Dietary Supplements Can Cause Liver Damage (cont.)
In the second phase, the drug is given to patients who actually have the condition that the drug is intended to treat. This phase usually involves up to fifty to one hundred patients. Once again, several different doses are tried to determine the effectiveness and toxicity of the various doses. The goal is to find the dose that achieves maximal efficacy with minimal (tolerable) side effects (toxicity).
The third phase usually involves a randomized controlled trial (RCT). In an RCT, each of usually two groups of several hundred patients with the specific condition is randomly assigned to receive one of two treatments. One treatment is the drug that is being evaluated and the other (the control) treatment is either a placebo (an inactive, so-called sugar pill) or the standard (effective) treatment for the specific condition. RCTs are usually carried out in a double blind (masked) fashion. This means that neither the patients nor the physicians caring for and evaluating them know which treatments the individual patients are receiving until the study is completed. A drug safety monitoring board consisting of independent experts that are unrelated to the manufacturer and researchers is usually appointed to oversee the study.
The FDA also reviews the data gathered at each phase to ensure safety before approving the next phase of testing. Then, at the end of phase three, all of the clinical data about the drug are submitted to the FDA for their review. In addition, before the drug can be approved, the FDA brings in an independent panel of experts to review all of the data and materials. Finally, after the drug has received FDA approval and can be prescribed, physicians are obliged to report any instances of possible adverse drug reactions to the FDA sponsored MedWatch program. This last type of monitoring is referred to as post-marketing surveillance.
Ironically, consumers, physicians, and the pharmaceutical industry have sometimes criticized this rigorous evaluation process for drugs. These critics claim that the process causes unnecessary delays in the release of potentially life-saving cures. I feel, however, that these procedures are necessary to safeguard the health of the public. Indeed, despite this demanding process, we still occasionally hear of previously unrecognized, terrible adverse reactions to drugs that already have been approved by the FDA. The diabetic drug, troglitazone (Rezulin), comes to mind.
Troglitazone was considered a novel medication for the treatment of adult onset diabetes. It was not until after the drug had received FDA approval and was in wide use that it became apparent that troglitazone could cause severe liver injury and death. (This tragic story actually came to light through the persistence of an investigative reporter at the LA Times.) The drug has since been removed from the market, but it reminds us that we must be vigilant when taking any medication or supplement.
Back to the dietary health supplements. More research, including clinical studies, is needed on the effectiveness and safety of dietary supplements. As a matter of fact, I am not aware of published data in peer-reviewed medical journals from Phase 1 or Phase 2 studies on these supplements. Nor do I know of randomized controlled trials that have been conducted on dietary supplements to show safety, let alone effectiveness.
On the other hand, it is important to recognize that few manufacturers of health supplements have the resources (money) to carry out valid RCTs because these trials are extremely expensive to run. Moreover, at present, no federal funding for the FDA is available to actively study and monitor the adverse events associated with these supplements. Nevertheless, more regulation of dietary supplements is needed and should be instituted. In this regard, a White House Commission on Complementary and Alternative Medicine (CAM) recently released its somewhat controversial report after two years of study. The good news is that the report called for more funding for valid scientific research on the benefits and hazards of CAM, including dietary supplements.
As a final note, I would like to caution our readers. A drug is a drug, whether it is a medication or a dietary supplement. Moreover, any drug can interact with another drug and result in a serious adverse event. For example ginkgo biloba, which is an herbal product touted to improve memory, can react with ibuprofen (Motrin) to cause severe internal bleeding. Don't go by what is said in an advertisement about a drug or dietary supplement. Rather, look critically at the data about the product. When you see your physicians, let them know about all drugs you are taking, including supplements. In your interest, they should know this. In fact, I have learned to ask, not just once but several times, whether my patients are taking any dietary supplements, especially herbal products. If you don't feel well, stop the supplement immediately and consult a physician. Don't withhold information from your physician about your supplements.
Last Editorial Review: 11/27/2006