Inverse Association between the Global Diet Quality Score and New-Onset Hypertension in Adults: A Nationwide Cohort Study.

BACKGROUND: The Global Diet Quality Score (GDQS) is a simple and practical dietary metric associated with a number of chronic diseases. The GDQS included various foods related to blood pressure, especially diverse plant-based foods that have shown to lower blood pressure. However, studies on the role of the GDQS in reducing the risk of new-onset hypertension and whether its performance differs from that of other dietary metrics are lacking. OBJECTIVE: We aimed to examine the association between the GDQS and new-onset hypertension and to compare its performance with that of other dietary patterns, including the Plant-based Diet Index (PDI), alternate Mediterranean diet (aMED) score, Alternative Healthy Eating Index-2010, and Dietary Approaches to Stop Hypertension (DASH) score in Chinese adults. METHODS: We included a total of 12,002 participants (5644 males and 6358 females) aged >18 y from the China Health and Nutrition Survey (1997-2015). Dietary intake was estimated using average food intakes from 3 consecutive 24-h dietary recalls. Multivariable relative risks (RRs) were computed for hypertension using modified Poisson regression models. RESULTS: With ≤18 y of follow-up (mean 8.7± 5.4 y), we ascertained 4232 incident cases of hypertension. Compared with participants with a low GDQS score (<15), the multivariable-adjusted RR of hypertension was 0.72 [95% confidence interval (CI): 0.62, 0.83] among participants with a high score (≥23). A 25% increment in the GDQS was associated with a 30% (RR, 0.70; 95% CI: 0.64, 0.76) lower risk of new-onset hypertension, which was comparable with the RRs of new-onset hypertension associated with every 25% increment in the PDI (RR, 0.84; 95% CI: 0.76, 0.93), DASH score (RR, 0.84; 95% CI: 0.78, 0.91), and aMED score (RR, 0.89; 95% CI: 0.84, 0.93). CONCLUSION: A higher GDQS was associated with a lower risk of new-onset hypertension, with comparable associations of new-onset hypertension with PDI, DASH, and aMED scores in Chinese adults.

SARS-CoV-2 spike protein potentiates platelet aggregation via upregulating integrin αIIbß3 outside-in signaling pathway.

Platelet hyperreactivity is one of the crucial causes of coagulative disorders in patients with COVID-19. Few studies have indicated that integrin αIIbß3 may be a potential target for spike protein binding to platelets. This study aims to investigate whether spike protein interacts with platelet integrin αIIbß3 and upregulates outside-in signaling to potentiate platelet aggregation. In this study, we found that spike protein significantly potentiated platelet aggregation induced by different agonists and platelet spreading in vitro. Mechanism studies revealed that spike protein upregulated the outside-in signaling, such as increased thrombin-induced phosphorylation of ß3, c-Src. Moreover, using tirofiban to inhibit spike protein binding to αIIbß3 or using PP2 to block outside-in signaling, we found that the potentiating effect of spike protein on platelet aggregation was abolished. These results demonstrate that SARS-CoV-2 spike protein directly enhances platelet aggregation via integrin αIIbß3 outside-in signaling, and suggest a potential target for platelet hyperreactivity in patients with COVID-19. HIGHLIGHTS: • Spike protein potentiates platelet aggregation and upregulates αIIbß3 outside-in signaling. • Spike protein interacts with integrin αIIbß3 to potentiate platelet aggregation. • Blocking outside-in signaling abolishes the effect of spike protein on platelets.

1,25-Dihydroxyvitamin D3 attenuates platelet aggregation potentiated by SARS-CoV-2 spike protein via inhibiting integrin αIIbß3 outside-in signaling.

Platelet hyperreactivity contributes to the pathogenesis of COVID-19, which is associated with a hypercoagulability state and thrombosis disorder. It has been demonstrated that Vitamin D deficiency is associated with the severity of COVID-19 infection. Vitamin D supplement is widely used as a dietary supplement due to its safety and health benefits. In this study, we investigated the direct effects and underlying mechanisms of 1,25(OH)2D3 on platelet hyperreactivity induced by SRAS-CoV-2 spike protein via Western blot and platelet functional studies in vitro. Firstly, we found that 1,25(OH)2D3 attenuated platelet aggregation and Src-mediated signaling. We further observed that 1,25(OH)2D3 attenuated spike protein-potentiated platelet aggregation in vitro. Mechanistically, 1,25(OH)2D3 attenuated spike protein upregulated-integrin αIIbß3 outside-in signaling such as platelet spreading and the phosphorylation of ß3, c-Src and Syk. Moreover, using PP2, the Src family kinase inhibitor to abolish spike protein-stimulated platelet aggregation and integrin αIIbß3 outside-in signaling, the combination of PP2 and 1,25(OH)2D3 did not show additive inhibitory effects on spike protein-potentiated platelet aggregation and the phosphorylation of ß3, c-Src and Syk. Thus, our data suggest that 1,25(OH)2D3 attenuates platelet aggregation potentiated by spike protein via downregulating integrin αIIbß3 outside-in signaling.

Coenzyme Q10 Attenuates Human Platelet Aggregation Induced by SARS-CoV-2 Spike Protein via Reducing Oxidative Stress In Vitro.

Platelet hyperreactivity and oxidative stress are the important causes of thrombotic disorders in patients with COVID-19. Oxidative stress, induced by the excessive generation of reactive oxygen species (ROS), could increase platelet function and the risk of thrombus formation. Coenzyme Q10 (CoQ10), exhibits strong antioxidative activity and anti-platelet effect. However, the effects and mechanisms of CoQ10 on attenuating platelet aggregation induced by spike protein have never been studied. This study aims to investigate whether the SARS-CoV-2 spike protein potentiates human platelet function via ROS signaling and the protective effect of CoQ10 in vitro. Using a series of platelet function assays, we found that spike protein potentiated platelet aggregation and oxidative stress, such as ROS level, mitochondrial membrane potential depolarization, and lipid damage level (MDA and 8-iso-PGF2α) in vitro. Furthermore, CoQ10 attenuated platelet aggregation induced by spike protein. As an anti-platelet mechanism, we showed that CoQ10 significantly decreased the excess production of ROS induced by spike protein. Our findings show that the protective effect of CoQ10 on spike protein-potentiated platelet aggregation is probably associated with its strong antioxidative ability.

Extraction, Characterization, and Platelet Inhibitory Effects of Two Polysaccharides from the Cs-4 Fungus.

Cardiovascular diseases are associated with platelet hyperactivity, and downregulating platelet activation is one of the promising antithrombotic strategies. This study newly extracted two polysaccharides (purified exopolysaccharides, EPSp and purified intercellular exopolysaccharides, IPSp) from Cordyceps sinensis Cs-4 mycelial fermentation powder, and investigated the effects of the two polysaccharides and their gut bacterial metabolites on platelet functions and thrombus formation. EPSp and IPSp are majorly composed of galactose, mannose, glucose, and arabinose. Both EPSp and IPSp mainly contain 4-Galp and 4-Glcp glycosidic linkages. EPSp and IPSp significantly inhibited human platelet activation and aggregation with a dose-dependent manner, and attenuated thrombus formation in mice without increasing bleeding risk. Furthermore, the EPSp and IPSp after fecal fermentation showed enhanced platelet inhibitory effects. The results have demonstrated the potential value of Cs-4 polysaccharides as novel protective ingredients for cardiovascular diseases.

The Association between the Diversity of Coenzyme Q10 Intake from Dietary Sources and the Risk of New-Onset Hypertension: A Nationwide Cohort Study.

Coenzyme Q10 (CoQ10) is a food active component with blood-pressure-improving properties. However, the association between the variety and quantity of different sources of dietary CoQ10 and new-onset hypertension remains uncertain. We aimed to investigate the associations between the diversity and quantity of CoQ10 intake from eight major food sources and new-onset hypertension risk. A total of 11,489 participants were included. Dietary intake was evaluated via three consecutive 24 h recalls and household food inventory. The diversity score of CoQ10 sources was calculated by the sum of food groups consumed in the ideal range. Cox proportional hazard models were used for evaluating their associations with hypertension. Model performance was assessed by ROC analyses and 200-times ten-fold cross-validation. The relationships between CoQ10 and hypertension were U-shaped for meat, egg, vegetable, and fruit sources, inverse J-shaped for fish, and nut sources, and L-shaped for dairy products sources (all p-values < 0.001). A higher diversity score was associated with lower hypertension risk (HR (95% CI): 0.66 (0.64, 0.69)). The mean areas under the ROC curves for 6, 12 and 18 years were 0.81, 0.80 and 0.78, respectively. There is a negative correlation between the diversity of CoQ10 with moderate intake from different sources and new-onset hypertension. One diversity score based on CoQ10 was developed.

L-shaped association between dietary coenzyme Q10 intake and high-sensitivity C-reactive protein in Chinese adults: a national cross-sectional study.

Background: Chronic inflammation contributes to the occurrence and progression of many diseases. Most previous clinical studies have explored the effect of high-dose CoQ10 supplements on inflammation. Food is another important source of CoQ10, but the relationship between the intake of CoQ10 from dietary sources and inflammation was unknown. We aimed to explore the dose-response association between the intake of dietary-derived CoQ10 and inflammation-related biomarkers. Methods: Seven thousand nine hundred and fifty-three Chinese adults from the China Health and Nutrition Survey (CHNS) were the subjects of this cross-sectional investigation. Dietary CoQ10 intake was assessed using dietary information from three days. High-sensitivity C-reactive protein (hsCRP) and white blood cell count (WBC) were assessed using fasting venous blood. Results: In an adjusted linear regression model, CoQ10 consumption from dietary sources was inversely associated with hsCRP, with effect sizes in each group: Q2 (ß = -0.85 mg L-1, 95% CI: -1.43 to -0.28 mg L-1, P = 0.004), Q3 (ß = -0.70 mg L-1, 95% CI: -1.28 to -0.12 mg L-1, P = 0.017), and Q4 (ß = -0.79 mg L-1, 95% CI: -1.39 to -0.19 mg L-1, P = 0.010). Moreover, restricted cubic splines (RCS) revealed a non-linear L-shaped association between dietary-derived CoQ10 consumption and hsCRP (Pnonlinear < 0.001). According to subgroup analyses, these relationships were more significant in males, or >45 years old (Ptrend < 0.05). Nevertheless, no significant relationship was found between dietary-derived CoQ10 intake and WBC. Conclusions: These findings suggested a significant negative association between dietary-derived CoQ10 and hsCRP levels.

Apolipoprotein E negatively regulates allergic airway inflammation and remodeling in mice with OVA-induced chronic asthma.

Apolipoprotein E (ApoE) is a corticosteroid-unresponsive gene that negatively regulates ovalbumin (OVA) -induced allergic airway inflammation in mice with acute asthma. However, whether ApoE negatively regulates airway remodeling in mice with OVA-induced chronic asthma remains unknown. This study aimed to investigate the effects of ApoE on OVA-induced chronic asthma in a murine model. ApoE knockout (ApoE-/-) and wild-type (WT) mice were sensitized and challenged with OVA for 10 weeks to establish the chronic asthma model. Compared with WT mice, the results demonstrated that ApoE deficiency exacerbated OVA-induced airway inflammation, including elevated numbers of inflammatory cells in the blood and bronchoalveolar lavage fluid (BALF), as well as increased T helper type 2 (Th2) cells in lung tissue, Th2 cytokines in BALF, and total IgE levels in plasma. Importantly, ApoE deficiency aggravated OVA-induced airway remodeling, as evidenced by higher plasma transforming growth factor (TGF)-ß1 levels, airway goblet cell hyperplasia, and collagen deposition compared with WT mice. These results revealed that ApoE deficiency aggravates airway remodeling and inflammation in mice with OVA-induced chronic allergic asthma.

Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation-Related Biomarkers: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials.

SCOPE: Coenzyme Q10 (CoQ10) has become a popular nutritional supplement due to its wide range of beneficial biological effects. Previous meta-analyses show that the attenuation of CoQ10 on inflammatory biomarkers remains controversial. This meta-analysis aims to assess the efficacy and optimal dose of CoQ10 supplementation on inflammatory indicators in the general population. METHODS AND RESULTS: Databases are searched up to December 2022 resulting in 6713 articles, of which 31 are retrieved for full-text assessment and included 1517 subjects. Double-blind randomized controlled trials (RCTs) of CoQ10 supplementation are eligible if they contain C reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). CoQ10 supplementation can significantly reduce the levels of circulating CRP (SMD: -0.40, 95% CI: [-0.67 to -0.13], p = 0.003), IL-6 (SMD: -0.67, 95% CI: [-1.01 to -0.33], p < 0.001), and TNF-α (SMD: -1.06, 95% CI: [-1.59 to -0.52], p < 0.001) and increase the concentration of circulating CoQ10. CONCLUSION: This meta-analysis provides evidence for CoQ10 supplementation to reduce the level of inflammatory mediators in the general population and proposes that daily supplementation of 300-400 mg CoQ10 show superior inhibition of inflammatory factors.

Effects of Coenzyme Q10 Supplementation on Biomarkers of Oxidative Stress in Adults: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials.

Evidence shows that exogenous CoQ10 supplementation may potentially attenuate oxidative stress status. However, its effective dose and evidence certainty require further evaluation in the general population via more updated randomized controlled trials (RCTs). Databases (PubMed, Embase and Cochrane Library) were searched up to 30 March 2022. Evidence certainty was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Thirty-four RCTs containing 2012 participants were included in this review. Pooled effects of significant increase in total antioxidant capacity (TAC) (standardized mean difference: 1.83, 95%CI: [1.07, 2.59], p < 0.001) and significant reduction in malondialdehyde (MDA) concentrations (−0.77, [−1.06, −0.47], p < 0.001) were shown after CoQ10 supplementation compared to placebo. However, we could not determine that there was a significant increase in circulating superoxide dismutase (SOD) levels yet (0.47, [0.00, 0.94], p = 0.05). Subgroup analyses implied that CoQ10 supplementation was more beneficial to people with coronary artery disease or type 2 diabetes. Additionally, taking 100−150 mg/day CoQ10 supplement had better benefits for the levels of TAC, MDA and SOD (all p < 0.01). These results to a statistically significant extent lent support to the efficacy and optimal dose of CoQ10 supplementation on attenuating oxidative stress status in adults.

Protective effects of konjac glucomannan on gut microbiome with antibiotic perturbation in mice.

This study assessed the protective effects of konjac glucomannan (KGM) on gut microbiome against the antibiotic perturbation in C57BL/6J mice. The native KGM (1.82 × 107) was partially hydrolyzed by endo-1,4-ß-mannanase, and two hydrolyzed fractions (KGM-eM with 3.82 × 105 Da and KGM-eL with 8.27 × 103 Da) were characterized and applied to mice with perturbation of antibiotics in comparison with the native KGM. The results showed that the native KGM better maintained the microbial diversity and composition in feces, and increased the production of the individual and total SCFAs in feces and serum with perturbation of antibiotics. In contrast, KGM with lower MW (KGM-eM and KGM-eL) increased the proportion of Lactobacillus and SCFA production with no antibiotics, however, the prebiotic effects were eliminated with perturbation of antibiotics. These results have demonstrated the protective effects of KGM with high MW on gut microbiome against the antibiotic perturbation in vivo.

Cyanidin-3-O-ß-Glucoside Attenuates Platelet Chemokines and Their Receptors in Atherosclerotic Inflammation of ApoE-/- Mice.

Platelet chemokines play well-established roles in the atherosclerotic inflammation. Cyanidin-3-O-ß-glucoside (Cy-3-g) is one of the main bioactive compounds in anthocyanins, but its effects on chemokines during atherosclerosis have not been determined yet. In the present study, ApoE-/- mice were fed on the chow diet, high-fat diet (HFD), and HFD-supplemented Cy-3-g at 200, 400, and 800 mg/kg diet. After 16 weeks, Cy-3-g significantly alleviated the atherosclerotic lesion and inhibited platelet aggregation and activation. Moreover, Cy-3-g significantly reduced inflammatory chemokines CXCL4, CXCL7, CCL5, CXCL5, CXCL12, and CCL2 in plasma and downregulated CXCR4, CXCR7, and CCR5 on platelets and peripheral blood mononuclear cells. Besides, Cy-3-g decreased the mRNA of TNFα, IFNγ, ICAM-1, VCAM-1, CD68, MMP7, CCL5, CXCR4, and CCR5 in the aorta of mice. Therefore, it suggests that Cy-3-g plays important preventive roles in the process of atherosclerosis via attenuating chemokines and receptors in ApoE-/- mice.

Effects of Coenzyme Q10 Supplementation on Lipid Profiles in Adults: A Meta-analysis of Randomized Controlled Trials.

CONTEXT: Previous meta-analyses have suggested that the effects of coenzyme Q10 (CoQ10) on lipid profiles remain debatable. Additionally, no meta-analysis has explored the optimal intake of CoQ10 for attenuating lipid profiles in adults. OBJECTIVE: This study conducted a meta-analysis to determine the effects of CoQ10 on lipid profiles and assess their dose-response relationships in adults. METHODS: Databases (Web of Science, PubMed/Medline, Embase, and the Cochrane Library) were systematically searched until August 10, 2022. The random effects model was used to calculate the mean differences (MDs) and 95% CI for changes in circulating lipid profiles. The novel single-stage restricted cubic spline regression model was applied to explore nonlinear dose-response relationships. RESULTS: Fifty randomized controlled trials with a total of 2794 participants were included in the qualitative synthesis. The pooled analysis revealed that CoQ10 supplementation significantly reduced total cholesterol (TC) (MD -5.53 mg/dL; 95% CI -8.40, -2.66; I2 = 70%), low-density lipoprotein cholesterol (LDL-C) (MD -3.03 mg/dL; 95% CI -5.25, -0.81; I2 = 54%), and triglycerides (TGs) (MD -9.06 mg/dL; 95% CI -14.04, -4.08; I2 = 65%) and increased high-density lipoprotein cholesterol (HDL-C) (MD 0.83 mg/dL; 95% CI 0.01, 1.65; I2 = 82%). The dose-response analysis showed an inverse J-shaped nonlinear pattern between CoQ10 supplementation and TC in which 400-500 mg/day CoQ10 largely reduced TC (χ2 = 48.54, P < .01). CONCLUSION: CoQ10 supplementation decreased the TC, LDL-C, and TG levels, and increased HDL-C levels in adults, and the dosage of 400 to 500 mg/day achieved the greatest effect on TC.

J-Shaped Association of Tomato Intake with New-Onset Hypertension in General Adults: A Nationwide Prospective Cohort Study.

We aim to examine the prospective association between the intake of dietary tomatoes and the risk of new-onset hypertension and its modifiable factors in general adults. A total of 11,460 adults without hypertension from the China Health and Nutrition Survey (CHNS) were enrolled, with follow-up beginning in 1997 and ending in 2015. Dietary tomato intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or diagnosed by physicians or under anti-hypertensive treatment during the follow-up. Finally, 4015 subjects developed new-onset hypertension during 92,335.5 person-years of follow-up. After multivariate adjustment for dietary and non-dietary risk factors, hazard ratios for increased consumption of dietary tomatoes were 0.42 (95% confidence interval, 0.37−0.47), 0.51 (0.46−0.57), and 0.82 (0.74−0.92) compared with non-consumers. Overall, cubic spline regression suggested a novel J-shaped association between dietary tomato intake and new-onset hypertension, with the lowest risk observed at approximately 10 to 13 g/day (p < 0.001 for curvature). Moreover, the association between dietary tomato intake and risk of new-onset hypertension was stronger in females or individuals who refrained from smoking or drinking (p = 0.024, p = 0.043, and p = 0.044 for interaction, respectively).

Effects of coenzyme Q10 supplementation on glycemic control: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials.

Background: Previous reviews reported that the effects of CoQ10 on glycemic control were inconsistent. There is no review exploring the optimal intake of CoQ10 for glycemic control. We aimed to investigate the efficacy of CoQ10 on glycemic control and evaluate the dose-response relationship via integrating the existing evidence from randomized control trials (RCTs). Methods: Databases (PubMed, Embase, and Cochrane Library) were searched to identify RCTs for investigating the efficacy of CoQ10 on fasting glucose, fasting insulin, HbA1c, and HOMA-IR up to March 12, 2022. We performed a meta-analysis on 40 RCTs of CoQ10. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated for net changes. Evidence certainty was assessed using GRADE. Dose-response relationships were evaluated using 1-stage restricted cubic spline regression model. The protocol was registered in PROSPERO (CRD42021252933). Findings: Forty studies (n = 2,424 participants) were included in this meta-analysis. CoQ10 significantly reduced fasting glucose (WMD: -5.22 [95% CI: -8.33, -2.11] mg/dl; P <0.001; I2 =95.10%), fasting insulin (-1.32 [-2.06, -0.58] µIU/ml; P < 0.001; I2 =78.86%), HbA1c (-0.12% [-0.23, -0.01]; P =0.04; I2 =49.10%), and HOMA-IR (-0.69 [-1.00, -0.38]; P <0.001; I2 =88.80%). The effect of CoQ10 on outcomes was greater in diabetes with lower heterogeneity. A "U" shape dose-response relationship curve revealed that 100-200 mg/day of CoQ10 largely decreased fasting glucose (χ 2 = 12.08, P nonlinearity =0.002), fasting insulin (χ 2 = 9.73, P nonlinearity =0.008), HbA1c (χ 2 = 6.00, P nonlinearity =0.049), HOMA-IR (χ 2 = 25.89, P nonlinearity <0.001). Interpretation: CoQ10 supplementation has beneficial effects on glycemic control, especially in diabetes, and 100-200 mg/day of CoQ10 could achieve the greatest benefit, which could provide a basis for the dietary guidelines of CoQ10 in patients with glycemic disorders. Funding: This work was supported by the National Natural Science Foundation of China (No. 82030098, 81872617 and 81730090), Shenzhen Science, Technology, and Innovation Commission (No. JCYJ20180307153228190), CNS Research Fund for DRI, and National innovation and entrepreneurship training program for undergraduate student (No. 202210558161).

Water-Soluble Tomato Concentrate, a Potential Antioxidant Supplement, Can Attenuate Platelet Apoptosis and Oxidative Stress in Healthy Middle-Aged and Elderly Adults: A Randomized, Double-Blinded, Crossover Clinical Trial.

Increased oxidative stress and platelet apoptotic in middle-aged and elderly adults are important risk factors for atherosclerotic cardiovascular disease (ASCVD). Therefore, it is of great significance to control the oxidative stress and platelet apoptosis in middle-aged and elderly adults. Previous acute clinical trials have shown that water-soluble tomato concentrate (WSTC) from fresh tomatoes could exert antiplatelet benefits after 3 h or 7 h, but its effects on platelet apoptosis and oxidative stress are still unknown, especially in healthy middle-aged and elderly adults. This current study aimed to examine the efficacies of WSTC on platelet apoptosis and oxidative stress in healthy middle-aged and elderly adults via a randomized double-blinded placebo-controlled crossover clinical trial (10 weeks in total). A total of 52 healthy middle-aged and elderly adults completed this trial. The results showed that WSTC could increase the serum total antioxidant capacity levels (p < 0.05) and decrease the serum malondialdehyde levels (p < 0.05) after a 4-week WSTC supplementation in healthy middle-aged and elderly adults. Platelet endogenous reactive oxygen species generation (p < 0.05), mitochondrial membrane potential dissipation (p < 0.05) and phosphatidylserine exposure (p < 0.05) were attenuated. In addition, our present study also found that WSTC could inhibit platelet aggregation and activation induced by collagen or ADP after intervention (p < 0.05), while having no effects on adverse events (p > 0.05). The results suggest that WSTC can inhibit oxidative stress and its related platelet apoptosis, which may provide a basis for the primary prevention of WSTC in ASCVD.

Dose-Response Effect of Coenzyme Q10 Supplementation on Blood Pressure among Patients with Cardiometabolic Disorders: A Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Previous studies have shown beneficial effects of coenzyme Q10 (CoQ10) supplementation on blood pressure (BP). However, the optimal intake of CoQ10 for BP regulation in patients with cardiometabolic disorders is unknown, and its effect on circulating CoQ10 is also unclear. We aimed to assess the dose-response relation between CoQ10 and BP, and quantify the effect of CoQ10 supplementation on the concentration of circulating CoQ10 by synthesizing available evidence from randomized controlled trials (RCTs). A comprehensive literature search was performed in 3 databases (PubMed/MEDLINE, Embase, and Cochrane Library) to 21 March, 2022. A novel 1-stage restricted cubic spline regression model was used to evaluate the nonlinear dose-response relation between CoQ10 and BP. Twenty-six studies comprising 1831 subjects were included in our meta-analysis. CoQ10 supplementation significantly reduced systolic blood pressure (SBP) (-4.77 mmHg, 95% CI: -6.57, -2.97) in patients with cardiometabolic diseases; this reduction was accompanied by a 1.62 (95% CI: 1.26, 1.97) µg/mL elevation of circulating CoQ10 compared with the control group. Subgroup analyses revealed that the effects of reducing SBP were more pronounced in patients with diabetes and dyslipidemia and in studies with longer durations (>12 wk). Importantly, a U-shaped dose-response relation was observed between CoQ10 supplementation and SBP level, with an approximate dose of 100-200 mg/d largely reducing SBP (χ2 = 10.84, Pnonlinearity = 0.004). The quality of evidence was rated as moderate, low, and very low for SBP, diastolic blood pressure (DBP), and circulating CoQ10 according to the Grading of Recommendations, Assessment, Development, and Evaluation approach (GRADE), respectively. The current finding demonstrated that the clinically beneficial effects of CoQ10 supplementation may be attributed to the reduction in SBP, and 100-200 mg/d of CoQ10 supplementation may achieve the greatest benefit on SBP in patients with cardiometabolic diseases. This study was registered on PROSPERO as CRD42021252933.

Four-Week Supplementation of Water-Soluble Tomato Extract Attenuates Platelet Function in Chinese Healthy Middle-Aged and Older Individuals: A Randomized, Double-Blinded, and Crossover Clinical Trial.

Background and Aims: Platelets are linked to atherosclerotic development and pathological thrombosis. Single dose of water-soluble tomato extract (WTE) which is a natural extraction can exert anti-platelet effects after 3 or 7 h in British healthy people. However, the effects of WTE supplementation on platelet function in Chinese healthy middle-aged and older individuals have not been studied, and the effects or safety of 4-week WTE supplementation also remain unclear. The present study aims to determine the effects of WTE on platelet function, and explore the safety of 4-week WTE supplementation in Chinese healthy middle-aged and older individuals. Methods: A randomized, double-blinded, and crossover clinical trial was conducted. Firstly, 105 individuals were randomly divided into two groups that received WTE (150 mg/day) or placebo for 4 weeks. Then, after a washout period of 2 weeks, two groups exchanged groups and continued for another 4-week intervention. Platelet aggregation, P-selectin, activated GPIIbIIIa, plasma platelet factor 4 (PF4), ß-thromboglobulin (ß-TG), and thromboxane B2 (TXB2) were tested at baseline, 4, 6, and 10 weeks. Results: Compared with the placebo group, 150 mg/day WTE supplement for 4 weeks significantly reduced ADP-induced or collagen-induced platelet aggregation (-10.8 ± 1.8 or -3.9 ± 1.5%, P < 0.05), ADP-induced or collagen-induced platelet P-selectin expression (-6.9 ± 1.5 or -6.6 ± 1.3%, P < 0.05), ADP-induced or collagen-induced activated GPIIbIIIa (-6.2 ± 2.0 or -3.8 ± 2.0%, P < 0.05). Besides, 4-week intervention of 150 mg WTE per day also resulted in significant reductions in plasma PF4 (-120.6 ± 33.2 ng/mL, P < 0.05) and ß-TG (-129.7 ± 27.5 ng/mL, P < 0.05) and TXB2 (-42.0 ± 4.0 ng/mL, P < 0.05), while had no effects on coagulation function and liver or renal function. Interestingly, 2-week washout period is enough to reverse the inhibitory effect of 4-week WTE supplementation on platelet function. Conclusion: WTE supplementation for 4 weeks could moderately reduce platelet activation, aggregation, and granule secretion in Chinese healthy middle-aged and older individuals, and these effects are safe. After 2-week washout period, the inhibitory effect of 4-week WTE on platelet function can be eliminated. Clinical Trial Registration: [http://www.chictr.org.cn/], identifier [ChiCTR-POR-17012927].

Coenzyme Q10 supplementation improves cholesterol efflux capacity and antiinflammatory properties of high-density lipoprotein in Chinese adults with dyslipidemia.

OBJECTIVES: Coenzyme Q10 (CoQ10) had shown promising effects in improving the lipid and glycemic profile in dyslipidemic individuals in our previous work, but little is known about how it affects high-density lipoprotein (HDL) function in patients with dyslipidemia. The aim of this study was to explore the effects of CoQ10 supplementation on HDL function in people with dyslipidemia. METHODS: A 24-wk, randomized, double-blind, placebo-controlled trial was conducted in 101 people with dyslipidemia. All patients were randomized into the CoQ10 group (120 mg/d, n = 51) or the placebo group (n = 50). High-density lipoprotein-mediated cholesterol efflux capacity (CEC), HDL inflammatory index (HII), and HDL intrinsic oxidation were measured at baseline, 12 wk, and 24 wk. RESULTS: CoQ10 supplementation for 24 wk significantly improved HDL-mediated CEC (mean change, 1.21±2.44 versus -0.12±2.94; P = 0.014) and reduced HII (mean change, -0.32±0.58 versus -0.05±0.49, P = 0.014) compared with placebo. However, there was no significant difference in the effect of CoQ10 on HDL intrinsic oxidation between the two groups after 24 wk (P = 0.290). A positive correlation was found between the changes in CEC and HDL cholesterol in the CoQ10 group (r, 0.30; P = 0.032). Furthermore, we also found that the improved HDL functions were more obvious in elderly, female, or non-obese individuals, which indicated a specific population that benefits most from CoQ10 intervention. CONCLUSIONS: This study suggested that supplementation of CoQ10 for 24 wk can significantly improve HDL-mediated CEC and antiinflammatory function of HDL in patients with dyslipidemia.

Anthocyanins, Anthocyanin-Rich Berries, and Cardiovascular Risks: Systematic Review and Meta-Analysis of 44 Randomized Controlled Trials and 15 Prospective Cohort Studies.

Objective: The associations between intake of anthocyanins and anthocyanin-rich berries and cardiovascular risks remained to be established. We aimed to quantitatively summarize the effects of purified anthocyanins and anthocyanin-rich berries on major surrogate markers of cardiovascular diseases (CVDs) and the longitudinal associations between dietary anthocyanins and CVD events. Methods: Meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies. Results: We included 44 eligible RCTs and 15 prospective cohort studies in this study. Pooled analysis of RCTs showed that purified anthocyanin supplementation could significantly reduce blood LDL cholesterol (weighted mean difference (WMD): -5.43 mg/dL, 95% CI: -8.96, -1.90 mg/dL; p = 0.003) and triglyceride (WMD: -6.18 mg/dL, 95% CI: -11.67, -0.69 mg/dL; p = 0.027) while increase HDL cholesterol (WMD: 11.49 mg/dL, 95% CI: 7.43, 15.55 mg/dL; p < 0.001) concentrations. Purified anthocyanins also markedly decreased circulating tumor necrosis factor alpha (WMD: -1.62 pg/mL, 95% CI: -2.76, -0.48 pg/mL; p = 0.005) and C-reactive protein (WMD: -0.028 mg/dL, 95% CI: -0.050, -0.005 mg/dL; p = 0.014). Besides, administration of anthocyanin-rich berries could significantly lower blood total cholesterol (WMD: -4.48 mg/dL, 95% CI: -8.94, -0.02 mg/dL; p = 0.049) and C-reactive protein (WMD: -0.046 mg/dL, 95% CI: -0.070, -0.022 mg/dL; p < 0.001). Neither purified anthocyanins nor anthocyanin-rich berries could cause any substantial improvements in BMI, blood pressure, or flow-mediated dilation. In addition, meta-analysis of prospective cohort studies suggested that high dietary anthocyanins were related to lower risk of coronary heart disease (CHD) (relative risk (RR): 0.83, 95% CI: 0.72, 0.95; p = 0.009), total CVD incidence (RR: 0.73, 95% CI: 0.55, 0.97; p = 0.030), and total CVD deaths (RR: 0.91, 95% CI: 0.87, 0.96; p < 0.001). Conclusion: Habitual intake of anthocyanins and anthocyanin-rich berries could protect against CVDs possibly via improving blood lipid profiles and decreasing circulating proinflammatory cytokines. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42020208782.