A Randomized Crossover Intervention Study on the Effect a Standardized Maté Extract (Ilex paraguariensis A. St.-Hil.) in Men Predisposed to Cardiovascular Risk.

(1) Background: Due to its richness in chlorogenic acids (CGAs), Maté (Ilex paraguariensis A. St.-Hil.) could be of interest in the prevention of cardiometabolic diseases, however clinical evidence are lacking. This trial aimed to evaluate the impact of maté CGAs, consumed in a daily dose achievable through traditional maté beverages, on parameters related to cardiometabolic risk. (2) Design: Thirty-four male volunteers aged 45-65 years and with at most one criteria of metabolic syndrome, were recruited for a randomized, double-blind, placebo-controlled, and crossover study. The volunteers were assigned to consume an encapsulated dry maté extract for four-weeks, providing 580 mg of caffeoyl quinic acid derivatives (CQAs) daily, or a placebo, with a two weeks washout between intervention periods. Anthropometric variables, blood pressure, plasma glucose, lipids, endothelial, and inflammatory biomarkers were measured in overnight-fasted subjects and after a glucose load. (3) Results: We found no significant effects of treatment on these parameters and the response to the glucose load was also similar between the two interventions. However, a significant decrease in fasting glucose was observed between day 0 and day 28 for the maté group only (-0.57 ± 0.11 mmol/L, p < 0.0002). In subjects with an intermediate to high Framingham risk score, consumption of maté extract induced a 10% increase of high-density lipoprotein (HDL)-c from baseline. In a subgroup representative of the study population, significant decreases in the C-reactive protein (CRP) (-50%) and interleukin-6 (IL-6) (-19%) levels were observed. (4) Conclusions: These clinical observations suggest that maté, naturally rich in CGAs, could improve some cardiometabolic markers in subjects with a higher predisposition to metabolic syndrome, even if that remains to be confirmed in new trials specifically targeting this population.

Acute Effects of the Consumption of Passiflora setacea Juice on Metabolic Risk Factors and Gene Expression Profile in Humans.

BACKGROUND: Passiflora setacea (PS) is a passionfruit variety of the Brazilian savannah and is a rich source of plant food bioactives with potential anti-inflammatory activity. This study aimed to investigate the effect of an acute intake of PS juice upon inflammation, metabolic parameters, and gene expression on circulating immune cells in humans. METHODS: Overweight male volunteers (n = 12) were enrolled in two double-blind placebo-controlled studies. Blood samples were collected from fasting volunteers 3 h after the consumption of 250 mL of PS juice or placebo (PB). Metabolic parameters (insulin, glucose, total cholesterol, high-density lipoprotein (LDL), high-density lipoprotein (HDL), and total triglycerides) and circulating cytokines were evaluated (study 1). Peripheral blood mononuclear cell (PBMC) from the same subjects were isolated and RNA was extracted for transcriptomic analyses using microarrays (study 2). RESULTS: Insulin and homeostatic model assessment for insulin resistance (HOMA-IR) levels decreased statistically after the PS juice intake, whereas HDL level increased significantly. Interleukin (IL)-17A level increased after placebo consumption, whereas its level remained unchanged after PS juice consumption. Nutrigenomic analyses revealed 1327 differentially expressed genes after PS consumption, with modulated genes involved in processes such as inflammation, cell adhesion, or cytokine-cytokine receptor. CONCLUSION: Taken together, these clinical results support the hypothesis that PS consumption may help the prevention of cardiometabolic diseases.

Impact of Foods and Dietary Supplements Containing Hydroxycinnamic Acids on Cardiometabolic Biomarkers: A Systematic Review to Explore Inter-Individual Variability.

Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790.

Breakthroughs in the Health Effects of Plant Food Bioactives: A Perspective on Microbiomics, Nutri(epi)genomics, and Metabolomics.

Plant bioactive compounds consumed as part of our diet are able to influence human health. They include secondary metabolites like (poly)phenols, carotenoids, glucosinolates, alkaloids, and terpenes. Although much knowledge has been gained, there is still need for studies unravelling the effects of plant bioactives on cardiometabolic health at the individual level, using cutting-edge high-resolution and data-rich holistic approaches. The aim of this Perspective is to review the prospects of microbiomics, nutrigenomics and nutriepigenomics, and metabolomics to assess the response to plant bioactive consumption while considering interindividual variability. Insights for future research in the field toward personalized nutrition are discussed.

Meta-Analysis of the Effects of Foods and Derived Products Containing Ellagitannins and Anthocyanins on Cardiometabolic Biomarkers: Analysis of Factors Influencing Variability of the Individual Responses.

Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.

Daily Intake of Chlorogenic Acids from Consumption of Maté (Ilex paraguariensis A.St.-Hil.) Traditional Beverages.

The main objective of this study was to investigate the daily intake of chlorogenic acids (CGAs) and methylxanthines by consumers of maté traditional beverages (MTBs), terere and chimarrão (Ilex paraguariensis A.St.-Hill). In the studied population (450 citizens from Toledo, PR, Brazil), 63% consume the chimarrão and 37% terere, with weighted mean daily intakes estimated at 648-2160 and 244-746 mL, respectively. For every 100 mL of beverage consumed, the average amount of total phenol compounds extracted was 673.6 mg for chimarrão and 1184.9 mg for terere. Regarding CGAs composition, caffeoylquinic acids (CQAs) constitute about 38.4% for chimarrão and 55.3% for terere, and dicaffeoylquinic acids (diCQAs) represent 61.6 and 44.7% of the extracted compounds, respectively. The daily intake of phenolic compounds by MTB consumers was estimated for chimarrão (512.5-1708.5 mg/day) and terere (583.0-1779.7 mg/day). These results allow us to conclude that MTBs are important dietary sources of CGAs, mainly CQAs and di-CQAs.

Dietary curcumin inhibits atherosclerosis by affecting the expression of genes involved in leukocyte adhesion and transendothelial migration.

SCOPE: The aim of the study was to examine the atheroprotective effect of dietary curcumin in a mouse model of atherosclerosis and to identify its cellular and molecular targets at the vascular level. METHODS AND RESULTS: ApoE(-/-) mice were fed with curcumin at 0.2% (wt/wt) in diet for 4 months. This supplementation reduced the extent of atherosclerotic lesion by 26% and induced changes in expression of genes implicated in cell adhesion and transendothelial migration or cytoskeleton organization, as revealed by a transcriptomic analysis in the aorta. Expression profile of these genes suggests reduction in both leukocyte adhesion and transendothelial migration. In agreement with this hypothesis, we observed a reduction (-37%) in macrophage infiltration in the plaque, as measured by immunohistochemistry, and, in vitro, a lower adhesion of monocytes to TNF-α-stimulated endothelial cells (-32%) after exposure to a nutritionally achievable concentration of curcumin. These changes in gene expression could be related to the observed increased expression of IκB protein and decrease of TNF-α-induced NF-κB/DNA binding and NF-κB-transcriptional activity upon exposure to curcumin. CONCLUSION: Our findings pointed out that the antiatherogenic effect of curcumin could be linked to its effect on gene networks and cell functions related to leukocyte adhesion and transendothelial migration via NF-κB-dependent pathways.

Citrus flavanones: what is their role in cardiovascular protection?

Flavanones, including hesperidin and naringin, are polyphenolic compounds highly and almost exclusively present in citrus. Epidemiological studies reported an inverse relationship between their intake and the risk of cardiovascular diseases. Clinical and experimental data further showed their antihypertensive, lipid-lowering, insulin-sensitizing, antioxidative, and anti-inflammatory properties, which could explain their antiatherogenic action in animal models. Although flavanones may be promising compounds that are particularly active in cardiovascular disease prevention, clinical data are still scarce and most in vitro data have been obtained under nonphysiologically relevant conditions. Moreover, the mechanisms responsible for flavanone action are not fully elucidated. Therefore, further research is needed to better evaluate and understand the protective effects of flavanones in cardiovascular diseases.

Differential effects of two citrus flavanones on bone quality in senescent male rats in relation to their bioavailability and metabolism.

The effect of hesperidin (Hp) and naringin (Nar), two major citrus flavanones, on the regulation of bone metabolism was examined in male senescent rats. Twenty -month -old gonad-intact male Wistar rats received a casein-based diet supplemented with or without either 0.5% hesperidin (Hp), 0.5% naringin (Nar) or a mix of both flavanones (Hp+Nar, 0.25% each). After 3 months, daily Hp intake significantly improved femoral bone integrity as reflected by improvements in total and regional bone mineral densities (BMD) (9.7%-12.3% improvements, p<0.05) and trabecular bone volume fraction (24.3% improvement, p<0.05) at the femur compared with control group. In contrast, naringin exerted site-specific effects on BMD (10.2% improvement at the distal metaphyseal area, p<0.05) and no further benefit to bone mass was observed with the mix of flavanones. Bone resorption (DPD) was significantly attenuated by Hp and Nar given alone (40.3% and 26.8% lower compared to control, p<0.05, respectively) but not by the mixture of the two. All treatments significantly reduced expression of inflammatory markers to a similar extent (IL-6, 81.0-87.9% reduction; NO, 34.7-39.5% reduction) compared to control. Bone formation did not appear to be strongly affected by any of the treatments (no effect on osteocalcin levels, modest modulation of tibial BMP-2 mRNA). However, as previously reported, plasma lipid-lowering effects were observed with Hp and Nar alone (34.1%-45.1% lower for total cholesterol and triglycerides compared to control, p<0.05) or together (46% lower for triglycerides, p<0.05). Surprisingly the plasma circulating level of naringin (8.15µM) was >5-fold higher than that of hesperidin (1.44µM) at equivalent doses (0.5%) and a linear reduction in plasma levels was observed upon co-administration (0.25% each) indicating absence of competition for their intestinal absorption sites and metabolism. The higher efficacy of Hp at a lower plasma concentration than naringin, as well as the identification of the major circulating metabolite of hesperidin (hesperetin-7-O-glucuronide) underlines the importance of flavanone bioavailability and metabolism in their biological efficacy and suggests a structure-function relationship in the mechanism of action of the active metabolites.

Antioxidant supplementation had positive effects in old rat muscle, but through better oxidative status in other organs.

OBJECTIVE: Aged muscle is characterized by a defect in the ability of leucine to stimulate protein synthesis. We showed previously that antioxidant supplementation improved the anabolic response to leucine of old muscle and reduced inflammation. The aim of the present study was to determine if the positive effects observed in muscle could be related to an improvement of local muscle oxidative status. METHODS: Two groups of 20-mo-old male Wistar rats were supplemented or not with rutin, vitamin E, vitamin A, zinc, and selenium during 7 wk. We measured body weight, food intake, oxidative status in muscle and other tissues, gastrocnemius muscle proteolytic activities, and liver glutathione metabolism. RESULTS: Antioxidant supplementation had no effect on muscle antioxidant capacity, superoxide dismutase activities, and myofibrillar protein carbonyl content and induced an increase in muscle cathepsin activities. In other tissues, antioxidant supplementation increased liver glutathione (reduced plus oxidized glutathione) content, reduced oxidative damage in the liver and spleen (as measured by γ-keto-aldehyde content), and reduced heart thiobarbituric acid-reactive substances. CONCLUSION: Our results showed that the positive effects of antioxidant supplementation observed previously on the anabolic response to leucine of old muscle were not directly related to an improvement of in situ muscle oxidative status. It could result from reduced systemic inflammation/oxidative stress. The dialog between muscle and other organs should be studied more thoroughly, especially during aging.

Atheroprotective effects of bilberry extracts in apo E-deficient mice.

Previous studies have demonstrated that the intake of berry foods was associated with a reduced risk of cardiovascular diseases. The aim of the present study was to evaluate the effects of two bilberry extracts, one rich in anthocyanins extracted from untreated bilberries (BE) and a second one extracted from yeast-fermented bilberries (FBE), on the development of atherosclerosis in apolipoprotein E-deficient mice (apo E(-/-)). Apo E(-/-) mice received for 16 weeks a diet supplemented with 0.02% of either BE or FBE. Atherosclerotic plaque area was measured in the aortic sinus. Supplementation of the diet with both bilberry extracts led to a significant inhibition of plaque development, whereas no effect on oxidative stress parameters or lipid profiles could be observed, suggesting the implication of other mechanisms of action. In addition, a better protection was observed with FBE, suggesting that the fermentation generates new bioactive compounds more effective in attenuating progression of the atherosclerotic lesions.

Increased bioavailability of hesperetin-7-glucoside compared with hesperidin results in more efficient prevention of bone loss in adult ovariectomised rats.

Hesperidin (Hp), a citrus flavonoid predominantly found in oranges, shows bone-sparing effects in ovariectomised (OVX) animals. In human subjects, the bioavailability of Hp can be improved by the removal of the rhamnose group to yield hesperetin-7-glucoside (H-7-glc). The aim of the present work was to test whether H-7-glc was more bioavailable and therefore more effective than Hp in the prevention of bone loss in the OVX rat. Adult 6-month-old female Wistar rats were sham operated or OVX, then pair fed for 90 d a casein-based diet supplemented or not with freeze-dried orange juice enriched with Hp or H-7-glc at two dose equivalents of the hesperetin aglycone (0.25 and 0.5 %). In the rats fed 0.5 %, a reduction in OVX-induced bone loss was observed regarding total bone mineral density (BMD):+7.0 % in OVX rats treated with Hp (HpOVX) and +6.6 % in OVX rats treated with H-7-glc (H-7-glcOVX) v. OVX controls (P < 0.05). In the rats fed 0.25 % hesperetin equivalents, the H-7-glcOVX group showed a 6.6 % improvement in total femoral BMD v. the OVX controls (P < 0.05), whereas the Hp diet had no effect at this dose. The BMD of rats fed 0.25 % H-7-glc was equal to that of those given 0.5 % Hp, but was not further increased at 0.5 % H-7-glc. Plasma hesperetin levels and relative urinary excretion were significantly enhanced in the H-7-glc v. Hp groups, and the metabolite profile showed the absence of eriodictyol metabolites and increased levels of hesperetin sulphates. Taken together, improved bioavailability of H-7-glc may explain the more efficient bone protection of this compound.

Catechin reduces atherosclerotic lesion development in apo E-deficient mice: a transcriptomic study.

Much experimental evidence supports a protective role of dietary flavonoids against cardiovascular diseases. The aim of the present study was to investigate the anti-atherosclerotic effects of catechin supplemented in the diet of apoE deficient mice at a low nutritional level and to explore the mechanisms of action by a transcriptomic approach. After 6 weeks of supplementation, atherosclerotic lesions were assessed by histomorphometry and several markers of lipid, inflammation and oxidative stress status were evaluated. Analysis of the global gene expression in the aorta was carried out using pangenomic arrays. Catechin supplementation reduced the mean atherosclerotic lesion area by 32% but had no effect on total cholesterol and triacylglycerol levels in the plasma and the liver. The plasma antioxidant capacity (FRAP) and inflammatory status (serum amyloid A) were unchanged. The expression of 450 genes was significantly modified by catechin supplementation. Some of the most significantly down-regulated genes included genes coding for adhesion molecules such as CD34 and PSGL-1 known to play a key role in leukocyte adhesion to the endothelium. Other genes involved in energy metabolism, lipid metabolism and lipids trafficking such as FABP4, LPL and SCARA5 were down-regulated and may contribute to the atheroprotective effect of catechin. This work shows that transcriptomic allows characterizing the biological effects of low doses of flavonoids where common markers were not significantly affected.

Apple polyphenols and fibers attenuate atherosclerosis in apolipoprotein E-deficient mice.

Atherosclerosis, which is closely linked to nutritional habits, is a major cause of mortality in Western countries. Most of the previous investigations carried out on health effects of apples have been focused on their capacity to lower lipid concentration as well as on their antioxidant effects. The aim of the present study was to investigate the antiatherosclerotic effects of apple polyphenols and fibers. A crude apple polyphenol extract and low-viscosity apple fibers isolated from cider apples were administered separately or in association with the diet of apo E-deficient mice. After 4 months of supplementation, lipemia and oxidative stress biomarkers were measured and atheroslerotic lesions assessed by histomorphometry. Total plasmatic cholesterol and triacylgycerol levels were not affected by supplementation, and hepatic cholesterol level was lower in the group supplemented with both fibers and polyphenols. Uric acid concentrations and antioxidant capacity (FRAP) in plasma were reduced in all groups supplemented with polyphenols or fibers. The mean lesion area was reduced by 17, 38, and 38%, respectively, for the polyphenol, fiber, and polyphenol + fiber groups. Apple constituents supplied at nutritional doses therefore limit the development of atherosclerotic lesions in the aorta of apo E-deficient mice. On the basis of the results, we hypothesize that apple fibers and polyphenols may play a role in preventing atherosclerosis disease by decreasing uric acid plasma level.

Chlorogenic acid is absorbed in its intact form in the stomach of rats.

The bioavailability of chlorogenic acid, a major polyphenol of the human diet that is particularly abundant in coffee and various fruits, was explored in rats. To identify the form under which it is absorbed through the gut mucosa and the site of absorption along the gastrointestinal tract, rats were fed a diet supplemented with chlorogenic acid (0.25%, wt:wt). Chlorogenic acid and its metabolites were estimated in the stomach, small intestine and cecal contents as well as in bladder urine and plasma by HPLC with coulometric detection at several time points (1.5, 3, 4.5, and 7 h) after the beginning of the meal. Minor hydrolysis of chlorogenic acid (<1%) occurred in the stomach and small intestine contents, whereas 15-32% of ingested chlorogenic acid was hydrolyzed into caffeic acid in the cecum. Chlorogenic acid and caffeic acid appeared early (at 1.5 h) in plasma and urine, suggesting an absorption of chlorogenic acid into the upper part of the gastrointestinal tract. Gastric absorption of chlorogenic acid was further examined by infusing chlorogenic acid in the ligated stomach of food-deprived rats. After 30 min of infusion, intact chlorogenic acid was found in the gastric vein and aorta. No other metabolites could be detected by HPLC-electrospray ionization-MS-MS. These results show for the first time that chlorogenic acid is quickly absorbed in the rat stomach in its intact form.

Polyphenol levels in human urine after intake of six different polyphenol-rich beverages.

Dietary polyphenols are suggested to participate in the prevention of CVD and cancer. It is essential for epidemiological studies to be able to compare intake of the main dietary polyphenols in populations. The present paper describes a fast method suitable for the analysis of polyphenols in urine, selected as potential biomarkers of intake. This method is applied to the estimation of polyphenol recovery after ingestion of six different polyphenol-rich beverages. Fifteen polyphenols including mammalian lignans (enterodiol and enterolactone), several phenolic acids (chlorogenic, caffeic, m-coumaric, gallic, and 4-O-methylgallic acids), phloretin and various flavonoids (catechin, epicatechin, quercetin, isorhamnetin, kaempferol, hesperetin, and naringenin) were simultaneously quantified in human urine by HPLC coupled with electrospray ionisation mass-MS (HPLC-electrospray-tandem mass spectrometry) with a run time of 6 min per sample. The method has been validated with regard to linearity, precision, and accuracy in intra- and inter-day assays. It was applied to urine samples collected from nine volunteers in the 24 h following consumption of either green tea, a grape-skin extract, cocoa beverage, coffee, grapefruit juice or orange juice. Levels of urinary excretion suggest that chlorogenic acid, gallic acid, epicatechin, naringenin or hesperetin could be used as specific biomarkers to evaluate the consumption of coffee, wine, tea or cocoa, and citrus juices respectively.

Apple pectin and a polyphenol-rich apple concentrate are more effective together than separately on cecal fermentations and plasma lipids in rats.

To evaluate the effect of apple components on cecal fermentations and lipid metabolism, rats were fed diets containing 5 g/100 g apple pectin (PEC), 10 g/100 g high polyphenol freeze-dried apple (PL) or both (PEC + PL). The cecal pH was slightly acidic (6.49) only in rats fed the PEC + PL diet (controls, 7.02). The cecal short-chain fatty acid pool was enlarged by all the apple fractions, with a peak of 560 micromol in rats fed the PEC + PL diet compared with 189 micromol in controls. Butyrate concentrations were 2-fold greater in rats fed the PL diet than in controls. Substantial concentrations of galacturonate and succinate (approximately 40 mmol/L) were found in the cecum of rats fed the PEC diet and, to a lesser extent, the PEC + PL diet. The PEC + PL diet significantly lowered plasma cholesterol, whereas both the PL and PEC + PL diets lowered plasma triglycerides. Liver cholesterol and triglyceride concentrations were lower in rats fed the PEC and PEC + PL diets. Fecal bile acid excretion was markedly reduced, whereas sterol excretion was significantly increased by dietary PEC. Rats fed the PEC and PEC + PL diets also had lower apparent cholesterol absorption than controls (30 compared with 43%). In conclusion, apple pectin and the polyphenol-rich fraction were more effective when fed combined together than when fed separately on large intestine fermentations and lipid metabolism, suggesting interactions between fibers and polyphenols of apple.

Mammalian lignan formation in rats fed a wheat bran diet.

The dietary origin of lignan phytoestrogens is still poorly understood more than 20 years after their discovery in human urine. Their level in urine has been associated with the consumption of dietary fiber. This paper reports the study of the excretion of enterolactone, assayed by a time-resolved fluoroimmunoassay, in rats fed a diet supplemented with 15% wheat bran, one of the main sources of fiber in Western countries. Enterolactone excretion regularly increased during the two weeks of the diet to reach a value of 45 nmol/day. The level of excretion also increased upon preadaptation to ferulic acid, structurally related to secoisolariciresinol, an established precursor of enterolactone in flaxseeds, and decreased upon preadaptation to potato starch rich in fiber. These results show that the formation of lignans from wheat bran is influenced by the diet, possibly because of an adaptation of the colonic microflora.

Lyophilized apple counteracts the development of hypercholesterolemia, oxidative stress, and renal dysfunction in obese Zucker rats.

Apples may have selective effects on abnormalities associated with the plurimetabolic syndrome. Therefore, the effects of 20% lyophilized apple supplementation on plasma and tissue lipids and on protection against susceptibility to oxidative stress and renal dysfunction were investigated in Zucker lean (Fa/-) or obese (fa/fa) rats. The experimental diets were equilibrated for sugar supply, contained 0.25 g/100 g cholesterol and provided only one third of the vitamin E requirement. Obese Zucker rats were hypercholesterolemic with cholesterol accumulation in LDL and HDL fractions. The apple diet lowered plasma and LDL cholesterol (-22 and -70%, respectively, P < 0.01) in obese Zucker rats and, in parallel, reduced triglyceride accumulation in heart and liver. Zucker rats fed the apple diet also had a larger intestinal pool and greater fecal excretion of bile acids. The heart concentration and urinary excretion of malondialdehyde were reduced by apple consumption in obese Zucker rats, suggesting better protection against peroxidation. Glucosuria and proteinuria in obese Zucker rats were also suppressed by the apple diet. In conclusion, despite their moderate fiber content, apples improve substantially the lipid status and peroxidative parameters in obese Zucker rats, suggesting that other plant constituents such as polyphenols are involved in these effects.