שנת סיום: 2022
כותרת עבודת הדוקטורט: The association of meat consumption and pro-inflammatory nutrients with colonic-neoplasia and metabolic, hepatic outcomes
מנחים: פרופ' שירה זלבר-שגיא ופרופ' רויטל קריב
Abstract
Background: In recent years, the association of meat consumption with colonic polyps and non-alcoholic fatty liver disease (NAFLD) has been investigated. Inappropriate meat preparation can produce unfavorable compounds such as heterocyclic amines (HCAs) and advanced glycation end products (AGEs). The variety and number of HCAs and AGEs depend, among other things, on meat type, cooking method, cooking time, and temperature. However, the prospective association of meat type, cooking method, and harmful compounds formed within the meat, with primary and advanced neoplastic and metabolic outcomes has not yet been studied.
Aim: To evaluate a comprehensive dietary profile focusing on meat type and cooking methods with various parameters such as AGEs and HCAs and colonic polyps and NAFLD.
Methods: Both cross-sectional and prospective studies included male and female participants, living in the center of Israel, who volunteered to participate in two metabolic surveys at the Tel-Aviv Medical Center (convenience sampling), at least five years apart. The dependent variables, colonic polyps and NAFLD, were measured by colonoscopy or liver ultrasonography examination, respectively. Polyp histology was reviewed by a gastro-intestinal pathologist and classified as an adenoma (advanced or non-advanced) or serrated polyp. Independent variables, meat type, and cooking method were measured using a self-report food frequency questionnaire (FFQ). High meat consumption was considered above the sample median. Dietary AGEs and HCAs were calculated based on specific databases. Serum sRAGE levels, as an indirect marker for AGEs, were measured. The interview included demographic characteristics, medical history, medications being taken, and a detailed questionnaire on physical activity and food intake habits, all are variables which may act as confounders or modifiers.
Cross-sectional study results: A total of 789 subjects were included (mean age 58.83±6.58 years, 52.60% men). Of those, 403 cases had polyps (328 adenomas, 166 advanced adenomas) and 386 were controls. High red and/or processed meat consumption was associated with all polyps and adenomas among heavy smokers (OR = 2.00, 1.03-3.89, P= 0.041; OR = 2.08, 1.01–4.27, P= 0.046, respectively). High intake of unprocessed red meat was associated with all polyps or adenomas among never smokers (OR = 1.77, 1.09–2.87, P= 0.021; OR = 1.76, 1.07–2.89, P= 0.026, respectively). There was no association between HCAs, AGEs, and colonic polyps.
In addition, 305 subjects (38.70%) were diagnosed with NAFLD. High consumption of total meat (OR=1.49, 1.05–2.13, P=0.028) red and/or processed meat (OR=1.47, 1.04–2.09, P=0.031) was independently associated with higher odds for NAFLD. High intake of meat cooked using unhealthy methods (OR=1.92, 1.12–3.30, P=0.018) and HCAs (OR=2.22, 1.28–3.86, P=0.005) were independently associated with higher odds for insulin resistance (IR). There was no significant association between HCAs and NAFLD.
A total of 743 subjects had sRAGE levels measurements. Low sRAGE levels (under the first sample tertile) were independently associated with NAFLD with elevated alanine aminotransferase (ALT) (OR= 2.17, 1.23–3.83, P= 0.007). High dietary AGE consumption was associated with IR (OR=2.04, 1.25–3.34 P= 0.004). There was no significant cross-sectional association between sRAGE levels and colonic polyps.
Prospective study results: A total of 316 subjects had completed two surveys and had a valid FFQ, mean a follow-up of 6.79±0.67 years (mean age 65.46±6.51 years, 56.60% male). Of those, 229 subjects had colonoscopy results: 95 cases with colorectal polyps (53 adenomas, 19 advanced adenomas), and 134 controls. In multivariate-adjusted analyses, high consumption of total meat (gr/d above the baseline gender-specific median) was associated with higher odds for persistent adenomas (OR=3.52, 1.13–10.97, P=0.030) and with new-onset or persistent advanced adenoma (OR=6.25, 1.57–24.86, P=0.009). High consumption of dietary AGEs at baseline was associated with higher odds for new-onset or persistent advanced adenoma (OR=5.53, 1.36–22.42, P=0.017). There was no prospective association between HCAs and colonic polyps.
New-onset or persistent NAFLD was found in 34.50% (n = 109/316) of subjects. From those 36 new cases of NAFLD. In multivariate-adjusted analyses, high consumption of red and/or processed meat (gr/d above the baseline gender-specific median) was associated with higher odds for NAFLD with elevated ALT incidence (OR=3.75, 1.21–11.62, P=0.022). Regarding meat consumption trajectories, 10% daily increments in total meat consumption were significantly associated with higher odds for new or persistent NAFLD and NAFLD incidence (OR=2.03, 1.17–3.65, P=0.012; OR=2.40, 1.01–5.75, P=0.049, respectively), and lower odds for NAFLD remission (OR=0.34, 0.14–0.82, P=0.017, respectively). In addition, increased consumption of dietary AGEs above 60% during the follow-up was associated with 1.9-fold higher odds for new-onset or persistent NAFLD (95%CI 1.01–3.62, P=0.047). There was no significant association between HCAs and NAFLD.
A total of 297 subjects had sRAGE level measurements. There was an inverse dose-response association between baseline sRAGE levels and odds for new-onset or persistence NAFLD. There was no prospective association between sRAGE levels and colonic polyps.
Importance of the study and implications for clinical practice: This study is one of the first to prospectively test the potential associations between meat type and its cooking methods with colonic polyps and liver damage. This study may further clarify the relations between nutrition, neoplasia, and metabolic processes and build practical personalized nutritional recommendations for preventing and treating highly prevalent neoplastic and metabolic alterations in the gastrointestinal tract that are a significant public health burden.