A three-arm, randomized, placebo-controlled clinical study was conducted to assess the impact of lyophilized pineapple extract with titrated bromelain (Brome-Inf®) and purified bromelain on pain, swelling, trismus, and quality of life (QoL) following the surgical extraction of the mandibular third molars. Furthermore, this study examined the need for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) by comparing their effects with a placebo group. This study enrolled 42 individuals requiring the extraction of a single mandibular third molar under local anesthesia. The patients were randomly assigned to receive Brome-Inf®, purified bromelain, or a placebo orally, initiating treatment on the day of surgery and continuing for the next 7 days. The primary outcome measured was the requirement for NSAIDs in the three groups. Pain, swelling, and trismus were secondary outcome variables, evaluated postoperatively at 1, 3, and 7 days. This study also assessed the comparative efficacy of freeze-dried pineapple extract and single-component bromelain. Ultimately, the placebo group showed a statistically higher need for ibuprofen (from days 1 to 7) at the study’s conclusion (p < 0.0001). In addition, reductions in pain and swelling were significantly higher in both the bromelain and pineapple groups (p < 0.0001 for almost all patients, at all intervals) than in the placebo group. The active groups also demonstrated a significant difference in QoL compared to the placebo group (p < 0.001). A non-significant reduction in trismus occurred in the treatment groups compared to the placebo group. Therefore, the administration of pineapple extract titrated in bromelain showed significant analgesic and anti-edema effects in addition to improving QoL in the postoperative period for patients who had undergone mandibular third molar surgery. Moreover, both bromelain and Brome-Inf® supplementation reduced the need for ibuprofen to comparable extents, proving that they are good alternatives to NSAIDs in making the postoperative course more comfortable for these patients. A further investigation with larger samples is necessary to assess the pain-relieving and anti-inflammatory impacts of the entire pineapple phytocomplex in surgical procedures aside from mandibular third molar surgery.

The fine balance between symbiotic and potentially opportunistic and/or pathogenic microorganisms can undergo quantitative alterations, which, when associated with low intestinal biodiversity, could be responsible for the development of gut inflammation and the so-called "intestinal dysbiosis". This condition is characterized by the disbalance of a fine synergistic mechanism involving the mucosal barrier, the intestinal neuroendocrine system, and the immune system that results in an acute inflammatory response induced by different causes, including viral or bacterial infections of the digestive tract. More frequently, however, dysbiosis is induced slowly and subtly by subliminal causal factors, resulting in a chronic condition related to different diseases affecting the digestive tract and other organs and apparatuses. Studies on animal models, together with studies on humans, highlight the significant role of the gut microbiota and microbiome in the occurrence of inflammatory conditions such as metabolic syndrome and cardiovascular diseases (CVDs); neurodegenerative, urologic, skin, liver, and kidney pathologies; and premature aging. The blood translocation of bacterial fragments has been found to be one of the processes linked to gut dysbiosis and responsible for the possible occurrence of "metabolic endotoxemia" and systemic inflammation, associated with an increased risk of oxidative stress and related diseases. In this context, supplementation with different probiotic strains has been shown to restore gut eubiosis, especially if administered in long-term treatments. The aim of this review is to describe the anti-inflammatory effects of specific probiotic strains observed in clinical trials and the respective indications, highlighting the differences in efficacy depending on strain, formulation, time and duration of treatment, and dosage used.

The crucial role of dyslipidaemia, especially hypercholesterolemia, in the development of atherosclerosis-related cardiovascular diseases has been extensively documented in genetic, pathologic, observational and intervention studies. The European guidelines for dyslipidaemia management include the possible use of lipid-lowering nutraceuticals to support a relatively large number of natural compounds. In this context, we have conducted a study to investigate whether dietary supplementation with a functional nutraceutical beverage, containing a standardized polyphenolic fraction from fruit, red yeast rice, phytosterols, and berberine complexed with β-cyclodextrin, could positively affect serum lipid concentration in 14 subjects with hypercholesterolemia. After 12 weeks of treatment, dietary supplementation with this nutraceutical combination was associated with significant improvements in total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B, compared to baseline. Compliance was excellent and no adverse effects were reported. In conclusion, this study demonstrates that 100 mL of a functional beverage containing lipid-lowering nutraceuticals safely leads to significant improvements in serum lipids in subjects with moderate hypercholesterolemia. Future research is needed to unravel the role that the polyphenols contained in fruit extracts play in the reduction of cholesterolemia and in cardiovascular disease prevention.

Currently, the nutraceutical approach to treat dyslipidaemia is increasing in use, and in many cases is used by physicians as the first choice in the treatment of patients with borderline values. Nutraceuticals represent an excellent opportunity to treat the preliminary conditions not yet showing the pathological signs of dyslipidaemia. Their general safety, the patient’s confidence, the convincing proof of efficacy and the reasonable costs prompted the market of new preparations. Despite this premise, many nutraceutical products are poorly formulated and do not meet the minimum requirements to ensure efficacy in normalizing blood lipid profiles, promoting cardiovascular protection, and normalizing disorders of glycemic metabolism. In this context, bioaccessibility and bioavailability of the active compounds is a crucial issue. Little attention is paid to the proper formulations needed to improve the overall bioavailability of the active molecules. According to these data, many products prove to be insufficient to ensure full enteric absorption. The present review analysed the literature in the field of nutraceuticals for the treatment of dyslipidemia, focusing on resveratrol, red yeast rice, berberine, and plant sterols, which are among the nutraceuticals with the greatest formulation problems, highlighting bioavailability and the most suitable formulations.

Objective: The effectiveness of statins in the primary and secondary prevention of cardiovascular (CV) diseases has been widely proven. However, the onset of adverse events associated with their use, prevents to achieve the therapeutic targets recommended by the guidelines (GL) for the management of dyslipidaemia. In the event of statin intolerance, is recommend to use bile acid sequestrants, fibrates and ezetimibe in monotherapy, but their benefits in improving lipid pattern are quite modest. This study aims at evaluating the effectiveness and safety of a nutraceutical compound (NC) associated with ezetimibe (E) on the lipid profile in statin-intolerant patients with moderate-to-high CV risk Design and method: Ninety-six statin-intolerant hypertensive and hyper-cholesterolemic subjects treated with E 10 mg daily, were randomised in open label (n = 48) to take for 3 months a NC containing Monacolin K (MK) 5 mg, Berberine Hydrochloride, t-Resveratrol, Quercetin, and Chromium, in the form of a gastro-resistant tablet that improves enteric bio-accessibility and bio-availability of these substances. The control group (n = 48), took only E in monotherapy at the same dosage; both groups followed a standardised lipid-lowering diet. The total serum cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine phosphokinase (CPK) levels were compared at the follow-up in both groups using Student's t-test. Results: TC and LDL levels reduced in both groups, but there lower in the group treated with E+ NC vs E alone (-25.9 vs -15%, p < 0.05 and -38.7 vs. -21.0%, p < 0.05, respectively). No changes were observed in either group regarding to a decrease in TG (-9.4 vs. -11.7%, NS) and an increase in HDLC (+ 4.2 vs. +1.1%, NS). The AST, ALT and CPK levels increased in the E + NC compared to the control group, but were still within the acceptable range. There was no difference for the lipid-lowering treatment between gender, and no patient withdrawn the study. Conclusions: In hypertensive and hyper-cholesterolemic subjects with statin-intolerance, the E + NC combination therapy is well-tolerated and effective in the short term in improving TC and LDLC levels.

The effectiveness of statins in the primary and secondary prevention of cardiovascular (CV) diseases has been widely proven. However, the onset of adverse events associated with their use prevents to achieve the therapeutic targets recommended by the guidelines (GL) for the management of dyslipidemia. In the event of statin intolerance, the GL recommend to use bile acid sequestrants, fibrates, and ezetimibe in monotherapy, but their benefits in improving lipid pattern are quite modest. This study aims at evaluating the effectiveness and safety of a nutraceutical compound (NC) associated with ezetimibe (EZE) on the lipid profile in statin-intolerant patients with moderate-to-high CV risk. Ninety-six statin-intolerant hypertensive and hypercholesterolemic subjects treated pharmacologically with EZE 10 mg daily were randomized in open label (n = 48) to take for 3 months a NC containing Monacolin-K (MK), Berberine Hydrochloride (BC), t-Resveratrol (RES), Quercetin (QUER), and Chromium (CH) in the form of a gastro-resistant tablet that improves enteric bioaccessibility and bioavailability of these substances. The control group (n = 48) took only EZE in monotherapy at the same dosage; both groups followed a standardized lipid-lowering diet. The total serum cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine phosphokinase (CPK) levels were compared at the follow-up in both groups using Student's t-test. TC and LDL levels reduced in both groups, but were lower in the group treated with EZE + NC (-25.9% vs. -15%, P < .05 and -38.7% vs. -21.0%, P < .05, respectively). No changes were observed in either group regarding a decrease in TG (-9.4% vs. -11.7%, NS) and an increase in HDLC (+4.2% vs. +1.1%, NS). The AST, ALT, and CPK levels increased in the group treated with the EZE + NC compared to the control group, but were still within the acceptable range. There was no difference concerning the lipid-lowering treatment between gender, and no patient withdrew from the study. In the short term, the EZE + NC combination therapy is well tolerated and effective in improving TC and LDLC levels in statin-intolerant patients with moderate-to-high CV risk.

OBJECTIVE To evaluate the efficacy of oral administration of a novel composition composed of Quercetin, Curcumin, Acetylcysteine in reducing pain in women affected by endometriosis, through the reduction of the inflammatory-hyperproliferative component of the ectopic endometrial tissue. METHODS 33 women with clinical diagnosis of endometriosis from at least 3 months have been enrolled. Patients have been treated daily with 200 mg of Quercetin, 210 mg of dry extract of Curcuma Longa (titrated at 95% in Curcuminoids) and 150 mg of Acetylcysteine (1 tablet of Alliendo) for 2 months. The overall symptomatology with specific reference to dysmenorrhea, pelvic pain and dyspareunia, together with the frequency of NSAID's drugs assumption have been evaluated at the beginning and at the end of the treatment. RESULTS Overall, the results collected at the end of the treatment according to the parameters evaluated and above mentioned on the 33 patients enrolled, show a significative improvement in the reduction of pain symptoms associated to endometriosis (p<0,001 for dysmenorrhea, pelvic pain and dyspareunia). The use of NSAID's together with an overall reduction of their dosage and time of assumption has been reduced as well. No significative side effects have been observed. CONCLUSIONS The aforementioned results suggest that administration of the composition described can represent a valuable adjuvant treatment in the reduction of pain symptomatology associated to endometriosis, triggered by inflammatory cascade and hyperproliferation of ectopic tissue.

Vitamin D3 (cholecalciferol) is a lipophilic vitamin universally recognized as the calcium-absorbing factor. This vitamin plays a pivotal role in the maintenance of calcium homeostasis but also represents a fundamental factor to sustain immune function. Despite the widespread use of Vitamin D3 in form of supplements and drugs the issue of its overall bioavailability, after oral assumption, is frequently misjudge and taken for granted. Because of the large interindividual differences in enteric absorption, bile secretion and comorbidity such as intestinal malabsorption syndromes, enteric villi atrophy and others, Vitamin D3 bioaccessibility and as consequence its enteric absorption can vary dramatically. In this study we compared the enteric bioaccessibility of Vitamin D3 from an oily not formulated form versus a novel micellar liquid system in which Vitamin D3 is finely dispersed. The assessment has been carried out through an in vitro enteric model coupled with a gastro-enteric digestion simulating machine. DLS characterization of Vitamin D3 micellar system and its dispersion in fasted state simulated intestinal fluid has been assessed as well. The data collected overall confirm that sole bile is not much effective in dispersing Vitamin D3, especially in enteric fasted state and that a finely dispersed water-based Vitamin D3 micellar system can effectively improve it. Experiments assessed substantially confirmed that micellar system herewith described is able of improving Vitamin D3 enteric bioaccessibility and significantly enhance its enteric permeation rate in comparison with Vitamin D3 unformulated oil.

The class of lipophilic compounds coming from vegetal source represents a perspective in the adjuvant treatment of several human diseases, despite their poor bioavailability in humans. These compounds are generally soluble in fats and poorly soluble in water. The major reason for the poor bioavailability of lipophilic natural compounds after oral uptake in humans is related to their reduced solubility in enteric water-based fluids, leading to an ineffective contact with absorbing epithelium. The main goal to ensure efficacy of such compounds is then creating technological conditions to deliver them into the first enteric tract as hydro-dispersible forms to maximize epithelial absorption. The present work describes and characterizes a new technological matrix (Lipomatrix, Labomar Research, Istrana, TV, Italy) based on a molten fats core in which Ascorbyl Palmitate is embedded, able to deliver lipophilic compounds in a well-dispersed and emulsified form once exposed to duodenal fluids. Authors describe and quantify Lipomatrix delivery of Serenoa repens oil through an innovative in vitro model of human gastro-enteric digestion, reporting results of its improved bioaccessibility, enteric absorption and efficacy compared with not formulated Serenoa repens oil-containing commercial products using in vitro models of human intestine and prostatic tissue.

Vitamins are key to human health. Although vitamins are involved in several metabolic pathways, humans cannot biosynthesize them except for vitamin D and vitamin B3, so adequate intake in the diet is crucial. Vitamins are classified as fat-soluble or water-soluble. Fat-soluble vitamins include vitamins A, D, E and K, while water-soluble vitamins include vitamins B and C. Avitaminosis due to imbalanced nutrition, disease or genetic impairment leads to disease, but consumption of vitamin supplements or fortified foods can counteract vitamin deficiency. However, their absorption depends on the type of meal and food matrix composition. Vitamins A, D and E are mainly influenced by lipid content which promotes intestinal uptake. Surprisingly, the fat-soluble vitamin K seems to be unaffected by type of diet, although it has better bioavailability as a food supplement. Water-soluble vitamin absorption is not significantly affected by prandial status or dietary composition. No data are reported for vitamin C, while the vitamin B group needs evaluation by coenzyme.

OBJECTIVE:Oncological treatments are associated with toxicities that may decrease compliance to treatment in most genitourinary cancer patients. Supplementation with pharmaceutical-standardized supplement may be a supplementary method to control the side effects after chemo- and radiotherapy and the increased oxidative stress associated to treatments. This registry study evaluated a natural combination of supplements containing curcumin, cordyceps, and astaxanthin (Oncotris™) used as supplementary management in genitourinary cancer patients who had undergone oncological therapy. PATIENTS AND METHODS:Patients with genitourinary cancers (prostate or bladder malignancies) who had undergone and completed cancer treatments (radiotherapy, chemotherapy or intravesical immunotherapy with increased oxidative stress and residual symptoms) were recruited in this registry, supplement study. Registry subjects (n = 61) freely decided to follow either a standard management (SM) (control group = 35) or SM plus oral daily supplementation (supplement group = 26). Evaluation of severity of treatment-related residual side effects, blood count test, prostate-specific antigen (PSA) test and plasma free radicals (oxidative stress) were performed at inclusion and at the end of the observational period (6 weeks). RESULTS:Two patients dropped out during the registry. Therefore, the analysis included 59 participants: 26 individuals in the supplementation group and 33 in the control group. In the supplement group, the intensity of signs and symptoms (treatment-related) and residual side effects significantly decreased at 6 weeks: minimal changes were observed in controls. Supplementation with Oncotris™ was associated with a significant improvement in blood cell count and with a decreased level of plasmatic PSA and oxidative stress. CONCLUSIONS:Naturally-derived supplements, specifically Oncotris™ (patent pending), could support the body to overcome the treatment-related toxicities - and the relative oxidative stress in cancer patients.

Increased non high-density lipoprotein (HDL)/low-density lipoprotein (LDL) cholesterol levels are independent risk factors for cardiovascular (CV) mortality with no documented threshold. A new combination of nutraceuticals (berberine 200 mg, monacolin K 3 mg, chitosan 10 mg and coenzyme Q 10 mg) with additive lipid-lowering properties has become available. The aim of the study is to test the efficacy of the nutraceutical formulation (one daily) in lowering non-HDL cholesterol vs. placebo at 12 weeks in individuals with non-HDL-cholesterol levels ≥160 mg/dL. 39 subjects (age 52 ± 11 years; 54% females; body mass index 27 ± 4 kg/m2) were randomized (3:1) in a double blind phase II placebo-controlled study. At baseline, 4 and 12 weeks main clinical/biohumoral parameters, pro-inflammatory cytokines, (gut)-hormones, proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and endothelial progenitor cell (EPC) number were assessed. Baseline characteristics were comparable in the two groups. The intervention significantly decreased non-HDL cholesterol (−30 ± 20 mg/dL; p = 0.012), LDL cholesterol (−31 ± 18 mg/dL, p = 0.011) and apolipoprotein (Apo) B (−14 ± 12 mg/dL, p = 0.030) levels compared to the placebo. Pro-inflammatory, hormonal, PCSK9 and EPC levels remained stable throughout the study in both groups. The intervention was well tolerated. Three adverse events occurred: Epstein Barr virus infection, duodenitis and asymptomatic but significant increase in creatine phosphokinase (following intense physical exercise) which required hospitalization. The tested nutraceutical formulation may represent a possible therapeutic strategy in dyslipidemic individuals in primary prevention.