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Fatigue and insomnia, potentially induced by inflammation, are distressing symptoms experienced by colorectal cancer (CRC) survivors. Emerging evidence suggests that besides the nutritional quality and quantity, also the timing, frequency and regularity of dietary intake (chrono-nutrition) could be important for alleviating these symptoms. We investigated longitudinal associations of circadian eating patterns with sleep quality, fatigue and inflammation in CRC survivors. In a prospective cohort of 459 stage I-III CRC survivors, four repeated measurements were performed between 6 weeks and 24 months post-treatment. Chrono-nutrition variables included meal energy contribution, frequency (a maximum of six meals could be reported each day), irregularity and time window (TW) of energetic intake, operationalised based on 7-d dietary records. Outcomes included sleep quality, fatigue and plasma concentrations of inflammatory markers. Longitudinal associations of chrono-nutrition variables with outcomes from 6 weeks until 24 months post-treatment were analysed by confounder-adjusted linear mixed models, including hybrid models to disentangle intra-individual changes from inter-individual differences over time. An hour longer TW of energetic intake between individuals was associated with less fatigue ( β : -6·1; 95 % CI (-8·8, -3·3)) and insomnia ( β : -4·8; 95 % CI (-7·4, -2·1)). A higher meal frequency of on average 0·6 meals/d between individuals was associated with less fatigue ( β : -3·7; 95 % CI (-6·6, -0·8)). An hour increase in TW of energetic intake within individuals was associated with less insomnia ( β : -3·0; 95 % CI (-5·2, -0·8)) and inflammation ( β : -0·1; 95 % CI (-0·1, 0·0)). Our results suggest that longer TWs of energetic intake and higher meal frequencies may be associated with less fatigue, insomnia and inflammation among CRC survivors. Future studies with larger contrasts in chrono-nutrition variables are needed to confirm these findings.

Unhealthy dietary habits can contribute to the development of colorectal cancer (CRC). Such habits may also be associated with post-treatment symptoms experienced by CRC survivors. Therefore, we aimed to assess longitudinal associations of post-treatment unhealthy dietary habits, i.e. intake of ultra-processed foods (UPF), red and processed meat, alcohol and sugar-sweetened drinks, with health-related quality of life (HRQoL), fatigue and chemotherapy-induced peripheral neuropathy (CIPN) in CRC survivors from 6 weeks up to 24 months post-treatment. In a prospective cohort among stage I-III CRC survivors ( n 396), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Dietary intake was measured by 7-d dietary records to quantify consumption of UPF, red and processed meat, alcohol and sugar-sweetened drinks. HRQoL, fatigue and CIPN were measured by validated questionnaires. We applied confounder-adjusted linear mixed models to analyse longitudinal associations from 6 weeks until 24 months post-treatment. We applied a post hoc time-lag analysis for alcohol to explore the directionality. Results showed that higher post-treatment intake of UPF and sugar-sweetened drinks was longitudinally associated with worsened HRQoL and more fatigue, while higher intake of UPF and processed meat was associated with increased CIPN symptoms. In contrast, post-treatment increases in alcohol intake were longitudinally associated with better HRQoL and less fatigue; however, time-lag analysis attenuated these associations. In conclusion, unhealthy dietary habits are longitudinally associated with lower HRQoL and more symptoms, except for alcohol. Results from time-lag analysis suggest no biological effect of alcohol; hence, the longitudinal association for alcohol should be interpreted with caution.

The World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) advise cancer survivors to follow their lifestyle recommendations for cancer prevention. Adhering to these recommendations may have beneficial effects on patient-reported outcomes after a cancer diagnosis, but evidence is scarce. We aimed to assess associations of the individual dietary WCRF/AICR recommendations regarding fruit and vegetables, fibre, fast foods, red and processed meat, sugar-sweetened drinks and alcohol consumption with patient-reported outcomes in colorectal cancer (CRC) survivors. Cross-sectional data of 150 stage I-III CRC survivors, 2-10 years post-diagnosis, were used. Dietary intake was measured by 7-d dietary records. Validated questionnaires were used to measure health-related quality of life (HRQoL), fatigue and neuropathy. Confounder-adjusted linear regression models were used to analyse associations of each WCRF/AICR dietary recommendation with patient-reported outcomes. Higher vegetable intake (per 50 g) was associated with better global QoL (β 2·6; 95 % CI 0·6, 4·7), better physical functioning (3·3; 1·2, 5·5) and lower levels of fatigue (-4·5; -7·6, -1·4). Higher fruit and vegetables intake (per 100 g) was associated with better physical functioning (3·2; 0·8, 5·5) and higher intake of energy-dense food (per 100 kJ/100 g) with worse physical functioning (-4·2; -7·1, -1·2). No associations of dietary recommendations with neuropathy were found. These findings suggest that adhering to specific dietary WCRF/AICR recommendations is associated with better HRQoL and less fatigue in CRC survivors. Although the recommendations regarding healthy dietary habits may be beneficial for the well-being of CRC survivors, longitudinal research is warranted to gain insight into the direction of associations.

B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5'-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r -0·33, Plinear < 0·0001), serum amyloid A (SAA) (r -0·23, Plinear = 0·003), IL-6 (r -0·39, Plinear < 0·0001), IL-8 (r -0·20, Plinear = 0·02) and TNFα (r -0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r -0·14), SAA (r -0·14) and TNFα (r -0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.

The lifestyle recommendations of the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) are primarily intended for cancer prevention. In the absence of specific recommendations for cancer survivors, we investigated adherence of colorectal cancer (CRC) survivors to the WCRF/AICR lifestyle recommendations and associations with health-related quality of life (HRQoL). The cross-sectional part of the Energy for life after ColoRectal cancer (EnCoRe) study was conducted in 155 CRC survivors (stage I-III), 2-10 years post diagnosis. Dietary intake, physical activity and general body fatness were measured by 7-d food diaries, by questionnaires and accelerometers and BMI, respectively. Adherence to each of the ten WCRF/AICR recommendations was scored as 0 (no/low adherence), 0·5 (moderate adherence) or 1 point (complete adherence), and summed into an overall adherence score (range: 0-10). HRQoL, disability and distress were assessed by validated questionnaires. Associations of the overall WCRF/AICR adherence score with HRQoL outcomes were analysed by confounder-adjusted linear regression. The mean adherence score was 5·1 (sd 1·4, range: 1·5-8·5). In confounder-adjusted models, a higher adherence score was significantly associated with the HRQoL dimension better physical functioning (β per 1 point difference in score: 2·6; 95 % CI 0·2, 5·1) and with less fatigue (β: -3·3; 95 % CI -6·4, -0·1). In conclusion, higher adherence of CRC survivors to WCRF/AICR lifestyle recommendations for cancer prevention was associated with better physical functioning and with less fatigue. This study adds to the limited knowledge on adherence to lifestyle behaviours in CRC survivors and relationships with quality of life. Prospective studies are needed to investigate longitudinal associations.