Cholesterol - Friend or Foe?

There is no doubt that the present notoriety of cholesterol has all but obscured its physiological importance and necessity in our bodies.

Cholesterol is not only the most common organic molecule in our brain; it is also distributed intimately throughout our entire body. It is an essential constituent of the membrane surrounding every cell.

The presence of cholesterol in this fatty double layer of the cell wall membrane adjusts the fluid level and rigidity the proper value for both cell stability and function. Not all that bad for a substance so maligned in today's media world that we can use the word to frighten small children. Children take heed for without cholesterol they would not even be here.

Cholesterol, a steroid in its chemical structure, is metabolized into other essential body steroids known as the steroid hormones and is therefore the sole substrate within our bodies for the formation of the very powerful chemicals that determine our sexuality, control the reproductive process and make possible our very existence.

This same substance that society has been taught to fear happens to be our sole source for androgen, estrogen and progesterone. Researchers marvel at the remarkable similarity in chemical structure these sex hormones have with each other and with the original cholesterol parent from which they were derived. One might say the glaring family resemblance attests to the mighty power of a methyl group here and a carboxyl group there. The destiny of us all is marvelously controlled by such seemingly minor changes.

This same notorious cholesterol substance is also the parent of a pair of steroid hormones called aldosterone and cortisol. They are of adrenal origin and we could not exist without them.

Aldosterone protects the body from excessive loss of sodium and water and is known in scientific circles as a mineral corticoid. It is absolutely vital for life. Without an adequate supply of aldosterone we would be like an ill-prepared desert traveler destined to die of thirst and dehydration under the glaring rays of a merciless sun as water and salt escape from his body.

Cortisol is known as a glucocorticoid because of its effect on glucose metabolism, but it also has powerful mineral corticoid and immune system functions and is fundamentally involved in the biologic response to the stress in our lives.

Both of these vital substances are created in the cortex, the outer shell of the adrenal glands. When the adrenal cortex is destroyed by accident, surgery or disease, death is inevitable within days unless another source of aldosterone and cortisol can be substituted.

Like the sex hormones mentioned above, there can be no aldosterone or cortisol unless an adequate supply of the parent substance, cholesterol, is available. So much of our life is dependent on this remarkable substance.

And where would we be without calcitrol? Another offspring of cholesterol, this remarkable steroid hormone is charged with the responsibility for maintaining the proper level of calcium in our bodies. Just as sodium must be maintained at proper levels for us to function, so must serum calcium be maintained within a very narrow range.

Without calcitrol the calcium we ingest would pass through our bowels unclaimed. The calcium in our teeth and bones would be rapidly depleted, leading to advanced osteoporosis, skeletal weakness and fractures. The interference with nerve transmission to our muscles would result in a hyper-excitable state. We have all seen cartoons and movies where a doctor gets an exaggerated knee jerk response while checking a patient's reflexes.

In a state of sufficiently low serum calcium there could result not only brisk reflexes but massive seizures of muscles, incompatible with life, in a condition known as generalized tetany. Such is the power of a simple element like calcium on our bodies if homeostatic levels are violated.

These observations reflect the labyrinthine complexity of physiologic inter-relationships as more and more of nature's secrets are discovered. As we refine our research techniques and our microscopes probe ever more deeply into the molecular chemistry of cholesterol, we discover far more mystery, puzzles and questions than we find answers.

Again, cholesterol is the basis of all these steroid hormones without which life, as we know it would not be possible. But, by no means is the list of cholesterol's contributions to body function exhausted, for there is another class of cholesterol's steroid offspring without which our metabolic well-being might be in serious jeopardy, the production of bile acids.

Secreted by the liver and stored in the gallbladder these steroids make it possible for us to emulsify fats and other nutrients enabling them to be digested and absorbed as food. In the absence of sufficient bile acids we would all be like those unfortunate souls whose intestinal villi are rudimentary or deficient, which causes them to produce voluminous stools of undigested material while they slowly starve.

The pharmaceutical industry would lead us to believe that rapidly bottoming out our natural cholesterol levels through the use of their highly touted statin drugs is a relatively innocuous process of definite benefit to society. But as we learn more each day of this ubiquitous and unique substance, we must question the veracity of their medical advisors.

Cholesterol is perhaps the most important substance in our lives. Researchers everywhere are learning how extraordinarily complex and often surprising are the pathways that produce and metabolize cholesterol in our bodies. Admittedly, even after decades of study of this remarkable chemical, we still have much to learn.

On 9 November 2001 a research news release from the Max Planck Society for the Advancement of Science announced to the world the discovery of the identity of the elusive synaptogenic factor responsible for the development of highly specialized contact sites between adjacent neurons in the brain known as synapses. For years the nature of this magic ingredient had been sought. Not surprisingly to specialists in the field, the synaptogenic factor finally was shown to be the notorious substance cholesterol!

The so-called glial cells of the brain, long suspected of providing certain housekeeping functions, were shown to produce their own supply of cholesterol for the specific purpose of providing nerve cells with this vital synaptic component.

As many of you may know, the neuronal synapse of the nervous system is the basis of neurotransmission connecting the brain with the rest of the body. The brain cannot tap the cholesterol supply in the blood, since the lipoproteins that mediate the transport of cholesterol, including both LDL and HDL, are too large to pass the blood-brain barrier, explains Dr. Frank Pfrieger leader of a research group which also included the National Center for Scientific Research in Strasbourg, France. The brain must depend upon its own cholesterol synthesis, which the glial cells provide.

This should be sobering news for those in the pharmaceutical industry developing drugs, which interfere with cholesterol biosynthesis, the mechanism of action of the newer Statins. One wonders how anyone knowing the mechanism of brain cholesterol synthesis can seriously challenge the inevitability of cognitive side effects from statin drug use.

The only surprise is that there are not more reported cases of memory impairment, amnesia, confusion and disorientation but even that, we suspect is due to the almost complete lack of physician awareness of the possibility of cognitive impairment from the statin class of drugs. When confronted with these complaints by an anxious patient on a statin drug, he almost always reassures them that they are older now and should expect senior moments, early senility or perhaps a touch of Alzheimer's.

This strikingly positive information about cholesterol is heady stuff, indeed, for a substance with such bad press.

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor



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