Contrary to popular belief, 80% of the cholesterol in the body is produced by the body. Only 20% of blood cholesterol comes from dietary sources. Although high blood cholesterol has been linked to coronary and artery disease, many people think the balances of low-density lipoprotein (LDL), or the cholesterol associated with clogged arteries, and high-density lipoprotein (HDL), the “good” cholesterol, is as important or more important than the overall combined cholesterol number. HDL performs several functions that improve overall health and results in both lower cholesterol levels and in lower incidents of artery disease. In addition to preventing LDL from binding to arterial walls, HDL plays an important role in transporting LDL cholesterol back to the liver where it is broken down.
Cholesterol is a fatty steroid made primarily in the liver. Once made by the liver, it enters the blood stream to be transmitted to the places where cholesterol is used. Cholesterol is not water soluble, so it remains in its natural form while in the blood stream. Although the liver is the largest producer of blood cholesterol, the intestines also produce some. Cholesterol is an important component in digestion, and a good part of the body’s cholesterol is used in the intestines. In addition to these two sources, a number of cells make a small amount of cholesterol for localized use in the body.
An important link also exists between dietary cholesterol absorption and cholesterol production. Inhibiting cholesterol synthesis increases cholesterol absorption, and decreasing cholesterol absorption increases cholesterol synthesis. This partially explains why it is difficult to achieve LDL targets in many patients. The intestinal pool of cholesterol is also an important source of blood cholesterol and is derived from biliary secretion and the diet. Approximately half of intestinal cholesterol is absorbed into the bloodstream. The absorption of excess cholesterol can increase the amount of cholesterol stored in the liver, resulting in increased very-low-density lipoprotein (VLDL) secretion and LDL cholesterol formation and downregulation of LDL receptor activity, leading to increased plasma LDL cholesterol levels.
Cholesterol has a number of functions in the body. It is very important in the maintenance of cellular membrane health and is an important component in the growth of new cell walls. Cholesterol is a very important part of the body’s hormone manufacturing system. Cholesterol is used as the body makes progesterone, testosterone, estradiol and cortisol. Cholesterol is a component in the production of bile salts that aid in food digestion. Bile salts play an important role in breaking down fats in food and other lipids during the digestive process. Once the bile salts have served their digestive function, they are re-absorbed by the body and transported back to the liver.
For many reasons, we know that it’s good to have a cholesterol level within the normal range. Normal range is defined as less than 200 mg/dL (milligrams per deciliter of blood) of total cholesterol. Now, we have more evidence that among the benefits of low cholesterol may be a lower risk for potentially deadly cancers. Cholesterol affect cancer cells at a level where it influences key signaling pathways controlling cell survival, Cancer cells use these survival pathways to evade the normal cycle of cell life and death.
Enhanced glucose and lipid metabolism is one of the most common properties of malignant cells. Targeting cholesterol metabolism is one route to treating and preventing cancer. The enzyme ATP citrate lyase (ACL) is fundamentally important in cancer cell growth. If this enzyme is inhibited, cancer cell growth stops. ACL controls the synthesis of fatty acids, cholesterol and isoprenoids in the cell. Of the three, isoprenoids are the most important. When a cancer cell grows, it expands twofold. It must make new lipids and cholesterol for continued membrane synthesis. Lipids and cholesterol derived from diet are useless. The lipids/cholesterol must be synthesized in the cell. Inhibitors of ACL do not induce apoptosis in cancer cells. To the contrary, they stop cancer cells from growing while forcing them to differentiate into normal cells. It is easy to understand how inhibitors of ACL or HMG CoA reductase can stop cancer cell growth. ACL is the key enzyme since it produces Acetyl CoA, the precursor of cholesterol, CoQ10, lipids and isoprenoids. Isoprenoids are a diverse group of lipid molecules that attach to signaling molecules such as the oncogene RAS. Mutated or over active RAS is found in over 30% of all cancers and leukemias. It is probably the most well studied oncogene known to science. 20-30% of acute myeloid leukemias and 50-70% of chronic myeloid leukemias harbor a mutated RAS gene. But these numbers are misleading. Cell growth in general is dependent on RAS signaling, whether mutated or not.
If the synthesis of these lipids is blocked, cell growth becomes impossible. This is exciting stuff, especially for leukemia. Naturally, many cancer cells cannot differentiate into normal cells, but some can. The lack of ACL activity may actually correct the defective stem cells and allow them to produce normal cells once again. There is no doubt that there are cancer stem cells. Many cancer cells will die all by themselves if left alone. But defective stem cells can and will replace this population of malignant cells. It is known, for example, that defective stem cells are responsible for the proliferation of most leukemia. If you remove these stem cells from a population of leukemia cells, these leukemia cells will not cause leukemia when injected into mice. The defective stem cells are clearly driving the malignancy process in many different cancers. ACL is naturally inhibited by hydroxycitric acid (HCA).
This molecule is an analog of citrate which blocks ACL activity. HCA is found in only a few plants, with one rich source being the rind of a little pumpkin-shaped fruit called Garcinia cambogia, which is native to Southeast Asia. This fruit (also called Malabar tamarind) is used as a condiment in dishes such as curry. Citrate can be burned in the mitochondria to produce ATP, thereby stabilizing the mitochondria, or it can be exported into the cytoplasm to make acetyl-CoA. Acetyl CoA is the precursor of lipids, cholesterol and other molecules. If ACL is inhibited, the citrate will diffuse back into the mitochondria where it will be metabolized to make ATP. This prevents mitochondrial instability and further inhibits programmed cell death. SinnolZym contains standardized levels of hydroxycitric acid (HCA), which has been clinically shown to inhibit cholesterol synthesis and the effects by inhibition of ACL activity.
References
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