Coronary Artery Disease and Atherosclerosis

L-arginine. This amino acid has attracted attention for its ability to improve endothelial function. L-arginine serves as the precursor of nitric oxide in the endothelium (Cockcraft JR 2005). Early studies with L-arginine to improve endothelial function have been small and have usually relied on intravenous L-arginine in high doses, however (Oka RK et al 2005). To find out whether L-arginine improved arterial function in people with peripheral arterial disease, as well as determine an optimal oral dose, a group of researchers from the University of California, San Francisco, looked at L-arginine’s ability to improve walking distance and walking speed among people with peripheral arterial disease. The research group found in a pilot study of 80 patients that 3 g L-arginine daily improved both walking speed and distance (Oka RK et al 2005). Another study looked at the effects of oral L-arginine versus vitamin C in patients with stable coronary artery disease. L-arginine therapy of 10 g daily improved brachial artery dilation, a measure of endothelial function (Yin WH et al 2005).

While the association between L-arginine and nitric oxide is clear, a few newer studies have suggested that supplemental L-arginine alone may not boost nitric oxide in patients who recently had a heart attack. One study from Johns Hopkins Medical Institutions in Baltimore was stopped after researchers found an increased risk of death in heart attack patients taking L-arginine. There are several possible reasons for this, including the important point that nitric oxide can generate free radicals. Life Extension, however, notes that studies questioning L-arginine’s effectiveness failed to provide the necessary antioxidants to counteract any elevation in free radicals caused by the supplement. Thus, Life Extension believes that any person taking L-arginine to lower blood pressure and improve blood flow should also take antioxidants, such as vitamin C and vitamin E.

Antioxidant and Anti-Inflammatory Nutrients

Interestingly, only about half the people with coronary artery disease have more traditional risk factors, such as elevated cholesterol, smoking, high blood pressure, and obesity. Yet all patients with atherosclerosis suffer from endothelial dysfunction and the damaging effects of oxidized LDL, which provides an important building block for plaque deposits. Antioxidant therapy is therefore important to limit the oxidization of LDL and improve the health of the endothelium by limiting the damage caused by inflammatory cytokines. The following antioxidants are some of the most effective studied in atherosclerosis:

Lipoic acid. This naturally occurring antioxidant serves as a coenzyme in energy metabolism of fats, carbohydrates, and proteins. It can regenerate thioredoxin, vitamin C, and glutathione, which in turn can recycle vitamin E. Lipoic acid also helps manage proper serum glucose levels in diabetic patients (Packer L et al 2001). In animal studies, it has been shown to reduce endothelial dysfunction (Lee WJ et al 2005a). Human studies have found that lipoic acid improves endothelial function among people with metabolic syndrome (Sola S et al 2005). Lipoic acid works best in combination with antioxidants including vitamin E, coenzyme Q10, carnitine, and selenomethionine (Mosca L et al 2002).

Garlic. Aged garlic extract has been studied for its ability to reduce inflammation and the damaging effects of cholesterol in the endothelium (Orekhov AN et al 1995). In one study of 15 men with coronary artery disease who were also being treated with statin drugs and low-dose aspirin, two weeks of supplementation with aged garlic extract significantly improved blood flow by improving endothelial function (Williams MJ et al 2005). Another study examined garlic’s ability to improve exercise capacity in patients with proven coronary artery disease. This study of 30 patients found that garlic oil significantly lowered heart rate during a stress test on a treadmill and otherwise eased the heart’s workload during the exercise (Verma SK et al 2005). Finally, high-dose garlic was studied in 152 people with atherosclerotic plaque. Over 48 months, the study participants experienced significantly less increase in plaque deposits than a control group, and an actual regression of plaque was seen in some participants, leading researchers to conclude that garlic had a “not only preventative but possibly also a curative role in arteriosclerosis therapy” (Koscielny J et al 1999).

Ginkgo biloba. Approximately one-third of Ginkgo biloba extract is made up of the flavone glycoside known as quercetin (Hibatallah J et al 1999). Quercetin has been shown to have antioxidant properties and inhibits LDL oxidation in experimental studies (Janisch KM et al 2004). Daily dosing with 120 mg Ginkgo biloba has been documented to reduce markers of lipid peroxidation in humans (Kudolo GB et al 2003). Higher doses (320 mg daily) have may be beneficial in reducing ischemia in patients with atherosclerosis (Mouren X et al 1994). Life Extension, however, cautions against using doses of ginkgo higher than 120 mg daily. This caution is based on the slight possibility that higher doses of ginkgo could induce too strong an antiplatelet effect, which could result in an internal blood vessel bleed.

Quercetin. The so-called French paradox is the phenomenon of low rates of heart disease in a country known for its high intake of fatty foods. Recent research suggests that one of the reasons French people are protected from heart disease is a high intake of quercetin, a potent antioxidant and polyphenol found in red wine (Kuhlman CR et al 2005). Numerous studies have examined quercetin and found it to be both a powerful antioxidant and a stimulator of nitric oxide, which inhibits endothelial proliferation, a hallmark of atherosclerosis (Kuhlman CR et al 2005). Studies have shown the following:

• In spontaneously hypertensive rats, quercetin, along with other bioflavonoids, preserved endothelial function by increasing nitric oxide and reducing blood pressure (Machha A et al 2005).
• A porcine study showed that quercetin has potent antioxidative properties and protects endothelial cells against induced dysfunction (Reiterer G et al 2004).

Green tea extract. Green tea extracts, which are rich in natural antioxidants and antiplatelet agents, are routinely used in Asia to lower blood pressure and reduce elevated cholesterol. In studies of smokers, 600 mL green tea (not extract) was shown to decrease markers of inflammation and decrease oxidized cholesterol, both of which are intimately involved in the development of atherosclerosis (Lee W et al 2005b). A Japanese study of 203 patients found that the more green tea patients drink, the less likely they are to suffer from coronary artery disease (Sano J et al 2004). This study supported an earlier study that found that greater green tea consumption was related to a reduced presence of coronary artery disease in Japanese men—although not in women (Sasazuki S et al 2000).

Vitamin C (ascorbic acid). Vitamin C inhibits damage caused by oxidative stress. In cigarette smokers, daily supplementation with 500 mg vitamin C significantly decreased the appearance of oxidative stress markers (Dietrich M et al 2002). Another study showed that supplementation with 500 mg vitamin C and 400 IU vitamin E daily significantly reduced the development of accelerated coronary arteriosclerosis following cardiac transplantation (Fang JC et al 2002). Vitamin C’s benefits seem especially profound in people who suffer from both diabetes and coronary artery disease. One study demonstrated that, in this group, vitamin C significantly improved vasodilation (Antoniades C et al 2004).

Vitamin K. Vitamin K is steadily gaining attention for its ability to reduce calcification and help prevent cardiovascular disease (Jie KSG et al 1996). Evidence for the ability of vitamin K to prevent calcification can also be found in an animal study in which researchers administered the anticoagulant warfarin to rats. Warfarin is known to deplete vitamin K. At the end of the study, all the animals had extensive calcification, suggesting they had lost the protective effect of vitamin K (Howe AM 2000).

Vitamin E. Vitamin E is often studied in conjunction with vitamin C for its potent antioxidant powers. It has been shown to decrease lipid peroxidation and inhibit smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, oxidized LDL uptake, and cytokine production—all of which occur during atherosclerosis (Munteanu A et al 2004; Harris A et al 2002). In cultured arterial endothelial cells, vitamin E increased the production of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation (Wu D et al 2004). Most vitamin E supplements come in the form of alpha tocopherol. Life Extension recommends about 400 IU alpha tocopherol a day, along with at least 200 mg gamma tocopherol and 100 mg of coenzyme Q10. There is a concern that taking only the “alpha” form of vitamin E could deplete the body of gamma tocopherol, a critically important antioxidant. Coenzyme Q10 helps regenerate oxidized vitamin E in the body.

Hormone Therapy for Healthy Arteries

Atherosclerosis is closely associated with hormonal changes in women. However, after menopause, as the levels of all sex hormones decline, the rates of atherosclerosis go up. Both men and women experience significant decline of hormones that play a role in maintaining healthy arterial function. Atherosclerosis is known to increase at the same time that hormone levels are decreasing as a result of age. Overall, levels of dehydroepiandrosterone (DHEA), testosterone, and other hormones decline in aging humans—the same group that is especially at risk for atherosclerosis.

DHEA. DHEA is a precursor to sex hormones such as testosterone and estrogen. Levels of steroid hormones, including DHEA, decline with the age-associated onset of a variety of medical conditions, including chronic inflammation, hypertension, and atherosclerosis. Levels of DHEA in humans are inversely correlated with inflammatory markers (Sondergaard HP et al 2004). Animal studies show a protective role for DHEA in preventing atherosclerosis. Providing DHEA to human vascular endothelial cells in culture increases nitric oxide synthesis, which boosts blood flow (Simoncini T et al 2003). A study showed that men with high levels of DHEA tended to have greater protection against aortic atherosclerosis progression (Hak AE et al 2002).

Phytoestrogens. Following menopause, circulating levels of estrogen are depleted. Phytoestrogens are plant hormones with estrogenic activity. In postmenopausal women, phytoestrogens appear to have estrogen-like benefits such as protection against osteoporosis (Atkinson C et al 2004; Crisafulli A et al 2004a) and possibly hot flashes (Crisafulli A et al 2004b). Phytoestrogens have also been shown to improve vascular function, which tends to decline with age. In one study genistein, a phytoestrogen, provided in a daily 54-mg supplement for one year, significantly improved endothelium-dependent vasodilation in postmenopausal women. Moreover, its benefits were as substantial as those observed in women receiving an estrogen-progestin regimen (Squadrito F et al 2003).

For more information on bioidentical hormone replacement, please see Female Hormone Restoration and Male Hormone Replacement.