Oxylipins and endocannabinoids (eCBs) both belong to superclasses of lipid mediators with potent inflammation modulatory activities. The adipose tissue (AT) plays a key role in metabolic syndrome-related inflammation, via altered adipocyte physiology, infiltrated macrophages and altered profile of eCBs. We previously reported that DHA is more potent than EPA at modulating systemic inflammation, but the underlying mechanisms remain unclear. The objective of this study was to compare the individual effect of high-dose DHA and of EPA on circulating lipid mediators, i.e. plasma oxylipins and eCBs, and AT-related inflammation. In a randomized double-blind crossover trial, 154 volunteers with abdominal obesity and low-grade inflammation were subjected to three 10-wk supplementation phases: 1- EPA (2.7 g/d); 2- DHA (2.7 g/d); 3- corn oil (control), each separated by a 9-wk washout. Supplements were provided as re-esterified triacylglycerols. Profiling of plasma oxylipins and eCBs was performed on 58 subjects after each phase. Abdominal subcutaneous AT biopsies were also obtained from 13 individuals after each phase. Plasma DHA-, EPA-, arachidonic acid-derived oxylipins were analyzed by LC-MS. eCBs and some of their bioactive congeners were analyzed in plasma and AT by LC-APCI-MS. Adipocyte diameter was determined by histological analysis and AT macrophage infiltration was quantified by double immunofluorescence. Compared with EPA, DHA increased plasma levels of hydroxy-docosahexaenoic acids (7-, 11-, 14-, 4-, 17-HDOHE; P < 0.0001) and palmitoylethanolamide (PEA; P = 0.04). Compared with DHA, EPA led to higher plasma level of hydroxy-eicosapentaenoic acids (12-, 15-, 5-HEPE; P < 0.0001). In the AT, EPA increased the level of oleoylethanolamide (OEA; P = 0.01) compared with DHA, but no other difference was observed between treatments in adipose eCBs and eCB-related lipids. DHA and EPA did not differentially modify adipocyte size distributions (P > 0.50) and proportions of M1-type and M2-type macrophages (P > 0.30). In conclusion, increased plasma levels of anti-inflammatory DHA-derived oxylipins and plasma PEA may be responsible, at least to some extent, for the more potent anti-inflammatory effects of DHA compared with EPA observed in the ComparED study. Conversely, subcutaneous AT does not seem to be involved in explaining such differences between EPA and DHA.

Excess dietary sodium plays an important role in hypertension, a leading risk factor for cardiovascular disease (CVD). To counteract some of the negative effects of sodium, an increased intake of potassium has shown beneficial effects on blood pressure. In fact, the sodium to potassium ratio might be a stronger risk factor for CVD than either sodium or potassium alone. The objective of the present study was to estimate the effect of A) a salt reduction strategy (providing salt reduced bread) and B) a salt reduction and potassium promoting strategy (providing salt reduced bread combined with dietary counselling), on intake of sodium, potassium and the sodium/potassium ratio. The study is a 4-month cluster randomized controlled trial with families randomly assigned to either intervention A, intervention B or control. Participants in intervention A received bread gradually reduced in salt content from 1.2 g salt/100 g to 0.6 g salt/100 g in ryebread and 0.4 g salt/100 g in wheat bread. Participants in intervention B received the same salt reduced bread and in addition dietary counselling on how to eat food with less salt and more potassium. The control group received standard bread (1.2 g salt/100g). Sodium and potassium intake were measured through three consecutive 24-hour urine measurements in adults and one in children at baseline and follow-up. Changes in outcomes were assessed using linear mixed models. Eighty-nine families, including 155 adults (46.5 % men) and 156 children (51.9 % boys), from the suburb of Copenhagen, Denmark, participated in the study. The sodium/potassium ratio was significantly reduced by -0.57 ± 0.19 mmol/L (P = 0.003) in intervention B compared to control group, resulting from a non-significant lower sodium and increased potassium intake. No significant differences were found between intervention A and control group (preliminary results). These findings support future actions to reduce salt intake, focusing on a combination of structural and educational strategies.

The association of MeHg exposure through fish consumption on human autoimmunity remains unclear. Fish also contain n-3 long chain polyunsaturated fatty acids (LCPUFA) that are known to regulate inflammation and mitigate autoimmune disease symptoms. We studied the association of low-level exposure to methylmercury (MeHg) through fish consumption in the SCDS. We examined this association at age 19 years in the SCDS Main Cohort (n = 497). We measured MeHg exposure at 3 time points [prenatal, weighted average (6 months to 19 years) and concurrent (19 years) and LCPUFA status and a panel of 13 autoimmune markers at age 19 years. The autoimmune markers included antinuclear antibodies (ANA), anti-dsDNA and anti-RNP, and total (non-specific) immunoglobulins (Ig) IgG, IgA, and IgM. A combined ANA variable was also calculated based on being within or above reference range for any of the ANA markers; 56% of the subjects met this criterion. Multivariable regression models adjusted for prenatal MeHg, sex and waist circumference, with and without adjustment for LCPUFA, were fit for the three MeHg exposure metrics and each immune marker. Mean (SD) prenatal, weighted average and concurrent MeHg was 6.84 (4.55), 7.46 (2.82), and 10.23 (6.02) ppm, respectively. Combined ANA was positively associated with concurrent MeHg following adjustment for the n6:n3 LCPUFA ratio (β = 0.036, 95%; CI: 0.001, 0.073). Prenatal and average MeHg exposures were not significantly associated with any individual ANA. IgM was negatively associated with concurrent (β = -0.016, 95%CI: -0.016, -0.002), and average (β = -0.042, 95%CI: -0.042, -0.009) MeHg exposure in the models adjusted for n-3, n-6 LCPUFA and when separately adjusted for the n6:n3 LCPUFA ratio. Total (19-year) n-3 PUFA status was negatively associated with anti-RNP (β = -20.355, 95%CI: -36.89, -4.34) and IgG (β = -1.384, 95%CI: -2.682, -0.087). Total n-3 LCPUFA was associated with lower markers of autoimmunity. MeHg exposure at 19 years was associated with higher ANA and lower IgM but only following adjustment for LCPUFA. The clinical significance of these findings is unclear and further research is warranted to determine if these associations precede autoimmune disease development.

Introduction: The Middle East and North Africa region features marked gender excess adiposity inequalities detrimental to women in a context of nutrition transition with major shifts in lifestyle and diet. We assessed gender inequalities in dietary intake with a focus on diet quality. Sociodemographic patterning of these gender dietary inequalities was explored.

Methods: A cross-sectional study in the Greater Tunis region (Tunisia) in 2009–2010 surveyed 20–49 y old adults of both genders (women n = 1689, men n = 930) using a stratified, two-stage cluster sample. Dietary intake was assessed using a 3-day food record. We assessed diet quality by the Diet Quality Index-International (DQI-I) /100 and sub-components (variety, adequacy, moderation, balance); DQI-I > 60 defined good diet quality. Gender inequalities measures were women vs. men differences of means for interval variables and odds-ratios (OR) for DQI-I > 60. Their variation with sociodemographic characteristics were estimated by models featuring gender x covariate interactions.

Results: Mean energy intake in kcal was 2300 ± 15 for women vs. 2859 ± 32 for men. By 1000 g/kcal/day women consumed more fruits and sweets but less red meat and soft drinks than men. Mean DQI-I was lower among women vs. men (58.6 ± 0.3 vs. 60.4 ± 0.3, diff = -1.8[-2.6;-1.0], P < 0.0001) as well as proportion of DQI-I > 60 (45.2% vs. 55.7%, OR = 0.7[0.5;0.8], P < 0.0001). Gender differences varied with the 4 sub-components: women vs. men had lower mean variety (10.1 ± 0.1 vs. 12.1 ± 0.2, diff = -2.0[-2.3;-1.6], P < 0.0001) and adequacy scores (30.8 ± 0.1 vs. 32.5 ± 0.1, diff = -1.8[-2.0;-1.5], P < 0.0001) (for the latter they scored a little better than men for the fruit item, but had much lower scores than men for iron and also calcium). But women scored better than men on the moderation score (14.2 ± 0.2 vs. 12.3 ± 0.2, diff = + 1.8[1.4;2.2], P < 0.0001), mostly due to their better score on the cholesterol and sodium items. There was no difference for the balance subcomponent. Adjusted gender inequalities in DQI-I decreased with age, were higher in larger households and were also higher in the extreme categories of education i.e. no-schooling and university vs. the middle categories.

Conclusions: Diet quality was overall average. It was lower for women than men. Women vs. men differences in diet quality varied somewhat according to sociodemographic indicators linked to different gender roles. We also showed that gender contrasts depend on which dimension of diet quality is considered (better moderation but worse adequacy and variety for women). That maybe a pathway for gender specific prevention.

Vitamin D is vital to bone health and prolonged severe deficiency can lead to rickets in children and osteomalacia/osteoporosis in adults. Vitamin D is an exceptional nutrient in that its main source is exposure of the skin to UV rays, whilst it can also be ingested through diet. This study aimed to investigate the relative contribution of vitamin D supplementation and individual sunlight exposure in raising vitamin D levels, throughout winter, in ethnically identical adult women living in opposite latitudes. Within two parallel placebo-controlled randomized controlled trials (RCT), with identical study designs, 135 Brazilian women, (England, n = 56, 51˚N; Brazil, n = 79, 16˚S), were randomized to receive daily 15 μg vitamin D3 supplements or placebo, for 12 weeks. Oral vitamin D supplementation of 15 μg daily was effective at raising 25-hydroxivitamin D [25(OH)D] concentrations over winter, regardless of latitude, and the response was dependent on baseline vitamin D status. In both latitudes, supplementation prevented the seasonal concomitant increase in plasma parathyroid hormone (PTH) levels. Additionally, the individual UV radiation level was strongly correlated with 25(OH)D concentrations. The research also showed: 1) an optimal vitamin D status for bone health around 70–80 nmol/l; 2) the required UV radiation to achieve this status was 1.5 SED; 3) the vitamin D dietary intakes required to achieve these serum levels were 4.5 μg/d at a low latitude (16˚S) and 37 μg/d at high latitude (51˚N). The strength of these results is the novel analysis that directly links human in vivo individual sunlight radiation, increased vitamin D intake and 25(OH)D status, within two parallel RCTs in opposite latitudes. This study demonstrated that a daily supplement of 15 μg vitamin D3 was an effective strategy to significantly raise vitamin D status throughout the winter months in adult females, with important implications for bone health through the simultaneous lowering of PTH, regardless of latitude. Our data gives a two-fold contribution to the vitamin D field: firstly it will help raise awareness of the risk for vitamin D deficiency in low latitude regions such as most countries in South America as well as amongst South-Americans living in higher latitudes, particularly in the UK; secondly it provides key data for setting appropriate vitamin D recommendations for Brazil (which currently follows US recommendations) as well as for similar latitudes.

Non-nutritive sweeteners (NNS) are suggested to reduce sugar and energy content of diet, but there is growing evidence that they can exacerbate obesity and diabetes through increasing appetite and energy intake. Stevia (stevioside extract), a natural sweetener, is being increasingly consumed, yet limited studies have looked at their effects on satiety and energy intake. The aim of this study is to investigate the effects of preloads of stevia on food intake, satiety and postprandial blood glucose levels when compared to water and sugar. Thirty participants (10 males/20 females; 26 ± 10.5 years; BMI: 23.44 ± 3.42 Kg/m2) took part in a three-arm single-blinded crossover trial. On separate test days, they received three different preloads (300 ml) containing water, sugar (60g) and stevia (1g) followed by an ad-libitum pizza lunch after 30 minutes. Breakfast was standardized. Blood glucose samples were collected before preload and lunch, and then at 30-minute intervals until 120 min post lunch. Volunteers recorded their feelings of satiety and hunger on visual analogue scales (VAS) before preload and after meal intake. A one-day diet diary was collected for each test day. Data was analysed using repeated measures ANOVA (SPSS Inc., Chicago, IL, USA). Despite the difference in energy content between preloads, there were no significant differences in energy intake at lunch between the three interventions (F (2, 56) = 0.25, p = 0.78). Furthermore, participants did not compensate by consuming more energy during the day after the stevia preload (1660 ± 584 Kcal) compared to sugar preload (1770 ± 763 Kcal, p = 0.82). There were no significant differences in VAS scores between stevia and sugar preloads, but participants scored significantly higher rates of hunger (before and after lunch) and desire to eat (before lunch) following water preload (p < 0.05). No significant differences between water, sugar and stevia were noted for postprandial glucose levels (120 min post lunch) when adjusted from baseline (F (2, 58) = 2.56, p = 0.09). Area under the curve (AUC) for glucose did not differ between water and stevia (p = 0.2). Results are in line with several clinical trials showing that the consumption of sweeteners does not lead to an increase in hunger and energy intake, and could therefore present a useful strategy to assist with weight loss. Further studies looking at long-term effects of stevia on weight regulation are needed to support these findings.

The food system is responsible for around 70% of global freshwater use. Pathways toward responsible consumption and production of food are therefore critically needed to ensure the planetary boundary for freshwater use is not transgressed. There is also an uneven spatial distribution of freshwater resources and human water demands, meaning that water-scarcity is acute in some regions but a lesser concern in others. Quantifying the water-scarcity impacts associated with food consumption is therefore a complex challenge due to the diversity of individual eating patterns, the very large number of individual food products available, and the many different regions where food is grown or processed. To our knowledge, this is the first study to calculate water footprints for a large number of self-selected diets. Life cycle assessment was used to model the water-scarcity footprints of 9,341 individual Australian adult diets obtained through 24-hour recall as part of the most recent Australian Health Survey. Three water-scarcity indicators were used, including the AWARE model recently developed by a project group working under the auspices of the United Nations Environment Programme (UNEP) / Society of Environmental Toxicology and Chemistry (SETAC) Life Cycle Initiative (www.lifecycleinitiative.org). In addition, a diet quality score was calculated for each of these diets. Our objective was to identify pathways toward healthier diets with lower water-scarcity impacts. Dietary water-scarcity footprints averaged 362 L-eq person-1 day-1 and were highly variable (sd. 218 L-eq person-1 day-1), reflecting the diversity of eating habits in the general community. The largest water-scarcity impacts were related to the excessive consumption of discretionary foods (alcoholic beverages, processed meat products, dairy desserts, cream, butter, muesli bars, confectionery, chocolate, biscuits, cakes, waffles, fried potato and extruded snacks, etc.). The potential to reduce dietary water-scarcity impacts is large, although the opportunity to intervene through amended dietary guidelines is not straightforward due to the large variations in water-scarcity footprint intensity between individual foods within a food group, and the inability of consumers to identify lower water-scarcity footprint products without food labeling. Reductions in the water-scarcity footprint of Australian food consumption are likely best achieved through reductions in food waste, technological change to improve water-use efficiency in food production, as well as the implementation of product reformulation and procurement strategies in the food manufacturing sector to avoid higher water-scarcity footprint intensity ingredients.

Breakfast cereals are known to provide a nutrient-dense meal and are a useful source of carbohydrate, fibre and micronutrients. However, in the UK cereal products are the primary contributor of free sugars in the diets of children aged 1.5 to 10 years; and are the second leading source of free sugars in children aged 11 to 18 years and adults aged 19 to 64 years. For this reason, breakfast cereals were included among food items recommended by the UK government for a 20% reduction in sugar by 2020 for childhood obesity prevention. Therefore, this study aimed to investigate the nutrient contents, including sugars, of breakfast cereals sold in the UK, in particular those marketed to children. Nutritional information and ingredients of cereal products available in five major online supermarkets in the UK, in 2018, were collected into a comprehensive database for analysis. A systematic process flow approach was utilised to separate products into nine distinct categories. Children's products were stratified both on being wholegrain rich (≥ 50%, WG) or not (NWG), and on total sugar content; with > 12.3g/100 g defined as ‘highly flavoured and sweetened’ (HFS) versus ‘plain’ containing ≤ 12.3g/100 g (the target set by the UK for industry sugar reduction). Of the 757 unique products surveyed, 97 cereals were categorised as children's. Cereals not explicitly marketed to children were categorised as either ‘family favourites’ (containing < 50% wholegrains), ‘free-from and organic’, ‘porridge and oats’, ‘healthier with dried fruits’, or ‘healthier without dried fruits’ (healthier defined as wholegrain rich, ≥ 50%). Children's HFS products (n = 78) contained by far the highest sugar contents of all cereals examined. While there was no difference in total sugar between NWG/HFS (n = 69, median [range]: 29.0g/100 g [12.4, 41.0]) and WG/HFS (n = 9, 22.0g/100 g [13.6, 26.0]) cereals; these were much higher (P < 0.01) than the median sugar contents (8.8–19.0g/100g) observed in the other seven product categories. Children's NWG cereals contained dramatically lower fibre (NWG/HFS: 3.5 [0, 8.7], NWG/Plain: 1.6g/100 g [1.3, 7.2]) than all other product categories (7.3–9.1g/100 g; P < 0.001). Similarly, NWG/HFS cereals were lower in protein content (7.4/100 g [3.6, 17.2]) than the non-children's cereals (8.8–11g/100 g; P < 0.05). In conclusion, children's categories of cereal contain significantly greater amounts of sugar and lower amounts of fibre and protein than other cereal categories. Despite their fortification with vitamins and minerals, reformulation of this food category should be a priority alongside additional sugar-reducing strategies.

D-Fagomine (1,2 dideoxynojirimycin) is an iminosugar, a carbohydrate analogue that includes an endocyclic nitrogen instead of oxygen, that is naturally present in buckwheat and buckwheat-based foodstuffs. This study examines the long-term functional effect of d-fagomine on sucrose-induced factors of metabolic syndrome and explores possible molecular mechanisms behind its action. We evaluated Wistar Kyoto rats fed a standard diet were given a 35% sucrose (glucose/fructose) solution with d-fagomine (or not, for comparison) or mineral water (controls) for 24 weeks. The variables measured were body weight and energy intake; glucose tolerance (oral glucose tolerance test); plasma leptin concentration; plasma lipid profile; the populations of Bacteroidetes, Firmicutes, bacteroidales, clostridiales, enterobacteriales, and Escherichia coli in feces; blood pressure; urine uric acid and F2t isoprostanes (F2-IsoPs); perigonadal fat deposition and hepatic histology and diacylglycerols (DAGs) in liver and adipose tissue. We found that d-Fagomine reduced sucrose induced hypertension, urine uric acid, F2-IsoPs as markers of oxidative stress (OS), steatosis and liver DAGs (32:1, 32:2, 34:1 and 36:2) without affecting perigonadal (visceral) fat deposition or DAG levels in visceral adipose tissue. It showed a slight tendency to reduce sugar induced impaired glucose tolerance. d-Fagomine also promoted excretion of enterobacteriales generated by the dietary intervention. We postulate that fructose increases visceral fat deposition independently of liver de novo liposynthesis and that d-fagomine attenuates steatosis and blood pressure mainly by reducing liver fructose levels. The reduction of blood pressure may be associated with an effect on uric acid synthesis while the reduced levels of selected active liver DAGs may explain the weak effect on sucrose-induced impaired glucose tolerance, which may be primarily induced by visceral fat deposition. In conclusion, the increased populations of excreted enterobacteriales may be connected to the levels of excreted uric acid. d-Fagomine counteracts sucrose-induced steatosis and hypertension presumably by reducing the postprandial levels of fructose in the liver as a consequence of intestinal sucrase inhibition.

Several dietary factors have been extensively investigated for associations with risk of breast cancer, but to date unequivocal evidence only exists for alcohol consumption. We sought to systematically evaluate the association between 92 dietary factors and breast cancer risk using a nutrient-wide association study approach. Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression with age as the time scale and adjustment for potential confounders, was used to quantify the association between each food or nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to evaluate in the independent replication cohort, the Netherlands Cohort Study (NLCS). During a median follow-up time of 15 years, 10,979 incident invasive breast cancers were identified in the women from the EPIC study. Six foods and nutrients were associated with risk of breast cancer when controlling the FDR at 0.05. Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% confidence interval (CI) 1.03–1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03–1.06 and 1.04, 95% CI 1.02–1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94–0.98; 0.96, 95% CI 0.94–0.99; and 0.96, 95% CI 0.95–0.98, respectively). When evaluated in the NLCS (2368 invasive breast cancer cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk of breast cancer in the NLCS. Our findings confirm the well-established increased risk of breast cancer associated with alcohol consumption, and suggest that higher intake of dietary fibre, and possibly fruit and carbohydrates, might be associated with reduced breast cancer risk.

Recently, increased attention has been drawn to the composition of the intestinal microbiota and its possible role in metabolic syndrome and type 2 diabetes (T2DM). However, potential variation in gut microbiota composition across ethnic groups is rarely considered despite observed unequal prevalence for these diseases. Our objective was therefore to study the gut microbiota composition across health, metabolic syndrome and T2DM in a multi-ethnic population residing in the same geographical area. 16S rRNA gene sequencing was performed on fecal samples from 3926 participants to the HELIUS cohort (Amsterdam, The Netherlands), representing 6 ethnic groups (Dutch, Ghanaians, Moroccans, Turks, Surinamese of either African or South-Asian descent). Included participants completed a questionnaire and underwent a physical examination and overnight fasted blood sampling. Gut microbiota composition was compared across metabolic status (diabetes with and without metformin use, metabolic syndrome and its subsequent components, health) and ethnicities using Wilcoxon-Mann-Withney tests and logistic regressions. Overall, the gut microbiota alpha-diversity (richness, Shannon index and phylogenetic diversity) decreased with worsening of the metabolic state (comparing health to metabolic syndrome to T2DM) but this was only partially reproduced in ethnic-specific analyses. In line, a lower alpha-diversity was found in relation to all metabolic syndrome components as well as in T2DM subjects using metformin compared to non-users. Alterations, mainly decreased abundances, were also observed at the genus level (many Clostridiales) in metabolic syndrome subjects and more strongly in T2DM subjects with differences across ethnic groups. In particular, we observed decreased abundances of members of the Peptostreptococcaceae family and of Turicibacter and an increased abundance of a member of the Enterobacteriaceae family. Our data highlight several compositional differences in the gut microbiota of individuals with metabolic syndrome or T2DM. These features, confirming prior observations, give some insights into potential key intestinal bacteria related to a worsening of metabolic state. Our results also underscore possible ethnic-specific profiles associated with these microbiota alterations that should be further explored.