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Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women
Abstract
Vascular endothelial function is declines with aging and is associated with an increased risk of cardiovascular disease. Lifestyle modification, particularly aerobic exercise and dietary adjustment, has a favorable effect on vascular aging. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. We investigated the effects of curcumin ingestion and aerobic exercise training on flow-mediated dilation as an indicator endothelial function in postmenopausal women. A total of 32 postmenopausal women were assigned to 3 groups: control, exercise, and curcumin groups. The curcumin group ingested curcumin orally for 8 weeks. The exercise group underwent moderate aerobic exercise training for 8 weeks. Before and after each intervention, flow-mediated dilation was measured. No difference in baseline flow-mediated dilation or other key dependent variables were detected among the groups. Flow-mediated dilation increased significantly and equally in the curcumin and exercise groups, whereas no changes were observed in the control group. Our results indicated that curcumin ingestion and aerobic exercise training can increase flow-mediated dilation in postmenopausal women, suggesting that both can potentially improve the age-related decline in endothelial function.
... Figure 4 illustrates the risk of bias in clinical trials. Two studies exhibited a low risk of bias across all domains [20,28], while for two studies, the risk of selection, reporting and other biases were unclear [28,29]. Figure 3 summarizes the risk of bias in animal studies. ...
... Figure 4 illustrates the risk of bias in clinical trials. Two studies exhibited a low risk of bias across all domains [20,28], while for two studies, the risk of selection, reporting and other biases were unclear [28,29]. Figure 3 summarizes the risk of bias in animal studies. ...
... Figure 4 illustrates the risk of bias in clinical trials. Two studies exhibited a low risk of bias across all domains [20,28], while for two studies, the risk of selection, reporting and other biases were unclear [28,29]. ...
The risk of developing cardiovascular disease (CVD) escalates in women during menopause, which is associated with increased vascular endothelial dysfunction, arterial stiffness, and vascular remodeling. Meanwhile, curcumin has been demonstrated to enhance vascular function and structure in various studies. Therefore, this study systematically reviewed the recent literature regarding the potential role of curcumin in modulating vascular function and structure during menopause. The Ovid MEDLINE, PubMed, Scopus, and Web of Science electronic databases were searched to identify relevant articles. Clinical and preclinical studies involving menopausal women and postmenopausal animal models with outcomes related to vascular function or structure were included. After thorough screening, seven articles were selected for data extraction, comprising three animal studies and four clinical trials. The findings from this review suggested that curcumin has beneficial effects on vascular function and structure during menopause by addressing endothelial function, arterial compliance, hemodynamic parameters, and the formation of atherosclerotic lesions. Therefore, curcumin has the potential to be utilized as a supplement to enhance vascular health in menopausal women. However, larger-scale clinical trials employing gold-standard techniques to evaluate vascular health in menopausal women are necessary to validate the preliminary results obtained from small-scale randomized clinical trials involving curcumin supplementation (INPLASY, INPLASY202430043).
... 86,91,93,94,98,102,103,105,106,108,110,112,113,115,[117][118][119]121,124,125,129,130,[132][133][134][135][136][139][140][141][142][143]147,148 Japan. 87,89,99,116,123 India. 97,104,109,146 Brazil. ...
... Nine studies were exclusively performed on female subjects. 87,89,121,127,129,130,132,139,147 four studies on male subjects. 96,109,114,137 and others on both genders. ...
... 86,92,97,100,102,105,112,113,116,122,134,139,144,145 healthy individuals. 85,[87][88][89]96,111,146 overweight and obese individuals. 91,114,128,129,131,137,148 patients on hemodialysis. ...
Introduction:
Numerous approaches have been assigned to treat dyslipidemia (DLP). Turmeric/curcumin have been widely investigated with this regard. In the current study, we explored the effect of curcumin/turmeric supplementation on lipid profile.
Methods:
Online databases were searched up to October 2022. The outcomes included triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), apolipoprotein B (Apo-B), and apolipoprotein A (Apo-A). We used the Cochrane quality assessment tool to evaluate the risk of bias. The effect sizes were estimated as weighted mean difference (WMD) and 95% confidence intervals (CIs).
Results:
Out of 4182 articles retrieved from the initial search, 64 randomized clinical trials (RCTs) were included in the study. Between-study heterogeneity was significant. Meta-analysis showed that turmeric/curcumin supplementation exerts statistically significant improvements on blood levels of TC (WMD = -3.99mg/dL; 95% CI = -5.33, -2.65), TG (WMD = -6.69mg/dL; 95% CI = -7.93, -5.45), LDL-c (WMD = -4.89mg/dL; 95% CI = -5.92, -3.87), and HDL-c (WMD = 1.80mg/dL; 95% CI = 1.43, 2.17). However, turmeric/curcumin supplementation was not associated with improvements in blood levels of Apo-A or Apo-B. The studies did not thoroughly address the issues of potency, purity, or consumption with other foods.
Conclusion:
Turmeric/curcumin supplementation seems to be effective in improving blood levels of TC, TG, LDL-c, and HDL-c; but may not be capable of improving their pertinent apolipoproteins. Since the evidence was assessed to be low and very low concerning the outcomes, these findings should be dealt with caution.
... See Figure 1 for the PRISMA flow diagram of studies pertaining to the identification, screening, eligibility, and inclusion. We identified nine relevant studies 11,14,[31][32][33][34][35][36]40 that included one randomized trial, 35 four RCTs, 14,32,34,40 three quasi-experiments, 31,33,36 and one pre-post design. 11 There were two studies that had more than one exercise intervention, 34,35 which enabled for 11 separate interventions (eg, high-intensity interval training [HIIT] and continuous training reported as separate interventions 35 ). ...
... See Figure 1 for the PRISMA flow diagram of studies pertaining to the identification, screening, eligibility, and inclusion. We identified nine relevant studies 11,14,[31][32][33][34][35][36]40 that included one randomized trial, 35 four RCTs, 14,32,34,40 three quasi-experiments, 31,33,36 and one pre-post design. 11 There were two studies that had more than one exercise intervention, 34,35 which enabled for 11 separate interventions (eg, high-intensity interval training [HIIT] and continuous training reported as separate interventions 35 ). ...
... 35 Together, these three study designs were considered controlled interventions but presented data that reflect pre-post analysis. Taken together, six comparisons were derived from five studies [31][32][33][34]40 and are collectively described herein as controlled interventions, comprising between-participant designs. In contrast, five comparisons were taken from four separate studies 11 Study characteristics, protocols, and quality Information pertaining to the study participant characteristics and FMD outcomes as determined from statistical analyses is detailed in Tables 1 and 2. Similarly, descriptions of FMD protocol, exercise interventions, and study quality are presented in Table 2. ...
Importance:
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality for menopausal individuals. Flow-mediated dilation (FMD), a surrogate marker of CVD, improves with aerobic exercise training in healthy and nonhealthy cohorts. However, systematic evaluation and precise estimate of this effect for menopausal individuals are unknown.
Objective:
We conducted a systematic review with meta-analysis to evaluate the influence of exercise training on FMD in postmenopausal individuals.
Evidence review:
Studies were identified from systematic search of major electronic databases (PubMed, ScienceDirect, and Cochrane Library) from inception to February 2021. Healthy, postmenopausal individuals were included, following an aerobic exercise intervention assessing FMD. A random-effects meta-analysis was used to calculate a pooled effect size (mean difference [MD]) with 95% confidence interval. Heterogeneity was assessed using I2 statistics. Metaregression was used to assess the association between changes in FMD and physical characteristics (eg, blood pressure, age, baseline FMD) and intervention details (metabolic equivalents and change in maximal oxygen uptake [ΔV˙o2max]). For variables that significantly correlated, a multiple metaregression model was used to assess the accounted variance in between-study ΔFMD%. Study quality was assessed using the National Heart, Lung, and Blood Institute assessment tool.
Findings:
Nine studies, including 11 interventions (6 controlled interventions and 5 pre-post interventions; N = 182), with age range of 52 ± 4 to 64 ± 7 years underwent quantitative pooling of data. Exercise training significantly improved ΔFMD% (MD, 0.99; 95% confidence interval, 0.46-1.52; P < 0.001). Between-study heterogeneity was large and statistically significant (I2 = 93.8%, P < 0.001). Post hoc analysis based on study design identified significant heterogeneity in the MD in ΔFMD% between controlled and pre-post study interventions (P < 0.05). According to multiple metaregression, diastolic and systolic blood pressure and ΔV˙o2max significantly predicted ΔFMD% (Q = 15.74, df = 3, P < 0.01, R2 = 0.72).
Conclusions and relevance:
Aerobic exercise training improves FMD for postmenopausal individuals, and this observation was greater among controlled versus pre-post interventions. A higher resting blood pressure and the greatest ΔV˙o2max yielded the largest improvements in FMD.
... The literature search results and research selection process were shown in Figure 1. Among the 1,426 articles identified, after reading the titles and abstracts, and then reading the full texts, 9 studies were considered eligible for meta-analysis (Nishiwaki et al., 2011;Pierce et al., 2011;Schaun et al., 2011;Akazawa et al., 2012;Swift et al., 2014;Serviente et al., 2016;Hunter et al., 2018;Bouaziz et al., 2019;Klonizakis et al., 2020). ...
... The main characteristics of participants and exercise interventions were shown in Table 1. Nine studies involved 221 participants, of which 5 studies directly explored the effects of aerobic exercise on vascular endothelial function (Schaun et al., 2011;Akazawa et al., 2012;Swift et al., 2014;Serviente et al., 2016;Bouaziz et al., 2019), 4 studies explored factors related to aerobic exercise and endothelial function (Nishiwaki et al., 2011;Pierce et al., 2011;Schaun et al., 2011;Serviente et al., 2016), these articles contained perimenopausal women and postmenopausal women (Nishiwaki et al., 2011;Pierce et al., 2011;Akazawa et al., 2012;Swift et al., 2014;Serviente et al., 2016;Hunter et al., 2018;Bouaziz et al., 2019;Klonizakis et al., 2020), only one article discussed all men (Schaun et al., 2011). According to the position statement of physical activity and training intensity (Norton et al., 2010), we adjusted the intensity classification of aerobic exercise according to the included research situation: 1.6 < METs < 3, 20% < maximal oxygen uptake (VO 2max ) < 40%, 40% < maximal heart rate (HR max ) < 55%, or 8 < RPE < 10 were determined as light-intensity; 3 < METs < 6, 40% < VO 2max < 60%, 55% < HR max < 70%, or 11 < RPE < 13 were determined as moderate-intensity; 6 < METs < 9, 60% < VO 2max < 85%, 70% < HR max < 90%, or 14 < RPE < 16 were determined as vigorous intensity. ...
... The main characteristics of participants and exercise interventions were shown in Table 1. Nine studies involved 221 participants, of which 5 studies directly explored the effects of aerobic exercise on vascular endothelial function (Schaun et al., 2011;Akazawa et al., 2012;Swift et al., 2014;Serviente et al., 2016;Bouaziz et al., 2019), 4 studies explored factors related to aerobic exercise and endothelial function (Nishiwaki et al., 2011;Pierce et al., 2011;Schaun et al., 2011;Serviente et al., 2016), these articles contained perimenopausal women and postmenopausal women (Nishiwaki et al., 2011;Pierce et al., 2011;Akazawa et al., 2012;Swift et al., 2014;Serviente et al., 2016;Hunter et al., 2018;Bouaziz et al., 2019;Klonizakis et al., 2020), only one article discussed all men (Schaun et al., 2011). According to the position statement of physical activity and training intensity (Norton et al., 2010), we adjusted the intensity classification of aerobic exercise according to the included research situation: 1.6 < METs < 3, 20% < maximal oxygen uptake (VO 2max ) < 40%, 40% < maximal heart rate (HR max ) < 55%, or 8 < RPE < 10 were determined as light-intensity; 3 < METs < 6, 40% < VO 2max < 60%, 55% < HR max < 70%, or 11 < RPE < 13 were determined as moderate-intensity; 6 < METs < 9, 60% < VO 2max < 85%, 70% < HR max < 90%, or 14 < RPE < 16 were determined as vigorous intensity. ...
Background
Previous studies have found that aerobic exercise was more effective in improving vascular endothelial function than resistance training, high-intensity interval training (HIIT), and other types of exercise, while the effects between different intensities and durations of aerobic exercise were unclear. Therefore, we performed this meta-analysis to investigate the effects of different intensities and durations of aerobic exercise on the vascular endothelial function of middle-aged and elderly people.
Methods
Databases were searched up to April 2021 for studies evaluating the influences of different intensities and durations of aerobic exercise on endothelial function assessed by flow-mediated dilation (FMD) among healthy middle-aged and elderly people. Data were pooled using random-effects models to obtain the weighted mean difference (WMD) and 95% confidence intervals (CIs).
Results
A total of 9 studies involving 221 participants fulfilled the inclusion criteria. Aerobic exercise improved the overall FMD of healthy middle-aged and elderly people [WMD, 1.33 (95% CI, 0.37–2.28), P < 0.05]. Specifically, vigorous-intensity exercise increased FMD significantly in healthy middle-aged and elderly people [WMD, 1.10 (95% CI, 0.27–1.93), P < 0.05], while moderate-intensity exercise had no significant association with FMD [WMD, 1.49 (95% CI, −0.62 to 3.60), P = 0.17]. In addition, long-term (8 weeks or above) aerobic exercise increased the FMD in healthy middle-aged and elderly people [WMD, 1.63 (95% CI, 0.61–2.66), P < 0.05], while one-time acute aerobic exercise had no significant association with FMD of healthy middle-aged and elderly people [WMD, 0.89 (95% CI, −1.47 to 3.24), P = 0.46]. Specifically, 8 weeks or above of vigorous-intensity exercise increased FMD significantly in healthy middle-aged and elderly people [WMD, 1.48 (95% CI, 1.06–1.90), P < 0.01], while 8 weeks or above of moderate aerobic exercise had no significant association with FMD [WMD, 1.49 (95% CI, −0.62 to 3.60), P = 0.17].
Conclusion
Aerobic exercise, especially 8 weeks or above of vigorous-intensity aerobic exercise, improved the endothelial function in healthy middle-aged and elderly people.
... Turmeric is commonly used in Southeast Asia, China, and India in food preparation and for medicinal purposes. Curcumin is the major bioactive component found in the roots of turmeric (Curcuma longa L.), which has been demonstrated, among others biological functions, to increase NO bioavailability (Boonla et al. 2014) and improve endothelial function (Akazawa et al. 2012;Oliver et al. 2016;Santos-Parker et al. 2017;Barber-Chamoux et al. 2018). The underlying mechanism for the beneficial vascular effects of curcumin is hypothesised to result mainly from its antioxidant properties (Santos-Parker et al. 2017) since reduced NO bioavailability may occur as a result of its interaction with ROS, specifically the superoxide anion. ...
... In that study, dietary curcumin administration on cerebrovascular endothelium-dependent relaxation was abolished by L-NG-Nitro arginine methyl ester (L-NAME, a NO synthase inhibitor) incubation, suggesting that the beneficial cerebrovascular effects of curcumin are NO-mediated. Furthermore, previous studies in humans have also demonstrated vascular benefits following acute (Barber-Chamoux et al. 2018) and chronic curcumin supplementation (Akazawa et al. 2012;Oliver et al. 2016;Santos-Parker et al. 2017). A possible explanation for the vascular benefit of curcumin is that its antioxidant properties could neutralise ROS in the vessels and lead to an increase in the NO bioavailability since one of the proposed mechanisms for endothelial dysfunction is a reduced bioavailability of NO as a result of its interaction with oxygen-derived species, specifically anion superoxide The symbol à denotes statistical difference at p < 0.05 (data are mean ± standard deviation; paired Student's t-test, n ¼ 12). ...
... Thus, an amount of $8 g curcumin would be expected to be present in the total amount of turmeric extract supplement ingested by the participants in the present study. Furthermore, evidence of vascular benefits in humans has been presented after oral doses of curcumin ranging from 150 mg to 5 g (Akazawa et al. 2012;Oliver et al. 2016;Santos-Parker et al. 2017;Barber-Chamoux et al. 2018;Choi et al. 2019). Unfortunately, we could not quantify circulating levels of curcuminoid compounds to evaluate whether changes following turmeric extract intake are correlated with the changes in cerebral hemodynamic. ...
Ageing is associated with endothelial dysfunction and reduced cerebral blood flow and oxygenation. The present study aimed to investigate whether turmeric supplementation could improve cerebral oxygenation and blood volume during brain activation via dynamic handgrip exercise in older males and females. Twelve older males and females were studied using a double-blind, placebo-controlled, cross-over design. Participants ingested turmeric root extract or placebo. Heart rate and blood pressure were measured before and 2 hours after supplementation. Afterward, the exercise protocol was started, and cerebral oxygenation and blood volume were evaluated. During exercise, changes in cerebral oxygenation were higher after turmeric extract supplementation, as was blood volume compared to placebo. Changes in heart rate, systolic blood pressure, and diastolic blood pressure were not significant. The current findings indicate the potential for curcumin as an intervention for improving cerebral oxygenation and blood volume changes in older males and females.
Clinical trial registry: NCT04119752.
... In the periphery, exercise with an aerobic component is associated with improved perfusion in older adults compared to their sedentary peers [18]. Specific to the cerebral cortex, a cross-sectional study showed blood flow velocity in the middle cerebral artery, probed using Doppler, was significantly higher in adults with high levels of cardiovascular fitness [26]. Of note, the decrease in basal cerebral blood flow is tapered in people who report higher levels of physical activity [27]. ...
... Thus, in both the periphery and the cortex, those with higher levels of cardiovascular fitness have improved CVR to stimulus. CVR was also shown to increase among stroke survivors after 6 months of aerobic training [26]. Our own pilot data, described in greater detail in the subsequent paragraphs, demonstrate a marked decline in CVR with age. ...
Background
Growing health care challenges resulting from a rapidly expanding aging population necessitate examining effective rehabilitation techniques that mitigate age-related comorbidity and improve quality of life. To date, exercise is one of a few proven interventions known to attenuate age-related declines in cognitive and sensorimotor functions critical to sustained independence.
Objective
This work aims to implement a multimodal imaging approach to better understand the mechanistic underpinnings of the beneficial exercise-induced adaptations to sedentary older adults’ brains and behaviors. Due to the complex cerebral and vascular dynamics that encompass neuroplastic change with aging and exercise, we propose an imaging protocol that will model exercise-induced changes to cerebral perfusion, cerebral vascular reactivity (CVR), and cognitive and sensorimotor task-dependent functional magnetic resonance imaging (fMRI) after prescribed exercise.
Methods
Sedentary older adults (aged 65-80 years) were randomly assigned to either a 12-week aerobic-based interval-based cycling intervention or a 12-week balance and stretching intervention. Assessments of cardiovascular fitness used the YMCA submaximal VO2 test, basal cerebral perfusion using arterial spin labeling (ASL), CVR using hypercapnic fMRI, and cortical activation using fMRI during verbal fluency and motor tapping tasks. A battery of cognitive-executive and motor function tasks outside the scanning environment will be performed before and after the interventions.
Results
Our studies and others show that improved cardiovascular fitness in older adults results in improved outcomes related to physical and cognitive health as well as quality of life. A consistent but unexplained finding in many of these studies is a change in cortical activation patterns during task-based fMRI, which corresponds with improved task performance (cognitive-executive and motor). We hypothesize that the 12-week aerobic exercise intervention will increase basal perfusion and improve CVR through a greater magnitude of reactivity in brain areas susceptible to neural and vascular decline (inferior frontal and motor cortices) in previously sedentary older adults. To differentiate between neural and vascular adaptations in these regions, we will map changes in basal perfusion and CVR over the inferior frontal and the motor cortices—regions we have previously shown to be beneficially altered during fMRI BOLD (blood oxygen level dependent), such as verbal fluency and motor tapping, through improved cardiovascular fitness.
Conclusions
Exercise is one of the most impactful interventions for improving physical and cognitive health in aging. This study aims to better understand the mechanistic underpinnings of improved health and function of the cerebrovascular system. If our hypothesis of improved perfusion and cerebrovascular reactivity following a 12-week aerobic exercise intervention is supported, it would add critically important insights into the potential of exercise to improve brain health in aging and could inform exercise prescription for older adults at risk for neurodegenerative disease brought on by cerebrovascular dysfunction.
Trial Registration
ClinicalTrials.gov NCT05932069; https://clinicaltrials.gov/study/NCT05932069
International Registered Report Identifier (IRRID)
DERR1-10.2196/58316
... In contrast, the beneficial effects of aerobic exercise training on endothelial function in postmenopausal women are more variable. We (60,64,65) and others (66)(67)(68)(69)(70)(71) have reported no significant effects of regular aerobic exercise on conduit and resistance artery endothelial function in healthy postmenopausal women, whereas others have reported beneficial effects (72)(73)(74)(75)(76)(77)(78)(79). The inconsistent findings in postmenopausal women may be attributed to differences in methodology and blood vessel assessment, and/or characteristics of the population (80). ...
... However, not all middle-aged/ older adults reap the same benefits of exercise in an equivalent manner (8,9). As discussed, some studies (60, 64-71), but not all (72)(73)(74)(75)(76)(77)(78)(79), report diminished or an absence of vascular adaptations to exercise training in estrogen-deficient postmenopausal women, particularly endothelium-specific benefits. The reasons for the exercise response variation in ageassociated vascular function between the sexes are not completely understood. ...
Vascular aging, featuring endothelial dysfunction and large elastic artery stiffening, is a major risk factor for the development of age-associated cardiovascular diseases (CVD). Vascular aging is largely mediated by an excessive production of reactive oxygen species (ROS) and increased inflammation leading to reduced bioavailability of the vasodilatory molecule nitric oxide and remodeling of the arterial wall. Other cellular mechanisms (i.e., mitochondrial dysfunction, impaired stress response, deregulated nutrient sensing, cellular senescence), termed "hallmarks" or "pillars" of aging, may also contribute to vascular aging. Gonadal aging, which largely impacts women but also impacts some men, modulates the vascular aging process. Regular physical activity, including both aerobic and resistance exercise, is a first-line strategy for reducing CVD risk with aging. Although exercise is an effective intervention to counter vascular aging, there is considerable variation in the vascular response to exercise training with aging. Aerobic exercise improves large elastic artery stiffening in both middle-age/older men and women and enhances endothelial function in middle-age/older men by reducing oxidative stress and inflammation and preserving NO bioavailability; however, similar aerobic exercise training improvements are not consistently observed in estrogen-deficient postmenopausal women. Sex differences in adaptations to exercise may be related to gonadal aging and declines in estrogen in women that influence cellular-molecular mechanisms, disconnecting favorable signaling in the vasculature induced by exercise training. The present review will summarize the current state of knowledge on vascular adaptations to regular aerobic and resistance exercise with aging, the underlying mechanisms involved, and the moderating role of biological sex.
... The lipidlowing effect of curcumin is mainly reflected by reducing serum LDL, triglyceride [192], and free fatty acid in diabetic patients [55]. It is interesting that curcumin attenuates abnormalities of the vascular system [56] and LV afterload [57] preferentially in postmenopausal women. The magnitudes of the improved endothelial function with curcumin, as reflected by an increase in flow-mediated dilation, are comparable to that obtained with exercise in normotensive postmenopausal women [56], suggesting that curcumin treatment may be a special alternative approach against CVD in normotensive postmenopausal women who are unable to exercise. ...
... It is interesting that curcumin attenuates abnormalities of the vascular system [56] and LV afterload [57] preferentially in postmenopausal women. The magnitudes of the improved endothelial function with curcumin, as reflected by an increase in flow-mediated dilation, are comparable to that obtained with exercise in normotensive postmenopausal women [56], suggesting that curcumin treatment may be a special alternative approach against CVD in normotensive postmenopausal women who are unable to exercise. Regular aerobic exercise improves endothelial function in association with increased NO bioavailability [193]. ...
The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease (CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction (CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas: (1) mechanisms underlying age-related cardiac remodeling; (2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women; (3) we select a few polyphenol or polyamine rich compounds as the CR-mimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.
... Based on these beneficial effects of curcumin in an animal model, efforts were focused on translating these findings to human subjects. In postmenopausal women, curcumin ingestion positively correlates with improved central arterial hemodynamics and reduced endothelial dysfunction [113,114]. Moreover, curcumin supplementation in healthy middle-aged and older adults is associated with an improvement in vascular endothelial function, underscoring the findings of the murine experiments [115]. ...
... Based on these beneficial effects of curcumin in an animal model, efforts were focused on translating these findings to human subjects. In postmenopausal women, curcumin ingestion positively correlates with improved central arterial hemodynamics and reduced endothelial dysfunction [113,114]. Moreover, curcumin supplementation in healthy middleaged and older adults is associated with an improvement in vascular endothelial function, underscoring the findings of the murine experiments [115]. ...
Cardiovascular diseases (CVDs) contribute to a large part of worldwide mortality. Similarly, two of the major risk factors for these diseases, aging and obesity, are also global problems. Aging, the gradual decline of body functions, is non-modifiable. Obesity, a modifiable risk factor for CVDs, also predisposes to type 2 diabetes mellitus (T2DM). Moreover, it affects not only the vasculature and the heart but also specific fat depots, which themselves have a major impact on the development and progression of CVDs. Common denominators of aging, obesity, and T2DM include oxidative stress, mitochondrial dysfunction, metabolic abnormalities such as altered lipid profiles and glucose metabolism, and inflammation. Several plant substances such as curcumin, the major active compound in turmeric root, have been used for a long time in traditional medicine and for the treatment of CVDs. Newer mechanistic, animal, and human studies provide evidence that curcumin has pleiotropic effects and attenuates numerous parameters which contribute to an increased risk for CVDs in aging as well as in obesity. Thus, curcumin as a nutraceutical could hold promise in the prevention of CVDs, but more standardized clinical trials are required to fully unravel its potential.
... Data from a randomized controlled double-blind prospective study involving 59 healthy adults revealed that curcumin oral supplementation (200 mg/day for 8 weeks) showed a concentration-mediated improvement in endothelial function, suggesting that it may reduce the risk of CVD in healthy adults (Oliver et al. 2016). Similarly, Akazawa et al. (2012) also found that postmenopausal women who received 150 mg/day theracurcumin for 8 weeks improved flow-mediated dilation (FMD). By contrast, it has been shown that postmenopausal and older women (mean 60 years old) have low baseline FMD (˂3%), implied that increased risk of CVD (Akazawa et al. 2012). ...
... Similarly, Akazawa et al. (2012) also found that postmenopausal women who received 150 mg/day theracurcumin for 8 weeks improved flow-mediated dilation (FMD). By contrast, it has been shown that postmenopausal and older women (mean 60 years old) have low baseline FMD (˂3%), implied that increased risk of CVD (Akazawa et al. 2012). A 12-week randomized double-blind placebocontrolled study on 118 type 2 diabetes patients showed that curcuminoids (1000 mg/day + piperine 10 mg/day) increased serum levels of high-density lipoprotein cholesterol (HDL-C) and decreased lipoprotein(a) (Lp(a)), non-HDL-C, and TC (Panahi et al. 2017b). ...
Aging is one of the key contributors to a broad spectrum of chronic diseases. Reactive oxygen species (ROS) increase oxidative stress in cells and thus induces inflammatory cascades. The antioxidant defense systems are declined during aging. Antioxidant controls the oxidative radical process by suppressing the formation of free radicals and interrupting the propagation and initiation of free radicals through several mechanisms. Considering the crucial roles of oxidative stress in age-related diseases, the manipulation of ROS levels would represent a useful option to delay age-related diseases and attenuate associated symptoms. Numerous compounds with antioxidant activity have demonstrated their potential to alleviate age-related diseases; however, mixed results are yielded. Therefore, this chapter discussed the potential of dietary antioxidants against age-related diseases. We also explored on how dietary choices dampen or exacerbate the inflammation and metabolic disorders. Collectively, this information may shed light on the discovery for potential intervention, and thus promoting healthy longevity.
... There have been several investigations of the effect of curcumin supplementation on endothelial function, arterial compliance, arterial stiffness, and blood pressure, which have yielded inconsistent results (Table 1). 30,[34][35][36][37] In a randomized, double-blinded, placebo-controlled trial of nonmedicated participants with type 2 diabetes (n ¼ 240), supplementation with 1500 mg/day curcumin for 6 months resulted in lower brachial-ankle pulse-wave velocity compared with that of the control group, at 3 and 6 months. 30 In contrast, curcumin supplementation of 150 mg/day for 8 weeks did not affect systolic blood pressure, carotid femoral pulse-wave velocity, augmentation index, carotid artery compliance, or flow-mediated dilation vs a placebo in postmenopausal women. ...
... 30 In contrast, curcumin supplementation of 150 mg/day for 8 weeks did not affect systolic blood pressure, carotid femoral pulse-wave velocity, augmentation index, carotid artery compliance, or flow-mediated dilation vs a placebo in postmenopausal women. 34,35,37 Similarly, supplementation with 2.8 g/day turmeric for 4 weeks did not affect systolic blood pressure or augmentation index in middle-aged women with overweight or obesity and systemic inflammation (C-reactive protein [CRP] level > 2 mg/L). 36 Inflammation and oxidative stress. ...
Herbs and spices are recommended to increase flavor and displace salt in the diet. Accumulating evidence suggests herbs and spices may improve risk factors for cardiometabolic diseases. In this narrative review, an overview of evidence from human clinical trials examining the effect of herbs and spices on risk factors for cardiometabolic diseases is provided. Human clinical trials examining supplemental doses of individual spices and herbs, or the active compounds, have yielded some evidence showing improvements to lipid and lipoprotein levels, glycemic control, blood pressure, adiposity, inflammation, and oxidative stress. However, cautious interpretation is warranted because of methodological limitations and substantial between-trial heterogeneity in the findings. Evidence from acute studies suggests intake of mixed herbs and spices as part of a high-saturated fat, high-carbohydrate meal reduces postprandial metabolic impairments, including lipemia, oxidative stress, and endothelial dysfunction. Limited studies have examined the postprandial metabolic effects of incorporating mixed herbs and spices into healthy meals, and, to our knowledge, no trials have assessed the effect of longer-term intake of mixed herbs and spices on risk factors for cardiometabolic diseases. To inform evidence-based guidelines for intake of herbs and spices for general health and cardiometabolic disease risk reduction, rigorously conducted randomized controlled trials are needed, particularly trials examining herb and spice doses that can be incorporated into healthy dietary patterns.
... However, the findings from studies conducted to investigate the effects of supplements, nutrients, isolated single foods, and whole diets on overall menopausal health issues are listed in Table 1 (Ref. [75,76,[89][90][91][92][93][94][95][96][97][98][99][100]) and those findings in postmenopausal women are conflicting and inconclusive [17][18][19][20]. ...
Cardiovascular disease (CVD) is a leading cause of death in women and risk of development is greatly increased following menopause. Menopause occurs over several years and is associated with hormonal changes, including a reduction in estradiol and an increase in follicle-stimulating hormone. This hormonal shift may result in an increased risk of developing abdominal adiposity, insulin resistance, dyslipidemia, vascular dysfunction, hypertension, type 2 diabetes mellitus (T2DM), metabolic dysfunction-associated fatty liver disease (MAFLD), and metabolic syndrome (MetS). Furthermore, with the onset of menopause, there is an increase in oxidative stress that is associated with impaired vascular function, inflammation, and thrombosis, further increasing the risk of CVD development. Despite the harmful consequences of the menopause transition being well known, women in premenopausal, perimenopausal, and postmenopausal stages are unlikely to be enrolled in research studies. Therefore, investigations on the prevention and treatment of cardiovascular and metabolic disease in middle-aged women are still relatively limited. Whilst lifestyle interventions are associated with reduced CVD risk in this population sample, the evidence still remains inconclusive. Therefore, it is important to explore the effectiveness of early intervention and potential therapeutic approaches to maintain cellular redox balance, preserve endothelium, and reduce inflammation. Glycine, N-acetylcysteine, and L-theanine are amino acids with potential antioxidant and anti-inflammatory activity and are identified as therapeutic interventions in the management of age-related and metabolic diseases. The benefits of the intake of these amino acids for improving factors associated with cardiovascular health are discussed in this review. Future studies using these amino acids are warranted to investigate their effect on maintaining the vascular health and cardiovascular outcomes of postmenopausal women.
... Curcumin is a curcuminoid from Curcuma longa L. root and rhizome, commonly known as turmeric, and widely consumed as a spice ingredient, especially in Asian countries. Curcumin has gained popularity in the scientific community due to its antioxidant properties and positive effects on endothelial function [13][14][15][16][17]. The antioxidant property of curcumin is one of the main reasons for its cardiovascular benefits, due to its ability to neutralize ROS, preventing their interaction with NO and subsequent formation of oxidizing agents [18]. ...
Introduction: Aging is associated with increased reactive oxygen species (ROS) and reduced bioavailability of nitric oxide (NO). Curcumin has been shown to increase NO bioavailability due to its ability to neutralize ROS, preventing oxidative stress. The present study aimed to investigate the effect of curcumin intake on skeletal muscle oxygen parameters and exercise tolerance in response to exercise in older people. Changes in circulating levels of NO metabolites were also investigated. Methods: Older subjects consumed 10 g of turmeric root extract from Curcuma longa L. (containing 95.33% of the total curcuminoids) or placebo in a randomized, double-blind, crossover study. A time of 2 h after ingestion, the participants performed one set of rhythmic handgrip exercise until the limit of tolerance, followed by 5 min of recovery. During exercise and exercise recovery, skeletal muscle oxygen saturation parameters were recorded. Results: During exercise, the amplitude of deoxyhemoglobin was greater after curcumin intake compared to placebo (CUR: 13.11 ± 9.52 vs. PLA: 10.22 ± 8.39 μM, p = 0.030). Furthermore, a faster skeletal muscle oxygen resaturation during exercise recovery was observed after curcumin compared to placebo (CUR: 1.01 ± 0.65 vs. PLA: 0.32 ± 0.20%.s⁻¹, p = 0.004). These results were associated with significant changes in plasma nitrite (CUR: 6.82 ± 11.68 vs. PLA: −4.94 ± 17.28%, p = 0.028). There was no statistical difference in the total hemoglobin, exercise time until fatigue, and plasma nitrate between groups. Conclusions: The present study suggests that curcumin improves muscle oxygenation status at the capillary level in older adults by possibly improving muscle oxygen extraction and/or delivery, with no effect on exercise tolerance.
... Studies have demonstrated positive effects on curcumin on central arterial hemodynamics and endothelial function among postmenopausal women, who are at higher risk for CVD compared to their male counterparts. 92,93 Curcumin has also been effective in preventing progression to overt diabetes in a placebo-controlled trial, with a low daily dose of just 0.5mg, highlighting its anti-aging capabilities. 94 A recent meta-analysis has confirmed the safety of curcumin at doses ranging from 80 mg to 4 grams, showing successful reduction of oxidative stress and subsequent inflammatory disease progression. ...
The aim of this manuscript is to provide a review of available options to enhance cardiovascular health and prevent cardiovascular disease (CVD) in the aging population using a systems-biology approach. These include the role of the gut microbiome, the early identification and removal of environmental toxins, and finally age related sex hormones and supplement replacement which all influence aging. Implementing such a comprehensive approach has the potential to facilitate earlier risk assessment, disease prevention, and even improve mortality. Further study in these areas will continue to advance our understanding and refine therapeutic interventions for a healthier cardiovascular aging process.
... Curcuma longa, which is prepared from the powdered roots of the plant. 23,24 Curcumin has antioxidant, anti-inflammatory, and anti-atherosclerotic benefits. It has pharmacological effects in psoriasis, diabetes, multiple sclerosis, Alzheimer, HIV, septic shock, cardiovascular and lung problems, arthritis, and inflammatory bowel diseases. ...
Introduction
Menopause is a condition for metabolic disorders. This study aimed to evaluate the effect of Nigella sativa (NS), curcumin nanomicelle (CN), lipid profile, glycemic status and 17-β estradiol (ES) levels in postmenopausal women.
Methods
Triple-blind randomized clinical trial was conducted on 120 postmenopausal women. Participants were randomly assigned to four groups: 1) NS capsule 1000 mg and CN placebo, 2) 80 mg CN capsule and NS placebo, 3) both NS and CN capsules and 4) NS and CN placebo. Participants received a single dose daily for 6 months. The serum lipid profile, glycemic control biomarkers, and ES were measured pre-and post-intervention using biochemical methods.
Results
Total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, fasting blood sugar (FBS), fasting insulin (FI), insulin resistance (IR), and ES showed significant improvement in NS group. CN significantly reduced TC, FI, and IR, and significantly increased ES. The combination of NS-CN significantly decreased TC, LDL, FI, and IR, and increased HDL and ES. The comparison of the studied with the placebo groups showed that these changes were significant in glycemic indices and NS significantly increased estrogen.
Conclusion
NS, CN and NS-CN improved lipid profiles, blood sugar, and hormone levels. However, this improvement was significant in glycemic indices and estrogen levels compared to the placebo group. No superiority of combined NS-CN over NS or CN was found in this trial.
... Additionally, curcumin administered to 32 postmenopausal women improved endothelial function by reducing systolic blood pressure (SBS) and elevating FMD and peak oxygen consumption (VO 2 peak). The treatment was also found to be safe, with no adverse effects 346 . ...
Turmeric (Curcuma longa) has been used for thousands of years for the prevention and treatment of various chronic diseases. Curcumin is just one of >200 ingredients in turmeric. Almost 7000 scientific papers on turmeric and almost 20,000 on curcumin have been published in PubMed. Scientific reports based on cell culture or animal studies are often not reproducible in humans. Therefore, human clinical trials are the best indicators for the prevention and treatment of a disease using a given agent/drug. Herein, we conducted an extensive literature survey on PubMed and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The keywords "turmeric and clinical trials" and "curcumin and clinical trials" were considered for data mining. A total of 148 references were found to be relevant for the key term "turmeric and clinical trials", of which 70 were common in both PubMed and Scopus, 44 were unique to PubMed, and 34 were unique to Scopus. Similarly, for the search term "curcumin and clinical trials", 440 references were found to be relevant, of which 70 were unique to PubMed, 110 were unique to Scopus, and 260 were common to both databases. These studies show that the golden spice has enormous health and medicinal benefits for humans. This Review will extract and summarize the lessons learned about turmeric and curcumin in the prevention and treatment of chronic diseases based on clinical trials.
... Among the less commonly studied disorders (Other, Figure 4), cardiovascular trial citations (5% of total citations, n = 20) [322][323][324][325][326][327][328][329][330][331][332][333][334][335][336][337][338][339][340][341] primarily focused on the vasculature (n = 11, e.g., compliance and endothelial function) [322][323][324][325][326][327][328][329][330][331][332]. These studies generally reported improvements in subjects who were healthy or had a range of dysfunction, excluding children (here with tetralogy of Fallot [332]), who, it should be noted, were rarely included in curcumin clinical trials. ...
Medicinal properties of turmeric (Curcuma longa L.), a plant used for centuries as an anti-inflammatory, are attributed to its polyphenolic curcuminoids, where curcumin predominates. Although “curcumin” supplements are a top-selling botanical with promising pre-clinical effects, questions remain regarding biological activity in humans. To address this, a scoping review was conducted to assess human clinical trials reporting oral curcumin effects on disease outcomes. Eight databases were searched using established guidelines, yielding 389 citations (from 9528 initial) that met inclusion criteria. Half focused on obesity-associated metabolic disorders (29%) or musculoskeletal disorders (17%), where inflammation is a key driver, and beneficial effects on clinical outcomes and/or biomarkers were reported for most citations (75%) in studies that were primarily double-blind, randomized, and placebo-controlled trials (77%, D-RCT). Citations for the next most studied disease categories (neurocognitive [11%] or gastrointestinal disorders [10%], or cancer [9%]), were far fewer in number and yielded mixed results depending on study quality and condition studied. Although additional research is needed, including systematic evaluation of diverse curcumin formulations and doses in larger D-RCT studies, the preponderance of current evidence for several highly studied diseases (e.g., metabolic syndrome, osteoarthritis), which are also clinically common, are suggestive of clinical benefits.
... Researchers took postmenopausal women as the research object,and found that after regular intake of curcumin, the systolic blood pressure of the subjects decreased, and the age-related endothelial dysfunction was improved. [51] Other studies have shown that curcumin can improve H 2 O 2 -induced HUVECs premature senility, reduce the positive rate of β-Gal and the expression of aging-related proteins, improve oxidative stress and apoptosis. The possible mechanism is that curcumin reduces oxidative stress injury by activating SIRT1. ...
Vascular senescence is the basic factor of many cardiovascular diseases. Vascular endothelium, as a protective barrier between blood and vascular wall, plays an important role in maintaining the integrity and homeostasis of vascular system. Endothelial cell senescence is an important pathological change of vascular senescence. In recent years, more and more studies have been conducted on vascular endothelial cell senescence, especially on its mechanism. Many research results showed that the mechanism is various, but the systematic elucidation still lacks. Western medicine has little choice in the prevention and treatment of endothelial cell senescence, and the control effect is also limited, while Chinese medicine makes up for the deficiency in this regard. The main mechanisms of vascular endothelial cell aging and the related research progress of traditional Chinese medicine in the prevention and treatment of vascular endothelial aging in recent years were summarized in this paper to provide reference for the research of traditional Chinese medicine in anti-vascular aging and the prevention and treatment of cardiovascular disease.
... . The majority assessed macrovascular endothelial function (16/29 intervention and 6/7 cross-sectional studies), and almost exclusively measured conduit endothelial function using FMD, most often in the brachial artery. Of the brachial artery FMD studies, 8 of 14 training studies found FMD improvement posttraining(Akazawa et al., 2012;Azadpour et al., 2017;Fetter et al., 2020;Jaime et al., 2019;Jo et al., 2020;Moreau et al., 2013;Swift et al., 2012;Yoshizawa et al., 2010) and 2 of 6 cross-sectional studies found ...
New findings:
What is the topic of this review? The aim of this systematic review was to evaluate and summarize all published literature examining the impact of various exercise training interventions on endothelial function in postmenopausal women. What advances does it highlight? There was a moderate effect of training on macrovascular and microvascular endothelial function and two thirds of studies demonstrated a significant increase in at least one measure of endothelial function in postmenopausal women. Factors including exercise intensity and duration, vessel type, clinical status, hormone therapy and menopausal status may influence the effects of training on endothelial function in postmenopausal women.
Abstract:
Women experience a rapid decline in endothelial function during menopause. Therefore, it is important to explore interventions, such as exercise training, that may prevent endothelial dysfunction in postmenopausal women. The aim of this systematic review was to evaluate and summarize all published literature examining the impact of various exercise training interventions on endothelial function in postmenopausal women. Three electronic databases (MEDLINE, EMBASE and Web of Science) were used to systematically select studies related to exercise training, endothelial function, and postmenopausal women. The major initial and secondary update systematic searches yielded 502 unique articles that were screened for eligibility. Thirty-five studies were included in the systematic review. Two thirds of all studies demonstrated a group level increase in at least one measure of endothelial function with training. Most studies investigating biomarkers of endothelial function showed improvement in at least one measured biomarker post-training. There was a moderate effect of training on both macrovascular and microvascular endothelial function in observational and randomized intervention studies. Variability in study designs, training protocols, and participant characteristics make it difficult to directly compare studies. Factors including exercise intensity and duration, vessel type, clinical status, hormone therapy and menopausal status may contribute to the inconsistent effects of training on endothelial function in postmenopausal women. Future research is needed in this population to understand the mechanisms driving inter-study and inter-individual differences in training-induced changes in endothelial function. This article is protected by copyright. All rights reserved.
... In this study, 32 postmenopausal women were divided into three groups (10 participants in the control group and 11 participants in each of the curcumin and the exercise groups), during which the curcumin group received a total of 6 tablets of 150 mg curcumin for 8 weeks daily. Consistent with our study, the results showed that regular consumption of curcumin or regular aerobic exercise helps to improve vascular function [35]. ...
Aims of the Study. Reducing estrogen levels due to menopause activates oxidative and inflammatory processes, which causes symptoms of menopause, anxiety, and sexual dysfunction. As a suggestion, potential anti-inflammatory and antioxidant agents such as curcumin and vitamin E could be used as an effective alternative treatment due to parsimony, suitable access, and fewer side effects. Therefore, the present study was conducted to find out whether supplementation with curcumin and vitamin E affects inflammatory-oxidative stress biomarkers and primary symptoms of menopause in healthy postmenopausal women. Methods Used to Conduct the Study. The present study is a triple-blind parallel randomized controlled trial. Eighty-four eligible postmenopausal women aged 40 to 60 years old were randomly assigned into three groups using block randomization with an allocation ratio of 1 : 1 : 1. The curcumin group received one capsule containing 500 mg curcumin twice a day, the vitamin E group received one 500 mg capsule of vitamin E twice a day, and the placebo group took two placebo capsules containing 500 mg of microcrystalline cellulose (MCC) daily for eight weeks. Demographic and anthropometric characteristics, dietary intake, and early symptoms of menopause were collected at baseline. Serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), and high sensitivity C-reactive protein (hs-CRP) were measured at baseline and after the intervention. Intervention safety and satisfaction with the intervention were also evaluated. Results of the Study. Eighty-one participants completed the trial and were finally analyzed. There were no statistically significant differences in demographic characteristics and dietary intake of participants (except for vitamin C intake, P=0.023) between the groups at baseline. The mean ± standard deviation (SD) score of total menopause symptoms, depression, anxiety, psychological, vasomotor, and physical domains significantly decreased within all groups (P<0.05). Between-group analyses indicated that decreasing the mean score of anxiety in the vitamin E group was significantly more than in the placebo group (P=0.026). The mean (SD) serum levels of MDA and hs-CRP significantly decreased only in the curcumin group (P=0.009 and P=0.025, respectively). Serum levels of TAC significantly increased in curcumin and vitamin E groups (P<0.001 and P=0.006, respectively). Conclusions Drawn from the Study and Clinical Implications. Curcumin could improve the oxidative stress (MDA and TAC) and inflammatory (hs-CRP) biomarkers. Vitamin E may also improve the antioxidant status by increasing the TAC levels. The alleviation of anxiety in the vitamin E group was more than in the placebo group. Clinical Trial Registration. The trial was registered at the Iranian Registry of Clinical Trials (https://irct.ir/IRCT20131009014957N6).
... Menopausal women are not exempt from age-associated endothelial function decline. Thirty-two menopausal women were enrolled in a study that evaluated the effect of curcumin vs. exercise on endothelial function [142]. The participants were divided into 3 groups: a control group, a group that underwent moderate aerobic training for 8 weeks and a group of participants that ingested curcumin for 8 weeks. ...
COVID-19 is an endothelial disease. All the major comorbidities that increase the risk for severe SARS-CoV-2 infection and severe COVID-19 including old age, obesity, diabetes, hypertension, respiratory disease, compromised immune system, coronary artery disease or heart failure are associated with dysfunctional endothelium. Genetics and environmental factors (epigenetics) are major risk factors for endothelial dysfunction. Individuals with metabolic syndrome are at increased risk for severe SARS-CoV-2 infection and poor COVID-19 outcomes and higher risk of mortality. Old age is a non-modifiable risk factor. All other risk factors are modifiable. This review also identifies dietary risk factors for endothelial dysfunction. Potential dietary preventions that address endothelial dysfunction and its sequelae may have an important role in preventing SARS-CoV-2 infection severity and are key factors for future research to address. This review presents some dietary bioactives with demonstrated efficacy against dysfunctional endothelial cells. This review also covers dietary bioactives with efficacy against SARS-CoV-2 infection. Dietary bioactive compounds that prevent endothelial dysfunction and its sequelae, especially in the gastrointestinal tract, will result in more effective prevention of SARS-CoV-2 variant infection severity and are key factors for future food research to address.
... In a clinical trial, CUR significantly increased vascular NO and reduced oxidative stress, improving endothelial function [107]. Vascular endothelial function was also improved after CUR supplementation in postmenopausal women compared to a control group [108]. ...
Chronic inflammatory diseases occur in a large portion of the population and are associated with a poor diet. Key natural products found in fruits and vegetables may assist in lowering inflammation associated with chronic diseases such as obesity, diabetes, cardiovascular diseases, and cancer. This review seeks to examine the roles of several natural products, resveratrol (RES), quercetin (QUE), curcumin (CUR), piperine (PIP), epigallocatechin gallate (EGCG), and gingerol (GIN), in their ability to attenuate inflammatory markers in specific diseases states. Additionally, we will discuss findings in past and ongoing clinical trials, detail possible phytochemical–drug interactions, and provide a brief resource for researchers and healthcare professionals on natural product and supplement regulation as well as names of databases with information on efficacy, indications, and natural product–drug interactions. As diet and over-the-counter supplement use are modifiable factors and patients are interested in using complementary and alternative therapies, understanding the mechanisms by which natural products have demonstrated efficacy and the types of drugs they interact with and knowing where to find information on herbs and supplements is important for practicing healthcare providers and researchers interested in this field.
... Praktische aanbevelingen voor het gemakkelijker toevoegen van meer curcumine aan het voedingspatroon zou kunnen zijn om kurkuma toe te voegen aan zoete gerechten die kaneel en gember bevatten [110]. alternatieve behandeling kan zijn voor patiënten die niet in staat zijn om lichamelijk te oefenen [52]. ...
De prikkelende, bittere, neus-samentrekkend ruikende fel geeloranje gouden (de alleppey kurkuma ook wel de Indiase kurkuma exemplaren genoemd hebben een diepgele tot oranjegele kleur) of (exclusief of) bruin (de Chinese kurkuma exemplaren hebben een typisch bruinachtige kleur) of (exclusief of) rood (welke rode kleur ontstaat door gedroogde kurkuma te combineren met calciumhydroxide poeder en wanneer het rood is wordt het ook wel het "kunkum" en "kumkuma" genoemd) kruidenpoeder van de gedroogde gemberachtige groente maar aan de binnenkant gekleurde wortelstelen en de wortelstokken van de meerjarige bloeiende kruidenplant die leeft in gebieden met tropisch warme temperaturen en veel regen nodig heeft om te gedijen welke gewoonlijk kurkuma genoemd met de soortnaam curcuma longa linnaeus (ookmeritorious earth", "Indiase saffraan" en "Indian saffron" omdat Marco Polo schreef dat het een groente is die alle eigenschappen heeft die echte saffraan ook heeft, waaronder de geur en de kleur, maar toch niet gelijk is aan echte saffraan) categoriseerbaar in het plantengeslacht curcuma (ook kurkuma genoemd, waarvan de naam kan zijn afgeleid van het Sanskriet "kuṅkuma" dat verwijst naar zowel kurkuma als saffraan) in de gemberfamilie zingiberaceae (en dus een relatief naaste verwant van gember) mogelijk omdat het de niet-steroïde polyfenolische (vanwege de meerdere chemisch gedefinieerde aromatische fenolringen) en de meervoudige hydroxylgroep (welke chemisch gedefinieerde aromatische fenolringen en meerdere hydroxylgroepen het zijn antioxiderende eigenschap geven) bevat het polair gemakkelijk in water oplosbaar potentieel krachtige antioxidant curcuminoïde diferuloylmethaan biologisch actieve verbinding molecuul kurkuma curcumine (ook wel "curcumine", "kurkumine" en "kurkumin" genoemd) dat aanwezig is en dus kan worden gevonden in kurkuma, aangezien het ongeveer 5 [%] van zijn massa uitmaakt [105] (waarvoor een handige nuttige pragmatische kanttekening zou zijn dat de biologische beschikbaarheid van curcumine in het bloedserum door verhoogde absorptie in de dikke darm synergetisch potentieel kan worden versterkt en dus verhoogd tot 2'000 [%] bij menselijke dieren bij gepaarde consumptie samen met de zwarte peper piper nigrum die de verbinding peperine [1] bevat die verantwoordelijk is voor ongeveer 5 [%] van zijn massa [106] en tevens ook verantwoordelijk is voor de scherpe smaak van peper en het remt inhibiterend ook het metabolische vermogen van de lever om stoffen in water oplosbaar te maken zodat ze gemakkelijker kunnen worden uitgescheiden hetgeen leidt tot verhoging van het biologisch beschikbare niveau van curcumine in de bloedbaan omdat wanneer het mechanisme niet wordt onderdrukt de lever actief probeert om er vanaf te komen en je dus maar een relatief kleine piek in bloodbuis niveau van crucumine ziet terwijl vergeleken met wanneer gepaard ook peperine wordt geconsumeerd met dezelfde hoeveelheid curcumine de biologische beschikbaarheid omhoog schiet tot wel 2000 [%] [ 1], waarvoor niet veel zwarte peper nodig is, aangezien een klein snuifje van 1/20 van een theelepel genoeg is om het niveau aanzienlijk te verhogen [107], een combinatie die bijvoorbeeld uitstekend zou werken in een curryrecept, omdat de biologische beschikbaarheid van curcumine normaal gesproken erg laag is en daarom is de voedingswaarde lager als het niet wordt geconsumeerd met zwarte peper, aangezien er slechts een klein beetje in onze bloedbaan komt na het eten van een lekkere curry, tenzij we wat zwarte peper toevoegen [1]; en een andere manier om de opname van curcumine te stimuleren, is door het in de vorm van kurkumawortel te consumeren (relatief vers of gedroogd als poeder) in vergelijking met een extract, omdat natuurlijke oliën in kurkumawortel en kurkumapoeder de biologische beschikbaarheid van curcumine kunnen verbeteren met een verschil van (zeven) tot 8 (acht) keer hogere biologische beschikbaarheid [107]; en wanneer het samen gegeten
... Praktische aanbevelingen voor het gemakkelijker toevoegen van meer curcumine aan het voedingspatroon zou kunnen zijn om kurkuma toe te voegen aan zoete gerechten die kaneel en gember bevatten [110]. alternatieve behandeling kan zijn voor patiënten die niet in staat zijn om lichamelijk te oefenen [52]. ...
Website link: www.nutritionfactsnederlands.nl/videoscript/2022/1/17/kurkuma-alomvattend-artikel [Turmeric-SOURCES BELOW] The pungent, bitter, astringent smelling brightly yellow-orange golden (the alleppey turmeric also called the Indian turmeric exemplars have a deep yellow to orange-yellow color) or (exclusive or) brown (the Chinese turmeric exemplars have typically a brownish color) or (exclusive or) red (which red color is created by combining dried turmeric with calcium hydroxide powder and when red it is also called "kunkum" and "kumkuma") spice powder from the dried ginger-like vegetable but colored on the inside root stalks and the rhizomes of the perennial flowering herb plant living in tropical warm temperature areas and needing plenty of rainfalls to thrive commonly named turmeric which species name is curcuma longa linnaeus (alsoIndiase saffraan" and "Indian saffron" since Marco Polo wrote a that it is a vegetable that has all the properties of true saffron as well as the smell and the color but yet it is not really saffron) categorizable in the plant genus curcuma (also called kurkuma which name may be derived from the Sanskrit "kuṅkuma" which is referring to both turmeric and saffron) in the ginger family zingiberaceae (and thus a relatively close relative of ginger) possibly because it contains the non-steroidal polyphenolic (because of the multiple chemically defined aromatic phenol rings) and multiple hydroxyl group (which aromatic phenol rings and hydroxyl groups give it its antioxidant property) containing the polar readily in water soluble potentially powerful antioxidant curcuminoid diferuloylmethane biologically active compound molecule turmeric curcumin (also called "curcumine", "kurkumine" and "kurkumin") that is contained and thus can be found in turmeric as it makes up of approximately 5 [%] of its mass [105] (for which a convenient useful pragmatic sidenote would be that curcumin's blood serum level bioavailability by increased absorption in the colon can be synergistically potentially boosted thus increased up to 2'000 [%] in human animals when consuming it together with the black pepper piper nigrum that contains the compound peperine [1] which is responsible for about 5 [%] of its mass [106] and which is also responsible for the pungent flavor of pepper and also inhibits the livers metabolism mechanism to make substances water-soluble so they can be more easily excreted suppressing this mechanism leading to higher blood levels of bioavailability of curcumin as within an hour you can see a little bump in the level in the bloodstream of curcumin when the mechanism is unsuppressed because the liver is actively trying to get rid of it while compared to when also consuming peperine with the same amount of curcumin consumed the bioavailability shoots up to 2'000 [%] [1], which does not take much black pepper since a little pinch of 1/20 of a teaspoon is enough to considerably boost levels [107], which concomitant combination would work great in a curry recipe for example since the bioavailability of curcumin is normally very low and thus the nutritional value is poorer when not consumed with black pepper since just a tiny bit gets into our bloodstream after eating a nice curry unless we add some black pepper [1]; and another way to boost the absorption of curcumin is to consume it in the whole food turmeric root form (relatively fresh or dried as a powder) as compared to an extract because natural oils found in turmeric root and turmeric powder can enhance the bioavailability of curcumin 7 (seven) to 8 (eight) fold [107]; and when eaten together with a relatively large amount of fatty acid containing foods such as nuts, e.g. walnuts, almonds or pecans, also ensures increased bioavailability as curcumin can be directly absorbed into the bloodstream through the lymphatic system and thus thereby in part bypassing the liver [107]) which curcumin pigment also gives turmeric its brightly deep yellow to orange-yellow golden color which turmeric is possibly usable as
... Our previous studies suggested that AGEs are involved in remodeling the heart and kidney, thus increasing the weight of these organs in rats [46,47]. Several reports have indicated that dietary supplementation with CU attenuates vascular dysfunction and hypertension due to its antioxidant and antihypertrophic properties [48]. Morimoto et al., reported that CU inhibits the acetylation and DNA binding ability of GATA binding protein, a key transcription factor involved in the hypertrophic response, thereby reducing cardiac hypertrophic growth in rat cardiomyocyte cells in vitro [49]. ...
The beneficial effect of curcumin (CU) on dietary AGEs (dAGEs) involves blocking the overexpression of proinflammatory cytokine genes in the heart and kidney tissues of experimental mice. The animals were divided into six groups (n = 6/group) and were fed a heat-exposed diet (dAGEs) with or without CU for 6 months. Their blood pressure (BP) was monitored by a computerized tail-cuff BP-monitoring system. The mRNA and protein expression levels of proinflammatory genes were analyzed by RT-PCR and western blot, respectively. A marked increase in BP (108 ± 12 mmHg vs 149 ± 15 mmHg) accompanied by a marked increase in the heart and kidney weight ratio was noted in the dAGE-fed mice. Furthermore, the plasma levels of proinflammatory molecules (C5a, ICAM-1, IL-6, MCP-1, IL-1β and TNF-α) were found to be elevated (3-fold) in dAGE-fed mice. mRNA expression analysis revealed a significant increase in the expression levels of inflammatory markers (Cox-2, iNOS, and NF-κB) (3-fold) in cardiac and renal tissues of dAGE-fed mice. Moreover, increased expression of RAGE and downregulation of AGER-1 (p < 0.001) were noticed in the heart and kidney tissues of dAGE-fed mice. Interestingly, the dAGE-induced proinflammatory genes and inflammatory responses were neutralized upon cotreatment with CU. The present study demonstrates that dietary supplementation with CU has the ability to neutralize dAGE-induced adverse effects and alleviate proinflammatory gene expression in the heart and kidney tissues of experimental mice.
... As an additional mechanism, CUR fixes lysosomal membranes and reduces the function of lysosomal acid hydrolases, thus preventing the aberrant deposition of different connective tissue components in aging endothelium. A similar upgrade in endothelial function was also observed in postmenopausal women after eight weeks of treatment [88], whereas in elderly with diabetes and cardiomyopathy, CUR mitigated hypertrophy in the aging heart via suppression of p300, the global transcription activator [89]. Beneficial effects of CUR on vascular aging also concern the development of age-related macular degeneration (AMD), one of the most important causes of blindness in elderly [90,91]. ...
Aging is characterized by a progressive inability to maintain homeostasis, self-repair, renewal, performance, and fitness of different tissues throughout the lifespan. Senescence is occurring following enormous intracellular or extracellular stress stimuli. Cellular senescence serves as an antiproliferative process that causes permanent cell cycle arrest and restricts the lifespan. Senescent cells are characterized by terminal cell cycle arrest, enlarged lysosome, and DNA double-strand breaks as well as lipofuscin granularity, senescence-associated heterochromatin foci, and activation of DNA damage response. Curcumin, a hydrophobic polyphenol, is a bioactive chemical constituent of the rhizomes of Curcuma longa Linn (turmeric), which has been extensively used for the alleviation of various human disorders. In addition to its pleiotropic effects, curcumin has been suggested to have antiaging features. In this review, we summarized the therapeutic potential of curcumin in the prevention and delaying of the aging process.
... The mechanism by which CUR affected renal hemodynamics was unclear. However, Akazawa et al. [24] reported that CUR ingestion improved blood flow, endothelial dysfunction, and vascular remodeling by increasing in the circulating NO and the suppression of inflammation and/or oxidative stress via down-regulation of TNF-α. ...
To evaluate curcumin's impact on postmenopausal women's health through a meta‐analysis. The databases searched included PubMed, Embase, Cochrane Library, and Web of Science, from their inception to July 2024. The Cochrane risk of Bias assessment tool was used to assess the quality of the included studies. This meta‐analysis reviewed 14 randomized controlled trials involving 982 participants (466 in the intervention group and 516 in the control group) and evaluated curcumin's effects across 30 indicators grouped into cardiovascular health, oxidative stress and antioxidant markers, bone health, metabolic health, and quality of life. We found that curcumin reduced systolic (SMD −0.51, 95% CI −0.83 to 0.19, p = 0.002) and diastolic blood pressure (SMD −0.63, 95% CI −0.96 to −0.30, p = 0.005), increased total antioxidant capacity (SMD 0.93, 95% CI 0.15 to 1.72, p = 0.020) and superoxide dismutase levels (SMD 0.30, 95% CI 0.04 to 0.56, p = 0.026), decreased aspartate aminotransferase (AST) (SMD −0.36, 95% CI −0.66 to −0.06, p = 0.020), and improved vasomotor (SMD −0.39, 95% CI −0.65 to −0.13, p = 0.003) symptoms. Curcumin positively impacts several indicators in postmenopausal women, highlighting its potential therapeutic role in managing cardiovascular risk factors, oxidative stress, hepatoprotective effects, and vasomotor symptoms. Due to variations in the purity and dosages across different studies and the lack of combinable data for certain indicators, the conclusions are still limited. These issues can be addressed through more comprehensive large‐scale trials later. A more in‐depth investigation into the mechanisms is also crucial.
This narrative review highlights the impact of exercise on vascular health in females over the lifespan with an emphasis on puberty, pregnancy and menopause. These events encompass substantial changes in sex hormone levels, particularly oestrogens and progesterone. They are also accompanied by distinct adaptations of the central, peripheral and cerebral vasculature. Regular exercise is an effective mechanism to reduce vascular risk in females of all ages, especially for those at higher risk for vascular disorders. However, there are large variabilities in the vascular adaptations to exercise in females that may be related to circulating sex hormone levels. In addition, exogenous hormones, such as oral contraceptives taken after puberty or hormonal replacement therapy taken to mitigate symptoms of menopause, may interact with exercise‐induced changes in vascular function. We highlight how more research is needed to understand the optimal exercise interventions to promote vascular health in females across the lifespan, especially during times of hormonal transition.
This review aimed to examine the effects of curcumin on chronic inflammatory metabolic disease by extensively evaluating meta-analyses of randomized controlled trials (RCTs). We performed a literature search of meta-analyses of RCTs published in English in PubMed®/MEDLINE up to 31 July 2023. We identified 54 meta-analyses of curcumin RCTs for inflammation, antioxidant, glucose control, lipids, anthropometric parameters, blood pressure, endothelial function, depression, and cognitive function. A reduction in C-reactive protein (CRP) levels was observed in seven of ten meta-analyses of RCTs. In five of eight meta-analyses, curcumin intake significantly lowered interleukin 6 (IL-6) levels. In six of nine meta-analyses, curcumin intake significantly lowered tumor necrosis factor α (TNF-α) levels. In five of six meta-analyses, curcumin intake significantly lowered malondialdehyde (MDA) levels. In 14 of 15 meta-analyses, curcumin intake significantly reduced fasting blood glucose (FBG) levels. In 12 of 12 meta-analyses, curcumin intake significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR). In seven of eight meta-analyses, curcumin intake significantly reduced glycated hemoglobin (HbA1c) levels. In eight of ten meta-analyses, curcumin intake significantly reduced insulin levels. In 14 of 19 meta-analyses, curcumin intake significantly reduced total cholesterol (TC) levels. Curcumin intake plays a protective effect on chronic inflammatory metabolic disease, possibly via improved levels of glucose homeostasis, MDA, TC, and inflammation (CRP, IL-6, TNF-α, and adiponectin). The safety and efficacy of curcumin as a natural product support the potential for the prevention and treatment of chronic inflammatory metabolic diseases.
Background
Significant scientific research has been conducted concerning menopausal syndrome(MPS), yet few bibliometric analyses have been performed. Our aim was to recognise the 100 most highly cited published articles on MPS and to analytically evaluate their key features.
Methods
To identify the 100 most frequently cited articles, a search was conducted on Web of Science using the term 'menopausal syndrome'. Articles that matched the predetermined criteria were scrutinised to obtain the following data: citation ranking, year of publication, publishing journal, journal impact factor, country of origin, academic institution, authors, study type, and keywords.
Results
The publication period is from January 1, 2000, to August 31, 2022. The maximum number of citations was 406 and in 2012. The median citations per year was 39.70. Most of the articles focused on treatment and complications. These articles were published in 36 different journals, with the Journal of MENOPAUSE having published the greatest number (14%). Forty-eight articles (48%) were from the United States, with the University of Pittsburgh being the leading institute (9%). Joann E. Manson was the most frequent first author (n = 6). Observational studies were the most frequently conducted research type (n = 53), followed by experimental studies (n = 33). Keyword analysis identified classic research topics, including genitourinary syndrome of menopause, bone mineral density (BMD), and anti-mullerian hormone (AMH) loci.
Conclusion
Using bibliometrics, we conducted an analysis to identify the inadequacies, traditional focal points, and potential prospects in the study of MPS across current scientific areas. Treatment and complications are at the core of MPS research, whereas prediction and biomarkers have less literature of high quality. There is a necessity for innovative analytical metrics to measure the real effect of these papers with a high level of citation on clinical application.
Aging is a gradual and irreversible process that is accompanied by an overall decline in cellular function and a significant increase in the risk of age-associated disorders. Generally, delaying aging is a more effective method than treating diseases associated with aging. Currently, researchers are focused on natural compounds and their therapeutic and health benefits. Curcumin is the main active substance that is present in turmeric, a spice that is made up of the roots and rhizomes of the Curcuma longa plant. Curcumin demonstrated a positive impact on slowing down the aging process by postponing age-related changes. This compound may have anti-aging properties by changing levels of proteins involved in the aging process, such as sirtuins and AMPK, and inhibiting pro-aging proteins, such as NF-κB and mTOR. In clinical research, this herbal compound has been extensively examined in terms of safety, efficacy, and pharmacokinetics. There are numerous effects of curcumin on mechanisms related to aging and human diseases, so we discuss many of them in detail in this review.
Menopause is associated with reduced nitric oxide bioavailability and vascular function. Although exercise is known to improve vascular function, this is blunted in estrogen-deficient females post-menopause (PM). Here, we examined the effects of acute exercise at differing intensities with and without inorganic nitrate (NO 3 ⁻ ) supplementation on vascular function in females PM. Participants were tested in a double-blinded, block-randomized design, consuming ~13mmol NO 3 ⁻ in the form of beetroot juice (BRJ; n=12) or placebo (PL; n=12) for 2 days prior to experimental visits and 2 hours prior to testing. Visits consisted of vascular health measures before (Timepoint 0) and every 30 minutes after (Timepoints 60, 90, 120, 150, 180) calorically matched high intensity exercise (HIE), moderate intensity exercise (MIE), and a non-exercise control (CON). Blood was sampled at rest and 5-minutes post-exercise for NO 3 ⁻ , NO 2 ⁻ , and ET-1. BRJ increased N-oxides and decreased ET-1 compared with PL, findings which were unchanged after experimental conditions ( p<0.05). BRJ improved Peak ∆ flow-mediated dilation (FMD) compared to PL ( p<0.05), defined as the largest ∆ FMD for each individual participant across all timepoints. FMD across time revealed an improvement ( p=0.05) in FMD between BRJ+HIE vs BRJ+CON, while BRJ+MOD had medium effects compared to BRJ+CON. In conclusion, NO 3 ⁻ supplementation combined with HIE improved FMD in post-menopausal females. NO 3 ⁻ supplementation combined with MIE may offer an alternative to those unwilling to perform HIE. Future studies should test whether long term exercise training at high intensities with NO 3 ⁻ supplementation can enhance vascular health in females PM.
Curcumin, a natural polyphenol, derived from Curcuma longa L. is extensively studied by various researchers across the globe and has established its immense potential in the management of several disorders at clinical level. The underlying mechanism of curcumin involves regulation of various molecular targets, namely, inflammatory cytokines, transcription factor, apoptotic genes, growth factors, oxidative stress biomarkers, and protein kinases. In clinical trials, curcumin as an adjuvant has significantly boost‐up the efficacy of many proven drugs in the management of arthritis, neurodegenerative disorder, oral infection, and gastrointestinal disorders. Moreover, clinical studies have suggested curcumin as an appropriate candidate for the prevention and/or management of various cancers via regulation of signaling molecules including NF‐kB, cytokines, C‐reactive protein, prostaglandin E2, Nrf2, HO‐1, ALT, AST, kinases, and blood profiles. This article highlights plethora of clinical trials that have been conducted on curcumin and its derivatives in the management of several ailments. Besides, it provides recent updates to the investigators for conducting future research to fulfill the current gaps to expedite the curcumin utility in clinical subjects bearing different pathological states.
There is a substantial literature gap related to the vascular response to different types of exercise training in middle-aged and older populations. Thus, this scoping review aimed to examine the outcomes of controlled trials testing the long-term effects of exercise interventions on vascular function-related outcomes in middle-aged and older populations. The literature search was conducted following PRISMA guidelines. Data sources: five databases were used (EBSCO, MEDLINE, Web of Science, Science Direct, and Google Scholar). Eligibility criteria: controlled trials, published in the last 10 years, in English, containing well-described exercise interventions, reporting vascular quantitative effects of exercise in middle-aged and older people. A total of 62 publications were included. The studies included distinct types and intensities of exercise and were heterogeneous in volume and frequency. The assessed vascular outcomes also presented considerable variability. Overall, most studies reported positive effects of exercise on vascular function outcomes, regardless of exercise characteristics. Different exercise interventions can be applied to improve vascular function in middle-aged and older adults. Studies on combined and stretching exercises reported encouraging results in improving vascular function. Stretching exercises rise as an effective alternative in promoting vascular function among older adults, while combined exercise delivered promising vascular benefits in both populations.
This study aimed to compare the effects of diet and exercise of different intensities on antioxidant function, aortic endothelial cell function and serum lipids in NAFLD (nonalcoholic fatty liver disease) rats. Fifty Sprague-Dawley (SD) rats (180-220g) were randomly divided into two experimental groups and fed either a standard rodent chow diet (CON; n=10) or a high-fat diet (HFD; n=40). After 16 weeks, the animals that received the HFD were randomly separated into a high-fat control group (HFC; n=10) or three ex-ercise training groups: HFD and low-intensity exercise (LE; n=10), HFD and moderate-intensity exercise (ME; n=10), and HFD and incremental intensity exercise (IE; n=10). These experimental rats keep sedentary or trained for the next six weeks. A detection kit was used to detect nitric oxide synthase (NOs), nitric oxide (NO), malondialdehyde (MDA) and other markers of aor-tic oxidative stress. The expression levels of endothelial nitric oxide synthase (e-NOS) and endothelin-1 (ET-1) were detected by immunohistochemistry. TC, TG, and other lipid metabolism parameters were detected by an auto-matic analyzer. Exercise with different intensities could improve lipid me-tabolism, enhance antioxidant function, reduce MDA (P<0.01), increase NO (P<0.01), and improve the expression of e-NOS and ET-1 (P<0.01) protein levels in NAFLD rats. Decreased blood lipids were exhibited in all exercise groups. Notably, the moderate-intensity exercise demonstrated more effecton increasing glutathione (GSH) contents (P<0.01) and decreased the ex-pression of ET-1protein levels (P<0.01). The results showed that exercise at different intensities improved lipid metabolism and enhanced anti-oxidation function. Moderate exercise could improve the function of aortic endothelial cells.
Background
Curcumin, a polyphenolic curcuminoid from Curcuma longa L. root and rhizome, presents a positive effect on cardiovascular disease. Since endothelial dysfunction precedes cardiovascular disease, many studies have suggested curcumin supplementation to improve endothelial function. However, the mechanisms by which curcumin can enhance endothelial function are poorly explored. Furthermore, formulated curcumin products have been utilized to improve curcumin bioavailability, which can have an additional impact on human health. Therefore, this narrative review aims to discuss the current evidence showing the effect of curcumin on endothelial function in humans, exploring the mechanisms by which curcumin can improve endothelial function. In addition, we discuss whether formulated curcumin products could generate a more robust impact on endothelial function than non-formulated curcumin.
Methods
Research articles were retrieved based on a search of the following databases: PubMed, ScienceDirect, and Google Scholar using the following keywords and synonyms combined: (“curcumin” or “turmeric” or “curcuma” or “curcuma longa” or “curcuma domestica”) AND (“endothelial function” or “vascular function” or “nitric oxide”).
Results
Curcumin supplementation seems to improve endothelial function in humans. Such effects can be attributed to curcumin's antioxidant and anti-inflammatory properties and the regulation of adhesion molecule levels, all of which can increase NO bioavailability.
Conclusion
Curcumin supplementation has been demonstrated to improve endothelial function, but the current data is insufficient to determine whether the delivery methods enhance such effects. Therefore, future studies investigating the impact of curcumin formulations on endothelial function are warranted.
Noncommunicable diseases (NCDs) are one of the major public health concerns globally. Most of the NCDs including insulin resistance, metabolic syndrome, type 2 diabetes mellitus, fatty liver disease, and coronary heart disease are related to obesity and are called obesity-related NCDs (OR-NCDs). However, adipocytes can reduce OR-NCDs by secreting adiponectin. Adiponectin has an inverse relationship with body fat. Obese people have impairment in differentiating pre-adipocytes to adipocytes, the process facilitated by adiponectin. Adiponectin directly increases insulin sensitivity and reduces obesity-related insulin resistance by down-regulating hepatic glucose production and increasing fatty acid (FA) oxidation in skeletal muscle. Considering the various beneficial effects of adiponectin on health, increasing adiponectin might be a promising approach to prevent and treat OR-NCDs. Recent studies have shown that nutraceuticals and medicinal compounds isolated from plants could prevent and treat various diseases, particularly cardiovascular diseases (CVDs), diabetes mellitus, obesity, and non-alcoholic fatty liver disease. However, to our knowledge, the effect of these natural products, including herbal supplements and functional foods on adiponectin, has not yet been fully reviewed. The main aim of this review is to summarize the effects of nutraceuticals and herbal bioactive compounds on plasma adiponectin concentrations based on clinical studies. It can be concluded that medicinal plants, and herbal bioactive compounds, particularly curcumin, anthocyanins, resveratrol, soy, walnut, and dihydromyricetin can be used as adjunct or complementary therapeutic agents to increase plasma adiponectin, which could potentially prevent and treat NCDs.
Background and Objectives: Clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD), including evidence of vascular dysfunction, can begin in childhood. Curcumin is a polyphenol found in turmeric that reduces vascular dysfunction in rodent models and humans without ADPKD. It also slows kidney cystic progression in a murine model of ADPKD. We hypothesized that oral curcumin therapy would reduce vascular endothelial dysfunction and arterial stiffness in children/young adults with ADPKD.
Design, Setting, Participants, and Measurements: In a randomized, placebo-controlled, double-blind trial, 68 children/ young adults 6-25 years of age with ADPKD and an estimated glomerular filtration rate >80 mL/min/1.73 m ² were randomized to either curcumin supplementation (25 mg/kg body weight/day) or placebo, administered in powder form for 12 months. The co-primary outcomes were brachial artery flow-mediated dilation [FMD BA ] and aortic pulse-wave velocity [aPWV]. We also assessed change in circulating/urine biomarkers of oxidative stress/inflammation and kidney growth (height-adjusted total kidney volume]) by magnetic resonance imaging. In a sub-group of participants ≥18 years, vascular oxidative stress was measured as the change in FMD BA following an acute infusion of ascorbic acid.
Results: Enrolled participants were 18±5 [mean±s.d.] years; 54% female; baseline FMD BA was 9.3±4.1 % change, and baseline aPWV was 512±94 cm/sec. Fifty-seven participants completed the trial. Neither co-primary endpoint changed with curcumin (estimated change [95% confidence interval] for FMD BA (% change): curcumin: 1.14 [-0.84, 3.13]; placebo: 0.33 [-1.34, 2.00]; estimated difference for change: 0.81 [-1.21, 2.84], p=0.48; aPWV (cm/sec: curcumin: 0.6 [-25.7, 26.9]; placebo: 6.5 [-20.4, 33.5]; estimated difference for change: -5.9 [-35.8, 24.0], p=0.67) (intent to treat). There was no curcumin-specific reduction in vascular oxidative stress, nor changes in mechanistic biomarkers. Height-adjusted total kidney volume also did not change as compared to placebo.
Conclusions: Curcumin supplementation does not improve vascular function or slow kidney growth in children/young adults with ADPKD.
Increased production of reactive oxygen species reduces nitric oxide (NO) bioavailability and impairs vascular function with aging. Curcumin is a polyphenolic compound found in the rhizome of turmeric (Curcuma longa) with antioxidant properties. An increasing number of studies have demonstrated improvement in the vasodilatory response of conduit arteries following curcumin supplementation, which has been associated with increased NO production. However, less is known about the effects of curcumin on resistance vessels response. Therefore, the present study aimed to investigate the effects of a high single dose of turmeric extract on skeletal muscle microvascular reactivity and plasma concentrations of NO metabolites in older adults. Twenty-one older adults consumed 10 g of turmeric extract (CUR) or placebo (PLA) in a randomized, double-blind, and crossover design. Blood samples were drawn to assay NO metabolites (NO2⁻ and NO3⁻), and changes in oxygen saturation parameters following arterial occlusion were used to evaluate microvascular reactivity. There were no significant changes in plasma concentrations of NO2⁻ and NO3⁻ as well the parameters of oxygen saturation were not affected after CUR. In conclusion, a high single dose of turmeric extract does not affect the plasma concentration of NO metabolites nor skeletal muscle microvascular reactivity in older adults.
Background: Cardiovascular diseases (CVDs) are among the deadliest non-communicable diseases, and millions of dollars are spent every year to combat CVDs. Unfortunately, the multifactorial etiology of CVDs complicates the development of efficient therapeutics. Interestingly, phytopigments show significant pleiotropic cardioprotective effects both in vitro and in vivo.
Purpose: This review gives an overview of the cardioprotective effects of phytopigments based on in vitro and in vivo studies as well as clinical trials.
Methods: A literature-based survey was performed to collect the available data on cardioprotective activities of phytopigments via electronic search engines such as Pubmed, Google Scholar, and Scopus.
Results: Different classes of phytopigments such as carotenoids, xanthophylls, flavonoids, anthocyanins, anthraquinones alleviate major CVDs (e.g., cardiac hypertrophy, atherosclerosis, hypertension, cardiotoxicities) via acting on signaling pathways related to AMPK, NF-κB, NRF2, PPARs, AKT, TLRs, MAPK, JAK/STAT, NLRP3, TNF-α, and RA.
Conclusion: Phytopigments represent promising candidates to develop novel and effective CVD therapeutics. More randomized, placebo-controlled clinical studies are recommended to establish the clinical efficacy of phytopigments.
Turmeric (Curcuma longa) is a flowering plant of the ginger family with a long history of medicinal use due to its potent anti-inflammatory properties. Its most active constituent is curcumin, which has been widely studied. However, curcumin has extremely limited bioavailability. Thus, it is essential to add a little piperine (from black pepper) to any turmeric preparation, particularly curcumin, to allow for adequate absorption. Turmeric has antibacterial, fungistatic, and wound-healing properties. This chapter examines some of the scientific research conducted on turmeric, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of the herb’s use in treating ophthalmological, oral and dental, pulmonary, cardiovascular, cardiometabolic, gastrointestinal, genitourinary, musculoskeletal, neurological, and psychiatric disorders, among many others. Finally, the chapter presents a list of turmeric’s active constituents, different Commonly Used Preparations and Dosage, and a section on “Safety and Precaution” that examines side effects, toxicity, and disease and drug interactions.
The last decade has seen an unprecedented rise in the prevalence of chronic diseases worldwide. Different mono-targeted approaches have been devised to treat these multigenic diseases, still most of them suffer from limited success due to the off-target debilitating side effects and their inability to target multiple pathways. Hence a safe, efficacious, and multi-targeted approach is the need for the hour to circumvent these challenging chronic diseases. Curcumin, a natural compound extracted from the rhizomes of Curcuma longa, has been under intense scrutiny for its wide medicinal and biological properties. Curcumin is known to manifest antibacterial, antiinflammatory, antioxidant, antifungal, antineoplastic, antifungal, and proapoptotic effects. A plethora of literature has already established the immense promise of curcuminoids in the treatment and clinical management of various chronic diseases like cancer, cardiovascular, metabolic, neurological, inflammatory, and infectious diseases. To date, more than 230 clinical trials have opened investigations to understand the pharmacological aspects of curcumin in human systems. Still, further randomized clinical studies in different ethnic populations warrant its transition to a marketed drug. This review summarizes the results from different clinical trials of curcumin-based therapeutics in the prevention and treatment of various chronic diseases.
Chronic kidney disease (CKD) represents a world-wide public health problem. Inflammation, endothelial dysfunction (ED) and vascular calcifications are clinical features of CKD patients that increase cardiovascular (CV) mortality. CKD-related CV disease pathogenic mechanisms are not only associated with traditional factors such as arterial hypertension and dyslipidemia, but also with ED, oxidative stress and low-grade inflammation. The typical comorbidities of CKD contribute to reduce the performance and the levels of the physical activity in nephropathic patients compared to healthy subjects. Currently, the effective role of physical activity on ED is still debated, but the available few literature data suggest its positive contribution. Another possible adjuvant treatment of ED in CKD patients is represented by natural bioactive compounds (NBCs). Among these, minor polar compounds of extra virgin olive oil (hydroxytyrosol, tyrosol and oleocanthal), polyphenols, and vitamin D seem to exert a beneficial role on ED in CKD patients. The objective of the review is to evaluate the effectiveness of physical exercise protocols and/or NBCs on ED in CKD patients.
Endothelial dysfunction is the common early stage of most cardiovascular afflictions. The endothelium is considered the main mediator of vascular homeostasis via its vasodilator, anti-inflammatory and anticoagulant properties. Among the different endothelial-derived mediators, nitric oxide is produced by nitric oxide synthase and has a critical role in regulating endothelial function. Physiological and pathological processes such as aging and diabetes mellitus are associated with disturbances of endothelial function which, at least at the earliest stage, can be reversed by lifestyle and pharmacological intervention to reduce the risk of incident cardiovascular diseases. Among dietary strategies, curcumin is a cheap and safe nutraceutical polyphenol with proven antioxidant and anti-inflammatory properties. Given the important role of such processes in the development of endothelium dysfunction, a role for curcumin in the prevention or treatment of this condition has been hypothesized. This review summarizes the available literature on the beneficial role of curcumin on vascular endothelial function.
Lifestyle modification (i.e., regular physical activity and diet) is effective in preventing the age-related increase in cardiovascular disease risks. Potential therapeutic effects of curcumin (diferuloylmethane) have been confirmed on various diseases, including cancer and Alzheimer's disease, but the effects of curcumin have not been tested on central arterial hemodynamics. The aim of this pilot study was to test the hypothesis that the regular endurance exercise combined with daily curcumin ingestion lowers the age-related increase in left ventricular (LV) afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women using a randomized, double-blind, placebo-controlled, parallel manner.
Forty-five women were randomly assigned to four interventions: "placebo ingestion" (n = 11), "curcumin ingestion" (n = 11), "exercise training with placebo ingestion" (n = 11), or "exercise training with curcumin ingestion" (n = 12). Curcumin or placebo pills (150 mg/day) were administered for 8 weeks. Aortic blood pressure (BP) and augmentation index (AIx), an index of LV afterload, were evaluated by pulse wave analysis from tonometrically measured radial arterial pressure waveforms.
There were no significant differences in baseline hemodynamic variables among four groups. After the interventions, brachial systolic BP (SBP) significantly decreased in both exercise-trained groups (P < 0.05 for both), whereas aortic SBP significantly decreased only in the combined-treatment (e.g., exercise and curcumin) group (P < 0.05). Heart rate (HR) corrected aortic AIx significantly decreases only in the combined-treatment group.
These findings suggest that regular endurance exercise combined with daily curcumin ingestion may reduce LV afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women.
More and more preclinical studies support the idea that curcumin, a plant-derived natural polyphenol, could be a promising anticancer drug. However, poor bioavailability has limited its efficacy in clinical trials, and plasma curcumin levels remain low despite patients taking gram doses of curcumin.
This study aimed to evaluate the safety and pharmacokinetics of newly developed nanoparticle curcumin with increased water solubility (named THERACURMIN). Six healthy human volunteers were recruited and received THERACURMIN at a single oral dose of 150 mg. After an interval of 2 weeks, the same subjects then received THERACURMIN at a single dose of 210 mg. Plasma curcumin levels were measured at 0, 1, 2, 4, 6, and 24 h after THERACURMIN intake using high-performance liquid chromatography (HPLC).
One subject reported grade 1 diarrhea after intake of 150 mg THERACURMIN. No other toxicities were observed in this study. C (max) for THERACURMIN at 150 and 210 mg was 189 ± 48 and 275 ± 67 ng/ml (mean ± SEM), respectively, and the area under the curve for 24 h was estimated to be 2,649 ± 350 and 3,649 ± 430 ng/ml × h (mean ± SEM), respectively. The t (1/2) was estimated to be 9.7 ± 2.1 h for 150 mg and 13.0 ± 3.3 h for 210 mg.
THERACURMIN can safely increase plasma curcumin levels in a dose-dependent manner at least up to 210 mg without saturating the absorption system. To the best of our knowledge, THERACURMIN is the first nanoparticle formulation of curcumin that demonstrates improved bioavailability in human subjects. We believe this compound could be a promising tool when testing the potential anticancer effects of curcumin in clinical trials.
Curcumin is a polyphenol that is commonly used for its perceived health benefits. However, the absorption efficacy of curcumin is too low to exhibit beneficial effects. We have successfully developed a highly absorptive curcumin dispersed with colloidal nano-particles, and named it THERACURMIN. The absorption efficacy of THERACURMIN was investigated and compared with that of curcumin powder. The area under the blood concentration-time curve (AUC) after the oral administration of THERACURMIN was found to be more than 40-fold higher than that of curcumin powder in rats. Then, healthy human volunteers were administered orally 30 mg of THERACURMIN or curcumin powder. The AUC of THERACURMIN was 27-fold higher than that of curcumin powder. In addition, THERACURMIN exhibited an inhibitory action against alcohol intoxication after drinking in humans, as evidenced by the reduced acetaldehyde concentration of the blood. These findings demonstrate that THERACURMIN shows a much higher bioavailability than currently available preparations. Thus, THERACURMIN may be useful to exert clinical benefits in humans at a lower dosage.
Endothelial dysfunction is now considered an important early event in the development of atherosclerosis, which precedes gross morphological signs and clinical symptoms. The assessment of flow-mediated dilation (FMD) was introduced almost 20 years ago as a noninvasive approach to examine vasodilator function in vivo. FMD is widely believed to reflect endothelium-dependent and largely nitric oxide-mediated arterial function and has been used as a surrogate marker of vascular health. This noninvasive technique has been used to compare groups of subjects and to evaluate the impact of interventions within individuals. Despite its widespread adoption, there is considerable variability between studies with respect to the protocols applied, methods of analysis, and interpretation of results. Moreover, differences in methodological approaches have important impacts on the response magnitude, can result in spurious data interpretation, and limit the comparability of outcomes between studies. This review results from a collegial discussion between physiologists with the purpose of developing considered guidelines. The contributors represent several distinct research groups that have independently worked to advance the evidence base for improvement of the technical approaches to FMD measurement and analysis. The outcome is a series of recommendations on the basis of review and critical appraisal of recent physiological studies, pertaining to the most appropriate methods to assess FMD in humans.
Peripheral conduit artery endothelium-dependent dilatation decreases with aging in humans. Lactotripeptides (LTPs) and regular exercise can improve endothelium-dependent dilatation, but combining these lifestyle modifications may be more effective than either treatment alone. We conducted a randomized, place-controlled trial with four different intervention arms.
A total of 43 postmenopausal women (50-65 years old) were randomly divided into placebo, LTP, exercise and placebo (Ex+placebo), or exercise and LTP (Ex+LTP) groups. LTP or placebo was administered orally for 8 weeks. The exercise groups completed an 8-week moderate aerobic exercise (walking or cycling) intervention.
There were no statistically significant differences in baseline flow-mediated dilatation (FMD) and most other key dependent variables among the groups. FMD significantly increased in the LTP, Ex+placebo, and Ex+LTP groups whereas no such changes were observed in the placebo control group. The magnitude of increases in FMD was significantly greater in the Ex+LTP group than other intervention groups.
We concluded that LTP ingestion combined with regular aerobic exercise improves endothelium-dependent dilatation to a greater extent than monotherapy with either intervention alone in postmenopausal women.
The augmentation index predicts cardiovascular mortality and is usually explained as a distally reflected wave adding to the forward wave generated by systole. We propose that the capacitative properties of the aorta (the arterial reservoir) also contribute significantly to the augmentation index and have calculated the contribution of the arterial reservoir, independently of wave reflection, and assessed how these contributions change with aging. In 15 subjects (aged 53 +/- 10 yr), we measured pressure and Doppler velocity simultaneously in the proximal aorta using intra-arterial wires. We calculated the components of augmentation pressure in two ways: 1) into forward and backward (reflected) components by established separation methods, and 2) using an approach that accounts for an additional reservoir component. When the reservoir was ignored, augmentation pressure (22.7 +/- 13.9 mmHg) comprised a small forward wave (peak pressure = 6.5 +/- 9.4 mmHg) and a larger backward wave (peak pressure = 16.2 +/- 7.6 mmHg). After we took account of the reservoir, the contribution to augmentation pressure of the backward wave was reduced by 64% to 5.8 +/- 4.4 mmHg (P < 0.001), forward pressure was negligible, and reservoir pressure was the largest component (peak pressure = 19.8 +/- 9.3 mmHg). With age, reservoir pressure increased progressively (9.9 mmHg/decade, r = 0.69, P < 0.001). In conclusion, the augmentation index is principally determined by aortic reservoir function and other elastic arteries and only to a minor extent by reflected waves. Reservoir function rather than wave reflection changes markedly with aging, which accounts for the age-related changes in the aortic pressure waveform.
Central arterial compliance plays an important role in the functional abilities of the vasculature. Two active tripeptides, valine-proline-proline and isoleucine-proline-proline, were isolated from sour milk and were referred to as lactotripeptides (LTP). Because LTP appears to act as an angiotensin-converting enzyme inhibitor, it is plausible to hypothesize that LTP improves arterial compliance. We determined the effects of LTP ingestion alone or in combination with regular aerobic exercise on arterial compliance. A total of 55 postmenopausal women (50-65 yr old) were randomly divided into four groups: placebo, LTP, exercise and placebo (Ex + placebo), or exercise and LTP (Ex + LTP). LTP or placebo was administered orally for 8 wk. The exercise groups completed an 8-wk moderate aerobic exercise intervention. There were no differences in baseline arterial compliance and most other key dependent variables among the groups. Carotid arterial compliance increased significantly in the LTP (0.93 + or - 0.07 vs. 0.99 + or - 0.08 mm(2)/mmHg x 10(-1)), Ex + placebo (0.92 + or - 0.04 vs. 1.00 + or - 0.05 mm(2)/mmHg x 10(-1)), and Ex + LTP groups (0.86 + or - 0.06 vs. 1.00 + or - 0.06 mm(2)/mmHg x 10(-1)), whereas no such changes were observed in the placebo control group (0.86 + or - 0.06 vs. 0.85 + or - 0.07 mm(2)/mmHg x 10(-1)). The magnitude of increases in carotid arterial compliance was significantly greater in the Ex + LTP group (19 + or - 4%) than in other groups. The improvements in arterial compliance with LTP were associated with the corresponding reductions in arterial blood pressure and plasma angiotensin II concentrations. We concluded that LTP ingestion improves carotid arterial compliance and that the combination of LTP ingestion and regular exercise is additive and synergistic in improving arterial compliance in postmenopausal women.
The parameters of wave intensity analysis are calculated from incremental changes in pressure and velocity. While it is clear that forward- and backward-traveling waves induce incremental changes in pressure, not all incremental changes in pressure are due to waves; changes in pressure may also be due to changes in the volume of a compliant structure. When the left ventricular ejects blood rapidly into the aorta, aortic pressure increases, in part, because of the increase in aortic volume: aortic inflow is momentarily greater than aortic outflow. Therefore, to properly quantify the effects of forward or backward waves on arterial pressure and velocity (flow), the component of the incremental change in arterial pressure that is due only to this increase in arterial volume--and not, fundamentally, due to waves--first must be excluded. This component is the pressure generated by the filling and emptying of the reservoir, Otto Frank's Windkessel.
Amplification of the pressure pulse between central and peripheral arteries renders pressure values in the upper limb an inaccurate measure of ascending aortic (AA) pressure. Accuracy could be improved by allowance for such amplification. Transfer functions (TF) for pressures between AA and brachial artery (BA):(BATF) and between AA and radial artery (RA):(RATF) were derived from high-fidelity pressure recordings obtained at cardiac catheterization in 14 patients under control conditions, and after sublingual nitroglycerine 0.3 mg. There was no significant difference in BATF under control conditions and with nitroglycerine; hence results were pooled. Control and nitroglycerine results were also pooled to obtain a single RATF. BATF and RATF moduli peaked at 5 Hz and 4 Hz, reaching 2.5 and 2.8 times the value at zero frequency respectively. Frequency-dependent changes in modulus and phase of BATF and RATF were attributable to wave travel and reflection in the upper limb. BATF and RATF were compared to published transfer functions and those derived from analysis of aortic and brachial or radial pressure waves in previous publications. Results were similar. Our BATF and RATF were used to synthesize AA pressure waves from published peripheral pulses. Correspondence was close, especially for systolic pressure which differed by 2.4 +/- 1.0 (mean +/- SEM) mmHg, whereas recorded systolic pressure differed by 20.4 +/- 2.6 (mean +/- SEM) mmHg between central and peripheral sites. Results indicate that in adult humans a single generalized TF can be used with acceptable accuracy to determine central from peripheral pressure under different conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased arterial stiffness is thought to contribute to the increased incidence of cardiovascular disease with age. Little, however, is known about the influence of aging on central and peripheral arterial stiffness in females. Moreover, it is unknown whether physical activity status influences age-related increases in arterial stiffness in females. Arterial pulse wave velocity (PWV) and augmentation index (AI, applanation tonometry) were measured in 53 healthy females, including 10 premenopausal (Pre-S) and 18 postmenopausal (Post-S) sedentary women, and 9 premenopausal (Pre-PA) and 16 postmenopausal (Post-PA) physically active women. In the sedentary women, there were no age-related differences in arterial blood pressure, but aortic PWV and carotid AI (measures of central arterial stiffness) were higher (P<.01) in Post-S versus Pre-S (1065+/-110 versus 690+/-80 cm/sec and 16.5%+/-1.8% versus 0.3%+/-1.6%, respectively); however, there were no significant differences in leg and arm PWV (measures of peripheral arterial stiffness). Systolic and mean arterial blood pressures were higher (P<.05) in Post-PA versus Pre-PA. Despite this and in contrast to the sedentary women, aortic PWV and AI were not different in Post-PA versus Pre-PA. Stepwise multiple regression indicated that maximal oxygen consumption, plasma total cholesterol, and plasma LDL-cholesterol were significant independent predictors and together explained up to 50% of the variability in central arterial stiffness. We concluded that (1) central, but not peripheral, arterial stiffness increases with age in sedentary healthy females in the absence of age-related increases in arterial blood pressure; (2) significant age-related increases in central arterial stiffness are not observed in highly physically active women; and (3) aerobic fitness and plasma total cholesterol and LDL-cholesterol levels are significant independent physiological correlates of central arterial stiffness in this population.
Although associations between hypertension, left ventricular hypertrophy (LVH), and coronary heart disease (CHD) have been described, it is less clear whether LVH is associated with increased rates of CHD in the absence of hypertension.
We examined this association with Cox regression analyses of data from 7924 adults 25 to 74 years of age from the Second National Health and Nutrition Examination Survey (NHANES II) Mortality Study (1976 to 1992). Covariates included age, race, sex, history of cardiovascular diseases and diabetes, cholesterol, body mass index, blood pressure, and smoking.
During 16.8 follow-up years, there were 462 (26%) deaths from CHD (ICD-9 410-414) and 667 (38%) deaths from diseases of the heart (ICD-9 390-398, 402, 404, 410-414, 415-417, 420-429). LVH prevalence was 13.3 per 1000 population. Hypertension prevalence was 29.1%. LVH prevalence was higher among hypertensive adults than among normotensive adults (29.9 vs 6.4 per 1000, P <.001). Persons with LVH were twice as likely to die of CHD (relative risk, 2.0; 95% confidence interval, 1.2, 3.5) and diseases of the heart (relative risk, 1.9; 95% confidence interval, 1.1, 3.0) after adjustment for hypertension and covariates. In age-adjusted predicted survival, probability plots for CHD, and diseases of the heart, normotensives with LVH had survival similar to hypertensive adults with LVH and lower survival than normotensive and hypertensive adults with no LVH.
Our results confirm previous findings that the presence of LVH is a strong predictor of future cardiovascular death. Although LVH appears to be rare among normotensives, clinicians should be aware that such individuals may have an increased risk for death similar to that of hypertensive adults with LVH.
The National High Blood Pressure Education Program Coordinating Committee published its first statement on the primary prevention of hypertension in 1993. This article updates the 1993 report, using new and further evidence from the scientific literature. Current recommendations for primary prevention of hypertension involve a population-based approach and an intensive targeted strategy focused on individuals at high risk for hypertension. These 2 strategies are complementary and emphasize 6 approaches with proven efficacy for prevention of hypertension: engage in moderate physical activity; maintain normal body weight; limit alcohol consumption; reduce sodium intake; maintain adequate intake of potassium; and consume a diet rich in fruits, vegetables, and low-fat dairy products and reduced in saturated and total fat. Applying these approaches to the general population as a component of public health and clinical practice can help prevent blood pressure from increasing and can help decrease elevated blood pressure levels for those with high normal blood pressure or hypertension.
We aimed to elucidate the possible role of phenotypic alterations and oxidative stress in age-related endothelial dysfunction of coronary arterioles. Arterioles were isolated from the hearts of young adult (Y, 14 weeks) and aged (A, 80 weeks) male Sprague-Dawley rats. For videomicroscopy, pressure-induced tone of Y and A arterioles and their passive diameter did not differ significantly. In A, arterioles L-NAME (a NO synthase blocker)–sensitive flow-induced dilations were significantly impaired (Y: 41±8% versus A: 3±2%), which could be augmented by superoxide dismutase (SOD) or Tiron (but not l -arginine or the TXA 2 receptor antagonist SQ29,548). For lucigenin chemiluminescence, O 2 ·− generation was significantly greater in A than Y vessels and could be inhibited with SOD and diphenyliodonium. NADH-driven O 2 ·− generation was also greater in A vessels. Both endothelial and smooth muscle cells of A vessels produced O 2 ·− (shown with ethidium bromide fluorescence). For Western blotting, expression of eNOS and COX-1 was decreased in A compared with Y arterioles, whereas expressions of COX-2, Cu/Zn-SOD, Mn-SOD, xanthine oxidase, and the NAD(P)H oxidase subunits p47 phox , p67 phox , Mox-1, and p22 phox did not differ. Aged arterioles showed an increased expression of iNOS, confined to the endothelium. Decreased eNOS mRNA and increased iNOS mRNA expression in A vessels was shown by quantitative RT-PCR. In vivo formation of peroxynitrite was evidenced by Western blotting, and immunohistochemistry showing increased 3-nitrotyrosine content in A vessels. Thus, aging induces changes in the phenotype of coronary arterioles that could contribute to the development of oxidative stress, which impairs NO-mediated dilations.
Objetivo
En este estudio se evalúa el efecto de un extracto de Curcuma longa sobre el desarrollo de aterosclerosis experimental (estrías grasas) en conejos, y su interacción con otros antioxidantes plasmáticos.
Métodos y resultados
Dos grupos de conejos macho New Zealand White, un grupo control y un grupo que recibió extracto de cúrcuma (CU), fueron alimentados con dieta aterogénica. El grupo CU fue tratado adicionalmente con un extracto hidroalcohólico de curcuma por vía oral. Seis animales de cada grupo se sacrificaron a los 10, 20 y 30 días. En comparación con el grupo CU, el grupo control presentó concentraciones plasmáticas de peróxidos lipídicos significativamente superiores en todos los tiempos ensayados (10, 20 y 30 días) y valores de d-tocoferol y coenzima Q significativamente menores a los 20 y 30 días. El análisis histológico de las estrías grasas reveló que la lesión en la aorta torácica abdominal fue significativamente menor en el grupo CU que en el grupo control a los 30 días.
Conclusiones
Los suplementos de Curcuma longa reducen el estrés oxidativo y atenúan el desarrollo de estrías grasas en conejos alimentados con una dieta rica en colesterol.
Atherosclerosis and arteriosclerosis are mainly caused by the dysfunction of arterial components, namely, vascular endothelial cells, smooth muscle cells, and the extracellular matrix. Endothelial dysfunction is well established as a predictive surrogate marker of cardiovascular events; however, little is known regarding the clinical implications of vascular smooth muscle dysfunction for cardiovascular disease and microangiopathy. In the present study, we aimed to clarify the association of arterial dysfunction with micro-/macroangiopathy and conventional cardiovascular risk factors in 181 type 2 diabetic patients (T2DM; age ± SD, 64 ± 10 years; duration of diabetes, 12 ± 10 years).
Flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were assessed to evaluate endothelial dysfunction and vascular smooth muscle dysfunction, respectively, by using a novel ultrasound device, UNEXEF18G (Unex Co. Ltd., Japan).
The FMD and NMD were 6.4 ± 3.9% and 13.4 ± 6.6%, respectively. No significant differences in FMD were noted between T2DM with and without micro- or macroangiopathy; however, NMD in T2DM patients with micro- and macroangiopathy was significantly lower than that in T2DM patients without angiopathy. NMD decreased with the progression of chronic kidney disease (CKD) stage (p = 0.005), but not FMD (p = 0.071). On multiple regression analysis, significant independent contributors to FMD were age, smoking, systolic blood pressure, glycosylated hemoglobin, and serum total cholesterol, while those for NMD were age, systolic blood pressure, and waist circumference.
The relationship of vascular complications and cardiovascular risk factors with NMD is different from that with FMD in type 2 diabetic patients.
1. Curcumin is the active ingredient of the dietary spice turmeric and has been consumed for medicinal purposes for thousands of years. Modern science has shown that curcumin modulates various signalling molecules, including inflammatory molecules, transcription factors, enzymes, protein kinases, protein reductases, carrier proteins, cell survival proteins, drug resistance proteins, adhesion molecules, growth factors, receptors, cell cycle regulatory proteins, chemokines, DNA, RNA and metal ions.
2. Because of this polyphenol’s potential to modulate multiple signalling molecules, it has been reported to possess pleiotropic activities. First demonstrated to have antibacterial activity in 1949, curcumin has since been shown to have anti-inflammatory, anti-oxidant, pro-apoptotic, chemopreventive, chemotherapeutic, antiproliferative, wound healing, antinociceptive, antiparasitic and antimalarial properties as well. Animal studies have suggested that curcumin may be active against a wide range of human diseases, including diabetes, obesity, neurological and psychiatric disorders and cancer, as well as chronic illnesses affecting the eyes, lungs, liver, kidneys and gastrointestinal and cardiovascular systems.
3. Although many clinical trials evaluating the safety and efficacy of curcumin against human ailments have already been completed, others are still ongoing. Moreover, curcumin is used as a supplement in several countries, including India, Japan, the US, Thailand, China, Korea, Turkey, South Africa, Nepal and Pakistan. Although inexpensive, apparently well tolerated and potentially active, curcumin has not been approved for the treatment of any human disease.
4. In the present article, we discuss the discovery and key biological activities of curcumin, with a particular emphasis on its activities at the molecular and cellular levels, as well as in animals and humans.
Curcumin (diferuloylmethane), the active ingredient in turmeric (Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities. The pleiotropic activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules. Curcumin has been shown to bind by multiple forces directly to numerous signaling molecules, such as inflammatory molecules, cell survival proteins, protein kinases, protein reductases, histone acetyltransferase, histone deacetylase, glyoxalase I, xanthine oxidase, proteasome, HIV1 integrase, HIV1 protease, sarco (endo) plasmic reticulum Ca(2+) ATPase, DNA methyltransferases 1, FtsZ protofilaments, carrier proteins, and metal ions. Curcumin can also bind directly to DNA and RNA. Owing to its β-diketone moiety, curcumin undergoes keto-enol tautomerism that has been reported as a favorable state for direct binding. The functional groups on curcumin found suitable for interaction with other macromolecules include the α, β-unsaturated β-diketone moiety, carbonyl and enolic groups of the β-diketone moiety, methoxy and phenolic hydroxyl groups, and the phenyl rings. Various biophysical tools have been used to monitor direct interaction of curcumin with other proteins, including absorption, fluorescence, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy, surface plasmon resonance, competitive ligand binding, Forster type fluorescence resonance energy transfer (FRET), radiolabeling, site-directed mutagenesis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), immunoprecipitation, phage display biopanning, electron microscopy, 1-anilino-8-naphthalene-sulfonate (ANS) displacement, and co-localization. Molecular docking, the most commonly employed computational tool for calculating binding affinities and predicting binding sites, has also been used to further characterize curcumin's binding sites. Furthermore, the ability of curcumin to bind directly to carrier proteins improves its solubility and bioavailability. In this review, we focus on how curcumin directly targets signaling molecules, as well as the different forces that bind the curcumin-protein complex and how this interaction affects the biological properties of proteins. We will also discuss various analogues of curcumin designed to bind selective targets with increased affinity.
Biological therapies can be beneficial in cancer patients. The present study aims to examine the inhibitory mechanism of curcumin on cancer cells in patients with colorectal cancer. The results showed that curcumin administration increased body weight, decreased serum TNF-alpha levels, increased apoptotic tumor cells, enhanced expression of p53 molecule in tumor tissue, and modulated tumor cell apoptotic pathway. We conclude that the curcumin treatment improves the general health of patients with colorectal cancer via the mechanism of increased p53 molecule expression in tumor cells and consequently speeds up tumor cell apoptosis.
An early return of reflected waves, the backward propagation of the arterial pressure wave from the periphery to the heart, is associated with the augmentation of central pulse pressure and cardiovascular risks. The locations of arterial pressure wave reflection, along with arterial stiffening, have a major influence on the timing of the reflected wave. To determine the influence of aging on the location of a major reflection site, arterial length (via 3D artery tracing of MRI) and central (carotid-femoral) and peripheral (femoral-ankle) pulse wave velocities were measured in 208 adults varying in age. The major reflection site was detected by carotid-femoral pulse wave velocity and the reflected wave transit time (via carotid arterial pressure wave analysis). The length from the aortic valve to the major reflection site (eg, effective reflecting length) significantly increased with aging. The effective reflecting length normalized by the arterial length demonstrated that the major reflection sites were located between the aortic bifurcation and femoral site in most of the subjects. The normalized effective reflecting length did not alter with aging until 65 years of age and increased remarkably thereafter in men and women. The effective reflecting length was significantly and positively associated with the difference between central and peripheral pulse wave velocities (r=0.76). This correlation remained significant even when the influence of aortic pulse wave velocity was partial out (r=0.35). These results suggest that the major reflection site shifts distally with aging partly because of the closer matching of impedance provided by central and peripheral arterial stiffness.
Pentraxin 3 (PTX3), which is mainly produced by endothelial cells, macrophages, and smooth muscle cells in the atherosclerotic region, has a cardioprotective effect. Endurance exercise training has also been known to offer cardioprotection. However, the effect of regular endurance exercise on PTX3 is unknown. This study aimed to investigate whether plasma PTX3 concentrations increase in endurance-trained men. Ten young endurance-trained men and 12 age- and gender-matched sedentary controls participated in this study.
We measured plasma PTX3 concentrations of the participants in each group. We also determined systemic arterial compliance (SAC) by using simultaneous M-mode ultrasound and arterial applanation tonometry of the common carotid artery and used HDL cholesterol (HDLC) as an index of cardioprotective effect.
Maximal oxygen uptake was significantly higher in the endurance-trained men than that in the sedentary controls. SAC and HDLC were significantly higher in the endurance-trained men than that in the sedentary controls (SAC = 1.74 ± 0.11 vs 1.41 ± 0.09 mL·mm Hg(-1), P < 0.05; HDLC = 70 ± 5 vs 57 ± 4 mg·dL(-1), P < 0.05). Plasma PTX3 concentrations were markedly higher in the endurance-trained men than that in the sedentary controls (0.93 ± 0.11 vs 0.68 ± 0.06 ng·mL(-1), P < 0.05). Relationships between plasma PTX3 concentrations and SAC and HDLC were linear.
This is the first study revealing that endurance-trained individuals had higher levels of circulating PTX3 than sedentary controls. PTX3 may play a partial role in endurance exercise training-induced cardioprotection.
We undertook a meta-analysis to determine whether changes in wave reflection substantiate the consensus explanation of why blood pressure (BP) changes with aging.
Consensus documents attribute the aging changes in BP to wave reflection moving progressively from diastole into systole. However, the extensive quantitative data on this phenomenon have never been systematically reviewed. Individual studies have been small, and limited to a narrow age range.
Using PubMed, Cochrane, and Web of Science databases, we identified 64 studies (including 13,770 subjects, age range 4 to 91 years) reporting the timing of wave reflection, defined as the time from the onset (foot) of the pressure waveform to the shoulder point (anachrotic notch).
In subjects of all ages, reflection times were well within systole. There was a small tendency for younger subjects to have later reflection, but this was only 0.7 ms per year, whereas the weighted mean reflection time was 136 ms (99% confidence interval: 130 to 141 ms) and the mean duration of systole was 328 ms (99% confidence interval: 310 to 347 ms). At this rate of change with age, arrival of wave reflection would only be construed to be in diastole at an extrapolated age of -221 years.
These findings challenge the current consensus view that a shift in timing of wave reflection significantly contributes to the changes in the BP waveform with aging. We should re-evaluate the mechanisms of BP elevation in aging.
This study was designed to facilitate clinical use of central pulse pressure (PP). We sought to determine a value that might predict adverse outcome and thereby provide a target for assessment of intervention strategies.
We previously documented that central PP more strongly relates to carotid hypertrophy and extent of atherosclerosis and, more importantly, better predicts incident cardiovascular disease (CVD) than brachial PP.
Radial applanation tonometry was performed in the third Strong Heart Study examination to determine central blood pressure. Cox regression analyses were performed using pre-specified covariates and quartiles of central and brachial PP.
Among 2,405 participants without prevalent CVD, 344 suffered CVD events during 5.6 +/- 1.7 years. Quartiles of central PP (p < 0.001) predicted outcome more strongly than quartiles of brachial PP (p = 0.052). With adjustment for covariates, only the event rate in the fourth quartile of central PP (> or =50 mm Hg) was significantly higher than that in the first quartile (hazard ratio [HR]: 1.69, 95% confidence interval [CI]: 1.20 to 2.39, p = 0.003). Central PP > or =50 mm Hg was related to outcome in both men (HR: 2.06, 95% CI: 1.39 to 3.04, p < 0.001) and women (HR: 2.03, 95% CI: 1.55 to 2.65, p < 0.001); in participants with (HR: 1.84, 95% CI: 1.41 to 2.39, p < 0.001) and without diabetes (HR: 1.91, 95% CI: 1.29 to 2.83, p = 0.001); and in individuals younger (HR: 2.51, 95% CI: 1.59 to 3.95, p < 0.001) and older (HR: 1.53, 95% CI: 1.19 to 1.97, p = 0.001) than the age of 60 years.
Central PP > or =50 mm Hg predicts adverse CVD outcome and may serve as a target in intervention strategies if confirmed in other populations and in prospective studies.
Augmentation index (AIx), a correlate of mortality, is thought to be influenced by left ventricular contractility and wave reflections. However, the relationship of AIx with left ventricular contractility changes has never been assessed, and the wave reflection theory has recently been questioned. This study sought to examine arterial waveform changes in response to reduced "wave reflection" and increased left ventricular contractility induced by dobutamine. Simultaneous radial tonometry (for AIx) and tissue Doppler echocardiography (for peak longitudinal systolic strain rate [SR] as an analogue of left ventricular contractility) were recorded at rest and peak dobutamine-induced stress in 50 patients (41 men; aged 62+/-10 years). From baseline to peak stress there was an increase in heart rate (70+/-11 to 127+/-17 bpm; P<0.001) and SR (-0.88+/-0.23 to -1.81+/-0.43 1/s; P<0.001), whereas AIx decreased (27+/-9% to -7+/-15%; P<0.001). There was also a greater increase in the systolic (compared with diastolic) pressure-time integral relative to cardiac cycle length (3.2+/-1.9 versus 1.8+/-1.1 mm Hg; P<0.001), indicating that wave reflection was not shifted into diastole as per the current belief. AIx was significantly associated with ejection duration (r=0.88), heart rate (r=-0.81), and SR (r=0.72; P<0.001 for all). However, when SR was heart rate corrected, there was no significant association with AIx (r=0.18; P=0.11). The strongest independent correlate of AIx was ejection duration, accounting for 78% variance (beta=0.88; model R2=0.77; P<0.001). Neither SR (beta=0.12; P=0.18) nor heart rate-corrected SR (beta=0.02; P=0.72) was associated with AIx. We conclude that AIx is determined by chronotropic rather than inotropic effects, as well as factors other than wave reflection.
Estrogen receptor alpha (ER alpha), a potent transcription factor expressed in vascular endothelial cells, plays a key role in regulating vascular function and health. We determined whether vascular endothelial cell expression of ER alpha is influenced by estrogen status and is related to vascular endothelial function in healthy women.
ER alpha protein expression was measured (quantitative immunofluorescence) in endothelial cells from peripheral veins of 16 healthy, premenopausal women during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle and 17 estrogen-deficient postmenopausal women. Endothelial-dependent dilation (EDD; brachial artery flow-mediated dilation) and endothelial nitric oxide synthase (eNOS) expression and activation were also measured in a subgroup of women.
In premenopausal women (n = 10), ER alpha expression was 30% lower (P < 0.001) during the EF (low estrogen) compared with the LF (high estrogen) phase of the menstrual cycle. In postmenopausal women, ER alpha expression was 33% lower (P < 0.001) compared with the LF phase of the menstrual cycle in premenopausal women. ER alpha expression was strongly related (r = 0.67; P < 0.001) to EDD, which was reduced in postmenopausal women. ER alpha abundance was positively related to expression of eNOS (r = 0.54; P = 0.009; n = 21) and ser1177 phosphorylated eNOS (r = 0.59; P = 0.006; n = 20).
These results provide the first evidence that expression of ER alpha in vascular endothelial cells is modulated by estrogen status and may be a key determinant of vascular endothelial function in healthy pre- and postmenopausal women. ER alpha expression may influence vascular endothelial function in women by affecting protein levels and activation of eNOS.
Curcumin (diferuloylmethane) is a polyphenol responsible for the yellow color of the curry spice turmeric. It has been used in a variety of diseases in traditional medicine. Modern scientific research has demonstrated its anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-thrombotic, and cardiovascular protective effects. In this review, we focused mainly on the effects of curcumin on the cardiovascular system. The antioxidant effects of curcumin have been shown to attenuate adriamycin-induced cardiotoxicity and may prevent diabetic cardiovascular complications. The anti-thrombotic, anti-proliferative, and anti-inflammatory effects of curcumin and the effect of curcumin in decreasing the serum cholesterol level may protect against the pathological changes occurring with atherosclerosis. The p300-HAT inhibitory effects of curcumin have been demonstrated to ameliorate the development of cardiac hypertrophy and heart failure in animal models. The inflammatory effects of curcumin may have the possibility of preventing atrial arrhythmias and the possible effect of curcumin for correcting the Ca(2+) homeostasis may play a role in the prevention of some ventricular arrhythmias. The preclinical studies from animal to clinical data in human are discussed.
The vascular endothelium may develop a proinflammatory profile with aging, but evidence is limited in humans. Expression of inflammatory proteins was determined in vascular endothelial cells (EC) obtained from peripheral veins of 24 young (23 +/- 1 years, mean +/- SE) and 36 older (63 +/- 1) healthy men and women using quantitative immunofluorescence. The older subjects had lower vascular endothelium-dependent dilation (forearm blood flow responses to acetylcholine, p < 0.05), and higher plasma concentrations of C-reactive protein, interleukin-6 (IL-6), and oxidized low-density lipoprotein (all p < 0.05), but not tumor necrosis factor-alpha (TNF-alpha). Total (O: 0.52 +/- 0.04 vs. Y: 0.33 +/- 0.05 NFkappaB/HUVEC intensity, p < 0.05) and nuclear (O: 0.59 +/- 0.04 vs. Y: 0.41 +/- 0.04) expression of nuclear factor kappa B p65 (NFkappaB), a proinflammatory gene transcription factor, was greater in EC from the older subjects (p < 0.05). EC expression of the inhibitor (of nuclear translocation) of NFkappaB (IkappaBalpha) was lower in the older subjects (O: 0.16 +/- 0.02 vs. Y: 0.24 +/- 0.03, p < 0.05), whereas IkappaB kinase (IkappaK) was not different. EC expression of the proinflammatory proteins IL-6 (O: 0.42 +/- 0.06 vs. Y: 0.29 +/- 0.03, p < 0.05), TNF-alpha (O: 0.52 +/- 0.06 vs. Y: 0.33 +/- 0.05, p < 0.05) and monocyte chemoattractant protein 1 (MCP-1) (O: 0.59 +/- 0.06 vs. Y: 0.38 +/- 0.02, p < 0.05) was greater in the older subjects, whereas cyclooxygenase 2 and the receptor for advanced glycation end-products did not differ. These findings indicate that impaired function with aging in healthy adults is associated with the development of a proinflammatory phenotype in the vascular endothelium that could be caused in part by reduced IkappaB-mediated inhibition of NFkappaB.
Inspection of the age-incidence curve of ischaemic heart disease in both sexes shows an increase in slope for women around the menopause, approaching that of men at older ages. Although the increase is likely to be related to the menopause, epidemiological evidence is not defined. Likewise, there is some suggestion that reproductive factors may be related to the subsequent risk of cardiovascular diseases, since a few studies found an elevated risk in women with an earlier first birth. In terms of prevention and public health considerations, treatments via exogenous hormones are, however, much more important. A systematic overview of the available epidemiological evidence indicates that oestrogen replacement treatment is protective against ischaemic heart disease. The overall relative risks based on 18 studies and greater than 3300 cases was 0.81, with a narrow 95% confidence interval (0.76-0.85), thus suggesting a protective effect of 15-25%. This protection has a plausible biological interpretation in terms of increased high density lipoprotein (HDL) levels. The serum lipoprotein pattern can be unfavourably influenced by progestin supplementation. With reference to oral contraceptives, the relative risk for cardiovascular mortality was increased about twofold in current users. There appears now to be convincing evidence that the elevated risk is restricted to current users.(ABSTRACT TRUNCATED AT 250 WORDS)
Arterial pressure waves were recorded noninvasively from the carotid, radial, femoral, or all three of these arteries of 1,005 normal subjects, aged 2-91 years, using a new transcutaneous tonometer containing a high fidelity Millar micromanometer. Waves were ensemble-averaged into age-decade groups. Characteristic changes were noted with increasing age. In all sites, pulse amplitude increased with advancing age (carotid, 91.3%; radial 67.5%; femoral, 50.1% from first to eighth decade), diastolic decay steepened, and diastolic waves became less prominent. In the carotid pulse, there was, in youth, a second peak on the downstroke of the waves in late systole. After the third decade, this second peak rose with age to merge with and dominate the initial rise. In the radial pulse, a late systolic wave was also apparent, but this occurred later; with age, this second peak rose but not above the initial rise in early systole, even at the eighth decade. In the femoral artery, there was a single systolic wave at all ages. Aging changes in the arterial pulse are explicable on the basis of both an increase in arterial stiffness with increased pulse-wave velocity and progressively earlier wave reflection. These two factors may be separated and effects of the latter measured from pressure wave-contour analysis using an "augmentation index," determined by a computer algorithm developed from invasive pressure and flow data. Changes in peak pressure in the central (carotid) artery show increasing cardiac afterload with increasing age in a normal population; this can account for the cardiac hypertrophy that occurs with advancing age (even as other organs atrophy) and the predisposition to cardiac failure in the elderly. Identification of mechanisms responsible offers a new approach to reduction of left ventricular afterload.
This study assessed whether aging is associated with progressive endothelial dysfunction, whether the pattern of any age-related decline in vascular health is different in men and women and whether any gender difference is consistent with known changes in hormonal status.
Coronary and cerebrovascular disease are much less common in young and middle-aged women compared with men, although the gender difference in death from atherosclerosis is less marked after the menopause. Endothelial dysfunction is an early event in atherogenesis and is important in dynamic plaque stenosis in later life. The effect of aging on endothelial function in men and women, however, is not well known.
We used high resolution ultrasound to study endothelium-dependent and endothelium-independent vascular responses. Brachial artery physiology was investigated in 238 subjects (103 men, 135 women; mean [+/- SD] age 38 +/- 17 years, range 15 to 72) with no known risk factors for atherosclerosis. The responses to reactive hyperemia (flow-mediated dilation, which is endothelium dependent) and to glyceryl trinitrate (an endothelium-independent dilator) were assessed for all the subjects and then for men and women separately.
On multivariate analysis for the whole group, reduced flow-mediated dilation was related to older age (r = -0.34, p < 0.0001). In men, flow-mediated dilation was preserved in subjects aged < or = 40 years but declined thereafter at 0.21%/year. In women, flow-mediated dilation was stable until the early 50s, after which it declined at 0.49%/year (p = 0.002 compared with men). In contrast, there was no significant change in the glyceryl trinitrate response with aging in either gender.
Aging is associated with progressive endothelial dysfunction in normal humans, and this appears to occur earlier in men than in women. In women, however, a steep decline commences at around the time of the menopause. This is consistent with a protective effect of estrogens on the arterial wall.
To evaluate the effect of endogenous estrogens on endothelial function in humans, we examined whether menopause is associated with impairment in endothelium-dependent vasodilation in normotensive and essential hypertensive women. In 73 normotensive subjects (37 women, 36 men) and 73 hypertensive patients (36 women, 37 men), we studied endothelial function by measuring forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1,2, and 4 micrograms/100 mL per minute), an endothelium-independent vasodilator. Women younger than 45 years had normal menstrual cycles. In essential hypertensive patients, responses to acetylcholine but not to sodium nitroprusside were significantly (P < .001) reduced compared with responses in normotensive subjects. Moreover, in both groups, vasodilation to acetylcholine showed a marked negative correlation with advancing age (normotensive subjects: r = -.88, P < .001; hypertensive patients: r = -.87, P < .001). In contrast, vasodilation to sodium nitroprusside showed a less evident negative correlation with advancing age (normotensive subjects: r = -46, P < .01; hypertensive patients: r = -.48, P < .01). However, in normally menstruating normotensive women, no endothelial dysfunction was observed, and age-related impairment in endothelium-dependent vasodilation was evident only after menopause. In normally menstruating hypertensive women, aging was associated with endothelial dysfunction although the deterioration of endothelium-dependent vasodilation was less marked than that in men. In contrast, after menopause, the age-related endothelial dysfunction in hypertensive women was similar to that observed in men. Finally, no sex-related difference in the response to sodium nitroprusside was observed in either normotensive subjects or essential hypertensive patients. Age-related endothelial dysfunction is attenuated in premenopausal normotensive and hypertensive women compared with men, whereas no sex-induced difference is observed after menopause, suggesting a protective effect of endogenous estrogens on endothelial function.
This study investigated the effect of age and gender on central arterial hemodynamic variables derived from noninvasive tonometric carotid pressure waveforms.
Women have a greater age-related increase in left ventricular (LV) mass than do men and are more likely to experience symptomatic heart failure after infarction despite their higher ejection fraction. In studies of these changes, ventricular afterload is incompletely defined by brachial blood pressure (BP) measurements. We hypothesized that there exist gender differences in pulsatile vascular load, as revealed by pressure waveform analysis, which may produce suboptimal afterload conditions in women.
Data from 350 healthy normotensive subjects (187 female) aged 2 to 81 years were analyzed in decade groups. Augmentation index (AIx, the difference between early and late pressure peaks divided by pulse pressure) was used as an index of pulsatile afterload, and the ratio of diastolic to systolic pressure-time integral gave a subendocardial viability index. Heart rate, BP, ejection duration and maximal rate of pressure rise (dP/dt(max)) were also determined.
Male subjects had a slightly higher systolic pressure until age 50. Female subjects had higher systolic pressure augmentation after the 1st decade, a difference that was significant after age 30 (p < 0.005 for each decade). In both males and females there was a strong age dependence for AIx (r = 0.77, p < 0.001 for females, r = 0.66, p < 0.001 for males). Although males had a larger body size and higher systolic pressure, systolic pressure-time integral was similar in males and females across all age groups. Diastolic pressure-time integral was consistently lower in females because of their shorter diastolic period. Subendocardial viability index was lower in females across the entire group. Differences in stature and heart rate may contribute to these findings.
These new data may help to explain previous findings in women of an age-related increase in LV mass and excess symptomatic heart failure that are not explained by differences in brachial BP.
Aging is associated with increased cardiovascular risk and endothelial dysfunction. Since exercise can improve endothelium-dependent vasodilation, in the present study we tested whether long-term physical activity could prevent aging-related endothelial dysfunction.
In 12 young and elderly (age 26.9+/-2.3 and 62.9+/-5.8 years, respectively) healthy sedentary subjects and 11 young and 14 elderly matched athletes (age 27.5+/-1.9 and 66.4+/-6.1 years, respectively), we studied (with strain-gauge plethysmography) forearm blood flow modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-dependent vasodilator, at baseline, during infusion of N(G)-monomethyl-L-arginine (L-NMMA) (100 microg/100 mL forearm tissue per minute), a nitric oxide-synthase inhibitor, vitamin C (8 mg/100 mL forearm tissue per minute), an antioxidant, and finally under simultaneous infusion of L-NMMA and vitamin C. The response to sodium nitroprusside (1, 2, and 4 microg/100 mL forearm tissue per minute) was also evaluated. In young athletes and sedentary subgroups, vasodilation to acetylcholine was inhibited by L-NMMA and was not changed by vitamin C. In elderly subjects, vasodilation to acetylcholine was blunted as compared with young subjects in both control subjects and athletes, whereas the response to sodium nitroprusside was similar. Moreover, in elderly athletes, vitamin C did not change the vasodilation to acetylcholine. In contrast, in elderly sedentary subjects, the response to acetylcholine was resistant to L-NMMA. In this subgroup, vitamin C increased the vasodilation to acetylcholine and restored the inhibiting effect of L-NMMA.
These results suggest that regular physical activity can at least in part prevent the age-induced endothelial dysfunction, probably the restoration of nitric oxide availability consequent to prevention of production of oxidative stress.
In sedentary humans endothelium-dependent vasodilation is impaired with advancing age contributing to their increased cardiovascular risk, whereas endurance-trained adults demonstrate lower age-related risk. We determined the influence of regular aerobic exercise on the age-related decline in endothelium-dependent vasodilation.
In a cross-sectional study, 68 healthy men 22 to 35 or 50 to 76 years of age who were either sedentary or endurance exercise-trained were studied. Forearm blood flow (FBF) responses to intra-arterial infusions of acetylcholine and sodium nitroprusside were measured by strain-gauge plethysmography. Among the sedentary men, the maximum FBF response to acetylcholine was 25% lower in the middle aged and older compared with the young group (P:<0.01). In contrast, there was no age-related difference in the vasodilatory response to acetylcholine among the endurance-trained men. FBF at the highest acetylcholine dose was almost identical in the middle aged and older (17.3+/-1.3 mL/100 mL tissue per minute) and young (17.7+/-1.4 mL/100 mL tissue per minute) endurance-trained groups. There were no differences in the FBF responses to sodium nitroprusside among the sedentary and endurance- trained groups. In an exercise intervention study, 13 previously sedentary middle aged and older healthy men completed a 3-month, home-based aerobic exercise intervention (primarily walking). After the exercise intervention, acetylcholine-mediated vasodilation increased approximately 30% (P:<0.01) to levels similar to those in young adults and middle aged and older endurance-trained men.
Our results indicate that regular aerobic exercise can prevent the age-associated loss in endothelium-dependent vasodilation and restore levels in previously sedentary middle aged and older healthy men. This may represent an important mechanism by which regular aerobic exercise lowers the risk of cardiovascular disease in this population.
Damage of large arteries is a major factor in the high cardiovascular morbidity and mortality of patients with end-stage renal disease (ESRD). Increased aortic pulse wave velocity (PWV) and brachial pulse pressure (PP) are the principal arterial markers of cardiovascular mortality described in these patients. Whether central (carotid) PP and brachial-carotid PP amplification may predict all-cause (including cardiovascular) mortality has never been investigated. A cohort of 180 patients with ESRD who were undergoing hemodialysis was studied between January 1990 and March 2000. The mean duration of follow-up was 52+/-36 months (mean+/-SD). Mean age at entry was 51.5+/-16.3 years. Seventy deaths occurred, including both cardiovascular and noncardiovascular fatal events. At entry, patients underwent carotid PP measurements (pulse wave analysis), echocardiography, and aortic PWV (Doppler ultrasonography), together with standard clinical and biochemical analyses. On the basis of Cox analyses, after adjustment of age, time on dialysis before inclusion, and previous cardiovascular events, 3 factors emerged as predictors of all-cause mortality: carotid PP, brachial/carotid PP, and aortic PWV. Adjusted hazard ratios for 1-SD increments were 1.4 (1.1 to 1.8) for carotid PP, 0.5 (0.3 to 0.8) for brachial/carotid PP, and 1.3 (1.0 to 1.7) for PWV. Brachial blood pressure, including PP, had no predictive value for mortality after adjustment. These results provide the first direct evidence that in patients with ESRD, the carotid PP level and, mostly, the disappearance of PP amplification are strong independent predictors of all-cause (including cardiovascular) mortality.
We aimed to elucidate the possible role of phenotypic alterations and oxidative stress in age-related endothelial dysfunction of coronary arterioles. Arterioles were isolated from the hearts of young adult (Y, 14 weeks) and aged (A, 80 weeks) male Sprague-Dawley rats. For videomicroscopy, pressure-induced tone of Y and A arterioles and their passive diameter did not differ significantly. In A, arterioles L-NAME (a NO synthase blocker)-sensitive flow-induced dilations were significantly impaired (Y: 41+/-8% versus A: 3+/-2%), which could be augmented by superoxide dismutase (SOD) or Tiron (but not L-arginine or the TXA(2) receptor antagonist SQ29,548). For lucigenin chemiluminescence, O(2)(.-) generation was significantly greater in A than Y vessels and could be inhibited with SOD and diphenyliodonium. NADH-driven O(2)(.-) generation was also greater in A vessels. Both endothelial and smooth muscle cells of A vessels produced O(2)(.-) (shown with ethidium bromide fluorescence). For Western blotting, expression of eNOS and COX-1 was decreased in A compared with Y arterioles, whereas expressions of COX-2, Cu/Zn-SOD, Mn-SOD, xanthine oxidase, and the NAD(P)H oxidase subunits p47(phox), p67(phox), Mox-1, and p22(phox) did not differ. Aged arterioles showed an increased expression of iNOS, confined to the endothelium. Decreased eNOS mRNA and increased iNOS mRNA expression in A vessels was shown by quantitative RT-PCR. In vivo formation of peroxynitrite was evidenced by Western blotting, and immunohistochemistry showing increased 3-nitrotyrosine content in A vessels. Thus, aging induces changes in the phenotype of coronary arterioles that could contribute to the development of oxidative stress, which impairs NO-mediated dilations.
This study evaluates the effect of a Curcuma longa extract on the development of experimental atherosclerosis (fatty streak) in rabbits and its interaction with other plasmatic antioxidants.
Two experimental groups of male New Zealand White rabbits, a control group and a curcuma-extract (CU) group, were fed an atherogenic diet. Additionally, the CU group received an oral curcuma hydroalcoholic extract. Six animals from each experimental group were killed after 10, 20, and 30 days. Compared with the CU group, the control group showed significantly higher plasma lipid peroxide at all experimental times (10, 20, and 30 days) and significantly lower alpha-tocopherol and coenzyme Q levels at 20 and 30 days. Histological results for the fatty streak lesions revealed damage in the thoracic and abdominal aorta that was significantly lower in the CU group than in the control group at 30 days.
Supplementation with Curcuma longa reduces oxidative stress and attenuates the development of fatty streaks in rabbits fed a high cholesterol diet.
Peripheral conduit artery flow-mediated dilatation decreases with ageing in humans. The underlying mechanisms and efficacy of preventive strategies are unknown. Brachial artery flow-mediated dilatation was determined at baseline and after ascorbic acid (vitamin C) intravenous infusion and chronic supplementation (500 mg day(-1) for 30 days) in three groups of healthy men: young sedentary (n= 11; 25 +/- 1 years, mean +/-s.e.m.), older sedentary (n= 9; 64 +/- 2), and older endurance-exercise trained (n= 9; 64 +/- 2). At baseline, flow-mediated dilatation (normalized for the hyperaemic stimulus) was approximately 45% lower in the older (0.015 +/- 0.001) versus young (0.028 +/- 0.004) sedentary men (P < 0.01), but was preserved in older exercising men (0.028 +/- 0.004). Ascorbic acid infusion increased plasma concentrations > 15-fold in all groups and restored flow-mediated dilatation in the sedentary older men (to 0.023 +/- 0.002; P > 0.1 versus other groups), with no effects in the other two groups. Oral ascorbic acid supplementation did not affect flow-mediated dilatation in any group. Brachial artery endothelium-independent dilatation (sublingual nitroglycerin) did not differ among the groups at baseline nor change with ascorbic acid administration. These results provide the first evidence for an important role of oxidative stress in both the impairment in peripheral conduit artery flow-mediated dilatation with sedentary human ageing and the preservation of flow-mediated dilatation with physically active ageing.
Brachial-ankle pulse wave velocity (baPWV) is a promising technique to assess arterial stiffness conveniently. However, it is not known whether baPWV is associated with well-established indices of central arterial stiffness. We determined the relation of baPWV with aortic (carotid-femoral) PWV, leg (femoral-ankle) PWV, and carotid augmentation index (AI) by using both cross-sectional and interventional approaches. First, we studied 409 healthy adults aged 18-76 years. baPWV correlated significantly with aortic PWV (r = 0.76), leg PWV (r = 0.76), and carotid AI (r = 0.52). A stepwise regression analysis revealed that aortic PWV was the primary independent correlate of baPWV, explaining 58% of the total variance in baPWV. Additional 23% of the variance was explained by leg PWV. Second, 13 sedentary healthy men were studied before and after a 16-week moderate aerobic exercise intervention (brisk walking to jogging; 30-45 min/day; 4-5 days/week). Reductions in aortic PWV observed with the exercise intervention were significantly and positively associated with the corresponding changes in baPWV (r = 0.74). A stepwise regression analysis revealed that changes in aortic PWV were the only independent correlate of changes in baPWV (beta = 0.74), explaining 55% of the total variance. These results suggest that baPWV may provide qualitatively similar information to those derived from central arterial stiffness although some portions of baPWV may be determined by peripheral arterial stiffness.
Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.
The aim of the current investigation was to test the hypothesis that age-related changes in augmentation index (AIx) are more prominent in younger individuals (<50 years), whereas changes in aortic stiffness per se are more marked in older individuals (>50 years).
Aging exerts a number of deleterious changes in the cardiovascular system, and, in particular, on the large arteries. Previous studies have suggested that AIx and pulse wave velocity (PWV) increase linearly with age, yet epidemiological data concerning pulse pressure suggest that large artery stiffening predominantly occurs later in life.
Peripheral and central blood pressure, augmentation pressure (AP), and AIx were determined in 4,001 healthy, normotensive individuals, aged 18 to 90 years. Aortic and brachial PWV were also determined in a subset of 998 subjects.
Peripheral and central pulse pressure, AP, AIx, and aortic and brachial PWV all increased significantly with age; however, the age-related changes in AIx and aortic PWV were non-linear, with AIx increasing more in younger individuals, whereas the changes in PWV were more prominent in older individuals.
These data suggest that AIx might be a more sensitive marker of arterial stiffening and risk in younger individuals but aortic PWV is likely to be a better measure in older individuals.
Turmeric (Curcuma longa rhizomes), commonly used as a spice is well documented for its medicinal properties in Indian and Chinese systems of medicine. It has been widely used for the treatment of several diseases. Epidemiological observations, though inconclusive, are suggestive that turmeric consumption may reduce the risk of some form of cancers and render other protective biological effects in humans. These biological effects of turmeric have been attributed to its constituent curcumin that has been widely studied for its anti-inflammatory, anti-angiogenic, anti-oxidant, wound healing and anti-cancer effects. As a result of extensive epidemiological, clinical, and animal studies several molecular mechanisms are emerging that elucidate multiple biological effects of curcumin. This review summarizes the most interesting in vitro and in vivo studies on the biological effects of curcumin.
Aging is associated with a decline in vascular endothelial function, manifesting in part as impaired flow-mediated arterial dilation (FMD), but the underlying mechanisms are uncertain. Impaired FMD may be mediated in part by a decrease in synthesis of nitric oxide by endothelial nitric oxide synthase, and in clinical populations this has been attributed to competitive inhibition of l-arginine binding sites by asymmetric dimethylarginine (ADMA). If this mechanism is involved in the age-associated decline in FMD, increasing l-arginine concentration may swing the competitive balance in favor of l-arginine binding, restoring nitric oxide synthesis, and enhancing FMD in older humans. To test this hypothesis, we measured FMD (brachial ultrasound) in 10 younger (21 +/- 1 yr) and 12 older healthy men and women (60 +/- 2 yr) following infusion of vehicle or vehicle + l-arginine. Baseline FMD in the older subjects was only approximately 60% of that in the younger subjects (P = 0.002). l-Arginine did not significantly increase FMD in either group despite 23-fold (older) and 19-fold (younger) increases in plasma l-arginine concentrations (P < 0.0001 vs. control). Protein expression (immunofluorescence) in vascular endothelial cells showed that ADMA and the enzyme isoform that controls its degradation, dimethylarginine dimethylaminohydrolase II, were not different in the younger and older subjects. Endothelium-independent vasodilation (sublingual nitroglycerine) was not different between age groups or conditions. We conclude that acutely increasing plasma concentrations of l-arginine do not significantly improve brachial artery FMD in healthy older subjects and thus does not restore the age-associated loss of FMD. Together with the finding that endothelial cell ADMA protein expression was not increased in older adults, these findings suggest that competitive inhibition of l-arginine binding sites on endothelial nitric oxide synthase by ADMA is not an important mechanism contributing to impaired conduit artery endothelium-dependent dilation with aging in healthy humans.
Aerobic exercise training is associated with lower central arterial stiffness, but little information exists on the effects of physical activity intensity or duration on central arterial stiffness. Using a cross-sectional and interventional approach, we tested the hypothesis that both moderate and vigorous physical activity reduce central arterial stiffness in postmenopausal women.
Carotid arterial stiffness (via ultrasound and applanation tonometry) and duration of physical activity at low, moderate, and vigorous intensities (via electronic accelerometer) were measured in 103 apparently healthy sedentary or recreationally active women 47 to 82 years of age. Moderate intensity physical activity was defined as 4.0 to 6.0 metabolic equivalents (MET) in subjects aged <65 years and as 3.0 to 5.0 MET in subjects >or=65 years. A subgroup of 17 sedentary subjects was randomly assigned to moderate (n = 8) or vigorous (n = 9) intensity cycling exercise training (900 kcal/week, three to five sessions per week, for 12 weeks). Carotid arterial stiffness was measured before and after training.
Carotid beta-stiffness index was significantly correlated with the duration of moderate and vigorous intensity physical activity (r = -0.25 and r = -0.22) even after adjustment for age, height, and mean BP. Carotid beta-stiffness index significantly decreased after moderate and vigorous intensity cycling training. There were no significant group differences in the magnitude of beta-stiffness index change even after adjustment for expected confounders (eg, baseline beta-stiffness index, height, body mass index, heart rate, and post-training body mass, body mass index, and mean BP).
These results suggest that both moderate and vigorous physical activities have favorable effects on central arterial stiffness in postmenopausal women.
TNF-alpha induces some proinflammatory cytokines including IL-1beta, IL-6, IL-8, and itself by activation of NF-kappaB or MAPKs (p38, JNK, ERK). These cytokines play important roles in various inflammatory skin diseases, such as psoriasis. Recently it was also reported that expression of cyclin E is up-regulated by ERK pathway after TNF-alpha treatment. However, it was unknown whether curcumin, showing inhibitory effects on NF-kappaB and MAPKs, attenuates the expression of TNF-alpha-induced IL-1beta, IL-6, IL-8, and TNF-alpha as well as cyclin E expression in HaCaT cells. In this study, we investigated the inhibitory effect of curcumin on expression of proinflammatory cytokines and cyclin E in TNF-alpha-treated HaCaT cells. We found that curcumin inhibited the expression of TNF-alpha-induced IL-1beta, IL-6, and TNF-alpha, but not IL-8, in TNF-alpha-treated HaCaT cells as well as the TNF-alpha-induced cyclin E expression. In addition, curcumin inhibited the activation of MAPKs (JNK, p38 MAPK, and ERK) and NF-kappaB in TNF-alpha-treated HaCaT cells. Taken together, curcumin exerts anti-inflammatory and growth inhibitory effects in TNF-alpha-treated HaCaT cells through inhibition of NF-kappaB and MAPK pathways.
Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Disruption of the blood-brain barrier occurs after stroke. Protection of the blood-brain barrier has become an important target of stroke interventions in experimental therapeutic. The objective of the present study was to determine whether curcumin prevents cerebral ischemia/reperfusion injury by protecting blood-brain barrier integrity. We report that a single injection of curcumin (1 and 2 mg/kg, i.v.) 30 min after focal cerebral ischemia/reperfusion in rats significantly diminished infarct volume, improved neurological deficit, decreased mortality, reduced the water content of the brain and the extravasation of Evans blue dye in ipsilateral hemisphere in a dose-dependent manner. In cultured astrocytes, curcumin significantly inhibited inducible nitric oxide synthase (iNOS) expression and NO(x) (Nitrites/nitrates contents) production induced by lipopolysaccharide (LPS)/tumor necrosis factor alpha (TNF(alpha)). Furthermore, curcumin prevented ONOO(-) donor SIN-1-induced cerebral capillaries endothelial cells damage. We concluded that curcumin ameliorates cerebral ischemia/reperfusion injury by preventing ONOO(-) mediated blood-brain barrier damage.