Nutriceuticals for cardiovascular health

T recently coined term “nutriceutical” is enjoying increasing popularity for describing a variety of nonprescription products that are used to enhance health. There are several interpretations (and variant spellings) of the term, but it is best reserved to describe products that are (1) naturally occurring substances (e.g., vitamins, amino acids, herbals) or formulations of these substances; (2) based on a strong scientific foundation; and (3) supported by clinical trials of their utility. Nutriceutical is a useful term for a physician to know because it is appearing more frequently in the lay press. However, this term has no legal standing. The US Food and Drug Administration (FDA) recognizes drugs, medical foods, dietary supplements, and food additives as distinct regulatory categories. Most “nutriceuticals” are dietary supplements, although a smaller percentage are medical foods and food additives. Cardiovascular nutriceuticals are agents in this category that have been shown to enhance cardiovascular health. For example, cardiovascular nutriceuticals may stimulate increased release of nitric oxide, block the production or enhance the degradation of superoxide anion, or have beneficial effects in preventing the oxidation of lipoproteins. The nutriceuticals to be discussed in this brief review include vitamin E, vitamin C, coenzyme Q10, carotenoids (beta carotene, lycopene), flavonoids, and Larginine (Table I). Vitamin E: A lipid-phase antioxidant, vitamin E (a-tocopherol) protects tissue lipids from attack by oxygen free radicals.1 This extensively investigated antioxidant vitamin increases resistance to lipid peroxidation and reverses endothelial vasodilator dysfunction. Several major studies have demonstrated the cardioprotective benefits of supplemental intake of vitamin E: (1) Cholesterol Lowering Atherosclerosis Study (CLAS)2—men who took $100 IU per day of supplementary vitamin E had less progression of coronary artery lesions than did men whose supplementary intake of vitamin E was ,100 IU per day; (2) Atherosclerosis Risk in Communities Study (ARIC)3—use of vitamin E slowed the progression of atherosclerosis, measured by intima–media thickness of the carotid artery wall, in both men (nonsignificant difference, p 5 0.13) and women (significant difference, p 5 0.033) .55 years old; and (3) Cambridge Heart Antioxidant Study (CHAOS)4—doses of 400– 800 IU of vitamin E decreased the relative risks of nonfatal myocardial infarction by 77% in patients with coronary atherosclerosis. Vitamin C: The major aqueous-phase antioxidant, vitamin C (ascorbate) traps peroxyl radicals in the aqueous phase before they can initiate lipid peroxidation.1 Vitamin C enhances the activity of vitamin E,1,5 and it improves and normalizes endothelial vasodilator function in patients with chronic heart failure by increasing the availability of the potent vasodilator nitric oxide.6,7 Improved endothelial function with vitamin C has also been observed in patients with hypertension, hypercholesterolemia, and diabetes mellitus.6–8 As was the case with vitamin E, the ARIC study found that vitamin C slowed the progression of atherosclerosis in men and women .55 years old.3 However, the CLAS study did not show any cardiovascular benefit with high intake of supplementary vitamin C.2 Coenzyme Q10: The lipid-phase antioxidant coenzyme Q10 is a free radical scavenger that regenerates vitamin E.1 It inhibits the oxidation of low-density lipoprotein. In both animal and human models, coenzyme Q10 protects left ventricular function from ischemia reperfusion injury,9 apparently through its antioxidant properties.9 The synthesis of coenzyme Q10 is inhibited by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (“statins”). At the present time, although it is a fairly popular (yet expensive) dietary supplement, there are insufficient clinical data to recommend the use of coenzyme Q10 as a cardiovascular agent. Carotenoids: There have been .600 naturally occurring carotenoids that have been identified. These substances are fat-soluble plant pigments that provide the bright color of various fruits and vegetables.10,11 They are transported in the body via lipoprotein.11 The singlet oxygen-quenching properties of carotenoids contribute to the prevention of lipid peroxidation.10 BETA CAROTENE: The most ubiquitous and thoroughly studied carotenoid is b carotene.1 The major precursor of vitamin A, b carotene is found in many yellow, orange, and dark green leafy vegetables and in some yellow fruits.12 In the Health Professionals Follow-up Study,5 men in the highest quintile of b carotene intake had a significantly lower risk of coronary artery disease than did those in the lowest quintile of intake. In the Nurses’ Health Study,13 women in the highest quintile of intake had a 22% reduction in risk of coronary artery disease compared with those in the lowest quintile. However, in studies among patients at high risk for lung cancer—Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) and Carotene and Retinol Efficacy Trial (CARET)—high doses of b carotene correlated with an increased risk of lung cancer.12,14 Neither of these studies, nor the Physicians’ Health Study, showed a protective effect of b carotene on cardiovascular disease.11 Indeed, in ATBC, particFrom the Falk Cardiovascular Research Center and Stanford University Medical Center, Stanford, California. Address for reprints: John P. Cooke, MD, PhD, Falk Cardiovascular Research Center, Stanford University Medical Center, 300 Pasteur Drive, Stanford, California 94305–5246.