The Effect of Dietary Supplementation with Plant Sterols on Total and LDL-Cholesterol in Plasma Is Affected by Adherence to Mediterranean Diet: Insights from the DESCO Randomized Clinical Study.

Plant sterols are well-known natural lipid-lowering agents. The DESCO (Diet and plant sterols in the control of cholesterolemia) study was a single-center, randomized, double-blind, placebo-controlled, two-way crossover clinical trial designed to investigate the effect of a once-a-day ready-to-drink dietary supplement containing 2.5 g of phytosterols on the lipid profile, also in relation to the quality of the diet, in a cohort of 50 Italian individuals with polygenic hypercholesterolemia and low global cardiovascular risk. Eligible individuals were enrolled in a run-in period of 2 weeks. Then, participants who qualified for continuation in the study were randomly allocated (1:1) to a 3-week treatment with either phytosterols or placebo. After a 2-week washout period, enrolled individuals were crossed over to receive the alternative treatment. Dietary supplementation with phytosterols was associated with significant improvement in plasma levels of total cholesterol (TC; -11.8 ± 4.0 mg/dL, p = 0.016), low-density lipoprotein cholesterol (LDL-C; -7.8 ± 7.7 mg/dL, p = 0.021), and apolipoprotein B-100 (Apo B-100, -3.7 ± 4.1 mg/dL, p = 0.048) compared to baseline. The changes in TC and LDL-C were also significant compared to placebo, and greater adherence to the Mediterranean diet was significantly associated with greater reductions in LDL-C. Dietary supplementation with phytosterols was well tolerated and adherence to treatment was high. According to the findings of DESCO, the once-a-day ready-to-drink dietary supplement we tested is able to quickly and significantly decrease plasma levels of TC, LDL-C, and Apo B-100, with a greater effect in individuals more adhering to the Mediterranean dietary pattern.

Nutraceuticals as Modulators of Immune Function: A Review of Potential Therapeutic Effects.

Dietary supplementation with nutraceuticals can promote optimal immune system activation, modulating different pathways that enhance immune defenses. Therefore, the immunity-boosting effects of nutraceuticals encompass not only immunomodulatory but also antioxidant, antitumor, antiviral, antibacterial, and antifungal properties, with therapeutic effects against diverse pathological conditions. However, the complexity of the pathways that regulate the immune system, numerous mechanisms of action, and heterogeneity of the immunodeficiencies, and subjects treated make their application in the clinical field difficult. Some nutraceuticals appear to safely improve immune system function, particularly by preventing viral and bacterial infections in specific groups, such as children, the elderly, and athletes, as well as in frail patients, such as those affected by autoimmune diseases, chronic diseases, or cancer. Several nutraceuticals, such as vitamins, mineral salts, polyunsaturated omega-3 fatty acids, many types of phytocompounds, and probiotic strains, have the most consolidated evidence in humans. In most cases, further large and long-term randomized clinical trials are needed to confirm the available preliminary positive data.

Evaluation of the effect of a dietary supplementation with a red yeast rice and fish oil-containing nutraceutical on lipid pattern, high sensitivity C-reactive protein, and endothelial function in moderately hypercholesterolaemic subjects: a double-blind, placebo-controlled, randomized clinical trial.

Introduction: Red yeast rice and omega-3 polyunsaturated fatty acids (PUFAs) are dietary supplements with well-known lipid-lowering, anti-inflammatory, and vascular health improving effects. However, they have rarely been tested in combination. The aim of our study was to test the short-term effect of a combined nutraceutical including red yeast rice and PUFAs on plasma lipids, jigh-sensitive C-reactive protein (hsCRP), and endothelial function in healthy subjects. Material and methods: We carried out a double-blind, randomized, placebo-controlled clinical trial with parallel groups testing the effect of 8 weeks of supplementation with softgels containing red yeast rice (2.8 mg monacolins) and PUFAs (588 mg of fish oil, standardized in PUFAs: 350 EPA, 45 mg DHA) versus placebo. A full lipid panel, hsCRP, and endothelial reactivity were measured at the baseline and after 8 weeks of treatment. Results: The tested combined nutraceutical was very well tolerated, and after 8 weeks of supplementation it was associated with a 17.3 ±3.4% reduction of lipid-density lipoprotein-cholesterol (LDL-C), a 12.1 ±2.2% reduction of total cholesterol (TC), a 22.3 ±4.3% reduction of apoB, and a -14.9 ±1.8% reduction of hsCRP, as well as a significant improvement of pulse volume change by 5.0 ±0.9%. Conclusions: The tested combined dietary supplement containing red yeast rice and PUFAs was very well tolerated and significantly improved LDL-C, TC, apoB, hsCRP and endothelial function in healthy subjects with suboptimal LDL-cholesterolaemia.

Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data.

A new application for omega-3 fatty acids has recently emerged, concerning the treatment of several mental disorders. This indication is supported by data of neurobiological research, as highly unsaturated fatty acids (HUFAs) are highly concentrated in neural phospholipids and are important components of the neuronal cell membrane. They modulate the mechanisms of brain cell signaling, including the dopaminergic and serotonergic pathways. The aim of this review is to provide a complete and updated account of the empirical evidence of the efficacy and safety that are currently available for omega-3 fatty acids in the treatment of psychiatric disorders. The main evidence for the effectiveness of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been obtained in mood disorders, in particular in the treatment of depressive symptoms in unipolar and bipolar depression. There is some evidence to support the use of omega-3 fatty acids in the treatment of conditions characterized by a high level of impulsivity and aggression and borderline personality disorders. In patients with attention deficit hyperactivity disorder, small-to-modest effects of omega-3 HUFAs have been found. The most promising results have been reported by studies using high doses of EPA or the association of omega-3 and omega-6 fatty acids. In schizophrenia, current data are not conclusive and do not allow us either to refuse or support the indication of omega-3 fatty acids. For the remaining psychiatric disturbances, including autism spectrum disorders, anxiety disorders, obsessive-compulsive disorder, eating disorders and substance use disorder, the data are too scarce to draw any conclusion. Concerning tolerability, several studies concluded that omega-3 can be considered safe and well tolerated at doses up to 5 g/day.

Middle-Term Dietary Supplementation with Red Yeast Rice Plus Coenzyme Q10 Improves Lipid Pattern, Endothelial Reactivity and Arterial Stiffness in Moderately Hypercholesterolemic Subjects.

AIM: The aim of our study was to investigate whether treatment with red yeast rice added with Coenzyme Q10 is associated with changes in endothelial function and arterial stiffness. METHODS: This double blind, placebo-controlled, randomized clinical trial was carried out on 40 non-smoker moderately hypercholesterolemic subjects (ClinicalTrial.gov ID NCT02492464). After 4 weeks of diet and physical activity, patients were allocated to treatment with placebo or with an active product containing 10 mg monacolins and 30 mg Coenzyme Q10, to be assumed for 6 months. Endothelial reactivity and arterial stiffness have been measured through the validated Vicorder® device. RESULTS: During monacolin treatment, patients experienced a more favorable percentage change in low density lipoprotein (LDL)-cholesterol (after monacolin treatment: -26.3%; after placebo treatment: +3.4%, p < 0.05). Endothelial reactivity (pulse volume displacement after monacolin treatment: +6.0%; after placebo treatment: -0.3%, p < 0.05), and arterial stiffness (pulse wave velocity (PWV) after monacolin treatment: -4.7%; after placebo: +1.1%, p < 0.05) also significantly improved only after monacolin treatment. CONCLUSION: The long-term assumption of the tested dietary supplement is associated with an improvement in LDL-cholesterolemia, endothelial reactivity and PWV in moderately hypercholesterolemic subjects.

Short-term effects of a combined nutraceutical of insulin-sensitivity, lipid level and indexes of liver steatosis: a double-blind, randomized, cross-over clinical trial.

BACKGROUND: Overweight subjects easily develop alterations of the glucose and lipid metabolism and are exposed to an increased cardiometabolic risk. This condition is potentially reversible through the improvement of dietary and behavioural habits. However, a well-assembled nutraceutical would be a useful tool to better improve the metabolic parameters associated to overweight and insulin resistance. METHODS: To evaluate the effect of a combined nutraceutical containing berberine, chlorogenic acid and tocotrienols, we performed a double blind, cross-over designed trial versus placebo, in 40 overweight subjects with mixed hyperlipidaemia. After the first 8 weeks of treatment (or placebo), patients were asked to observe a 2-week washout period, and they were then assigned to the alternative treatment for a further period of 8 weeks. Clinical and laboratory data associated to hyperlipidaemia and insulin resistance have been obtained at the baseline, at the end of the first treatment period, after the washout, and again after the second treatment period. RESULTS: Both groups experienced a significant improvement of anthropometric and biochemical parameters versus baseline. However, total cholesterol, LDL cholesterol, triglycerides, non-HDL cholesterol, fasting insulin, HOMA-IR, GOT and Lipid Accumulation Product decreased more significantly in the nutraceutical group versus placebo. CONCLUSIONS: This combination seems to improve a large number of metabolic and liver parameters on the short-term in overweight subjects. Further studies are needed to confirm these observations on the middle- and long-term.

Berberine and monacolin effects on the cardiovascular risk profile of women with oestroprogestin-induced hypercholesterolemia.

INTRODUCTION: One of the most frequent side effect of oral contraceptives use is a stable alteration of the lipid profile. This could be even more relevant in women affected by polycystic ovary syndrome (PCOS). AIM: Considering the importance of a balanced lipid profile in cardiovascular prevention and that the exposure to the drugs could be many years long, our aim was to investigate the possible beneficial effect of a largely tested low-dosed combined lipid-lowering nutraceutical on dyslipidemias induced by oestroprogestins prescribed to young women for different indications. METHODS: We prospectively enrolled 84 patients in primary cardiovascular disease prevention, with low estimated cardiovascular disease risk (<5 % according to the ESC/EAS guidelines), and LDL-C increased above normal value (LDL-C >130 mg/dL) after the use of at least two different oral oestroprogestins treatments. Forty-four women were prescribed oral oestroprogestins for PCOS, while 40 for pure contraception. The tested nutraceutical contained berberine 500 mg/tab and monacolins 3 mg/tab was prescribed to all enrolled patients, associated the previously prescribed standard lipid-lowering diet. RESULTS: After 3 months of nutraceutical treatment, we observed a significant improvement in BMI (-1.5 ± 0.8 %, p < 0.001), FPG (-6.9 ± 5.8 %, p < 0.001), HOMA index (-3.5 ± 5.6 %, p < 0.001), TC (-20.1 ± 6.6 %, p < 0.001), LDL-C (-25.3 ± 8.9 %, p < 0.001), HDL-C (+14.1 ± 2.2 %, p < 0.001), TG (-29.9 ± 25.2 %, p < 0.001) and hsCRP (-2.5 ± 2.4 %, p = 0.019). Similar results have been obtained even repeating the analysis by subgroups, beyond hsCRP that significantly improved in PCOS patients compared to both the baseline and the non-PCOS group. CONCLUSION: It appears that the tested combined lipid-lowering nutraceutical is able to equally improve lipid metabolism in oral contraceptive induced hypercholesterolemia in women affected or not by PCOS.

Combined nutraceutical approach to postmenopausal syndrome and vascular remodeling biomarkers.

OBJECTIVE: Menopause is associated with broad, though generally not massive changes in a large number of metabolic parameters. The aim of our study was to evaluate the efficacy and tolerability of a combined nutraceutical approach on a large number of cardiometabolic risk markers and menopause symptoms in otherwise healthy, mildly dyslipidemic postmenopausal women. DESIGN/SETTING: Forty women were enrolled in the context of a controlled, randomized, prospective study with parallel groups at the Lipid Clinic of the University of Bologna. INTERVENTION: The women were randomized to treatment with a nutraceuticals containing soy isoflavones (60 mg) and berberine (500 mg) or a placebo at a dosage of one tablet daily between meals for 12 weeks. RESULTS: All patients completed the study without significant side effects. Anthropometric measures, blood pressure, HOMA index, and basal homocysteinemia significantly improved in isoflavones-berberine-treated group when compared to the baseline, but not when compared to the placebo-treated patients. Compared to placebo-treated patients, those treated with isoflavones-berberine experienced a significant improvement in plasma lipid and metalloproteinase serum levels, as well as the main menopausal symptoms. CONCLUSION: The short-term consumption of a nutraceutical containing isoflavones and berberine was well-tolerated and improved menopausal symptoms, plasma lipid level, and serum levels of matrix metalloproteinases in a cohort of mildly dyslipidemic postmenopausal women when compared with a neutral control.

Hemodynamic effects of lactotripeptides from casein hydrolysate in Mediterranean normotensive subjects and patients with high-normal blood pressure: a randomized, double-blind, crossover clinical trial.

Contrasting data partially support a certain antihypertensive efficacy of lactotripeptides derived from enzymatic treatment of casein hydrolysate. We carried out a randomized, double-blind, crossover clinical study to investigate the antihypertensive efficacy of a short-term treatment with lactotripeptides in Mediterranean subjects with normal or high-normal blood pressure (BP). We consecutively enrolled 55 untreated subjects (men:women = 30:25), 40.3 ± 9.8 years old, with normal or high-normal BP. After 4 weeks of dietary standardization, they were allocated to treatment with a fruit juice containing 3 mg of added Ile-Pro-Pro/Val-Pro-Pro lactotripeptides or with placebo for 4 weeks. After a 4-week washout period, they were then assigned to the alternative treatment for a further period of 4 weeks. Overall, no significant difference has been observed in office BP comparing baseline data with those posttreatment. Repeating the analysis by basal BP level, a mild but significant reduction in systolic BP (-1.7 ± 2.3 mm Hg; t = 3.5, P = .002) has been observed only in subjects with high-normal BP after treatment with lactotripeptides. With regard to 24-hour BP measurement, after lactotripeptide treatment only, the subjects experienced a significant reduction in diurnal diastolic BP (-1.6 ± 5.4 mm Hg; P = .042), diurnal mean BP (-2.1 ± 5.9 mm Hg; P = .19), and 24-hour (-5.4 ± 14.2 mm Hg; P = .011) and diurnal (-7.1 ± 19.2%; P = .014) diastolic BP value measurements relative to normal values. No modification has been observed in relation to plasma renin activity and aldosteronemia. In conclusion, diurnal diastolic BP is significantly reduced by lactrotripeptide supplementation in untreated Mediterranean subjects with normal or high-normal BP. Office systolic BP is reduced only in subjects with high-normal BP.