Omega-3 supplementation and outcomes of heart failure: A systematic review of clinical trials.

BACKGROUNDS: Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits. METHODS: A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials. RESULTS: The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events. CONCLUSION: Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.

Promising Nutritional Fruits Against Cardiovascular Diseases: An Overview of Experimental Evidence and Understanding Their Mechanisms of Action.

Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality in both developed and developing countries, affecting millions of individuals each year. Despite the fact that successful therapeutic drugs for the management and treatment of CVDs are available on the market, nutritional fruits appear to offer the greatest benefits to the heart and have been proved to alleviate CVDs. Experimental studies have also demonstrated that nutritional fruits have potential protective effects against CVDs. The aim of the review was to provide a comprehensive summary of scientific evidence on the effect of 10 of the most commonly available nutritional fruits reported against CVDs and describe the associated mechanisms of action. Relevant literatures were searched and collected from several scientific databases including PubMed, ScienceDirect, Google Scholar and Scopus. In the context of CVDs, 10 commonly consumed nutritious fruits including apple, avocado, grapes, mango, orange, kiwi, pomegranate, papaya, pineapple, and watermelon were analysed and addressed. The cardioprotective mechanisms of the 10 nutritional fruits were also compiled and highlighted. Overall, the present review found that the nutritious fruits and their constituents have significant benefits for the management and treatment of CVDs such as myocardial infarction, hypertension, peripheral artery disease, coronary artery disease, cardiomyopathies, dyslipidemias, ischemic stroke, aortic aneurysm, atherosclerosis, cardiac hypertrophy and heart failure, diabetic cardiovascular complications, drug-induced cardiotoxicity and cardiomyopathy. Among the 10 nutritional fruits, pomegranate and grapes have been well explored, and the mechanisms of action are well documented against CVDs. All of the nutritional fruits mentioned are edible and readily accessible on the market. Consuming these fruits, which may contain varying amounts of active constituents depending on the food source and season, the development of nutritious fruits-based health supplements would be more realistic for consistent CVD protection.

Simultaneous Pharmacokinetic Analysis of Nitrate and its Reduced Metabolite, Nitrite, Following Ingestion of Inorganic Nitrate in a Mixed Patient Population.

PURPOSE: The pharmacokinetic properties of plasma NO3- and its reduced metabolite, NO2-, have been separately described, but there has been no reported attempt to simultaneously model their pharmacokinetics following NO3- ingestion. This report describes development of such a model from retrospective analyses of concentrations largely obtained from primary endpoint efficacy trials. METHODS: Linear and non-linear mixed effects analyses were used to statistically define concentration dependency on time, dose, as well as patient and study variables, and to integrate NO3- and NO2- concentrations from studies conducted at different times, locations, patient groups, and several studies in which sample range was limited to a few hours. Published pharmacokinetic studies for both substances were used to supplement model development. RESULTS: A population pharmacokinetic model relating NO3- and NO2- concentrations was developed. The model incorporated endogenous levels of the two entities, and determined these were not influenced by exogenous NO3- delivery. Covariate analysis revealed intersubject variability in NO3- exposure was partially described by body weight differences influencing volume of distribution. The model was applied to visualize exposure versus response (muscle contraction performance) in individual patients. CONCLUSIONS: Extension of the present first-generation model, to ultimately optimize NO3- dose versus pharmacological effects, is warranted.

The role of diet and nutrition in heart failure: A state-of-the-art narrative review.

Heart Failure (HF) incidence is increasing steadily worldwide, while prognosis remains poor. Though nutrition is a lifestyle factor implicated in prevention of HF, little is known about the effects of macro- and micronutrients as well as dietary patterns on the progression and treatment of HF. This is reflected in a lack of nutrition recommendations in all major HF scientific guidelines. In this state-of-the-art review, we examine and discuss the implications of evidence contained in existing randomized control trials as well as observational studies covering the topics of sodium restriction, dietary patterns and caloric restriction as well as supplementation of dietary fats and fatty acids, protein and amino acids and micronutrients in the setting of pre-existing HF. Finally, we explore future directions and discuss knowledge gaps regarding nutrition therapies for the treatment of HF.

Why a d-ß-hydroxybutyrate monoester?

Much of the world's prominent and burdensome chronic diseases, such as diabetes, Alzheimer's, and heart disease, are caused by impaired metabolism. By acting as both an efficient fuel and a powerful signalling molecule, the natural ketone body, d-ß-hydroxybutyrate (ßHB), may help circumvent the metabolic malfunctions that aggravate some diseases. Historically, dietary interventions that elevate ßHB production by the liver, such as high-fat diets and partial starvation, have been used to treat chronic disease with varying degrees of success, owing to the potential downsides of such diets. The recent development of an ingestible ßHB monoester provides a new tool to quickly and accurately raise blood ketone concentration, opening a myriad of potential health applications. The ßHB monoester is a salt-free ßHB precursor that yields only the biologically active d-isoform of the metabolite, the pharmacokinetics of which have been studied, as has safety for human consumption in athletes and healthy volunteers. This review describes fundamental concepts of endogenous and exogenous ketone body metabolism, the differences between the ßHB monoester and other exogenous ketones and summarises the disease-specific biochemical and physiological rationales behind its clinical use in diabetes, neurodegenerative diseases, heart failure, sepsis related muscle atrophy, migraine, and epilepsy. We also address the limitations of using the ßHB monoester as an adjunctive nutritional therapy and areas of uncertainty that could guide future research.

Zinc Deficiency and Heart Failure: A Systematic Review of the Current Literature.

Zinc is an essential micronutrient that impacts the cardiovascular system through modulation of oxidative stress. It is unknown whether zinc levels are affected in heart failure (HF), and whether the association, if present, is causal. A systematic search for publications that report coexisting zinc deficiency in patients with HF was performed to provide an overview of the pathophysiological and epidemiological aspects of this association (last search April 2019). Review of the literature suggests multiple potential pathophysiologic causes for zinc deficiency in HF as a result of impaired micronutrient consumption, hyper-inflammatory state, upregulation of the renin-angiotensin-aldosterone axis, diminished absorption, and hyperzincuria from HF medications. In a longitudinal study of patients with HF in the setting of intestinal malabsorption, there was partial cardiomyocyte and left ventricular ejection fraction recovery with intravenous selenium and zinc supplementation. Two randomized double-blind control trials evaluating micronutrient and macronutrient supplementation including zinc in patients with HF found improvement in echocardiographic findings compared with placebo. Two recently completed studies evaluated the role for zinc supplementation in 2 different HF populations: a trial of zinc supplementation in patients with non-ischemic HF, and a trial of micronutrient supplementation (including B vitamins, vitamin D, and zinc) in veterans with systolic dysfunction; the results of which are still pending. Several pathobiological pathways to link zinc deficiency with the development and deterioration of HF are presented. Preliminary clinical data are supportive of such an association and future studies should further investigate the effects of zinc supplementation on outcomes in patients with HF.

Influence of nutrition support therapy on readmission among patients with acute heart failure in the intensive care unit: A single-center observational study.

BACKGROUND & AIMS: The effect of nutrition support therapy on prevention of readmission among patients with acute heart failure (HF) in an intensive care unit (ICU) setting remains unclear. We hypothesized that nutrition support therapy might decrease the readmission rate among these patients. Thus, we conducted a single-center prospective observational study to verify this hypothesis. METHODS: Patients diagnosed with acute HF admitted to the ICU for more than 14 days between April 2016 and March 2017 were included in the analysis. The primary outcome was the relationship between nutritional intake and HF-related hospital readmission due to HF at 180 days after discharge. We divided the participants into 2 groups: patients who were not readmitted to hospital within 180 days after discharge (non-readmission group) and patients who were readmitted within this timeframe (HF-related readmission group). Data were expressed as median (interquartile range). RESULTS: Sixty patients required readmission due to HF-related events (HF-related readmission group). On the other hand, 127 patients did not require readmission (non-readmission group). The calorie and protein intake on day 3 after ICU admission in the HF-related readmission group was significantly higher than that in the non-readmission group [20.5 (14.2, 27.8) vs. 27.7 (22.5, 31.2) kcal/kg/day, p < 0.001; 0.7 (0.5, 0.9) vs. 0.9 (0.7, 1.2) g/kg/day, p < 0.001, respectively]. Similarly, the protein intake values on day 7 were also significantly higher in the HF-related readmission group [0.8 (0.6, 1.0) vs. 0.9 (0.7, 1.2) g/kg/day, p = 0.04]. Multivariate analysis indicated that total caloric intake on day 3 was an independent factor affecting readmission (odds ratio = 1.05, 95% confidence interval = 1.01-1.09, p = 0.006). In addition, when the cut off value of calorie intake was set to 18 kcal/kg/day, the group ingesting ≥18 kcal/kg/day on day 3 had a significantly higher readmission rate within 180 days after discharge. CONCLUSIONS: Our data showed that total calorie intake ≥18 kcal/kg/day on day 3 might increase the readmission rate among patients with acute HF.

Nutraceuticals in Patients With Heart Failure: A Systematic Review.

BACKGROUND: Nutraceuticals are pharmacologically active substances extracted from vegetable or animal food and administered to produce health benefits. We recently reviewed the current evidence for nutraceuticals in patients diagnosed with heart failure as part of the writing of the Australian Guidelines for the prevention, diagnosis, and management of heart failure. METHODS: A systematic search for studies that compared nutraceuticals to standard care in adult patients with heart failure was performed. Studies were included if >50 patients were enrolled, with ≥6 months follow-up. If no studies met criteria then studies <50 patients and <6 months follow-up were included. The primary outcomes included mortality/survival, hospitalization, quality of life, and/or exercise tolerance. Iron was not included in this review as its role in heart failure is already well established. RESULTS: Forty studies met the inclusion criteria. The strongest evidence came from studies of polyunsaturated fatty acids, which modestly decreased mortality and cardiovascular hospitalizations in patients with mostly New York Heart Association class II and III heart failure across a range of left ventricular ejection fraction. Coenzyme Q10 may decrease mortality and hospitalization, but definite conclusions cannot be drawn. Studies that examined nitrate-rich beetroot juice, micronutrient supplementation, hawthorn extract, magnesium, thiamine, vitamin E, vitamin D, L-arginine, L-carnosine, and L-carnitine were too small or underpowered to properly appraise clinical outcomes. CONCLUSION: Only one nutraceutical, omega-3 polyunsaturated fatty acid, received a positive recommendation in the Australian heart failure guidelines. Although occasionally showing some promise, all other nutraceuticals are inadequately studied to allow any conclusion on efficacy. Clinicians should favor other treatments that have been clearly shown to decrease mortality.

A defined, plant-based diet as a potential therapeutic approach in the treatment of heart failure: A clinical case series.

BACKGROUND: Individuals diagnosed with congestive heart failure (CHF) have a 50% five-year mortality rate and approximately 650,000 new cases of CHF are diagnosed annually. Plant-based diets are known to improve plasma lipid concentrations, reduce blood pressure, and as part of a lifestyle intervention, lead to the regression of atherosclerotic lesions. However, a paucity of data exists with regards to plant-based diets in the treatment of CHF. METHODS: Three patients diagnosed with CHF opted to undergo a dietary intervention consisting of a defined plant-based diet as an adjunct to standard medical treatment for CHF. Cardiac magnetic resonance imaging was performed. Patients' consumed the defined plant-based diet for an average of ˜79 days. RESULTS: Follow-up cardiac magnetic resonance images revealed a 92% increase in ejection fraction [mean ±â€¯standard deviation for all data] (22.0 ±â€¯6.9% vs 42.2 ±â€¯18.4%), 21% reduction in left ventricular mass (214 ±â€¯90 g vs 170 ±â€¯102 g), 62% increase in stroke volume (55.8 ±â€¯24.3 cc vs 90.3 ±â€¯30.6 cc) and a 17% increase in cardiac output (3.6 ±â€¯1.2 L/min vs 4.2 ±â€¯1.6 L/min). In patient 1, 90-95% ostial stenosis of the left anterior descending artery nearly completely regressed following the dietary intervention. All patients subjectively reported significant clinical improvements, including less angina, shortness of breath and fatigue. CONCLUSION: As an adjunct treatment, a defined plant-based diet may contribute to the reversal of cardiac morphological and functional abnormalities in the setting of CHF.

Omega-3 Fatty Acid and Cardiovascular Outcomes: Insights From Recent Clinical Trials.

PURPOSE OF REVIEW: Omega-3 fatty acids (ω-3 FA) are among the most well-recognized health supplements but their cardiovascular benefits have long been controversial owing to inconsistent results from previous cardiovascular outcomes trials (CVOT). In this article, we provide a short review of existing literature followed by recent randomized clinical trial data, with a discussion of the potential clinical implications of these new findings. RECENT FINDINGS: Data from the randomized, controlled trial REDUCE-IT, when viewed within the context of other recently published trials ASCEND and VITAL, add to a growing body of evidence on the use of ω-3 FA therapies in the treatment of atherosclerotic cardiovascular disease (ASCVD). Given the different formulations, dosages, and patient populations studied, CVOTs of ω-3 FA have provided valuable insight into the use of these agents in cardioprotection. Current data suggest that higher dosages of pure eicosapentaenoic acid ω-3 FA formulations provide additional benefit in reduction of ASCVD events.

Benefits of multiple micronutrient supplementation in heart failure: A comprehensive review.

BACKGROUND: Multiple micronutrient supplementation has been suggested to have a role on health outcomes in patients with heart failure (HF), but the evidence is inconclusive. OBJECTIVE: To elucidate the role of multiple micronutrient supplementation in heart failure we performed a comprehensive review of the literature. METHODS AND RESULTS: The search in databases included PUBMED (until June 2018) to detect randomized controlled trials (RCTs) and meta-analyzes that investigated the impact of micronutrient supplementation in HF. RESULTS: With more than 2357 titles and abstracts reviewed, we included only the studies suitable for the final review. Whether alone or in combination, micronutrients have been found to improve the health outcomes of patients with HF by improving symptoms, work capacity and left ventricular ejection fraction (LVEF), thus increasing the quality of life in these patients. CONCLUSION: Future studies are needed to document the effects of multiple micronutrient associations in order to include them in nutritional guidelines to increase survival and to improve quality of life in patients with heart failure.

Vitamin D Dietary Supplementation: Relationship with Chronic Heart Failure.

It is estimated that over 1 billion people worldwide have a deficiency of vitamin D, also known as hypovitaminosis D, which the World Health Organization has defined as a public health problem. Beyond its historical homeostasis regulatory function of calcium and phosphorus, in relation to the preservation of the skeletal system, several studies show today a close connection between hypovitaminosis D and the genesis of rheumatic, autoimmune, neoplastic, and cardiovascular diseases. With exclusive reference to cardiovascular aspects, multiple heart diseases such as hypertension, myocardial ischemia, and heart failures might have deficiency in vitamin D as an important causative factor. Because of the influence of concomitant pathologies caused by antibiotic-resistant agents, the function of this vitamin should be critically evaluated. However, the role of vitamin D remains to be established; only a few studies have tested the effects of its supplementation in patients with chronic heart failure diseases, and reported results are unclear. It is important to implement studies in this field in order to assess the real benefits induced by vitamin D supplementation in cardiovascular patients and, in particular, in patients with heart failure. Should the research confirm actual clinical improvement after treatment with vitamin D, such a supplementation might represent a new low-cost therapeutic approach to improving quality of life.

Effects of vitamin D supplementation on inflammatory markers in heart failure: a systematic review and meta-analysis of randomized controlled trials.

Vitamin D is reported to have anti-inflammatory properties; however the effects of vitamin D supplementation on inflammation in patients with heart failure (HF) have not been established. We performed a systematic review and meta-analysis examining effects of vitamin D supplementation on inflammatory markers in patients with HF. MEDLINE, CINAHL, EMBASE, All EBM, and Clinical Trials registries were systematically searched for RCTs from inception to 25 January 2017. Two independent reviewers screened all full text articles (no date or language limits) for RCTs reporting effects of vitamin D supplementation (any form, route, duration, and co-supplementation) compared with placebo or usual care on inflammatory markers in patients with heart failure. Two reviewers assessed risk of bias and quality using the grading of recommendations, assessment, development, and evaluation approach. Seven studies met inclusion criteria and six had data available for pooling (n = 1012). In meta-analyses, vitamin D-supplemented groups had lower concentrations of tumor necrosis factor-alpha (TNF-α) at follow-up compared with controls (n = 380; p = 0.04). There were no differences in C-reactive protein (n = 231), interleukin (IL)-10 (n = 247) or IL-6 (n = 154) between vitamin D and control groups (all p > 0.05). Our findings suggest that vitamin D supplementation may have specific, but modest effects on inflammatory markers in HF.

Dietary nitrate supplementation opposes the elevated diaphragm blood flow in chronic heart failure during submaximal exercise.

Chronic heart failure (CHF) results in a greater cost of breathing and necessitates an elevated diaphragm blood flow (BF). Dietary nitrate (NO3‾) supplementation lowers the cost of exercise. We hypothesized that dietary NO3‾ supplementation would attenuate the CHF-induced greater cost of breathing and thus the heightened diaphragm BF during exercise. CHF rats received either 5days of NO3‾-rich beetroot (BR) juice (CHF+BR, n=10) or a placebo (CHF, n=10). Respiratory muscle BFs (radiolabeled microspheres) were measured at rest and during submaximal exercise (20m/min, 5% grade). Infarcted left ventricular area and normalized lung weight were not significantly different between groups. During submaximal exercise, diaphragm BF was markedly lower for CHF+BR than CHF (CHF+BR: 195±28; CHF: 309±71mL/min/100g, p=0.04). The change in diaphragm BF from rest to exercise was less (p=0.047) for CHF+BR than CHF. These findings demonstrate that dietary NO3‾ supplementation reduces the elevated diaphragm BF during exercise in CHF rats thus providing additional support for this therapeutic intervention in CHF.

The effects of a low-carbohydrate diet on oxygen saturation in heart failure patients: a randomized controlled clinical trial / Efecto de una dieta baja en hidratos de carbono sobre la saturación de oxígeno en pacientes con insuficiencia cardiaca: ensayo clínico aleatorizado

Introduction: Nutritional therapy in heart failure (HF) patients has been focused on fluid and sodium restriction with the aim of decreasing volume overload. However, these recommendations are not well established and sometimes controversial. Objective: To evaluate the effect of the consumption of a low-carbohydrate diet on oxygen saturation, body composition and clinical variables during two months of follow-up in chronic, stable heart failure patients. Methods: In a parallel group randomized controlled clinical trial, 88 ambulatory patients were randomly assigned to a low-carbohydrate diet group (40% carbohydrates, 20% protein and 40% fats [12% saturated, 18% monounsaturated and 10% polyunsaturated]) or a standard diet group (50% carbohydrates, 20% protein and 30% fats [10% saturated, 10% monounsaturated and 10% polyunsaturated]) for two months. Diets were normocaloric in both groups. At baseline and at two months of follow-up, the variables evaluated were: oxygen saturation, dietary intake, body composition and handgrip strength. Results: After two months of follow-up, the low-carbohydrate diet group decreased the carbohydrate consumption and had improved oxygen saturation (93.0 ± 4.4 to 94.6 ± 3.2, p = 0.02), while the standard diet group had decreased (94.90 ± 2.4 to 94.0 ± 2.9, p = 0.03). There were also differences between the groups at the end of the study (p = 0.04). No significant differences showed in handgrip strength in both groups, low-carbohydrate diet group (26.4 ± 8.3 to 27.2 ± 8.3 kg, p = 0.07) and standard diet group (25.4 ± 8.9 to 26.1 ± 9.5 kg, p = 0.14). Conclusions: Low-carbohydrate diet may improve the oxygen saturation in patients with chronic stable heart failure (AU)

Introducción: la terapia nutricional en pacientes con insuficiencia cardiaca (IC) ha sido enfocada en la restricción de líquidos y de sodio con el objetivo de reducir la sobrecarga de volumen. Sin embargo, estas recomendaciones no están bien establecidas y en algunos casos son controvertidas. Objetivo: evaluar el efecto del consumo de una dieta baja en hidratos de carbono sobre la saturación de oxígeno, composición corporal y variables clínicas durante dos meses de seguimiento en pacientes con insuficiencia cardiaca estable. Métodos: ensayo clínico aleatorizado paralelo en 88 pacientes ambulatorios que fueron asignados aleatoriamente al grupo dieta baja en hidratos de carbono (40% hidratos de carbono, 20% proteínas y 40% lípidos [12% saturadas, 18% monoinsaturadas y 10% poliinsaturadas]) o al grupo dieta estándar (50% hidratos de carbono, 20% proteínas y 30% lípidos [10% saturadas, 10% monoinsaturadas y 10% poliinsaturadas]) por dos meses. Las dietas fueron normocalóricas en ambos grupos. En la medición basal y a los dos meses de seguimiento, las variables evaluadas fueron: saturación de oxígeno, ingesta dietética, composición corporal y fuerza de presión de mano. Resultados: después de dos meses de seguimiento, el grupo de dieta baja en hidratos de carbono disminuyó el consumo de hidratos de carbono y mejoró la saturación de oxígeno (93.0 ± 4.4 to 94.6 ± 3.2, p = 0.02), mientras que el grupo de dieta estándar disminuyó (94.90 ± 2.4 to 94.0 ± 2.9, p = 0.03). También se observó diferencia entre los grupos al fi nal del estudio (p = 0.04). No se observaron diferencias estadísticamente significativas en fuerza de mano en ambos grupos: dieta baja en hidratos de carbono (26.4 ± 8.3 to 27.2 ± 8.3 kg, p = 0.07) y dieta estándar (25.4 ± 8.9 to 26.1 ± 9.5 kg, p = 0.14). Conclusiones: la dieta baja en hidratos de carbono mejora la saturación de oxígeno en pacientes con insuficiencia cardiaca estable (AU)

Oral nutritional supplement use in relation to length of stay in heart failure patients at a regional medical center.

RATIONALE, AIMS, AND OBJECTIVES: Improving the nutritional status of hospitalized patients has been shown to reduce length of stay (LOS), hospital costs, readmission rates, complication rates, and mortality. Provision of nutrient-rich, liquid, oral nutrition supplements (ONS) is one approach to improve nutritional status. Little information is available on ONS use and LOS among heart failure patients. METHODS: This study used a retrospective design to examine whether routine ONS use was associated with hospital LOS among 570 heart failure inpatients (89 ONS = yes; 481 ONS = no) at a regional medical center, adjusting for significant personal, locational, and time variables using multiple logistic regression analysis. RESULTS: Oral nutrition supplement use was associated with high LOS in this sample (odds ratio = 2.43). High LOS was also associated with higher Charlson comorbidity index values, discharge destination, hospital room location, and dietitian consults. CONCLUSIONS: These results show that ONS orders alone are not adequate to reduce LOS among heart failure patients. Continued research is needed on ways to improve care to reduce LOS among hospitalized patients.

Effect of vitamin D on all-cause mortality in heart failure (EVITA): a 3-year randomized clinical trial with 4000 IU vitamin D daily.

AIMS: Circulating 25-hydroxyvitamin D (25OHD) levels <75 nmol/L are associated with a nonlinear increase in mortality risk. Such 25OHD levels are common in heart failure (HF). We therefore examined whether oral vitamin D supplementation reduces mortality in patients with advanced HF. METHODS AND RESULTS: Four hundred HF patients with 25OHD levels <75 nmol/L were randomized to receive 4000 IU vitamin D daily or matching placebo for 3 years. Primary endpoint was all-cause mortality. Key secondary outcome measures included hospitalization, resuscitation, mechanical circulatory support (MCS) implant, high urgent listing for heart transplantation, heart transplantation, and hypercalcaemia. Initial 25OHD levels were on average <40 nmol/L, remained around 40 nmol/L in patients assigned to placebo and plateaued around 100 nmol/L in patients assigned to vitamin D. Mortality was not different in patients receiving vitamin D (19.6%; n = 39) or placebo (17.9%; n = 36) with a hazard ratio (HR) of 1.09 [95% confidence interval (CI): 0.69-1.71; P = 0.726]. The need for MCS implant was however greater in patients assigned to vitamin D (15.4%, n = 28) vs. placebo [9.0%, n = 15; HR: 1.96 (95% CI: 1.04-3.66); P = 0.031]. Other secondary clinical endpoints were similar between groups. The incidence of hypercalcaemia was 6.2% (n = 10) and 3.1% (n = 5) in patients receiving vitamin D or placebo (P = 0.192). CONCLUSION: A daily vitamin D dose of 4000 IU did not reduce mortality in patients with advanced HF but was associated with a greater need for MCS implants. Data indicate caution regarding long-term supplementation with moderately high vitamin D doses. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov Idenitfier: NCT01326650.

Vitamins in Heart Failure: Friend or Enemy?

BACKGROUND: The failing heart is characterized by a depleted metabolic energy reserve and the upregulation of several molecular mechanisms leading to cardiac hypertrophy, inflammation, fibrosis, angiogenesis, and apoptosis. Dietary or non-dietary supplementation of vitamins could potentially benefit energy balance. OBJECTIVE: The objective of the present study was to evaluate all available information on vitamins supplementation in patients with chronic HF for possible beneficial effect on metabolic, inotropic, chronotropic and hemodynamic indices. METHOD: We searched MEDLINE via Pubmed by using the following terms: "chronic heart failure" OR "cardiomyopathy" AND "vitamins", "vitamin A", "B complex vitamins", "vitamin C", "ascorbic acid", "vitamin D", "retinol", "vitamin E", "thiamine", "riboflavin", "niacin", "pyridoxine", "cobalamin", "folate", "pantothenic acid", "biotin", "tocopherol" and combinations of them. RESULTS: Data regarding supplementation of micronutrients in HF for most vitamins were sparse, and the inference about cardiovascular outcomes was obscured by the heterogeneity of studies, high inherent morbidity, and mortality of this group of high-risk patients, limited sample sizes in certain studies, unclear design and lack of head to head comparisons. Most vitamins in human trials failed to offer survival, or robust beneficial effect. Mostly indirect favorable evidence is derived from patients with deficiencies of certain micronutrients rather than their ad hoc supplementation. CONCLUSION: While vitamins and micronutrients are promising compounds for optimizing myocardial metabolism and homeostasis in HF, additional randomized clinical trials of larger scale are warranted to demonstrate the benefits of their supplementation in this high risk group of patients.