Folic acid and plasma lipids: Interactions and effect of folate supplementation.

Dyslipidaemia and hyperhomocysteinemia are known risk factors for cardiovascular disease. While it is evident that optimization of plasma lipid is associated with low risk of cardiovascular disease in the general population, it is not yet fully clear whether reduction of homocysteinemia is associated with an improvement in risk in all subjects. The aim of our narrative review is to highlight eventual effects of folate supplementation on LDL-C levels, LDL-C oxidation and atherosclerosis-related complications. A comprehensive literature search was done in electronic database, including PubMed, Web of Science, Cochrane, and Scopus from inception up to January 2024. Based on the available evidence, epidemiological data, pathophysiological observations and meta-analyses of randomized clinical trials suggest that folic acid supplementation may modestly but significantly improve plasma lipid levels, lipid atherogenicity, and atherosclerosis-related early vascular damage, and that folic acid supplementation may significantly reduce the risk of cerebrovascular disease. Considering the low-cost and high safety profile of folic acid, its long-term supplementation could be considered for dyslypidaemic patients in secondary prevention for cardiovascular disease.

Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (Urrah Project).

PURPOSE: Recently, a novel index (triglyceride-glucose index-TyG) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population. Moreover, in consideration of the well-recognized role of serum uric acid (SUA) on CV risk and the close correlation between SUA and IR, we also evaluated the combined effect of TyG and SUA on mortality risk. METHODS: The analysis included 16,649 participants from the URRAH cohort. The risk of all-cause and CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. RESULTS: During a median follow-up of 144 months, 2569 deaths occurred. We stratified the sample by the optimal cut-off point for all-cause (4.62) and CV mortality (4.53). In the multivariate Cox regression analyses, participants with TyG above cut-off had a significantly higher risk of all-cause and CV mortality, than those with TyG below the cut-off. Moreover, the simultaneous presence of high levels of TyG and SUA was associated with a higher mortality risk than none or only one of the two factors. CONCLUSIONS: The results of this study indicate that these TyG (a low-cost and simple non-invasive marker) thresholds are predictive of an increased risk of mortality in a large and homogeneous general population. In addition, these results show a synergic effect of TyG and SUA on the risk of mortality.

Serum Uric Acid/Serum Creatinine Ratio and Cardiovascular Mortality in Diabetic Individuals-The Uric Acid Right for Heart Health (URRAH) Project.

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied (n = 2230). The risk of CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.

Lifestyle and Lipoprotein(a) Levels: Does a Specific Counseling Make Sense?

Lipoprotein(Lp)(a) is a variant of low-density lipoprotein (LDL), bound to apolipoprotein B100, whose levels are associated with a significant increase in the risk of atherosclerosis-related cardiovascular events, but also to aortic stenosis and atrial fibrillation. Since plasma levels of Lp(a) are commonly considered resistant to lifestyle changes, we critically reviewed the available evidence on the effect of weight loss, dietary supplements, and physical activity on this risk factor. In our review, we observed that relevant body weight loss, a relatively high intake of saturated fatty acids, the consumption of red wine, and intense physical exercise seems to be associated with significantly lower plasma Lp(a) levels. On the contrary, foods rich in trans-unsaturated fatty acids are associated with increased Lp(a) levels. With regard to dietary supplements, coenzyme Q10, L-Carnitine, and flaxseed exert a mild but significant lowering effect on plasma Lp(a).

Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

BACKGROUND: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort. METHODS AND RESULTS: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P<0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P=0.004) and 1.150 (95% CI, 1.021-1.295, P=0.02), respectively. CONCLUSIONS: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

Dietary inflammation index association with serum levels of nitric oxide, prostacyclin, and thromboxane B2 among prinzmetal angina patients and healthy persons.

BACKGROUND AND AIM: This study aimed to assess the association between dietary inflammation index with serum Nitric oxide, Prostacyclin, and Thromboxane B2 among Prinzmetal angina patients and healthy persons. METHODS AND RESULTS: This case-control study was conducted among 120 Prinzmetal angina patients and 120 healthy persons referred to the Ardabil Imam Khomeini Hospital between 2021 and 2022. Blood samples were gained from all study participants for measurement of serum Nitric oxide, Prostacyclin, and Thromboxane B2. The serum Nitric oxide in patients who had higher DII was less than in patients with less dietary inflammation index (ß = -0.75 p = 0.02). The serum Prostacyclin level in patients with greater dietary inflammation index was 0.68 ng/ml less than in patients with less dietary inflammation index (ß = -0.68 p = 0.04). The level of serum Thromboxane B2 had a positive association with dietary inflammation index (ß = 0.81 p = 0.04). CONCLUSION: In Prinzmetal angina patients, more dietary inflammation index can increase the serum Thromboxane B2 and decrease the serum Nitric oxide and Prostacyclin. More clinical trial study is needed to confirm these results.

Effect of dietary supplementation with a new nutraceutical formulation on cardiometabolic risk factors: a double-blind, placebo-controlled, randomized clinical study.

Introduction: The scientific community and consumers are increasingly interested in the potential cholesterol-lowering effect of various nutraceuticals and their combinations. The aim of our study was to test the short-term effect of a new lipid-lowering nutraceutical formulation in mildly hypercholesterolemic patients. Material and methods: We consecutively enrolled 80 mildly hypercholesterolemic patients with low-density lipoprotein-cholesterol (LDL-C) between 130 and 190 mg/dl with a low-estimated cardiovascular disease risk. After a 8 week-stabilization diet, the enrolled subjects were randomized to take 1 pill/evening of Zeta Colest (including: 400 mg of Berberis aristata dry extract with 340 mg of berberine, 98 mg of red yeast rice extract with 2.9 mg of total monacolins, 87.5 mg of milk thistle dry extract with 70 mg of silymarin, 50 mg of guggul dry extract with 1.3 mg of guggulsterones) or placebo for 8 weeks. Patients were followed up for metabolic and haemodynamic parameters. Results: After 8 week-supplementation with the tested combined nutraceuticals, we observed a significant reduction in total cholesterol (-15.2 ±1.4%), LDL-C (-18.1 ±1.9%), non-high-density lipoprotein cholesterol (-17.7 ±1.8%), apoB (-16.9 ±1.9%) and high-sensitivity C-reactive protein (-3.7 ±0.7%), versus both baseline (p < 0.05) and the control group (p < 0.05). No other metabolic or liver parameters significantly changed during the observation period. Endothelial reactivity also mildly but significantly improved by 2.96 ±0.23% with the tested product. Conclusions: In the short term, the tested combined nutraceutical improved lipid metabolism, systemic inflammation and vascular function in mildly hypercholesterolemic overweight subjects.

Sex X Time Interactions in Lp(a) and LDL-C Response to Evolocumab.

The aim of this study was to evaluate whether there were significant sex x time interactions in lipoprotein(a) (Lp(a)) and low-density lipoprotein cholesterol (LDL-C) response to treatment with the Proprotein Convertase Subtilisin/Kexin type 9 inhibitor (PCSK9i) Evolocumab, in a real-life clinical setting. For this purpose, we pooled data from 176 outpatients (Men: 93; Women: 83) clinically evaluated at baseline and every six months after starting Evolocumab. Individuals who had been on PCSK9i for less than 30 months and nonadherent patients were excluded from the analysis. Over time, absolute values of Lp(a) plasma concentrations significantly decreased in the entire cohort (p-value < 0.001) and by sex (p-value < 0.001 in men and p-value = 0.002 in and women). However, there were no sex-related significant differences. Absolute plasma concentrations of LDL-C significantly decreased over time in the entire cohort and by sex (p-value < 0.001 always), with greater improvements in men compared to women. The sex x time interaction was statistically significant in LDL-C (all p-values < 0.05), while absolute changes in Lp(a) were not influenced by either sex or time (all p-value > 0.05). Our data partially reinforce the presence of differences in response to treatment to PCSK9i between men and women and are essential to gain a better understanding of the relationship between LDL-C and Lp(a) lowering in response to PCSK9i. Further research will clarify whether these sex-related significant differences translate into a meaningful difference in the long-term risk of ASCVD.

Estimating the Prevalence and Characteristics of Patients Potentially Eligible for Lipoprotein(a)-Lowering Therapies in a Real-World Setting.

High lipoprotein(a) (Lp(a)) plasma levels are significantly associated with an increased risk of developing atherosclerotic cardiovascular diseases (ASCVD). The aim of this analysis was to estimate the prevalence and characteristics of patients potentially eligible for Lp(a)-lowering therapies in a real-world setting (i.e., patients with ASCVD and Lp(a) levels > 70 mg/dL). For this reason, we pooled data from a large cohort of Italian outpatients (N = 5961; men: 2879, women: 3982) with dyslipidemia. A binary logistic regression analysis was used to determine the significant predictors of ASCVD in the cohort, which were age (Odds Ratio (OR): 1.158, 95% Confidence Interval (CI): 1.114 to 1.203, p < 0.001), low-density lipoprotein cholesterol at entry (OR: 1.989, 95% CI: 1.080 to 1.198, p = 0.020) and Lp(a) (OR: 1.090, 95% CI: 1.074 to 1.107, p < 0.001). In our cohort, almost half of patients with ASCVD (44.7%) may be eligible to be treated with Lp(a)-lowering agents. Interestingly, patients who do not meet the treatment criteria despite high Lp(a) (50-70 mg/dL), respectively, account for 4.7% and 7.3% of those in primary and secondary ASCVD prevention. In conclusion, in our large cohort of outpatients with dyslipidemia, the prevalence of individuals with ASCVD and very high Lp(a) plasma levels is quite high, even with a conservative estimation.

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.

Assessment of Apolipoprotein(a) Isoform Size Using Phenotypic and Genotypic Methods.

Apolipoprotein(a) (apo(a)) is the protein component that defines lipoprotein(a) (Lp(a)) particles and is encoded by the LPA gene. The apo(a) is extremely heterogeneous in size due to the copy number variations in the kringle-IV type 2 (KIV2) domains. In this review, we aim to discuss the role of genetics in establishing Lp(a) as a risk factor for coronary heart disease (CHD) by examining a series of molecular biology techniques aimed at identifying the best strategy for a possible application in clinical research and practice, according to the current gold standard.

Comparative effect of a nutraceutical compound based on a flavonoid complex from bergamot on plasma lipids, glucose metabolism, and liver enzymes: a 3-arm, double-blind, placebo-controlled, randomized clinical trial.

Introduction: Bergamot and opuntia (prickly pear cladodes) standardized extracts have been demonstrated to have positive metabolic effects in preclinical and clinical models. Material and methods: The aim of this study was to evaluate the metabolic effect of a combined nutraceutical containing 150 mg of Opuntia ficus Indica extract, 400 mg of plant sterols, 12.5 mg of thiamine, and 200 mg of Brumex® a phytocomplex from bergamot fruit (Citrus bergamia Risso et Poiteau, fructus) standardized 40% in total flavonoids and min 5% in 3-hydroxy-3-methylglutaryl-flavanones. Thus, we carried out a randomized, double-blind, placebo-controlled clinical trial on 75 hypercholesterolaemic subjects randomized to take the active compound (2 tablets per day), placebo (2 tablets per day), or both (1 per product per day). Results: After 12 weeks of treatment with 1 tablet per day, we observed a significant reduction of a number of metabolic parameters: total cholesterol (TC) (-14.6%), low-density lipoprotein cholesterol (LDL-C) (-19.9%), non-high-density lipoprotein cholesterol (non-HDLC) (-22.1%), triglycerides (TG) (-13.1%), Apolipoprotein B (-16%) (all p < 0.05 both versus baseline and versus placebo), fasting plasma glucose (-5.1%), glutamate oxaloacetate transaminase (-7.8%), glutamate pyruvate transaminase (-7.3%), and γ-glutamyl transferase (-34.4%) (all p < 0.05 versus baseline). High-density lipoprotein cholesterol (HDL-C) was increased 6.9% by the use of 1 tablet per day (p < 0.05 versus baseline). All parameters were reduced to the same extent when taking the full dose (2 tablets), beyond TG. Conclusions: the tested nutraceutical compound based on a flavonoid complex from bergamot and opuntia showed a short-term positive impact on plasma lipids, fasting plasma glucose, and liver enzyme in overall healthy subjects affected by hypercholesterolaemia with low cardiovascular risk.

Three arms, double-blind, non-inferiority, randomized clinical study testing the lipid-lowering effect of a novel dietary supplement containing red yeast rice and artichoke extracts compared to Armolipid Plus® and placebo.

Introduction: There is growing interest in head-to-head comparison between different lipid-lowering nutraceuticals. The aim of our study was to test the lipid-lowering effect of dietary supplementation with low-dose monacolins from red yeast rice (2.8 mg per daily dose) combined with berberine (Armolipid Plus®) or highly standardized artichoke extract versus placebo. Material and methods: 60 overall healthy adult volunteers with polygenic hypercholesterolemia (baseline low-density lipoprotein cholesterol (LDL-C) = 160.2 ±9.2 mg/dl) were enrolled in a 3-arm, double-blind, non-inferiority, randomized, parallel-group clinical trial. After 4-week diet standardization, enrolled individuals were randomized to be treated for 8 weeks with red yeast rice and highly standardized artichoke extracts (ATC group), Armolipid Plus®, or placebo. Results: At the enrolment visit, LDL-C values were similar in the compared groups. After 8 weeks, all actively treated subjects experienced significant improvements in baseline total cholesterol (TC), LDL-C and apolipoprotein B (Apo-B) (all p < 0.01) (ATC group: TC = -18.9%, LDL-C = -26.7% (placebo-corrected: -12.4%), Apo-B = -19.6%; Armolipid Plus®: TC = -18.4%, LDL-C = -25.8% (placebo-corrected: -12.1%), Apo-B = -23.2%; placebo: TC = -6.2%, LDL-C = -8%, Apo-B = -8.4%). Participants in the ATC group attained significantly lower body mass index (BMI) values (-2.1%), while individuals treated with Armolipid Plus® showed improvements in baseline high-density lipoprotein cholesterol (HDL-C) (+8.7%) and triglyceride (TG) (+17.5%) levels. Finally, baseline hepatic steatosis index (HSI) values significantly decreased in both actively treated groups (by -2.4% and -2.4% in ATC and in Armolipid Plus®, respectively). Conclusions: Patients with polygenic hypercholesterolemia experienced a significant improvement in several cardiovascular risk factors in both ATC and Armolipid Plus® groups.

Metabolic and vascular effect of a new standardized bergamot phytocomplex: a three-arm, placebocontrolled, double-blind clinical trial.

Introduction: In addition to healthy lifestyle and balanced diet, nutraceutical supplementation may be useful to maintain overall metabolic wellness. The aim of the present study was to assess the metabolic and vascular effects of a new, highly standardized bergamot phytocomplex supplement in healthy volunteers with the features of metabolic syndrome. Material and methods: We carried out a double-blind, randomized, placebo-controlled, three-arm, parallel-group clinical trial in 90 adult subjects (30 per group) treated for 12 weeks with two different dosages of a highly standardized bergamot phytocomplex (Endoberg by AKHYNEX and Kalita by Giellepi) or placebo. Lipid plasma levels, glycemia, plasma hs-CRP, HOMA-IR, body fat, endothelial reactivity and fatty liver index were assessed at baseline, after 6 weeks and at the end of treatment in all subjects. Results: At the end of treatment, both tested bergamot extract doses were able to significantly improve atherogenic dyslipidemia and insulin sensitivity (p < 0.05) compared to placebo. In the high-dose treated group, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) improved versus placebo (p < 0.05) just after 6 weeks of treatment. After 12 weeks of treatment, TC decreased by 13.2 ±2.1%, LDL-C by 17.7 ±3.2%, non-HDL-C by 17.5 ±3.1%, TG by 16.6 ±3.3%, TG/HDL-C by 22.5 ±4.4%, homeostasis insulin resistance index (HOMA-IR) by 12.2 ±2.1%, γ-glutamyl transferase (GGT) by 22.2 ±4.6%, and high-sensitivity C-reactive protein (hs-CRP) by 17.9 ±3.4% versus baseline (p < 0.05) and vs. placebo (p < 0.05). Percentage body fat and endothelial reactivity improved versus baseline, but not versus placebo, in the high-dose treatment only (p < 0.05). Conclusions: The tested bergamot phytocomplex was able to significantly improve glucose and lipid metabolism, as well as inflammation, and might represent a novel multi-target approach to control metabolic syndrome.

Beyond statins: New pharmacological targets to decrease LDL-cholesterol and cardiovascular events.

The pharmacological treatment of dyslipidemia, a major modifiable risk factor for developing atherosclerotic cardiovascular disease (ASCVD), remains a debated and controversial issue, not only in terms of the most appropriate therapeutic range for lipid levels, but also with regard to the optimal strategy and sequence approach (stepwise vs upstream therapy). Current treatment guidelines for the management of dyslipidemia focus on the intensity of low-density lipoprotein cholesterol (LDL-C) reduction, stratified according to risk for developing ASCVD. Beyond statins and ezetimibe, different medications targeting LDL-C have been recently approved by regulatory agencies with potential innovative mechanisms of action, including proprotein convertase subtilisin/kexin type 9 modulators (monoclonal antibodies such as evolocumab and alirocumab; small interfering RNA molecules such as inclisiran), ATP-citrate lyase inhibitors (bempedoic acid), angiopoietin-like 3 inhibitors (evinacumab), and microsomal triglyceride transfer protein inhibitors (lomitapide). An understanding of their pharmacological aspects, benefit-risk profile, including impact on hard cardiovascular endpoints beyond LDL-C reduction, and potential advantages from the patient perspective (e.g., adherence) - the focus of this evidence-based review - is crucial for practitioners across medical specialties to minimize therapeutic inertia and support clinical practice.

The role of nutraceuticals in heart failure muscle wasting as a result of inflammatory activity. The International Lipid Expert Panel (ILEP) Position Paper.

Muscle wasting is one of the main causes for exercise intolerance and ventilatory inefficiency in patients with heart failure and a strong predictor of frailty and reduced survival. The prevalence of sarcopenia is at least 20% in patients with heart failure. Patients with heart failure often have subclinical systemic inflammation, which may exert sustained effects on skeletal muscle. Besides exercise, nutrition should also be carefully evaluated as an appropriate diet with selected nutraceuticals may be able to stimulate muscle anabolism and inhibit muscle catabolism. This review summarizes the epidemiological and clinical trial evidence supporting the recommendations for the use of nutraceuticals with anti-inflammatory properties in heart failure and provides an overview of the state of the evidence for nutraceutical supplementation to prevent and/or mitigate heart failure muscle wasting.

An Evolving Definition of a "Healthy Diet".

Throughout life, most of us eat at least three meals a day for 365 days a year [...].

Effect of dietary supplementation with Diuripres® on blood pressure, vascular health, and metabolic parameters in individuals with high-normal blood pressure or stage I hypertension: The CONDOR randomized clinical study.

Our aim was to evaluate if a nutritional intervention with a dietary supplement (Diuripres®) containing magnesium, standardized extract of orthosiphon, hawthorn, and hibiscus could positively affect blood pressure (BP), vascular health, and metabolic parameters in 60 individuals with high-normal BP or stage I hypertension. Participants followed a low-fat low-sodium Mediterranean diet for 4 weeks before being randomly allocated to 8-week treatment with two pills each day of either Diuripres® or placebo. Diuripres® significantly decreased systolic BP compared to placebo after 4 weeks (3.1 ± 0.8 mmHg; p < 0.05) and more consistently after 8 weeks (3.4 ± 0.9 mmHg; p < 0.05). At 8-week follow-up, after correction for multiple testing, dietary supplementation with Diuripres® was associated with significant improvements in diastolic BP (-3.1 ± 0.6 mmHg; p < 0.05), aortic BP (-4.3 ± 0.4 mmHg; p < 0.05), and high-sensitivity C-reactive protein (hs-CRP; 0.04 ± 0.01 mg/dL; p < 0.05) in comparison with baseline. The reductions in diastolic BP (--3.8 ± 0.7 mmHg; p < 0.05), aortic BP (-5.2 ± 1.0 mmHg; p < 0.05), and hs-CRP (-0.03 ± 0.01 mg/dL; p < 0.05) were also significant compared to placebo. Therefore, our study shows that dietary supplementation with Diuripres® may be useful in individuals with high-normal BP or stage I hypertension.