• A chronic intestinal malabsorption disorder caused by an intolerance to gluten
• Bulky, pale, frothy, foul-smelling, greasy stools with increased fecal fat
• Weight loss and signs of multiple vitamin and mineral deficiencies
• Increased blood levels of endomysial, anti-tissue transglutaminase, and anti-gliadin antibodies
Celiac disease, also known as nontropical sprue, gluten-sensitive enteropathy, or celiac sprue, is characterized by symptoms of varying severity, from very mild gastrointestinal discomfort to serious malabsorption (e.g., diarrhea, malodorous flatulence, abdominal bloating, and increased amounts of fat and undigested food particles in the stool). It is also characterized by abnormalities in small intestine structure that revert to normal with removal of gluten and more specifically its smaller derivative, gliadin, found primarily in wheat, barley, and rye grains. Symptoms most commonly appear during the first three years of life, after gluten-containing foods are introduced into the diet. However, a second peak incidence occurs during early adulthood. While celiac disease is often thought of as a disease diagnosed early in life, more diagnoses are made in adulthood than childhood.1
The prevalence of celiac disease has increased dramatically, and this is not simply due to increased detection. Until a few decades ago celiac disease was believed to be relatively rare (estimated before as 1 case in 5,000 in the United States), but celiac disease is now thought to affect as many as 1% of all Americans, though it remains largely undiagnosed.1–3 Undetected celiac disease carries with it an increased risk of morbidity (disease) and early mortality (death), so widespread screening may be economically justified.
In the past, the definitive diagnosis of celiac disease involved taking a biopsy of the small intestine. Now there are blood tests that measure specific antibodies to gluten components. These tests include endomysial antibodies, anti-tissue transglutaminase antibodies, and anti-gliadin antibodies. In patients with celiac disease, anti-gliadin antibody is an antibody produced against gliadin in the diet, and endomysial and anti-tissue transglutaminase antibodies are antibodies produced against the body’s own tissues as an unfortunate side effect of the immune system’s reaction to gliadin.
Causes
Celiac disease appears to have a strong genetic component. There is an increased frequency of celiac disease in people with some specific genetic markers known as HLA-B8 and DRw3 that appear on the surface of cells, similar to the genetic markers of blood type.3,4 For example, the HLA-B8 marker has been found in 85 to 90% of celiac patients, as compared with 20 to 25% of normal subjects. There is a low frequency of HLA-B8 within long-standing agrarian (farming) populations, as in Asia, while the frequency in northern and central Europe and the northwest part of the Indian subcontinent is much higher.3 Wheat cultivation in these high HLA-B8 areas is a relatively recent development (1000 B.C.). The prevalence of celiac disease is much higher in these areas than in other parts of the world. In the United States, with its diverse genetic background, the frequency rate is now roughly 1 in 100. The early introduction of cow’s milk is also believed to be a major causative factor.1–4 Research in the past few years has clearly indicated that breastfeeding and delayed administration of cow’s milk and cereal grains are the primary preventive steps that can greatly reduce the risk of developing celiac disease.5–7
Mortality and Morbidity Risks
A landmark study that looked at almost 30,000 patients from 1969 to 2008 found a higher than normal risk of early death associated with sensitivity to gluten.8 Those with full-blown celiac disease had a 39% increased risk of early death compared with controls; those with inflammation of the intestine but not full-blown celiac disease had a 72% increased risk; and those with gluten sensitivity (elevated gluten antibodies) but negative intestinal biopsy had a 35% increased risk.
A review article listed 55 health conditions linked to celiac disease and gluten sensitivity, including irritable bowel disease, inflammatory bowel disease, anemia, migraines, epilepsy, fatigue, canker sores, osteoporosis, rheumatoid arthritis, lupus, multiple sclerosis, and almost all other autoimmune diseases.9 Thyroid abnormalities, insulin-dependent diabetes, psychiatric disturbances (including schizophrenia), dermatitis herpetiformis, and urticaria have also been linked to gluten intolerance.1 A more ominous association is the increased risk for malignant cancers seen in celiac patients, especially for non-Hodgkin lymphoma.10
There is also evidence from population-based, clinical, and experimental studies that gluten is a contributing factor in some cases of schizophrenia.11–13 Digested particles of wheat gluten have demonstrated activity similar to opiates (morphine-like compounds).14 This opiate activity is believed to be the factor responsible for the association between wheat consumption and schizophrenia.
Gluten sensitivity has also been weakly linked to lower mood scores, impairment of mental function, and autism.15–17
Therapeutic Considerations
Celiac disease often leads to the development of multiple food allergies, lactose intolerance, and increased intestinal permeability.18 Improving nutritional status appears to produce significant improvement in quality of life in patients with celiac disease. Even something as simple as taking a B-complex supplement produces considerable benefits. In one double-blind study, 65 celiac patients on a strict gluten-free diet for several years were randomly assigned to either a daily dose of 800 mcg folic acid, 500 mcg vitamin B12 (cyanocobalamin), and 3 mg vitamin B6 (pyridoxine) or a placebo for six months.19 Following vitamin supplementation, the levels of homocysteine, a factor implicated in cardiovascular disease and some cancers, dropped an average of 34%, and this decrease led to significant improvement in feelings of well-being, reduced anxiety, and improved mood.
Once the diagnosis has been established, a gluten-free diet is indicated. This diet does not contain any wheat, rye, barley, triticale, or oats. Buckwheat and millet are often excluded as well; although buckwheat is not in the grass family and millet appears to be more closely related to rice and corn, buckwheat and millet contain compounds known as prolamins with antigenic activity similar to that of gliadin.
Many gluten-free products are available in natural foods stores and online catalogs, but it’s important to read labels carefully, because some “wheat-free” products add gluten—the source of gliadin—to improve the quality of baked goods. Grains that can be used to replace gluten-containing grains include amaranth, quinoa, and various types of rice (brown, red, black, and wild). In addition, recent evidence suggests that complete elimination of gluten-related compounds (e.g., secalins, hordeins, and avenins) may not be necessary for many patients. This statement is particularly true of oats. In a five-year study in which one group followed a gluten- and oat-free diet and another followed a gluten-free diet while consuming oats, no differences were seen with respect to duodenal villous architecture, inflammatory cell infiltration of the duodenal mucosa, or antibody titers.20
Detailed studies of celiac disease patients who eat oats have shown no evidence of immune activation.21–24 For example, in one study, 116 children with newly diagnosed celiac disease were randomly assigned to one of two groups: one group was given a standard gluten-free diet (GFD-std) and one group was given a GFD with additional wheat-free oat products (GFD-oats). After one year, the GFD-oats and GFD-std groups did not differ significantly regarding blood markers for celiac disease or small bowel mucosal architecture, including numbers of lymphocytes within intestinal cells.21
NA = No data available; + to +++ = degree of reactivity; — = no reactivity
aPrimarily gliadin.
bPrimarily gluten.
Data from Baker PG, Lancet 1975;ii:1307; Friis SU, Clin Chim Acta 1988;178:261–270; Chartrand LJ, Russo PA, Duhaime AG, et al. J Am Diet Assoc 1997;97:612–618.
Detailed studies of celiac disease patients who eat oats have shown no evidence of immune activation.21–24 For example, in one study, 116 children with newly diagnosed celiac disease were randomly assigned to one of two groups: one group was given a standard gluten-free diet (GFD-std) and one group was given a GFD with additional wheat-free oat products (GFD-oats). After one year, the GFD-oats and GFD-std groups did not differ significantly regarding blood markers for celiac disease or small bowel mucosal architecture, including numberaas of lymphocytes within intestinal cells.21
One point, however, is that while oat ingestion may not activate the disease, it may increase gastrointestinal symptoms. In one study, 39 celiac disease patients were randomly assigned to take either 50 g oats-containing gluten-free products per day or to continue without oats for one year.24 Patients taking oats suffered significantly more often from diarrhea, but there was a simultaneous trend toward a more severe average constipation symptom score. The lining of the intestine was not disturbed, but more signs of inflammation and allergy were evident in the oats group. It appears that oats provide an alternative in the gluten-free diet, but celiac patients should be aware of the possible increase in intestinal symptoms. If symptoms appear or become exacerbated, oats can be excluded. Ultimately, it depends on the sensitivity of each person. While many with celiac can eat rice and oats, some cannot.
In addition, other foods should be rotated, and milk and milk products should be eliminated until the patient redevelops an intestinal structure and function returns to normal.
Usually with gluten elimination, clinical improvement will be obvious within a few days or weeks (30% respond within three days, another 50% within a month, and 10% within another month). However, 10% of patients respond only after 24 to 36 months of gluten avoidance.1 If a patient does not appear to respond, either the diagnosis is not correct or there may be some obstacle to a cure, such as zinc deficiency (celiac disease symptoms will not respond to gluten elimination if an underlying zinc deficiency is present).25 The importance of a multivitamin and mineral supplement in celiac disease cannot be emphasized enough. In addition to treating any underlying deficiency, supplementation provides the necessary cofactors for growth and repair.
QUICK REVIEW
• Celiac disease is characterized by varying symptoms of severity, from very mild gastrointestinal discomfort to malabsorption (e.g., diarrhea, malodorous flatulence, abdominal bloating, increased amounts of fat and undigested food particles in the stool).
• Celiac disease is caused by the immune system’s response to a protein known as gluten.
• A gluten-free diet is curative.
• Pancreatic enzyme supplementation enhances the benefit of a gluten-free diet during the first 30 days after the initial diagnosis.
• Preparations containing DPP-IV are often recommended in order to safeguard against any hidden sources of gluten.
Pancreatic Enzymes
The effect of pancreatic enzyme therapy in the two months following the initial diagnosis of celiac disease was investigated in one double-blind study.26 The study sought to clarify the benefit of pancreatic enzyme therapy because previous studies had shown pancreatic insufficiency in 8% to 30% of celiac patients. In this study patients followed a gluten-free diet, the standard treatment for celiac disease, and received with each meal either two capsules of pancreatic enzymes (each capsule containing 5,000 IU lipase, 2,900 IU amylase, and 330 IU protease) or two placebo capsules. Results indicated that pancreatic enzyme supplementation enhanced the clinical benefit of a gluten-free diet during the first 30 days but did not provide any greater benefit than the placebo after 60 days. These results support the use of pancreatic enzyme preparations in the first 30 days after diagnosis of celiac disease.
Alternatively, a better choice than pancreatic enzymes may be enzyme preparations containing dipeptidyl peptidase IV (DPP-IV) from fungal sources. This enzyme targets both gliadin and casein (milk protein) and is resistant to breakdown by other digestive enzymes. DPP-IV is thought to be one of the key enzymes responsible for the digestion of these proteins and is known to be found in lower amounts in the intestinal mucosa of individuals with celiac disease and also to have an inverse correlation with the level of mucosal damage among those with celiac disease as well as those without the disease. In other words, the lower the DPP-IV the more significant the damage to the intestinal lining. Use of preparations containing DPP-IV is often recommended in order to safeguard against any hidden sources of gluten.
TREATMENT SUMMARY
The therapeutic approach is quite straightforward: eliminate all sources of gluten (see the table earlier in this chapter), eliminate dairy products initially, correct underlying nutritional deficiencies, treat any associated conditions, and determine and eliminate all food allergens.
Maintenance of a strict gluten-free diet is quite difficult in the United States because of the ubiquitous presence of gliadin and other activators of celiac disease in processed foods. People with celiac disease must read labels carefully in order to avoid hidden sources of gliadin, such as some brands of soy sauce, modified food starch, ice cream, soup, beer, wine, vodka, whiskey, and malt. We also recommend consulting the following resources.
Gluten Intolerance Group
15110 10 Ave. SW, Suite A
Seattle, WA 98166-1820
Celiac Sprue Association
P.O. Box 31700
Omaha, NE 68131-0700
Celiac Disease Foundation
13251 Ventura Blvd., Suite 1
Studio City, CA 91604
• A high-potency multiple vitamin and mineral formula as described in the chapter “Supplementary Measures”
• Vitamin D3: 2,000 to 4,000 IU per day (ideally, measure blood levels and adjust dosage accordingly)
• Fish oils: 1,000 mg EPA + DHA per day
• One of the following:
Grape seed extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Pine bark extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Some other flavonoid-rich extract with a similar flavonoid content, super greens formula, or another plant-based antioxidant that can provide an oxygen radical absorption capacity (ORAC) of 3,000 to 6,000 units or more per day
• Specialty supplements:
Probiotic (active lactobacillus and bifidobacteria cultures): a minimum of 5 billion to 10 billion colony-forming units per day
Enzyme preparations containing dipeptidyl peptidase IV (DPP-IV)