European Journal of Nutrition (v.57, #6)

A systematic review of vitamin D status in southern European countries by Yannis Manios; George Moschonis; Christina-Paulina Lambrinou; Konstantina Tsoutsoulopoulou; Panagiota Binou; Alexandra Karachaliou; Christina Breidenassel; Marcela Gonzalez-Gross; Mairead Kiely; Kevin D. Cashman (2001-2036).
Despite an acknowledged dearth of data on serum 25-hydroxyvitamin D (25(OH)D) concentrations from Southern European countries, inter-country comparison is hampered by inconsistent data reporting. The purpose of the current study was to conduct a systematic literature review of available data on serum 25(OH)D concentrations and estimate vitamin D status in Southern European and Eastern Mediterranean countries, both at a population level and within key population subgroups, stratified by age, sex, season and country.A systematic review of the literature was conducted to identify and retrieve scientific articles reporting data on serum 25(OH)D concentration and/or vitamin D status following standard procedures.Data were extracted from 107 studies, stratified by sex and age group, representing 630,093 individuals. More than one-third of the studies reported mean 25(OH)D concentrations below 50 nmol/L and ~ 10% reported mean serum 25(OH)D concentrations below 25 nmol/L. Overall, females, neonates/ infants and adolescents had the higher prevalence of poor vitamin D status. As expected, there was considerable variability between studies. Specifically, mean 25(OH)D ranged from 6.0 (in Italian centenarians) to 158 nmol/L (in elderly Turkish men); the prevalence of serum 25(OH)D < 50 nmol/L ranged from 6.8 to 97.9% (in Italian neonates).Contrary to expectations, there was a high prevalence of low vitamin D status in the Southern Europe and the Eastern Mediterranean regions, despite abundant sunshine. These data further emphasize the need for strategies, such as fortification of foods with vitamin D and/or vitamin D supplementation, which will be tailored to the needs of specific population groups with higher risk of insufficiency or deficiency, to efficiently tackle the pandemic of hypovitaminosis D in Europe.
Keywords: Vitamin D; South Europe; East Mediterranean; Prevalence

Effect of probiotics and synbiotics consumption on serum concentrations of liver function test enzymes: a systematic review and meta-analysis by Saman Khalesi; David Wayne Johnson; Katrin Campbell; Susan Williams; Andrew Fenning; Sonia Saluja; Christopher Irwin (2037-2053).
The gut–liver interaction suggests that modification of gut bacterial flora using probiotics and synbiotics may improve liver function. This systematic review and meta-analysis aimed to clarify the effect of probiotics and synbiotics consumption on the serum concentration of liver function enzymes. PubMed (MEDLINE), Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library (Central) were searched from 1980 to August 2017 for studies where adults consumed probiotics and/or synbiotics in controlled trials and changes in liver function enzymes were examined.A total of 17 studies (19 trials) were included in the meta-analysis. Random effects meta-analyses were applied. Probiotics and synbiotics significantly reduced serum alanine aminotransferase [− 8.05 IU/L, 95% confidence interval (CI) − 13.07 to − 3.04; p = 0.002]; aspartate aminotransferase (− 7.79 IU/L, 95% CI: − 13.93 to − 1.65; p = 0.02) and gamma-glutamyl transpeptidase (− 8.40 IU/L, 95% CI − 12.61 to − 4.20; p < 0.001). Changes in the serum concentration of alkaline phosphatase and albumin did not reach a statistically significant level. Changes to bilirubin levels were in favour of the control group (0.95 μmol/L, 95% CI 0.48–1.42; p < 0.001). Subgroup analysis suggested the existence of liver disease at baseline, synbiotics supplementation and duration of supplementation ≥ 8 weeks resulted in more pronounced improvement in liver function enzymes than their counterparts.Probiotics and synbiotics may be suggested as supplements to improve serum concentration of liver enzymes, especially when synbiotics administered for a period ≥ 8 weeks and in individuals with liver disease.
Keywords: Liver function; Liver enzyme; Probiotics; Synbiotics; Systematic review

Associations between fruit and vegetable variety and low-grade inflammation in Portuguese adolescents from LabMed Physical Activity Study by Juliana Almeida-de-Souza; Rute Santos; Luis Lopes; Sandra Abreu; Carla Moreira; Patrícia Padrão; Jorge Mota; Pedro Moreira (2055-2068).
The dietary guidelines for the consumption of a variety of fruits and vegetables have been recognized as an important factor for achieving healthy eating patterns to reduce the risk of chronic disease throughout the lifespan. Our aim is to assess the association between fruit and vegetable variety and low-grade inflammation in adolescents.This cross-sectional analysis was conducted with 412 adolescents (ages 14.4 ± 1.7 years; 52% girls). The consumption of a variety of fruits and vegetables was assessed with a food-frequency questionnaire, considering the number of individual/category of fruit or vegetable intake at least once month, and categorized into tertiles. Blood samples were collected to determine C-reactive protein (CRP), interleukin-6 (IL-6), complement component 3 (C3), and 4 (C4). We created categories of lower or higher (inflammatory state) for each biomarker, considering sex- and age-adjusted median values. Then, we computed an overall inflammatory score, by adding all points awarded wherein one point was assigned if biomarker was higher or zero if lower, and created categories of 0–1 or 2–4 biomarkers above the median. The odds ratio (OR) and 95% interval confidence (95% CI) were calculated from binary logistic regression to estimate the magnitude of association between fruit and vegetable variety and inflammatory biomarkers.Adolescents with a greater variety of vegetable consumption (≥13 categories/month) had lower odds of having a higher CRP (OR 0.31, 95% CI 0.15–0.64, p trend = 0.004) when compared to those with lower variety consumption (≤6 categories/month), independent of vegetable quantity intake. However, a greater variety of fruit consumption (≥12 categories/month) had higher odds of having a higher IL-6 (OR 4.41, 95% CI 1.67–11.71, p trend = 0.012), C3 (OR 3.30, 95% CI 1.23–8.86, p trend = 0.047), and inflammatory score (OR 4.90, 95% CI 1.62–14.86, p trend = 0.017), when compared to those with lower variety consumption (≤9 categories/month), independent of fruit quantity intake, only for girls.The consumption of a variety of vegetables is inversely associated with lower CRP. This finding supports the current dietary guidelines regarding the consumption of a variety of vegetables. The role of fruit variety in low-grade inflammation should be further studied.
Keywords: C-reactive protein; Interleukin 6; Complement C3; Complement C4; Inflammatory score; Variety of diet

The effect of almonds on vitamin E status and cardiovascular risk factors in Korean adults: a randomized clinical trial by Hana Jung; C.-Y. Oliver Chen; Jeffrey B. Blumberg; Ho-Kyung Kwak (2069-2079).
Almonds have shown to beneficially modify some cardiovascular risk factors in clinical trials conducted in diverse ethnic populations but this relationship has never been tested in Koreans. Thus, we tested the impact of almonds consumed as a snack within the context of a typical Korean diet on cardiovascular risk factors.We conducted a randomized, crossover trial in a free-living setting with a 2-week run-in period, two 4-week intervention phases, and a 2-week washout period between interventions. Eighty four overweight/obese participants (11 M/73 F; 52.4 ± 0.6 year; 25.4 ± 0.22 kg/m2) consumed either 56 g of almonds or isocaloric cookies daily for 4 weeks.Mean % daily energy intake at baseline was 64.8, 21.3, and 14.9% from carbohydrate, fat, and protein, respectively. The addition of 56 g of almonds daily decreased carbohydrate energy to 55.0%, increased fat to 32.0%, and maintained protein at 14.7%. Consuming the almonds increased intake of MUFA by 192.3%, PUFA by 84.5%, vitamin E by 102.7%, and dietary fiber by 11.8% and decreased % energy from carbohydrate by 14.1%. Total caloric intake was increased by the almonds, but body weight, waist circumference, and body composition were not affected. Almonds in overweight and obese Korean adults decreased TC, LDL-C, and non-HDL-C by 5.5, 4.6, and 6.4%, respectively, compared to the cookie control (P ≤ 0.05). Almonds increased plasma α-tocopherol by 8.5% (P ≤ 0.05) from the baseline and tended to increase its value as compared to cookies (P = 0.055). Neither the almonds nor cookies altered plasma protein carbonyls, MDA or oxLDL. Of serum inflammatory markers, IL-10 was decreased by almond intake (P ≤ 0.05), and ICAM-1, IL-1β, and IL-6 tended to be lower with almonds, compared to the cookies.Almonds at 56 g/day consumed as a snack favorably modified the Korean diet by increasing MUFA, PUFA, vitamin E, and dietary fiber intake and decreasing % energy intake from carbohydrate. Almonds also enhanced plasma α-tocopherol status and serum TC and LDL-C in overweight and obese Koreans. Thus, including almonds in typical Korean diets as a snack can help healthy overweight/obese individuals improve nutritional status and reduce their risk for CVD.
Keywords: Almonds; Cholesterol; α-Tocopherol; Cardiovascular risk factor; Oxidative stress; Inflammation; Human

Amelioration of obesity-related characteristics by a probiotic formulation in a high-fat diet-induced obese rat model by Joo-Hyun Shin; Myung Hee Nam; Hyerim Lee; Joong-Su Lee; Hojun Kim; Myung-Jun Chung; Jae-Gu Seo (2081-2090).
Obesity is a major public health concern. Despite its multi-factorial etiology, alterations in intestinal microbiota and the immune system are frequently observed. We investigated the effect of Duolac Gold (DG), a probiotic formulation containing 2 Lactobacillus strains (L. acidophilus LA1 and L. rharmnosus LR5), 3 Bifidobacterium (B. bifidum BF3, B. lactis BL3, and B. longum BG7), and Streptococcus thermophilus ST3, on morphometric and metabolic parameters, intestinal microbiota, and intestinal immune responses in a high-fat diet (HFD)-induced obese rat model.Rats received either a conventional balanced diet or HFD with or without water containing DG for 8 weeks. HFD-induced adiposity, intestinal microbiota, and changes in inflammatory cytokine, chemokine, and metabolite levels in serum were evaluated.DG administration effectively decreased HFD-induced body weight and modulated morphometric and metabolic parameters. Quantitative analysis of fecal microbiota showed that obese rats given DG exhibited significantly increased levels of Bacteroidetes, Lactobacillus, and Bifidobacterium, with significant decreases in the level of Firmicutes. Serum levels of the inflammatory cytokines and the chemokine were also altered. Serum metabolite analysis revealed that DG administration modulated HFD-induced changes in serum metabolites, including fatty acids (FA), lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidylcholine (PC), and triacylglycerol (TAG).DG administration appears to have the potential to alleviate HDF-induced obesity through the modulation of intestinal microbiota, immune responses, and host metabolism, which supports the use of probiotics to treat obesity.
Keywords: Probiotics; High-fat diet; Obesity; Intestinal microbiota

Chronic treatment with prebiotics, probiotics and synbiotics attenuated cardiac dysfunction by improving cardiac mitochondrial dysfunction in male obese insulin-resistant rats by Wannipa Tunapong; Nattayaporn Apaijai; Sakawdaurn Yasom; Pongpan Tanajak; Keerati Wanchai; Titikorn Chunchai; Sasiwan Kerdphoo; Sathima Eaimworawuthikul; Parameth Thiennimitr; Anchalee Pongchaidecha; Anusorn Lungkaphin; Wasana Pratchayasakul; Siriporn C. Chattipakorn; Nipon Chattipakorn (2091-2104).
In metabolic syndrome, the composition of gut microbiota has been disrupted, and is associated with left ventricular (LV) dysfunction. Several types of prebiotics, probiotics, and synbiotics have been shown to exert cardioprotection by restoring gut microbiota from dysbiosis and reducing systemic inflammation. However, the effects of prebiotics such as xylooligosaccharides (XOS); probiotics such as Lactobacillus paracasei STII01 HP4, and synbiotics on metabolic and LV function in obese insulin-resistant rats have not been investigated. In this study, we hypothesized that prebiotics and probiotics improve metabolic parameters, heart rate variability (HRV), blood pressure (BP), and LV function by attenuating cardiac mitochondrial dysfunction, systemic inflammation, and oxidative stress, and that synbiotics provide greater efficacy than a single regimen in obese insulin resistance.Rats were fed with either normal diet or high-fat diet (HFD) for 12 weeks and then rats in each dietary group were randomly subdivided into four subgroups to receive either a vehicle, prebiotics, probiotics, or synbiotics for another 12 weeks. Metabolic parameters, BP, HRV, LV function, cardiac mitochondrial function, systemic inflammation, and oxidative stress were determined.HFD-fed rats had obese insulin resistance with markedly increased systemic inflammatory marker [Serum LPS; ND; 0.6 ± 0.1 EU/ml vs. HFD; 5.7 ± 1.2 EU/ml (p < 0.05)], depressed HRV, and increased BP and LV dysfunction [%ejection fraction; ND; 93 ± 2% vs. HFD; 83 ± 2% (p < 0.05)]. Prebiotics, probiotics, and synbiotics attenuated insulin resistance by improving insulin sensitivity and lipid profiles. All interventions also improved HRV, BP, LV function [%ejection fraction; HFV; 81 ± 2% vs. HFPE; 93 ± 3%, HFPO; 92 ± 1%, HFC; 92 ± 2% (p < 0.05)] by attenuating mitochondrial dysfunction, oxidative stress, and systemic inflammation in obese insulin-resistant rats.Prebiotics, probiotics, and synbiotics shared similar efficacy in reducing insulin resistance and LV dysfunction in obese insulin-resistant rats.
Keywords: Prebiotics; Probiotics; Synbiotics; Obese insulin resistance; Cardiac mitochondria; Systemic inflammation

Transport of long-chain polyunsaturated fatty acids in preterm infant plasma is dominated by phosphatidylcholine by Wolfgang Bernhard; Christoph Maas; Anna Shunova; Michaela Mathes; Katrin Böckmann; Christine Bleeker; Julia Vek; Christian F. Poets; Erwin Schleicher; Axel R. Franz (2105-2112).
Docosahexaenoic (C22:6) and arachidonic (C20:4) acids are long-chain polyunsaturated fatty acids (LC-PUFA) essential to neonatal development, being present in the glycerophospholipids of all organs, particularly the brain. In plasma, LC-PUFAs are mainly present in lipoprotein lipids, which are neutral lipids (triglycerides and cholesterol esters) and glycerophospholipids, like choline containing phosphatidylcholine (PC).To guide future supplementation strategies of C22:6 and C20:4 in combination with choline, we determined the distribution of C20:4 and C22:6 between PC and neutral lipid.Preterm infant plasma (N = 59, postmenstrual age [PMA] 33.9 wk (32.4–36.0)) and cord plasma (N = 34, PMA 34.0 wk (30.86–38.4)) were investigated. PC and neutral lipids were extracted and analyzed using tandem mass spectrometry and gas chromatography, respectively. Data are reported as medians and 25th/75th percentiles.In cord blood, C20:4-PC and C22:6-PC comprised 36.1% (34.2–38.6) and 10.2% (8.8–12.8) of total PC, respectively. In preterm infant plasma, values were only 20.8% (19.2–23.1) and 5.7% (5.2–6.0), respectively (p < 0.001 each). Nevertheless, in preterm infant plasma, 80.6% (77.6–83.0) of C20:4 and 86.0% (83.0–88.9) of C22:6 were found in PC. These values exceeded the proportions of C20:4 and C22:6 in PC of cord plasma [71.3% (67.8–72.9) and 79.2% (75.2–85.4), respectively] (p < 0.0001 each).Irrespective of the low proportions of C20:4-PC and C22:6-PC in preterm infant plasma lipids, PC is the major transporter for C20:4 and C22:6. Our data support the hypotheses that choline deficiency may impair end-organ availability of these LC-PUFA in preterm infants. Therefore, supplementation of C20:4 and C22:6 might better be accompanied by choline supplementation.
Keywords: Arachidonic acid; Choline deficiency; Docosahexaenoic acid; Neonate; Neurological development; Polyunsaturated fatty acids; Preterm infants; LC-PUFA transport

Soft drinks consumption is associated with nonalcoholic fatty liver disease independent of metabolic syndrome in Chinese population by Ge Meng; Bo Zhang; Fei Yu; Chunlei Li; Qing Zhang; Li Liu; Hongmei Wu; Yang Xia; Xue Bao; Hongbin Shi; Qian Su; Yeqing Gu; Liyun Fang; Huijun Yang; Bin Yu; Shaomei Sun; Xing Wang; Ming Zhou; Qiyu Jia; Huanli Jiao; Bangmao Wang; Qi Guo; Livia A. Carvalhoa; Zhong Sun; Kun Song; Ming Yu; Kaijun Niu (2113-2121).
Excessive consumption of soft drinks is associated with nonalcoholic fatty liver disease (NAFLD). However, the association between soft drinks consumption and NAFLD is unclear in non-Caucasian adults with relatively low soft drinks consumption. The aim of this study was to assess the association between soft drinks consumption and NAFLD in Chinese adults.A cross-sectional study was conducted with 26,790 adults living in Tianjin, China. NAFLD (with elevated alanine aminotransferase [ALT]) was diagnosed by the liver ultrasonography and serum ALT concentrations. Soft drinks consumption was assessed using a validated self-administered food frequency questionnaire, and it was summarized as three categories for analysis: almost never (reference), <1 cup/week, and ≥1 cups/week. Metabolic syndrome (MetS) was defined according to the criteria of the American Heart Association scientific statements of 2009. The association between soft drinks consumption and NAFLD was assessed by multiple logistic regression analysis.The prevalence of NAFLD and NAFLD with elevated ALT was 27.1 and 6.5%, respectively. After adjustment for potential confounding variables (including MetS), the odds ratios (95% confidence intervals) for NAFLD or NAFLD with elevated ALT across soft drinks consumption were 1.00 (reference) for almost never, 1.14 (1.02–1.27) or 1.16 (0.98–1.37) for <1 cup/week, and 1.26 (1.14–1.40) or 1.32 (1.13–1.53) for ≥1 cups/week (both P for trend <0.001), respectively.This is the first study to demonstrate that soft drinks consumption is associated with NAFLD independent of MetS in Chinese adults with relatively low soft drinks consumption. These results suggest that reducing soft drinks consumption might be beneficial to the prevention of NAFLD.
Keywords: Alanine aminotransferase; Metabolic syndrome; Nonalcoholic fatty liver disease; Soft drinks

Habitual consumers of different coffee types may vary in socioeconomic status (SES), which is an important determinant of diet quality. Nonetheless, research on diet quality among coffee consumers was scarce. We aimed to compare the diet quality of coffee consumers with different preferences towards coffee type and additive usage.In this cross-sectional analysis, intake data of food, coffee, and additive usage from the adult respondents of the 2011–2012 Australian Health Survey were used. Participants were grouped according to the type of coffee (espresso and ground coffee, E&G; coffee made from coffee mixes and instant coffee, M&I; non-consumers, NC) and additives (milk, sugar, and intense sweetener) consumed. Adjusted food group intake was compared between consumption groups using general linear model.E&G drinkers had better SES than M&I and NC. After adjusting for covariates, the mean dairy intake of E&G drinkers was 22.2% higher than M&I drinkers (p < 0.001) and 33.1% higher than NC (p < 0.001). Mean discretionary food intake of E&G drinkers was 12.1% lower than M&I (p = 0.003) and 12.3% lower than NC (p = 0.001). In terms of additive usage, non-users of coffee additive had the lowest dairy food intake and the highest discretionary food intake.Coffee consumers’ different preferences towards coffee type and additive usages reflected significant variations in their diet quality, even after adjustment of SES. Therefore, future epidemiological studies should consider separating coffee drinkers according to their habitual consumption of different types of coffee.
Keywords: Coffee type; Diet quality; Sugar; Australia; Coffee additive; Coffee

Serum antioxidant capacity, biochemical profile and body composition of breast cancer survivors in a randomized Mediterranean dietary intervention study by Maria Skouroliakou; D. Grosomanidis; P. Massara; C. Kostara; P. Papandreou; D. Ntountaniotis; G. Xepapadakis (2133-2145).
Increasing evidence suggests that Mediterranean Diet (MD) is correlated with reduced risk of breast cancer (BC) and cancer mortality, since it modifies patients’ serum antioxidant capacity, body composition and biochemical parameters. The aim of the study was to investigate whether a dietary intervention based on MD has a beneficial effect on these factors.In this intervention study, seventy female BC survivors were randomly assigned to (1) the intervention group (personalized dietary intervention based on MD) and (2) the control group (received the updated American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and ad libitum diet). Both groups were assessed twice [beginning, end of study (after 6 months)] regarding their anthropometric and biochemical parameters, serum vitamin C, vitamin A, a-tocopherol and CoQ10 levels, dietary intake and adherence to MD. An additional intermediate analysis was conducted on participants’ body composition and biochemical profile.Concerning the intervention group, body weight, body fat mass, waist circumference, body mass index as well as HDL-cholesterol were significantly decreased (P < 0.2%). An increase was observed in the vitamin C levels in blood (P < 0.2%). In the control group, body weight, body fat mass and serum total cholesterol rose (P < 0.2%). At the end of the study the two groups were significantly different considering blood glucose, vitamin C, polyunsaturated fatty acids, vitamin A and a-tocopherol levels.This randomized dietary intervention based on MD managed to ameliorate serum antioxidant capacity, body composition, adherence to MD and glycemic profile of postmenopausal BC survivors.
Keywords: Breast cancer survivors; Mediterranean diet; Dietary antioxidants; Body composition; Biochemical profile

We aimed to systematically review available data on the association between adherence to MD and BMD as well as risk of fractures and to summarize this information through a meta-analysis.Previous studies in the field of adherence to MD in relation to BMD and risk of fracture were selected through searching PubMed, Scopus, ISI Web of Science and Google Scholar databases prior to June, 2016 using Mesh and non-Mesh relevant keywords.In the meta-analysis of four effect sizes, obtained from three studies, we found that adherence to MD was associated with a 21% reduced risk of hip fracture (overall RR 0.79; 95% CIs 0.72–0.87). Adherence to MD was positively associated with lumber spines (mean difference of BMD comparing highest and lowest categories of MD score 0.12; 95% CI 0.06–0.19 g/cm2), femoral neck (0.10; 0.06–0.15 g/cm2) and total hip (0.11; 0.09–0.14 g/cm2) BMD. Meta-regression of included observational studies revealed a significant inverse linear association between Mediterranean diet score and risk of hip fracture, such that one unit increase in the score of Mediterranean diet was associated with a reduction in the risk of hip fracture (RR 0.95, 95% CI 0.92–0.98 p = 0.01).Adherence to MD was associated with a reduced risk of fracture as well as with a higher mean BMD.
Keywords: Mediterranean diet; Fracture; Bone mineral density; Meta-analysis; Systematic review

Cellular zinc homeostasis modulates polarization of THP-1-derived macrophages by Laura Dierichs; Veronika Kloubert; Lothar Rink (2161-2169).
Polarization of macrophages by environmental stimuli leads to the characteristic of different phenotypes that exhibit distinct functions, ranging in a continuous spectrum from pro-inflammatory M1 up to immunoregulatory and wound-healing M2 macrophages. Diseases like cancer, allergic asthma or diabetes are associated with an M1/M2 imbalance. Owing to the importance of the essential trace element zinc for the immune system and its involvement in signal transduction as a second messenger, we investigated the impact of zinc on M1 and M2 polarization of macrophages in vitro.A polarization model with human THP-1 cells was established and validated with previously described markers using quantitative real-time PCR, Western blot and flow cytometry. Intracellular free Zn2+ was determined with FluoZin-3-AM.Whereas pSTAT1 and HLA-DR or pSTAT6 and Dectin-1 distinguish between M1 and M2 macrophages, respectively, CD86 and CD206 failed. Depending on the used markers, both zinc supplementation in physiological dose (50 µM) and zinc deficiency promote M1 polarization of THP-1-derived macrophages. Furthermore, zinc supplementation strongly inhibits M2 polarization.For the first time, we show a modulating effect of zinc for the polarization of human macrophages. The strong inhibitory effect of zinc supplementation on M2 polarization indicates a relevance regarding M2-dominated diseases like allergic asthma or cancer. All in all, zinc achieves a great potential for modulating macrophage polarization.
Keywords: Zinc; NaCl; Macrophage polarization; M1; M2

Chronic consumption of fructose in combination with trans fatty acids but not with saturated fatty acids induces nonalcoholic steatohepatitis with fibrosis in rats by Sugeedha Jeyapal; Uday Kumar Putcha; Venkata Surekha Mullapudi; Sudip Ghosh; Anil Sakamuri; Suryam Reddy Kona; Sai Santosh Vadakattu; Chandana Madakasira; Ahamed Ibrahim (2171-2187).
Consumption of Western diet high in fat and fructose has been attributed to the recent epidemic of nonalcoholic fatty liver disease (NAFLD). However, the impact of specific fatty acids on the progression of NAFLD to nonalcoholic steatohepatitis (NASH) is poorly understood. In the present study, we investigated the chronic effects of consumption of fructose in combination with saturated fatty acids (SFA) or trans fatty acids (TFA) on the development of NAFLD.Male Sprague–Dawley rats were randomly assigned to six isocaloric starch/high fructose (44% of calories), high fat (39% calories) diet containing either starch–peanut oil, fructose–peanut oil, fructose–palmolein, fructose–clarified butter, fructose–coconut oil or fructose–partially hydrogenated vegetable oil and fed for 24 weeks. Palmolein, clarified butter and coconut oil were used as the source of SFA whereas partially hydrogenated vegetable oil was used as the source of TFA. Peanut oil was used as the reference oil.Long-term feeding of fructose in combination with SFA or TFA induced hepatic steatosis of similar extent associated with upregulation of stearoyl CoA desaturase-1. In contrast, fructose in combination with TFA induced NASH with fibrosis as evidenced by upregulation of hepatic proinflammatory cytokine and fibrogenic gene expression, increased hepatic oxidative stress and adipocytokine imbalance. Histopathological analysis revealed the presence of NASH with fibrosis. Further, peanut oil prevented the development of NAFLD in fructose-fed rats.Fructose in combination with TFA caused NASH with fibrosis by inducing oxidative stress and inflammation, whereas, fructose in combination with SFA caused simple steatosis, suggesting that the type of fatty acid is more important for the progression of NAFLD.
Keywords: Western diet; High fructose; High fat; Saturated fatty acids; Trans fatty acids; Inflammation; Oxidative stress; Gene expression; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Fibrosis

The dietary form of choline during lactation affects maternal immune function in rats by N. S. Dellschaft; C. Richard; E. D. Lewis; S. Goruk; R. L. Jacobs; J. M. Curtis; C. J. Field (2189-2199).
The present study was designed to determine the effects of both choline form and availability on maternal immune function during lactation.Sprague–Dawley rats were randomized to one of the three diets 24–48 h before parturition and fed ad libitum until 21 days postnatal: 1 g/kg choline as free choline (C, n = 11), the current form, and amount of choline in commercial diets; 1 g/kg choline as phosphatidylcholine (PC1, n = 11); or 2.5 g/kg choline as PC (PC2.5, n = 8). Choline metabolites in offspring stomach contents were quantified. At 21 days, lymphocytes from mothers’ mesenteric lymph nodes and spleens were isolated and phenotypes and ex vivo cytokine production after mitogen exposure were determined.There was a higher proportion of choline and a lower proportion of lyso-PC in stomach contents (representing dam’s milk) of C pups compared to PC1. In the mesenteric lymph nodes, feeding PC1 compared to C led to a higher IL-2 production after Concanavalin A (ConA) stimulation and a higher proportion of T cells (CD3+) and a lower proportion of B cells [immunoglobulin (Ig)κ, CD45RA+, and IgM+; P < 0.05]. Splenocytes from the PC1 group produced more IL-6 and TNF-α after lipopolysaccharides stimulation compared to C (P < 0.05). Splenocytes from the PC2.5 group produced more IL-2 and IL-6 after ConA stimulation compared to PC1 (P < 0.05).Feeding choline as PC in the maternal diet improved the ability of immune cells to respond ex vivo to mitogens and increasing the amount of PC in the diet further improved T cell proliferation.
Keywords: Lactation; Choline; Phosphatidylcholine; Immune function; Mesenteric lymphocytes; Splenocytes

Whole grain exhibits potential for regulating lipid levels, possibly because of its antioxidant activity. This study aims to investigate the antioxidant activity of whole grain highland hull-less barley (WHLB) and its effect on liver protein expression profiles in rats fed with high-fat diets.Antioxidant activity of WHLB was investigated in vitro by analyzing phenolic and pentosan contents and oxygen radical absorbance capacity (ORAC). Proteins involved in lipid regulation were investigated in vivo by analyzing liver protein expression profiles in Sprague–Dawley rats fed with high-fat diet (HFD) with or without WHLB.WHLB possessed high total phenolic content (259.90 mg/100 g), total pentosan content (10.74 g/100 g), and ORAC values (418.05 ± 5.65 μmol/g). Rats fed with WHLB diet exhibited significantly (P < 0.05) lower liver lipid levels than those fed with the control HFD diet. Seven differentially expressed proteins were detected through liver proteome analysis and were found to be correlated with 11 pathways, including lipid metabolism, through annotation with Kyoto Encyclopedia of Genes and Genomes. Quantitative real-time polymerase chain reaction analysis showed that rats given with WHLB diet exhibited down-regulated expression of heat shock protein 60 (HSP60) and phosphatidylethanolamine binding protein 1 (PEBP1) and up-regulated expression of enoyl-coenzyme A hydratase (ECH) and peroxiredoxin 6 (PRDX6).HSP60, PEBP1, ECH, and PRDX6 may be involved in the lipid regulatory effect of WHLB. Moreover, the regulation of PRDX6 may be related to the antioxidant activity of WHLB.
Keywords: Whole grain; Highland barley; Antioxidant activity; Differential proteins; Lipid regulation

Advanced glycation endproducts (AGEs) are produced endogenously and also enter the body during the consumption of AGEs present in heat-processed food. It is unknown whether AGEs of dietary origin accumulate within the body of healthy individuals. AGEs can deposit within skin tissue long-term by crosslinking extracellular matrix proteins. The fluorescent nature of many AGEs enables their detection within the skin by non-invasively measuring skin autofluorescence (SAF). This study aimed to identify habitual dietary and lifestyle behaviours cross-sectionally associated with SAF in an adult population sample.251 Healthy adult volunteers completed validated food frequency and physical activity questionnaires. Waist circumference, BMI, blood pressure and blood glucose was also measured. SAF was measured using an AGE Reader.Significant positive correlations were found between SAF and chronological age (r = 0.63, P < 0.001), waist circumference (r = 0.28, P < 0.01), body weight (r = 0.24, P < 0.05), BMI (r = 0.23, P < 0.05) and consumption of meat and meat products (r = 0.22, P < 0.05). A negative correlation was found between SAF and cereal consumption (r = −0.21, P < 0.05). Cigarette smokers also had a significantly higher SAF than non-smokers (2.4 vs 2.0 U, P < 0.05). Regression analysis identified age, cigarette smoking, waist circumference and intake of meat products as significant predictors of SAF. The regression model explained 48% of the variation in SAF.Age, cigarette smoking, waist circumference and dietary consumption of meat/meat products were positively associated with SAF in this sample. Further research is required to determine whether frequent consumption of foods containing large quantities of dietary AGEs contribute to pathological disease processes in healthy individuals.
Keywords: Advanced glycation endproducts (AGEs); Maillard reaction; Diet; Skin autofluorescence; Healthy adults

Use of polypharmacy in the treatment of diabetes is the norm; nonetheless, optimal control is often not achieved. Konjac-glucomannan-based fibre blend (KGB) and American ginseng (AG) have individually been shown to improve glycaemia and CVD risk factors in type 2 diabetes. The aim of this study was to determine whether co-administration of KGB and AG could improve diabetes control beyond conventional treatment.Thirty-nine participants with type 2 diabetes (6.5 > A1c < 8.4%) were enrolled between January 2002 and May 2003 at the Risk Factor Modification Centre at St Michaels Hospital in a randomized, placebo-controlled, crossover trial with each intervention lasting 12-weeks. Medications, diet and lifestyle were kept constant. Interventions consisted of 6 g of fibre from KGB together with 3 g of AG (KGB and AG) or wheat bran-based, fibre-matched control. Primary endpoint was the difference in HbA1c levels at week 12.Thirty participants (18M:12F; age: 64 ± 7 years; BMI: 28 ± 5 kg/m2; HbA1c: 7.0 ± 1.0%) completed the study, and consumed 5.5 and 4.9 g/day of fibre from KGB and wheat bran control, respectively, and 2.7 g/day of AG. At week 12, HbA1c levels were 0.31% lower on the KGB and AG compared to control (p = 0.011). Mean (±SEM) plasma lipids decreased on the KGB and AG vs control by 8.3 ± 3.1% in LDL-C (p = 0.002), 7.5 ± 2.4% in non-HDL-C (p = 0.013), 5.7 ± 1.9% in total-C (p = 0.012), 4.1 ± 2.1% in total-C:HDL-C ratio (p = 0.042), 9.0 ± 2.3% in ApoB (p = 0.0005) and 14.6 ± 4.2% in ApoB:ApoA1 ratio (p = 0.049).Co-administration of KGB and AG increases the effectiveness of conventional therapy through a moderate but clinically meaningful reduction in HbA1c and lipid concentrations over 12 weeks in patients with type 2 diabetes.NCT02806349 (
Keywords: Type 2 diabetes; Dietary fibre; American ginseng; Konjac mannan; Glucomannan; Xanthan

A modified response of NAFLD patients with non-significant fibrosis in nutritional counseling according to GCKR rs1260326 by Andriana C. Kaliora; Ioanna Panagiota Kalafati; Aristea Gioxari; Anastasia Diolintzi; Alexandros Kokkinos; George V. Dedoussis (2227-2235).
To investigate the association between GCKR gene and nutritional treatment in NAFLD-related biomarkers.This was an open-label and single-arm clinical trial in 44 overweight or obese adults with NAFLD receiving nutritional counseling for 6 months. Nutritional data, MedDietScore, clinical, biochemical, inflammatory and oxidative stress biomarkers were evaluated before and after intervention. Further, we genotyped GCKR rs1260326 and in T-allele carriers and non-Τ-carriers we assessed associations between the GCKR variant and nutritional counseling related to change in all biomarkers evaluated.Anthropometric measurements were significantly reduced after the end of the intervention in patients assigned to nutritional counseling. Liver imaging and fibrosis were significantly improved. GCKR rs1260326 T-allele frequency was 46.7%. T-carriers responded better to nutritional counseling regarding fasting blood glucose levels (mean6-0 change = −4.94 mg/dL (±9.33), p = 0.005), whereas non-T-carriers did not benefit from the intervention regarding glucose. On the other hand, levels of oxLDL decreased in the non-T-carriers group after the intervention, but not in T-carriers.Our results show that GCKR rs1260326 T-allele is associated with better response of NAFLD patients to nutritional treatment regarding fasting blood glucose, but not oxLDL levels. Despite this important finding in the field of nutrigenetics, it is tricky to generalize this effect unless larger studies are conducted.
Keywords: NAFLD; Nutrition; Genetics; GCKR; Response; Counseling; Fasting glucose; oxLDL

Effects of endurance training on autophagy and apoptotic signaling in visceral adipose tissue of prolonged high fat diet-fed rats by Sílvia Rocha-Rodrigues; Inês O. Gonçalves; Jorge Beleza; António Ascensão; José Magalhães (2237-2247).
Autophagy and apoptosis play critical roles in both development and tissue homeostasis in response to (patho)physiological stimuli, such as high-fat diet (HFD) and endurance training (ET). Therefore, we aimed to investigate how ET modulates autophagy and apoptotic-related signaling in visceral adipose tissue of long-standing HFD-fed rats.The study was conducted over a 17-week period on Sprague–Dawley rats, which were divided into four groups (n = 8/group): standard diet sedentary (STD+SED), high-fat diet sedentary (HFD+SED), standard diet ET (STD+ET) and high-fat diet ET (HFD+ET). After 9 weeks of dietary regimens, ET groups were trained for 8 weeks on treadmill (5 days/week at 25 m/min for 60 min/day), while maintaining dietary regimens. Autophagy and apoptotic-signaling markers in epididymal white adipose tissue (eWAT) were determined using RT-qPCR, Western blot and spectrometry techniques.ET reduced body weight, visceral fat mass and HOMA-IR in standard and HF diet-fed animals. Moreover, ET reverted the HFD-induced increases in the percentage of larger adipocytes and also reduced the percentage of smaller adipocytes. The HFD decreased pre-adipocyte factor 1 (DLK1/PREF1) and increased the pro-apoptotic markers (Bax protein and caspase 3-like activity), while having no impact on autophagy markers. However, ET increased DLK1/PREF1 and Bcl-2 in both diet types, while decreasing Bax and caspases 9, 8 and 3-like activities in HFD feeding rats. Additionally, Beclin-1 and p62 protein significantly increased in ET groups of both diet types.Data demonstrate that 8 weeks of ET was effective in attenuating apoptotic-related signaling in long-standing HFD-fed rats. Moreover, HFD and ET had no impact on VAT autophagy markers.
Keywords: Exercise; Visceral adiposity; Beclin-1; p62; Bcl-2

Dietary iron intake and availability are related to maternal education level in overweight/obese adolescents by Chaleelak Thongprasert; Carol Hutchinson; Warapone Satheannoppakao; Mathuros Tipayamongkholgul (2249-2260).
To compare intakes of dietary iron and enhancers and inhibitors of iron absorption between overweight/obese (OW/OB) adolescents and their normal weight (NW) peers, and between parental education levels stratified by weight status.This was a comparative cross-sectional study of adolescents (n 121 OW/OB and n 102 NW) aged 12–14 years, attending a secondary school in Nonthaburi province, Thailand. Socio-demographic data were obtained from participants’ parents using a questionnaire. Participants recorded their intakes for 3 non-consecutive days, using a prospective food record.Compared with NW adolescents, OW/OB adolescents consumed more total protein and animal protein after adjustment for energy intake (both p = 0.047). OW/OB adolescents whose mothers were less educated consumed more total iron and available iron after adjustment for energy intake, compared with their OW/OB peers whose mothers were more educated (p = 0.045 and p = 0.040). NW adolescents with more highly educated mothers had higher absolute and energy-adjusted fibre intakes (both p = 0.047). However, NW adolescents of mothers with a high–intermediate level of education consumed less calcium, after adjustment for energy intake (p = 0.028).OW/OB adolescents with less educated mothers had higher energy-adjusted intakes of iron and available iron. Dietary differences in OW/OB adolescents relative to maternal education, and other socioeconomic indicators, should be explored in a nationally representative data set.
Keywords: Iron; Enhancer; Inhibitor; Adolescent; Overweight/obese; Parental education

Epidemiologic evidence on the associations between dietary glycemic index (GI) and glycemic load (GL) and depressive symptoms is not only limited, particularly in Asian populations where dietary GI and GL are typically higher than in Western countries, but also inconclusive. This cross-sectional study examined these associations in Japanese women.Subjects were 3963 young (age 18-years) and 3826 middle-aged (mean age 47.8 years) Japanese women. Dietary GI and GL were assessed using a validated diet history questionnaire. Depression symptoms were defined as present when subjects had a Center for Epidemiologic Studies Depression score ≥16.The prevalence of depressive symptoms was 50.2% for young women and 27.3% for middle-aged women. The mean (SD) values of energy-adjusted dietary GI and GL (GI for glucose = 100) were, respectively, 64.9 (4.3) and 142.0 (27.4) for young women and 65.0 (4.1) and 142.2 (29.5) for middle-aged women. After adjustment for potential confounding factors, higher dietary GI was associated with a lower prevalence of depressive symptoms. Adjusted OR (95% CI) for depressive symptoms in the highest compared to lowest quintiles of dietary GI was 0.66 (0.52, 0.82) for young women (P for trend = 0.001) and 0.75 (0.60, 0.96) for middle-aged women (P for trend = 0.046). Conversely, there was no association between dietary GL and depressive symptoms in either age group.Dietary GI, but not GL, was inversely associated with depressive symptoms in a group of young and middle-aged Japanese women with relatively high dietary GI and GL.
Keywords: Depressive symptoms; Glycemic index; Glycemic load; Japanese women; Cross-sectional study

The anti-inflammatory activity of sardine protein hydrolysates (SPH) obtained by hydrolysis with proteases from brewing yeast surplus was ascertained.For this purpose, a digested and desalted SPH fraction with molecular weight lower than 10 kDa was investigated using an endothelial cell line (EA.hy926) as such and in a co-culture model with an intestinal cell line (Caco-2). Effects of SPH <10 kDa on nitric oxide (NO) production, reactive oxygen species (ROS) inhibition and secretion of monocyte chemoattractant protein 1 (MCP-1), vascular endothelial growth factor (VEGF), chemokine IL-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1) were evaluated in TNF-α-treated and untreated cells.Upon TNF-α treatment, levels of NO, MCP-1, VEGF, IL-8, ICAM-1 and endothelial ROS were significantly increased in both mono- and co-culture models. Treatment with SPH <10 kDa (2.0 mg peptides/mL) significantly decreased all the inflammation markers when compared to TNF-α-treated control. This protective effect was more pronounced in the co-culture model, suggesting that SPH <10 kDa Caco-2 cells metabolites produced in the course of intestinal absorption may provide a more relevant protective effect against endothelial dysfunction. Additionally, indirect cross-talk between two cell types was established, suggesting that SPH <10 kDa may also bind to receptors on the Caco-2 cells, thereby triggering a pathway to secrete the pro-inflammatory compounds.Overall, these in vitro screening results, in which intestinal digestion, absorption and endothelial bioactivity are simulated, show the potential of SPH to be used as a functional food with anti-inflammatory properties.
Keywords: Sardine protein hydrolysate; Brewer’s spent yeast; Anti-inflammatory activity; Co-culture model; TNF-α

Soy isoflavone consumption and age at pubarche in adolescent males by Gina Segovia-Siapco; Peter Pribis; Keiji Oda; Joan Sabaté (2287-2294).
Isoflavones have estrogenic properties that may adversely affect pubertal development of boys. We examined if soy isoflavone consumption is associated with age at pubarche (first onset of pubic hair) in a male population with a wide range of soy intake.Boys aged 12–18 years (n = 248) who attended schools around Adventist universities in Southern California and Michigan self-reported their age at pubarche. Intake of soy isoflavones was assessed using a validated Web-based food frequency questionnaire; consumption levels were designated as low, moderate, and high. Descriptives, time-to-event analysis, and Cox proportional hazards regression that controlled for confounders were performed.Energy-adjusted mean intakes were 0.8–54.9 mg/d for total isoflavones, 0.4–22.1 mg/d for daidzein, and 0.4–28.0 mg/d for genistein. Moderate and high total soy isoflavone intake were significantly associated with earlier adjusted median age at pubarche: 12.58 years [RR (95% CI): 1.58 (1.06, 2.36)] for moderate and 12.50 years [RR (95% CI): 1.63 (1.03, 2.60)] for high vs. 13.00 years for low consumers. Similarly, daidzein and genistein consumption was also significantly associated with age at pubarche. No significant associations were found for facial hair for any of the isoflavones.Age at pubarche in this male population widely exposed to soy is within the reported range for boys’ pubarcheal age; moderate/high consumers tend to have it earlier compared to low consumers. Further studies are needed to ascertain that substantial exposure to soy isoflavones does not adversely affect pubertal development of boys.
Keywords: Adolescents; Males; Pubarche; Puberty; Soy; Isoflavones; Adventist

Consumption of fruit and vegetables in relation with psychological disorders in Iranian adults by Faezeh Saghafian; Hanieh Malmir; Parvane Saneei; Ammar Hassanzadeh Keshteli; Mohammad Javad Hosseinzadeh-Attar; Hamid Afshar; Fereydoun Siassi; Ahmad Esmaillzadeh; Peyman Adibi (2295-2306).
Findings from observational studies on the relationship between fruit and vegetables consumption and risk of mental disorders are contradictory. We aimed to examine the association between fruit and vegetables intake and prevalence of depression, anxiety, and psychological distress in a large group of Iranian adults.This cross-sectional study was conducted on 3362 people of Iranian adults working in 50 health centers. Dietary data were collected using a validated dish-based 106-item semi-quantitative food frequency questionnaire (FFQ). The Iranian-validated version of Hospital Anxiety and Depression Scale (HADS) was used to screen for anxiety and depression. The General Health Questionnaire (GHQ) was used to assess psychological distress.The prevalence of depression, anxiety, and high psychological distress among the study population was 30.0, 15.2, and 25.0%, respectively. Women in the top quintile of fruit intake, compared with those in the bottom quintile, had 57, 50, and 60% lower odds of depression, anxiety, and psychological distress. Consumption of vegetables was significantly associated with lower odds of depression (OR 0.65; 95% CI 0.46, 0.93) in women and lower odds of anxiety (OR 0.43; 95% CI 0.22, 0.87) in men. In addition, after adjustment for potential confounders, women in the highest quintile of fruit and vegetables intake, compared with those in the bottom quintile, had significantly lower odds of depression (OR 0.55; 95% CI 0.37, 0.80) and psychological distress (OR 0.60; 95% CI 0.40, 0.90). Furthermore, high intake of total fruit and vegetables was associated with lower odds of psychological distress (OR 0.42; 95% CI 0.21, 0.81) in men.We found significant inverse associations between high intake of fruit with depression, anxiety, and psychological distress in Iranian women. High consumption of vegetables was also associated with lower risk of depression and anxiety, respectively, in women and men. In addition, high intake of total fruit and vegetable was associated with lower odds of depression and psychological distress in women and men.
Keywords: Fruit; Vegetables; Depression; Anxiety; Distress

Reply to ZT Lopez-Ixta by Parvane Saneei; Fereydoun Siassi; Ahmad Esmaillzadeh (2309-2310).

Correction to: Challenges in the assessment of total fluid intake in children and adolescents: a discussion paper by Janet Warren; Isabelle Guelinckx; Barbara Livingstone; Nancy Potischman; Michael Nelson; Emma Foster; Bridget Holmes (2311-2311).
In the original publication of the article, a mistake was introduced in affiliation of Dr. Michael Nelson.