European Journal of Nutrition (v.49, #2)

Lupin protein compared to casein lowers the LDL cholesterol:HDL cholesterol-ratio of hypercholesterolemic adults by Kristin Weiße; Corinna Brandsch; Bianca Zernsdorf; Germaine S. Nkengfack Nembongwe; Kathleen Hofmann; Klaus Eder; Gabriele I. Stangl (65-71).
Lupin protein had hypocholesterolemic effects in laboratory animals. However, the effect in humans has not been elucidated till now.To investigate the effect of lupin protein on circulating cholesterol in plasma and lipoproteins of hypercholesterolemic subjects.A randomised, double-blind, placebo-controlled, parallel trial (23 females and 20 males completed the trial) was conducted to compare the effects of lupin protein versus casein as control protein on plasma lipids and amino acids. Thirty-five grams of the test protein were consumed daily for 6 weeks.Both lupin protein and casein resulted in a reduction of circulating plasma cholesterol (−0.50 ± 0.64 and −0.47 ± 0.79 mM; P < 0.05) from baseline to week 6. The reduction of plasma cholesterol was mainly caused by a reduction of LDL cholesterol in the lupin protein group (−0.31 ± 0.46 mM; P < 0.05), while in the casein group HDL cholesterol significantly declined (−0.17 ± 0.15 mM; P < 0.05). Comparing the lupin protein group with the casein group yielded a difference in the net changes from baseline to week 6 in the LDL:HDL cholesterol-ratio of −0.24 (95% CI: −0.007, −0.479; P < 0.05). No significant differences in net changes were observed for plasma concentrations of triglycerides, glucose, homocysteine, taurine and most of the amino acids.Lupin protein compared to casein slightly lowered the concentration of LDL cholesterol in hypercholesterolemic subjects, without altering HDL cholesterol. No or minor effects of lupin protein were observed on circulating glucose, homocysteine and plasma amino acids.
Keywords: Lupin protein; Plasma lipids; Hypercholesterolemic subjects

Amaranth is a crop that can be grown in different soils and climates, being resistant to high temperatures, drought, and some pests. The amaranth plant has nutritional qualities and desirable biological properties.The aim of the study is to investigate the potential antitumor properties of Amaranthus-mantegazzianus-protein isolate (MPI) and to elucidate the possible mechanism of action.We use four different tumor-derived and in vitro-transformed cell lines with different morphology and tumorigenicity (MC3T3E1, UMR106, Caco-2, and TC7).The MPI showed an antiproliferative effect on four cell lines with different potencies. The tumor-cell line UMR106 was the most sensitive (IC50: 1 mg/ml). This antiproliferative effect of the MPI was enhanced by protease treatment (IC50: 0.5 after 30% hydrolysis). In addition, the MPI produced morphological changes and caused a rearrangement of the cytoskeleton in UMR106 cell line. In an attempt to elucidate the mechanism of action, we observed that the MPI inhibited cell adhesion and induced apoptosis and necrosis in the UMR106 cell line. In reversibility studies, we were able to observe both temporary and permanent cytostatic and cytotoxic effects on the part of the MPI, depending on its concentration.we report a protein isolate from the seeds of Amaranthus mantegazzianus that exhibit potential antitumor properties and propose a putative mechanism of action.
Keywords: Functional foods; Peptides; Amaranth; Antitumor; Cell culture

Dietary sucrose intake is related to serum leptin concentration in overweight pregnant women by Sanna Vähämiko; Erika Isolauri; Ullamari Pesonen; Pertti Koskinen; Ulla Ekblad; Kirsi Laitinen (83-90).
Overweight, characterized by low-degree systemic inflammation, predisposes women to impaired glucose metabolism during pregnancy. Adipokine leptin participates in the regulation of energy balance and immune action.Objective of the study was to evaluate if aberrations in glucose metabolism during pregnancy are related to leptin concentration and whether serum leptin concentration is affected by diet composition.Normal-weight (n = 61) and overweight or obese (BMI > 25, n = 42) pregnant women visited study clinic at third trimester of pregnancy and one month postpartum. Serum fasting leptin and insulin as well as plasma glucose concentrations were measured, insulin resistance (HOMA) and sensitivity (QUICKI) calculated, and dietary intake from food records determined.In overweight women leptin concentration was significantly higher both in pregnancy, 45.27 (95% CI 39.40–51.14) ng/ml, and postpartum, 31.84 (27.38–36.30) ng/ml, than in normal-weight women, 31.09 (95% CI 27.80–34.37) ng/ml and 16.23 (13.93–18.53) ng/ml, respectively. Equally, blood glucose concentration during pregnancy was higher, 4.82 (4.67–4.97)mmol/l, and insulin concentration, 15.34 (12.00–18.68) mU/l, more pronounced in overweight compared to normal-weight women, 4.51 (4.42–4.61) mmol/l and 8.28 (7.21–9.36) mU/l, respectively. Significantly higher HOMA and lower QUICKI were also detected in overweight compared to normal-weight women. At third trimester of pregnancy, leptin concentration correlated positively with insulin concentration in normal-weight (r = 0.561, P = 0.002) and overweight women (r = 0.736, P < 0.001), as well as with HOMA (r = 0.568, P = 0.002 and r = 0.731, P < 0.001, respectively) whereas negative association was found with QUICKI in normal-weight (r = −0.484, P = 0.011) and overweight women (r = −0.711, P < 0.001). Importantly, serum leptin concentration was affected by dietary sucrose intake both as quantitatively (r = 0.424, P = 0.009) and relative to energy intake (r = 0.408, P = 0.012) in overweight but not in normal-weight pregnant women.Overweight-related elevation in serum leptin is associated with impaired regulation of glucose metabolism during pregnancy. The novel finding that dietary sucrose intake is related to serum leptin concentration is in line with the current dietary recommendations to overweight pregnant women with impaired glucose metabolism advising the lower intake of sucrose during pregnancy.
Keywords: Leptin; Pregnancy; Overweight; Glucose; Sucrose

Predictors of adherence to a Mediterranean-type diet in the PREDIMED trial by Itziar Zazpe; Ramón Estruch; Estefanía Toledo; Ana Sánchez-Taínta; Dolores Corella; Mónica Bulló; Miquel Fiol; Pablo Iglesias; Enrique Gómez-Gracia; Fernando Arós; Emilio Ros; Helmut Schröder; Lluis Serra-Majem; Xavier Pintó; Rosa Lamuela-Raventós; Valentina Ruiz-Gutiérrez; Miguel Ángel Martínez-González (91-99).
Determinants of dietary changes obtained with a nutritional intervention promoting the Mediterranean diet have been rarely evaluated.To identify predictors of higher success of an intervention aimed to increase adherence to a Mediterranean diet (MeDiet) in individuals at high cardiovascular risk participating in a trial for primary prevention of cardiovascular disease: the PREDIMED (PREvención con DIeta MEDiterránea) trial. Candidate predictors included demographic and socioeconomic characteristics, cardiovascular risk factors, and baseline dietary habits.A total of 1,048 asymptomatic subjects aged 55–80 years allocated to the active intervention groups (subjects in the control group were excluded). Participants’ characteristics were assessed at baseline among subjects. Dietary changes were evaluated after 12 months. Main outcome measures were: attained changes in five dietary goals: increases in (1) fruit consumption, (2) vegetable consumption, (3) monounsaturated fatty acid (MUFA)/saturated fatty acid (SFA) ratio, and decreases in (4) sweets and pastries consumption, (5) and meat consumption. Univariate and multivariate logistic regression analyses were used to examine associations between the candidate predictors and likelihood of attaining optimum dietary change (improved adherence to a MeDiet).Among men, positive changes toward better compliance with the MeDiet were more frequent among non-diabetics, and among those with worse dietary habits at baseline (higher consumption of meat, higher SFA intake, lower consumption of fruit and vegetables). Among women, marital status (married) and worse baseline dietary habits (high in meats, low in fruits and vegetables) were the strongest predictors of success in improving adherence to the MeDiet.Some participant characteristics (marital status and baseline dietary habits) could contribute to predicting the likelihood of achieving dietary goals in interventions aimed to improve adherence to a MeDiet, and may be useful for promoting individualized long-term dietary changes and improving the effectiveness of dietary counseling.
Keywords: Dietary predictors; Dietary adherence; Mediterranean diet; Cardiovascular risk; PREDIMED study

There is a growing interest in identifying putative insulin sensitizers from the herbal sources.The present study explores the effects of naringenin, a bioflavonoid, in the high fructose-induced model of insulin resistance.Adult male Wistar rats were divided into two groups and were fed either a starch-based control diet or a high fructose diet (60 g/100 g) for 60 days. From the 16th day, rats in each group were divided into two, one of which was administered naringenin (50 mg/kg b.w.) and the other was untreated for the next 45 days. Oral glucose tolerance test (OGTT) was done on day 59. On day 60, the levels of glucose, insulin, triglycerides (TG), free fatty acids (FFA) in blood, and the activities of insulin-inducible and suppressible enzymes in the cytosolic and mitochondrial fractions of liver and skeletal muscle were assayed. The extent of protein tyrosine phosphorylation in response to insulin was determined by assaying protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) in liver. Liver histology with periodic acid-Schiff (PAS) staining was done to detect glycogen.Fructose administration increased the plasma levels of glucose, insulin, TG, and FFA as compared to control rats. Insulin resistance was indicated by alterations in insulin sensitivity indices. Alterations in enzyme activities and reduced glycogen content were observed in fructose-fed rats. PTP activity was higher, while PTK activity was lower suggesting reduced tyrosine phosphorylation status. Administration of naringenin improved insulin sensitivity and enhanced tyrosine phosphorylation in fructose-fed animals, while it did not affect the parameters in control diet-fed rats.Naringenin improves insulin signaling and sensitivity and thereby promotes the cellular actions of insulin in this model.
Keywords: Fructose; Insulin resistance; Rats; Naringenin; Tyrosine phosphorylation

Very high plant stanol intake and serum plant stanols and non-cholesterol sterols by Helena Gylling; Maarit Hallikainen; Markku J. Nissinen; Piia Simonen; Tatu A. Miettinen (111-117).
Today, consumers meet abundant supply of functional foods with plant stanol increments for serum cholesterol lowering purposes. However, efficacy and safety of plant stanols intake beyond 4 g/day have remained unexplored.We evaluated the effects of very high daily intake of plant stanols (8.8 g/day) as esters on cholesterol metabolism, and serum levels of plant sterols and stanols.In a randomized, double-blind, parallel study of 49 hypercholesterolemic subjects (mean age 62 years, range 41–73) consumed a test diet without (control, n = 24), and with added plant stanol esters (staest, n = 25) over 10 weeks followed by 4 weeks on home diet. Serum lipids, lipoprotein lipids, and non-cholesterol sterols were determined at baseline, during intervention, and 4 weeks afterwards. Cholesterol precursor sterol lathosterol reflected cholesterol synthesis, and serum plant sterols and cholestanol mirrored cholesterol absorption.When compared with controls, 8.8 g/day of plant stanols reduced serum and LDL cholesterol by 12 and 17% (P < 0.01 for both). Synthesis marker lathosterol was increased by 30%, while absorption markers decreased up to 62% when compared with controls (P < 0.001 for both). Serum plant stanols increased slightly, but significantly compared with controls (serum sitostanol during intervention, controls: 16 ± 1 μg/dL, staest: 37 ± 2 μg/dL, serum campestanol during intervention, controls: 0.5 ± 0 μg/dL, staest: 9 ± 1 μg/dL, P < 0.001 for both). Changes in serum cholesterol, non-cholesterol sterols, and plant stanols were normalized during post-treatment weeks.Serum plant stanol levels remained at comparable low levels as in studies with daily intake of 2–3 g, and were normalized in 4 weeks suggesting that daily intake of 8.8 g of plant stanols might not increase systemic availability of plant stanols, but reduces effectively serum cholesterol and plant sterol levels.
Keywords: Plant stanol ester; Sitostanol; Campestanol; Sitosterol; Cholesterol

Astaxanthin suppresses scavenger receptor expression and matrix metalloproteinase activity in macrophages by Yoshimi Kishimoto; Mariko Tani; Harumi Uto-Kondo; Maki Iizuka; Emi Saita; Hirohito Sone; Hideaki Kurata; Kazuo Kondo (119-126).
Astaxanthin is a red carotenoid pigment which has significant potential for antioxidant activity. The macrophages in atherosclerotic lesions, known as activated macrophages, express scavenger receptors responsible for the clearance of pathogenic lipoproteins. In addition, the expression and secretion of proteolytic enzymes, matrix metalloproteinases (MMPs), and pro-inflammatory cytokines are remarkably promoted in activated macrophages.In this study, we investigated the effects of astaxanthin on the expression of scavenger receptors, MMPs, and pro-inflammatory cytokines in macrophages.THP-1 macrophages were incubated with 5–10 μM astaxanthin for 24 h. The expression levels of scavenger receptors, MMPs, and pro-inflammatory cytokines were determined by Western blot analysis or real-time RT-PCR. The MMP-9 and -2 activities were examined by gelatin zymography and total MMP activity was measured by fluorometry.We found that astaxanthin remarkably decreased the class A scavenger receptor and CD36 expression in the protein and mRNA levels. Astaxanthin also reduced MMP-1, -2, -3, -9, -12, and -14 activity and expression. The mRNA expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 were significantly suppressed by astaxanthin. Furthermore, astaxanthin inhibited the phosphorylation of nuclear factor-κB.These results indicate that astaxanthin has inhibitory effects on macrophage activation, such as scavenger receptors up-regulation, MMPs activation, and pro-inflammatory cytokines secretion.
Keywords: Astaxanthin; Macrophage; Scavenger receptor; Matrix metalloproteinase; Atherosclerosis

Arabinoxylan-oligosaccharides (AXOS) reduce preneoplastic lesions in the colon of rats treated with 1,2-dimethylhydrazine (DMH) by Angelo Pietro Femia; Maddalena Salvadori; Willem F. Broekaert; Isabelle E. J. A. François; Jan A. Delcour; Christophe M. Courtin; Giovanna Caderni (127-132).
Prebiotics are non-digestible compounds that beneficially affect the host by stimulating the growth and/or activity of one or a limited number of resident colonic bacteria in the gut. Reported beneficial effects of prebiotics include reduced gut infections, better absorption of minerals, and notably, antitumorigenic effects. Arabinoxylan (AX)-oligosaccharides (AXOS) have been suggested to exert prebiotic effects in the gut, but their effect on colon carcinogenesis has not been studied so far.To test the effect of AXOS in a rat colon carcinogenesis model.We determined the occurrence of two types of preneoplastic lesions [aberrant crypt foci (ACF) and mucin depleted foci (MDF)] in the colon of rats treated with the colon carcinogen 1,2-dimethylhydrazine (DMH) and fed either a control diet or a diet containing AXOS (4.8% w/w) (15 rats in each group).Thirteen weeks after DMH treatment, MDF counts were significantly lower in the entire colon of AXOS fed rats (MDF/colon were 7.5 ± 0.6 and 5.5 ± 0.6, in Control and AXOS groups, respectively, means ± SE, P < 0.05). Although the number of ACF in the entire colon was not significantly different between Control and AXOS fed rats, AXOS fed rats had significantly fewer ACF in the distal part of the colon than Control group rats (ACF/distal colon were 135.5 ± 15 and 84.4 ± 11, in Control and AXOS groups, respectively, means ± SE, P < 0.05).The present study shows that dietary intake of AXOS by rats reduces the occurrence of two types of preneoplastic lesions, thus suggesting a chemopreventive effect on colon carcinogenesis that should be confirmed in a long-term carcinogenesis experiment.
Keywords: Colon carcinogenesis; Arabinoxylan-oligosaccharides; Preneoplastic lesions