"It takes a wise doctor to know when to prescribe, and at times the greater skill consists in not applying remedies."
B. Gracian
The Art Of Worldly Wisdom
Over-Medication
Judicious use of medications can bring about therapeutic outcomes or can have dire consequences. In medicine, it is truly an art form to balance the two, more than a science. Science however can provide a better understanding of what ancient doctors like Hippocrates or others in the last half century have known as wisdom and deep experience showed them.
'Mindless Statinators'
(Thanks Barkeater for that phrase) Growing evidence shows that statins have 'differential' effects on people who take them. The lower the insulin resistance, the less the small LDL particles are reduced. In fact, two studies have shown that the most potent statin Crestor/rosuvastatin in fact raises small LDL concentrations when Triglycerides (TG, Trig) are less than 120 mg/dl (see first table, above, Kostapanos MS et al. Clin Ther 2007).
Or if Trigs are less than 88 mg/dl(1.0 mmol/L)... (see below Caslake MJ et al. Atherosclerosis 2003)
Or if Trigs are less than 177 mg/dl (2.0 mmol/L)... (see below, significant data points sdLDL% increased)
WOWO. Trigs are low in nearly all low-carb compliant TYP'ers! And definitely 100% of people on low carb PALEO.
Crestor is QUITE potent.
At 40mg daily it is THE most potent statin on the market for sledge-hammering down all the LDL particles (large v. small). Caslake et al (Table 2) found that for normotriglyceridemic individuals LDLIII (small dense) % increased from 15.3% to 21.9% (delta = +6.6% sdLDL%) after 8wks only on Crestor 40mg daily (see below graph with comments, the authors failed to put zero on the x-axis...wtf. So please look at how sdLDL increases as the Trigs are less than 88 mg/dl = 1.0 mmol/L).
Terrible counterproduct, ANTI-REGRESSIVE adverse drug effect.
TYP Goal for Regression: small LDL NEAR-ZERO or downward trend The goal for combatting heart disease and to invoke regression/ reversal/ eradication of plaque is to achieve a lower concentration of small dense LDL. Regression on EBT is seen even before TYP goals are met! Like dense ignorant people, we want the least amount of density and a transformation to lighter, more buoyant, more athero-protective LDL particles.
Statins can hurt people as we know (myositis, peripheral nerve effects, brain damage, etc).
Statins in fact can hinder EBT regression I strongly believe and examples unfortunately exist (the REGRESSION 10yr-subanalysis is an example of higher mortality on statins where Trigs were low). When the individual temporarily stops or backs off on the dose, the large LDL appear and the concentration of small LDL (in other words, the sdLDL%) decrease. The sdLDL is not exceptionally great compared to results from low LOW carb, mod-high fat diets or ketotic diets, but they DO IMPROVE noticeably. One individual had sdLDL%=700/700=100% improve to 700/900= 78% after stopping Crestor for 1-2mos (Trigs were maintained and were excellent less than 88 mg/dl without the aid of Crestor).
EBT Calcification Progression? Y E S . I see statins continue to allow coronary calcification progression on EBT when these drugs are overused when Trigs hit Dr. Davis' TYP goal of less than 60 mg/dl. To achieve EBT regression, dramatic reductions in sdLDL concentration are necessary. Most with coronary disease have ALL small dense LDL particles. One hundred percent is not uncommon at the start of a TYP progrm.
To reach Dr. Davis' goal of 10% (or even 30%) concentration of sdLDL, those with heart disease need 70 to 90% reduction in sdLDL%. This is not occuring in those who persist in over-statinating when the Trigs are excellent less than 150 mg/dl. The signs and symptoms of over-statinating are subtle. They involve persistly high sdLDL concentrations that do not decrease with TYP strategies, low carb dieting and even the addition of fats (omega-3, eggs, coconut oil, krill oil, etc). In fact, sometimes (yikes!) the statin effect appears to lead to HIGHER small LDL particle counts. Sadly these individuals (to me... IMHO) have disappointing EBT progressions of 10-25% despite all their wonderful, hard work, good intentions and optimism.
Those who are statin-less (Mr. 'H', Mr. 'C', Dr. 'K') on the other hand witness large sdLDL% reductions with each NMR or VAP lipoprotein test, perfect increases in large LDL and beautiful reductions in small LDL (even 'NONE') and consequently they often report EBT regression. 'Pretty lipoproteins' do not equal regression... it is how the pretty lipoproteins are achieved and the trends with the minimization of iatrogenic drug effects.
All Statins Increase Small Dense LDL If Trigs Are Low Crestor is not alone.
The other statins are NOT exempt.
Lipitor does it too.
They are in fine company. The off-patent generic statins do it as well.
No Starches, High Fat Diet in 6 wks lowers sdLDL% by (-)10% I will review this in more detail later but this short trial excellently demonstrates the efficacy and safety for post-CAD-event men and women of a ketotic diet in producing dramatic lipoprotein changes in only 6wks by eliminating starches and restricting fruit and increasing protein and dietary cholesterol and fat. Concentrations of small dense LDL reduced from 35% to 25%. These patients were on lipid-lowering medications and the average LDL was 100 mg/dl (not high whopper doses of statins apparently).
Effect of a high saturated fat and no-starch diet on serum lipid subfractions in patients with documented atherosclerotic cardiovascular disease.Hays JH, DiSabatino A, Gorman RT, Vincent S, Stillabower ME.Mayo Clin Proc. 2003 Nov;78(11):1331-6.
ReferencesA 12-week, prospective, open-label analysis of the effect of rosuvastatin on triglyceride-rich lipoprotein metabolism in patients with primary dyslipidemia.(A significant increase in mean LDL particle size after rosuvastatin treatment (mean [SD], from 26.4 [0.4] to 26.9 [0.4] rim; P = 0.02) was observed only in patients with baseline TG levels greater than or =120 mg/dL.)
Kostapanos MS, Milionis HJ, Filippatos TD, Nakou ES, Bairaktari ET, Tselepis AD, Elisaf MS.
Clin Ther. 2007 Jul;29(7):1403-14.
PMID: 17825691
Phenotype-dependent and -independent actions of rosuvastatin on atherogenic lipoprotein subfractions in hyperlipidaemia. Caslake MJ, Stewart G, Day SP, Daly E, McTaggart F, Chapman MJ, Durrington P, Laggner P, Mackness M, Pears J, Packard CJ.
Atherosclerosis. 2003 Dec;171(2):245-53.
PMID: 14644393
Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study).(Lipitor raises sdLDL% !!wtf, Crestor largely does not lower sdLDL concentrations much UNLESS NIACIN IS ON BOARD; Both Crestor and Lipitor !!wtf raise Lp(a), the most toxic, atherosclerosis-accelerating blood component carried by 17-25% of the general population) McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, McGovern ME.
Atherosclerosis. 2007 Jun;192(2):432-7. Epub 2007 Jan 19.
PMID: 17239888
Baseline triglyceride levels and insulin sensitivity are major determinants of the increase of LDL particle size and buoyancy induced by rosuvastatin treatment in patients with primary hyperlipidemia. Kostapanos MS, Milionis HJ, Lagos KG, Rizos CB, Tselepis AD, Elisaf MS.
Eur J Pharmacol. 2008 Aug 20;590(1-3):327-32. Epub 2008 Jun 7.
PMID: 18585701
Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels.(Table 3 shows Lipitor INCREASES wtf sdLDL% +10% and Crestor 40mg makes virtually no change in sdLDL% at this dose (-5%)) Ai M, Otokozawa S, Asztalos BF, Nakajima K, Stein E, Jones PH, Schaefer EJ.
Am J Cardiol. 2008 Feb 1;101(3):315-8. Epub 2007 Dec 20.
PMID: 18237592
Over-Medication
Judicious use of medications can bring about therapeutic outcomes or can have dire consequences. In medicine, it is truly an art form to balance the two, more than a science. Science however can provide a better understanding of what ancient doctors like Hippocrates or others in the last half century have known as wisdom and deep experience showed them.
'Mindless Statinators'
(Thanks Barkeater for that phrase) Growing evidence shows that statins have 'differential' effects on people who take them. The lower the insulin resistance, the less the small LDL particles are reduced. In fact, two studies have shown that the most potent statin Crestor/rosuvastatin in fact raises small LDL concentrations when Triglycerides (TG, Trig) are less than 120 mg/dl (see first table, above, Kostapanos MS et al. Clin Ther 2007).
Or if Trigs are less than 88 mg/dl(1.0 mmol/L)... (see below Caslake MJ et al. Atherosclerosis 2003)
Or if Trigs are less than 177 mg/dl (2.0 mmol/L)... (see below, significant data points sdLDL% increased)
WOWO. Trigs are low in nearly all low-carb compliant TYP'ers! And definitely 100% of people on low carb PALEO.
Crestor is QUITE potent.
At 40mg daily it is THE most potent statin on the market for sledge-hammering down all the LDL particles (large v. small). Caslake et al (Table 2) found that for normotriglyceridemic individuals LDLIII (small dense) % increased from 15.3% to 21.9% (delta = +6.6% sdLDL%) after 8wks only on Crestor 40mg daily (see below graph with comments, the authors failed to put zero on the x-axis...wtf. So please look at how sdLDL increases as the Trigs are less than 88 mg/dl = 1.0 mmol/L).
Terrible counterproduct, ANTI-REGRESSIVE adverse drug effect.
TYP Goal for Regression: small LDL NEAR-ZERO or downward trend
The goal for combatting heart disease and to invoke regression/ reversal/ eradication of plaque is to achieve a lower concentration of small dense LDL. Regression on EBT is seen even before TYP goals are met! Like dense ignorant people, we want the least amount of density and a transformation to lighter, more buoyant, more athero-protective LDL particles.
Statins can hurt people as we know (myositis, peripheral nerve effects, brain damage, etc).
Statins in fact can hinder EBT regression I strongly believe and examples unfortunately exist (the REGRESSION 10yr-subanalysis is an example of higher mortality on statins where Trigs were low). When the individual temporarily stops or backs off on the dose, the large LDL appear and the concentration of small LDL (in other words, the sdLDL%) decrease. The sdLDL is not exceptionally great compared to results from low LOW carb, mod-high fat diets or ketotic diets, but they DO IMPROVE noticeably. One individual had sdLDL%=700/700=100% improve to 700/900= 78% after stopping Crestor for 1-2mos (Trigs were maintained and were excellent less than 88 mg/dl without the aid of Crestor).
EBT Calcification Progression? Y E S .
I see statins continue to allow coronary calcification progression on EBT when these drugs are overused when Trigs hit Dr. Davis' TYP goal of less than 60 mg/dl. To achieve EBT regression, dramatic reductions in sdLDL concentration are necessary. Most with coronary disease have ALL small dense LDL particles. One hundred percent is not uncommon at the start of a TYP progrm.
To reach Dr. Davis' goal of 10% (or even 30%) concentration of sdLDL, those with heart disease need 70 to 90% reduction in sdLDL%. This is not occuring in those who persist in over-statinating when the Trigs are excellent less than 150 mg/dl. The signs and symptoms of over-statinating are subtle. They involve persistly high sdLDL concentrations that do not decrease with TYP strategies, low carb dieting and even the addition of fats (omega-3, eggs, coconut oil, krill oil, etc). In fact, sometimes (yikes!) the statin effect appears to lead to HIGHER small LDL particle counts. Sadly these individuals (to me... IMHO) have disappointing EBT progressions of 10-25% despite all their wonderful, hard work, good intentions and optimism.
Those who are statin-less (Mr. 'H', Mr. 'C', Dr. 'K') on the other hand witness large sdLDL% reductions with each NMR or VAP lipoprotein test, perfect increases in large LDL and beautiful reductions in small LDL (even 'NONE') and consequently they often report EBT regression. 'Pretty lipoproteins' do not equal regression... it is how the pretty lipoproteins are achieved and the trends with the minimization of iatrogenic drug effects.
All Statins Increase Small Dense LDL If Trigs Are Low
Crestor is not alone.
The other statins are NOT exempt.
Lipitor does it too.
They are in fine company. The off-patent generic statins do it as well.
No Starches, High Fat Diet in 6 wks lowers sdLDL% by (-)10%
I will review this in more detail later but this short trial excellently demonstrates the efficacy and safety for post-CAD-event men and women of a ketotic diet in producing dramatic lipoprotein changes in only 6wks by eliminating starches and restricting fruit and increasing protein and dietary cholesterol and fat. Concentrations of small dense LDL reduced from 35% to 25%. These patients were on lipid-lowering medications and the average LDL was 100 mg/dl (not high whopper doses of statins apparently).
Effect of a high saturated fat and no-starch diet on serum lipid subfractions in patients with documented atherosclerotic cardiovascular disease.Hays JH, DiSabatino A, Gorman RT, Vincent S, Stillabower ME.Mayo Clin Proc. 2003 Nov;78(11):1331-6.
References
A 12-week, prospective, open-label analysis of the effect of rosuvastatin on triglyceride-rich lipoprotein metabolism in patients with primary dyslipidemia.(A significant increase in mean LDL particle size after rosuvastatin treatment (mean [SD], from 26.4 [0.4] to 26.9 [0.4] rim; P = 0.02) was observed only in patients with baseline TG levels greater than or =120 mg/dL.)
Kostapanos MS, Milionis HJ, Filippatos TD, Nakou ES, Bairaktari ET, Tselepis AD, Elisaf MS.
Clin Ther. 2007 Jul;29(7):1403-14.
PMID: 17825691
Phenotype-dependent and -independent actions of rosuvastatin on atherogenic lipoprotein subfractions in hyperlipidaemia.
Caslake MJ, Stewart G, Day SP, Daly E, McTaggart F, Chapman MJ, Durrington P, Laggner P, Mackness M, Pears J, Packard CJ.
Atherosclerosis. 2003 Dec;171(2):245-53.
PMID: 14644393
Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study).(Lipitor raises sdLDL% !!wtf, Crestor largely does not lower sdLDL concentrations much UNLESS NIACIN IS ON BOARD; Both Crestor and Lipitor !!wtf raise Lp(a), the most toxic, atherosclerosis-accelerating blood component carried by 17-25% of the general population)
McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, McGovern ME.
Atherosclerosis. 2007 Jun;192(2):432-7. Epub 2007 Jan 19.
PMID: 17239888
Baseline triglyceride levels and insulin sensitivity are major determinants of the increase of LDL particle size and buoyancy induced by rosuvastatin treatment in patients with primary hyperlipidemia.
Kostapanos MS, Milionis HJ, Lagos KG, Rizos CB, Tselepis AD, Elisaf MS.
Eur J Pharmacol. 2008 Aug 20;590(1-3):327-32. Epub 2008 Jun 7.
PMID: 18585701
Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels.(Table 3 shows Lipitor INCREASES wtf sdLDL% +10% and Crestor 40mg makes virtually no change in sdLDL% at this dose (-5%))
Ai M, Otokozawa S, Asztalos BF, Nakajima K, Stein E, Jones PH, Schaefer EJ.
Am J Cardiol. 2008 Feb 1;101(3):315-8. Epub 2007 Dec 20.
PMID: 18237592