Title: Vitamin overdose?

Key words: megadose, citrus fruits, scurvy, limeys, vitamins, vitamin B, vitamin C, vitamin E, beta-carotene, safe levels, premenstrual syndrome, antioxidants, lung cancer, coronary disease, low density lipoproteins, stroke, heart attack, fruit and vegetables, digestive tract cancers

Date: April 2001

Category: Materia Medica

Type: Article



Megadoses of vitamins can seriously damage your health, but nobody knows how high you can safely go

In 1794, a Royal Navy squadron set sail with enough raw lemon juice to last a 23-week voyage. The Admiralty had finally got round to testing the ideas of the Scottish surgeon James Lind, who had discovered in 1747 that citrus fruits can stave off scurvy. The experiment proved so successful that the Admiralty made its ships carry supplies of citrus fruit, and British sailors quickly became known as "limeys" because of their lime juice ration. Scientists realised for the first time that the body needed essential trace nutrients that later came to be called vitamins.

Two hundred years later, just about the only thing scientists know for sure about vitamin C is that 60 milligrams a day will prevent scurvy. Nevertheless, many people pop pills containing thousands of milligrams, hoping to prevent cancers or ward off the common cold. Linus Pauling, the Nobel prizewinner who in his old age extolled the benefits of vitamin C, reportedly stirred 18 grams into his daily orange juice. He lived to the ripe old age of 93. Last April, however, researchers at the University of Leicester reported that a supplement of as little as 500 milligrams of vitamin C a day may produce free radicals, which can damage DNA and cause cancer (Nature, vol 392, p 559).

Although this study was widely criticised for being flawed, it highlights a growing worry about high doses of vitamins. Long regarded as worthless but harmless, megadoses have come under heightened scrutiny after two large studies showed that beta-carotene can increase the risk of cancer. Many European countries have already laid down maximum limits for vitamin tablets that are sold to the public and last year the European Commission issued a discussion document on the maximum safe levels.

But what should be the maximum limit? There is a lack of hard data. The studies that have been carried out frequently contradict each other. And the public likes its vitamins. In Britain last year the government proposed limiting the intake of vitamin B6 by banning the sale of tablets containing more than 10 milligrams, because of worries that high doses could cause nerve damage. But women who take up to 200 milligrams as a diuretic to relieve premenstrual syndrome reacted with dismay and forced the government to back down in July last year.

The Ministry of Agriculture, Fisheries and Food's advisory group on vitamins and minerals is now considering whether to recommend maximum doses for vitamin supplements. The US Institute of Medicine is due to issue a report this autumn recommending intakes of antioxidants, including vitamin C, vitamin E and beta-carotene. Antioxidants can neutralise free radicals and they have been touted as cure-alls for a whole range of diseases.

But the evidence for the beneficial effects of antioxidants is ambiguous. One study, conducted by the National Cancer Institute in the US and Finland's National Public Health Institute, tested the hypothesis that antioxidants would help to prevent cancer in smokers. The researchers recruited 29 000 male Finnish smokers, dividing them into four groups. From 1985 to 1993, one group was given a daily pill with 50 milligrams of alpha-tocopherol (a form of vitamin E), one group took 20 milligrams of beta-carotene, one group took both vitamins, and the rest took a placebo. To the researchers' horror, the risk of cancer among the group on the beta-carotene supplement increased by 16 per cent (The New England Journal of Medicine, vol 330, p 1029). "It was a huge shocker to the whole field," says Susan Taylor Mayne of Yale University.

Further analysis of the data showed that heavy smokers and people who drank alcohol seemed worst affected. This theory gained support from a second long-term trial, led by Gilbert Omenn of the Fred Hutchinson Cancer Research Center in Seattle. Omenn and his colleagues looked at 18 000 American men and women at risk of lung cancer (The New England Journal of Medicine, vol 334, p 1150). Smokers, former smokers and workers exposed to asbestos took either a placebo or supplements of vitamin A and beta-carotene for an average of four years. The researchers stopped the study in January 1996 because the group on supplements had a 28 per cent higher incidence of lung cancer (see Diagram). The investigators could not explain the findings, which they described as "troubling".


Beta-carotene increases risk of cancer

Mayne believes that oxidising gases in cigarette smoke may degrade beta-carotene and produce harmful byproducts in the lung. "I'm concerned about all of these nutrients that people go out and take in massive doses. These nutrients may have adverse effects," she says.


Supplementary risks

But John Hathcock of the Council for Responsible Nutrition in Washington DC, which represents the manufacturers of supplements, argues that "Beta-carotene is safe for everyone except long-term smokers who smoke while they are taking beta-carotene." He says: "If we had taken that policy thirty years ago, we would have missed out on vitamin E," he argues.

Several large studies have recently suggested that large doses of vitamin E can prevent deaths from cardiovascular disease. In one study, researchers at the Harvard School of Public Health in Boston asked around 40 000 male doctors about their usual daily intake of nutrients. After four years of follow-up, they found fewer instances of coronary disease in those taking vitamin E supplements of between 60 and 100 milligrams (The New England Journal of Medicine, vol 328, p 1450).

Scientists think that vitamin E prevents free radicals from oxidising low-density lipoprotein (LDL), which contributes to heart disease. But too much vitamin E can also promote bleeding. "Some of the large studies have seen a modest increase in haemorrhagic stroke," says Manfred Steiner of the East Carolina University School of Medicine in Greenville, North Carolina. "I feel uncomfortable that people can go to a drug store and get free access to vitamin E in any dosage they want." Some doctors prescribe as much as 400 milligrams to prevent a second heart attack. But experts advising the French government recommend a maximum limit for vitamin E of 40 milligrams a day, because of the risk of strokes among people taking more than 50 milligrams a day.

Often the very medical condition that seems to require a supplement can make a vitamin dangerous. Alcoholics suffer from a deficiency of vitamin A, for example. So Charles Lieber of the Mount Sinai School of Medicine in New York considered supplementing their diet with beta-carotene, a precursor of vitamin A. But his studies showed that alcohol also hinders the conversion of beta-carotene to vitamin A, and high blood levels of beta-carotene can damage the liver.

Lieber believes it is time to set maximum limits for supplements. "It's useful in the sense that people will be more aware that they can't just take these things," he says. "In our society, we have a lot of problems with excess."

French move to prevent vitamin overdose

High-dose mineral and vitamin supplements could be banned in France as a result of a review by the government's health advisers. The review, by a group of experts set up by the Superior Council for Public Health, sets new limits for many popular over-the-counter supplements.

The French limits could lead to a wider crackdown on the sale of high-dose vitamins and minerals. French officials say they plan to push the European Commission to adopt similar limits to regulate the multi-million-pound trade in supplements.

Based on a review of existing toxicity studies, the council has set safety limits for three minerals, selenium, zinc and fluoride and seven vitamins: A, C, D, E, B6, niacin and folic acid. The limits have mostly been set at a tenth of the minimum dose at which studies have found toxic effects.

The limits are generally around twice the daily consumption recommended in the French government's nutritional guidelines. But the limit for vitamin C has been set higher, at 1000 milligrams a day - twelve times the recommended allowance. This high limit was set because vitamin C has few known toxic effects, although scientists remain divided over the benefits of taking huge doses.

"Over the past decade preventative healthcare has become fashionable and people are willing to try all sorts of miracle drugs, including vitamins," says Jean-Jacques Bernier, the government's senior food adviser. "When regular doses are taken over long periods the risks become apparent. We are now seeing toxic effects at smaller and smaller doses."

According to Pierre Louisot of the public health council, "there is a total absence of critical sense when it comes to vitamins". He says that people believe every small study extolling the ability of vitamins and minerals to prevent diseases such as cancer. "Human nutrition is based on a very fragile balance and when this balance is disrupted there are side effects," says Louisot.

Even though the council says that the antioxidant Vitamin E is not very toxic, its daily limit was set at 40 milligrams. This is far below the doses of 100 to 300 milligrams recommended by some doctors for treating high cholesterol levels or health problems among smokers and alcoholics.

The French limit reflects the recent findings of a Finnish study which found a higher incidence of strokes among people taking vitamin E supplements of 50 milligrams per day. Gerard Pascal, director of the French National Centre for Coordination of Studies on Nutrition and Food, says that contrary to popular belief, people can take too many antioxidants.

Pascal says the French generally consume a satisfactory amount of vitamins and minerals in their diet. He says that people should only take supplements for specific reasons such as pregnancy or malnutrition after they have consulted a doctor.

"After an exhaustive search of the scientific literature on food and cancer the only indisputable conclusion which can be drawn is that eating lots of fruits and vegetables offers some protection from digestive tract cancers," Pascal says.

© Copyright New Scientist, RBI Ltd 2000