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Cholesterol Myth, Source-History


http://qjmed.oxfordjournals.org/content/qjmed/104/10/867.full.pdf#   This articles goes into the why those with familial hypercholesterolemia (FH) do not develop atherosclerosis because of high blood levels of cholesterol, but because the genetic defect causes the loss of cholesterol receptors, and this “impair flexibility of cell walls in arteries making them more brittle and therefore more liable to hydrodynamic damage, 868.”  Moreover, “feeding excessive amounts of cholesterol to laboratory animals only produces harmless fatty streaks, never a vascular accident” 868. The results here are consistent with Prof. Uffe Ravnskov, Ignore the Awkward, chapter 3, on FH.  Ravnskov in that chapter sites footnotes 1-9, studies which found either no increased risk of death from MI, or that those with FH loved longer then the average Dutchman… because back then of lower death from infectious diseases” 30.   This relationship is supported by the immune function of LDL and HDL, see for immune function, and http://healthfully.org/rl/id5.html for Ravnskov on the cholesterol myth  

The great cholesterol myth; unfortunate consequences of Brown and Goldstein’s mistake

D. D. Adams, 20 June 2011, 867-870

ABSTRACT:  Following their Nobel Prize-winning discovery of the defective gene causing familial hypercholesterolaemia, Brown and Goldstein misunderstood the mechanism involved in the pathogenesis of the associated arterial disease. They ascribed this to an effect of the high levels of cholesterol circulating in the blood. In reality, the accelerated arterial damage is likely to be a consequence of more brittle arterial cell walls, as biochemists know cholesterol to be a component of them which modulates their fluidity, conferring flexibility and hence resistance to damage from the ordinary hydrodynamic blood forces. In the absence of efficient receptors for LDL cholesterol, cells will be unable to use this component adequately for the manufacture of normally resilient arterial cell walls, resulting in accelerated arteriosclerosis. Eating cholesterol is harmless, shown by its failure to produce vascular accidents in laboratory animals, but its avoidance causes human malnutrition from lack of fat-soluble vitamins, especially vitamin D.

  • The Author 2011. Published by Oxford University Press on behalf of the Association of


Q J Med 2011;  104:867–870.   doi:10.1093/qjmed/hcr087   Advance  Access Publication  20 June 2011


The great  cholesterol myth; unfortunate consequences

of Brown and Goldstein’s  mistake



D.D. ADAMS’—Converted from the PDF http://qjmed.oxfordjournals.org/content/qjmed/104/10/867.full.pdf#


From the Faculty of Medicine,  University of Otago,  Dunedin,  New Zealand.


Address  correspondence to  Dr  Duncan   Adams,  Faculty  of Medicine,  University  of Otago,  P.O.  Box 913, Dunedin,  New Zealand.  email: duncan.adams@stonebow.otago.ac.nz


Received  16 March 2011  and in revised form 3 May 2011




Following  their  Nobel  Prize-winning  discovery  of the defective gene causing familial hypercholesterolaemia,  Brown and Goldstein  misunderstood the mechanism involved in the pathogenesis of the associated  arterial disease.  They ascribed  this to an effect  of the  high  levels  of cholesterol   circulating in  the  blood.   In  reality,  the  accelerated  arterial damage  is likely to be a consequence of more brittle arterial cell walls, as biochemists  know  cholesterol to be a component of them  which  modulates  their fluidity, conferring flexibility and hence resistance to damage  from the ordinary  hydrodynamic blood forces. In the absence  of efficient receptors  for LDL cholesterol,   cells  will be  unable  to  use  this component  adequately for the manufacture  of normally resilient arterial cell walls, resulting in accelerated arteriosclerosis.    Eating   cholesterol    is   harmless, shown  by its failure to produce  vascular  accidents in  laboratory   animals,   but  its  avoidance  causes human  malnutrition  from  lack  of  fat-soluble  vitamins, especially  vitamin D.







When  post-mortem  examinations  are made  of elderly people, opening of the aorta and smaller arteries often reveals atheroma,  rough yellow plaques disfiguring the smooth pink lining of these blood  vessels and  impinging  on  the  lumen.  Often  the  extent  of the atheroma  formation  makes  one  marvel  at how long the patient has lived before succumbing to a vascular  accident  from obstruction  or rupturing  of an important  artery.


Atheromatous          plaques      contain     cholesterol. Accordingly, research workers have repeatedly fed laboratory  animals  large amounts  of cholesterol  in their diets,1 expecting  this to produce  vascular accidents. It never has, which  shows that despite the presence   of  cholesterol   in  atheromatous  plaques these lesions are not caused by eating cholesterol. Before describing the strong evidence  that hydro- dynamic   stresses  cause   the  arterial  degeneration responsible  for ischaemic  heart disease and strokes, we shall recount  description2  of the spectacular deviation from reality caused by a mistaken interpretation  made  by Goldstein  and  Brown after they had  brilliantly  discovered   the  defective  gene  that causes  familial hypercholesterolaemia (FH).




Familial hypercholesterolaemia


A famous book is Victor McKusick’s Mendelian Inheritance  in  Man.3  This is a  catalogue  of thousands  of inherited  diseases  caused  by mutations  in germ-line genes. The diseases are divided into three classes, depending on whether the defective gene is dominant, recessive or sex-linked. One of these genetic   diseases   is FH, where   blood   cholesterol levels  are  raised.   Heterozygous   cases,   with one normal gene and one defective gene, have blood cholesterol     levels    of    250–450 mg/dl,    whereas Text Box: Downloaded from by guest on November 15, 2014homozygotes with both alleles defective have levels >500, compared to normal  people  with  levels  of 150–250.  There is accelerated arteriosclerosis with premature   deaths from vascular accidents in the forth and fifth decade in heterozygotes and earlier in homozygotes. In most populations  the frequency of the  homozygotes is 1  in  a  million  and  that  of the  heterozygotes   about  1  in  500,  comparable  to the frequency of the defective gene causing cystic fibrosis.



Brown and Goldstein’s discoveries4,5


One  of the most famous  ever partnerships  in medical research  was that of Michael Brown and Joseph Goldstein, who received the 1985 Nobel Prize in Physiology and Medicine  for discovering that the defective gene in FH codes for a cell surface receptor for cholesterol  in the form of low-density lypoprotein (LDL). In a succession of brilliant research achievements, Brown  and  Goldstein  developed a culture technique for skin from both normal individuals   and   patients   with   FH.   The   cultured   skin cells were then analysed biochemically by Brown. In  1973,   Brown   and   Goldstein   discovered   the rate-limiting   enzyme    in   cholesterol    production, 3-hydroxy-3-methylglutaryl coenzyme  A (HMG- CoA) reductase,  which  could  be  regulated  in cultured normal  skin fibroblasts by the amount  of LDL in  the  medium.   Adding  LDL to  the  normal  cells switched   off  HMG-CoA  reductase   and   the  cells ceased    making   cholesterol.    However,    the   skin cells  from FH patients  continued to make  cholesterol  with  even   very  high  levels  of  LDL in  the medium.  Brown and Goldstein  correctly concluded that  the  genetic  mutation  must  involve  a  receptor that  bound  LDL and  enabled   cholesterol  to  enter the cell. Drugs were developed that would inhibit HMG-CoA reductase  and thus decrease  the cellular production of cholesterol.   Lovastatin [Mevacor]  was  the  first such drug marketed in the hope of decreasing  the occurrence of heart attacks, on the mistaken assumption that high blood cholesterol caused such attacks.



Brown and Goldstein’s  mistake, the cholesterol hypothesis4–6


Unfortunately, Brown and Goldstein failed to realize that it is the loss of a functional cholesterol  receptor, causing  impaired  ability to absorb  and  use cholesterol, which is the probable  cause of the accelerated arteriosclerosis    occurring    in   FH.   Instead,   they assumed that the cause is the high level of blood cholesterol,  which  ‘salts out’ into the arterial walls, causing the vascular impairment. This was an understandable mistake, because  as mentioned  above, the atheromatous plaques of arteriosclerosis contain cholesterol,   which   causes   a  bulge  impinging  on the lumen. In angioplasty, cardiologists use mechanical  pressure  to  flatten  such  bulges,  with  therapeutic benefit to the flow of blood. However, pathologists  realize  that  deposition   of  cholesterol in the arterial walls seems to be secondary  to hydro- dynamic  damage,7  followed  by inflammation,  with cell multiplication  and somatic  gene  mutation.  The first awareness  of this came from the finding that it is not possible to produce arteriosclerosis by feeding excessive  amounts  of cholesterol  to laboratory  animals.  Only  harmless  ‘fatty streaks’ are  produced,1 never a vascular accident. Biochemists know that cholesterol  is a component of cell walls that modulates their fluidity.8  With the loss of the cholesterol receptor, the impaired ability to absorb cholesterol is likely to impair flexibility of cell walls in arteries, making   them   more   brittle   and   therefore   more liable to hydrodynamic damage.  This accounts for deaths from occurrence of vascular accidents  in the fourth and  fifth decades  in patients  with heterozygous  FH,  including   two  cousins   of  the   author, who were identical twins, thereby doubling the misfortune.2



Evidence for the haemodynamic hypothesis  of arteriosclerosis


1. Hypertension causes accelerated arteriosclerosis and vascular accidents.

2. The absence of arteriosclerosis in the pulmonary circulation  that has one third of the pressure of the systemic circulation.  Furthermore, in cases of pulmonary hypertension typical fibrous atheromatous plaques occur in the pulmonary  artery and its major branches.7

3.  The sites of arterial damage  are where  hydrodynamic forces   act,   e.g.   left  anterior   descending  coronary, where  a powerful  jet of blood  from the aorta hits the wall of the branch  artery.

4.  Race  horses  with  high  blood  pressure  during  daily hours of training die around  20 years of age compared to 40 years for untrained  horses. 



False claim from the Lipids Research Clinics Primary Prevention Trial


In 1985, every  doctor  in New  Zealand  received  a report saying it was now proven that lowering blood cholesterol  levels in normal people  reduces  the risk Text Box: Downloaded from by guest on November 15, 2014of coronary heart disease. The report cited a study in which  a group  of 1906  men  took the bile sequestrant, cholestyramine resin, for 7 years in comparison with 1900 men who took a placebo. L’Abbe and colleagues  in Toronto9  noted  with disapproval  that the investigators had made  a post hoc relaxation  of the level of significance from the originally proposed <0.001 to <0.05. Check of the statistics, showed that even this low level of significance had not been reached.10  The investigators  had  cheated by using a  one-tailed   Student’s  t-test  instead  of the  proper two-tailed  one.



Lenfant’s complaint

In a flush of success,  Brown and  Goldstein6  wrote a 1996 editorial for Science  entitled, ‘Heart attacks: gone with the century?’ In the year 2000, Claude Lenfant,        Director, National Heart Institute, National  Institutes of Health,  wrote  the Forward to a book by Grundy evaluating  clinical trial evidence for benefit  of cholesterol-lowering therapy.  Dr Lenfant asks rhetorically  if Brown and Goldstein’s prediction had been fulfilled and stated,11 ‘Unfortunately,  the answer  is no’.



Unfortunate consequences of Brown and Goldstein’s  mistake


Brown and Goldstein’s burst of fascinating information dazzled the medical profession, most of whom consequently accepted the false cholesterol  hypothesis. This has led to unfortunate  consequences that include:


1.  Waste of money  on misdirected  research.

2.  Waste of money  on blood  cholesterol  tests.

3.  Waste of money  on statins.

4.  Malnutrition from lack of fat-soluble vitamins (A,D,K,E) present in butter, full-cream milk and animal fat but lacking in margarine  and skim milk (green-top bottles in New Zealand).

5.  Fear of eating eggs, contributing  to unhealthy,  starchy diets.

6.  Ricketts in middle-aged  men  from lack  of vitamin  D due to use of margarine  and skim-milk.

7.  Distortion  of the Dairy Industry, causing  unnecessary marketing  of skim milk.

8.  Distortion of the Meat Industry with unnecessary  production  of lean meat.




Recently, LaRosa et al.12 reported  on a huge  study by thousands  of people,  comparing  the therapeutic efficacy of two doses  of Atorvastin, 80 mg/day  and 10 mg/day,  on  the  frequency   of  adverse   cardiac events.  Notably, there was no difference in overall mortality between the two doses. However, LaRosa drew a graph depicting cardiovascular event percentage and LDL cholesterol level, in patients from four statin trial groups and his own study. The graph, in his Figure 4, is misleading.  It shows a rising slope for cardiovascular events against LDL cholesterol levels. However, all the statin groups,  in black, are on the left of the graph and all the placebo  groups in white are on  the  right of the  graph,  so  the  slope simply  depicts   the  cholesterol-lowering  effect  of the statins. To test whether statins reduce the cardio- vascular events, the statin and placebo sections of the individual trials must be compared. Reading by eye from the graphs, the  statin components of the four trials average 13 events compared to 17 events from the placebo  components, Student’s t-test showing no significant difference. The fact that of the thousands  of people  involved in achieving  this spurious result did not include a single elementary mathematician with intellectual  independence is in accord  with the whole sorry story of the great cholesterol myth, starting with the false statistics used in analysing the Framingham data.10 The meta-analysis of Ray et al.,13  showing  no prolongation of life by use of statins in randomized controlled  trials involving 65 229 participants,  is the final nail in the coffin of the great cholesterol  myth.  [One needs to do more than merely look at a graph to ferret out pharma’s marketing deception.  For example, a minor endpoint, such as angina, is added to the list to MI and death, for to get the marketing answer, benefit.  Adams merely took LaRosa’s evidence at face value, though Adams has uncovered deliberate deception by LaRosa--why not more?—jk.]


There is a popular  fear of eating fat, triglycerides, which was reduced  to fear of saturated fats to accommodate  the   finding   that   Eskimos,  the   Inuit people,   were  found  to  eat  much  unsaturated  fat without early heart disease.  It seems likely that fear of fat is unreal based on a carry-on of the cholesterol fear.


In the world  of religion,  it is often taught  that it is virtuous to believe something without adequate proof and virtuous to convert others to the same misbelief.  This  has  overlapped  into  Medicine   in regard  to  the  cholesterol  hypothesis,  as  described in   my   previous   paper.2    The   great   strength   of Medicine  is its scientific  basis,  which  we  must all have the courage  and intellectual  flexibility to preserve.






The author is indebted  to Pro-Vice Chancellor  Peter Crampton for encouragement and administrative support.


Conflict of interest: None  declared,


Text Box: Downloaded from by guest on November 15, 2014References

1.  Cappell  DF,  Anderson  JR. Muir’s Textbook  of  Pathology. th edn.  London, Edward Arnold, 1924.


3.  McKusick  VA.  Mendelian   Inheritance   in  Man.  7th  edn. Baltimore, The Johns Hopkins  University Press, 1986.

4.  Brown  MS,  Goldstein   JL.   How   LDL receptors   influence cholesterol     and    atherosclerosis.   Sci   Am   1984;    251: 52–60.

5.  Brown MS, Goldstein  JL.  A receptor-mediated pathway  for cholesterol  homeostasis.  Science  1986;  232:34–47.

6.  Brown MS, Goldstein  JL. Heart  attacks:  gone  with the century? (Editorial). Science  1996;  272:629.

7.  Benditt EP, Schwartz SM. Blood vessels. In: Rubin E, Farber JL, eds,  Pathology.   2nd  edn.  Philadelphia,  Lippincott,  1994: 455–501.

8.  Stryer L. Membrane  fluidity is controlled  by fatty acid com- position   and  cholesterol   content.   Biochemistry.  3rd  edn. New York, Freeman,  1988:297–8.

9.  L’Abbe K, Detsky A, Logan A. The Lipids Research  Clinics Coronary Primary Prevention  Trial. JAMA 1985;  253:3091.

10.  Adams DD. Lowering cholesterol  and  the incidence of coronary heart disease.  JAMA 1985;  253:3090–1.

11.  Lenfant   C.   Foreward.   In:  Grundy   SM,  ed.   Cholesterol Therapy. Evaluation of Clinical Trial Evidence. New York, Marcell Decker,  2000:iii–iv.

12.  LaRosa  JC, Grundy  SM,  Waters  DD,  Shear  C,  Barter  P, Fruchart  JC, et  al.  Intensive  lipid  lowering  Atorvastin  in patients  with  stable  coronary  disease.  N  EnglJ Med  2005; 352:1425–35.

13.  Ray KK, Seshasai SR, Erqou S, Sever P, Jukema JW, Ford I, et al. Statins and all cause mortality in high risk primary prevention:   a  meta-analysis   of  11  randomised   controlled trials involving  65,229  participants.  Arch Intern Med 2010; 170:1024–31.


^^^^^^^^   Plaque in veins and branches of arteries ^^^^^^^

This raises two issues; both have the same basic answer.  Why is it often that there is on an average more plaque where the artery branches into two and this is a common location for the blockage that results in an acute ischemic event, a myocardial infraction?  Second why is it that veins are not subject to atherosclerosis with the exception of when they are attached to an artery from a bypass operation?  On turning to the journal literature for answers, the evidence base is subjected to the distortions worked by pharma; given the answers affect the sales of cholesterol lowering drugs and antihypertensive drugs.


A person who has atherosclerotic coronary arteries has significant occlusion not just in the main arteries coronary arteries but also the arterioles.   When there is occlusion downstream in the arterioles, the point of branching will be subjected to greater pressure and turbulence.  This would promote increase in endothelial dysfunction from the reactive chemicals and pathogens in the blood. 


As for vein grafts being subjected to atherogenesis, the frequency is high.[1]  Telling is the time frame for changes, which is indicative of a process totally different from that of the formation of plaque in coronary arteries.  In a study of 97 saphenous veins from coronary artery bypass grafts, intimal fibrin was found in 73% of graphs in the group who had died 1 to 12 following surgery, 74% 1 to 20 days and this was present prior to the finding of foam cells, and 75% 1 to 54 months.   However, the cause for the occlusion is different than in arteries both in substance of plaque and timing.  The early onset in itself indicates a different biological process than occurs with the atherogenesis of arteries.   Other post-mortem studies have similar results of early development of plaque.   The cause is that of natural circulating growth factors which stimulates remodeling.  The process which promotes healing during the inflammation process of arteries also applies to the vein grafts.  A vein’s wall is less than half as thick as that of an artery.  The process of growing new muscle cells in the wall is in response to an inadequacy of the grafted coronary vessel patch—see 1997.  The growth within the grafted veins would result in the partial occlusion observed. The main article on the plaque is at http://circ.ahajournals.org/content/55/1/163.full.pdf+html  

[1] A study of 95 bypass grafted saphenous veins found atherosclerotic plaque in 43% of samples from the group of 14 diseased patients--period since bypass was from 1 to 54 months. 

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