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



To assess the effect on mast cell count and the efficacy of palmithoylethanolamide/polydatin in patients with IBS.



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.



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).



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.
Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy.
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0000-0002-7777-2936
C
Cremon
Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy.
V
V
Stanghellini
Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy.
M R
MR
Barbaro
Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy.
R F
RF
Cogliandro
Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy.
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L
Bellacosa
Digestive System Research Unit, Departments of Gastroenterology, Institut de Recerca Vall d'Hebron Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona (Departamento de Medicina) Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
J
J
Santos
Digestive System Research Unit, Departments of Gastroenterology, Institut de Recerca Vall d'Hebron Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona (Departamento de Medicina) Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
M
M
Vicario
Digestive System Research Unit, Departments of Gastroenterology, Institut de Recerca Vall d'Hebron Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona (Departamento de Medicina) Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
M
M
Pigrau
Digestive System Research Unit, Departments of Gastroenterology, Institut de Recerca Vall d'Hebron Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona (Departamento de Medicina) Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
C
C
Alonso Cotoner
Digestive System Research Unit, Departments of Gastroenterology, Institut de Recerca Vall d'Hebron Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona (Departamento de Medicina) Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
B
B
Lobo
Digestive System Research Unit, Departments of Gastroenterology, Institut de Recerca Vall d'Hebron Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona (Departamento de Medicina) Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
F
0000-0002-7327-960X
F
Azpiroz
Institut des Maladies de l'Appareil Digestif, Hotel Dieu, Nantes, France.
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S
Bruley des Varannes
Institut des Maladies de l'Appareil Digestif, Hotel Dieu, Nantes, France.
M
M
Neunlist
Department of Pharmacy, University of Naples "Federico II", Naples, Italy.
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D
DeFilippis
Department of Pharmacy, University of Naples "Federico II", Naples, Italy.
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T
Iuvone
Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.|Epitech Group SpA, Saccolongo, Italy.
S
S
Petrosino
Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.
V
V
Di Marzo
Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy.
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G
Barbara
D015746:Abdominal Pain / Q000178:diet therapy* / Q000276:immunology; D000328:Adult; D000577:Amides; D000700:Analgesics / Q000627:therapeutic use*; D002452:Cell Count; D019587:Dietary Supplements; D004311:Double-Blind Method; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000178:diet therapy* / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology; D008875:Middle Aged; D010169:Palmitic Acids / Q000627:therapeutic use*; D013267:Stilbenes / Q000627:therapeutic use*; D055815:Young Adult
D000577:Amides; D000700:Analgesics; D004983:Ethanolamines; D005960:Glucosides; D010169:Palmitic Acids; D013267:Stilbenes; C005958:palmidrol; C058229:polydatin