Antioxidants + heart drugs = bad medicine?

Science News, August 11, 2001 by J. Raloff

Many adults take medicine to control their cholesterol--usually statin drugs and sometimes the vitamin niacin. Adding antioxidant supplements to such a daily drug regimen may not be a good idea--at least for people with low concentrations of the so-called good cholesterol, a new study concludes.

Two major classes of lipoproteins shuttle cholesterol around in blood. Low-density lipoproteins, or LDLs, deliver cholesterol to vessel walls, where it can foster artery-clogging plaque. High-density lipoproteins, or HDLs, appear to remove cholesterol from the vascular system.

As a rule of thumb, each 1 percent rise in LDL concentration in the blood or 1 percent decrease in HDL concentration increases a person's risk of coronary heart disease by 1 percent, explains B. Greg Brown of the University of Washington School of Medicine in Seattle.

Of the two concentrations, HDL's is far harder for people to modify through drugs or diet. Brown's group therefore focused on HDL. The researchers recruited 153 heart patients with especially low HDL concentrations. Each participant also had plaque deposits significantly narrowing the interior of at least one artery.

One-quarter of the volunteers received a statin drug and niacin in doses at which it's considered a drug. Another quarter got a daily combination of the antioxidants beta-carotene, vitamin C, vitamin E, and selenium. A third group received placebos, while the fourth got both drugs and antioxidants.

After a year, the drug therapy had triggered big benefits, including a 34 percent drop in LDL and 25 percent rise in HDL concentrations. Participants who had received the placebos or just antioxidants showed minimal improvements in their blood-lipid concentrations. Those getting the drug-antioxidant combo experienced about the same drop in LDL concentration as those receiving only the drugs did, though they showed only an 18 percent increase in HDL values.

Among the HDLs, however, concentrations of [HDL.sub.2]--the one most predictive of heart attack risk---climbed a whopping 42 percent in the participants who took the drugs only, but they didn't rise at all in those also getting antioxidants. Observes Brown, this lack of [HDL.sub.2] improvement is disturbing, especially since participants in this trial started with "strikingly low" [HDL.sub.2] values.

Brown's team reports its findings in the August ATHEROSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY.

In an accompanying editorial, Lewis H. Kuller of the University of Pittsburgh notes that the Seattle researchers presented findings at a March meeting linking the lipoprotein changes observed in the study to buildup of fatty plaque. The drug-antioxidant group had a 7 percent plaque increase, compared with a 4 percent decrease in the drug-only group, he notes.

Kuller concludes that physicians should advise heart patients that taking antioxidant supplements could be hazardous.

The other result is that "these patients do benefit from a statin--and perhaps a niacin," says Charles H. Hennekens of the University of Miami School of Medicine. Most doctors are aware of studies finding little heart benefit from antioxidants, he says, so few prescribe them.

But Ishwarlal Jialal's group at the University of Texas Southwestern Medical Center at Dallas does. In the February CURRENT OPINION IN LIPIDOLOGY, the team cited several major studies reporting heart benefits from large supplements of vitamin E and other antioxidants.

Earlier this week, Jialal conferred with researchers at the University of Oxford in England who are testing a statin-antioxidant combo. He reports that in heart patients getting this therapy, the British team didn't see a negative effect on HDL concentrations, nor has his own team over the years. Jialal therefore suspects that any HDL risk may trace to pairing niacin with antioxidants.