Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome.

BACKGROUND: Intestinal immune activation is involved in irritable bowel syndrome (IBS) pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation. Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation. AIM: To assess the effect on mast cell count and the efficacy of palmithoylethanolamide/polydatin in patients with IBS. METHODS: We conducted a pilot, 12-week, randomised, double-blind, placebo-controlled, multicentre study assessing the effect of palmithoylethanolamide/polydatin 200 mg/20 mg or placebo b.d. on low-grade immune activation, endocannabinoid system and symptoms in IBS patients. Biopsy samples, obtained at screening visit and at the end of the study, were analysed by immunohistochemistry, enzyme-linked immunoassay, liquid chromatography and Western blot. RESULTS: A total of 54 patients with IBS and 12 healthy controls were enrolled from five European centres. Compared with controls, IBS patients showed higher mucosal mast cell counts (3.2 ± 1.3 vs. 5.3 ± 2.7%, P = 0.013), reduced fatty acid amide oleoylethanolamide (12.7 ± 9.8 vs. 45.8 ± 55.6 pmol/mg, P = 0.002) and increased expression of cannabinoid receptor 2 (0.7 ± 0.1 vs. 1.0 ± 0.8, P = 0.012). The treatment did not significantly modify IBS biological profile, including mast cell count. Compared with placebo, palmithoylethanolamide/polydatin markedly improved abdominal pain severity (P < 0.05). CONCLUSIONS: The marked effect of the dietary supplement palmithoylethanolamide/polydatin on abdominal pain in patients with IBS suggests that this is a promising natural approach for pain management in this condition. Further studies are now required to elucidate the mechanism of action of palmithoylethanolamide/polydatin in IBS. ClinicalTrials.gov number, NCT01370720.

Poorer prognosis in older patients with endometrial adenocarcinoma.

It has been suggested that there are two types of endometrial carcinoma: the first arises in younger women who have hyperestrogenism and has a favorable prognosis and the second occurs in older women, is not associated to estrogen stimulation, and has a poorer prognosis. This study examined the hypothesis that more aggressive carcinomas are found in older patients with no evidence of estrogen stimulation. A retrospective review of all patients (N = 82) with endometrial carcinoma diagnosed and treated at our institution between 1978 and 1990 was undertaken. The following data were analyzed: age at diagnosis, stage, race, histologic type, grade, depth of myometrial invasion, absence or presence of associated hyperplasia, and survival. The mean age of the patients was 64.8 years. Sixty (73%) of the 82 patients were considered estrogen-positive either because of obesity (body mass index > or = 27.3) or the use of unopposed exogenous estrogen. There were no statistically significant differences between estrogen-positive and estrogen-negative patients. Patients > or = 65 years had a 5-year survival of 60% compared with 74% for younger patients. There was a trend toward higher histologic grade among the older patients. Otherwise no statistically significant differences were found between these two groups. Estrogen-negative women > or = 65 years had the worst prognosis with a 5-year survival of 29%. As identified by other investigators, age at diagnosis is a significant indicator of prognosis in patients with endometrial carcinoma. In this series, thin, older (> or = 65 years) women who developed endometrial carcinoma had the worst prognosis.