Cholesterol Limbo: Can You Go Too Low?

For many years cholesterol has been denigrated as a factor in heart disease, when all along it was only a spectator at the scene of the accident. Although it’s been the topic of many conversations throughout its public life, cholesterol is misunderstood by many people… who don’t really know what it is. Because it isn’t soluble in water, but only in organic solvents, cholesterol is classified as a lipid. It’s the major steroid in the body, with the greatest concentrations in the myelin sheath that surrounds nerves and in the plasma membrane that encircles each of the trillions of cells from which we are made.  In the membrane, it prevents deformation and decreases permeability to small water-soluble molecules. Without cholesterol, such as in a bacterium or plant, our cells would need cell walls. Beyond its stability-inducing structural role, where it sits parallel to the phospholipids that afford both structure and function to the membrane, cholesterol exerts its character in the manufacture of several hormones, including cortisol, cortisone, and aldosterone in the adrenal glands, and in the formation of the sex hormones progesterone, estrogen, and testosterone. Without it, the body can make neither vitamin D from exposure to the sun, nor the bile made by the liver for the digestion of fats.

Though cholesterol may eventuate cardiovascular entailments for those so susceptible, as would be such for people with existing coronary disease, heavy smokers, those with a family history of CVD (Cardio Vascular Disease), or those who have already suffered a cardiac episode, it is a generally benign molecule that supports membrane function and fluidity. That cholesterol which exists outside the membrane as an extracellular entity may contribute to the cascade of events that leads to the cell proliferation characteristic of the early stages of atherosclerosis.

But low cholesterol may also be a concern, where a disturbed balance between the uptake of cholesterol from lipoproteins and cholesterol efflux may cause the formation of foam cells, which can accumulate in the linings of arteries and cause additional accretion of platelets and other components of blood that can form an atheroma, or plaque. In Chapman’s work it was noted that massive foam cell formation by tissue macrophages may occur despite the absence of lipid accumulation in the vascular wall (Chapman, 2008). Outside the realm of cardiac episodes reside pathologies attributable to hypocholesterolemia (low cholesterol). Such is the case with endotoxic infections that occasionally accompany critical illness and contribute to capillary permeability and fever. This latter condition may arise following the death of a (usually gram-negative) bacterium that gets broken down in the body. In the attempt to rectify the matter, healthcare workers are advised to correct hypolipidemia by administering a reconstituted high-density lipoprotein preparation as both prevention and treatment (Gordon, 1996). Additionally, a correlation has been made between low cholesterol and the presence of immune markers called interleukins, which are regulatory proteins released by cells in the immune system (Gordon, 2001). Herein lies the inference that cholesterol has immunomodulatory properties (Miguez, 2010) (Bukrinsky, 2006).

From other perspectives, cholesterol levels below 160 mg/dL are associated with all-cause mortality other than cardiovascular disease, especially with cancer, respiratory and digestive diseases, violent deaths that include suicide, and hemorrhagic stroke, leading researchers to question the validity of prescribing anti-cholesterol drugs for those persons without additional CVD risks (Meilahn, 1995) (Nago, 2011). In the Honolulu Heart Study, it was noted in six thousand subjects that falling levels of cholesterol were linked to an excess risk of liver disease and cancer, but that stable levels were not (Iribarren, 1995). Previous work identified low cholesterol as causative of early death, where it was concluded that women in particular experience no relationship between high cholesterol levels and cardiovascular events, but that the opposite may apply to most men, leading to a decision not to treat females unless there exists active coronary disease (Hulley, 1992). Hemorrhagic stroke risk may increase by twofold in males with cholesterol levels below 160, but higher values may be protective against cancers of the lung and the lymphatic and hematopoietic systems, and COPD (Chronic Obstructive Pulmonary Disease) (Neaton, 1992). From these and other studies, we may infer that any prolonged treatment with statin or other drugs be closely watched, especially in light of the indication that low cholesterol levels are also associated with suicide and depression (Atmaca, 2008) (Lester, 2002) (Partonen, 1999). Basically, then, control of cholesterol levels needs consistency for cell signaling mechanisms to function at peak efficiency, else the machinery deals with faulty information and results in sickness.

The Canadians have decided that cholesterol intake is not a concern, since dietary cholesterol, as found in eggs, for example, does not become part of serum cholesterol, and even if it did, influence is insignificant. Simultaneously, saturated and trans fats instead are deemed to be primary determinants of serum total cholesterol and troublesome LDL (McDonald, 2004). Life exists at the cellular level. Without cholesterol, membranes would be too fluid. Like the masts that hold a circus tent erect, cholesterol maintains the architecture of the cell and keeps phospholipids far enough apart to prevent them from clumping and becoming disorganized. In this way, everything walks to the beat of the same drummer.

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