The 1998 Nobel Prize in Physiology or Medicine was awarded to Louis J. Ignarro, PhD, I for ground-breaking research into nitric oxide (NO), a naturally occurring molecule in the body that may be the key to cardiovascular health. Bottom Line/Health has reported on the importance of Dr. Ignarro's discovery and its relevance to heart health. Dr. Ignarro's discovery has prompted every major pharmaceutical company to conduct research into the benefit of NO on heart and circulatory systems. The results include...


Viagra (sildenafil citrate) was the first drug to utilize the NO pathway. In the late 1980s, researchers at Pfizer who were testing a new angina (chest pain due to heart disease) drug realized that about 75% of male patients who took it reported more frequent and firmer erections. Pfizer quickly decided to market the drug for erectile dysfunction instead of angina.


NO is now used in hospitals to treat persistent pulmonary hypertension—a form of hypertension that only affects blood vessels in the lungs—in newborns. In the past, newborns with this condition were unlikely to survive. NO gas, given via inhalation for one to five days, can completely reverse this condition.


A drug (nebivolol) developed in Europe—now  approved by the USFDA—is the first beta-blocker that also elevates NO. Millions of Americans take beta-blockers (also called beta-adrenergic blocking agents), drugs for treating heart disease, hypertension and many other conditions. They cause the heart to beat more slowly and with less force, reducing blood pressure and improving circulation.

The drug is mainly used for hypertension and treating elderly patients with heart failure. Because it raises NO, it also reduces blood clots and arterial buildups that can lead to heart disease/ heart attack. It's the only beta-blocker that produces these benefits.


Nitric oxide (NO) causes blood vessels to dilate, prevents blood clots, regulates blood pressure and may inhibit the accumulation of arterial plaque—the underlying cause of most heart attacks. It's possible that most cases of heart disease could be eliminated by elevating NO.

It isn't yet known how much NO is normally present in the body, or what levels are optimal. NO is difficult to measure because it's a gas that breaks down almost instantly with air exposure. Simpler tests will be needed before doctors can measure NO as a standard part of patient care.

It's thought that NO levels remain at normal levels until early adulthood, and then gradually decline.

Reason: Damage to the endothelial cells from factors such as lifetime exposure to high blood pressure, a high-fat diet, a sedentary lifestyle, arterial inflammation and oxidation from free radicals. Damage to the cells causes a reduction in NO.

Increasing NO is a critical component of heart-disease prevention.

The difficulty: Developing ways to administer it. Because it's an unstable gas that's destroyed by hemoglobin in the blood, it can't be taken as a drug/supplement. However, patients can take other supplements that increase production of NO in the blood vessels. Lifestyle changes, including not smoking, can cause levels to rise.

Important steps…

  • Take L-arginine. It's an amino acid found in nuts, meats, grains, fish, etc. It passes through the intestine into the blood. From the blood it enters endothelial cells, where it's converted to NO. A Mayo Clinic study found that patients taking L-arginine had significant improvements in endothelial function and blood flow, compared to those taking placebos.

Recommended: 5,000 to 6,000 milligrams (mg) of arginine daily.

Eat nuts: A cup of peanuts contains about 5,000 milligrams of arginine. Fish and soy milk are also good sources. Or take arginine supplements—2,000 to 3,000 mg, twice daily.

  • Combine L-arginine with L-citrulline. Supplemental arginine doesn't enter cells readily unless it's combined with L-citrulline, another amino acid. Melons are the richest food sources of L-citrulline, but don't provide high enough levels to significantly increase NO. Supplemental amounts are probably required.

Recommended dose: 200 to 1,000 mg, taken once daily.

  • Get more antioxidants. We now believe that vitamin E and other antioxidant nutrients may protect NO by reducing its breakdown by free radicals. This might be the main reason that antioxidants promote cardiovascular health. Helpful...
  • A daily multi that includes vitamin E. Don't take high-dose vitamin E supplements; recent studies suggest that patients taking daily doses of 400 IU or more may have more disease than those who don't supplement at these levels. The amount of vitamin E in most multi-vitamin-mineral supplements, usually about 50 IU, is well within the safety zone—and can promote NO production.
  • 500-1,000 mg vitamin C daily. Like vitamin E, it reduces oxidation in the blood vessels and may cause a rise in NO. A study in the journal Circulation that looked at 11,000 patients found that those who consumed high levels of vitamin C experienced less thickening of the carotid arteries. A reduction in arterial plaque is associated with higher NO levels.
  • Exercise at least 20 minutes three days a week. It stimulates endothelial cells to continuously produce more NO, even on days you don't exercise.
  • Minimize saturated fat. It contributes to the accumulation of arterial plaque and impairs NO production.

Better: Olive, canola or other vegetable oils, along with the omega-3 fatty acids found in fish and flaxseed. These fats help protect the endothelium by elevating levels of beneficial HDL cholesterol and lowering the harmful, LDL form.

  • Get more fiber. The dietary fiber in grains, fruits and other plant foods lowers blood pressure and LDL cholesterol and raises HDL, thereby protecting endothelial cells.

Bonus: Many of the foods that contain fiber are also rich in antioxidants, which can protect NO.

Recommended amount: At least 25 g fiber daily. Patients who follow the government's dietary recommendations get at least this much.

  • Enjoy a glass of red wine. It contains resveratrol, a powerful antioxidant that can delay the breakdown of NO. It's about 1,000 times more potent than vitamin c.

If you don't drink wine: Have a daily glass of pomegranate or grape juice. They contain many of the same antioxidants as red wine.

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