beta-carotene and Heart-Failure

Randomized controlled trials are generally regarded as the gold standard of study designs to determine causality. The inclusion of a placebo group in these trials, when appropriate, is critical to access the efficacy of a drug or supplement. The placebo response itself has received some attention in the medical literature over the past fifty years. The recent increasing utilization of dietary supplements and herbal medications by patients makes it imperative to reevaluate the placebo response in conventional and alternative medicine. This article will review some of the negative and positive results from randomized trials utilizing dietary supplements (androstenedione, beta-carotene, CoQ10, garlic, soy, vitamin C and E...) for a number of non-urologic and urologic conditions, including cancer.

Topics: Androstenedione; Antioxidants; beta Carotene; Coenzymes; Complementary Therapies; Dehydroepiandrosterone; Garlic; Heart Failure; Hot Flashes; Humans; Libido; Neoplasms; Placebo Effect; Randomized Controlled Trials as Topic; Ubiquinone; Vitamin E

Several recent studies have suggested an increased cancer risk among patients with heart failure (HF). However, these studies are constrained by limited size and follow-up, lack of comprehensive data on other health attributes, and adjudicated cancer outcomes.. This study sought to determine whether HF is associated with cancer incidence and cancer-specific mortality.. The study assembled a cohort from the Physicians' Health Studies I and II, 2 randomized controlled trials of aspirin and vitamin supplements conducted from 1982 to 1995 and from 1997 to 2011, respectively, that included annual health evaluations and determination of cancer and HF diagnoses. In the primary analysis, the study excluded participants with cancer or HF at baseline and performed multivariable-adjusted Cox models to determine the relationship between HF and cancer, modeling HF as a time-varying exposure. In a complementary analysis, the study used the landmark method and identified cancer-free participants at 70 years of age, distinguishing between those with and without HF, and likewise performed Cox regression. Sensitivity analyses were performed at 65, 75, and 80 years of age.. Among 28,341 Physicians' Health Study participants, 1,420 developed HF. A total of 7,363 cancers developed during a median follow-up time of 19.9 years (25th to 75th percentile: 11.0 to 26.8 years). HF was not associated with cancer incidence in crude (hazard ratio: 0.92; 95% confidence interval: 0.80 to 1.08) or multivariable-adjusted analysis (hazard ratio: 1.05; 95% confidence interval: 0.86 to 1.29). No association was found between HF and site-specific cancer incidence or cancer-specific mortality after multivariable adjustment. Results were similar when using the landmark method at all landmark ages.. HF is not associated with an increased risk of cancer among male physicians.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; beta Carotene; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Forecasting; Heart Failure; Humans; Incidence; Male; Middle Aged; Neoplasms; Prognosis; Provitamins; Retrospective Studies; Risk Assessment; Risk Factors; Survival Rate; United States

The causal association between circulating β-carotene concentrations and cardiovascular disease (CVD) remains controversial. We conducted a Mendelian randomization study to explore the effects of β-carotene on various cardiovascular diseases, including myocardial infarction, atrial fibrillation, heart failure, and stroke. Three single nucleotide polymorphisms (SNPs) associated with the β-carotene levels were obtained by searching published data and used as instrumental variables. Genetic association estimates for 4 CVDs (including myocardial infarction, atrial fibrillation, heart failure, and stroke) in the primary analysis, blood pressure and serum lipids (high-density lipoprotein [HDL] cholesterol, LDL cholesterol, and triglycerides) in the secondary analysis were obtained from large-scale genome-wide association studies (GWASs). We applied inverse variance-weighted as the primary analysis method, and 3 others were used to verify as sensitivity analysis. Genetically predicted circulating β-carotene levels (natural log-transformed, µg/L) were positively associated with myocardial infarction (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.18, P = .011) after Bonferroni correction. No evidence supported the causal effect of β-carotene on atrial fibrillation (OR 1.02, 95% CI 0.96-1.09, P = .464), heart failure (OR 1.07, 95% CI 0.97-1.19, P = .187), stroke (OR 1.03, 95% CI 0.93-1.15, P = .540), blood pressure (P > .372) and serum lipids (P > .239). Sensitivity analysis produced consistent results. This study provides evidence for a causal relationship between circulating β-carotene and myocardial infarction. These findings have important implications for understanding the role of β-carotene in CVD and may inform dietary recommendations and intervention strategies for preventing myocardial infarction.

Topics: Atrial Fibrillation; beta Carotene; Cardiovascular Diseases; Cholesterol, HDL; Genome-Wide Association Study; Heart Failure; Humans; Mendelian Randomization Analysis; Myocardial Infarction; Polymorphism, Single Nucleotide; Stroke; Triglycerides

Topics: beta Carotene; Heart Failure; Humans; Male; Population Surveillance; Risk Assessment

Fruit and vegetable intake has been associated with lower risk for cardiovascular diseases, but data on congestive heart failure (CHF) are inconsistent. The association of serum carotenoids, biomarkers reflecting fruit and vegetable intake, with the risk of CHF has not been well documented in previous studies. We therefore examined the association between carotenoid levels and the risk of CHF.. Data were available for 1031 males aged 46 to 65 years participating in the Kuopio Ischaemic Heart Disease Risk Factor Study (Finland). Baseline data for the present study were collected between 1991 and 1993. The association between serum concentrations of carotenoids and the risk of CHF was examined by using Cox proportional hazard models.. During the median of 17.8 follow-up years, CHF occurred in 72 patients. Age and examination year adjusted risk (hazard ratio, HR) for CHF among men within the lowest quartile of serum β-carotene was 4.08 (95% CI, 1.90-8.78, p<0.001) as compared to men in the highest quartile of serum β-carotene. After further adjustment for many potential confounders, men with the lowest quartile of β-carotene had almost 3-fold increased risk of CHF (HR=2.78, 95% CI, 1.23-6.25, p=0.014). However, serum concentrations of lycopene and α-carotene were not related to the risk of CHF.. The present study suggests that low concentrations of serum β-carotene may be associated with an increased risk of CHF.

Topics: Aged; beta Carotene; Biomarkers; Blood Pressure; Chromatography, High Pressure Liquid; Finland; Follow-Up Studies; Forecasting; Heart Failure; Humans; Incidence; Male; Middle Aged; Population Surveillance; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Survival Rate

Our objectives were to explore novel metabolic risk factors for development of heart failure (HF).. In the past decade, considerable knowledge has been gained from limited samples regarding novel risk factors for HF, but the importance of these in the general population is largely unexplored.. In a community-based prospective study of 2,321 middle-aged men free from HF and valvular disease at baseline, variables reflecting glucose and lipid metabolism and variables involved in oxidative processes were compared with established risk factors for HF (prior myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, obesity, and serum cholesterol) using Cox proportional hazards analyses.. During a median follow-up time of 29 years, 259 subjects developed HF. In a multivariable Cox proportional hazards backward stepwise model, a 1-SD increase of fasting proinsulin (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.15 to 1.66) and apolipoprotein B/A-I-ratio (HR 1.27, 95% CI 1.09 to 1.48) increased the risk, whereas a 1-SD increase in serum beta-carotene (HR 0.79, 95% CI 0.66 to 0.94) decreased the risk of HF. These variables also remained significant when adjusting for acute myocardial infarction during follow-up.. Novel variables reflecting insulin resistance and dyslipidemia, together with a low beta-carotene level, were found to predict HF independently of established risk factors. If confirmed, our observations could have large clinical implications, as they may offer new approaches in the prevention of HF.

Topics: Antioxidants; Apolipoproteins; beta Carotene; Comorbidity; Diabetes Mellitus; Heart Failure; Humans; Insulin Resistance; Male; Middle Aged; Oxidative Stress; Prognosis; Proinsulin; Proportional Hazards Models; Prospective Studies; Risk Factors

Antioxidant vitamins reduce cardiac oxidative stress and cardiomyocyte apoptosis produced by exogenous norepinephrine (NE) and attenuate cardiac dysfunction in animals with pacing-induced congestive heart failure (CHF). This study was carried out to determine whether the mitogen-activated protein kinase (MAPK) signal transduction pathways are involved in oxidative stress-induced myocyte apoptosis. Rabbits with rapid pacing-induced CHF and sham operation were randomized to receive either a combination of antioxidant vitamins (beta-carotene, ascorbic acid, and alpha-tocopherol), alpha-tocopherol alone, or placebo for 8 wk. Compared with sham-operated animals, CHF animals exhibited increased oxidative stress as evidenced by decreased myocardial reduced-to-oxidized glutathione (GSH/GSSG) ratio (27 +/- 7 vs. 143 +/- 24, P < 0.05), myocyte apoptosis (77 +/- 18 vs. 17 +/- 4 apoptotic nuclei/10,000 cardiomyocytes, P < 0.05), increased total and phosphorylated c-Jun NH2-terminal protein kinase (p-JNK; 1.95 +/- 0.14 vs. 1.04 +/- 0.04 arbitrary units, P < 0.05) and phosphorylated p38 kinase (p-p38), and decreased phosphorylated extracellular signal-regulated kinase (p-ERK). Administration of antioxidant vitamins and alpha-tocopherol attenuated oxidative stress, myocyte apoptosis, and cardiac dysfunction, with reversal of the changes of total JNK, p-JNK, and p-ERK in CHF. Furthermore, because NE infusion produced changes of JNK, p-p38, and p-ERK similar to those in CHF, we conclude that NE may play an important role in the production of oxidative stress, MAPK activation, and myocyte apoptosis in CHF.

Topics: alpha-Tocopherol; Animals; Antibodies, Monoclonal; Antioxidants; Apoptosis; Ascorbic Acid; beta Carotene; Blotting, Western; Cardiac Pacing, Artificial; Chromans; DNA, Single-Stranded; Glutathione; Heart Failure; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase 9; Mitogen-Activated Protein Kinases; Myocardium; Myocytes, Cardiac; Norepinephrine; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Rabbits; Superoxide Dismutase; Sympathomimetics

Plasma levels of malondialdehyde (MDA), vitamin A, and of antioxidant micronutrients including vitamin E, lutein, zeaxanthin, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene were measured in 30 patients with class II and III congestive heart failure (CHF) according to the New York Heart Association (NYHA) classification and in 55 controls. Ejection fraction was evaluated by echocardiography in all patients as a measure of the emptying capacity of the heart. Plasma levels of all measured compounds were significantly lower and MDA significantly higher in patients compared to controls (p <.001). Class II NYHA patients showed significantly lower MDA levels and significantly higher levels of vitamin A, vitamin E, lutein, and lycopene than class III patients. Ejection fraction was inversely correlated with MDA levels and directly correlated with vitamin A, vitamin E, lutein, and lycopene levels in patients. The present study supports the concept that an increased consumption of vitamin-rich fruits and vegetables might help in achieving cardiovascular health.

Topics: Aged; Aged, 80 and over; beta Carotene; Carotenoids; Echocardiography; Female; Heart Failure; Humans; Lipid Peroxidation; Lutein; Male; Malondialdehyde; Middle Aged; Severity of Illness Index; Stroke Volume; Vitamin A; Vitamin E; Xanthophylls; Zeaxanthins

We administered antioxidant vitamins to rabbits with pacing-induced cardiomyopathy to assess whether antioxidant therapy retards the progression of congestive heart failure (CHF).. Although oxidative stress is increased in CHF, whether progression of heart failure could be prevented or reduced by antioxidants is not known.. Rabbits with chronic cardiac pacing and sham operation were randomized to receive a combination of beta-carotene, ascorbic acid and alpha-tocopherol, alpha-tocopherol alone or placebo over eight weeks. Echocardiography was used to measure cardiac function weekly. Resting hemodynamics and in vivo myocardial beta-adrenergic responsiveness were studied at week 8. Animals were then sacrificed for measuring myocardial beta-receptor density, norepinephrine (NE) uptake-1 site density, sympathetic neuronal marker profiles, tissue-reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and oxidative damage of mitochondrial DNA (mtDNA).. Rapid cardiac pacing increased myocardial oxidative stress as evidenced by reduced myocardial GSH/GSSG ratio and increased oxidized mtDNA and produced cardiac dysfunction, beta-adrenergic subsensitivity, beta-receptor downregulation, diminished sympathetic neurotransmitter profiles and reduced NE uptake-1 carrier density. A combination of antioxidant vitamins reduced the myocardial oxidative stress, attenuated cardiac dysfunction and prevented myocardial beta-receptor downregulation and sympathetic nerve terminal dysfunction. Administration of alpha-tocopherol alone produced similar effects, but the effects were less marked than those produced by the three vitamins together. Vitamins produced no effects in sham-operated animals.. Antioxidant vitamins reduced tissue oxidative stress in CHF and attenuated the associated cardiac dysfunction, beta-receptor downregulation and sympathetic nerve terminal abnormalities. The findings suggest that antioxidant therapy may be efficacious in human CHF.

Topics: alpha-Tocopherol; Analysis of Variance; Animals; Antioxidants; Ascorbic Acid; beta Carotene; DNA, Mitochondrial; Down-Regulation; Echocardiography; Glutathione; Heart Failure; Hemodynamics; Myocardium; Neurotransmitter Agents; Oxidative Stress; Rabbits; Receptors, Adrenergic, beta; Sympathetic Nervous System

Chronic heart failure (CHF) seems to be associated with increased oxidative stress. However, the hypothesis that antioxidant nutrients may contribute to the clinical severity of the disease has never been investigated.. To examine whether antioxidant nutrients influence the exercise capacity and left ventricular function in patients with CHF.. Dietary intake and blood levels of major antioxidant nutrients were evaluated in 21 consecutive CHF patients and in healthy age- and sex-matched controls. Two indexes of the severity of CHF, peak exercise oxygen consumption (peak VO2) and left ventricular ejection fraction (LVEF), were measured and their relations with antioxidants were analysed.. Whereas plasma alpha-tocopherol and retinol were in the normal range, vitamin C (P=0.005) and beta-carotene (P=0.01) were lower in CHF. However, there was no significant association between vitamins and either peak VO2 or LVEF. Dietary intake (P<0.05) and blood levels of selenium (P<0.0005) were lower in CHF. Peak VO2 (but not LVEF) was strongly correlated with blood selenium: r=0.76 by univariate analysis (polynomial regression) and r=0.87 (P<0.0005) after adjustment for age, sex and LVEF.. Antioxidant defences are altered in patients with CHF. Selenium may play a role in the clinical severity of the disease, rather than in the degree of left ventricular dysfunction. Further studies are warranted to confirm the data in a large sample size and to investigate the mechanisms by which selenium and other antioxidant nutrients are involved in CHF.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cardiomyopathies; Chronic Disease; Feeding Behavior; Female; Heart Failure; Humans; Male; Middle Aged; Oxidative Stress; Selenium; Ventricular Function, Left