Heart-protective effect is independent of antioxidants.

If red wine protects against heart disease, it's probably not because of the antioxidants that the drink contains, two new studies in mice suggest.

Many scientists presume that oxidation of low-density lipoprotein cholesterol--bad cholesterol--is a major cause of atherosclerosis, the fatty plaques that can accumulate inside the arteries around the heart.

Therefore, an often-proposed explanation of red wine's protective effects has been its abundant supply of the antioxidants called polyphenols. However, two studies in the January American Journal of Clinical Nutrition report no sign of reduced oxidation within the arteries of heart-disease-prone mice given alcoholfree red wine. Nevertheless, the mice drinking that wine had fewer fatty plaques in their arteries than animals drinking plain water did.

A team led by biochemist Kevin D. Croft of the University of Western Australia in Perth monitored the concentrations of three markers of oxidized fat in blood and tissue of the aorta, the large artery leaving the heart. A hundred mice genetically engineered to develop atherosclerosis were fed a high-fat, high-cholesterol diet. Half of the mice also received alcoholfree wine in an amount equivalent to a person's drinking two to four glasses each day. The scientists had removed the wine's alcohol because alcohol oxidizes fat and so would affect the arterial oxidation being tracked.

During the 20-week study, the mice receiving the wine developed only 60 percent as many artery plaques as the others did, the researchers report. However, the markers of oxidized fat were identical in the two groups.

"These results suggest that ... the protective action of red wine polyphenols is independent of any antioxidant action of these compounds," Croft and his colleagues conclude. Polyphenols instead may stimulate the production of nitric oxide inside the arteries. In cell studies by other researchers, nitric oxide has inhibited atherosclerosis.

In a second study with mice, a team led by biochemist Roland Stocker of the University of New South Wales in Sydney, Australia, fed a normal diet to 100 of the same type of genetically engineered mice that Croft's group used. For 6 months, half the animals also received alcoholfree wine in an amount equivalent to a person's drinking one glass a day.

The wine-drinking mice had significantly fewer plaques in their aortas but not a lower concentration of the oxidation marker that the team measured. In fact, the wine drinkers displayed more of this marker. Stocker and his colleagues also measured the inner walls of the animals' aortas and found those in mice receiving wine to be thinner--a sign of healthy arteries.

Both studies' findings are "controversial" and "important,' says biochemist Balz Frei of Oregon State University in Corvallis. In previous reports, Stocker's team had asserted that atherosclerosis isn't linked to oxidation of bad cholesterol, says Frei. He adds that Croft's team is the first to report independent findings that support that conclusion.