No Verdict Yet on Vitamin C
Long before hundreds of bottles of herbs, minerals and multivitamin concoctions lined drugstore shelves, vitamin C supplements were there.
Considered a staple by nutritional supplement users, vitamin C has been thought a possible immune-system booster and preventive against heart disease and cancer.
Then came a study released last month at a La Jolla meeting of the American Heart Assn. Those findings indicated that high doses of vitamin C could worsen heart disease.
“The study sort of sent shock waves through the general public, especially people who use supplements,” said Dr. Howard Hodis, a cardiologist and associate professor of preventive medicine at the Keck School of Medicine at USC.
The study, by epidemiologist James Dwyer, also of USC, suggested that vitamin C supplements could worsen heart disease, especially among smokers.
Dwyer’s conclusion rattled many scientists in the large field of antioxidant research, which examines such substances as vitamins C and E and beta carotene and their ability to help prevent heart disease, cancer and other disorders. Nonetheless, scientists are cautioning consumers not to give up on antioxidants.
“We need to look at this in the total scheme of things,” said Hodis, who points to contradictory data. “There is a large amount of epidemiological data showing that, in terms of heart disease, vitamin C has a neutral or moderately positive effect. Certainly, there has been nothing so negative in the literature. We shouldn’t go cold on antioxidants because of this.”
But the value of high doses of antioxidants to prevent disease remains in doubt. That was made clear last week when a prestigious government health panel urged only a slight increase in the recommended dietary allowances of vitamins C and E.
The federal Institute of Medicine panel declined to recommend a specific amount of beta carotene, saying there is no evidence of its value except to help prevent vitamin A deficiency because it converts to vitamin A in the body.
“A direct connection between the intake of antioxidants and the prevention of chronic disease has yet to be established,” said Dr. Norman I. Krinsky, chairman of the panel and a biochemist at Tufts University School of Medicine in Boston.
In fact, said Krinsky, the new recommended intakes for vitamins C and E are so modest that supplements appear unnecessary for most people.
“The majority of the population are already meeting these RDA values through their diet. For those not eating enough, we recommend improving the diet. At no point in the recommendations do we suggest dietary supplements are necessary to meet the RDAs.”
The panel, which was convened two years ago by the National Academy of Sciences to recommend RDA updates (which the U.S. Food and Drug Administration is then free to use in requiring labeling changes), even cautioned against taking high doses of the antioxidants because of possible adverse effects.
Hodis and other antioxidant experts acknowledge that they don’t know whether high doses--on the order of 200 to 500 milligrams of vitamin C and 300 to 600 international units of vitamin E--can help reduce heart disease and cancer.
But they say it’s premature to abandon antioxidant supplementation.
Antioxidants protect cells from being attacked and broken down by harmful oxygen particles called free radicals. Free-radical damage to cells has been suspected as a link to the development of both heart disease and cancer.
There are varying degrees of support for taking vitamins C, E or beta carotene to bolster antioxidant protection. In the case of vitamin C, most studies have been epidemiological studies, which means they can only draw an association between the vitamin and disease rates.
Still, unlike the Dwyer study, most research on vitamin C, including four large studies published in the 1990s, suggests that it benefits the heart.
“But none of these studies can show a cause-and-effect relationship. We need a lot more clinical study,” said Balz Frei, a biochemist at the Linus Pauling Institute at Oregon State University in Corvallis.
Several major clinical trials (comparing a group of people taking antioxidants to a group taking a placebo) will be completed within the next few years. Hodis estimates 18 to 20 clinical trials are underway examining antioxidants’ effects on heart disease prevention.
“These trials span a wide field of end points. Some look at preventing heart attacks and deaths. Others measure [the progress of disease in] arteries,” he said. “Within the next three to five years, there will be enough randomized, clinical trial data in the public realm that one can start making more educated recommendations for supplementing.”
The study presented by Dwyer, of 573 men and women, found that people taking at least 500 milligrams of vitamin C daily developed, over 18 months, an inner artery wall layer 2.5 times thicker than people not taking supplements. Among smokers taking vitamin C, the thickening was five times greater. Arterial wall thickening is part of the process leading to atherosclerosis.
However, the thickening could have been caused by something else, Hodis said.
“One has to step back and ask, ‘Why did we find this?’ There is nothing that I’m aware of that could cause such a rapid growth in the disease process, let alone a vitamin.”
Dwyer said his study only raises questions that require further study.
“It’s one piece of evidence--that’s all,” he said. “The randomized, controlled trials will answer the question people are really interested in as to whether the benefits of antioxidants outweigh the risks and whether people should be using supplements.”
There is other evidence that vitamin C may contribute to cardiovascular health, Frei said. For example, studies have demonstrated that it can lower blood pressure and relax blood vessels.
“There are many papers out there, randomized, controlled trials, showing vitamin C can improve how the blood vessel opens up. That is a very significant effect,” he said.
And, added Hodis, as for the enthusiasm for vitamin C: “What led us to where we are today is an immense amount of literature in labs and in animals and in epidemiology. But it still has to be proven.”
As for vitamin E--another very popular supplement--the picture is a little more complicated. Some studies have shown a positive effect on heart disease while others have found no effect. But many of the current antioxidant studies are focusing on vitamin E, including a USC trial looking at the artery wall thickening in healthy people who take vitamin E.
Finally, there is beta carotene, which was eliminated as a prime candidate for cancer and heart disease prevention when several large studies over the past decade showed it increased risk.
“Beta carotene bombed completely,” Frei said. “One study found no effect whatsoever on heart disease risk or cancer risk. And two of three studies found it causes an increase of cancer among smokers.”
Even though there aren’t a lot of reasons to endorse antioxidant supplements, some doctors still recommend them to people older than 40 because the body is less efficient at absorbing nutrients as we age. Typical doses range from 200 to 500 milligrams of vitamin C daily and 200 milligrams of vitamin E daily.
“Taking these vitamins doesn’t hurt and it may help,” Frei said. “I think there are still high hopes and a lot of reasons to believe that antioxidants can lower risk.”
Krinsky, who led the government panel, agreed that research may eventually yield support for even higher RDAs of antioxidants.
“There are many studies underway. This is a snapshot of what the recommendations are today. It’s conceivable that other studies will come out and will alter future recommendations.”
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Vitamin C, Vitamin E, Selenium
A government panel last week slightly raised the recommended dietary allowances for the antioxidant vitamins C and E, and adjusted the level of selenium, a mineral that also has antioxidant properties. The levels are below what some researchers believe may help prevent heart disease, cancer and other chronic ailments. The government panel also suggested maximum daily doses for the following antioxidants to avoid adverse side effects.
Vitamin C, Vitamin E, Selenium
60 milligrams men 10 IU* men 70 micrograms
women 8 IU women 55 micrograms
New RDA men 90 milligrams 22 IU 55 micrograms
women 75 milligrams
smokers add 35 milligrams
Typical doses
used in 250-500 milligrams 300-600 IU 50-100 micrograms
current
research
Recommended
upper 2,000 milligrams 1,500 IU 400 micrograms
limits
* Vitamin E can be measured in either milligrams or international units. The RDA for vitamin E is 15 milligrams or 22 IU of alpha-tocopherol, a natural form of vitamin E. The upper limit is 1,000 milligrams or 1,500 IU of alpha-tocopherol, or 1,100 IU of dl-alpha-tocopherol, a synthetic version of vitamin E.
Source: Institute of Medicine’s “Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium and Carotenoids”
