By Duane Graveline, MD, MPH
Lipoprotein(a) has been around a long time, some say as much as 45 million years. Its molecular structure suggests it was a trade-off, then, of our ability to synthesize vitamin C for this highly thrombogenic substance. That was about the time our remote ancestors were giving up their primarily arboreal existence to descend to the ground and explore the spreading savannahs.
My thinking on this is that our proto-human forebears had relatively little need for vitamin C synthesis in the tree-tops surrounded as they were by twigs, fruit and leaves, all likely sources of vitamin C. Their need, as they began to explore the surface of the ground, was for enhanced thrombosis as they began to experience bites and cuts from surface carnivores.
Those of our ancestors who survived a serious bite by promptly stopping their blood loss, would live to pass on their good fortune to their progeny. Therefore, any molecular mutations favoring thrombogenesis would have a strong selection advantage.
This sequence of events could well explain the progressive transmutation of our original vitamin C synthesis molecular structure into the Lp(a) in today's surface dwellers. No longer do we daily face tooth and claw. Excess Lp(a) now is a liability favoring arterial occlusion. It is no wonder that researchers have found Lp(a) strongly associated with myocardial infarctions ( heart attacks ) yet this substance is indispensable to our health in the event of traumatic injury and blood vessel rupture.
Using data from the Copenhagen City Heart Study - a study of 8,637 people with 16 years of follow-up and 599 myocardial infarction ( MI ) events; the Copenhagen General Population Study - a study of almost 30,000 individuals from 2003 to 2006 with 994 MI events; and the Copenhagen Ischemic Heart Disease Study - a study from 1991 to 2004 of 2,461 people with 1,231 MI events, Kamstrup and others of Copenhagen, Denmark reported a strong association of elevated Lp(a) and risk of myocardial infarctions, sufficient even to support a causal relationship.
Lipoprotein(a) resembles cholesterol and often has been mistaken for LDL cholesterol. However Lp(a) is not LDL cholesterol. Studded with specialized receptors for collagen particles, it is one of the most "sticky" substances in the human body, binding freely with lysine and proline fragments of our collagen matrix. Any endothelial damage sufficient to expose collagen components results in a firm and protracted binding of Lp(a) to these components at the damage site, effectively sealing it.
Hence Lp(a) is called thrombogenic. It is responsible for many of the toxic effects formerly attributed to cholesterol and its LDL carrier. It may damage the cardiovascular system even more actively in the presence of homocysteine - another risk factor for cardiovascular disease.
Lp(a) is found only in humans and other primates, guinea pigs and fruit-eating bats that also share the inability to make their own vitamin C. Most other animals make their own vitamin C in amounts we would consider mega doses, have no Lp(a) and rarely have significant cardiovascular disease.
Having been the first to differentiate Lp(a) from LDL cholesterol, Pauling and Rath did most of the early study of Lp(a), emphasizing that vitamin C is critical both to collagen quality and to levels of Lp(a). They have shown that optimum levels of vitamin C are associated with low levels of Lp(a) and low cardiovascular risk levels. Their recommended levels of vitamin C supplementation range from 2-4gms daily and even higher under stress conditions. They recommend supplemental lysine and proline as well for high risk individuals.
Aspirin is recommended by some based on a study using 81 mg of aspirin on 70 patients with either coronary artery disease or cerebral infarction, finding that aspirin substantially lowered serum Lp(a) concentrations especially in those with high concentrations over 300mg/L. The benefit of aspirin use is most likely that of platelet inhibition thereby partially off-setting the thrombogenic effect of high Lp(a). The mechanism of action whereby aspirin actually reduces Lp(a) levels is unknown
Although niacin is commonly recommended at doses of 1.5 -2 gms/day for lowering Lp(a), patient complaints about this supplement are such that few experienced doctors find this treatment satisfactory. For those fortunate individuals who can tolerate this substance, its use is both economical and effective.
Statins are considered to be generally ineffective for Lp(a) reduction, however, the thrombogenic effect of elevated Lp(a) can be reduced by dosing statins at low, anti-inflammatory rather than cholesterol reducing doses. Those at high risk for cardiovascular disease on the basis of personal and family history would benefit most from this approach. This statin benefit is mediated by nuclear factor kappa B inhibition of platelet function.
CoQ10 has been shown to have a significant effect on lowering Lp(a). In a study of acute coronary disease patients The use of CoQ10 at doses of 120 mg/day was found to give a 22% reduction of Lp(a) levels compared with placebo controls.