Strategies for successful aging, including the use of food supplements, are part of the approach to support skin youthfulness. To demonstrate the efficacy of fermented bilberry extract (FBE) against skin aging and uneven complexion, a clinical trial was carried out on 66 subjects with visible \"crow\'s feet\" wrinkles, mild-to-moderate skin slackness, and uneven skin tone. The wrinkle depth, skin smoothness (Ra) and roughness (Rz), skin firmness (R0) and elasticity (R2), skin coloration (ITA°), and skin antioxidant capacity were measured before and after 28 (D28), 56 (D56), and 84 (D84) days of product use (either FBE or a placebo). These parameters were also integrated with a clinical evaluation, carried out by a dermatologist, and a self-assessment questionnaire to align the measured efficacy with the visual or perceived efficacy. At D84, the wrinkle depth had decreased by 10.6%, Ra had improved by 7.9%, Rz had decreased by 7.3%, R0 had improved by 13.3%, R2 had improved by 12.4%, and skin antioxidant capacity had increased by 20.8%. ITA° increased by 20.8% and was accompanied by a decrease in the skin\'s redness component by 16.8% and an increase in the lightness component by 2.2%. The variation of all the above-mentioned parameters was statistically significant between the FBE and PL groups. Our findings demonstrate the efficacy of FBE in improving skin aging and complexion evenness.

(1) Background: Two Caucasian blueberries Vaccinium myrtillus L. and Vaccinium arctostaphylos L. are famous berry bushes growing in the Caucasus region and used to treat neurological diseases, but the chemistry and bioactivity of leaf extracts are still poorly studied. (2) Methods: Phenolic compounds of V. myrtillus and V. arctostaphylos leaf extracts were profiled and quantified by HPLC-PDA-ESI-tQ-MS. The neurotropic potential of Vaccinium extracts was studied using the model of middle cerebral artery permanent occlusion to determine cerebral blood flow, the area of the brain tissue necrosis, and antioxidant enzyme activity (including superoxide dismutase, succinate dehydrogenase, and cytochrome C oxidase), as well as the concentration of TBARS. (3) Results: Hydroxycinnamates and flavonoids were identified in the leaves of V. myrtillus and V. arctostaphylos, and the dominant metabolite of both extracts was 5-O-caffeoylquinic acid in the amount of 105-226 mg/g. The studied extracts enhanced the cerebral hemodynamics and decreased the frequency of necrotic and lipooxidative processes in the brain tissue, accompanied by an increase in the activity of antioxidant enzymes. The positive effect of V. arctostaphylos was stronger and exceeded the effectiveness of Ginkgo biloba standardized extract. (4) Conclusion: The leaf extracts of Caucasian blueberries V. myrtillus and V. arctostaphylos as a new source of hydroxycinnamates demonstrated a protective effect of the brain ischemia pathology and can be used as therapeutic agents to treat neurological diseases.

SAMITAL®, a botanical drug containing three highly standardized extracts (Vaccinium myrtillus, Macleaya cordata and Echinacea angustifolia), has shown promising results in treating or preventing oral mucositis (OM) in adult patients, but it has not been fully investigated in children. In this study, we assessed the feasibility of SAMITAL administration in pediatric patients receiving anticancer treatment to prevent or treat OM, focusing on identifying an appropriate dose and evaluating safety and tolerability and palatability and treatment compliance.
We conducted an open-label, monocentric, prospective study on 18 children receiving anticancer therapy to prevent or treat OM.
No SAMITAL®-related side effects were observed or reported during the study; moreover, no systemic absorption of SAMITAL® metabolites was detected in the bloodstream. However, compliance to SAMITAL® was unsatisfactory and variable (from 2 to 100%), and patients reported low palatability (median taste of 4.8; range 1.0-8.0).
SAMITAL® administration appears to be safe in the pediatric population, as it is not absorbed in the bloodstream and does not cause any local or systemic side effects. However, the current formulation is only partially suitable for children, and future studies on SAMITAL® in children would need an adapted formulation to increase compliance.

Some dietary interventions with berry fruits, berry fruit extracts, and purified anthocyanins have been reported to beneficially alter lipoprotein profiles in hyperlipidemic participants. The major anthocyanins in human diets are glycosides of cyanidin and delphinidin, and structure can influence both absorption and bioactivity. The aim of this study is to determine the effects of two major types of anthocyanins on low-density lipoprotein cholesterol and other cardiometabolic markers for cardiovascular disease (CVD) risk in hyperlipidemic individuals.
Fifty-two hyperlipidemic participants complete this randomized, placebo-controlled, double-blind, three arm crossover trial. Participants ingest capsules containing 320 mg of anthocyanins (bilberry trihydroxy-type or black rice dihydroxy-type) or placebo once daily for 28 days. Biomarkers of CVD risk are measured before and after the intervention period. Compared to the placebo, neither anthocyanin treatment significantly (p < 0.05) changes circulating levels of lipoproteins (total-/high-density lipoprotein (HDL)-/low-density lipoprotein (LDL)-cholesterol, triglycerides, Apolipoprotein B (ApoB)), biomarkers of glycemic control (fasting glucose, fructosamine), biomarkers of HDL function (ApoA1, HDL3, paraoxonase-1 (PON1) arylesterase, and lactonase activities), or plasma bile acids.
These data do not support the notion that regular consumption of anthocyanins beneficially affects glycemic control or lipoprotein profiles or functions. It is possible the no effect observation is due to the relatively short duration of treatments.

Background and Aim: Several evidences have shown how, in hemorrhoidal disease, phlebotonic flavonoid agents such as quercetin reduce capillary permeability by increasing vascular walls resistance, how rutin and vitamin C have antioxidant properties, and that Centella asiatica has reparative properties towards the connective tissue. A retrospective study was designed in order to evaluate the efficacy and safety of a compound consisting of micronized flavonoids in combination with vitamin C and extracts of C. asiatica, Vaccinium myrtillus, and Vitis vinifera for grade II and III hemorrhoidal disease. Patients and Methods: Data of 49 patients, over 18, who were following a free diet regimen, not on therapy with other anti-hemorrhoid agents, treated with a compound consisting of 450 mg of micronized diosmin, 300 mg of C. asiatica, 270 mg of micronized hesperidin, 200 mg of V. vinifera, 160 mg of vitamin C, 160 mg of V. myrtillus, 140 mg of micronized quercetin, and 130 mg of micronized rutin (1 sachet or 2 tablets a day) for 7 days were collected. Hemorrhoid grade according to Goligher\'s scale together with anorectal symptoms (edema, prolapse, itching, thrombosis, burning, pain, tenesmus, and bleeding) both before treatment (T0) and after 7 days of therapy (T7) were collected. Primary outcomes were the reduction of at least one degree of hemorrhoids according to Goligher\'s scale assessed by proctological examination and compound safety. The secondary outcome was the reduction of anorectal symptoms assessed by questionnaires administered to patients. Results: Forty-four patients (89.8%) presented a reduction in hemorrhoidal grade of at least one grade (p < 0.001). No adverse events with the use of the compound were noted. A significant reduction was observed in all anorectal symptoms evaluated (p < 0.05). No predictors of response to the compound were identified among the clinical and demographic variables collected. Conclusion: The compound analyzed was effective and safe for patients with grade II and III hemorrhoidal disease according to Goligher\'s scale.

BACKGROUND: Bilberries from Sweden, rich in polyphenols, have shown cholesterol-lowering effects in small studies, and the cholesterol-lowering properties of oats, with abundant beta-glucans and potentially bioactive phytochemicals, are well established. Both may provide cardiometabolic benefits following acute myocardial infarction (AMI), but large studies of adequate statistical power and appropriate duration are needed to confirm clinically relevant treatment effects. No previous study has evaluated the potential additive or synergistic effects of bilberry combined with oats on cardiometabolic risk factors. Our primary objective is to assess cardioprotective effects of diet supplementation with dried bilberry or with bioprocessed oat bran, with a secondary explorative objective of assessing their combination, compared with a neutral isocaloric reference supplement, initiated within 5 days following percutaneous coronary intervention (PCI) for AMI.
METHODS: The effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI) trial is a double-blind, randomized, placebo-controlled clinical trial. A total of 900 patients will be randomized post-PCI to one of four dietary intervention arms. After randomization, subjects will receive beverages with bilberry powder (active), beverages with high-fiber bioprocessed oat bran (active), beverages with bilberry and oats combined (active), or reference beverages containing no active bilberry or active oats, for consumption twice daily during a 3-month intervention. The primary endpoint is the difference in LDL cholesterol change between the intervention groups after 3 months. The major secondary endpoint is exercise capacity at 3 months. Other secondary endpoints include plasma concentrations of biochemical markers of inflammation, metabolomics, and gut microbiota composition after 3 months.
CONCLUSIONS: Controlling hyperlipidemia and inflammation is critical to preventing new cardiovascular events, but novel pharmacological treatments for these conditions are expensive and associated with negative side effects. If bilberry and/or oat, in addition to standard medical therapy, can lower LDL cholesterol and inflammation more than standard therapy alone, this could be a cost-effective and safe dietary strategy for secondary prevention after AMI.
BACKGROUND: ClinicalTrials.gov NCT03620266 . Registered on August 8, 2018.

Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in high-fat diet (HFD)-fed mice for up to 16 wk and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men [mean age 51.5 yr, body mass index (BMI) 27.6 kg·m-2] for 4 wk. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain, whereas lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63-supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by principal coordinate analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an oral glucose tolerance test was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5 g·day-1) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multitargeted action on different metabolic organs.NEW & NOTEWORTHY Totum-63 is a novel polyphenol-rich natural composition developed to reduce the risk of T2D. Totum-63 showed beneficial effects on glucose homeostasis in HFD-fed mice, presumably through a multitargeted action on different metabolic organs. Totum-63 was well tolerated in humans and improved postprandial glucose and insulin responses to a high-carbohydrate breakfast test.

A 12-week-long randomized, double-blind, placebo-controlled, parallel-group comparison trial was conducted to determine the effects of long-term standardized bilberry extract (SBE) intake on tonic accommodation of ciliary muscle caused by visual display terminal (VDT) tasks. This study was compliant with the accordance with CONSORT 2010 statement. A total of 109 healthy adult men and women aged 20-60 years were recruited and randomized into SBE and placebo groups. The subjects in the SBE and placebo groups were administered 240 mg of SBE and placebo, respectively, once daily for 12 weeks. Tests were performed before and after VDT tasks at week 0, 4, 8, and 12; high-frequency component (HFC)-1 value was the evaluation outcome. Results showed that post-load HFC-1 values at weeks 8 and 12 were significantly improved in the SBE group than in the placebo group (p = 0.014 and 0.017, respectively). Regarding the difference between before and after the task load (ΔHFC-1), the values were significantly better in the SBE group than in the placebo group at week 4 and 12 (p = 0.018 and 0.049, respectively). This study shows that oral consumption of 240 mg SBE extract for 12 weeks relieves the tonic accommodation of the ciliary muscle caused by VDT tasks and near-vision tasks.

This randomized, double-blinded, crossover study measured the acute effect of ingesting a mixed flavonoid-caffeine (MFC) supplement compared to placebo (PL) on energy expenditure (EE) and fat oxidation (FATox) in a metabolic chamber with premenopausal women (n = 19, mean ± SD, age 30.7 ± 8.0 year, BMI 25.7 ± 3.4 kg/m2). The MFC supplement (658 mg flavonoids, split dose 8:30, 13:00) contained quercetin, green tea catechins, and anthocyanins from bilberry extract, and 214 mg caffeine. Participants were measured twice in a metabolic chamber for a day, four weeks apart, with outcomes including 22 h EE (8:30-6:30), substrate utilization from the respiratory quotient (RQ), plasma caffeine levels (16:00), and genotyping for the single-nucleotide polymorphism (SNP) rs762551. Areas under the curve (AUC) for metabolic data from the MFC and PL trials were calculated using the trapezoid rule, with a mixed linear model (GLM) used to evaluate the overall treatment effect. The 22 h oxygen consumption and EE were significantly higher with MFC than PL (1582 ± 143, 1535 ± 154 kcal/day, respectively, p = 0.003, trial difference of 46.4 ± 57.8 kcal/day). FATox trended higher for MFC when evaluated using GLM (99.2 ± 14.0, 92.4 ± 14.4 g/22 h, p = 0.054). Plasma caffeine levels were significantly higher in the MFC versus PL trial (5031 ± 289, 276 ± 323 ng/mL, respectively, p < 0.001). Trial differences for 22 h EE and plasma caffeine were unrelated after controlling for age and body mass (r = -0.249, p = 0.139), and not different for participants with the homozygous allele 1, A/A, compared to C/A and C/C (p = 0.50 and 0.56, respectively). In conclusion, EE was higher for MFC compared to PL, and similar to effects estimated from previous trials using caffeine alone. A small effect of the MFC on FATox was measured, in contrast to inconsistent findings previously reported for this caffeine dose. The trial variance for 22 h EE was not significantly related to the variance in plasma caffeine levels or CYP1A2*1F allele carriers and non-carriers.

Bilberries, Vaccinium myrtillus, have a high content of phenolic compounds including anthocyanins, which could provide cardiometabolic health benefits following acute myocardial infarction (AMI). We hypothesized that standard medical therapy supplemented with freeze-dried bilberry after AMI would have a more beneficial effect on cardiovascular risk markers and exercise capacity than medical therapy alone. Patients were allocated in a 1:1 ratio within 24 hours of percutaneous coronary intervention in an 8-week trial either to V myrtillus powder (40 g/d, equivalent to 480 g fresh bilberries) and standard medical therapy or to a control group receiving standard medical therapy alone. High-sensitivity C-reactive protein and exercise capacity measured with the 6-minute walk test were the primary biochemical and clinical end points, respectively. Fifty subjects completed the study. No statistically significant difference in high-sensitivity C-reactive protein was detected between groups. The mean 6-minute walk test distance increased significantly more in the bilberry group compared to the control group: mean difference 38 m at follow-up (95% confidence interval 14-62, P = .003). Ex vivo oxidized low-density lipoprotein was significantly lowered in the bilberry group compared to control, geometric mean ratio 0.80 (95% confidence interval 0.66-0.96, P = .017), whereas total cholesterol and low-density lipoprotein cholesterol did not differ significantly between groups. Anthocyanin-derived metabolites in blood increased significantly in the bilberry group during the intervention and were different after 8 weeks between the bilberry group and control. Findings in the present study suggest that bilberries may have clinically relevant beneficial effects following AMI; a larger, double-blind clinical trial is warranted to confirm this.