Exercise plus nutritional supplements boost nitric oxide to protect against cardiovascular disease

May 24, 2004
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Life Extension Update Exclusive:

Exercise plus nutritional supplements boost nitric oxide to protect against cardiovascular disease



Featured Products:

L-Arginine capsules

Gamma E Tocopherol softgels

Life Extension Update Exclusive

Exercise plus nutritional supplements boost nitric oxide to protect against cardiovascular disease
A study conducted at the University of California Los Angeles by Nobel Laureate Louis J Ignarro and colleagues has found that antioxidants, L-arginine and exercise reduce the risk of atherosclerosis in mice bred to have elevated cholesterol levels.

In the study, published the week of May 24 2004 in the online edition of the Proceedings of the National Academy of Sciences (, the researchers administered a high cholesterol diet, the same diet with vitamins C and E, or the diet with the vitamins plus the amino acid L-arginine, to hypercholesterolemic mice for eighteen weeks. After two weeks on their various dietary regimens, some of the mice in each group were put on a moderate exercise regimen.

All of the mice who exercised experienced a decline in weight and total cholesterol compared to mice that did not exercise or receive supplements. While the mice who exercised and did not receive supplements experienced a 35 percent reduction in atherosclerotic lesions, those did not exercise but did receive supplements experienced a 40 percent reduction. Dr Ignarro commented, "This is interesting, because it shows that the supplements work well even in the absence of exercise.”

In exercising mice who received antioxidants combined with arginine, the effect was magnified, and the animals experienced a significant regression of their atherosclerotic lesions compared to the other groups. The researchers attribute this to the increased nitric oxide produced by exercise and arginine. Nitric oxide lowers blood pressure, prevents excessive clotting and inflammation associated with coronary artery disease, and protects against heart attack and stroke.

By removing oxidants from the blood, vitamins C and E stabilize the nitric oxide, which allows it to rise to higher levels, producing greater benefits. “It wasn't just exercise, it was exercise combined with two common dietary supplements,” Dr Ignarro stated. “This is the first study that shows that if you exercise in addition to taking dietary supplements you have a markedly enhanced production of nitric oxide--in science, we like to call it a synergistic effect."

Dr Ignarro recommends moderate exercise and a low fat diet enhanced with dietary supplements. "I would say just do it. It works in mice, it'll work in humans,” he said.


Atherosclerosis is a factor in several conditions including coronary heart disease (CHD), myocardial infarction (MI), angina pectoris, cerebral vascular disease (CVD), thrombotic stroke, transient ischemic attacks (TIAs), insufficient blood supply to lower limbs and feet (claudication), organ damage, and vascular complications of diabetes (NIH 2003).

Because symptoms can be few or minor in the early stages, atherosclerosis is referred to as “the silent killer" because it can progress undetected for years, particularly in individuals who are at high risk for heart disease.

Elevated blood pressure is associated with many factors (obesity, lack of exercise, increased blood sugar, and cholesterol levels), but high blood pressure can also be an indication of atherosclerosis. Increases in blood pressure generally occur gradually, concurrent with signs of advancing atherosclerotic disease. A study of 18,682 healthy American males (age 40-84 years; follow-up of 11.7 years) confirmed that blood pressure readings of 140/90 or higher were a risk factor for cardiovascular disease (including stroke and cardiovascular death). Hypertension is a major cardiovascular risk factor and borderline, isolated, systolic hypertension deserves special attention as a cardiac risk factor. Systolic hypertension has greater prognostic significance than diastolic hypertension. It is now recognized that the effective treatment of systolic hypertension proportionally reduces cardiac risk (O'Donnell et al. 1997; Izzo 2000).

Precisely what causes atherosclerosis is not known, but several theories have been proposed. Scientists think atherosclerosis begins with damage to the endothelium (the inner layer of an artery). Possible causes of damage to the arterial wall are free-radical reactions; elevated levels of oxidized serum cholesterol, triglycerides, fibrinogen, homocysteine, insulin, high blood pressure, obesity; chronic inflammation, lifestyle factors (physical inactivity and tobacco smoking); and diabetes (AHA 2002b).

Evidence demonstrates that vitamin E protects against development of atherosclerosis by retarding oxidation of LDL, inhibiting proliferation of smooth muscle cells, reducing platelet adhesion and aggregation, and altering the expression and function of adhesion molecules. Vitamin E attenuates the synthesis of leukotrienes and potentiates release of prostacyclin (which inhibits platelet aggregation and acts as a vasodilator) by up-regulating the expression of cytosolic phospholipase A2. These biological functions of vitamin E may protect against the development of atherosclerosis (Chan 1998).

Featured Products

L-Arginine capsules

L-arginine is an essential amino acid. It is required for the body to synthesize nitric oxide, which enables the arterial system to retain its youthful elasticity. Nitric oxide also helps to produce endothelial relaxation factor, which is needed by the arterial system to expand and contract with each heartbeat.


Gamma E Tocopherol softgels

The term “vitamin E” refers to a family of eight related, lipid-soluble, antioxidant compounds widely distributed in plants. The tocopherol and tocotrienol subfamilies are each composed of alpha, beta, gamma, and delta vitamers having unique biological effects. Different ratios of these compounds are found in anatomically different parts of a plant. For example, the green parts of a plant contain mostly alpha tocopherol and the seed germ and bran contain mostly tocotrienols.

When this family of compounds was first discovered and determined to be essential for health, a standardized test for its activity was devised for which the members of the family were rated for their biological activity. In one test, alpha tocopherol scored highest and was rated 100% with all others having lower ratings. In accordance with this rating, alpha tocopherol was deemed to be the essential compound and was called vitamin E. One International Unit (IU) of vitamin E activity is the activity under this rating of 1 mg of the plant-derived form of alpha tocopherol.

Since the original rating method was established, many additional important biological effects of these compounds have been discovered and many nutritional scientists now consider that rating method to be incomplete.

Questions? Comments? Send them to or call 954 766 8433 extension 7716.

For longer life,

Dayna Dye
Editor, Life Extension Update
1100 West Commercial Boulevard
Fort Lauderdale FL 33309
954 766 8433 extension 7716

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