Chronic Fatigue / Lassitude / Tiredness

What Is Chronic Fatigue?

Chronic fatigue or lassitude is a state of weariness not relieved by rest and the inability to do normal physical or mental work.

Q: What are causes of chronic fatigue?

A: Chronic fatigue can be a feature of many disorders including nutritional problems like poor diet or malabsorption, sleep problems, systemic conditions like anemia or heart disease, respiratory disorders like COPD or asthma, infectious disease like tuberculosis, endocrine disorders like diabetes, autoimmune disease like thyroid disease, and cancer.

Fatigue greatly reduces quality of life in all aspects including the desire and ability to socialize and find fullfillment in new and interesting ways.

What Is Chronic Fatigue In Celiac Disease and/or Gluten Sensitivity?

• Relationship between chronic fatigue and celiac disease. Chronic fatigue that is unexplained is a classic symptom of celiac disease and a frequent presentation in visiting the doctor.

• Relationship between chronic fatigue and diet.  In a study of 5912 celiac support group members with a biopsy-confirmed diagnosis of celiac disease or dermatitis herpetiformis, the length of time on a gluten free diet was positively associated with symptom recovery. In persons adhering to a gluten free diet, 44% reported fatigue as a reaction to gluten exposure.1

• Relationship between chronic fatigue and diet in children. There is a statistically significant decrease in the incidence of chronic fatigue in children compliant with a gluten free diet compared to children at diagnosis and children who were not compliant.2

• Relationship between chronic fatigue and gut symptoms. The presence or absence of gastrointestinal symptoms does not correlate with fatigue score.3 This means that the severity of fatigue should not be considered in terms of gut symptoms but rather that fatigue develops from nutritional deficiencies.

• Relationship between chronic fatigue and depression. In adult patients with celiac disease, fatigue is a common finding and is strictly correlated with depression.4

• Relationship between chronic fatigue and body mass index. Adult celiac disease patients with chronic fatigue showed a significantly lower body mass index than controls, meaning they were thinner, and lower serum iron.3

• Relationship between fatigue and stress. Psychological stress is produced in celiac disease both by the effects of gluten and by insufficiency of many nutrients. Such stress activates multiple physiological processes aimed at maintaining balance within the body. However, these physiological processes also have the capacity to influence the composition of microbial communities in the digestive tract, and research now indicates that exposure to stressful stimuli leads to gut dysbiosis.5 Importantly, dysbiosis in turn worsens fatigue.

• Relationship between chronic fatigue and quality of life. A study investigating fatigue and quality-of-life in 51 patients showed that the greater the fatigue the worse the quality of life scores (inversely correlated). Fatigue severity was also greater in patients with worse quality of life (13 vs. 2). Multiple regression analysis showed fatigue to be an independent determinant of quality of life.6

How Prevalent Is Chronic Fatigue In Celiac Disease and/or Gluten Sensitivity?

Study results vary:

• In a Canadian questionnaire involving 5912 adults with a biopsy-confirmed diagnosis of celiac disease or dermatitis herpetiformis nationwide, extreme tiredness before diagnosis was reported by 74.2% of respondents. In less than a year, 42% recovered from fatigue. Within 5 years, 72.4% recovered from fatigue.1
• Chronic fatigue is a common complaint at diagnosis in 75% of patients.7
• In a study of 106 consecutive Irish patients with adult celiac disease, the prevalence of fatigue  was 8%.8
• Fatigue was found in 33% of the children with gluten sensitivity. Histology revealed normal to mildly inflamed mucosa (Marsh stage 0-1) in these children with gluten sensitivity.9
• In the reverse, the prevalence of celiac disease was found to be 3.3% in research participants with chronic fatigue.10

What Are The Symptoms Of Chronic Fatigue?

• Chronic fatigue is marked by a sense of exhaustion, and
• Decreased capacity to do normal physical or mental work.

How Does Chronic Fatigue Develop In Celiac Disease and/or Gluten Sensitivity?

• Chronic fatigue results from inflammation in the body due to gluten, and/or
• Nutritional deficiencies from malabsorption in celiac disease that most commonly involve carbohydrates, proteins, vitamin B1 (thiamin), vitamin C, vitamin D, iron, calcium, zinc, and magnesium. Please visit each of these nutrient posts to see which ones are causing your fatigue. For example, while vitamin D deficiency itself is a cause of fatigue, it will lead to calcium deficiency as an additional cause of fatigue plus all the other problems that come with these deficiencies.

Does Chronic Fatigue Respond To Gluten-Free Diet?

Yes. Celiac disease-related fatigue responds to a strict gluten free diet in most, but not all, patients.11 Supplementation may be required at diagnosis and thereafter for nutritional deficiencies that persist.

It has been established that many persons do not regain absorption of all nutrients even when the small intestinal mucosa heals with elimination of gluten. On the other hand mucosal recovery was reported in only 66% of adults with celiac disease after five years of treatment with a gluten free diet.12 As a cause, gluten ingestion perpetuates intestinal damage and malabsorption causing nutritional deficiencies.

Follow-up with a physician and a dietitian is essential for all patients with celiac disease, especially for patients who experience difficulty maintaining a gluten free diet.11

6 Steps To Improve Chronic Fatigue In Celiac Disease and/or Gluten Sensitivity:

• 1Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

• 2 Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

• 3 Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• 4 Manage Your Medications Safely:

• 5Nutritional Supplements To Help Correct Deficiencies:

• 6Manage Natural Remedies: 

What Do Medical Research Studies Tell About Chronic Fatigue In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Clinical, serologic, and histologic features of gluten sensitivity in children.”  This study seeking to describe the clinical, serologic, and histologic characteristics of children with gluten sensitivity demonstrated findings that support the existence of gluten sensitivity in children across all ages with clinical, serologic, genetic, and histologic features similar to those of adults. Fatigue was found in 33% of the children with gluten sensitivity.

 Subjects were 15 children (10 males and 5 females; mean age, 9.6 ± 3.9 years) with gluten sensitivity who were diagnosed based on a clear-cut relationship between wheat consumption and development of symptoms, after excluding celiac disease and wheat allergy, along with 15 children with active celiac disease (5 males and 10 females; mean age, 9.1 ± 3.1 years) and 15 controls with a functional gastrointestinal disorder (6 males and 9 females; mean age, 8.6 ± 2.7 years). All children underwent celiac disease panel testing (native antigliadin antibodies IgG and IgA, anti-tissue transglutaminase antibody IgA and IgG, and anti-endomysial antibody IgA), hematologic assessment (hemoglobin, iron, ferritin, aspartate aminotransferase, erythrocyte sedimentation rate), HLA typing, and small intestinal biopsy (on a voluntary basis in the children with gluten sensitivity).

Abdominal pain was the most prevalent symptom in the children with gluten sensitivity (80%), followed by chronic diarrhea in (73%), tiredness (33%), bloating (26%), limb pain, vomiting, constipation, headache (20%), and failure to thrive (13%). Native antigliadin antibodies IgG was positive in 66% of the children with gluten sensitivity. No differences in nutritional, biochemical, or inflammatory markers were found between the children with gluten sensitivity and controls. HLA-DQ2 was found in 7 children with gluten sensitivity. Histology revealed normal to mildly inflamed mucosa (Marsh stage 0-1) in the children with gluten sensitivity.9

“The Pediatric Symptom Checklist as screening tool for neurological and psychosocial problems in a paediatric cohort of patients with coeliac disease.” This study investigating neurological and behavioral disorders in a pediatric cohort of patients with newly diagnosed celiac disease compared with treated patients in order to detect possible differences related to compliance with gluten-free diet found that gluten-free diet had a positive impact on chronic fatigue.

A cohort of 139 patients was divided into three groups: A (40 patients with newly diagnosed CD), B (54 patients with CD in remission after gluten-free diet) and C (45 patients with potential CD). Patients first underwent a screening neurological visit, detecting signs associated with CD, and then were evaluated with Pediatric Symptom Checklist (PSC), a psychosocial screen for cognitive, emotional and behavioural problems.

RESULTS: In the group B as compared to group A, there was a statistically significant decrease (p < 0.05) in the incidence of chronic fatigue, headache and inattention. The same applied to patients compliant to gluten-free diet vs. non-compliant. Potential celiacs turning into overt CD had a higher incidence of headache and inattention compared with potential celiacs showing normal mucosa. The PSC mean score in group A was statistically higher than in group B.17

“Clinical features and symptom recovery on a gluten-free diet in Canadian adults with celiac disease.” This study investigating the clinical features and symptom recovery on a gluten-free diet in a Canadian adult celiac population found that many patients report continuing symptoms despite adhering to a gluten-free diet for more than 5 years, with women experiencing more symptoms and a lower recovery rate than men. 74.2% reported extreme tiredness at diagnosis; 72.4% reported recovery from fatigue after 5 years on a gluten free diet.

All adult members (n=10,693) of the two national celiac support organizations, the Canadian Celiac Association and Fondation québécoise de la maladie coeliaque, were surveyed using a questionnaire.

A total of 5912 individuals (18 years of age or older) with biopsy-confirmed celiac disease and⁄or dermatitis herpetiformis completed the survey. The female to male ratio was 3:1. Mean time to diagnosis after onset of symptoms was 12.0 ± 14.4 years. In addition to tiredness, symptoms of abdominal pain and bloating (84.9%), diarrhea (71.7%) and anemia (67.8%) were the most commonly reported at the time of diagnosis. Sex differences were reported in clinical features before diagnosis, recovery after being on gluten-free diet and perceived quality of life, with women experiencing more difficulties than men.

Delays in diagnosis of celiac disease in Canada remain unacceptably long despite wider availability of serological screening tests. Awareness of celiac disease needs improvement, and follow-up with a physician and a dietitian is essential for all patients with celiac disease.11

“Adult celiac disease in Ireland: a case series.” The aim of this Irish study was to analyse the presenting symptoms, associated conditions and complications in a consecutive series of patients with adult celiac disease. Data were obtained from database on patients with celiac disease between 1988 and 2004.

One hundred and six patients (69 females to 37 males, mean age: 46, range: 23-95 years) were included. The modes of presentation were diarrhoea in 44 patients (45%), weight loss in 41 (42%), anaemia in 37 (38%), abdominal pain in 15 (15%), fatigue in 8 (8%), hypocalcaemia in 4 (4%) and steatorrhoea in 4 (4%). Associated conditions included thyroid disorders in 7 patients (7%), bipolar affective disorder in 4 (4%), major depression in 3 (3%), rheumatoid disease in 3 (3%), inflammatory bowel disease in 4 (4%) and type I diabetes mellitus in 2 (2%). Malignancy emerged as a major complication in 15 patients (15%).8

“Fatigue as a determinant of health in patients with celiac disease.” This prospective, cross-sectional study investigating the influence of fatigue on perception of health in celiac disease patients determined as their quality of life found that fatigue is a major concern in untreated celiac disease patients, which impacts their quality of life.

Instruments used were the D-FIS to measure fatigue and the generic EuroQol5D to measure quality of life. An additional question on the frequency of problems due to fatigue, scored on a 7-point Likert scale, was used to evaluate the importance of fatigue.

51 patients were included (13 untreated and 38 treated with a gluten-free diet). D-FIS score was significantly worse in untreated celiacs (16 vs. 3). Scores on the frequency scale of fatigue-related problems were also worse in untreated celiacs (2 vs. 6). Fatigue and quality-of-life scores were inversely correlated. Fatigue severity was also greater in patients with worse quality of life (13 vs. 2). Multiple regression analysis showed fatigue to be an independent determinant of quality of life.6

“Fatigue in adult celiac disease.” This study evaluating the prevalence, characteristics and associations of fatigue in adult celiac disease patients found that fatigue is a common finding, which ameliorates with the gluten-free diet and is strictly correlated to depression.

A total of 130 coeliac disease patients were consecutively recruited in both treated (59 on gluten-free diet) and untreated conditions (71 on normal diet). The control group was made up of 80 healthy controls. Celiac disease patients and healthy controls underwent laboratory tests, a set of questionnaires for studying fatigue: visual analogue scale for fatigue,chronic fatigue syndrome questionnaire, fatigue severity scale and a modified version of the Zung self-rating depression scale.

Celiac disease patients showed a significantly lower body mass index than controls and lower serum iron. The entire cohort of celiac disease patients reported greater modified version of the Zung self-rating depression scale score, greater visual analogue scale for fatigue score and greater chronic fatigue syndrome questionnaire score compared with healthy controls.

Celiac disease patients on a gluten-free diet had a significantly higher modified version of the Zung self-rating depression scale score than celiacs on a normal diet. The prevalence of pathological modified version of the Zung self-rating depression scale score was 17% in all celiac disease patients and 0% in healthy controls. A significant correlation was found between modified version of the Zung self-rating depression scale score and fatigue scale scores in celiacs on a normal diet. Presence/absence of gastrointestinal symptoms did not show any significant correlation with modified version of the Zung self-rating depression scale score and fatigue scale scores.18

“Antigliadin antibodies in the absence of celiac disease.” This study measuring IgG and IgA isotypes and IgG subclasses demonstrated significantly higher proportion of patients with positive IgA gliadin antibodies reported chronic fatigue.19

1. Pulido O, Zarkadas M, Dubois S, Macisaac K, Cantin I, La Vieille S, Godefroy S, Rashid M. Clinical features and symptom recovery on a gluten-free diet in Canadian adults with celiac disease. Can J Gastroenterol. 2013 Aug;27(8):449-53. [↩] [↩]
2. Terrone G, Parente I, Romano A, Auricchio R, Greco L, Del Giudice E. The Pediatric Symptom Checklist as screening tool for neurological and psychosocial problems in a paediatric cohort of patients with coeliac disease. Acta Paediatr. 2013 Jul;102(7):e325-8. doi: 10.1111/apa.12239. [↩]
3. Siniscalchi M1, Iovino P, Tortora R, Forestiero S, Somma A, Capuano L, Franzese MD, Sabbatini F, Ciacci C. Fatigue in adult coeliac disease. Aliment Pharmacol Ther. 2005 Sep 1;22(5):489-94. [↩] [↩]
4. Siniscalchi M1, Iovino P, Tortora R, Forestiero S, Somma A, Capuano L, Franzese MD, Sabbatini F, Ciacci C. Fatigue in adult coeliac disease. Aliment Pharmacol Ther. 2005 Sep 1;22(5):489-94. [↩]
5. Galley JD, Bailey MT. Impact of stressor exposure on the interplay between commensal microbiota and host inflammation. Gut Microbes. 2014 May 1;5(3):390-396. Epub 2014 Apr 1. [↩]
6. Jordá FC, López Vivancos J. Fatigue as a determinant of health in patients with celiac disease. J Clin Gastroenterol. 2010 Jul;44(6):423-7. doi: 10.1097/MCG.0b013e3181c41d12. [↩] [↩]
7. Gregory C, Ashworth M, Eade OE, Holdstock G, Smith CL, Wright R. Delay in diagnosis of adult coeliac disease. Digestion. 1983;28(3):201-4. [↩]
8. Saleem A, Connor HJ, Regan PO. Adult coeliac disease in Ireland: a case series. Ir J Med Sci. 2012 Jun;181(2):225-9. doi: 10.1007/s11845-011-0788-z. [↩] [↩]
9. Francavilla R, Cristofori F, Castellaneta S, Polloni C, Albano V, Dellatte S, Indrio F, Cavallo L, Catassi C. Clinical, serologic, and histologic features of gluten sensitivity in children. J Pediatr. 2014 Mar;164(3):463-7.e1. doi: 10.1016/j.jpeds.2013.10.007. [↩] [↩]
10. Sanders DS, Patel D, Stephenson TJ, et al. A primary care cross-sectional study of undiagnosed adult coeliac disease. European Journal of Gastroenterology and Hepatology. Apr 2003;15(4)407-13. [↩]
11. Pulido O, Zarkadas M, Dubois S, Macisaac K, Cantin I, La Vieille S, Godefroy S, Rashid M. Clinical features and symptom recovery on a gluten-free diet in Canadian adults with celiac disease. Can J Gastroenterol. 2013 Aug;27(8):449-53. [↩] [↩] [↩]
12. Rubio-Tapia A, Rahim MW, See JA, Lahr BD, Wu TT, Murray JA. Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet. Am J Gastroenterol. 2010;105:1412–20. [↩]
13. Cummins AG, Thompson FM, Butler RN, et al. Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease. Clinical Science. Apr 2001;100(4):379-86. [↩]
14. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩] [↩] [↩] [↩] [↩] [↩]
15. Ganio MS, Armstrong LE, Casa DJ, McDermott BP, Lee EC, Yamamoto LM, Marzano S, Lopez RM, Jimenez L, Le Bellego L, Chevillotte E, Lieberman HR. Mild dehydration impairs cognitive performance and mood of men. Br J Nutr. 2011 Nov;106(10):1535-43. doi: 10.1017/S0007114511002005. [↩]
16. Szinnai G, Schachinger H, Arnaud MJ, Linder L, Keller U. Effect of water deprivation on cognitive-motor performance in healthy men and women. Am J Physiol Regul Integr Comp Physiol. 2005 Jul;289(1):R275-80. [↩]
17. Terrone G, Parente I, Romano A, Auricchio R, Greco L, Del Giudice E. The Pediatric Symptom Checklist as screening tool for neurological and psychosocial problems in a paediatric cohort of patients with coeliac disease. Acta Paediatr. 2013 Jul;102(7):e325-8. doi: 10.1111/apa.12239. [↩]
18. Siniscalchi M1, Iovino P, Tortora R, Forestiero S, Somma A, Capuano L, Franzese MD, Sabbatini F, Ciacci C. Fatigue in adult coeliac disease. Aliment Pharmacol Ther. 2005 Sep 1;22(5):489-94. [↩]
19. Kamaeva OI, Reznikov IuP, Pimenova NS, Dobritsyna LV. Antigliadin antibodies in the absence of celiac disease. Klinicheskaia Meditsina. 1998;76(2):33-5. [↩]