Dorothy Klimis-Zacas

Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity

The aim of this study was to examine the effect of a polyphenol-rich extract (PrB) of Vaccinium angustifolium (wild blueberries) introduced intraperitoneally (i.p.) at 30 (PrB30) and 60 (PrB60) mg/kg body weight for 7 days, on cognitive performance, brain oxidative status and acetylcholinesterase activity in adult, male, 3-4-month-old Balb-c mice. Evaluation of rodent learning and memory was assessed by a step-through test on day 6 after a double training and an initial acquisition trial on day 5. Antioxidant status was determined by ferric reducing antioxidant power (FRAP), ascorbic acid concentration (FRASC), malondialdehyde and reduced glutathione levels in whole brain homogenates. Acetylcholinesterase (AChE) activity was determined by Ellmans colorimetric method. Results showed that the PrB60-treated mice exhibited a significant improvement in learning and memory (step-through latency time of 228+/-38 s compared to 101+/-32 s of the control group). PrB extract administration also resulted in reduced lipid peroxidation products (38 and 79%) and higher brain ascorbic acid levels (21 and 64%) in both PrB30 and PrB60-treated groups, respectively, and higher glutathione levels (28%) in the PrB60-treated group. Furthermore, salt- and detergent soluble AChE activity significantly decreased in both PrB-treated groups. Thus, the significant cognitive enhancement observed in adult mice after short-term i.p. supplementation with the blueberry extract concentrated in polyphenols, is closely related to higher brain antioxidant properties and inhibition of AChE activity. These findings stress the critical impact of wild blueberry bioactive components on brain function.

Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors

PurposeWild blueberries (WB) (Vaccinium angustifolium) are rich sources of polyphenols, such as flavonols, phenolic acids and anthocyanins (ACNs), reported to decrease the risk of cardiovascular and degenerative diseases. This study investigated the effect of regular consumption of a WB or a placebo (PL) drink on markers of oxidative stress, inflammation and endothelial function in subjects with risk factors for cardiovascular disease.MethodsEighteen male volunteers (ages 47.8xa0±xa09.7xa0years; body mass index 24.8xa0±xa02.6xa0kg/m2) received according to a cross-over design, a WB (25xa0g freeze-dried powder, providing 375xa0mg of ACNs) or a PL drink for 6xa0weeks, spaced by a 6-week wash-out. Endogenous and oxidatively induced DNA damage in blood mononuclear cells, serum interleukin levels, reactive hyperemia index, nitric oxide, soluble vascular adhesion molecule concentration and other variables were analyzed.ResultsWild blueberry drink intake significantly reduced the levels of endogenously oxidized DNA bases (from 12.5xa0±xa05.6xa0% to 9.6xa0±xa03.5xa0%, pxa0≤xa00.01) and the levels of H2O2-induced DNA damage (from 45.8xa0±xa07.9xa0% to 37.2xa0±xa09.1xa0%, pxa0≤xa00.01), while no effect was found after the PL drink. No significant differences were detected for markers of endothelial function and the other variables under study.ConclusionsIn conclusion, the consumption of the WB drink for 6xa0weeks significantly reduced the levels of oxidized DNA bases and increased the resistance to oxidatively induced DNA damage. Future studies should address in greater detail the role of WB in endothelial function. This study was registered at www.isrctn.org as ISRCTN47732406.

Six-Week Consumption of a Wild Blueberry Powder Drink Increases Bifidobacteria in the Human Gut

Wild blueberries are a rich source of polyphenols and other compounds that are highly metabolized by the intestinal microbiota and may, at the same time, affect the intestinal environment itself. A repeated-measure, crossover dietary intervention on human volunteers was designed to study the effect of six week consumption of a wild blueberry ( Vaccinium angustifolium ) drink, versus a placebo drink, in modulating the intestinal microbiota. Relative to total eubacteria, Bifidobacterium spp. significantly increased following blueberry treatment (P ≤ 0.05), while Lactobacillus acidophilus increased after both treatments (P ≤ 0.05). No significant differences were observed for Bacteroides spp., Prevotella spp., Enterococcus spp., and Clostridium coccoides . Bifidobacteria, which have been largely proposed to be of benefit for the host, appeared to be selectively favored suggesting an important role for the polyphenols and fiber present in wild blueberries. Results obtained suggest that regular consumption of a wild blueberry drink can positively modulate the composition of the intestinal microbiota.

Anthocyanin absorption, metabolism, and distribution from a wild blueberry-enriched diet (Vaccinium angustifolium) is affected by diet duration in the Sprague-Dawley rat.

The effect of wild blueberry consumption on anthocyanin (ACNs) distribution and metabolism in Sprague-Dawley (SD) rats was investigated. Thirty-two rats were fed for 4 or 8 weeks with a control (C) or a wild blueberry-enriched diet (8%) (WB). Anthocyanin profile in plasma, urine, feces, brain, and liver was evaluated by LC-MS/MS, and significantly increased in urine and not in feces after 8 weeks on the WB diet compared to that in 4 weeks, but no anthocyanins were detected in plasma, liver, and brain samples either in the C or WB groups. Metabolites of ACNs were detected in the plasma, urine, feces, and tissues of both the C and WB groups, but the urinary excretion of hippuric acid increased significantly after 4 and 8 weeks of WB consumption. Thus, it seems that ACNs are metabolized by the intestinal microflora to respective phenyl-alkyl acids, which can be further metabolized to benzoic acid. In conclusion, ACNs are bioavailable in rats, and the extent of their metabolism and excretion is based on diet duration. Additionally, urinary hippuric acid content could represent a potential biomarker of ACNs absorption and metabolism in the SD rat under the present experimental conditions.

Wild blueberry (Vaccinium angustifolium) consumption improves inflammatory status in the obese Zucker rat model of the metabolic syndrome

The metabolic syndrome (MetS) is a major public health problem in the United States. Chronic inflammation is a critical component of the MetS, leading to dramatically increased risk of type II diabetes and cardiovascular disease. This study investigates the ability of a wild-blueberry-enriched diet to improve the proinflammatory status associated with MetS in the obese Zucker rat (OZR). Circulating levels of key inflammatory markers and their expression in the liver and abdominal adipose tissue were examined in OZR and its genetic control, the lean Zucker rat (LZR), after feeding a control or an 8% wild blueberry diet (WB) for 8 weeks from age 8 to 16 weeks. In the OZR, WB consumption resulted in decreased plasma concentrations of tumor necrosis factor (TNF)-α (-25.6%, P<.05), interleukin (IL)-6 (-14.9%, P<.05) and C-reactive protein (CRP) (-13.1%, P<.05) and increased adiponectin concentration (+21.8%, P<.05). Furthermore, expression of IL-6, TNF-α and nuclear factor (NF)-kB was down-regulated in both the liver (-65%, -59% and -25%, respectively) and the abdominal adipose tissue (-64%, -52% and -65%), while CRP expression was down-regulated only in the liver (-25%). In the abdominal adipose tissue, similar trends were also observed in LZR following WB treatment, with decreased liver expression of NF-kB, CRP, IL-6 and TNF-α (-24%, -16%, -21% and -50%) and increased adiponectin expression (+25%). Results of this study suggest that wild blueberry consumption exerts an overall anti-inflammatory effect in the OZR, a model of the metabolic syndrome.

A single portion of blueberry (Vaccinium corymbosum L) improves protection against DNA damage but not vascular function in healthy male volunteers

It has been suggested that anthocyanin-rich foods may exert antioxidant effects and improve vascular function as demonstrated mainly in vitro and in the animal model. Blueberries are rich sources of anthocyanins and we hypothesized that their intake could improve cell protection against oxidative stress and affect endothelial function in humans. The aim of the study was to investigate the effect of one portion (300 g) of blueberries on selected markers of oxidative stress and antioxidant protection (endogenous and oxidatively induced DNA damage) and of vascular function (changes in peripheral arterial tone and plasma nitric oxide levels) in male subjects. In a randomized cross-over design, separated by a wash out period ten young volunteers received one portion of blueberries ground by blender or one portion of a control jelly. Before and after consumption (at 1, 2, and 24 hours), blood samples were collected and used to evaluate anthocyanin absorption (through mass spectrometry), endogenous and H(2)O(2)-induced DNA damage in blood mononuclear cells (through the comet assay), and plasma nitric oxide concentrations (through a fluorometric assay). Peripheral arterial function was assessed by means of Endo-PAT 2000. Blueberries significantly reduced (P < .01) H(2)O(2)-induced DNA damage (-18%) 1 hour after blueberry consumption compared to control. No significant differences were observed for endogenous DNA damage, peripheral arterial function and nitric oxide levels after blueberry intake. In conclusion, one portion of blueberries seems sufficient to improve cell antioxidant defense against DNA damage, but further studies are necessary to understand their role on vascular function.

Vascular reactivity is affected by dietary consumption of wild blueberries in the Sprague-Dawley rat.

We have previously reported that consumption of blueberry-enriched (BB) diets attenuates the arterial contractile response to alpha(1)-adrenergic stimuli and affects vasomotor tone via endothelium-related pathways. The present study was designed to evaluate vascular function and responsiveness in aortas of weanling male Sprague-Dawley rats fed a control (C) or a BB diet for 7 weeks. Vascular ring studies were conducted in 3-mm isolated rat aortic ring preparations to investigate vasoconstriction induced by L-phenylephrine (Phe) (10(-8)-3 x 10(-6) M) and vasorelaxation induced by acetylcholine (ACh) (10(-8)-3 x 10(-6) M). Agonists were used alone and in the presence of nitric oxide (NO) synthase and cyclooxygenase (COX) inhibitors. We observed a significantly diminished vasoconstrictor response to Phe in aortic rings from rats fed the BB diet. Inhibition of NO synthase but not COX caused a significant increase in the constrictor response in both dietary groups, with the BB group having the greater response. Similarly, the participation of the NO pathway in endothelium-dependent vasorelaxation induced by ACh was greater in the rats fed a BB diet, while COX inhibition showed no effect on maximum ACh-induced vasorelaxation in any diet group. The vessel sensitivity of BB aortic rings to the vasoconstrictor and vasodilator was significantly reduced when compared to controls. We have concluded that diets enriched with blueberries, fed for 7 weeks in Sprague-Dawley rats, seem to affect NO metabolic pathways in the aorta at basal and stimulated levels.

Dietary enrichment with wild blueberries (Vaccinium angustifolium) affects the vascular reactivity in the aorta of young spontaneously hypertensive rats.

We have previously reported on the positive effects of wild blueberries on arterial contractile response to alpha(1) adrenergic stimuli and on endothelium-mediated vasorelaxation. Our present study was designed to evaluate the effects of the dietary enrichment with wild blueberries on aortic function and reactivity in the developmental phase of essential hypertension in spontaneously hypertensive rats (SHR). We investigated the possible influence blueberries may have on the acetylcholine (Ach)-induced endothelium-dependent vasorelaxation and phenylephrine-induced vasoconstriction in young SHRs, as well as the contribution of the nitric oxide (NO) synthase and cyclooxygenase (COX) pathways in each of the above responses in an animal model with dysfunctional endothelium. Vascular ring studies were conducted in 3-mm isolated rat aortic ring preparations to investigate vasoconstriction induced by l-Phenylephrine (Phe, 10(-8) to 3x10(-6)M) and vasorelaxation induced by acetylcholine (Ach, 10(-9) to 3x10(-6)M). The major findings of our study were that in Phe-induced vasoconstriction, SHR-BB aortas relaxed to a greater degree in comparison to controls when mefenamic acid (MFA) was present and that the incubation with this COX inhibitor failed to restore - and in fact decreased - the maximum vasodilator response to Ach, in comparison to controls. Our vessel reactivity index (pD(2)) observations indicate that blueberries appear to modulate cell membrane-agonist (Ach) interactions primarily in response to Ach in the young SHR model, but not to the alpha(1) adrenoreceptor agonist. Incorporating wild blueberries in the diet seems to affect the endothelium-dependent vasorelaxation by modulating alternative metabolic pathway(s) (such as affecting the production/activity of COX-derived products) in the young SHR aorta.

Differential Modulation of Human Intestinal Bifidobacterium Populations after Consumption of a Wild Blueberry (Vaccinium angustifolium) Drink

Bifidobacteria are gaining increasing interest as health-promoting bacteria. Nonetheless, the genus comprises several species, which can exert different effects on human host. Previous studies showed that wild blueberry drink consumption could selectively increase intestinal bifidobacteria, suggesting an important role for the polyphenols and fiber present in wild blueberries. This study evaluated the modulation of the most common and abundant bifidobacterial taxonomic groups inhabiting the human gut in the same fecal samples. The analyses carried out showed that B. adolescentis, B. breve, B. catenulatum/pseudocatelulatum, and B. longum subsp. longum were always present in the group of subjects enrolled, whereas B. bifidum and B. longum subsp. infantis were not. Furthermore, it was found that the most predominant bifidobacterial species were B. longum subsp. longum and B. adolescentis. The results obtained revealed a high interindividual variability; however, a significant increase of B. longum subsp. infantis cell concentration was observed in the feces of volunteers after the wild blueberry drink treatment. This bifidobacterial group was shown to possess immunomodulatory abilities and to relieve symptoms and promote the regression of several gastrointestinal disorders. Thus, an increased cell concentration of B. longum subsp. infantis in the human gut could be considered of potential health benefit. In conclusion, wild blueberry consumption resulted in a specific bifidogenic effect that could positively affect certain populations of bifidobacteria with demonstrated health-promoting properties.

Disordered eating attitudes: An emerging health problem among Mediterranean adolescents

Aim of the present study was to investigate eating attitudes in a group of Mediterranean high school students. One hundred and twenty high school students participated in this survey. The Eating Attitudes Test (EAT-26) was used for evaluating symptoms and attitudes associated with disordered eating. Body composition and dietary intake were also assessed. Using the cut-off point of 20 in the total EAT, 13 females (20.3%) and 4 males (7.3%) exhibited disordered eating behavior. Overweight students had significantly higher scores in the dieting scale than those in the normal BMI range. Percent fat mass was positively related to the total EAT (r=0.326, p<0.001) and the dieting scale (r=0.489, p<0.001). Waist/hip ratio was negatively related to total EAT and its scales. In conclusion, a significant percentage of students in this urban Mediterranean adolescent population found to have abnormal eating attitudes. This finding may be partly explained by the effect of cultural transition.