European Journal of Nutrition (v.53, #8)

Greater body fatness has been associated with increased risk of gout in several studies; however, the strength of the association has differed between studies, and it is not clear whether the association differs by gender. We conducted a systematic review and meta-analysis of prospective studies to clarify the association between adiposity and risk of gout.PubMed and Embase were searched up to August 30, 2013. Summary relative risks (RRs) were calculated using a random effects model.Ten prospective studies of body mass index (BMI) and gout risk with 27,944 cases and 215,739 participants were included (median follow-up 10.5 years). The summary RR for a 5 unit increment was 1.55 [95 % confidence interval (95 % CI) 1.44–1.66, I 2 = 67 %] for all studies combined. The heterogeneity was explained by one study, which appeared to be an outlier. The summary RR per 5 BMI units was 1.62 (95 % CI 1.33–1.98, I 2 = 79 %) for men and 1.49 (95 % CI 1.32–1.68, I 2 = 30 %) for women, p heterogeneity = 0.72. The relative risks were 1.78, 2.67, 3.62, and 4.64 for persons with BMI 25, 30, 35, and 40 compared with persons with a BMI of 20. BMI in young adulthood, waist-to-hip ratio, and weight gain from age 21–25 to midlife were also associated with increased risk, but few studies were included in these analyses.Greater body mass index increases risk of gout. Further studies are needed on adiposity throughout the life course, waist-to-hip ratio, and weight changes in relation to gout as there were few studies that had published on these exposures.
Keywords: Body mass index; Waist-to-hip ratio; Weight gain; Gout; Meta-analysis

Polyphenol-rich extract from blackcurrant pomace attenuates the intestinal tract and serum lipid changes induced by a high-fat diet in rabbits by Adam Jurgoński; Jerzy Juśkiewicz; Zenon Zduńczyk; Paulius Matusevicius; Krzysztof Kołodziejczyk (1603-1613).
The consumption of a high level of dietary extract from blackcurrant pomace rich in polyphenols was hypothesised to exert beneficial effects on the serum lipid profile, the markers of insulin resistance and the antioxidant status of the host without negative changes in the intestinal tract.This hypothesis was tested on 20 male New Zealand white rabbits randomly assigned to four groups of five individuals each. For 4 weeks, the animals were subjected to the following dietary treatments: two control groups were fed a standard or a high-fat diet (7 and 32 % energy from fat, respectively), and two experimental groups were fed a standard or a high-fat diet with the addition of 1.5 % blackcurrant polyphenolic extract. The extract obtained from blackcurrant fruit pomaces was characterised by high concentrations of anthocyanins and flavonols (48.9 and 17.9 %, respectively).The high-fat feeding regimen led to a series of unfavourable changes, such as increased body weight, disturbance of fermentative processes in the hindgut as well the induction of oxidative stress, hyperlipidaemia and insulin resistance. Dietary supplementation with blackcurrant extract decreased the concentration of putrefactive metabolites (ammonia and putrefactive SCFA) and β-glucuronidase activity in the hindgut digesta. Additionally, the extract ameliorated hyperlipidaemia by decreasing triglyceride, total cholesterol, non-HDL cholesterol and free fatty acid concentrations in the serum and increased the antioxidant capacity of the serum.This study suggests that a polyphenol-rich extract from blackcurrant pomace ingested at relatively high amounts may be a useful therapeutic option in the reversal of dysfunctions related to obesity and its complications.
Keywords: Blackcurrant; Polyphenols; Pomace; Serum lipids; Antioxidant status; Caecum

Dietary carrot consumption and the risk of prostate cancer by Xin Xu; Yunjiu Cheng; Shiqi Li; Yi Zhu; Xianglai Xu; Xiangyi Zheng; Qiqi Mao; Liping Xie (1615-1623).
Previous studies regarding the association between carrot intake and prostate cancer risk have reported inconsistent results. We conducted a meta-analysis to summarize evidence on this association and to quantify the potential dose–response relationship. A systematic literature search of papers published in August 2013 was conducted using PubMed, EMBASE, Scopus, Web of Science, the Cochrane register, and the Chinese National Knowledge Infrastructure databases, and the references of the retrieved articles were screened. The summary risk estimates with 95 % confidence intervals (CIs) for the highest versus the lowest intake of carrots were calculated. A dose–response meta-analysis was also conducted for the studies reporting categorical risk estimates for a series of exposure levels.We found a significantly decreased risk of prostate cancer associated with the intake of carrots (odds ratio 0.82, 95 % CI 0.70–0.97). In addition, the dose–response meta-analysis indicated that for each serving per week, or 10 g per day increment of carrot intake, the risk estimate of prostate cancer was 0.95 (0.90–0.99) or 0.96 (0.94–0.99). There was no evidence of significant publication bias based on Begg’s funnel plot (P = 1.000) or Egger’s test (P = 0.804).Carrot intake might be inversely associated with prostate cancer risk. Because of the limited number of cohort studies and substantial heterogeneity observed between studies in this meta-analysis, further well-designed prospective studies are warranted to confirm the findings from our study.
Keywords: Carrot; Prostatic neoplasms; Meta-analysis; Epidemiology

Combination of low dose of the anti-adipogenic agents resveratrol and phenelzine in drinking water is not sufficient to prevent obesity in very-high-fat diet-fed mice by C. Carpéné; S. Gomez-Zorita; R. Gupta; S. Grès; C. Rancoule; T. Cadoudal; J. Mercader; A. Gomez; C. Bertrand; Z. Iffiu-Soltész (1625-1635).
Resveratrol inhibits lipid accumulation but suffers from limited bioavailability. The anti-depressive agent phenelzine limits adipogenesis in various models of cultured preadipocytes, and this hydrazine derivative also inhibits de novo lipogenesis in mature adipocytes. It was therefore tested whether resveratrol effects on adiposity reduction and glucose tolerance improvement could be reinforced by co-administration with phenelzine.Mice fed a very-high-fat diet (VHFD, 60 % calories as fat) were subjected to drinking solution containing low dose of resveratrol (0.003 %) and/or 0.02 % phenelzine for 12 weeks. Body fat content, glucose tolerance, food and water consumption were checked during treatment while fat depot mass was determined at the end of supplementation. Direct influence of the agents on lipogenesis and glucose uptake was tested in adipocytes.Epididymal fat depots were reduced in mice drinking phenelzine alone or with resveratrol. No limitation of body weight gain or body fat content was observed in the groups drinking resveratrol or phenelzine, separately or in combination. The altered glucose tolerance and the increased fat body composition of VHFD-fed mice were not reversed by resveratrol and/or phenelzine. Such lack of potentiation between resveratrol and phenelzine prompted us to verify in vitro their direct effects on mouse adipocytes. Both molecules inhibited de novo lipogenesis, but did not potentiate each other at 10 or 100 μM. Only resveratrol inhibited hexose uptake in a manner that was not improved by phenelzine.Phenelzine has no interest to be combined with low doses of resveratrol for treating/preventing obesity, when considering the VHFD mouse model.
Keywords: Adipocyte lipogenesis; Resveratrol; Phenelzine; Glucose tolerance; Adiposity; Combination

Dose–response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels by Sergej M. Ostojic; Marko Stojanovic; Patrik Drid; Jay R. Hoffman (1637-1643).
Guanidinoacetic acid (GAA) is an intermediate in the biosynthesis of creatine (Cr), yet its use in human nutrition is limited due to a lack of a clear understanding of its’ dose–response effect. Thus, the purpose of this study was to investigate the effect of three different dosages of GAA (1.2, 2.4 and 4.8 g/day) administered for 6 weeks on serum and urinary variables related to GAA metabolism.Forty-eight healthy volunteers participated in the randomized, placebo-controlled, double-blind, repeated-measure study. At baseline, after 1, 2, 4 and 6 weeks, participants provided both fasting blood samples and 24-h urine.GAA intervention significantly increased serum and urinary GAA, Cr and creatinine as compared to placebo (P < 0.05). Differences were found for serum GAA and Cr responses between the three GAA dosages, with high-dose GAA resulting in a greater increase (P < 0.05) in the plasma concentration of both variables as compared to other GAA dosages. In GAA groups, fasting plasma total homocysteine (T-Hcy) increased by 3.5 μmol/L on average at post-administration, yet no dose–response differences were found between trials. Serum B vitamins were not affected by either placebo or GAA intervention (P > 0.05).Results indicate that low-to-high dosages of exogenous GAA can increase serum concentrations of Cr and T-Hcy while not depleting the B vitamins pool available for remethylation of homocysteine. Clinical trial registration:, identification number NCT01133899.
Keywords: Creatine; Creatinine; Bioenergetics; Homocysteine; Supplementation

Effects of regular consumption of vitamin C-rich or polyphenol-rich apple juice on cardiometabolic markers in healthy adults: a randomized crossover trial by Alberto Soriano-Maldonado; María Hidalgo; Patricia Arteaga; Sonia de Pascual-Teresa; Esther Nova (1645-1657).
The aim of the present study was to investigate the effects of the consumption of two cloudy apple juices with different polyphenol and vitamin C contents on antioxidant status, cardiometabolic and inflammation markers in healthy young adults.Twenty subjects, aged 21–29 years, completed a randomized crossover study. At each 4-week intervention period, the volunteers randomly consumed two glasses (2 × 250 mL/day) of either a vitamin C-rich apple juice (VCR) (60 mg/L vitamin C and 510 mg catechin equivalent/L) or a polyphenol-rich (PR) juice (22 mg/L vitamin C and 993 mg catechin equivalent/L). Blood and urine samples were collected throughout the study, and markers of antioxidant status, glucose metabolism, lipid profile and inflammation were measured.The comparison of the post-intervention minus pre-intervention change revealed differential results in HOMA index, total cholesterol, ICAM-1 and VCAM-1 (P < 0.05) across juices. During the VCR period, plasma antioxidant activity (FRAP) increased (P = 0.031), while ICAM-1 and total cholesterol showed a trend to decrease (P = 0.060 and P = 0.094, respectively). During the PR period, plasma insulin and HOMA increased, and total glutathione decreased (P < 0.05).A joint consumption of apple juice natural antioxidants such as vitamin C and polyphenols might provide mild favorable effects on cardiometabolic markers, as compared to apple polyphenols alone.
Keywords: Apple juice; Vitamin C; Polyphenols; Antioxidant activity; Cardiometabolic markers

Influence of oral supplementation with sesamin on longevity of Caenorhabditis elegans and the host defense by Yukie Yaguchi; Tomomi Komura; Noriko Kashima; Miho Tamura; Eriko Kage-Nakadai; Shigeru Saeki; Keiji Terao; Yoshikazu Nishikawa (1659-1668).
Nutritional control has been proposed as a potential therapy for slowing the senescence of immune function and decreasing mortality. This study investigated whether sesamin could modify host defense systems and extend the lifespan of the nematode Caenorhabditis elegans.Nematodes were fed standard food (the bacterium Escherichia coli strain OP50) supplemented with various doses of sesamin/γ-cyclodextrin inclusion compounds starting from young adulthood. The mean lifespan, muscle function, lipofuscin accumulation, protein carbonyl content, and stress resistance of the worms were examined. Then, C. elegans mutants harboring loss-of-function lesions in longevity- and host defense-related signaling pathways were supplemented with sesamin to identify the genes involved in the longevity effects.Worms supplemented with sesamin displayed higher locomotion and prolongevity and produced offspring at levels similar to unsupplemented control animals. The growth curves of nematodes were similar to those of controls, suggesting that sesamin did not induce prolongevity effects through dietary restriction. Notably, sesamin made the worms more resistant to infection by Legionella pneumophila and more resistant to oxidative stressors such as paraquat and hydrogen peroxide and prolonged the lifespan of a mev-1 mutant that produces abundant superoxide anions. However, the accumulation of protein carbonyls and lipofuscin was similar in sesamin-exposed and control worms, suggesting that sesamin is unlikely to work simply as an antioxidant. Sesamin supplementation failed to extend the lifespan of loss-of-function mutants of daf-2, daf-16, pmk-1, and skn-1.Sesamin enhances the host defense of C. elegans and increases the average lifespan via activation of both skn-1 (encoding a component of the p38 MAPK pathway) and daf-16 (encoding a component of the IGF-1 pathway).
Keywords: Longevity; Nematodes; Sesamin; Aging; Host defense

Maternal obesity is a risk factor for metabolic diseases in offspring. The aim of this study was to investigate whether quercetin administration during gestation and lactation could have any protective effect against the impact of maternal obesity on increased sensitivity to obesity and metabolic disorders in offspring.Female Sprague–Dawley rats were fed a high-fat diet to induce obesity. Obese dams were administered 0, 50, 100 or 200 mg/kg body weight (BW) quercetin intragastrically during gestation and lactation. Normal weight dams were used as controls. The F1 generation was fed with a standard diet after weaning, and blood glucose, lipids and inflammatory factors were assessed. Expression of biomarkers involved endoplasmic reticulum (ER) stress, and related inflammatory pathways in liver and adipose tissues were analyzed at postnatal day 100.Maternal obesity resulted in increased birth weight, postnatal BW gain, hyperglycemia, hyperlipemia, hyperinsulinemia, increased serum levels of inflammatory factors, and up-regulated biomarkers involved in ER stress and related inflammatory pathways in the offspring. Maternal quercetin intervention (QI) had significant ameliorating effects on maternal blood lipids, especially cholesterol, which resulted in improved glucose metabolism and insulin sensitivity and alleviated ER stress and related inflammation in the grown offspring of obese dams.Maternal QI in obese dams during gestation and lactation reduced birth weight and postnatal BW gain in the offspring, and helped to improve insulin sensitivity and lipid metabolism of the mature offspring via reducing ER stress and related inflammation in the liver and adipose tissue.
Keywords: Maternal obesity; Offspring; Quercetin; Endoplasmic reticulum stress; Inflammation

Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro by Giorgio Biasiotto; Marialetizia Penza; Isabella Zanella; Moris Cadei; Luigi Caimi; Cristina Rossini; Annika I. Smeds; Diego Di Lorenzo (1685-1697).
The focus was directed to the study of two of the most lignan-rich food sources: sesame and flaxseeds. Recent epidemiological and experimental evidences suggesting that these foods may improve metabolic functions underlying metabolic syndrome (MetS).To characterize the effect of these oilseeds on metabolic functions, we conducted an experimental study aimed at preventing adiposity and metabolic imbalance in a mouse model of high-fat diet (HFD)-induced MetS. Statistical analysis was performed by two-way analysis of variance test followed by post hoc Bonferroni analysis.We studied the effect of the oilseeds sesame and flaxseed on metabolic parameters in mice on a HFD. When the HFD was integrated with 20 % of sesame or flaxseed flours, the mice showed a decrease in body fat, already at day 15, from time 0. The size of the adipocytes was smaller in epididymal fat, liver steatosis was inhibited, and insulin sensitivity was higher in mice on the supplemented diets. The supplemented diets also resulted in a significant increase in the serum levels of the lignan metabolites enterodiol and enterolactone compared with the controls. The expression of genes associated with the inflammatory response, glucose metabolism, adipose metabolism and nuclear receptor were altered by the oilseed-supplemented diets. Some of the most abundant lignans in these oilseeds were studied in 3T3-L1 preadipocyte cells and were effective in inhibiting adipocyte differentiation at the minimal dose of 1 nM.The consumption of sesame and flaxseed may be beneficial to decrease metabolic parameters that are generally altered in MetS.
Keywords: Oilseeds; Lignans; Metabolic syndrome; Adipose deposition; 3T3-L1 differentiation

Inhibition of angiotensin-converting enzyme by aqueous extract of tomato by Dipankar Biswas; Md. Main Uddin; Lili L. Dizdarevic; Aud Jørgensen; Asim K. Duttaroy (1699-1706).
To investigate the presence of anti-angiotensin converting enzyme (ACE) factors in aqueous extract of tomato.The bio-guided fractionation of the aqueous extract of tomato produced a sugar-free, heat-stable fraction with molecular mass <1,000 Da from tomatoes. The sugar-free tomato extract (TE) was tested for its anti-ACE activity using human plasma and rabbit lung pure ACE. In addition, its effect on human platelet aggregation induced by ADP, collagen or arachidonic acid was determined. The mechanism of platelet inhibitory action of TE was investigated by measuring platelet factor 4 (PF4) release and cAMP synthesis by platelets.Typically, 100 g tomatoes produced 72.2 ± 4.7 mg of TE. This extract inhibited both platelet aggregation and plasma ACE activity in a dose-dependent manner. It inhibited platelet aggregation in response to ADP, collagen or arachidonic acid, and inhibitory action was mediated in part by reducing platelet PF4 release and by stimulating cAMP synthesis. The IC50 value of TE for ADP-induced platelet aggregation was 0.4 ± 0.02 mg/ml, whereas the IC50 value for ACE enzyme inhibition was 1.40 ± 0.04 mg/ml. Both the TE and commercially available sugar-free TE, Fruitflow®-2 had similar amount of catechin, and also had equal inhibitory potencies against platelet aggregation and plasma ACE activity.Together these data indicate that aqueous extract of tomatoes contain anti-ACE factors in addition to previously described anti-platelet factors.
Keywords: Platelet; Tomatoes; Tomato extract; Angiotensin converting enzyme (ACE); Platelet aggregation; cAMP; Platelet factor 4 (PF4)

Oleic acid modulates mRNA expression of liver X receptor (LXR) and its target genes ABCA1 and SREBP1c in human neutrophils by María Edith Reyes-Quiroz; Gonzalo Alba; Javier Saenz; Consuelo Santa-María; Isabel Geniz; Juan Jiménez; Remedios Ramírez; José Martín-Nieto; Elizabeth Pintado; Francisco Sobrino (1707-1717).
Regulation of liver X receptors (LXRs) is essential for cholesterol homeostasis and inflammation. The present study was conducted to determine whether oleic acid (OA) could regulate mRNA expression of LXRα and LXRα-regulated genes and to assess the potential promotion of oxidative stress by OA in neutrophils.Human neutrophils were treated with OA at different doses and LXR target gene expression, oxidative stress production, lipid efflux and inflammation state were analyzed.We describe that mRNA synthesis of both LXRα and ABCA1 (a reverse cholesterol transporter) was induced by OA in human neutrophils. This fatty acid enhanced the effects of LXR ligands on ABCA1 and LXR expression, but it decreased the mRNA levels of sterol regulatory element-binding protein 1c (a transcription factor that regulates the synthesis of triglycerides). Although OA elicited a slight oxidative stress in the short term (15–30 min) in neutrophils, it is unlikely that this is relevant for the modulation of transcription in our experimental conditions, which involve longer incubation time (i.e., 6 h). Of physiological importance is our finding that OA depresses intracellular lipid levels and that markers of inflammation, such as ERK1/2 and p38 mitogen-activated protein kinase phosphorylation, were decreased by OA treatment. In addition, 200 μM OA reduced the migration of human neutrophils, another marker of the inflammatory state. However, OA did not affect lipid peroxidation induced by pro-oxidant agents.This work presents for the first time evidence that human neutrophils are highly sensitive to OA and provides novel data in support of a protective role of this monounsaturated acid against the activation of neutrophils during inflammation.
Keywords: Oleic acid; LXRα; Transcriptional regulation; Nutrition science; Inflammation; MAP kinases

Effect of chicken, fat and vegetable on glycaemia and insulinaemia to a white rice-based meal in healthy adults by Lijuan Sun; Dinesh Viren Ranawana; Melvin Khee-Shing Leow; Christiani Jeyakumar Henry (1719-1726).
White rice is the main staple for the majority in the world. The effects of protein, fat and vegetables on the glycaemic and insulinaemic responses to a white rice-based meal have not been reported. The aim of this study was to determine the effect of co-ingesting a high-protein food (breast chicken), a fat (ground nut oil), a leafy vegetable or all three on the glycaemic and insulinaemic responses of white rice in healthy adults.This was a randomized crossover trial conducted at the Clinical Nutrition Research Centre in Singapore. Twelve healthy volunteers were given five test meals (white rice alone, white rice with chicken, white rice with oil, white rice with vegetable and white rice with chicken, oil and vegetable) once and the reference food (glucose solution) three times in a random order at 1-week intervals. Capillary blood samples were then drawn serially for 3 h, and glucose and insulin were analysed.The glycaemic response (GR) to white rice with chicken breast, ground nut oil and vegetable was significantly lower than to white rice alone. The glycaemic index (GI) of pure white rice was 96, whereas combined with chicken breast, ground nut oil and vegetable, it was 50. The addition of oil delayed the peak glucose response and reduced the iAUC, resulting in a GI value of 67. The addition of chicken and vegetable resulted in a GI value of 73 and 82, respectively. The insulinaemic index (II) of the white rice-based meals varied between 54 and 89. Chicken breast in the meal increased the insulinaemic response and decreased the GR. White rice II was lower than the glucose control, which indicated that the former was not as insulinogenic as the latter. White rice with vegetable had the lowest II.Co-ingesting chicken, oil or vegetable with white rice considerably influences its glycaemic and insulinaemic responses. Co-ingesting white rice with all three components attenuates the GR to a greater degree than when it is eaten with any single one of them, and that this is not at the cost of an increased demand for insulin.
Keywords: White rice; Glycaemic index; Insulinaemic index; Chicken protein

The impact of cereal grain consumption on the development and severity of non-alcoholic fatty liver disease by Michael Georgoulis; Meropi D. Kontogianni; Nafsika Tileli; Aikaterini Margariti; Elisabeth Fragopoulou; Dina Tiniakos; Rodessa Zafiropoulou; George Papatheodoridis (1727-1735).
There is evidence that dietary habits contribute to the presence and severity of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to explore any associations between consumption of grains and the development and severity of NAFLD.Seventy-three consecutive NAFLD patients were enrolled. Additionally, 58 controls matched for age, sex and body mass index with 58 patients were also included. Consumption of grains was estimated through a semi-quantitative food frequency questionnaire. Medical history, anthropometric indices, body composition analysis, physical activity data, biochemical and inflammatory markers were available for all the participants. Liver stiffness measurement by transient elastography was performed in 58 and liver biopsy in 34 patients.In patients, consumption of whole grains was associated with lower abdominal fat level (β = −0.24, p = 0.02) and lower levels of insulin resistance index (β = −0.28, p = 0.009), while it also correlated inversely with interleukin-6 levels (ρ = −0.23, p = 0.05). Consumption of whole grains was associated with lower likelihood of having histological steatohepatitis (OR 0.97, 95 % CI 0.94–1.000), after adjusting for sex and energy intake, but the association became weaker after further adjusting for abdominal fat or interleukin-6 levels. In the case–control analysis, consumption of refined grains was associated with higher odds of having NAFLD (OR 1.021, 95 % CI 1.001–1.042), after adjusting for age, sex, energy intake, abdominal fat level, HOMA-IR, LDL, adiponectin and TNF-α.Although refined grain consumption increased the likelihood of having NAFLD, whole-grain consumption favorably affected clinical characteristics of patients with NAFLD and tended to be associated with less severe disease.
Keywords: Non-alcoholic fatty liver; Cereals; Inflammation; Insulin resistance; Case–control