Cholesterol- Should We Fear It?

Category : Lifestyle Disease Connection
Author : Dr. Namita Tyagi

Disclaimer: This blog is for informational purposes only and should not be construed as medical advice. The reader should consult their health care provider before self diagnosing or altering their treatment based on anything they read here. 

Often when people mention cholesterol they are confusing it with the particles called lipoproteins that carry cholesterol and other fatty molecules in the blood. Medical professionals have fuelled this confusion by, erroneously, referring to certain subtypes of lipoproteins as good and bad cholesterol.  One subclass, the Low Density Lipoproteins (LDLs) has been referred to as bad cholesterol, whilst another, the High Density Lipoproteins (HDLs) have been called good cholesterol.

Until recently the prevailing paradigm in health care has been that higher circulating cholesterol is likely to play a causal role in the development of atherosclerosis. Atherosclerosis is an age-related, chronic, inflammatory condition affecting the arterial blood vessels in our bodies. This disease, which is the single biggest cause of death and disease worldwide, results in progressive narrowing and ultimately, occlusion of arteries supplying life blood to important organs such as the heart and brain. The resultant lack of blood supply to these organs is manifested as ischaemic heart disease, sudden cardiac death and strokes. With this in mind, dietary guidelines across the world, have focussed on limiting the intake of all fats, particularly saturated fats, which are high in cholesterol. Cholesterol rich foods of animal origin (such as eggs, red meat, chicken, fish and dairy) have been especially maligned in popular media on the basis, largely, of observational studies linking high cholesterol diets to a higher incidence of atherosclerotic arterial disease. The glaring reality, often omitted in media, is that there is a complete lack of scientific evidence in support of a causal link between dietary cholesterol and atherosclerosis. The unnecessary vilification of cholesterol has, understandably, made most people fearful of it. 

In reality, cholesterol is an organic molecule which is vital for human health and survival, so much so that it is synthesized in virtually every cell in the body. In effect without cholesterol, there is no life. 

Cholesterol is an important structural component of all cellular membranes giving them their necessary fluidity, as well as being involved in cellular signalling

Cholesterol also forms the raw-material backbone for steroid hormone synthesis in our reproductive organs i.e. for the synthesis of oestrogen and progesterone by our ovaries, that of testosterone by our testes and the corticosteroids by our adrenal glands. The steroid hormone producing tissues do not synthesize all the cholesterol they require. Instead they import at least some of their required cholesterol from the lipoproteins transported in the blood stream. 

In our liver, cholesterol is utilized for the synthesis of bile acids, which are secreted into the intestine via the gall bladder following ingestion of fats in food. The bile acids facilitate optimal digestion and absorption of dietary fats and fat soluble vitamins from the intestine. The cholesterol (both from food and bile acids) which is not reabsorbed into the blood stream from the small intestine is expelled from the body in faeces. 

In skin cells, 7 dehydrocholesterol (a metabolite of cholesterol) is converted (by exposure to Ultraviolet radiation in sunlight), to Vitamin D3. Contrary to popular belief, Vitamin D3 is not actually a vitamin but a hormone which has a direct regulatory effect on the expression and function of hundreds of human genes. It is noteworthy that human breast milk is a rich source of 7 dehydrocholestrol.

In our brain, cholesterol makes up more than 25% of the organ (by weight) and here it is essential for the normal synthesis and function of neuro-transmitters, which regulate our complex neurobiology. 

It is worth noting that dietary cholesterol contributes a very tiny proportion of our bodies stores of cholesterol, most of which are produced locally in every individual cell of our body. The liver produces about 25% of total body's cholesterol which is used for the synthesis of bile acids and the remainder is disseminated throughout the body. A proportion of the cholesterol excreted in bile acids from the liver is reabsobed in the terminal part of the small intestine. Ingested cholesterol contributes a mere 10-15% to this reabsorbed cholesterol fraction. 

The process of cholesterol biosynthesis and absorption from the gut is tightly regulated through a process called cholesterol homeostasis. This process ensures that the amount of cholesterol inside all cells stays within very narrow boundaries. Excessive cholesterol can crystallize inside cells. This crystallized form of cholesterol is highly toxic to cells and it evokes a strong inflammatory response, ultimately causing cell death. Cholesterol homeostasis requires its regulated transportation throughout our body (via the blood stream) along with the other fats i.e. free fatty acids and triglycerides. The latter two are the usable and storage forms of fats, respectively, which can be broken down or metabolized by the body for energy production. Cholesterol, on the other hand, cannot be used for energy production. 

All these fat based molecules are hydrophobic [i.e. unable to mix with water]. As blood is an aqueous or water-based fluid, our bodies have evolved a sophisticated transportation system for blood lipids. The system comprises complex molecules called lipoproteins which can be likened to boats or submarines. They have an outer, water soluble or hydrophilic, membrane comprising specific proteins called apoproteins bound together by a phospholipid layer. An inner cargo of water insoluble or hydrophobic cholesterol esters and triglycerides are carried within these lipoproteins. In addition, the lipoproteins transport fat soluble vitamins, and other hydrophobic molecules such as Coenzyme Q10. 

Most lipoproteins (excluding the chylomicrons) are packaged in the liver. These include the Very Low Density Lipoproteins (VLDL), the Intermediate Density Lipoproteins (IDL), the Low Density Lipoproteins (LDL) and the High Density Lipoproteins (HDL). The chylomicons are the largest particles which are used to transport cholesterol and other lipids from the gut to the liver and other cells. They have a very short half-life and are only found in the blood stream for a few minutes after a meal containing fats. The different subtypes of lipoproteins are distinguished by the density of their particles and the identity of a specific proteins (called apoproteins) which are embedded in their outer membranes. The apoprotein helps the lipoproteins move around the body and facilitates their interaction with the various body cells. Most cells possess receptors which recognize and bind specifically to these proteins, thereby enabling the cells to internalize the valuable lipid rich cargo. In liver cells, the lipoprotein receptors are used to bind the LDL particles whereupon the partlcles are engulfed by the cells. This enables effective clearance of lipoproteins (which have fulfilled their role) from the blood stream so they can be broken down and their components recycled to make fresh VLDL particles. This continual refreshing of the lipoprotein pool minimizes the accumulation of modified or functionally abnormal lipoproteins. Following modification by binding to blood sugars (a process called glycation) or to oxygen free radicals (a process called oxidation) the particles are not easily cleared by the liver cells and thus accumulate in the blood circulation contributing, along with multiple other factors, to the generation of arterial disease. 

It is important to understand that a standard blood cholesterol test provides very little insight into the actual levels of cholesterol present in our cells at any given time. For instance, if we reduce our dietary intake of cholesterol in an attempt to reduce our blood cholesterol, our bodies will synthesize more cholesterol and/or absorb [recycle] more of it from the gut to meet its requirements for this essential molecule. In fact it has been demonstrated, empirically, that increasing dietary intake of saturated fats and hence cholesterol has little or no impact on circulating levels of cholesterol in the blood. It is also now becoming clear that increasing dietary fat and therefore cholesterol whilst simultaneously restricting the consumption of carbohydrates makes the circulating lipoprortein particles healthier and less atherogenic. 

The unfair demonization of dietary fats especially cholesterol has unsurprisingly, led to a greater reliance on carbohydrates (principally refined sugars and starches) to meet one’s energy requirements. A high glycemic diet (which causes a spike in blood sugar levels) has an insulin elevating effect (also known as hyperinsulinaemia). Chronically high levels of blood insulin are known to promote generalized obesity (including abdomainal obesity) and chronic, systemic inflammation. In the arterial wall, it results in abnormal function of endothelial cells (which line the inside of wall) making it more permeable to lipoprotein particles which are more likely to get trapped in there if damaged by glycation or oxidation. These damaged particles, once trapped within the vessel wall, elicit a strong inflammatory repsonse, setting off a cascade of changes which culminate in the development of an atherosclerotic plaque and hence atherosclerosis.  In addition, hyperinsulinaemia has been strongly and causally implicated in the world-wide epidemic of other chronic diseases such as type II diabetes, cancer and neurodegeneration.

In conclusion there is a growing body of evidence in the field of biomedical research which points to excess dietary carbohydrates as the true villian in vascular disease causation rather than cholesterol.