Journal of the American College of Cardiology Vol. 46, No. 1, 2005 2005 by the American College of Cardiology Foundation ISSN 0735-1097/05/$30.00 Published by Elsevier Inc.
ACCF COMPLEMENTARY MEDICINE EXPERT CONSENSUS DOCUMENT Integrating ComplementaryMedicine Into Cardiovascular Medicine A Report of the American College of Cardiology FoundationTask Force on Clinical Expert Consensus Documents(Writing Committee to Develop an Expert ConsensusDocument on Complementary and Integrative Medicine) WRITING COMMITTEE MEMBERS
When citing this document, the American College of Cardiology Foundation Copies: This document is available on the World Wide Web site of the American College would appreciate the following citation format: Vogel JHK, Bolling SF, Costello RB, of Cardiology Reprints of this document may be purchased for $10 each by Guarneri EM, Krucoff MW, Longhurst JC, Olshansky B, Pelletier KR, Tracy CM, calling 1-800-253-4636, ext. 694, or by writing to the American College of Cardiology, Vogel RA. Integrating complementary medicine into cardiovascular medicine: a Educational Services, 9111 Old Georgetown Road, Bethesda, MD 20814-1699.
report of the American College of Cardiology Foundation Task Force on Clinical Permissions: Multiple copies, modification, alteration, enhancement, and/or dis- Expert Consensus Documents (Writing Committee to Develop an Expert Consensus tribution of this document are not permitted without the express permission of the Document on Complementary and Integrative Medicine). J Am Coll Cardiol American College of Cardiology Foundation. Please direct requests to: 2005;46:184 –221.
JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document TABLE OF CONTENTS
practitioners, payers, and other interested parties of many evolving areas of clinical practice and/or technologies asso- Introduction .185 ciated with this topic that are widely available or new to the Organization of Committee and Evidence Review .185 practice community. Topics chosen for coverage by CECD are so designated because the evidence base and experience Purpose of This CECD .186 II. Nutrition and Supplements .187 with technology or clinical practice are not considered sufficiently well developed to be evaluated by the formal Bioactive Components in Foods .188 American College of Cardiology/American Heart Associa- Vitamin and Mineral Supplements .191 tion (ACC/AHA) Practice Guidelines process. Often, the Herbal Preparations.194 topic is the subject of considerable ongoing investigation.
Herb-Drug Interactions: What We Need to Know.196 The Task Force on CECDs recognizes that considerable Related Alternative Therapy .199 debate exists regarding the clinical utility of alternative III. Mind/Body and Placebo.200 The Mind/Body Relationship and its Correlation medicine practices. By their nature, alternative medicine practices differ widely in their scientific support. Despite Impact of Stress on CVD Risk Factors.201 this varying evidence base, these practices are widely em- Depression and the Development of CVD .202 ployed by patients, including those with CVD. Many practitioners are not familiar with many alternative medi- IV. Acupuncture.203 cine techniques. Thus, the reader should view this CECD V. Bioenergetics (Energy Medicine) .205 as the best attempt of the ACCF to inform and guide Methods to Study Bioenergy .205 clinical practice in an area where rigorous evidence is not yet Forms of Bioenergetics.206Caveats.207 available or the evidence to date is not widely accepted.
Where feasible, CECDs include indications or contraindi- VI. Spirituality/Intentionality .207 cations. The ACC/AHA Practice Guidelines Committee Spirituality in Cardiovascular Applications.207 may subsequently address some topics covered by CECDs.
The Task Force on Clinical Expert Consensus Docu- Review Articles and Meta-Analyses.208 ments makes every effort to avoid any actual or potential Specific Reports of Spirituality and conflicts of interest that might arise as a result of an outside Cardiovascular Care.208Key Issues in Spirituality Applied to relationship or personal interest of a member of the writing Cardiovascular Care.209 panel. Specifically, all members of the writing panel are Delivery Roles, Accreditation, and Certification asked to provide disclosure statements of all such relation- ships that might be perceived as real or potential conflicts of Summary and General Recommendations.210 interest. These statements are reviewed by the parent task force and updated as changes occur. Please see Appendix I Appendix I: Relationships With Industry .210 for the relationship with industry information pertinent to Appendix II: Glossary.210 this document.
The following additional appendices are located on Robert A. Vogel, MD, FACC Chair, ACCF Task Force on Clinical Expert Appendix III: Internet Sources for Complementary Medicine Appendix IV: Review of the Literature for Cardiovascular-Related Integrative Medicine Appendix V: Dietary Supplement Intake Form Organization of Committee and Evidence Review
Appendix VI: Books and Compendia on Spirituality in Cardio- vascular Applications The Writing Committee consisted of acknowledged experts Appendix VII: Structured Reviews and Meta-Analyses of Spiritual in the field of complementary, alternative, and integrative Descriptors and Therapies and Their Correlations With medicine. Both the academic and private sectors were (Noncardiology) Clinical Outcomes represented. The document was reviewed by five officialreviewers nominated by the ACCF, representatives from the American Association of Critical Care Nurses, AHA, This document was commissioned by the American College American Nurses Association, Preventive Cardiovascular of Cardiology Foundation (ACCF) Task Force on Clinical Nurses Association, and the Society of Thoracic Surgeons, Expert Consensus Documents (CECDs) to provide a per- as well as 20 content reviewers nominated by the Writing spective on the current state of complementary, alternative, Committee. This document will be considered current until and integrative medical therapies specifically as they relate the Task Force on CECDs revises or withdraws it from to cardiovascular diseases (CVDs). It is intended to inform Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 and integrate those benefits into routine care and lifestylemanagement.
Alternative medical therapies encompass a broad spectrum The most complete and comprehensive findings to date of practices and beliefs From a historical standpoint, on Americans' use of CAM were released on May 27, 2004, they may be defined as, " . . practices that are not accepted by the National Center for Complementary and Alternative as correct, proper, or appropriate or are not in conformity Medicine (NCCAM) and the National Center for Health with the beliefs or standards of the dominant group of Statistics (NCHS, part of the Centers for Disease Control medical practitioners in a society" The Institute of and Prevention) The new data came from a detailed Medicine (IOM) has recently reviewed complementary and survey on CAM included for the first time in 2002 in the alternative medical practices in the U.S. from a general National Health Interview Survey (NHIS). The NHIS, a viewpoint This document will focus on cardiac aspects survey done annually by the NCHS, interviews people in of complementary medicine. From a functional standpoint, tens of thousands of American households about their alternative (also known as "complementary" or "integrative") health- and illness-related experiences.
therapies may be defined as interventions neither taught The findings are yielding (and will continue to yield, widely in medical schools nor generally available in hospitals through future analyses) a wealth of information on who Ernst et al. contend that "complementary medical uses CAM, what they use, and why. In addition, researchers techniques [complement] mainstream medicine by contrib- can examine CAM use as it relates to many other factors uting to a common whole, by satisfying a demand not met such as age, race/ethnicity, place of residence, income, by orthodoxy or by diversifying the conceptual frameworks educational level, marital status, health problems, and the of medicine." The terminology currently in use to describe practice of certain behaviors that impact health (such as these practices remains controversial. Many commonly used smoking cigarettes or drinking alcohol).
labels (e.g., "alternative," "unconventional," or "unproven") The survey showed that a large percentage of American are judgmental and may inhibit the collaborative inquiry and adults are using some form of CAM—36% When discourse necessary to distinguish useful from useless tech- prayer specifically for health reasons is included in the niques Complementary and alternative medicine (CAM) definition of CAM, that figure rises to 62%. Dr. Stephen E.
is the language currently used by the National Institutes of Straus, NCCAM Director, said, "The survey data will provide Health (NIH) to describe this field of inquiry. The term new and more detailed information about CAM use and the "integrative medicine" has been used with increased fre- characteristics of people who use CAM. One benefit will be to quency. Several recently published studies and editorials help us target NCCAM's research, training, and outreach wrestle with the challenges of properly labeling and describ- efforts, especially as we plan NCCAM's second five years, 2005 ing this field of inquiry Herbs, vitamins, and non-herbal dietary products, as well as therapies conducted There is little doubt that CAM represents a revolution around issues such as spirituality, bioenergetics (i.e., acu- within our health care delivery system. Nevertheless, our puncture and energy fields), and mind/body, are all consid- traditional views of the medical establishment do not fully ered to be forms of complementary, alternative, or integra- support CAM. There is a lack of significant instruction of tive medicine.
CAM in medical schools, there is a paucity of CAM in mostmajor hospitals, and there is little solid research published in Purpose of This CECD
peer-reviewed journals. Compensation by insurance compa-nies for CAM is also an issue.
The purpose of this CECD is to put the emerging area of A recent report of the IOM entitled "Complementary CAM treatment and investigation into focus in order to and Alternative Medicine in the U.S." described and enable the physician to provide better patient care in a characterized CAM therapies used by the American public.
meaningful and safe manner. The document will be con- Additionally, the IOM sought to identify major scientific cerned with the most recent advances and utilization of policy and practice issues related to CAM research and to CAMs and therapies in a traditional cardiovascular practice.
the translation of validated therapies into conventional In 2000, nearly 50% of all Americans sought the help of practice. In short, the report recommended that the same an alternative health care practitioner. This represents over principles and standards of evidence of treatment effective- 600 million visits Nearly $30 billion was spent in the ness apply to all treatments, whether currently labeled as year 2001 on CAM Many CAM interventions, conventional medicine or CAM. Although randomized including numerous herbal supplements, have been em- controlled trials (RCTs) remain the "gold standard" of ployed in an attempt to treat CVD. Of prime importance is evidence for treatment efficacy, the IOM noted that other putting CAM into perspective with its potential benefits study designs can be used to provide information about the and knowledge of important interactions with traditional effectiveness when RCTs cannot be done or may not be cardiovascular medicines. In response to an enormous in- generalizable to CAM practice. Other acceptable clinical volvement in CAM, medical facilities have developed spe- research designs included: preference RCTs (trials that cialized CAM centers to investigate the potential benefits include both randomized and non-randomized treatment JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document arms); observational and cohort studies; case-control stud- C-reactive protein; and decreases high-density lipoprotein ies; studies of bundles (combinations) of therapies; studies (HDL) cholesterol. Even modest weight reduction can that specifically incorporate, measure, or account for placebo improve these atherogenic markers Weight loss only or expectation effects; and attribute-treatment interaction occurs when caloric intake is less than caloric expenditure.
analyses. Prioritization criteria were also proposed to assist The daily caloric requirement for sedentary and physically researchers regarding which CAM therapies might warrant active individuals, respectively, is about 12 and 15 kcal per lb of ideal weight. A 3,500 kcal deficit results in approximately Integrating CAM into medicine must be guided by 1 lb of weight loss. On the average, a deficit or excess of 500 compassion, but enhanced by science, and made meaningful calories a day brings about weight loss or gain at the rate of through solid doctor-patient relationships. Most impor- 1 lb a week. Increasing physical activity also results in tantly, CAM involves a commitment to the core mission of weight loss. One mile walked or jogged is equivalent to caring for patients on a physical, mental, and spiritual level.
about 100 calories burned. The most successful weight loss This document attempts to enable us to fulfill these objec- programs use calorie restriction, exercise, counseling, and tives. A glossary of terms is contained in Appendix II. For group support.
additional information on CAM, please refer to Extremely low-carbohydrate or ketotic diets have become for Appendix III: Internet Sources for Complementary popular for weight loss Some randomized trials have Medicine Information and Appendix IV: Review of the found that obese individuals lose more weight on low- Literature for Cardiovascular-Related Integrative Medicine.
carbohydrate diets than on low-fat diets, although thedifference is not uniformly significant The mecha- II. NUTRITION AND SUPPLEMENTS nisms by which extremely low-carbohydrate diets facilitateweight loss include osmotic diuresis, glycogen and associ- This section provides a discussion of general nutrition and ated water depletion, anorexia due to ketosis, and exclusion dietary supplements, including vitamins, minerals, and of foods. Although LDL cholesterol decreases during the herbs that are related to the prevention and reduction of risk weight loss phase of low-carbohydrate dieting, levels return of CVD. Please see Appendix V at for a to baseline in the long term. Two benefits of extremely sample dietary supplement intake form.
low-carbohydrate diets are a decrease in triglycerides and anincrease in insulin sensitivity. The long-term cardiovascular effects of low-carbohydrate/high-fat diets are unknown, but Diet is a major determinant of cardiovascular health. Gen- epidemiologic data suggest that they would increase athero- eral nutrition affects body weight, lipoproteins, blood pres- sure, blood glucose, endothelial function, inflammation, and Extremely low-fat diets have been used to treat estab- coagulation. Dietary modification is an important compo- lished coronary artery disease (CAD) One small study nent of primary and secondary prevention of coronary heart has demonstrated modest CAD regression Extremely disease (CHD) and hypertension. The essentials of proper low-fat diets are difficult to apply widely. Low-fat diets are nutrition include appropriate caloric intake and consump- consistent with the general epidemiologic finding that tion of the essential macronutrients (carbohydrate, proteins, atherosclerosis prevalence correlates with saturated fat in- and fats) and micronutrients (vitamins, minerals). Specific take, and more specifically, with trans fat intake. However, nutrients can either accelerate or retard the development of low-fat diets can increase small LDL particles. These diets also do not recognize the cardiovascular benefits that can be Obesity. Obesity contributes to CHD, diabetes, and hy-
derived from omega-3 fatty acids. They also may increase pertension Obesity (body mass index [BMI] greater triglyceride levels and decrease insulin sensitivity.
than 30 kg/m2) increased 50% in this country from 1991 to Macronutrients. Fatty acids can be generally characterized
1998 Almost one-third of Americans are now obese into saturated, trans, monounsaturated, and polyunsaturated and another one-third are overweight (BMI 25 to 30 classes depending on the number and configuration of kg/m2). The major cause of this recent increase in obesity is double bonds. Saturated and trans fatty acids increase serum a 150 to 200 kcal increase in our daily caloric intake, mainly LDL cholesterol and directly impair endothelial function from snacks A decrease in physical activity associated Trans fatty acids also decrease HDL cholesterol with more television viewing has also contributed. A third Considerable data suggest an association between factor has been an increase in sugar consumption, which dietary saturated and trans fats and CHD Dietary now averages 150 lbs per person per year The latter cholesterol is also associated with CHD, but elevations in factor has also contributed to an increased prevalence of type serum cholesterol are individually variable with dietary intake. Monounsaturated fatty acids have neutral effects on Weight loss is often an important part of the manage- serum LDL and HDL cholesterol Polyunsaturated ment of CHD, diabetes, and hypertension Excess fatty acids reduce HDL cholesterol, but their use in ran- weight increases low-density lipoprotein (LDL) cholesterol, domized trials is associated with decreased cardiovascular triglycerides, and markers of inflammation, such as Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 Omega-3 fatty acids have three to six double bonds, the Mediterranean diet. The prevalence of CVD is consider-
first one occurring between the third and fourth carbon ably less in Mediterranean and Pacific Rim countries than in from the methyl end. The omega-3 fatty acids have the U.S. at equivalent cholesterol levels Common to such societies is a diet high in fruits, vegetables, beans, and anti-inflammatory properties Omega-3 fatty acids whole-grain carbohydrates, nuts, fish, and monounsaturated include alpha-linolenic, eicosapentaenoic, and decosahexae- and polyunsaturated oils. Dairy products are consumed in noic acids. The former is contained in plant oils, whereas low-to-moderate amounts and little red meat is eaten.
the latter two are contained in fish oils. Prospective ran- Alcohol is consumed in moderation. The Lyon Diet Heart domized trials have demonstrated that consuming plant and Study tested the effectiveness of a Mediterranean- fish omega-3 fatty acids reduces cardiovascular events, type diet, modified by substitution of an alpha-linolenic sudden death, and overall mortality acid-enriched canola oil margarine for olive oil, on cardio- Carbohydrates include monosaccharides, such as sugars, vascular risk after a first myocardial infarction. After an oligosaccharides, and polysaccharides or starches. Complex average follow-up of 46 months, subjects following the carbohydrates consist of starches and indigestible fiber.
modified Mediterranean-style diet had 72% fewer cardio- Fiber adds bulk to food and slows carbohydrate digestion.
vascular events and 60% lower all-cause mortality. Findings Soluble fiber in the form of psyllium, guar gum, and oat from the Lyon Diet Study have been reproduced recently bran reduces serum LDL cholesterol The blood using an Indo-Mediterranean diet in subjects with CHD glucose raising property of a food per 50 g of carbohydrate The intervention diet recommending increased con- and per portion is measured by its glycemic index and load, sumption of fruits, vegetables, nuts, whole grains, and respectively High glycemic load foods such as cookies, mustard and soybean oils reduced cardiovascular events by rice, and potatoes increase serum triglycerides, decrease 45% and sudden cardiac death by 66%. Additionally, rec- insulin sensitivity, and probably facilitate obesity.
ommendations to increase fruit, vegetables, and low-fat Dietary recommendations. There are two types of dietary
dairy product consumption has been found to lower blood guidelines. The first type recommends specific quantities of pressure in the Dietary Approaches to Stop Hypertension macronutrients, such as less than 200 mg of cholesterol per day and less than 7% of calories as saturated fat, as in the Summary of general nutritional recommendations.
AHA Step 2 diet A second type recommends consump-tion and exclusion of specific foods, often in combination.
• Achieve and maintain ideal body weight by limiting An example is the recommendation to eat stanol/sterol ester foods high in calories and low in nutrient density, margarines, soy products, soluble fiber, and walnuts or including those high in sugar, such as soft drinks and almonds to lower LDL cholesterol The latter specific food portfolio recommendation has been found to • Eat a variety of fruits, vegetables, legumes, nuts, soy lower LDL cholesterol more (29%) than an AHA Step 2 products, low-fat dairy products, and whole grain breads, approach (8%) In general, diets containing unsaturated cereals, and pastas.
fats, whole grains, fruits, vegetables, fish, and moderate • Eat baked or broiled fish at least twice per week.
alcohol are optimal for preventing heart disease In • Choose oils and margarines low in saturated and trans fat October 2000, the AHA revised its dietary guidelines for and high in omega-3 fat, such as canola, soybean, walnut, Americans The new guidelines retain the principles of and flaxseed oils, including those fortified with stanols the Step 1 and Step 2 diet but place emphasis on foods and and sterols.
an overall eating pattern (see the following text) rather than • Avoid foods high in saturated and trans fats, such as red on percentages of food components such as fat.
meat, whole milk products, and pastries.
The National Cholesterol Education Program (NCEP) • If you drink alcohol, limit consumption to no more than has issued new practice guidelines on the prevention and 2 drinks per day for a man or 1 drink per day for a management of high cholesterol in adults The Third Adult Treatment Panel (ATPP III) of the NCEP further • Eat less than 6 g of salt or less than 2,400 mg of sodium modified its dietary recommendations to include a more intense and effective eating plan than previously advocated.
• Be physically active. Get 30 min of exercise daily.
The new Therapeutic Lifestyle Changes (TLC) treatment Bioactive Components in Foods
plan complements that of the AHA guidelines and recom-mends less than 7% of calories from saturated fat and less Food components recommended for lowering the risk of than 200 mg of dietary cholesterol daily. Total allowed fat CVD include plant sterols, soluble fiber, omega-3 fatty ranges from 25% to 35% of total daily calories provided that acids, nuts, and soy. Additional foods, such as garlic and saturated fats and trans fatty acids are kept low. The ATP teas, and moderate alcohol use will be discussed.
III encourages the use of foods that contain plant stanols Omega-3 fatty acids. Individual fatty acids have remark-
and sterols or are rich in soluble fiber, to achieve greater ably diverse effects on coronary risk factors and vascular LDL cholesterol-lowering power.
biology Omega-3 and -6 fatty acids are essential JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document nutrients. Dietary fatty acids affect eicosanoid products (e.g., significant reduction in serum total (12%) and LDL (17%) thromboxanes, leukotrienes, prostaglandins) responsible for cholesterol levels in individuals taking a stable dose of a vasoregulation, inflammation, and coagulation. Omega-3 statin drug No trials have studied the effects of fatty acids may also affect CHD outcomes by decreasing stanol/sterol esters on cardiovascular risk. Stanol and sterol triglyceride levels, ventricular arrhythmias, decreasing fi- esters should be avoided by the rare individual with familiar brinogen levels and platelet counts, modestly reducing blood pressures, and decreasing cell proliferation. Improvements Garlic (Allium sativum). Garlic is an herb that has been
in arterial compliance and endothelial function have also used for thousands of years as a food and spice. Garlic been documented with fish oil, a major supply of dietary potentially affects plasma lipids, fibrinolytic activity, platelet omega-3 fatty acids. There are changes in autonomic tone aggregation, blood pressure, and blood glucose Various (as observed by improvement in heart rate variability mea- formulations/preparations of garlic and different study de- sures) and in mood (depression) signs have led to contradictory results. The Agency for Epidemiologic studies have generally shown an Healthcare Research and Quality (AHRQ) noted on inverse correlation between consumption of fish or other review of 36 randomized trials modest, short-term effects of sources of dietary omega-3 fatty acids and cardiovascular garlic supplementation on lipid and antithrombotic factors.
events. Conversely, other epidemiologic studies Various garlic preparations led to small but significant have failed to document the benefits of fish consumption.
reductions in total cholesterol at one month and at three Good plant sources of the 18 carbon omega-3 fatty acid, months (range of average pooled reductions 11.6 to 24.3 alpha-linolenic acid, include flaxseed, canola, pumpkin seed, mg/dl). Eight six-month controlled trials showed no signif- walnut, and soybean oil.
icant reductions. Effects on clinical outcomes are not estab- Omega-3 fatty acids have been tested in several secondary lished, and effects on glucose and blood pressure are none to prevention trials. Four prospective, controlled intervention minimal. A similar meta-analysis conducted by Stevinson et trials with either oily fish or omega-3 fatty acid capsules al. that included 13 randomized, placebo-controlled have demonstrated reduced cardiovascular trials concluded that the use of garlic for hypercholesterol- events. However, in the DART trial, fish consumption emia was of questionable value. Superko and Krauss reduced overall mortality early after myocardial infarction demonstrated in a randomized, placebo controlled trial in (MI) but was associated with higher risk over the hypercholesterolemic subjects that garlic has no effect on subsequent three years of the study The GISSI- major plasma lipoproteins and that it does not impact HDL Prevenzione study is the largest of the controlled trials subclasses, Lp(a), apolipoprotein B, postprandial triglycer- investigating omega-3 fatty acid supplements (1 g per day) ides, or LDL subclass distribution.
and CHD risk. In this trial, total mortality was reduced by Soy. Soy-based foods have cholesterol-lowering, estro-
20% and sudden death by 45% in an intention-to-treat genic, and antioxidant properties. The mechanism underly- analysis. Mortality was reduced through a decreased inci- ing the cholesterol-lowering effect of soy is likely multifac- dence in sudden death.
torial. Soy-based foods reduce lipid oxidation, promote Studies published to date are mixed regarding a role for increased vascular reactivity, and improve arterial compli- dietary omega-3 fatty acids in the prevention of restenosis ance Favorable effects of soy phytoestrogens on lipid after percutaneous coronary angioplasty They have profiles, vascular reactivity, thrombosis, and cellular prolif- not been found to reduce coronary atherosclerosis progres- eration have been reported Dietary intake of foods sion to a significant extent One study demonstrated containing phytoestrogens is associated with a favorable that occlusion of aortocoronary venous bypass grafts was cardiovascular risk profile as was demonstrated in 939 reduced after one year by daily ingestion of 4 g of fish-oil postmenopausal women participating in the Framingham Off-Spring Study The consumption of soy protein can Stanol/sterol esters. Plant sterols or phytosterols have
improve lipid profiles in hypercholesterolemic individuals been known to have a cholesterol-lowering effect since the above a background NCEP Step I diet. Soy decreases LDL 1950s. The esterification of plant stanols renders them cholesterol more in hypercholesterolemic individuals. Soy soluble in dietary fat, an effective vehicle for delivering plant supplementation may also increase the levels of HDL stanols and sterols to the site of cholesterol absorption in the cholesterol regardless of whether an individual is hypercho- small intestine. Commercially available margarines that pro- lesterolemic or not. A meta-analysis of 38 trials of soy vide 3.4 to 5.1 g a day of plant stanol esters can significantly protein demonstrated reductions in total cholesterol of reduce serum total and LDL cholesterol levels without 9.3%, LDL cholesterol of 12.9%, and triglyceride levels of affecting HDL cholesterol or triglycerides A de- 10.5%, accompanied by an increase of 2.5% in HDL crease in LDL cholesterol levels of 9% to 20% can be cholesterol However, more recent studies in post- achieved with consumption of approximately 2 g per day of menopausal women fail to show improvements in plasma plant sterol esters In a randomized, eight-week lipids A recent placebo-controlled study in 108 men placebo-controlled trial in 167 subjects, using plant stanol and 105 postmenopausal women randomized to either soy esters incorporated into an oil-based margarine, there was a protein isolate or casein placebo for three months demon- Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 strated an increase in levels of Lp(a) on soy supplementation CHD risk reduction of approximately 40% to 50% found in with no improvement in indices of arterial function the epidemiologic studies. Nuts, especially walnuts and Extracts of soy isoflavones given to human subjects do not almonds, are high in arginine, magnesium, folate, plant result in cardiovascular benefits except for improvements in sterols, and soluble fiber. Some nuts contain high levels of systemic arterial compliance omega-3 essential fatty acids (e.g., walnuts), and they are an The clinical benefit of isoflavones is unclear. In light of excellent source of vitamin E. In a prospective study of the recent findings about estrogen from the Women's 86,016 women between the ages of 34 to 59 years, without Health Initiative, the U.S. Preventive Services Task Force previously diagnosed CHD, eating 5 oz of nuts per week has stated that the evidence is inconclusive to determine was associated with a relative risk (RR) of 0.66 (95% whether phytoestrogens, such as soy isoflavones, are effec- confidence interval [CI] 0.47 to 0.93, p for trend ⫽ 0.005) tive for reducing the risk of CVD of coronary events adjusted for risk factors and independent Soluble fiber. Soluble or viscous fibers, such as oat bran,
of fiber, fruit, and vegetable supplements Recent psyllium, guar, and pectin, are thought to reduce heart disease prospective data from the Physicians' Health Study demon- by lowering total and LDL cholesterol levels without affecting strated consumption of nuts two or more times a week serum triglycerides. Conversely, insoluble wheat fiber and significantly reduced the risk of sudden cardiac death (RR) cellulose have no cholesterol-lowering effects unless used in the of 0.53 (95% CI 0.30 to 092, p for trend ⫽ 0.01) and a RR diet to replace foods supplying saturated fats or cholesterol of 0.70 (95% CI 0.50 to 0.98, p for trend ⫽ 0.06) for total Increasing dietary fiber has been recommended as a safe CHD deaths compared with men who rarely or never and practical approach to cholesterol reduction. Large epide- consumed nuts The association between nut consump- miologic studies have demonstrated a reduced risk for tion and sudden cardiac death became stronger after adjust- MIs and death from CHD in both men and women who ment for lifestyle, cardiac risk factors, and diet. Like some consume higher amounts of dietary fiber. These studies pro- nuts, canola oil and flaxseed oil are the richest known source vide strong support linking dietary fiber intake to protection of alpha-linolenic acid, an omega-3 fatty acid.
from CHD. These data are supported by numerous ecological, Tea. Tea drinking appears to be protective against CHD in
cohort, case-comparison, population-based, and, most re- a number of epidemiologic studies In the older cently, clinical trials demonstrating an inverse relationship cohort of the Rotterdam Study, an inverse association was between dietary fiber consumption and atherosclerotic CVD demonstrated between tea drinking and advanced aortic atherosclerosis Data from a more recent follow-up of The hypocholesterolemic effects of psyllium guar the Rotterdam Study highlighted a strong inverse relation gum and oat bran are documented by meta- between tea intake (greater than 375 ml/day) and MI with analyses A meta-analysis of 67 controlled trials study- the relation being stronger in women than in men. The ing the cholesterol lowering effect of four types of soluble inverse association with tea drinking was stronger for fatal fiber (oat, psyllium, pectin, and guar gum) reported small but events than for nonfatal events. For flavonoid (quercetin ⫹ significant reductions in total cholesterol (1.7 mg/dl per g kaempferol ⫹ myricetin) intake, a strong association with soluble fiber) and LDL (cholesterol (1.9 mg/dl per g soluble MI was observed only in women Results are incon- fiber) Hypercholesterolemic subjects with initially clusive for clinical and case control studies. However, a higher cholesterol levels experienced the most significant recent prospective cohort study of 1,900 patients hospital- reductions. Triglycerides and HDL cholesterol were not ized with an acute MI followed for 3.8 years found a significantly influenced by soluble fiber. The magnitude of significantly reduced hazard ratio for subsequent total and lipid lowering was found to be similar for oat, psyllium, or cardiovascular mortality of 0.56 (95% CI 0.37 to 0.84) for heavy tea drinkers (more than 14 cups/week) compared to Because of the favorable effect of soluble fiber on LDL non-tea drinkers A recent clinical study has shown cholesterol levels, the ATP III panel recommends that the that consumption of black tea improves brachial artery diet be enriched by foods that provide a total of at least 5 to flow-mediated dilation in patients with CAD De- 10 g of soluble fiber daily Dietary fiber also reduces spite the favorable epidemiology and mechanistic investiga- blood pressure, obesity, insulin resistance, and clotting tions, no studies have prospectively documented a reduction factors—all independent risk factors for CHD in cardiovascular risk with tea drinking.
Nuts. The few studies that have looked at the consumption
Alcohol. Epidemiologic studies have shown that the inci-
of whole nuts in relation to CHD have reported a consistent dence of MI, angina pectoris, and coronary-related deaths and substantial protective effect. Three of the largest nutri- are inversely related to moderate alcohol intake, as defined tional epidemiologic prospective studies evaluating multiple by 1 to 3 drinks daily. Although many mechanisms for this population groups, ages, races, and gender have found a effect have been suggested, the best documented effect is an consistent inverse relationship between nut consumption increase in HDL cholesterol by alcohol Recent and coronary risk studies have shown that moderate drinkers are less likely to The improvement in serum lipids associated with the suffer ischemic stroke peripheral vascular disease consumption of nuts does not explain the magnitude of the and death following an acute MI Cooper et al.
JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document found that light-to-moderate drinkers with left ven- complications by retarding LDL oxidation and by inhibiting tricular systolic dysfunction had fewer adverse outcomes. In the proliferation of smooth muscle cells, platelet adhesion the Framingham Heart Study, Walsh et al. found that and aggregations, the expression and function of adhesion the incidence of congestive heart failure was lower in molecules, and the synthesis of leukotrienes Antioxi- subjects who consumed moderate amounts of alcohol.
dants may improve endothelial function, reduce ischemia, Abramson et al. were able to demonstrate that and stabilize atherosclerotic plaques to prevent plaque subjects who consumed moderate levels of alcohol had a significantly lower risk of developing heart failure.
Moderate consumption of alcohol-containing beverages VITAMIN E. Primary Prevention Trials. A potential benefit
does not appear to result in significant morbidity; however, of vitamin E in CHD is suggested by two large prospective heavy alcohol consumption can result in cardiomyopathy, epidemiologic trials, which found lower event rates in hypertension, hemorrhagic stroke, cardiac arrhythmia, and subjects who took at least 100 units of vitamin E per day sudden death. Alcohol ingestion poses such a number of However, 50 mg of vitamin E in the Alpha- health hazards with irresponsible consumption that the Tocopherol, Beta-Carotene (ATBC) cancer prevention trial AHA recommends that physicians and patients discuss the of male smokers did not decrease nonfatal MIs, and adverse and potentially beneficial aspects of moderate drink- increased hemorrhagic stroke Vitamin E use was not associated with decreased stroke in the Health Profes- Overview of dietary supplements. The Dietary Supple-
sionals Follow-Up Study the Nurses Health Study ment Health and Education Act (DSHEA) of 1994 defined and the Iowa Women's Health Study Most dietary supplements as a product (other than tobacco) recently, the Collaborative Group of the Primary Prevention intended to supplement the diet for such ingredients as Project (PPP) found no decrease in cardiovascular events in vitamins, minerals, herbs, or other botanicals, amino acids, 4,495 subjects with one or more risk factors after 3.6 years and substances such as enzymes, organ tissues, glandulars, of synthetic vitamin E (300 units) therapy compared to and metabolites. Whatever their form, the DSHEA places none These data have been confirmed by a recent dietary supplements in a special category under the general pooled analysis of nine cohort studies (Pooling Project of umbrella of "foods," not drugs, and requires that every Cohort Studies on Diet and Coronary Disease) in 293,172 supplement be labeled a dietary supplement. The establish- subjects free of CHD. A lower CHD risk at higher intake ment of dietary supplements as foods limited the Food and of dietary vitamin E was present when adjusted for age and Drug Administration (FDA)'s premarketing regulatory au- energy intake. However, supplemental vitamin E intake was thority and placed the FDA in a reactive, postmarketing found not to be significantly related to a reduced risk of role. Thus, for the FDA to remove a supplement from the market it most prove that the supplement presents a Secondary Prevention Trials. Only one of several con- significant or unreasonable risk of injury or illness when trolled trials of vitamin E has shown a reduction in some used as recommended on the label. Recently, the IOM has aspect of cardiovascular risk. In the Cambridge Heart urged that the U.S. Congress and federal agencies, in Antioxidant Study (CHAOS) vitamin E reduced the conjunction with industry, research scientists, consumers, risk of nonfatal MI, but not of fatal MI. The Heart and other stakeholders, amend DSHEA and the current Outcomes Prevention Evaluation (HOPE) study found no regulatory practices for dietary supplements in an effort to effect of vitamin E for several of primary and secondary improve product consistency and reliability (IOM, 2005).
CVD end points, including disease progression monitored Just prior to the release of the IOM report on Complemen- by carotid ultrasound The GISSI-Prevenzione trial tary and Alternative Medicine in the U.S., the FDA failed to show benefit from vitamin E supplementation announced three major regulatory initiatives designed to on CHD or stroke in almost 8,000 patients. The Vitamin E further implement DSHEA Atherosclerosis Prevention Study (VEAPS) provided addi- docket no. 2004N-0458). These initi- tional evidence that vitamin E supplementation (400 units) atives serve to inform the dietary supplement industry on a did not reduce the progression of atherosclerosis as evalu- regulatory strategy involving the monitoring and evaluation ated by change in intimal medial thickness A meta- of product and ingredient safety, assurance of product analysis of seven randomized trials of vitamin E (50 units to quality via good manufacturing practice (CGMP regula- 800 units) in 81,788 patients confirmed that vitamin E did tions), and monitoring and evaluation of product labeling.
not reduce mortality, decrease cardiovascular death, or At the same time these new initiatives will give consumers cerebrovascular accident A more recent and larger a higher level of assurance about the safety of dietary (135,967 participants in 19 clinical trials) meta-analysis that supplement products and the reliability of their labeling.
considered the dose dependent effects of vitamin E supple-mentation noted that at high dosage (400 units/day or Vitamin and Mineral Supplements
more) a pooled risk difference of 34 per 10,000 persons Antioxidant vitamins. Antioxidant therapies are poten-
(95% CI 5 to 63 per 10,000 persons, p ⫽ 0.022). However, tially useful in preventing both atherosclerosis and its it is unclear whether the investigators isolated the effects of Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 vitamin E from those of other supplements. Most of the therapies. Lack of benefit for combination vitamin E (400 evidence for an elevated mortality risk came from two trials units) and vitamin C (500 mg) was also documented in 423 that administered vitamin E together with beta-carotene. It postmenopausal women with CAD participating in the is uncertain whether an increased risk for death from Women's Angiographic Vitamin and Estrogen (WAVE) high-dose vitamin E based on this most recent analysis of In contrast to the aforementioned negative trials, the Antioxidant Supplementation in Atherosclerosis Prevention VITAMIN C. Primary Prevention. When examined individu-
(ASAP) study of 440 hypercholesterolemic patients ran- ally, most observational and prospective cohort studies donot demonstrate a relationship between vitamin C intake domized to vitamins E and C, reported that combination and CVD and there have been no RCTs specif- therapy decreased the rate of atherosclerosis progression ically examining the effects of vitamin C supplementation (especially in men) over a six-year period as measured by on cardiovascular end points In the Iowa Wom- carotid artery intima-media thickness. This study selected en's Health Study, women in the top quintile of vitamin C subjects with high oxidative stress and maximized absorp- intake versus the lowest quintile had a nonsignificant tion of the antioxidants by giving them with meals increased risk for CHD mortality and a borderline signifi- In summary, aside from the recent pooled analysis of cant trend toward increased stroke Long-term use of vitamin C cohort studies, the consensus of antioxidant vitamin C in a large prospective investigation was not vitamin study results do not support a cardiovascular benefit associated with a reduced risk of stroke, as well related to the use of vitamins E and C and beta-carotene However, a more recent analysis from the Nurses' Health Study indicates that women in the highest quintile of intake FOLIC ACID, VITAMIN B , AND VITAMIN B . Elevated homo-
for vitamin C (greater than 360 mg per day from diet and cysteine levels are associated with increased risk of coronary supplements) compared with the lowest quintile (less than artery and vascular disease. The mechanisms by which or equal to 93 mg per day), had a 27% lower risk for CHD, elevated homocysteine impairs vascular function are not and women taking supplemental vitamin C had a 28% lower completely understood, but may involve the stimulation of risk of nonfatal MI and fatal CHD compared with women vascular smooth muscle cell growth and collagen synthesis, who took no vitamin C In the recent pooled analysis oxidative-endothelial injury and dysfunction, lipid peroxi- from the Pooling Project of Cohort Studies on Diet and dation and platelet activation, and hypercoagulability Coronary Disease those subjects with higher supple- Intakes of folate, vitamins B6, and B12 are inversely related mental vitamin C intake (greater than 700 mg/day) had a to homocysteine levels as all three vitamins are directly 25% reduced risk of CHD. Nevertheless, the current con- involved in the metabolism of homocysteine. Beginning in sensus does not find a value for supplemental vitamin C in 1996 and mandatory in 1998, the FDA issued a regulation preventing heart disease requiring all enriched grain products be fortified with folic BETA-CAROTENE. Trials of beta-carotene have demon-
acid (140 mcg/100 g serving portion), primarily for the strated no cardiovascular benefit, and one demonstrated an reduction of congenital neural tube defects. The fortification adverse clinical outcome. An increased incidence of lung of enriched grain product with folic acid has been associated cancer and CVD mortality were observed in the ATBC with an improvement in the folate status of middle-aged cancer prevention study Beta-carotene supplementa- and older adults In the Framingham Offspring Study tion was also associated with a slight increase in the cohort, mean homocysteine levels decreased from 10.1 to frequency of angina pectoris A meta-analysis of eight 9.4 ␮mol/l with the introduction of fortified products trials evaluating beta-carotene in 138,113 patients revealed a Initial retrospective case-control studies and small but significant increase in all-cause mortality and prospective studies suggested an inverse relation- cardiovascular death Thus, beta-carotene supplemen- ship between homocysteine and CVD. A recent meta- tation is discouraged analysis, combining 30 prospective and retrospective studies, Combination Vitamin Trials. The Heart Protection Study concluded that elevated homocysteine is less strongly related (HPS) randomized 20,536 subjects at high risk for CHD to to ischemic heart disease and stroke risk in healthy popu- 40 mg simvastatin daily or placebo and vitamin E (600 mg), lations than has been suggested A meta-analysis of 14 vitamin C (250 mg), and beta-carotene (20 mg) or placebo.
prospective cohort studies, using the inclusion criterion of After 5.5 years of study, no benefit from combination time to first cardiac or cerebrovascular event, found that vitamin therapy was evident A small RCT, the HDL elevated homocysteine levels moderately increased the risk Cholesterol Atherosclerosis Treatment Study (HATS), of a first cardiovascular event, regardless of age and duration found that vitamin C (1 g), vitamin E (800 units), beta- carotene (50 mg), and selenium (100 mcg) reduced the In secondary prevention studies, two nonrandomized benefit of simvastatin plus niacin therapy on CAD progres- trials in patients with vascular disease found an inverse sion and cardiovascular events suggesting a potential relationship between the intake of folic acid and vitamin B6 drug/supplement interaction affecting the efficacy of statin and vascular events One study conducted in open- JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document label fashion in 593 patients with coronary artery disease on placebo group In patients with congestive heart statin therapy showed no benefit of folic acid in reducing failure (CHF), a population at high risk for magnesium cardiovascular events despite an 18% lowering in homocys- deficiency, oral magnesium replacement decreases the fre- quency of ventricular arrhythmias Most recently, a trial of folic acid (1 mg), vitamin B12 Dietary intakes of magnesium are suboptimal in the U.S.
(400 units), and pyridoxine (B6) (10 mg) found a signifi- as evidenced by recent NHANES survey intake data cantly reduced homocysteine levels, rate of restenosis, and Diets rich in magnesium and magnesium supplementation need for revascularization in a group of 553 CAD patients may be helpful in preventing CVD, especially hypertension.
at one year of follow-up A similar RCT of 626 Other bioactive supplements. COENZYME Q10. Coenzyme
patients treated with B-vitamin therapy following coronary Q10 (CoQ10) is involved in oxidative phosphorylation and stenting procedures, however, found increased rates of the generation of adenosine triphosphate (ATP). The restenosis, particularly in patients receiving bare-metal CoQ10 acts as a free radical scavenger and membrane stents and major adverse cardiac events in the vitamin stabilizer. There have been over 40 controlled trials of the treated group after one year of follow-up. The rate of clinical effect of CoQ10 on CVD, a majority of which show restenosis in the homocysteine-lowering group was 35% benefit in subjective (quality of life, decrease in hospitaliza- compared with 27% in the group receiving placebo tions) and objective (increased left ventricular ejection frac- Although striking differences exist between the study pop- tion, stroke index) parameters. A recent review and ulations, it raises the potential of possible harm from use of meta-analysis have shown benefit of CoQ10 as high-dose B-vitamins. Strong evidence for a benefit for B adjunctive treatment in patients with CHF. The largest trial vitamins in CVD is pending; there remain a number of to date was a one-year, placebo-controlled study of CoQ10 ongoing trials, including WACS, SEARCH, PACIFIC, in 651 New York Heart Association (NYHA) functional NORVIT, and CHAOS-2 class III or IV CHF patients These investigators Minerals. MAGNESIUM. Magnesium metabolism is in-
found a significant decrease (38% to 61%) in the number of volved in insulin sensitivity and blood pressure regulation, hospitalizations, incidences of pulmonary edema, and epi- and magnesium deficiency is common in both diabetes and sodes of cardiac asthma. No differences in death rates were hypertension. The links among magnesium, diabetes, and documented. However, two of the most recent placebo- hypertension suggest the possibility that magnesium can controlled trials found that the addition of 100 to 200 affect CVD Magnesium depletion is associated mg/day of oral CoQ10 to conventional medical therapy did with electrocardiographic changes, arrhythmias, and in- not result in significant improvement in left ventricular creased sensitivity to cardiac glycosides Epidemio- ejection fraction, peak oxygen consumption, exercise per- logic studies have suggested that ingesting hard water that formance, or quality of life in patients with advanced heart contains magnesium, consuming a diet higher in magne- sium, or using magnesium supplements decreases CVD A mortality benefit for CoQ10 has not been established The Honolulu Heart Program found a 1.7- to in contrast to angiotensin-converting enzyme inhibitors, 2.1-fold excess risk of CHD among those subjects in the beta-blockers, and aldosterone antagonists. Case reports lowest versus highest quintile of magnesium intake after 15 associate CoQ10 therapy with decreased internation nor- years of follow-up Similarly, epidemiologic evidence malized ratio (INR) in patients taking warfarin suggests that magnesium may play a role in regulating blood however, CoQ10 had no effect on the INR in patients on pressure A recent meta-analysis of 20 random- warfarin in a randomized, double-blind, placebo-controlled, ized studies including both normotensive and hypertensive crossover trial Caution is advised if patients are taking subjects detected a dose-dependent blood pressure reduc- CoQ10 and warfarin. The HMG-CoA reductase inhibitors tion with magnesium supplementation The DASH may inhibit the natural synthesis of CoQ10, and reduced intervention study demonstrated that a diet of fruits and levels of CoQ10 have been documented in small controlled vegetables, which increased magnesium intake from an clinical trials in patients on statin therapies Reduced average of 176 to 423 mg per day, significantly lowered levels of CoQ10 may place the patient at increased risk for blood pressure in adults who were not classified as hyper- myopathy however, studies of CoQ10 for de- tensive However, studies in hypertensive patients creasing myalgias and myositis are not definitive. One have led to conflicting results. Ascherio et al. found an unique formulation of CoQ10 has received FDA Orphan inverse correlation between the intake of magnesium and Drug status for treating mitochondrial disorders. The value the risk of stroke.
of CoQ10 in CVD and with statin use has not been clearly Magnesium intake has been found to be inversely asso- ciated with carotid artery thickness in women but not inmen Oral magnesium therapy (365 mg twice daily for L-CARNITINE. In 1986, the FDA-approved L-carnitine for
6 months) in 187 patients with CAD demonstrated a 14% use in primary carnitine deficiency, which manifests as a improvement in exercise duration combined with a decrease disruption in the transport of free fatty acids across the in exercise-induced chest pain compared to no change in the mitochondrial membrane for energy production. In myo- Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 pathic carnitine deficiency, muscle weakness is paramount losis Oral L-arginine appears to have potential Convincing evidence is lacking for the use of carni- benefit in CHD, but hard evidence for its value is currently tine in patients without carnitine deficiency undergoing not available.
cardiac surgery, in patients with angina pectoris, acute myocardial infarction, shock, and peripheral vascular diseaseUrinary carnitine excretion is known to be increased In the U.S. today, herbs may be marketed as dietary in patients with heart failure Several clinical RCTs supplements providing their intended use is not to diagnose, have evaluated the addition of L-carnitine to standard treat, cure, or prevent disease. A number of approved drug medial therapy for heart failure with mixed results substances have their origin in plants, such as digoxin, Significant improvements in maximum exercise times atropine, reserpine, and amiodarone. However, only a few and ejection fractions were reported by Mancini et al. herbal products available in the U.S. have been tested for in 60 patients with NYHA functional class II or III CHF cardiovascular purposes: hawthorn (heart failure and coro- who were randomized either to propionyl-L-carnitine (50 nary insufficiency), garlic (atherosclerosis), ginkgo (arterial mg t.i.d.) or placebo for 180 days. Two other small trials occlusive disease), and horse chestnut (chronic venous reported similar results, and one trial showed improvement insufficiency) Few U.S. products benefit from rigor- at a higher dose. In a double-blind randomized trial in 155 ous characterization and standardization necessary for clin- patients with claudication, a significant improvement in exercise treadmill performance (54% increased walking Hawthorn (Crataegus). Hawthorn has positive inotropic
time) and functional status was achieved with oral effects and is a peripheral vasodilator. It increases myocar- propionyl-L-carnitine 2 g/day for 6 months Differ- dial perfusion and stroke volume and reduces afterload.
ences in effect may be due to the dose and formulation of Antiarrhythmic effects have been reported in an ischemia- carnitine. In contrast, the investigators of the Study on reperfusion model. Orally, hawthorn leaf extract has been Propionyl-L-Carnitine in Chronic Heart Failure did not used for CHF, cor pulmonale, ischemic heart disease, show improved exercise tolerance on L-carnitine supple- arrhythmias, blood pressure reduction, atherosclerosis, and cerebral insufficiency Preparations made from flowers At present, it is unclear whether L-carnitine provides any with leaves are sold as a prescription medication in parts of benefit beyond well-established therapies. A more definitive Europe and Asia. For example, in Germany, hawthorn can answer will come from the Carnitine Ecocardiografia Digi- be prescribed for "mild cardiac insufficiency." talizzata Infarto Miocardico (CEDIM-2) trial, which will Several double-blind clinical studies of patients diagnosed assess the efficacy of L-carnitine in approximately 4,000 with heart failure have shown objective improvement in patients with acute MI over six months Supplements cardiac performance using bicycle ergometry or containing D- or DL-carnitine, often present in over the spiroergometry. In one study, hawthorn was found to be as counter preparations and dietary supplements, should not be effective as captopril in improving exercise tolerance. Based substituted for L-carnitine. Carnitine frequently causes on ergometric performance parameters, the minimum ef- nausea, pyrosis, dyspepsia, and diarrhea. Concomitant use fective daily dose of hawthorn extract is 300 mg. In most of carnitine with warfarin may potentiate warfarin's antico- trials, the maximum benefit was seen after 6 to 8 weeks of agulant effects.
therapy. Weikl et al. demonstrated an improvement inexercise performance in 136 stage II CHF subjects receiving L-ARGININE. L-arginine is the precursor of nitric oxide
160 mg hawthorn special extract WS 1442 (leaves and (NO) and has been shown to improve coronary and brachial flowers). The efficacy and safety of hawthorn extract WS artery endothelial function and reduce monocyte/ 1442 (900 and 1,800 mg) were evaluated in a 16-week endothelial cell adhesion In patients with recur- randomized, controlled trial in 209 patients with NYHA rent chest pain, improvements in coronary blood flow in functional class III heart failure. The investigators found a response to acetylcholine have also been documented. In dose-dependent effect of WS 1442 on enhancing exercise hypercholesterolemic subjects, dietary supplementation with capacity and reducing heart failure-related signs and symp- L-arginine over two weeks has been shown to normalize the toms. The preparation was shown to be well-tolerated and adhesiveness of mononuclear cells and reduce platelet safe A recent pharmacokinetic study was conducted aggregability However, in a study in 30 patients with in 8 healthy subjects consuming 0.25 mg digoxin alone or CAD, supplemental L-arginine did not affect measures of with hawthorn extract WS 1442, which demonstrated no NO bioactivity and NO-regulated markers of inflammation significant alterations in the pharmacokinetic parameters for digoxin Clinical trials are underway in the U.S. to There are a few documented reports of adverse effects evaluate further the safety and efficacy of hawthorn in from oral use of L-arginine. Several patients with hepatic patients with heart failure.
impairment and a recent history of spironolactone use were Hawthorn may offer some advantages over digoxin in reported to develop severe hyperkalemia upon initiation or mild heart failure. Compared to digitalis, hawthorn has a arginine hydrochloride for management of metabolic alka- wider therapeutic range, lower risk in case of toxicity, has JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document less of an arrhythmogenic potential, is safer to use in renal occurring coumarin constituents is possible. Also, HCSE impairment, and can be safely used with diuretics and has been suspected of causing hypoglycemic effects laxatives However, hawthorn can markedly enhance The German Commission E has approved the use of the activity of digitalis and care should be taken when HCSE in chronic venous insufficiency. It may be effective in combining it with beta-blockers and class III antiarrhythmics.
Ginkgo biloba (ginkgo leaf extract). Ginkgo has been
Guggulipid (guggul gum). Guggulipid has a long history
used for relief of intermittent claudication in patients with of use in Ayurvedic medicine, which is an ancient Indian peripheral arterial occlusive disease. Ginkgo leaf, obtained system that uses an integrated approach (diet, lifestyle, from the Ginkgo biloba tree, and its extracts, or GBE, herbs, exercise, and meditation) to the prevention and contain several bioactive constituents including flavonoids, treatment of illness by maintaining harmony among the terpenoids, and organic acids. As with other phytomedi- mind, body, and forces of nature. Both guggul and its cines, several constituents of ginkgo extracts may contribute purified extracts have been used as hypolipidemic agents in to its therapeutic effect. The mechanism of benefit is patients with ischemic heart disease, hypercholesterolemia, unknown. Two meta-analyses of the efficacy of ginkgo leaf and obesity Clinical studies performed in India have extract for the treatment of intermittent claudication con- demonstrated that 25 mg of guggulsterone extracts t.i.d.
cluded that only modest benefits resulted from its use may be an effective treatment for hypercholesterolemia and In the meta-analysis performed by Pittler and hypertriglyceridemia. Reductions in total cholesterol levels Ernst eight randomized, placebo-controlled, double- of approximately 24% and reductions in triglycerides of 16% blind studies involving a total of 415 participants were to 23% have been reported The majority of these evaluated. All of the studies used pain-free walking distance trials were not randomized.
as the primary outcome measure. Several different formula- In one randomized, controlled study of 125 hyperlipid- tions of ginkgo were used with doses ranging from 120 to emic patients, a standardized extract of guggulsterone was 160 mg a day. The majority of trials lasted 24 weeks.
compared with clofibrate with mean reductions in serum Statistical pooling of the results from the eight trials showed cholesterol and triglycerides of 11% and 16%, respectively that ginkgo significantly increased pain-free walking dis- In the first randomized, controlled trial of guggulipid tance by 34 m. The clinical relevance of this increase is outside of India, 103 healthy adults with hypercholesterol- emia given 1,000 or 2,000 mg guggulipid containing 2.5% Ginkgo is considered relatively safe, with a few docu- guggulsterones experienced no improvement in their lipid mented adverse effects being mild gastrointestinal upset and levels. A hypersensitivity rash was reported in a small headache. Ginkgo has been reported to increase the risk of number of subjects Effects of guggulipids on HDL bleeding. The concomitant use with aspirin, non-steroidal were mixed. A standard dose is 75 to 100 mg of guggul- anti-inflammatory drugs (NSAIDs), and anticoagulants, sterones daily divided into three doses. Guggulipids can such as warfarin and heparin, is not advised. Ginkgo can cause gastrointestinal upset, headache, mild nausea, belch- increase blood pressure in patients taking thiazide diuretics ing, hiccups and rash Concomitant oral ad- Ginkgo does not appear to interact or adversely affect ministration can reduce propranolol and diltiazem bioavail- concomitant therapy with cardiac glycosides, and it appears ability and might reduce the therapeutic effects of these to provide a small benefit in the treatment of peripheral drugs Although in vitro studies suggest a plausible arterial disease.
mechanism of action for guggulipid as a cholesterol- Horse chestnut (Aesculus hippocastanum). Horse chestnut
lowering agent definitive safety and efficacy data are seed extract (HCSE) contains escin, a triterpene glycoside, and the toxic glycoside aesculin, a hydroxycoumarin deriv- Red yeast rice (Monascus purpureas). Red yeast is the rice
ative that is used to treat venous insufficiency A fermentation product of a mixture of several species of systematic review of 14 randomized, placebo-controlled Monascus fungi, principally Monascus purpureas. It contains trials (a total of 1,071 subjects) was recently completed monacolin K (lovastatin, mevinolin) and other HMG-CoA evaluating the efficacy of HCSE for the treatment of reductase inhibiting compounds. Red yeast has been used to chronic venous insufficiency. The HCSE was found to be reduce cholesterol levels In a 12-week placebo- superior to placebo and as effective as compression therapy controlled study conducted in the U.S. in 83 healthy in decreasing lower leg volume and leg circumference at the subjects with hyperlipidemia 2.4 g of red yeast rice calf and ankle. Symptoms such as leg pain, pruritus, and significantly reduced total cholesterol by 16%, LDL choles- feeling of fatigue and tenseness were also reduced terol levels by 22%, and total triglycerides by 7% compared Side effects are uncommon, but gastrointestinal irritation with placebo. No serious side effects were reported, but and toxic nephropathy may occur additional longer-term studies are needed.
Contraindications to use include hypersensitivity to escin Red yeast should be treated as an HMG-CoA reductase or horse chestnut and renal or hepatic impairment At inhibitor, with all the possible side effects, drug interactions, present there is no human drug interaction data available, and precautions associated with this class of drugs. Red but the increased risk of bleeding due to the naturally yeast rice is no longer marketed with standardized lovastatin Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 Table 1. Herbs Containing Stimulants Adverse Cardiac Effects
Bitter orange (Citrus aurantium) Weight loss, nasal congestion Cardiovascular toxicity, hypertension Cola nut (1% to 3.5% caffeine) Short-term relief of mental and physical fatigue Arrhythmias, increased heart rate, Country mallow (Heartleaf) Weight loss to burn fat, increase energy, impotence, Arrhythmias, increased blood pressure, (0.8 to 1.2% ephedrine) sinus, allergy, asthma, bronchitis Ephedra (Ma huang) alkaloid constituents Diseases of respiratory tract (bronchospasm, asthma, Increased heart rate, diastolic and systolic contain ephedrine and pseudoephedrine bronchitis, nasal congestion), appetite suppressant Green tea (2% to 4% caffeine) Improves cognitive performance, diuretic, lower Arrhythmias, increased heart rate, cholesterol and triglycerides Guarana (2.5% to 7% caffeine) Central nervous system stimulant, weight loss, Increased heart rate, central nervous system enhance athletic performance, reduces fatigue Depression, fatigue, obesity Increased blood pressure, palpitations, Wahoo root bark (Euonymus atropurpiuretus) Indigestion, stimulates bile production Shortness of breath, circulatory problems, (2% to 4% caffeine) large quantities affect the heart Yerba mate (0.2% to 2.0% caffeine) Appetite suppressant, mental stimulant Arrhythmias, increased heart rate (contains theophylline and theobromine) Reprinted with permission from Nykamp DL, et al. Ann Pharmacother 2004;38:812– 6 levels in U.S. owing to legal issues, and it is now sold tis, and lethal cardiac arrhythmias. Dietary supplements that without lovastatin levels declared. Because of the availability contain ephedra alkaloids were widely promoted and used in of statins, its use is not recommended.
the U.S. for weight loss and increased energy. Their use was Policosanol. Policosanol is a sugar cane extract that con-
associated with a number of adverse events, including MI, tains a mixture of aliphatic alcohols. Lipid-lowering effects stroke, arrhythmias, and death and in December of policosanol have been shown in a variety of animal 2003 the FDA announced a ban on the sale of ephedra species; however, little is known about its mechanism of products in the U.S. Of developing concern is the herbal action or its exact composition. Over 1,000 subjects have Citrus aurantium, or bitter orange, which contains similar been studied for periods of six weeks to one year in 15 stimulant amines as ephedra and is now being marketed in randomized, placebo-controlled trials using policosanol (5 weight loss products. The Joint National Committee to 20 mg per day) for lipid lowering. At doses of 10 to 20 (JNC)-7 guidelines list it as a possible cause of resistant mg per day, significant reductions were observed for total hypertension One case report of acute MI has been cholesterol (17% to 21%) and LDL cholesterol (21% to associated with its use as contained in a multi-ingredient 29%) with increases in HDL cholesterol (8% to 15%) weight loss product. provides a list of herbs There are no data on efficacy determined by clinical end points. Although policosanol appears to be well-tolerated, Oleander (Nerium oleander/Thevetia peruviana). Oral
caution should be exercised when combining policosanol oleander was once used for treating mild heart failure, but is with antiplatelet or anticoagulant agents, including garlic, now considered too dangerous for medicinal use All ginkgo, and high doses of vitamin E as policosanol parts of the oleander plant contain the cardiac glycosides has been shown to inhibit platelet aggregation in both oleandrin, oleandroside, nerioside, and digitoxigenin, which healthy and diseased patients The majority of the have positive inotropic and negative chronotropic actions.
existing studies have been conducted in Cuba, and indepen- Oleander poisoning resembles digitalis toxicity, with pre- dent verification is needed before its use can be recom- dominant symptoms of nausea and vomiting, and cardiac toxicity with conduction delays that may last up to three to Ephedra (Ma huang). Ephedra, together with its principal
six days. Reports suggest that yellow oleander toxicity can be alkaloid ephedrine, was one of the first of the Chinese reversed by infusion of antidigoxin Fab fragments. Use of herbal medicines to be used in Western medicine. Ephedra this herb is contraindicated in patients on digoxin and is used to treat bronchospasm, asthma, bronchitis, allergic should not be used with other cardiac glycoside-containing disorders, and nasal congestion, or as a central nervous herbs In view of the availability of digoxin, its use is system stimulant Ephedrine acts by stimulating not recommended.
alpha, beta-1, and -2 adrenergic receptors, and indirectly byreleasing norepinephrine from body stores. The cardiovas- Herb-Drug Interactions: What We Need to Know
cular effects of ephedrine last 10 times longer than those ofepinephrine and consist primarily of increased heart rate and The increased use of herbal and phytomedicines by both peripheral vascular resistance. Ephedrine and related alka- health professionals and consumers has raised questions loids have been associated with adverse cardiovascular about herb-supplement and herb-drug interactions because events, including acute MI, severe hypertension, myocardi- herbs are making a resurgence in the U.S. market. Kaufman JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document Table 2. Loss of Serum Potassium, Which May Potentiate the Table 3. Potential Adverse Effects of Herbal Remedies and Effects of Cardiac Glycosides and Antiarrhythmics Their Major Constituents* (Potassium deficiency increased by the simultaneous use of thiazide Neurotoxicity or Convulsions
diuretics, corticosteroids, or licorce root) Aconite root tuber Aconite root tuber Laxatives containing anthraquinone glycosides with laxative effects: Herbs rich in cardioactive Alocasia macrorthiza root tuber† Senna fruit and leaf (Cassia senna) Artemisia species rich in santonin Aloe latex (aloe vera or aloe ferox) Herbs rich in colchicine Essential oils rich in ascaridole Buckthorn bark and berry Essential oils rich in thujone Cascara sagrada bark (Rhamnus purshiana) Ginkgo seed or leaf‡ Herbs rich in colchicine Pokeweek leaf or root Herbs rich in podophyllotoxin Indian tobacco herb et al. described the patterns of prescription and Squirting cucumber† nonprescription drugs in the U.S. population, noting that: • 14% of the population took supplements and herbals over Certain herbs rich in anthranoids Certain herbs rich in • 16% of prescription drug users also took herbs or sup- protoberberine alkaloids Yellow jessamine rhizome Chaparral leaf or stem Germander species • 40% of the population used one or more mineral or Green tea leaf† Beta-aescin (saponin mixture vitamin supplements Herbs rich in coumarin from horse-chestnut seed) Herbs rich in podophyllotoxin In 1997, an estimated 15 million adults took prescription Herbs rich in toxic pyrrolizidine medications along with herbal remedies and/or high dose Certain essential oils vitamins These individuals are potentially at risk for Chaparral leaf or stem† adverse herb-supplement or herb-drug interactions. The Herbs rich in aristolochic acids following tables delineate possible drug interactions with herbal or botanical products. lists herbs that may potentiate the effect of cardiac glycosides and antiarrhyth- Skullcap pennyroyal oil Squirting cucumber† mics. lists the potential adverse effects of herbal Soy phytoestrogens† remedies and their major constituents. lists poten- *The full version of this table is available from the National Auxiliary Publications tial interactions between some herbal medicinal products Service (NAPS). (See NAPS document no. 05609 for 33 pages of supplementalmaterial. To order, contact NAPS, c/o Microfiche Publications, 248 Hempstead and cardiovascular drugs. lists the interference of Tpke., West Hempstead, NY 11552.) Adverse effects of multiple-herb therapies are herbal products in therapeutic drug monitoring.
not included. Case reports do not always provide adequate evidence that the remedyin question was labeled correctly. As a result, it is possible that some of the adverseevents reported for a specific herb were actually due to a different, unidentified Summary of recommendations for bioactive food compo-
botanical or another adulterant or contaminant. †A single case was reported without nents and dietary supplements. Supplements/interventions
reference to previous cases. ‡Convulsions have been observed after large doses ofyinguo (ginkgo seed), a traditional Asian food and medicine, which contains the that can be recommended convulsive agent 4=-O-methylpyridoxine (MPN) Recently, anecdotalreports have associated ginkgo-containing preparations available on the Western 1. Omega-3 supplements 1 to 2 g per day if insufficient market with seizures and these adverse events have also been reported in omega-3 intake from fish patients with seizure disorders stabilized by valproate How Western ginkgopreparations might induce seizures is still unclear. MPN has been detected in ginkgo 2. Stanol/sterol ester margarines (2 g per day) leaf and preparations that contain ginko, but usually at subtoxic levels Reliable 3. Soluble fiber (5 to 20 g per day) information concerning herb-drug interactions can be obtained from the followingWeb sites: and 4. Soy foods and soy protein (equivalent to 25 g soy protein 1. Folic acid supplementation if homocysteine is not ele- Possibly useful for indications noted vated for vascular disease 2. Garlic for lipid lowering 1. Moderate alcohol intake (1/2 to 2 drinks per day—a 3. Soy isoflavones for lipid lowering drink is 5 oz of wine, 12 oz of beer or 1.5 oz of 80 proof 4. L-arginine supplementation for nutritional support whiskey) for cardiovascular risk reduction 5. CoQ10 for nutritional support 2. Tea (1 to 2 cups daily) for cardiovascular risk reduction 6. Hawthorn for mild heart failure 3. Recommended dietary intake of magnesium (RDA adult men 420 mg; women 320 mg daily). Consider 7. Ginkgo biloba for peripheral vascular disease supplementation for those at risk (poor dietary intake or 8. HCSE for peripheral vascular disease conditions that increase renal magnesium losses).
Supplements/interventions not recommended (possibly 4. Folic acid supplementation (plus vitamins B6 and B12) if homocysteine is elevated.
Cannot recommend at this time (for some individuals in 1. Levels exceeding the upper tolerable limits (IOM, 2001) some situations, probably not harmful) for vitamins C (2,000 mg/day) and E (1,000 mg/day); Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 Table 4. Potential Interactions* Between Some Herbal Medicinal Products and Cardiovascular Drugs Usage or Relevant
Adonis (Adonis vemalis) Contains cardiac glycosides and may enhance other such drugs; increases (adverse) effects of quinodine, calcium saluretics, laxatives,glucosteroids, beta-blockers, calcium channel blockers, and digitalis Aloe vera (Aloe barbadensis) Various, e.g., wound healing With chronic use, potentiation of cardiac glycosides or antiarrhythmic (topical) or antidiabetic (oral) drugs due to loss of potassium Arnica (Arnica montana) Decreases effects of antihypertensives and anticoagulants Bearberry (Arctostaphylos uva ursi) Increases effects of cardiac glycosides through potassium depletion: may alter blood level of drugs metabolized in the liver due to hepaticenzyme induction Bilberry (Vaccinium myrtillus L) Circulatory disorders Increases effects of anticoagulants Black cohosh (Cimicifuga racemosa) Increases effects of antihypertensives Blue cohosh (Caulophyllum) Smooth muscle stimulant Decreases effects of antihypertensives Bogbean (Menyanthes trifoliate) Diuretic, analgesic Increases effects of anticoagulants Boldo (Bolodo folium) Increases effects of cardiac glycosides (potassium depletion) Broom (Cystisus scoparius) Antiarrhythmic, diuretic Increases effects of antidepressants, beta-blockers, and cardiac glycosides: induces circulatory collapse with quinidine, haloperidol,or moclobemide Buchu (Barosma betulina) Increases effects of anticoagulants and cardiac glycosides (potassium Buckthorn (Rhamnus cathartica) Laxative, cathartic Causes loss of potassium with chronic use; potentiates cardiac glycosides or antiarrhythmic drugs Butchers broom (Busus aculeatus) Decreases effects of alpha-blockers Capsicum (Capsicum anuum L) Appetite stimulant May interfere with antihypertensives and MAO inhibitors; can stimulate the hepatic metabolism of drugs Cascara (Rhamnus purshiana) Laxative, cathartic Causes loss of potassium with chronic use; potentiates of cardiac glycosides or antiarrhythmic drugs Cats claw (Uncaria tomentosa) Increases effects of anticoagulants and antihypertensives; can interfere with protein-based drugs and chemotherapy May potentiate effects of anticoagulants through its coumarin content Cinchona (Cinchonae cortex) Increases effects of anticoagulants Coltsfoot (Tussilaga farfara) Asthma, bronchitis May antagonize antihypertensives: increases hepatotoxicity of other Cordyceps (Cordyceps sinensis) Tonic, stress management Increases effects of anticoagulants and MAO inhibitors Cowslip (Primula veris) Increases effects of diuretics and antihypertensives Dandelion (Taraxatum officinale) Laxative, diuretic Increases effects of antihypertensives, diuretics, and hypoglycemics Feverfew (Tanacetum parthenium) Migraine prevention Increases effects of warfarin Increases effects of anticoagulants and hypoglycemics: may decrease absorption of other drugs Figwort (Scrophularia nodosa) Increases effects of beta-blockers, calcium channel blockers, and cardiac Fumitory (Fumaria officinalis) Antibacterial, diuretic, laxative Increases effects antihypertensives, beta blockers, calcium channel blockers, and digoxin Ginseng, Siberian May interact with cardiac drugs, hypo- and hypertensives, and Goldenseal (Hydrastis canadensis) Increases effects of antihypertensives, calcium channel blockers, and digoxin; may decrease anticoagulant effects; many herbalists believethat goldenseal generally enhances the activity of other drugs Gossypol (Gossypium hirsutum) Antifertility drug May lead to potassium depletion with diuretics; can enhance renal toxicity of other drugs Hawthorn (Crataegus laevigata) Can increase hypotensive effects of nitrates, antihypotensives, cardiac glycosides, and CNS stimulants Increases effects of anticoagulants Horsetail (Equisetum arvense) Increases effects of CNS stimulants and diuretics Ilex (Ilex paraguarensis) Diuretic, analgesic Can increase effects of diuretics; hepatic microsomal enzyme inhibitors may decrease clearance and cause toxicity Indian snake root (Rauwolfia) Cardiac glycosides, bradycardiabarbiturates (and other CNS depressants); potentiation; levodopa; neutralization; extrapyramidalsymptoms; sympathomimetics; hypertension Irish moss (Chondrus crispus) Demulcent for ulcers or gastritis Increases effects of anticoagulants and antihypertensives Kelp (Laminaria digitata) Antitumour effects, antiobesity Increases effects of anticoagulants and antihypertensives Continued on next page JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document Table 4 Continued
Usage or Relevant
Khella (Ammi visnaga) Increases effect of anticoagulants, calcium channel blockers, and other antihypotensive drugs Lily of the valley Congestive heart failure Increases effects of quinodine, calcium, salureties, laxatives, glucosteroids, beta-blockers, calcium channel blockers, and digitalis Lovage (Levisticum officinale) May potentiate effects of anticoagulants Nettle (Urtica dioica) May potentiate effects of other diuretics Night-blooming cereus Increases effects of hypoglycemics; may enhance effects of cardiac glycosides, angiotensin-converting enzyme inhibitors,antiarrhythmics, beta-blockers, and calcium channel blockers Parsley (Petroselinum crispum) Increases effects of antihypertensives; enhances toxicity of MAO Pau d'arco (Tabebuia impetiginosa) Increases effects of anticoagulants; decreases effects of iron supplements Pineapple (Anannas comosus) Constipation, jaundice, obesity, Overanticoagulation through coumarin contents; may antagonize effects on bradykinin with angiotensin-converting enzyme inhibitors(bromelain) Plantains or psyllium Can delay absorption of other drugs (e.g., lithium); increases effects of cardiac glycosides Poplar (Populus alba) Increases effects of anticoagulants Increases effects of anticoagulants Pumpkin seed (Curcubita) Anthelmintic, diuretic Can increase effect of diuretics Red clover (Trifolium partense) Increases effect of anticoagulants on digoxin; interferes with oral Diuretic, psoriasis Increases absorption of digitalis, glycosides, bismuth; accelerates elimination of hypnotics Senna (Cassia) Causes loss of potassium with chronic use; increases effects of cardiac glycosides, antiarrhythmic drugs, calcium channel blockers,clamodium antagonists, and indomethacin; may decrease effects ofsenna preparations Sorrel (Rumex acetosella) Antiseptic, diuretic Increases effects of other diuretics; increases hepatotoxicity of other Hepatic enzyme inducer; increases activity of P-glycoprotein, thereby reducing plasma levels of many drugs Strophantus (Strophantus kombe) Contains cardiac glycosides and may enhance effects of other such Sweet clover (Meliloti herba) Venous insufficiency Contains coumarins, which may enhance effects of anticoagulants Tonka bean (Dipteryx odorata) Increases effects of anticoagulants; increases hepatotoxicity of other Turmeric (Curcuma longa) Cancer prevention Enhances effects of antiplatelet drugs; decreases effects of Vervain (Verbena officinalis) Increases effects of anticoagulants and hypnotics Willow (Salix alba) Causes transient potentiation of phenytoin; increases effects of Woodruff (Asperula odorata) Contains coumarins, which may enhance effects of anticoagulants Yarrow (Achillea millefolium) Increases effects of anticoagulants, antihypertensives and CNS depressants; increases hepatotoxicity of other drugs Cardiovascular adverse effect of herbal medicines: a systematic review of the recent literature. Reprinted with permission from Ernst E. Can J Cardiol 2003;19:818 –27 Data extracted from Fugh-Berman A. Lancet 2000;355:134 – 8 *Not all effects are true interactions (some are, for instance, additive effects). †Plant source in parentheses.
‡Not comprehensive.
CNS ⫽ central nervous system; MAO ⫽ monoamine oxidase.
and beta-carotene supplementation not recommended; U.S. in 1997. Chelation therapy consists of a series of limit to food sources.
intravenous infusions containing disodium ethylene diamine 2. Ephedra, oleander, and other herbs/botanicals with tetraacetic acid (EDTA) in combination with other sub- well-defined contraindications to cardiovascular drug stances, such as vitamins. Use of EDTA has been found to and/or CVD conditions.
be effective in chelating and removing toxic heavy metalsfrom the blood It is purported that the removal of Related Alternative Therapy
polyvalent cations, notably calcium ions, can lead to the Chelation. Chelation therapy is a form of alternative med-
regression of atherosclerotic plaques by a yet undefined icine utilized in the treatment of atherosclerotic CVD. Over mechanism. Use of EDTA chelation therapy is FDA- 800,000 patient visits were made for chelation therapy in the approved in treating lead poisoning and toxicity from other Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 Table 5. Laboratory Analysis and Treatment Guidelines for Specific Herbal Preparation and Their Critical Contaminants Suggested Laboratory Analysis
Serum digoxin, potassium Serum digoxin, potassium Serum digoxin, potassium Serum digoxin, potassium Central nervous system toxins Jimsonweed (Datura) Gastrointestinal toxins Serum electrolytes Potassium repletion Serum electrolytes Potassium repletion Serum electrolytes Potassium repletion Serum electrolytes Potassium repletion Serum electrolytes Potassium repletion Ag, As, Au, Cd, Cr, Cu, Hg, Pb, Th, or Zn Abdominal radiograph Hematologic toxins Pyrrolizidine alkaloids Medicated oils, etc.
Sodium bicarbonate, multiple dose activated charcoal, hemodialysis Apricot pits (cyanide) Cyanide antidote kit Autumn crocus (colchine) Cyanide antidote kit Periwinkle (vincristine) Potassium repletion Sodium bicarbonate, magnesium Reproduced with permission from Toxicologic Emergencies, 7th edition, Goldfrank LR, et al. McGraw-Hill Medical Publishing Division ALT ⫽ alanine aminotransferase; AST ⫽ aspartate; BUN ⫽ blood urea nitrogen; INR ⫽ international normalized ratio; WBC ⫽ white blood cell.
heavy metals. The FDA has not approved the use of large-scale clinical trial to determine the safety and efficacy chelation therapy to treat CAD.
of EDTA chelation therapy in individuals with coronary The bulk of the evidence supporting the use of EDTA artery disease. The five-year Trial to Assess Chelation chelation therapy is in the form of case reports and case series.
Therapy (TACT) will involve over 2,300 patients at more A systematic review on chelation therapy for peripheral arterial than 100 research sites across the country. The study will occlusive disease has shown that chelation therapy is not determine whether EDTA chelation and/or high-dose vi- superior to placebo and is associated with considerable risks tamin supplements improve event-free survival, whether At present, the benefit of chelation therapy remains these are safe for use, improve the quality of life, and are controversial as highlighted by a recent Cochrane Review cost-effective. The primary end point in the trial will be a of five randomized controlled studies in small numbers of composite of death, MI, stroke, hospitalization for angina, subjects evaluating outcomes of disease severity and subjective and coronary revascularization.
measures of improvement.
The ACC position statement reapproved in 1990 states "that there is insufficient scientific evidence to justify the III. MIND/BODY AND PLACEBO application of chelation therapy for atherosclerosis on a The Mind/Body Relationship and its Correlation to CVD
clinical basis. At the present time, therefore, chelationtherapy for atherosclerosis should be applied only under an Reviewing the mind/body relationship and its clinical cor- investigation protocol." relates to CVD is a union of both the social and biological.
In an effort to advance the evidence base for the use of Although physicians easily grasp measurable physiological chelation therapy, the NCCAM and the National Heart, phenomena (e.g., the concept of acid production, blood Lung, and Blood Institute (NHLBI) have launched the first pressure elevation, and the angiographic narrowing of a JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document coronary artery), it is much more difficult to understand pressure elevations and by increasing the amount of vaso- social relationships, isolation, anger, depression, and their constricting hormones. Stress factors leading to hyperten- manifestation in disease. Sterling and Eyer have sion include job strain, social environment, emotional stress, illustrated how the development of modern society is and white coat hypertension. Overall, studies conclude that, associated with a disruption of human relationships. These although stress does not directly cause hypertension, it can disruptions cause chronic psychological arousal, which is clearly affect its development. Stress leads to sympathetic defined as stress. The body's physiological mechanisms are nervous system activation with excessive amounts of corti- altered by chronic psychological arousal and this leads to sol, epinephrine, and aldosterone. The combination of pathology and disease.
increased cardiac output and vasoconstriction may tran- The function of arousal is to help the individual "cope" siently raise blood pressure. Feelings of frustration, exhaus- with environmental demands. Coping may be defined as tion, and helplessness can activate the pituitary and adre- "contending" or "struggling." This behavior frequently re- nocortical hormones. Non-pharmacological treatments to quires excess physical or emotional energy to deal with a manage stress such as meditation, acupuncture, biofeedback, difficult situation. Studies have shown that patients entering and music therapy have been found to be effective in a hospital for diagnostic tests have elevated norepinephrine, decreasing blood pressure and the development of hyper- epinephrine, cortisol, and growth hormone levels Because these patients have little control over their Although not a substitute for pharmacological therapy, situation, there is little effective coping behavior. Under certain non-drug therapies offer support for individuals with these circumstances, in which limited control over the hypertension. Steelman studied the effect of tranquil environment is possible, the stress hormones are maximized.
music on blood pressure and anxiety in surgery patients. The Likewise, students during examination periods demonstrate experimental group listened to music during the intraoper- a rise in cortisol, epinephrine, serum blood sugar, choles- ative period. The control group received usual care. Music terol, and blood pressure levels. Under exam stress, these appeared to reduce blood pressure in the experimental same students exhibit a decline in white blood cells group. Pender studied the effect of progressive muscle This drop in white blood cells in part relaxation (PMR) training in hypertensive patients. Those explains the high rate of physical illness under stressful individuals who received PMR training reported less anxi- situations. Tax accountants have been shown to have large ety. Decreased anxiety correlated with decreased systolic increases in serum cholesterol (independent of diet) and a blood pressure. Older African-Americans who were taught decrease in blood clotting time during tax season the transcendental meditation technique had a significant Arousal, and as a consequence stress, will be high not only reduction in diastolic and systolic blood pressure among individuals with little control over life circumstances, Diabetes, like hypertension, remains an important risk but also among individuals with a high demand for perfor- factor for the development of CVD. Chronic arousal can mance. Arousal that results from a lack of control will contribute to diabetes in two ways. With arousal, there is an frequently manifest with anger or fear. Although high- increase in catabolic hormones, most notably epinephrine, demand situations are frequently accompanied by anxiety, cortisol, growth hormone, and glucagon. These hormones they may result in extreme pleasure if the coping style is antagonize the actions of insulin by mobilizing glucose, fatty successful. However, this success in the end does not mean acids, and protein breakdown. Furthermore, glucagon and that the metabolic costs to the body are less.
norepinephrine act to suppress the secretion of insulin. Theresulting hyperglycemia, hyperinsulinemia, and hyperlipid- Impact of Stress on CVD Risk Factors
emia all accelerate pathology.
In the Framingham Heart Study hypertension was In addition to hypertension and diabetes mellitus, studies involved in over 80% of all cardiovascular deaths. In addi- linking stress and cholesterol date back to the 1950s. These tion, hypertension was at least twice as strong a predictor of older studies suggest that stress associated with time pres- death as smoking or elevated blood cholesterol. Over 50 sure, repetitive assembly line work, and increased responsi- million Americans are currently hypertensive. In about 5%, bility may raise serum cholesterol Both a specific pathology such as a renal artery stenosis can be cortisol and epinephrine have been linked in humans to identified. In the remaining 95%, the blood pressure in- serum cholesterol elevation. In many animal experiments, crease is not attributed to a specific pathology. Different stress has accelerated atherosclerosis. Rabbits on a high-fat mechanisms can contribute to the development of hyper- diet when stressed with electrical stimulation over 10 tension. Acute arousal leads to sympathetic stimulation and months have an increased number of atheromas in compar- an increase in cardiac output. When arousal is maintained ison with non-stressed controls. The administration of for long periods of time, the elevation in blood pressure epinephrine to cholesterol-fed rabbits further intensifies remains even if the inciting stimulus is removed. At this lipid infiltration of the aortic intima. As mentioned previ- stage, the hypertension is not sustained by increased cardiac ously, accountants show continuous monthly rises in cho- output but by increased vascular resistance.
lesterol, despite maintaining a constant diet, which peaks at Stress may lead to hypertension through repeated blood the end of the fiscal year Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 Depression and the Development of CVD
Increased use of selective serotonin reuptake inhibitors (SSRIs) and their demonstrated safety in patients with A growing body of evidence suggests that depression may CVD raises the question of whether early pharmaceutical predispose to cardiovascular events Individuals with treatment for depression in cardiac patients will improve mental stress during daily life have twice the risk of clinical outcome Yet despite this low-risk pro- myocardial ischemia. In addition, those patients with file, very little research exists regarding the benefit of SSRIs post-MI depression have higher mortality rates than non- in patients with CVD. The Sertraline Antidepressant Heart depressed controls. Depression is common after acute MI Randomized Trial (SADHART) has evaluated the efficacy and is associated with an increased risk of mortality for at and safety of sertraline therapy in patients with acute heart least 18 months. One reason for this higher morbidity and disease without evidence of statistically significant benefit mortality within the first few months following an MI is Until meaningful data are obtained, the use of that depressed patients are less likely to follow recommen- antidepressants in cardiac patients requires a weighing of dations to reduce further cardiac events.
the risks versus potential benefit.
Ziegelstein et al. found that patients who were In addition to affecting lipids, enhancing weight loss and identified with at least mild-to-moderate depression or improving exercise tolerance, cardiac rehabilitation provides major depression reported lower adherence to a low-fat diet, emotional support, reduces depression, improves quality of life regular exercise, and stress management. Individuals with scores, and decreases mortality by 25% Such major depression and/or dysthymia reported taking their programs serve as the logical place to screen cardiac patients for medication less often than prescribed. Those findings, in psychosocial risk factors such as depression and anxiety. Once part, explain why depression in the hospital is related to identified, appropriate intervention can be initiated.
long-term prognosis in patients recovering from an MI.
In conclusion, although post-MI depression is a predictor In addition, acute MI patients with unstable angina who of one-year cardiac mortality, high levels of social support were identified as depressed in the hospital were more likely appear to decrease the magnitude of depression. High levels to experience cardiac death or nonfatal MI than other of social support also predict improvements in depression patients The impact of depression on 430 patients symptoms over the first post-MI year in those individuals with unstable angina (41.4% depressed) remained after with baseline depression.
controlling for other prognostic factors such as left ventric-ular ejection fraction and number of diseased vessels Summary of recommendations for mind/body relation-
In addition to depression, other research suggests that ship. Several complementary and alternative medicine
social support may influence prognosis following an acute techniques have been used as adjuncts to traditional thera- MI. In a study of 887 post-MI patients, Frasure-Smith et al.
pies in the treatment of CVD as follows: found that 32% had mild-to-moderate depression.
After one year, follow-up interviews were conducted and a. Coronary artery disease demonstrated that elevated Beck depression scores were 1. Stress reduction related to cardiac mortality. The relationship between de- pression and cardiac mortality decreased with increasing support. Furthermore, of those one-year survivors who weredepressed at baseline, higher baseline social support was related to greater than expected improvement in depression 2. Stress management The Enhancing Recovery in Coronary Heart Disease Patients Study (ENRICHD) was sponsored by the NHLBI. The study enrolled 2,481 patients at 73 hospitals 1. Guided imagery within 28 days of an MI; participants had major or minordepression, low social support, or both. Patients were assigned to either a "treatment" or "usual medical care" 1. Stress management group Cognitive therapy was provided by the treat- ment group for six months. At the end of six months, e. Congestive heart failure patients in the treatment group scored significantly better on the Hamilton depression (57% reduction in depression versus 47% reduction in the usual medical care group) scale.
Likewise, patients low in social support demonstrated a 27% improvement in this parameter versus 18% for the usual care group. However, despite the treatment groups' improve- ment in depression and social isolation, there was no improvement in heart disease survival.
4. Pet acquisition JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document quantitate the benefit of either the placebo effect or shamprocedure.
"Placebo," Latin for "I shall please," can be derived from a Hrobjartsson and Gotzsche suggest there is little device, a drug, or complementary medicine modalities. A evidence that placebos in specific conditions, comparing no placebo is not necessarily a sham therapy but a potential therapy to placebo therapy, had powerful clinical effects. Yet response due to an interaction between the intent of the healer this is likely disease specific as many placebo-controlled and the expectations of the patient. The response can be studies showed enormous benefits of the placebo powerful, but the longevity of the response can vary by Another form of the placebo response is relief to a patient condition and type of placebo. Several reports in cardiology— when serious disease is excluded. Patients who have an BHAT CHF-STAT trial and the Coronary evaluation ("tests") for atypical chest pain are less likely to be Drug Project have shown a remarkably strong effect disabled than those who do not have such an evaluation regarding compliance with placebo. The reduction in mor- tality for those who take their placebo compared to thosewho are non-compliant is highly significant, but the mech-anism is unknown.
Shapiro indicated that the physician was important in Acupuncture has gained increasing acceptance by the lay the dyadic dance of healing and proposed that perhaps doctors, public, partly as a result of increasing communication independent of what they did, were actually potent placebos in between the U.S. and China since the early 1970s their own right. He and others enumerated a number of Texts on acupuncture date back to 206 BC, although the specific variables that might endow some physicians with Yellow Emperor, Huang Di, the originator of traditional particular curative manna: enthusiasm for treatment, apparent Chinese medicine lived in 2,697 BC Acupuncture has warm feelings for the patient, confidence, and authority. Some been used for a wide variety of conditions, but it is most physicians may be able to exhibit a placebo effect more accepted for treatment of pain Increasing evi- intensely than others, but the mechanism for this and the dence suggests that acupuncture may also be useful in extent of it are not understood.
treating patients with neurological disease, including disor- The placebo effect has been described as a nonspecific ders of the autonomic nervous system, hypertension, and psychological or psychophysiologic therapeutic effect, but other forms of CVD. The World Health Organization this may not be correct and the response may be a crucial (WHO) has noted that acute infection and inflammation, synergistic adjunct to any cardiovascular therapy. Placebos dysfunction of autonomic nervous system, pain, and can elicit a real and substantial response, the extent of which peripheral and central neurological diseases each repre- is related to the type of the placebo, the condition being sent conditions for which acupuncture may be indicated treated, and the response being elicited. No multivariate The mechanism by which acupuncture is analysis has detected which specific patient characteristics believed to benefit the subject is through its ability to are most associated with a profound placebo effect. The modulate neural activity in several regions of the brain and placebo response in major depression ranges from thus reduce sympathetic outflow to the heart and vascular 32% to 70% and can equal that of a drug intervention. After all, what occurs during psychotherapy is a form of placebo There are four areas of CVD for which acupuncture response. The importance of understanding the mecha- eventually may be indicated. These include ischemic CVD, nisms responsible for the placebo response is crucial to hypertension, heart failure, and arrhythmias. Studies from understanding the basic nature of healing Expect- several groups, including Ballegaard and Richter ancy, beliefs, anxiety, hope, trust, and intent can alter have examined the role of acupuncture in treatment outcomes regarding disease of patients with stable angina. Ballegaard, in an initial study, The placebo response may involve disease expression, was unable to document a decrease in angina in humans as specific neuroendocrine, neuronal and immune intermediary measured by a decrease in the rate of anginal attacks, pathways, neuropeptides, enkephalins, endorphins, cholecys- consumption of nitroglycerin or exercise tolerance, compar- tokinin, neurohormones (including glucocorticoids and prolac- ing true acupuncture to sham acupuncture the tin), neurotransmitters (including 5-hydroxytryptamine, nor- group concluded that true acupuncture cannot be distin- epinephrine, dopamine), and other messengers such as nitric guished from sham acupuncture in which needles were acid and prostaglandins. The power of expectancy of im- placed outside traditional meridians. Two other studies by provement was emphasized by controlled trials of arthro- the same group showed an acupuncture-related improve- scopic surgery and of neurosurgery. Osteoarthritis of the ment in exercise capacity and rate-pressure product knee responds as well to arthroscopic debridement, arthro- particularly when acupuncture reduces sympathetic neural scopic lavage, and placebo surgery. Similarly, sham neuro- outflow Separately, Richter observed that surgery improved Parkinson patients as well as cell implants acupuncture exerted a beneficial effect in patients with and sham cardiovascular surgery improves patient chest pain severe stable angina who had been aggressively treated with as often as 90% of the time It is, however, difficult to medical therapy. Manual acupuncture reduced the number Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 of anginal attacks per week, the severity of chest pain, hypothalamus, midbrain, and medulla that electrocardiographic evidence of myocardial ischemia, and are concerned with processing information that ultimately increased the workload required to provoke angina in influences sympathetic neural activity. Thus, by releasing patients with CAD and stable angina The latter study endorphins, endomorphins, or enkephalins which act used a tablet placebo control. These studies involved small as neuromodulators that likely reduce function of excitatory numbers of patients, were unblinded, and did not use the neurotransmitters, acupuncture appears to be able to inhibit most appropriate sham controls.
sympathetic outflow and clinical events associated with Prolonged peripheral vasodilation, measured by periph- heightened sympathetic activity. Other neurotransmitters eral thermography, occurs following electroacupuncture that might be associated with the influence of acupuncture Acupuncture or its non-invasive surrogate, transcu- on sympathetic neural activity important in cardiovascular taneous electrical nerve stimulation (TENS), appears to regulation include gamma-aminobutyric acid (GABA), se- influence peripheral blood flow in patients with Raynaud's rotonin or 5-hydroxydopamine (5-HT), acetylcholine, and syndrome skin flap survival in experimental prepara- nociceptin High-frequency electroacupuncture (100 tions and skin temperature in patients with Hz) may influence the cardiovascular system through an- polyneuropathy The primary form of Raynaud's other opioid neurotransmitter/neuromodulator, dynorphin cold-induced vasoconstriction, assessed by Doppler flow- metry and clinical symptoms, is reduced by acupuncture Acupuncture can be stimulated either manually by simply compared to sham treatment Secondary forms of inserting a needle in an acupuncture point, then either Raynaud's appear to be less influenced by acupuncture.
leaving it in place or twisting and thrusting the needle or by Survival of ischemic musculocutaneous skin flaps is in- stimulating the needles with a small amount of electrical creased in experimental preparations treated with either current at low frequency (2 to 4 Hz) Electro- manual or electroacupuncture Similarly, patients acupuncture appears to be the strongest form of acupuncture undergoing reconstructive surgery who are treated with and can induce a long clinical response in rats lasting from TENS experience improved microvascular flow and reduced 1 to 12 h These responses have led to treatment edema and capillary stasis relative to placebo TENS regimens of 30 to 45 min of acupuncture administered two Low-frequency TENS leads to a prolonged increase in skin to three times per week for 2 to 4 weeks. Although there are temperature in patients with diabetic polyneuropathy no well-controlled studies in humans, there is a suggestion Most studies on the peripheral circulatory effects of acu- that one to four courses of 10 days' treatment with acupunc- puncture are small and were not blinded; confirmation of ture lowers blood pressure (5 to 25 mm Hg) in some (e.g., their observations is needed.
borderline and essential hypertension) but not in all types of Several small trials suggest that hypertension may be hypertension Many practitioners use manual improved by acupuncture The magnitude of the acupuncture at several acupoints including acupoints within effect of acupuncture on blood pressure in patients with the same spinal segment, called "segmental acupuncture," or hypertension is small but significant; reductions of 5 to 10 a combination of segmental and distant acupoints (i.e., mm Hg have been noted. These and other small studies auricular acupuncture). In the treatment of pain, there are from outside the U.S. have led to funding of at least two numerous variations of these techniques, including inserting ongoing clinical trials by the NCCAM to test the hypoth- needles at myofascial trigger points and at the specific site of esis that acupuncture can lower blood pressure in patients pain There are no data on the efficacy of different with hypertension.
techniques of acupuncture with respect to cardiovascular Experimental studies indicate that acupuncture reduces demand-induced myocardial ischemia in felines Specific acupuncture points, such as the Neiguan or catecholamine- or stress-induced hypertension Zusanli acupoints, overlying the median and deep peroneal or genetically associated hypertension These studies nerves, respectively, have been used extensively for treat- also demonstrate that acupuncture limits myocardial isch- ment of cardiovascular abnormalities although the emia by reducing myocardial oxygen demand rather than by issue of point specificity for treating specific organ system increasing coronary blood flow in a feline model ailments requires further research. The NIH has published Acupuncture also can inhibit ventricular extrasystoles in- a consensus statement indicating that a number of issues duced by stimulating the hypothalamus paraventricu- related to acupuncture concerning its efficacy, sham effects, lar nucleus or following administration of BaCl2 adverse reaction, acupuncture points, training and creden- tialing, and mechanisms of action need further exploration The rationale for using acupuncture to treat myocardial ischemia, hypertension, and arrhythmias stems from its The response to acupuncture has been suggested to be ability to inhibit sympathetic outflow Numerous related to the placebo effect Because placebo effects experimental studies have shown that acupuncture, partic- can occur in as many as 40% of patients and because ularly low frequency (2 to 4 Hz) electroacupuncture, causes acupuncture seems to be efficacious in only approximately the release of opioids in a number of regions in the 70% of patients, there appears to be a narrow window JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document between placebo and what might be a true response (i.e., believed by some to affect psychological states and physio- 30% of patients) Nevertheless, one mechanism of logical processes of the nervous, endocrine, and immune placebo appears to involve the endogenous opioid system systems (psychoneuroimmunology). It is likely that con- Most practitioners check for symptoms of tingling, sciousness manifested as thought, emotion, memories, fears, local warmth, heaviness, or fullness, termed DeQi, to and self-concept can create physical changes in the body, confirm proper placement of needles in acupoints. Such and this appears modulated by many circulating mediators symptoms indicate stimulation of underlying neural path- such as tumor necrosis factor (TNF)-alpha, which may ways, but do not guarantee a true acupuncture versus a reduce or eliminate a reward response in animals and may be placebo response. Although experimental preparations cir- manifest by conditions such as MI. Blockers of TNF-alpha cumvent this criticism, because the animals generally are (etanercept) restore the reward response anesthetized, clinical investigation in the future will need to No sound scientific evidence demonstrates existence of include adequate sham controls to provide rigorous tests of bioenergy fields. Scientific or not, bioenergy concepts are the acupuncture hypothesis.
deeply ingrained and has gained popularity. Out-of-hand Worldwide, more than 40% of physicians recommend dismissal of influence of bioenergetics by a physician may acupuncture to their patients and more than 15% of physi- disrupt a relationship to a believing patient and cause the cians want to add this modality to their therapeutic arma- patient to turn elsewhere.
mentarium Although not required for licensed phy- The mind can influence health, life, and death sicians, the practice of acupuncture by others, such as those Energy that facilitates connectedness, harmony, and health trained in traditional Chinese medicine (i.e., acupunctur- can be as simple as emotional release in the form of mirthful ists), currently is regulated by more than 35 state boards in laughter or tears. Mirthful laughter can improve immune the U.S. Furthermore, the FDA regulates use of the system functioning This form of bioenergy can be disposable stainless steel acupuncture needles. Recently, a harnessed to improve a patient's well-being and outcome.
workshop held by the NHLBI and the NCCAM identified Belief in the benefit of treatment can improve outcome areas of needed research in complementary medicine in even if the treatment is a placebo. Controlled studies general and acupuncture specifically showing benefit of bioenergy approaches over placebo raise Areas of needed research in acupuncture include clinical the issue of a potential mechanism of effect with functional efficacy, mechanisms of action, and side effects. Most magnetic resonance imaging (MRI) that can show blood authorities agree that the risk of an adverse event resulting flow changes during brain mapping.
from acupuncture is small, generally below 10% if per- Many cardiovascular symptoms are not treated easily with formed by physicians. However, the risk of a serious event present medical therapy. Functional complaints, such as such as pneumothorax, the most common severe side effect, chest pain, palpitations, dyspnea, fatigue, and weakness not is significantly lower (2%), and although spinal cord lesions, associated with measurable physical abnormalities are poorly hepatitis and HIV infections, endocarditis, arthritis, and understood, and methods to eliminate consequences could osteomyelitis have been reported, they are rare. The risk of greatly improve health Reinterpretation of the symp- an adverse event for non-physician acupuncturists is higher toms and their severity by the patient (mental energy) may but again the risk of a serious event is low.
have an influence on outcome. The real benefit of thesetreatments might be as an adjunct to improve patient V. BIOENERGETICS (ENERGY MEDICINE) optimism and outcomes by their psychosocial effects A sense of peace, serenity, calm, power, or emotional Since ancient times, many cultures and religious disciplines connection can have potent influence on outcomes have considered that an aura, a life force, a radiant energy Removal of stress (not yet well defined) by a technique field can emanate from, and surround, living things utilizing bioenergy may modify severe disabling symptoms This poorly understood vital energy (Hindu prana, Chinese even if the therapy has no proven benefit. Such an approach qi, chi, and Japanese ki) associated with the soul, spirit, and can be advocated as long as it does not exclude standard mind, impinges on the potential boundaries of modern therapy and does not cause harm.
physics and the relationship of the mind to the physicalworld Bioenergetics offers the possibility to harness a Methods to Study Bioenergy
healing life force The wide array of questionableenergy-healing approaches opens the possibility of medical Although bioenergy may be immeasurable, patients—and quackery that can put patients with serious underlying therapists—will continue to use bioenergy approaches if diseases at risk especially if standard, accepted, and effective convinced of their efficacy, no matter the resolve of a specific therapies are overlooked.
scientific, or medical community to discount benefits even if Bioenergy, "life energy," is thought by some to influence there is scientific demonstration of inefficacy. Adjusting mind/body, mind/mind (person to person) and mind/mind bioenergy fields through acupuncture, therapeutic touch, Qi (person to infinite spirit) relationships and is altered Gong, Johrei, Reiki, crystal therapy, and magnet therapy may by conscious and unconscious efforts Bioenergy is improve health, but data are too preliminary to recommend Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 any therapy If they do have an effect, both the extent Over 1,300 references on Qi Gong suggests benefit to of benefit and the mechanisms responsible are unknown.
treat hypertension, respiratory diseases, and cancer. For Traditional Chinese medicine encompasses folk practices hypertension, lower stroke and mortality rates have been based on mysticism and bioenergy A recent analysis shown in preliminary studies Qi Gong may benefit of 2,938 clinical trials reported in Chinese medical journals some patients with atherosclerotic obstruction of the lower shows these data to be inconclusive Chinese trials extremities and breathing approaches might influence were qualitative, short-term, small, poorly controlled, rarely symptoms in patients with mitral valve prolapse blinded, and contained inadequate data.
Reiki. Reiki is believed to use "healing energy" to enhance
vitality, resiliency, and health for both practitioner and
Forms of Bioenergetics
patient There are over 500,000 practitioners.
The techniques share common features: focus on "bioen- The technique's most profound effect is deep relaxation. It ergy" by practitioners and "energy transfer" leads to benefi- works, supposedly, only if the receiver can detect the subtle, cial effects.
personal, unconscious energy. A practitioner "attuned" to Relaxation. Relaxation therapy in 192 men having two or
the energy places his hands onto or just above the patient's more risk factors for CAD was associated with better body at strategic points (chakras) to transfer energy. Chan- outcomes compared to a control group "Type A" neling this energy is purported to have a positive effect, but persons tending to have a higher incidence of hypertension scientifically demonstrable cardiovascular effects have not and death from CVD may benefit from a relaxation re- sponse Progressive muscle relaxation techniques Healing and therapeutic touch. Healing touch (HT) and
have been associated with improved cardiovascular out- therapeutic touch (TT) use the concept of energy fields comes, but data are still preliminary.
(auras), energy centers (chakras), and energy tracts (medi- Yoga. Movements and positions in yoga and the breathing
ans) to empower healing similar to Reiki.
exercises can lower the blood pressure and alter breathing Healing touch, developed by Janet Mentgen, RN patterns Among other improvements in physical is used extensively by nurses (68,000 participants in the fitness, yoga can increase absolute and relative maximal U.S.) at all levels of health care, but it based on little oxygen uptake by 7% and 6%, respectively, after eight weeks supportive controlled data. Universal energy is believed to be in a controlled setting Yoga has been associated with channeled to work with human "energy fields" to restore improved heart rate variability and respiratory variables harmony and balance. The technique utilizes the hands to There can be a decrease in sympathetic response clear, energize and balance the human energy fields, thus and changes in baroreflex sensitivity Yoga affecting physical, emotional, mental, and spiritual health.
may influence the progression and regression of atheroscle- Healing TT is a therapeutic intervention, an educational rosis and may beneficially alter the lipid profile program, and an international organization that provides but the data are too preliminary to make a sound recom- healing touch certification and formulates standards of mendation in favor of yoga.
Qi Gong. Qi Gong has increased dramatically. Qi means
In therapeutic touch, hands are used to direct healing life-force energy and Gong is "practicing skill." Practitioners energy. Healing supposedly results from transfer of "excess believe that vital energy circulates through "meridians," energy" from healer to patient. Therapeutic touch was connecting all organs, and illness is an imbalance, or conceived in the 1970s by Dolores Krieger Thera- interruption, of Qi. Qi Gong is said to re-balance the energy peutic touch involves "centering" (align the healer to the patient's energy level), "assessment" (hands detect forces Internal Qi Gong involving deep breathing, concentra- from the patient), "unruffling the field" (sweeping stagnant tion, and relaxation is a self-discipline that trains body and energy downward to prepare for energy transfer), and energy mind to alter flow of "vital energy." In 76 post-MI patients, transfer (from practitioner to patient) Qi Gong was associated with improvement in respiratory Therapeutic touch was evaluated in a meta-analysis by rate, heart rate, and respiratory sinus arrhythmia In Astin et al. Of the 11 trials reviewed, 7 showed a similar study, hospitalization was reduced in post-MI pa- positive treatment effect and at least one outcome. These tients learning Qi Gong relaxation techniques In included a 17% decrease in anxiety in cardiac care unit hypertensive patients, Qi Gong was associated with an (CCU) patients, reduced need for postoperative pain med- improvement in levels of prostoglandin ication, and improved wound healing.
"External Qi Gong" is performed by "masters" who claim Healing TT may reduce anxiety but no sound scientific to cure with energy from their fingertips. Control Qi is evidence supports the postulated "energy transfer" benefits claimed to diagnose and cure various conditions Qi claimed. Benefits reported may simply be a placebo effect, Gong may influence and reduce respiratory rate, heart rate, literally a "laying on of hands" blood pressure, and accentuate vagal tone demonstrated by Distance healing. Similar to TT and distance (interces-
changes in heart rate variability However, th sory) prayer, "distance healing" is energy transfer that is said clinical significance and mechanisms are unclear to occur over very long distances. Beutler et al. showed JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document small but significant changes in diastolic blood pressure in a been shown to alter the natural course of CVD These double-blind controlled study of distance healing. One therapeutic approaches may appear to have benefit as an study showed benefit of distance (blinded) prayer on auto- adjunct to standard medical therapies and for patients with nomic tone based on skin conductance levels and "blood severe functional, yet symptomatic, complaints, but actual benefits are difficult to measure. Bioenergy approaches Applied kinesiology. This technique of kinesiology is per-
should not be considered substitutes for standard medical formed by therapists using acupressure points and a muscle- care; they may offer false hope to patients and at an testing method to diagnose nutritional and glandular "defi- expensive price.
ciencies," which are then "corrected" by manipulation or Practitioners and patients who use these techniques will nutrition supplements. There is little substantiated support- likely continue to employ them even without a scientific foundation. Practitioner qualifications are difficult to mea- Meditation. Meditation, not universally considered bioen-
ergy therapy, can alter blood distribution in the brain "Benefits" may represent the natural course of a disease or observed by magnetic resonance imaging scans and can the patient's or therapist's interpretation of the condition.
increase delta wave activity observed on the electroenceph- Positive results may represent experimenter biases not ob- alogram. Rage behavior decreases. Transcendental medita- vious from the study design. Patients may undergo "energy tion has been linked to reduction in cardiovascular mortality healing" and be cured of a condition that they do not have It can lower blood pressure Zen or they may be misdiagnosed. A bioenergy practitioner meditation has been associated with improved heart rate might exaggerate or create an illusion of the benefit of variability and slowing of respiratory rate These data therapy. Biases for, and against, bioenergy healing make it are preliminary and techniques cannot be recommended yet.
even more difficult to assess the quality of the data.
Vibrational medicine. Practitioners of vibrational medi-
Ongoing studies including those funded by the NCCAM cine consider humans as dynamic energy systems ("body/ are evaluating energy healing approaches.
mind/spirit" complexes). People are influenced by subtle emotional, spiritual, nutritional, and environmental energiesthat affect health These concepts involve vibrational Conditions for which bioenergy therapies are not contrain- medicine: aromatherapy, chakra rebalancing, distance heal- dicated (but not specifically recommended) include: ing; flower essence therapy, homeopathy; Kirlian photogra- 1. If a bioenergy treatment does not interfere with stan- phy, moxibustion, orthomolecular medicine; past-life re- dard, accepted, and proven therapy.
gression, radionics; and other unfounded approaches.
2. If standard therapies do not provide optimal symptom- Magnetotherapy. "Magnetotherapy" is applied through
atic improvement, or for a condition that is potentially the use of permanent or fluctuant magnetic fields, but there functional or has functional overlay.
are no proven benefits for the CVD Scherlag hasbeen evaluating, in an animal model, low-level gauss fields No bioenergy therapy should be considered a substitute to affect atrial arrhythmias in preliminary studies for standard, accepted, and approved therapies. If any Homeopathy. Water is believed to retain the memory of
bioenergy approach is considered, one should choose a and be energized by compounds that existed in it. Scanning practitioner who has a good reputation, appears to have of water by MRI suggests there might be some, but no data good results, and is willing to work with medical profes- has demonstrated health benefits for CVD A meta- analysis of homeopathic treatments in the Lancet of morethan 80 studies indicated, compared to placebo, that ho- meopathic treatments might be effective Al- Spirituality in Cardiovascular Applications
though the results were significant as a whole, concerningany one-disease entity, no significant treatment could be Anectdotally the will to live, a strong life force spirit or faith, discerned. The therapies were not standardized.
a loving family or community, or the absence of thesefeatures has been considered related to outcomes in cardio- vascular care. Synchrony between belief systems or other Potential beneficial effects of these approaches may be in "connections" between patient and healer are also widely part due to an undefined psychological impact that might considered important on an intuitive basis.
ultimately create a physiological effect. The approaches have Some indigenous master healers from various cultures not been tested for safety. There are no specific proven and faiths assert that medicines and procedures constitute cardiovascular benefits from any of these therapies to treat only about 20% of what heals and that 80% is mediated through the spirit With remarkable uniformity Potential adverse influences may be the release of inhibi- across these healers, the "spirit" is considered an integral tions causing anger, hostility, "negative" energy, or reduc- element of optimal diagnosis and therapy tion of needed sympathetic tone. No bioenergy therapy has The ramifications of such claims, if even partly true, are Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 staggering. It is currently impossible to assess the accuracy 3. There is a notable consistency across reports suggesting of such claims based on available data. The ubiquitous presence of spiritual beliefs and practices present since 4. There are no obvious safety issues attendant to spiritual ancient times mandates systematic examination Intuitively, the role of spirituality in modern cardiovas- Specific Reports of Spirituality and Cardiovascular Care
cular care offers both the potential to better understand andsupport patients who face cardiac death and provide new Epidemiologic evidence correlating individual spiritual questions for therapeutic interventions. Thousands of ob- practice, involvement within a spiritual community, and of servational, instructional, anecdotal, theological, and philo- communities characterized by their spiritual practices with sophical treatises suggest the potential impact of the spirit in improved cholesterol levels, more normative blood pressure, health, including passages from the Bible, the Koran, the other risk factor modulations, incidence of clinically recog- Upanishads, the transcribed teachings of Buddha and other nized coronary disease, incidence of MI, post-coronary artery bypass graft (CABG) survival, and improved survivaloverall provides an intriguing context for other observationsof psychosocial descriptors—including personality type, hostility, depression, isolation, and cardiac outcomes A number of well-referenced overviews or comprehensive As with all epidemiologic data, however, it remains compendia of references have been compiled on scientific unclear whether or not there is actually a causal relationship investigations into spiritual and religious practices correlated between these spiritual features and the clinical outcomes.
with cellular, physiologic, somatic and psychosomatic heal- Reports of palliation of subjectively perceived stress ing applications. These books and compendia can be found and/or pain levels in patients admitted to the CCU or on the ACCF Web site as Appendix VI and include undergoing cardiac catheterization constitute another area references using broad arrays of study designs with a intriguing both for its consistency and for its apparent heterogeneous nomenclature and definitions specific to the overlap with the use of imagery, relaxation, and other heart. Two consistent themes include epidemiologic obser- biofield and energy healing techniques in similar patients vations that both personal and social spirituality have Only one preliminary report, however, has correlations with selected outcomes measures, and that actually correlated such palliative end points with clinical spirituality, particularly prayer, may have efficacy in healing applications. Data quality, selection bias, interpretative bias, Four prospective, randomized, double-blinded clinical publication bias, and details of safety issues are not discern- trials examining the influence of off-site prayer on clinical ible from these compendia.
outcomes in cardiac patients have been reported In three of the studies, CCU patients were assigned either Review Articles and Meta-Analyses
to off-site intercessory prayer or no prayer in addition tostandard care. In two of the CCU studies, a combined index Various structured reviews and meta-analyses of spiritual of hospital course and complications severity was derived descriptors and therapies and their correlations with clinical specifically for study purposes Although findings outcomes (not specific to cardiology) have also emerged in were reported as significantly improved in each cohort the peer review literature and can be found on the ACCF treated with off-site prayer, clinical interpretation of these web site as Appendix VII. This literature overall is wellsummarized in the Astin et al. recent meta-analysis of findings is difficult. In the third CCU study no clinical studies involving spirituality. The researchers ac- significant differences existed in clinical outcomes, although knowledge that available reports were so heterogeneous in the study was powered to a higher treatment effect than may structure, methods, population, and end points measured have been observed. The fourth study was a feasibility pilot that their attempt to perform a classical meta-analysis had to examining an array of CAM practices in patients with acute be "abandoned." The present writing group's consensus coronary syndromes undergoing invasive catheterization overview of these reviews suggest: and angioplasty Using major adverse cardiac events(MACE) and blindly analyzed continuous electrocardio- 1. The literature in this area is devoid of mechanistic graphic evidence of post-angioplasty ischemia, absolute insight and is heterogeneous as to the quality of study reductions were observed in the prayer group relative to the standard therapy group; however, these difference did not 2. There is no scientific evidence in the literature reach statistical significance Two additional prospec- sufficiently definitive or compelling to provide a basis tive, multicenter clinical studies of double blind off-site for specific recommendations on the use of spiritual prayer in patients undergoing CABG and percutaneous intervention for healing purposes in a cardiology coronary intervention, respectively, have completed enroll- ment and will soon be reported JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document Key Issues in Spirituality Applied to Cardiovascular Care
ethnic affiliations, and/or the use of ancillary componentssuch as music, soft abdominal breathing, humming or Support versus spiritual therapy. Careful consideration
chanting, a prescribed body posture or the like. Quantitative must be given to the important differences between render- features, such as the number of individuals praying, the ing spiritual support for patients and families and the study duration of the prayers, and the proximity to the patient, are of experimental, directed spiritual therapy.
also of potential interest.
Spiritual support constitutes the response of the health Mechanism of action and surrogate measures. "Divine
care system to the self-perceived spiritual needs of the intervention," "life force," "love," "joy," and "spirit" all share patient and family. Access to a chapel, the presence of a a common feature—the absence of any satisfactory mecha- chaplain, awareness of and sensitivity to spiritual and ethnic nistic explanation as to how they operate in health or preferences—spiritual support services can broadly be seen disease. Three explanations are widely discussed: as the health care system's readiness and sensitivity to needsidentified by patient and family, particularly in the face of 1. These forces are divine, and so cannot be compre- life-threatening illness. Spiritual support might be a com- hended, particularly within a deterministic model.
ponent of therapy focused on recovery from illness, or it may 2. These forces cannot be measured because they do not be involved as tools for coping, for grief, or for transcendence of impending death. It is generally appropriate for spiritual 3. These forces are self-evident, and we simply have not support services to be assessed and advanced through a quality yet developed measurement tools.
assurance/quality improvement (QA/QI) process. External In the absence of discrete measurements or appreciable agencies appropriate for overview of QA/QI include the mechanisms of action, and in the presence of spiritual Joint Commission for Hospital Accreditation.
practice imbued in the culture of patients, families, com- Spiritual therapy implies a healing objective actively munities, and health care staff, a pure control group for sought and documented through experimental intervention.
spirituality trials is difficult, if not impossible, to develop.
Formal research protocols, Institutional Review Board pro- Thus, studies in this area can currently examine incremen- cesses, and informed consent from patients are appropriate.
tal, but not absolute, therapeutic effects.
Specific considerations of methodology, mechanism, dose Safety and efficacy end points in spiritual therapy studies.
and dose response, and other aspects fundamental to work Selection of efficacy end points for study in this area must be with any new therapeutic agent in cardiology patients are all consistent with the population studies. For patients with applicable. Peer-review grant funding for spiritual therapy very advanced heart disease, where end of life issues may protocols is currently identifiable at the NCCAM and other become ascendant over mortality per se, the influence of agencies at the NIH. New standards and recommendations spiritual interventions on end of life measures would be a for study in this area have recently been published Conversely, if spiritual therapy shows a therapeutic effect Spirituality and religion. "Religion," the "religious," and
it may be capable of causing harm. As with any new therapy the "spiritual" are terms used synonymously to refer to that whose mechanism is undefined, it is unreasonable to simply which connects the mortal being to the highest sense of assume safety and study efficacy—addressing safety, with meaning and order at a transpersonal level. In other usage, Data Safety Monitoring Boards, should be formally in- the term "religion" implies established ethnic and cultural cluded in trials as a safety and efficacy study design.
groups, and in some cases evokes the concept of a divinity, Similarly, as research with potential safety issues atten- whereas "spiritual" implies a more generic attribute.
dant, clinical trials applying spiritual intervention to cardi- Unique baseline spirituality patient descriptors. Epide-
ology patients as an investigational therapy should do so miologic evidence is compelling that baseline spirituality with the informed consent of the patient.
descriptors characterized by established questionnaires are Sensitivity, privacy, and ethics. Spiritual matters consti-
associated with certain cardiac outcomes In one tute one of the most private and personal areas for both report, the degree of the spirituality effect was equivalent to patients and staff. Sensitivity to the broad array of belief a history of cigarette smoking Further study and systems and to the highly symbolic nature of certain terms, especially prospective multivariate models will be important concepts, or icons is paramount to develop spiritual support to better understand the predictive information content of systems and studies of spiritual therapy. Incorporation of baseline spirituality in conjunction with other classical spiritual assessments as part of standard nursing admission cardiac predictors of outcome (e.g., age, ejection fraction, procedures or the acquisition of spirituality survey informa- tion in conjunction with research protocols must be con- Methods and spiritual therapy. No discrete measurements
ducted with strict attention to whether the patient finds the report intensity or "dose" of spiritual therapies. Qualitative queries objectionable and to the confidentiality of the features include descriptions of the practice itself, the material and with informed consent.
content of the prayer, meditation, intention or imagery Cultural preconceptions and bias regarding spirituality used, the experience level of the practitioner, any notable are substantial, with some issues that are primarily philo- Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 sophical, not subject to scientific study or resolution, and of spirituality and healing, delivery roles, practice standards, likely to be contentious when discussed broadly. Crucial and certification issues is suggested.
How do we know when God answers prayer? Christine W. McEntee, Chief Executive Officer Does one religion have more powerful prayer? Dawn R. Phoubandith, MSW, Associate Director, Clinical How would a negative study of prayer be interpreted? Policy and Documents Is death a negative end point? Ana Patricia Jones, Senior Coordinator, Clinical Policy and Is technology necessary in the setting of true faith? It seems reasonable to examine spiritual therapy as an adjunct to modern technology, not as competition or a APPENDIX I: RELATIONSHIPS WITH INDUSTRY replacement for standard care. It is reasonable to assess the Writing committee members were asked to identify all safety and efficacy of spiritual interventions with reasonable relationships with industry that were relevant— or could be but rigorous science and clinical trial designs. It is reason- perceived as relevant—to this document. One member, Dr.
able to investigate physiologic signals that might provide Kenneth Pelletier, declared that he had past (not current) either a marker of the presence of spiritual influence or even research grants with Medtronic and Merck. The other a key to mechanisms through which spiritual influence is authors of this document declared that they had no relevant relationships with industry pertinent to this topic.
Extension of dialogue across the disciplines and constit- uencies concerned with spiritual support and spiritual ther- APPENDIX II: GLOSSARY apy is timely and important.
Acupressure. Acupressure is an ancient Asian healing art
Delivery Roles, Accreditation, and Certification Standards
that uses the fingers to press key points on the surface of theskin. Practitioners believe this stimulates the body's immune Optimal spiritual support or therapy requires considerable system to self heal. When stimulated, these points may re-thinking regarding the relative roles of the patient, the relieve muscular tension and promote the release of endor- family, the community, the clergy, and hospital staff. As phins—neurochemicals that relieve pain. Acupressure uses Don Carlos Peete stated in his 1955 book The Psychosomatic the same points and meridians (patterns of energy flow) as Genesis of Coronary Artery Disease: "I believe the most acupuncture, but instead of needles it treats with gentle, successful physician will instill into his patient hope, cour- firm pressure of fingers and hands.
age, and patience. He can do so only if he has these virtues Acupuncture. Acupuncture is a treatment based on an
himself. The discipline necessary to face the responsibilities ancient Chinese medicine. Acupuncture places extremely that are ours as individuals and as a people can be attained thin, sharp needles (that are sometimes connected to a only when we understand and use both the spiritual and low-voltage power source) along a network of "lines of physical laws in our daily lives" energy" or meridians on the body surface. Chinese medicinepractitioners believe these meridians conduct energy Summary and General Recommendations
throughout the body. However, recent (Western) evidence Spiritual needs, influences, and therapeutic claims are an- indicates that the needles stimulate sensory nerves underly- cient and ubiquitous. Spirituality issues are pertinent to ing meridians to alter neurotransmitter release in regions of patients with heart disease. Recommendations include: the central nervous system concerned with regulation of theautonomic nervous system and hence the heart and blood 1. Development of health care responsive to the spiritual vessels. Acupuncture is believed by clinicians practicing needs of patients and families.
traditional Chinese medicine (TCM) to balance the oppos- 2. No practice guidelines for spiritually based therapy in ing forces of yin and yang, keep the normal flow of energy cardiovascular care can be currently recommended.
unblocked, and maintain or restore health to the body and 3. Clinical research of spiritual interventions in cardiology settings is reasonable, should be conducted as safety and accessed September 18, 2002). Eastern scientists have trans- efficacy trials, and ethically must include the informed lated these TCM concepts into a neurophysiologic para- consent of patients.
digm in which acupuncture, by evoking the release of 4. The use of unique baseline descriptors of spirituality in inhibitory neurotransmitters (endorphins, enkephalins, and clinical trials is suggested.
possibly endomorphins) in the hypothalamus, midbrain, 5. Development of a common nomenclature, use of stan- and medulla, in turn, reduces activity of premotor neurons dardized measures, and detailed methodological de- concerned with sympathetic outflow to the heart and scriptions in clinical trials of spiritual interventions are AHA dietary guidelines. October 2000 revision of the
The cultivation of multidisciplinary forums on concepts AHA dietary guidelines to Americans JACC Vol. 46, No. 1, 2005 Vogel et al.
July 5, 2005:184 –221 ACCF Complementary Medicine Expert Consensus Document Applied kinesiology. This chiropractic technique is per-
Hydrotherapy. The concept behind this technique is that
formed by therapists, using acupressure points and a water is "energized" by compounds in extremely dilute muscle-testing method. Practitioners believe they are able to amounts. Practitioners believe that water retains the mem- diagnose nutritional and glandular "deficiencies" that are ory of the compounds that existed in it. This may reflect then "corrected" by manipulation or nutrition supplements.
dilute amounts of the retained original compound.
Atkins diet. Developed by Dr. Robert Atkins, this diet
Hypnosis. Hypnotic techniques induce states of selective
limits carbohydrates to 20 g initially for rapid weight loss.
attentional focusing or diffusion combined with enhanced This is done by eliminating high carbohydrate foods such as imagery. They are often used to induce relaxation and also bread, potatoes, pasta, fruit, juices, and candy. Fats and may be a part of cognitive behavioral therapy. The tech- proteins are the main source of fuel on this diet. Meat, eggs, niques have both pre- and post-suggestion components.
butter, and most cheeses can be eaten without restriction.
The pre-suggestion component involves attentional focus- Bioenergy (bioenergetics). Bioenergetics is a loosely col-
ing through the use of imagery, distraction, or relaxation, lected series of healing "disciplines" that attempt to harness and has features that are similar to other relaxation tech- natural forces and powers to influence natural healing niques. Subjects focus on relaxation and passively disregard processes. Bioenergy fields are thought to be altered by intrusive thoughts. The suggestion phase is characterized by conscious and unconscious efforts Bioenergy medi- introduction of specific goals; for example, analgesia may be cine uses bioenergy (HT and TT, Qi Gong, Johrei, Reiki, specifically suggested. The post-suggestion component in- crystal therapy, relaxation therapy, distance healing, applied volves continued use of the new behavior following termi- kinesiology, and magnet therapy) to heal nation of hypnosis Biofeedback. Biofeedback (BF) techniques are treatment
Magnetotherapy. This therapy is applied through the use
methods that use monitoring instruments of various degrees of permanent or fluctuant magnetic fields.
of sophistication. The BF techniques provide patients with Meditation. Meditation is a self-directed practice for re-
physiologic information that allows them to reliably influ- laxing the body and calming the mind. Various meditationtechniques are in common use; each has its own proponents.
ence psychophysiological responses of two kinds: 1) re- Meditation generally does not involve suggestion, autosug- sponses not ordinarily under voluntary control, and 2) gestion, or trance responses that ordinarily are easily regulated, but for which Mediterranean diet. This is a diet high in fruits, vegeta-
regulation has broken down. Technologies that are com- bles, bread and other cereals, potatoes, beans, nuts, and monly used include electromyography (EMG BF), electro- seeds. Olive oil is an integral part of the diet and is an encephalography, thermometers (thermal BF), and galva- important source of monounsaturated fat. Dairy products, nometry (electrodermal BF) fish, and poultry are eaten in low to moderate amounts and Crystal therapy. Practitioners believe that crystals contain
little red meat is consumed. Up to four eggs are consumed or possess energy fields that can be used to heal. Practitio- weekly and wine is drunk with meals in low to moderate ners believe that each crystal is associated with different energy fields or emotions.
Mental physics. This is purported to be a practical, holis-
Distance healing. There is much overlap among TT,
tic, futuristic science that manifests "hidden meaning" of the distance healing, and distance prayer. Spiritual healing Bible and involves "astral travel;" aura reading chanting; practiced when the patient is not present is called distance meditation, pranayama ("deep scientific breathing exer- healing and is similar to prayer. It can be practiced in groups cises"); "pranic therapy" (a variant of channeling); reflexol- or individually.
ogy; shiatsu; and individualization of diet according to Guided imagery. A patient is asked to focus deliberately on
a particular image in order to "relax, manage stress, or Mind/body. Mainstream mind-body medicine, as defined
alleviate a specific symptom" Key to this therapy is by Chiarmonte is "based on the premise that mental that the patient is in control of the image and can redirect or emotional processes (the mind) can affect physiologic it. The image does not have to be physiologically true, as in function (the body)." Lazar elaborates on this point the case of a cancer patient imagining being free of cancer, further, saying that mind-body medicine is an integrative or even real in the sense that the patient has or would ever discipline that examines the relationship between psycho- experience what the image depicts. Imagery may be just logical states and psychological interventions and between simple visualization or a sensory perception such as a smell, physiology and pathophysiological processes. Conversely, a touch, or a sound Although imagery uses most practitioners of CAM—which takes a different ap- the conscious mind, it may also be utilized to tap into the proach to mind/body medicine— hold that the mind's unconscious or less conscious mind.
impact on the body is not unidirectional; rather, there is an Ho'oponopono. This Hawaiian approach alleges to find
integrated process in which both mind and body affect each the divine within oneself to remove stress and release problems. It involves repentance and "transmutation" to Music therapy. Music therapy is the prescribed use of
provide spiritual freedom, love, peace, and wisdom music by a qualified person to effect positive changes in the Vogel et al.
JACC Vol. 46, No. 1, 2005 ACCF Complementary Medicine Expert Consensus Document July 5, 2005:184 –221 psychological, physical, cognitive, or social functioning of meaning to life's events In the absence of insight into individuals with health or educational problems the mechanism, the entire area of spirituality and cardio- Nutrition. This concerns cardioprotective diets, including
vascular health remains highly anecdotal, intuitive and AHA Step I and Step II; Mediterranean; NCEP ATP III; speculative. As patients and families of loved ones who have DASH, low-fat and low-sugar diets. Also includes garlic, heart disease face mortality in a very personal and immedi- nuts, teas, and alcohol use.
ate way, however, there is widespread interest in how Placebo. A placebo is defined as an inert or innocuous
cardiologists think about and approach spiritual issues in treatment that works not because of the therapy itself but practice and in research.
because of its suggestive effect. It is considered a mind/body Supplements. The Dietary Supplement Health and Edu-
modality, but with some distinct differences. Placebo ther- cation Act (DSHEA) of 1994 defined dietary supplements apy depends on the power of a patient's belief that the as a product (other than tobacco) intended to supplement therapy will be effective the diet that bears or contains one or more of the following Pranic psychotherapy. Pranic psychotherapy includes re-
ingredients: vitamins, minerals, herbs, or other botanicals, moval and disintegration of "traumatic psychic energy," amino acids, and substances such as enzymes, organ tissues, disintegration of "negative elementals" ("bad spirits"), and glandulars, and metabolites. Whatever their form, DSHEA creation of a "positive thought entity." places dietary supplements in a special category under the Progressive muscle relaxation (PMR). Progressive muscle
general umbrella of "foods," not drugs, and requires that relaxation focuses on reducing muscle tone in major muscle every supplement be labeled a dietary supplement groups. Each of 15 major muscle groups is tensed and then relaxed in sequence.
ber 18, 2002). Other examples include antioxidants, plant Qi Gong. Qi is life force energy and Gong is "practicing
sterols, soluble fiber, omega-3 fatty acids and soy; herbs, skill." Practitioners of Qi Gong believe that vital energy such as Ginkgo biloba, guggulipid, and HCSE; and other circulates through "meridians," connecting all organs. Illness supplements, such as, L-arginine, L-carnitine, and CoQ10.
is attributed to an imbalance, or interruption, of Qi. Qi Gong Therapeutic touch. Practitioners believe that their hands
is said to re-balance "yin" and "yang" are used to direct healing energy. Healing supposedly resultsfrom transfer of "excess energy" from healer to patient.
Internal Qi Gong. Involves deep breathing, concentration, Transcendental meditation. Transcendental meditation
and relaxation. It is a self-discipline that trains body and focuses on a "suitable" sound or thought (the mantra) mind to alter flow of "vital energy," for self-reliance and without attempting to actually concentrate on the sound or adjustment, to cure disease, and to strengthen and prolong life.
Vibrational medicine. Considers humans as dynamic en-
External Qi Gong. Affects things outside one's body. It is ergy systems ("body/mind/spirit" complexes). The dynamic performed by "masters" who claim to cure with energy energy system, the life force, is influenced by subtle emo- released from their fingertips.
tional, spiritual, nutritional, and environmental energies.
Reiki. Rei is "universal," or "spiritual," and Ki is "life force
Health and illness originate in "subtle energy systems." energy." It is a form of laying on the hands Yoga. Developed in India, yoga is a psycho-physical discipline
Relaxation. Relaxation techniques are a group of behav-
with roots dating back about 5,000 years. Today, most yoga ioral therapeutic approaches that differ widely in their practices in the West focus on the physical postures, termed philosophical bases as well as in their methodologies and "asanas," breathing exercises called "pranayama," and medita- techniques. Their primary objective is the achievement of nondirected relaxation, rather than direct achievement of a Zen meditation. This technique is a form of Buddhism
specific therapeutic goal. They all share two basic compo- originating in Asia; it teaches that desires are the primary nents: 1) repetitive focus on a word, sound, prayer, phrase, cause of suffering. Meditative absorption in which all body sensation, or muscular activity, and 2) adoption of a dualistic distinctions are eliminated (source: passive attitude toward intruding thoughts and a return to the focus. These techniques induce a common set of physiologic changes that result in decreased metabolicactivity. Relaxation techniques may also be used in stress management (as self-regulatory techniques) and have beendivided into deep and brief methods 1. Krauss RM, Eckel RH, Howard B, et al. AHA Dietary Guidelines: Reversal diet. The Ornish reversal diet consists of 10% fat
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ORDERED BY Patient Name Primary Tumor Site: Brain, NOS Ordering Physician Case Number: TN13-111111 Specimen Site: Cerebellum The Cancer Center Date Of Birth: XX/XX/1995 Specimen Collected: XX/XX/2013 City Gate, St. Jakobsstrasse 123ABC, Basel, CH-4052 Sex: Male

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