Current Geriatric Diagnosis & Treatment, 1st Edition

Section IV - Special Situations

45. Anti-Aging & Complementary Therapies

Alfred Fisher MD, PhD

John E. Morley MBBCh

Most older Americans expect to live longer and more independently than previous generations, and many seek increasingly to be involved in their own health through diet, exercise, and participation in health care. Never before has information about health, disease, and treatments been more available through conventional media and the Internet. Ironically, during an era when the number of seniors has grown dramatically, the societal focus on youthfulness has remained strong. The combination of the desire to be involved in health care, the ready access to information which can create consumer demand, the wish to promote health and avoid aging, and interest in new ways to approach problems have created tremendous interest both in therapies designed to prevent or retard aging and in complementary and alternative approaches to health care.

ANTI-AGING THERAPIES

Knowledge about the biological mechanisms involved in aging and the physiological changes associated with aging provides a rational basis for the quest for anti-aging therapies. An anti-aging therapy could act by 1 or more of the following 3 mechanisms:

  1. Modify the biochemical and molecular events that cause aging.
  2. Correct physiological changes that cause signs or symptoms associated with aging.
  3. Lessen the susceptibility of an individual to diseases associated with aging.

Practices that act through the third mechanism (eg, colonoscopy, blood pressure reduction, cholesterol reduction, and other practices that aim to prevent age-associated diseases) are common in medical practice and are dealt with in Chapter 3 and elsewhere in this book.

Antioxidants: Vitamin A, Vitamin C, Vitamin E, Beta Carotene

Aging has long been hypothesized to be due, in part, to oxidative stress. Many cellular processes produce reactive oxygen or reactive nitrogen species, which via a free radical mechanism can chemically modify and hence damage proteins, DNA, and lipids. Aged animals show accumulation of oxidative damage, with markers of oxidative damage being elevated 2- to 3-fold between reproductive maturity and death. Experimental studies in animals have supported a role for oxidative damage in aging. For example, in the worm, Caenorhabditis elegans, and in mice, genetic mutations enhance endogenous antioxidant defense pathways and increase life span by 30-100%. Also experimental treatment with antioxidants has increased their life span by 10-50%, maintained mobility in worms, and preserved cognition in mice.

In humans, oxidative damage may contribute to atherosclerosis, cancer, Parkinson's disease, and Alzheimer's disease. The antioxidants most commonly used in people are vitamin A and its precursor beta carotene, vitamin C, and vitamin E. When vitamins are used as anti-aging therapies, they are often used in doses that are higher than the replacement doses that are appropriate for vitamin deficiencies. Although ingestion of vitamin supplements was not associated with increased life span in participants in the U.S. National Health and Nutrition Examination Surveys, it has been hoped that antioxidants might prevent diseases associated with oxidative damage.

  1. VITAMIN E

Vitamin E is the safest of the lipid-soluble vitamins and is most commonly given as α-tocopherol in doses ranging from 150 IU/day-2000 IU/day. Side effects include nausea, flatulence, diarrhea, and inhibition of vitamin K.

Vitamin E (800 IU/day) may be used in patients with end-stage renal disease and coronary artery disease to prevent myocardial infarction and other cardiovascular end points. There is no compelling evidence, however, that vitamin E prevents coronary artery disease or its sequelae in other clinical situations. In fact, vitamin E could be harmful in patients with low high-density lipoprotein (HDL) and normal low-density lipoprotein. An antioxidant cocktail including vitamin E blunted the effects of niacin and simvastatin on raising HDL, reducing progression of atherosclerosis and reducing cardiovascular events. With regard to primary prevention, 1 study found no effect of vitamin E during

P.469


3.6 years of follow-up in patients with cardiovascular risk factors but no history of cardiovascular disease. Similarly, the Alpha-Tocopherol and Beta Carotene Cancer Prevention Study (ATBC) showed no effect of vitamin E on the development of angina or myocardial infarction in patients without coronary artery disease. With regard to secondary prevention, several studies showed no effect of vitamin E supplementation on cardiac outcomes; these findings contrast to a 50% reduction in recurrent myocardial infarction attributed to vitamin E in the smaller Cambridge Heart Antioxidant study. Other studies have found no beneficial effect of vitamin E on progression of carotid atherosclerosis or the development of abdominal aortic aneurysm or peripheral vascular disease.

The effect of vitamin E on the progression of Alzheimer's disease of moderate severity may be promising. In an analysis adjusting for baseline Mini-Mental State Examination, progression was delayed as indicated by longer time to the composite end point of death, institutionalization, loss of ability of 2 of 3 basic activities of daily living, or development of severe dementia (670 days vs. 440 days). However, falls were more frequent in patients treated with vitamin E.

The effect of vitamin E on rates of cancer is not fully defined. Among smokers, the ATBC study found no effect on the development of lung cancer, an increase in the incidence of stomach cancer, and fewer cases of prostate and colorectal cancer. The decrease in prostate cancer seen in the ATBC study has been suggested to be due in part to lowered serum androgen levels because patients receiving vitamin E had significantly lower serum levels of testosterone and androstenedione. Observational studies of vitamin E in the prevention of colorectal cancer have produced mixed results. One study found no effect of vitamin E on the development of breast cancer.

In patients with preexisting age-related macular degeneration, a combination of antioxidants including vitamin E decreased progression to advanced macular degeneration in the Age-Related Eye Disease Study. In contrast, vitamin E for 6 years had no effect on the incidence of age-related macular degeneration in smokers in the ATBC trial. The development of cataracts was not prevented by an antioxidant regiment including vitamin E in another study.

  1. VITAMIN A

Vitamin A and its precursor, beta carotene, are lipid-soluble vitamins that affect vision, cell growth, and differentiation by interacting with retinoic acid receptors to control gene expression. Both vitamin A and beta carotene have antioxidant properties. The recommended daily allowance of vitamin A is 5000 IU (1.5 mg)/day; intake of 10,000 IU/day is considered safe. Vitamin A is the most toxic of the lipid-soluble vitamins, and both acute toxicity and chronic toxicity are seen. Acute toxicity requires the ingestion of large quantities substantially greater than 200,000 IU. Chronic toxicity occurs with the ingestion of 50,000 IU/day for > 3 mo. Symptoms of chronic toxicity include hair loss, mouth sores, nausea and vomiting, dry skin, hepatomegaly, and increased intracranial pressure, which can result in headaches and altered mental status. Vitamin A consumption in the 10,000 IU/day range may result in an elevated risk of hip fracture in postmenopausal women. This may be due in part to increased production of parathyroid hormone with resultant hypercalcemia. In contrast, the consumption of the provitamin beta carotene is believed to be safe, apart from causing yellowing of the skin, because its conversion to vitamin A is regulated. As a result of these safety issues, most studies use beta carotene instead of vitamin A.

Despite benefits seen in observational studies of vitamin A or beta carotene supplements, experimental studies provide no evidence of benefit for and potential harm in smokers, former smokers, and postmenopausal women. In observational studies, higher intake of fruits and vegetables containing beta carotene was associated with lower risks of cancer and cardiovascular disease. These benefits were not confirmed, however, by randomized trials of beta carotene for preventive effects with respect to cancer and cardiovascular disease. Finnish male smokers treated with beta carotene, as part of the ATBC study, had no decrease in cancer at the major sites and instead had an increase in the incidence of lung, prostate, and stomach cancers. The finding of a possible link to increased risk of lung cancer was supported by the Beta Carotene and Retinol Efficacy trial, which treated smokers, former smokers, and workers exposed to asbestos with vitamin A and beta carotene for 4 years. This study found no change in the incidence of cancer at other sites. The Physician's Health Study found no impact of beta carotene on the incidence of cancer, including lung cancer, during 12 years of treatment. In the Women's Health Study, women treated with beta carotene for ~2 years and then monitored for 2 years had no change in the incidence of cancer. With regard to cardiovascular disease, the ATBC study, Physician's Health Study, the Beta Carotene and Retinol Efficacy trial, and Women's Health Study found no effect of beta carotene on cardiovascular outcomes such as myocardial infarction or stoke. Subgroup analysis of the ATBC trial found no effect of beta carotene in the prevention of myocardial infarction in either primary or secondary prevention. Also, results from the HDL-Atherosclerosis Study suggest that antioxidant cocktails including beta carotene could be harmful to patients with normal LDL and low HDL levels treated with niacin and simvastatin: The

P.470


use of the antioxidants blunted the effects of niacin and simvastatin on raising HDL, reducing progression of atherosclerosis, and reducing cardiovascular events.

In patients with preexisting age-related macular degeneration, a combination of antioxidants including beta carotene decreased progression to advanced macular degeneration in the Age-Related Eye Disease Study. In contrast, beta carotene for 6 years had no effect on the incidence of age-related macular degeneration over 6 years in the smokers studied in the ATBC trial.

  1. VITAMIN C

Vitamin C is water-soluble vitamin that is involved in multiple oxidation-reduction reactions in vivo, including the synthesis of collagen. Vitamin C also has antioxidant properties. The recommended daily allowance for vitamin C is 90 mg/day for men and 75 mg/day for women. Supplementation beyond these levels has progressively less effect on the serum levels of vitamin C because both the absorption from the gastrointestinal (GI) tract and excretion via the urine is tightly regulated. Vitamin C has low toxicity, even in large doses. The most common side effects include GI upset, flatulence, and diarrhea. Oxalate kidney stones are also a concern as a result of the metabolism of vitamin C to oxalate. Vitamin C also impairs tests measuring glucose in blood and urine. There is a theoretical concern that supplementation with 500 mg/day of vitamin C could lead to oxidative damage to DNA because levels of 8-oxoadenine, a form of adenine produced by oxidative damage, are increased in patients taking vitamin C daily for 6 weeks.

There is no compelling evidence that vitamin C prevents or retards cardiovascular disease or prevents cancer. However, in patients with precancerous lesions of the stomach, the rate of progression to stomach cancer was lower in those given vitamin C.

Vitamin C may be helpful in preventing progression to advanced macular degeneration and in improving appearance in patients with photodamage. Vitamin C was part of the combination of antioxidants that decreased progression to advanced macular degeneration in the Age-Related Eye Disease Study. Topical vitamin C improved appearance and the synthesis of new collagen in patients with photodamage when applied topically.

  1. ALPHA-LIPOIC ACID

Alpha-lipoic acid is considered to be a potent antioxidant because it can oxidize and regenerate other antioxidants such as vitamin E and glutathione. Studies have suggested that it may be helpful in treating diabetic neuropathy and have a role in retarding the progression of neurodegenerative diseases. Alpha-lipoic acid is not recommended, however, before further studies.

LIMITED EFFICACY OF ANTIOXIDANTS & THE ANTIOXIDANT THEORY OF AGING

How should the largely negative results of randomized studies of the antioxidant vitamins be interpreted? Some have suggested that these findings draw into question the oxidative damage theory of aging, as does the observation that transgenic mice that overproduce CuZn superoxide dismutase do not have any increase in life span. Others have pointed out that the negative results could be due to reasons other than the role of oxidative damage in aging. For example, dose finding studies have not been performed to determine optimal dosages. Also, the antioxidants studied may be unable to reach adequate levels in the proper anatomic or cellular locations. One study using vitamin E found increased serum levels of serum vitamin E in patients taking increasing doses of the vitamin, but the increased serum levels did not translate into changes in measures of lipid peroxidation as a measure of membrane oxidative damage. This study questions both the dosages of vitamin E used in existing studies and the appropriateness of using vitamin E as an antioxidant in patients eating a standard American diet. Finally, it is unclear when during the life course antioxidants would be most effective. Most animal studies treated animals for their entire lives, whereas clinical studies used antioxidants for limited periods of time, generally in adult patients. Interest in newer antioxidants, such as the catalase/superoxide dismutase mimetics, will it is hoped lead to future studies designed to address both clinical concerns as well as these more practical concerns.

Age-Related Eye Disease Study Research Group: A randomized, placebo-controlled, clinic trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS reportno. 8. Arch Ophthalmol 2001;119:1417. [PMID: 11594942]

Brown BG et al: Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. NEngl J Med 2001;345:1583. [PMID: 11757504]

Guarente L, Kenyon C: Genetic pathways that regulate ageing in model organisms. Nature 2000;408:255. [PMID: 11089983]

Huang TT et al: Ubiquitous overexpression of CuZn superoxide dismutase does not extend life span in mice. J Gerontol A Biol Med Sci 2000;55:B5. [PMID: 10719757]

Meagher EA et al: Effects of vitamin E on lipid peroxidation in healthy persons. JAMA 2001;285:1178. [PMID: 11752359]

Willett WC, Stampfer MJ: Clinical practice. What vitamins should I be taking, doctor? N Engl J Med 2001;345:1819. [PMID: 11752359]

Yu BP: Approaches to anti-aging intervention: the promises and the uncertainties. Mech Ageing Dev 1999;111:73. [PMID: 10656527]

P.471

 

Growth Hormone

Growth hormone secretion reaches its maximum during the growth spurt accompanying puberty before beginning a steady decline with age in both men and women. Much of this decline is due to a selective reduction in the nocturnal pulsatile secretion of growth hormone. Some of the changes associated with aging are reminiscent of those seen in adult patients with frank growth hormone deficiency, such as reduction in lean body mass, increase in body fat (especially abdominal obesity), decrease in muscular strength, and difficulty with cognitive functioning. As a result, there has been much interest in supplementing growth hormone in the elderly.

Responses to growth hormone or growth hormone secretagogues as measured by serum insulin-like growth factor (IGF-1) levels, which is made by the liver and muscle in response to growth hormone, persist in the elderly. Most studies have titrated the doses of growth hormone or secretagogues to produce IGF levels in thelow- to mid-normal range seen in young adults. Treatment with growth hormone increases lean body mass, skin thickness, and vertebral bone mineral density and decreases fat mass. These changes were more pronounced in elderly men than in postmenopausal women. Growth hormone-induced increases in muscle mass were not accompanied by increases in physical strength, stamina, or functional status, however. Effects of exogenous growth hormone on cognition and memory have not been well studied. Short-term use of growth hormone or secretagogues improves sleep.

Side effects of growth hormone include fluid retention, arthralgias, glucose intolerance, headache, and carpal tunnel syndrome. Growth hormone treatment is associated with 2 additional risks. The first is a possible increase in cancer related to the cell growth stimulant properties of IGF-1. The second relates to emerging evidence that growth hormone and IGF-1 signaling shorten life span rather than prolong it. In both worms and fruit flies, increased activity of IGF-1 like signaling pathways shortens life span. Mice deficient in growth hormone live longer than those with normal growth hormone levels, and treatment with supplemental growth hormone in adulthood has led to premature aging. Also, mice treated with caloric restriction not only live longer but also have lower serum IGF-1 levels than normally fed control mice. In a study of Paris policemen, those with physiologically high growth hormone levels died at a higher rate than those with growth hormone in the lower third of the normal range. In summary, the limited benefits of growth hormone, its high cost, and potential long-term risks weigh against the use of growth hormone in the elderly.

Anawalt BD, Merriam GR: Neuroendocrine aging in men andropause and somatopause. Endocrinol Metab Clin North Am 2001;30:647. [PMID: 11571935]

Khorram O: Use of growth hormone and growth hormone secretagogues in aging: help or harm. Clin Obstet Gynecol 2001;44: 893. [PMID: 11600869]

Hormone Replacement

  1. TESTOSTERONE

In men, testosterone levels peak during late adolescence then decrease by roughly 0.5-1% per year. Hypogonadism is present in ≤ 10% of men aged 50-69 years and in ≤ 30% of men 70 years of age and older. In parallel with the declines in testosterone levels, aging men experience decreases in muscle mass and strength, bone mass, sexual interest and potency, and cognitive function and increases in fat mass. It is unknown, however, whether these changes can be attributed to declines in testosterone levels.

Several studies have reported on the supplementation of testosterone in men with low testosterone levels via either injections or a scrotal patch (Table 45-1). Most studies have shown increases in lean body mass and bone mineral density and decreases in fat mass and bone mineral density. Accompanying the increase in muscle mass has been an increase in either upper or lower extremity strength. However, only 1 experimental study has shown an increase in functioning with testosterone replacement. Sexual function has shown mixed results with supplementation, and men with lower initial testosterone levels tend to have the most significant improvements. Three studies have suggested small improvements in cognitive function in middle-aged men receiving testosterone.

Concerns have been raised regarding potential effects of supplementation on prostate disease, cardiovascular risk, and erythrocytosis. Testosterone supplementation does not worsen prostatic hypertrophy, and it is unknown whether it increases risk of prostate cancer. Administration of testosterone leads to no change or slight decreases in total cholesterol and LDL cholesterol combined with no change or slight decreases in HDL cholesterol. Testosterone therapy decreases angina, causes coronary artery dilation, and decreases ST depression during exercise stress testing. Erythrocytosis can be seen in up to 25% of patients receiving treatment. This can be easily managed by either decreasing the dose of testosterone given or using phlebotomy.

Hypogonadism can be detected by the Androgen Deficiency in Aging Males Questionnaire followed by direct measurement of a bioavailable testosterone. This questionnaire also identifies patients with depression,

P.472


which should be treated before replacement therapy is considered.

Table 45-1. Hormone replacement & its actions.

Hormone

Actions

Evidence

Testosterone

   Males

Increase lean body mass

++

Decrease fat mass

++

Increase bone mineral density

++

Increase sexual functioning

+

   Females

Increase libido

+

Increase bone mineral density

+/-

Increase muscle mass

+/-

Hormone replacement therapy with estrogen

   Females

Decrease vasomotor symptoms

++

Prevent osteoporosis

++

Prevent coronary artery disease

-

Prevent dementia

+/-

Prevent colon cancer

+/-

Improve mental health

-

Dehydroepiandrosterone

   Females

Increase sense of well-being

+

Increase bone mineral density

+

Increase sexual interest (those older than 70)

+

Decrease skin pigmentation

+

Decrease skin sebum production

+

   Males

Increase sense of well-being

+

Increase strength

+

Increase skin thickness

+

Increase skin hydration

+

Pregnenolone

Increase memory

-

Improve sleep

+

Testosterone levels decline from age 20 to menopause in females. Levels then stay constant through the menopausal transition and then increase after menopause. Estrogen therapy increases sex hormone-binding globulin and, therefore, decreases free testosterone levels. Testosterone replacement therapy in menopausal women improves libido and increases bone mineral density and muscle mass (see Table 45-1). Further studies are required to determine the role of testosterone in women as an anti-aging hormone.

Anawalt BD, Merriam GR: Neuroendocrine aging in men andropause and somatopause. Endocrinol Metab Clin North Am 2001;30:647. [PMID: 11571935]

Hermann M, Berger P: Hormonal changes in aging men: a therapeutic indication? Exp Gerontol 2001;36:1075. [PMID: 11404052]

Morley JE, Perry HM: Androgen deficiency in aging men: role of testosterone replacement therapy. J Lab Clin Med 2000;135: 370. [PMID: 10811051]

Morley JE, Unterman TG: Hormonal fountains of youth. J Lab Clin Med 2000;135:364. [PMID: 10811049]

Morley JE et al: Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism 2000;49:1239. [PMID: 11016912]

  1. HORMONE REPLACEMENT THERAPY WITH ESTROGEN/PROGESTIN

The changes in estrogen that occur with menopause are well known, and hormone replacement therapy (HRT) to address these changes has been widely used. Large-scale randomized trials demonstrate, however, that HRT leads to increased rates of coronary events, stroke, pulmonary embolism, and breast cancer that are not outweighed by decreased rates of hip fracture and colon cancer. Moreover, HRT did not make asymptomatic or mildly symptomatic women feel better or improve cognition.

Vasomotor symptoms are relieved by HRT, most often with < 1 year of therapy. In women with bothersome vasomotor symptoms, estrogen may be started at a low dose, increased until symptoms are relieved, and tapered every 6 mo until they can be discontinued. In a 50-year-old woman, this strategy will lead to an extra serious adverse event for every 1000 women

P.473


treated for 1 year. Vasomotor symptoms may also be treated with clonidine, selective serotonin reuptake inhibitors (SSRIs), vitamin E, or phytoestrogens, but these approaches are not as effective as estrogen.

Grady D: Postmenopausal hormones therapy for symptoms only. N Engl J Med 2003;348:1835. [PMID: 12642636]

Hays J et al: Effects of estrogen plus progestin on health-related quality of life. N Engl J Med 2003;348:1893. [PMID: 12642637]

Hlatky MA et al: Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy: results from the Heart and Estrogen/Progestin Replacement Study (HERS) trial. JAMA 2002;287:591. [PMID: 11829697]

Manson JE, Martin KA: Clinical practice. Postmenopausal hormone-replacement therapy. N Engl J Med 2001;345:34. [PMID: 11439947]

New England Journal of Medicine: http://www.content.nejm.org/cgi/reprint/NEJMp030038v1.pdf.

New England Journal of Medicine: http://www.content.nejm.org/cgi/reprint/NEJMoa030311v1.pdf.

  1. DEHYDROEPIANDROSTERONE

Dehydroepiandrosterone (DHEA) and its sulfated derivative, DHEAS, are synthesized by the adrenal cortex and are the most abundant steroid hormones in young adults. After age 30, serum levels of DHEA declines ~2% per year. As a result, in 80-year-olds, DHEA levels are 10-20% of levels in young adults. Low levels of DHEA have been correlated with an increased risk of breast cancer in premenopausal women, an increase in cardiovascular disease and mortality in elderly men, a lower bone mineral density in perimenopausal women, a higher likelihood of depressed mood in elderly women, and a higher likelihood of cognitive decline in both sexes.

Several short-term studies in older persons have supplemented DHEA levels to those seen in young adults with 50-100 mg/day doses (see Table 45-1). In women, DHEA supplementation led to an improved sense of well-being, increased bone mineral density, and, in women older than 70, increased sexual interest and satisfaction. In men, DHEA supplementation has led to improved well-being, increased strength, and decreased fat mass. In both sexes, DHEA supplementation improved skin thickness, hydration, sebum production, and pigmentation. Adverse effects on lipid profile and glycemic control were not seen.

In conclusion, short-term DHEA supplementation appears safe, but the effects have been modest. Routine supplementation is not recommended until long-term studies have demonstrated the safety and benefits of DHEA supplementation.

Gurnell EM, Chatterjee VK: Dehydroepiandrosterone replacement therapy. Eur J Endocrinol 2001;145:103. [PMID: 11454504]

  1. PREGNENOLONE

Pregnenolone is the precursor of all steroid hormones. In the 1940s, pregnenolone was shown to increase attention and decrease arthritic pain. In mice, pregnenolone is the most potent known memory enhancer. However, pregnenolone fails to improve memory in humans, but it does enhance sleep in humans (see Table 45-1). Currently, there is no evidence to support the use of pregnenolone as an anti-aging hormone.

Vallee M et al: Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging. Brain Res Brain Res Rev 2001;37:301. [PMID: 11744095]

COMPLEMENTARY & ALTERNATIVE MEDICINE

General Considerations

Complementary and alternative therapies have been defined as therapies that either fall outside of the conventional thought and approach to a given disease or that are not taught in U.S. medical schools or widely provided by U.S. hospitals. The National Center for Complementary and Alternative Medicine divides these therapies into 5 major domains.

  1. Alternative medical systems, which consist of complete systems of theory and practice that are completely independent of a biomedical approach (eg, traditional oriental medicine, homeopathy, naturopathic medicine, and urvedic medicine).
  2. Mind-body interventions, which target the potential for the mind to affect the body's basic function and reaction to disease (eg, meditation, prayer and mental healing, hypnosis).
  3. Biological therapies, which consist of using herbs, dietary manipulation, supplements, or mixtures prepared from biological sources to enhance health or treat disease (eg, herbal remedies such as ginseng and ginkgo, supplements such as glucosamine or vitamin E, and mixtures such as shark cartilage).
  4. Manipulative and body-based systems in which therapies such as massage, chiropractic manipulation, or osteopathic manipulation use a relationship between form and function to treat disease.
  5. Energy therapies, which modify internal sources or flow of energy or alternately apply external sources of energy to modify body function or health (eg, use of magnets or electromagnetic fields, which involve external sources of energy, or the practice of Qi Gong or therapeutic touch,

P.474


which involve manipulating the internal balance or flow of energy).

Barrett B: Complementary and alternative medicine: what's it all about? West Med J 2001;100:20. [PMID: 11816777]

National Institutes of Health, National Center for Complementary and Alternative Medicine: http://www.nccam.nih.gov

Prevalence of Use

Among seniors, the most commonly used complementary and alternative therapies are chiropractic therapy, herbal remedies, relaxation techniques, and high dose or megavitamins.

Patients using complementary and alternative therapies often do not report their use to their physicians. Physicians should ask specifically whether patients are using them or seeing practitioners. Some therapies such as herbs may have side effects or may interact with conventional therapies. Asking about interest in and use of complementary and alternative therapies may also strengthen the physician-patient relationship and facilitate exploration of a patient's needs and expectations.

Eisenberg DM et al: Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998;280:1569. [PMID: 9820257]

Eisenberg DM et al: Perceptions about complementary therapies relative to conventional therapies among adults who use both: results from a national survey. Ann Intern Med 2001;135: 344. [PMID: 11529698]

Foster DF et al: Alternative medicine use in older Americans. J Am Geriatr Soc 2000;48:1560. [PMID: 11129743]

Pappas S, Perlman A: Complementary and alternative medicine. The importance of doctor-patient communication. Med Clin North Am 2002;86:1. [PMID: 11795082]

Wolsko PM et al: Insurance coverage, medical conditions, and visits to alternative medicine providers: results of a national survey. Arch Intern Med 2002;162:281. [PMID: 11822920]

Legal Aspects of Use

Physicians looking to incorporate complementary and alternative therapies into their practice should consider the potential legal and malpractice implications, which may require consultation with legal or risk management experts.

Each state regulates the practice of medicine, allied health professions, and complementary and alternative therapy practitioners differently. Practitioners of complementary and alternative therapies may need to be formally licensed to be able to practice their discipline, may need to be certified not to practice but instead to use a specific title, or may need to register their name and location of practice with the state before opening a practice. Additionally, each state limits the scope of practice for practitioners. Usually, medical doctors are given unlimited authority to diagnose and treat medical illnesses. The scope of practice for complementary and alternative therapy providers is usually more limited. These limits can take the form of prohibitions against the practice of medicine or surgery or against the practice of services granted legally to other disciplines. For example, state statues may bar an acupuncturist from performing massage or providing psychological counseling because these abilities have been granted to licensed massage therapists and psychologists, respectively. Before contacting or referring patients, it is important that physicians learn about relevant state statutes to ensure that providers are appropriately licensed, certified, or registered and adhere to their appropriate scope of practice.

Malpractice consists of care that deviates from the current standard of care, lacks professional skill, and results in harm to a patient. Because all complementary and alternative therapies lie outside widely accepted conventional medical therapies, the integration of these therapies into medical practice could risk malpractice. Physicians can mitigate this risk by choosing therapies that have supporting data presented in peer-reviewed journals, especially mainstream medical journals, using therapies in an adjuvant manner along with traditional treatments for the same condition, initiating therapy only after obtaining informed consent from the patient wherein the patient has chosen to assume the risk of a given treatment, or using therapies only after standard treatments have failed or proved to be intolerable. Referring patients to practitioners of complementary and alternative therapies instead can also expose physicians to malpractice liability in a few specific situations. These situations include referring a patient for a condition for which a conventional therapy would be more appropriate, referring a patient to a provider whose record of lack of skill or judgment deems him or her a “known incompetent,” or referring a patient to a practitioner who is connected to the physician within a joint practice, such as working for the same multispecialty practice, clinic, or health maintenance organization.

Cohen MH: Legal issues in complementary and integrative medicine. Med Clin North Am 2002;86:185. [PMID: 11799969]

Massage/Chiropractic

Massage therapy and chiropractic therapy are the most widely used complementary and alternative therapies in the United States. Swedish massage, the Trager method, and reflexology are the most commonly used types of massage. Swedish massage involves using smooth stroking and kneading movements often with the use of a massage oils. The Trager method involves holding the joints of the arms and legs in specific positions

P.475


and gently rocking the joint. Reflexology is based on an alternate medical system in which parts of the body are represented by points on the feet, hands, and ears. Manipulation of these points transmits energy to the appropriate body part and can affect its function. Often massage therapy involves the use of multiple techniques tailored to a patient's symptoms.

Studies have consistently found benefit for massage therapy in the treatment of pain. Massage has been evaluated for the treatment of back pain, fibromyalgia, and headaches with positive results. Massage has also been found to be of benefit in the palliative care of terminal cancer pain. The improvements include decreases in pain, anxiety, and depression along with improved sleep. Massage has also been found to be a potentially helpful adjunct to conventional therapies for HIV and breast cancer. These studies looked at levels of anxiety and depression as well as markers of physiological stress such as cortisol and catecholamines. These later studies did not address clinical outcomes such as survival, alteration in responses to treatments, rates of hospitalization, or physical functioning. Hence, it is unclear whether these improvements have any impact on patients beyond improvements in psychological well-being.

Chiropractic medicine is a manipulation-based practice, which has spinal manipulation as the core clinical activity. Originally, chiropractic was envisioned to be an alternate medical system based on the tenet that neurological dysfunction at the spine was the cause of most disease and that spinal manipulation could correct the dysfunction. Over time, the field has moved away from this tenet and redefined its practice. Some within chiropractic have sought to incorporate other alternative therapies along with exercise, nutrition, and smoking cessation education to create a primary care practice. Others have viewed chiropractic as a limited medical specialty such as dentistry or podiatry. Most patients seem to view chiropractic in the latter sense as the vast majority of patients seek chiropractic care for back, neck, or head pain. Chiropractic treatment involves a history and physical exam, with the exam focusing on joint, muscle, and soft tissues. Plain x-ray films can also be an important part of the evaluation. On the basis of history, exam, and x-ray findings, the chiropractor determines whether the patient's condition will be amenable to chiropractic treatment and also plans a treatment regimen. Treatment involves spinal manipulation with or without adjunctive treatments such as heat, cold, electricity, and counseling about exercise, fitness, nutrition, weight loss, and relaxation techniques.

Chiropractic treatment has been studied for back and neck pain in > 50 individual studies. Several systematic reviews have found sufficient evidence to support the beneficial use of chiropractic therapy for acute and chronic back pain but not for neck pain or sciatica. Chiropractic treatment has not been shown to be effective treatment of nonmusculoskeletal illnesses such as hypertension, dysmenorrhea, and asthma.

Common side effects of manipulation include localized pain, headache, and fatigue. More serious side effects include cauda equina syndrome from lumbar manipulation or stroke resulting from vertebral artery dissection have been reported. The risk of serious complications from lumbar manipulation have been estimated to be 1 in 100 million manipulations. The risk of stroke from cervical manipulation is low, but higher than lumbar manipulation, estimated at between 1 in 400,000 to 2 million manipulations.

Field T: Massage therapy. Med Clin North Am 2002;86:163. [PMID: 11795087]

Meeker WC, Haldeman S: Chiropractic: a profession at the crossroads of mainstream and alternative medicine. Ann Intern Med 2002;163:216. [PMID: 118277498]

Acupuncture

Acupuncture is a popular alternative therapy that involves the use of needles to stimulate points on the surface of the body. Acupuncture derives from an alternate medical system that holds that a vital energy called Qi circulates through the body along 12 pathways known as meridians. Alterations in the flow of Qi result in illness. Meridians have internal and surface projections, and stimulation of appropriate points on the surface restores the proper flow and restores health. Practitioners assess patients using either a more traditional Chinese medicine approach involving examination of the tongue, pulse, abdomen, and acupuncture points or a more Western approach involving a medical history and exam. From the evaluation, an acupuncture regimen is selected. Treatments consist of weekly to biweekly sessions involving the insertion of up to 15 needles at selected points for times ranging from several seconds to 30 min. The needles are solid disposable stainless steel and are ~37 gauge in size. Once inserted, the needles can be stimulated manually or with electricity, heat, or burning herbs.

Acupuncture has been shown to be efficacious in the treatment of postoperative and dental pain and for the management of nausea and vomiting resulting from a wide variety of causes. Acupuncture has also been used to treat chronic pain, osteoarthritis, headache, and back pain, but its efficacy in treating these conditions has not been established. A systematic review of the use of acupuncture in the treatment

P.476


of chronic pain found insufficient evidence of benefit, and one randomized trial found acupuncture to have no benefit in the treatment of chronic back pain. Reviews of the evidence supporting the use of acupuncture for back pain have had conflicting results.

The 2 most common adverse effects are pain from needles and bleeding or hematoma. Other minor but common adverse effects are fatigue, nausea, and dizziness. The most serious, but rare, adverse events have been pneumothorax from needle insertion on the thorax and needle fracture requiring surgical removal. Patients should be cautioned to ensure that practitioners count needles before and after a session, use only new needles, and only insert needles to recumbent patients to minimize harm from fainting.

Cherkin DC et al: Randomized trial comparing traditional Chinese medical acupuncture, therapeutic massage, and self-care education for chronic low back pain. Arch Intern Med 2001; 161:1081. [PMID: 11322842]

Ernst E: Complementary therapies in palliative cancer care. Cancer 2001;91:2181. [PMID: 11777363]

Ernst E, White AR: Prospective studies of the safety of acupuncture: a systematic review. Am J Med 2001;110:481. [PMID: 11331060]

Ezzo J et al: Is acupuncture effective for the treatment of chronic pain? A systematic review. Pain 2000;86:217. [PMID: 10812251]

Kotani N et al: Preoperative intradermal acupuncture reduces postoperative pain, nausea and vomiting, analgesic requirement, and sympathoadrenal responses. Anesthesiology 2001;95: 349. [PMID: 11506105]

Herbs/Supplements

Herbs are the second most common complementary or alternative therapy used by older persons. In contrast to pharmaceuticals, the production, marketing, and sale of herbs and supplements is regulated only by the Dietary Supplement Health and Education Act, which does not regulate the purity, quality, or standardization of preparations. As a result, active ingredients can vary among manufacturers and even from lot to lot for a given manufacturer. Patients and physicians should select products made by larger, more reputable companies, which specify the amounts of ingredients and standardization of the active ingredients to an accepted standard.

Ernst E, Pittler MH: Herbal medicine. Med Clin North Am 2002; 86:149. [PMID: 10793599]

Massey PB: Dietary supplements. Med Clin North Am 2002; 86:127.

http://www.home.mdconsult.com/das/book/17756751/view/862 (Complete German Commission E Monograph on herbal medications.)

  1. GINKGO

Ginkgo is the top-selling herbal medicine in the United States. The clinical use of ginkgo can be traced to Chinese medicine more than 2000 years ago. In Germany, a standardized ginkgo extract, Egb 761, has been approved for the treatment of intermittent claudication and cognitive impairment. Gingko extracts are prepared from ginkgo leaves and contain several active constituents, such as ginkgolides, bilobides, and flavone glycosides. Good-quality extracts contain 22-27% flavone glycosides and 5-7% terpin lactones, which include the ginkgolides and bilobides. The daily dosage used in clinical trials ranged from 120-320 mg/day; the most common dose is 40 mg 3 times/day (Table 45-2). Common side effects include headache, GI upset, and nausea, all of which are mild. There are also concerns about antiplatelet and warfarin-like effects, so patients should be cautioned about the potential for bleeding and gingko should be avoided in patients taking anticoagulants.

Ginkgo is clinically used for dementia, memory impairment, tinnitus, and intermittent claudication (see Table 45-2). A qualitative systemic review and a meta-analysis have addressed the effectiveness of ginkgo in the treatment of dementia and found positive results. The pooled effect size on cognitive function is comparable to that of donepezil. The pooled studies did not address whether ginkgo is useful in the treatment of other manifestations of dementia such as global functional status or problem behaviors. Ginkgo has also been studied for the treatment of memory impairment, or cerebral insufficiency. These terms encompass memory impairment associated with aging and probably clinically reflect mild cognitive impairment or age-related declines in memory. The studies of ginkgo for these indications are overall weak with regard to methodology, but a qualitative systemic review and a meta-analysis, including only the better studies, have found evidence of benefit. A qualitative systemic review of the studies examining the effectiveness of ginkgo for tinnitus found that only 1 of 5 studies used sound methodology. This study revealed that ginkgo produced a small but statistically significant reduction in the perception of tinnitus. Finally, a meta-analysis that included 8 randomized controlled trials of gingko for intermittent claudication found a statistically relevant increase in pain-free walking distance of 34 m compared with placebo. The results for gingko are similar to those for pentoxifylline but less than those seen with walking exercises. Hence, there is reasonable evidence to support the use of gingko for dementia or intermittent claudication and weaker evidence to support its use for memory impairment in nondemented patients and for tinnitus.

Ernst E: The risk-benefit profile of commonly used herbal therapies: ginkgo, St. John's wort, ginseng, Echinacea, saw palmetto, and kava. Ann Intern Med 2002;136:42. [PMID: 11777363]

P.477

 

Massey PB: Dietary supplements. Med Clin North Am 2002;86: 127. [PMID: 11795085]

Table 45-2. Herbal medicines: dose & use.

Herb/supplement

Dose

Use

Evidence

Gingko

40 mg tid

Dementia

++

Cerebral/insufficiency

+

Tinnitus

+

Claudication

++

St. John's wort

300 mg tid

Depression

-

Glucosamine

1500-2000 mg qd or divided bid

OA

++

Chondroitin

1000-1500 mg qd or divided bid

OA

++

S-adenosyl methionine

1600 mg bid to qid

Depression

+

OA

++

Saw palmetto

320 mg divided bid to tid

Benign prostatic hypertrophy

+/-

Shark cartilage

750 mg qd to 1 g/kg tid

Cancer treatment

-

Cancer prevention

Valerian root

300-900 mg 30-60 min before bedtime

Insomnia

+/-

Ginseng

200-600 mg qd or divided bid

Physical performance

+/-

Psychomotor performance

+/-

Immune system function

+/-

Garlic

600-900 mg qd

Hypercholesterolemia

+

Hypertension

-

Cancer prevention

+/-

Ginger

0.5-1.0 g qd

Vertigo

+

Motion sickness

+

Postoperative nausea

+/-

OA

+

tid, 3 times/day; bid, 2 times/day; qd, every day; qid, 4 times/day; OA, osteoarthritis.

  1. ST. JOHN' WORT

St. John's wort is widely used in Europe to treat depression. Preparations include both hypericin and hyperforin, which are believed to be at least 2 of the active ingredients. Good-quality extracts are usually standardized to a 0.3% hypericin content. St. John's wort is believed to work through selective inhibition of the reuptake of serotonin, dopamine, and norepinephrine in thebrain. The dose used in most clinical trials is 900mg/day (300 mg 3 times/day); effects take at least 2-3 weeks to appear (see Table 45-2). Side effects are mild; nausea, photosensitivity, and headache are most common. Given the role of serotonin, dopamine, and norepinephrine reuptake in the action of St. John's wort, patients should not take tricyclic antidepressants, SSRIs, or monoamine oxidase inhibitors while taking St. John's wort. St. John's wort activates P450 enzymes, so care should be used in treating patients also taking warfarin, digoxin, or other drugs with hepatic metabolism.

Several meta-analyses and qualitative systemic reviews have reported on the use of St. John's wort for either first-time or recurrent depression. These studies have found St. John's wort to be superior to placebo and comparable to tricyclic antidepressants. These studies also included 2 trials that compared St. John's wort with fluoxetine and sertraline and found roughly equal effectiveness. Early studies had substantial methodological flaws, however, and 2 multicenter randomized controlled trials found no effect of St. John's wort in patients with significant depression. Until more data are available, St. John's wort may be used cautiously in the treatment of mild depression but should not be used for moderate to severe depression, which should be treated with pharmacological or cognitive-behavioral interventions of proven efficacy (see Table 45-2).

Ernst E: The risk-benefit profile of commonly used herbal therapies: ginkgo, St. John's wort, ginseng, echinacea, saw palmetto, and kava. Ann Intern Med 2002;136:42. [PMID: 11777363]

Hypericum Depression Trial Study Group: Effect of Hypericum perforatum (St. John's wort) in major depressive disorder: a randomized controlled trial. JAMA 2002;287:1807. [PMID: 11939866]

Massey PB: Dietary supplements. Med Clin North Am 2002; 86:127. [PMID: 11795086]

Shelton RC et al: Effectiveness of St. John's wort in major depression: a randomized controlled trial. JAMA 2001;285:1978. [PMID: 11308434]

P.478

 

  1. GLUCOSAMINE/CHONDROITIN

Glucosamine and chondroitin are commonly used for the treatment of osteoarthritis (see Table 45-2). Both glucosamine and chondroitin are components of proteoglycans found in articular cartilage and synovial fluid. How oral glucosamine or chondroitin work physiologically is not clear, and there is little evidence that patients with osteoarthritis are deficient in these substances or that oral glucosamine or chondroitin is selectively taken to joints. Glucosamine is usually taken at dosages of 1500-2000 mg/day every day or divided twice daily (see Table 45-2). Chondroitin sulfate is usually taken at 1000-1500 mg/day every day or divided twice daily. Combination pills containing both glucosamine and chondroitin are also available. Glucosamine alone tends to be most inexpensive of the preparations. Studies have found these substances to be very safe, with no more side effects than placebo.

Meta-analyses of early clinical trials of glucosamine and chondroitin have shown both to be superior to placebo in improving pain and disability (see Table 45-2). A randomized trial provides further evidence of efficacy: Patients with osteoarthritis of the knee who were treated with glucosamine and chondroitin had less pain, disability, and joint space narrowing after 3 years. Small studies have shown that glucosamine and chondroitin may also improve pain resulting from osteoarthritis of the TMJ. It is unknown whether glucosamine and chondroitin improve symptoms of osteoarthritis at other sites such as the hand or hip.

Ernst E: Complementary and alternative medicine for pain management in rheumatic disease. Curr Opin Rheumatol 2002; 14:58. [PMID: 11790998]

Reginster JY et al: Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001;357:251. [PMID: 11214126]

Thie NM et al: Evaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trial. J Rheumatol 2001;28:1347. [PMID: 11409130]

  1. S-ADENOSYLMETHIONINE

S-adenosylmethionine (SAMe) is used to treat osteoarthritis and depression. The oral dose of SAMe is 400-1600 mg/day. Most studies use a 1600 mg dose divided 2-4 times daily (see Table 45-2). This dosage costs ≥ $120/mo. Side effects are rare and include mild GI upset, headache, dizziness, insomnia, hypersomnia, and anxiety. Mania has developed in some patients treated for depression.

In studies of patients with depression (see Table 45-2), SAMe consistently leads to significant but modest improvements compared with placebo. Studies comparing SAMe and tricyclic antidepressants have found both to be roughly equivalent, although the doses of tricyclic antidepressant used or the follow-up period were often inadequate to see effects of the tricyclic agent. No studies compared SAMe with newer antidepressants such as SSRIs. More studies are needed before SAMe can be recommended for the treatment of moderate to severe depression.

In the treatment of osteoarthritis, SAMe is equivalent to NSAIDs in pain relief except that SAMe may require several weeks of treatment for full effect. SAMe has a lower incidence of side effects than NSAIDs, and patients rate its tolerability higher. SAMe has not been compared with acetaminophen in terms of pain control or side effects.

SAMe has also been studied for use in patients with cirrhosis or cholestasis and has proven beneficial. For example, in cirrhosis a significant decrease in death or need for a liver transplant was seen in patients with alcoholic cirrhosis treated for 2 years.

Echols JC et al: SAMe (S-adenosylmethionine). Harv Rev Psychiatry 2000;8:84. [PMID: 10902097]

Massey PB: Dietary supplements. Med Clin North Am 2002;86: 127. [PMID: 11795086]

  1. SAW PALMETTO

Saw palmetto is made from the berries of the American dwarf palm and is commonly used to treat symptoms of benign prostatic hypertrophy (BPH). In western Europe, saw palmetto is used much more commonly than finasteride or α-blockers for BPH. Saw palmetto ingredients inhibit the 5α-reductase enzyme that converts testosterone to 5-dehydrotestosterone and may also inhibit prostaglandin synthesis and growth factor actions. Saw palmetto is usually given at a dose of 320 mg divided either 2 or 3 times daily (see Table 45-2). Side effects are infrequent and mild and include headache, diarrhea, constipation, nausea, and decreased libido.

Saw palmetto was superior to placebo in reducing nocturia and increasing peak urinary flow in 2 meta-analyses and was equivalent to finasteride in 1 (see Table 45-2). Its overall effect on BPH symptoms has not been determined, however, and its effects relative to α-blockers are unknown. Until more data are available, saw palmetto is appropriate for patients who prefer it to either α-blockers or finasteride.

Ernst E: The risk-benefit profile of commonly used herbal therapies: ginkgo, St. John's wort, ginseng, echinacea, saw palmetto, and kava. Ann Intern Med 2002;136:42. [PMID: 11777363]

Lowe FC: Phytotherapy in the management of benign prostatic hyperplasia. Urology 2001;58:71. [PMID: 11750257]

P.479

 

  1. SHARK CARTILAGE

Shark cartilage is used as an anticancer supplement without compelling supporting evidence. Available preparations often contain capsules with 750 mg of shark cartilage powder with dosing ranging from 750 mg/day to 1 g/kg divided 3 times/day (see Table 45-2). A phase I/II study in patients with advanced cancer found no benefit for shark cartilage (1 g/kg divided 3 times/day) in survival and quality of life. Observed toxicity was low and limited mainly to mild GI upset, nausea, and constipation. Further trials are underway.

Ernst E, Cassileth BR: How useful are unconventional cancer treatments? Eur J Cancer 1999;35:1608. [PMID: 10673970]

Gonzalez RP et al: Shark cartilage as source of antiangiogenic compounds: from basic to clinical research. Biol Pharm Bull 2001;24:1097. [PMID: 11642310]

Hillman JD et al: Treatment of Kaposi sarcoma with oral administration of shark cartilage in a human herpesvirus 8-seropositive, human immunodeficiency virus-seronegative homosexual man. Arch Dermatol 2001;137:1149. [PMID: 11559209]

  1. VALERIAN ROOT

Valerian root is often used as a sleep aid. The active ingredient is not known, but extracts bind directly to γ-aminobenzoic acid (GABA) receptors, enhance the release of GABA, and decrease the reuptake and degradation of GABA. Valerian root can either be consumed as a tea from 3-5 g of dried root with straining after 15 min of brewing or taken as commercial supplements that range in dose from 300-900 mg taken 30-60 min before bedtime (see Table 45-2). Side effects are infrequent and consist of dizziness, headache, and “hangover.” Valerian root appears to have mild impacts on concentration, reaction time, motor skill, and vigilance 1 h after ingestion and essentially no impact the next day. However, the effect on these parameters in older patients is not known. Addiction to valerian root has not been described, but a case report of possible withdrawal symptoms after termination of chronic use, with successful treatment with midazolam, has been published.

The evidence that valerian root helps patients with insomnia is not compelling (see Table 45-2). Three of 9 studies of prolonged continuous use of valerian root showed a tendency toward benefit, but there were inconsistencies among studies. Maximum benefit may require 2-4 weeks of continued use. The 6 studies of intermittent dosing of valerian root were inconclusive.

Assemi M: Herbs affecting the central nervous system: gingko, kava, St. John's wort, and valerian. Clin Obstet Gynecol 2001;44:824. [PMID: 11600863]

Stevinson C, Ernst E: Valerian for insomnia: a systematic review of randomized clinical trials. Sleep Med 2000;1:91. [PMID: 10767649]

  1. GINSENG

Ginseng is among the best selling herbal supplements. It is also one of the herbs with the most reported benefits, including central nervous system effects of increased vigilance, increased concentration, increased sense of well-being, and increased relaxation along with systemic anticancer, antidiabetic, and aphrodisiac effects. There are multiple types of ginseng, and most studies have used Asian ginseng, Panax ginseng. Ginseng is made from dried roots, and among the ingredients of ginseng extracts are > 25 different kinds of ginsenosides as well as panaxans. The usual dosage of ginseng is 200-600 mg of standardized extract either given every day or divided 2 times/day (see Table 45-2).

The incidence of side effects is low, but some can be serious, such as vaginal bleeding or Stevens-Johnson syndrome. Most side effects are less serious and include insomnia, diarrhea, euphoria, headache, mastalgia, and nausea. Interactions between ginseng and warfarin have been reported, so caution should be exercised. High doses of ginseng have also been shown to lower blood glucose levels, so patients should take ginseng with meals to minimize the risks of hypoglycemia. Ginseng abuse syndrome is believed to be due to contaminants in the preparation instead of ginseng itself.

There is insufficient evidence that ginseng improves physical performance, psychomotor performance, and immune function. One study attempted to determine the evidence for the multiple health claims made for ginseng (see Table 45-2). The review found significant methodological issues with most studies and possible publication bias.

Ernst E: The risk-benefit profile of commonly used herbal therapies: ginkgo, St. John's wort, ginseng, echinacea, saw palmetto, and kava. Ann Intern Med 2002;136:42. [PMID: 11777363]

Vogler BK et al: The efficacy of ginseng. A systematic review of randomized clinical trials. Eur J Clin Pharmacol 1999;55: 567. [PMID: 10541774]

  1. GARLIC

Garlic is widely advertised and used in the United States with the aims of lowering cholesterol and blood pressure and preventing cancer. The active ingredient is allicin, and most preparations are standardized to contain 0.6-1.3% allicin. The most widely studied form is the Kwai powder, which contains 1.3% allicin. Studies of this preparation have used doses of 600-900 mg/day (see Table 45-2). Side effects include odor, flatulence, diarrhea, and stomach upset. The most serious, although rare, side effect is increased bleeding, which may be due to reductions in platelet aggregation.

P.480

 

Garlic has been found to be superior to placebo in reducing total cholesterol but not blood pressure (see Table 45-2). The total reduction in cholesterol is 12-25 mg/dL at 3 mo, which is similar to the effect of dietary intervention and less than the effect of statins. None of the underlying studies lasted more than 10 mo, and 1 meta-analysis suggested that the benefit of garlic may not last beyond 6 mo.

Garlic was associated with reduced rates of stomach and colorectal cancer in cohort and case-control studies, but there are no randomized studies of garlic for these indications. The effect of garlic on cancer at other sites has not been studied sufficiently to support any conclusions.

Ackermann RT et al: Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med 2001;161:813. [PMID: 11268223]

Fleischauer AT, Arab L: Garlic and cancer: a critical review of the epidemiologic literature. J Nutr 2001;131:1032S. [PMID: 11238811]

Stevinson C et al: Garlic for treating hypercholesterolemia. A meta-analysis of randomized clinical trials. Ann Intern Med 2000; 133:420. [PMID: 10975959]

  1. GINGER

Ginger has been used in Chinese and Ayurvedic medicine for > 2500 years for the treatment of musculoskeletal pain and GI illnesses. Ginger is prepared from the root of plants in the Zingiberaceae family, which includes the genera Zingiber and Alpinia. Most studies have used extracts from Zingiber officinale, but it is unclear whether extracts from ginger plants in other genera and species would have similar effects. Ginger can be given as powdered root, 0.5-1 g/day (see Table 45-2). Alternately, extracts made from Zingiber and Alpiniaroots are also available, and these have been used 2-3 times/day. Side effects are mild; dyspepsia, heartburn, and nausea are most common.

Ginger has been studied for the prevention of postoperative nausea and motion sickness and the treatment of vertigo and osteoarthritis pain (see Table 45-2). Studies of ginger in the prevention of postoperative nausea have produced mixed results. Small studies found ginger to be effective in reducing vertigo from caloric stimulation and preventing vomiting and sweating from sea sickness. The study of sea sickness found nonstatistically significant reductions in nausea and vertigo as well. Two studies evaluated ginger for the treatment of osteoarthritis pain; the 3-week study found mild to no effect, whereas the 6-week study found significant improvement in pain with more improvement from weeks 2-6 than weeks 0-2. Hence, the effect of ginger on osteoarthritis pain may require several weeks to appear.

Altman RD, Marcussen KC: Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum 2001; 44:2531. [PMID: 11710709]

Bliddal H et al: A randomized, placebo-controlled, cross-over study of ginger extracts and ibuprofen in osteoarthritis. Osteoarthr Cartil 2000;8:9. [PMID: 10607493]

Ernst E, Pittler MH: Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials. Br J Anaesth 2000;84:367. [PMID: 10793599]

Homeopathy

Homeopathy is an alternative medical system based on the vitalistic theory that illness results from imbalances in the patient's vital force. The goal of homeopathy is to use medications to restore the balance and then to rely on the self-healing potential of the body to lead to a cure. The practice relies on 2 tenets: the principle of similars and the principle of dilution. The principle of similars suggests that an effective treatment can come from a diluted form of a substance that causes similar symptoms in a healthy person. The principle of dilution holds that high dilutions of these substances are equally or more effective than more concentrated solutions. Although this latter principle draws most skepticism, it is important to note that most homeopathic remedies are not infinite dilutions but instead contain small but measurable amounts of the active ingredients. A practitioner selects a remedy, after a thorough history and physical exam, by matching symptoms and findings to remedies.

Homeopathic remedies have been shown to be effective. However, studies have been limited by methodological flaws and publication bias. In particular, the studies of better methodological quality were more likely to report negative results. Until rigorous studies have validated the use of specific remedies, it would be prudent to approach their use with caution.

Cucherat M et al: Evidence of clinical efficacy of homeopathy. A meta-analysis of clinical trials. Eur J Clin Pharmacol 2000; 56:27. [PMID: 10853874]

Merrel WC, Shalts E: Homeopathy. Med Clin North Am 2002; 86:47. [PMID: 11795090]

Aromatherapy

The practice of aromatherapy consists of using volatile essential oils extracted from plants for therapeutic benefit. Essential oils can be topically applied, aerosolized, or used in massage.

Aromatherapy partially relieves anxiety, and the favorable side effect profile makes aromatherapy a useful adjunctive therapy. The aerosolized and massage use of essential oils has been best studied with respect to calming and anxiolytic effects. A systematic review found evidence

P.481


to support a mild anxiolytic effect of essential oils when combined with massage. Essential oils combined with massage have been tried in terminal cancer patients receiving palliative care and hospitalized dementia patients. In cancer patients, aromatherapy massage using Roman chamomile resulted in decreased anxiety and improvements in physical and psychological symptoms as well as quality of life. Topical use of essential oils can also be directed at the treatment of a given skin condition, and tea tree oil has been shown to have benefits in the treatment of acne and onychomycosis. A study of dementia patients found essentially no benefit of massage with essential oils. The side effects related to aromatherapy are low and are almost exclusively limited to either topical or massage use. These side effects include allergic reactions and photosensitivity.

Cooke B, Ernst E: Aromatherapy: a systematic review. Br J Gen Pract 2000;50:493. [PMID: 10962794]

Smallwood J et al: Aromatherapy and behaviour disturbances in dementia: a randomized controlled trial. Int J Geriatr Psychiatry 2001;16:1010. [PMID: 11607948]