Anthocran® Phytosome®: Prevention of Recurring Urinary Infections and Symptoms after Catheterization.

In this preliminary pilot registry study, we investigated the effects of the oral supplementation of a standardized cranberry extract (Anthocran® Phytosome®, Indena) delivered by a lecithin-based system, for the prophylactic management of recurrent-urinary tract infections (R-UTIs). We included 64 otherwise healthy subjects who underwent a surgical procedure and required post-surgical urinary catheterization for high-risk UTIs or a previous history of R-UTIs. Patients were given supplementation with the standardized cranberry extract at the dose of either 120 mg/day (n = 12) or 240 mg/day (n = 12) or assigned to a control group consisting of standard management (SM; n = 18) or nitrofurantoin administration (n = 22) for 4 weeks. After 4 weeks, patients receiving the standardized cranberry supplementation reported to have a more effective reduction in UTI symptoms, as assessed on the visual analogue scale, compared with patients in the SM or nitrofurantoin groups. The occurrence of hematuria and urine bacterial contamination were decreased among patients treated with the supplement compared with controls (p < 0.05). The cranberry extract was also superior to the control management in terms of recurrence of signs/symptoms, with none of the patients in this group suffering from a R-UTI in the 3 months following the study end (p < 0.05). The supplementation showed an optimal safety profile, with no significant adverse events and no drop-outs in the supplement group. This registry shows that this cranberry extract is effective as a supplementary, preventive management in preventing post-operative, post-catheter UTIs; the product has a good tolerability profile.

A 60-Day Green Tea Extract Supplementation Counteracts the Dysfunction of Adipose Tissue in Overweight Post-Menopausal and Class I Obese Women.

Menopause is characterized by weight gain and increased visceral fat, which acts as an endocrine organ secreting proinflammatory adipocytokines, with consequent increased risk of metabolic disorders. The aim of this double-blind, placebo-controlled randomized trial was to evaluate the effects of a 60-day dietary supplementation using Camellia sinensis leaf extract on adipose tissue dysfunction in overweight or class I obese post-menopausal, sedentary women. Primary endpoints were the respiratory quotient (RQ), the percentage of carbohydrates (%CHO), the percentage of fat oxidation (%FAT), and the resting energy expenditure (REE) measured by indirect calorimetry. Secondary endpoints included body composition, by dual x-ray absorptiometry (DXA), glucose profile, lipid profile, inflammatory state, liver and kidney function, hormonal status regarding satiety, and status of catecholamines. Twenty-eight women were randomized into two groups: 14 (BMI 31.1 ± 3.5) were supplemented and 14 (BMI 31.9 ± 2.2) received placebo. In regards to the between-group differences over time (ß), a statistically significant difference between the supplemented and placebo group was observed for: RQ (ß = -0.04, p = 0.009), % fat oxidation (ß = 11.04, p = 0.0006), insulin (ß = -1.74, p = 0.009), HOMA (ß = -0.31, p = 0.02), waist circumference (ß = -1.07, p = 0.007), REE (ß = 83.21, p = 0.009), and CRP (ß = -0.14, p = 0.02). These results demonstrate that a 60-day green tea extract supplementation counteracts the dysfunction of adipose tissue in overweight post-menopausal and class I obese women.

Positive Effects of a Lecithin-Based Delivery Form of Boswellia serrata Extract in Acute Diarrhea of Adult Subjects.

Acute diarrhea is a frequent problem worldwide, mostly due to gastrointestinal infections or food poisoning. Boswellia serrata could be active in the treatment of acute diarrhea due to its anti-inflammatory, antispasmodic, and antimicrobial activity. In this randomized, double-blind, placebo-controlled clinical study, 49 adults with acute diarrhea were randomly allocated to receive 250 mg of a lecithin-based delivery form of Boswellia serrata (CASP) or placebo for 5 days. The time it took to become healthy with stoppage of diarrhea (primary end point) was significantly shorter in the intervention group (3.08 vs. 4.44 days: p-value < 0.0001). The probability of subjects treated with CASP to recover sooner was equal to 80.2%. A significantly lower number of stools was observed in the CASP group over time (ß = −0.17, p-value < 0.0001). A significant difference was observed between the two groups for abdominal pain, nausea, and GAE (global assessment of efficacy). In conclusion, the lecithin-based delivery form of Boswellia serrata extract could be a useful addition to the treatment of acute diarrhea in adults. CASP is safe and reduces the time it takes to become healthy, the frequency of stools, the abdominal pain and nausea of subjects with acute diarrhea. Further studies are needed to confirm these promising results.

Beneficial Effects on Abdominal Bloating with an Innovative Food-Grade Formulation of Curcuma longa and Boswellia serrata Extracts in Subjects with Irritable Bowel Syndrome and Small Bowel Dysbiosis.

Bloating is a symptom frequently reported by subjects with irritable bowel syndrome (IBS) and small bowel dysbiosis, and Low FODMAP's diet (LFD) has been used to treat them. Extracts of Curcumalonga and Boswelliaserrata share anti-inflammatory and antimicrobial effects that could be useful in the management of these clinical conditions. The aim of this study was to evaluate the efficacy of curcumin and boswellia extracts (as Curcumin Boswellia Phytosome, CBP) and LFD on the relief of abdominal bloating in IBS subjects with small bowel dysbiosis, in comparison to LFD alone, in a 30-day supplementation, randomized trial. IBS participants were randomized to either the intervention (500 mg bid of CBP and LFD) or control arm (LFD). Small bowel dysbiosis has been defined by an increase of urinary indican with normal urinary skatole. A total of 67 subjects were recruited. The intervention group (33 subjects) showed a significant decrease (p < 0.0001) of bloating, abdominal pain, and indican values at the end of the study, when compared to the control group (34 subjects). Moreover, the subjects of the intervention group showed a significantly better (p < 0.0001) global assessment of efficacy (GAE) as compared to controls. In conclusion, in subjects with IBS and small bowel dysbiosis, abdominal bloating can be successfully reduced with a supplementation with CBP and LFD.

Shedding light on curcumin stability.

The stability of molecular curcumin (purcumin, 1a) in solution is strongly light-dependent. Under laboratory artificial light, a relative stability is observed only at neutral pH, while more intense light and/or solar light can trigger degradation via a combination of hydrolytic and oxidative fragmentation of the heptadiendione moiety. Minor curcuminoids in commercial curcumin (purcuminoids) can improve the stability of molecular curcumin, but only under conditions of low irradiation. While confirming earlier observations alerting to the instability of purcumin, our results provide new rationales for unexplained differences between previous studies, question the biological relevance of a non-enzymatic degradation for the bioactivity profiles that have been reported for purcumin, and highlight the need of a better characterization of the degradation of purcuminoids under visible light irradiation.

Efficacy of artichoke and ginger extracts with simethicone to treat gastrointestinal symptoms in endurance athletes: a pilot study.

BACKGROUND: Exercise-induced gastrointestinal (GI) symptoms are frequently reported by athletes during training and competitions. A standardized combination of artichoke leaves and ginger root extracts has shown beneficial effects in managing GI discomfort in otherwise healthy subjects. METHODS: In this pilot study, we assessed the effectiveness of artichoke leaves and ginger root extracts combination associated with simethicone in reducing exercise-related GI symptoms in endurance athletes. The effects of the combination on upper/lower GI and systemic symptoms were assessed at baseline and after 4 weeks through a questionnaire. RESULTS: Fifty endurance athletes took the extracts' combination 320 mg + simethicone 40 mg chewable pills. The extracts combination and simethicone were effective in reducing the mean intensity of upper GI (86.6%) lower GI (85.9%) and systemic symptoms (81.9%), with superior results compared to placebo. The most remarkable effects were reported in the lower GI tract, with a significant decrease in flatulence, intestinal cramps, loose stools and diarrhea. Athletes also benefited from a reduction in belching and bloating and in dizziness, headache and muscle cramps, although the decrease in systemic symptoms was not significant. CONCLUSIONS: The supplementation of standardized artichoke and ginger extracts, combined with simethicone, may be effective in decreasing digestive discomfort and alteration of gastric motility not only in healthy subjects but also in endurance athletes.

Development of an Innovative Berberine Food-Grade Formulation with an Ameliorated Absorption: In Vitro Evidence Confirmed by Healthy Human Volunteers Pharmacokinetic Study.

OBJECTIVE: To evaluate in vitro solubility, bioaccessibility, and cytotoxic profile, together with a pharmacokinetic profile by oral administration to healthy volunteers of a novel food-grade berberine formulation (BBR-PP, i.e., berberine Phytosome®). RESULTS: An in vitro increase of solubility in simulated gastric and intestinal fluids and an improved bioaccessibility at intestinal level along with a lower cytotoxicity with respect to berberine were observed with BBR-PP. The pharmacokinetic profile of the oral administration to healthy volunteers confirmed that berberine Phytosome® significantly ameliorated berberine absorption, in comparison to unformulated berberine, without any observed side effects. The berberine plasma concentrations observed with both doses of BBR-PP were significantly higher than those seen after unformulated berberine administration, starting from 45 min (free berberine) and 30 min (total berberine). Furthermore, BBR-PP improved berberine bioavailability (AUC) was significantly higher, around 10 times on molar basis and with observed dose linearity, compared to the unformulated berberine. CONCLUSION: These findings open new perspectives on the use of this healthy berberine formulation in metabolic discomforts.

Effect of Acute and Chronic Dietary Supplementation with Green Tea Catechins on Resting Metabolic Rate, Energy Expenditure and Respiratory Quotient: A Systematic Review.

The consumption of green tea catechins (GTC) is associated with modulations of fat metabolism and consequent weight loss. The aim of this systematic review was to investigate the effect of GTC on resting metabolic rate (RMR), energy expenditure (EE), and respiratory quotient (RQ). Eligible studies considered both the chronic and acute intake of GTC-based supplements, with epigallocatechin gallate (EGCG) doses ranging between 100-800 mg. Findings from 15 studies (n = 499 participants) lasting 8-12 weeks (for chronic consumption) or 1-3 days (for acute intake) are summarized. This review reveals the positive effects of GTC supplementation on RQ values (272 subjects). Regarding the effects of acute and chronic GTC supplementation on RMR (244 subjects) and EE (255 subjects), the results did not allow for a definitive conclusion, even though they were promising, because some reported a positive improvement (two studies revealed an increase in RMR: one demonstrated an RMR increase of 43.82 kcal/day and another demonstrated an increase of 260.8 kcal/day, mainly when subjects were also engaged in resistance training exercise). Considering GTC daily dose supplementation, studies in which modifications of energetic parameters occurred, in particular RQ reduction, considered GTC low doses (100-300 mg). GTC may be useful for improving metabolic profiles. Further investigations are needed to better define adequate doses of supplementation.

Grape Seed Extract Positively Modulates Blood Pressure and Perceived Stress: A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Volunteers.

It is well established that maintaining healthy blood pressure is fundamental in order to avoid disorders to the heart and blood vessels. In prevention, and alongside pharmacological therapy, the use of natural substances has been proven to be extremely helpful for pre- and mild hypertensive subjects. Our study was therefore focused on the effects, both in vitro and in humans, of a grape seed extract, Enovita (GSEe), a highly standardized extract in polyphenols of Vitis vinifera L. The in vitro human umbilical vein endothelial cells (HUVEC) model was chosen to explore the extract properties related to vascular inflammation/vasodilation. A significant reduction of both soluble Inter-Cellular Adhesion Molecule-1 (sICAM) and endothelin-1 secretion/release was induced by GSEe in HUVEC cells. A randomized, double-blind, placebo-controlled clinical study in healthy volunteers was further performed to investigate GSEe benefits. In healthy volunteers, both supplementations significantly modulated blood pressure, with a pronounced effect after GSEe tablets (300 mg/day for 16 weeks) in respect to placebo. In the male gender subgroup, no placebo effect was observed as it was for the female group. As an additional outcome, an overall GSEe positive modulation emerged on mood related to stress perception. Thus, GSEe resulted in a benefit of modulating endothelial functionality and blood pressure. It was noteworthy that GSEe relieved the perceived stress, promising new future perspectives on mood comfort.

In vitro (poly)phenol catabolism of unformulated- and phytosome-formulated cranberry (Vaccinium macrocarpon) extracts.

Cranberries (Vaccinium macrocarpon) represent an important source of anthocyanins, flavan-3-ols and flavonols. This study aimed at investigating in vitro the human microbial metabolism of (poly)phenols, principally flavan-3-ols, of unformulated- and phytosome-formulated cranberry extracts. After powder characterization, a 24-h fermentation with human faecal slurries was performed, standardizing the concentration of incubated proanthocyanidins. Cranberry (poly)phenol metabolites were quantified by uHPLC-MS2 analyses. The native compounds of both unformulated- and phytosome-formulated cranberry extracts were metabolized under faecal microbiota activity, resulting in twenty-four microbial metabolites. Although some differences appeared when considering different classes of colonic metabolites, no significant differences in the total amount of metabolites were established after 24 h of incubation period. These results suggested that a different formulation had no effect on flavan-3-ol colonic metabolism of cranberry and both unformulated- and phytosome-formulated extract. Both formulations displayed the capability to be a potential source of compounds which could lead to a wide array of gut microbiota metabolites in vitro.

Artichoke and Bergamot Phytosome Alliance: A Randomized Double Blind Clinical Trial in Mild Hypercholesterolemia.

Botanicals are natural alternatives to pharmacological therapies that aim at reducing hypercholesterolemia. In this context, despite bergamot being effective in modulating lipid profile, some subjects failed to achieve a satisfactory response to supplementation. The aim of this study was to evaluate whether the association of 600 mg of bergamot phytosome® (from Citrus Bergamia Risso) and 100 mg of artichoke leaf standardized dry extract (from Cynara cardunculus L.) can be an alternative in patients with mild hypercholesterolemia who are poor responders to bergamot in a 2-month randomized placebo-controlled trial. Sixty overweight adults were randomized into two groups: 30 were supplemented and 30 received a placebo. The metabolic parameters and DXA body composition were evaluated at the start, after 30 and 60 days. Between the two groups, total and LDL cholesterol in the supplemented group (compared to placebo) showed significant decreases overtime. A significant reduction of waist circumference and visceral adipose tissue (VAT) was recorded in the supplemented group (compared to placebo), even in subjects who did not follow a low-calorie diet. In conclusion, the synergism between Citrus Bergamia polyphenols and Cynara cardunculus extracts may be an effective option and may potentially broaden the therapeutic role of botanicals in dyslipidemic patients.

Bergamot phytosome improved visceral fat and plasma lipid profiles in overweight and obese class I subject with mild hypercholesterolemia: A randomized placebo controlled trial.

Bergamot has been traditionally used for the relief of diseases related to oxidative stress. Our aim was to investigate the effect of bergamot phytosome on visceral adipose tissue (VAT) and on metabolic profile, in overweight and obese subjects with mild hypercholesterolemia. A total of 64 participants were randomized into two groups for 12 weeks: a supplemented group (33 individuals, BMI 27 ± 3 kg/m2 receiving 500 mg of bergamot phytosome, two daily tablets) and placebo group (31 subjects, BMI 28 ± 3 kg/m2 , two daily tablets). As to the within differences, the parameters of VAT, total and LDL-cholesterol were significantly decreased in the bergamot phytosome group, but not in the placebo group. As to between-group differences, a statistically significant interaction between time and group, that is, the change in score over time differs between the two groups was observed 30 days after supplementation for VAT (p-value = .005), total cholesterol (p-value <.0002), and LDL (p = .004) in respect to placebo. The other parameters (glucose, insulin, Homeostasis Model Assessment, high-density lipoprotein cholesterol, triglycerides, fat free mass, fat mass) were not significant. In conclusion, this clinical study gives evidence that bergamot phytosome provides beneficial effects, such as decrease of VAT and modulation of metabolic alterations, after just 30 days of supplementation, resulting a very promising protection of cardiovascular health.

The Metabolic Effects of Cynara Supplementation in Overweight and Obese Class I Subjects with Newly Detected Impaired Fasting Glycemia: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

Impaired fasting glucose (IFG) is a condition that precedes diabetes and increases the risk of developing it. Studies support the hypoglycemic effect of Cynarascolymus (Cs) extracts due to the content of chlorogenic acid, which is a potent inhibitor of glucose 6-phosphate translocase and of dicaffeoylquinic acid derivatives that modulate the activity of alpha-glucosidase. Given this background, we investigated whether a new highly standardized Cs extract could improve glycemic control, insulin sensitivity and other metabolic parameters (total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) Triglycerides, Apolipo protein B (ApoB), Apolipo protein A (ApoA), waist circumference, visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry (DXA) in overweight subjects with newly diagnosed IFG. Fifty-four subjects (females/males 26/28, mean ± SD age 51.5 ± 6.2) were randomly assigned to the supplemented group (n = 27) and placebo (n = 27). After multiple testing correction, statistically significant interactions between time and group were observed for the primary endpoint glycemia (ß = 0.36, p < 0.0001) and for the secondary endpoints HDL (ß = -0.10, p < 0.0001), total cholesterol/HDL (ß = 0.27, p < 0.0001), LDL (ß = 0.15, p = 0.005), LDL/HDL (ß = 0.23, p = 0.001), insulin (ß = 1.28, p = 0.04), glycated hemoglobin (ß = 0.21, p = 0.0002), A1c-derived average glucose (ß = 0.34, p = 0.0002), ApoB (ß = 6.00, p = 0.01), ApoA (ß = -4.50, p = 0.04), ApoB/ApoA (ß = 0.08, p = 0.003), waist circumference (ß = 1.89, p = 0.05), VATß = 222.37, p = 0.005). In conclusion, these results confirm that Cs supplementation has a significant effect on metabolic parameters in IFG patients.

The Use of a New Food-Grade Lecithin Formulation of Highly Standardized Ginger (Zingiber officinale) and Acmella oleracea Extracts for the Treatment of Pain and Inflammation in a Group of Subjects with Moderate Knee Osteoarthritis.

PURPOSE: To evaluate the efficacy of a new food-grade lecithin formulation of standardized extracts of Zingiber officinale and Acmella oleracea on pain and inflammation. PATIENTS AND METHODS: Pilot study with one-group pretest-posttest quasi-experimental design in which 50 subjects with moderate knee osteoarthritis (OA) (mean age: 62.46±8.45) were supplied for four weeks with two tablets/day. RESULTS: Primary outcomes were 1) the evaluation of pain intensity, by a 30-day visual analogue scale (VAS) and 2) the assessment of knee function by WOMAC (Western Ontario and McMaster Universities Arthritis) Index and by Tegner Lysholm Knee Scoring collected at baseline, at 15 and 30 days after treatment. Secondary outcomes were 3) health-related quality of life, by the ShortForm36 (SF-36); 4) inflammation grade by C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR); and 5) body composition by dual-energy X-ray absorptiometry (DXA) measured at baseline and 30 days after treatment. Data showed significant effects of supplement intake for WOMAC (ß=-3.27, p<0.0001), Lysholm (ß=1.06, p=0.0003), CRP (ß=-0.13, p=0.006), ESR (ß=-3.09, p=0.004), physical activity (ß=4.3, p=0.009) and fat-free mass (ß=376.7, p=0.046). A significant VAS's decrease over time was observed in ï»¿both knees (left: ß=-0.08, p<0.0001; right: ß=-0.07, p<0.0001). CONCLUSION: The tested formulation seems to be effective and also free of side effects.

Acmella oleracea for pain management.

Despite advances in medicine and numerous agents that counteract pain, millions of patients continue to suffer. Attention has been given to identify novel botanical interventions that produce analgesia by interacting with nociceptive-transducing channels. The aim of this review is to provide an overview of the actual knowledge of Acmella oleracea (L.) and its activities, particularly those that are anti-inflammatory, anti-oxidant, and painkiller. These activities are attributed to numerous bioactive compounds, such as phytosterols, phenolic compounds and N-alkylamides (spilanthol, responsible for many activities, primarily anesthetic). This review includes 99 eligible studies to consider the anti-inflammatory, anti-oxidant, and painkiller of Acmella. Studies reported in this review confirmed anti-inflammatory and anti-oxidant activities of Acmella, postulating that transcription factors of the nuclear factor-κB family (NF-κB) trigger the transcription iNOS and COX-2 and several other pro-inflammatory mediators, such as IL-6, IL-1ß, and TNF-α. The antinociceptive effects has been demonstrated and have been related to different processes, including inhibition of prostaglandin synthesis, activation of opioidergic, serotoninergic and GABAergic systems, and anesthetic activity through blockage of voltage-gated Na Channels. acmella oleracea represents a promise for pain management, particularly in chronic degenerative diseases, where pain is a significant critical issue.

Profiling Vaccinium macrocarpon components and metabolites in human urine and the urine ex-vivo effect on Candida albicans adhesion and biofilm-formation.

The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran®). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran® were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran™ Phytosome™, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone was found effective thus confirming the ex-vivo results.

The Role of Glutamine in the Complex Interaction between Gut Microbiota and Health: A Narrative Review.

The scientific literature has demonstrated that glutamine is one of the main beneficial amino acids. It plays an important role in gut microbiota and immunity. This paper provides a critical overview of experimental studies (in vitro, in vivo, and clinical) investigating the efficacy of glutamine and its effect on gut microbiota. As a result of this review, we have summarized that glutamine could affect gut microbiota via different mechanisms including the reduction in the ratio of Firmicutes to Bacteroidetes, with the activation of NF-κB and PI3K-Akt pathways, reducing the intestinal colonization (Eimeria lesions) and bacterial overgrowth or bacterial translocation, increasing the production of secretory immunoglobulin A (SIgA) and immunoglobulin A+ (IgA+) cells in the intestinal lumen, and decreasing asparagine levels. The potential applications of glutamine on gut microbiota include, but are not limited to, the management of obesity, bacterial translocation and community, cytokines profiles, and the management of side effects during post-chemotherapy and constipation periods. Further studies and reviews are needed regarding the effects of glutamine supplementation on other conditions in humans.

A New Food-grade Coenzyme Q10 Formulation Improves Bioavailability: Single and Repeated Pharmacokinetic Studies in Healthy Volunteers.

BACKGROUND: Coenzyme Q10 is a fundamental endogenous factor involved in cell energy production that shows protective properties in oxidative stress, mainly in skeletal and heart muscle. Coenzyme Q10 supplementation appears to benefit athletes in strenuous training and in the elderly, demonstrating ant-inflammatory properties by reducing inflammatory cytokines. Improved absorption of coenzyme Q10 via a new delivery system would represent an important step forward in the use of coenzyme Q10 as a dietary supplement. OBJECTIVE: The aim of the study was to evaluate the solubility and oral absorption in human healthy volunteers of a new food grade coenzyme Q10 phytosome formulation. METHODS: Solubility studies were performed in vitro in simulated gastrointestinal fluids; human studies were conducted in healthy volunteers to evaluate oral absorption in a Single dose study, in comparison with the coenzyme Q10 capsules, and in a repeated study at two increasing doses. RESULTS: The highest solubility shown by coenzyme Q10 phytosome in simulated intestinal fluids results in an improvement in oral absorption of coenzyme Q10 in healthy volunteers, three times more than the coenzyme Q10 according to AUC (area under the time/concentration curve) values. When two increasing doses (one and two capsules) were administered to healthy volunteers within a two-week schedule, the plasmatic levels of coenzyme Q10 resulted in 0.864±0.200 µg/ml (Mean±S.D.+41%) and 1.321±0.400 µg/ml (+116%), respectively versus baseline (0.614±0.120 µg/ml one capsule, 0.614±0.160 µg/ml two capsules). This detected dose-related bioavailability of coenzyme Q10 phytosome was even observed with no alterations in vital signs, neither in the physical examination nor in ECG, and no changes of clinical and biochemical parameters were observed. CONCLUSION: These findings, taken together, support the safety profile and significantly improved coenzyme Q10 oral absorption in humans with this new phytosome delivery formulation.

Improved Oral Absorption of Quercetin from Quercetin Phytosome®, a New Delivery System Based on Food Grade Lecithin.

BACKGROUND AND OBJECTIVES: The importance of quercetin and flavonoids in the diet and as food supplements is well known, and literature studies support their potential use to treat several human diseases. Many beneficial properties have been described for quercetin, so much effort has been directed into overcoming the major drawbacks of this natural compound-its poor solubility and low oral absorption. The aims of this study were to compare a new food-grade lecithin-based formulation of quercetin, Quercetin Phytosome®, to unformulated quercetin in terms of solubility in simulated gastrointestinal fluids and oral absorption in a randomized crossover pharmacokinetic study of healthy volunteers. METHODS: The solubility of the new formulation was determined by in vitro incubation in simulated gastrointestinal fluids, and quercetin was detected by ultra performance liquid chromatography. A single-dose, randomized, six-sequence/three-period crossover clinical trial (3 × 3 × 3 crossover design) with a balanced carryover effect was conducted in healthy volunteers under fasting conditions. Twelve healthy volunteers of both sexes with an age range of 18-50 years were recruited; one dose of quercetin and two different doses of Quercetin Phytosome were administered orally as film-coated tablets. Pharmacokinetic samples were collected at twelve time points (from 0 h to 24 h) after administration, and quercetin levels were measured by HPLC/MS/MS. Data were analyzed using the Phoenix WinNonlin (v.6.4) software package, and the most significant pharmacokinetic parameters were calculated. Statistical analysis involved performing a two-way ANOVA with repeated measures followed by post hoc analysis (Tukey's test). RESULTS: Significant improvements in both in vitro solubility and oral absorption (in terms of both exposure and maximum concentration achieved) by healthy volunteers in a human clinical study were obtained with the Quercetin Phytosome formulation as compared to unformulated quercetin. CONCLUSIONS: A more soluble formulation of quercetin based on lecithin, Quercetin Phytosome, has recently been developed, and was found to facilitate the attainment of very high plasma levels of quercetin-up to 20 times more than usually obtained following a dose of quercetin-when the novel formulation was administered orally in human volunteers, and it did not have any notable side effects. These results suggest that Quercetin Phytosome allows the oral administration of quercetin in a safe and bioavailable manner, thus facilitating the effective utilization of this natural compound to treat various human diseases.

Hypoglycemic and Hypolipemic Effects of a New Lecithin Formulation of Bergamot Polyphenolic Fraction: A Double Blind, Randomized, Placebo- Controlled Study.

OBJECTIVE: Hyperlipemia represents an independent risk factor in the development of atherosclerosis in patients undergoing type 2 diabetes mellitus (DM). Moreover, the pharmacological treatment of dyslipemia in patients undergoing type 2 DM (e.g. by means of statins), is accompanied by relevant side effects and oral supplementation with natural antioxidants, such as Citrus polyphenols, has recently been suggested to improve cardioprotection in such patients. However, due to the poor gastrointestinal absorption of polyphenols, novel formulations have recently been developed for getting a better bioavailability of polyphenolic rich fractions of citrus species extract rich in polyphenols. METHODS: Here, we investigated the effect of standard bergamot polyphenolic fraction (BPF®) as well as of its phytosomal formulation (BPF Phyto), in patients with type 2 DM and hyperlipemia. A randomized, double blind, placebo-controlled study was carried out in 60 patients suffering from type 2 DM and mixed hyperlipemia. Patients were divided into three groups: one receiving placebo, the second receiving standard BPF and the third BPF Phyto. RESULTS: In the groups receiving BPF and BPF Phyto, a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides accompanied by increased HDL cholesterol was observed. This effect was associated with significant reduction of small dense atherogenic LDL particles, as detected by means of proton NMR Spectroscopy, thus confirming the hypolipemic and hypoglycemic effect of bergamot extract both when using standard formulation as well as BPF Phyto. No differences were seen in the therapeutic response among groups receiving BPF and BPF Phyto, thus suggesting a substantial bioequivalence in their hypoglycemic and hypolipemic profile. However, when comparing the pharmacokinetic profile of naringin (the major component of BPF) and its metabolites, in patients treated with BPF Phyto, an at least 2,5 fold increase in its absorption was found, confirming in human studies the better profile of BPF Phyto compared to standard BPF. CONCLUSION: These data suggest that better absorption and tissue distribution of BPF Phyto formulation represents an innovative approach in supplementation treatments of cardiometabolic disorders.