The Cholesterol Times, Issue #005 -- A 72-Year Metabolic Mystery Unfolds
September 10, 2005
A Publication of Cholesterol-And-Health.com
Issue #005, September 10, 2005
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--Chris Masterjohn, Editor
In This Issue
Site Updates
Best of the 'Net
Research Watch
Breaking News in Research
Weston A. Price Foundation Conference
Copyright and Disclaimer
Search
Feedback
Site Updates
Cholesterol Guidelines Turn Healthy People Into Patients
By Dr. Uffe Ravnskov, MD, PhD, with permission to distribute. A classic article.
Best of the 'Net
The Aging Enigma
A fascinating article on the emerging science of aging, covering newly discovered genes related to aging, how diet and environment affect the expression of those genes, and the prospect of an anti-aging drug.
The article discusses the effect of calorie restriction on lengthening life span, but not the less-studied effect of intermittent fasting that exerts its effects without restricting calories (Read the second study testing this phenomenon here.) The book The Warrior Diet is based on this concept. Another interesting study on aging not discussed in this article found that the life span of the worm C. elegans is regulated by the senses of smell and taste, possibly accounting for part of the effect of diet seen in other studies-- which you can read here.
Most Studies Are Probably Wrong
A new study, reports the New Scientist, has found that, due to statistical and other errors, the findings of any randomly chosen study have a less than 50% chance of being true. And even the raw data often leaves plenty of room for massaging it into the shape of the author's pet theory.
LDL: Bad Cholesterol or Bad Science?
Anthony Colpo reviews the junk science claim that LDL is the "bad cholesterol" in the Journal of the American Physicians and Surgeons. Since this link goes directly to the .pdf, you can download it directly by right-clicking on it and choosing "save target as" from the drop-down menu. You will need Adobe Acrobat Reader to read this file-- chances are you already have it.
Native American Societies Were Technologically Advanced
"Scholars have known for decades that Native American societies were in many ways more technologically sophisticated than their European counterparts. So why do we still find this fact so surprising?"
The Boston Globe reports.
Research Watch
A 72-Year Metabolic Mystery Unfolds: Why Eating Cholesterol Doesn't Raise Cholesterol Levels
In 1933, Rudolph Schoenheimer discovered the first evidence of a biofeedback system where the end product of a synthetic pathway inhibited that synthetic pathway, when he discovered that mice fed large amounts of cholesterol made very little of it in their bodies, while mice fed very small amounts of cholesterol made large amounts of it in their bodies.
In the 1950s, Gordon Gould found that this system operated specifically in the liver. A new study published in the Journal of Clinical Investigation continues to unravel the intricate workings of this biofeedback system.
Proteins called "sterol regulatory element-binding proteins" (SREBPs) start out in the endoplasmic reticulum (ER), from which they are transported by vesicles to the Golgi Complex, permitted by their complexing to another protein called Scap. Once at the Golgi, SREBPs are modified in a way that they can gain access to DNA in the nucleus and stimulate the production of enzymes that synthesize cholesterol.
Yet when cholesterol concentrations rise, cholesterol binds to Scap, which causes Scap to change shape and become bound to other ER proteins called Insigs, which anchor Scap to the ER, so that the Scap-SREBPs complex cannot leave to be transported to the Golgi. Thus, cholesterol synthesis drops.
In addition, Insigs cause the degradation of HMG CoA-Reductase, an enzyme involved in cholesterol synthesis-- the same enzyme inhibited by cholesterol-lowering statin drugs. (See our flow chart.)
This study found that knocking out the genes for Insig 1 and Insig 2 in mice caused a dramatic decrease in the ability to regulate cholesterol synthesis in response to diet.
Knocking out the Insig genes did not effect the level of SREBPs-- since Insigs are involved in anchoring them, not making them-- but caused dramatic elevation of HMG CoA-reductase, as well as the RNA that makes it-- since Insigs are involved in both its degradation and the prevention of its synthesis. This led to an up to 6-fold increase in liver triglycerides (fats), and a 15-fold increase in liver cholesterol esters.
In the genetically altered mice, cholesterol synthesis did not alter in response to cholesterol feeding. But in the normal mice, cholesterol synthesis declined dramatically in response to feeding cholesterol, so that the highest amount of cholesterol (1.5% of diet by weight-- a massive amount), resulted in a 93% reduction in cholesterol synthesis.
Brain cholesterol was not affected by diet whatsoever, either in the control mice or the genetically altered mice. Even though the evidence suggests that eating cholesterol has no effect on brain cholesterol, if you've read our article debunking the myth that cholesterol causes Alzheimer's Disease you're familar with the bogus idea that a "brain-healthy" diet is one low in cholesterol.
Engelking et al., "Schoenheimer effect explained - feedback regulation of cholesterol synthesis in mice mediated by Insig proteins," J Clin Invest. 2005 Sep;115(9):2489-98. Epub 2005 Aug 11.
Omega-3 Fatty Acids Are More Effective than Statins and Other Drugs at Reducing Mortality and Heart disease
A review in the Archives of Internal Medicine looked at all of the trials to date with lipid-lowering agents that studied a single treatment, were randomized, controlled, involved followup, and measured mortality data, and found that omega-3 fatty acids are more protective than any drug out there, as well as the standard dietary advice.
Omega-3 fatty acids reduced the risk of overall mortality by 23%, compared to statins, which reduced the risk of overall mortality by 13%. Omega-3 fatty acids also beat statins for reducing cardiac mortality specifically, 32% to 22%.
The review found that the older form of cholesterol-lowering drugs called fibrates had no effect on overall mortality, but were positively associated with non-cardiac mortality, and found "little evidence" that dietary intervention reduced the risk of heart disease.
Interestingly, omega-3 fatty acids had no effect on cholesterol levels. On average, they reduced cholesterol by 2% (inconsistently), but some subsets of omega-3 trials found that they raise cholesterol slightly. Yet they were much more effective (almost twice as much) at reducing mortality than statins, which lowered cholesterol by 20% on average.
Niacin, which reduced cholesterol by 11%, had only a non-statistically-significant 4% reduction of overall mortality, with an 81% lilihood of this correlation being due to chance. Fibrates reduced cholesterol by 8%, but had no effect on mortality. Diet reduced cholesterol by 10%, but had only a non-statistically significant (likely to be due to chance) 3% reduction in mortality.
Quite clearly, the effect on mortality has no relationship whatsoever to the effectiveness of cholesterol-lowering.
The meta-regression analysis indicated a "positive association of fibrates with overall mortality." Figure C, showing Mortality From Causes Other Than Cardiovascular Diseases shows that diet, niacin, resin, and fibrate trials tended to show more benefit to control groups than those taking the treatment (meaning the treatment was harmful), while only omega-3 fatty acids and statins favored the treatment group (meaning the treatment was helpful).
Table 2 shows that trials were much less likely to show a positive effect for statins when allocation of statins was blinded (about half as likely), as well as when the patients and caregivers were blinded, whereas omega-3 fatty acids were equally likely to show positive effects regardless of whether allocation was blinded, and were more than twice as likely to show benefit when the patients and caregivers were blinded.
In trials where patients and caregivers were blinded, omega-3 fatty acids reduced mortality by 41%, while statins reduced mortality by 13%.
By contrast, statins were more likely to be effective when outcome assessors were blinded. Yet omega-3 fatty acids showed the same trend to a greater degree, so that omega-3 fatty acids were shown to be almost twice as protective as statins when outcome assessment was blinded.
On the other hand, a greater follow-up was associated with a better outcome for statins and a lower outcome for omega-3s, though the latter was still considerably more effective than the former.
On the whole, the trend is that higher-quality statin trials found lower effectiveness, while higher-quality omega-3 trials found more effectiveness.
This study not only shows that cholesterol-lowering treatments show no relationship between their ability to lower cholesterol and their ability to treat diseases, but also shows how unsound it is to fund a $26 billion/year-- and rapidly growing-- statin industry, when much more effective, safer, and wildly cheaper nutritional supplements are available without a prescription, with other benefits, and without the side effects.
Unfortunately, this study did not address the separation of current-use, ever-use, former-use, and never-use for statin patients. In Issue #003 I reported on a study that seemed to indicate that about 1/3 of statin users were dropping statins between one and three years of use, probably because of side effects, and were suffering for this short-term use of statins with a dramatically increased risk of dementia. Therefore, simply looking at "statin use" is too vague a category to tell us the truth about what is going on here, and whether or not statins are damaging some people considerably despite helping others.
Studer, et al., "Effect of different antilipidemic agents and diets on mortality: a systematic review," Arch Intern Med. 2005 Apr 11;165(7):725-30. Review.
Breaking News in Research
The following two studies were not yet available in full-text at the time this newsletter was prepared. The information reported is based on the abstracts only.
Cholesterol Kills Candida
Some oxygenated derivatives of cholesterol have been found to have effective anti-fungal activity against the common pathogenic fungus Candida albicans, which is now the fourth most common blood infection in the United States, the organism responsible for thrush, vaginal yeast infections, and many other health problems.
The highest activity was found with hydroxy-ketone 2, a cholesterol derivative that exhibited high activity against candida, including strains of candida that are resistant to the anti-fungal drugs Amphotericine B and miconazole.
Brunel et al., "Synthesis and antifungal activity of oxygenated cholesterol derivatives," Steroids. 2005 Aug 31; [Epub ahead of print]
Chemical in Red Wine Lowers Heart Disease -- But Doesn't Lower Cholesterol
A study due to be published in October found that red wine, dealcoholized red wine, and resveratrol, a chemical found in red wine, effectively lowered paramaters of vascular disease in hypercholesterolemic rabbits, without lowering cholesterol.
The rabbits-- which are, unlike humans, herbivorous animals-- were fed a 1.5% cholesterol diet, which is equivalent to a human on a 2000 calorie diet eating 23 egg yolks per day, which produced atherosclerotic lesions and reduced the flow-mediated dilation of blood vessels by 25%.
Yet the feeding of red wine, dealcoholized red wine, or resveratrol effectively reduced the size, density, and mean area of the atherosclerotic placques and the thickness of the intima layer, and completely abolished the reduction in flow-mediated dilation. These changes were effected despite no reduction in cholesterol levels!
This study is yet one more showing that protection against heart disease is simply not about lowering cholesterol levels.
Wang, et al, "Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels." Int J Mol Med. 2005 Oct;16(4):533-40.
Weston A. Price Foundation Annual Conference
Conference Details
Friday, November 11, through Sunday, November 13, The Weston A. Price Foundation will be holding its Sixth Annual Wise Traditions Conference.
Conferences in the past have featured Dr. Uffe Ravnskov's presentation of his hypothesis that cholesterol protects against infectious diseases, Dr. Kilmer McCully discussing his revolutionary work on homocysteine, Dr. Russel Blaylock's presentation of his work on excitotoxins, and many other excellent presentations.
This year's conference will feature social activities, workshops on fertility awareness and fermentation of beverages, 2 main tracks on heart disease and cancer, and a long list of featured speakers, including Dr. John Cannell, President of the Vitamin D Council, and Dr. Noel Solomons, Director of the CeSSIAM International Nutrition Foundation.
For more information on the conference, click here.
Travel and Lodging.
You can get a conference-related discount at the Westfield Marriot where the conference is being held of $139/night for double, triple, and quadruple occupancy by making reservations here.
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Copyright and Disclaimer
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