New Article by Simeon Margolis, MD, PHD; Editor of the Johns Hopkins White Papers

Alternative or Complementary Medicine in Middle Aged Men

Let me begin by trying to define alternative medicine - a task that is not as easy as you might think. At one time a common definition of alternative medicine was the use of medical practices that are not taught in American medical schools. But that definition is no longer appropriate. The widespread use of alternative medicine has led most U.S. medical schools to incorporate teaching of at least some aspects of alternative medicine into their curriculum. A more suitable definition may be the following: practices that differ from the conventional medical practices commonly used by most internists, family doctors, and other physicians. Complementary and alternative medicine (CAM) means the use by patients of both alternative and conventional medicine. Since most users of alternative medicine in this country combine it with conventional medicine, I will use the abbreviation CAM for the sake of simplicity.

Before reading on, you should know my own attitude toward alternative medicine. Physicians and organized medicine have been accused of opposing CAM because they fear that alternative medicine threatens their prestige and income. I can only express my own sincere hope that some alternative medicine products and approaches will help to alleviate or cure the many disorders that have not been conquered by conventional medicine. And it is hard for me to believe that any self-respecting physician would reject any form of treatment that would alleviate discomfort or prolong life for his or her patients. For herbal products, there is real hope for success since so many potent prescription remedies, such as aspirin and digitalis, to name just two of many, were first discovered in plants or other botanicals.

It is extremely upsetting to me, however, to see people lured by outlandish claims and promotions into investing large amounts of money and hope into unproven, and possibly dangerous, practices. I generally do not favor the use of any aspect of alternative medicine until their safety and effectiveness have been proven. In this regard my position is in concert with those of the editors of two major medical journals: the Journal of the American Medical Association (JAMA) and the New England Journal of Medicine. For example, the editors of JAMA have made the following statements:

There is no alternative medicine. There is only scientifically proven, evidence based medicine supported by solid data, or unproven medicine for which scientific evidence is lacking. Most alternative therapies have not been evaluated using rigorously conducted scientific tests of efficacy. Until solid evidence is available that demonstrates the safety, efficacy, and effectiveness of specific alternative medicine interventions, uncritical acceptance of untested and unproven alternative medicine therapies must stop.

How is this scientific evidence to be obtained? Promoters of alternative methods or products are unlikely to supply the answers. They are doing a booming business, so why should they invest the time and large amounts of money needed to carry out studies that might show their product is ineffective or unsafe? And even if both safety and efficacy are proven in one of their studies, they will not profit from the results because they are unlikely to gain patent protection for their product. The Office of Alternative Medicine was established at the National Institutes of Health in 1990 as a possible way to solve this dilemma. Although little gain is evident thus far from their research investments, their sponsorship of scientific studies of alternative medicine shows promise. Their studies, however, face many problems. The biggest problem is how to choose, from the literally thousands of forms of alternative medicine, which ones to investigate with the expenditure of large amounts of taxpayer money. A second huge problem is that our present laws allow manufacturers of a product to continue selling it even if careful studies show that it is worthless.

Table 1 lists the more common types of alternative medicine, though many question whether some of them, like prayer, should be included. Surveys have shown that almost half of Americans use some form of CAM every year, and that its use has grown steadily since the first large survey in 1990. CAM is used more often by men who are better educated and have higher incomes than average. Among the many reasons for the popularity of CAM are
o the expectation of better health and well being, often in the absence of any illness;
o unhappiness with physicians who often appear more interested in finding and treating illnesses than in preventing them, or who are unwilling or unable to take the time to listen to their patients;
o lack of emotional or spiritual support from conventional treatment;
o failure of conventional medical practices to alleviate symptoms or cure an illness;
o fear of the side effects or risks of conventional medications and procedures;
o promises of spectacular benefits from CAM, proclaimed in media ads (including now the Internet) or described by friends and relatives;
o desire for natural remedies; and
o saving the time and money involved in seeing a doctor.

Table 1

(Some) Approaches used in alternative medicine

Two arguments are frequently put forth by advocates of CAM in support of the benefits of CAM practices. One is that they are natural and therefore safe compared to the drugs used in conventional medicine. But natural is not always safe, as shown, for example, by hurricanes, tornadoes, floods, earthquakes, dangerous mushrooms, and poison ivy. And man-made chemicals are not necessarily any more dangerous than the natural chemicals found in plants. A second argument put forth for CAM practices is that many have been used for thousands of years. But long usage does not prove that a practice is effective. Blood letting is an example of an ineffective and dangerous practice that had been used to treat many illnesses for centuries - since the time of Hippocrates and the ancient Greeks.

It is important to recognize that there is no solid scientific proof for the efficacy of most forms of alternative medicine. In addition, CAM can have both direct and indirect harmful effects. (Table 2) Direct harm can result from the presence of dangerous natural chemicals, contaminants, and added prescription drugs in some dietary supplements, as well as possible adverse interactions between herbal supplement and other herbs or prescription drugs. One potentially harmful indirect effect is a dangerous delay in the initiation of effective treatments while ineffective alternative practices are used alone to treat serious illnesses that could be cured if conventional medical practices were started in a timely fashion. Another indirect harmful effect is the money wasted on useless products and practices (many billions of dollars in the US).

                             Direct toxicity
Lack of documented toxicity does not equal safety
            Not true that "natural" substances are safe

                             Indirect harm
Delayed use of proven treatments
            Unnecessary costs

Most forms of CAM fall into three general categories: physical manipulations, dietary supplements, and mind-body interventions, such as meditation and prayer. Concerning this last category, as of now there is no convincing evidence that these practices cure any disease or prolong life in people with serious illnesses like cancer. Yet, many people are certain that prayer or meditation alleviates the constant stresses of modern life and improves their well-being. These practices are safe, and my advice is to follow them if they work for you. The rest of this presentation will briefly address two forms of physical manipulation (chiropractic and acupuncture), but focus primarily on dietary supplements.

Chiropractic
Chiropractic is a system of therapy based on the belief that many diseases are caused by abnormalities in the alignment of the spinal column and that these disorders can be cured by manipulations to adjust and correct these abnormalities. Acute low back pain is one of the most frequent problems for which people seek treatment is, and this complaint is probably the most common reason why people turn to chiropractic. In most instances attacks of acute low back pain get better without any specific treatment at all. As a result, it has been difficult to determine whether chiropractic is as good or better than conventional treatments - or even no treatment at all. Nonetheless, chiropractic manipulations appear to be at least as effective, and probably less expensive, for the relief of acute low back pain as the efforts of family doctors, internists, and orthopedic surgeons. The Agency for Health Care Policy and Research (AHCPR) and the U.S. Department of Health and Human Services have stated spinal manipulation is recommended and efficacious for at least the first month for acute low back pain problems in the adult. Less certain is the value of chiropractic for chronic low back pain, pain that has persisted for three months or longer.

Of concern, however, is the promotion of chiropractic treatments for such conditions as earaches and kidney disorders, which seem highly unlikely to respond to spinal manipulation. Many chiropractors have also added sales of dietary supplements to the long-standing practice of spinal manipulation.

Acupuncture
Acupuncture involves various manipulations of fine needles placed at specific sites under the skin to alleviate pain or other symptoms and to treat many illnesses. Acupuncture, which originated in China and has been practiced there for thousands of years, has seen an upsurge of popularity in this country. Table 3 shows the conclusions concerning the safety and efficacy of acupuncture reached by a conference held in 1997 by the National Institutes of Health. There seems little doubt that acupuncture is safe, but it has been difficult to determine its effectiveness in alleviating symptoms and treating various disorders. Those attending the conference noted that there are only a small number of high quality, controlled research studies on acupuncture - and to be fair, it is not easy to figure out how to control for a procedure that inserts needles. From the limited evidence then available, the effectiveness of acupuncture seemed to vary over a wide range for different health problems: from ineffective for helping people to stop smoking to a high likelihood of success for treating the nausea and vomiting that occurs in the post-operative period, during chemotherapy, and in the early months of pregnancy.

Table 3

An NIH Consensus Development Statement Concerning Acupuncture

Safety

The procedure is safe

Efficacy

There is a paucity of high-quality research assessing its efficacy

Clear evidence for benefits for the nausea and vomiting that occurs in the post-operative period and in association with chemotherapy, and possibly for the pain during child birth

Some evidence supports benefits for postoperative dental pain

Reasonable studies suggest alleviation of:pain from menstrual cramps, tennis elbow, and fibromyalgia

Evidence is less convincing for treatment of addictions, stroke, headache, carpal tunnel syndrome, and osteoarthritis

No efficacy shown for smoking cessation

Dietary supplements
In 1994 Congress passed the Dietary Supplement Health Education Act (DSHEA), which broadly defines herbs, vitamins, and many other substances as dietary supplements. DSHEA has prevented the Food and Drug Administration (FDA) from overseeing the composition, safety, and effectiveness of these supplements. As a result, dietary supplements may contain toxic plant chemicals or added drugs; the amount of a particular ingredient in a given product often varies from one manufacturer to another, and even in different lots made by the same manufacturer; and the label may not match the content of the bottle. Although manufacturers can not claim that a supplement treats or cures a specific disorder, such as coronary heart disease, they can state that their product affects the structure or function of the body, promotes heart health for example, without the need to provide any evidence to support the accuracy of their claim. In addition, stores selling a dietary supplement are allowed to place next to the product a brochure which claims it does prevent or treat a specific disease. The FDA can only ban the sale of a product if harmful effects can be proven. Because the sale of dietary supplements is a big business in the US - in 2001 17.8 billion dollars were spent on dietary supplements, with $4.2 billion going for herbs and other botanicals - manufacturers have spent large sums in ads and lobbying to prevent any change in the laws governing these supplements.

Safety (Table 4)
Table 4

                        Problems with herbal products

Inaccurate labeling

Plant sources may be misidentified
Amount and type of content varies from batch to batch
           and from one manufacturer to another

Safety

Some natural chemicals are harmful
Contamination of products with
            Infectious agents
            Bacterial toxins
            Pesticides
            Heavy metals
Adulteration by adding prescription drugs

Adverse effects
Like prescription drugs, herbs may contain chemical substances with powerful biological effects. Some troublesome side effects of a few common herbal products are listed in Table 5. Of greater concern are the more serious adverse effects of herbal products. Some herbs, such as chaparral, germander, and others have long been recognized to contain plant-made, natural chemicals that can damage the liver. Over the course of the past year the FDA has issued warnings - remember the agency is not allowed to ban a dietary supplement without more evidence for its harmful effects - that several commonly used herbs, comfrey, kava, and herbs containing aristolochic acid, are associated with an increased risk of cancer and damage to the liver and kidneys.

Table 5*

Adverse effects reported for selected herbal products

*None of these side effects is common, and they all tend to occur with high doses of the herbal preparation.

Composition of herbal products

Herbal remedies may be contaminated with bacteria and their toxic products, pesticides, and dangerous heavy metals. A report from the California Department of Health in 1998 indicated that 10 to 15 percent of Asian patent medicines contained the heavy metals lead, mercury, or arsenic. In addition, another study reported in 2000 that manufacturers had adulterated 23 percent of the traditional Chinese herbs they tested by adding prescription drugs to products claimed to contain only natural ingredients. The most commonly added drugs that have been found in herbal products include the diuretic hydrocholothiazide, pain medications (indomethacin, acetaminophen, and phenylbutazone), the glucose-lowering drug glyburide, sildenafil (Viagra) for erectile dysfunction, colchicine for the treatment of gout, adrenal steroids, the anti-depressant alprazolam, and fenfluramine, a banned appetite suppressant. No wonder some of these herbs work, you might think.

Interactions with prescription drugs or other supplements

Another risk of herbal products is the potential for interactions with other herbs or with prescription drugs to delay or prevent their therapeutic effects. The number of possible interactions with conventional drugs is too large to detail. Some examples include the following:
o St. John's wort decreases blood levels of cyclosporine, with possible rejection of transplants, and drugs used to treat HIV
o ginkgo biloba can cause bleeding reactions when taken with aspirin or coumadin
o garlic reduces blood levels of the HIV drugs ritonavir and saquinavir

Problems associated with two herbal supplements

PC-SPES The patented product PC-SPES, a combination of eight Chinese herbs, had shown some promise in the treatment of prostate cancer. Men taking PC-SPES were shocked during the past year when it was removed from the market because analyses showed that it contained various combinations of the prescription drugs diethylstilbestrol, indomethacin, and warfarin. Now it is unclear whether the herbs or the additives brought some benefits against the cancer.

Ma huang and ephedra: An extract of the Chinese herb ma huang is a component of many supplements that are used to promote weight loss or to increase energy. Ma huang contains ephedra (ephedrine) which is chemically similar to the dangerous amphetamine drugs and to the hormone epinephrine (adrenalin) that is naturally produced by the adrenal glands. Like epinephrine, ephedrine can speed the heart rate and raise blood pressure. The FDA has received more than a thousand adverse event reports of fatal heart attacks, strokes, seizures, and heart rhythm disturbances from the use of products containing ephedrine. Even though FDA banned prescription pills containing ephedrine plus caffeine used for weight loss more than 20 years ago, DSHEA ties their hands regarding a ban of dietary supplements containing ephedrine. Instead, the FDA has asked the Justice Department to initiate a criminal investigation of the adverse events reported to Metabolife International, the leading manufacturer of weight loss products containing ephedra. Their billion dollars in sales has naturally led Metabolife to claim that the many reports of adverse effects are anecdotal and do not prove that these events were caused by the ephedrine in their products. Of course, the company has not carried out any studies to prove that their products are either safe or effective, criteria that must be met before FDA will approve a prescription drug. Leaving adverse effects aside, people taking weight loss supplements, or following dietary programs for weight loss, need to recognize that more than 90% of those who lose weight with diet supplements, or in any other way, regain the lost weight, or more, within a year or two.

Ephedrine-containing products are also widely advertised and used to boost energy Ephedrine does enhance alertness and appears to increase energy, just as the release of epinephrine has these desirable effects when we are confronted with an emergency situation. But is it wise or safe for teenagers to take an ephedrine fix before a football game?

Effectiveness
All of the potential disadvantages of dietary supplements might be acceptable if they were proven to be effective. The gold standard to show the effectiveness of a drug (or dietary supplement) is a randomized, double-blind trial - one that compares the test substance in a random fashion with a placebo (sugar pill) or a drug known to be effective in treating the disorder, when neither the physician nor the subject knows whether the active material or placebo is taken. Few dietary supplements have been subjected to such a test. The limited studies that have been done are often poorly designed, contain too few subjects, or are carried out for too short a time. Instead, the purported effectiveness of dietary supplements is based on a number of small, short studies. In the case of some supplements a systematic review or a meta-analysis has combined the published results of a number of such studies, most of which are inconclusive on their own, to suggest the effectiveness of a supplement. Another problem with such analyses is that studies are often not published if they fail to show any benefits from a supplement. It is evident that improper conclusions can be reached by combining the results of inadequate studies and from the inablility to include the results of unpublished studies. As computer people often say about poor data,

Agarbage in = garbage out.

Limitations of time and space allow consideration of the effectiveness of only a few of the large number of available supplements.

Gingko biloba
Two long-term, randomized trials showed some modest benefit of Gingko biloba for the treatment of Alzheimers disease, but these results were not corroborated in another study. Many otherwise healthy older people have been taking gingko to improve memory. In a careful randomized trial of healthy men and women over the age of 65, researchers administered gingko to 115 subjects and a placebo to another 115 subjects . After 6 weeks no differences were detected between the two groups in a number of different tests of learning, memory, attention, concentration, or other aspects of mental function. Though more studies are needed, it appears that gingko may produce some short-lived improvements in patients with Alzheimers disease, but the herb does not improve the memory loss or decline in mental performance that may accompany normal aging.

St. John's wort
A number of studies and systematic reviews suggest that St. John's wort is more effective than a placebo for the treatment of mild to moderate depression. A guideline from the American College of Physicians - American Society of Internal Medicine even stated that St. John's wort might be considered for the short-term treatment of acute mild depression. Two new rigorous trials of people with major depression showed that St. John's wort was no more effective than placebo in improving the symptoms of depression. (A troublesome finding of one of these trials was that a commonly used antidepressant drug (sertraline) was no more effective than placebo either.) While St. John's wort may help people with mild depression, it does not appear useful for those with severe depression, which is an extremely debilitating and often life-threatening disease. The concern is that depressed people may take an over-the-counter preparation of St. John's wort without recognizing that the severity of their illness requires professional help and possibly more powerful medication.

Echinacea
Despite the lack of agreement on its effectiveness, echinacea has recently become almost as popular as chicken soup for the treatment of the common cold. A recent rigorous trial examined the effect of an echinacea preparation over a 10 day period, beginning on the day of onset, in 148 college students with a typical common cold. They found no significant differences between echinacea and placebo in the severity or duration of cold symptoms. It is, of course, possible that echinacea would limit the discomfort of a cold in older or less health individuals. (Earlier studies had shown that two other treatments, zinc and large doses of vitamin C, did not relieve the symptoms of a cold either.)

Hormone replacement
A growing trend is the replacement of natural hormones - growth hormone, testosterone, and DHEA, that decline as men grow older. Growth hormone replacement does increase muscle mass that declines with age and decreases the fat stores that increase with age. Growth hormone replacement has not met the promise of improving mental function and is often associated with a rise in blood pressure and joint pains. Even worse, the Internet is laden with advertisements for growth hormone pills; but they cannot work because, to be effective, growth hormone must be injected, at a cost of about $1000 a month. DHEA pills do increase blood levels of the hormone, but there is as yet no proof for the multiple benefits of DHEA that are promoted in advertisements and books. It is unclear whether testosterone will rejuvenate older men, but its use is accompanied by an increased risk of an enlarged prostate (benign prostatic hyperplasia) and prostate cancer.

Bottom line
Concerning dietary supplements, the bottom line is beware. Beware that they, like other aspects of CAM, may not work, are costly, can cause adverse effects on their own, and may interfere with the action of other medications. It is most important to tell your doctors about your use of any dietary supplement or other form of alternative medicine. Even better, bring all of your supplements along when you visit your doctor. Your doctors may not ask what you are taking. They may even recommend that you stop, but it is still important for them to know everything you are doing for your health and well being. Important for the future of dietary supplements is the need to make their regulation possible through changes in the present laws tht govern them. Urgently needed, as well, is much more proper research to allow the American public to select those products that are proven to be effective and safe.