Lipoprotein (a), Cholesterol and Homocysteine in Atherosclerosis


Doctor Kilmer McCully labored for three decades to prove the innocence of natural cholesterol in the cardiovascular disease process. His landmark discovery of the importance of homocysteine in the development of atherosclerosis triggered a major shift in our thinking.

He determined arterial wall inflammation secondary to homocysteine elevation was a major player in cardiovascular disease, accounting for perhaps 40% of heart attacks and strokes.

That homocysteine levels are under the control of the vitamins B6, B12 and folic acid is now widely known. Many people are born having a genetic predisposition to deficiencies in one or more of these vitamins. Others may acquire deficiencies in these vitamins because of dietary deficiency or disease. As a result, their homocysteine can rise to levels toxic to their arteries.

McCully cited other factors such as genetically pre-ordained platelet dysfunction, coagulation factors, anti-oxidant deficiencies, omega 6 and Trans fats as also contributing to the cardiovascular disease process by triggering inflammatory responses in the linings of the arteries. Others have acknowledged well-known hemodynamic factors as accounting for the common localization of plaques to those areas of the arteries subject to the greatest hemodynamic stress. This is particularly true for coronary and carotid lesions.

Meanwhile the team of Pauling and Rath had been working for decades on another trigger to the atherosclerosis process that of lipoprotein(a) - Lp(a) - so similar to LDL that it was not recognized as a distinct entity until only the past decade or so. Even McCully lacked the technical resources to separate Lp(a) when he was defining cholesterol's role in atherosclerosis. Research supporting Lp(a) was first presented to the scientific community in 1991 but over-ruled by the mindset of the anti-cholesterol bandwagon - the same mindset that cost McCully some 25 years of delay in presenting his truths to his colleagues.

The story of Lp(a) goes back in our history some 40 million years ago when a mutation in our ancestors caused man and all primates to lose their preexisting ability to make vitamin C, relying instead on Lp(a), a surrogate. For many years researchers in this field failed to recognize the structural similarity between LDL and Lp(a). It was not LDL these researchers kept finding in the sub-endothelial matrix of the arteries, it was Lp(a).

Remember scurvy? With insufficient vitamin C our blood vessels broke down with extravasation of blood. One hundred percent of our vitamin C now must come from dietary sources but in those days we produced our own. We are always just two oranges and a lime away from bleeding! Is it any surprise that throughout our evolution the pressure was on our forebear's biologic systems to stop bleeding and stabilize vascular leaks with fibrin, all the factors predisposing to thrombogenesis and atherogenesis - and all triggered by our vitamin C surrogate, Lipoprotein(a).

It is easy to understand the survival advantage of Lp(a) when one imagines the "tooth and claw" to come with descent from an arboreal to a terrestrial existence. The ultimate result of all this is yet another stimulus to arterial inflammation and another nail planted firmly in the coffin of both cholesterol and LDL as etiologic factors. Incidentally we share this thrombogenic factor only with other primates (and guinea pigs, according to Pauling).

Now we must add one more dietary factor to our growing list of those food items having special focus on atherosclerosis. To vitamins B6, B12 and folic acid now must be added vitamin C.

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

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