European Journal of Nutrition (v.51, #6)

Critical review: vegetables and fruit in the prevention of chronic diseases by Heiner Boeing; Angela Bechthold; Achim Bub; Sabine Ellinger; Dirk Haller; Anja Kroke; Eva Leschik-Bonnet; Manfred J. Müller; Helmut Oberritter; Matthias Schulze; Peter Stehle; Bernhard Watzl (637-663).
Vegetables and fruit provide a significant part of human nutrition, as they are important sources of nutrients, dietary fibre, and phytochemicals. However, it is uncertain whether the risk of certain chronic diseases can be reduced by increased consumption of vegetables or fruit by the general public, and what strength of evidence has to be allocated to such an association.Therefore, a comprehensive analysis of the studies available in the literature and the respective study results has been performed and evaluated regarding obesity, type 2 diabetes mellitus, hypertension, coronary heart disease (CHD), stroke, cancer, chronic inflammatory bowel disease (IBD), rheumatoid arthritis (RA), chronic obstructive pulmonary disease (COPD), asthma, osteoporosis, eye diseases, and dementia. For judgement, the strength of evidence for a risk association, the level of evidence, and the number of studies were considered, the quality of the studies and their estimated relevance based on study design and size.For hypertension, CHD, and stroke, there is convincing evidence that increasing the consumption of vegetables and fruit reduces the risk of disease. There is probable evidence that the risk of cancer in general is inversely associated with the consumption of vegetables and fruit. In addition, there is possible evidence that an increased consumption of vegetables and fruit may prevent body weight gain. As overweight is the most important risk factor for type 2 diabetes mellitus, an increased consumption of vegetables and fruit therefore might indirectly reduces the incidence of type 2 diabetes mellitus. Independent of overweight, there is probable evidence that there is no influence of increased consumption on the risk of type 2 diabetes mellitus. There is possible evidence that increasing the consumption of vegetables and fruit lowers the risk of certain eye diseases, dementia and the risk of osteoporosis. Likewise, current data on asthma, COPD, and RA indicate that an increase in vegetable and fruit consumption may contribute to the prevention of these diseases. For IBD, glaucoma, and diabetic retinopathy, there was insufficient evidence regarding an association with the consumption of vegetables and fruit.This critical review on the associations between the intake of vegetables and fruit and the risk of several chronic diseases shows that a high daily intake of these foods promotes health. Therefore, from a scientific point of view, national campaigns to increase vegetable and fruit consumption are justified. The promotion of vegetable and fruit consumption by nutrition and health policies is a preferable strategy to decrease the burden of several chronic diseases in Western societies.
Keywords: Vegetables; Fruit; Prevention; Chronic diseases; Epidemiology

A maternal erythrocyte DHA content of approximately 6 g% is the DHA status at which intrauterine DHA biomagnifications turns into bioattenuation and postnatal infant DHA equilibrium is reached by Martine F. Luxwolda; Remko S. Kuipers; Wicklif S. Sango; Gideon Kwesigabo; D. A. Janneke Dijck-Brouwer; Frits A. J. Muskiet (665-675).
Higher long-chain polyunsaturated fatty acids (LCP) in infant compared with maternal lipids at delivery is named biomagnification. The decline of infant and maternal docosahexaenoic acid (DHA) status during lactation in Western countries suggests maternal depletion. We investigated whether biomagnification persists at lifelong high fish intakes and whether the latter prevents a postpartum decline of infant and/or maternal DHA status.We studied 3 Tanzanian tribes with low (Maasai: 0/week), intermediate (Pare: 2–3/week), and high (Sengerema: 4–5/week) fish intakes. DHA and arachidonic acid (AA) were determined in maternal (m) and infant (i) erythrocytes (RBC) during pregnancy (1st trimester n = 14, 2nd = 103, 3rd = 88), and in mother–infant pairs at delivery (n = 63) and at 3 months postpartum (n = 104).At delivery, infants of all tribes had similar iRBC-AA which was higher than, and unrelated to, mRBC-AA. Transplacental DHA biomagnification occurred up to 5.6 g% mRBC-DHA; higher mRBC-DHA was associated with “bioattenuation” (i.e., iRBC-DHA < mRBC-DHA). Compared to delivery, mRBC-AA after 3 months was higher, while iRBC-AA was lower. mRBC-DHA after 3 months was lower, while iRBC-DHA was lower (low fish intake), equal (intermediate fish intake), and higher (high fish intake) compared to delivery. We estimated that postpartum iRBC-DHA equilibrium is reached at 5.9 g%, which corresponds to a mRBC-DHA of 6.1 g% throughout pregnancy.Uniform high iRBC-AA at delivery might indicate the importance of intrauterine infant AA status. Biomagnification reflects low maternal DHA status, and bioattenuation may prevent intrauterine competition of DHA with AA. A mRBC-DHA of about 6 g% during pregnancy predicts maternal–fetal equilibrium at delivery, postnatal iRBC-DHA equilibrium, but is unable to prevent a postnatal mRBC-DHA decline.
Keywords: Biomagnification; Bioattenuation; Pregnancy; Long-chain polyunsaturated fatty acids; Docosahexaenoic acid; Arachidonic acid; Equilibrium

Oleic acid inhibits store-operated calcium entry in human colorectal adenocarcinoma cells by Celia Carrillo; M. del Mar Cavia; Sara R. Alonso-Torre (677-684).
Much evidence indicates the association between dietary fat and colorectal cancer risk. However, most of the studies focus on polyunsaturated fatty acids, and little is known about the role of monounsaturated ones and their precise mechanism of action. Being store-operated Ca2+ entry (SOCE) a Ca2+ influx pathway involved in the control of multiple cellular and physiological processes including cell proliferation, we studied the effect of oleic acid in Ca2+ signals of colorectal cancer cells, paying particular attention to SOCE.Carbachol was used to induce SOCE in Fura 2-loaded HT29 cells. We tested a saturated fatty acid to compare the physiological relevance of our results.We show that oleic acid is a potent inhibitor of SOCE. By contrast, stearic acid failed to have a SOCE-inhibitory effect. The SOCE-inhibition induced by oleic acid was protein kinase C-independent and restored by albumin. We also demonstrated that oleic acid induced increases in [Ca2+]i. The novelty of our report is that little variability in the concentration could end in a large different physiological effect.In conclusion, we suggest a physiological pathway for the beneficial effect of oleic acid in colon carcinoma cells.
Keywords: Oleic acid; Ca2+ signals; SOCE; HT29 cells

Effect of iodine source and dose on growth and iodine content in tissue and plasma thyroid hormones in fattening pigs by Qimeng Li; Christiane Mair; Karl Schedle; Sabine Hammerl; Katharina Schodl; Wilhelm Windisch (685-691).
The aim of the present feeding trial with iodine was to assess pigs’ growth performance and carcass characteristics, the iodine accumulation in tissues, and their influences on the thyroid hormones in plasma.Eighty pigs (33–115 kg body weight) were allotted to 5 dietary treatments: a control group (150 μg I/kg), two potassium iodide [KI] groups (4,000 and 10,000 μg I/kg), and two potassium iodate [KIO3] groups (4,000 and 10,000 μg I/kg). Iodine concentration was determined in thyroid gland, liver, kidney, muscle, fat, and skin by ICP-MS. Furthermore, thyroxine (T4) and triiodothyronine (T3) in plasma were evaluated. High dietary iodine tended to have a negative effect on younger animals' growth (average daily gain, ADG). However, during the entire growth period, the growth performance and carcass characteristics were not influenced by iodine dosages or sources. Irrespective of iodine source, higher iodine doses of diets affected higher iodine stores in all tested tissues except for abdominal fat. Thus, iodine supplementation with 10,000 μg I/kg feed significantly increased iodine content in thyroid gland (+122%), liver (+260%), kidney (+522%), muscle (+131%), and skin (+321%) compared to the control group. However, there was no significance of thyroid hormones in plasma.As a result, pork and fat of pigs showed only low iodine accumulation even in the high-iodine groups. Thus, there should be no risk of an iodine excess in human nutrition and animal health, and the EU-upper level for iodine in pig feed can be maintained.
Keywords: KI; KIO3 ; Iodine dosages; Growth performance; Tissue accumulation; Thyroid hormone; Fattening pigs

Health authorities around the world advise citizens to increase their intake of foods rich in dietary fibre because of its inverse association with chronic disease. However, a few studies have measured the impact of increasing mixed dietary fibres directly on the composition of the human gut microbiota.We studied the impact of high-level mixed dietary fibre intake on the human faecal microbiota using an in vitro three-stage colonic model.The colonic model was maintained on three levels of fibre, a basal level of dietary fibre, typical of a Western-style diet, a threefold increased level and back to normal level. Bacterial profiles and short chain fatty acids concentrations were measured.High-level dietary fibre treatment significantly stimulated the growth of Bifidobacterium, Lactobacillus-Enterococcus group, and Ruminococcus group (p < 0.05) and significantly increased clostridial cluster XIVa and Faecalibacterium prausnitzii in vessel 1 mimicking the proximal colon (p < 0.05). Total short chain fatty acids concentrations increased significantly upon increased fibre fermentation, with acetate and butyrate increasing significantly in vessel 1 only (p < 0.05). Bacterial species richness changed upon increased fibre supplementation. The microbial community and fermentation output returned to initial levels once supplementation with high fibre ceased.This study shows that high-level mixed dietary fibre intake can up-regulate both colonic fermentation and the relative abundance of saccharolytic bacteria within the human colonic microbiota. Considering the important role of short chain fatty acids in regulating human energy metabolism, this study has implications for the health-promoting potential of foods rich in dietary fibres.
Keywords: Dietary fibre; Faecal microbiota; Fermentation; Short chain fatty acids

Combined fish oil and astaxanthin supplementation modulates rat lymphocyte function by Rosemari Otton; Douglas Popp Marin; Anaysa Paola Bolin; Rita de Cássia Santos Macedo; Thais Regina Campoio; Claudio Fineto Jr.; Beatriz Alves Guerra; José Roberto Leite; Marcelo Paes Barros; Rita Mattei (707-718).
Higher intakes of n-3 polyunsaturated fatty acids that are abundant in marine fishes have been long described as a “good nutritional intervention” with increasing clinical benefits to cardiovascular health, inflammation, mental, and neurodegenerative diseases. The present study was designed to investigate the effect of daily fish oil (FO—10 mg EPA/kg body weight (BW) and 7 mg DHA/kg BW) intake by oral gavage associated with the antioxidant astaxanthin (ASTA—1 mg/kg BW) on the redox metabolism and the functional properties of lymphocytes from rat lymph nodes.This study was conducted by measurements of lymphocyte proliferation capacity, ROS production [superoxide (O 2 •− ) and hydrogen peroxide (H2O2)], nitric oxide (NO) generation, intracellular calcium release, oxidative damage to lipids and proteins, activities of major antioxidant enzymes, GSH/GSSG content, and cytokines release.After 45 days of FO + ASTA supplementation, the proliferation capacity of activated T- and B-lymphocytes was significantly diminished followed by lower levels of O 2 •− , H2O2 and NO production, and increased activities of total/SOD, GR and GPx, and calcium release in cytosol. ASTA was able to prevent oxidative modification in cell structures through the suppression of the oxidative stress condition imposed by FO. l-selectin was increased by FO, and IL-1β was decreased only by ASTA supplementation.We can propose that association of ASTA with FO could be a good strategy to prevent oxidative stress induced by polyunsaturated fatty acids and also to potentiate immuno-modulatory effects of FO.
Keywords: Antioxidant; Astaxanthin; Carotenoid; Fish oil; Leukocytes; Lymphocyte; Oxidative stress; n-3 fatty acids

Akt/GSK-3β/eNOS phosphorylation arbitrates safranal-induced myocardial protection against ischemia–reperfusion injury in rats by Saurabh Bharti; Mahaveer Golechha; Santosh Kumari; Khalid Mehmood Siddiqui; Dharamvir Singh Arya (719-727).
Traditional medicine has been appropriately identified as the most productive soil for the cultivation and harvesting of modern medicines. Herein, we postulate that safranal, an active constituent of Crocus sativus, owing to its strong antioxidant and anti-apoptotic potential, could be a valuable molecule in alleviating myocardial ischemia–reperfusion (IR) injury.To evaluate this hypothesis, safranal (0.1–0.5 mL/kg/day, i.p.) or saline were administered to rats for 14 days, and on 15th day, one-stage ligation of left anterior descending coronary artery for 45 min was performed, followed by 60 min reperfusion.We concluded that safranal not only significantly decreased infarct size, but also improved left ventricular functions and the overall hemodynamic status of the myocardium. Interestingly, safranal enhanced phosphorylation of Akt/GSK-3β/eNOS and suppressed IKK-β/NF-κB protein expressions in IR-challenged myocardium. Our findings also imply that safranal exhibits strong anti-apoptotic potential, as evidenced by upregulated Bcl-2 expression and downregulated Bax and caspase3 expression with decreased TUNEL positivity. Moreover, safranal dose-dependently normalized myocardial antioxidant and nitrotyrosine levels, cardiac injury markers (LDH and CK-MB), and decreased TNF-α level in IR-insulted myocardium. Histopathological and ultrastructural findings correlated with the functional and biochemical outcomes showing preserved myocardial architecture and decreased inflammatory cells and edema.Taken together, these results provide convincing evidence of safranal as an invaluable molecule in myocardial IR setting probably due to its fortified antioxidant and anti-apoptotic potential.
Keywords: Safranal; Myocardial ischemia–reperfusion injury; Akt/GSK-3β/eNOS; Oxidative stress; Apoptosis

Mangiferin decreases inflammation and oxidative damage in rat brain after stress by Lucía Márquez; Borja García-Bueno; José L. M. Madrigal; Juan C. Leza (729-739).
Stress exposure elicits neuroinflammation and oxidative damage in brain, and stress-related neurological and neuropsychiatric diseases have been associated with cell damage and death. Mangiferin (MAG) is a polyphenolic compound abundant in the stem bark of Mangifera indica L. with antioxidant and anti-inflammatory properties in different experimental settings. In this study, the capacity of MAG to prevent neuroinflammation and brain oxidative damage induced by stress exposure was investigated.Young–adult male Wistar rats immobilized during 6 h were administered by oral gavage with increasing doses of MAG (15, 30, and 60 mg/Kg), respectively, 7 days before stress.Prior treatment with MAG prevented all of the following stress-induced effects: (1) increase in glucocorticoids (GCs) and interleukin-1β (IL-1β) plasma levels, (2) loss of redox balance and reduction in catalase brain levels, (3) increase in pro-inflammatory mediators, such as tumor necrosis factor alpha TNF-α and its receptor TNF-R1, nuclear factor-kappa B (NF-κB) and synthesis enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), (4) increase in lipid peroxidation.These multifaceted protective effects suggest that MAG administration could be a new therapeutic strategy in neurological/neuropsychiatric pathologies in which hypothalamic/pituitary/adrenal (HPA) stress axis dysregulation, neuroinflammation, and oxidative damage take place in their pathophysiology.
Keywords: Mangiferin; Polyphenols; Stress; Oxidative/nitrosative damage; Neuroinflammation

Dietary supplementation of herring roe and milt enhances hepatic fatty acid catabolism in female mice transgenic for hTNFα by Bodil Bjørndal; Lena Burri; Hege Wergedahl; Asbjørn Svardal; Pavol Bohov; Rolf K. Berge (741-753).
The beneficial effects of a seafood-rich diet are highly documented and can be attributed to both n-3 polyunsaturated fatty acids and other less studied nutritional components including protein and antioxidants. The aim of the work was to investigate whether an under-utilized seafood source, eggs (roe) and sperm (milt) from herring (Clupea harengus), can affect lipid metabolism and inflammation in a mouse model transgenic for human tumor necrosis factor alpha (hTNFα).A high-fat control diet (25% total fats, 20% protein, w/w) or high-fat diets supplemented with herring roe (3.7% fat, 15% protein, w/w), or milt (1.3% fat, 15% protein) were administered to female C57BL/6 hTNFα mice. After 2 weeks, hepatic enzyme activity, gene expression, lipid and fatty acid composition, fatty acid composition of epididymal adipose tissue, and plasma lipid and cytokine levels were determined.Animals fed herring roe and milt displayed an increased hepatic fatty acid β-oxidation and reduced fatty acid synthase activity. However, while plasma TAG was reduced, hepatic TAG and plasma and hepatic cholesterol levels were increased by the herring diets. Both herring diets led to a substantial shift in the n-6:n-3 ratio in both liver and ovarian white adipose tissue. The herring diets also increased plasma carnitine and reduced the carnitine precursor trimethyllysine. Plasma short-chained acylcarnitine esters were significantly increased, which may reflect an increased β-oxidation of long-chained fatty acids. In addition, the diets tended to reduce the plasma levels of pro-inflammatory cytokines.Herring roe or milt diets enhanced lipid catabolism and influenced the chronic inflammatory state in hTNFα-transgenic mice.
Keywords: Herring roe; Herring milt; TNF alpha; High-fat diet; Lipid catabolism and inflammation

Scientific literature has consistently shown the effects of certain diets on health but regional variations of dietary habits, and their relationship colorectal cancer (CRC) has been poorly studied in Argentina. Our aims were to identify dietary patterns and estimate their effect on CRC occurrence and to quantify the association between family history of CRC and CRC occurrence by applying multilevel models to estimate and interpret measures of variation.Principal components factor analysis was performed to identify dietary patterns that were then used in a multilevel logistic regression applied to an ongoing case–control data about dietary exposure and CRC occurrence taking into account familiar clustering.Three dietary patterns were identified: “Southern Cone pattern” (red meat, wine, and starchy vegetables), “High-sugar drinks pattern”, and “Prudent pattern”. The study considered 41 cases and 95 controls. There was a significant promoting effects on CRC of “Southern Cone” (OR 1.5, 95%CI 1.0–2.2) and “High-sugar drinks” (OR 3.8, 95%CI 2.0–7.1) patterns, whereas “Prudent pattern” (OR 0.3, 95%CI 0.2–0.4) showed a significant protective effect at third tertile level. BMI, use of NSAIDs, and to have medical insurance showed significant effects. Variance of the random effect of family history of CRC was highly significant.This novel approach for Argentina showed that Southern Cone and High-sugar drinks patterns were associated with a higher risk of CRC, whereas the Prudent pattern showed a protective effect. There was a significant clustering effect of family history of CRC.
Keywords: Dietary patterns; Argentina; Meat intake; Colorectal cancer; Multilevel

l-Theanine extends lifespan of adult Caenorhabditis elegans by Kim Zarse; Saskia Jabin; Michael Ristow (765-768).
Compounds that delay aging in model organisms may be of significant interest to anti-aging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. We here aimed to test whether pharmaceutical concentrations of l-theanine, a putative anti-cancer, anti-obesity, blood pressure-lowering, and neuroprotective compound contained in green tea (Camellia sinensis), are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans.Adult C. elegans roundworms were maintained on agar plates, were fed E. coli strain OP50 bacteria, and l-theanine was applied to agar to test (1) whether it may increase survival upon paraquat exposure and (2) whether it may promote longevity by quantifying survival in the presence and absence of the compound. l-theanine increases survival of C. elegans in the presence of paraquat at a concentration of 1 micromolar. l-theanine extends C. elegans lifespan when applied at concentrations of 100 nM, as well as 1 and 10 micromolar.In the model organism C. elegans, l-theanine is capable of promoting paraquat resistance and longevity suggesting that this compound may as well promote healthy lifespan in mammals and possibly humans.
Keywords: Amino acids; Aging; Anti-aging; Lifespan; Signaling; Pharmacology; Nutrition; Nutrients; Phytochemicals; Tea; Model organisms; Metazoans; Nematodes; Caenorhabditis elegans ; Calorie restriction mimetics; Exercise mimetics; Hormesis; Mitohormesis