Tag Archives: placebo

DNA study shows Placebo (and Nocebo) can affect your body at a molecular level

Researchers gave 223 people wrong DNA-test results — and they did it on purpose. Not out of spite, but rather to see if this can trigger a placebo effect and physically change the participants’ body. The effects show just how much our beliefs can affect our body, even at a molecular level.

The placebo effect (and its dark cousin, the nocebo) can be surprisingly powerful. Image credits: Patrick Nygren.

DNA testing has become increasingly popular in recent years, with approximately 1 in 25 Americans already testing their genetic background largely through commercial companies. The two most common reasons people do these tests is to check their genetic ancestry and to look for signs of genetic disorders or conditions. But the test results themselves could also have an important impact.

Previous studies have shown that when people read the results of these tests they can exhibit significant emotional and behavioral changes. Now, researchers want to take this one step further and see whether they can even have a physiological effect and actually change participants’ bodies. Brad Turnwald and Alia Crum, devised two clever (and sneaky) experiments.

They gave half of the participants wrong test results. The first group received false information regarding a gene variant they had CREB1 — which can cause increased body temperature when working out, lower aerobic exercise capacity, and reduced cardiovascular improvements when working out. Essentially, people were told they have a genetic predisposition to worse results of physical activity. All participants carried out a treadmill test before and after being given the results. Participants who were told they have this gene variant reported feeling more worried and less in control of their exercise — a significant psychological effect. But the effect went much deeper: they demonstrated statistically significant physiological changes that signaled decreased exercise capacity, such as a lower maximum capacity for CO₂:O₂ gas exchange. They also stopped running significantly sooner than in the initial test.

Meanwhile, another group of people were told they had the opposite (protective) variant of this gene. For the second trial, they exhibited no significant physiological changes, but were able to run significantly longer before reporting that the exercise felt hard.

This is a clear indication of the placebo effect, as well as its gloomier cousin, the nocebo effect (which is like a placebo, but with negative effects). This isn’t really surprising, as the placebo effect was previously documented to have a physiological effect. For instance, when people believe they are being administered a painkiller, their brain can start to release natural painkillers known as endorphins.

To see whether the results are valid for other types of genetic tests, researchers also carried a secondary experiment, this time centered around FTO gene, one of the best-studied genetic risk factors for obesity. The high-risk form of the FTO gene is associated with lower self-reported and physiological satiety — people with it take longer to feel full. Participants consumed a 480-calorie meal after fasting overnight and reported how full they felt at various points before and after eating. A week later, they had to do the same thing, after being told whether they have the “good” or “bad” variant of the FTO gene.

Compared to the baseline session, participants who were told they had the protective genotype reported a 1.4-fold increase in how full they felt after eating. They also experienced a 2.5-fold increase in levels of GLP-1 — a peptide that signals satiety to the brain. So not only is their mind being put into a very specific mindset, but the body starts to act on it too.

“Mindset matters,” agrees Catharine Wang,  who studies community health at Boston University and was not involved in the study. “This study reminds us to think about how some types of genetic information might lead to unintended consequences. If we give genetic risk information on [certain] traits, it’s easy to see how a self-fulfilling prophecy would kick in.”

This doesn’t really get us closer to understanding what placebo really is, but it does show how strong of an effect it can have. Even in the case of a relatively new scenario such as a genetic test, its effects can be surprisingly severe and quite damaging — the self-fulfilling prophecy Wang mentions.

However, it’s not like we should stop people from getting genetic tests, researchers say. Instead, we need to pay more attention to how these results are presented. In a longer scheme of things,  we should pay great attention to the mindset we place ourselves in. It could very well change our life for the better — or for the worse.

“What we hypothesize could happen [over the long term], based on other work on mindset and placebo effects, is that there is a potential for these effects to grow and fester over time,” he says. He points to the exercise framework as a possible example: “If I learn that my capacity to exercise is lower, for instance, it may become easier for me to recall times in which I got tired faster than other people,” he notes. “The next time I exercise, it may feel more difficult, which may lead me to quit my exercise sooner or worry that there’s no point in exercising anyway.”

The studies were published in Nature Human behavior.

People who trust their doctor tend to feel better, new study finds

Having confidence in the medical staff caring for you might not solve your problems, but it will definitely help you feel better.

Image credits: Vic / Flickr

The effects of placebo are wide and far-reaching, as numerous studies have proven over the years. Although it seems like a no-brainer at first, it’s quite intriguing that your mind can have such a strong impact on your body and how you feel. A meta-analysis wanted to see if trust in doctors, therapists and nursing staff has any clinical effects on patients.

Researchers from the Department of Psychology at the University of Basel and Harvard Medical School examined 47 studies from Europe, Asia, North America, and Australia which deal with the relationship between trust and an improved state of health in people undergoing medical treatment. The researchers looked at two things: the objective, clinical wellbeing of patients and the subjective wellbeing that the patients themselves reported.

There were no obvious results when it came to clinical effects. In other words, trusting your doctor doesn’t really solve your medical problems — but, as authors note, it can definitely make you feel better. Patients which reported high trust in the medical staff enjoyed boosted satisfaction, health-related behavior, and quality of life.

“The results of our meta-analysis are a clear indication of the value of patients’ trust in their medical professionals. They emphasize the need to make developing and safeguarding trust an integral part of clinical education and practice,” says Professor Jens Gaab, co-author of the study.

This study emphasizes how important it is to establish a trusted relationship between patients and medical staff. For doctors, earning the trust of their patients is already a well-established principle in the ethical guidelines and professional codes — regardless of field. Yet this is the first meta-analysis to show just how important this principle is. In many parts of the world, trust in the medical system is dwindling with no clear-cut solution in sight.

No one likes to go to the doctor, that much is clear. But if you must go, trusting in the medical staff can make a big difference. As this study showed, if you don’t trust them you’ll end up feeling worse and the overall trust in the medical system will drop even more, creating a domino effect. A properly functioning health care system lies at the core of every functional society.

Journal Reference: Johanna Birkhäuer, Jens Gaab, Joe Kossowsky, Sebastian Hasler, Peter Krummenacher, Christoph Werner, Heike Gerger — Trust in the health care professional and health outcome: A meta-analysis.
PLOS ONE (2017), doi: 10.1371/journal.pone.0170988

Study finds how to predict which brains respond to placebo treatments

A new study offers insight into why a simple sugar pill can work to significantly reduce pain for some patients while having no effect on others.

Image credits Patrik Nygren / Flickr.

A team from the Northwestern Medicine and the Rehabilitation Institute of Chicago (RIC) used fMRI to identify the brain area responsible for the placebo effect in pain relief. This region, known as the mid-frontal gyrus (MFG), is located at the front of the brain and also plays a key role in our decision making and emotional state. The data was recorded in two clinical trials involving 95 patients with chronic pain from osteoarthritis. The team found that participants who had better connectivity between the MFG and other brain areas were more likely to respond to the placebo effect.

The findings could be used to better tailor pain medication to each patient’s brain structure, offering a safer and more efficient alternative to the current trial-and-error approach. In Germany, half of all doctors prescribe placebos for non-chronic illnesses — they might be on to something.

“Given the enormous societal toll of chronic pain, being able to predict placebo responders in a chronic pain population could both help the design of personalized medicine and enhance the success of clinical trials,” said Marwan Baliki, PhD, a research scientist at RIC and assistant professor of physical medicine and rehabilitation at Northwestern University Feinberg School of Medicine.

Also, these differences in brain structure could be the reason why some drugs — such as pregabalin, commercially known as Lyrica — provide pain relief in some patients, but not others. By understanding how each patient responds to pain medication, those predisposed to the placebo effect can be eliminated from clinical trials, making future research far more reliable.

“This can help us better conduct clinical studies by screening out patients that respond to placebo and we can just include patients that do not respond. And we can measure the efficacy of a certain drug in a much more effective manner,” he added.

“If we do the same with Lyrica, maybe we can find another area of the brain that can predict the response to that drug.”

Professor of physiology at Feinberg and study co-author Vania Apkarian said that the findings will allow physicians to see what brain regions become active while a patient feels pain, then decide on a drug that specifically targets that area.

“It also will provide more evidence-based measurements. Physicians will be able to measure how the patient’s pain region is affected by the drug,” she added.

The full paper “Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials” has been published in the journal PLOS Biology.

Expensive Placebos Work Better Than Cheap Placebos

Although generic drugs are often identical to their brand-name expensive counterparts, the effect might not the same. It’s not because the more expensive drugs do something different or better – in fact, it’s all in your head. A new study has found that expensive placebos can work better than cheap placebos.

Image via Wikipedia.

The placebo effect holds a very special role in modern medicine; it works, it can be very effective, but we basically don’t know why. A placebo is an ineffective or just a sham treatment or procedure which actually has a medical improvement on the patient.

“Even a condition with objectively measured signs and symptoms can improve because of the placebo effect,” argues Henry Ford West Bloomfield Hospital neurologist, Dr. Peter LeWitt.

Now, a new study had found that the price of the drug makes a significant difference in its efficiency – regardless of what the drug actually has inside.

In a rather unusual clinical trial, researchers from University of Cincinnati used two dummy pills and gave it to two groups of people with “moderately advanced” Parkinsons disease. The patients were told they will be given two separate drugs of the same effectiveness – with the only difference being that one is 15 times more expensive than the other. In truth, both of them were actually saline. Researchers describe their study:

“Eight of the participants said they did have greater expectations of the ‘expensive’ drug and were amazed at the extent of the difference brought about by their expectations. Interestingly, the other four participants said they had no expectation of greater benefits of the more expensive drug, and they also showed little overall changes.”

The first thing that researchers report is that both treatments improved the motor skills and reduced hand shaking to some extent. However, the “more expensive” drug was more efficient, showing a better improvement, by 9%. In total, 58% of patients had improvement with the allegedly cheap drug while 67% improved with the other one.

According to researchers, it’s the patients’ expectations which are the main cause here.

“Patients’ expectations play an important role in the effectiveness of their treatments, and the placebo effect has been well documented, especially in people with Parkinson’s disease,” explains study author Alberto J. Espay, of the University of Cincinnatti, in Ohio. The American Academy of Neurology Fellow continues, “We wanted to see if the people’s perceptions of the cost of the drug they received would affect the placebo response.”

It seems quite likely that the same thing could happen for other, more common drugs as well. Many relatively cheap drugs have a more expensive counterpart (or even more), generally created by the big pharma companies. This study also shows that we could potentially use the patients’ expectations to generate better results with placebo treatments.

“If we can find strategies to harness the placebo response to enhance the benefits of treatments, we could potentially maximize the benefit of treatment while reducing the dosage of drugs needed and possibly reducing side effects.”

Leukemia drug found to dramatically boost immune system

A class of drugs currently used to treat leukemia has been found to have some severe side effects – positive ones, that is. The drug was found to drastically boosting immune responses against many different cancers, reports a new study.

The drug class is referred to as p110´ inhibitors. Recently, it has been used with significant success against certain leukemias in recent clinical trials; patients were given a placebo, and after a while, they were given the actual drug – and it started to work right away. However, until now, it hasn’t been tested against other cancers.

The new study, which was published in Nature, shows that p110δ inhibitors have remarkable effects against a broad range of cancers, especially reducing the chance of relapse. Basically, these drugs inhibit the p110δ enzyme, boosting the body’s immune system, enabling it to kill more tumor cells.

“Our study shows that p110δ inhibitors have the potential to offer effective immunity to many types of cancer by unleashing the body’s own immune response,” says study co-leader Professor Bart Vanhaesebroeck of the UCL Cancer Institute, who first discovered the p110δ enzyme in 1997. “p110δ is highly expressed and important in white blood cells, called ‘leukocytes’. Given that leukemias are the result of leukocytes becoming cancerous, they are a natural target for p110δ inhibitors. Now, we have shown that blocking p110δ also has the remarkable effect of boosting the body’s immune response against leukemias as well as other cancers.”

Initially, they tested it on mice, and the results were very exciting. However, many drugs which have good results in mice don’t work that well in humans – which is why this study is particularly interesting. ollowing p110δ inhibition, the immune system develops a sort of memory, enabling it to be more efficient with cancer in future battles, massively reducing relapse rates.

An electron scan of T-cells. Image via Wikipedia.

“Our work shows that p110δ inhibitors can shift the balance from the cancer becoming immune to our body’s defenses towards the body becoming immune to the cancer, by disabling regulatory T cells,” says study co-leader Dr Klaus Okkenhaug of the Babraham Institute. “This provides a rationale for using these drugs against both solid and blood cancers, possibly alongside cancer vaccines, cell therapies and other treatments that further promote tumor-specific immune responses.”

Aside for having obvious potential applications, this study also raises some questions about how the body fights against cancers. The gene p110δ regulates immune function; the enzyme is especially important for the regulation of T-cells, a type of white blood cells which play a crucial role in cell-mediated immunity. What they describe in this study is that P110δ inhibition reshapes the body’s immune system; regulatory T-cells become inactive, and instead a sub-population of T-cells, CD8+ cytotoxic T-cells become hyper-activated and hunt down and kill any rogue cancer cells lying around the body which may cause cancerous relapse to happen. It’s still not entirely clear why this is happening – the beauty and the curse of science.

Scientific Reference: Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer. Nature, 2014; DOI: 10.1038/nature13444



There probably is no such thing as gluten intolerance, study shows


This is one of those science stories where it gives to show that even scientists can be biased and, most of all, that it’s only when you stand-up and become willing to contradict yourself that you come closer to the truth. Peter Gibson, a professor of gastroenterology at Monash University and director of the GI Unit at The Alfred Hospital in Melbourne, Australia, published in 2011 a paper that suggested gluten triggers gastrointestinal distress in patients without celiac disease, an autoimmune disorder unequivocally triggered by gluten. Since then, a whole frenzy around gluten-free diets has risen and, of course, a multi-billion dollar industry. Three years later, Gibson concludes that gluten isn’t the likely culprit, but a combination of psychological factors and other food stuff (preservatives, poorly absorbed carbo-hydrates, etc).

Non-celic gluten sensitivity: myth and fallacy

The gluten-free mania has grown to tremendous proportions in the past few years, with 30% of Americans stating they’d like to eat less-gluten. Consequently, sales of gluten-free products have soured to the point they’re expected to reach $15 billion by 2016 or 50% more than in 2013. Clearly, people care about their health. It’s unclear, however, that gluten is the culprit.

When Gibson and his team first reached their conclusions they were pretty strict about their experiments, performing them double-blinded, randomized, and placebo-controlled. Still, the research was unable to come up with tantalizing clues as to why the gluten was causing these observed physiological changes. This bugged Gibson, so he set out to perform an even stricter study, one where less variables are at play.

He recruited 37 subjects, all of whom self-professed having gluten sensitivity and who were confirmed to not have celiac’s disease. For two weeks they were fed a diet low in FODMAPs (poorly absorbed short-chain carbohydrates), then were given one of three diets for a week: 16 grams per day of added gluten (high-gluten), 2 grams of gluten and 14 grams of whey protein isolate (low-gluten), or 16 grams of whey protein isolate (placebo). Each subject shuffled through every single diet so that they could serve as their own controls, and none ever knew what specific diet he or she was eating.

The nocebo

Again, Gibson and team want to be really strict this time, so the researchers asked 22 of the original study participants to shuffle through the three different diets for three days each.

The researchers found that each treatment diet, whether it included gluten or not, prompted subjects to report a worsening of gastrointestinal symptoms to similar degrees. In other words, it was all in their heads! In their minds they were expecting not to feel good, so their body acted accordingly. Even in the second experiment, when the placebo diet was identical to the baseline diet, the subjects still reported pain, bloating, nausea, and gas when in fact nothing of the sorts should have happened. The finding led Gibson to the opposite conclusion of his 2011 research:

“In contrast to our first study… we could find absolutely no specific response to gluten.”

If this is the case why do so many people report feeling much better after changing to a gluten-free diet? Jessica Biesiekierski, a gastroenterologist at Monash University and lead author of the study alongside Gibson, noted that when participants consumed the baseline low-FODMAP diet, almost all reported that their symptoms improved!

“Reduction of FODMAPs in their diets uniformly reduced gastrointestinal symptoms and fatigue in the run-in period, after which they were minimally symptomatic.”

One of the most important sources of FODMAPs are bread products which are the first to be removed under a gluten-free diet. This means that coincidentally when people chose a particular diet for a particular reason (no-gluten), they were actually feeling the beneficial effects caused by some other reason (no-FODMAPs).

Scientific reference paper

Wind Turbines are quieter than a heartbeat, study finds

Among the criticism that wind energy gets, one main idea some people complain about is that wind turbines are noisy; some people have even went as far as to claim that even though most of the created noise is way below the range of human hearing (infrasounds), it can cause health problems, including heart issues and vertigo. Now, a study conducted by acoustical experts from Australia has shown that this idea is nothing more than pseudo science mumbo jumbo.

Picture Source.

Picture Source.

The Association of Australian Acoustical consultants found that that infrasound generated by wind turbines is less loud than the infrasound created by a human heartbeat. Even though the noise increases as the wind speed increases, you’re never going to hear it – it will always be masked by the natural noise of the wind as it passes through the environment. The acoustic engineers showed that “those investigations conclude that infrasound levels adjacent to wind farms are below the threshold of perception and below currently accepted limits set for infrasound.”

So even though the created noise is relative, people are subjected to far more significant sources of noise every day in every urban environment – the sound of cars, aircraft, wind, and waves – all do much more noise than wind turbines, and all are still in the tolerated limits.

“Our environment has lots of infrasound already in it, the levels generated by wind farms from our point of view are quite low in comparison and they’re no higher than what is already out there in the natural environment. … People themselves generate infrasound through things like their own heartbeat, through breathing and these levels of infrasound can be substantially higher than an external noise source.”

So why did people believe that it was the turbines causing them harm? Some even went to the doctors reporting symptomes of what came to be called “Wind Turbine Syndrome”. As it turns out, they were simply suffering from a nocebo (the negative, opposite of a placebo); people simply think they hear sounds which will make them sick, and they suggestion themselves into becoming sick. The human mind is a wonderful place.

Picture Source

Picture Source

Half of all German doctors have prescribed placebo’s

A new study conducted by the German Medical Association reported that about half of the doctors in Germany have prescribed placebo at some point, and no less than 88% of GPs in Bavaria have sent patients home with placebo treatments.

Placebo’s are still a matter of debate throughout the medicine world and not only, and there are still so many things we don’t understand about them; basically, a placebo is an inert tablet, a vitamin pill, something that has no direct real impact on the patient – even a sham operation. Sometimes, the patient will report a significant improvement in health that can only be linked with the imaginary treatment, a phenomenon known as the placebo effect.

What’s perhaps even more interesting is that the German Medical Association (BÄK), who published the report, welcome the findings, although stating they don’t really understand how placebo’s work.

“Placebos have a stronger impact and are more complex than we realised. They are hugely important in medicine today,” says Christoph Fuchs, the managing director of the BÄK.

All’s good here, but were they any good ? Pretty much, yes; no less than 59% of patients who had been suffering from an upset stomach were cured with placebos, and in a third of the cases, it was just as good as antidepressants. How does the success rate vary ? Well a placebo can work or not work depending on many factors, such as the degree of trust the patient has in the doctor, as well as the price of the treatment – the more expensive it is, the higher the chance of succeeding. Even more, it also depends on the size and colour of the pill.

However, placebo’s are still a grey area from many points of view; even legally. Few doctors even know if they are allowed to prescribe such a treatment. But the German medical association recommends such prescriptions if the patient has a minor illness that cannot get any worse, and they also ask for internationally recognized guidelines in order to create a framework for the use of placebo’s. Could you even imagine such a thing in the US ?