How we can lower cholesterol?
GENERAL CONSIDERATIONS.
Is Cholesterol the villain of all our maladies?. Not really. Cholesterol is vital for life, as it is the source for all steroids and hormones.
You might have elevated cholesterol and not know it. High Cholesterol is usually asymptomatic until it is too late when we get heart or brain attacks. It is not like high blood sugar that can give us certain signals, such as thirst, frequent urination, fatigue, bad breath, etc.
The elevated Cholesterol is called Hypercholesterolhemia, a condition that lead to Atherosclerosis, or clogging of the arterial blood vessels.
Atherosclerosis is the leading cause of death in the developed world and is becoming the leading cause of mortality globally. Despite the effectiveness of the modern therapy, the global burden of mortality from ischemic cardiac and cerebral diseases is predicted to double from 1990 to 2020.
METABOLISM OF LIPIDS
A- Endogenous Cholesterol pathway.
B- Exogenous Cholesterol pathway.
Endogenous Cholesterol Pathway
The Endogenous Pathway, start with the formation and mobilization of Chylomicrons, from the absorption at the intestinal Jejunum to the lymphatic circulation. The Cholesterol enters the intestinal villi and is transported by way of Neiman-Pick C1Ll( NPCILI) and is converted to Cholesteryl Ester by ALyl CoA Acyl Transferase CA CAT-2). Seemingly Free Fatty Acids (FFA) enter the intestinal cells by way of Mono Acyl Glycerol (MAG), to join both the Cholesteryl – Ester. The Tryglyceride (TG) and the Apo protein B48 to form Cholesteryl Ester Triglyceride (CETG)by way of Microsomal TG Transfer Protein (MTTP). Then the CETG moves to the surface of the intestinal cell to be excited to the lymphatic circulation
Exogenous Cholesterol Pathway
The hepatic Cholesterol is metabolized mainly as very Low Density Lipoprotein (VLDL), which in turn is converted to intermediate Density Lipoprotein Lipase enzyme(LPL) IDL further convert to Low Density Lipoprotein (LDL) that then go to the peripheral tissues (muscles , fat tissue, etc) for utilization and or storage. Seemingly the formed TG degrades to FFA and Glycerol to its destination peripheral tissue and also TG is converted to HDL2 which in turn is converted to Cholesterol Ester and then to its final destinations: VLDL. The hepatic Cholesterol is directly disposed as Biliary Cholesterol and Bile Acids.
ATHEROSCLEROSIS
Atherosclerosis is a progressive disease that first affects the vessels with elastic lining, such as aorta, carotids, coronary and popliteal arteries. It starts as a fat streak of lipid-filled foam cells, that then form a fibrous plaque, that then form larger atherosclerotic plaques, initiating and sustaining an inflammatory response inside the blood vessel. Such plaques, ultimately progressively occludes the arterial lumen. ft is estimated that most clinical symptoms appear when the occlusion reaches approximately 70%. The most dangerous Cholesterol is LDL.
NON LIPID MEDIATED RISK FACTORS FOR CARDIOVASCULAR AND CEREBROVASCULAR DISEASES.
A-non modifying: Age, Male gender and Family history.
Modifying risks: Arterial Hypertension, Tobacco smoking, Diabetes, Obesity, Sedentarism , High Saturated Fat Diet and Hypercystinemia.
CLASSIFICATION ON LIPOPROTEIN DISORDERS.
A- Primary Dyslfpidemias
B- Secondary Dyslipidemias.
A-Primary Dyslipidemias: mostly Genetic or hereditary.
- A1 Familial
- A2 Autosomal Recessive.
B-Secondary Dyslipidemias.
B1-Secondary causes of high cholesterol: hypothyroidism, obstructive liver disease, anorexia nervosa, acute intermittent porphyria, use of certain drugs, such as progesterone, cyclosporine and thiazide.
B2- Secondary causes of high triglycerides: Obesity, diabetes, chronic renal failure, alcohol abuse, ileal bypass, pregnancy, acute hepatitis, stress, sepsis, SLE, use of certain drugs: estrogens, B adrenergic agonists, steroids, bile acid sequestrants and thiazides.
TREATMENTS FOR THE PREVENTION ON CARDIOVASCULAR AND CEREBROVASCULAR DISEASES.
HMG CoA REDUCTASE INHIBITORS: STATINS.
HMG stands for Hydroxy Methyl Glutaryl CoA.
These drugs reduce the synthesis of intracellular Cholesterol, primarily LDL. The firs of such drugs was introduced in the market was MEVASTATIN, around 1971, and then simvastatin (Zocor) by 1990.
HMG CoA is normally catabolized to MELAVONATE which then converts to cholesterol. Therefore when the Reductase is blocked, there is no formation of Cholesterol.
There are numerous STATINS
A-Fungal derivatives: Lovastatins (Mevacor) ,Pravastatin (Pravacol) and Simvastatin (Zocor).
B-Synthetic Statins: Atorvastatin (Lipitor), Fluvastatin (Lescol) and Rosuvastatin (Crestor). The latter is the most potent.
Almost all Statins have potential bad side effects, mainly muscle and liver dysfunction, peripheral neuropathy, lymphomas, thrombocytopenias and others. Check AST and ALT hepatic function tests periodically.
BILE ACID SEQUESTRANTS
These are non absorbable resins that bind to bile acids in the terminal ileum: Cholestyramine (Questran) Cholestipol (Colestil) and Colesevelam (Welcol).
CHOLESTEROL ABSORPTION INHIBITORS: Ezetimab (Ezetia), It blocks the absorption in the intestine thus reduces the absorption of cholesterol upto 50%. However, does not seem to reduce TG. Usual dose 1 G a day. Available in the market alone or in combination with sinsvastatin as Vytorin.
NICOTINIC ACID
One of the oldest and most potent drugs. They are part of vitamin B complex, increases HDL by 30%-40% can be used in combination with Statins. Most people don’t tolerate it because produces annoying flush and itching, but if starting in low doses and titrate, it can be tolerated better. May be available as Niaspan which is extende release in caps of 500, 750 and 1000 mg.
OMEGA-3 FATTY ACIDS
Reduces TG by acting of VLDL synthesis. Can be used in combination with Statins if necessary. It has econdary benefits such as lowering the BP, modulate heart rate and rythm and has also anti-inflammatory properties.
A-Long chain: a) EPA (EisosaPentaenoic Acid) and b) DPA (DecasaPentaenoic Acid).
B-Short chain: alpha linolenic acid (ALA).
OTHER TREATMENTS:
Fibrates.
OrIlstat (Alli and Xenical) that act by accelerating the fat elimination in stools.
Surgery (Partial ileal bypass). Not to be confused with bariatic bypass to reduce weight.
Therapeutic life style changes: reduce 10-20% body weight, exercises, stop smocking, reduce or eliminate saturated fat consumption, reduce alcohol consumption, special diet such as Mediterranean diet, prolonged fasting.
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