Authors' Response to Letter

Abstract

Reply: We appreciate the interest of Drs Saavedra and Yolken and their thoughts regarding probiotic infant formula and focusing their discussion on Bifidobacteria species. We would like to address their comments in the following paragraphs. Regarding the analogy with antibiotics, perhaps a more appropriate comparison is with live vaccines, in which such a concept of general safety is highly relevant. The comments regarding safety issues in our guidelines are supported by evidence, with relevant citations provided. The market for probiotics continues to rely heavily on health claims made by manufacturers and retailers. The comments brought by a commercial entity interested in bringing Bifidobacterium lactis strain Bb12 to market in infant formula, although important, can pose a conflict of interest but is an interesting concept and worthy of investigation. As Drs Saavedra and Yolken rightfully point out, there is a long history of ingestion of probiotic-type organisms in foods (1,2), but only recently have high-dose probiotic preparations become available for ingestion. The different forms of probiotics can vary greatly (3). Comparison studies of freeze-dried probiotic preparations versus foods naturally containing probiotics or foods that have had probiotics added are lacking. Thus, there remains an unmet need for appropriate and adequate studies in the area of health benefits of probiotics. The safety and use of probiotics in dietetic products for infants was beyond the scope of our review (4), and as stated in our document, the reader is referred to a document written by the Nutrition Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (5), the conclusion of which was that there was no evidence at that time to support long-term clinical benefit of probiotic infant formulae. We feel the comment that “the greatest evidence of safe use in infants and children, including high-risk populations, has accumulated for Bifidobacteria, etc.” is not substantiated based on the presently published evidence. There are a few studies in which safety was a primary study outcome. Drs Saavedra and Yolken are to be commended for their interest to investigate the safety of probiotics (6). Clearly, more studies are needed so that large numbers of infants are followed over longer periods of time. However, the use of Bifidobacteria species in immune-compromised children has not been adequately studied, and thus claims of safety in high-risk populations await confirmation. The study cited in the letter (7), which was funded by Nestlé Nutrition, refers to the use of this probiotic agent in infants born to mothers with HIV, but only in abstract form and without safety data. With regard to the regulatory oversight of commercially available probiotics, there are important differences in regulation of claims regarding nutritional versus pharmaceutical products, with the latter being considerably more rigorous. Coming back to the authors' analogy with antibiotics (or more appropriately vaccines), no antibiotic or live vaccine could be marketed to the public in the way that probiotics are being marketed with the comparable current level of evidence, or lack thereof. The US Food and Drug Administration (FDA) considers articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease as drugs under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (21 USC § 321[g][1][B]). According to a recent communication with the FDA, there is no probiotic preparation of any form that has been approved by the FDA as a drug in the United States. Therefore, it will remain the sole responsibility of the prescribing clinician to understand the various strains and preparations commercially available and be able to advise patients accordingly. Finally, the discussion implying that the incorporation of these bacteria into daily foods may decrease the incidence of autoimmune diseases is interesting, but highly speculative.