Anxiety, Chronic

What Is Anxiety?

[dropcap]A[/dropcap]nxiety or worry is a distressing emotional state of mind or mood that is characterized by a vague uneasiness, unpleasant feelings of apprehension or anticipation of danger and by interference with normal functioning, ranging from mild qualms and easy startling to occasional panic.

Q: What causes anxiety?

A: Anxiety can be a normal response to stress such as making an important decision, illness, divorce, problems at work or preparing for an exam.

In a dangerous situation, profound physiological changes rapidly prepare us for a “fight or flight” response by release of adrenalin hormone. Adrenalin speeds up metabolism to make available quick energy, tightens muscles in readiness, and speeds up the heartbeat and breathing so that more oxygen is made available to the brain and muscles.

Anxiety becomes a maladaptive disorder when it is excessive, unrealistic, or not provoked and impairs the ability to lead a normal life.

Anxiety that is part of a person’s personality is called “trait anxiety.” Anxiety that comes and goes is “state anxiety,” as in state of mind, and is usually due to unresolved stress or an underlying health problem.

What Is Chronic Anxiety in Celiac Disease?

• Relationship between anxiety and celiac disease: Chronic anxiety that is “state anxiety” is a common psychological feature of untreated celiac disease and can be a presenting symptom at diagnosis of celiac disease.
• Relationship between anxiety and malabsorption: Anxiety that develops in celiac disease is maladaptive. It is not the type that exists as a personality trait or unresolved stress or as the result of an underlying disease process, such as thyroid or adrenal gland problems. Rather, it results from deficiency of amino acids and vitamins needed to make the brain chemicals (neurotransmitters) that control mood and could be linked to immunological disregulation in celiac disease patients.¹
• Relationship between anxiety and tryptophan/ niacin: The malnutritional impact causing anxiety is shown by lack of the amino acid tryptophan and the B3 vitamin niacin. Tryptophan deficiency results in insufficient production of the brain chemical serotonin. Serotonin calms the mind while awake and at night, converts to melatonin, which is needed for sleep. Niacin helps balance brain chemicals like serotonin and counters the effects of stress.

If both niacin and tryptophan are low, the case becomes robbing one anti-anxiety nutrient to make another. The need for niacin is critical to all cells of the body. While our bodies can use tryptophan to make niacin, this is a low conversion process that requires adequate levels of co-factors iron, vitamin B2 (riboflavin), and vitamin B6 (pyridoxine). Therefore, if tryptophan is also deficient and/or the co-factors are deficient, then this avenue is closed to niacin production.

• Relationship between anxiety and vitamin B deficiencies: Most vitamin B deficiencies result in anxiety.² On the other hand, anxiety itself causes depletion of vitamins and minerals through excess sweating, urination, and in some persons, loose bowels, which then furthers anxiety.
• Relationship between anxiety and sleep:  Both state and trait anxiety in celiac disease result in poor sleep.³
• Relationship between anxiety and response to gluten after diagnosis. Fully gluten free diet adherent patients are more likely to have symptomatic responses to dietary gluten (SRDG) less than 1hr than patients who are partial/none adherent as are those patients at risk of both anxiety and depression. That is, anxiety and depression enhance the speed of symptom onset, and inadvertent exposure to dietary gluten in the fully gluten free diet adherent group is more likely to result in a severe SRDG in comparison to symptoms arising prior to consistent gluten free diet adherence.⁴

How Prevalent is Anxiety In Celiac Disease and/or Gluten Sensitivity?

Anxiety is common in untreated celiac disease and can be the only manifestation.¹,⁵

In research, celiac disease patients showed high levels of state anxiety in a significantly higher percentage compared to controls (71.4% vs, 23.7%).⁶

In a postal survey of 224 biopsy-proven patients with celiac disease, prevalence of  anxiety numbered 30 (13%) while anxiety and depression numbered 72 (32%).⁴

What Are The Symptoms of Anxiety?

Symptoms of anxiety include:

• Restlessness.
• Irritability.
• Trouble focusing attention.
• Cold and/or sweaty palms and feet.
• Dry mouth.
• Trembling.
• Muscle tension.
• Headaches.
• Fatigue.
• Poor sleep (insomnia).
• Low blood sugar.
• A faster heart rate than normal.
• Skipped heartbeats.
• Chest pains.
• Elevated blood pressure.
• Rapid breathing.
• Dizziness.
• Frequent need to urinate.
• Problems swallowing.

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

Anxiety results from an unclear etiology involving these mechanisms:

• Inflammation of brain tissue and/or cerebral blood vessels caused by gluten exposure.
• Biochemical alterations in the brain caused by malabsorption of multiple nutrients in celiac disease including calcium, magnesium, iron, potassium, B vitamins, and tryptophan which cause cognitive, sleep and emotional problems.
• The effects of low blood sugar (hypoglycemia) on metabolism, the nervous system, and the cardiovascular system.
• Alteration in cerebral blood flow (brain blood flow abnormalities) which diminishes the necessary delivery of oxygen and blood sugar to brain tissue. Cerebral single photon emission CT scan showed 73% of untreated celiac disease patients with anxiety had at least one hypoperfused (abnormally low blood flow to) brain region compared with only 7% of patients on a gluten free diet and none of controls.⁷

Does Anxiety Respond To Gluten-Free Diet?

Yes. In celiac disease-related anxiety withdrawal of gluten usually results in disappearance of symptoms.¹ Deficiencies may need to be corrected.

B vitamin supplements should be considered in people advised to follow a gluten-free diet.⁸

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

• [dropcap]1[/dropcap]Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

[box type=”shadow” ]Treatment. This condition responds to the complete elimination of gluten, which is the required treatment that improves both anxiety and gut health.

• Gut health is the foundation to restore ALL health. Restored health will enable you to maintain a strict gluten free diet, just as other life tasks will be easier.
• A strict gluten free diet means removing 100% of wheat, barley, rye and oats from the diet.
• Cutting out bread and other obvious sources of gluten is not good enough for recovery. Even 1/8th teaspoon of flour or bread crumb is enough to sustain the inflammation that is damaging your small intestine, causing increased permeability (leaky gut) and allowing undigested gluten to enter your body where it can damage structures and function, and instigate immune inflammatory responses.

Correct Your Individual Nutritional Needs.

• Eat foods that can replenish missing nutrients. Find them under NUTRIENT DEFICIENCIES.
• Take nutritional supplements as needed. Find them under NUTRIENT DEFICIENCIES.

Recovery. You should begin to feel better within a week and notice more energy as inflammation subsides and the  absorbing cells that make up the surface lining of your small intestine are better able to function.

• Intestinal lining cells are replaced every 5 days. The healing process is like sunburn where the damaged surface layer of skin sloughs off and is replaced with new normal cells.
• Leaky gut normally resolves in two month after starting a gluten free diet and brings about a big improvement in health. Improvement in intestinal permeability precedes morphometric recovery (cell appearance and structure) of the small intestine in celiac disease.⁹
• The intestinal lining may take up to a year to heal.[/box]

• [dropcap]2[/dropcap] 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).

[box type=”shadow” ]Here Are Major Inflammatory Food Types That Reduce Healing:

• Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk disrupts intestinal permeability causing leaky gut.¹⁰
• Allergenic Foods. Includes foods that trigger the immune sytem to produce IgE antibodies. Allergy testing is the usual way to discover these offending foods.
• Shelf Stable Processed Foods. Includes any that contain additives and preservatives. Look for them on the nutrition label of the box or package. Additives and preservatives also disrupt intestinal permeability causing leaky gut.¹⁰ Many cause cancer such as polysorbate 60, potassium bromate, and sodium nitrate.
• Fats. Limit deep fried foods, trans-fats, saturated fats (animal fat/butter), and EXCESSIVE omega-6 fatty acid oils like corn oil. Rancid fats, sodium caprate (a medium chain fat), and sucrose monester fatty acid (a food grade surfactant) induce significant disruption of the intestinal barrier that causes leaky gut.¹⁰.
• Excessive Refined White Flours (bran layer removed). Includes products made from them such as cookies, bread, cakes, pies. Bran contains the vitamins and minerals that metabolize grains and slows the otherwise rapid entry of sugar from their digestion into the bloodstream. Also disrupt intestinal permeability causing leaky gut.¹⁰
• Refined Sugars.  Includes white sugar, corn fructose and high fructose corn syrup.
• Artificial sweeteners. Includes Aspartame, Sucralose, and Saccharin which are also linked to cancer and autoimmune disease.
• Certain Spices. Includes paprika and cayenne pepper which disrupt intestinal permeability causing leaky gut.¹⁰
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.¹⁰[/box]

[box type=”shadow” ]Here Are Important Anti-Inflammatory Food Types to Promote Health:

• Fruits. Contain ample amounts of vitamins, minerals and phytochemicals which are naturally occuring components in plants that detoxify toxins, carcinogens (reducing the risk by 50%) and mutagens.
• Non-Starchy Vegetables. Support intestinal integrity and provide ample amounts of vitamins, minerals and phytochemicals. Includes lettuce, kale, onion, broccoli, garlic, and others.
• High Quality Complex Carbohydrates. Provide vitamins, minerals, and fiber while boosting serotonin levels to help you relax and feel calm. Includes whole grains, legumes, and root vegetables such as carrots, parsnips, sweet potatoes, turnips, red beets, and others.
• Antioxidants. Protect the body from inflammatory oxidant molecules that continually occur and help us handle stress and reduce irritability. Includes vitamin C-containing foods such as lemon, grapefruit, apricot, Brussels sprouts and strawberries, and others. Also, includes vitamin E-containing foods such as nuts, seeds, avocado, olive oil, and others. Cocoa is good, too.
• Omega-3 Fatty Acids. Balance opposing omega-6 fatty acids and bad fats. Fish sources includes tuna, salmon, cod, and others. Plants sources include flax, chia seeds, canola oil, and others.
• Probiotics. Supply normal microbes needed for colon health and health of the body such as these fermented foods: yogurt, kefir, and unpasteurized apple cider vinegar.
• Prebiotics/ High Fiber Foods.  Food with fiber keeps our population of colonic microbes healthy.
• Protective Herbs and Spices.  See below #6 below for examples.[/box]

• [dropcap]3[/dropcap] Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• [dropcap]4[/dropcap] Manage Your Medications Safely:

[box type=”shadow” ]

Certain prescription drugs used for anxiety can cause nutritional deficiencies. Ask your doctor or pharmacist about this possible adverse effect especially if you are prescribed these drugs (do not stop without supervision):

• Benzodiazepines deplete melatonin, a brain chemical needed for sleep. These include:
  • Valium® (diazepam), Tranxene® (clorazepate dipotassium), Ativan® (lorazepam), Klonopin®, Xanax® (alprazolam).

Caution: If you are taking anti-anxiety drugs, discuss taking herbals such as Kava-Kava and St John’s Wort with a licensed health care professional before trying them (at the same time) because they can have an additive effect.  

For example, Kava-Kava is very effective for anxiety. However, it modifies the same receptors that benzodiazepines bind. 
Combined administration of St. John’s wort with alprazolam decreases the blood levels of alprazolam and should be avoided unless otherwise directed by a licensed health care professional.¹¹[/box]

• [dropcap]5[/dropcap]Nutritional Supplements To Help Correct Deficiencies:

[box type=”shadow” ]

• Multivitamin/mineral combination once a day is useful to improve overall nutrient levels. This is a safe dose, but always check with your doctor to avoid interactions with medications.
• 100% of the B vitamins, or as prescribed by a doctor. About B Vitamin Complex supplements:  some labeling can be confusing, for example, “B 100” does not mean 100%. If the ingredient list shows  an excessive amount like 3000% or more, look for another brand because this excessive amount will cause the loss of mineral in the urine.
• 100% of any of these that are deficient:  Calcium as Calcium Citrate, Iron as Ferrous Fumarate (bloodwork first), Chelated Magnesium, Potassium (bloodwork first).

Storage Note: Store container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet – not in the bathroom or on the kitchen table.[/box]

• [dropcap]6[/dropcap]Manage Natural Remedies: 

[box type=”shadow” ]Hydration is very important in managing anxiety:

Research in young men showed that even mild dehydration induces adverse changes in vigilance and increased tension/anxiety and fatigue.¹²

Research investigating how mental performance is affected by slowly progressive moderate dehydration induced by water deprivation shows that subjective ratings by subjects of mental performance changed significantly toward increased tiredness and reduced alertness, and higher levels of perceived effort and concentration necessary for test accomplishment during dehydration.¹³

• Eight glasses of water are recommended per day unless there is a contraindication such as kidney or heart disease. The Institute of Medicine recommends approximately 2.7 liters (91 ounces) of total water, from all beverages and foods, each day for women and 3.7 liters (125 ounces) daily of total water for men.
• If you are thirsty, drink water. Add fresh, squeezed lemon to water. Lemon is anti-inflammatory, alkalizing and provides vitamin C that improves anxiety.
• Hydration Test: Urine should be pale yellow. Fingertips should be plump, without pruning but this may not be reliable when fingers are swollen with edema. Lips should be plump, without puckering. The feeling of thirst can be unreliable.
• What is wrong with soda, coffee, tea, and alcohol? These drinks are dehydrating, increase acid, and deplete nutrients.[/box]

[box type=”shadow” ]Carminatives. The following anti-inflammatory plant sources called carminatives help heal the digestive tract. They tone the digestive muscles which improves peristalsis, thus aiding in the expulsion of gas from the stomach and intestine to relieve digestive colic and gastric discomfort which are often part of chronic anxiety.

Carminative Food Remedies:

• Raspberry.
• Carrot is also a cleansing digestive tonic.
• Grape is also bile stimulating and a cleansing remedy for sluggish digestion and laxative.
• Redbeets also stimulate and improve digestion and are easily digested.
• Cabbage also stimulates and improves digestion and is also a liver decongestant.
• Lettuce also stimulates and improves digestion and is also an alterative, meaning it improves the function of organs involved with the digestion and excretion of waste products to bring about a gradual change.
• Potatoes are antispasmodic (due to atropine like properties) and a liver remedy.

Carminative Herb Remedies:

• Sage is also a digestive, astringent, bile stimulant and energy tonic that heals the mucosa.  Drink as tea or use in cooking.
• Chamomile, lemon balm, and fennel, (as a tea) also help relieve nervous tension.
• Parsley also relieves indigestion.
• Rosemary as a tea and in cooking acts as a nervous system tonic for stress and fatigue thanks to carnosic acid, which enhances blood circulation in the brain, improves thinking, and specifically blocks free-radical damage to brain tissue. Rosemary also stimulates bile and helps relieve headaches and indigestion.
• Thyme is also soothing remedy useful for stimulating digestion of rich, fatty foods.

Carminative Spice Remedies:

• Cloves are also antispasmodic.
• Nutmeg is also useful for indigestion.
• Ginger.[/box]

[box type=”shadow” ]Exercise Helps:

Exercise stimulates the brain to produce anti-anxiety chemicals and get rid of stress hormones.

• Walking is aerobic exercise that reconditions the whole body to improve stamina. Read more about Exercise and Fitness.
• Weight training builds muscle. Read more about Exercise and Fitness.
• Stretching improves flexibilty. Read more about Exercise and Fitness.

Note: Exercise is important, but the amount and type of exercise undertaken depends on your health. Your first priority is to heal. [/box]

What Do Medical Research Studies Tell About Anxiety in Celiac Disease?

RESEARCH STUDY SUMMARIES

“Factors influencing the type, timing and severity of symptomatic responses to dietary gluten in patients with biopsy-proven coeliac disease.” This study investigating the type, timing and severity of symptomatic responses (SRDG) to dietary gluten with reference to a range of disease-related factors found that patients with consistent gluten free diet adherence experience a SRDG faster and more severe in comparison to prior gluten exposure possibly demonstrating an adept immunological response. Anxiety and depression also enhance the speed of symptom onset and co-existing visceral hypersensitivity is a risk factor for severe reactions to dietary gluten.

Method of study: Postal survey of 224 biopsy-proven patients including gluten-free diet adherence, symptom checklist, ROME II criteria and The Hospital Anxiety & Depression Scale. Case-note review was also conducted.

26% of respondents were male. Full gluten free diet adherence numbered 159 (70%). Irritable bowel syndrome (IBS) numbered 50 (22%). Anxiety numbered 30 (13%); Depression numbered 33 (14%); Anxiety & Depression numbered 72 (32%). Pruritus, fatigue and bloating were a more common SRDG in the partial/none gluten free diet adherent group. Co-existing IBS was associated with a greater prevalence of nausea and fatigue in response to gluten.

Fully gluten free diet adherent patients are more likely to have SRDG less than 1hr than partial/none adherent as are a third of patients with co-existing IBS and those patients at risk of both anxiety and depression. Inadvertent exposure to dietary gluten in the fully gluten free diet adherent group is more likely to result in a severe SRDG in comparison to symptoms arising prior to consistent gluten free diet adherence.⁴

“Anxiety and depression in adult patients with celiac disease on a gluten-free diet.” The aim of this large German study comparing anxiety and depression levels in adult patients with celiac disease on a gluten-free diet with controls found that living alone was associated with a reduced risk of an anxiety disorder which highlights the difficulty of maintaining a Gluten Free Diet when living with people eating gluten. Study results of the questionnaire showed that Gluten Free Diet may reduce psychological symptoms due to malabsorption of tryptophan, but may also increase psychological distress associated with the financial and social restrictions of Gluten Free Diet and disease-related worries. A higher psychosocial burden on female Celiac Diseases because of buying and preparing food for the family can be presumed.¹⁴

“The quality of sleep in patients with celiac disease.” The aim of this study was to evaluate the quality of sleep in coeliac disease. Study subjects were: 1) patients at diagnosis of celiac disease; 2) patients with celiac diseases on a gluten-free diet at follow-up, and 3) healthy volunteers. Results found significant differences between celiacs and volunteers. PSQI score was inversely associated with the quality of the physical and mental component scores. The sleep quality scores were related to depression, fatigue, state anxiety and trait anxiety.¹⁵

“Gluten encephalopathy with psychiatric onset: case report.” A 38-year-old man was admitted as an inpatient for worsening anxiety symptoms and behavioural alterations. After the addition of second generation antipsychotic to the therapeutic regimen, the patient presented neuromotor impairment with high fever, sopor, leukocytosis, raised rhabdomyolysis-related indicators. Neuroleptic malignant syndrome was strongly suspected. After worsening of his neuropsychiatric conditions, with the onset of a frontal cognitive deficit, bradykinesia and difficulty walking, dysphagia, anorexia and hypoferraemic (low iron) anaemia, SPET revealed a reduction of cerebral perfusion and ENeG results were compatible with a mainly motor polyneuropathy. Extensive laboratory investigations gave positive results for anti-gliadin antibodies, and an appropriate diet led to a progressive remission of the encephalopathy.¹⁶

“Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet.” The aim of this study was to assess the biochemical and clinical effects of B vitamin supplementation in adults with longstanding celiac disease. In a double blind placebo controlled multicenter trial, 65 coeliac patients (61% women) aged 45-64 years on a strict gluten-free diet for several years were randomized to a daily dose of 0.8 mg folic acid, 0.5 mg vitamin B12 and 3 mg pyridoxine or placebo for 6 months. The outcome measures were psychological general well-being and the plasma total homocysteine level which is a marker of B vitamin status.

Results found normalized homocysteine, which dropped a median of 34%, accompanied by significant improvement in well-being, notably anxiety and depressed mood for patients with poor well-being. Conclusion: B vitamins should be considered in people advised to follow a gluten-free diet.¹⁷

“Psychoneurotic symptoms and alexithymia in celiac disease.” The aim of this study was to evaluate whether patients with coeliac disease suffer from psychoneurotic symptoms by means of applying the Crown-Crisp Experiential Index (CCEI) and its six subscales to measure neurotic psychopathology, and whether a gluten-free diet has an impact on the symptoms. Study found that somatic anxiety was higher in coeliac disease patients before the introduction of the gluten-free diet than after adhering to the diet.¹⁸

“Regional cerebral hypoperfusion in patients with celiac disease.” The aim of this study was to evaluate cerebral perfusion (blood flow) in untreated celiac disease patients with no neurologic or psychiatric disorder other than anxiety or depression. Study demonstrated evidence of significant regional cerebral blood flow alteration. Cerebral single photon emission CT examination showed 73% of untreated celiac disease patients had at least one hypoperfused (abnormally low blood flow to) brain region compared with only 7% of patients on a gluten free diet and none of controls.¹⁹

“Anxiety but not depression decreases in celiac patients after one year gluten-free diet: a longitudinal study.” The aim of this study was to evaluate the real nature of anxiety in newly diagnosed celiac disease patients (classic type) by means of the State and Trait Anxiety Inventory test demonstrated that anxiety is present in a predominantly reactive form rather than as a personality trait. This study found that after one year on gluten free diet, a significant decrease in the percentage of state anxiety was found while there were no significant changes in the percentage of trait anxiety.²⁰

CASE REPORT SUMMARIES

“Neuropsychiatric symptoms and celiac disease.” This case report describes the diagnosis of celiac disease in a patient suffering from chronic, treatment-resistant symptoms of depression and anxiety. The diagnosis of celiac disease and introduction of an elimination diet caused a significant improvement in mental state and everyday functioning in the presenting patient.

The reporting physicians state, “The presence of persistent anxiety and depressive symptoms, with a poor reaction to pharmacological treatment, indicates a need to identify somatic reasons for the underlying condition. It is important to remember that celiac disease can occur at any age, not only in childhood. The presence of this somatic cause of persistent depressive and anxiety symptoms should be considered in the diagnostic process in adults.²¹

Sources:

1. Potocki P, Hozyasz K. Psychiatric symptoms and celiac disease. Psychiatria Polska. Jul-Aug 2002; 36(4):567-78. [↩] [↩] [↩]
2. Hallert C, Svensson M, Tholstrup J, Hultberg B. Clinical trial: B vitamins improve health in patients with celiac disease living on a gluten-free diet. Aliment Pharmacol Ther. 2009 Apr 15; 29(8):811-6. doi: 10.1111/j.1365-2036.2009.03945.x. Epub 2008 Jan 20. [↩]
3. Zingone F, Siniscalchi M, Capone P, Tortora R, Andreozzi P, Capone E, Ciacci C. The quality of sleep in patients with coeliac disease. Aliment Pharmacol Ther. 2010 Oct;32(8):1031-6. doi: 10.1111/j.1365-2036.2010.04432.x. Epub 2010 Aug 16. [↩]
4. Barratt SM, Leeds JS, Sanders DS. Factors influencing the type, timing and severity of symptomatic responses to dietary gluten in patients with biopsy-proven coeliac disease. J Gastrointestin Liver Dis. 2013 Dec;22(4):391-6. [↩] [↩] [↩]
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6. Addolorato G, Capristo E, Ghittoni G, et al. Anxiety, but not depression, decreases in celiac patients after one year gluten-free diet: a longitudinal study. Scandinavian Journal of Gastroenterology. May 2001; 36(5):502-6. [↩]
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15. Zingone F, Siniscalchi M, Capone P, Tortora R, Andreozzi P, Capone E, Ciacci C. The quality of sleep in patients with coeliac disease. Aliment Pharmacol Ther. 2010 Oct;32(8):1031-6. doi: 10.1111/j.1365-2036.2010.04432.x. [↩]
16. Nicola Poloni, Simone Vender, Emilio Bolla, Paola Bortolaso, Chiara Costantini, and Camilla Callegari Gluten encephalopathy with psychiatric onset: case report. Clin Pract Epidemiol Ment Health. 2009; 5: 16. [↩]
17. Hallert C, Svensson M, Tholstrup J, Hultberg B. Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet. Aliment Pharmacol Ther. 2009 Apr 15; 29(8):811-6. doi: 10.1111/j.1365-2036.2009.03945.x. [↩]
18. Collin P, Kaukinen K, Mattila AK, Joukamaa M. Psychoneurotic symptoms and alexithymia in coeliac disease. Scand J Gastroenterol. 2008;43(11):1329-33. doi: 10.1080/00365520802240248. [↩]
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