In contrast to drugs, dietary supplements do not need FDA approval before being marketed. However, manufacturers need to notify FDA before marketing a product. According to DSHEA, the manufacturer is responsible for determining that the dietary supplements that it manufactures or distributes are safe and that any representations or claims made about them are substantiated by adequate evidence to show that they are not false or misleading; the manufacturers need not provide FDA with evidence that substantiates the safety or purported benefits of their products, either before or after marketing. If a dietary supplement contains a new dietary ingredient that was not sold before October 15, 1994, then the manufacturer is required to notify FDA and demonstrate to FDA before marketing why the ingredient is reasonably expected to be safe for use in a dietary supplement. On June 22, 2007, FDA announced a final rule establishing Current Good Manufacturing Practice requirements for dietary supplements. To ensure the identity, purity, quality, strength, and composition of dietary supplements, those who manufacture, package, or hold dietary supplements must follow these regulations (17). Also, since implementation of the Dietary Supplement and Nonprescription Drug Consumer Protection Act in 2006, manufacturers and distributors of dietary supplements have been required to record and forward to FDA any directly received reports of serious adverse events associated with use of their products. MedWatch Form 3500A (www.fda.gov/downloads/Safety/MedWatch/HowToReport/DownloadForms/ucm082728.pdf) must be completed by the manufacturer or distributor and submitted to FDA. FDA encourages voluntary reporting of adverse events by healthcare professionals, consumers, or patients on MedWatch Form 3500 (www.fda.gov/downloads/Safety/MedWatch/HowToReport/DownloadForms/ucm082725.pdf) (18).

According to FDA, “health claims describe a relationship between a food, food component, or dietary supplement ingredient, and reducing risk of a disease or health-related condition.” In contrast, a structure/function claim describes the process by which the dietary supplement, conventional food, or drug maintains normal functioning of the body and does not need FDA approval before marketing. The data substantiation requirements for the claims described above vary greatly. Before a health claim is authorized, a petition containing the scientific evidence supporting the claim is reviewed by FDA. The systematic review process for a health claim involves defining the relationship between probiotic and disease and identifying relevant studies supporting the claim. Clinical studies are then rated on the basis of quality and strength of evidence. Only data obtained from studies conducted in healthy populations are evaluated because health claims are usually directed at the general population or certain subgroups (e.g. elderly patients). The data supporting a health claim must be published and therefore apply to any product meeting the criteria for the claim (21).

The Consultation recommends that specific health claims on labeling material on probiotic food items be allowed when sufficient scientific evidence is available and that the product manufacturer take responsibility for ensuring that an independent third party reviews and evaluates the scientific evidence. Since development of these guidelines, only a few manufacturers have conducted small, randomized, controlled studies in humans to prove efficacy and safety of their products. Until more stringent regulations are in place, when assessing therapeutic potential for a probiotic product, clinicians must weigh the available evidence as outlined above. In addition, the manufacturer should take on the responsibility (albeit not required by law) of providing guidance to consumers or clinicians about the type and extent of safety assessments that have been conducted on its products.

Several factors constitute excessive and undue risk for development of Saccharomyces fungemia during probiotic administration. These factors are the patient’s immunocompromised state during critical illness, the potential for live yeast spore contamination of healthcare workers’ hands during preparation of the probiotic capsule for administration, and introduction of live yeast from contaminated hands to catheter sites (and patient’s bloodstream).

Probiotic products contain different genera, different species, or even different strains of the same species. Although the safety concerns noted here for S. boulardii may not be extrapolated to other probiotics such as lactobacilli, bifidobacteria, and others, use of any probiotic dietary supplement as a drug in diseased or immunocompromised populations requires specific evaluation of safety in that population.

Albeit rare, serious complications (i.e., fungemia) in other than healthy populations receiving probiotics have been reported in the literature. Specifically, most complications related to the administration of S. boulardii have occurred in immunocompromised or critically ill patients or in those who had central venous catheters serving as a portal of entry of organisms from healthcare workers’ contaminated hands to patients’ bloodstream during administration. Careful risk assessment for patients and proper handling of the probiotic during administration need to be conducted before using probiotics as drugs in institutional settings. Vigilant reporting of adverse events resulting from probiotic use is necessary to establish the safety profile of these agents when they are used in other than healthy populations.