Vitamins: stop taking the pills
Everyone loves vitamins. Derived from the Latin word vita, meaning "life", vitamins are necessary for the conversion of food into energy. Millions of people believe that taking daily vitamins makes them feel better and live longer.
Thirteen vitamins have been identified. When people don't get enough of them, they suffer diseases such as beriberi, pellagra, scurvy and rickets (caused, respectively, by deficiencies of vitamins B1, B3, C and D).
The problem with most vitamins is that they aren't made inside the body; they're available only in foods or supplements. So the question isn't, "Do people need vitamins?" They do. The real questions are: "How much do they need?" and "Do they get enough in foods?" Nutrition experts and vitamin manufacturers are split on the answers to these questions. Nutrition experts argue that all people need is the recommended daily allowance (RDA), typically found in a routine diet. Industry representatives argue that foods don't contain enough vitamins and that larger quantities are needed.
In October 2011, researchers from the University of Minnesota found that women who took supplemental multivitamins died at rates higher than those who didn't. Two days later, researchers from the Cleveland Clinic found that men who took vitamin E had an increased risk of prostate cancer.
These findings weren't new. Seven previous studies had already shown that, for certain groups, some vitamins increased the risk of cancer and heart disease, and shortened lives. Still, in 2012, more than half of all Americans took some form of vitamin supplements and 35% of Britons took them regularly. What few people realise, however, is that their fascination with vitamins can be traced back to one man: a man who was so spectacularly right that he won two Nobel prizes and so spectacularly wrong that he was arguably the world's greatest quack.
In 1931, Linus Pauling published a paper entitled The Nature Of The Chemical Bond, for which he won the Nobel prize in chemistry. He was 30 years old. Not only did Pauling go on to give birth to the field of molecular biology, and contribute to the understanding of the structure of DNA, he showed that humans had diverged from gorillas about 11m years ago, much earlier than scientists had suspected. And he was one of the world's most recognised peace activists. In 1962, he won the Nobel peace prize - the first person ever to win two unshared Nobel prizes.
Then all the rigour and hard work that had made Pauling a legend disappeared. The turning point came in March 1966, when he was 65. He had just received the Carl Neuberg medal. "During a talk in New York City," Pauling recalled, "I mentioned how much pleasure I took in reading about the discoveries made by scientists in their various investigations of the nature of the world, and stated that I hoped I could live another 25 years in order to continue to have this pleasure. On my return to California, I received a letter from a biochemist, Irwin Stone, who had been at the talk. He wrote that if I followed his recommendation of taking 3,000 milligrams of vitamin C, I would live not only 25 years longer, but probably more." Stone, who referred to himself as Dr Stone, had spent two years studying chemistry in college. Later, he received an honorary degree from the Los Angeles College of Chiropractic and a "PhD" from Donsbach University, a non-accredited correspondence school in southern California.
Pauling followed Stone's advice. "I began to feel livelier and healthier. In particular, the severe colds I had suffered several times a year all my life no longer occurred. After a few years, I increased my intake of vitamin C to 10 times, then 20 times, then 300 times the RDA: now 18,000mg per day."
From that day forward, people would remember Linus Pauling for one thing: vitamin C.
In 1970, Pauling published Vitamin C And The Common Cold, urging the public to take 3,000mg of vitamin C every day (about 50 times the RDA). Pauling believed that the common cold would soon be a historical footnote. His book became an instant bestseller. Sales of vitamin C doubled, tripled, and quadrupled. By the mid-1970s, 50 million Americans were following Pauling's advice. In the UK, where vitamin C was known as "Pauling's powder", vitamin sales soon topped £550m annually. Vitamin manufacturers called it "the Linus Pauling effect".
Scientists weren't as enthusiastic. In December 1942, about 30 years before Pauling published his first book, Donald Cowan, Harold Diehl and Abe Baker, from the University of Minnesota, published a paper in the Journal of the American Medical Association entitled Vitamins For The Prevention Of Colds. The authors concluded: "Under the conditions of this controlled study, in which 980 colds were treated there is no indication that vitamin C alone, an antihistamine alone, or vitamin C plus an antihistamine have any important effect on the duration or severity of infections of the upper respiratory tract."
Other studies followed. After Pauling's pronouncement, researchers at the University of Maryland gave 3,000mg of vitamin C every day for three weeks to 11 volunteers, and a sugar pill (placebo) to 10 others. Then they infected volunteers with a common cold virus. All developed cold symptoms of similar duration. At the University of Toronto, researchers administered vitamin C or placebo to 3,500 volunteers. Again, vitamin C didn't prevent colds, even in those receiving as much as 2,000mg a day. In 2002, Dutch researchers administered multivitamins or placebo to more than 600 volunteers. Again, no difference. At least 15 studies have shown that vitamin C doesn't treat the common cold.
Pauling wasn't finished. Next, he claimed that vitamin C, when taken with massive doses of vitamin A (25,000 international units) and vitamin E (400 to 1,600 IU), as well as selenium (a basic element) and beta-carotene (a precursor to vitamin A), could do more than just prevent colds: they could treat cancer, along with virtually every disease known to man. Pauling claimed that vitamins and supplements could cure heart disease, mental illness, pneumonia, hepatitis, polio, tuberculosis, measles, mumps, chickenpox, meningitis, shingles, fever blisters, cold sores, canker sores, warts, ageing, allergies, asthma, arthritis, diabetes, retinal detachment, strokes, ulcers, shock, typhoid fever, tetanus, dysentery, whooping cough, leprosy, hay fever, burns, fractures, wounds, heat prostration, altitude sickness, radiation poisoning, glaucoma, kidney failure, influenza, bladder ailments, stress, rabies and snake bites. When the Aids virus entered the US in the 1970s, Pauling claimed vitamins could treat that, too.
In April 1992, the cover of Time declared, "The Real Power Of Vitamins: New research shows they may help fight cancer, heart disease, and the ravages of ageing." The article, written by Anastasia Toufexis, echoed Pauling's ill-founded, disproved notions about the wonders of megavitamins.
Although studies had failed to support him, Pauling believed that vitamins and supplements had one property that made them cure-alls, a property that continues to be hawked on everything from ketchup to pomegranate juice, and that, for sales impact, rivals words such as natural and organic: antioxidant.
Antioxidation v oxidation has been billed as a contest between good and evil. The battle takes place at a cellular level, where the body converts food to energy, a process that requires oxygen and so is called oxidation. One consequence of oxidation is the generation of electron scavengers called free radicals (evil). Free radicals can damage DNA, cell membranes and the lining of arteries; not surprisingly, they've been linked to ageing, cancer and heart disease. To neutralise free radicals, the body makes its own antioxidants (good). Antioxidants can also be found in fruits and vegetables - specifically, selenium, beta-carotene and vitamins A, C and E. Studies have shown that people who eat more fruits and vegetables have a lower incidence of cancer and heart disease, and live longer. The logic is obvious: if people who eat lots of fruit and vegetables are healthier, then people who take supplemental antioxidants should also be healthier. In fact, they can be less healthy.
In 1994, the National Cancer Institute, in collaboration with Finland's National Public Health Institute, studied 29,000 Finnish men, all long-term smokers over 50 years old. This group was chosen because they were at high risk of cancer and heart disease. Subjects were given vitamin E, beta-carotene, both or neither. The results were clear: those taking vitamins and supplements were more likely to die from lung cancer or heart disease than those who didn't take them - the opposite of what researchers had anticipated.
In 1996, investigators from the Fred Hutchinson Cancer Research Centre in Seattle studied 18,000 people who, because they had been exposed to asbestos, were at increased risk of lung cancer. Again, subjects received vitamin A, beta-carotene, both or neither. Investigators ended the study abruptly when they realised that those who took vitamins and supplements were dying from cancer and heart disease at rates 28% and 17% higher, respectively, than those who didn't.
In 2004, researchers from the University of Copenhagen reviewed 14 randomised trials involving more than 170,000 people who took vitamins A, C, E and beta-carotene to see whether antioxidants could prevent intestinal cancers. Again, antioxidants didn't live up to the hype. The authors concluded: "We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers; on the contrary, they seem to increase overall mortality." When these same researchers evaluated the seven best studies, they found that death rates were 6% higher in those taking vitamins.
In 2005, researchers from the Johns Hopkins School of Medicine evaluated 19 studies involving more than 136,000 people and found an increased risk of death associated with supplemental vitamin E. Dr Benjamin Caballero, director of the Centre for Human Nutrition at the Johns Hopkins Bloomberg School of Public Health, said: "This reaffirms what others have said. The evidence for supplementing with any vitamin, particularly vitamin E, is just not there. This idea that people have that [vitamins] will not hurt them may not be that simple." That same year, a study published in the Journal of the American Medical Association evaluated more than 9,000 people who took high-dose vitamin E to prevent cancer; those who took vitamin E were more likely to develop heart failure than those who didn't.
In 2007, researchers from the National Cancer Institute examined 11,000 men who did or did not take multivitamins. Those who took multivitamins were twice as likely to die from advanced prostate cancer. In 2008, a review of all existing studies involving more than 230,000 people who did or did not receive supplemental antioxidants found that vitamins increased the risk of cancer and heart disease. In October 2011, researchers from the University of Minnesota evaluated 39,000 older women and found that those who took supplemental multivitamins, magnesium, zinc, copper and iron died at rates higher than those who didn't. They concluded: "Based on existing evidence, we see little justification for the general and widespread use of dietary supplements."
But studies haven't hurt sales. In 2010, the vitamin industry grossed $28bn, up 4.4% on the year before. "The thing to do with [these reports] is just ride them out," said Joseph Fortunato, chief executive of GNC, the largest chain of vitamin, mineral and supplement stores in the US. "We see no impact on our business."
How could this be? Given that free radicals clearly damage cells - and given that people who eat diets rich in substances that neutralise free radicals are healthier - why did studies of supplemental antioxidants show they could be harmful?
The most likely explanation is that free radicals aren't as evil as advertised. Although it's clear that free radicals can damage DNA and disrupt cell membranes, that's not always a bad thing. People need free radicals to kill bacteria and eliminate new cancer cells. But when people take large doses of antioxidants, the balance between free radical production and destruction might tip too much in one direction, causing an unnatural state in which the immune system is less able to kill harmful invaders. Researchers have called this "the antioxidant paradox". Whatever the reason, the data is clear: high doses of vitamins and supplements increase the risk of heart disease and cancer; for this reason, not a single national or international organisation responsible for the public's health recommends them.
In May 1980, during an interview at Oregon State University, Pauling was asked, "Does vitamin C have any side-effects on long-term use of, let's say, gram quantities?" His answer was quick and decisive. "No," he replied. Seven months later, his wife died of stomach cancer. In 1994, Linus Pauling died of prostate cancer.
Despite a wealth of scientific evidence, most people don't realise megavitamins can be unsafe. So why don't more people know this? And why haven't regulatory agencies sounded an alarm? The answer is predictable: money and politics.
The vitamin and supplement industry has successfully created a false dichotomy. On one side are natural products: vitamins, minerals, dietary supplements, plants and herbs. Because they're natural, they're safe. On the other side are drugs. Because drugs are man-made, they're supposedly more dangerous. However, many drugs, including antibiotics, are derived from nature. Furthermore, the notion that natural products aren't dangerous is fanciful.
The possibility of harm caused by natural products sold in health food stores isn't theoretical. Blue cohosh can cause heart failure; nutmeg can cause hallucinations; comfrey, kava, chaparral, crotalaria, senecio, jin bu huan, usnea lichen and valerian can cause hepatitis; monkshood and plantain can cause heart arrhythmias; wormwood can cause seizures; stevia leaves can decrease fertility; concentrated green tea extracts can damage the liver; milkweed seed oil and bitter orange (Citrus aurantium) can cause heart damage; thujone can cause neurological damage; and concentrated garlic can cause internal bleeding. Indeed, one of the worst dietary supplement disasters in history occurred in 1992, when about 100 people developed kidney failure from a "slimming" mixture found to contain the plant aristolochia; at least 70 patients required kidney transplants or dialysis, and many later developed bladder cancers. In 2008, more than 200 people - including a four-year-old - were poisoned by massive doses of selenium contained in Total Body Formula and Total Body Mega. The products were supposed to contain 200 micrograms of selenium per serving; instead they contained 40,800 micrograms.
Herbal remedies can also cause harm: two infants died from a tea containing pennyroyal and another from a decongestant containing capsaicin. Because the dietary supplement industry is unregulated, only 170 (0.3%) of the 51,000 new products brought to market since the 1994 Supplement Act have documented safety tests.
In Europe, drugs are regulated by the European Agency for the Evaluation of Medicinal Products. Like the FDA, the EMEA holds drugs to a high standard of safety and efficacy before licensure. But the EMEA doesn't regulate vitamins, minerals, dietary supplements and herbs. Rather, regulation falls to the European Food Safety Authority (EFSA), which has a much lower bar. Lax regulation by the US and Europe of dietary supplements isn't the only problem. All countries have to be concerned about the illegal sale of counterfeit vitamins, nutrients and supplements over the internet.
When pharmaceutical companies make drugs and biologicals, the rules are clear. Company scientists first test the product in animals. If the results are promising, they take the next step, testing it in progressively larger numbers of people. If the results are still promising, they perform a definitive (so-called phase III) study, proving that the product is safe and that it works.
The situation for plants, herbs and dietary supplements is different. If researchers find that dietary supplements don't work or have harmful side-effects, they publish their results in scientific journals. No product recall. No change in the label. No warnings. If people don't read scientific journals, they won't know that claims on the label are false.
Terms such as conventional and alternative medicine are misleading. If a clinical trial shows that a therapy works, it's not an alternative. And if it doesn't work, it's also not an alternative. In a sense, there's no such thing as alternative medicine.
Although mainstream medicine hasn't found a way to treat dementia or enhance memory, practitioners of alternative medicine claim they have: ginkgo biloba. As a consequence, ginkgo is one of the 10 most commonly used natural products. Unfortunately, sales exceed claims. Between 2000 and 2008, the National Institutes of Health funded a collaborative study to determine whether ginkgo worked. More than 3,000 elderly adults were randomly assigned to receive ginkgo or a placebo. Decline in memory and onset of dementia were the same in both groups. In 2012, a study of more than 2,800 adults found that ginkgo didn't ward off Alzheimer's disease.
Another example is St John's wort. Depression is a serious illness; to treat it, scientists have developed medicines that alter brain chemicals such as serotonin. Called selective serotonin reuptake inhibitors (SSRIs), these drugs are licensed. Because they've been shown to help with severe depression, doctors recommend them. Alternative medicine practitioners, however, have a better idea - a more natural, safer way to treat depression: St John's wort. Between November 1998 and January 2000, 11 academic medical centres randomly assigned 200 outpatients to receive St John's wort or a placebo, finding no difference in any measure of depression.
Milk thistle is a popular remedy. In 2011, Dr Michael Fried of the University of North Carolina led a group of investigators in determining whether milk thistle helped patients with chronic hepatitis C. More than 150 people infected with the virus were given either milk thistle or a placebo. Then investigators determined the amount of liver damage, as well as the quantities of hepatitis C virus in blood. They found no difference between the two groups.
One of the most popular herbal remedies is echinacea. Used to treat colds, it's a $130m-a-year business. In 2003, James Taylor and co-workers at the University of Washington in Seattle studied more than 400 children with colds who had received either echinacea or a placebo for 10 days. The only difference: children taking echinacea were more likely to develop a rash.
Not all the news is grim. Some dietary supplements actually might be of value. Of the 51,000 new supplements on the market, four might be of benefit for otherwise healthy people: omega-3 fatty acids to prevent heart disease; calcium and vitamin D in postmenopausal women, to prevent bone thinning; and folic acid during pregnancy, to prevent birth defects.
In the end, if a medicine works, it's valuable, and if it doesn't work, it's not. "There's a name for alternative medicines that work," says Joe Schwarcz, professor of chemistry and the director of the Office for Science and Society at McGill University in Canada. "It's called medicine."