Cardiovascular autonomic modulation during passive heating protocols: a systematic review.

Objective.To conduct a systematic review of the possible effects of passive heating protocols on cardiovascular autonomic control in healthy individuals.Approach.The studies were obtained from MEDLINE (PubMed), LILACS (BVS), EUROPE PMC (PMC), and SCOPUS databases, simultaneously. Studies were considered eligible if they employed passive heating protocols and investigated cardiovascular autonomic control by spontaneous methods, such as heart rate variability (HRV), systolic blood pressure variability (SBPV), and baroreflex sensitivity (BRS), in healthy adults. The revised Cochrane risk-of-bias tool (RoB-2) was used to assess the risk of bias in each study.Main results.Twenty-seven studies were included in the qualitative synthesis. Whole-body heating protocols caused a reduction in cardiac vagal modulation in 14 studies, and two studies reported both increased sympathetic modulation and vagal withdrawal. Contrariwise, local-heating protocols and sauna bathing seem to increase cardiac vagal modulation. A reduction of BRS was reported in most of the studies that used whole-body heating protocols. However, heating effects on BRS remain controversial due to methodological differences among baroreflex analysis and heating protocols.Significance.Whole-body heat stress may increase sympathetic and reduce vagal modulation to the heart in healthy adults. On the other hand, local-heating therapy and sauna bathing seem to increase cardiac vagal modulation, opposing sympathetic modulation. Nonetheless, further studies should investigate acute and chronic effects of thermal therapy on cardiovascular autonomic control.

The Impact of Selenium Deficiency on Cardiovascular Function.

Selenium (Se) is an essential trace element that is necessary for various metabolic processes, including protection against oxidative stress, and proper cardiovascular function. The role of Se in cardiovascular health is generally agreed upon to be essential yet not much has been defined in terms of specific functions. Se deficiency was first associated with Keshan's Disease, an endemic disease characterized by cardiomyopathy and heart failure. Since then, Se deficiency has been associated with multiple cardiovascular diseases, including myocardial infarction, heart failure, coronary heart disease, and atherosclerosis. Se, through its incorporation into selenoproteins, is vital to maintain optimal cardiovascular health, as selenoproteins are involved in numerous crucial processes, including oxidative stress, redox regulation, thyroid hormone metabolism, and calcium flux, and inadequate Se may disrupt these processes. The present review aims to highlight the importance of Se in cardiovascular health, provide updated information on specific selenoproteins that are prominent for proper cardiovascular function, including how these proteins interact with microRNAs, and discuss the possibility of Se as a potential complemental therapy for prevention or treatment of cardiovascular disease.

Curcumin and cardiovascular diseases: Focus on cellular targets and cascades.

Cardiovascular diseases (CVDs) are one of the leading causes of the most considerable mortality globally, and it has been tried to find the molecular mechanisms and design new drugs that triggered the molecular target. Curcumin is the main ingredient of Curcuma longa (turmeric) that has been used in traditional medicine for treating several diseases for years. Numerous investigations have indicated the beneficial effect of Curcumin in modulating multiple signaling pathways involved in oxidative stress, inflammation, apoptosis, and proliferation. The cardiovascular protective effects of Curcumin against CVDs have been indicated in several studies. In the current review study, we provided novel information on Curcumin's protective effects against various CVDs and potential molecular signaling targets of Curcumin. Nonetheless, more studies should be performed to discover the exact molecular target of Curcumin against CVDs.

Vitamin D and Vascular Disease.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Vitamin D deficiency has been identified as a potential risk factor for a number of diseases unrelated to the classical skeletal pathophysiology, such as cancer and CVD, but the effects of vitamin D supplementation are less clear. Purpose of this narrative review is to discuss the evidence suggesting an association between vitamin D status and CVD as well as the results of supplementation studies. Vitamin D deficiency has been associated with CVD risk factors such as hypertension, dyslipidemia and diabetes mellitus as well as with cardiovascular events such as myocardial infarction, stroke and heart failure. While vitamin D deficiency might contribute to the development of CVD through its association with risk factors, direct effects of vitamin D on the cardiovascular system may also be involved. Vitamin D receptors are expressed in a variety of tissues, including cardiomyocytes, vascular smooth muscle cells and endothelial cells. Moreover, vitamin D has been shown to affect inflammation, cell proliferation and differentiation. While observational studies support an association between low plasma vitamin D levels and increased risk of CVD, Mendelian randomization studies do not support a causal association between the two. At present, high quality randomized trials do not find evidence of significant effects on CVD endpoints and do not support supplementation of vitamin D to decrease CVD events.

Effect of Standardized Hydroalcoholic Extract of Saffron Stamen on High Blood Pressure and Baroreflex Sensitivity in Anesthetized Rats.

OBJECTIVE: The stamen is a byproduct of saffron (Crocus sativus) flowers. Herein, its cardiovascular effects were evaluated on hypertension induced by angiotensin II (AngII) and NG-nitro-Larginine methyl ester (L-NAME), as well as baroreflex sensitivity (BRS). METHODS: Rats were randomly divided into 10 groups: 1) control, 2) AngII (50 ng/kg, i.v.), 3) losartan (10 mg/kg, i.p.) + AngII, 4) L-NAME (10 mg/kg, i.v.), 5) sodium nitroprusside (SNP) (50 mg/kg, i.p.) + L-NAME, 6, 7) saffron stamen extract (SS) (100 and 200 mg/kg, i.p.) + AngII and 8, 9) SS (100 and 200 mg/kg) + L-NAME, and 10) SS (200 mg/kg) + phenylephrine (Phen, i.v.). The treated rats first received two doses of SS, 30 min after the injection of L-NAME, AngII, and Phen in separate groups. The cardiovascular parameters were recorded by the PowerLab apparatus via an angiocatheter inserted into the femoral artery. The maximal changes (Δ) of mean arterial pressure (MAP), systolic blood pressure (SBP), and heart rate (HR) in the treated groups were compared with those of the hypertensive and control groups. The changes in MAP and HR induced by Phen were used for BRS evaluation. RESULTS: The SS extract did not significantly affect the basal cardiovascular parameters. The injection of AngII significantly increased the MAP and SBP (P<0.01-P<0.001) with no significant effect on the HR. The SS extract significantly attenuated the pressor effect induced by AngII (P<0.001). Increased MAP and SBP induced by L-NAME (P<0.001) were also significantly attenuated by the SS extract (P<0.01). The effect of SS extract on L-NAME was significantly higher than that of AngII (P<0.05). Moreover, BRS was significantly improved by the SS extract. CONCLUSION: Our findings provide evidence that the SS extract has anti-hypertensive effects that are probably mediated by an inhibitory effect on AngII, increasing nitric oxide production, or improving baroreflex sensitivity.

The importance of selenium and zinc deficiency in cardiovascular disorders.

Cardiovascular diseases often linked with lifestyle are among the main causes of death, especially in the elderly population. The role of trace elements in health and disease has been emphasized in multiple scientific research. Moreover, supplementation of trace elements to improve health is becoming increasingly popular. The following paper presents current views on the relationship between the concentration of trace elements such as selenium and zinc in the body, as well as morphology and function of the cardiovascular system. Research discussing the effect of selenium and zinc supplementation on the function of the heart and blood vessels was also reviewed. The relationship between selenium and zinc concentration and morphology and function of the cardiovascular system is equally unclear, and therefore there is currently no scientific evidence for its supplementation for preventing cardiovascular diseases. It seems justified to continue scientific research on this subject due to the small number of experimental studies available on the topic of selenium and zinc deficiency and their impact on the cardiovascular system.

The Possible Regulatory Mechanisms of Aqueous, Ethyl Acetate and NHexane Fractions of the Ribes khorassanicum Extract on Acute Hypertension in Rats.

OBJECTIVE: Our previous studies showed the antihypertensive effect of Ribes khorassanicum (R. khorassanicum), a medicinal herb growing in the North Khorasan Province of Iran. For further evaluation, the present study investigated the effect of n-hexane (HX), ethyl acetate (EA), and aqueous (AQ) fractions of hydroalcoholic R. khorassanicum extract on cardiovascular responses in angiotensin II (AngII) and NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. METHODS: Wistar rats were randomly divided into 11 groups (n=5): 1) control, 2) AngII (50 ng/kg, i.v), 3) AngII + losartan (Los, 10 mg/kg, i.p), 4) L-NAME (10 mg/kg, i.v), 5) L-NAME+ sodium nitroprusside (SNP) (50 mg/kg, i.p), 6, 7, 8) one dose of each fraction of R. khorassanicum (AQ/EA/HX (50 mg/kg, i.p)) +AngII, Los 9, 10, 11) one dose of each fraction of R. khorassanicum (AQ/EA/HX (50 mg/kg, i.p)) + L-NAME. Treated rats received three fractions 30 min before the injection of L-NAME and AngII in separate groups. The cardiovascular parameters were recorded by the Power Lab instrument via an angiocath inserted into the femoral artery. The peak changes (Δ) of Mean Arterial Pressure (MAP), Systolic Blood Pressure (SBP), and Heart Rate (HR) in treated groups were compared with those of the hypertensive and control groups. RESULT: AngII and L-NAME significantly increased ΔMAP and ΔSBP and attenuated by pretreatment of Los and SNP, respectively. Pretreatment with polar (AQ) and semipolar (EA) fractions of R. khorassanicum reduced the peak changes of MAP and SBP in both AngII and L-NAME-treated groups. Only the fraction of the herb attenuated the HR increased in the L-NAME group. The HR in other groups did not demonstrate any significant difference. CONCLUSION: All fractions of R. khorassanicum have an antihypertensive effect. However, the effect of polar fractions is more salient. It is also conceivable that the antihypertensive effect of fractions is mostly mediated by the inhibition of AngII.

Clinical approach to the inflammatory etiology of cardiovascular diseases.

Inflammation is an obligatory marker of arterial disease, both stemming from the inflammatory activity of cholesterol itself and from well-established molecular mechanisms. Raised progenitor cell recruitment after major events and clonal hematopoiesis related mechanisms have provided an improved understanding of factors regulating inflammatory phenomena. Trials with inflammation antagonists have led to an extensive evaluation of biomarkers such as the high sensitivity C reactive protein (hsCRP), not exerting a causative role, but frequently indicative of the individual cardiovascular (CV) risk. Aim of this review is to provide indication on the anti-inflammatory profile of agents of general use in CV prevention, i.e. affecting lipids, blood pressure, diabetes as well nutraceuticals such as n-3 fatty acids. A crucial issue in the evaluation of the benefit of the anti-inflammatory activity is the frequent discordance between a beneficial activity on a major risk factor and associated changes of hsCRP, as in the case of statins vs PCSK9 antagonists. In hypertension, angiotensin converting enzyme inhibitors exert an optimal anti-inflammatory activity, vs the case of sartans. The remarkable preventive activity of SLGT-2 inhibitors in heart failure is not associated with a clear anti-inflammatory mechanism. Finally, icosapent ethyl has been shown to reduce the CV risk in hypertriglyceridemia, with a 27 % reduction of hsCRP. The inflammation-based approach to arterial disease has considerably gained from an improved understanding of the clinical diagnostic strategy and from a better knowledge on the mode of action of numerous agents, including nutraceuticals.

Cardiovascular diseases: a therapeutic perspective around the clock.

Biological rhythms are a ubiquitous feature of life. Most bodily functions, including physiological, biochemical, and behavioral processes, are coupled by the circadian rhythm. In the cardiovascular system, circadian fluctuations regulate several functions, namely heart rate, blood pressure, cardiac contractility, and metabolism. In fact, current lifestyles impose external timing constraints that clash with our internal circadian physiology, often increasing the risk of cardiovascular disease (CVD). Still, the mechanisms of dysregulation are not fully understood because this is a growing area of research. In this review, we explore the modulatory role of the circadian rhythms on cardiovascular function and disease as well as the role of chronotherapy in the context of CVD and how such an approach could improve existing therapies and assist in the development of new ones.

Safety of Short-Term Supplementation with Methylliberine (Dynamine®) Alone and in Combination with TeaCrine® in Young Adults.

Methylliberine (Dynamine®; DYM) and theacrine (Teacrine®; TCR) are purine alkaloids purported to have similar neuro-energetic effects as caffeine. There are no published human safety data on DYM, and research on TCR is limited. The purpose of this study was to examine the effect of four weeks of DYM supplementation with and without TCR on cardiovascular function and blood biomarkers. One-hundred twenty-five men and women (mean age 23.0 yrs, height 169.7 cm, body mass 72.1 kg; n = 25/group) were randomly assigned to one of five groups: low-dose DYM (100 mg), high-dose DYM (150 mg), low-dose DYM with TCR (100 mg + 50 mg), high-dose DYM with TCR (150 mg + 25 mg) , and placebo. Regardless of group and sex, significant main effects for time were noted for heart rate, systolic blood pressure, and QTc (p < 0.001), high-density lipoproteins (p = 0.002), mean corpuscular hemoglobin (p = 0.018), basophils (p = 0.006), absolute eosinophils (p = 0.010), creatinine (p = 0.004), estimated glomerular filtration rate (p = 0.037), chloride (p = 0.030), carbon dioxide (p = 0.023), bilirubin (p = 0.027), and alanine aminotransferase (p = 0.043), among others. While small changes were found in some cardiovascular and blood biomarkers, no clinically significant changes occurred. This suggests that DYM alone or in combination with TCR consumed at the dosages used in this study does not appear to negatively affect markers of health over four weeks of continuous use.

Effects of fish oil and curcumin supplementation on cerebrovascular function in older adults: A randomized controlled trial.

BACKGROUND AND AIMS: Chronic conditions such as obesity, which contribute to endothelial dysfunction in older adults, can cause impairments in cerebrovascular perfusion, which is associated with accelerated cognitive decline. Supplementing the diet with bioactive nutrients that can enhance endothelial function, such as fish oil or curcumin, may help to counteract cerebrovascular dysfunction. METHODS AND RESULTS: A 16-week double-blind, randomized placebo-controlled trial was undertaken in 152 older sedentary overweight/obese adults (50-80 years, body mass index: 25-40 kg/m2) to investigate effects of fish oil (2000 mg docosahexaenoic acid + 400 mg eicosapentaenoic acid/day), curcumin (160 mg/day) or a combination of both on cerebrovascular function (measured by Transcranial Doppler ultrasound), systemic vascular function (blood pressure, heart rate and arterial compliance) and cardiometabolic (fasting glucose and blood lipids) and inflammatory (C-reactive protein) biomarkers. The primary outcome, cerebrovascular responsiveness to hypercapnia, was not affected by the interventions. However, cerebral artery stiffness was significantly reduced in males following fish oil supplementation (P = 0.007). Furthermore, fish oil reduced heart rate (P = 0.038) and serum triglycerides (P = 0.006) and increased HDL cholesterol (P = 0.002). Curcumin did not significantly affect these outcomes either alone or in combination with fish oil. CONCLUSION: Regular supplementation with fish oil but not curcumin improved biomarkers of cardiovascular and cerebrovascular function. The combined supplementation did not result in additional benefits. Further studies are warranted to identify an efficacious curcumin dose and to characterize (in terms of sex, BMI, cardiovascular and metabolic risk factors) populations whose cerebrovascular and cognitive functions might benefit from either intervention. CLINICAL TRIAL REGISTRATION: ACTRN12616000732482p.

Role of Vitamin D in Athletes and Their Performance: Current Concepts and New Trends.

We are currently experiencing a vitamin D (VITD) deficiency pandemic across the world. Athletes have the same predisposition to low levels of vitamin D, the majority of its concentrations being below 20 ng/mL in a wide range of sports, especially in the winter months. Vitamin D is important in bone health, but recent research also points out its essential role in extraskeletal functions, including skeletal muscle growth, immune and cardiopulmonary functions and inflammatory modulation, which influence athletic performance. Vitamin D can also interact with extraskeletal tissues to modulate injury recovery and also influence the risk of infection. The data presented in this paper has triggered investigations in relation to the importance of maintaining adequate levels of vitamin D and to the possible positive influence supplementation has on immune and musculoskeletal functions in athletes, benefiting their performance and preventing future injuries. The objective of this review is to describe the latest research conducted on the epidemiology of vitamin D deficiency and its effects on sports performance and musculoskeletal health.

Effect of vitamin D3 supplementation on vascular and metabolic health of vitamin D-deficient overweight and obese children: a randomized clinical trial.

BACKGROUND: Obese children are vulnerable to vitamin D deficiency and impaired cardiovascular health; vitamin D replenishment might improve their cardiovascular health. OBJECTIVES: The aims were to determine, in vitamin D-deficient overweight and obese children, whether supplementation with vitamin D3 1000 or 2000 IU/d is more effective than 600 IU/d in improving arterial endothelial function, arterial stiffness, central and systemic blood pressure (BP), insulin sensitivity (1/fasting insulin concentration), fasting glucose concentration, and lipid profile and to explore whether downregulation of adipocytokines and markers of systemic inflammation underlies vitamin D effects. METHODS: We conducted a randomized, double-masked, controlled clinical trial in 225 10- to 18-y-old eligible children. Change in endothelial function at 6 mo was the primary outcome. RESULTS: Dose-response increases in serum 25-hydroxyvitamin D concentrations were significant and tolerated without developing hypercalcemia. Changes at 3 and 6 mo in endothelial function, arterial stiffness, systemic-systolic BP, lipids, and inflammatory markers did not differ between children receiving 1000 or 2000 IU vitamin D and children receiving 600 IU. Some secondary outcomes differed between groups. Compared with the 600-IU group, central-systolic, central-diastolic, and systemic-diastolic BP was lower at 6 mo in the 1000-IU group [-2.66 (95% CI: -5.27, -0.046), -3.57 (-5.97, -1.17), and -3.28 (-5.55, -1.00) mm Hg, respectively]; insulin sensitivity increased at 3 and 6 mo and fasting glucose concentration declined at 6 mo (-2.67; 95% CI: -4.88, -0.46 mg/dL) in the 2000-IU group. CONCLUSIONS: Correction of vitamin D deficiency in overweight and obese children by vitamin D3 supplementation with 1000 or 2000 IU/d versus 600 IU/d did not affect measures of arterial endothelial function or stiffness, systemic inflammation, or lipid profile, but resulted in reductions in BP and fasting glucose concentration and in improvements in insulin sensitivity. Optimization of children's vitamin D status may improve their cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01797302.

Herbal Medicine for Slowing Aging and Aging-associated Conditions: Efficacy, Mechanisms and Safety.

Aging and aging-associated diseases are issues with unsatisfactory answers in the medical field. Aging causes important physical changes which, even in the absence of the usual risk factors, render the cardiovascular system prone to some diseases. Although aging cannot be prevented, slowing down the rate of aging is entirely possible to achieve. In some traditional medicine, medicinal herbs such as Ginseng, Radix Astragali, Ganoderma lucidum, Ginkgo biloba, and Gynostemma pentaphyllum are recognized by the "nourishing of life" and their role as anti-aging phytotherapeutics is increasingly gaining attention. By mainly employing PubMed here we identify and critically analysed 30 years of published studies focusing on the above herbs' active components against aging and aging-associated conditions. Although many plant-based compounds appear to exert an anti-aging effect, the most effective resulted in being flavonoids, terpenoids, saponins, and polysaccharides, which include astragaloside, ginkgolide, ginsenoside, and gypenoside specifically covered in this review. Their effects as antiaging factors, improvers of cognitive impairments, and reducers of cardiovascular risks are described, as well as the molecular mechanisms underlying the above-mentioned effects along with their potential safety. Telomere and telomerase, PPAR-α, GLUTs, FOXO1, caspase-3, bcl-2, along with SIRT1/AMPK, PI3K/Akt, NF-κB, and insulin/insulin-like growth factor-1 pathways appear to be their preferential targets. Moreover, their ability to work as antioxidants and to improve the resistance to DNA damage is also discussed. Although our literature review indicates that these traditional herbal medicines are safe, tolerable, and free of toxic effects, additional well-designed, large-scale randomized control trials need to be performed to evaluate short- and long-term effects and efficacy of these medicinal herbs.

Inorganic Nitrate Supplementation for Cardiovascular Health.

Nitric oxide (NO) is continually produced by the enzyme nitric oxide synthase (NOS) and is essential to the control and effectiveness of the cardiovascular system. However, there is a substantial reduction in NOS activity with aging that can lead to the development of hypertension and other cardiovascular complications. Fortunately, NO can also be produced by the sequential reduction of inorganic nitrate to nitrite and then to NO. Nitric oxide from inorganic nitrate supplementation has been found to have the same cardioprotective benefits of NO produced by NOS. Moreover, it can effectively compensate for declining NOS activity due to aging or NOS inhibition by oxidative stress, hypoxia, or other factors. This review covers some of the major cardiovascular regulatory actions of NO and presents evidence that NO from inorganic nitrate supplementation can provide (1) compensation when NOS activity is inadequate, and (2) cardioprotective benefits beyond that provided by a healthy NOS system. In addition, it discusses how to obtain a safe and efficacious range of inorganic nitrate.

Impact of a Stroke Recovery Program Integrating Modified Cardiac Rehabilitation on All-Cause Mortality, Cardiovascular Performance and Functional Performance.

OBJECTIVE: Using a feasibility analysis and matched subgroup analysis, this study investigated the implementation/safety/outcomes of a stroke recovery program (SRP) integrating modified cardiac rehabilitation for stroke survivors. DESIGN: This prospective cohort study of 783 stroke survivors were discharged from an inpatient rehabilitation facility to an outpatient setting; 136 SRP-participants completed a feasibility study and received the SRP including modified cardiac rehabilitation, 473 chose standard of care rehabilitation (nonparticipants), and a group (n = 174) were excluded. The feasibility study assessed the following: safety/mortality/pre-post cardiovascular performance/pre-post function/patient/staff perspective. In addition to the feasibility study, a nonrandomized subgroup analysis compared SRP-participants (n = 76) to matched pairs of nonparticipants (n = 66, with 10 nonparticipants used more than once) for mortality/pre-post function. RESULTS: The feasibility study showed the SRP to have the following (a) excellent safety, (b) markedly low 1-yr poststroke mortality from hospital admission (1.47%) compared with national rate of 31%, (c) improved cardiovascular performance over 36 sessions (103% increase in metabolic equivalent of tasks times minutes), (d) improved function in Activity Measure of Post-Acute Care domains (P < 0.001), (e) positive reviews from SRP-participants/staff. Subgroup analysis showed the SRP to (a) positively impact mortality, nonparticipants had a 9.09 times higher hazard of mortality (P = 0.039), and (b) improve function in Activity Measure of Post-Acute Care domains (P < 0.001). CONCLUSIONS: Stroke survivors receiving a SRP integrating modified cardiac rehabilitation may potentially benefit from reductions in all-cause mortality and improvements in cardiovascular performance and function.

Dispositional mindfulness predicts cortisol, cardiovascular, and psychological stress responses in adolescence.

BACKGROUND: Past studies investigating the link between mindfulness and stress responding (i.e., emotional, psychological, and physiological responses to perceived threat or challenge) have focused on mindfulness training and on adult populations. In addition, research has not directly examined whether high mindfulness is particularly beneficial under conditions of high stress. To fill these gaps, the current study examined whether dispositional mindfulness predicts reduced cortisol, psychological, and cardiovascular stress responding in adolescence, and whether these effects are moderated by perceived life stress. METHODS: Adolescents (N = 150; 14-21yrs) completed measures of dispositional mindfulness, perceived life stress, emotional reactivity, and appraisals of the Trier Social Stress Test (TSST). Cortisol and blood pressure responses were measured. RESULTS: Higher dispositional mindfulness predicted reduced emotional and cardiovascular responding to the TSST, as well as less-negative task appraisals. In contrast, higher dispositional mindfulness predicted greater cortisol reactivity (or increases in cortisol in response to the TSST), particularly for adolescents experiencing lower perceived life stress. CONCLUSION: These findings add to the body of literature indicating that greater mindfulness predicts improved stress responding, but do not suggest that mindfulness buffers the effects of high stress on adolescent stress responding.

Clinical inertia in hypertension: a new holistic and practical concept within the cardiovascular continuum and clinical care process.

Purpose: Recognition of clinical inertia is essential to improve the control of chronic diseases. Although it is very intuitive, a better interpretation of the concept of clinical inertia is lacking, likely due to its high complexity. Materials and Methods: After a review of the published articles, we propose a practical vision of inertia, contextualized within the clinical process of hypertension care. Results: This new vision enables the integration of previous terms and definitions of clinical inertia, as well as proposing specific strategies for its reduction. Conclusion: Although some concepts should be considered as 'justified inertia' or 'investigator inertia', the idea that inertia may be present throughout the continuum of care gives physicians a holistic view of the problem that is easily applicable to their clinical practice. Measures to overcome inertia are complicated because of the intrinsic complexity of the concept.

Calcium and Vitamin D Supplementation. Myths and Realities with Regard to Cardiovascular Risk.

Vitamin D and calcium are considered crucial for the treatment of bone diseases. Both vitamin D and calcium contribute to bone homeostasis but also preserve muscle health by reducing the risk of falls and fractures. Low vitamin D concentrations result in secondary hyperparathyroidism and contribute to bone loss, although the development of secondary hyperparathyroidism varies, even in patients with severe vitamin D deficiency. Findings from observational studies have shown controversial results regarding the association between bone mineral density and vitamin D/calcium status, thus sparking a debate regarding optimum concentrations of 25-hydroxyvitamin D and calcium for the best possible skeletal health. Although most of the intervention studies reported a positive effect of supplementation with calcium and vitamin D on bone in patients with osteoporosis, this therapeutic approach has been a matter of debate regarding potential side effects on the cardiovascular (CV) system. Thus, the aim of this review is to consider the current evidence on the physiological role of vitamin D and calcium on bone and muscle health. Moreover, we provide an overview on observational and interventional studies that investigate the effect of vitamin D and calcium supplementation on bone health, also taking into account the possible CV side-effects. We also provide molecular insights on the effect of calcium plus vitamin D on the CV system.