The NCEP/ATP III Cholesterol Guidelines Bogus: 'Cholesterol Limits Lose Their Lustre'
Conventional
medicine at this time uses Big Pharma-funded assessment and treatment
guidelines which promote the use of statins as first line in order to
'treat' the LDL (goal less than 70, 100, or 130
mg/dl) to targets based on risk stratification, e.g. age, prior family
history coronary events, low HDL, smoking and presence of
hypertension.
What are the true root causes of these 'risk factors' in light of evolution (if you believe in evo)? Is LDL really 'bad'?
Indeed.
Hormonal
havoc and energy balance dysregulation caused by neolithic excess of
refined n-6 vegetable oils, high fructose GMO-corn syrup, intestinal
permeability, refined carbohydrates, sugar,
mercury/arsenic/lead/cadmium, gut dysbiosis, failures of vitamin/mineral
absorption by the action of phytates and lectins, and
endocrine-disrupting consequences of pesticides and other environmental
persistent-organic toxins are more likely factors.
And they have nothing to do with LDL. Half of heart attacks occur in individuals where the LDL is already less than 70 mg/dl.
The old cholesterol guidelines NCEP/ATP-III that were first put out over a decade ago are now being revamped. Nature has a new article on the future NCEP/ATP-IV.
'Since
2002, when ATP III called on doctors to push LDL levels below set
targets, the concept of low cholesterol has become synonymous with heart
health. Patients brag about their cholesterol scores, physicians joke
about adding statins to drinking water, and some hospitals reward
doctors when patients hit cholesterol targets.'
~~~~~~~~~~~~~~~~~
LDL Affected by Apo E Alleles
Amount of LDL-C and LDL-P Determined by ApoE
We
each individually and uniquely have widely varied lipoprotein patterns
(LDL, TG, HDL) determined by our genetics, the microniche our
ancestors evolved and survived in, and our apolipoprotein E. Apo E is
mainly found in HDL and LDL particles but also free form in the
circulation as well. It aids lipoprotein particles in docking up to
cell membranes to unload contents into a destination cell or the liver.
Apo E determines the LDL-quantity. Three alleles for apoE exist and we each have 2 copies from a mix from our parents - E2, E3 or E4. ApoE
to me is like a special key to unlock troubled doors. Those with E4
alleles have lipoproteins with the least apoE (perhaps true H-G, more
cholesterol hung out longer in circulation).
Geographically the incidence of E4 rises toward a northern distribution in Europe, away from the equator.
Those
with E2, more apoE (perhaps more agarian adapted). Energy flux
patterns and metabolism are mildly different: E4, more carbohydrate
sensitive; E2, less.
Many
'cardiac' rat models use apoE-deficient mice because these animals
inevitably develop horrific plaque and atherosclerotic disease and
blocked arteries, on high carb rat chow.
The
lower the apo E alleles, the lower the total cholesterol [ref 2]. The
researchers (above) demonstrate the LDL and HDL trend in parallel with
total cholesterol and the higher the E. Conversely, triglycerides grow
higher, the lower the apo E.
It
seems finally that the medical community be viewing the true science
and questioning the BS. If LDL is genetically determined by the apoE
type and is a false coronary risk factor, then what is the true cause of
coronary events, MIs, angina and plaque destabilization?
Naturally
if one is apoE 4/4 (rare), then one is likely to have the highest LDL
amongst friends and aquaintances. Is it harmful? Depends. ApoE 4/4 are
more likely to be HIGHLY insulin resistant, inflamed and carbohydrate
sensitive. In the modern industrial environment where whole food,
ancestrally-inclined meals are endangered species... perhaps.
Are
apoE 4/4 the true survivors of Earth? They are less likely to suffer
from infections or starvation which were the major reasons for mortality
outside of predation prior to neolithic times. Add to that vascular
protection from Lp(a) from vitamin C-deficiency hemolysis and one has a
winning combination for longevity given the right circumstances when
inflammation is well regulated and gene-protein expression optimal.
The higher the LDL, the higher the Lp(a), the better survival?
Size of LDL Determined by Diet and Lifestyles: Microecological Niche
Environment dictates the LDL-particle-size.
Exercise, high saturated fat, cholesterol-intake, low carb, low
fructose, low omega-6/omega-3 ratio and antioxidants/flavonoids are
factors that high influence and create more large, buoyant,
resistant-to-oxidation LDL-particle-sizes, despite apoE status.
LDL Less Than 70 mg/dL is Dangerous
So why are cardiac 'experts' prescribing a one-size-fits-all LDL goal of less than 70 mg/dl and statins
for all individuals with heart disease, diabetes, aneurysms, chronic
kidney disease, and other atherosclerotic equivalents?
Does this take into account apoE status and genetically-predetermined LDL amounts?
An LDL less than 70 mg/dl is not magic. At TYP, very rarely did I observe CAC Agatson coronary artery calcification reversal. Members were on potent statins or suppressed their LDL to (unnatural) goals of 60 mg/dl.
Seth Roberts did achieve reversal, by consuming cholesterol (butter). No pharmaceuticals.
I
have noticed countless, sad times where statins do nothing to regress
or stop the progression plaque. In fact, they are associated with
progression in 12 out 14 published coronary calcification studies.
Many
studies show that statins are also highly associated with cancer,
increased incidence of congestive heart failure (CHF), accidents,
violent death, depression/suicide, and all-cause mortality.
Low
cholesterol and low LDL, independently, additionally are significantly
correlated to cancer, increased incidence of chronic heart failure and
all-cause mortality.
Let's probe this... because statins lost their allure years ago for me.
Overview of Transporters
Every
vital vitamin, hormone and steroid exists both 'free' and available in
the blood circulatory system and bound to degrees to a transporter-protein. Some vitamins, hormones and steroids interact directly with receptors on cell membranes and other cases the transporter-protein
interacts with receptors on cell membranes to translocate the vitamin,
hormone or steroid into the cell. From the gut to the liver, food gets
processed into free fatty acids, triglycerides (3 fatty acids attached
to one sugar backbone) and bundled into particles with antioxidants
for circulation and storage in peripheral tissues like the muscles,
adipose, gonads, and adrenals.
Cholesterol
Every
cell membrane is composed of cholesterol -- this is the asphalt and
infracture of our communication highways. Another way to appreciate
these conductors of electronic charge is to recognize that cholesterol
in our cellular membranes is analogous to the DSL or Comcast cables of
our high-speed computers, our brain and nervous systems.
How do 'dropped signals' feel? Perhaps your cholesterol is impaired?
Roles of cholesterol:
a) formation of cellular walls
b) formation of aldosterone (important for blood pressure regulation)
c) formation of the sex hormones
d) formation of Vitamin D
e) formation of bile to eliminate and recycle wasted and precious fat-soluble molecules
f) formation of corticosteroids which are involved with glucose regulation and suppressing inflammation
g) formation of steroidal derivatives including the vital and potent antioxidant Ubiquinol/ CoenzymeQ10
h) antioxidant with scavenger functions for harmful microbial endotoxins
Without
cholesterol, humans cannot survive, brain and organ function
deteriorate, and eventually cancer and other inflammatory conditions are
triggered. Without sufficient cholesterol, cortisol, testosterone,
progesterone, estrogens and other potent steroidal hormones cannot be
made.
Statins Lower Testosterone
As
one would expect, statin pharmaceuticals which block the rate-limiting
enzyme for cholesterol production in the liver and all extrahepatic
sites (e.g. BRAIN, ADRENALS, TESTICLES, etc), HMG-CoA reductase, are
highly associated in reduction of total testosterone and subsequent low
testosterone signs and symptoms [ref 3-9].
Low
testosterone is also considered a risk factor for heart disease due to
the inflammatory state that occurs including obesity, metabolic
syndrome, hyperinsulinemia, poor immunity and diabetes[ref 7]. I
question the prudence in the strategy behind initiating a statin and
potentially lowering testosterone further, thereby inducing yet another cardiac risk factor. Would you like to be a eunuch?
Diabetic eunuch? Chuckle with Peter at Hyperlipid:
Sta'ins, CoQ, diabetes and Dr Andreas Eenfeldt's link
Ancient Transporters
Our
lymphatics and blood vessels form the highways that transport
nutrition, oxygen and necessary constituents for organ maintenance and
rebuilding. They also remove wastes, CO2 and recycled cellular parts and
spent steroid hormones for elimination via the gut or 'recycling' via
enterohepatic recirculation.
How
are antioxidants, pro-vitamins, vitamins, pro-hormones and hormones
from our food and endocrine glands/tissues carried to the peripheral
sites? Ancient tranports have evolved (if you believe in evolution) in
all living systems for the role of carrying these items to the
appropriate target tissues.
Vitamin A (retinol): free and bound to RBP (retinol-binding protein)
Vitamin D (cholecalciferol): free and bound to VDBP (vitamin D binding protein, aka Gc globulin)
Estrogen (E1 E2 E3): free and bound to SHBG (sex-hormone binding globulin) and EBP (estrogen-binding protein)
Testosterone, DHT: free and bound to SHBG and ABP (androgen-binding protein)
Progesterone: free and bound to SHBG and PBP (progesterone-binding protein)
DHEA: free and bound in HDL particles
Cortisol: free and bound to CBP (cortisol binding protein)
Ubiquinol/CoQ10: bound in HDL and LDL
Menaquinones (MK4 to 9; vitamin K2): bound in HDL and LDL
Retinoids (vitamin A): bound in HDL and LDL
Carotenoids (vitamin A): bound in HDL and LDL
Tocopherols, tocotrienols (vitamin E): bound in HDL and LDL
Minerals - iodine zinc selenium copper: Free form and bound in HDL and LDL
Cholesterol: Free form and bound as Esters in HDL and LDL
See prior animal pharm: LDL, HDL Transporters
Purpose of LDL and HDL Transporters: Evo Perspective
Lipid
transport and delivery systems existed in the earliest animals
including insects. Our lipoprotein systems are not that dissimilar [ref
1]. Fat-soluble nutrients like cholesterol, carotenoids, vitamin E and
coenzyme Q10 would form a two-layered oil-vinegar like concoction in
our blood circulatory system if it were not for specialized transporters for fat-like substances.
HDLs
are much more compact and smaller in size than LDL. They fit between
the gap and communication junctions in the endothelium (lining of blood
vessels). Whereas, LDL particles are larger and barely fit between
normal gap junctions of endothelium. If the LDL particles however are
'small' their purpose is different. They are more oxidizable and denser.
This tighter conformation allows movement into damaged endothelium and
traumatized and inflammed tissues to provide ammunitions for
macrophages to do their work and relinquish the waste and end products
for disposal. I don't read French (see below if you do).
Once HDL and LDL are done, they can re-enter the blood stream, return to the liver for future processing.
Ubiquinol Protects Against Failure of the Heart and All Organs
Ubiquinol
is lowered by statins since ubiquinol and its derivatives are
cholesterol structures [ref 19]. Unfortunately ubiquinol is necessary in
all cells and mitochondria where it serves a role as mandatory
antioxidant and a recycling nazi [16-18]. Low ubiquinol in the blood is
associated with faster progression of heart failure [ref 17].
Statins
lower the LDL contents of ubiquinol and all fat-soluble nutrients,
vitamin E and carotenoids. Does this have consequences?
Prior animal pharm: Role of Ubiquinol
Higher the Cholesterol, Higher the CHF Survivorship
Our
understanding of survival and the evolution of insulin resistance
provides the foundation to understand the causes of all diseases of
modern civilizations including CHF. The studies bear this out in which
the higher glucose and higher insulin resistance, the higher the association to mortality in CHF [ref 12-16]. Interestingly several studies demonstrate the lower the cholesterol, the higher the
CHF mortality. Some clinicians raised the potential risks of statins
in light of these adverse outcomes in individuals with CHF [ref 31].
In
patients with progressive CHF, their LDL are all small packages which
can barely hold vital antioxidants like ubiquinol. Add a statin which
deplete the crucial functioning ubiquinol for pumping heart muscles,
spelling catastrophe.
Low Cholesterol Associated With Increased Cancer Incidence: 17-Year Basel Study 
The
prospective 17-year Basel study showed a 2-7 fold increase in cancer
mortality in males at various cancer sites with low serum cholesterol.
This study confirms what some of the other cancer epidemiology studies
have already shown. Researchers tested blood from 2974 participants
stored from 1971-1973. Co-founders such as vitamin blood levels were
adjusted for in the analysis.
Quality will always trump quantity of LDL.
Prior animal pharm: Cardio Controversies -- Tale of 2 LDLs
Carcinogenicity of Statins: The Lower the Final LDL, the Higher Cancer Rate
Finally
the statin and lipid-lowering drug trials themselves have demonstrated
that the lower the cholesterol, the higher mortality from cancer in a
meta-analysis in JACC, 2007 by Alsheikh-Ali et al [ref 27]. Plotting
final LDL with cancer, the graph depicts a firm association between the
lower the LDL and increased cancer incidences.
References:
1. Circulatory lipid transport: lipoprotein assembly and function from an evolutionary perspective.
Van der Horst DJ, Roosendaal SD, Rodenburg KW.
Mol Cell Biochem. 2009 Jun;326(1-2):105-19.
2. Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis.
Dallongeville J, Lussier-Cacan S, Davignon J.
J Lipid Res. 1992 Apr;33(4):447-54.
3. The Effect of Statin Therapy on Testosterone Levels in Subjects Consulting for Erectile Dysfunction.
Corona G, Boddi V, Balercia G, Rastrelli G, De Vita G, Sforza A, Forti G, Mannucci E, Maggi M.
J Sex Med. 2010 Feb 5. [Epub ahead of print]
4. A
multi-center, open label, crossover designed prospective study
evaluating the effects of lipid lowering treatment on steroid synthesis
in patients with Type 2 diabetes (MODEST Study).
Kanat M, Serin E, Tunckale A, Yildiz O, Sahin S, Bolayirli M, Arinc H, Dirican A, Karagoz Y, Altuntas Y, Celebi H, Oguz A.
J Endocrinol Invest. 2009 Nov;32(10):852-6. Epub 2009 Sep 11.
5. Statin therapy is associated with lower total but not bioavailable or free testosterone in men with type 2 diabetes.
Stanworth RD, Kapoor D, Channer KS, Jones TH.
Diabetes Care. 2009 Apr;32(4):541-6. Epub 2008 Dec 29.PMID: 19114614 [PubMed - indexed for MEDLINE]Free PMC ArticleFree text
6. Do statins affect androgen levels in men? Results from the Boston area community health survey.
Hall SA, Page ST, Travison TG, Montgomery RB, Link CL, McKinlay JB.
Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1587-94.PMID: 17684132 [PubMed - indexed for MEDLINE]Free Article
7. Evaluation of the male reproductive organs after treatment with continuous sustained delivery of statin for fracture healing.
Adah F, Benghuzzi H, Tucci M, Russell G, Tsao A, Olivier J, England B.
Biomed Sci Instrum. 2005;41:54-61.
8. Effects of high-dose simvastatin on adrenal and gonadal steroidogenesis in men with hypercholesterolemia.
Dobs AS, Schrott H, Davidson MH, Bays H, Stein EA, Kush D, Wu M, Mitchel Y, Illingworth RD.
Metabolism. 2000 Sep;49(9):1234-8.
9. Testosterone deficiency: a risk factor for cardiovascular disease?
Jones TH.
Trends Endocrinol Metab. 2010 Apr 6.
10. The dark side of testosterone deficiency: III. Cardiovascular disease.
Traish AM, Saad F, Feeley RJ, Guay A.
J Androl. 2009 Sep-Oct;30(5):477-94. Epub 2009 Apr 2. Review.
11. Better
memory functioning associated with higher total and low-density
lipoprotein cholesterol levels in very elderly subjects without the
apolipoprotein e4 allele.
West R, Beeri MS, Schmeidler J, Hannigan CM, Angelo G, Grossman HT, Rosendorff C, Silverman JM.
Am J Geriatr Psychiatry. 2008 Sep;16(9):781-5.
12. [Cholesterol
and glucose levels belong to independent predictors of death and
hospitalizations in patients with chronic systolic heart failure]
Smetanina IN, Deev AD, Gratsianskiĭ NA.
Kardiologiia. 2007;47(8):12-6. Russian.
13. The relationship between cholesterol and survival in patients with chronic heart failure.
Rauchhaus M, Clark AL, Doehner W, Davos C, Bolger A, Sharma R, Coats AJ, Anker SD.
J Am Coll Cardiol. 2003 Dec 3;42(11):1933-40.
14. Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure.
Doehner W, Rauchhaus M, Ponikowski P, Godsland IF, von Haehling S, Okonko DO, Leyva F, Proudler AJ, Coats AJ, Anker SD.
J Am Coll Cardiol. 2005 Sep 20;46(6):1019-26.
15. The relationship between cholesterol and survival in patients with chronic heart failure.
Rauchhaus M, Clark AL, Doehner W, Davos C, Bolger A, Sharma R, Coats AJ, Anker SD.
J Am Coll Cardiol. 2003 Dec 3;42(11):1933-40.
16. Coenzyme Q10: an independent predictor of mortality in chronic heart failure.
Molyneux SL, Florkowski CM, George PM, Pilbrow AP, Frampton CM, Lever M, Richards AM.
J Am Coll Cardiol. 2008 Oct 28;52(18):1435-41.
17. Coenzyme Q10 and statins: biochemical and clinical implications.
Littarru GP, Langsjoen P.
Mitochondrion. 2007 Jun;7 Suppl:S168-74. Epub 2007 Mar 27. Review.
18. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments.
Littarru GP, Tiano L.
Mol Biotechnol. 2007 Sep;37(1):31-7. Review.
19.
The clinical use of HMG CoA-reductase inhibitors and the associated
depletion of coenzyme Q10. A review of animal and human publications.
Langsjoen PH, Langsjoen AM.
Biofactors. 2003;18(1-4):101-11. Review.
20. Effects
of diet and simvastatin on serum lipids, insulin, and antioxidants in
hypercholesterolemic men: a randomized controlled trial.
Jula A, Marniemi J, Huupponen R, Virtanen A, Rastas M, Rönnemaa T.
JAMA. 2002 Feb 6;287(5):598-605.
21. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol.
Stocker R, Bowry VW, Frei B.
Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1646-50.
22. Serum
lipid and antioxidant responses in hypercholesterolemic men and women
receiving plant sterol esters vary by apolipoprotein E genotype.
Sanchez-Muniz FJ, Maki KC, Schaefer EJ, Ordovas JM.
J Nutr. 2009 Jan;139(1):13-9. Epub 2008 Dec 3.
23. [A new property of known proteins: specific binding of thyroid hormones by human plasma apolipoproteins] [apoE]
Sviridov OV.
Biokhimiia. 1994 May;59(5):625-38. Review. Russian.
24. High-density lipoproteins can act as carriers of glycophosphoinositol lipid-anchored CD59 [protectin] in human plasma.
Väkevä A, Jauhiainen M, Ehnholm C, Lehto T, Meri S.
Immunology. 1994 May;82(1):28-33.
25. LDL isolated from plasma-loaded red wine procyanidins resist lipid oxidation and tocopherol depletion.
Lourenço CF, Gago B, Barbosa RM, de Freitas V, Laranjinha J.
J Agric Food Chem. 2008 May 28;56(10):3798-804. Epub 2008 May 3.
26.
Comparative antioxidant activity of tocotrienols and other natural
lipid-soluble antioxidants in a homogeneous system, and in rat and human
lipoproteins.
Suarna C, Hood RL, Dean RT, Stocker R.
Biochim Biophys Acta. 1993 Feb 24;1166(2-3):163-70.
27. Effect
of the magnitude of lipid lowering on risk of elevated liver enzymes,
rhabdomyolysis, and cancer: insights from large randomized statin
trials.
Alsheikh-Ali AA, Maddukuri PV, Han H, Karas RH.
J Am Coll Cardiol. 2007 Jul 31;50(5):409-18.
28. Carcinogenicity of lipid-lowering drugs.
Newman TB, Hulley SB.
JAMA. 1996 Jan 3;275(1):55-60. Review.
29. Use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors is associated with risk of lymphoid malignancies.
Iwata
H, Matsuo K, Hara S, Takeuchi K, Aoyama T, Murashige N, Kanda Y, Mori
S, Suzuki R, Tachibana S, Yamane M, Odawara M, Mutou Y, Kami M.
Cancer Sci. 2006 Feb;97(2):133-8.
30.
Coenzyme Q10: clinical benefits with biochemical correlates suggesting
a scientific breakthrough in the management of chronic heart failure.
Mortensen SA, Vadhanavikit S, Muratsu K, Folkers K.
Int J Tissue React. 1990;12(3):155-62. Review.
31. Statins in the treatment of chronic heart failure: biological and clinical considerations.
van der Harst P, Voors AA, van Gilst WH, Böhm M, van Veldhuisen DJ.
Cardiovasc Res. 2006 Aug 1;71(3):443-54. Epub 2006 Apr 27. Review.
32. Schurgers LJ, Vermeer C.
Differential lipoprotein transport pathways of K-vitamins in healthy subjects.
Biochim Biophys Acta 2002;1570:27–32. [PubMed]
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