Complementary and Alternative Medical Lab Testing Part 5: Gastrointestinal
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About this ebook
Complementary and Alternative Medical Lab Testing (CAM Labs) contains summaries of the published research on lab tests, primarily from PubMed trials on humans. Each chapter (disease) begins with a brief summary of conventional lab tests, followed by additional lab tests, including diabetes, insulin resistance, metabolic syndrome, inflammation, etc. There are sections on endocrine hormones (thyroid, adrenal, sex steroids) and environmental medicine (toxic heavy metals). The nutritional assessments section includes minerals, vitamins and amino acids.
CAM Labs 5 – Gastrointestinal
1. Aphthous Stomatitis
2. Appendicitis
3. Celiac Disease
4. Crohns Disease
5. Diverticulosis and Diverticulitis
6. Esophagitis
7. Gastritis
8. Gastroenteritis
9. Gastroparesis
10. Gastroesophageal Reflux Disease (GERD)
11. Helicobacter pylori
12. Hypochlorhydria
13. Inflammatory Bowel Disease
14. Intestinal Permeability
15. Irritable Bowel Syndrome
16. Peptic Ulcer Disease
17. Ulcerative Colitis
Ronald Steriti
Dr. Ronald Steriti is a graduate of Southwest College of Naturopathic Medicine and currently is researcher for Jonathan V. Wright at the Tahoma Clinic.
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Complementary and Alternative Medical Lab Testing Part 5 - Ronald Steriti
Chapter 1. Aphthous Stomatitis
Aphthous stomatitis or recurrent aphthous ulcers (canker sores) are one of the most common oral mucosal lesions.
Conventional Lab Tests
CBC, ESR
Iron, ferritin, folate, and vitamin B6 and B12 (Compilato et al., 2010)
Tzanck smears, viral cultures, skin biopsy to exclude herpes simplex virus
Additional Lab Tests
Fasting Glucose, Hemoglobin A1C
A recent article published in Medical Hypotheses proposes that pre-diabetes may aggravate recurrent oral aphthous stomatitis. (Cakir, 2013)
Immunoglobulin E
Forty-nine patients with RAS responded to a questionnaire that included demographic background, stress status, smoking habits, history and course of RAS episodes. They were also subjected to relevant laboratory tests, including determination of serum IgE levels. A familial history of RAS was reported by 47.9% of the patients, stress in the previous year by 51.1% and smoking by 18.4%. Non-Caucasian origin, familial history of RAS, stress and smoking were associated with increased severity of RAS episodes. Haematological deficiencies were observed in 18.7% of RAS patients. Average IgE levels were increased and were significantly associated with younger age,
Digestive Assessments
Helicobacter pylori
Forty-six patients with minor aphthous lesions were enrolled. The number of RAS lesions at last 6 months and vitamin B(12) levels were recorded. All patients were detected for H. pylori with endoscopic biopsy. H. pylori was positive in 30 patients and negative in 16 patients. H. pylori-positive 30 patients received eradication therapy. Three months after therapy, patients were re-evaluated with urea breath test; 18 patients were negative (eradicated), and the remainders (12 patients) were positive (non-eradicated) for H. pylori. 6 months after eradication, vitamin B(12) levels and number of aphthous lesions at 6 months were recorded. Vitamin B(12) levels were significantly increased in H. pylori-eradicated group (P = 0.001), whereas no significant change was found in non-eradicated group (P = 0.638). Mean number of aphthous lesions (per 6 months) of H. pylori-eradicated group was significantly decreased after eradication (P = 0.0001); in the non-eradicated group, no significant change was found (P = 0.677). In Hp-positive group, number of RAS lesions and vitamin B(12) levels were negatively correlated when evaluated both before and after eradication. (Tas et al., 2013)
Seven case-control studies containing 339 cases and 271 controls were eventually selected for analysis. A total of 100 (29.50 %) RAS patients had H. pylori infection, which was significantly greater than the 54 (19.93 %) non-RAS controls with H. pylori infection (OR = 1.85, 95 % CI: 1.24-2.74, P = 0.002). This result persisted in a hospital-based control subgroup (OR = 2.72, 95 % CI: 1.57-4.72). Based on this meta-analysis, H. pylori infection is associated with an increased risk of RAS. (Li et al., 2014)
Forty-three patients with RAS and 44 non-RAS controls were evaluated. Sixteen individuals in the RAS patients (37.2%) and 14 individuals in the control group (31.8%) had a positive urea breath test. The difference was not considered statistically significant (p=0.597). (Maleki et al., 2009)
A total of 105 children and adolescents were investigated--53 patients with RAS (case group) and 52 patients without lesions (control group). Helicobacter pylori was present in six patients of the case group (11.3%) and in three of the control group (5.8%). When the site of infection was studied, 9.4% of the RAS lesions were PCR positives. In the case group and control group, 5.7 and 1.9% of the specimens from dental plaque, respectively, and 5.7 and 3.8% of the specimens from the intact oral mucosa, respectively, were PCR positives. There was no association between RAS lesions and infection of the oral cavity by H. pylori in children and adolescents (P = 0.254). (Fritscher et al., 2004)
Celiac Disease
A study consisted of 82 patients, all of whom had a history of recurrent aphthous stomatitis. The control group included 82 patients who did not have aphthous stomatitis. One patient (1.2%) out of 82 in the study group was diagnosed with celiac disease by biopsy. Gastroesophageal reflux disease symptoms, heartburn and regurgitation were determined to be of higher incidence in the study group (p<0.001 and p<0.001, respectively). None of the 82 patients in the control group were diagnosed as having celiac disease. (Yasar et al., 2012)
Two hundred and forty seven patients with RAS were included. The patients had at least three aphthous attacks per year. Patients were screened by IgA anti-endomysial antibody (EMA), IgA anti tissue transglutaminase (TTG) and serum IgA level. Those with a positive serology underwent endoscopic biopsies of the duodenal mucosa and patients with negative serology were excluded. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histology. For patients with GSE, gluten free diet was recommended. Six out of 247 RAS patients had positive TTG test alone, and one had positive EMA and TTG. All 7 patients with positive serologic tests underwent duodenal biopsies. Histological findings were compatible with GSE in all of them (Marsh I in four patients, Marsh II in two patients and Marsh IIIB in one another.). The mean age of GSE patients was 27.42 +/- 10.56 (range, 13 to 40) years old. They were suffering from RAS for an average duration of 4.5 years. All of the 7 GSE patients had not responded to the routine anti-aphthae medications, including topical corticosteroids, tetracycline and colchicine. Four patients who adhered to a strict gluten-free diet showed noticeable improvement in their aphthous lesions over a period of 6 months. A significant minority (e.g. 2.83%) of RAS patients have GSE. This could be compared with the 0.9% prevalence of GSE in the general population of Iran. (Shakeri et al., 2009)
A study evaluated the frequency of coeliac disease anti-endomysial (or anti-transglutaminase) antibodies in patients with recurrent aphthous stomatitis. Blood samples from 42 patients were evaluated and 2/42 (4.7%) were IgA- and IgG-endomysial antibody-positive. None of the 42 persons in the control group had antibodies, which was not statistically different from the patient group. The two antibody-positive patients had episodes of mild gastrointestinal symptoms only, but histopathology of duodenal mucous membranes confirmed coeliac disease. All symptoms related to aphthous stomatitis responded well to a gluten-free diet. We conclude that every patient with recurrent aphthous stomatitis should be asked about a history of gastrointestinal complaints and screened for markers of coeliac disease, since recurrent aphthous stomatitis may in some cases respond to a gluten-free diet. (Olszewska et al., 2006)
The study group consisted of patients having a history of recurrent aphthous stomatitis. The control group included patients not having aphthous stomatitis. Antibodies to gliadin IgG and IgA and antibodies to endomysium were determined from the serum samples of all patients. Biopsies were obtained from the distal part of the duodenum. Biopsies of two patients (4.8%) out of 41 belonging to the study group were diagnosed as celiac disease. In serum samples of both, antibodies to gliadin IgA and antibodies to endomysium were found to be positive. Antibodies to gliadin IgG antibody were positive in only one of these two patients. None of the 49 patients in the control group was diagnosed as celiac disease. (Aydemir et al., 2004)
Food Allergy or Sensitivity
Forty patients with recurrent aphthous ulceration (RAU) were investigated to ascertain the possibility of food sensitivity being a significant precipitating factor in their recurrent oral ulceration. All patients were hematologically normal and did not respond to vitamin B1 and B6 therapy. Patch testing (Standard European Series) was undertaken in 21 patients. Twenty patients showed a positive reaction to a number of substances which were considered clinically relevant. Professional advice on avoidance of the allergen was given, resulting in an improvement in eighteen patients. It is concluded that food sensitivity and allergies to other substances should be considered as an etiologic factor in hematologically normal patients with recurrent oral ulceration. (Nolan et al., 1991)
The leukocytes from sixty patients with recurrent aphthous stomatitis were tested for histamine release in response to environmental and food antigens. Eighteen patients (30 percent of the population studied) were atopic, and this history of respiratory allergy was confirmed by an in vitro histamine release assay. The nonatopic patients with recurrent aphthous stomatitis had a significantly higher incidence of in vitro histamine release to foods than did control subjects. The leukocytes from twenty-three patients (38 percent) released histamine to food antigens. Patients eliminated foodstuffs in a double-blind trial to correlate the in vitro histamine release to the development of oral ulcers. Only 30 percent of the patients had a decreased incidence of ulcers after eliminating foods which had induced in vitro histamine release. On rechallenge in the double-blind trial, 30 percent of the foods which caused histamine release also correlated to increased incidence of oral lesions. In eight patients ingestion of certain foodstuffs was correlated to oral ulceration by food diaries and elimination-rechallenge in an open-trial basis. However, dietary manipulation did not completely eliminate the ulceration in any of the patients. The results suggest that food sensitivity may play a minor role in the development of recurrent aphthous stomatitis. (Wray et al., 1982)
Twenty selected patients with recurrent aphthous stomatitis in whom celiac disease had been specifically excluded were placed on a gluten-free diet. Five patients (25%) showed a favorable response to gluten withdrawal and a positive gluten challenge. Jejunal morphology was normal in all patients indicating gluten sensitivity without enteropathy. Gluten withdrawal provides a further method of treating some patients with recurrent aphthous stomatitis. (Wray, 1981)
Comprehensive Adrenal Panel
Cortisol
A measurement of cortisol employing Enzyme-Linked Immuno Sorbent Assay (ELISA) was carried out in samples of unstimulated saliva from 20 patients with active lesions of RAS and 10 healthy individuals used as controls. Increased levels of salivary cortisol were detected in 3 cases, all of them within the group of patients with RAS. In none of the control group patients the level of salivary cortisol was increased. The mean level of salivary cortisol was 0.64 mg / dl (range 0.2 to 1.62) for patients with RAS and 0.57 mg / dl (range 0.25 to 1.09) for controls. Salivary cortisol levels are not statistically higher in patients with active lesions of RAS. (Eguia-del Valle et al., 2013)
The concentrations of salivary and serum cortisol were measured in 38 patients with recurrent aphthous stomatitis, and 38 healthy controls. Salivary and serum cortisol levels were measured using a Luminenscent Immunoassay (LIA) method. Anxiety levels were evaluated using Spielberger's State-Trait Anxiety Inventory which measures both trait anxiety as a general aspect of personality (STAI-T) and state anxiety as a response to a specific situation (STAI-S). The salivary cortisol levels were 1.44 (+/- 0.58) microg dl(-1) in RAS patients and 0.91 (+/- 0.56) microg dl(-1) in controls (p = 0.001), while the serum cortisol levels were 3.13 (+/- 1.59) microg dl(-1) in RAS patients and 1.89 (+/- 1.11) microg dl(-1) in controls (p = 0.001). The state anxiety levels (STAI-S) were 48.85 (+/- 9.7) in RAS group and 39.45 (+/- 7.5) in control group (p = 0.001). The trait anxiety levels (STAI-T) were 49.78 (+/- 13.02) in RAS group and 38.49 (+/- 10.31) in control group (p = 0.001). Salivary and serum cortisol concentrations and state and trait anxiety levels in RAS were significantly higher than those in the control group. The results suggest that stress may be involved in the pathogenesis of RAS. (Albanidou-Farmaki et al., 2008)
Anxiety and salivary cortisol were measured in two groups of patients with recurrent aphthous ulceration. One group of patients had persistent aphthae (Group 1) and the others had been relieved of their aphthae following correction of detected hematinic deficiency states (Group 2). Anxiety was measured using the Hospital Anxiety and Depression scale and radioimmunoassay of salivary cortisol. There was a statistically significant increased proportion of borderline or clinically anxious patients in Group 1 compared to Group 2 (P < 0.05). Median salivary cortisol levels also showed a statistically significant elevation in Group 1 (P < 0.01). It is concluded that stress may play a role in the etiology of recurrent aphthous stomatitis, particularly in patients who have an underlying anxiety trait. (McCartan et al., 1996)
Comprehensive Thyroid Panel
Ninety patients and 30 healthy volunteers were included into the study. In RAS patients, the fT3, TT3 levels were higher; whereas the fT4 levels were lower that the control group (P < 0.05). The anti-thyroid antibody was positive in 31.11% of the patients with RAS, and in only 10% of the individuals in the control group (P < 0.05). The mean anti-TG level was also higher in the RAS group. Ultrasonography revealed nodules in 28.8% of the patients with RAS and in 16.7% of the individuals in the control group (P < 0.05). The sT4 levels were lower and the TSH, anti-TPO and anti-TG levels were significantly higher in the RAS patients with thyroid nodules than the RAS patients without nodules (P < 0.05). These results may be related to either the advance age of the patients or the increased duration of the autoimmune activation that may affect the thyroid. The frequency of thyroid autoimmune-related problems was higher in patients with RAS. (Ozdemir et al., 2012)
Nutritional Assessments
Malondialdehyde (MDA, Oxidative Stress)
Twenty-two patients with RAS and 23 healthy controls were recruited. The study found decreased catalase and glutathione peroxidase activities and antioxidant potential levels in the erythrocytes, and decreased antioxidant potential and increased MDA plasma levels in patients with RAS in comparison with control subjects. (Cimen et al., 2003)
MDA and Vitamins A, E and C
Thirty patients with RAU and 20 healthy controls were recruited. Vitamins A, E, and C and malondialdehyde (MDA) levels were measured in both serum and saliva of patients with RAU and control subjects by high performance liquid chromatography. Levels of vitamins A, E and C in both fluids were significantly lower (p < 0.05 for vitamins A and E, and p < 0.005 for vitamin C, respectively) in patients with RAU than in healthy control subjects. Conversely, the levels of MDA in serum and saliva were significantly higher (p < 0.005) in patients with RAU than in the control group. Furthermore, strong and highly significant correlation was found between serum and salivary levels of vitamins A, E and C, and MDA in patients with RAU (r > or = 0.90, p < 0.0001). (Saral et al., 2005)
MDA and Vitamins E and Selenium
Patients with RAS (n = 26) and age- and sex-matched healthy control subjects (n = 20) were included in this study. Oxidative stress was confirmed by the significant elevation in plasma malondialdehyde levels and by the significant decrease in glutathione peroxidase activities, vitamin E and selenium levels (P < 0.001). (Arikan et al., 2009)
MDA and Copper / Zinc
Patients with RAS (n = 33) and age- and sex-matched healthy control subjects (n = 30) were enrolled in this study. Oxidative stress was confirmed by the significant elevation in plasma MDA, and by the significant decrease in CAT, SOD1, and GPx (p < 0.05). When compared to controls, Zn and Se levels were significantly lower in patients, whereas Cu levels was higher in RAS patients than those in controls (p < 0.05). In addition, the correlation results of this study were firstly shown that there were significant and positive correlations between Se-CAT, Se-GPx, and Cu-MDA parameters, but negative correlations between Se-Cu, Se-MDA, Cu-CAT, Cu-SOD1 and Cu-GPx parameters in RAS patients. Furthermore, the ratios of Cu/Zn and Cu/Se were significantly higher in the patients than the control subjects (p < 0.05). Our results indicated that lipid peroxidation associated with the imbalance of the trace elements seems to play a crucial role in the pathogenesis of RAS. Furthermore, the serum Cu/Zn and Cu/Se ratios may be used as biochemical markers in these patients. (Ozturk et al., 2013)