Aspects of dietary carbohydrate intake are not related to risk of colorectal polyps in the Tennessee Colorectal Polyp Study

Purpose: High digestible carbohydrate intakes can induce hyperglycemia and hyperinsulinemia and collectively have been implicated in colorectal tumor development. Our aim was to explore the association between aspects of dietary carbohydrate intake and risk of colorectal adenomas and hyperplastic polyps in a large case–control study.

Methods: Colorectal polyp cases (n = 1,315 adenomas only, n = 566 hyperplastic polyps only and n = 394 both) and controls (n = 3,184) undergoing colonoscopy were recruited between 2003 and 2010 in Nashville, Tennessee, USA. Dietary intakes were estimated by a 108-item food frequency questionnaire. Unconditional logistic regression analysis was applied to determine odds ratios (OR) and corresponding 95 % confidence intervals (CI) for colorectal polyps according to dietary carbohydrate intakes, after adjustment for potential confounders.

Results: No significant associations were detected for risk of colorectal adenomas when comparing the highest versus lowest quartiles of intake for total sugars (OR 1.03; 95 % CI 0.84–1.26), starch (OR 1.01; 95 % CI 0.81–1.26), total or available carbohydrate intakes. Similar null associations were observed between dietary carbohydrate intakes and risk of hyperplastic polyps, or concurrent adenomas and hyperplastic polyps.

Conclusion: In this US population, digestible carbohydrate intakes were not associated with risk of colorectal polyps, suggesting that dietary carbohydrate does not have an etiological role in the early stages of colorectal carcinogenesis.

Combining vitamin C and carotenoid biomarkers better predicts fruit and vegetable intake than individual biomarkers in dietary intervention studies

PURPOSE: The aim of this study was to determine whether combining potential biomarkers of fruit and vegetables is better at predicting FV intake within FV intervention studies than single biomarkers.

DESIGN: Data from a tightly controlled randomised FV intervention study (BIOFAV; all food provided and two meals/day on weekdays consumed under supervision) were used. A total of 30 participants were randomised to either 2, 5 or 8 portions FV/day for 4 weeks, and blood samples were collected at baseline and 4 weeks for plasma vitamin C and serum carotenoid analysis. The combined biomarker approach was also tested in three further FV intervention studies conducted by the same research team, with less strict dietary control (FV provided and no supervised meals).

RESULTS: The combined model containing all carotenoids and vitamin C was a better fit than either the vitamin C only (P < 0.001) model or the lutein only (P = 0.006) model in the BIOFAV study. The C-statistic was slightly lower in the lutein only model (0.85) and in the model based upon factor analysis (0.88), and much lower in the vitamin C model (0.68) compared with the full model (0.95). Results for the other studies were similar, although the differences between the models were less marked.

CONCLUSIONS: Although there was some variation between studies, which may relate to the level of dietary control or participant characteristics, a combined biomarker approach to assess overall FV consumption may more accurately predict FV intake within intervention studies than the use of a single biomarker. The generalisability of these findings to other populations and study designs remains to be tested. 

Interventions Targeting Child Undernutrition in Developing Countries May Be Undermined by Dietary Exposure to Aflatoxin

Child undernutrition, a form of malnutrition, is a major public health burden in developing countries. Supplementation interventions targeting the major micronutrient deficiencies have only reduced the burden of child undernutrition to a certain extent, indicating that there are other underlying determinants that need addressed. Aflatoxin exposure, which is also highly prevalent in developing countries, may be considered to be an aggravating factor for child undernutrition. Increasing evidence suggests that aflatoxin exposure can occur in any stage of life including in utero through a trans-placental pathway and in early childhood (through contaminated weaning food and family food). Early life exposure to aflatoxin is associated with adverse effects on low birth weight, stunting, immune suppression and liver function damage. The mechanisms underlying impaired growth and aflatoxin exposure are still unclear but intestinal function damage, reduced immune function and alteration in the insulin-like growth factor axis caused by liver damage, are suggested hypotheses. Given the fact that both aflatoxin and child undernutrition are common in sub-Saharan Africa, effective interventions aimed at reducing undernutrition cannot be satisfactorily achieved until the interactive relationship between aflatoxin and child undernutrition is clearly understood, and an aflatoxin mitigation strategy has taken effect in those vulnerable mothers and children.

Investigating Intra-individual Dietary Changes and Radiocarbon Ages Using High Resolution δ13C, δ15N Isotope Ratios and 14C Ages Obtained From Dentine Increments

Ten medieval permanent teeth were subjected to incremental dentine sectioning and stable isotope analysis to investigate dietary changes in high resolution. In addition to this, eight increments were also selected for 14C measurements to examine possible intra-individual age differences. Results reveal the cessation of weaning, various dietary profiles and in some cases significantly different 14C ages obtained from a single tooth. This case study illustrates how 14C measurements can function as a proxy alongside the commonly used carbon and nitrogen stable isotope values to interpret the diet of past individuals

A randomised controlled trial to evaluate the efficacy of a 6-month dietary and physical activity intervention for patients receiving androgen deprivation therapy for prostate cancer

PURPOSE: Treatment of prostate cancer with androgen deprivation therapy (ADT) is associated with an increased fat mass, decreased lean mass, increased fatigue and a reduction in quality of life (QoL). The aim of this study was to evaluate the efficacy of a 6-month dietary and physical activity intervention for prostate cancer patients receiving ADT, to help minimise these side effects.

METHODS: Patients (n = 94) were recruited to this study if they were planned to receive ADT for prostate cancer for at least 6 months. Men randomised to the intervention arm received a dietary and exercise intervention, commensurate with UK healthy eating and physical activity recommendations. The primary outcome of interest was body composition; secondary outcomes included fatigue, QoL, functional capacity, stress and dietary change.

RESULTS: The intervention group had a significant (p < 0.001) reduction in weight, body mass index and percentage fat mass compared to the control group at 6 months; the between-group differences were -3.3 kg (95 % confidence interval (95 % CI) -4.5, -2.1), -1.1 kg/m(2) (95 % CI -1.5, -0.7) and -2.1 % (95 % CI -2.8, -1.4), respectively, after adjustment for baseline values. The intervention resulted in improvements in functional capacity (p < 0.001) and dietary intakes but did not significantly impact fatigue, QoL or stress scores at endpoint.

CONCLUSIONS: A 6-month diet and physical activity intervention can minimise the adverse body composition changes associated with ADT.

IMPLICATIONS FOR CANCER SURVIVORS: This study shows that a pragmatic lifestyle intervention is feasible and can have a positive impact on health behaviours and other key outcomes in men with prostate cancer receiving ADT.

Elevated NCOR1 disrupts a network of dietary-sensing nuclear receptors in bladder cancer cells

Increasingly invasive bladder cancer cells lines displayed insensitivity toward a panel of dietary-derived ligands for members of the nuclear receptor superfamily. Insensitivity was defined through altered gene regulatory actions and cell proliferation and reflected both reduced receptor expression and elevated nuclear receptor corepressor 1 (NCOR1) expression. Stable overexpression of NCOR1 in sensitive cells (RT4) resulted in a panel of clones that recapitulated the resistant phenotype in terms of gene regulatory actions and proliferative responses toward ligand. Similarly, silencing RNA approaches to NCOR1 in resistant cells (EJ28) enhanced ligand gene regulatory and proliferation responses, including those mediated by peroxisome proliferator-activated receptor (PPAR) gamma and vitamin D receptor (VDR) receptors. Elevated NCOR1 levels generate an epigenetic lesion to target in resistant cells using the histone deacetylase inhibitor vorinostat, in combination with nuclear receptor ligands. Such treatments revealed strong-additive interactions toward the PPARgamma, VDR and Farnesoid X-activated receptors. Genome-wide microarray and microfluidic quantitative real-time, reverse transcription-polymerase chain reaction approaches, following the targeting of NCOR1 activity and expression, revealed the selective capacity of this corepressor to govern common transcriptional events of underlying networks. Combined these findings suggest that NCOR1 is a selective regulator of nuclear receptors, notably PPARgamma and VDR, and contributes to their loss of sensitivity. Combinations of epigenetic therapies that target NCOR1 may prove effective, even when receptor expression is reduced.

Multigenerational Undernutrition Increases Susceptibility to Obesity and Diabetes that Is Not Reversed after Dietary Recuperation

People in developing countries have faced multigenerational undernutrition and are currently undergoing major lifestyle changes, contributing to an epidemic of metabolic diseases, though the underlying mechanisms remain unclear. Using a Wistar rat model of undernutrition over 50 generations, we show that Undernourished rats exhibit low birth-weight, high visceral adiposity (DXA/MRI), and insulin resistance (hyperinsulinemic-euglycemic clamps), compared to age-/gender-matched control rats. Undernourished rats also have higher circulating insulin, homocysteine, endotoxin and leptin levels, lower adiponectin, vitamin B12 and folate levels, and an 8-fold increased susceptibility to Streptozotocin-induced diabetes compared to control rats. Importantly, these metabolic abnormalities are not reversed after two generations of unrestricted access to commercial chow (nutrient recuperation). Altered epigenetic signatures in insulin-2 gene promoter region of Undernourished rats are not reversed by nutrient recuperation, and may contribute to the persistent detrimental metabolic profiles in similar multigenerational undernourished human populations.

Dietary exposure to aflatoxin and micronutrient status among young children from Guinea

SCOPE: Aflatoxin exposure coincides with micronutrient deficiencies in developing countries. Animal feeding studies have postulated that aflatoxin exposure may be exacerbating micronutrient deficiencies. Evidence available in human subjects is limited and inconsistent. The aim of the study was to investigate the relationship between aflatoxin exposure and micronutrient status among young Guinean children.

METHOD AND RESULTS: A total of 305 children (28.8 ± 8.4 months) were recruited at groundnut harvest (rainy season), of which 288 were followed up 6 months later post-harvest (dry season). Blood samples were collected at each visit. Aflatoxin-albumin adduct levels were measured by ELISA. Vitamin A, vitamin E and β-carotene concentrations were measured using HPLC methods. Zinc was measured by atomic absorption spectroscopy. Aflatoxin exposure and micronutrient deficiencies were prevalent in this population and were influenced by season, with levels increasing between harvest and post-harvest. At harvest, children in the highest aflatoxin exposure group, compared to the lowest, were 1.98 (95%CI: 1.00, 3.92) and 3.56 (95%CI: 1.13, 11.15) times more likely to be zinc and vitamin A deficient.

CONCLUSION: Although children with high aflatoxin exposure levels were more likely to be zinc and vitamin A deficient, further research is necessary to determine a cause and effect relationship. 

Dietary Micronutrient Intake and Micronutrient Status in Patients With Chronic Stable Heart Failure: An Observational Study.

BACKGROUND: Observational studies suggest that patients with heart failure have a tendency to a reduced status of a number of micronutrients and that this may be associated with an adverse prognosis. A small number of studies also suggest that patients with heart failure may have reduced dietary intake of micronutrients, a possible mechanism for reduced status.

OBJECTIVE: The aims of this study were to assess dietary micronutrient intake and micronutrient status in a group of patients with heart failure.

METHODS: Dietary intake was assessed in 79 outpatients with chronic stable heart failure with a reduced ejection fraction using a validated food frequency questionnaire. Blood concentrations of a number of micronutrients, including vitamin D, were measured in fasting blood samples, drawn at the time of food frequency questionnaire completion.

RESULTS: More than 20% of patients reported intakes less than the reference nutrient intake or recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, and iodine. More than 5% of patients reported intakes less than the lower reference nutrient intake or minimum recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, selenium, and iodine. Vitamin D deficiency (plasma total 25-hydroxy-vitamin D concentration <50 nmol/L) was observed in 75.6% of patients.

CONCLUSIONS: Vitamin D deficiency was common in this group of patients with heart failure. Based on self-reported dietary intake, a substantial number of individuals may not have been consuming enough vitamin D and a modest number of individuals may not have been consuming enough riboflavin, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, or iodine to meet their dietary needs.

Acid-labile protein-adducted heterocyclic aromatic amines in human blood are not viable biomarkers of dietary exposure: A systematic study.

Heterocyclic aromatic amines (HCA) are carcinogenic mutagens formed during cooking of protein-rich foods. HCA residues adducted to blood proteins have been postulated as biomarkers of HCA exposure. However, the viability of quantifying HCAs following hydrolytic release from adducts in vivo and correlation with dietary intake are unproven. To definitively assess the potential of labile HCA-protein adducts as biomarkers, a highly sensitive UPLC-MS/MS method was validated for four major HCAs: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx). Limits of detection were 1e5 pg/ml plasma and recoveries 91e115%. Efficacy of hydrolysis was demonstrated by HCA-protein adducts synthesised in vitro. Plasma and 7-day food diaries were collected from 122 fasting adults consuming their habitual diets. Estimated HCA intakes ranged from 0 to 2.5 mg/day. An extensive range of hydrolysis conditions was examined for release of adducted HCAs in plasma. HCA was detected in only one sample (PhIP, 9.7 pg/ml), demonstrating conclusively for the first time that acid-labile HCA adducts do not reflect dietary HCA intake and are present at such low concentrations that they are not feasible biomarkers of exposure. Identification of biomarkers remains important. The search should concentrate on stabilised HCA peptide markers and use of untargeted proteomic and metabolomic approaches.