Subjective food hypersensitivity: Studies on enterochromaffin cell secretion products and effects of seal oil therapy

Background: Perceived food hypersensitivity is a prevalent condition which often remains medically unexplained. The etiology of this subjective condition is not fully understood, mainly because of a lack of specific diagnostic methods, together with limited knowledge about underlying pathogenetic mechanisms. Thus, the management of such patients is challenging. Aim: The objective of the present thesis was to assess the potential beneficial effects of seal oil on symptoms, and to develop a novel sample protocol to investigate the putative role of enteroendocrine secretorial compounds in patients with subjective food hypersensitivity. Results: In study I, a single dose of duodenal administered seal oil significantly influenced neither gastric accommodation, as examined by two dimensional (2D) ultrasonographic scanning, nor meal-induced gastrointestinal symptoms, as assessed by visual analogue scales (VAS). After 10 days’ treatment, duodenal administered seal oil, as compared to soy oil, significantly reduced meal-induced gastrointestinal symptoms. However, the symptomatic improvement was not associated with improvements in gastric accommodation. In study II, patients with subjective food hypersensitivity received a 10-day open treatment with duodenal administered seal oil. Before and after treatment, and 1 month post-treatment, the patients filled in the Subjective Health Complaints (SHC) Inventory for nongastrointestinal symptoms, the short form of the Nepean Dyspepsia Index (SF-NDI) for evaluation of quality of life (QoL), and the Ulcer Esophagitis Subjective Symptoms Scale (UESS) score and the Gastrointestinal Symptom Rating Scale (GSRS) for assessment of gastrointestinal symptoms. Both intestinal and extra-intestinal complaints were significantly improved from baseline, both at 10 and 30 days post-treatment. In study III, a novel method for direct determination of serotonin (5-HT) in gut lavage fluid using liquid chromatography mass spectrometry was achieved. This method was applied in study IV. In study IV, analyses of chromogranin A (CgA) in serum and 5-HT in gut lavage fluid were performed. Serum levels of CgA were significantly lower in patients with subjective food hypersensitivity as compared to healthy controls. No significant differences in gut lavage 5- HT levels were detected between patients with subjective food hypersensitivity, patients with inflammatory bowel disease (IBD) and healthy controls. Conclusion: The present thesis suggests a beneficial effect of duodenal administered seal oil on both intestinal and extra-intestinal complaints in patients with subjective food hypersensitivity. Impaired gastric accommodation seems to play a limited role in the pathophysiology, as the positive effect of seal oil was not associated with improvements in gastric accommodation. The mechanism of action may involve the anti-inflammatory and immune-modulating properties of the long-chain omega-3 polyunsaturated fatty acids (PUFAs), and further studies addressing this aspect are needed. Decreased systemic CgA levels suggest a role for enteroendocrine alterations in the pathophysiology of subjective food hypersensitivity, such as impaired enterochromaffin (EC) cell function, and the potential of using granins as biomarkers for functional gastrointestinal disorders should be explored in future studies. Taken together, the hypothesis-generating studies of the present thesis encourage further investigations to elucidate causal relationships between the patients’ unexplained symptoms and possible pathophysiological mechanisms

Duodenal administered seal oil for patients with subjective food hypersensitivity: an explorative open pilot study

Short-term duodenal administration of n-3 polyunsaturated fatty acid (PUFA)-rich seal oil may improve gastrointestinal complaints in patients with subjective food hypersensitivity, as well as joint pain in patients with inflammatory bowel disease (IBD). The aim of the present explorative pilot study was to investigate whether 10-day open treatment with seal oil, 10 mL self-administrated via a nasoduodenal tube 3 times daily, could also benefit nongastrointestinal complaints and quality of life (QoL) in patients with subjective food hypersensitivity. Twenty-six patients with subjective food hypersensitivity, of whom 25 had irritable bowel syndrome (IBS), were included in the present study. Before and after treatment and 1 month posttreatment, patients filled in the Ulcer Esophagitis Subjective Symptoms Scale (UESS) and the Gastrointestinal Symptom Rating Scale (GSRS) for gastrointestinal symptoms and subjective health complaints (SHC) inventory for nongastrointestinal symptoms in addition to short form of the Nepean dyspepsia index (SF-NDI) for evaluation of QoL. Compared with baseline, gastrointestinal, as well as nongastrointestinal, complaints and QoL improved significantly, both at end of treatment and 1 month posttreatment. The consistent improvements following seal oil administration warrant further placebo-controlled trials for confirmation of effect

Subjective food hypersensitivity: assessment of enterochromaffin cell markers in blood and gut lavage fluid

Background: Food hypersensitivity is commonly suspected, but seldom verified. Patients with subjective food hypersensitivity suffer from both intestinal and extraintestinal health complaints. Abnormalities of the enterochromaffin cells may play a role in the pathogenesis. The aim of this study was to investigate enterochromaffin cell function in patients with subjective food hypersensitivity by measuring serum chromogranin A (CgA) and 5-hydroxytryptamine (5-HT, serotonin) in gut lavage fluid. Methods: Sixty-nine patients with subjective food hypersensitivity were examined. Twenty-three patients with inflammatory bowel disease and 35 healthy volunteers were included as comparison groups. CgA was measured in serum by enzyme-linked immunosorbent assay. Gut lavage fluid was obtained by administering 2 L of polyethylene glycol solution intraduodenally. The first clear fluid passed per rectum was collected and 5-HT was analyzed by liquid chromatography tandem mass spectrometry. Results: Serum levels of CgA were significantly lower in patients with subjective food hypersensitivity than in healthy controls (P 0.04). No differences were found in 5-HT levels in gut lavage fluid between patients with subjective food hypersensitivity and the control groups. There was no correlation between serum CgA and gut lavage 5-HT. Conclusion: Decreased blood levels of CgA suggest neuroendocrine alterations in patients with subjective food hypersensitivity. However, 5-HT levels in gut lavage fluid were normal

Effects of Seal Oil on Meal-Induced Symptoms and Gastric Accommodation in Patients with Subjective Food Hypersensitivity: A Pilot Study

Background: Food hypersensitivity is a prevalent condition with poorly characterized underlying mechanisms. In the present pilot study we investigated effects of seal oil and soy oil on meal-induced symptoms and gastric accommodation in patients with subjective food hypersensitivity (FH). Single dose experiment: On three consecutive days, 10 mL of seal oil, soy oil, or saline were randomly administered into the duodenum of 10 patients with subjective FH and 10 healthy volunteers through a nasoduodenal feeding tube 10–20 minutes before the ingestion of a test meal. Short-term treatment study: 24 patients with subjective FH were randomly allocated to 10 days’ treatment with either 10 mL of seal or soy oil, self-administrated through an indwelling nasoduodenal feeding tube, 3 times daily. In both experiments meal-induced abdominal symptoms and gastric accommodation were measured by visual analogue scales and external ultrasound respectively. Results: Symptoms and gastric accommodation were not significantly influenced by single doses of seal or soy oil. When given daily for 10 days, seal oil, but not soy oil, reduced total symptom scores significantly (P = 0.03). The symptomatic improvement was not associated with improvements in gastric accommodation. Conclusion: Daily administration of seal oil may benefit patients with subjective FH. The beneficial effect of seal oil in patients with subjective FH can not be ascribed to improved gastric accommodation