Complementary and alternative medicine

Author : Dr Stephen Bent University of California, San Francisco

2008-06-10

I. What is Complementary and Alternative Medicine?

Complementary and Alternative Medicine (CAM) is variably defined but generally refers to medical therapies and practices that are not commonly taught at medical schools or available at major hospitals and clinics in the United States^{1, 2} (in contrast to “traditional” or “conventional” medicine, which refers to therapies that are provided in most hospitals and clinics). 

Sometimes complementary medicine is described as non-traditional therapies that are used in conjunction with traditional therapies (to complement their action), while alternative medicine is used to describe non-traditional therapies that are used in place of (as an alternative to) traditional therapies. Practically speaking, most non-traditional therapies are simply classified under the general rubric: CAM therapies. A related term used in some settings is integrative medicine, which highlights the belief that CAM therapies are best used when integrated with (rather than replacing) conventional medical care.

II. What are the major types of CAM?

There are many different ways to categorize CAM therapies. The National Center for Complementary and Alternative Medicine (NCCAM – see: http://nccam.nih.gov/) is the scientific branch of the National Institutes of Health that provides research funding for CAM. It outlines four “domains” of CAM and also describes “whole medical systems,” which refers to different theories of medical practice (such as Traditional Chinese Medicine or Homeopathic Medicine) that may involve several domains of CAM treatments.

A. The Four NCCAM domains of CAM:

1) Mind-Body Medicine – techniques used to “enhance the mind’s capacity to affect bodily functions and symptoms,” including meditation, prayer, mental healing, and therapies that use creative outlets such as art, music, and dance.

2) Biologically-Based Practices – products found in nature, such as herbs and vitamins, which may act similarly to drugs by affecting some biological pathway.

3) Manipulative and Body-Based Practices – practices such as chiropractic and massage that involve the manipulation of body parts.

4) Energy Medicine – practices that are designed to affect proposed “energy fields” surrounding the body (examples include qi gong, Reiki, and Therapeutic touch), as well as the use of conventional electromagnetic fields to affect diseases or symptoms.

Whole medical systems may involve different types of therapies – for example, Traditional Chinese Medicine (TCM) may involve the use of herbs, a change in diet or routine, and acupuncture. 

B. Passive vs. Active Therapies:

CAM therapies may also be categorized by the “level of involvement” of the patient into three main groups:

1) Dietary supplements: which are taken in a similar fashion to drugs (for example, chondroitin for knee pain or Echinacea for the common cold).

2) Passive therapies: require the patient to visit a provider and receive some form of treatment (examples include acupuncture, massage, chiropractic, and certain forms of energy healing).

3) Active therapies: require the patient to learn a technique or skill and practice that on their own. Examples include diet, exercise, yoga, meditation, and stress reduction techniques.

In many ways, the “active” therapies are the most desirable, because they provide the patient with a tool or skill that they can use indefinitely and at low cost. Interestingly, although diet, exercise, meditation, and stress reduction are sometimes viewed as CAM therapies, there is strong scientific evidence that many of these “common sense” and “lifestyle interventions” lead to marked improvements in the outcomes of many conditions. However, they are often still viewed as CAM therapies, as many hospitals and clinics do not provide programs that teach these techniques.

III. Why do patients use CAM therapies?

Although the use of CAM has likely been common for decades, the issue received widespread media attention after the publication of two national surveys (conducted in 1990 and 1997) that found that 33.8% of the population (1990) and 42.1% of the population (1997) reported using a CAM therapy in the past year.^{1, 2} Perhaps even more surprising was the fact that the total visits to CAM providers in 1997 numbered 629 million, which exceed the number of visits to all US primary care physicians; in other words, the population at large was seeing CAM providers more commonly than traditional physicians! Also, the out-of-pocket expenditures for CAM therapies in 1997 were estimated to be $27 billion, which was comparable to the out-of-pocket expenditures for all physician services in the US. These landmark studies shed light on the fact that almost half of the population was using CAM therapies, and that patients were contributing similar amounts of their own financial resources to CAM and traditional care. These studies were a major factor in the rising public interest and awareness of CAM, reflected by the Congressional action to establish the National Center for Complementary and Alternative Medicine at the National Institutes of Health in October of 1998. NCCAM was charged with conducting research into the safety and efficacy of CAM, providing training for scientists to conduct research, and disseminating information about CAM to the public.

A separate national survey, conducted in 1998, sought to determine why people use CAM.³ Interestingly, this study found that most patients do not use CAM due to dissatisfaction with conventional care, but rather because CAM was more “congruent with their own values.” Use of CAM was more common in persons with:

            1) more education

            2) poorer health status

            3) a self-described holistic orientation to health

4) a prior “transformational experience” that changed the person’s worldview

5) any of the following health problems: anxiety, back problems, chronic pain, urinary tract infections

6) classification in a cultural group identifiable by their commitment to environmentalism, feminism, or interest in spiritual and personal growth psychology.

This study and others have borne out the conclusion that the use of CAM is particularly common among patients who have disorders that have not responded well to traditional medical therapies. Examples include such problems as chronic pain, psychiatric illness (anxiety, depression, insomnia), gastrointestinal disease (abdominal pain, constipation, diarrhea), or generalized complaints (fatigue, malaise) where a significant percentage of patients have unsatisfactory outcomes. After exhausting traditional options (for example, pain medicines, steroid injections, or surgery for chronic back pain), many patients seek CAM treatments to relieve symptoms.

IV. Which CAM therapies are most commonly used?

The most recent and extensive national survey of CAM use was released in 2004 and involved a national sample of 31,044 interviews of adults over the age of 18 in 2002.⁴ The most commonly used CAM therapies are shown in the attached figure (double-click figure for a larger view of the text).

When prayer used specifically for health reasons was excluded, the study found that 36% of adults had used some form of CAM therapy in the past year. The most commonly used CAM therapy was natural products (18.9%), which includes herbal medicines, functional foods (such as garlic), and animal-based products (such as glucosamine). Deep breathing (11.6%), meditation (7.5%), chiropractic (7.5%), yoga (5.1%), and massage (5.0%) were among the most commonly used CAM therapies.

The overall use of CAM (36%, excluding prayer) was lower than in the national survey conducted in 1997 (which concluded that 42.1% of adults had used CAM).¹ This may reflect a true decline in the use of CAM, or may be due to differences in survey design (including the use of different definitions of specific CAM practices and differences in the group of patients that were surveyed). Regardless, it is clear the use of CAM is still very common in the United States.

V. Which CAM therapies are effective?

 As with any medical therapy, a determination of the efficacy of a specific CAM therapy is based on a review of scientific evidence, which may come in several different forms

A. Background on evaluating scientific evidence:

 The highest-quality scientific study for evaluating the efficacy of any intervention (CAM or traditional) is the double-blind, placebo-controlled, randomized trial. These studies create groups of patients with similar characteristics (similar age, similar socioeconomic status, similar severity of medical conditions such as diabetes, heart disease, etc) by randomly assigning patients to a treatment or control group. The use of double-blinding indicates that neither the patient nor the persons conducting the study know whether any given patient is receiving the “real” treatment or an identical, inactive placebo treatment. Therefore, patients and study personnel should not be influenced when judging whether they have improved (because they do not know whether they are taking the active or the placebo treatment). Once the study is completed, the investigators “unblind” the data, and determine if patients in the active group improved more or less than patients in the placebo group.

Unfortunately, there have been few high quality randomized controlled trials conducted on the vast majority of CAM interventions. A review of studies examining the efficacy of CAM therapies concluded that most randomized controlled trials in this field are of poor quality.⁵

Most of the evidence regarding the efficacy of CAM interventions comes from anecdotal reports (also known as case reports when they are published in the medical literature). These reports generally describe a patient (who for example, might have had severe back pain) who was given a CAM treatment (such as acupuncture) and who improved. These reports provide preliminary evidence that a therapy might be effective, but they are extremely limited for several reasons:

1)      Case reports have no comparison group, so it is not clear whether similar patients (or the same patient) would have improved without the intervention (this problem is sometimes referred to as a lack of information about the “natural history of the disease”).

2)      Case reports are not blinded, so both the patient and the person assessing the outcome are aware of the treatment. This may lead to a biased interpretation of the effect (for example, an acupuncturist might firmly believe in the efficacy of the intervention, and might tend to overestimate the effect). Also, the lack of blinding can lead to a placebo effect, where the observed benefit is not due to the intervention, but to an expectation of benefit (though one can certainly argue that there is nothing wrong with a good placebo effect!).

3)      Case reports often involve one or just a few patients, and it is not clear if they are representative of the larger group of patients who suffer from similar conditions.

There are many examples in traditional medicine where widely held medical beliefs (based on case reports or other similar “observational studies”) were later proven incorrect by the higher-quality randomized controlled trials. For example, for decades it was well established medical practice that when post-menopausal women were given estrogen, they seemed to have less heart disease. It was not until several large randomized controlled trials were conducted that it was discovered that estrogen had no beneficial effects on heart disease.⁶ The original observations of benefit were likely due to the fact that women who went to the doctor to get estrogen were more health-conscious and did other things that reduced their risk of heart disease.

However, it should also be mentioned that many of the most important scientific discoveries originally came from case reports, and the value of case reports to suggest important possibilities should not be underestimated. For example, the phenomenon of a group of 11 men (who were either homosexual or intravenous drug users) becoming immune deficient was originally described in a case series.⁷ This “anecdotal” observation or case series led to the discovery of the AIDS virus.

Historical use is often mentioned as an important consideration regarding the efficacy of CAM interventions, many of which have been used for hundreds or thousands of years. Unfortunately, historical use does not provide strong evidence of efficacy, as it is essentially just a “very large case series” and suffers from the same problems noted above.

For the vast majority of CAM therapies, there is little or no evidence to document efficacy. However, the lack of evidence should NOT be equated with a conclusion that a therapy is ineffective. In the absence of scientific evidence, there is an equal chance that any therapy will be beneficial or harmful.

Also, each CAM therapy must be evaluated for efficacy for a specific indication or medical problem. For example, it is too broad to ask the question, “Is acupuncture effective?” and scientific evidence must be more narrowly focused to answer a question such as, “Is acupuncture effective for the treatment of chronic low back pain?”

B. Brief review of the evidence for efficacy for the most commonly used CAM therapies:

Herbs and other dietary supplements: Herbs and other natural products are the most commonly employed CAM therapies, used by 18.9% or roughly 1 in 5 adults in the US.⁴ The vast majority of these natural products are orally ingested, although a small percentage is applied topically. A recent review article examined the evidence of herbs’ efficacy from systematic reviews (which are extensive reviews of all studies of a particular agent for a particular indication). The results are summarized in the table below.⁸

Herb	Herbal Sales, 2001*	Common Use	Efficacy
1. Echinacea	6.5%	Common Cold	Inconclusive
2. Garlic	6.1%	Lowering Cholesterol	Likely effective, reducing cholesterol by 4-6%
3. Ginkgo biloba	4.2%	Dementia	Likely effective, with small benefit
4. Saw palmetto	4.2%	Urinary problems from enlarged prostate	Inconclusive
5. Ginseng	3.4%	Physical performance	Not effective
6. Grape seed	3.2%	Venous insufficiency	No evidence
7. Green tea	3.1%	Cancer	Limited evidence
8. St. John’s wort	3.0%	Depression	Likely effective for mild-moderate depression but not major depression
9. Bilberry	3.0%	Vision impairment	No evidence
10. Aloe	2.9%	Wound healing	Limited evidence

*Herbal sales refers to the percent of all herbal products sold in retail natural product stores in 2001.

Concerns with the use of herbal products:

• It has been estimated that there are approximately 20,000 herbal products available in the United States.⁹ The evidence for efficacy is very limited for the ten most commonly used herbs, and is extremely limited or non-existent for the remainder of the 20,000 herbal products.
• Consistency of the content of herbal products has been problematic. Herbs contain many different organic chemicals, and it is difficult to know which, if any of these components, have important biological effects. Even when specific active ingredients are identified, many studies have shown that the contents of these herbal products vary widely.⁸
• Safety studies of herbal products are also very limited (see safety, below). There have been many case reports of severe adverse effects, possibly due to active ingredients in the herbs, contaminants in the product, or resulting from interactions with drugs.
• The Food and Drug Administration has very limited oversight of herbs and other dietary supplements. Herbal products can be produced and marketed without FDA approval, and the manufacturer, not the FDA, is responsible for ensuring the safety of a dietary supplement. As a result, there are many herbal products that are contaminated with heavy metals, drugs, incorrectly labeled herbs, or incorrect doses of active ingredients.
• False and misleading marketing information is common with dietary supplements,¹⁰ which may give consumers unrealistic expectations of safety or efficacy.

Commonly used non-herb dietary supplements:

1. Glucosamine and Chondroitin sulfate – there is ongoing controversy regarding the possible efficacy of glucosamine and chondroitin sulfate for the treatment of osteoarthritis of the knee. A recent systematic review concluded that the symptomatic benefit of chondroitin is minimal or non-existent.¹¹ A large, high-quality randomized controlled trial found that the combination of glucosamine and chondroitin sulfate was not effective for the overall group of patients with knee pain, but that it was likely effective in the subgroup of patients with moderate-to-severe pain.¹² Ongoing studies may shed more light on the question of efficacy for this supplement.
2. Omega-3 fatty acids - there is strong scientific evidence from randomized controlled trials that the regular intake of omega-3 fatty acids (either from a diet high in fish or from the use of supplements) reduces the risk of heart disease. The American Heart Association now recommends that patients with heart disease take about 1 gm of long-chain omega-3 fatty acids per day.¹³ Dietary content of omega-3 fatty acids varies substantially. Fish is a major source, and a 3 gram serving of an “oilier” fish (such as tuna, sardines, salmon, mackerel, and herring) contains roughly 1 gm of omega-3 fatty acids. Plant sources of omega-3 fatty acids include flaxseed oil, canola oil, soybean oil, and certain nuts including walnuts. Numerous available supplements contain 1 gm of omega-3 fatty acids.

Bottom-line for herbs and other dietary supplements:There are certainly many herbs that have active ingredients that are potentially beneficial for treating certain disorders. It is estimated that 1/3 of currently used drugs originally came from plants. However, the current problems of poor consistency, safety concerns, scant data to support efficacy, and inadequate oversight limit the usefulness of herbal products. Certain non-herb dietary supplements such as omega-3 fatty acids have strong data to support efficacy. These products are often simpler than herbs (and therefore easier to study), because they have only one or a few components.

Passive therapies:

Acupuncture

1. Acupuncture –

• Acupuncture is a component of Traditional Chinese Medicine that dates back over 2,000 years and involves the insertion of small needles at specific points in the body. The use of acupuncture is based on the theory that there are patterns of energy flow through the body (known as Qi – pronounced “chee”), and that disease states are due to impaired flow of this energy. The use of acupuncture is believed to improve disease states and symptoms by restoring the normal flow of Qi.
• There is controversy regarding the efficacy of acupuncture for specific conditions. Some studies and reviews have concluded that acupuncture is effective for:

1. post-operative and chemotherapy-induced nausea and vomiting
2. post-operative dental pain
3. other pain syndromes including menstrual cramps, tennis elbow, fibromyalgia, and back pain

·        However, a recent review of systematic reviews re-examined prior evidence, and set a “higher bar” for establishing efficacy of acupuncture (requiring at least 4 randomized controlled trials with valid outcome measures and a total of at least 200 patients). This study concluded that there is currently no robust evidence that acupuncture works for any indication.¹⁴

·        A recent, large-scale, high-quality randomized controlled trial in 1162 patients with chronic low  back pain found that both acupuncture and a “sham” or fake acupuncture led to a much larger percentage of patients improving compared with standard treatment (47.6% of patients with “real acupuncture” and 44.2% of patients with “sham acupuncture” improved compared to only 27.4% of patients in the conventional therapy group).¹⁵

·        Similarly, a study in 1007 patients with osteoarthritis of the knee found that both acupuncture and sham acupuncture led to higher success rates than conventional therapy (53.1% success with acupuncture, 51.0% with sham acupuncture, and 29.1% with conventional therapy).¹⁶  Conventional therapy refers to the use of anti-inflammatory pain medicines.

·        Bottom line: Acupuncture is almost certainly effective for back pain, knee pain from osteoarthritis, and probably for other syndromes of chronic pain. The mechanism of this benefit (and whether it is a placebo effect or a physiological effect of the needle placement) is unknown.

2. Chiropractic –

• Although there are mentions of certain forms of spinal manipulations dating back centuries, modern chiropractic care began in the United States in 1895 when Dr. David Palmer established the profession and soon after founded the first school. Chiropractic practice grew in popularity, and chiropractors are now the third largest group of health professionals in the United States (after physicians and dentists). Chiropractors are licensed in all 50 states, and 45 states have state-mandated benefits for chiropractic care.¹⁷
• Chiropractic care is believed to act through corrections of malalignments of the spine (termed subluxations) through the use of spinal manipulation (called spinal adjustments). Chiropractic care may also involve advice about exercise, nutrition, and lifestyle changes.
• A systematic review of the efficacy of chiropractic care (spinal manipulation) for low back pain found that it was no more effective than general practitioner care, analgesics, physical therapy, or exercises.¹⁸
• Other reviews have found that there is insufficient evidence to support the efficacy of chiropractic care for asthma and menstrual cramps.^{19, 20}
• One review found that chiropractic care may be effective for the prevention of migraine headaches.²¹
• Bottom Line: Despite the widespread popularity of chiropractic care, there is limited high-quality scientific evidence that it leads to improved outcomes for specific disorders.

3. Massage –

• Massage is commonly used by patients with disabling, painful, or terminal conditions, and has one of the highest physician referral rates of all CAM therapies. Research into the effectiveness of massage for specific indications is limited and complicated by the difficulties of designing appropriate control or placebo groups.
• There is strong scientific evidence that massage is effective for the relief of chronic back pain, and the benefit is greater than that found with relaxation, self-care, or acupuncture.²²
• In pregnant women, massage of the perineal region 1-2 times per week has been shown to reduce the frequency of perineal trauma during childbirth. ²²
• Massage of pre-term or low birth weight infants improves daily weight gain and may improve weight and reduce post-natal complications at 4-6 months. ²²
• Current evidence is insufficient to determine if massage is effective for a variety of other indications, including cancer, asthma, fecal incontinence and constipation associated with neurological disorders, neck pain, tendonitis, and work-related upper extremity pain.
• Bottom Line – massage has been shown to be effective for chronic back pain, weight gain in low-weight infants, and prevention of perineal trauma during childbirth. Evidence for the efficacy of massage for other indications is limited.

4. Energy healing –

• Research investigating the use of therapies that are believed to modify energy fields surrounding the body (such as Reiki, Therapeutic Touch, and Healing Touch) is preliminary. These therapies are commonly used to treat anxiety, improve relaxation, achieve stress reduction, enhance wound healing, and to reduce pain.
• Bottom Line: Currently, there is insufficient scientific evidence to make conclusions regarding the efficacy of these interventions.

Active therapies:

1. Meditation –

• Meditation has been practiced for centuries in many different cultures throughout the world. While there are many different styles and practices of meditation, a recent review of all styles found the common theme of “achieving a well-defined state of thoughtless awareness focusing attention to the present moment and away from the unchangeable past or the undetermined future…”²³
• There is promising, though not definitive evidence, that meditation may be helpful for epilepsy, menstrual cramping, menopausal symptoms, mood and anxiety disorders, autoimmune diseases, and emotional disturbances in patients with cancer.²³  Further research is needed to define the potential benefits of this therapy.

2. Yoga –

• Yoga is an ancient practice that originated in India and literally means “union” in Sanskrit, referring to a union between the mind, body, and spirit. While the ancient practice of yoga involves many aspects of mental and spiritual well being, the modern practice of yoga often refers to the physical postures or poses designed to improve strength, flexibility, and balance. These are often coupled with deep breathing and relaxation or meditative techniques.
• There is strong scientific evidence that yoga is more effective than self-care for chronic low back pain, resulting in improved function and reduced pain.²⁴
• There is preliminary evidence that yoga may be helpful for improving stress-related symptoms and quality of life in patients with cancer.²⁵ Some evidence also suggests that yoga may be effective for the treatment of depression and anxiety.^{26, 27}

3.   Diet and Exercise –

• There are numerous studies documenting the health benefits of diet and exercise for a variety of conditions from reductions in death and disability from diabetes and heart disease to improvements in mood and overall quality of life. While these therapies may not be considered “complementary and alternative,” the traditional care environments (most clinics and hospitals) often do a poor job of providing access to these therapies and assisting patients to develop healthy diet and exercise practices. Therefore, many CAM practitioners devote more time and energy to emphasizing and implementing diet and exercise strategies. Hence, these therapies are often included in the CAM “umbrella” of services. There are many different forms of diet and exercise, and an analysis of particular strategies is beyond the scope of this review.

VI. Are CAM therapies safe?

There are significant concerns about the safety and efficacy of herbs and other dietary supplements and their potential to interact with prescription medications. Many severe, life-threatening, and fatal side effects to dietary supplements have been reported in the medical literature. The unresolved problems of limited regulation, difficulty creating consistent products, contamination, and little or no safety testing for most dietary supplements creates great potential for side effects from these products.⁸

There is little information regarding the safety of most other CAM therapies as well, though most appear to be relatively safe. Acupuncture is widely used, but there have been only rare reports of any side effects, and most of these are minor (fainting, minor bleeding, worsening of symptoms). The standard use of disposable needles in this country has reduced the concern over the risk of infection or disease transmission.²⁸ Similarly, there are few concerns regarding the safety of massage, although some patients will report pain or discomfort or worsening of symptoms, particularly with more forceful treatments. Serious complications of chiropractic care have also been reported only rarely, and have been generally attributed to improper technique.²⁸

One of the greatest safety concerns with all CAM therapies is that the use of CAM may delay the diagnosis or traditional treatment of a disorder (which could ultimately worsen the outcome for some patients). For this reason, patients are always encouraged to discuss CAM treatments (and the symptoms or reasons that prompted their use) with their regular clinical care provider. Unfortunately, only a minority of patients discuss their use of CAM with the traditional care providers. This is a complex problem that involves perceptions from patients that doctors will not support their use of CAM as well as a lack of openness to discuss and support the use of CAM therapies on the part of some care providers.

VII. Resources to learn more and help decide whether to use a CAM therapy

1. National Center for Complementary and Alternative Medicine (NCCAM) –is the Federal Government's lead agency for scientific research on CAM, and is 1 of the 27 institutes and centers that make up the National Institutes of Health (http://nccam.nih.gov/). NCCAM supports research and training and disseminates information to the public.

2. Natural Standard – is a Web-based information service (subscription required) that conducts extensive reviews of the safety and efficacy of CAM therapies and provides summaries for both patients and clinical providers (www.naturalstandard.com/).

3. Natural Medicines Comprehensive Database – is a Web-based information service (subscription required) that also conducts extensive searches of the medical literature and summarizes information about natural products (dietary supplements) for patients and clinical providers (www.naturaldatabase.com/).

4. Consumerlab.com – is a Web-based information service (subscription required) that analyzes the content of dietary supplements to determine if the label correctly reports the actual ingredients and whether the products meet current accepted standards for contents of specific products (www.consumerlab.com).

References:

1.         Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA. Nov 11 1998;280(18):1569-1575.

2.         Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins DR, Delbanco TL. Unconventional medicine in the United States. Prevalence, costs, and patterns of use. N Engl J Med. Jan 28 1993;328(4):246-252.

3.         Astin JA. Why patients use alternative medicine: results of a national study. JAMA. May 20 1998;279(19):1548-1553.

4.         Barnes PM, Powell-Griner E, McFann K, Nahin RL. Complementary and alternative medicine use among adults: United States, 2002. Adv Data. May 27 2004(343):1-19.

5.         Linde K, Jonas WB, Melchart D, Willich S. The methodological quality of randomized controlled trials of homeopathy, herbal medicines and acupuncture. Int J Epidemiol. Jun 2001;30(3):526-531.

6.         Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. Aug 19 1998;280(7):605-613.

7.         Masur H, Michelis MA, Greene JB, et al. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N Engl J Med. Dec 10 1981;305(24):1431-1438.

8.         Bent S, Ko R. Commonly used herbal medicines in the United States: a review. Am J Med. Apr 1 2004;116(7):478-485.

9.         Winslow LC, Kroll DJ. Herbs as medicines. Arch Intern Med. Nov 9 1998;158(20):2192-2199.

10.       Morris CA, Avorn J. Internet marketing of herbal products. JAMA. Sep 17 2003;290(11):1505-1509.

11.       Reichenbach S, Sterchi R, Scherer M, et al. Meta-analysis: chondroitin for osteoarthritis of the knee or hip. Ann Intern Med. Apr 17 2007;146(8):580-590.

12.       Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. Feb 23 2006;354(8):795-808.

13.       Harris WS. Fish oil supplementation: evidence for health benefits. Cleve Clin J Med. Mar 2004;71(3):208-210, 212, 215-208 passim.

14.       Derry CJ, Derry S, McQuay HJ, Moore RA. Systematic review of systematic reviews of acupuncture published 1996-2005. Clin Med. Jul-Aug 2006;6(4):381-386.

15.       Haake M, Muller HH, Schade-Brittinger C, et al. German Acupuncture Trials (GERAC) for chronic low back pain: randomized, multicenter, blinded, parallel-group trial with 3 groups. Arch Intern Med. Sep 24 2007;167(17):1892-1898.

16.       Scharf HP, Mansmann U, Streitberger K, et al. Acupuncture and knee osteoarthritis: a three-armed randomized trial. Ann Intern Med. Jul 4 2006;145(1):12-20.

17.       Shekelle PG. What role for chiropractic in health care? N Engl J Med. Oct 8 1998;339(15):1074-1075.

18.       Assendelft WJ, Morton SC, Yu EI, Suttorp MJ, Shekelle PG. Spinal manipulative therapy for low back pain. A meta-analysis of effectiveness relative to other therapies. Ann Intern Med. Jun 3 2003;138(11):871-881.

19.       Hondras MA, Linde K, Jones AP. Manual therapy for asthma. Cochrane Database Syst Rev. 2005(2):CD001002.

20.       Proctor ML, Hing W, Johnson TC, Murphy PA. Spinal manipulation for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev. 2006;3:CD002119.

21.       Bronfort G, Nilsson N, Haas M, et al. Non-invasive physical treatments for chronic/recurrent headache. Cochrane Database Syst Rev. 2004(3):CD001878.

22.       Ezzo J. What can be learned from Cochrane systematic reviews of massage that can guide future research? J Altern Complement Med. Mar 2007;13(2):291-295.

23.       Arias AJ, Steinberg K, Banga A, Trestman RL. Systematic review of the efficacy of meditation techniques as treatments for medical illness. J Altern Complement Med. Oct 2006;12(8):817-832.

24.       Sherman KJ, Cherkin DC, Erro J, Miglioretti DL, Deyo RA. Comparing yoga, exercise, and a self-care book for chronic low back pain: a randomized, controlled trial. Ann Intern Med. Dec 20 2005;143(12):849-856.

25.       Bower JE, Woolery A, Sternlieb B, Garet D. Yoga for cancer patients and survivors. Cancer Control. Jul 2005;12(3):165-171.

26.       Kirkwood G, Rampes H, Tuffrey V, Richardson J, Pilkington K. Yoga for anxiety: a systematic review of the research evidence. Br J Sports Med. Dec 2005;39(12):884-891; discussion 891.

27.       Pilkington K, Kirkwood G, Rampes H, Richardson J. Yoga for depression: the research evidence. J Affect Disord. Dec 2005;89(1-3):13-24.

28.       Cherkin DC, Sherman KJ, Deyo RA, Shekelle PG. A review of the evidence for the effectiveness, safety, and cost of acupuncture, massage therapy, and spinal manipulation for back pain. Ann Intern Med. Jun 3 2003;138(11):898-906.