Essentials of Complementary and Alternative Medicine (June 1999)

THE SAFETY OF SELECTED COMPLEMENTARY PRACTICES
This section of the book gives summary information from the published literature on adverse affects from manipulation, acupuncture, herbals, vitamins, mineral and 
other nutritional supplements, and homeopathy. The practitioner can use these chapters to review and refer to specific products and practices in CAM. One difficulty 
is that little is known about the prevalence of many of these events. The best sources of information on prevalence and adverse effect rates are from postmarketing 
surveillance studies, poison control centers, and randomized controlled trials.
Poison Control Centers
Perharic (
105
) and others have surveyed the toxicological problems resulting from traditional remedies and food supplements reported to a poison control center. Of 
the 5536 contacts, 657 (12%) had symptoms indicative of adverse effects from the ingestion. Most of these were children under 5 years of age who had ingested 
vitamins in overdose. Forty-two of these had some probability of being linked to the ingestion and two had high-probability. The rates of adverse effects calculated for 
vitamins were 343 in 4000 (8%), for food supplements 17 in 141 (12%), and for herbal products 245 in 968 (25%) (
Table 4
)(
105
). This information gives a sense of 
the rate of serious adverse events in situations of abuse but does not provide information about adverse effects rates under competent use.
Table 4. Adverse Effects from Misuse Reported to Poison Control Centers
Randomized Controlled Trials
Adverse effects reported in randomized controlled trials of alternative and complementary medicine as published in the conventional peer-reviewed literature would be 
the best type of evidence for identifying the true rate of hypothesis-driven, attributable adverse effects from the use of such interventions under normal conditions. 
This is because inflated effects would not likely be found from blinded trials that were using randomized assignment to therapy and that were specifically reporting on 
adverse effects and published in non-advocacy journals.
To access this information, we downloaded all of the citations from the National Library of Medicine (MEDLARS system) that dealt with alternative and complementary 
medicine, from double-blind, randomized control trials that specifically looked for and reported on adverse effects. Studies that involved extracted or purified plant 
toxins (e.g., podophyllotoxin) that were being used in combination with or as chemotherapeutic agents for cancer or were commonly used in conventional medicine 
(e.g., TENS therapy, direct electrical muscle stimulation, conventional chemotherapeutic agents [vincristine]) were excluded.
A total of 121 studies were found. Of these, 27 were found to meet the inclusion criteria and were evaluated for the type of therapy, the duration of the trial, the 
diagnosis and indication, the number in the trial, and the rate of adverse effects as compared with the control group (either conventional therapy or placebo). For 
alternative therapies compared to conventional therapies, we assessed whether the rate of adverse effects was lower, higher, or equal, and for the placebo trials 
whether the therapeutic efficacy of the trial was positive. Twenty-two of the studies involved plant or herbal preparations, two used megadose vitamins, two involved 
Traditional Chinese Medicine, and one involved electromagnetic pulsed fields. Mean duration of the trials was 10.3 weeks with a range of 1 to 52 weeks (sd = 11.4 
weeks). Type of condition ranged from cholesterol reduction and hay fever to nephrotic syndrome and advanced cancer. The average number of subjects enrolled in 
the trials was 89 with a range of 15 to 263 (sd = 73.1) (
Table 5
).

Table 5. Adverse Effects as Found in Hypothesis-Driven, Randomized Double-Blind Controlled Trials
The total number of adverse effects in those studies that reported on patient numbers was 17 of 565 patients, or a rate of 3%. Nine studies compared the 
complementary therapy with a conventional therapy in a direct randomized fashion. Of these, six reported decreased side effects from a complementary therapy. All 
six reported that the complementary therapy was equally efficacious as the conventional therapy for the condition. One study reported increased side effects from the 
complementary therapy. This involved patients treated with the herb  Serona repens for benign prostatic hypertrophy. The two remaining direct, comparative trials 
reported equal rates of adverse effects in both complementary and conventional therapy (
Table 5
). Two studies done in Third World countries using megadoses of 
vitamin A in healthy children are not included in this analysis. Both of these very large trials reported an increased rate of short-term (within 24 hours) vomiting, 
diarrhea, colds, rhinitis, and coughs among those receiving the megadose of vitamin A instead of placebo. Odds ratios were small, in the range of 1.02 to 1.18.
Assessing the use of complementary medical therapies under conditions that minimize indirect adverse effects and maximize an accurate estimate of attribution 
indicates an adverse effect rate of approximately 3%. It is important to note that the duration of these studies was short (mean 10.3 weeks), and the total numbers in 
each group were small (mean n = 45 per arm).
SUMMARY
Complementary medicine must deal seriously with the issue of safety and establish systems for addressing direct, indirect, and definitional issues that impact on the 
risk-benefit ratio of these practices. Purity and standardization of both the products and the training (competence) in these practices are primary. Without assurance 
of a good product and a well-trained practitioner to deliver the therapy, the risk-benefit ratio will be higher than necessary. The prevalence of adverse effects in 
homeopathy, acupuncture, manipulation, herbal products, and mind-body therapies appears to be low, probably lower than comparable therapies in conventional 
medicine. These therapies are also at low risk for acute toxicity if used for short durations in the traditional manner or in controlled trials.
Important exceptions to this general rule exist, however. Especially of concern is possible heavy metal contamination of traditional herbal products. Almost no good 
data exist on the potential long-term adverse effects that might occur from chronic use of these practices. In addition to the issues of training and competence, it 
appears that many alternative diagnostic systems have been inadequately tested and may pose a real risk of exposing individuals to unnecessary anxiety, further 
testing, unnecessary treatment, and excessive costs. Misuse and poisonings do occur with symptomatic rates of approximately 12%. True attributable adverse effect 
rates appear to be in the range of 3%, especially for herbal and vitamin products, and probably less for practices such as homeopathy, acupuncture, and mind/body 
therapies. Safety testing is needed, using appropriate, hypothesis-generated prospective randomized methods with blinded evaluators.
Finally, methods for reporting toxicity and adverse effects need improvement. Current systems used in conventional medicine must be applied with a specific 
understanding of their use and limitations for obtaining accurate information about safety. Information from poison control centers, adverse effects-reporting hotlines, 
postmarketing surveillance studies, preclinical research, and phase I and II trials all have different purposes and limitations for determining the true attributable 
incidence and severity of adverse effects from complementary medical practices. Safety, as well as efficacy, must be evaluated under the conditions of proper use. 
Ultimately, only direct randomized comparative trials can give us the relative risk-benefit ratios needed for judging optimal therapy and the extent of misapplication. In 
the meantime, assessing the risks of misuse, educating the public about proper use, clarifying indications (versus claims) and precautions, and assuring competency 
of practitioners who use and refer for complementary and alternative medicine are the best ways to maximize the safety and benefit of these practices (
106
).
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I
NTRODUCTION:
 C
OMMON
 A
SPECTS OF
 T
RADITIONAL
 H
EALING
 S
YSTEMS
 A
CROSS
 C
ULTURES
Essentials of Complementary and Alternative Medicine