin A and Riboflavin B2. Going grain-free and eating Paleo easily ameliorates Vitamin A deficiency. In the mean time, supplementation provides a bridge until optimal health is achieved.

Read more about Vitamin A: HERE

Saturated Fats as Potent Anti-Atherogenic Drugs

I hope we are not still scarred by the long onslaught of ingrained sat-fat nonsense over the last few decades?

SCAR TISSUE from Red Hot Chili Peppers
ALBUM: Californication

Courtesy of Youtube.com

LAURIC ACID (12C MEDIUM-CHAIN SATURATED FATTY ACID) ASSOCIATED WITH RELATIVELY HIGHER HDL2b AND LOWER HDL3c

In the previous entry, conclusions from the same research below was discussed. They went further and looked at the lipoprotein subfractions including HDL2b and HDL3c. Mensink et al found that the higher the phospholipid transfer protein (PLTP) activity and the lower the cholesterol ester transfer protein (CETP) activity, the higher the relative abundance of HDL2b, the regression particle, and the lower the HDL3c, a small dense atherogenic particle. Lauric acid produced the highest ratio of PLTP to CETP activity when compared with the control, palmitic or oleic diets after 6-weeks.

Their assessment was "It is now clearly established that CETP and PLTP can modulate the size distribution of serum lipoprotein fractions. On the one hand, CETP can replace lipoprotein cholesteryl esters by hydrolyzable triglycerides which are derived from the triglyceride-rich lipoproteins, favoring the emergence of small-sized LDL, pre-beta-HDL and small-sized alpha-HDL [40]. On the otherhand, PLTP has been shown to promote the formation of both pre-beta-HDL and large-sized alpha-HDL through an inter-HDL fusional mechanism [40]. In the present study, no significant differences in the size distribution of either HDL or LDL fractions were observed in sera from subjects consuming either of the three experimental diets... Despite the absence of modifications of the size distribution of HDL, significant relationships between lipid transfer activities andthe relative abundance of HDL subpopulations were observed among (INDIVIDUAL) subjects consuming the same, standardized diet. Overall, CETP correlated positively with small HDL, but negatively with large HDL, whereas opposite tendencies were observed with PLTP that correlated negatively with small HDL, but positively with the large ones (ie, HDL2b)."

Variations in serum cholesteryl ester transfer and phospholipid transfer activities in healthy women and men consuming diets enriched in lauric, palmitic or oleic acids. Lagrost L, Mensink RP, Guyard-Dangremont V, Temme EH, Desrumaux C, Athias A, Hornstra G, Gambert P. Atherosclerosis. 1999 Feb;142(2):395-402. Email for PDF.







BALANCE OF CETP AND PLTP NECESSARY

Minimization and maximization, respectively, as the Mensink study showed.

What are the dangers of artificially inhibiting CETP and ignoring PLTP activity?

What are the dangers of raising only HDL3c (small dense atherogenic HDL) and lowering HDL2b (the regressive, large/fluffy HDL)??!

The story of Torcetrapib...is one with an extremely unhappy unending...

Well...for one Pfizer is now out of the lipid-heart-disease business (Lipitor® RIP 2011 when it goes generic). Read the TYP report on this CETP-inhibitor and the surprising outcome HERE. Pfizer's $20B Torcetrapib HDL-raising drug unfortunately failed big time (in low-fat, low cholesterol, low saturated fat populations). Not only was an increase of 50% in total HDL observed in humans but also coronary regression was demonstrated in animal studies. Oddly this curious drug was associated with nearly double the deaths in the single human morbidity/mortality trial. Are animal brains as functional or large as human brains? What is the purpose of cholesterol? Are humans brains not laden with cholesterol? In fact 23% of the whole body pool of cholesterol is found in the brain and central nervous system. Although the brain only weighs 2.1% of our total weight, the cholesterol content is the highest compared with any other tissue (23 mg chol/gram). How much cholesterol is in an egg yolk? A measly ~200 mg. Barely enough to support or maintain a smidgeon of your SUPER SAVANT BRAIN. And we're told to have no more than an egg a day? Can you spell autism? Well... probably neither can the great-grandchildren of the geniuses who proposed these low-cholesterol indictments. How many more generations will be affected by the policies propagating the low-fat hypothesis? Are we de-evolving as a species *hint....WALL*E *?

Thematic review series: Brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. Journal of Lipid Research, Vol. 45, 1375-1397, August 2004.





BIOACTIVE LIPIDS -- BEST BALANCE -- BETTER THAN Torcetrapib

Fish oil EPA + DHA and seafood naturally lower CETP activity (preventing cholesterol transfer) and power up PLTP (moving phospholipids out of lipoprotein fractions). I had a hard time locating any VAP/NMR data on effects of fish oil components EPA and DHA, but two studies below demonstrate the outcome of EPA and DHA ingestion in depleting phospholipids out of LDL and HDL particles.

(1) Small supplements of N-3 fatty acids change serum low density lipoprotein composition by decreasing phospholid and apolipoprotein B concentrations in young adult women. Terpstra AH et al. Eur J Nutr. 1999 Feb;38(1):20-7.

(2) The effect of dietary n-3 polyunsaturated fatty acids on HDL cholesterol in Chukot residents vs Muscovites. Astakhova T et al. Lipids. 1991 Apr;26(4):261-5.

Native Chukot Peninsula residents, in contrast to Muscovites, consume a diet rich in n-3 polyunsaturated fatty acids. This dietary peculiarity is reflected in differences in plasma lipid and apolipoprotein contents. The Chukot residents have lower contents of total cholesterol, triglyceride, LDL (low density lipoprotein) cholesterol and apolipoprotein B, but higher HDL (high density lipoprotein) cholesterol levels than do Muscovites. The apolipoprotein A-I levels were identical in both groups. A higher HDL cholesterol to apolipoprotein A-I ratio was determined in the coastline Chukot residents (0.52 +/- 0.01) than in Muscovites (0.43 +/- 0.01; p less than 0.01). In contrast to Muscovites, the coastline Chukot residents also had higher n-3 and lower n-6 polyunsaturated fatty acid percentages in plasma and erythrocyte lipids, and lower phosphatidylcholine and higher sphingomyelin or phosphatidylethanolamine levels in HDL2b and HDL3. The higher HDL cholesterol levels in the plasma of the coastline Chukot residents appears to reflect the higher cholesterol-scavenging capacity of their HDL. We conclude from this study that the regular consumption of dietary n-3 polyunsaturated fatty acids by the coastline Chukot residents decreased LDL cholesterol transfer from plasma to peripheral cells, and enhanced cholesterol efflux from cellular membranes toward HDL.

A WONDERFUL COMPREHENSIVE REVIEW THAT I *HEART*

Nagao K, Yanagita T. Bioactive lipids in metabolic syndrome. Prog Lipid Res. 2008 Mar;47(2):127-46.

"This review explores the physiological functions and molecular actions of bioactive lipids, such as n-3 polyunsaturated fatty acids, conjugated fatty acids, sterols, medium-chain fatty acids (LIKE SATURATED FAT LAURIC, CAPRIC, CAPROIC, CAPRYLIC ACIDS), diacylglycerols and phospholipids, in the development of metabolic syndrome. Dietary bioactive lipids suppress the accumulation of abdominal adipose tissue and lipids in the liver and serum, and alleviate hypertension and type 2 diabetes through the transcriptional regulation of lipid and glucose metabolism. "

[DRUM ROLL...] DIETARY SATURATED FATTY ACIDS ACT LIKE NIACIN

Fatty acids including saturated fatty acids also bind PUMA-G and HM74 receptors. This is the receptor family that Niacin binds to and exerts its potent abilities to regress plaque (raise HDL2b 200-300%, lower TGs 40-60%) and evoke its anti-inflammatory effects. See Table 1 full list of the range of ketone body and the saturated fatty acids and their relative receptor affinities.

Taggart A, Waters MG et al. (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem. 2005 Jul 22;280(29):26649-52. Full 'accelerated publication' PDF here.

Other fatty acids which bind this astounding receptor PUMA-G are in listing of decreasing potency:
--Hydroxy-butyrate (ketone bodies associated with exercise training and intermittent fasting)
--Lactate (by-product of anaerobic exercise, strength training, intense exercise like CALIfornication)
--Acetate (C2), Proprionate (C3)
--Decanoate (C10) = caprylic acid, a medium chain saturated fatty acid (MC SFA)
--Heptanoic acid (C7)
-- Butyrate (C4) = short chain saturated fatty acid from butter oil and produced by gut flora from ingested fiber like oat bran, pectin, etc
--Octanoate (C8) = capric acid, MC SFA
--Pentanoic acid (C5)
--Hexanoate (C6) = caproic acid, MC SFA
--Nicotinic acid (niacin, SLO-NIACIN, NIASPAN) -- binds with high affinity to HM74 receptors