Vitamins, supplements, herbal medicines, and arrhythmias

Nutritional and herbal supplements may have harmful or beneficial effects on arrhythmias. Potential supplements that may have antiarrhythmic activity include omega-3 polyunsaturated fatty acids (N-3 PUFA), coenzyme Q10, and carnitine. Clinical studies show that N-3 PUFA or fish oil supplementation appears to reduce mortality and sudden death. Coenzyme Q10, used in treatment of heart failure, and carnitine and its derivatives may have beneficial effects on arrhythmias, although clinical studies have been limited. Antioxidant supplements may be beneficial, but large studies with vitamin E have been disappointing in that it does not reduce mortality. Correction of electrolyte disturbances has been long advised and magnesium supplementation has been beneficial in the treatment of torsades de pointes and in some studies after cardiac surgery. However, routine electrolyte supplementation with empiric potassium or magnesium in non-deficient patients has not been convincingly beneficial. Several herbal supplements have also been promoted to have antiarrhythmic activity. However, clinical studies are lacking to support routine use of these herbal medications. In addition, some herbal supplements may cause serious proarrhythmia, and many supplements significantly interact with warfarin and digoxin.     

Vitamin E status during dietary fish oil supplementation in rheumatoid arthritis

The primary objective of this study was to determine whether it is the fish oil itself or the alpha-tocopherol that is added to the fish oil preparations (to prevent peroxidation) that is responsible for the beneficial effects of dietary supplementation with fish oil in patients with rheumatoid arthritis (RA). One group of RA patients took fish oil supplements and another group took alpha-tocopherol-enriched coconut oil supplements (placebo controls), both for 3 months. Clinical and laboratory indices of RA activity in relation to cellular and plasma vitamin E levels were assessed at the beginning and the end of the trial. The results of the study provide evidence that the beneficial effects of fish oil supplementation cannot be ascribed to the antioxidizing properties of the alpha-tocopherol per se.     

Dietary fish oil and rheumatic diseases

Dietary fish oil supplementation can induce several metabolic changes relevant to rheumatic diseases. Both experimental and clinical evidence show that dietary fish oil supplementation modulates inflammatory and immune responses. Many studies have shown beneficial, albeit modest, effects in the treatment of rheumatoid arthritis. Studies in murine models of systemic lupus erythematosus have been encouraging, but few studies have been performed to assess the effects of dietary fish oil in the human disease or in other systemic rheumatic diseases. Further study on the efficacy of dietary fish oil supplementation in the treatment of specific rheumatic diseases is warranted.     

Fish Oil for Primary and Secondary Prevention of Coronary Heart Disease

Fish consumption and fish oils rich in omega-3 fatty acids were reported to be cardioprotective in both retrospective and prospective studies undertaken over the past two to three decades. In the past several years, there is mounting clinical trial data as well as basic science information supporting the use of fish oil supplements in both primary and secondary cardiovascular prevention. In addition, there appear to be additional benefits to the use of fish oil, including lowering significantly elevated triglyceride levels, preventing atrial fibrillation, reducing mortality rates in congestive heart failure patients, and perhaps stabilizing atherosclerotic plaques. These data have led to specific recommendations for use of omega-3 fatty acids in several cardiovascular areas.     

The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects

OBJECTIVE: Evaluation of the effects of supplementation of n-3 and n-6 fatty acids on vascular tone and endothelial function in healthy men and women aged 40 to 65 years. METHODS: In a double-blind, randomised, placebo controlled study, 173 healthy volunteers took one of six oil supplements for 8 months. Supplements were placebo, oleic acid rich sunflower oil, evening primrose oil, soya bean oil, tuna fish oil, and tuna/evening primrose oil mix. Endothelium-dependent and independent vascular responses were measured in the forearm skin using laser Doppler imaging following iontophoretic applications of acetylcholine and sodium nitroprusside, respectively. RESULTS: Acetylcholine, but not sodium nitroprusside responses were significantly improved after tuna oil supplementation (P=0.02). Additionally, there were significant positive correlations between acetylcholine responses and n-3 fatty acid levels in the plasma and erythrocyte membrane phospholipids after tuna oil supplementation. No significant changes in vascular response were seen after supplementation with any of the other oils. CONCLUSIONS: Fish oil supplementation has a beneficial effect on endothelial function, even in normal healthy subjects. Modification of the diet by an increase of 6% in eicosapentaenoic acid and 27% in docosahexaenoic acid (equivalent to eating oily fish 2-3 times/week) might have significant beneficial effects on cardiovascular function and health.     

Vitamin D and heart

The authors briefly review the biological effects of vitamin D on the heart and discuss the experimental and clinical studies related to the potential protective effect of vitamin D on the cardiovascular system. Experimental and observational studies in man strongly suggest that vitamin D supplementation can benefit heart failure patients and improve cardiovascular health in the population. However, presently there are limited randomized controlled studies. The authors highlight the hypothesis that vitamin D-induced mechanisms activating calcium channels may represent a novel target for therapy in patients with heart failure.     

Delayed and indirect effects of antiarrhythmic drugs in reducing sudden cardiac death

In the USA, two-thirds of sudden cardiac deaths (SCDs) are caused by sustained ventricular tachycardia and ventricular fibrillation. Implantable cardioverter defibrillator (ICD) therapy has been demonstrated to decrease mortality caused by these arrhythmias, when used both for primary and secondary prevention. However, ICD use is expensive, has proarrhythmic effects and does not prevent ventricular arrhythmias. Antiarrhythmic drugs (AADs) can be used for acute or chronic therapy to prevent ventricular arrhythmias and SCD. Most commonly, AADs are often used in patients with an ICD who have recurrent ICD shocks due to ventricular arrhythmias. Class I AADs are used in patients with a structurally normal heart and are contraindicated in patients with structural heart disease. β-blockers have been demonstrated to be beneficial in preventing mortality and malignant tachyarrhythmias in postmyocardial infarction and congestive heart failure patients, and in patients who have an ICD. Amiodarone has a neutral effect on mortality, while other class III drugs may increase mortality in certain subgroups of patients. Dronedarone, a new class III drug, may reduce mortality, but sufficient data are not available to allow for its use in the prevention of malignant tachyarrhythmias. Few drugs that are not classified as AADs can also prevent arrhythmias, via their beneficial effects on cardiovascular remodeling. These non-ADDs have delayed and indirect effects, which are mediated by the renin-angiotensin-aldosterone system and lipid metabolism - n-3 polyunsaturated fatty acids (fish oil), and statins, and can thus can reduce the likelihood of future malignant ventricular arrhythmias in patients with coronary artery disease or congestive heart failure. The role of chronic drug therapy alone for primary and secondary prevention of SCD is less than desirable because of proarrhythmic and adverse side effects. The non-ADDs are well tolerated and have no proarrhythmic actions, thus their benefit could outweigh risks, although currently there are no concrete data to suggest this.     

Coenzyme Q10 in cardiovascular disease with emphasis on heart failure and myocardial ischaemia

The vitamin-like nutrient CoQ₁₀ (ubiquinone), discovered in 1957 and first used in human illness in 1967, has a crucial role in cellular ATP production as the coenzyme for mitochondrial complexes I, II and III. CoQ₁₀ is also a lipid soluble antioxidant with cell protective effects. The past 30 years of clinical study have focused on congestive heart failure, ischaemic heart disease, angina, and myocardial protection during open-heart surgery. Measurably low blood and tissue levels of CoQ₁₀ are evident in heart failure and may be normalised with oral CoQ₁₀ supplementation, which has in turn been associated with measurable clinical improvement. Benefits observed in angina as well as objective measurement of ischaemia are believed to be related to both the bioenergetic and antioxidant properties of CoQ₁₀ Recent studies of CoQ₁₀ supplementation during open heart surgery showing an improvement in postoperative recovery have suggested a myocardial protective effect. The growing appreciation of the clinical relevance of CoQ₁₀ depletion has caused concern over the CoQ₁₀-lowering effect of the increasingly more potent and popular HMG-CoA reductase inhibitors (statins). Overall, CoQ₁₀ appears to be a unique addition to standard medical therapy for cardiovascular disease.     

Stem-cell transplantation in myocardial infarction: a status report

Myocardial infarction is the leading cause of congestive heart failure and death in the industrialized world. Current therapy is limited in preventing the progression of ventricular remodeling and congestive heart failure. Recent interest has focused on stem cells, which are undifferentiated and pluripotent cells that can proliferate, potentially self-renew, and differentiate into cardiomyocytes. Myocardial regeneration with stem-cell transplantation is a possible treatment option to reverse the deleterious hemodynamic and neurohormonal effects that occur after myocardial infarction and can lead to congestive heart failure. Various preclinical animal studies show the potential to regenerate myocardium and improve perfusion to the infarct area to improve cardiac function but also suggest that stem cells may have proarrhythmic effects. Early phase I clinical studies indicate that stem-cell transplantation is feasible and may have beneficial effects on ventricular remodeling after myocardial infarction. Future randomized clinical trials will establish the magnitude of the benefit and the effects on arrhythmias after stem-cell therapy.     

Modification of experimental and clinical atherosclerosis by dietary fish oil

A number of experimental studies have reported that dietary fish oil can attenuate the development of atherosclerosis in cholesterol-fed rats, quails, rabbits, pigs, and monkeys. Epidemiologic studies suggest that dietary fish oil can reduce the development of cardiovascular disease in humans. Data are limited but suggest that laboratory animals, normal volunteers, and patients with hyperlipidemia show similar responses to the consumption of fish oil. The major effect of dietary fish oil on serum lipoproteins is a reduction in plasma triglyceride levels, with inconsistent effects on plasma cholesterol and HDL-cholesterol. Dietary fish oil induces a significant reduction of platelet aggregation associated with a prolonged bleeding time. This antithrombotic effect may be partially related to a decreased thromboxane A2 and to an increased prostacyclin level. Dietary fish oil may also have anti-inflammatory and anti-immunologic effects through an elevation of prostaglandins and a reduction in the level of leukotriene B4. Recent experimental data suggest that either fish oil or verapamil can bring on a regression in atherosclerosis in cholesterol-fed rabbits put on a normal diet; however, there was no additive effect of the combination of these agents. Overall, data suggest that fish oil may have a role in attenuating the development of atherosclerosis.     

The role of fish oil in arrhythmia prevention

Numerous epidemiological studies, case-control series, and randomized trials have demonstrated the ability of fish oil to reduce major cardiovascular events, particularly sudden cardiac death and all-cause mortality. We discuss the potential benefits of fish oil therapy to improve overall autonomic tone and potentially reduce the risk of major ventricular and atrial arrhythmias. Specifically, this review focuses on how fish oil therapy has performed in 3 primary prevention trials in patients with implantable cardioverter defibrillators, reviews the effects that fish oil has on the autonomic nervous system, focuses on the use of fish oil as a novel therapy for atrial fibrillation, and revisits other beneficial properties of fish oil (ie, ability to lower serum triglycerides, anti-inflammatory effects, and possible improvements in arterial pressure/diastolic function). We also discuss the safety profile of fish oil, including effects on bleeding time and bleeding complications as well as provide commentary regarding fish oil supplementation in light of increasing contaminants contained in fish. In summary, any patient with documented coronary heart disease and those with risk factors for sudden cardiac death, such as left ventricular dysfunction, left ventricular hypertrophy, prior myocardial infarction, or high-grade ventricular dysrhythmias, should consider fish oil supplementation. The American Heart Association recommends four 3-ounce servings of oily fish weekly. For those who cannot eat fish or do not have access to fish, as well as those who would prefer not to eat fish regularly, capsules of fish oil are readily available in various concentrations. At the present time, we recommend doses of eicosapentanoic acid and docosahexanoic acid in the combined range of 800 to 1000 mg/day for primary and secondary prevention of cardiovascular disease.     

The role of enhanced external counterpulsation in the treatment of angina and heart failure

As the incidence of angina and heart failure continue to rise, new therapeutic options will be needed to treat patients who remain symptomatic or who are intolerant to current treatment. Enhanced external counterpulsation (EECP) is a noninvasive modality being investigated in both angina and congestive heart failure patients. It has been proven to provide symptomatic benefit in angina patients, but has not been proven to show an increase in life expectancy or decrease in cardiovascular events. EECP in heart failure has been proven to be safe, but its efficacy is still uncertain. The present paper summarizes the current literature on the clinical use of EECP in angina and heart failure.     

Chronic heart failure and multiple micronutrient supplementation: realistic hope or idealistic conjecture?

Recent studies have demonstrated the inefficacy of nutritional supplements containing various combinations of vitamins and minerals for otherwise healthy elderly people and patients with ischemic heart disease. However, patients with chronic heart failure (CHF) have, up until recently, been excluded from such studies. CHF has a high mortality and morbidity and patients are often elderly with poor general nutrition and high levels of micronutrient deficiency. It is in this population that nutritional supplementation has the most potential benefit. Evidence is accumulating that a strategy of long-term highdose multiple micronutrient supplementation might improve symptoms and cardiac function in elderly patients with CHF. In this article, we review the effects of individual micronutrients and how they might impact on CHF, and present recent data that dietary supplementation might offer an addition to standard therapy for CHF.     

The natural treatment of hypertension

The goal of this review is to evaluate the efficacy of commonly available dietary supplements in the treatment of hypertension, using the average blood pressure reduction achieved with the implementation of lifestyle modifications as a standard. For this reason, the authors focus on the antihypertensive potential of these agents rather than pharmacology, pharmacokinetics, adverse effects, or supplement-drug interactions. For the purpose of this review, dietary supplements are defined as exhibiting some evidence of benefit if a systolic blood pressure reduction of 9.0 mm Hg or greater and/or a diastolic blood pressure reduction of 5.0 mm Hg or greater has been observed in previously published, peer-reviewed trials. These defining limits are based on the average blood pressure reduction associated with the implementation of certain lifestyle modifications. Agents with some evidence of benefit include coenzyme Q10, fish oil, garlic, vitamin C, and L-arginine.     

Clinical trials update from the American Heart Association: REPAIR-AMI, ASTAMI, JELIS, MEGA, REVIVE-II, SURVIVE, and PROACTIVE

This article provides information and a commentary on trials presented at the American Heart Association meeting held in November 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. In REPAIR-AMI an improvement in ejection fraction was observed in post-MI patients following infusion of bone marrow stem cells. However, the ASTAMI study showed no benefit of stem cell implantation in a similar patient cohort. The JELIS study reported a reduction in major coronary events in patients receiving statins plus fish oil compared to statins alone. MEGA showed that low dose statins in a low risk population reduce the incidence of major cardiovascular events. Two studies of levosimendan in acute heart failure gave conflicting results, in the REVIVE-II study levosimendan was reported to have a superior effect on the composite primary outcome compared to placebo, however, in SURVIVE despite a trend to early benefit with levosimendan, there was no difference in effect on long-term outcome versus dobutamine. The PROACTIVE study showed encouraging results for the use of pioglitazone in post-myocardial infarction patients with concomitant type 2 diabetes.     

A systematic review and meta-analysis of the impact of omega-3 fatty acids on selected arrhythmia outcomes in animal models

Epidemiological studies and clinical trials report the beneficial effects of fish or fish oil consumption on cardiovascular disease outcomes including sudden death. We performed a systematic review of the literature on controlled animal studies that assessed the effects of omega-3 fatty acids on selected arrhythmia outcomes. On the basis of predetermined criteria, 27 relevant animal studies were identified; 23 of these were feeding studies, and 4 were infusion studies. Across species, fish oil, eicosapentaenoic acid, and/or docosahexaenoic acid appear to have beneficial effects on ventricular tachycardia (VT) and fibrillation (VF) in ischemia- but not reperfusion-induced arrhythmia models; no effect on the incidence of death and infarct size; and inconsistent results with regard to arrhythmia score, VF threshold, ventricular premature beats or length of time in normal sinus rhythm, compared to omega-6, monounsaturated, or saturated fatty acids, and no treatment controls. In a meta-analysis of 13 studies using rat models, fish oil but not alpha-linolenic acid supplementation showed a significant protective effect for ischemia- and reperfusion-induced arrhythmias by reducing the incidence of VT and VF. It is not known whether omega-3 fatty-acid supplementation has antiarrhythmic effects in other disease settings not related to ischemia.     

Fish, Long-Chain Omega-3 Polyunsaturated Fatty Acids and Prevention of Cardiovascular Disease—Eat Fish or Take Fish Oil Supplement?

The association between fish consumption and risk of cardiovascular disease (CVD) has been extensively studied. Although the results are inconsistent, the majority of studies are in favor of cardioprotective effects of fish consumption. There is little doubt that long-chain ω-3 polyunsaturated fatty acids (LCn-3PUFAs) in fish are the key nutrients responsible for the benefits and are important for CVD prevention. Although fish is valued as a source of these fatty acids, it also provides other nutrients that may have cardioprotective effects. It is likely that the beneficial effects of fish consumption on the risk of CVD are the synergistic effects among nutrients in fish, and the integrative effects of fish consumption may reflect the interactions of nutrients and contaminants in fish. This review summarizes the epidemiology of fish or LCn-3PUFAs with major CVD risk factors as well as coronary heart disease mortality and stroke. This review also discusses the possible difference between whole fish as a nutrient package and fish oil supplements as a source of LCn-3PUFAs with respect to CVD prevention. Further studies are needed to investigate the potential adverse effects of contaminants in fish and the possible different effects from different types of fish and cooking methods.     

Diet and rheumatoid arthritis: a review of the literature

INTRODUCTION: Rheumatoid arthritis is a common inflammatory condition. A large number of patients seek alternative or complementary therapies of which diet is an important component. This article reviews the evidence for diet in rheumatoid arthritis along with the associated concept of oral tolerization. METHODS: References were taken from Medline from 1966 to September 2004. The keywords, rheumatoid arthritis, diet, n-3 fatty acids, vitamins, and oral tolerization, were used. RESULTS: Randomized controlled trials (RCTs) indicate that dietary supplementation with n-3 fatty acids provides modest symptomatic benefit in groups of patients with rheumatoid arthritis. Epidemiological studies and RCTs show cardiovascular benefits in the broader population and patients with ischemic heart disease. A number of mechanisms through which n-3 fats may reduce inflammation have been identified. In a small number of patients with rheumatoid arthritis, other dietary manipulation such as fasting, vegan, and elimination diets may have some benefit. However, many of these diets are impractical or difficult to sustain long term. CONCLUSIONS: Dietary manipulation provides a means by which patients can a regain a sense of control over their disease. Dietary n-3 supplementation is practical and can be easily achieved with encapsulated or, less expensively, bottled fish oil.     

Dietary fatty acid supplementation alters stress reactivity and performance in man

Certain dietary polyunsaturated fatty acids, gamma linolenic (18:3n-6) and eicosapentaenoic (20:5n-3) acid, attenuate cardiovascular reactivity to stress in rats. To study their effects on cardiovascular reactivity to acute stress in man, 30 men were randomly assigned to one of three groups and given 28 day supplements of borage oil (containing 18:3n-6), fish oil (containing 20:5n-3), or olive oil (placebo). Reactivity to the Stroop colour-word conflict test was assessed prior to and following treatment. Borage oil alone attenuated blood pressure and heart rate responses to stress, increased skin temperature, and improved task performance. These data suggest that diet may be used to alter stress reactivity in man.     

A prospective,randomized, and double-blind trial on the effect of fish oil on the incidence of restenosis following ptca

Restenosis after successful coronary angioplasty (PTCA) occurs in 25–35% of all procedures. To date, most pharmacologic strategies have failed to reduce the restenosis rate significantly. However, recent studies have suggested a potential benefit of dietary supplementation with omega-3 fatty acids (fish oil) on restenosis following PTCA. The benefit of omega-3 polyunsaturated fatty acids on the incidence of coronary artery restenosis following elective PTCA was assessed in 212 consecutive patients (41 female, 171 male). Following a successful angioplasty, 204 patients a dietary supplementation with either nine capsules containing fish oil (3.15 g omega-3 fatty acids) or nine placebo capsules containing olive oil. Treatment was started immediately after PTCA and maintained over 4 mon. Compliance was assessed by analysis of lipid fatty acids prior to angioplasty and at 4 mon follow-up. The angiographically determined incidence of restenosis (stenosis diameter > 50%) was 31.2% per lesion in patients receiving fish oil and 33.7% in patients receiving olive oil. Gross progression of coronary artery disease in vessels not subjected to angioplasty was 17% and 16%, respectively. In conclusion, low dose fish oil supplementation begun on the day of a successful coronary angioplasty failed to demonstrate any effect on coronary artery restenosis. © 1993 Wiley-Liss, Inc.