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 everycell'smembrane.
Statins Indirectly Affect PPAR/Pleiotropy, Therefore Raise HDL2
Statins also 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!! Strong work Jimmy!!
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 lowerHDL2.
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... small. Or dense.
Like small muscles...where's the (sex) appeal?
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].)
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.
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
--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
--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)
--Generation of ketone bodies (low carb, mod-high prot/fat)
--Exercise (avoid excessive endurance training)
--Reduction in belly/visceral fat
--Reduction in insulin (eliminating wheat, reducing carbs)
--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 - 20xxx 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.
Below: 4.5 g/d x6wks EPA + DHA resulted inHDL2 increase of 74% 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 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.