2nd International Scientific Conference on Complementary, Alternative and Integrative Medicine Research

April 12-14, 2002, Boston, Massachusetts

Desiree Lie, MD, MSEd

June 17, 2002

Conference Background

The National Institutes of Health (NIH) National Center for Complementary and Alternative Medicine (NCCAM) defines complementary and alternative medicine (CAM) as "healthcare practices outside the realm of conventional medicine which are yet to be validated using scientific methods."[1] Various other taxonomies have also been used to define CAM.[2-4] Integrative medicine is conceptualized as a broader field, where patients are viewed "as whole people with minds and spirits as well as bodies."[5] These dimensions are specifically included in the approach to diagnosis and treatment.

The NCCAM was established by the United States Congress in 1998, and replaced the Office of Alternative Medicine, which was established in 1992. The mission of this organization is to "prevent and alleviate human suffering through research on the safety and effectiveness of CAM modalities and through research training and information dissemination for healthcare providers and consumers."[1] The Office of Dietary Supplements (ODS) was separately established to specifically study dietary and herbal supplements.[6]

The 2nd International Conference on Complementary, Alternative and Integrative Medicine Research took place April 12-14, 2002, in Boston, Massachusetts. It was jointly coordinated by faculty from Harvard University and the University of California, San Francisco, and supported in part by NCCAM.

Overview of CAM

A series of consumer surveys conducted between 1990 and the present have tracked CAM use in the United States by prevalence, cost, and use patterns.[7-10] Findings from these studies included the following:

  • The prevalence of CAM use increased from 25% in 1990 to 42% in 1997. This growth represents increased usage among all socioeconomic groups. The prevalence of herbal remedy use increased by 380% during the same time period.

  • Total visits to CAM providers in 1997 (629 million) exceeded total visits to all primary care physicians (386 million) during that year.

  • Estimated consumer expenditures for CAM professional services in 1997 totaled $21 billion.

  • In 1997, an estimated 15 million adults took prescription medications concurrently with herbal remedies or high-dose vitamins, and were thus at risk for drug-herb or drug-supplement interactions.

  • The extent to which patients disclose CAM use to physicians remains low. In both 1990 and 1997, fewer than 40% of CAM therapies used were disclosed to a physician.

  • CAM use appears to increase with age. Three in 10 pre-baby boomers, 5 in 10 baby-boomers, and 7 in 10 post-baby boomers reported use of at least 1 CAM therapy by the age of 33 years.

  • Reasons for CAM use included perceived efficacy, particularly in combination with conventional therapies; more congruence with patient values and beliefs; and failed conventional treatment.

  • The majority of participants surveyed believed that physicians know little about dietary supplements. An estimated 72% would continue using these even if a government scientific study showed negative effects; 81% supported FDA regulation of products prior to sale of the product.[11]

Some of these observations have been replicated in Europe, Canada, and Australia.[12-15]

The conference focused on research aspects of CAM and new findings that have emerged from recent studies. The research in this area has been particularly challenged by the following issues:

  • the need for adequate and generally acceptable definitions of specific therapies including purity, dosage, and delivery systems;

  • the validity of placebos used as comparisons in studies of efficacy;

  • defining and selecting adequate and appropriate outcome measure;

  • accounting for the baseline placebo effect of both conventional and unconventional modalities; and

  • the need to control for patient expectation as an independent variable in studies of efficacy.[16,17]

Some examples of recently published consensus reports, clinical trials, and reviews that have suggested possible efficacy warranting further clinical investigation include:

  • mind/body techniques for treatment of pain and insomnia[18];

  • acupuncture for recurrent headaches,[19] fibromyalgia,[20] and postoperative nausea[21];

  • homeopathy for treatment of vertigo[22] and allergic rhinitis[23];

  • massage and chiropractic for treatment of low back pain[24];

  • Chinese herbs for treatment of irritable bowel syndrome[25];

  • Tai chi for treatment of balance disorders[26]; and

  • glucosamine and chondroitin for treatment of osteoarthritis.[16]

Other recent clinical trials suggested possible lack of efficacy in other areas. These included use of acupuncture for neuropathy and tinnitus, and herbal remedies for asthma, hand warts, muscle soreness, and obesity.

Other recent studies examining the mechanism of CAM effects have included functional studies of brain magnetic resonance imaging (MRI) on acupuncture subjects,[17] animal models of cancer cell suppression by supplements and herbals,[27] and responses to placebo in analgesia control.[28,29]

Abstracts presented at this year's conference reflected the diversity of topics in CAM research. Some examples of the diverse scope included studies of the efficacy of kava and valerian for anxiety and insomnia; the mechanism of American ginseng in suppression of breast cancer cells injected into nude mice; the efficacy of acupuncture in treatment of chronic neck pain; emerging issues in HIV patients seeking advice from health food stores; and CAM use among American women in 4 different ethnic groups.

Award-Winning Research

Awards were given for original research presentations and abstracts representing scientific rigor in methodology and analysis in the areas of clinical and basic science and health services research. These award-winning studies are summarized below.

Acupuncture is an ancient traditional Chinese therapy relying on the concept of stimulation by needling of the "meridians" (or pathways) in the body in order to treat conditions such as pain and nausea. A sensation called "chi" is produced by acupuncture. In China, acupuncture has been used to provide perioperative analgesia. Schools of acupuncture in the United States, some of which are accredited, currently provide training to practitioners wishing to use this modality.

The NIH consensus report of 1998 suggested that "acupuncture may be useful as an adjunct treatment or an acceptable alternative or included in a comprehensive management program for many medical conditions."[30] More specifically, a recent meta-analysis evaluating the injection of the P6 acupoint in adults suggested efficacy in reducing the incidence of postoperative nausea and vomiting (PONV).[21] Vomiting in children undergoing surgery for strabismus was also significantly reduced by acupuncture.[31] These data provided the basis of an investigation assessing the use of the P6 acupoint to treat postoperative nausea and vomiting in children.[32]

Method. Subjects were children ages 7-16 whose parents were contacted by telephone 1-2 weeks prior to their children's surgery. This double-blind, sham-placebo-controlled study randomized subjects into 1 of the following groups:

  • acupoint (intravenous [IV] saline and bilateral P6 acupoint injections);

  • droperidol (IV droperidol and sham bilateral P6 acupoint injection);

  • sham point (IV saline and bilateral sham, ie non-P6 point injections); or

  • P6 sham-point therapy (IV saline and bilateral sham P6 point injections).

The primary outcome was the incidence of PONV in the postanesthesia care unit during the first 24 hours postoperatively. All treatments were administered in response to reported symptoms. Data were obtained on 187 participants; 50 received acupoint treatment, 49 were treated with droperidol, and 43 and 45, respectively, were assigned to the 2 sham-point control groups.

Results. Groups were similar in characteristics of age, sex, type of surgery, and incidence of PONV. Results showed that the incidence of postoperative nausea within 24 hours was significantly lower in the P6 acupoint group (group 1), compared with the sham-point group (32% vs 56%, P = .029) (group 3) and the P6 sham-group (32% vs 64%. P = .002) (group 4). However, compared with the droperidol group (group 2), no significant difference in postoperative nausea was found (32% vs 46%).

Similarly, when used for treatment of vomiting, subjects in the P6 acupoint group (group 1) had a significantly lower incidence compared with group 3 (12% vs 33%, P = .026) and group 4 (12% vs 31%, P = .029), but not the droperidol group (group 2) (12% vs 18%, P = nonsignificant). In addition, a significantly smaller number of subjects in the acupoint group required rescue therapy with IV ondansetron (P = .024) compared with those in all other groups.

Conclusion. In children, P6 acupoint injections are as effective as droperidol in preventing early postoperative nausea and, probably, vomiting. This result supports previous studies conducted with adults. The physiologic mechanism of P6 acupoint injections for control of nausea and vomiting is as yet not understood. In this study, subjects experiencing vomiting were small in number. Future larger studies powered to detect differences in the control of vomiting will be helpful. In addition, studies of basic science mechanism will help elucidate specific pathways for the action of acupoint injection, and may lead to other therapeutic interventions.

Extracts from the resin of the Commiphora mukul (guggul) tree have been used for centuries in Ayurvedic medicine to treat hypercholesterolemia, particularly in India, where reports of efficacy have been published.[33,34]Gugulipid contains 2.5% guggulsterones and is available as a dietary supplement in the United States. To date, no studies have been conducted among Western populations to examine the efficacy of this supplement. Szapary[35] tested the hypothesis that Gugulipid can reduce cholesterol, in particular low-density-lipoprotein (LDL) cholesterol, in individuals with elevated LDL.

Method. A total of 103 healthy subjects with LDL cholesterol levels ranging from 118 to 223 mg/dL (mean LDL = 159 mg/dL) were stratified according to LDL level (greater or less than 160 mg/dL) to 1 of the following 3 groups:

  • 1000 mg Gugulipid 3 times/day (standard-treatment group, n = 36);

  • 2000 mg Gugulipid 3 times/day (high-dose-treatment group, n = 29); or

  • matching placebo tablets (n = 30).

All treatment was continued for 8 weeks. Each 1000-mg Gugulipid capsule contained at least 20 mg of E and Z guggulsterones, as measured by independent standardized high-performance liquid chromatography.

Results. Subjects were healthy adults without clinical evidence of atherosclerosis or ischemic heart disease, with moderately elevated cholesterol as described above. After 2 months of therapy, directly measured LDL cholesterol dropped 3% (P = .2 vs baseline) in the placebo group and increased by 4.5% (P = .031 vs placebo) in the standard-treatment group. LDL levels increased by 6.5% in the high-dose treatment group compared with placebo (P = .0065). There was no difference in percentage of change between the standard-dose group and the high-dose group LDL levels (P = .52).

Conclusion. The investigator concluded that in Western hypercholesterolemic patients, treatment with Gugulipid did not reduce serum cholesterol, and may actually increase LDL. He also noted an unexpectedly high incidence of clinically significant skin rash (akin to Stevens-Johnson syndrome) in 5 subjects in the treatment groups. This side effect has not been reported in previous studies of Gugulipid -- previously considered a safe herbal, non-FDA-approved supplement.

The finding of lack of efficacy of guggul extract for moderately elevated cholesterol directly contradicted the results from previous studies, suggesting that clinicians need to exercise caution before accepting this supplement as an adjunct or treatment for hypercholesterolemia. There is a suggestion that guggul extract may in fact have the opposite effect of elevating cholesterol. This finding deserves confirmation in a larger study.

Stroke is 4 times more prevalent among patients with type 2 diabetes mellitus (DM) compared with individuals without DM.[36] The primary mechanism for this is believed to be mediated by increased platelet sensitivity leading to blood clot formation.[37] Kudolo[38] evaluated Ginkgo biloba extract, a plant herbal supplement used for indications ranging from dementia to improvement of cognitive function and stroke prevention. Although the mechanism of action of the supplement is not well understood, it is widely marketed as "improving circulation to the brain." He hypothesized that Ginkgo biloba may reduce the risk of stroke in individuals with DM by reducing platelet-collagen interaction, thus reducing the risk of blood clots. This investigator had previously studied the effect of Ginkgo biloba on pancreatic cell function in DM and non-DM subjects.[39,40]

Method. Venous blood was drawn from 20 individuals with DM (mean age, 53 years). The blood sample was then converted to platelet-rich plasma prepared by centrifugation. Platelet aggregation was then induced by adding collagen to the sample. After addition of collagen, platelet aggregation was measured by optical transmission. Aggregation was measured either alone or after the addition of an aqueous solution of Ginkgo biloba (240, 480, or 960 mcg/mL) for 1 minute. The reaction was terminated after 5 minutes using indomethacin. Collagen-induced platelet aggregation was compared between the 3 sample groups.

Results. There was a dose-dependent collagen-induced increase of the maximal platelet aggregation at 5 minutes, with no significant differences between the 3 groups tested. Preincubation with Ginkgo biloba before challenging with collagen produced a dose-dependent inhibition of platelet aggregation. There was also a highly significant correlation between inhibition of platelet aggregation and platelet thromboxane (TXB2) production (P < .001).

Conclusion. This in vitro study supported a possible mechanism for the postulated clinical effect of Ginkgo biloba: "thinning" the blood. Preincubation of hypersensitive platelets from individuals with DM with Ginkgo biloba reduced platelet aggregation stimulated by collagen. Thus, this study suggests a physiologic mechanism for an observed effect of Ginkgo biloba on stroke prevention in patients with DM. However, further larger, long-term, randomized clinical trials of efficacy will be needed before clinicians recommend this supplement for the specific indication of stroke prevention.

Recent surveys of CAM use have focused on adults, but little information had been known about the use of CAM therapies by children and adolescents.[5,6] Yussman and colleagues[41] obtained data from the 1996 Medical Expenditure Panel Survey (MEPS), a nationally representative household sample, and performed a secondary analyses of CAM use reported by parents.

Method. Data from 7371 individuals younger than 22 years of age, were collected. Parents or heads of households were asked if their children had visited a CAM provider "for health reasons." Prevalence of CAM use was defined by visits to CAM providers compared with conventional providers. CAM therapies included acupuncture, massage, biofeedback, homeopathy, meditation, hypnosis, Ayurvedic and Chinese medicine, spiritual healing, and other modalities. Use of self-prescribed therapies such as prayer, herbs, and dietary or vitamin supplements were not considered CAM therapy in this study.

Results. The overall prevalence of CAM use was low: 2%. The distribution of use varied by age: 52% for age 0-10 years; 19% for 11-14 years; 14% for 15-17 years; and 15% for 18-21 years. Prevalence of use by ethnicity also varied; 51% for whites, 16% for blacks, 29% for Hispanics, and 4% for "others." Predictors of CAM use included:

  • both parents being users of CAM (odds ratio [OR] = 47.2);

  • mother only using CAM (OR = 8.8);

  • 6 or more visits to a conventional provider per year (OR = 4.4);

  • lower satisfaction with conventional provider (OR = 2.8);

  • older age (18-21 years) (OR = 3.2); and

  • female sex (OR = 1.6).

Conclusion: This is the first nationally representative study of CAM use in the pediatric and adolescent population without a self-selection bias. It included individuals in all socioeconomic levels. However, it was a phone survey restricted to English-speaking respondents. It was done as a head-of-household report, and included a limited number of modalities. Therefore, it is likely to have underestimated CAM use in the age groups studied. Future studies will be aimed at questioning adolescents directly, addressing non-English-speaking populations, and expanding the range of modalities assessed.

The incidence of diabetes in the United States varies from 10% in the general population to over 20% in high-risk groups such as Native Americans and Latinos. This study attempted to characterize the use of CAM therapies among individuals with DM, when used as specific treatment for this condition.[42]

Method. Using data from a nationally conducted telephone survey, 4.6% of all respondents were identified as having a DM diagnosis. The mean respondent age for the sample with DM was 57 years. Among those identified with DM, 91% were diagnosed after age 25 and 30% required insulin.

Results. Thirty-five percent reported use of CAM therapies specifically for DM in the past year, including prayer and spiritual practices (28%), commercial diets (6%), herbal remedies (7%), and folk remedies (3%). Of respondents identifying as CAM users, 61% found CAM therapies to be "very helpful." However, when prayer was excluded from the analysis, only 20% of respondents reported condition-specific use of CAM therapies.

Conclusion. This was a low rate of CAM use, compared with previously established rates of 64% use by individuals with back and neck pain, 55% with anxiety/depression, and 42% overall use among US adults.[5] The investigator estimated that 6 million people with DM use CAM therapies in the United States, but that prevalence of use was lower for DM than for other conditions. Several reasons could account for this pattern of relatively low usage. For example, patients with DM may perceive conventional medical treatment alone to be efficacious. This might reflect confidence in DM prescription medications and physician management. Or, perhaps patients with DM are treating only "troublesome" symptoms (such as infections or polyuria) with CAM modalities, rather than treating the condition of DM itself. Qualitative studies examining patient perceptions of DM as a condition or disease should yield clinically useful information in this area. The investigator suggested that additional studies be conducted to characterize CAM use in DM.

Summary

The 1st International Scientific Conference on Complementary, Alternative and Integrative Medicine Research in 2001 focused on the concept and definition of the placebo effect in CAM research. The abstracts presented at the 2nd International Conference highlighted the need for rigorously conducted scientific studies to examine the efficacy of CAM modalities, including use of valid outcome measures. This will allow enhanced understanding of cellular, immune, neurologic, cytologic, and other basic mechanisms underlying observed effects, as well as the replication of small studies with larger, adequately powered trials.

The abundance of well-conducted, original research and the continued visibility of NCCAM at this conference was a strong reassurance to the public that knowledge in many CAM modalities will increase through future larger, interinstitutional collaborative trials supported by the NIH. This will hopefully facilitate informed, shared decision-making by patients and providers confronted with the uncertainty of selecting the best therapies for, and integrative approaches to, health and disease.

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  41. Yussman S, Auinger P, Weitzman M. Complementary and alternative medicine use by children and adolescents in the United States. Program and abstracts of the 2nd International Scientific Conference on Complementary, Alternative and Integrative Medicine Research; April 12-14, 2002; Boston, Massachusetts.

  42. Yeh G. Complementary and alternative therapy use among persons with diabetes mellitus (DM) in a national survey. Program and abstracts of the 2nd International Scientific Conference on Complementary, Alternative and Integrative Medicine Research; April 12-14, 2002; Boston, Massachusetts.