Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans. Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations. Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (OR_{quartile 4 vs quartile 1}= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk. This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.

Gut microbial-derived short-chain fatty acids (SCFAs) may regulate energy homeostasis and exert anti-carcinogenic, immunomodulatory and anti-inflammatory effects. Smaller trials indicate that dietary weight loss may lead to decreased SCFA production, but findings have been inconclusive. SCFA concentrations were measured by HPLC-MS/MS in plasma samples of 150 overweight or obese adults in a trial initially designed to evaluate the metabolic effects of intermittent (ICR) versus continuous (CCR) calorie restriction (NCT02449148). For the present post hoc analyses, participants were classified by quartiles of weight loss, irrespective of the dietary intervention. Linear mixed models were used to analyze weight-loss-induced changes in SCFA concentrations after 12, 24 and 50 weeks. There were no differential changes in SCFA levels across the initial study arms (ICR versus CCR versus control) after 12 weeks, but acetate concentrations significantly decreased with overall weight loss (mean log-relative change of −0.7 ± 1.8 in the lowest quartile versus. −7.6 ± 2 in the highest, p = 0.026). Concentrations of propionate, butyrate and other SCFAs did not change throughout the study. Our results show that weight-loss, achieved through calorie restriction, may lead to smaller initial decreases in plasma acetate, while plasma SCFAs generally remain remarkably stable over time.

Non-alcoholic fatty liver disease (NAFLD) can lead to functional liver impairment and severe comorbidities. Beyond energy balance, several dietary factors may increase NAFLD risk, but human studies are lacking. The aim of this cross-sectional study was to investigate the associations between food consumption (47 food groups, derived Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diet quality scores) and liver fat content (continuous scale and NAFLD, i.e., >5% liver fat content). Liver fat content was measured by magnetic resonance imaging (MRI) in 136 individuals (BMI: 25–40 kg/m², age: 35–65, 50.7% women) and food intake was recorded by food frequency questionnaires (FFQs). Associations between food items and liver fat were evaluated by multi-variable regression models. Intakes of cake and cookies as well legumes were inversely associated with liver fat content, while positive associations with intakes of high-fat dairy and cheese were observed. Only cake and cookie intake also showed an inverse association with NAFLD. This inverse association was unexpected, but not affected by adjustment for reporting bias. Both diet quality scores were inversely associated with liver fat content and NAFLD. Thus, as smaller previous intervention studies, our results suggest that higher diet quality is related to lower liver fat, but larger trials with iso-caloric interventions are needed to corroborate these findings.

Although intermittent calorie restriction (ICR) has become popular as an alternative weight loss strategy to continuous calorie restriction (CCR), there is insufficient evidence on diet quality during ICR and on its feasibility over longer time periods. Thus, we compared dietary composition and adherence between ICR and CCR in a follow-up analysis of a randomized trial. A total of 98 participants with overweight or obesity [BMI (kg/m²) 25–39.9, 35–65 years, 49% females] were randomly assigned to ICR, operationalized as a “5:2 diet” (energy intake: ~100% on five non-restricted (NR) days, ~25% on two restricted (R) days), or CCR (daily energy intake: ~80%). The trial included a 12-week (wk) intervention phase, and follow-up assessments at wk24, wk50 and wk102. Apart from a higher proportion of energy intake from protein with ICR vs. CCR during the intervention (wk2: p < 0.001; wk12: p = 0.002), there were no significant differences with respect to changes in dietary composition over time between the groups, while overall adherence to the interventions appeared to be good. No significant difference between ICR and CCR regarding weight change at wk102 was observed (p = 0.63). However, self-reported adherence was worse for ICR than CCR, with 71.1% vs. 32.5% of the participants reporting not to or only rarely have followed the regimen to which they were assigned between wk50 and wk102. These results indicate that within a weight management setting, ICR and CCR were equivalent in achieving modest weight loss over two years while affecting dietary composition in a comparable manner.

Background: Bone marrow fat is implicated in metabolism, bone health and haematological diseases. Thus, this study aims to analyse the impact of moderate weight loss on bone marrow fat content (BMFC) in obese, healthy individuals. Methods: Data of the HELENA-Trial (Healthy nutrition and energy restriction as cancer prevention strategies: a randomized controlled intervention trial), a randomized controlled trial (RCT) among 137 non-smoking, overweight or obese participants, were analysed to quantify the Magnetic Resonance Imaging (MRI)-derived BMFC at baseline, after a 12-week dietary intervention phase, and after a 50-week follow-up. The study cohort was classified into quartiles based on changes in body weight between baseline and week 12. Changes in BMFC in respect of weight loss were analysed by linear mixed models. Spearman’s coefficients were used to assess correlations between anthropometric parameters, blood biochemical markers, blood cells and BMFC. Results: Relative changes in BMFC from baseline to week 12 were 0.0 ± 0.2%, −3.2 ± 0.1%, −6.1 ± 0.2% and −11.5 ± 0.6% for Q1 to Q4. Across all four quartiles and for the two-group comparison, Q1 versus Q4, there was a significant difference (p < 0.05) for changes in BMFC. BMFC was not associated with blood cell counts and showed only weaker correlations (<0.3) with metabolic biomarkers. Conclusion: Weight loss is associated with a decrease of BMFC. However, BMFC showed no stronger associations with inflammatory and metabolic biomarkers.

Background: Preliminary evidence suggests that weight loss among obese has differential metabolic effects depending on the presence of non-alcoholic fatty liver disease (NAFLD). We assessed whether NAFLD predisposes to differential changes in liver fat content, liver function, and metabolic parameters upon diet-induced weight loss in a 50-week intervention trial. Methods: 143 overweight and obese non-smokers underwent a 12-week dietary intervention and a 38-week follow-up. Diet-induced changes in anthropometric measures, circulating biomarkers, and magnetic resonance (MR)-derived liver fat content and adipose tissue volumes were evaluated by mixed linear models stratifying by NAFLD at baseline. Results: The prevalence of NAFLD at baseline was 52%. Diet-induced weight loss after 12 (NAFLD: 4.8 ± 0.5%, No NAFLD: 5.1 ± 0.5%) and 50 weeks (NAFLD: 3.5 ± 0.7%, No NAFLD: 3.5 ± 0.9%) was similar in both groups, while the decrease in liver fat was significantly greater in the NAFLD group (week 12: 32.9 ± 9.5% vs. 6.3 ± 4.0%; week 50: 23.3 ± 4.4% vs. 5.0 ± 4.2%). Decreases in biomarkers of liver dysfunction (GGT, ALT, AST) and HOMA IR were also significantly greater in the NAFLD group. Other metabolic parameters showed no significant differences. Conclusion: Our data suggest that individuals with NAFLD show greater improvements of liver function and insulin sensitivity after moderate diet-induced weight loss than individuals without NAFLD.