4) We have identified a molecular "grappling hook," a peptide, that LDL sinks into the free-radical damaged artery linings.
First, lets take a brief look at the new studies that show antioxidant nutrients prevent heart disease.

Antioxidant Nutrients Prevent Heart Disease
My research in 1973 showed that dietary cholesterol didn't cause heart disease. [5] For those who are still skeptical, please read the confirming studies in the thirteen cited references. [6-18] In 1974, I conducted an epidemiological study that showed vitamin E protected against the artery damage that leads to plaque (the so-called cholesterol deposits) and heart disease. [19-21]

In my study, where persons consumed 400 IU or more daily of vitamin E for more than two years, their rate of heart disease was significantly lower than normal. The amount of heart disease in any age group decreased proportionally with the length of time that vitamin E had been taken. In fact, the length of time was more important than quantity after a minimum of 400 IU daily was taken.

Several researchers, including Dr. William Hermann of the Methodist Hospital in Houston and Dr. Staurt Hartz of Tufts University, have now reported that vitamin E supplements raise HDL. [22] A 1987 study has found that 500 IU of vitamin E daily for three months produces a significantly improved HDL level, Apolipoprotein A level, and Apolipoprotein A to Apolipoprotein B ratio. [23]

Vitamin C has also been shown to raise HDL significantly. [24]

And, of course, selenium has been shown to be protective. [25] Epidemiological studies have shown that persons with low-selenium diets have two-to-three times greater risk of heart disease than those eating selenium rich diets. [26] In a clinical study, patients with blockage of all three coronary arteries had low blood selenium levels, while those with high blood selenium levels were healthy and free of coronary heart disease. [27] Strikingly, those with one diseased coronary artery had the next highest blood selenium levels, and those with two blocked coronary arteries had the second lowest blood selenium levels.

The role of antioxidant nutrients is not just in preventing the artery damage that leads to atherosclerotic plaques, but in protecting against the formation of blood clots when blood is squeezed through plaque-narrowed arteries. Vitamin E reduces the stickiness of blood. Sticky blood due to high blood platelet adhesion is what causes blood to clot in the coronary arteries resulting in heart attacks. [28] Dr. Rudolph Riemersa of the University of Edinburgh in Scotland and Dr. Fred Gey of the University of Berne in Switzerland have found that men with higher-than-average blood levels of beta-carotene, vitamin C and vitamin E --particularly vitamin E -- were less likely to have clinical symptoms of heart disease than those with lower-than-average levels of these nutrients. [29]

Two months ago, I discussed the Harvard Physicians' Health Study, in which approximately 22,000 male physicians took either beta-carotene or a placebo alternating with either aspirin or a placebo. Physicians who took the 50 milligrams (xx,000 USP) of beta-carotene every other day had about half as many heart attacks, strokes, cardiac arrests, bypass operations or angioplasties to remove embolisms. Among a sub-group of 333 physicians with a previous history of heart disease, those taking a combination of aspirin and beta-carotene suffered no heart attacks in six years of study! [30]

Lipoprotein(a)
As for LDL and HDL relationships, a better marker for heart disease risk is the lipoprotein(a) [Lp(a)]. There is no correlation between Lp(a) levels and cholesterol plasma levels, and in heart patients having normal blood cholesterol levels, the only risk factor found is elevated Lp(a) or decreased vitamin C and vitamin E levels.

Drs. Matthias Rath and Linus Pauling have published a revealing paper linking heart disease, Lp(a) and vitamin C deficiency. Lp(a) shares with LDL its lipid and apoprotein composition -- mainly apoprotein B-100 (apo B), but the unique thing about Lp(a) is an additional glycoprotein, apoprotein(a) or apo(a). This difference will be discussed in a later installment of this series.

Lp(a) levels are elevated in heart disease patients. Lp(a) blood levels above 30 milligrams per deciliter of blood doubles the risk of coronary heart disease. If, in addition, LDL is elevated,the risk is increased by a factor of five. There is no correlation between Lp(a) levels and blood cholesterol levels. In heart disease patients having normal blood cholesterol levels, the only risk factor is found to be elevated Lp(a).

Lp(a) can be normalized by vitamin C. [31] Another 1990 report showed that vitamin C reduces risk for heart disease. [32]

Oxidized LDL and Antioxidants
As discussed in last month's column, the initiation of atherosclerosis results from injury to the layer of endothelial calls which normally form the luminal surface of blood vessel walls.

Such injury disturbs local vascular homeostasis resulting in platelet deposition, aggregation and release of factors which promote smooth muscle proliferation and eventual fibrosis. The damaged endothelium also becomes permeable to lipoproteins, particularly oxidized LDL and macrophages which invade the site of injury, accumulate cholesterol as cholesterylester, and develop into foam cells and then fatty streaks.

Eventually, a rather complicated structure, the atherosclerotic plaque, develops consisting of lipids (fats) complex carbohydrates, blood, blood products, fibrous tissue and calcium deposits. A raised blood LDL-cholesterol concentration has been recognized as a risk factor for heart disease because it appears to be the donor of cholesterol deposited in the atherosclerotic plaque. Raised LDL is associated more with heart disease incidence than is blood cholesterol level, but HDL/LDL ratio correlates better, and better yet, lipoprotein(a). The roles of these cholesterol carriers will become clearer in later installments of this series.

The accumulation of LDL-borne cholesterol by macrophages is something of a paradox, however, since the cell has few LDL-receptors and is able to down regulate the receptor number when the LDL-cholesterol concentration is increased. The resolution of this paradox may lie in one of two closely related explanations. The first explanation is that the oxidation of LDL produces a molecule which is no longer recognized by the LDL receptor but by a non-regulated scavenger receptor. The macrophages can then accumulate cholesterol from this oxidized LDL.

The second explanation is that oxidized LDL is attacked by the macrophages and the macrophages are unable to digest the LDL particles and "die". The fat-filled "dead" macrophages accumulate and injure the arterial lining resulting in plaque.

Antioxidants can prevent or slow the accumulation of cholesterol that is due to the modification or oxidation of LDL. Antioxidant nutrients inhibit the oxidation of human LDL. The synergistic protection of vitamins A and C against LDL being oxidized has been shown. [33] Dr. K. Sato and colleagues at the University of Tokyo has found that LDL is oxidized by a free radical chain mechanism. Vitamin E halts this process within the fatty portions of the LDL complex, while vitamin C is stops the free radical damage in the watery medium. The two antioxidant vitamins act simultaneously and cooperatively to reduce oxidation of LDL.

Dr. J. C. Fruchart and colleagues at the Pasteur Institute in Lille, France found that when they gave volunteers with high LDL 1,000 IU of vitamin E daily for two months, they produced fewer "dead" fat filled macrophages and had lower blood cholesterol levels.

Antioxidant nutrients also protect the artery cell membranes lining the arteries. A study at the University of Kentucky by Dr. B. Hennig showed that when artery tissues were well-nourished with vitamin E, they were protected from injury. [34] However, when they were vitamin E deficient, oxidative stress caused many deleterious changes in the arteries. Related findings have been reported by researchers at the Institute of Biochemical Science in Italy. [35]

In the Harvard Physicians Health Study mentioned earlier, Dr. Gaziano noted that beta-carotene discourages the formation of oxidized LDL, but there is more to antioxidant protection than that. Dr. Daniel Steinberg of the University of California at San Diego adds that "you're dealing with men in the study who have established atherosclerosis, so it may be that oxidized LDL's cytotoxicity is involved in thrombosis (clotting). Oxidized LDL may be involved in fatty streak formation and precipitation of the coronary event." [36]