For most of us, the “placebo effect” is synonymous with the power of positive thinking; it works because you believe you're taking a real drug. But a new study rattles this assumption.Researchers at Harvard Medical School's Osher Research Center and Beth Israel Deaconess Medical Center (BIDMC) have found that placebos work even when administered without the seemingly requisite deception.
Placebos—or dummy pills—are typically used in clinical trials as controls for potential new medications. Even though they contain no active ingredients, patients often respond to them. In fact, data on placebos is so compelling that many American physicians (one study estimates 50 percent) secretly give placebos to unsuspecting patients. Because such “deception” is ethically questionable, HMS associate professor of medicine Ted Kaptchuk teamed up with colleagues at BIDMC to explore whether or not the power of placebos can be harnessed honestly and respectfully.
To do this, 80 patients suffering from irritable bowel syndrome (IBS) were divided into two groups: one group, the controls, received no treatment, while the other group received a regimen of placebos—honestly described as “like sugar pills”—which they were instructed to take twice daily. “Not only did we make it absolutely clear that these pills had no active ingredient and were made from inert substances, but we actually had 'placebo' printed on the bottle,” says Kaptchuk. “We told the patients that they didn't have to even believe in the placebo effect. Just take the pills.”
For a three-week period, the patients were monitored. By the end of the trial, nearly twice as many patients treated with the placebo reported adequate symptom relief as compared to the control group (59 percent vs. 35 percent). Also, on other outcome measures, patients taking the placebo doubled their rates of improvement to a degree roughly equivalent to the effects of the most powerful IBS medications. “I didn't think it would work,” says senior author Anthony Lembo, HMS associate professor of medicine at BIDMC and an expert on IBS. “I felt awkward asking patients to literally take a placebo. But to my surprise, it seemed to work for many of them.”
The authors caution that this study is small and limited in scope and simply opens the door to the notion that placebos are effective even for the fully informed patient—a hypothesis that will need to be confirmed in larger trials. “Nevertheless,” says Kaptchuk, “these findings suggest that rather than mere positive thinking, there may be significant benefit to the very performance of medical ritual. I'm excited about studying this further. Placebo may work even if patients knows it is a placebo.”
This study was funded by the National Center for Complementary and Alternative Medicine and Osher Research Center, Harvard Medical School.
About 10 to 15 percent of children experience recurrent abdominal pain, the researchers said. The pain can be due to irritable bowel syndrome — which is usually relieved by defecation — or can be “functional abdominal pain,” which is not explained by another disease. While LGG has been tested before in children with abdominal pain, the studies were small and showed mixed results. The new study, which involved 141 children with irritable bowel syndrome or functional abdominal pain, was conducted in Italy between 2004 and 2008. Researchers gave the kids either the probiotic or a placebo for eight weeks. Neither the doctors nor the patients were aware which treatment they received.
Following the treatment, the patients were followed up for another 8 weeks. During the treatment and follow-up, the severity and frequency of abdominal pain decreased for both groups, but the probiotic group experienced a more drastic reduction. For instance, after 12 weeks, patients who took the probiotic reported experiencing, on average, 1.1 episodes of pain per week, compared with 3.7 weekly episodes before the treatment. Those who took the placebo reported experiencing 2.2 pain episodes per week, compared with 3.5 episodes initially.
And a greater percentage of parents of children who took the probiotic reported that their children experienced a decline in pain,compared with those whose kids took the placebo. Among kids who took the probiotic, it was mostly children with irritable bowel syndrome who showed improvements, the researchers said.
Why does it work?
The results suggest LGG may be specifically beneficial for those with irritable bowel syndrome, the researchers said. It's possible that children with irritable bowel syndrome have an imbalance of good and bad bacteria in their guts, which contributes to the pain, and the probiotics relieves pain by restoring the proper balance, Francavilla said. Probiotics have also been suggested to reduce inflammation in the gut, as well as stimulate the release of analgesic substances that relieve pain. The researchers noted they cannot be sure whether the beneficial effects will last for more than a few weeks after treatment is stopped.
The results were published in the journal Pediatrics.
Researchers employed imaging techniques to examine and analyze brain anatomical differences between 55 female IBS patients and 48 female control subjects. Patients had moderate IBS severity, with disease duration from one to 34 years (average 11 years). The average age of the participants was 31.
Investigators found both increases and decreases of brain grey matter in specific cortical brain regions.
Even after accounting for additional factors such as anxiety and depression, researchers still discovered differences between IBS patients and control subjects in areas of the brain involved in cognitive and evaluative functions, including the prefrontal and posterior parietal cortices, and in the posterior insula, which represents the primary viscerosensory cortex receiving sensory information from the gastrointestinal tract.
“The grey-matter changes in the posterior insula are particularly interesting since they may play a role in central pain amplification for IBS patients,” said study author David A. Seminowicz, Ph.D., of the Alan Edwards Centre for Research on Pain at McGill University. “This particular finding may point to a specific brain difference or abnormality that plays a role in heightening pain signals that reach the brain from the gut.”
Decreases in grey matter in IBS patients occurred in several regions involved in attentional brain processes, which decide what the body should pay attention to. The thalamus and midbrain also showed reductions, including a region – the periaqueductal grey – that plays a major role in suppressing pain.
“Reductions of grey matter in these key areas may demonstrate an inability of the brain to effectively inhibit pain responses,” Seminowicz said.
The observed decreases in brain grey matter were consistent across IBS patient sub-groups, such as those experiencing more diarrhea-like symptoms than constipation.
“We noticed that the structural brain changes varied between patients who characterized their symptoms primarily as pain, rather than non-painful discomfort,” said Mayer, director of the UCLA Center for Neurobiology of Stress. “In contrast, the length of time a patient has had IBS was not related to these structural brain changes.”
Mayer added that the next steps in the research will include exploring whether genes can be identified that are related to these structural brain changes. In addition, there is a need to increase the study sample size to address male-female differences and to determine if these brain changes are a cause or consequence of having IBS.
The study was funded by the National Institutes of Health.
Additional authors include M. Catherine Bushnell, Ph.D., of McGill University, and Jennifer B. Labus, Joshua A. Bueller, Kirsten Tillisch and Bruce D. Naliboff, Ph.D., all of UCLA.
Lead researcher Dr. Jeffrey M. Lackner from the State University of New York, Buffalo said cognitive behavioral therapy was known to be a very promising treatment for IBS, with the current findings helping to identify which patients would likely maintain a positive response.
Lackner and his colleagues are conducting a larger, longer-term study, as the current study being a small one, it remains unclear how long the benefits of cognitive behavioral therapy may last i. e. do they carry over to 9 months, a year or more.
IBS symptoms include bouts of abdominal cramps, bloating and changes in bowel habits i. e. diarrhoea or constipation, or alternating episodes of both. While, no one knows the exact cause of the disorder, there are certain symptom triggers like particular foods, large meals and emotional stress.
Cognitive behavioral therapy helps IBS patients to recognize their symptom triggers and manage them. Other treatment options include general diet changes, like reducing gas-producing foods; fibre supplements, if constipation is a primary symptom; and anti-diarrhoeal medications, when diarrhoea is a primary symptom.
There are two prescription medications for specific IBS cases: Lotronex, for women with diarrhoea dominant IBS not responding to other treatments; and Amitiza, for constipation dominant IBS.
Around 20% of people have IBS symptoms, with women affected at about twice the rate of men
For the first time, in a large prospective study, researchers have identified an association between high protein intake and a significantly increased risk of inflammatory bowel disease (IBD). While doctors have long suspected that diet contributes to IBD, little has been assessed, and the studies conducted have been retrospective, which are less informative because they rely on the study participants' ability to recall what they have consumed in the past. This study examined the effects of different sources and amounts of protein.
Using participants in France's E3N cohort study, researchers led by Prevost Jantchou, MD, of the Center for Research in Epidemiology and Population and colleagues identified 77 women ages 40 to 65 with validated cases of IBD. In each case, the onset of IBD occurred after the first dietary questionnaire was administered, thereby assuring that they could be studied prospectively.
Dr. Jantchou examined participants' macronutrient (protein, fat and carbohydrate) intake, and determined that more than two-thirds of them had elevated levels of protein intake. Participants were divided into three groups based on their mean protein intake: the lowest intake group had a mean daily protein intake of 1.08 grams/kg of body weight; the middle group had 1.52 grams/kg; and the highest group had 2.07 grams/kg. The FDA recommends a daily intake of 0.8 grams of protein per kilogram of body weight.
When examining the effects of specific types of protein, Jantchou found that animal protein represented a threefold risk of developing IBD in the highest group compared to the lowest group. Specifically, animal protein from meat and fish, not dairy, created an increased risk, while vegetable protein created no increased risk of developing IBD.
Researchers found that the increased risk from animal protein intake were the same for Crohn's disease and ulcerative colitis. They also found that smoking and hormonal therapy, two factors known to be related to the risk of IBD, did not change their results.
“Our findings represent a tremendous step forward in our understanding of inflammatory bowel disease,” said Dr. Jantchou. “For years we've known there was a connection between diet and IBD, and we now know specifically which aspect of diet is related to disease occurrence. The next step is to look at the effect of animal protein in patients already diagnosed with IBD to be able to give them better dietary advice.”