Probiotics and Lessons Learned from Vitamin C
Limes, oranges, and lemons were probably the first clinically documented functional foods. James Lind noted in 1742 that scurvy—a common malady leading to significant loss of life during lengthy voyages at sea—could be cured and prevented by the administration of these fruits. Unfortunately, it was another 62 years before the British navy adopted the use of “limes” to avoid scurvy.
Modern science suggests that there is more to citrus fruits than their antiscorbutic properties. Similarly, there appears to be more to fermented milk products, especially the cultures used in many fermentation processes, than what Eli Metchnikoff discovered a century ago. A contemporary definition of probiotics indicates that these are living microorganisms, using lactic acid bacteria, that when consumed in sufficient quantities can provide health benefits.
Major challenges confronting the scientific community and regulatory agencies relative to these bacteria are strain identification, mechanisms of action, and establishment of clinically relevant bio-markers of health. Emerging studies addressing these challenges now include proteomics, metabolomics, and genomics as tools to investigate and support effects of body functions relative to novel food ingredients, such as probiotics. The clinical aspects, including possible modulation of the inflammatory components of cardiovascular disease, atopy, digestive disorders, cancer, and diabetes, lie far beyond the traditional expectations of lactose digestibility, microflora modulation, and diarrhea management.
Despite a relative paucity of clinical interest, between 1999 and 2003 nearly 200 randomized and nonrandomized clinical trials with Lactobacillus and approximately 40 such studies with Bifidobacterium were published.
Based on the emerging scientific interest and clinical evidence, the World Health Organization/Food Agriculture Organization published two guidelines that provide scientific advice in relation to the nutritional and safety assessment of probiotics, and general guidance for the assessment of the pathogenicity, toxicity, allergencity, and other specific features relevant to their nutritional properties or safety. These guidelines may be found at http://who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf and www.fao.org/es/esn/food/foodandfood_probio_en.stm.
Our own clinical experience affirms the utility of probiotic strains (readily available in the retail setting) among patients presenting routine gastrointestinal disorders such as irritable bowel syndrome (IBS) and antibiotic-associated diarrhea. In more serious illness such as inflammatory bowel disease (IBD), the introduction of probiotics may contribute significantly to management of the pathology.
The potential implications of probiotics as adjuncts to conventional pharmacologic therapies is tempered by the realization that we must not generalize either the positive or negative effects of one strain with those of other strains. It is also noteworthy that most of the clinical studies to date involve a limited number of subjects, since the application is generally among populations at risk, such as those with IBD or IBS. The potential role of probiotics as a prophylactic in the general population is uncertain, since the measurable medical outcomes, other than the absence of disease, have not been identified.
Future research will involve at least six key elements: dosage, mode of action, genetic stability, antimicrobial resistance, health claims, and physical stability. There is a lack of consensus as to whether health benefits are associated with a single strain or a cocktail of organisms, their doses, the time of introduction (infancy vs adulthood), the duration of exposure, and the appropriate physiologic condition under which the strain is introduced. The molecular interactions of probiotics with the normal flora and host mucosal cells are not well defined. The genetic stability may be important for permanent or transient “colonization,” survival, and functionality of the organisms, as well as safety of the probiotic-containing product.
The absence of antimicrobial resistance is an issue stipulated in the WHO guidelines. Yet, our genetic analysis and that of others indicate that many organisms used in commercial products, such as cheeses, yogurts, and kefirs, have an innate antimicrobial resistance without any apparent negative health impact on the consumer. The physical stability without refrigeration is critical throughout the food supply chain. And, with the growing interest in health claims, the public health implications need stronger validation.
Research on probiotics sets the tone and standard for research and understanding of other “functional food” ingredients as we attempt to provide food with benefits beyond classical nutrition. Let’s not delay the research process another 62 years, as with vitamin C, or even a century, before embracing the possibility of health and nutritional benefits of probiotics.
by ROGER CLEMENS, Dr.P.H.
Director, Analytical Research
Professor, Molecular Pharmacology & Toxicology
USC School of Pharmacy, Los Angeles, Calif.
by PETER PRESSMAN, M.D.
Geller, Rudnick, Bush & Bamberger
Beverly Hills, Calif.