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The cholesterol hypothesis. How did it get started?

METAMORA, Mich., May 10, 2019 -- In 1908, a Russian scientist (Alexander Ignatowski) thought that eating too much protein would speed up the aging process in humans. To test this hypothesis, he fed rabbits meat, milk and eggs and found ‘fatty streaks’ accumulated in the arteries. In 1913, another Russian, Nikolai Anichkov, repeated the experiment with just egg yolk and produced the ‘fatty streaks’; this gave birth to the “cholesterol hypothesis” and was hailed as one of the “greatest discoveries in cardiology of the 20th century”.


In perspective, the rabbit is an herbivore and the egg yolk diet is therefore foreign to its metabolic system, thereby accumulating as a ‘fatty streak’ or ‘foam cells’ in the arteries. Prolonged feeding of cholesterol is toxic because the rabbit does not have a functional enzyme (cholesterol hydroxylase) to flush it out of the system. Humans are omnivores equipped with cholesterol hydroxylase to process diet cholesterol to bile and prevent accumulation.


In the 1920s, the advent of the industrial revolution marked an increasing incidence of coronary heart disease due to sedentary lifestyle and a high-fat, highly-processed diet. However, in 1955, Ancel Keys, a University of Minnesota nutritionist embraced the “cholesterol hypothesis”; that dietary cholesterol poses higher risk of heart disease in humans just like rabbits. Thus, in 1961, Keys and the American Heart Association (AHA) drafted a dietary guideline to reduce cholesterol intake, particularly limiting eggs to ‘not more than 3/week’. (Note: this guideline was reversed in 2015, citing no evidence to link dietary cholesterol to heart disease).


The focus on cholesterol-lowering methods inspired Akira Endo of Japan (Sankyo) in 1971 to screen for drugs that inhibit cholesterol synthesis (statins), targeting the enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase. The first statin, Compactin, was effective in vitro but was subsequently dropped because it was proven toxic and failed to lower plasma cholesterol in rats and mice. The 2nd statin, Lovastatin, discovered in 1979 by Merck, also failed to lower cholesterol in animals and was dropped. However, per the recommendations of Michael Brown and Joseph Goldstein (Merck consultants and Nobel Prize winner for their discovery in 1973 of the genetic cause of familial hypercholesterolemia, FH), Lovastatin was resurrected and tested clinically on FH patients. Lovastatin lowered cholesterol in FH patients and was approved in 1987.


In 1985, Ancel Keys and the AHA lobbied to legislate a “war on cholesterol”, which resulted in an AHA/National Institutes of Health (NIH) partnership. In 1987, the AHA/NIH partnership established the National Cholesterol Educational Program (NCEP); the same year Lovastatin was approved. To assess the cholesterol-lowering effect of Lovastatin, the “lipid panel” was introduced by William Friedewald of the NIH. The lipid panel calculates blood cholesterol (LDL, HDL) and fats (triglycerides) and an initial Lovastatin goal of <130 mg/dL LDL. Subsequently, more statins were developed to achieve the LDL target goal. Gimmicks to highlight the utility of the ‘panel’ include designating LDL as ‘bad cholesterol’ and HDL as ‘good cholesterol’, which inspired ‘HDL-boosting’ drugs and triglyceride drugs such as antihypertensives.


Dr. Tunac and Arterez pose this important question is the ‘cholesterol hypothesis’ and all drugs targeting components of the lipid panel a ‘wishful thinking’ academic exercise given that cardiovascular disease and related healthcare costs continue to increase in the US and worldwide? An inescapable fact is that cardiovascular disease (CVD), particularly coronary heart disease (CHD), remains the No. 1 disease killer in the world despite record numbers of statins being prescribed year after year. By 2030, 23.6 million people are predicted to die from CVD (World Heart Federation report).


The Arterez platform of emerging product innovations may represent a profound breakthrough in the pursuit to reach beyond treatment of symptoms leading to predictive, preventive and curative outcomes for CVD/CHD. Embotricin™ is the first ever anti-thromboembolic pill proven to be effective in preventing and eliminating plaque formation in murine animal models. Moreover, it is an oral, non-toxic drug with a safety index of 20X the effective dose. GlycoCardia™ (pre-episodic diagnostic panel/s) measures the level of glycocalyx disruption per levels of shed components in addition to other patent pending markers that will result in targeted, 3-4 marker diagnostic ‘panels’ designed to detect and monitor the progression of various forms of cardiovascular and coronary heart diseases.


Arterez, LLC is a Michigan-based bio-pharmaceutical company focused on the development of first-in-class diagnostic panels as well as a triple compound oral therapy targeting the multi-factorial root causes of cardiovascular disease including the repair and maintenance of the Endothelial Glycocalyx, while minimizing the damaging effects of oxidation and reducing inflammation.


For more information, contact Mike Brennan, mike@arterez.com, 248-931-9091 or visit https://www.arterez.com/

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