Different Sources of Fiber Intake and Risk of 17 Specific Cancers and All Cancers Combined: Prospective Study of 364,856 Participants in the UK Biobank.

Inverse associations between dietary fiber (DF) and colorectal cancer risk are well-established. However, evidence is limited in relation to other cancer sites. This study, of 364,856 participants from the UK Biobank, aimed to evaluate the associations between total and source-specific partial DF and risk of 17 specific cancers and all cancers combined. Partial DF was derived from baseline touchscreen questionnaire data on cereal, bread, fruit, and vegetable intake. The outcomes were incident cancer at 17 sites and all cancers combined. Cox proportional hazards models were applied. Over a median 8.8-year follow-up period, 30,725 people were diagnosed with cancer. After adjusting for sociodemographic and lifestyle factors, those in the highest quintile of partial DF compared with the lowest quintile (<9.6 vs ≥19.1 g/day) had 10% lower risk of cancer overall, with the greatest risk reductions observed for cervical (hazard ratio (HR) = 0.33, 95% confidence interval (CI): 0.14; 0.82), esophageal (HR = 0.66, 95% CI: 0.52; 0.84), lung (HR = 0.67, 95% CI: 0.59; 0.76), bladder (HR = 0.72, 95% CI: 0.56; 0.91), and kidney (HR = 0.75, 95% CI: 0.61; 0.92) cancers. Associations between DF and lung cancer were observed only in current and former smokers. Higher DF intake, in particular cereal fiber and fruit and vegetable fiber, was associated with a lower risk of overall and multiple site-specific cancers.

Still too little evidence: the role of diet in colorectal cancer survivorship - a systematic review.

Colorectal cancer incidence (CRC) is influenced by dietary factors, yet the impact of diet on CRC-specific mortality and recurrence-free survival (RFS) remains unclear. This review provides a narrative summary of existing research on dietary factors affecting CRC-specific mortality, RFS, and disease-free survival (DFS). This study searched electronic databases to identify cross-sectional/prospective research investigating dietary intake on CRC-specific mortality, RFS, or DFS. Twenty-eight studies were included in the corpus. Because of high study heterogeneity, we performed a narrative synthesis of studies. Limited, but suggestive evidence indicates beneficial effects of adhering to the American Cancer Society (ACS) guidelines and a plant rich low-carbohydrate diet on risk of CRC-specific mortality, potentially driven by fiber from cereals, vegetables, and wholegrains, but not fruit. For RFS and DFS, a Western dietary pattern, high intake of refined grains, and sugar sweetened beverages correlated with increased risk of CRC recurrence and development of disease/death. Conversely, greater adherence to the ACS dietary and alcohol guidelines, higher ω-3 polyunsaturated fatty acids, and dark fish consumption reduced risk. Our findings underscore the need for (i) standardized investigations into diet's role in CRC survivorship, including endpoints, and (ii) comprehensive analyses to isolate specific effects within correlated lifestyle components.

Association of five diet scores with severe NAFLD incidence: A prospective study from UK Biobank.

AIM: This study aimed to contrast the associations of five common diet scores with severe non-alcoholic fatty liver disease (NAFLD) incidence. MATERIALS AND METHODS: In total, 162 999 UK Biobank participants were included in this prospective population-based study. Five international diet scores were included: the 14-Item Mediterranean Diet Adherence Screener (MEDAS-14), the Recommended Food Score (RFS), the Healthy Diet Indicator (HDI), the Mediterranean Diet Score and the Mediterranean-DASH Intervention for Neurodegenerative Delay score. As each score has different measurements and scales, all scores were standardized and categorized into quartiles. Cox proportional hazard models adjusted for confounder factors investigated associations between the standardized quartiles and severe NAFLD incidence. RESULTS: Over a median follow-up of 10.2 years, 1370 participants were diagnosed with severe NAFLD. When the analyses were fully adjusted, participants in quartile 4 using the MEDAS-14 and RFS scores, as well as those in quartiles 2 and 3 using the HDI score, had a significantly lower risk of severe incident NAFLD compared with those in quartile 1. The lowest risk was observed in quartile 4 for the MEDAS-14 score [hazard ratio (HR): 0.76 (95% confidence interval (CI): 0.62-0.94)] and the RFS score [HR: 0.82 (95% CI: 0.69-0.96)] and as well as in quartile 2 in the HDI score [HR: 0.80 (95% CI: 0.70-0.91)]. CONCLUSION: MEDAS-14, RFS and HDI scores were the strongest diet score predictors of severe NAFLD. A healthy diet might protect against NAFLD development irrespective of the specific approach used to assess diet. However, following these score recommendations could represent optimal dietary approaches to mitigate NAFLD risk.

Effects of non-digestible carbohydrates on gut microbiota and microbial metabolites: a randomised, controlled dietary intervention in healthy individuals.

The gut microbiome is impacted by certain types of dietary fibre. However, the type, duration, and dose needed to elicit gut microbial changes, and whether these changes also influence microbial metabolites, remains unclear. This study investigated the effects of supplementing healthy participants with two types of non-digestible carbohydrates (resistant starch (RS) and polydextrose (PD)), on the stool microbiota and microbial metabolite concentrations in plasma, stool, and urine, as secondary outcomes in the Dietary Intervention Stem Cells and Colorectal Cancer (DISC) Study.The DISC Study was a double-blind, randomised controlled trial that supplemented healthy participants with RS and/or PD or placebo for 50 days in a 2*2 factorial design. DNA was extracted from stool samples collected pre- and post-intervention, and V4 16S rRNA gene sequencing was used to profile the gut microbiota. Metabolite concentrations were measured in stool, plasma, and urine by high-performance liquid chromatography.A total of 58 participants with paired samples available were included. After 50 days, no effects of RS or PD were detected on composition of the gut microbiota diversity (alpha- and beta-diversity), on genus relative abundance, or on metabolite concentrations. However, Drichlet's multinomial mixture clustering-based approach suggests that some participants changed microbial enterotype post-intervention.The gut microbiome and faecal, plasma, and urinary microbial metabolites were stable in response to a 50-day fibre intervention in middle aged adults. Larger and longer studies, including those which explore the effects of specific fibre sub-types, may be required to determine the relationships between fibre intake, the gut microbiome, and host-health.

Association of a dietary inflammatory index with cardiometabolic, endocrine, liver, renal and bones biomarkers: cross-sectional analysis of the UK Biobank study.

BACKGROUND AND AIMS: Research into the relationship between an Energy-adjusted Diet-Inflammatory Index (E-DII) and a wider health-related biomarkers profile is limited. Much of the existing evidence centers on traditional metabolic biomarkers in populations with chronic diseases, with scarce data on healthy individuals. Thus, this study aims to investigate the association between an E-DII score and 30 biomarkers spanning metabolic health, endocrine, bone health, liver function, cardiovascular, and renal functions, in healthy individuals. METHODS AND RESULTS: 66,978 healthy UK Biobank participants, the overall mean age was 55.3 (7.9) years were included in this cross-sectional study. E-DII scores, based on 18 food parameters, were categorised as anti-inflammatory (E-DII < -1), neutral (-1 to 1), and pro-inflammatory (>1). Regression analyses, adjusted for confounding factors, were conducted to investigate the association of 30 biomarkers with E-DII. Compared to those with an anti-inflammatory diet, individuals with a pro-inflammatory diet had increased levels of 16 biomarkers, including six cardiometabolic, five liver, and four renal markers. The concentration difference ranged from 0.27 SD for creatinine to 0.03 SD for total cholesterol. Conversely, those on a pro-inflammatory diet had decreased concentrations in six biomarkers, including two for endocrine and cardiometabolic. The association range varied from -0.04 for IGF-1 to -0.23 for SHBG. CONCLUSION: This study highlighted that a pro-inflammatory diet was associated with an adverse profile of biomarkers linked to cardiometabolic health, endocrine, liver function, and renal health.

Socio-demographic variation in adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations within the UK Biobank prospective cohort study.

BACKGROUND: The 2018 (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are evidence-based lifestyle recommendations which aim to reduce the risk of cancer worldwide. Sociodemographic factors modulate lifestyle behaviours, and both cancer incidence and survival are socio-economically patterned. We investigated adherence to these recommendations and examined patterns of adherence across sociodemographic subgroups in the UK Biobank cohort. METHODS: We included 158 415 UK Biobank participants (mean age 56 years, 53% female). Total adherence scores were derived from dietary, physical activity and anthropometric data using the 2018 WCRF/AICR standardized scoring system. One-Way analysis of variance (ANOVA) was used to test for differences in total scores and in values for individual score components according to sociodemographic factors and Pearson's Χ2 test to investigate associations between sociodemographic factors according to tertiles of adherence score. RESULTS: Mean total adherence score was 3.85 points (SD 1.05, range 0-7 points). Higher total scores were observed in females, and older (>57 years), Chinese or South Asian, and more educated participants. We found significant variations in adherence to individual recommendations by sociodemographic factors including education, Townsend deprivation index and ethnicity. CONCLUSIONS: Identifying and understanding lifestyle and dietary patterns according to sociodemographic factors could help to guide public health strategies for the prevention of cancers and other non-communicable diseases.

Adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations and cancer risk: A systematic review and meta-analysis.

BACKGROUND: The World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations are lifestyle-based guidelines that aim to reduce cancer risk. A systematic review and meta-analysis of studies investigating associations between a score for adherence to the 2018 Cancer Prevention Recommendations and cancer risk was conducted. METHODS: MEDLINE, Embase, Web of Science, and Scopus were searched for studies published to November 28, 2022. In meta-analysis, the estimated risk ratios and 95% CIs for adherence score as a continuous (per 1-point increment) and categorical (highest vs. lowest score category) variable using random-effects models were estimated. RESULTS: Eighteen studies (11 cohort; seven case-control) were included investigating incidence of breast (n = 7), colorectal (n = 5), prostate (n = 2), lung (n = 2), pancreatic (n = 1), endometrial (n = 1), unknown primary cancer (n = 1), chronic lymphocytic leukemia (n = 1), and overall (any) cancer (n = 1). The summary risk ratio per 1-point increment in adherence score was 0.89 (95% CI, 0.85-0.93; I2  = 76.5%; n = 7) for breast cancer, 0.88 (95% CI, 0.84-0.91; I2  = 26.2%; n = 4) for colorectal cancer, and 0.92 (95% CI, 0.86-0.98, I2  = 66.0%; n = 2) for lung cancer. There were no significant associations with prostate or other cancers. Meta-analysis results using categorical adherence score variables were consistent with these findings. CONCLUSIONS: Greater adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations was associated with lower risk of breast, colorectal, and lung cancers. Future studies investigating associations with risk of other forms of cancer are warranted. PROSPERO REGISTRATION NUMBER: CRD42022313327.

Adherence to the 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations and risk of 14 lifestyle-related cancers in the UK Biobank prospective cohort study.

BACKGROUND: The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are lifestyle-based recommendations which aim to reduce cancer risk. This study investigated associations between adherence, assessed using a standardised scoring system, and the risk of all cancers combined and of 14 cancers for which there is strong evidence for links with aspects of lifestyle in the UK. METHODS: We used data from 94,778 participants (53% female, mean age 56 years) from the UK Biobank. Total adherence scores (range 0-7 points) were derived from dietary, physical activity, and anthropometric data. Associations between total score and cancer risk (all cancers combined; and prostate, breast, colorectal, lung, uterine, liver, pancreatic, stomach, oesophageal, head and neck, ovarian, kidney, bladder, and gallbladder cancer) were investigated using Cox proportional hazard models, adjusting for age, sex, deprivation index, ethnicity, and smoking status. RESULTS: Mean total score was 3.8 (SD 1.0) points. During a median follow-up of 8 years, 7296 individuals developed cancer. Total score was inversely associated with risk of all cancers combined (HR: 0.93; 95%CI: 0.90-0.95 per 1-point increment), as well as breast (HR: 0.90; 95%CI: 0.86-0.95), colorectal (HR: 0.90; 95%CI: 0.84-0.97), kidney (HR: 0.82; 95%CI: 0.72-0.94), oesophageal (HR: 0.84; 95%CI: 0.71-0.98), ovarian (HR: 0.76; 95%CI: 0.65-0.90), liver (HR: 0.78; 95%CI: 0.63-0.97), and gallbladder (HR: 0.70; 95%CI: 0.53-0.93) cancers. CONCLUSIONS: Greater adherence to lifestyle-based recommendations was associated with reduced risk of all cancers combined and of breast, colorectal, kidney, oesophageal, ovarian, liver, and gallbladder cancers. Our findings support compliance with the Cancer Prevention Recommendations for cancer prevention in the UK.

Effects of obesity, and of weight loss following bariatric surgery, on methylation of DNA from the rectal mucosa and in cell-free DNA from blood.

BACKGROUND: DNA methylation is an epigenetic mechanism through which environmental factors including nutrition and inflammation influence health. Obesity is a major modifiable risk factor for many common diseases including cardiovascular diseases and cancer. In particular, obesity-induced inflammation resulting from aberrantly-methylated inflammatory genes may drive risk of several non-communicable diseases including colorectal cancer (CRC). This study is the first to investigate the effects of weight loss induced by bariatric surgery (BS) on DNA methylation in the rectum and in cell-free DNA (cfDNA) from blood. SUBJECTS AND METHODS: DNA methylation was quantified in rectal mucosal biopsies and cfDNA from serum of 28 participants with obesity before and 6 months after BS, as well as in 12 participants without obesity (control group) matched for age and sex from the Biomarkers Of Colorectal cancer After Bariatric Surgery (BOCABS) Study. DNA methylation of LEP, IL6, POMC, LINE1, MAPK7 and COX2 was quantified by pyrosequencing. RESULTS: BMI decreased significantly from 41.8 kg/m2 pre-surgery to 32.3 kg/m2 at 6 months after BS. Compared with the control group, obesity was associated with lower LEP methylation in both the rectal mucosa and in cfDNA from serum. BS normalised LEP methylation in DNA from the rectal mucosa but not in cfDNA. BS decreased methylation of some CpG sites of LINE1 in the rectal mucosal DNA and in cfDNA to levels comparable with those in participants without obesity. Methylation of POMC in rectal mucosal DNA was normalised at 6 months after BS. CONCLUSION: BS reversed LINE1, POMC and LEP methylation in the rectal mucosa of patients with obesity to levels similar to those in individuals without obesity. These findings support current evidence of effects of BS-induced weight loss on reversibility of DNA methylation in other tissues. The DNA methylation changes in the rectal mucosa shows promise as a biomarker for objective assessment of effects of weight loss interventions on risk of cancer and other diseases.

Effects of a mediterranean diet on the gut microbiota and microbial metabolites: A systematic review of randomized controlled trials and observational studies.

Consumption of the Mediterranean dietary pattern (MedDiet) is associated with reduced risk of numerous non-communicable diseases. Modulation of the composition and metabolism of the gut microbiota represents a potential mechanism through which the MedDiet elicits these effects. We conducted a systematic literature search (Prospero registration: CRD42020168977) using PubMed, The Cochrane Library, MEDLINE, SPORTDiscuss, Scopus and CINAHL databases for randomized controlled trials (RCTs) and observational studies exploring the impact of a MedDiet on gut microbiota composition (i.e., relative abundance of bacteria or diversity metrics) and metabolites (e.g., short chain fatty acids). Seventeen RCTs and 17 observational studies were eligible for inclusion in this review. Risk of bias across the studies was mixed but mainly identified as low and unclear. Overall, RCTs and observational studies provided no clear evidence of a consistent effect of a MedDiet on composition or metabolism of the gut microbiota. These findings may be related to the diverse methods across studies (e.g., MedDiet classification and analytical techniques), cohort characteristics, and variable quality of studies. Further, well-designed studies are warranted to advance understanding of the potential effects of the MedDiet using more detailed examination of microbiota and microbial metabolites with reference to emerging characteristics of a healthy gut microbiome.

Association of meat, vegetarian, pescatarian and fish-poultry diets with risk of 19 cancer sites and all cancer: findings from the UK Biobank prospective cohort study and meta-analysis.

BACKGROUND: The associations of cancer with types of diets, including vegetarian, fish, and poultry-containing diets, remain unclear. The aim of this study was, therefore, to investigate the association of type of diet with all cancers and 19 site-specific incident cancers in a prospective cohort study and then in a meta-analysis of published prospective cohort studies. METHODS: A total of 409,110 participants from the UK Biobank study, recruited between 2006 and 2010, were included. The outcomes were incidence of all cancers combined and 19 cancer sites. Associations between the types of diets and cancer were investigated using Cox proportional hazards models. Previously published prospective cohort studies were identified from four databases, and a meta-analysis was conducted using random-effects models. RESULTS: The mean follow-up period was 10.6 years (IQR 10.0; 11.3). Compared with meat-eaters, vegetarians (hazard ratio (HR) 0.87 [95% CI: 0.79 to 0.96]) and pescatarians (HR 0.93 [95% CI: 0.87 to 1.00]) had lower overall cancer risk. Vegetarians also had a lower risk of colorectal and prostate cancers compared with meat-eaters. In the meta-analysis, vegetarians (Risk Ratio (RR): 0.90 [0.86 to 0.94]) and pescatarians (RR 0.91 [0.86; 0.96]) had lower risk of overall and colorectal cancer. No associations between the types of diets and prostate, breast, or lung cancers were found. CONCLUSIONS: Compared with meat-eaters, vegetarians and pescatarians had a lower risk of overall, colorectal, and prostate cancer. When results were pooled in a meta-analysis, the associations with overall and colorectal cancer persisted, but the results relating to other specific cancer sites were inconclusive.

Obesity and Roux-en-Y gastric bypass drive changes in miR-31 and miR-215 expression in the human rectal mucosa.

BACKGROUND/OBJECTIVES: Obesity increases colorectal cancer (CRC) risk. However, the effects of weight loss on CRC risk are unclear. Epigenetic mechanisms involving microRNAs that lead to dysregulated gene expression may mediate the effects of obesity and weight loss on CRC risk. We examined the effects of obesity and weight loss following Roux-en-Y gastric bypass (RYGB) on microRNA expression in the human rectal mucosa. SUBJECTS/METHODS: We collected rectal mucosal biopsies from obese patients (n = 22) listed for RYGB and age- and sex-matched healthy non-obese Controls (n = 20), at baseline and six months post-surgery. We quantified microRNA expression in rectal mucosal biopsies using Next Generation Sequencing and bioinformatics analysis to investigate the likely functional consequences of these epigenetic changes. RESULTS: Compared with non-obese individuals, obese individuals showed differential expression of 112 microRNAs (p < 0.05). At six-months post-RYGB, when mean body mass had fallen by 27 kg, 60 microRNAs were differentially expressed, compared with baseline (p < 0.05). The expression of 36 microRNAs differed significantly between both i) obese and non-obese individuals and ii) obese individuals pre- and post-RYGB. Quantitative polymerase chain reaction (qPCR) demonstrated that expression of miR-31 and miR-215 was significantly (p < 0.05) higher, 143-fold and 15-fold respectively, in obese than in non-obese individuals. Weight loss, following RYGB, reduced expression of miR-31 and miR-215 to levels comparable with Controls. These differentially expressed microRNAs are implicated in pathways linked with inflammation, obesity and cancer. CONCLUSION: Our findings show, for the first time, that obesity is associated with dysregulated microRNA expression in the human rectal mucosa. Further, surgically-induced weight loss may normalise microRNA expression in this tissue.

Resistant starch supplementation increases crypt cell proliferative state in the rectal mucosa of older healthy participants.

There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and WNT-pathway-related markers of bowel cancer risk.

Bowel cancer risk is strongly influenced by lifestyle factors including diet and physical activity. Several studies have investigated the effects of adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations on outcomes such as all-cause and cancer-specific mortality, but the relationships with molecular mechanisms that underlie the effects on bowel cancer risk are unknown. This study aimed to investigate the relationships between adherence to the WCRF/AICR cancer prevention recommendations and wingless/integrated (WNT)-pathway-related markers of bowel cancer risk, including the expression of WNT pathway genes and regulatory microRNA (miRNA), secreted frizzled-related protein 1 (SFRP1) methylation and colonic crypt proliferative state in colorectal mucosal biopsies. Dietary and lifestyle data from seventy-five healthy participants recruited as part of the DISC Study were used. A scoring system was devised including seven of the cancer prevention recommendations and smoking status. The effects of total adherence score and scores for individual recommendations on the measured outcomes were assessed using Spearman's rank correlation analysis and unpaired t tests, respectively. Total adherence score correlated negatively with expression of Myc proto-oncogene (c-MYC) (P=0·039) and WNT11 (P=0·025), and high adherers had significantly reduced expression of cyclin D1 (CCND1) (P=0·042), WNT11 (P=0·012) and c-MYC (P=0·048). Expression of axis inhibition protein 2 (AXIN2), glycogen synthase kinase (GSK3ß), catenin ß1 (CTNNB1) and WNT11 and of the oncogenic miRNA miR-17 and colonic crypt kinetics correlated significantly with scores for individual recommendations, including body fatness, red meat intake, plant food intake and smoking status. The findings from this study provide evidence for positive effects of adherence to the WCRF/AICR cancer prevention recommendations on WNT-pathway-related markers of bowel cancer risk.

Nutrition and Ageing.

The ageing trajectory is plastic and can be slowed down by lifestyle factors, including good nutrition, adequate physical activity and avoidance of smoking. In humans, plant-based diets such as the Mediterranean dietary pattern are associated with healthier ageing and lower risk of age-related disease, whereas obesity accelerates ageing and increases the likelihood of most common complex diseases including CVD, T2D, dementia, musculoskeletal diseases and several cancers. As yet, there is only weak evidence in humans about the molecular mechanisms through which dietary factors modulate ageing but evidence from cell systems and animal models suggest that it is probable that better dietary choices influence all 9 hallmarks of ageing. It seems likely that better eating patterns retard ageing in at least two ways including (i) by reducing pervasive damaging processes such as inflammation, oxidative stress/redox changes and metabolic stress and (ii) by enhancing cellular capacities for damage management and repair. From a societal perspective, there is an urgent imperative to discover, and to implement, cost-effective lifestyle (especially dietary) interventions which enable each of us to age well, i.e. to remain physically and socially active and independent and to minimise the period towards the end of life when individuals suffer from frailty and multi-morbidity.

Effects of dietary interventions on DNA methylation in adult humans: systematic review and meta-analysis.

DNA methylation is a key component of the epigenetic machinery that is responsible for regulating gene expression and, therefore, cell function. Patterns of DNA methylation change during development and ageing, differ between cell types, are altered in multiple diseases and can be modulated by dietary factors. However, evidence about the effects of dietary factors on DNA methylation patterns in humans is fragmentary. This study was initiated to collate evidence for causal links between dietary factors and changes in DNA methylation patterns. We carried out a systematic review of dietary intervention studies in adult humans using Medline, EMBASE and Scopus. Out of 22 149 screened titles, sixty intervention studies were included, of which 65% were randomised (n 39). Most studies (53%) reported data from blood analyses, whereas 27% studied DNA methylation in colorectal mucosal biopsies. Folic acid was the most common intervention agent (33%). There was great heterogeneity in the methods used for assessing DNA methylation and in the genomic loci investigated. Meta-analysis of the effect of folic acid on global DNA methylation revealed strong evidence that supplementation caused hypermethylation in colorectal mucosa (P=0·009). Meta-regression analysis showed that the dose of supplementary folic acid was the only identified factor (P<0·001) showing a positive relationship. In summary, there is limited evidence from intervention studies of effects of dietary factors, other than folic acid, on DNA methylation patterns in humans. In addition, the application of multiple different assays and investigations of different genomic loci makes it difficult to compare, or to combine, data across studies.

Non-digestible carbohydrates supplementation increases miR-32 expression in the healthy human colorectal epithelium: A randomized controlled trial.

Colorectal cancer (CRC) risk is modulated by diet and there is convincing evidence of reduced risk with higher non-digestible carbohydrates (NDCs) consumption. Resistant starch (RS), a NDC, positively modulates the expression of oncogenic microRNAs, suggesting that this could be a mechanism through which NDCs protect against CRC. The present study aimed to investigate the effects of supplementation with two NDCs, RS, and polydextrose (PD), on microRNA expression in the macroscopically-normal human rectal epithelium using samples from the DISC Study, a randomized, double-blind, placebo-controlled dietary intervention. We screened 1008 miRNAs in pooled post-intervention rectal mucosal samples from participants allocated to the double placebo group and those supplemented with both RS and PD. A total of 111 miRNAs were up- or down-regulated by at least twofold in the RS + PD group compared with the control group. From these, eight were selected for quantification in individual participant samples by qPCR, and fold-change direction was consistent with the array for seven miRNAs. The inconsistency for miR-133b and the lower fold-change values observed for the seven miRNAs is probably because qPCR of individual participant samples is a more robust and sensitive method of quantification than the array. miR-32 expression was increased by approximately threefold (P = 0.033) in the rectal mucosa of participants supplemented with RS + PD compared with placebo. miR-32 is involved in the regulation of processes such as cell proliferation that are dysregulated in CRC. Furthermore, miR-32 may affect non-canonical NF-κB signaling via regulation of TRAF3 expression and consequently NIK stabilization.

Abbreviated Score to Assess Adherence to the 2018 WCRF/AICR Cancer Prevention Recommendations and Risk of Cancer in the UK Biobank.

BACKGROUND: The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are lifestyle-based guidelines which aim to reduce cancer risk. This study investigated, in the UK Biobank, associations between an abbreviated score to assess adherence to these Recommendations and the risk of all cancers combined and of 14 cancers for which there is strong evidence for links with diet, adiposity, and physical activity. METHODS: We used data from 288,802 UK Biobank participants (mean age 56.2 years), cancer-free at baseline. An abbreviated version of the 2018 WCRF/AICR Score was calculated to assess adherence to five Recommendations on (i) body weight, (ii) physical activity, (iii) fruits, vegetables, and dietary fiber, (iv) red and processed meat, and (v) alcohol. Multivariable Cox proportional hazards models were used to analyze associations between the abbreviated score (range, 0-5 points) and cancer incidence, adjusting for confounders. RESULTS: During a median follow-up of 8.2 years (interquartile range, 7.4-8.9), 23,448 participants were diagnosed with cancer. The abbreviated score was inversely associated with risk of cancer overall [HR: 0.93; 95% confidence interval (CI): 0.92-0.95 per 1-point increment], and breast (HR: 0.90; 95% CI: 0.87-0.94), colorectal (HR: 0.86; 95% CI: 0.83-0.90), lung (HR: 0.89; 95% CI: 0.84-0.94), kidney (HR: 0.83; 95% CI: 0.76-0.90), pancreatic (HR: 0.86; 95% CI: 0.79-0.94), uterine (HR: 0.79; 95% CI: 0.73-0.86), esophageal (HR: 0.82; 95% CI: 0.75-0.90), stomach (HR: 0.89; 95% CI: 0.79-0.99), and liver (HR: 0.80; 95% CI: 0.72-0.90) cancers. CONCLUSIONS: Greater adherence to the Cancer Prevention Recommendations, assessed using an abbreviated score, was associated with reduced risk of all cancers combined and of nine site-specific cancers. IMPACT: Our findings support compliance to these Recommendations for cancer prevention.

Adherence to the Eatwell Guide and cardiometabolic, cognitive and neuroimaging parameters: an analysis from the PREVENT dementia study.

BACKGROUND: The Eatwell guide reflects the UK government's recommendations for a healthy and balanced diet. Previous research has identified associations between healthy eating patterns and both cardiovascular and brain health, although there is little evidence specifically focusing on the Eatwell Guide. To date no research has investigated associations between the Eatwell Guide and risk for future dementia. METHODS: Data from the PREVENT dementia cohort study baseline visit was used in this analysis. Binary and graded Eatwell Guide scores (BEWG, GEWG) were created from a self-reported Food Frequency Questionnaire. The CAIDE score was included as the primary outcome measure to represent risk for future Alzheimer's disease. Secondary outcome measures included cardiometabolic health measures and brain health measures. Generalised additive models were run in R. RESULTS: A total of 517 participants were included in the analysis, with a mean BEWG score of 4.39 (± 1.66) (out of a possible 12 points) and GEWG score of 39.88 (± 6.19) (out of a possible 60 points). There was no significant association between either Eatwell Guide score and the CAIDE score (BEWG ß: 0.07, 95% confidence interval (CI): -0.07, 0.22; GEWG ß: 0.02, 95% CI: -0.02, 0.06) or any measures of brain health. There was a significant association between higher GEWG score and lower systolic and diastolic blood pressure and body mass index (BMI) (systolic ß: -0.24, 95% CI: -0.45, -0.03; diastolic ß: -0.16, 95% CI: -0.29, -0.03; BMI ß: -0.09, 95% CI: -0.16, -0.01). CONCLUSIONS: Although not directly associated with the CAIDE score, the Eatwell Guide dietary pattern may be beneficial for dementia prevention efforts through the modification of hypertension and obesity, which are both known risk factors for dementia. Future work could replicate these findings in other UK-based cohorts as well as further development of Eatwell Guide scoring methodologies.

Adherence to the Eatwell Guide and population and planetary health: A Rank Prize Forum report.

This report summarises a Forum conducted in June 2023 to explore the current state of the knowledge around the Eatwell Guide, which is the UK government's healthy eating tool, in relation to population and planetary health. The 1.5-day Forum highlighted the limited, albeit promising evidence linking higher adherence to the Eatwell Guide with favourable health outcomes, including reduced overall mortality risk, lower abdominal obesity in post-menopausal women and improved cardiometabolic health markers. Similarly, evidence was presented to suggest that higher adherence to the Eatwell Guide is associated with reduced greenhouse gas emissions. Presentations were given around cultural adaptations of the Eatwell Guide, including African Heritage and South Asian versions, which are designed to increase the acceptability and uptake of the Eatwell Guide in these communities in the United Kingdom. Presentations highlighted ongoing work relevant to the applications of the Eatwell Guide in randomised controlled trials and public health settings, including the development of a screening tool to quantify Eatwell Guide adherence. The Forum ended with a World Café-style event, in which the strengths and limitations of the Eatwell Guide were discussed, and directions for future research were identified. This Forum report serves as a primer on the current state of the knowledge on the Eatwell Guide and population and planetary health and will be of interest to researchers, healthcare professionals and public health officials.