Pomegranate Extract Supplementation in Colorectal Cancer Patients (POMEcolon)

Phase I-II Study of Pomegranate Extract Formulations in Colorectal Cancer Patients: Metabolic and Gene Expression Profiling in Tumoral and Normal Colon Tissues

The most relevant pomegranate phenolics (ellagitannins and ellagic acid) are extensively metabolized by the human gut microbiota to yield a number of metabolites called urolithins (mainly Uro-A). Urolithins have been reported to regulate in vivo the expression of genes involved in inflammation and cancer. Our hypothesis is that urolithins can be detected in the human colon mucosa where these metabolites can exert anti-inflammatory and anti-cancer activities. After colonoscopy and diagnosis, colorectal cancer patients will consume capsules containing three different pomegranate extract formulations until surgery. The aims of this trial are: To evaluate the disposition of pomegranate phenolics and urolithins in tumoral and normal colon tissues. To evaluate gene expression profiling and protein markers in tumoral and normal colon tissues from these patients. To compare different pomegranate extract formulations on the above.

Pomegranate, Urolithins, Colorectal cancer, Colon cancer, Metabolite, Gene expression, microRNA, Nutraceutical, Food supplement, Polyphenol, Gut microbiota

Occurrence of phenolics and gut-microbiota derived metabolites in tumoral and colon tissues, urine and plasma.

Change in markers involved in hepatic and renal functions: GGT, AST, ALP, ALT, CPK, urate, creatinin, albumin, bilirubin, LDH. Change in hematological variables: leucocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin, hematocrit, mean corpuscular volume, mean platelet volume, platelets, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration. Intolerance, dyspepsia, allergic reactions, constipation, diarrhea, abdominal pain, nausea.

Inclusion Criteria: Colorectal cancer diagnosis. Surgery required. WHO status: between 0 and 2. Hemoglobin >10 g/dL ALT >2.5-fold above the normal value. Serum Bilirubin >1.5-fold above the normal value. Creatinine <140 micromol/L Exclusion Criteria: Patients who do not satisfy inclusion criteria and, Active pectic ulcer. Pregnancy or breastfeeding. Alcoholism. Chemotherapy or radiotherapy a month prior to recruitment. Treatment with steroids or other anti-inflammatory drugs a week prior to recruitment.

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Nunez-Sanchez MA, Gonzalez-Sarrias A, Garcia-Villalba R, Monedero-Saiz T, Garcia-Talavera NV, Gomez-Sanchez MB, Sanchez-Alvarez C, Garcia-Albert AM, Rodriguez-Gil FJ, Ruiz-Marin M, Pastor-Quirante FA, Martinez-Diaz F, Tomas-Barberan FA, Espin JC, Garcia-Conesa MT. Gene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial. J Nutr Biochem. 2017 Apr;42:126-133. doi: 10.1016/j.jnutbio.2017.01.014. Epub 2017 Jan 27.