Antioxidants Report Sets Ceilings

"It's too early to say." That was the recurring theme of the report on four antioxidants--vitamin C, vitamin E, selenium, and carotenoids--issued in April by the National Academy of Sciences (NAS).(1)

Although the NAS made minor changes in the Recommended Dietary Allowances (RDAs) for vitamins C and E and selenium, most noteworthy was what wasn't said. The scientists set no numbers for carotenoids like lutein, lycopene, and beta-carotene. And they concluded that it's too early to say whether antioxidants could help prevent major threats like cancer, heart disease, diabetes, or Alzheimer's disease.

"Does taking larger doses of dietary antioxidants help limit the gradual buildup of cellular damage that one day may turn into chronic disease?" asked NAS panel chair Norman Krinsky of the Tufts University School of Medicine in Boston.

"After a comprehensive review of the scientific evidence, our panel concluded that too little is known at present to provide a definitive answer."

It's not surprising that the scientists stopped short of more sweeping advice. In fact, the evidence is still in the promising-but-not-conclusive stage--which means that reasonable people could decide to either take or not take high-dose antioxidant supplements (see NAH, April 2000).

The most useful part of the report: The panel set Tolerable Upper Intake Levels (ULs). "ULs are a ceiling," says Krinksky. "They're the largest amount that healthy individuals can take each day, from food and supplements, without risking adverse health effects." Here's the rundown on the NAS's Upper Levels for the four widely consumed antioxidants.

Vitamin C--2,000 mg a day

The panel set an Upper Level for vitamin C based on reports of diarrhea in several small studies. But after two scary headlines the month before the NAS report, the possibility of diarrhea must have sounded downright reassuring to vitamin-C-takers.

Doses of 500 mg a day or more could clog arteries that feed the brain, warned one wave of earlier media reports. But the results of that study, which haven't been published, are too shaky to act on (and are so preliminary that the NAS panel never considered them).

The study measured blockages in the carotid arteries of 570 healthy middle-aged men and women on two occasions, 18 months apart. Arteries clogged faster in those who reported taking 500 mg or more of vitamin C a day than in those who said they took less. The link was even stronger among smokers. But questions remain.

"The blood levels in vitamin-C-takers were lower than they should have been in people taking supplements," says Mark Levine, a vitamin-C expert at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland. That suggests that people didn't actually take the amount of vitamin C they said they took.

What's more, in the larger, well-designed Atherosclerosis Risk in Communities study,(2) "researchers saw fewer arterial lesions with increasing intakes of vitamin C," says Iswarlal Jialal, an NAS panel member from the University of Texas Southwestern Medical Center in Dallas.

The bottom line: Sit tight. "We can't review the unpublished data because it's only an abstract," says Levine. "There are offen surprises when a full study is published."

Soon after that alarm died down, another one went off. "High doses of vitamin C may interfere with cancer treatments," cautioned headlines.

The source was David Golde of the Memorial Sloan-Kettering Cancer Center in New York. His conclusion was based on a published study in which mice were injected with human cancer cells from the breast, prostate, and blood. The tumors that later developed readily absorbed vitamin C.(3)

"Now we know exactly how tumors acquire and retain large amounts of vitamin C," said Golde. "It's conceivable that vitamin C might make cancer treatment less effective, and therefore reasonable that cancer patients undergoing chemotherapy should avoid taking large amounts of this vitamin."

But not everyone agrees.

"It's been known for years that tumor tissues accumulate vitamin C, just as healthy tissues do," says Levine. "But we have no data from human studies to say whether or not vitamin C promotes tumor growth or prevents radiation or chemotherapy from working."

Without data, it's impossible to make any recommendations, he adds. "The only way to know is to do a study."

Vitamin E--1,100 IU (synthetic) or 1,500 IU (natural) a day

The NAS panel based its Upper Level for vitamin E on studies showing that very high doses can cause hemorrhages in rats. "But there are no good data to show that vitamin E in high doses is toxic to humans," says Jialal.

The experts did note that a trial on 29,000 Finnish men found a slightly higher risk of hemorrhagic stroke in those who were given 50 IU (International Units) of vitamin E a day. But in three other trials in people with heart disease who were given 300 IU to 800 IU a day, researchers saw no signs of hemorrhage.

"And in two of those trials, some of the participants also got either fish oil or aspirin, which would increase the potential for bleeding," notes Jialal.