Insulin and The Paleo-Ancestral Diet: Frassetto et al 10-Day Study

This site is all about evolutionary changes, health from the ancient/paleo perspective, and how our genes are imprinted to adapt and survive (whether we want to or not).




Role of Hyperinsulinemia = ENERGY DIES

Chronically high insulin (from high refined carbs, from gluten/food-stressors, hypothyroidism, low progesterone, adrenal dysfunction, metal toxicity, endocrine disruptors, etc) raises insulin resistance in our organs which can lead to increased small dense LDL, high TG and low HDLs. A cascade of further hormone changes and vascular adjustments occurs. Vascular blood pressure may increase. Pre-clinical hypertension can develop and eventually atherosclerosis ('scarring' in affected vessels) and diabetes (inappropriate and chronically elevated blood glucoses). Later, the natural progression of this hormonal storm of insulin dysfunction includes diabetes complications or target organs (kidney, eye, nerve damage), heart failure and heart events (revascularization surgery, heart attack, angina, sudden death, bypass and/or stent placements).





Keep The Insulin Low

Lamarche B et al wrote an editorial in 1996 (see Ref 1) and NEJM (N Engl J Med. 1996 Apr 11;334(15):952-7.) and wrote that the higher quintiles of insulin were highly associated with higher rates of atherosclerosis and heart events in the Quebec Cardiovascular trial. 67 pmol/L (= 9.3 mIU/L) was used as odds ratio = 1.0 (it's still high IMHO; goal = 4 mIU/L in other words less than ~28 pmol/L). See above bar graph (Ref 1).

Convert pmol/L by dividing 7.175 for mIU/L. More about 'normal' fasting insulin HERE.

The Lamarche B et al state "For example, an 11-fold increase in ischaemic heart disease [IHD] risk was noted among men with both hyperinsulinaemia and elevated apo B levels, these two metabolic abnormalities being common among individuals with abdominal obesity, especially when associated with high levels of visceral (intra-abdominal) adipose tissue.




Visceral (Intra-Abdominal) Adipose Tissue

What is Visceral Adipose Tissue? Do you have any? I do. On my belly. In my head... from the ravages of the high carb S.A.D., high omega-6 intoxification, high trans-fat/F*CK-TOSE intake from my childhood/teens/early-20s-30s (OK. a long time, most of my life), sedentary lifestyle, undiagnosed Hashimoto's autoimmune hypothyroidism, stress of LIFE, et cetera.



Fatty calcified livers (e.g. NASH, fatty liver, NAFLD, foie gras) ?

Fatty calcified atherosclerotic plaque?

Fatty calcified atherosclerotic plaque in arteries: Renal, Carotid, Coronary, Peripheral, PENILE (e.g. ***Erectile Dysfunction BABY -- you do not have a Viagra-deficiency) ?

Fatty calcified thyroids ?

Fatty calcified adrenal glands ?

Fatty calcified pineal glands (e.g. insomnia) ?

Fatty calcified pancreas glands (e.g. metabolic syndrome, diabetes) ?

Fatty calcified gallbladders (e.g. GERD, dyspepsia, heartburn, gas/bloating)?

Fatty calcified ovaries/ fallopian tubes/ fibroids/endometriosis/ PCOS?








Keep The Insulin Relatively LOW

Many benefits improve on lower carb Paleo/ancestral diets. Why? It works and best matches our DNA genetic expression.

Lamarche B et al in Quebec, Canada have elucidated a few things about insulin, e.g. chronically high insulin and insulin resistance (IR).

Insulin and IR are related to high TG, low HDL, and high dense LDL and high visceral fat and high belly circumferences.

MOREOVER... More morbidity. More mortality.



From their JAMA publication (see Ref 2 and below Table 2) they showed in the Quebec Cardiovascular trial that 3 factors are highly associated with death and cardiovascular events:

(1) elevated fasting INSULIN

(2) elevated TRIGLYCERIDES (because these reflect HIGH dietary carbohydrates and LOW essential saturated dietary and omega-3 polyunsaturated fatty acids)

(3) apoB, any amount sdLDL, high sdLDL (refers to 'small dense LDL' not total LDL -- total LDL is total CR*P and though the authors talk about total LDL here they correct and clarify themselves in Ref #3, 5, and 8; these French Canadian investigators are not full of cr*p)




Lamarche B et al Also Showed That...

Associated with coronary plaque in the French-Canadian Quebec Cardiovascular trial (see reference list):

--Ref 3: presence of sdLDL

--Ref 4: low HDL2, the 'good' large HDL particles which are highly associated with regression of disease (the higher, the better in normal bell-shaped curves)

--Ref 5: Beyond LDL... total-LDL is meaningless, only sdLDL really matters. Conventional cholesterol panels and LDL are CR*P. The lipoproteins need to be fractionated by size and buoyancy for a progressive,  accurate and sensitive reliable metric.

--Ref 6: visceral fat, it'll kill ya if exceeds a threshold

--Ref 7: high fibrinogen (which reflects high carbs, low n-3, low sat fat) + Lp(a) associated with DEATH and cardiovascular events

--Ref 8: 13 years later after the Quebec Cardiovascular STUDY... only thing that matters is sdLDL... the small dense LDL subfraction... related to death and cardiovascular events. Large LDL do not matter, the authors concluded. In fact many experts believe large buoyant LDL are anti-atherogenic and antioxidants. I highly agree. The larger, the PHATTER, the merrier.








Paleo Works. In Only Ten Days: Lynda Frassetto MD et al

Why is eating a (semi) unrefined, ancient-styled diet the way to go for reversal of chronic diseases and longevity? No simple answers but Paleo lowers chronic hyperinsulinemia. Frassetto et al at the University of California, San Francisco recently published a 10-day trial comparing metabolic changes and hypertension improvements on the paleolithic diet.

Paleo controls insulin better than Zone 40/30/30 and of course WAY way better than the S.A.D.

HOMA is a measurement of insulin resistance. Paleo (despite being high carb and low sat fat) achieved a 72% reduction in insulin resistance, HOMA (p=0.07). This was a high carb, low glycemic index with carbohydrates at ~~ 200 g/day diet. It was matched to the SAD diet. What an ingenius diet trial! Lower carb of course may be preferred for those with significant insulin resistance and fat-burning challenges. Higher sat fat, IDEAL in my opinion.

In this trial (see below Table 3), in terms of lipoproteins, Trigs were still high (e.g. excessive dietary carbs in the form of honey, pineapple, carrot juice, melon and excessive n-6 mayo) and HDLs still marginally suboptimal (e.g. saturated fat deficiency). HDLs often mirror the LDL particle size.


Lower carb high sat fat Paleo would have improved these parameters. See prior animal pharm posts:
Benefits of High Saturated Fat Diets: My Paleo PEEPS With High HDLs


The premise is to alter the neolithic, post-agriculture diet macronutrients and micronutrients (glycemic load, glycemic index, gluten, lectins/phytic acid, legumes and dairy). Amazing insulin changes happen.

Is this what our genes were designed for 2.5 million years to do? We don't live in a land of honey, sweets and fruit. We are meant to starve sporadically, lift heavy things occasionally, move intensely intermittently, relax daily, play, hug, make babies (umm.. do I need to elaborate?) and eat foods that our ancestors thrived on. Complying to the genetic programming and optimizing where the genes and genetic expression are screwed up will provide a reprieve in these neolithic times IMHO.

"CONCLUSIONS: Even short-term consumption [10 days worth] of a paleolithic type diet [no grains, no legumes, no dairy, low glycemic index, ALBEIT HIGH CARB matching the s.a.d. diet] improves BP and glucose tolerance, decreases insulin secretion, increases insulin sensitivity and improves lipid profiles without weight loss in healthy sedentary humans." [some were overweight UCSF medical school students]




UCSF Frassetto et al Shows Paleo Controls IR and Insulin

Compared with the 'usual diet' (e.g. standard American diet), the Paleolithic Hunter-Gatherer diets controlled insulin, HOMA (insulin resistance) better than the usual S.A.D. in overweight men and women ages 18+ years old. These results are nothing short of phenomenal in a Big Pharma-dominated medicine tradition. No drug replicates these results, especially in only 7-10 days. No drugs (except glandular, hormonal or omega-3 fish oil pharmaceuticals) are disease reversing; they serve only to band-aid and hide in my experience. In modern, conventionally-schooled medicine, no cause or pathophysiology is assigned to the disease known as hypertension. Apparently the role of insulin and refined dietary carbohydrates (or other endocrine disrupting factors) are not considered. Conventional weight loss, diet ('low fat') and exercise are always prescribed yet rarely in my observations is hypertension stopped or reversed by these means successfully and long-term. Why?


Previous blogosphere hits on Frassetto's seminal study:

--Dr. Mike Eades MD discussed HERE.

--Mark Sisson of Mark's Daily Apple HERE 

--Matt Metzgar recently discussed as well HERE.

--Even Lyle discussed briefly HERE.

--My bud master Chris @conditionresearch.com which is one website that lead to my rapid health reveral discusses naturally of course HERE.

--Dr. Briffa discussed HERE.

--My bud O Primitivo discusses HERE in Portuguese.

--And even Dr. Davis discusses HERE linking back to the inimitable, matchless Protein Power Dr. Mike Eades.




Aging and Insulin: EORS (Epigenetic Oxidative Redox Shift)

Aging and oncogenesis are related to insulin.

Brewer (Ref #10) has explained how aging is related to insulin and insulin resistance. What degrades mitochondrial efficiency?

In the modern Western diet (now currently imported globally to Europe and China along with Western diseases), high refined carbs, refined fructose, industrial pesticides, toxic heavy metals, and refined vegetable oils brimming with omega-6 PUFAs are the typical culprits adding to the insulin resistance and hyperinsulinemia burden. Chronically elevated blood insulin leads to an overall fattening effect which can calcify and harden the liver, the arteries, and many other organs (thyroid, adrenals, arteries, endothelium, vasculature, pancreas, gallbladder, brain etc).

Brewer describes "This metabolic shift is epigenetically enforced, as is insulin resistance to reduce mitochondrial turnover. The low mitochondrial capacity for efficient production of energy reinforces a downward spiral of more sedentary behavior leading to accelerated aging, increased organ failure with stress, impaired immune and vascular failures and brain aging. Several steps in the pathway are amenable to reversal for exit from the vicious cycle of EORS. Examples from our work in the aging rodent brain as well as other aging models are provided."

Low carbohydrate diet (15%) in rodents extends longevity and minimizes tumour growth compared with S.A.D. low fat, high carb diet. See Ref #12.

Resistance training reverses aging. See Ref #13. Burn baby burn.




References


1. Risk factors for ischaemic heart disease: is it time to measure insulin?
Després JP, Lamarche B, Mauriège P, Cantin B, Lupien PJ, Dagenais GR.
Eur Heart J. 1996 Oct;17(10):1453-4.

2. Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease.
Lamarche B, Tchernof A, Mauriège P, Cantin B, Dagenais GR, Lupien PJ, Després JP.
JAMA. 1998 Jun 24;279(24):1955-61.

3. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study.
Lamarche B, Tchernof A, Moorjani S, Cantin B, Dagenais GR, Lupien PJ, Després JP.
Circulation. 1997 Jan 7;95(1):69-75.

4. Associations of HDL2 and HDL3 subfractions with ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study.
Lamarche B, Moorjani S, Cantin B, Dagenais GR, Lupien PJ, Després JP.
Arterioscler Thromb Vasc Biol. 1997 Jun;17(6):1098-105.

5. Atherosclerosis prevention for the next decade: risk assessment beyond low density lipoprotein cholesterol.
Lamarche B, Lewis GF.
Can J Cardiol. 1998 Jun;14(6):841-51. Review.

6. Visceral obesity and the risk of ischaemic heart disease: insights from the Québec Cardiovascular Study.
Lamarche B, Lemieux S, Dagenais GR, Després JP.
Growth Horm IGF Res. 1998 Apr;8 Suppl B:1-8. Review.

7. Is lipoprotein(a) an independent risk factor for ischemic heart disease in men? The Quebec Cardiovascular Study.
Cantin B, Gagnon F, Moorjani S, Després JP, Lamarche B, Lupien PJ, Dagenais GR.
J Am Coll Cardiol. 1998 Mar 1;31(3):519-25.

8. 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.
St-Pierre AC, Cantin B, Dagenais GR, Mauriège P, Bernard PM, Després JP, Lamarche B.
Arterioscler Thromb Vasc Biol. 2005 Mar;25(3):553-9.

9. Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet. [Free PDF CLICK]
Frassetto LA, Schloetter M, Mietus-Synder M, Morris RC Jr, Sebastian A.
Eur J Clin Nutr. 2009 Aug;63(8):947-55. Epub 2009 Feb 11.

10. Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories.
Brewer GJ.
Exp Gerontol. 2009 Nov 26.

12. A low carbohydrate, high protein diet slows tumor growth and prevents cancer initiation.

Ho VW, Leung K, Hsu A, Luk B, Lai J, Shen SY, Minchinton AI, Waterhouse D, Bally MB, Lin W, Nelson BH, Sly LM, Krystal G.

Cancer Res. 2011 Jul 1;71(13):4484-93.

13.  Resistance exercise reverses aging in human skeletal muscle.
Melov S, Tarnopolsky MA, Beckman K, Felkey K, Hubbard A.
PLoS One. 2007 May 2;2(5):e465.

[Revised from my Nephropal blogpost]

HDL, LDL Transporters (and Clive Owen)

Hypnotic... Lancome loves Clive Owen
Lancome isn't the only one...

[Directed by Wong Kar Wai]

The HAAAWT Transporter

Clive Owen was featured in a series of vignettes as a BMW driver transporting goods -- of unknown origin to known destinations.

BMW 'The Hire' Film Series
--Starring Clive Owens
--One vignette directed by Wong Kar Wai 'The Follow'
--Other vignettes directed by: John Frankenheimer, Ang Lee, Guy Ritchie, Alejandro Gonzalez Inarritu






LDL and HDL are Transporters (like Clive Owen)

Our energy and immunological systems use LDL and HDL to transport things... Cholesterol (mandatory for all hormone and steroid synthesis, cell membranes, BRAIN, etc), phospholipids (cell 'walls' of every cell), triglycerides (converted carb and lipid energy) and antioxidants (coenzyme Q10, tocopherols, tocotrienols, carotenoids -- beta-carotene, lutein, lycopene, astaxanthin, etc.)

How? From the gut to the liver to our circulatory system to the ultimate destination of the cells where nutrients are required, food is transformed to more easily transportable entities. Complex carbs are broken down to glucose. Complex carbs are also re-transformed to carbon chains which are then transformed to fatty acids known as triglycerides. Dietary fats are also transported as Trigs but dietary carbs generate more and for longer durations.





Build a Bionic HDL3 Particle for LONGEVITY

Recently researchers built a bionic HDL3 (denser HDL) made of 3 components (1) Apo A1, (2) CHOLESTEROL, and (3) Phospholipids (Small, dense HDL3 particles attenuates apoptosis in endothelial cells: Pivotal role of apolipoprotein A-I. de Souza et al. J Cell Mol Med (2009)). These particles in a petri dish blasted away oxLDL and 'displayed twofold superior intrinsic cytoprotective activity'. Impressive.

HDL are triglyceride containing lipoprotein particles. It is very interesting to me these reconstituted HDL particles contained no triglyercerides. Triglycerides are formed post-prandially (after meals) to circulate food -- fats and carb energy. In the morning after a 12-hour fast, we have the least amount of triglycerides circulating. This is why your doctor orders a 'fasting' lipid panel. When is it the highest?



In vivo data for 'bionic HDL'?

YES it exists as well. Centenarian subpopulations not only exhibit what conventional cardiologists would think of as 'harmful' atherogenic profiles of high Lp(a) but also high HDL3. It turns out perhaps this only makes sense in the context of an anti-inflammatory state. Centenarians tend to display high HDL, high HDL2 (large fluffy) and high HDL3 (smaller denser). See prior animal pharm Ashkenazi long-living Jewish probands -- benefits of high saturated fat diets part II.

Thanxxx Mr. Jack C for your contributions and pointing out the MARS (Krauss et al 1996) which showed that only baseline HDL3 made any difference in the outcomes for reduction in progression of heart disease -- lovastatin made no difference, LDL-reduction made no difference. Only HDL3 at baseline. Thank you kind Sir. Lipoprotein subclasses in the Monitored Atherosclerosis Regression Study (MARS). Treatment effects and relation to coronary angiographic progression.

How do we prevent excessive Triglycerides from cluttering our HDL3?
--avoid excessive carbohydrates
--start an evo/paleo diet plan -- no grains, no legumes, limited fruit and n-6, plenty of fiber/greens, plenty of OMEGA-3
--meat meat meat
--fat fat fat
--eliminate hyperinsulinemia (sleep, relax, exercise, balance hormones -- cortisol thyroid sex, avoid minimeral/vitamin deficiencies, avoid xenobiotics, avoid pesticides, avoid PHARMACEUTICAL POISONS)
--exercise, lift some weights, move around, yoga



In vivo and ex vivo data:

o Prior animal pharm: Despite Genotype apoE 2/3/4 -- the SFA diet produced higher ApoA1 and higher HDLs
o Prior animal pharm: 6 eggs daily (~12oo mg cholesterol daily) with the highest SFA:PUFA ratio (4:1) produced the highest HDL (10% greater), highest HDL2 (~4X), HDL3 lightest wt% (fluffier) and highest ApoA1 in lipoprotein particles (PDF HERE)
0 Lipoproteins, vascular-related genetic factors, and human longevity
o Plasma LDL and HDL characteristics and carotenoid content are positively influenced by egg consumption in an elderly population.
o Plasma LDL and HDL subspecies are heterogenous in particle content of tocopherols and oxygenated and hydrocarbon carotenoids. Relevance to oxidative resistance and atherogenesis.
o Effect of particle size and lipid composition of bovine blood high density lipoprotein on its function as a carrier of beta-carotene.
0 In vitro and in vivo LIPOLYSIS of plasma triglycerides increases the resistance to oxidative modification of low-density lipoproteins.
0 Susceptibility of LDL to oxidation in vitro and antioxidant capacity in familial combined hyperlipidemia: comparison of patients with different lipid phenotypes.
o 17beta-estradiol affects in vivo the low density lipoprotein composition, particle size, and oxidizability.
0 Vitamin E, LDL, and endothelium. Brief oral vitamin supplementation prevents oxidized LDL-mediated vascular injury in vitro.
o Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size. [Krauss et al, the higher the CHOLESTEROL CONTENT, the more resistance to oxidative stress]






Can You Build a Bionic HDL3?

How do we add Cholesterol, Apo A1 and Phosphopids to our HDL3?
--eat cholesterol (A2 dairy, ghee, egg yolks, animal/fish, krill oil, etc)
--eat saturated fats (ditto above + virgin coconut/palm oil)
--avoid statins and other poisons/pollution which knock off cholesterol, testosterone and other steroidal hormones and their precursors and the optimal balance
--eat phospholipids (A2 dairy, ghee, egg yolks, animal/fish PHATS, krill oil, etc)
--minimize excessive carbohydrates






Simple? Bionic is easy.

Ok a quickie aside...

Pemmican Fans (yes -- Danny Roddy this is you BABE)

Steve Phinney on Pemmican and Indigenous Diets (Interview at Me and My Diabetes)

o Discusses the Masai warriors -- meat, milk, B-L-O-O-D to make warrior MUSCLES (A2 goat milk)
o Pemmican is good stuff
o I like my asian style Pemmican on high carb days with rice (glutinous rice is even better *Hhhmmmm!). PORK SUNG (courtesy of wiki).

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: 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

Hecht HS, Superko HR. Electron beam tomography and National Cholesterol Education Program guidelines in asymptomatic women. J Am Coll Cardiol. 2001 May;37(6):1506-11.

Nasir K, Santos RD, Roguin A, Carvalho JA, Meneghello R, Blumenthal RS. Relationship of subclinical coronary atherosclerosis and National Cholesterol Education Panel guidelines in asymptomatic Brazilian men. Int J Cardiol. 2006 Mar 22;108(1):68-75.

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.

Superko HR. Small, dense, low-density lipoprotein and atherosclerosis. Curr Atheroscler Rep. 2000 May;2(3):226-31.

Superko HR, Hecht HS. Metabolic disorders contribute to subclinical coronary atherosclerosis in patients with coronary calcification. Am J Cardiol. 2001 Aug 1;88(3):260-4.

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.

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)

Show Me Your Lipids!

If you have great HDLs please let me know your HDLs and lipid panel!

If you have an LDL particle size and count, as Robb Wolf suggests getting at his Crossfit Nutrition certifications (yes, I am certified . . . be scared), that would be bangin as well...

HDL2 = Quintessional Regression Particle and Ways To Maximize It

It's true. We do use some statins at TYP. Primarily they may have value until insulin resistant/hyperinsulinemia/Metabolic situations are improved via diet, hormone, vitamin D, and exercise/wt loss. Also they may have a role for FH (familial hypercholesterolemia) again until diet/lifestyles/vitamin D kick in.

Statins are by no means mandatory for regression or stabilization.

Or maximal health or lifespan extension.

In Dr. Davis' experience, in fact, a great majority of his patients experience statin intolerance and myopathy (muscle pains). Low grade muscle breakdown affects more individuals on statins than probably estimated in the literature. Most of these individuals likely have some kind of mitochondrial dysfunction and/or dietary cholesterol deficiency (and since statins BLOCK CHOLESTEROL SYNTHESIS, the drugs only exacerbate such situations). Muscles cannot function without...cholesterol and its downstream intermediaries...Including... Testosterone... Cortisol. Like 25(OH)D Calcidiol (vitamin D). Like estrogen!! Like DHEA. Like Pregnenolone.


In fact...all the HORMONES that make us what we are. Cholesterol is also a vital component of our BRAIN, myelin sheaths, nervous system, immune system and every cell's membrane.




Statins Indirectly Affect PPAR/Pleiotropy, Therefore Raise HDL2
Statins work marginally because they affect PPAR-alpha. (and other research shows PPAR-gamma as well HERE and HERE)

Recall, again, saturated fats and fish oil hit this receptor known as PPAR too. PPAR is the master controller of pleiotropic actions in our body. PPAR controls CETP reduction and PTLP maximization also.

Pleiotropic PPAR properties: endothelial function, oxidized low-density lipoprotein, inflammation, plaque stability, vascular remodeling, hemostasis/coagulation, vasomotor, cardiac muscle, anti-arrhythmic, and nervous system (brain and conduction pathways to the heart, organs, muscles)

Power up your PPAR...and you will attain immortality.




Not with statin monotherapy.
Clinical significance of pleiotropic effects of statins: lipid reduction and beyond.
Comprehensive lipid management versus aggressive low-density lipoprotein lowering to reduce cardiovascular risk.
Non-lipid effects of statins: emerging new indications.
Statin pleiotropy: fact or fiction?
Ongoing clinical trials of the pleiotropic effects of statins.
Beyond lipid lowering: the role of statins in vascular protection.
[Statins: intervention studies, facts and perspectives] "Questions still remain unanswered. To what extent do we have to lower LDL-cholesterol? What are the risks of an aggressive treatment with statins?"

In fact, a recent EBT trial by Raggi et al (2009 Atherosclerosis) lead to conclusions by leading cardiologists that LDL and LDL-reduction really have nothing to do with plaque.
Non-HDL cholesterol is strongly associated with coronary artery calcification in asymptomatic individuals.



If you have Lp(a), a toxic sticky lipoprotein that accelerates many diseases including coronary and vascular calcifications, then statins won't help you at all. In fact, anecdotally, certain high dose statins (like Lipitor) make Lp(a) concentrations higher. Studies estimate that 17-25% of the population are carriers of Lp(a). I estimate that a much greater percentage have this. In fact, all Metabolic Syndrome individuals appear to me to display very accelerated heart disease even if only a small amount of Lp(a) is present (for instance 6-20 mg/dl). What lowers Lp(a)? Everything that raises HDL2 naturally and non-synthetically. (Not statins, not Zetia, not Fibrates; Actos, a PPAR-gamma drug, a little; fish oil, fats, forgoing carbs/grains -- A LOT)
Increased lipoprotein(a) in metabolic syndrome: is it a contributing factor to premature atherosclerosis? Y E S

The below authors discuss: "bezafibrate as a pan-PPAR activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism, insulin sensitivity and pancreatic beta cell protection. Because fibrates, niacin, ezetimibe, omega-3 fatty acids..."
Optimal management of combined dyslipidemia: what have we behind statins monotherapy?

In addition to niacin and omega-3 fats, how about other dietary fats/IF/strength training/anaerobic exercise/LC-diet?

*sigh* ....the best pan-PPAR activators...





HDL2 is Cardioprotective

We like HDL2 at TYP.

HDL2 is like wealth and health...You can never have too much balanced wealth or balanced health!

HDL2 is in fact an antioxidant and provides immunoprotection as well as cardioprotection. One of the labs ordered at TYP to assess health status is the NMR (or VAP) which separate out the lipoproteins by size and density and provide a 'count' of the absolute number of particles. The larger the particles, the better. HDL2 is one of the largest, most buoyant particles, and most desirable.

The more dense, the more deadly. Like dense fuddy-duds, we don't like dense particles. Read more at TYP here (members now; later free).

These are all good: HDL2, HDL1, LDL2, LDL1, Large-HDL, Large-LDL

Bad: sdLDL (small dense LDL), HDL3, Small-HDL, LDL3, Small-LDL



Jimmy Moore recently interviewed our beloved Dr. Davis. Jimmy's Large-LDL (and presumably HDL2's) are phenomenal!! He reported that he had virtually no small dense LDL -- it's all large -- the good stuff.

Jimmy's labs aren't dense!

Strong work Jimmy!!
http://heartscanblog.blogspot.com/2009/01/another-interview-with-livin-la-vida.html




Many things increase HDL2...


PPAR-alpha drugs, like Fibrates, do certainly hit PPAR -- but not in a natural configuation because these are synthetic/FAKE chemical entities. Fibrates artificially increase total HDL but have been shown adversely affect the particle sizing. They increase HDL3 and lower HDL2.

wtf... bad bad bad...

This explains why fibrate trials are like statin trials. So far only a very limited reduction in mortality, obstructive events and interventions have been demonstrated: approx only 15-25% reductions in CAD.

Remember, it's not the quantity of HDL you have, it's the quality of HDL subparticles -- large v. small.

You don't want... s m a l l. Or dense.

Like small muscles...where's the (sex) appeal?

What's the...point?


These researchers from Switzerland 'get it'... (sorta -- they still push pharmaceuticals *sigh*) "Recent findings suggest that the mechanism of HDL modification rather than a sole increase in HDL-C determines the efficacy of anti-atherosclerotic drug therapy. " Yes, these are my observations from the medical literature and at TYP. The ones who fail to achieve stablization or regression have VERY HIGH HDL-3 and VERY very low HDL-2. Their CAC progresses 10%+ annually and they are befuddled.
Modulation of high-density lipoprotein cholesterol metabolism and reverse cholesterol transport.
Marine lipids normalize cholesteryl ester transfer in IDDM.
Change in alpha1 HDL concentration predicts progression in coronary artery stenosis.



Statins work to regress plaque by affecting PPAR receptors in our body. Yes, LDL reduction is part of their novelty but by and large the regression pattern is secondary to its significant anti-inflammatory effects (via PPAR) and its plaque remodeling effects (via PPAR) and HDL-2 raising effects (via PPAR).

These encompass all the pleiotropic actions of PPAR.

PPAR is powerful.

(And who knows? Statins may help regress plaque by raising vitamin D blood levels as well. Yes, indeedddeeyyy, statins raise [25(OH)D] HERE and HERE.)

Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I.
The effects of statins on high-density lipoproteins.
Comparing the effects of five different statins on the HDL subpopulation profiles of coronary heart disease patients.




Low-Fat, Low-Muscle, and HIGH-CARBS Lower HDL2

What degrades HDL2??
--AHA Low Fat/Step 2 diet -- makes you dense, your particles, I mean--Exercise deficiency or excessiveness (eg, overtraining)
--Lack of lean muscle tissue
--Preponderance of belly/visceral fat
--Excessive insulin
--Cortisol (stress)
--Carbs carbs carbs (high carb, grain-based diet)
--Soda, fructose (esp high fructose corn syrup), excessive fruit, grains, wheat (which also triggers stress responses), processed foods, cereal, etc
--Drugs/pharmaceuticals (Zetia, Lipitor high dose, statins high dose, Fibrates: Lopid/gemfibrozil, Tricor/fenofibrate)
--Insufficient dietary cholesterol, fish oil, monoun- or saturated fat intake
--Smoking
--Excessive alcohol (2-3 or more drinks for men; 2 or more, women)


What raises HDL2?
--The paleo prescription, eg, this blog, TYP and other resources--Niacin (see below)
--Intermittent fasting
--Generation of ketone bodies (low carb, mod-high prot/fat)
--Starvation
--Exercise (avoid excessive endurance training)
--Strength/resistance training
--Reduction in belly/visceral fat
--Reduction in insulin (eliminating wheat, reducing carbs)
--Tobacco cessation
--Elimination/moderation of alcohol
--Eating protein, esp Leucine, Taurine, etc
--Vitamin D (see Dr. Davis' blog)
--Carotenoids (astaxanthin, krill oil, seafood, grassfed meat, etc)
--Fish oil/EPA+DHA: supplemention, grassfed meat/dairy; fatty fish, mackerel, tuna, herring, hamachi, trout, cod liver oil, mollusks, krill, crustaceans, etc
--[If high inflammatory state: Ultra high dose 8-10 g/day EPA DHA fish oil for 6-18mos (Goal: fatty acid profile test, omega-6 to omega-3 ratio = 1.5)]
--ALA, monounsat fats: flaxseed oil, olive oil, nuts/seeds, etc
--Casein-free butter oil (rich in phytosterols, vitamin K2, CLA, short-chain and medium-chain saturated fatty acids, EPA+DHA and a bounty of other HDL-boosting nutritional factors); organic, grassfed ghee
--Eating some saturated fats (not TRANSFATS which are toxic to HDL2)
--Eating some CHOLESTEROL (via omega-3 eggs, seafood, grassfed meat/dairy, etc)






Niacin and HDL2

Remember niacin increases HDL2 by 200-300% (and reduces HDL3) in a 18-36 mos period of time... (niacin works indirectly on PPAR too)

Crestor only increases HDL2 by 21%??


Is that why Niacin (+low dose simvastatin) resulted in a 90% reduction in mortality and heart events in the unprecedented HATS trial?
Niacin-based therapy for dyslipidemia: past evidence and future advances.
Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia.


May it have anything to do with HDL2 subfractions increasing by 10 - 20 xxx with Niacin Therapy vs. Statin Monotherapy??!

Ten to twenty TIMES greater HDL2 increases...WOWO.

Why do statins fail to STACK UP when compared to niacin???

Billions of dollars have been pored into research (which is great and we're all grateful) but still they fail to regress/stabilize plaque as durably and effectively as Niacin, a common B vitamin which costs $12.99 for #150 tablets at Costco.

Why does Niacin trump all statins?

Niacin trumps Crestor, gorilla-statin... which can have gorilla effects on muscle soreness and kidney failure (via increases MMP-9 in the kidneys; unless one is taking fish oil/vitamin D which reduce systemic MMPs).




Fish Oil and HDL2

Of course, Fish Oil trumps statins in regression as well.

It's a dose dependent and time dependent effect.

(is more better? sorta. depends on your inflammatory status. if you have unstabilized CAD or an autoimmune disorder or cancer, you are inflammed.)
Here is one 1999 double-blind RCT in coronary male patients where low dose ~3 g/d EPA+DHA for 3 mos then switched to low, LOW dose 1.6 g/d EPA+DHA for 21 mos showed more regression than placebo . The Germans are always advanced with CAM (complementary alternative medicine).

The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial.

von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H.
Ann Intern Med. 1999

RESULTS: Pairs of angiograms (one taken at baseline and one taken at 2 years) were evaluated for 80 of 112 placebo recipients and 82 of 111 fish oil recipients.

At the end of treatment, 48 coronary segments in the placebo group showed changes (36 showed mild progression, 5 showed moderate progression, and 7 showed mild regression) and 55 coronary segments in the fish oil group showed changes (35 showed mild progression, 4 showed moderate progression, 14 showed mild regression, and 2 showed moderate regression) (P = 0.041).

Loss in minimal luminal diameter, as assessed by quantitative coronary angiography, was somewhat less in the fish oil group (P greater than 0.1).

Fish oil recipients had fewer cardiovascular events (P = 0.10); other clinical variables did not differ between the study groups.

Below: 4.5 g/d x6wks EPA+DHA resulted in a 74% HDL2 increase with a concomitant 19% decrease of HDL3-C
Omega-3 fatty acids selectively raise high-density lipoprotein 2 levels in healthy volunteers.

Below: 4 g/day x6wks DHA only related to 29% increased HDL2 (EPA 4 g/day only reduced HDL2 6.7%) in Obese Men
Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men.


Below: 4 g/day x8wks EPA+DHA induced 40% increase HDL2 and reduction in HDL3 (this condition has genetically low HDL/high TG)
An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia.


Below: 6 g/d EPA+DHA x12 wks increased HDL2 47.8% (reduced HDL3 6.6%)
Dose-response effects of fish-oil supplementation in healthy volunteers.





Fish Oil and Genetics

Fish oil may be even more tremendously beneficial for those with apoE4 (eg, the Alzheimer marker). ApoE4 has also been implicated in the pathogenesis of heart disease and other vascular diseases. In the below trial, low dose fish oil 0.7g/day EPA DHA, compared with higher dose 1.8 g/ day, was also effective at lower TG and raising HDL, especially in men.

Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study.
Caslake MJ, Miles EA, Kofler BM, Lietz G, Curtis P, Armah CK, Kimber AC, Grew JP, Farrell L, Stannard J, Napper FL, Sala-Vila A, West AL, Mathers JC, Packard C, Williams CM, Calder PC, Minihane AM.
Am J Clin Nutr. 2008 Sep;88(3):618-29.