The 'Nocebo Effect’ and Irritable Bowel Syndrome

By Dr. Caroline Seiler

Many people find that wheat or gluten cause them to react in some way: Some people have a wheat allergy, some have the autoimmune condition celiac disease, but the majority find they have some sort of intolerance or sensitivity to wheat and gluten.

This is challenging to diagnose because there still aren’t any reliable biomarkers to confirm gluten or wheat sensitivity, and clinicians typically rely on patient self-reports.

In irritable bowel syndrome (IBS), patients experience gastrointestinal symptoms without any visible damage to the digestive tract. Many patients with IBS believe that specific foods, like gluten or wheat, trigger their symptoms, prompting them to exclude these foods from their diets without consulting a dietitian or their doctor.

Unsurprisingly, about a third of IBS patients develop disordered eating habits and perceptions about food that may cause symptoms in and of themselves, such as orthorexia, or an unhealthy preoccupation with healthy eating. This may cause a “nocebo effect,” where patients experience symptoms due to their beliefs and expectations about a substance they assume is causing their issues but is actually inert — a “nocebo.”

As a nutrition researcher at McMaster University’s Farncombe Institute, I’m a member of a team that ran a clinical trial to find out whether wheat, gluten or a gluten-free nocebo caused symptoms in IBS. And the results were surprising: even though some patients experienced worse symptoms from gluten or wheat, they weren’t very different from the nocebo, with similar proportions of patients reacting to each.

These results are similar to other published studies. Identifying the true sensitivities for patients with IBS is a controversial research area, with some studies finding gluten avoidance to be beneficial versus others finding it to have no significant effect.

Researchers from the United Kingdom and the Netherlands published an innovative study from the Lancet medical journal. Patients with reported gluten sensitivity were divided into four groups: Two groups were given gluten-free bread, but one of these groups was told it contained gluten and one was told it didn’t. Two other groups were given bread that did contain gluten, with one group believing it was gluten-free and the other believing it contained gluten.

The results showed that the patients who ate gluten and were also told they were eating gluten had significantly worse symptoms than the other three groups.

Gluten Misinformation

Given the controversial evidence that not only gluten, but other wheat components like fermentable carbohydrates or immune-stimulating proteins, may exacerbate IBS symptoms, it’s possible for this hot topic to get blown out of proportion or taken out of context, contributing to nutrition misinformation.

All of these factors — that it is often diagnosed by excluding all other options, the significant psychological component, the division in the scientific community and clinicians who often discount patients’ experiences — make treatment difficult for patients with this disorder.

As a result, patients with IBS are often left to navigate conflicting online resources and test new diets to treat their symptoms. When researchers challenge patients with gluten, wheat or a nocebo, they rarely report the personalized results back to the patients and see how this information impacts patient behaviour.

At McMaster University, we wanted to see how presenting personalized nutrition information would affect our patients. After providing them with personal results about their gluten and wheat reactions, we followed up with patients after six months or more to see how this impacted their beliefs, behaviours and symptoms.

Again, we were in for a surprise! Patients largely kept similar beliefs about gluten, maintained a gluten-free diet and had consistent symptoms even after learning that most of them did not react to gluten or wheat. This begs the question: when people more generally learn new information that conflicts with an existing belief, what may help them to change accordingly?

Psychological Treatment

IBS has been long understood as a disorder of the gut-brain interaction. Psychological treatments are being increasingly investigated to minimize patient fears of foods, or nocebo effects, and to treat IBS symptoms more generally. At Harvard, a recent study found that exposure-based cognitive behavioural therapy (CBT) showed promise to improve IBS symptoms in five sessions with a nurse practitioner.

Similarly, CBT correlated with shifts in brain networks and the gut microbiome, or gut bacteria, that were also correlated with improvements in gastrointestinal symptoms. At the University of Calgary, virtually delivered yoga was highly feasible and helped improve symptoms for patients with IBS.

However, IBS is a complex disorder which may be exacerbated due to many different causes, and psychological treatment will likely be only one component of an effective treatment plan for many patients.

Diet plays an important role in human health, but how it does so — especially among those with gastrointestinal diseases — becomes complicated by the emotional aspects of eating and the real needs for people to have nutritious, well-balanced diets without risking malnutrition. If you have concerns that certain foods, like gluten, trigger your symptoms, it’s a good idea to consult your doctor or a registered dietitian.

Caroline Seiler, PhD, is a clinical researcher who studied at McMaster University in Ontario, Canada. She receives funding from the Canadian Institutes of Health Research.

This article originally appeared in The Conversation and is republished with permission.

Autoimmune Disease Patients Struggle with Diagnosis and Costs

By Andy Miller, KFF Health News

After years of debilitating bouts of fatigue, Beth VanOrden finally thought she had an answer to her problems in 2016 when she was diagnosed with Hashimoto’s disease, an autoimmune disorder.

For her and millions of other Americans, that’s the most common cause of hypothyroidism, a condition in which the thyroid, a butterfly-shaped gland in the neck, doesn’t produce enough of the hormones needed for the body to regulate metabolism.

There’s no cure for Hashimoto’s or hypothyroidism. But VanOrden, who lives in Athens, Texas, started taking levothyroxine, a much-prescribed synthetic thyroid hormone used to treat common symptoms, like fatigue, weight gain, hair loss, and sensitivity to cold.

Most patients do well on levothyroxine and their symptoms resolve. Yet for others, like VanOrden, the drug is not as effective.

For her, that meant floating from doctor to doctor, test to test, and treatment to treatment, spending about $5,000 a year.

“I look and act like a pretty energetic person,” said VanOrden, 38, explaining that her symptoms are not visible. “But there is a hole in my gas tank,” she said. And “stress makes the hole bigger.”

Autoimmune diseases occur when the immune system mistakenly attacks and damages healthy cells and tissues. Other common examples include rheumatoid arthritis, lupus, celiac disease, and inflammatory bowel disease. There are more than 80 such diseases, affecting up to an estimated 50 million Americans, disproportionately women. Overall, the cost of treating autoimmune diseases is estimated at more than $100 billion annually in the U.S.

‘Patients Feel Dismissed’

Despite their frequency, finding help for many autoimmune diseases can prove frustrating and expensive. Getting diagnosed can be a major hurdle because the range of symptoms looks a lot like those of other medical conditions, and there are often no definitive identifying tests, said Sam Lim, clinical director of the Division of Rheumatology at Emory University School of Medicine in Atlanta. In addition, some patients feel they have to fight to be believed, even by a clinician. And after a diagnosis, many autoimmune patients rack up big bills as they explore treatment options.

“They’re often upset. Patients feel dismissed,” Elizabeth McAninch, an endocrinologist and thyroid expert at Stanford University, said of some patients who come to her for help.

Insufficient medical education and lack of investment in new research are two factors that hinder overall understanding of hypothyroidism, according to Antonio Bianco, a University of Chicago endocrinologist and leading expert on the condition.

Some patients become angry when their symptoms don’t respond to standard treatments, either levothyroxine or that drug in combination with another hormone, said Douglas Ross, an endocrinologist at Massachusetts General Hospital in Boston. “We will have to remain open to the possibility that we’re missing something here,” he said.

Jennifer Ryan, 42, said she has spent “thousands of dollars out-of-pocket” looking for answers. Doctors did not recommend thyroid hormone medication for the Huntsville, Alabama, resident — diagnosed with Hashimoto’s after years of fatigue and weight gain — because her levels appeared normal. She recently switched doctors and hopes for the best.

“You don’t walk around hurting all day long and have nothing wrong,” Ryan said.

And health insurers typically deny coverage of novel hypothyroidism treatments, said Brittany Henderson, an endocrinologist and founder of the Charleston Thyroid Center in South Carolina, which sees patients from all 50 states. “Insurance companies want you to use the generics even though many patients don’t do well with these treatments,” she said.

Meanwhile, the extent of Americans’ thyroid problems can be seen in drug sales. Levothyroxine is among the five most prescribed medications in the U.S. every year. Yet research points to some overprescribing of the drug for those with mild hypothyroidism.

A recent study, paid for by AbbVie — maker of Synthroid, a brand-name version of levothyroxine — said a medical and pharmacy claims database showed that the prevalence of hypothyroidism, including milder forms, rose from 9.5% of Americans in 2012 to 11.7% in 2019.

The number of people diagnosed will rise as the population ages, said McAninch. Endocrine disruptors — natural or synthetic chemicals that can affect hormones — could account for some of that increase, she said.

In their search for answers, patients sometimes connect on social media, where they ask questions and describe their thyroid hormone levels, drug regimens, and symptoms. Some online platforms offer information that’s dubious at best, but overall, social media outlets have increased patients’ understanding of hard-to-resolve symptoms, Bianco said.

They also offer one another encouragement.

VanOrden, who has been active on Reddit, has this advice for other patients: “Don’t give up. Continue to advocate for yourself. Somewhere out there is a doctor who will listen to you.” She has started an alternative treatment — desiccated thyroid medication, an option not approved by the FDA — plus a low dose of the addiction drug naltrexone, though the data is limited. She’s feeling better now.

Research of autoimmune thyroid disease gets little funding, so the underlying causes of immune dysfunction are not well studied, Henderson said. The medical establishment hasn’t fully recognized hard-to-treat hypothyroid patients, but increased acknowledgment of them and their symptoms would help fund research, Bianco said.

“I would like a very clear, solid acknowledgment that these patients exist,” he said. “These people are real.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues  

Gluten-Free Diet May Relieve Neuropathy Pain

By Pat Anson, Editor

A small study by British researchers suggests that a strict gluten-free diet may help protect against the nerve pain caused by gluten sensitivity.

"These findings are exciting because it might mean that a relatively simple change in diet could help alleviate painful symptoms tied to gluten neuropathy," said lead author Panagiotis Zis, MD, a senior lecturer at the University of Sheffield. "While our study shows an association between a self-reported gluten-free diet and less pain, it does not show that one causes the other."

Gluten sensitivity has been associated with peripheral neuropathy -- a condition in which peripheral nerves become damaged, causing weakness, numbness and pain in the hands and feet. Diabetic neuropathy can also cause these symptoms, but when diabetes is ruled out and a person is sensitive to gluten – the pain and numbness might be caused by gluten neuropathy.

The British study involved 60 mostly elderly people who had gluten neuropathy. They were asked about the intensity of their pain, mental health and whether they followed a strict gluten-free diet. About half of the participants had pain with their neuropathy.

People who were following a gluten-free diet were significantly more likely to be free of pain than those who did not. Over half of those without pain were on a gluten-free diet, while 21 percent who were gluten-free still experienced pain.

After adjusting for age, sex and mental health status, researchers found that people following the strict diet were 89 percent less likely to have pain.  

The study also found that people with painful gluten neuropathy scored significantly worse on their mental health assessment, which had a range of zero to 100 with 100 being best. Those with painful gluten neuropathy had an average score of 76, as opposed to the average score of 87 for those with painless gluten neuropathy.

"This study is promising because it shows that a gluten-free diet may help lower the risk of pain for people with gluten neuropathy," Zis said. "More research is needed to confirm these results and to determine whether the gluten-free diet led to the reduction in pain."

Further results of the study will be presented at the annual meeting of the American Academy of Neurology in April.

Gluten is a protein found in wheat, rye, barley, oats and other cereal grains. Gluten is found in many types of food, including bread, pasta, cereal, sauces and salad dressing.

When people with celiac disease eat gluten, it triggers an immune response that attacks the small intestine, causing pain and inflammation. About 1-2% of the population has celiac disease, but most cases go undiagnosed and untreated. Celiac disease is hereditary and runs in families.

People with non-celiac gluten sensitivity (NCGS) may also develop gastrointestinal symptoms, as well as headaches, chronic fatigue, fibromyalgia and allergies. Abdominal pain and irregular bowel movements are frequently reported with NCGS, which can make it difficult to distinguish from irritable bowel syndrome (IBS).

Research about the relationship between gluten and chronic pain conditions is rather slim, although there are many anecdotal reports that a gluten free diet reduces pain. In PNN columns, Donna Gregory Burch said going gluten-free helped reduce her fibromyalgia symptoms, while Lisa Ayres found that eliminating gluten quickly relieved her arthritis symptoms.  

Wheat Protein Could Worsen Chronic Illness

By Pat Anson, Editor

Gluten isn’t the only reason why some people should avoid eating wheat.

German researchers have discovered a second protein in wheat that triggers inflammation and worsen symptoms of multiple sclerosis, lupus, rheumatoid arthritis and other chronic illnesses. The finding could help explain why some people who are not gluten intolerant and do not have celiac disease still benefit from going on a gluten-free diet.

Researchers say a family of proteins called amylase-trypsin inhibitors (ATIs) make up only about 4% of the protein found in wheat. But they can trigger powerful immune system reactions outside the digestive system, in the lymph nodes, kidneys, spleen and brain.

"As well as contributing to the development of bowel-related inflammatory conditions, we believe that ATIs can promote inflammation of other immune-related chronic conditions outside of the bowel,” said lead researcher, Professor Detlef Schuppan of Johannes Gutenberg University.

“The type of gut inflammation seen in non-celiac gluten sensitivity differs from that caused by celiac disease, and we do not believe that this is triggered by gluten proteins. Instead, we demonstrated that ATIs from wheat, that are also contaminating commercial gluten, activate specific types of immune cells in the gut and other tissues, thereby potentially worsening the symptoms of pre-existing inflammatory illnesses.”

Schuppan presented his findings at United European Gastroenterology Week. He said future clinical studies will explore the role that ATIs play on chronic health conditions in more detail.

"We are hoping that this research can lead us towards being able to recommend an ATI-free diet to help treat a variety of potentially serious immunological disorders," said Schuppan.

Celiac disease is a gastrointestinal inflammation caused by the ingestion of wheat, barley, rye, and other foods containing gluten. About 1-2% of the population has celiac disease, but most cases go undiagnosed and untreated.

People with non-celiac gluten sensitivity (NCGS) may also develop gastrointestinal symptoms, as well as headaches, chronic fatigue, fibromyalgia and allergies. Abdominal pain and irregular bowel movements are frequently reported with NCGS, which can make it difficult to distinguish from irritable bowel syndrome (IBS).

The symptoms typically appear after the consumption of gluten-containing food and improve rapidly on a gluten-free diet, even though gluten does not appear to cause the condition. Schuppan says the real culprit may be ATIs.

"Rather than non-celiac gluten sensitivity, which implies that gluten solitarily causes the inflammation, a more precise name for the disease should be considered," he said.

My Life with Migraines

By Sara Batchelder, Guest Columnist

I have had migraine disease since I was 22. My first migraine was in 1992, the year I graduated from college. 

I am now 45, and my migraines have become chronic and daily.  I have lost two jobs, many friendships, my social life, and my relationship of eleven years.  This year, I also lost my ability to work full-time at a regular job.  The only reason I can still work part-time is that my ex employs me and allows me to work whenever I am able.  Thank goodness for that. Working gives me a purpose and makes me feel like a productive member of society.  It is an extreme struggle to work twenty hours a week though. 

I also have thyroid disease (my thyroid gland was removed when I was 29), celiac disease (I have been 100% gluten free for a year), depression, anxiety, infertility, and extreme allergies to many things, such as food, pollen, dust, cats, you name it. 

I now have a multi-pronged approach to my treatment.  For migraine, I have botox injections every three months, I see a “natural MD” for various treatments, and I take Relpax (a triptan) and opioids (Norco and morphine). 

I am still learning a lot about celiac disease, but I stay ever vigilant that I do not ingest any gluten whatsoever, even one molecule.  It’s a learning experience and constantly challenging.  For instance, I will visit a restaurant that I consider safe, get “glutened” and cross that restaurant off the list.  I am down to four restaurants that I can eat at. 

Since I am too sick to cook for myself most of the time, I graze on various packaged food - some good, some not so good.  I eat protein bars when traveling, although I do not travel often anymore.  It’s a lot of work to make sure all the food I eat is gluten-free and free of all of my other food allergies. 

sara met with sen. barbara boxer while advocating for migraine research

I’ve been dealing with allergies for all of my 45 years.  My “natural MD” (my voodoo doctor, as I jokingly call him) gives me small doses of LDA shots, which are helping a bit.  He also believes that I have a lyme-like disease called Bartonella, which he is treating me for.  I am on so many vitamins that I won’t even go there. I take Wellbutrin for depression, nothing for anxiety, and since I am now 45, the infertility has played itself out. 

Deep breath. That’s a lot of illness and treatment.

Even with all of this, my scariest problem today is the government’s war on pain patients who take opioids.  After the DEA stormed one of my doctors’ offices in bulletproof vests with guns drawn (to request appointments with two doctors -- couldn't that have been done by phone?), all of my doctors, but one, have withdrawn ALL narcotic treatments for ALL migraineurs. 

It baffles me why this policy exists.  This is discrimination plain and simple.  I want to sue, but no lawyer will take the case.  I know that many addicts lie and tell doctors that they are migraine patients, since migraine is an invisible disease that cannot be diagnosed with blood tests, MRI’s, or anything else, but these are doctors whom I have a 10 year relationship with! 

They are either petrified of the DEA or always thought that I was an addict, and didn’t care enough to deal with that.  Either way, what the heck I am supposed to do?  Without my weekly pain shots, I can no longer work full-time.  If I still didn’t have one doctor on my side, I’m pretty sure I would have committed suicide. 

My private disability was denied due to some technicality.  SSI pays less than I can make part-time and SSI doesn’t allow the disabled to work part-time anyway (don’t get me started on that). 

I am very, very fortunate to work in California, where I have been on part-time disability.  But it will only last for one year, so I will be on my own again soon anyway.  I don’t know about other people, but there is no way I can survive in California on half-pay.  I was barely making ends meet while working full-time.  Now that I am single again, I cannot rely on someone else to support me. It is terrifying!!!

I have met and will soon meet again with members of Congress to discuss more funding for migraine and headache research through an organization called Headache on the Hill. That organization does not support opioid treatment for migraine at this time, but I still want to address the opioid issue with other pain patients.  Who will join me?
 

Sara Batchelder lives in California, where she received an MBA with honors from the University of San Francisco and works as a controller for small architecture firm. Sara volunteers at her local credit union and tries to advocate for migraineurs as much as she can.

Pain News Network invites other readers to share their stories with us. 

Send them to:  editor@PainNewsNetwork.org.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.