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Hawthorn extract for treating chronic heart failure
Abstract
Hawthorn extract (made from the dried leaves, flowers and fruits of the hawthorn bush) may be used as an oral treatment option for chronic heart failure. In this review, 14 double-blind, placebo controlled randomised clinical trials (RCTs) were found. They did not all measure the same outcomes and several did not explain what other heart failure treatments patients were receiving. Those trials that could be included in a meta-analysis showed improvements in heart failure symptoms and in the function of the heart. The results, therefore, are suggestive of a benefit from hawthorn extract used in addition to conventional treatments for chronic heart failure.
... Traditional European medicine also emphasizes hawthorn's medicinal importance. In the early 19th century, Irish doctors observed hawthorn's effectiveness in treating heart conditions, which led to its subsequent incorporation into the British Herbal Pharmacopoeia [87,88]. The Crataegus genus boasts over 280 species [89], creating a broad spectrum of plant types with similar medicinal properties. ...
... Hawthorn's rich phytochemical composition underpins its therapeutic potential, particularly concerning cardiovascular health [93]. The primary bioactive compounds in hawthorn include flavonoids, oligomeric procyanidins, and triterpene acids, all contributing protective effects on cardiac and vascular health [80,87]. Flavonoids are a class of polyphenols recognized for their potent antioxidant properties [94]. ...
... There are an array of clinical trials affirming the beneficial potential of hawthorn in navigating conditions such as heart failure and hypertension, amongst other CVDs. A comprehensive meta-analysis spearheaded by Pittler et al. attests to the medicinal potential of hawthorn extract regarding chronic heart failure [87]. They delve into ten randomized clinical trials encompassing 855 patients, concluding that hawthorn extract brings about a marked increase in maximal workload, exercise tolerance, and ejection fraction. ...
Cardiovascular diseases are a broadly understood concept focusing on vascular and heart dysfunction. Lack of physical exercise, type 2 diabetes, obesity, hypertension, dyslipidemia, thromboembolism, and kidney and lung diseases all contribute to the development of heart and blood vessel dysfunction. Although effective and important, traditional treatment with diuretics, statins, beta blockers, calcium inhibitors, ACE inhibitors, and anti-platelet drugs remains a second-line treatment after dietary interventions and lifestyle changes. Scientists worldwide are still looking for an herbal product that would be effective and free from side effects, either taken together with or before the standard pharmacological intervention. Such herbal-originated medication therapy may include Morus alba L. (white mulberry), Elaeagnus rhamnoides (L.) A. Nelson (sea-buckthorn), Allium sativum L. (garlic), Convallaria majalis L. (lily of the valley), Leonurus cardiaca L. (motherwort), and Crataegus spp. (hawthorn). Valuable herbal raw materials include leaves, fruits, seeds, and even thorns. This short review focuses on six herbs that can constitute an interesting and potential therapeutic option in the management of cardiovascular disorders.
... European traditional medicine also emphasizes hawthorn's medicinal importance. During the early 19 th century, Irish doctors observed hawthorn's effectiveness in treating heart conditions, which led to its subsequent incorporation into the British Herbal Pharmacopoeia [90,91]. The Crataegus genus boasts over 280 species [92], creating a broad spectrum of plant types possessing similar medicinal properties. ...
... Hawthorn's rich phytochemical composition underpins its therapeutic potential, particularly concerning cardiovascular health [96]. The primary bioactive compounds in hawthorn include flavonoids, oligomeric procyanidins, and triterpene acids, all contributing protective effects on cardiac and vascular health [82,90]. Flavonoids are a class of polyphenols recognized for their potent antioxidant properties [97]. ...
... There is an array of clinical trials affirming the beneficial potential of hawthorn in navigating conditions such as heart failure and hypertension, amongst other CVDs. A comprehensive metaanalysis spearheaded by Pittler et al., attests to the medicinal potential of hawthorn extract regarding chronic heart failure [90]. They delved into ten randomized clinical trials encompassing 855 patients, concluding that hawthorn extract brings about a marked increase in maximal workload, exercise tolerance, and ejection fraction. ...
Cardiovascular diseases are a broadly understood concept focusing on vascular and heart dys-function. Lack of physical exercise, type 2 diabetes, obesity, hypertension, dyslipidemia, throm-boembolism, kidney, and lung diseases all contribute to the development of heart and blood vessel dysfunction. Although effective and important, traditional treatment with diuretics, statins, beta–blockers, calcium inhibitors, ACE inhibitors, and anti–platelet drugs remain a second–line treatment after dietary intervention and lifestyle changes. Scientists worldwide are still looking for an herbal product that would be quite effective and free from side effects, either taken together or before the standard pharmacological intervention. Such herbal–originated medication therapy may include Morus alba L. (white mulberry), Elaeagnus rhamnoides (L.) A. Nelson (sea–buckthorn), Allium sativum L. (garlic), Convallaria majalis L. (lily of the valley), Leonurus cardiaca L. (mother-wort), and Crataegus spp. (hawthorn). Valuable herbal raw materials include leaves, fruits, seeds, and even thorns. This short review focuses on six herbs that can constitute an interesting and po-tential therapeutic option in the management of cardiovascular disorders.
... A significant amount of preclinical and clinical research has been performed to scientifically underpin the traditional use of Crataegus in the treatment of heart failure; the first clinical trials date back to the 1990s [4,7,[22][23][24][25][26][27][28][29][30]. Leaf and flower extracts have been approved by the German Commission E for cardiac failure stage II according to the New York Heart Association (NYHA) [31,32]. ...
... The similar incidence rates of adverse reactions between the placebo and Crataegus groups, as reported in the studies included in the scoping, may suggest that Crataegus products are safe to use. This is in line with other reviews describing that either mild or no adverse reactions were associated with the use of Crataegus-containing products [3,7,28,29,46,84,85]. However, it is important to realise and to take into consideration that serious adverse reactions have been reported during the pharmacovigilance of Crataegus-containing products. ...
Background/Objectives: Products from various parts of Crataegus species are traditionally applied as a cardiotonic. In Europe and the USA, mainly Crataegus monogyna Jacq. (Lindm.) and Crataegus laevigata (Poir.) DC (synonym Crataegus oxyacantha L.) are used, but worldwide, other Crataegus species are also used. Phytotherapeutic preparations with a standardised content of flavonoids and/or oligomeric procyanidins are commercially available. The products are generally considered as safe and are at most associated with minor and atypical adverse reactions. The aim of this study was to critically assess the information about the safety of Crataegus-containing products in humans. Methods: A scoping review of the literature about adverse reactions associated with Crataegus-containing products was performed. Next, individual case safety reports (ICSRs) were assessed, which were included in VigiBase (the World Health Organisation’s global database of adverse event reports for medicines and vaccines) and in the database of the Netherlands Pharmacovigilance Centre Lareb. The findings are discussed in relation to the literature. Results: The scoping review yielded 23 clinical studies with single-herb and 14 with multi-herb preparations, from which only a few minor gastrointestinal and cardiac events had been reported. A total of 1527 reports from VigiBase, from 1970 to 2023, were analysed, as well as 13 reports from Lareb. The most frequently reported adverse reactions belonged to the system organ classes ‘gastrointestinal disorders’, ‘skin and subcutaneous tissue disorders’, ‘general disorders and administration site conditions’, ‘cardiac disorders’ or ‘nervous system disorders’. In 277 reports of VigiBase, a single-herb product was the only suspect for causing the adverse reaction(s). Of these, 12.6% were graded as serious. Conclusions: The results of our study provide deeper insight in the adverse reaction profile of Crataegus-containing products and should contribute to their safe application in the treatment of less severe forms of cardiac failure.
... [9,[13][14][15][16]. Conflicting results were presented based on between-study variances, with values ranging from 0 to 24.56 (as shown in S2 Table) [17], despite some of these methods having similar methodologies. The majority of these methods are based on the method of moments [18]. ...
... Each study compares a treatment group with a control group. We select each sample sizes n ij randomly, (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), and generate observations for each group using μ i + z ij + θ j + e ijk . The data of z ij , θ j and e ijk are generated as independent and identically distributed with z ij � Nð0; s 2 z Þ, y j � Nð0; s 2 y Þ, and e ijk � Nð0; s 2 e Þ, respectively, i = 1, 2 and j denotes the number of studies. ...
Meta-analysis is a statistical technique that combines the results of different environmental experiments regarding the populations, location, time, and so on. These results will differ more than the within-study variance, and the true effects being evaluated differ between studies. Thus, heterogeneity is present and should be measured. There are different estimators that were introduced to estimate between-study variance, which has received a lot of criticism from previous researchers. All of the estimators encountered the same problem, which was the correlation. To minimize the potential biases caused by interventions between the three estimators (i.e., overall effect size, within-study variance, and between-study variance), we proposed a new measure of heterogeneity known as the Environmental Effect Ratio (EER), the treatment-by-lab variability relative to the experimental error, under individual participant data (IPD) using the linear mixed model approach. We assume different between-study variances instead of constant between-study variances. The simulation of this study focuses on the performance of meta-analyses with small sample sizes. We compared our proposed estimator under two different expressions (τ ^ 1 E E R 2, and τ ^ 2 E E R 2) with the best estimator nominated from previous studies to determine which one is the best performance. Based on the findings, our estimator (τ ^ 2 E E R 2) was better for estimating between-study variance.
... • There is a considerable body of research, in vitro, in vivo, and ex vivo, supporting its 2 cardiovascular effects (positive inotropic activity, ability to increase the integrity of the blood vessel wall and improve coronary blood flow, and positive effects on oxygen utilization) resulting in improved cardiac function, reduction in blood pressure, reduction in lipid levels, plus antioxidant effects (Tankanow et al. 2003;Daniele et al. 2006, Furey andTassell 2008;Guo et al. 2008;Tassell et al. 2010). • Flavonoids and procyanidins are considered the main pharmacologically active constituent fractions, including (to date) a wide range of individual active compounds such as hyperoside, vitexin, rutin, quercitrin, chlorogenic acid, ursolic acid, epicatechin, catechin, and procyanidins (B2, B5, C1) (Edwards et al. 2012;Jurikova et al. 2012;Wang et al. 2013;Wu et al. 2014). ...
... • Flavonoids and procyanidins are considered the main pharmacologically active constituent fractions, including (to date) a wide range of individual active compounds such as hyperoside, vitexin, rutin, quercitrin, chlorogenic acid, ursolic acid, epicatechin, catechin, and procyanidins (B2, B5, C1) (Edwards et al. 2012;Jurikova et al. 2012;Wang et al. 2013;Wu et al. 2014). • A recent Cochrane review by Guo et al. (2008) 2 supports a significant benefit in symptom control and physiologic outcomes from Crategus as an adjunctive treatment for chronic heart failure. A meta-analysis of 14 randomized, double-blind, placebo-controlled trials found that Crataegus was superior to placebo in its effects in the following areas: maximal workload, pressure-heart rate product, exercise tolerance, dyspnea, and fatigue. ...
Extracts of Crataegus spp. have been the subject of extensive in vivo and in vitro investigations, primarily for the treatment of cardiovascular diseases. Effects include antioxidant, hypolipidemic, hypotensive, positive inotropic activity, increased blood vessel wall integrity, improved coronary blood flow, and positive oxygen utilization, among others. Flavonoids and procyanidins are the principle constituents. This chapter reviews published English language scientific literature for evidence of indications of interactive combination effects including synergistic effects and/or multiple target effects within the body. Synergistic effects have only been reported using effect‐based measurement approaches. There was considerable diversity among the studies regarding their methodology, substrate type and their analysis, which made direct comparisons challenging. The authors suggest the need for universal use of consistent and standardized methods, using activity‐led, systems‐based reverse analysis or “omic” research, owing to the multifactorial requirements of plant‐based studies.
... A meta-analysis of monotherapy hawthorn trials reported that mostly mild to moderate adverse events were found in 5577 patients in the analysis, including dizziness/vertigo and gastrointestinal complaints, which were similar to those in our study. 39,40 There are a number of limitations in this study, such as not controlling all of the relevant variables, especially controlling the amount of calorie intake, which may have influenced the results. Besides, 15% (w/w) sucrose was added to the hawthorn beverage to improve the palatability and to avoid gastrointestinal reactions, which may not only increase the risk of weight gain and cardiovascular risk factors, but also mask the benefits of hawthorn itself. ...
Objectives: The purpose of this study was to examine the effect of hawthorn extract drink in mildly hypertensive and/or hyperlipidaemic Chinese patients. Methods: We performed a randomized double-blind placebo-controlled crossover study. Subjects who were randomly divided into 2 groups and asked to consume either hawthorn fruit extract drink or placebo with the same sugar content for 8-weeks with crossover to the alternative drink separated by a 4-weeks washout period. Adverse effects, lipid profile, fasting plasma glucose and blood pressure were recorded. Results: In 61 participants, body weight increased by mean (95% CI) 0.42 kg (−0.85, 1.69 kg) with the hawthorn drink and 0.94 kg (0.52, 1.36 kg) with placebo (P > .05). Systolic blood pressure and plasma total cholesterol increased significantly with both treatments and cholesterol sub-fractions showed no significant changes. Significant increases were seen in fasting plasma glucose with placebo. The increase in plasma glucose was reversed during the 4-week washout period. Conclusions: Although our results didn’t show significant effects of hawthorn drink compared to placebo, there was a trend toward fewer adverse metabolic effects. A longer study with hawthorn fruit extract without additional calories would be useful to determine if beneficial effects occur in patients with mild hyperlipidaemia or hypertension.
... The analysis indicated that hawthorn supplementation was associated with a significant reduction in both systolic and diastolic pressure. The research suggested that hawthorn could be considered an adjunct treatment for hypertension [7]. ...
Hypertension, a prevalent cardiovascular condition characterized by elevated blood pressure, poses a significant global health challenge. This paper reviews the potential of garlic, hibiscus, hawthorn, and olive leaf in reducing hypertension and improving one’s health. A survey was conducted among first year pharmacy students. The survey included 5 knowledge-based and 5 opinion-based questions, focusing on the four herbal remedies. The knowledge-based questions showed a correct answer rate of 61.1%, with the statement that garlic is generally safe to include in one’s diet, but excessive consumption can lead to adverse effects garnering a 91.1% correct response rate. 58.3% of the respondents failed to know the simple definition of hypertension. Opinion-based questions revealed a positive attitude towards herbal remedies with an average of 81% showing agreement on the potential benefits. Nearly 83% believed in consulting health professionals before integrating olive leaf extract, and about 89% agreed that garlic should be used as an approach to manage hypertension.
... [30] Hawthorn extract might aid in ameliorating heart failure symptoms and reducing blood pressure. [31] Resveratrol, found in red wine and select berries, boasts antioxidant properties and could enhance blood vessel function. [32] Alzheimer's disease Some research indicates that an increased consumption of Omega-3 fatty acids might lower the risk of cognitive decline in Alzheimer's disease. ...
Nutraceuticals, bridging nutrition and medicine, form a billion-dollar global industry. With dissatisfaction over costly medical treatments, consumers turn to healthier diets and nutraceuticals for an alternative. Recent scientific advances introduce concepts such as nutraceuticals, promising disease prevention, and reduced health-care costs. These compounds, categorized by natural sources, offer personalized, long-term solutions with a focus on holistic health. They play key roles in managing conditions from cardiovascular issues to neurodegenerative diseases, reducing oxidative stress, inhibiting cancer cell growth, and boosting cognitive function. As we look forward, genetics and personalized medicine will customize nutraceutical interventions, and the market for functional foods and plant-based nutraceuticals will expand as consumers seek healthier options. Ongoing research, technology, and regulatory standards will continue shaping healthcare’s future, making nutraceuticals a key player in disease prevention and holistic well-being
... According to the intervention review by Pittler and co-workers [182], which included randomized, placebo-controlled, double-blind trials, parameters such as heart working capacity (physiologic outcome of maximal workload, exercise tolerance, shortness of breath and fatigue) have been improved. Moreover, Crataegus showed hypotensive activity and enhanced an index of cardiac oxygen consumption. ...
Cardiovascular diseases are the leading cause of mortality worldwide. The World Health Organization has presented alarming data stating that in 2019, 17.9 million people globally died due to cardiovascular diseases, constituting 32% of all deaths. Despite increasingly advanced pharmacological and procedural treatment methods for these diseases, there is still a quest for new therapeutic possibilities that promise even greater efficacy and safety. The overriding purpose of this study is to provide an insight into the traditional uses of species from the Apiaceae and Rosaceae families as well as to systematize knowledge regarding their scientifically proven cardiovascular activities (animal studies and clinical trials). The review is intended to indicate knowledge gaps for future studies concerning plants used in traditional medicine but without scientific research. As a result, various plant species from both Apiaceae and Rosaceae family have been collected and described based on their study that has proven their effectiveness and uses in cardiovascular diseases. Most of these plants have a hypotensive effect, followed by anti-hyperlipidemic, vasorelaxant, antithrombotic, and diuretic activity. These are the mechanisms that contribute to various cardiovascular diseases, such as heart attack, coronary heart disease, hypertension, and stroke.
... [30][31][32] Hawthorn extract improved exercise tolerance, decreased cardiac oxygen consumption, and improved shortness of breath and fatigue in patients with heart failure. [33] However, it failed to show a significant reduction in cardiac death, nonfatal myocardial infarction, and heart failure hospitalization. [34,35] Antioxidants, which include beta-carotene, anthocyanins, coenzyme Q10, flavonoids, lipoic acid, selenium, and vitamins C and E, looked to be promising in observational studies; however, a systematic review of large RCTs failed to find any significant beneficial effects of antioxidant supplements for primary or secondary prevention of CVDs. ...
The cardio-metabolic disorders are now the leading cause of morbidity and mortality all around the world. Though genetics play a role, most of these diseases have a causal relationship with smoking, environmental pollution, unhealthy food habits, sedentary lifestyle, and alcohol abuse. Poor mental state, depression, and stress have also been found to aggravate the risk to develop these diseases. These diseases are thus clubbed under diseases related to unhealthy lifestyle. The pathogenesis of these diseases is atherosclerosis or hardening of the blood vessels that occur due to constant inflammatory stress aggravated by the above-said risk factors. Since last decade, every third death is caused by a cardiovascular disease. Apart from high mortality, these are chronic disorders with no permanent cure requiring life-long medication and lifestyle changes. The patients suffering from these diseases not only undergo a decrease in their physical endurance and functional capacity but also suffer from depression, self-pity, and financial burden leading to an unhealthy lifestyle and a vicious cycle. This causes a huge burden on the health care system in the country and hence requires a wholesome approach to the prevention and management of these diseases. The integrated wellness encompasses the best of conventional medicine and evidence-based complementary medicine and lifestyle measures to provide the patient a wholesome management plan. This aims to a better patient-doctor relationship, better compliance, trust, and better lifestyle choices. The center of the integrated wellness remains the patient rather than the disease.
... Ethanolic extract and its fractions; dichloromethane and n -butanol. ↓BP; ↓LDL ( Guo et al., 2008 ), ( Tadi ć et al., 2008 ), ( Kocyildiz et al., 2006 ) ( continued on next page ) ↓BP; ↓G; ↓W. ( Tajmohammadi et al., 2018 ) BP; blood pressure, G; blood glucose, IS; insulin sensitivity, LDL; low density lipoprotein, TG; triglycerides, W; body weight. ...
Metabolic syndrome (MetS) is a bunch of metabolic defects comprising hypertension, insulin resistance, visceral obesity, fatty liver, and atherogenic cardiovascular diseases. Lifestyle modification is the first step for controlling the MetS progression. If left untreated, MetS is significantly related to a high danger of evolving type 2 diabetes and atherogenic cardiovascular diseases. Thus, MetS is a prominent cause of morbidity and mortality internationally and has been become very important to investigate novel therapies in this context to decrease the heavy burden of the disease. Though, there is no single treatment for MetS and the currently available pharmacother-apy and related comorbidities demand the continued use of multiple drugs that is challenging for patients as the polypharmacy and reduced accordance. There is increasing concern in the use of nutraceuticals in the management of MetS. This review follows MetS with an emphasis on the risk factors and how to control it, epidemiology, pathogenesis, pathophysiology, diagnosis, and treatments. Moreover, the review recaps on the health benefits of natural products in the management of the MetS to give a complete guide to other researchers for new natural products investigation. Novelty Statement MetS is significantly related to develop type 2 diabetes and car-diovascular diseases as well as MetS is considered a prominent reason of morbidity and mortality worldwide. Thus, it is critical to explore new treatments in this circumstance. However, there is no single treatment for MetS and the existing pharmacotherapy require the continuous use of numerous drugs that is challenging for patients as the polypharmacy and diminished accordance. There is rising interest in the utilization of nutraceuticals in the management of MetS. Also, the investigation of an efficient approach to manage those complications not studied well, where the authors highlighted this point in our manuscript. We presented in this review a wide information concerning the risk factors, patho
... Only one trial reported five deaths (three in the active group), but did not provide any details. 4 Another trial with 897 patients, who were treated with HRE, reported the occurrence of cardiac disorders at a frequency of 30% as a side effect. Nonetheless, the authors did not define the cardiac conditions, nor did the report provide further details on the nature of the side effects. ...
The use of extracts from the hawthorn plant as cardiovascular agents dates back to the 1st century; recently, they have also been made available online as weight loss aids. Herein, we present a case of intentional intoxication with hawthorn root extract (HRE) in an adult patient that resulted in death. A 20-year-old female patient, who was clinically diagnosed with depression, developed hypotension, bradycardia, and depressed consciousness after ingestion of this extract. An electrocardiogram recorded a sinus arrest with a slow nodal rhythm, which rapidly deteriorated, leading to cardiac arrest. This case report illustrates the potentially fatal consequences of HRE for which the constituents have not yet been characterized. All physicians, especially those in the emergency department, should be aware of the dangerous, even potentially fatal interactions of HRE with prescription medications.
... Hawthorn was utilized as an adjuvant to standard treatment for chronic heart failure in the majority of studies. When compared to placebo, symptoms like shortness of breath and exhaustion improved dramatically with hawthorn administration (Pittler et al. 2008;Sieniawska 2015). ...
Tannins are an interesting class of polyphenols, characterized, in almost all cases, by a different degree of polymerization, which, inevitably, markedly influences their bioavailability, as well as biochemical and pharmacological activities. They have been used for the process of tanning to transform hides into leather, from which their name derives. For several time, they have not been accurately evaluated, but now researchers have started to unravel their potential, highlighting anti-inflammatory, antimicrobial, antioxidant and anticancer activities, as well as their involvement in cardiovascular, neuroprotective and in general metabolic diseases prevention. The mechanisms underlying their activity are often complex, but the main targets of their action (such as key enzymes modulation, activation of metabolic pathways and changes in the metabolic fluxes) are highlighted in this review, without losing sight of their toxicity. This aspect still needs further and better-designed study to be thoroughly understood and allow a more conscious use of tannins for human health.
... Before resorting to a pharmacological approach, it is worth considering the use of botanicals, which is generally characterized by a lower incidence of side-effects, a reduced risk of real drug interactions, and consequently, greater ease of use [11] . bathmotropic action [21][22][23][24][25][26] . ...
Nutritional modulation can be a factor in sleep quality, with the potential to cause insomnia. Insomnia has negative consequences both on the outcomes of treatment and on health in general. In this retrospective case-control evaluation, individuals with insomnia likely induced by diet therapy treatment and with a reduced tolerance to Bromazepam therapy, were evaluated on the effects obtainable with the administration of a multi-layered, differentiated release nutraceutical formulation containing highly standardized and titrated extracts of valerian (Valeriana officinalis L.), passionflower (Passiflora incarnata L.) and hawthorn (Crataegus oxyacantha L.) distributed under the commercial name of Neurofast ®. A double-check was carried out against individuals with insomnia likely induced by diet therapy who were tolerant to Bromazepam therapy or who, by personal choice, preferred the use of nutraceuticals from the outset. The results demonstrate how the use of the nutraceutical product both as a first solution therapy and as a replacement for Bromazepam therapy significantly reduces insomnia and psychosomatic and autonomic symptoms. The Bromazepam therapy participants showed significantly effective, rapid results leading to complete remission of insomnia. When Bromazepam therapy was replaced with the nutraceutical product clinical remission was maintained, demonstrating a potentially comparable effect in the complete absence of rebound effect. Notably, the symptom 'morning sleepiness', which can be considered an adverse effect of Bromazepam, was detectable at a severe level in the Bromazepam therapy group but completely absent in nutraceuticals groups. The modified release multilayer nutraceutical formulation distributed under the trade name of Neurofast ® proves to be a safe and effective solution in the management of insomnia symptoms even in the presence of autonomic and psychosomatic symptoms. Further studies, more structured and carried out on a larger and selected sample with more stringent criteria, will be necessary to further clarify the aspects taken into consideration.
... Adding up, hawthorn extract acted as an adjunct in controlling symptoms of chronic heart failure treatment (Pittler, Guo, & Ernst, 2008). ...
... Hawthorn extract has traditionally been used as herbal remedy in complementary and alternative medicine [170]. Nowadays, hawthorn preparations are mostly used for the treatment of angina, hypertension, arrhythmias, congestive heart failure, and hyperlipidemia [171,172]. Only a few publications have examined the effect of C. monogyna on CNS. ...
Anxiety and insomnia are among the most common mental health disorders and are a
major cause of disability around the world. Traditional herbal medicines are receiving significant attention in global health debates. Several Italian regions maintain rural traditions and are among the most extensively studied areas of Europe regarding medicinal plant uses. The present overview aims to highlight the use of wild and cultivated plants, specifically as sedatives and for insomnia treatment in Italy, and to collect, analyze, and summarize the available literature about their pharmacological
activity as well as clinical and pre-clinical studies concerning the most cited plants. In total, 106 wild taxa are used in Italy for sedative purposes. The plant species belong to 76 genera and 32 families, of which the most cited are Asteraceae (24.2%) and Lamiaceae (21.1%). Leaves (29%) and flowers (27%) are the plant parts mostly used as infusion (70%) and decoction (25%). Out of 106 taxa documented, only the most cited are analyzed in this overview (A. arvensis L., C. nepeta L., C. monogyna Jacq., H. lupulus L., L. nobilis L., L. angustifolia Mill., M. sylvestris L., M. chamomilla L., M. officinalis L., O.
basilicum L., P. rhoeas L., P. somniferum L., R. officinalis L., T. platyphyllus Scop., and V. officinalis L.). Among the fifteen species selected, only seven have been studied for their pharmacological activity as hypnotic-sedatives. Future pre-clinical and clinical studies are needed to better clarify the mechanism of action of bioactive compounds and confirm the potential of these alternative therapies.
... Generally safe. Possible adverse events: gastrointestinal symptoms, dizziness, cardiac complaints [58]. ...
Vestibular disorders may generate complex signs and symptoms, which may alter pa-tients' balance and the quality of life. Dizziness and vertigo can strongly affect daily activities and relations. Despite the presence of conventional drugs, maneuvers, and surgery, another interesting therapeutic opportunity is offered by nutraceuticals. These molecules are often used in the treatment of dizziness and vertigo, but the rationale of their application is not always solidly demonstrated by the scientific evidence. Several substances have shown a variable level of efficacy/useful-ness in this field, but there is lack of important evidence for most of them. From a medico-legal point of view, specific information must be provided to the patient regarding the efficacy and possibilities that the use of these preparations can allow. Administering the right nutraceutical to the proper patient is a fundamental clinical skill. Integrating conventional drug treatment with nutraceutical administration seems to be easy, but it may be difficult considering the (in part unexplored) phar-macodynamics and pharmacokinetics of nutraceuticals. The aim of the scientific community should be to elevate nutraceuticals to the same law and technical dignity of conventional drugs.
... Finally, we included and analyzed 31 RCTs in the review. We also screened sixteen CSRs of CHF [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60]. ...
Background
Traditional Chinese medicine (TCM) has gained widespread application in treating chronic heart failure (CHF) secondary to coronary heart disease (CHD). However, the sound clinical evidence is still lacking. Corresponding clinical trials vary considerably in the outcome measures assessing the efficacy of TCM, some that showed the improvement of clinical symptoms are not universally acknowledged. Rational outcome measures are the key to evaluate efficacy and safety of each treatment and significant elements of a convincing clinical trial. We aimed to summarize and analyze outcome measures in randomized controlled trials (RCTs) of TCM in treating CHF caused by CHD, subsequently identify the present problems and try to put forward solutions.
Methods
We systematically searched databases including Embase, PubMed, Cochrane Library, CBM, CNKI, VIP and Wanfang from inception to October 8, 2018, to identify eligible RCTs using TCM interventions for treating CHF patients caused by CHD. Cochrane Database of Systematic Reviews (CDSR) was searched to include Cochrane systematic reviews (CSRs) of CHF. Two authors independently assessed the risk of bias of the included RCTs according to the Cochrane Handbook. Outcome measures of each trial were extracted and analyzed those compared with the CSRs. We also evaluated the reporting quality of the outcome measures.
Results
A total of 31 RCTs were included and the methodology quality of the studies was generally low. Outcome measures in these RCTs were mortality, rehospitalization, efficacy of cardiac function, left ventricular ejection fraction (LVEF), 6 min’ walk distance (6MWD) and Brain natriuretic peptide (BNP), of which mortality and rehospitalization are clinical end points while the others are surrogate outcomes. The reporting rate of mortality and rehospitalization was 12.90% (4/31), the other included studies reported surrogate outcomes. As safety measure, 54.84% of the studies reported adverse drug reactions. Two trials were evaluated as high in reporting quality of outcomes and that of the other 29 studies was poor due to lack of necessary information for reporting.
Conclusions
The present RCTs of TCM in treating CHF secondary to CHD did not concentrate on the clinical end points of heart failure, which were generally small in size and short in duration. Moreover, these trials lacked adequate safety evaluation, had low quality in reporting outcomes and certain risk of bias in methodology. For objective assessment of the efficacy and safety of TCM in treating CHF secondary to CHD, future research should be rigorous designed, set end points as primary outcome measures and pay more attention to safety evaluation throughout the trial.
... Different hawthorn species have been found to exert various effects in all populations. Those species are usually used in association with other drugs as antispasmodic, diuretic, febrifuge, hypertensive, analgesic, sedative, and antidepressant agents (Kirakosyan et al. 2003;Guo et al. 2008;Zhao et al. 2012;Ku et al. 2015;Li et al. 2015). As shown by Popovic-Milenkovic et al. 2014, Crataegus monogyna leaves and flowers contained a high abundance of flavonoids and displayed a significant biological effect (Mudge et al. 2016). ...
Crataegus monogyna is an important plant of the Rosaceae family, widely used in traditional medicine to treat various conditions such as cardiovascular diseases, cancer, diabetes, asthma, and nephritis. The aim of the current study was to assess the chemical composition, antioxidant, and antibacterial activity of leaves’ extracts against Bacillus cereus, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The total amounts of polyphenols and flavonoids contained in the dry extracts of plants were estimated by colorimetric methods. DPPH assay was utilized to measure the antioxidant activity of C. monogyna. The phytochemical compounds were determined through HPLC technique, and the minimum inhibitory concentration (MIC) of ethanol extract was performed using the broth dilution method. The ethanol extract represented the richest extract in polyphenol with 473.4 mg GAE g⁻¹ and flavonoids 80.9 mg CE g⁻¹ and showed considerable antioxidant potential IC50 =22.50 µg/ml. The antibacterial susceptibility test against Staphylococcus aureus 0.512 mg/mL.
... OPC-rich extracts of hawthorn (Crataegus oxyacantha) have long been employed in the clinical management of HF, and their high-molecular weight OPCs have likewise been found to activate eNOS in vitro via PI3K/Akt [307,308]. Although results of clinical studies with hawthorn extracts have yielded inconsistent results, a meta-analysis of randomized controlled trials has concluded that treatment with standardized OPC-rich hawthorn extracts can indeed confer symptomatic benefit in HF, increasing exercise capacity and lessening shortness of breath and fatigue [309]. ...
Although well documented drug therapies are available for the management of ventricular hypertrophy (VH) and heart failure (HF), most patients nonetheless experience a downhill course, and further therapeutic measures are needed. Nutraceutical, dietary, and lifestyle measures may have particular merit in this regard, as they are currently available, relatively safe and inexpensive, and can lend themselves to primary prevention as well. A consideration of the pathogenic mechanisms underlying the VH/HF syndrome suggests that measures which control oxidative and endoplasmic reticulum (ER) stress, that support effective nitric oxide and hydrogen sulfide bioactivity, that prevent a reduction in cardiomyocyte pH, and that boost the production of protective hormones, such as fibroblast growth factor 21 (FGF21), while suppressing fibroblast growth factor 23 (FGF23) and marinobufagenin, may have utility for preventing and controlling this syndrome. Agents considered in this essay include phycocyanobilin, N-acetylcysteine, lipoic acid, ferulic acid, zinc, selenium, ubiquinol, astaxanthin, melatonin, tauroursodeoxycholic acid, berberine, citrulline, high-dose folate, cocoa flavanols, hawthorn extract, dietary nitrate, high-dose biotin, soy isoflavones, taurine, carnitine, magnesium orotate, EPA-rich fish oil, glycine, and copper. The potential advantages of whole-food plant-based diets, moderation in salt intake, avoidance of phosphate additives, and regular exercise training and sauna sessions are also discussed. There should be considerable scope for the development of functional foods and supplements which make it more convenient and affordable for patients to consume complementary combinations of the agents discussed here. Research Strategy: Key word searching of PubMed was employed to locate the research papers whose findings are cited in this essay.
... 5 Exercise tolerance was shown to be significantly increased with hawthorn extract consumption and symptoms such as shortness of breath and fatigue improved. 6 Digoxin, a cardiac glycoside, is found in the foxglove plant (Digitalis lantana). The main pharmacologic effects of digoxin include a dose-dependent increase in myocardial contractility and a negative chronotropic action. ...
Context.—Hawthorn is an herb indicated for treating cardiac illness. Because a patient taking digoxin may also take hawthorn, we investigated potential interference of hawthorn in serum digoxin measurements using immunoassays as well as pharmacodynamic interaction between hawthorn and digoxin. Hawthorn contains alkaloids that are structurally similar to digoxin and may interfere with serum digoxin measurement using immunoassays. In addition, hawthorn has cardioactive properties similar to digoxin.
Objective.—To study potential pharmacodynamic interaction between hawthorn and digoxin.
Design.—The effects of hawthorn extract on serum digoxin measurements using Digoxin III (Abbott Laboratories, Abbott Park, Illinois) and the Tina-Quant digoxin assay (Roche Diagnostics, Indianapolis, Indiana) were investigated using 2 different brands of extract. To study the pharmacodynamic interaction between hawthorn and digoxin, we used an isolated adult rat cardiomyocyte system, measuring calcium transients by real-time fluorescence spectrophotometry.
Results.—Hawthorn interfered only with the Digoxin III immunoassay but had no effect on the Tina-Quant assay. Both hawthorn extracts increased intracellular calcium levels, but the lack of additive response with digoxin suggests both may bind to the same site of Na, K adenosine triphosphatase.
Conclusion.—Because of interference of hawthorn with a digoxin immunoassay and pharmacodynamic interaction with digoxin, a patient receiving digoxin should avoid hawthorn.
... More recently it has been used for the treatment of various cardiovascular diseases such as high cholesterol (Dalli, Colomer, et al., 2011;Littleton et al., 2013;Littleton, Miller, & Hove, 2012), platelet anti-aggregation (Dalli, Vallés, et al., 2011), tachycardia, hypertension and arteriosclerosis (Guo et al., 2008;Holubarsch et al., 2008;Long et al., 2006;Rajendran et al., 1996;Schmidt et al., 1994;Schröder et al., 2003;Swaminathan et al., 2010;Tadić et al., 2008;Tassell et al., 2010;Tauchert, 2002;Walker et al., 2006;Wang et al., 2013;Zapfe, 2001;Zick et al., 2009). For example, treatment for 8 weeks with an aqueous ethanol extract from fresh fruits of C. laevigata and C. monogyna, corresponding to a daily dose of 6.4 mg of procyanidins and 12.7 mg total phenolic compounds, significantly improved the exercise ability of patients with congestive heart failure (Degenring et al., 2003). ...
This account presents information on all aspects of the biology of Crataegus laevigata (Poir.) DC (Midland hawthorn) (C. oxyacanthoides Thuill.) that are relevant to understanding its ecological characteristics and behaviour. The main topics are presented within the standard framework of the Biological Flora of the British Isles: distribution, habitat, communities, responses to biotic factors, responses to environment, structure and physiology, phenology, floral and seed characters, herbivores and disease, history and conservation.
Crataegus laevigata is primarily a shade‐tolerant shrub or small tree up to 12‐m tall of ancient woodlands (of which it is an indicator plant) and occasionally old hedges, usually on heavy clay soils and avoiding limestone and chalk. It is native to central and northern Europe and in the British Isles is native to southeast England, occurring naturally up to the Midlands, hence the common name. It is largely absent naturally from Scotland, Wales and Ireland.
Flowers usually have two styles, varying from (rarely) 1 to 5 with an equal number of pyrenes in the fruit, differentiating it from C. monogyna with usually one style and pyrene. Pollination is by insects and fruit are dispersed primarily by birds. Fruit has traditionally been used for food, and with the leaves and flowers have a long tradition in herbal medicine.
Disturbance and fragmentation have allowed C. monogyna to permeate into old woodlands and hybridise with C. laevigata. These two species are inter‐fertile and barriers to hybridisation are primarily spatial separation thus allowing extensive introgression such that in many parts of Europe, pure C. laevigata is becoming scarce.
... Clinical studies have reported an increase in LVEF, exercise tolerance and improvement in heart failure-related symptoms. The use of extracts of hawthorn leaf with flower is approved by German 62 Congestive Heart Failure: Current Treatment and Therapies under Realm of Research Commission E for patients with New York Heart Association (NYHA) class II symptoms [36]. ...
... Additionally, it has been recommended that Hawthorn can inhibit lipid absorption in the intestine and cholesterol synthesis in the liver Tao et al., (2011). A Cochrane database of systemic review has revealed that hawthorn may recover maximal workload, pressure, left ventricular ejection fraction (LVEF), heart rate, and exercise tolerance in patients with CHF (NYHA functional class I to III) (Pittler et al., 2008). Additionally, a significant recovery from fatigue, palpitations, and shortness of breath was established in individuals that were getting Hawthorn as compared with the placebo. ...
Many cultivated and wild plants are used for the management of various diseases, specifically renal and hepatic diseases and those of the immune and cardiovascular systems. In China, medicinal plants from ancient to modern history have been used in patients with angina pectoris, congestive heart failure (CHF), systolic hypertension, arrhythmia, and venous insufficiency for centuries. The latest increase in the fame of natural products and alternative medicine has revived interest in conventional remedies that have been consumed in the management of CVD. The cardio-protective properties of the various herbs are possibly due to their anti-oxidative, antihypercholesterolemic, anti-ischemic activities, and inhibition of platelet aggregation that reduce the risk of CVD. Ethno-pharmacological and biological properties of these plants are explored, based upon published scientific literature. Although a majority of medicinal plants having a biological mechanism that linked with CVD management, to date, published literature pertaining to their promising scientific properties are still poorly understood. Compared with synthetic medicines, alternative medicines do not need scientific studies before their formal approval from the government sector and due to this purpose; their safety, as well as efficacy, still remain elusive. Taken together, we addressed all accessible evidence on alternative medicines commonly consumed in CVD management. Our comprehensive analysis of the scientific literature indicated that many TCMs are available and valuable herbal medication would be the best alternative for the management of CVD as a complementary therapy. Furthermore, practitioners should always discuss possible benefits-risks of alternative medicines with patients so that they are aware of the consumption of alternative medications.
Alıç (Crataegus monogyna); sert iklimlere dayanıklı bir bitki olduğundan hemen her türlü iklimde yetişen Doğu Asya, Avrupa ve Doğu Kuzey Amerika'da yoğunlaşan kuzey ılıman bölgelere özgü yaklaşık 280 türe sahip bir Rosaceae (gül ailesi) bir bitkidir. Crataegus monogyna (Alıç)’nın Tıp biliminde, endüstri sektöründe, kozmetik sanayinde ve tarım alanlarındaki kullanılmaktadır. Türkiye’de, alıç ve doğal olarak
yetişen, farklı kullanım alanlarına sahip olan diğer türlerinde araştırılması ve çoğaltılması önem arz etmektedir. Elazığ ili Ağın kırmızısı, Baskil Tavşanuşağı ve Sütlüce kırmızısı alıç çeşitlerinin yağ asidi ve özellikle esansiyal yağ asidi bileşimi bakımından yüksek içeriğe sahip olduğu gözlenmiştir. Bu iki yağ asidi dışındaki yağ asitleri metabolik olarak glukozdan sentezlenmekte ve ∆9 desatüraz enzimi veya steroil CoA desatüraz enzimi tarafından 9-10. C atomları arasına bir çift bağı girişini sağlamakta olduğu anlaşılmıştır. Sonuç olarak farklı bölgelerden toplanan alıç meyvelerinin biyokimyasal içerikleri ve antioksidan kapasitelerine bakıldığında; Ağın kırmızısı olarak ifade edilen alıç meyvesindeki değerlerin yüksek olduğu gözlenmiştir. Esensiyal yağ asidi içeriği bakımdan da her üç alıç meyvesindeki esensiyal yağ asidi içeriğinin toplam yağ asidi içinde % 36- 45 arasında bulunması önemli bir ölçüt olarak görülmüştür. Başta Ağın kırmızı olmak üzere SK ve T olarak ifade edilen meyvelerin insan beslenmesinde faydalı bir meyve olduğu, Elazığ alıçlarının tıbbi kullanım açısından önem arz ettiği sonucu ortaya konulmuştur.
Millions of people worldwide suffer from chronic lifestyle diseases mostly referred to as non-communicable diseases (NCDs) and conditions. The most frequent of them are cardiovascular disease, stroke, diabetes, obesity, metabolic syndrome, chronic obstructive pulmonary disease, and some types of cancer, followed by depression, dementia, arthritis and osteoporosis, asthma, chronic liver and kidney diseases, and other diseases. NCDs became the leading contributors to morbidity and mortality responsible for 74% of all global deaths. The management of lifestyle diseases consists of risk factors reduction or elimination, early non-pharmacological and pharmacological treatment of disease, preventing its outcomes to preserve workability and quality of life. According to WHO, 85% of people worldwide use medicinal plants for treatment, 80% of people in developing countries use traditional and complementary medicine for their primary health care needs in the prevention, diagnosing, or treatment of physical and mental illness even if not approved by the regulatory agencies. The trends driving integration of HM in contemporary healthcare are: high rates of chronic diseases globally, chronic diseases are not adequately prevented and treated, high rates of adverse side effects, drug interactions because of aging population, multimorbidity and polypharmacy, high cost of healthcare, high utilization of TCAM by general public without informing physicians, inadequate education of health professionals about TCAM methods, the growing interest of physicians in TCAM education for integrative medicine, the increasing amount of research and clinical guidelines from health organizations for the inclusion of TCAM practices.
This chapter will discuss the role of some herbal medicines in the treatment of major NCDs, current challenges, and some future perspectives for herbal medicines.
Crataegus species (hawthorn) have been commonly used in traditional medicine, especially for the treatment of congestive heart failure. Many studies confirmed that they are rich in polyphenols, thus exhibiting strong antioxidant activity, which contribute to the beneficial effects of hawthorn on the cardiovascular system. In the market, there are many herbal medicinal products based on hawthorn, which consumption as adjuvant therapy in heart-related issues is supported by European Medicines Agency. Since there is a global trend of making homemade herbal preparations, this study aimed to compare whether there is a difference in polyphenol profile and antioxidant potential between homemade and commercial ethanol extracts of hawthorn. Polyphenol profile was evaluated by determination of total phenolic and flavonoid contents, and by quantitative analysis of selected polyphenols by LC-MS/MS. Antioxidant potential was examined by DPPH, FRAP, and lipid peroxidation inhibition assays. The results of this study suggest that homemade ethanol extracts of hawthorn flowers, leaves and fruits are just as good source of polyphenols and antioxidants as commercial ones, and their utilization should be supported. Furthermore, hawthorn extracts made of leaves and flowers are better source of bioactive polyphenols and have higher antioxidant activity compared with the same of fruits, regardless of the method of preparation.
Araştırma; Elazığ ilinde kırmızı alıç meyvelerinin biyokimyasal özelliklerinin belirlenmesi amacıyla yürütülmüştür. Alıç meyvelerinin biyokimyasal
içerikleri ve antioksidan kapasitelerine bakıldığında; Ağın Kırmızısı olarak ifade
edilen alıç meyvesindeki değerlerin yüksek olduğu gözlenmiştir. Esensiyal yağ
asidi içeriği bakımdan da her üç alıç meyvesindeki esensiyal yağ asidi içeriğinin
toplam yağ asidi içinde % 36- 45 arasında bulunması önemli bir ölçüt olarak
görülebilir. Başta Ağın Kırmızı olmak üzere Sütlüce Kırmızısı ve Tavşanuşağı
Kırmızısı olarak ifade edilen alıç meyvelerin insan beslenmesinde faydalı bir
meyve olduğu sonucu teyit edilmiştir
Cardiovascular disease is the leading cause of premature death and hence an important public health problem. Hypertension is the most prevalent risk factor for cardiovascular disease. Herbal medicines, a complementary approach for treating hypertension and other cardiovascular diseases, have been traditionally used worldwide for many years, either alone or in combination. In order to understand the mechanisms of antihypertensive action of plants, the mechanisms that are effective in the development of hypertension should be examined. In this study, the mechanisms of action of traditionally used plants on hypertension and the efficacy and safety of these plants were investigated.
Based on ethnobotanical studies and surveys, 15 plants commonly used in Turkey were selected. The data on these plants obtained from various literature sources were compiled for this study.
As a result of the evaluation of ethnobotanical studies and surveys, 15 commonly used medicinal plants were selected: Allium sativum, Crataegus spp., Olea europaea, Punica granatum, Nigella sativa, Camellia sinensis, Citrus spp., Melissa officinalis, Urtica dioica, Viscum album, Lavandula stoechas, Petroselinum crispum, Rosa canina, Teucrium polium, and Tribulus terrestris. The data obtained from various literature sources about these 15 medicinal plants were compiled for this study. In addition to the general uses of these plants, preclinical and clinical studies were examined to elucidate the pharmacological action mechanisms of compounds that may be effective against hypertension. Drug interactions, contraindications, and side effect profiles were investigated to evaluate their safety.
Clinical studies on the use of plants in hypertension are insufficient, and more clinical studies are needed to prove their efficacy and safety in humans.
The clinical presentation and diagnosis of Tejocote root toxicity causing Mobitz Type 1 remains a scarcely clinical phenomenon, often resulting in delayed diagnosis and treatment. This case report highlights a 30-year-old female presenting with a constellation of symptoms, including fatigue, dizziness, chest pressure, myalgias, nausea, vomiting, and peripheral tingling. Significantly, the patient had been using Tejocote root as an over-the-counter laxative acquired from Mexico. Laboratory findings revealed detectable Digoxin levels in her bloodstream, while an electrocardiogram (EKG) indicated sinus bradycardia with Mobitz Type 1 heart block. The patient was treated with a single dose of atropine 0.5 mg IV push. A repeat EKG before discharge showed resolution of the Mobitz type 1. This case underscores the potential cardiovascular repercussions of Tejocote root consumption and emphasizes the importance of heightened clinical awareness, especially in regions where such herbal supplement usage is prevalent.
Traditional Chinese medicine offer unique advantages in mitigating and preventing early or intermediate stage for treating heart failure (HF). The purpose of this study was to assess the in vivo therapeutic efficacy of Xin-shu-bao (XSB) at different stages of HF following induction of a myocardial infarction (MI) in mice and use mass spectrometry-based proteomics to identify potential therapeutic targets for different stages of HF based on the molecular changes following XSB treatment. XSB had high cardioprotective efficacy in the pre-HF with reduced ejection fraction (HFrEF) stages, but had a weak or no effect in the post-HFrEF stages. This was supported by echocardiographic measurements showing that XSB decreased ejection fraction and fractional shortening in HF. XSB administration improved cardiac function in the pre- and post-HFrEF mouse model, ameliorated deleterious changes to the morphology and subcellular structure of cardiomyocytes, and reduced cardiac fibrosis. Proteomics analysis showed that XSB intervention exclusively targeted thrombomodulin (THBD) and stromal interaction molecule 1 (STIM1) proteins when administered to the mice for both 8 and 6 weeks. Furthermore, XSB intervention for 8, 6, and 4 weeks after MI induction increased the expression of fibroblast growth factor 1 (FGF1) and decreased arrestin β1 (ARRB1), which are classic biomarkers of cardiac fibroblast transformation and collagen synthesis, respectively. Overall, the study suggests that early intervention with XSB could be an effective strategy for preventing HFrEF and highlights potential therapeutic targets for further investigation into HFrEF remediation strategies.
Complementary and alternative medicines (CAM) are commonly used across the world by diverse populations and ethnicities but remain largely unregulated. Although many CAM agents are purported to be efficacious and safe by the public, clinical evidence supporting the use of CAM in heart failure remains limited and controversial. Furthermore, health care professionals rarely inquire or document use of CAM as part of the medical record, and patients infrequently disclose their use without further prompting. The goal of this scientific statement is to summarize published efficacy and safety data for CAM and adjunctive interventional wellness approaches in heart failure. Furthermore, other important considerations such as adverse effects and drug interactions that could influence the safety of patients with heart failure are reviewed and discussed.
Purpose
E-OJ-01 (OxyjunTM), a proprietary, standardized aqueous extract of Terminalia arjuna (TA) bark, has previously shown promising cardiovascular health benefits in healthy young athletic adults and is now being tested to determine its ability to support left ventricular ejection fraction and associated parameters in a diverse population.
Participants and Methods
Healthy adults aged 30–70 years (n=72) were included in the study to investigate the effect of 400 mg/day of E-OJ-01 when administered for 8 weeks on myocardial pumping capacity, primarily left ventricular ejection fraction (LVEF). The secondary endpoints were improvement in diastolic filling (E/A) ratio, rate pressure product (RPP), and fatigue severity scale (FSS) score. The effect of the intervention on blood lipids and gamma-glutamyltransferase (GGT) levels was also explored. The safety of the intervention was evaluated by monitoring adverse events, vitals (heart rate (HR), blood pressure (BP), and body temperature (BT)), and liver (serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT)) and kidney function (serum creatinine).
Results
E-OJ-01 increased the LVEF by 6.28% (percentage change) from the baseline compared with 0.24% (percentage change) in the placebo group (p<0.05). It reduced fatigue (22.52%), RPP (1.54%), and GGT levels (5.90%) from the baseline. No adverse events related to the intervention were observed during the study.
Conclusion
The study showed that E-OJ-01 could improve cardiac pumping capacity by significantly increasing LVEF and reducing fatigue in a diverse, healthy population.
Hawthorn, as one of widely‐used Chinese herbal medicines, has been used to treat blood stasis syndrome in clinic, but its blood‐activating components are unclear. This study combined the ultra‐high‐performance liquid chromatography‐quadruple exactive‐orbitrap mass spectrometry with chemometrics to identify the blood‐activating components of hawthorn. Different polar fractions of hawthorn aqueous extracts were extracted and mixed to prepare 14 samples. The contents of 25 chemical components for 14 samples were determined by the proposed quantitative method which was validated in terms of linearity, precision, stability, repeatability, and recovery, while the blood‐activating effect was evaluated by measuring the whole blood viscosity, plasma viscosity, and plasma fibrinogen levels. Then the partial least squares model was established on the spectrum‐effect relationship. The result showed that vitexin‐2’’‐O‐rhamnoside, rutin, citric acid, malic acid, gallic acid and fumaric acid could reduce the whole blood viscosity, plasma viscosity, and plasma fibrinogen levels in blood stasis model rats, and these components were the blood‐activating components of hawthorn. This study provided scientific basis for clarifying the blood‐activating components of hawthorn, and the spectrum‐effect approach proved to be an effective approach to discover the bioactive components of Chinese herbal medicines. This article is protected by copyright. All rights reserved
Crataegi Fructus, a medicinal and edible herb in China, has been considered a popular dietary supplement globally. It is used for the treatment of dyspepsia and chronic heart failure according to the Chinese Pharmacopoeia (2020). However, fungal contamination in Crataegi Fructus affects its quality and safety, thus preventing its global promotion. In this study, we comprehensively studied the fungal community in processed products of Crataegi Fructus by high-throughput sequencing. A total of 21 Crataegi Fructus samples were collected from five provinces in China, and the samples were divided into five groups based on collection areas, as well as into three groups based on processing methods. We then targeted the internal transcribed spacer 2 sequence through the Illumina Miseq PE300 platform to investigate fungal composition and diversity. Results showed that all 21 samples were detected with fungal contamination, and Ascomycota was dominant at the phylum level. In the groups based on collection areas, Dothideomycetes, Pleosporaceae, and Alternaria were dominant at the class, family, and genus levels, respectively. In the groups based on processing methods, Dothideomycetes, Aspergillaceae, and Alternaria were the most abundant at the class, family, and genus levels, respectively. Differences in fungal communities between various groups were also observed. Furthermore, a total of 115 species were identified, among which seven were potential toxigenic, namely, Trichothecium roseum, Alternaria tenuissima, Aspergillus carbonarius, Penicillium brevicompactum, Aspergillus fumigatus, Rhizopus microspores, and Pichia fermentans. In conclusion, this study reveals great fungal richness and diversity of Crataegi Fructus, providing references for the prevention and control of fungal contamination of Crataegi Fructus in practical production.
Hawthorn, as one of widely-used traditional Chinese medicines, has been used to treat dyspepsia, hyperlipidemia, and cardiovascular disease in clinic. Our previous study revealed that gallic acid, neochlorogenic acid, cryptochlorogenic acid, vitexin, and quercetin were active components of hawthorn. In this study, a simple, precise and reliable LC-MS method was developed for simultaneous quantification of five components in rat serums. The separation was achieved on the Hypersil GOLD C18 column, and the mobile phases consisted of 0.1% acetic acid water and methanol at a flow rate of 0.3 mL/min. The MS data acquisition was performed on a Q-Extractive-Orbitrap MS with an ESI source in negative ion mode. The proposed LC-MS method was validated in terms of linearity, intra- and inter-precision, accuracy, recoveries, matrix effects, and stability. Then this newly proposed LC-MS method was successfully applied to a pharmacokinetic study on rats after oral administration of hawthorn aqueous extracts. This study provided relevant information on the pharmacokinetics of active components of hawthorn, and explained the underlying mechanism of their bioactivity. This article is protected by copyright. All rights reserved.
The aim of this study was to investigate the effects of dietary consumption of Crataegus oxyacantha extract on some biochemical parameters in rats. The 32 rats were randomly divided into 4 groups with 8 rats each, equally divided as 4 female and 4 male rats: Group I (Control group): no hawthorn extract administered; Group II: 25 mg/kg/day hawthorn extract per oral for 4 weeks; Group III: 50 mg/kg/day hawthorn extract per oral for 4 weeks; Group IV: 100 mg/kg/day hawthorn extract per oral for 4 weeks. The results indicated that serum glucose levels were lower and serum triglyceride and VLDL levels were higher in females compared to males in the rats administered Crataegus oxyacantha extract. Accordingly, controlled consumption of Crataegus oxyacantha extract is recommended after taking into account gender-and dosage-related differences.
Hawthorn (Crataegus oxycantha) is one of the best cardiovascular herbs because it is both cardiotonic and antiarrhythmic. Its medicinal properties come from its flowers, leaves, and berries. Hawthorn is also sedating, adaptogenic, antioxidant, vasodilating, diuretic, and hypotensive. It may be beneficial for hypertension, coronary artery disease, congestive heart failure, orthostatic hypotension, and nonalcoholic fatty liver disease. The oligomeric procyanidins in hawthorn have been shown to have antioxidant properties. This chapter examines some of the scientific research conducted on hawthorn, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of hawthorn’s use in treating cardiovascular disorders, including hypertension, coronary artery disease, congestive heart failure, and orthostatic hypotension, as well as gastrointestinal and psychiatric diseases. Finally, the chapter presents a list of hawthorn’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.
Heart failure (HF) is a complex clinical syndrome that represents a major cause of morbidity and mortality in Western countries. Several nutraceuticals have shown promising clinical results in term of HF prevention as well as in the management of symptoms associated to the early stages of the disease. Clinical trials reported that the intake of some nutraceuticals (Hawthorn, Coenzyme Q10, L-carnitine, D-ribose, Carnosine, Vitamin D, Probiotics, Omega-3 PUFAs, Beet nitrates) is associated with improvements in self-perceived quality of life and/or functional parameters such as ejection fraction, stroke volume and cardiac output in HF patients, with minimal or no side effects. Those benefits tended to be greater in earlier HF stage. Evidence suggests that the supplementation with some nutraceuticals may be a useful option to improve HF management. However, in no case, the use of nutraceuticals can replace the consolidated pharmacological treatment of HF. Further long-term clinical trials are needed to investigate the effects of nutraceuticals supplementation on hard outcomes.
Crataegi folium have been used as medicinal and food materials worldwide due to its pharmacological activities. Although the leaves of Crataegus songorica (CS), Crataegus altaica (CA) and Crataegus kansuensis (CK) have rich resources in Xinjiang, China, they can not provide insights into edible and medicinal aspects. Few reports are available on the qualitative and quantitative analysis of flavonoids compounds of their leaves. Therefore, it is necessary to develop efficient methods to determine qualitative and quantitative flavonoids compounds in leaves of CS, CA and CK. In the study, 28 unique compounds were identified in CS versus CK by qualitative analysis. The validated quantitative method was employed to determine the content of eight flavonoids of the leaves of CS, CA and CK within 6 min. The total content of eight flavonoids was 7.8–15.1 mg/g, 0.1–9.1 mg/g and 4.8–10.7 mg/g in the leaves of CS, CA and CK respectively. Besides, the best harvesting periods of the three species were from 17th to 26th September for CS, from 30th September to 15th October for CA and CK. The validated and time-saving method was successfully implemented for the analysis of the content of eight flavonoids compounds in CS, CA and CK for the first time.
The chief motive of this chapter is to present an outline about the use of plants for diagnosis and treatment of an ailment. Phytotherapeutics came into the picture when cases of synthetic drug resistance started to surface. Many researchers and scientists are rigorously working on developing some alternatives to this problem, and phytotherapeutics present the perfect solution. Also, the medicines under synthetic drugs are usually a modification of a naturally occurring substance. Often, plants are called “living factories” because they are involved in synthesizing a huge range of medicinally important substances. These substances comprise of primary metabolites (growth regulators) and secondary metabolites (plant defense system). Although the evidence supporting the benefits of phytotherapy is still lacking, phytotherapy may be used as an alternative treatment when classical therapy is not giving satisfactory results. But a close eye has to be kept on the side effects of this alternative treatment and, as a precautionary measure, it should be stopped after surgery or chemotherapy until complete knowledge about its effect in such condition is available.
Hawthorn, a well‐known traditional Chinese medicine is used for treatment of dyspepsia syndrome, cardiovascular disease and hyperlipidemia. Hawthorn has complex composition, therefore, the effective fraction and mechanisms of action in alleviating hyperlipidemia are unknown. Therefore, the aim of this study was to evaluate effects of four different polar components of hawthorn on hyperlipidemia rats, and to explore underlying mechanisms of action through LC‐MS based plasma metabolomics. Hyperlipidemia rat model was established by feeding rats using high‐fat diet. High‐fat model rats were then treated with 4 polar components of hawthorn for 14 consecutive days. Plasma samples were collected and subjected to biochemical and metabolomics analysis. Biochemical analysis showed that hawthorn n‐butanol and ethyl acetate extracts had the highest efficacy on hyperlipidemia rats. Water fraction showed a partial effect, whereas petroleum ether extract was not effective against hyperlipidemia rats. Furthermore, LC‐MS metabolomics analysis showed that the most effective fraction of hawthorn reversed the metabolic disorder in plasma of hyperlipidemia rats. Metabolomics analysis showed that hawthorn exerts its activity by modulating lipid metabolism, energy metabolism, oxidative stress and amino acid metabolism.
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Heart failure (HF) is a complex clinical syndrome that represents a major cause of morbidity and mortality in Western countries. Several nutraceuticals have shown interesting clinical results in HF prevention as well as in the treatment of the early stages of the disease, alone or in combination with pharmacological therapy. The aim of the present expert opinion position paper is to summarise the available clinical evidence on the role of phytochemicals in HF prevention and/or treatment that might be considered in those patients not treated optimally as well as in those with low therapy adherence. The level of evidence and the strength of recommendation of particular HF treatment options were weighed up and graded according to predefined scales. A systematic search strategy was developed to identify trials in PubMed (January 1970 to June 2019). The terms 'nutraceuticals', 'dietary supplements', 'herbal drug' and 'heart failure' or 'left verntricular dysfunction' were used in the literature search. The experts discussed and agreed on the recommendation levels. Available clinical trials reported that the intake of some nutraceuticals (hawthorn, coenzyme Q 10 , L-carnitine, D-ribose, carnosine, vitamin D, probiotics, n-3 PUFA and beet nitrates) might Abbreviations: 25(OH)D, 25-hydroxyvitamin D; 6MWT, 6-min walking test; AA, amino acid; BNP, brain natriuretic peptide be associated with improvements in self-perceived quality of life and/or functional parameters such as left ventricular ejection fraction, stroke volume and cardiac output in HF patients, with minimal or no side effects. Those benefits tended to be greater in earlier HF stages. Available clinical evidence supports the usefulness of supplementation with some nutraceuticals to improve HF management in addition to evidence-based pharmacological therapy.
A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990.
To document trends in alternative medicine use in the United States between 1990 and 1997.
Nationally representative random household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997, respectively.
A total of 1539 adults in 1991 and 2055 in 1997.
Prevalence, estimated costs, and disclosure of alternative therapies to physicians.
Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8% in 1990 to 42.1% in 1997 (P < or = .001). The therapies increasing the most included herbal medicine, massage, megavitamins, self-help groups, folk remedies, energy healing, and homeopathy. The probability of users visiting an alternative medicine practitioner increased from 36.3% to 46.3% (P = .002). In both surveys alternative therapies were used most frequently for chronic conditions, including back problems, anxiety, depression, and headaches. There was no significant change in disclosure rates between the 2 survey years; 39.8% of alternative therapies were disclosed to physicians in 1990 vs 38.5% in 1997. The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 (64.0%) and 1997 (58.3%) (P=.36). Extrapolations to the US population suggest a 47.3% increase in total visits to alternative medicine practitioners, from 427 million in 1990 to 629 million in 1997, thereby exceeding total visits to all US primary care physicians. An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and/or high-dose vitamins (18.4% of all prescription users). Estimated expenditures for alternative medicine professional services increased 45.2% between 1990 and 1997 and were conservatively estimated at 12.2 billion paid out-of-pocket. This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations. Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $27.0 billion, which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services.
Alternative medicine use and expenditures increased substantially between 1990 and 1997, attributable primarily to an increase in the proportion of the population seeking alternative therapies, rather than increased visits per patient.
Introdution
Meta-analysis has received a mixed reception since the outset. Some people have rejected what they see as exercises in “mega-silliness,”1 while the purveyors of a highly distinguished series of meta-analyses of perinatal medical care2 have been dismissed as “an obstetrical Baader-Meinhof gang.”3 To some clinicians objecting to the findings of meta-analyses, “a tool has become a weapon.”4 At the other end of the spectrum, the application of a technique that basically consists of calculating a weighted average has been hailed as “Newtonian,”5 and it has been suggested that meta-analysis has left no place for the narrative review article.6 The truth is likely to lie somewhere between these extreme views.
Summary points
Bias can be introduced in many ways into the process of locating and selecting studies for inclusion in meta-analysisStudies with significant results are more likely to get published than studies without significant results, leading to publication biasAmong published studies, those with significant results are more likely to get published in English, more likely to be cited, and more likely to be published repeatedly, leading to English language bias, citation bias, and multiple publication biasIn less developed countries, studies with significant results may be more likely to get published in a journal indexed in a literature database, which can introduce database biasCriteria for including studies in a meta-analysis may be influenced by knowledge of the results of the set of potential studies, leading to inclusion biasThe likely presence or absence of bias should be routinely examined in sensitivity analyses and funnel plots
That meta-analysis holds potential problems can be illustrated by contrasting the conclusions of two meta-analyses comparing low molecular weight heparins and standard heparin in the prevention of thrombosis after surgery.7 8 One group concluded that “low molecular weight …
Publication bias is the tendency on the parts of investigators, reviewers, and editors to submit or accept manuscripts for publication based on the direction or strength of the study findings. Much of what has been learned about publication bias comes from the social sciences, less from the field of medicine. In medicine, three studies have provided direct evidence for this bias. Prevention of publication bias is important both from the scientific perspective (complete dissemination of knowledge) and from the perspective of those who combine results from a number of similar studies (meta-analysis). If treatment decisions are based on the published literature, then the literature must include all available data that is of acceptable quality. Currently, obtaining information regarding all studies undertaken in a given field is difficult, even impossible. Registration of clinical trials, and perhaps other types of studies, is the direction in which the scientific community should move.
Heart failure is a malignant condition with high rates of morbidity and mortality even in so called mild cases. Left ventricular dysfunction is the main cause of heart failure, and echocardiography can quickly distinguish less common but reversible causes. The most effective medical treatments for heart failure and diuretics, usually a loop diuretic, and angiotensin converting enzyme inhibitors. If patients remain symptomatic or cannot tolerate angiotensin converting enzyme inhibitors, other treatments such as hydralazine and isosorbide dinitrate or digoxin may be used, and as a last resort cardiac transplantation may be considered. Concomitant problems that may need treatment are atrial fibrillation, angina, and ventricular arrhythmia.
There is a wealth of evidence that angiotensin converting enzyme (ACE) inhibitors improve symptoms, morbidity and mortality in patients with heart failure. In this context the use of ACE inhibitors could be considered a tool with which to assess the effect of trial design and methodology on the ability to detect improvement in symptoms and exercise performance.
Thirty-five published, double-blind, randomized placebocontrolled trials, involving a total of 3411 patients, which compared the effect of ACE inhibitors and placebo on exercise capacity in patients with symptomatic chronic heart failure were identified. Studies were examined in relation to whether they used cross-over or parallel group study design, study size, use of treadmill vs bicycle exercise test, year of publication, patient entry criteria, duration of follow-up and the particular ACE inhibitor used.
Exercise duration improved in 23 of the studies, while symptoms improved in 25 of the 33 studies which evaluated this. In the majority of the trials (27 of 33) there was concordance between the effect on symptoms and on exercise capacity. There were six trials which showed discrepant results. Study size, duration of follow-up and method of exercise testing used were found to be major factors affecting the outcome. Trials using treadmill exercise tests were more likely to be positive than those using bicycle ergometry. All nine trials with study size more than 50, follow-up of 3–6 months and using treadmill exercise tests showed improved exercise capacity as well as symptoms. These findings may be useful in designing future trials for evaluating treatment for heart failure.
In a randomized controlled double-blind study, the efficacy of Crataegutt® novo film tablets (60 mg T>I>D>, totalling 180 mg/day) has been compared against placebo in 60 patients with a stable form of angina pectoris (NYHA stages I and II). Assessment of the therapeutical efficacy was performed by evaluation of standardized ergotomy. In this trial we were able to demonstrate, with Crataegutt novo, a significant rise in ergometric tolerance as the expression of an increased coronary perfusion and economizing of myocardial oxygen consumption, apart from an improvement or normalization of pathological ECG findings prior to the study. Our data confirm that Crataegutt novo is suitable for a treatment of stable forms of angina pectoris in NYHA stages I and II which is efficacious and free of side-effects. Under consideration of therapeutic benefit and risk, Crataegutt novo forms an alternative in the treatment of angina pectoris in stages not yet requiring nitrates, β-receptor blocking agents and calcium antagonists.
Herbal medicines are becoming more and more popular. The safety aspects of this widespread use are under-researched. This applies in particular to the possibility of herb/drug interactions. This systematic review summarises the indirect published evidence on this topic. Its results show that numerous suggestions about such interactions exist. Serious doubts, however, remain as to the reliability of this information. The implications of herb/drug interactions are potentially serious. Therefore, more rigorous research is urgently required.
Crataegus (common hawthorn) extracts traditionally are used for the treatment of early stages of cardiac failure. Recent pharmacological studies revealed remarkable positive inotropic, antiarrhythmic, antioxidative and cardioprotective effects. Presently this is attributed to the oligomeric procyanidines, which are important constituents of the extract. In recent clinical trials with patients suffering from NYHA II cardiac failure, an increase in exercise capacity and also other favorable cardiovascular effects could be demonstrated after several weeks' treatment with daily doses of 900 mg dry extract. In ongoing studies the effects of hawthorn extract on several cardiovascular parameters and on cardiovascular endpoints of patients with NYHA II-III cardiac failure are under investigation. Hopefully, crataegus extract which is very well tolerated, could complete the standard treatment of chronic cardiac failure in the future.
In 30 patients with stage NYHA II cardiac insufficiency, a placebo-controlled randomized double-blind study was carried out to determine the efficacy of the Crataegus special extract WS 1442. Treatment duration was 8 weeks, and the substance was administered at a dose of 1 capsule taken twice a day. The main target parameters were alteration in the pressure-x-rate product (PRP) under standardised loading on a bicycle ergometer, and a score of subjective improvement of complaints elicited by a questionnaire. Secondary parameters were exercise tolerance and the change in heart rate and arterial blood pressure. The active substance group showed a statistically significant advantage over placebo in terms of changes in PRP (at a load of 50 W) and the score, but also in the secondary parameter heart rate. In both groups, systolic and diastolic blood pressure was mildly reduced. No adverse reactions occurred.
940 medical practitioners have established by documentary evidence tolerance and effectiveness of a high dosed Crataegus extract (3 x 300 mg of whitethorn [leaves and blossoms] extract) given to 3664 patients suffering from cardiac insufficiency phase I and II according to NYHA in a therapy accompanying observation. Clinical symptoms of 66.5% of the patients (2/2) could be related to NYHA phase II. The high dosed Crataegus extract proved to be well tolerated by the patients: 48 of them reported from 72 undesirable events during the observation period but only in the case of 26 patients these events could be exploited by the Crataegus treatment. A possible connection to Crataegus extract was determined in 22 cases and only 5 events could really be explained by whitethorn extract. Effectiveness of whitethorn therapy has been documented at 1476 patients who were given no other medication to treat their cardiac insufficiency. A score of 9 typical symptoms of cardiac insufficiency was established and used to diagnose changes in condition depending on whitethorn therapy after 4 and after 8 weeks of application. At the end of the observation period especially patients suffering from cardiac insufficiency phase I according to NYHA have rather had no more clinical symptoms. The average score was reduced from 6.9 points at the beginning to 1.7 at the end of the eighth week of treatment. The average pressure frequency product was reduced from 117.0 mmHg/min x 100 to 105.7 mmHg/min x 100. Work tolerance at bike ergometry was increased from 93.5 to 109.7 Watt. The numerous application observating data and experimental results about pharmacological effectiveness and protective effects on the myocard caused a discussion among pathophysiologists about a possible causal therapy with Crataegus extract especially for patients suffering from a stimulated sympothoadrenergic system (borderline hypertension, tachycardia arrhythmic).
The effectiveness of hawthorn extract in patients with NYHA stage II heart failure was investigated in a randomised, double-blind placebo controlled trial. 85 male and female patients were enrolled in the trial. The dosage was 3 x 100 mg extract p.d. and the trial lasted 4 weeks. The confirmatory parameter was bicycle ergometry exercise tolerance; in addition, the typical symptoms as well as tolerability and final global assessment by the investigators and patients were evaluated as a score. Exercise tolerance, pressure-rate product and clinical symptomatology all showed a trend toward - but no statistically significant - superiority of verum over placebo. The lack of significance may be attributable to the low baseline symptomatology or, above all, to the fact that the optimum dosage and duration were not reached in this trial.
A placebo-controlled cross-over study was conducted to compare the effects of 900 mg Crataegus extract with those of 0.3 mg medigoxin on the cutaneous microcirculation of 12 healthy subjects aged 25 ± 4 years. The preparations were taken as a single dose. Immediately before, as well as 1, 3 and 6 hours after taking the dose, the subjects' haematocrit, erythrocyte aggregability, plasma viscosity, erythrocyte pre- and postischaemic flow rate in the nail bed capillaries as well as heart rate and blood pressure were measured. Six hours after taking Crataegus the haematocrit had dropped by a mean of 3.2% (p < 0.05); erythrocyte aggregation increased by a mean of 19% (p < 0.01) 3 hours after taking the digoxin preparation. No significant changes were recorded for the remaining target parameters.
In a multicentre, double-blind comparative study 132 patients with NYHA stage II stable heart failure were treated with 3 x 300 mg of the Crataegus extract LI 132 or 3 x 12.5 mg Captopril for 8 weeks. The confirmatory parameter was exercise tolerance at sitting bicycle ergometry on the days -7, 28 and 56. Secondary criteria were the pressure-rate product and a score for 5 typical symptoms. Exercise tolerance increased statistically significantly during the course of treatment in both treatment groups from 83 to 97 watts (LI 132) and from 83 to 99 watts (Captopril), respectively. The pressure-rate product was reduced in both groups. The incidence and severity of the symptoms also decreased by around 50% in both groups. None of the target parameters showed any significant difference between the Crataegus preparation and the reference drug. One patient treated with Captopril had to discontinue therapy on account of adverse effects. No serious adverse events were reported unter treatment with LI 132.
After a wash-out phase 78 male and female patients aged from 45-73 with NYHA stage II heart failure received a daily dose of 600 mg hawthorn extract or placebo for eight weeks. The confirmatory parameter for assessing efficacy was bicycle ergometry exercise tolerance in which an increase in tolerance of at least 12,5 watt under verum therapy was regarded as a clinically relevant treatment result. While tolerance under the hawthorn preparation improved by a mean of more than one watt level (+28 watts) by the 56th day of treatment, it remained virtually unchanged under placebo (+5 watts). This difference was statistically significant (p < 0,001). At the highest exercise grade under placebo the systolic pressure, heart rate and the pressure-rate product decreased. The score for clinical symptoms also improved significantly. Tolerability proved to be very high, and only two patients in each group reported mild adverse events.
In a placebo-controlled randomised double-blind clinical trial the effect of Crataegus Special Extract WS® 1442 on left ventricular function in patients suffering from heart failure with impaired left ventricular ejection fraction (LVEF <55%) was determined. A total of 40 patients suffering from coronary heart disease were included into the study and treated for 4 weeks with either 2 capsules containing 80 mg of Crataegus Special Extract WS® 1442 t. i. d. or placebo. The primary outcome variable was the intra-individual difference of the LYEF at bicycle exercise between start and end of therapy measured with radionuclide angiocardiography. A small but statistically significant increase in LVEF of 2.5% was determined in the verum group at resting condition whereas in the placebo group LVEF decreased by 0.3% (p=0.0001). Accordingly, at bicycle exercise in the WS® 1442 group the LVEF increased by 1.5% whereas LVEF in the placebo group decreased by 0.2% (p=0.0002). The tolerability of WS® 1442 was very good; adverse events did not occur in neither of the treatment groups.
In a randomised double-blind study with 72 patients (mean age 51 ± 10 years), 36 patients each were treated with Crataegus extract at a dosage of 3 x 300 mg p.d. or placebo. The patients had clinical and ergospirometric examinations at study start and after 8 weeks' oral therapy. The confirmatory parameters were defined as the oxygen uptake as well as the tolerance period until the patients reached the anaerobic threshold and when exercise was discontinued. Of the selected criteria the exercise time taken to reach the anaerobic threshold (AT) was longer in the verum patients than in the placebo group. The mean increase in the verum group was 30 seconds, that in the placebo group only 2 seconds. There was also a significant improvement in the verum group in terms of the subjective assessment of the patients' symptoms. No relevant side effects were observed.
In a randomised, double-blind, placebo-controlled, parallel study, in which patients were stratified according to physical performance, patients received either hawthorn/passion flower extract or placebo. Exercise capacity and improvement in symptoms were evaluated in a total of 40 patients aged 53 to 86 years, with dyspnoea commensurate with a NYHA functional class II. Over the 6 week trial period, the patients received oral drops (2 ml) three times daily. A 6-minute walking test and bicycle ergometer test were conducted to assess changes in exercise capacity. Blood lactate levels, heart rate, and blood pressure were also measured during exercise. Also recorded were improvements in symptoms, particularly dyspnoea, and changes in urine and blood biochemical parameters. The results show that exercise capacity, measured in terms of a walking test, increased significantly in those patients receiving the hawthorn/passion flower extract (p < 0.05, two-tailed test). Maximum exercise capacity measured during a bicycle ergometer test increased by about 10% over the baseline in both groups, but changes between groups did not differ significantly. The subjective symptom of breathlessness improved in both the extract and placebo groups, by approximately 40% and 30% respectively. Physical performance capacity at the aerobic transition threshold of 2 mmol lactate/l blood increased by 6.5% in the group receiving the extract, while it fell by 4.4% in the placebo group. This difference was, however, not statistically significant (p > 0.05). In the group receiving the extract there was a slight but significant fall in heart rate at rest and in mean diastolic blood pressure during exercise (p < 0.05, two-tailed test). There was a significant decrease in total plasma cholesterol levels in the group receiving the extract in comparison with the placebo group (p < 0.01, two-tailed test).
The aim of this meta-analysis was to assess the evidence from rigorous clinical trials of the use of hawthorn extract to treat patients with chronic heart failure. We searched the literature using MEDLINE, EMBASE, the Cochrane Library, CINAHL, CISCOM, and AMED. Experts on and manufacturers of commercial preparations containing hawthorn extract were asked to contribute published and unpublished studies. There were no restrictions about the language of publication. Two reviewers independently performed the screening of studies, selection, validation, data extraction, and the assessment of methodological quality. To be included, studies were required to state that they were randomized, double-blind, and placebo controlled, and used hawthorn extract monopreparations. Thirteen trials met all inclusion criteria. In most of the studies, hawthorn was used as an adjunct to conventional treatment. Eight trials including 632 patients with chronic heart failure (New York Heart Association classes I to III) provided data that were suitable for meta-analysis. For the physiologic outcome of maximal workload, treatment with hawthorn extract was more beneficial than placebo (weighted mean difference, 7 Watt; 95% confidence interval [CI]: 3 to 11 Watt; P < 0.01; n = 310 patients). The pressure-heart rate product also showed a beneficial decrease (weighted mean difference, -20; 95% CI: -32 to -8; n = 264 patients) with hawthorn treatment. Symptoms such as dyspnea and fatigue improved significantly with hawthorn treatment as compared with placebo. Reported adverse events were infrequent, mild, and transient; they included nausea, dizziness, and cardiac and gastrointestinal complaints. In conclusion, these results suggest that there is a significant benefit from hawthorn extract as an adjunctive treatment for chronic heart failure. (C) 2003 by Excerpta Medica Inc.
A controlled double blind study was conducted in patients with heart disease of ischaemic and/or hypertensive origin (NYHA Stages II and III), to evaluate the efficacy of Crataegutt in comparison with an inactive placebo used as the control drug. The total number of patients was 102, 14 were excluded for non-adherence to the test plan and a further eight dropped out. 80 patients were left for analysis. 35 of these belonged to group C and 45 to group P. No deviations were noted in the overall clinical condition of the patients in groups C and P. Care was taken to maintain the equality between the two groups. Concerning the general improvement and the improvement of cardiac function, group C was better with p < 0.01, and concerning the improvement of subjective symptoms with p < 0.001. Considering individual subjective symptoms, group C was better with significant improvement of dyspnoea and palpitation at p < 0.01 and with significant improvement of cardiac edemas at p < 0.05. No differences between the two groups were noted in the improvement of the ECG. Side-effects were observed in one patient of group C, but were not severe enough to require discontinuation of the test.
Seventy-eight male and female patients between the ages of 45 and 73, who were affected by chronic heart failure defined as NYHA functional class II, were treated either with Crataegus extract or with a placebo preparation. The extract LI 132 was administered to the patients in the form of 3 dragées a day (verum preparation) corresponding to a daily dose of 600 mg. Treatment was continued over a period of 8 weeks, with a wash-out phase of one week. The confirmatory parameter used to asses the efficacy of the preparation was the patients' working capacity which was measured using an ergometer bicycle. Before the start of the study, an increase in the patients' working capacity of at least half an exercise step on the ergometer bicycle (12.5 watt) was determined to be clinically relevant. Apart from the compatibility of the preparation, a score system was used to assess the severity level of the typical symptoms. From day 0 to day 56 of the trial, the median values obtained for the working capacity of the patients treated with the verum preparation were found to have increased by 28 watt, while the increase in the working capacity of the placebo patients was as little as 5 watt. The difference was statistically significant (p < 0.001). Apart from that, a significant reduction of the systolic blood pressure, of the heart rate and of the pressure/rate product was observed for the patients treated with the verum preparation, compared to the patients treated with the placebo preparation. Also, the clinical symptoms (score system) were found to have improved significantly. There were no severe side effects observed.
According to the results of experimental investigations, standardized Crataegus extracts differ markedly from other inotropic drugs used for the treatment of heart failure. Crataegus has positive inotropic, positive chronotropic, positive dromotropic but negative bathmotropic effects, increases coronary and myocardial perfusion, lowers peripheral resistance and has antiarrhythmic and economising action with respect to oxygen and energy consumption. In randomised double-blind clinical trials, key surrogates required for demonstration of efficacy in heart failure were improved. Defined Crataegus extracts accordingly represent an alternative to synthetic drugs in patients with NYHA Grade II heart failure.
Herbs and dietary supplements can have significant physiological effects. Garlic (Allium sativum) has shown beneficial lipid effects in a majority of trials; dried garlic preparations are superior to oil preparations. There is preliminary evidence that indicates that hawthorn (Crataegus species) may provide benefit in congestive heart failure. Coenzyme Q also may be of benefit in congestive heart failure. Although observational studies indicate a protective effect of dietary or supplemental vitamin E, controlled trials have not shown a beneficial effect on angina and have been mixed on whether supplementation decreases major cardiac events. Although several observational studies have noted that fish intake protects against cardiovascular disease, prospective studies are less impressive. Fish oil supplementation may have a mild beneficial effect on hypertension, but there is no effect on total cholesterol levels. Trials are inconsistent on whether fish oil reduces restenosis rates following coronary angioplasty. Carnitine appears to have beneficial effects on congestive heart failure and angina; there is also preliminary evidence that arginine may benefit patients with congestive heart failure or angina. Herbs and supplements have been associated with adverse effects and interactions; for example, garlic inhibits platelet aggregation and can cause significant anticoagulation, and the Chinese herb danshen (Salvia miltiorrhiza) appears to potentiate warfarin. Several herbs and supplements hold promise as adjuncts in the prevention and treatment of cardiovascular disease. There is a need for definitive research on the potential risks and benefits of these compounds, including appropriate dosages and formulations, and delineation of adverse events and interactions
Overviews of clinical trials are an efficient and important means of summarizing information about a particular scientific area. When the outcome is a continuous variable, both treatment effect and variance estimates are required to construct a confidence interval for the overall treatment effect. Often, only partial information about the variance is provided in the publication of the clinical trial. This paper provides heuristic suggestions for variance imputation based on partial variance information. Both pretest-posttest (parallel groups) and crossover designs are considered. A key idea is to use separate sources of incomplete information to help choose a better variance estimate. The imputation suggestions are illustrated with a data set.
In a retrospective survey, 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987, were studied for evidence of publication bias. As of May, 1990, 285 of the studies had been analysed by the investigators, and 52% of these had been published. Studies with statistically significant results were more likely to be published than those finding no difference between the study groups (adjusted odds ratio [OR] 2.32; 95% confidence interval [Cl] 1.25-4.28). Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor. An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results, and with increasing sample size. The tendency towards publication bias was greater with observational and laboratory-based experimental studies (OR = 3.79; 95% Cl = 1.47-9.76) than with randomised clinical trials (OR = 0.84; 95% Cl = 0.34-2.09). We have confirmed the presence of publication bias in a cohort of clinical research studies. These findings suggest that conclusions based only on a review of published data should be interpreted cautiously, especially for observational studies. Improved strategies are needed to identify the results of unpublished as well as published studies.
Exercise intolerance is one of the primary characteristics of chronic congestive heart failure (CHF). Therefore, exercise testing has been widely used in the assessment of CHF patients, both to define the severity of the disease and to assess the efficacy of pharmaceutical agents in clinical trials. A number of different exercise tests can be used, although maximal exercise testing is the most common. Maximal exercise capacity can be determined by measuring exercise duration during incremental exercise, or maximal oxygen (O2) consumption, or it can be estimated by anaerobic threshold.
While baseline exercise testing in CHF patients accurately identifies and quantifies cardiac failure and determines prognosis, it is of limited value in assessing changes that occur as a result of drug therapy. A key drawback of exercise testing as a measurement of drug effect is the fact that exercise changes produced by drug intervention do not correlate well with changes in the mortality rate. Several examples of the lack of correlation between exercise testing and mortality rates have been observed in clinical trials with angiotensin converting enzyme (ACE) inhibitors and vasodilators. ACE inhibitors have a modest effect on maximal exercise capacity but they improve survival. It is thought that neuroendocrine activation more closely reflects mortality rates and also the changes in survival observed with pharmacological intervention compared with other modes of evaluation.
To document the prevalence of digitalis use and the incidence of hospitalization caused by digitalis toxicity.
Observational cohort followed for 6 years.
Urban community.
Persons were eligible if they were (1) enrolled in the Yale Health and Aging Project and (2) using digitalis when interviewed in 1982 or 1985. The Project comprises a sample of noninstitutionalized persons aged 65 years and over living in New Haven, Connecticut.
Between 1982 and 1988 when a Project participant was hospitalized in New Haven, a researcher reviewed the medical record and coded up to 16 International Classification of Diseases-Class 9 (ICD-9) diagnoses. To identify hospitalizations caused by digitalis, we reexamined records with ICD-9 codes suggesting toxicity. We confirmed the admission illness was an adverse drug reaction with a decision algorithm.
The prevalence of digitalis use was 13% in 1982 and 12% in 1985. The incidence of hospitalization caused by definite or probable toxicity was 4.2% (95% confidence interval = 0.3% to 8.1%) over 6 years. Manifestations of toxicity were malaise or gastrointestinal symptoms (two patients) and heart block plus malaise or gastrointestinal symptoms (six patients). Use of quinidine was associated (P < .05) with toxicity.
Knowledge about the incidence of severe, morbid toxicity may help clinicians estimate and compare the risks and benefits of digitalis and alternate therapies.
Diuretics, together with other drugs and general measures, are of prime importance in the medical treatment of most heart failure patients, namely those with acute pulmonary oedema and overt congestive heart failure. Their beneficial effects result not only from preload and afterload reduction, but also because diuretics are able to improve responses to nitrates and ACE-inhibitors. The appropriate utilisation of diuretics in heart failure therapy frequently involves the use of efficient small doses and drug associations, namely between loop diuretics, thiazides, potassium sparing agents and spirolactone. Physicians must choose the drug carefully, its dosage, time and route of administration, according to the patient's characteristics: heart failure clinical syndrome, age, activity level, systolic or diastolic, left or right ventricular dysfunction, and associated diseases. The role of diuretics in the treatment asymptomatic systolic left ventricular dysfunction and oligosymptomatic diastolic ventricular dysfunction is unclear and should remain under investigation; diuretics may be of benefit in treating those patients with associated diseases, for example arterial hypertension and mild chronic renal failure.
Using isolated perfused guinea pig hearts experiments were performed to investigate the influence of crataegus extract LI 132 (Faros 300, CRA) in comparison to other inotropic drugs--epinephrine (adrenaline, ADR), amrinone (AM), milrinone (MIL) and digoxin (DIG)--on different functional parameters, with special emphasis on the effective refractory period of the myocardium. The simultaneous registration of appropriate parameters allowed to relate the effect on the refractory period to the inotropic, chronotropic, dromotropic and coronary actions of these compounds at each concentration level. All substances--with the exception of CRA--shortened the effective refractory period concentration-dependently besides their known other functional effects (max.: 1 x 10(-5) mol/l ADR by 38%, 7 x 10(-7) mol/l DIG by 26%, 1 x 10(-4) mol/l MIL by 13% and 5 x 10(-4) mol/l AM by 1.6%). Related to the positive inotropy the shortening was most effective under MIL (1.32 ms/mN), followed by AM (0.65 ms/mN), DIG (0.40 ms/mN) and ADR (0.28 ms/mN). On the contrary, CRA produced a prolongation of the effective refractory period by maximally 10% resp. by 2.54 ms/mN. Thus, the pharmacologic profile of CRA differs from that of other inotropic compounds mainly in this parameter (with potentially reduced arrhythmogenic risk).
The ideal therapy for patients with chronic heart failure should reduce symptoms related to pulmonary congestion or low perfusion, prevent the progression of left ventricular dysfunction and, ultimately, should reduce mortality. Extensive studies in humans have investigated the effects of angiotensin-converting enzyme (ACE) inhibitors on these goals of therapy. As an example, the ACE inhibitor cilazapril significantly improved exercise tolerance, as borne out by a meta-analysis of six placebo-controlled, randomized 3-month trials. Comparison of the effects of cilazapril and captopril vs. placebo in one of the trials documented similar improvement in exercise tolerance (14 vs. 17%). Results from other randomized comparative trials suggest that the improvement in symptoms represents a class effect of ACE inhibitors. A beneficial effect of ACE inhibition on the progression of left ventricular dysfunction has also been demonstrated in the SOLVD trial, and a reduction of mortality has been amply documented in several mortality trials (CONSENSUS I, SOLVD, V-HeFT-II, SAVE, AIRE, SMILE) in patients with or without preceding myocardial infarction. Reports that ACE inhibitors also reduce the incidence of reinfarction after myocardial infarction have not been confirmed in all studies but raise the interesting concept that ACE inhibition may interact, in a beneficial but thus far not well-understood way, with key processes in the development of atherosclerosis, thereby preventing plaque rupture, thrombus formation, and myocardial infarction. Taken together, a large database convincingly demonstrates that ACE inhibitors are effective not only in improving symptoms but also in the prevention of progression of left ventricular dysfunction, in the reduction of mortality, and possibly in stabilizing the atherosclerotic disease process.
In a multicenter, placebo-controlled double-blind study, the efficacy of the Crataegus-Specialextrakt WS 1442 in patients with NYHA stage II cardiac insufficiency was investigated. A total of 136 patients with this diagnosis were admitted to the study and, following a 2-week run-in phase, treated with Crataegus-Specialextract or placebo over a period of 8 weeks. The primary target parameter was the change in the difference of the pressure, heart rate product (systolic blood pressure x heart rate/100) (PHRP 50 W load vs. rest) measured at the beginning and end of treatment.
On the basis of this variable, a clear improvement in the performance of the heart was shown in the group receiving the test substance, while the condition of the placebo group progressively worsened. The therapeutic difference between the groups was statistically significant. The positive result for the objective efficacy parameter was confirmed by a statistically obvious superiority of Crataegus in the patient's own assessment of improvement in the main symptoms (reduced performance, shortness of breath, ankle edema etc.). In addition, active treatment led, in comparison with placebo, to a considerably better quality of life for the patient, in particular with respect to mental well-being. The tolerability of the active substance proved to be very good-as shown by comprehensive laboratory investigations and the recording of undesirable events.
All in all, the results of the present clinical investigation confirm those of previous studies showing that Crataegus-Specialextrakt WS 1442 is an effective and low-risk phytotherapeutic form of treatment in patients with NYHA II cardiac insufficiency.
Several randomized trials have reported that beta-blocker therapy improves left ventricular function and reduces the rate of hospitalization in patients with congestive heart failure. However, most trials were individually too small to assess reliably the effects of treatment on mortality. In these circumstances a systematic overview of all trials of beta-blocker therapy in patients with congestive heart failure may provide the most reliable guide to treatment effects.
Details were sought from all completed randomized trials of oral beta-blocker therapy in patients with heart failure of any aetiology. In particular, data on mortality were sought from all randomized patients for the scheduled treatment period. The typical effect of treatment on mortality was estimated from an overview in which the results of all individual trials were combined using standard statistical methods. Twenty-four randomized trials, involving 3141 patients with stable congestive heart failure were identified. Complete data on mortality were obtained from all studies, and a total of 297 deaths were documented during an average of 13 months of follow-up. Overall, there was a 31% reduction in the odds of death among patients assigned a beta-blocker (95% confidence interval 11 to 46%, 2P = 0.0035), representing an absolute reduction in mean annual mortality from 9.7% to 7.5%. The effects on mortality of vasodilating beta-blockers (47% reduction SD 15), principally carvedilol, were non-significantly greater (2P = 0.09) than those of standard agents (18% reduction SD 15), principally metoprolol.
Beta-blocker therapy is likely to reduce mortality in patients with heart failure. However, large-scale, long-term randomized trials are still required to confirm and quantify more precisely the benefit suggested by this overview.
Some randomised controlled trials (RCTs) done in German-speaking Europe are published in international English-language journals and others in national German-language journals. We assessed whether authors are more likely to report trials with statistically significant results in English than in German.
We studied pairs of RCT reports, matched for first author and time of publication, with one report published in German and the other in English. Pairs were identified from reports round in a manual search of five leading German-language journals and from reports published by the same authors in English found on Medline. Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors' identities, affiliations, and other characteristics of trial reports. Main study endpoints were selected by two investigators who were unaware of trial results. Our main outcome was the number of pairs of studies in which the levels of significance (shown by p values) were discordant.
62 eligible pairs of reports were identified but 19 (31%) were excluded because they were duplicate publications. A further three pairs (5%) were excluded because no p values were given. The remaining 40 pairs were analysed. Design characteristics and quality features were similar for reports in both languages. Only 35% of German-language articles, compared with 62% of English-language articles, reported significant (p < 0.05) differences in the main endpoint between study and control groups (p = 0.002 by McNemar's test). Logistic regression showed that the only characteristic that predicted publication in an English-language journal was a significant result. The odds ratio for publication of trials with significant results in English was 3.75 (95% CI 1.25-11.3).
Authors were more likely to publish RCTs in an English-language journal if the results were statistically significant. English language bias may, therefore, be introduced in reviews and meta-analyses if they include only trials reported in English. The effort of the Cochrane Collaboration to identify as many controlled trials as possible, through the manual search of many medical journals published in different languages will help to reduce such bias.
To determine whether adverse drug reactions (ADRs) to herbal remedies would be reported differently from similar ADRs to conventional over-the-counter (OTC) medicines by herbal-remedy users.
Face-to-face interviews (using a structured questionnaire) with 515 users of herbal remedies were conducted in six pharmacy stores and six healthfood stores in the UK. The questionnaire focused on the likely course of action taken by herbal-remedy users after experiencing an ADR associated with a conventional OTC medicine and a herbal remedy.
Following a 'serious' suspected ADR, 156 respondents (30.3%) would consult their GP irrespective of whether the ADR was associated with the use of a herbal remedy or a conventional OTC medicine, whereas 221 respondents (42.9%) would not consult their GP for a serious ADR associated with either type of preparation. One hundred and thirty-four respondents (26.0%) would consult their GP for a serious ADR to a conventional OTC medicine, but not for a similar ADR to a herbal remedy, whereas four respondents (0.8%) would consult their GP for a serious ADR to a herbal remedy, but not for a similar ADR to a conventional OTC medicine. Similar differences were found in attitudes towards reporting 'minor' suspected ADRs.
Consumers of herbal remedies would act differently with regard to reporting an ADR (serious or minor) to their GP depending on whether it was associated with a herbal remedy or a conventional OTC medicine. This has implications for herbal pharmacovigilance, particularly given the increasing use of OTC herbal remedies. The finding that a high proportion of respondents would not consult their GP or pharmacist following ADRs to conventional OTC medicines is also of concern.