The aim of this study was to elucidate the relationship between the urinary metabolic fingerprint and the effects of cocoa and cocoa fibre on body weight, hormone metabolism, intestinal immunity and microbiota composition. To this effect, Wistar rats were fed, for 3 weeks, a diet containing 10 % cocoa (C10) or two other diets with same the proportion of fibres: one based on cocoa fibre (CF) and another containing inulin as a reference (REF) diet. The rats’ 24 h urine samples were analysed by an untargeted 1H NMR spectroscopy-based metabonomic approach. Concentrations of faecal IgA and plasma metabolic hormones were also quantified. The C10 diet decreased the intestinal IgA, plasma glucagon-like peptide-1 and glucagon concentrations and increased ghrelin levels compared with those in the REF group. Clear differences were observed between the metabolic profiles from the C10 group and those from the CF group. Urine metabolites derived from cocoa correlated with the cocoa effects on body weight, immunity and the gut microbiota. Overall, cocoa intake alters the host and bacterial metabolism concerning energy and amino acid pathways, leading to a metabolic signature that can be used as a marker for consumption. This metabolic profile correlates with body weight, metabolic hormones, intestinal immunity and microbiota composition.

A growing body of evidence suggests that capsaicin ingestion may lead to desirable metabolic outcomes; however, the results in humans are equivocal. Whether or not benefits may be gained from ingestion of capsaicin via a commercially available meal has not been determined. The objectives of this randomised, cross-over intervention study were to compare the 2 h postprandial effects of a standard commercially prepared meal containing chilli (HOT, 5·82 mg total capsaicinoids) with a similar meal with no chilli (CON, <1·0 mg total capsaicinoids) on resting energy expenditure, plasma insulin, glucose, serum high sensitivity C-reactive protein (hs-CRP) concentrations, core body temperature and forearm microvascular reactivity responses in overweight individuals. A total of thirty-four apparently healthy individuals (sixteen men and eighteen women) between 18 and 50 years of age, with a BMI >25 kg/m2 and a waist circumference >94 cm (men) or 80 cm (women), were studied. Participants had normal glucose tolerance and were accustomed, but were not regular chilli eaters. A paired t test indicated that insulin AUC was smaller following the HOT meal (P=0·002). Similarly, there was a tendency for glucose AUC to be reduced following the HOT meal (P=0·056). No discernable effects of the HOT meal were observed on metabolic rate, core temperature, hs-CRP concentrations and endothelial-dependent microvascular reactivity. The results from this study indicate that a standard restaurant meal containing a relatively small dose of capsaicin delivered via African bird’s eye chilli, which is currently available to the public, results in lower postprandial insulin concentrations in overweight individuals, compared with the same meal without chilli.

Balance between adipocyte and osteoblast differentiation is the key link of disease progression in obesity and osteoporosis. We have previously reported that formononetin (FNT), an isoflavone extracted from Butea monosperma, stimulates osteoblast formation and protects against postmenopausal bone loss. The inverse relationship between osteoblasts and adipocytes prompted us to analyse the effect of FNT on adipogenesis and in vivo bone loss, triggered by high-fat diet (HFD)-induced obesity. The anti-obesity effect and mechanism of action of FNT was determined in 3T3-L1 cells and HFD-induced obese male mice. Our findings show that FNT suppresses the adipogenic differentiation of 3T3-L1 fibroblasts, through down-regulation of key adipogenic markers such as PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα) and sterol regulatory element-binding protein (SREBP) and inhibits intracellular TAG accumulation. Increased intracellular reactive oxygen species levels and AMP-activated protein kinase (AMPK) activation accompanied by stabilisation of β-catenin were attributed to the anti-adipogenic action of FNT. In vivo, 12 weeks of FNT treatment inhibited the development of obesity in mice by attenuating HFD-induced body weight gain and visceral fat accumulation. The anti-obesity effect of FNT results from increased energy expenditure. FNT also protects against HFD-induced dyslipidaemia and rescues deterioration of trabecular bone volume by increasing bone formation and decreasing bone resorbtion caused by HFD. FNT’s rescuing action against obesity-induced osteoporosis commenced at the level of progenitors, as bone marrow progenitor cells, obtained from the HFD mice group supplemented with FNT, showed increased osteogenic and decreased adipogenic potentials. Our findings suggest that FNT inhibits adipogenesis through AMPK/β-catenin signal transduction pathways and protects against HFD-induced obesity and bone loss.

Although non-alcoholic fatty liver disease (NAFLD) is the leading aetiology of liver disorders in the world, there is no proven treatment for NAFLD patients with normal or low BMI. The aim of this study was to evaluate the efficacy of synbiotics supplementation in NAFLD patients with normal or low BMI. In this randomised, double-blind, placebo-controlled, clinical trial, fifty patients with NAFLD were assigned to take either a synbiotic supplement or a placebo capsule for 28 weeks. Both groups were advised to follow a healthy lifestyle. At the end of the study, hepatic steatosis and fibrosis reduced in both groups; however, the mean reduction was significantly greater in the synbiotic group rather than in the placebo group (P<0·001). Furthermore, serum levels of fasting blood sugar, TAG and most of the inflammatory mediators reduced in the synbiotic group significantly compared with the placebo group (P<0·05). Our results provide evidence that synbiotic supplementation improves the main features of NAFLD in patients with normal and low BMI, at least partially through reduction in inflammatory indices. Further studies are needed to address the exact mechanism of action of these effects.

Low heart rate variability (HRV) predicts sudden cardiac death. Long-chain (LC) n-3 PUFA (C20–C22) status is positively associated with HRV. This cross-sectional study investigated whether vegans aged 40–70 years (n 23), whose diets are naturally free from EPA (20 : 5n-3) and DHA (22 : 6n-3), have lower HRV compared with omnivores (n 24). Proportions of LC n-3 PUFA in erythrocyte membranes, plasma fatty acids and concentrations of plasma LC n-3 PUFA-derived lipid mediators were significantly lower in vegans. Day-time interbeat intervals (IBI), adjusted for physical activity, age, BMI and sex, were significantly shorter in vegans compared with omnivores (mean difference −67 ms; 95 % CI −130, −3·4, P<0·05), but there were no significant differences over 24 h or during sleep. Vegans had higher overall HRV, measured as 24 h standard deviation of normal-to-normal intervals (SDNN) (mean adjusted difference 27 ms; 95 % CI 1, 52, P=0·039). Conversely, vegans presented with decreased 8 h day-time HRV: mean adjusted difference in SDNN −20 ms; 95 % CI −37, −3, P=0·021, with no differences during nocturnal sleep. Day-time parameters of beat-to-beat HRV (root of the mean of the sum of the squares of differences between adjacent normal-to-normal intervals, percentage of adjacent normal-to-normal intervals that differ by >50 % and high-frequency power) were similarly lower in vegans, with no differences during sleep. In conclusion, vegans have higher 24 h SDNN, but lower day-time HRV and shorter day-time IBI relative to comparable omnivores. Vegans may have reduced availability of precursor markers for pro-resolving lipid mediators; it remains to be determined whether there is a direct link with impaired cardiac function in populations with low-n-3 status.

Serum uric acid (SUA), a causative agent for gout among others, is affected by both genetic and dietary factors, perhaps differentially by sex. We evaluated cross-sectional (SUAbase) and longitudinal (SUArate) associations of SUA with a genetic risk score (GRS), diet and sex. We then tested the interactive effect of GRS, diet and sex on SUA. Longitudinal data on 766 African-American urban adults participating in the Healthy Aging in Neighborhood of Diversity across the Lifespan study were used. In all, three GRS for SUA were created from known SUA-associated SNP (GRSbase (n 12 SNP), GRSrate (n 3 SNP) and GRStotal (n 15 SNP)). Dietary factors included added sugar, total alcohol, red meat, total fish, legumes, dairy products, caffeine and vitamin C. Mixed-effects linear regression models were conducted. SUAbase was higher among men compared with that among women, and increased with GRStotal tertiles. SUArate was positively associated with legume intake in women (γ=+0·14; 95 % CI +0·06, +0·22, P=0·001) and inversely related to dairy product intake in both sexes combined (γ=−0·042; 95 % CI −0·075, −0·009), P=0·010). SUAbase was directly linked to alcohol consumption among women (γ=+0·154; 95 % CI +0·046, +0·262, P=0·005). GRSrate was linearly related to SUArate only among men. Legume consumption was also positively associated with SUArate within the GRStotal’s lowest tertile. Among women, a synergistic interaction was observed between GRSrate and red meat intake in association with SUArate. Among men, a synergistic interaction between low vitamin C and genetic risk was found. In sum, sex–diet, sex–gene and gene–diet interactions were detected in determining SUA. Further similar studies are needed to replicate our findings.

Increased dietary intake and tissue status of the long-chain n-3 PUFA, EPA and DHA, is associated with cardiovascular benefits. Epidemiological and animal studies suggest that concomitant nutritive intake of flavonoids may increase the conversion of α-linolenic acid (ALA) to longer-chain n-3 fatty acids EPA and DHA. We investigated the effects of increased ALA intake on fatty acid composition of serum phospholipids and erythrocytes in metabolically healthy men and women and whether fatty acid profiles and ALA conversion were affected by regular quercetin intake or sex. Subjects (n 74) were randomised to receive at least 3·3 g/d ALA with either 190 mg/d quercetin (ALA+quercetin) or placebo (ALA+placebo) in a double-blinded, placebo-controlled, crossover trial with 8-week intervention periods separated by an 8-week washout period. A total of seven subjects dropped out for personal reasons. Data from the remaining sixty-seven subjects (thirty-four males and thirty-three females) were included in the analysis. Both interventions significantly increased serum phospholipid ALA (ALA+placebo: +69·3 %; ALA+quercetin: +55·8 %) and EPA (ALA+placebo: +37·3 %; ALA+quercetin: +25·5 %). ALA + quercetin slightly decreased DHA concentration by 9·3 %. Erythrocyte ALA and EPA significantly increased with both interventions, whereas DHA decreased. Fatty acid composition did not differ between sexes. We found no effect of quercetin. Intake of 3·6 g/d ALA over an 8-week period resulted in increased ALA and EPA, but not DHA, in serum phospholipids and erythrocytes. Neither quercetin supplementation nor sex affected the increment of ALA and relative proportions of n-3 PUFA in serum phospholipids and erythrocytes.

Given the importance of prevention of complications in type 2 diabetes (T2D), we aimed to examine changes over time in consumption of fruits, vegetables and juice among men who were diagnosed with T2D in comparison with men without diabetes. The prospective Cohort of Swedish Men, aged 45–79 years in 1997, was used to examine changes in diet after diagnosis of T2D. Dietary intake was assessed using FFQ in 1997 and 2009. In all, 23 953 men who were diabetes free at baseline (1997) and completed both FFQ were eligible to participate in the study. Diagnosis of T2D was reported by subjects and ascertained through registers. Multivariable linear mixed models were used to examine changes in mean servings/week over time. In total, 1741 men developed T2D during the study period. Increased consumption of vegetables and fruits was observed among those who developed T2D (equivalent to 1·6 servings/week, 95 % CI 1·08, 2·03) and men who remained diabetes free (0·7 servings/week, 95 % CI 0·54, 0·84). Consumption of juice decreased by 0·6 servings/week (95 % CI −0·71, −0·39) among those who developed T2D and increased by 0·1 servings/week (95 % CI 0·05, 0·15) in those who were diabetes free. Changes over time and between groups were statistically significant. Although improvements in diet were observed, only 36 % of those with T2D and 35 % of those without diabetes consumed ≥5 servings of fruits and vegetables/d in 2009.

Lutein, a fat-soluble carotenoid with antioxidant properties, may have an effect on respiratory health. However, the evidence is inconsistent. We aimed to cross-sectionally investigate the association between lutein intake and lung function by measuring forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC% in adults (aged 45–79 years). We included 4402 participants from the Rotterdam Study, a prospective cohort study in The Netherlands. Lutein intake was assessed using a validated FFQ. Lung function was assessed using spirometry around the same time point as the dietary assessment. No independent association was found between lutein intake and FEV1 (−12·17 (95 % CI −34·21, 9·87) ml per sd increase in lutein) after adjustment for age, sex, height, cohort effect, ethnicity, education, weight, total daily energy intake, smoking status, physical activity, and intakes of fatty acids, dietary fibre, alcohol, β-carotene, β-crypotoxanthin, lycopene and zeaxanthin. There was also no association between lutein and FVC or FEV1/FVC%. However, after stratification by smoking status, lutein intake was significantly associated with lower FEV1/FVC% in current smokers (−1·69 (95 % CI −2·93, −0·45) % per sd increase of lutein) independent of other carotenoids. The present study does not support an independent association between lutein intake and lung function in adults. However, future studies should focus on the potential inverse association between high lutein intake and lung function in specific risk groups such as smokers.

Vitamin A deficiency has been associated with impaired fetal pancreatic development and increased risk of developing type 2 diabetes mellitus (T2DM). In 1962, mandatory margarine fortification with vitamin A was increased by 25 % in Denmark. We aimed to determine whether offspring of mothers who had been exposed to the extra vitamin A from fortification during pregnancy had a lower risk of developing T2DM in adult life, compared with offspring of mothers exposed to less vitamin A. Individuals from birth cohorts with the higher prenatal vitamin A exposure (born 1 December 1962–31 March 1964) and those with lower prenatal exposure (born 1 September 1959–31 December 1960) were followed up with regard to development of T2DM before 31 December 2012 in the Danish National Diabetes Registry and National Patient Register. Logistic and Cox regression analyses were performed to determine the risk of T2DM by vitamin A exposure level. A total of 193 803 individuals were followed up until midlife. Our results showed that individuals exposed prenatally to extra vitamin A from fortified margarine had a lower risk of developing T2DM than those exposed to lower levels: OR 0·88; 95 % CI 0·81, 0·95, P=0·001, after adjustment for sex. Fetal exposure to small, extra amounts of vitamin A from food fortification may reduce the risk of T2DM. These results may have public health relevance, as they demonstrate that one of the most costly chronic diseases may be prevented by food fortification – a simple and affordable public health nutrition intervention.

The effect of fruit and vegetable intake on breast cancer prognosis is controversial. Thus, a meta-analysis was carried out to explore their associations. A comprehensive search was conducted in PubMed, Web of Science, OVID, ProQuest and Chinese databases from inception to April 2016. The summary hazard ratios (HR) and 95 % CI were estimated using a random effects model if substantial heterogeneity existed and using a fixed effects model if not. Subgroup analyses and sensitivity analyses were also performed. In total, twelve studies comprising 41 185 participants were included in the meta-analysis. Comparing the highest with the lowest, the summary HR for all-cause mortality were 1·01 (95 % CI 0·72, 1·42) for fruits and vegetables combined, 0·96 (95 % CI 0·83, 1·12) for total vegetable intake, 0·99 (95 % CI 0·89, 1·11) for cruciferous vegetable intake and 0·88 (95 % CI 0·74, 1·05) for fruit intake; those for breast cancer-specific mortality were 1·05 (95 % CI 0·77, 1·43) for total vegetable intake and 0·94 (95 % CI 0·69, 1·26) for fruit intake; and those for breast cancer recurrence were 0·89 (95 % CI 0·53, 1·50) for total vegetable intake and 0·98 (95 % CI 0·76, 1·26) for cruciferous vegetable intake. This meta-analysis found no significant associations between fruit and vegetable intake and breast cancer prognosis.

No study has analysed how protein intake from early childhood to young adulthood relate to adult BMI in a single cohort. To estimate the association of protein intake at 2, 11, 15, 19 and 22 years with age- and sex-standardised BMI at 22 years (early adulthood), we used linear regression models with dietary and anthropometric data from a Filipino birth cohort (1985–2005, n 2586). We used latent growth curve analysis to identify trajectories of protein intake relative to age-specific recommended daily allowance (intake in g/kg body weight) from 2 to 22 years, then related trajectory membership to early adulthood BMI using linear regression models. Lean mass and fat mass were secondary outcomes. Regression models included socioeconomic, dietary and anthropometric confounders from early life and adulthood. Protein intake relative to needs at age 2 years was positively associated with BMI and lean mass at age 22 years, but intakes at ages 11, 15 and 22 years were inversely associated with early adulthood BMI. Individuals were classified into four mutually exclusive trajectories: (i) normal consumers (referent trajectory, 58 % of cohort), (ii) high protein consumers in infancy (20 %), (iii) usually high consumers (18 %) and (iv) always high consumers (5 %). Compared with the normal consumers, ‘usually high’ consumption was inversely associated with BMI, lean mass and fat mass at age 22 years whereas ‘always high’ consumption was inversely associated with male lean mass in males. Proximal protein intakes were more important contributors to early adult BMI relative to early-childhood protein intake; protein intake history was differentially associated with adulthood body size.

Eating fruit and vegetables (FV) offers important health benefits for children and adolescents, but their average intake is low. To explore if negative trends with age exist as children grow, this study modelled differences in FV consumption from childhood to young adulthood. A pseudo-panel was constructed using years 1–4 (combined) of the Rolling Programme of the UK National Diet and Nutrition Survey (NDNS) (2008/2009–2011/2012). Intake of FV in the NDNS was recorded using 4-d unweighted food diaries. The data consisted of 2131 observations of individuals aged 2–23 years. Age-year-cohort decomposition regression analyses were used to separate age effects from year and cohort effects in the data. Total energy intake was included to account for age differences in overall energy consumption. Fruit intake started to decrease from the age of 7 years for boys and girls, and reached its lowest level during adolescence. By 17 years, boys were consuming 0·93 (P=0·037) less fruit portions compared with the age of 2 years. By 15 years, girls were consuming 0·8 fruit portions less (P=0·053). Vegetable intake changed little during childhood and adolescence (P=0·0834 and P=0·843 for change between 7 and 12 years, boys and girls, respectively). There was unclear evidence of recovery of FV intakes in early adulthood. Efforts to improve FV intake should consider these trends, and focus attention on the factors influencing intake across childhood and adolescence in order to improve the nutritional quality of diets during these periods.