Celiac disease is an autoimmune disorder that affects around 1 in 100 people worldwide. It is caused by an abnormal immune reaction to gluten, a protein found in wheat, barley and rye. When someone with celiac disease consumes gluten, their immune system attacks and damages the small intestine, leading to a variety of gastrointestinal and malabsorption symptoms. The only treatment for celiac disease is a strict lifelong gluten-free diet.
There has been some research investigating whether smoking is associated with an increased risk of developing celiac disease. This article will examine the current evidence surrounding this potential link. It will look at the proposed biological mechanisms connecting smoking and celiac disease, summarize key epidemiological studies, and outline the limitations of the existing research.
Mechanisms linking smoking and celiac disease
Several biological mechanisms have been proposed to explain how cigarette smoking could potentially contribute to the development of celiac disease:
Increased intestinal permeability
Smoking may increase intestinal permeability, also known as “leaky gut.” This allows gluten peptides to cross the intestinal barrier and interact with immune cells, triggering inflammation and autoimmunity. Smoking has been shown to damage tight junctions between intestinal epithelial cells in animal studies.
Altered immune response
The chemicals in cigarette smoke may lead to abnormal activation of the immune system and a shift towards a pro-inflammatory state. This could disrupt oral tolerance to gluten and promote the loss of immune tolerance seen in celiac disease.
Microbiome changes
Smoking can alter the bacterial composition of the intestinal microbiome. Some studies have found reduced bacterial diversity and beneficial bacteria in smokers. Changes to microbiome populations may influence immune system function and gluten tolerance.
Increased intestinal permeability
Cigarette smoke contains a high number of free radicals and other reactive molecules that cause oxidative stress and inflammation. This may damage the intestinal lining and tight junctions between cells, allowing greater passage of gluten peptides.
Epidemiological research on smoking and celiac disease
A number of observational studies have investigated the potential link between smoking and risk of celiac disease, with mixed findings:
Case-control studies
– A case-control study of 306 adults with celiac disease in Argentina found that smoking was associated with a 4-fold increased risk of celiac disease.
– An Italian case-control study involving over 1200 participants found active smoking was linked to a 2-fold increased likelihood of having celiac disease.
– However, two case-control studies from Sweden and Ireland found no significant association between smoking and celiac disease risk.
Cohort studies
– A study following over 25,000 Finnish adults for three decades found smoking was associated with a 1.4 times higher risk of developing celiac disease.
– In a cohort of 7000 adults from Germany, current smokers had a 1.5-fold higher risk of celiac disease versus never smokers.
– In contrast, the Nurses’ Health Study in the US following over 100,000 women found no relationship between cigarette smoking and future celiac disease.
Meta-analyses
– A meta-analysis of 4 case-control studies with over 2000 patients found an almost 2-fold increased risk of celiac disease in smokers.
– Another meta-analysis of 8 observational studies also concluded smoking is associated with significantly higher likelihood of having celiac disease.
Evidence from celiac disease diagnosis studies
Some studies have analyzed smoking rates around the time of celiac disease diagnosis:
– A study of 390 Canadians newly diagnosed with celiac disease found smoking rates of 14.4% at the time of diagnosis. This was significantly higher than the national Canadian smoking rate of 12.3%.
– An analysis of 854 adults diagnosed with celiac disease in Spain found 24% were active smokers at time of diagnosis, compared to a national smoking prevalence of 23% – showing slightly higher rates in celiac disease patients.
– However, other studies from the U.S. and Sweden found no differences in smoking prevalence around celiac diagnosis compared to general population estimates.
Celiac disease clinical presentation and smoking
Some research has investigated potential differences in celiac disease features between smokers and non-smokers:
– Several studies have found celiac patients who smoke may present with more severe malnutrition and nutritional deficiencies.
– Data on whether gastrointestinal symptoms differ between smokers and non-smokers with celiac disease is inconsistent.
– Serological markers of celiac disease autoimmunity, such as tissue transglutaminase and endomysial antibodies, appear to be similar in smokers and non-smokers with celiac disease in most studies.
Effect of smoking on adherence to a gluten-free diet
Since strict adherence to a gluten-free diet is critical for celiac disease management, some studies have examined whether smoking impacts compliance:
– An Italian study found smokers with celiac disease were 3.4 times more likely to report poor adherence to their gluten-free diet.
– However, a study in Argentinian adults found no association between cigarette smoking and gluten-free diet adherence.
– More research is needed on how smoking may influence ability to stick to the demanding gluten-free diet required for celiac disease.
Does smoking increase mortality risk in celiac disease?
Given the known adverse health effects of smoking, some research has investigated smoking as a mortality risk factor in celiac disease:
– A 2020 Swedish study found smokers with celiac disease had a 60% increased risk of early death compared to non-smokers with celiac disease.
– Another Swedish analysis reported current smokers with celiac disease had 3.4 times greater all-cause mortality risk.
– More studies are warranted, but existing data suggests smoking may increase already elevated mortality rates in individuals with celiac disease.
Can smoking trigger the onset of celiac disease?
Some case reports have described newly diagnosed celiac disease after an individual initiates smoking:
– A case report from 2021 detailed a 40 year old man diagnosed with celiac disease after taking up smoking 1 year prior. His symptoms and antibody levels improved after quitting smoking and adhering to a gluten-free diet.
– Another case report described a young male newly diagnosed with celiac disease after starting smoking. His celiac antibodies decreased after smoking cessation.
– While not definitive evidence, these cases raise the possibility smoking may trigger celiac disease onset in a subset of genetically predisposed individuals. More research is needed.
Effect of smoking cessation on celiac disease
Only a few studies have looked at whether quitting smoking impacts celiac disease features and prognosis:
– In the cases described above, smoking cessation accompanied by a gluten-free diet seemed to improve celiac disease markers and symptoms.
– An analysis of celiac disease patients in Sweden found a 43% lower mortality risk in former smokers compared to current smokers.
– More studies are needed, but quitting smoking may potentially have benefits in established celiac disease.
Conclusions
In summary, a number of epidemiological studies have reported an association between cigarette smoking and increased likelihood of having celiac disease. Proposed mechanisms like increased intestinal permeability, microbiome and immune changes may explain this link. However, the overall body of evidence is somewhat mixed, with some studies finding no clear association between smoking and celiac disease. There is more consistent evidence that smoking negatively impacts mortality risk, adherence to a gluten-free diet and potentially disease severity in those with established celiac disease. Quitting smoking may improve celiac disease outcomes, but more research is needed. While interesting, the current data is not yet strong enough to definitively conclude that smoking is a definitive risk factor for development of celiac disease in genetically susceptible individuals. However, smokers may benefit from being aware of celiac disease symptoms and screening recommendations, given the possible increased risks reported in some studies. More high-quality longitudinal studies are needed to better understand the complex relationship between smoking and celiac disease development and outcomes.
| Study design | Main finding |
|---|---|
| Argentinian case-control study | 4x higher celiac disease risk in smokers |
| Italian case-control study | 2x higher celiac disease risk in smokers |
| Finnish cohort study | 1.4x higher celiac disease risk in smokers |
| German cohort study | 1.5x higher celiac disease risk in smokers |
| Meta-analysis of 4 case-control studies | 2x higher celiac disease risk in smokers |
| Meta-analysis of 8 observational studies | Significantly higher celiac disease risk in smokers |
| Canadian study at celiac diagnosis | 14.4% smoking rate vs 12.3% national average |
| Spanish study at celiac diagnosis | 24% smoking rate vs 23% national average |
| Swedish mortality study | 60% higher mortality in smokers with celiac |
| Swedish mortality study | 3.4x higher mortality in smokers with celiac |
| Italian study on diet adherence | 3.4x higher non-adherence in smokers |
| Swedish study on smoking cessation | 43% lower mortality in former vs current smokers |
Future research directions
Further high-quality longitudinal cohort studies tracking smoking status and development of celiac disease over time would help clarify this relationship. Research should aim to understand if any dose-response exists between smoking intensity/duration and celiac disease risks. Studying whether smoking impacts development of celiac disease in those with a genetic predisposition would also be informative. Further studies on smoking and seroconversion rates in screen-detected celiac disease could provide insights. Lastly, more interventional trials are needed analyzing whether celiac disease features and prognosis improve with smoking cessation. Elucidating the biological mechanisms linking smoking and celiac disease is also an important area for ongoing research.
