Herbal Products: Use with caution

(6/1/10)- A recently released report, prepared by the Government Accountability Office, indicated that nearly all of the herbal dietary supplements that they tested contained trace amount of lead and other contaminants. The report also indicated that the sellers of these products made illegal false claims as to the curative abilities of their products.

The report was prepared for the Senate Special Committee on Aging which is chaired by Herb Kohl, a Democrat from Wisconsin. The levels of heavy metals found in the products did not exceed thresholds considered dangerous.

Sixteen of the forty supplements tested contained pesticide residues that appeared to exceed legal limits, and 8 of the products made illegal health claims.

Any product that claims to treat, cure, prevent or mitigate a disease is considered a drug and must go through strict regulatory reviews.

Dr. Todd Cooperman, president of Consumer Lab.com, a company that has tested over 2,000 dietary supplements made by more than 300 manufacturers testified at the hearing. His company found that about one in four of the products that his company tested had quality problems.

Nearly all of the supplement suppliers have located overseas, mostly in China. The FDA almost never inspects their plants.

(4/18/05)- Judge Tena Campbell of the U.S. District Court in Salt Lake City, Utah has overturned the FDA's ban on the sale of products that contained the herbal supplement ephedra. The ban went into effect in April 2004, and although this ruling only applies to the state of Utah, its implications could spread to the 49 other states.

Judge Campbell ruled that the FDA had failed to prove that the small amount of ephedra that was included in a herbal supplement manufactured by Nutracell Corporation of Park City, Utah was dangerous. Without proving that a supplement is dangerous, the agency lacks the authority under the law covering herbal supplements that was enacted in 1994. Judge Campbell called for the FDA to devise new rules for ephedra.

Ephedra came into the limelight when Steve Bechler, a 23-year-old pitcher with the Baltimore Orioles collapsed during a workout at Fort Lauderdale Stadium on February 16 2003, and died the next day. The FDA has not as yet decided whether or not to appeal the ruling.

Under the 1994 dietary supplements are defined as food, which is assumed to be safe unless federal regulators can prove otherwise. Because the research on ephedrta is incomplete, the FDA could not prove that low doses of the supplement were unsafe. Under the 1994 the burden of proof is on the federal agency to prove that the supplement is unsafe. The burden is not on the manufacturer to prove that the benefits of a supplement outweigh the risks associated with it.

(7/1/04)-The World Health Organization has called on governments around the world to tighten their regulations for overseeing the herbal products industry. The growing usage of natural medicines is posing an increasing risk to global health. "Natural doesn't mean safe," says Xiaorui Zhang, coordinator of Traditional Medicine at the World Health Organization in Geneva.

A survey published by the National Center for Complementary and Alternative Medicine, a division of the HIH, found that about 35% if American adults use some form of alternative medicine or treatment. Some countries including Germany, China, Canada and Australia regulate at least some herbal products as they do regular drugs. In the U.S., herbal products are considered dietary supplements, not drugs, so they are not subject to the stringent rules imposed by the FDA

One study has concluded that St. John's Wort compromises the cancer drug Gleevec, potentially increasing the patients risk for a cancer relapse. Ginko biloba may lead to spontaneous bleeding if it is combined with blood-thinning drugs. Some fortified foods like calcium enriched orange juice can interfere with antibiotics, according to a study published last year in the Journal of Clinical Pharmacology.

The FDA has sent warning letters to about two dozen companies that make and distribute products containing androstenedione (andro), asking them to stop selling the supplements. Mark McGwire, the former St. Louis Cardinal home run slugger admitted using it back when he was an active ballplayer. The Bush administration will conduct a major crackdown on the steroid-like substance.

The planned enforcement campaign could include seeking court permission to seize the merchandise if the manufacturers do not comply. The NCAA, the International Olympic Committee and the National Football League have already banned andro, but so far Major League Baseball has failed to act on this matter. Sales of andro have dropped to about $15 million in 2003 from $55 million in 2001, but there are other formulations of steroids that have grown to replace it.

Before companies can sell a new dietary-supplement ingredient that was not available before 1994, they are required to give the FDA 75 days advance notice along with evidence that the product is safe. While andro does not meet the legal definition of an anabolic steroid, it is believed to produce similar effects. Anaboic steroids are versions of testerone, and as such are considered controlled substances that are not supposed to be sold over-the-counter Senators Orin Hatch, (Rep.-Utah) and Joseph Biden (Dem.-Del.) have introduced a bill in Congress that would place andro and other steroid precursors uncer the same restrictions that apply to anabolic steroids.

The FDA has announced that the agency will step up its scrutiny of the health effects of a number of other herbal supplements besides ephedra. Among them are bitter orange, or citrus aurantium, which is being marketed as a substitute of ephedra. Others include usnic acid, whichis derived from lichens,and has been used as a weight loss aid, and aristolochic acid, which is sold for weight loss and to alleviate gastrointestinal problems.

The agency will move more aggressively to proactively gather data it needs in order to measure if a herbal supplement poses serious health risks. In additional to gathering information about adverse reactions to supplements the agency will also gather pharmacological evidence and clinical studies from small controlled groupings.

The FDA has decided that there is sufficient evidence to warrant the banning of ephedra since it poses "an unreasonable risk to the public health". This will be the first time that the FDA bans a dietary supplement since 1994, when Congress enacted a law to restrict the agency's ability to do so in connection with herbal products. Tommy Thompson, the secretary of the Department of Health and Human Services said that he fully expects a court challenge to the ban from the manufacturers of ephedra. The ban will not take effect for several months.

Dietary supplements are not subject to FDA review before they come to market. Manufacturers can market dietary supplements as long as they do not make claims that their products affect the "structure or function" of the body. California, Illinois and New York have already banned ephedra as does the National Football League.

The federal act of 1994 requires that the FDA must be able to prove that a dietary supplement poses an unreasonable risk to the public health before it can be banned. The FDA does not have the power to require that the manufacturers of dietary supplements conduct safety studies before bringing the product to market.

The burden of proof is on the FDA to prove scientifically that a product is unsafe. In order to make its case against ephedra, the agency reviewed 16,000 reports of adverse reactions to the supplement. The agency commissioned a study to be done by the RAND Corporation, a nonprofit research agency. The FDA invited comments from the public on this matter. The RAND study found about 20 "sentinel events", including heart attacks, stroke and sudden death.

The ban will take effect 60 days after the FDA publishes a regulation stating its reasons for withdrawing ephedra from the market. Publication is not expected for several months but the agency has advised all manufacturers of the supplement that they will have to stop manufacturing the product shortly.

The sports world was "shocked" by the news of the death of a young Baltimore Oriole pitcher named Steve Bechler. In order to gain a spot on the pitching staff of the Orioles, Bechler was using ephedra for weight reduction. Ephedra has been implicated in his death. Three years ago a University of Arkansas pharmacologist, found that half the brand-name ephedra products had other drugs mixed in to the pills that should have been on the label. Recently, warnings had been published about the adverse effects of this dietary supplement.

On Friday, March 3, 2003, the FDA took a step that would force manufacturers of dietary supplements to clean up their act by making clear and accurately labeled products. They published a 547-page document detailing new regulations for the dietary supplement industry. A 90-day period of comments from industry and consumers now takes place before any action can be done on the matter. After that period, the rules become binding on the manufacturers of the supplements and some of the shoddy companies among the1000 domestic and foreign companies that make the dietary supplements may be put out of business.

Consumers should be aware that these regulations would not tell consumers whether the supplements are dangerous or even if they work. The regulations that the FDA published stated rules for designing and building plants, for controlling quality, testing ingredients, keeping detailed records and handling consumer complaints about harm done by the products. There are no requirements to show that it is safe or effective. Hopefully, it would put a stop to many of the gross errors that consumer groups have pointed out to the FDA.

In the report published on March 3, 2003, the FDA cited specific cases of mislabeled and contaminated drugs: a product contained lead; a company recalled a niacin product when it was found to have serious side effects including heart attack, vomiting and liver damage due to a manufacturing mistake; five of 18 soy or red clover products tested by a private laboratory had as little as half the amounts of isoflavones they claimed. We previously reported on a similar type of study of St. John's wort that indicated the same improper listing of the active ingredients.

A new Web site from Memorial Sloan Kettering offers consumers a fast, free way to find out about supplement safety. The site, www.mskcc.org/aboutherbs , contains information on about 140 products and is updated regularly. The National Institute of Health's Office of Dietary Supplements also posts recent safety warnings on its Web site, http://dietary-supplements.info.nih.gov as does the National Center for Complementary and Alternative Medicine at http://nccam.nih.gov/health/ . The USDA Food and Nutrition Center's Web site www.nal.usda.gov offers a "dietary supplements resource list" of books, magazines and Web sites about the science behind supplements.

Dietary supplements are a $10 billion to $15 billion- industry, with indications that more than 6 out of 10 individuals over 65 take such supplements. The FDA is the agency that is empowered to control the quality of the products. With this regulation they are moving strongly in the direction of providing the consumer protection from improper labeling of contents. They still have to go further to ensure/guarantee that the consumer will not be defrauded or even injured because the supplement does not work.

According to a research study from the psychology and mathematics departments at Williams College in Williamstown, Mass. Ginko Biloboa "did not produce objective benefit" in any of the 14 standard tests of concentration and memory skills that were used on 219 older adults over a six-week test period.

The study was performed on healthy individuals who were 60 years or older. Patients were either given the Biloboa or a placebo on a randomized basis. The research was funded in part by the National Institute on Aging in Bethesda, Md.

According to a study done at the Rotterdam Cancer Institute in the Netherlands, it was determined that St. John's wort decreased blood levels of the chemotherapy drug, Camptosar, by 40 percent. Dr. Ron Mathijssen, the leader of the study asserted that the herb reduced the effectiveness of the drug for several weeks, even after the patient stopped taking the herb.

Biological activity of a herbal product depends not only on its active constituents but also on its inactive ones. Pharmacologically inactive substances can interfere with or enhance the potency of active compounds. An example of this can be found in the following chart, which lists the active constituents of St. John’s wort as well as the biochemical class these constituents belong within. Hyperforin is now considered the most active substance in St. John’s wort, but the other constituents may play a role in its action. Consider also that the concentration of these constituents vary among the species of St. John’s wort and is also affected by a variety of factors such as growing conditions, time of harvest, preparation of material and exposure to light.

Biochemical Class	Active Constituents
Naphthodianthrones	Hypericin, Pseudohypericin
Phloroglucinol Derivatives	Hyperforin, Adhyperforin
Xanthones	Kielcorin, Norathyriol
Essential Oils	Monoterpenes, Alcohols
Flavonoids	Quercetin, Hyperoside, Quercitrin, Isoquercitin
Procyanides	Catechin, Tannic acid
Amino Acids	Cysteine, Glutamine, Leucine

Valerian is another product in which the active components responsible for its potential therapeutic effects have yet to be identified. There are approximately 170 pink-flowered perennial valerian plants that grow in temperate regions of North America, Europe and Asia. There is evidence of different effects from Japanese, Chinese, Nepalese and European Valerian; Japanese valerian contains 4% to 8% volatile oil, but European valerian usually contains 0.5% to1% volatile oil. The mode of chemical processing also influences the constituents of the resulting product and its effect. It has been speculated that multiple constituents (valepotriates, volatile oils, eugenyl esters, and valerenic) are responsible for its sedative effects. Valerenic acid and eugenyl esters have muscle relaxant effects. Confusing, and no wonder the primary physician suggest caution in its use.

All research into safety and efficacy of herbal drugs is on a weak footing because of the variability of the product. (See our articles on St. John’s wort on this topic.) Nonetheless, published data tends to support a medicinal role for saw palmetto and St. John’s wort, but are weaker for gingko biloba and are contradictory for echinacea. (Chart below identifies some of the key findings to date.) Just be careful in how you use such drugs, in the dame way you would be careful as to how you use prescribed drugs.

Medical concerns arise when sicker patients use herbal drugs, when more potent herbs are used and when other drugs are used concurrently. Pharmaceutical companies view herbal drugs and supplements as unfair competition and readily cite studies which question the contents of the over-the counter herbal drug or supplements. They regularly point out the fact that these nutritional supplements and herbal drugs do not have to go through the rigorous standards of development, efficacy and time that prescription drugs must follow in order to be approved by the FDA. Efficacy studies tell us if the medication has ability greater than chance to improve the specific condition it is being used for. These studies involved multiple steps/phases, lasting 7-9 years. Effectiveness studies tell us whether the drug is able to achieve its mission in a more realistic condition.

The dividing line between food and drugs is less clear than it once was. For example, it is known that grapefruit juice may interact with certain medications because it inhibits a form of cytochrome P450, an enzymatic system that contributes to the metabolism of many basic drugs in the liver. Metabolism of a drug by the cytochromes P450 is often required before the drug can be readily eliminated from the body. The bioflavonoids in grapefruit juice (naringenins and /or coumarins) inhibit intestinal P450 CYP3A4 and may cause clinically significant drug interactions with felodipine, cyclosporine, terfenadine, and diazepam.

A thoughtful program must be developed that puts consumer needs first while respecting those of growers and manufacturers. Since the elderly use herbal products more than any other cohort group, there must be a commitment to invest whatever is needed to protect this population and enable the elderly to experience a good old age. This calls for equivalent standards to those applied to medicinal drugs, as well as consistency of content of each batch of herbal products produced by the manufacturer. (See specific reference to this in St. John’s wort part II)

Standards need to include relevant assays of biological potency in addition to meaningful determinants of the content in active ingredients in light of fact that specific washing and drying can significantly change the concentration of the chemical constituents.

Adequate and well-controlled clinical trials can then proceed to establish the role of herbal drugs in disease management and drug interactions studies can identify potential problems with agents that are likely to be used by people who are taking multiple drugs for multiple diseases.

The following table summarizes results of double-blind randomized controlled clinical trials of four herbal drugs. It is from Currier SJ, Johnston PD & Gorelick KJ. Herbal Medicine Science & Medicine 2000; 7(1).

The citations below are the source of the data and conclusions used in this article.

Saw palmetto: Timothy J. Wilt et al. JAMA. 1998; 280:1604-1609
St. John’s wort: Klaus Linde et al. BMJ 1996; 313:253-258.
Gingko biloba: Pierre L. LeBass et al. JAMA 1997; 278:1327-1332.
A.Kanowski et al. Pharmcopsychology 1996; 29:47-56
K. Werner et al. Human Psychopharmacology 1987; 2:151-169
Echinacea: Dieter Melchart et al. Archives of Family Medicine 1998; 7:541-545.
A.Melchart et al. J of Alternative & Complementary Medicine 1995; 1:145-160
Wolfram Grimm and Hans-Helge Muller Amer J of Med. 1999; 106:138-143

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Herbal drug	Number of studies	Total No. of Patients	Key findings
Saw Palmetto	18	2939	Improved symptoms of prostate related disorders, minimal side effects (less sexual dysfunction than with fluoxetine)
St. John’s wort	23	1757	Significant improvement in clinical depression: few side effects
Gingko biloba	3	597	Improved memory; stable or slowed deterioration in Alzheimer’s disease; few side effects
Echinacea	3	545	Contradictory report of efficacy in prevention of upper respiratory infections; possible shortening of duration and improvement of upper respiratory symptoms; few side effects.