Psychiatrist Dr Jessica Hellings, mental health researcher Dr Deanna Kelly and psychiatric physician assistant Sharon Pugh examine the emerging evidence on the link between gluten sensitivity and depressive symptoms—and how a gluten-free diet could transform your mental health
Depression, or major depressive disorder, is one of the most common mental illnesses in the world. It is estimated to affect some 5 percent of the world’s population at any given time and ranks among the leading causes of disability.1 It’s also thought to be a factor in at least half of all suicides.2
While the potential causes of depression are broad and often complex, mounting evidence suggests that for some people, untreated celiac disease (CD)—an immune reaction to eating gluten—and gluten intolerance, also known as non-celiac gluten sensitivity (NCGS), could be playing a big role in depressive symptoms.
Here’s a look at the key evidence connecting gluten and depression—and how to recognize whether it could be affecting you or someone you know.
The link between depressive symptoms and intestinal disease was first described in 1932 when Dr Thaysen, a Danish researcher, observed unusual levels of fatigue in people with “sprue” (now called CD), an inflammatory disease of the small intestine that prevents normal absorption of nutrients.
Two decades later, a researcher proposed that a gluten-free diet could improve mood in adults with CD.3 And in 1956, another researcher observed that avoiding gluten appeared to improve behavior in children with CD and that adults with CD who did not eat a gluten-free diet developed headaches, insomnia and depression.4
In 1970, David Goldberg at the Institute of Psychiatry in London studied a sample of 80 people with diseases of the small intestine and found that over a third of them had mood disorders. While they did not have CD, their diagnoses were Crohn’s disease, idiopathic steatorrhea (a condition of fat malabsorption) or a form of lactose intolerance.5
Although Goldberg did not attribute the mood symptoms directly to malabsorption, he noted that these people with intestinal diseases had stronger family histories of psychiatric illness as well. His findings strengthened the idea that there is a connection between the gut and the brain.
Another group of researchers studied CD-gluten antibodies in 60 people with mood disorders (depressive disorders and bipolar disorder) and compared them with 48 healthy controls. They found those with mood disorders had much higher levels of the antibodies than controls did.
Each unit increase in the antibodies corresponded to a 5 percent increase in the likelihood of having a mood disorder.6 These results demonstrate a direct relationship between the antibody levels and mood disorders.
Today, the connection between CD and depression is fairly well established. Several large analyses have shown that people with CD are more likely to have a history of depression than people in the general population.7 Still, other studies have shown no difference in such prevalence.8
One study of over 2,000 people with CD showed 39 percent had suffered from depressive symptoms at some point, which means that more than one in three people with CD will have depression in their lifetime.9 But is it actually the autoimmune condition itself that’s causing the depression, or could it be the difficulty of living with a chronic illness?
A meta-analysis (pooled analysis of multiple studies) analyzing depression and anxiety in adults with CD showed that depression was more common and severe in adults with CD than in healthy adults. But it also found depression was as common and severe in CD as in other types of chronic physical illness.10
Other studies have shown the severity of gastrointestinal symptoms correlates with depression in CD,11 suggesting people may feel more depressed due to experiencing more physical symptoms and discomfort. And some researchers have found that people with CD who had gastrointestinal and other physical symptoms scored worse on quality-of-life measures than those with silent or atypical symptoms.12
This underscores the idea that distress about gastrointestinal symptoms could be a cause of depression. The theory is also supported by studies showing that sticking to a strict gluten-free diet might reduce depressive symptoms in people with CD, possibly by relieving gastrointestinal symptoms.13
Likewise, in a few studies, poor adherence to a gluten-free diet in people with CD has been linked to an increase in depression.14 Other studies, however, have suggested a strict gluten-free diet is actually a cause of depression in CD.15
One study showed little difference in quality of life between people who fully versus partially adhered to a gluten-free diet. But the risk of developing anxiety and depression increased the more people struggled to stick to the diet.16 The authors noted that dietitians should address these issues, especially since depression may make following a gluten-free diet more challenging.
But there are theories suggesting a more direct physiological link between CD and depression. They suggest the gut immune response in people with CD results in inflammation in the brain and leads to symptoms of psychiatric illness.
A study looking at intestinal biopsies from patients in Sweden showed the risk of suicide was higher in patients with CD than in the general population. But it found suicide was also more common among those with intestinal inflammation. People with positive blood tests for CD but without intestinal inflammation in their biopsy results didn’t have a higher suicide risk.17
Interestingly, when gluten was reintroduced in a study of over 200 people with CD, those who had been stricter about following a gluten-free diet experienced a more severe relapse in depressive symptoms.18 Going back to gluten after strictly avoiding it may contribute to a more severe rebound inflammatory response.
In addition to CD, depression has been linked to other gastrointestinal disorders including NCGS (see Celiac disease vs non-celiac gluten sensitivity, below), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).
While IBS and CD share many of the same symptoms, they are thought to have different causes, and correctly diagnosed IBS does not cause the sort of damage to the intestinal tract seen in people with CD (see Celiac disease vs non-celiac gluten sensitivity, below). But some people with IBS may be sensitive to gluten, as in NCGS, and in some cases this sensitivity may be associated with depressive symptoms.
In one study, researchers evaluated the effects of a gluten-free diet on people with IBS. The participants did not have CD but did have certain markers for CD. Results showed that the gluten-free diet decreased their anxiety and depression scores after six weeks as well as after 18 months.19
Another study of adults with IBS measured depression scores after switching to three separate diet plans—a placebo diet without gluten or whey, a diet with 16 g of gluten per day or a diet with 16 g of whey per day. Depression scores were higher on the gluten diet than on the placebo diet.20
In another study of people with IBS, a diet restricting FODMAPs was found to decrease depressive symptoms.21 FODMAPS (fermentable oligo-, di- and monosaccharides and polyols) are carbohydrates found in wheat, garlic, onions, beans and several fruits that can be difficult to digest.
And in a study of people with IBD without CD whose symptoms were controlled on a gluten-free diet, eating gluten caused physical symptoms, including fatigue,22 which is common in both gluten sensitivity and depression.
While these IBS studies may have included people with NCGS, there are also reports linking those with known NCGS to depression. Almost one in five people with NCGS have depressive symptoms, according to one study.23
In a trial of people with NCGS who ate a gluten-free diet or a gluten-containing diet for one week, then switched, the researchers found that eating gluten increased depressive symptoms, but the gluten-free diet didn’t.24 Interestingly, one study that enrolled primarily women with fibromyalgia and NCGS found depressive symptoms dropped on a gluten-free diet.25
Another study comparing antibody levels in people with depression, people with IBS and healthy controls reported the depressed group had higher levels of antibodies to gluten.26
Others have found these antibodies disappeared after six months in over 90 percent of those with NCGS who fully complied with a gluten-free diet. At the same time, their gastrointestinal symptoms and depression improved.
On the other hand, the antibodies disappeared in only 60 percent of those in the study with CD.27 This difference was likely related to the immune differences between CD and NCGS.
There are many psychological and biological ways in which gluten and depression may be related. Brain fog and fatigue may cause difficulties in managing the many stressors in life. People with CD or NCGS may experience depressive symptoms related to having a chronic illness or chronic, painful intestinal and extra-intestinal symptoms. They may also be depressed as a psychological reaction to a strict diet that impacts their social life and enjoyment of food.
But what about biological mechanisms linking gluten-related autoimmunity in the brain to depressive symptoms?
Biological mechanisms may be particularly relevant in NCGS. Many symptoms of depression, such as fatigue, poor concentration, sleep difficulties, appetite changes and brain fog, overlap with symptoms of CD and NCGS. What mechanisms might be underlying these symptoms, and could they be related both to malabsorption of essential nutrients and to an autoimmune reaction in the brain?
People with intestinal inflammation do not absorb vitamins and nutrients normally, and vitamin deficiencies may contribute to symptoms of depression. Also, supplementing B vitamins can significantly reduce depressed mood in people with CD on a gluten-free diet.28
Inflammation in the gut caused by gluten may also lead to lower absorption of dietary tryptophan, the essential amino acid that the body needs to make serotonin, one of the main neurotransmitters implicated in depression.29 Interestingly, since the gut is where 90 percent of total serotonin production occurs, diseases of the gut may affect mood due to direct signaling between the gut and the brain.30
One study compared thyroid function tests as well as depression and anxiety rates in adults with CD to those of healthy controls with no family history of CD. It found the CD patients were more likely to have had major depressive disorder and/or panic disorder, both in their lifetimes and in the past six months.
And those with CD and anti-thyroid antibodies were especially likely to have had major depression and panic disorder. Subclinical thyroid autoimmune disease could be a big risk factor for these mental health conditions, the researchers concluded.31
Both depression and gluten sensitivity are linked to higher general inflammation in the body, which can also lead to stress and local inflammation in the brain.32 Intestinal inflammation can result in leaky gut, in which small breaches in the lining of the intestine allow substances like bacterial toxins or inflammatory molecules into the bloodstream.
The general state of inflammation associated with gluten sensitivity can also make the blood-brain barrier lining the brain’s blood vessels leaky, which allows some of these molecules and gluten antibodies to cross into the brain and contribute to impairments and damage.33
These bacterial fragments and inflammatory substances do not cause issues like major infections, but they can disrupt normal brain function and lead to psychiatric symptoms, including depression.
Evidence shows that foods containing gluten may be linked not just to depression but also to a host of psychiatric symptoms via an immune response—in up to one in 17 people. Few medical clinicians are aware of this although studies have documented the link for over 10 years now.
Even more surprising is the simplicity of the treatment program for those who need it: removing gluten from the diet can improve psychiatric and neurological symptoms, the research suggests.
We’re not preaching that there’s a cure-all or implying that diet should replace medications a person may be taking. Not everyone with psychiatric and neurological issues is gluten sensitive, and there are often many contributors to mental and physical illnesses.
But for those who are, or those with undiagnosed CD, a gluten-free diet may bring huge benefits. Still, continue to work with your provider and do not stop any medications before discussing it with them.
Gluten is a Latin word meaning “glue” that refers to the stickiness in wheat-based dough used to make bread and pasta.1 It’s a mix of several proteins found in certain grains, such as wheat, barley and rye.
There are many varieties and crossbreeds of wheat, known by different names, that also contain gluten. These include triticale (a cross between wheat and rye), durum, spelt, farro and semolina, and they developed partly due to wheat’s ability to self-pollinate.2
Oats are naturally gluten-free, but cross-contamination with gluten-containing grains during processing can occur and trigger a gluten reaction in those with CD and NCGS.
CD and NCGS are both related to gluten consumption, but there are several differences between the two.
Celiac disease (CD)
CD is a lifelong autoimmune condition in which gluten consumed in wheat, rye or barley, by individuals who are genetically susceptible, affects the mucous membrane, also known as the mucosal lining (the moist soft-tissue lining of organs and cavities in the gastrointestinal, respiratory and reproductive systems) of the small intestine and may trigger gastrointestinal and other symptoms.
Not all people affected this way will have symptoms; however, most people with CD will continue to have damage to their small intestines when they eat gluten, even if they don’t have outwardly visible symptoms.
Risk factors for CD include the presence of specific gene variants, also called biomarkers (biological signs that can be measured and identified in a person) as well as a family history of CD or other autoimmune disorders.1
On biopsy of the duodenum (first part of the small intestine), CD is identified by a characteristic finding of atrophy (flattening) of the villi, which are finger-like projections in the lining of the intestines that increase the surface area to maximize absorption of nutrients from food.
Symptoms of CD may include gastrointestinal problems such as diarrhea, constipation, nausea, vomiting, abdominal pain, bloating, increased gas and/or lactose intolerance due to small-intestinal damage. Extra-intestinally (outside the gastrointestinal system), signs and symptoms can occur in every other system in the body.
About half of those with CD do not have gastrointestinal symptoms. Instead they have other symptoms, or non-specific symptoms like anemia, weight loss and vitamin deficiencies due to malabsorption of nutrients.2
Non-celiac gluten sensitivity (NCGS)
Like CD, NCGS is associated with both gastrointestinal and extra-intestinal symptoms that worsen after consuming gluten and are relieved by a gluten-free diet. But, unlike CD, NCGS is not believed to be an autoimmune disorder. Instead, it’s thought to be a separate type of immune reaction, an “innate immune response.”
Many NCGS patients have increases in lymphocytes and mast cells, which are types of immune cells in their gut, as well as inflammatory cytokines in their blood. While there is no confirmed test for NCGS, in just over half of those with the condition, the native AGA IgG antibodies are elevated, which suggests NCGS.
NCGS is much more common than CD. It’s thought to affect some 13 percent of the population,3 while the prevalence of CD is around 1–2 percent.
A 22-year-old woman consulted a psychiatrist for severe depressive symptoms. She had experienced alternating diarrhea and constipation in her first year of life, leading to hospitalization and diagnosis of subocclusive syndrome (a disorder of gut motility). However, her intestinal symptoms had resolved after age two and did not return.
During adolescence, she had developed severe depression, anxiety and insomnia and had withdrawn significantly from her social life.
By age 22 her depressive symptoms were severely impacting her quality of life. She began the tricyclic antidepressant clomipramine but experienced only transient improvement during the summer months. Additionally, her symptoms improved slightly during her first pregnancy but then returned, and treatment with a different tricyclic medication, imipramine, was ineffective.
She also tried fluoxetine and paroxetine, both selective serotonin reuptake inhibitors (SSRIs), for long periods but continued to experience recurrent depressive episodes.
After her three-year-old child was diagnosed with CD, blood tests and an intestinal biopsy were completed on the woman and she too was diagnosed with CD.
She started a gluten-free diet and experienced rapid improvement in depressive symptoms within three months. She was able to stop taking all psychiatric medication and remained psychiatrically stable nearly two years later.1
Switching to a gluten-free diet requires some effort and is not a decision to be taken lightly. It’s important to consider which foods you should eat to minimize excess sugar and fat while addressing potential diet-associated nutrient deficiencies. But here’s a quick guide to what you can eat on a gluten-free diet.
A gluten-free diet includes foods that are naturally gluten-free and foods that are made gluten-free by manufacturing and purification. Foods that are naturally free of gluten include fresh fruit, vegetables, legumes, nuts, fish/seafood, meat, poultry and most dairy products.
Foods that would normally contain gluten, like bakery items, pasta and prepackaged foods, can be prepared as gluten-free by using gluten-free ingredients like almond flour, buckwheat, rice, corn, quinoa, millet and amaranth.1
Pseudocereals or pseudograins are plants that produce seeds or fruits that function like grains but are not grasses like true grains. For example, quinoa (a gluten-free seed) functions as a cereal but is not a member of the grass family and is gluten-free. Oats are generally gluten-free but may contain gluten, depending on their processing. So it’s important to look for a “certified gluten-free” label on oats.
Non-wheat flours made from legumes such as chickpeas, peas and carob flour may also be used in gluten-free products. Though not a full list, the table below includes naturally gluten-free foods, common gluten-free cereals, pseudocereals and other non-grain foods.2
| Naturally gluten-free foods | Gluten-free cereals | Gluten-free pseudocereals |
| Vegetables | Corn** | Buckwheat** |
| Fruits | Rice** | Quinoa** |
| Legumes: peanuts, peas, beans, lentils | Sorghum** | Amaranth |
| Soybeans*** | Oats**** | |
| Milk | Millet | |
| Plain meat | Teff | |
| Fish and seafood | Fonio | |
| Eggs | ||
| Butter | ||
| Cheese (most) | ||
| Vegetable oils | ||
| Nuts | ||
| Tapioca |
**Available as substitutes for wheat flour3
***Soybeans in their natural form and soybean oil are gluten-free; however, soy sauce, unless labeled “gluten-free,” contains gluten
****Often contaminated with gluten during processing; check the label
Adapted from Get Your Brain Off Grain: How a Gluten-Free Diet Could Improve Your Mental and Neurological Health (Hammersmith Health Books, 2025) by Jessica Hellings, Deanna Kelly and Sharon Pugh
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