A Unified Theory of Human Cardiovascular Disease Leading the Way to the Abolition of This Disease as a Cause for Human Mortality

Until now therapeutic concepts for human cardiovascular disease (CVD) were targeting individual pathomechanisms or specific risk factors. On the basis of genetic, metabolic, evolutionary, and clinical evidence we present here a unified pathogenetic and therapeutic approach. Ascorbate deficiency is the precondition and common denominator of human CVD. Ascorbate deficiency is the result of the inability of man to synthesize ascorbate endogenously in combination with insufficient dietary intake. The invariable morphological consequences of chronic ascorbate deficiency in the vascular wall are the loosening of the connective tissue and the loss of the endothelial barrier function. Thus human CVD is a form of pre-scurvy. The multitude of pathomechanisms that lead to the clinical manifestation of CVD are primarily defense mechanisms aiming at the stabilization of the vascular wall. After the loss of endogenous ascorbate production during the evolution of man these defense mechanisms became life-saving. They counteracted the fatal consequences of scurvy and particularly of blood loss through the scorbutic vascular wall. These countermeasures constitute a genetic and a metabolic level. The genetic level is characterized by the evolutionary advantage of inherited features that lead to a thickening of the vascular wall, including a multitude of inherited diseases. 1. Linus Pauling Institute of Science and Medicine, 440 Page Mill Road, Palo Alto. CA 94306. The metabolic level is characterized by the close connection of ascorbate with metabolic regulatory systems that determine the risk profile for CVD in clinical cardiology today. The most frequent mechanism is the deposition of lipoproteins, particularly lipoprotein(a) [Lp(a)], in the vascular wall. With sustained ascorbate deficiency, the result of insufficient ascorbate uptake, these defense mechanisms overshoot and lead to the development of CVD. Premature CVD is essentially unknown in all animal species that produce high amounts of ascorbate endogenously. In humans, unable to produce endogenous ascorbate, CVD became one of the most frequent diseases. The genetic mutation that rendered all human beings today dependent on dietary ascorbate is the universal underlying cause of CVD. Optimum dietary ascorbate intake will correct this common genetic defect and prevent its deleterious consequences. Clinical confirmation of this theory should largely abolish CVD as a cause for mortality in this generation and future generations of mankind.