Scientists are exploring the link between gluten and an array of mental health conditions. Photo / Getty Images
If you’re feeling depressed or run down it might be time to avoid gluten.
Could the bread in your sandwich, the pasta in your salad or the wheat in your breakfast be making you depressed?
That is the theory that scientists are avidly exploring with studies showing a link between gluten and an array of mental health conditions, from ADHD to schizophrenia.
Deanna L. Kelly is a professor of psychiatry for Mental Illness Research at the University of Maryland School of Medicine, who has spent the past 17 years leading clinical trials in schizophrenia and severe mental illness, as well as being active in psychopharmacology research.
“I would have been sceptical if you’d told me I’d end up studying this connection,” says Kelly. “My line of thinking was therapy and medications; I didn’t know food and diet could actually be good medicine.”
Her scientific journey began by analysing data from soldiers during the Second World War. It showed that during wheat shortages hospitalisations went down.
Kelly and her colleagues then looked at the work in the 1970s of Curtis Dohan, a psychiatrist, who was publishing cases of people with schizophrenia recovering on a wheat-free diet.
Dohan also visited remote islands in Papua New Guinea, where wheat was not part of the diet and found schizophrenia to be virtually absent, compared to its occurrence in wheat-eating populations elsewhere.
Kelly then had the opportunity to run a large clinical trial looking at the antibodies produced by the body in a reaction to gluten. What she found was very high rates of antibodies to gluten in the bodies of people with schizophrenia.
Her findings have now led her to believe there is a strong connection between brain function and people who have gluten sensitivity. And she is not alone.
Evidence shows that consuming foods containing gluten may be linked to a host of psychiatric symptoms, via an immune response, in up to one in 17 people.
Get Your Brain Off Grain, the book she has co-authored, draws together the most up-to-date research on the subject.
“There’s really been this disconnect between gastroenterology and psychiatry. We don’t know everything. But it’s another step closer connecting the dots about these illnesses.”
Gluten is a group of proteins found in wheat, barley and rye. These are key grains found in breads, pastas, pastries and many other of our favourite foods. Some people are sensitive to gluten. This means their immune system “fights” against gluten as a foreign invader in the body.
Coeliac disease is the most well-known type of gluten-related autoimmune disease. It causes damage to the digestive tract leading to a range of gastro-intestinal symptoms such as diarrhoea, bloating and stomach pain, as well as fatigue, weight loss and skin rashes. Coeliac disease runs in families and is diagnosed via a blood test or intestinal biopsy. It is related to another type of gluten sensitivity, often called non-coeliac gluten sensitivity (NCGS), which is about 10 times more prevalent than coeliac disease. However tests for coeliac disease are often negative in those with NCGS.
“It’s challenging for someone to be diagnosed with non coeliac gluten sensitivity,” says Kelly.
Gluten was only introduced into our diets about 6000 years ago. “The idea of breaking it down is really challenging for our bodies and it never breaks down completely,” says Kelly.
When a person with gluten sensitivity eats something with gluten in it – even “healthy” brown pasta or bread – their body produces antibodies to fight against the gluten.
While two types of protein join to make gluten, gliadin and glutenin, it is the former that induces an immune response. This can cause inflammation and contribute to damage in the gut, which leads to the development of “leaky gut”.
The weakened gut wall allows the antibodies to gliadin to leak from the intestine into the general bloodstream. “When it gets across the stomach lining, the body sees it as a foreign substance for some people,” says Kelly.
Consequently, inflammation may occur in other parts of the body, including a person’s brain. When the antibodies’ fight gets to the brain, symptoms that develop may include not only foggy thinking, and lack of energy, but also poor emotional control, anxiety, mood changes, hallucinations and/or seizures, that are often resistant to treatment with medications.
“There’s a specific peptide sequence called 33-mer [found in wheat] that is highly associated with an immune response,” says Deanna. “If you look at the structure of that, it’s very similar to one of the structures of the GRINA receptor, a receptor in the brain. So our bodies potentially can’t tell the difference.”
It is one of Kelly’s theories that in some people their immune system might be attacking some of the tissue in the brain because it looks like gluten.
“We have a paper showing that these antibodies to the receptors to the brain are higher in people who have the antigliadin antibodies.”
The area of the brain called the amygdala functions to help calm fear and anxiety. People with anxiety disorders have been shown to have an exaggerated amygdala response when exposed to events that evoke anxiety.
Serotonin, a chemical messenger in the nervous system and part of the brain’s communication system, is believed to be a key neurotransmitter involved in anxiety disorders. Interestingly, the gut provides approximately 95% of the body’s total serotonin and production is influenced by the particular balance of gut microbes in the individual person.
Of course, not everyone with psychiatric and neurological issues is gluten sensitive.
However, what is interesting, says Kelly, is that: “All these disorders that we write about, the literature now is leaning towards them all having inflammation as a cause.
“The immune system is likely not working right in some people. And that leads to inflammatory markers and inflammation. My suggestion is that to some people, gluten is one of the culprits in this immune inflammatory reaction.”
The most common symptoms Kelly sees among her psychiatric patients are brain fog, anxiety or depressive symptoms. “They sometimes have headaches and migraines. Joint pain is common too.”
Coeliac disease and NCGS diagnoses are more common in individuals with ADHD symptoms than in the general population.
The link between coeliac disease and depression is well-established. One large study of over 2000 people with coeliac disease showed a 39% lifetime prevalence of depressive symptoms.
“One theory is that depression stems from the difficulty of living with a chronic illness,” says Kelly. “But there are studies showing a more direct physiological link between coeliac disease and depression.”
There is even clearer clinical data that those with schizophrenia can be helped by following a gluten-free diet.
One patient of Kelly’s suffering from schizophrenia always saw her illness worsen after having gluten.
“She was doing well in the community but when she had gluten she would be hospitalised.
“When she got into the hospital they would give her gluten because they wouldn’t believe the family that that mattered. Each time the family would have to fight about it at every hospital.”
Other proteins are also linked to inflammation of the brain. “Casein from milk is another protein that is highly immunogenic.”
Outside of the gluten realm there’s a movement towards understanding the impact of ultra-processed foods on our health.
“There’s evidence to show that depression and anxiety and most mental health conditions are higher in people who eat high levels of UPFs, especially in the western diet.”
And wheat is part of that. Wheat is now the most widely cultivated crop in the world, and it supplies 20% of all food calories and protein consumed by the global population.
“The data is showing us that there are more people sensitive to gluten than before, we think that’s due to a higher gluten content in UPFs.”
One of the reasons why gluten may now cause a more severe immune response is that there has been a six-fold increase in the gliadin content of wheat over time. This may be down to the use of high-nitrogen fertilisers and how wheat is processed.
One young woman who came to Kelly suffering from anxiety and brain fog had previously been tested for gluten sensitivity by her gastroenterologist.
“She was told she didn’t have coeliac disease or gluten sensitivity. So I brought her in to take part in my study, and sure enough her antibody response was the biggest I’d ever seen.
“I actually found antibodies to suggest coeliac disease, which are called TTG. I gave her the paperwork and said, ‘please go back to your doctor’. When she went back, they did a biopsy and they found she had coeliac disease. It had been missed.”
She is one of almost 1000 people in the general population that Kelly has tested for gluten antibodies.
“When people have these antibodies, once I say, ‘You’re positive for this, it might be worth trying a gluten free diet’, most people report their joint pain went away, or their brain fog, or their anxiety and depression improved.”
She has published 24 peer-reviewed studies around these antibodies and the relationship of gluten to neurological and psychiatric illnesses.
“Thirty per cent of my patients with schizophrenia have antibodies to gliadin. That means their body is having an immune response to wheat.”
Her work has changed her diet. Kelly now eats a low carb, almost gluten-free.
“I’m not a fad diet person,” she says. “If you’d told me I would be studying this I would have laughed. But science took me there.”
From looking at animal studies, the data would suggest that gluten could be bad for everyone. “We haven’t gone so far as to say that,” says Kelly, cautiously. “But when you start to dig into it, and you’ve seen what a brain looks like of an animal of gluten, it really makes me think twice about how much should be in my diet.”
Still, not everybody should be on a gluten-free diet. About 10% of the population have NCGS. And Kelly sees lots of people who have no immune response at all. “Their bodies handle it fine. But then there are lots of people who have the antibodies and coeliac in their families and that’s where removal could really help people.”
While it’s not going to be a cure-all for everybody, typically Kelly sees changes in her patients in as little as three weeks. Brain imaging data has also shown how the blood flow in their brain improves on a gluten-free diet.
“We do recommend talking to your dietitian or doctor beforehand. That’s because many foods that contain gluten are fortified with minerals and vitamins that our body needs, but struggles to get from our diet. Things like folic acid. You need folate for your brain.”
She also notes that for those who have a psychiatric disorder, such as depression or schizophrenia, eating a gluten-free diet can be a challenge.
“Once you are sick, it’s easier to just continue to eat gluten because it’s cheap and you don’t have to spend time cooking. When you’re not feeling well you don’t want to spend time cooking fresh vegetables. It becomes a cycle.”
Over 2000 years ago Hippocrates said, “let food be thy medicine and medicine be thy food”.
“All this time later we are now starting to pay attention to the impact of the food we put in our body,” says Kelly.
The parents of one young man with a seizure disorder noticed that every time he had a big spaghetti meal his seizures were worse. “And no one thought that that was related,” says Kelly, who was consulted by a neurologist on the case. “While he didn’t test positive for coeliac disease, he did have antibodies to gliadin. And so we suggested a gluten free diet and he has been seizure free since.”
However, it is challenging for people to understand that a gluten-free diet helps their brain.
She is used to resistance to new ideas, that is the lot of the scientist. However she says: “We now have the technology. We can look at brain imaging and antibodies and show that it actually connects. We know for a fact that the brain is impacted by what we put into our gut and now we have to unravel all the mysteries there.”