Helen Chen

Introduction.  Mediterranean diet meets the suggested dietary guidelines for Americans to increase overall health outcomes, and adherence to this diet has been associated with a decrease in 10% risk in overall cancer mortality.^1,2 However, the specific mechanisms for how this diet causes a decrease in inflammation and cancer mortality have not been explored. Understanding these mechanisms could provide insight into novel therapeutic treatments. Methods. Mice were separated into four cohorts and placed on different diets (low-fat diet, low-fat diet mixed with Mediterranean diet or LF-MD-MIX, high-fat diet, and high-fat diet mixed with Mediterranean diet or HFWD-MD-MIX) to observe the effects of how diet effected colorectal lesion incidences and inflammation upon administration of the procarcinogen Azoxymethane.³ Gene expression markers, tumor incidences, and gut microbiota were measured from these mice and statistical analysis was done using one-way two-tailed ANOVA followed by multiple comparison post-hoc test.³  Another study used extra virgin olive oil (EVOO) on tumor-derived human colon cancer cell line (Caco-2) in vitro to test for changes in DNA methylation of the CpG islands in CNR1 promotor region.⁴ Follow up studies measured Mediterranean diet score and folate intake using a food frequency questionnaire and pyro sequence analysis to measure LINE-1 methylation levels.⁵ Results. In the cohort with 4 types of mice, the number of colonic lesions and inflammation developed in both the LF-MD-MIX and HFWD-MD-MIX were decreased but through two different mechanisms.³ The LF-MD-MIX cohort had upregulated the Bax/Bcl2 ratio suggesting that they had an increased ability to induce apoptosis of transformed cells.³ The HFWD-MD-MIX cohort had a microbiota profile most similar to normal healthy HFWD mice suggesting that they were able to counteract the carcinogen induced microbiome unbalances.³ EVOO caused Caco-2 cell line to upregulate CNR1 gene expression causing an increase in CB₁ levels that have an antiproliferative effect.⁴ Hypomethylation of LINE-1 is associated with increase genomic instability, especially increased risk of bladder or cancer and people with a dietary pattern of folate deficiency or low fruit consumption had increased levels of LINE-1 hypomethylation.⁵ Conclusions. Mediterranean diet is recognized as having the ability to prevent diseases due to its high macronutrient intake. Potential therapies include adopting the Mediterranean diet to decrease inflammation and gut microbiota dysregulation, or supplementing with EVOO to upregulate tumor suppressor genes.^3,4

1. Romagnolo, D. F., & Selmin, O. (2017). Mediterranean Diet and Prevention of Chronic Diseases. Nutrition Today,52(5). doi:10.1097/nt.0000000000000241
2. Schwingshackl, L., & Hoffmann, G. (2015). Adherence to Mediterranean diet and risk of cancer: An updated systematic review and meta-analysis of observational studies. Cancer Medicine,4(12), 1933-1947. doi:10.1002/cam4.539
3. Piazzi G, Prossomariti A, Baldassarre M, et al. A Mediterranean Diet Mix Has Chemopreventive Effects in a Murine Model of Colorectal Cancer Modulating Apoptosis and the Gut Microbiota. Front Oncol. 2019 Mar 12;(9):140. Doi: 10.3389/fonc.2019.00140.
4. Di Francesco A, Falconi A, Di Germanio C, et al. Extravirgin olive oil up-regulates CB₁ tumor suppressor gene in human colon cancer cells and in rat colon via epigenetic mechanisms. J Nutr Biochem. 2015 Mar;26(3):250-8. Doi: 10.1016/j.jnutbio.2014.10.013.
5. Agodi A, Barchitta M, Quattrocchi A, et al. Low fruit consumption and folate deficiency are associated with LINE-1 hypomethylation in women of a cancer-free population. Genes Nutr. 2015. Doi: 10.1007/s12263-015-0480-4