The Effects of a Cinchona Supplementation on Satiety, Weight Loss and Body Composition in a Population of Overweight/Obese Adults: A Controlled Randomized Study.

Obesity is a risk factor for several diseases present worldwide. Currently, dietary changes and physical activity are considered the most effective treatment to reduce obesity and its associated comorbidities. To promote weight loss, hypocaloric diets can be supported by nutraceuticals. The aim of this study was to evaluate the effects of a hypocaloric diet associated with Cinchona succirubra supplementation on satiety, body weight and body composition in obese subjects. Fifty-nine overweight/obese adults, were recruited, randomized into two groups and treated for 2 months. The first group (32 adults) was treated with a hypocaloric diet plus cinchona supplementation (the T-group); the second one (27 adults) was treated with a hypocaloric diet plus a placebo supplementation (the P-group). Anthropometric-measurements as well as bioimpedance analysis, a Zung test and biochemical parameters were evaluated at baseline and after 60 days. T-group adults showed significant improvement in nutritional status and body composition compared to those at the baseline and in the P-group. Moreover, T-group adults did not show a reduction in Cholecystokinin serum levels compared to those of P-group adults. In conclusion, our data demonstrate that a hypocaloric diet associated with cinchona supplementation is effective in inducing more significant weight loss and the re-establishment of metabolic parameters than those obtained with a hypocaloric diet.

Pharmacomicrobiomics of Classical Immunosuppressant Drugs: A Systematic Review.

The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.

Caloric Restriction (CR) Plus High-Nitrate Beetroot Juice Does Not Amplify CR-Induced Metabolic Adaptation and Improves Vascular and Cognitive Functions in Overweight Adults: A 14-Day Pilot Randomised Trial.

Caloric restriction (CR) and dietary nitrate supplementation are nutritional interventions with pleiotropic physiological functions. This pilot study investigates the combined effects of CR and nitrate-rich beetroot juice (BRJ) on metabolic, vascular, and cognitive functions in overweight and obese middle-aged and older adults. This was a two-arm, parallel randomized clinical trial including 29 participants allocated to CR + BRJ (n = 15) or CR alone (n = 14) for 14 days. Body composition, resting energy expenditure (REE), and hand-grip strength were measured. Resting blood pressure (BP) and microvascular endothelial function were measured, and Trail-Making Test A and B were used to assess cognitive function. Salivary nitrate and nitrite, and urinary nitrate and 8-isoprostane concentrations were measured. Changes in body composition, REE, and systolic and diastolic BP were similar between the two interventions (p > 0.05). The CR + BRJ intervention produced greater changes in average microvascular flux (p = 0.03), NO-dependent endothelial activity (p = 0.02), and TMT-B cognitive scores (p = 0.012) compared to CR alone. Changes in urinary 8-isoprostane were greater in the CR + BRJ group (p = 0.02), and they were inversely associated with changes in average microvascular flux (r = -0.53, p = 0.003). These preliminary findings suggest that greater effects on vascular and cognitive functions could be achieved by combining CR with dietary nitrate supplementation.

The Synergic Effect of a Nutraceutical Supplementation Associated to a Mediterranean Hypocaloric Diet in a Population of Overweight/Obese Adults with NAFLD.

Overweight/obesity is often associated with a non-alcoholic fatty liver disease (NAFLD). The study aim was to investigate the effects of a nutraceutical supplementation associated to a Mediterranean-hypocaloric-diet (MHD) on ultrasound-liver-steatosis (ULS) grade improvement in overweight/obese patients with NAFLD. A total of 68 subjects (BMI ≥ 25 kg/m2) with NAFLD were recruited, randomized into 2 groups and treated for 3 months: the Nutraceutical group was treated with MHD plus nutraceutical supplementation (Vitamin E, L-glutathione, silymarin and hepato-active compounds); the Control-group only with a MHD. Anthropometric measurements, body composition, biochemical parameters and Hepatic steatosis index (HSI) were evaluated at baseline and after 3 months; patients with HSI >36 underwent a liver ultrasound to determine liver steatosis grade (3 severe, 2 moderate, 1 mild). In all patients, a significant improvement in nutritional and biochemical parameters was observed after treatment. After treatment, the nutraceutical group showed a significant improvement in hepatic steatosis, either according to ULS-grade (11.1% and 5.6% of patients with mild and moderate liver steatosis, respectively, showed a complete NAFLD regression; 33.3% and 22.2% of patients with moderate and severe liver steatosis, respectively showed a regression to mild liver steatosis), or according to HSI (49.3 ± 10.1 vs. 43.3 ± 9.0, p = 0.01), suggesting that a healthy diet is still the best choice, although the use of specific supplements can enhance the efficacy of dietary intervention in overweight/obese patients with NAFLD.

The Effects of Angiotensin II or Angiotensin 1-7 on Rat Pial Microcirculation during Hypoperfusion and Reperfusion Injury: Role of Redox Stress.

Renin-angiotensin systems produce angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7), which are able to induce opposite effects on circulation. This study in vivo assessed the effects induced by Ang II or Ang 1-7 on rat pial microcirculation during hypoperfusion-reperfusion, clarifying the mechanisms causing the imbalance between Ang II and Ang 1-7. The fluorescence microscopy was used to quantify the microvascular parameters. Hypoperfusion and reperfusion caused vasoconstriction, disruption of blood-brain barrier, reduction of capillary perfusion and an increase in reactive oxygen species production. Rats treated with Ang II showed exacerbated microvascular damage with stronger vasoconstriction compared to hypoperfused rats, a further increase in leakage, higher decrease in capillary perfusion and marker oxidative stress. Candesartan cilexetil (specific Ang II type 1 receptor (AT1R) antagonist) administration prior to Ang II prevented the effects induced by Ang II, blunting the hypoperfusion-reperfusion injury. Ang 1-7 or ACE2 activator administration, preserved the pial microcirculation from hypoperfusion-reperfusion damage. These effects of Ang 1-7 were blunted by a Mas (Mas oncogene-encoded protein) receptor antagonist, while Ang II type 2 receptor antagonists did not affect Ang 1-7-induced changes. In conclusion, Ang II and Ang 1-7 triggered different mechanisms through AT1R or MAS receptors able to affect cerebral microvascular injury.

Rat Pial Microvascular Changes During Cerebral Blood Flow Decrease and Recovery: Effects of Cyanidin Administration.

The reactive oxygen species (ROS) are known to play a major role in many pathophysiological conditions, such as ischemia and reperfusion injury. The present study was aimed to evaluate the in vivo cyanidin (anthocyanin) effects on damages induced by rat pial microvascular hypoperfusion-reperfusion injury by cerebral blood flow decrease (CBFD) and subsequent cerebral blood flow recovery (CBFR). In particular, the main purpose was to detect changes in ROS production after cyanidin administration. Rat pial microvasculature was investigated using fluorescence microscopy through a cranial window (closed); Strahler's method was utilized to define the geometric features of pial vessels. ROS production was investigated in vivo by 2'-7'-dichlorofluorescein-diacetate assay and neuronal damage was measured on isolated brain sections by 2,3,5-triphenyltetrazolium chloride staining. After 30 min of CBFD, induced by bilateral common carotid artery occlusion, and 60 min of CBFR, rats showed decrease of arteriolar diameter and capillary perfusion; furthermore, increase in microvascular leakage and leukocyte adhesion was observed. Conversely, cyanidin administration induced dose-related arteriolar dilation, reduction in microvascular permeability as well as leukocyte adhesion when compared to animals subjected to restriction of cerebral blood flow; moreover, capillary perfusion was protected. ROS generation increase and marked neuronal damage were detected in animals subjected to CBFD and CBFR. On the other hand, cyanidin was able to reduce ROS generation and neuronal damage. In conclusion, cyanidin treatment showed dose-related protective effects on rat pial microcirculation during CBFD and subsequent CBFR, inducing arteriolar dilation by nitric oxide release and inhibiting ROS formation, consequently preserving the blood brain barrier integrity.

Laser Speckle Imaging of Rat Pial Microvasculature during Hypoperfusion-Reperfusion Damage.

The present study was aimed to in vivo assess the blood flow oscillatory patterns in rat pial microvessels during 30 min bilateral common carotid artery occlusion (BCCAO) and 60 min reperfusion by laser speckle imaging (LSI). Pial microcirculation was visualized by fluorescence microscopy. The blood flow oscillations of single microvessels were recorded by LSI; spectral analysis was performed by Wavelet transform. Under baseline conditions, arterioles and venules were characterized by blood flow oscillations in the frequency ranges 0.005-0.0095 Hz, 0.0095-0.021 Hz, 0.021-0.052 Hz, 0.052-0.150 Hz and 0.150-0.500 Hz. Arterioles showed oscillations with the highest spectral density when compared with venules. Moreover, the frequency components in the ranges 0.052-0.150 Hz and 0.150-0.500 were predominant in the arteriolar total power spectrum; while, the frequency component in the range 0.150-0.500 Hz showed the highest spectral density in venules. After 30 min BCCAO, the arteriolar spectral density decreased compared to baseline; moreover, the arteriolar frequency component in the range 0.052-0.150 Hz significantly decreased in percent spectral density, while the frequency component in the range 0.150-0.500 Hz significantly increased in percent spectral density. However, an increase in arteriolar spectral density was detected at 60 min reperfusion compared to BCCAO values; consequently, an increase in percent spectral density of the frequency component in the range 0.052-0.150 Hz was observed, while the percent spectral density of the frequency component in the range 0.150-0.500 Hz significantly decreased. The remaining frequency components did not significantly change during hypoperfusion and reperfusion. The changes in blood flow during hypoperfusion/reperfusion caused tissue damage in the cortex and striatum of all animals. In conclusion, our data demonstrate that the frequency component in the range 0.052-0.150 Hz, related to myogenic activity, was significantly impaired by hypoperfusion and reperfusion, affecting cerebral blood flow distribution and causing tissue damage.

Dietary protein intake in sarcopenic obese older women.

OBJECTIVE: To determine the prevalence of sarcopenia in a population of obese older women and to assess the effect of a diet moderately rich in proteins on lean mass in sarcopenic obese older women. MATERIALS AND METHODS: A total of 1,030 females, >65 years old, body mass index >30 kg/m(2), were investigated about their nutritional status. Muscle mass (MM) was estimated according to the Janssen equation (MM =0.401× height(2)/resistance measured at 50 kHz +3.825× sex -0.071× age +5.102). Sarcopenia was defined according to the MM index, MM/height2 (kg/m(2)), as two standard deviations lower than the obesity-derived cutoff score (7.3 kg/m(2)). A food-frequency questionnaire was used to measure participants' usual food intake during the previous 3 months. Moreover, a group of sarcopenic obese older women (n=104) was divided in two subgroups: the first (normal protein intake [NPI], n=50) administered with a hypocaloric diet (0.8 g/kg desirable body weight/day of proteins), and the second treated with a hypocaloric diet containing 1.2 g/kg desirable body weight/day of proteins (high protein intake [HPI], n=54), for 3 months. Dietary ingestion was estimated according to a daily food diary, self-administered, and three reports of nonconsecutive 24-hour recall every month during the follow-up. RESULTS: The 104 women were classified as sarcopenic. After dieting, significant reductions in body mass index were detected (NPI 30.7±1.3 vs 32.0±2.3 kg/m(2), HPI 30.26±0.90 vs 31.05±2.90 kg/m(2); P<0.01 vs baseline). The MM index presented significant variations in the NPI as well as in the HPI sarcopenic group (NPI 6.98±0.1 vs 7.10±0.2 kg/m(2), HPI 7.13±0.4 vs 6.96±0.1 kg/m(2); P<0.01 vs baseline). CONCLUSION: A diet moderately rich in proteins was able to preserve MM in sarcopenic women. Therefore, adequate protein intake could contribute to the prevention of lean-mass loss associated with weight reduction in obese older people.

Effects of intentional weight loss on physical and cognitive function in middle-aged and older obese participants: a pilot study.

OBJECTIVES: Obesity is a risk factor for cognitive decline and dementia. Whether weight loss improves cognition in older obese adults is not known. The objective was to investigate the effects of intentional weight loss on physical and cognitive function in middle-aged and older obese adults attending a weight loss clinic. METHOD: Eleven male and 39 female nonsmoking, adult obese (body mass index 30-50 kg/m(2)) participants were recruited. Participants were stratified by age: middle aged (30-59 years) and older aged (≥ 60 years). The weight loss target for each subject was 8% to 12% of initial body weight. Information on anthropometry, bioelectrical impedance, hand-grip strength, Mini-Mental State Examination (MMSE), Short Portable Mental Status Questionnaire (SPMSQ), and Trail-Making Test (TMT) A and B were collected at baseline and after weight loss. RESULTS: At baseline, older participants showed a nonsignificant trend for lower global cognitive function (MMSE, SPMSQ) and significantly slower processing speed (TMT-A). Twenty-one participants completed the weight loss study. The average weight loss relative to baseline was 9.7% ± 2.1%. Weight loss was associated with significant improvements in hand-grip strength and cognitive function (MMSE, TMT-A, and TMT-B). MMSE scores improved significantly only in older obese participants (p < 0.05). CONCLUSIONS: Weight loss in middle-aged and in older obese participants has a beneficial effect on cognitive and physical function. If confirmed in future trials, weight loss can significantly affect public health strategies for the prevention of dementia as well as on the clinical management of obesity.