Why Has It Always Been So Hard to Treat the Common Cold
Paul A. Offit on What Actually Works
Common colds are common for three reasons:
They’re hard to prevent. The virus most likely to cause a cold is called rhinovirus (literally, “nose virus”); about one hundred different strains have been identified. Other viruses, such as influenza, parainfluenza, respiratory syncytial virus, and adenovirus, can also cause colds. Like rhinovirus, about one hundred different strains of adenovirus have also been described. All these viruses cause runny nose, congestion, sneezing, sore throat, headache, and fever. Because so many different strains of viruses cause the common cold, it’s been impossible to make a vaccine to prevent it.
They’re hard to treat. Antibiotics don’t treat viruses. Although antiviral medications have been invented for some viruses, such as influenza and herpes, none has been invented to treat rhinoviruses.
They’re easy to spread. Common cold viruses, which are spread primarily by sneezing, coughing, or even talking, can also be spread by shaking hands or by touching a doorknob or an ATM machine or any other surface that an infected person recently touched.
For centuries, we’ve tried, largely in vain, to treat the common cold. We’ve taken cough suppressants, pain and fever medicines, antihistamines, expectorants, and natural products such as camphor, eucalyptus oil, zinc, and echinacea—all without much benefit and some, as in the case of antihistamines, that are dangerous for young children.
As a general rule, when so many different medicines are claimed to work, none of them probably does. Dr. William Osler, one of the founders of Johns Hopkins Hospital, lamented his profession’s utter failure to deal with this disease. “The best way to treat the common cold,” he said, “is with contempt.”
Then someone had a better idea: an “all-natural” product that he believed not only treated colds but prevented them.“The failure of vitamin C supplementation to reduce the incidence of colds in the general population indicates that routine vitamin C supplementation is not justified.”
Linus Pauling was born on February 28, 1901, in Portland, Oregon. In 1931, he published a scientific paper showing an alternative way for atoms to interact, marrying quantum physics with chemistry. It revolutionized the field. For this single paper, Pauling was named the most outstanding young chemist in the United States, became the youngest person ever elected to the National Academy of Sciences, was made a full professor at Caltech, and won the Nobel Prize in Chemistry. He was only thirty years old.
In 1949, Pauling published another paper, showing that the hemoglobin of patients with sickle cell anemia had a slightly different electrical charge—giving birth to the field of molecular biology.
In 1951, Pauling published a paper showing the unique way that some proteins folded upon themselves. He called one configuration the alpha-helix—later used by James Watson and Francis Crick to explain the structure of DNA. Again, Pauling was decades ahead of his peers.
In 1961, Pauling showed that mutations in hemoglobin could be used as a kind of evolutionary clock, proving that humans diverged from apes much sooner than scientists had suspected. A colleague later remarked, “At one stroke, he united the fields of paleontology, evolutionary biology, and molecular biology.” That same year, Pauling appeared on the cover of Time magazine’s “Men of the Year” issue, hailed as one of the greatest scientists who ever lived.
In the midst of these scientific accomplishments, Pauling took time to become the world’s most recognized peace activist; his efforts led to the Nuclear Test Ban Treaty. As a consequence, in 1962, he won the Nobel Peace Prize, the first person ever to win two unshared Nobel Prizes.
Although Pauling’s research never involved treating or preventing colds, that would soon change. By the early 1970s, the American public would come to know Linus Pauling for one thing and one thing only: vitamin C.
In March 1966, when he was sixty-five years old and giving a talk in New York City, Pauling said that he hoped he would live another twenty-five years. On his return to California, he received a letter from a man named Irwin Stone, who had been at the talk. Stone had spent two years studying chemistry in college, later rceiving an honorary degree from the Los Angeles College of Chiropractic and a “PhD” from Donsbach University, a nonaccredited correspondence school. Stone wrote that if Pauling took 3,000 milligrams of vitamin C every day, he would live at least another twenty-five years.
Pauling followed Stone’s advice. “I began to feel livelier and healthier,” he recalled. “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, and then 300 times the Recommended Dietary Allowance (RDA): now 18,000 milligrams per day!”
In 1970, Pauling published Vitamin C and the Common Cold, urging the public to take six large 500-milligram tablets (3,000 milligrams) of vitamin C every day (about fifty times the RDA). Pauling’s book was an instant bestseller. When the paperback edition hit the shelves, sales of vitamin C doubled, then tripled, then quadrupled. Drugstores couldn’t keep up with the demand. Wholesale stocks were depleted. By the mid-1970s, 50 million Americans were following Pauling’s advice. Vitamin manufacturers called it “the Linus Pauling Effect.”
The only thing that Pauling’s bestselling book lacked was scientific evidence proving that he was right—evidence that wasn’t particularly hard to generate. All researchers had to do was divide volunteers into two groups. One group would receive vitamin C either at the time of illness or throughout the cough-and-cold season. The other group would receive a placebo pill that looked and tasted like vitamin C but wasn’t. If vitamin C worked, then recipients would either have fewer colds or less severe colds, or both. Indeed, at the time Pauling published his book, two of these studies had already been done.
In 1939, researchers at the University of Minnesota divided four hundred undergraduate students into two groups. One group was given 200 milligrams of vitamin C every day throughout the winter season, about twenty-eight weeks. Fifty of these students also took 500 milligrams of vitamin C during the first two days of a cold. The other group was given placebo tablets. Students were told to report to the student health center at the first sign of illness. When the winter season ended, the researchers found no differences between the two groups in the frequency, severity, or duration of colds.
Ten years later, these same investigators performed a similar study at the same school. This time, however, the dose of vitamin C was much greater. At the beginning of the 1948 school year, students were given 667 milligrams of vitamin C throughout the winter as well as an antihistamine. Other groups received an antihistamine alone, vitamin C alone, or placebo pills. Students were also asked to take 3,000 milligrams of vitamin C at the first sign of a cold and to continue taking it every day until symptoms were gone. Although the study design was different, the results were the same. The authors concluded that vitamin C didn’t “have any important effect on the duration or severity of these infections.”
Pauling refused to believe the Minnesota studies. In 1970, he wrote a letter to the New York Times decrying the investigators’ conclusions. Pauling argued that the researchers had ignored positive results. He insisted that had they looked more closely they would have seen that some of these students had actually benefited from vitamin C. On December 26, 1970, the lead author on the Minnesota studies, Dr. Harold S. Diehl, the dean of medical sciences at the University of Minnesota, wrote a rebuttal letter that was also published in the New York Times. Diehl argued that Pauling had completely ignored critical data—in essence, that he didn’t know what he was talking about.
Ironically, the same year that Linus Pauling criticized the Minnesota studies, the study to end all studies was performed by researchers at the University of Maryland School of Medicine on twenty-one prisoner volunteers at the House of Correction in Jessup, Maryland. First, blood specimens were taken from each of the volunteers and tested for immunity to a particular strain of a common cold virus called rhinovirus type 44. For two weeks, eleven of them were given 3,000 milligrams of vitamin C every day, and ten were given a placebo. Then all the men were inoculated intranasally with the strain of rhinovirus to which they were all susceptible. After the virus was inoculated, the vitamin C group continued to receive the vitamin for another week, and the placebo group continued to receive the placebo. Every day, the men were examined by physicians and their symptoms were recorded. And every day, nasal washings were obtained to determine the amount of rhinovirus that was excreted from the nose. As had been the case in the Minnesota trials, no differences were found in the frequency or severity of symptoms. In addition, no differences were found in the amount of rhinovirus that was shed during illness.
If you can get past the seemingly contradictory phrase “prisoner volunteers,” in many ways, the Maryland study was perfect. Unlike trials of vitamin C in the general population, where people may be more or less susceptible to the strains of rhinovirus circulating in the community, the prisoner trial controlled for susceptibility to the challenge virus. Also, in the general population, people will be exposed to different quantities of virus, which will result in different severities of symptoms; the prisoner trial controlled for the dose of virus. Furthermore, whereas studies in the general population depend on self-reporting, the prisoner trial was supervised by physicians who examined the prisoners every day, providing a more accurate record of the frequency and severity of symptoms. The prisoner trial also determined the amount of rhinovirus that was shed from the nose in those who did or didn’t receive vitamin C; no other studies before or since have done this. Finally, this trial controlled for the amount of vitamin C ingested; by definition, no one went off protocol, which often happens in studies of the general population where researchers depend on volunteers to do exactly what they are asked to do.
The prisoner study was so clear, so definitive, so well controlled, and so groundbreaking that Jane Brody, the highly quoted, highly acclaimed health reporter for the New York Times, wrote about it. Under the title “Vitamin C Study Rebuts Pauling,” Brody described the details of the Maryland experiment. Again, Pauling refused to believe it, criticizing the study as “a poor investigation.” He argued that the experiment was too small and that it was performed under unnatural conditions. It was becoming apparent that Linus Pauling possessed something that no scientist should ever possess: a non-falsifiable belief.
Because he stood on the platform of two Nobel Prizes, Linus Pauling was an influential man. When he said that the studies performed in Minnesota and Maryland didn’t make sense, people believed him. And so, the studies continued, all with the hope that someone somewhere would prove Linus Pauling right and that finally we would have something to treat or prevent a disease that has been untreatable and unpreventable.
In 1974, researchers at the University of Toronto divided 2,300 volunteers into seven groups. Three groups received either 250, 1,000, or 2,000 milligrams of vitamin C every day throughout the winter months; two groups received 4,000 or 8,000 milligrams at the start of illness; and two groups received placebo tablets. Again, researchers found no differences in the frequency or severity of infections.
One year later, in 1975, two independent groups of researchers reviewed fourteen more studies. One research group, using italics to emphasize their point, wrote that “a review of the controlled studies of the efficacy of [vitamin C] in the prophylaxis and therapy of the common cold . . . reveals little convincing evidence to support claims of clinically important efficacy.” The other group, noting that not all studies were well performed, stated that “the minor benefits of questionable validity are not worth the potential risk [of vitamin C], no matter how small that might be.”
Still, the studies continued.
In 1977, researchers in Australia divided one thousand subjects into two groups. One group was given 1,000 milligrams of vitamin C every day during the winter season and 3,000 milligrams at the beginning of illness for three days. The other group was given placebo tablets. Again, no difference. The researchers concluded, “It is becoming clear from this and other work that the effect of [vitamin C] on the common cold is at best elusive and probably trivial.”
Twenty years later, in 1997, researchers reviewed the results of six more studies of vitamin C, involving more than five thousand episodes of illness, concluding that “it is shown that the common cold incidence is not reduced in the vitamin C supplemental groups compared with placebo groups.”
Nonetheless, in what apparently had become an endless quest to prove Linus Pauling right, the studies continued.
In 2001, researchers at the Australian National University in Canberra divided four hundred healthy volunteers into four groups; one group received only 30 milligrams of vitamin C at the onset of colds, to be taken for two days (the placebo group); two groups received either 1,000 or 3,000 milligrams; the fourth group received 3,000 milligrams plus a popular product called Bio-C, which contained a variety of natural substances such as rose hip extract and bioflavonoids. Again, the authors found no differences in the frequency, duration, or severity of cold symptoms.
Finally, in 2013, researchers reviewed the results of twenty-nine more studies of vitamin C, involving more than eleven thousand participants, concluding, “The failure of vitamin C supplementation to reduce the incidence of colds in the general population indicates that routine vitamin C supplementation is not justified.”
Because the evidence is clear, the Food and Drug Administration, the American Academy of Pediatrics, the American Medical Association, the Academy of Nutrition and Dietetics, the Center for Human Nutrition at Johns Hopkins Hospital, and the Department of Health and Human Services do not recommend supplemental vitamin C for the prevention or treatment of colds.
Linus Pauling never wavered. Up until the day he died, on August 19, 1994, he continued to promote vitamin C in speeches, popular articles, and books, refusing to believe that he could ever be wrong. When he appeared before the media with cold symptoms, he said he was suffering from allergies.There is, however, one treatment for the common cold that really does work. And unlike supplemental vitamin C, it’s cheap and harmless.
In medicine, if something works to treat or prevent an illness, it’s been relatively easy to prove it. Insulin treats diabetes. Chemotherapies treat certain cancers. Vaccines prevent viral and bacterial infections. Researchers in these situations didn’t have to perform dozens of studies before they showed that their interventions worked. So, given that vitamin C has consistently been proved to be useless in treating or preventing colds, why does it remain so popular?
The answer shouldn’t be surprising.
In February 2012, the pharmaceutical giant Pfizer bought Alacer Corporation, the makers of a popular vitamin C product called Emergen-C. “We are very pleased that the Emergen-C family of products will become part of Pfizer’s portfolio,” said Paul Sturman, president of Pfizer Consumer Healthcare. Although financial terms of the purchase weren’t disclosed, it’s not hard to understand why Sturman was excited. At the time of the purchase, Alacer was producing about 500 million packets of Emergen-C a year, with revenues exceeding $220 million. Emergen-C was sold in health food stores, supermarkets, drugstores, and campus bookstores. And Alacer was only one of many vitamin C manufacturers.
We continue to take vitamin C for our colds because manufacturers spend millions of dollars every year convincing us that it’s the right thing to do. Medical and scientific journals, on the other hand, don’t financially benefit from the results of their studies; not surprisingly, these journals don’t spend money advertising their findings.
Also, apart from the fact that vitamin C isn’t free, the downside of taking something that clearly doesn’t work is that, as is true for any medication, it can have side effects. According to the Mayo Clinic, large quantities of supplemental vitamin C can cause headache, nausea, vomiting, dizziness, inflammation of the esophagus, flushing, and fatigue.
There is, however, one treatment for the common cold that really does work. And unlike supplemental vitamin C, it’s cheap and harmless. It’s also been recommended by mothers for decades: chicken soup. But it’s not the chicken or the broth or the celery or the carrots or the noodles or the rice that makes a difference; it’s the steam.
Researchers have always known that rhinoviruses survive better at the colder temperatures found in the nose (91.4 to 95 degrees) than at core body temperature (98.6 degrees). In 2015, in a paper published in the prestigious Proceedings of the National Academy of Sciences, researchers at Yale University School of Medicine reported on their investigation of this phenomenon. They took airway cells from mice and exposed them to a strain of rhinovirus at lower temperatures and higher temperatures. As expected, rhinovirus couldn’t reproduce at the higher temperatures. Then they found out why. The higher temperatures triggered airway cells to produce an antiviral substance called interferon, which limited the ability of rhinoviruses to replicate.
As it turns out, after all these years, a treatment for the common cold that offers some benefit has been right under our nose.
From Overkill by Paul A. Offit M.D. Used with the permission of Harper.