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Probiotics: Viable single or mixed culture of microorganisms which when applied to animal or man, beneficially affects their host by improving the properties of the indigenous microflora.1 Over the last decade, other definitions have been applied to the term, but they all basically agree, at least in general terms. The increased interest in defining exactly what probiotics are has arisen, in large part, from the increasing demand for probiotics. Probiotics have found application in a wide variety of products including, yogurt, dietary supplement capsules, tablets, milk, butter, cheese, salami, soy sauce, sour dough.2 They are even being used as antimicrobials for the poultry industry due to their ability to inhibit salmonella growth in chickens. Probiotics are clearly here to stay and the market, despite its incredible growth over the last few years, is still in its infancy. Presently, there are identifiable trends in the use of probiotics. These trends can be generalized as a heightened awareness of differing quality in the organisms. From the manufacturing side, that includes such things as production of well-document, clinically-backed strains, ability to survive gastric acid and bile salts, adherence, long-term stability. Also issues such as milk/casein-free are important for products addressing that. 3,4 From the end-user or medical perspective all the above are important, but there are additional considerations. The additional considerations all boil down to; what is the best way to use the probiotics in the most clinically efficacious manner? Ten years ago, most probiotic products contained either Lactobacillus acidophilus or Bifidobacterium lactis (bifidum). If one was really lucky, they could find a combination of the two and possible a couple of yogurt strains (i.e., Lactobacillus bulgariucus) thrown in. Many of these contain only a few hundred million viable cells at the time of manufacture. While that may sound like a lot of organisms, especially when we are conditioned to think of bacteria as being "bad", current data tells us that those numbers were probably far too low to be doing very much good. At least in the short-term, therapeutic application of the probiotics. As more and more data comes in, it is becoming apparent that at least a billion organism are need per dose to achieve any real clinical significance. In a recent study, ten billion Bifidobacterium in milk per day were given and immune markers measured.5 A significant increase in phagocytic activity of granulocytes was observed. In a randomized, double-blind placebo controlled study, the
prophylactic effect of probiotics on infections in neutropenic
patients undergoing cytoreductive chemotherapy for acute leukemia
was studied. Thirty patients (35 episodes) were included in
the study. The lactobacilli were given as two capsules thrice
daily for 30 days, starting at the initiation of chemotherapy.
The occurrence of fever was significantly (P = 0.033, Mann-Whitney
rank sum test) postponed from a median time of 8 days to 12
days. Capsules contained 50/50 Bifidobacterium lactis/lactobacillus
acidophilus containing 4billion / capsule.6 Probiotic supplementation has been demonstrated to be very safe and effective for a wide variety of disturbances including antibiotic side effects, diarrhea/constipation, lactose malabsorption, and cholesterol reduction. Dosages ranging from one to almost 500 billion organism have been used without complications.9,10 Current trends seem to indicate a range of 10-100 billion live organisms as being efficacious for the variety of conditions mentioned above. At least two different companies have "high-dose" products on the market with 20 and 30 billion organisms per capsule.11,12 These products should serve as a portent for the market as they were both originally designed for different markets, the environmentally challenged and autism (and down syndrome), respectively. These are excellent demonstrations of two principles that are developing. First, is a need for high-dose probiotics to treat selective conditions. Second, is the need for a variety of products. What we are learning is while a low-dose run-of-the-mill L. acidophilus (providing it is well produced) can be great for a general maintenance program, often times a much higher dose is required to achieved clinical significance. Additionally, it is becoming increasingly apparent that the inclusion of other strains, such as Lactobacillus rhamnosus or Lactobacillus plantarum (an exciting up-and-coming star) can have a dramatic effect.13-15 The inclusion of multiple strains is not only beneficial for the specific conditions, but also may play another important role in the application of probiotics. Increasingly, with the use of mono- or bi-strain products, there are reports of a reduction of clinical effects seen over time. For instance, in the case of autism, a child that pre-treatment had either diarrhea, or some other gastrointestinal distress, improves dramatically when first supplemented with those products. The child starts producing well-formed stools on a regular basis. However, in some cases, the child can undergo a reversion to the previous distressed state. Two approaches seem to have found a resolution for this consternating phenomenon. First, is the "pulse" method. Here, when the clinical effect begins to change, the physician can cease the probiotic supplementation for a period of time, followed by a repeat application. The body appears to be "resetting" itself after cessation of the therapy. During this period, changes are occurring in the gastrointestinal tract that may be making the local environment more hospitable to the probiotics. Additionally, there are certainly changes in the immune functioning of the gut. It is well established that the intestines are a major source of immune competence.16 It is also well established that there are genetic elements that respond to heavy metals, and in particular to mercury.17 What may be happening is that upon initial exposure to the probiotics, the gut associated immune system is mobilized and may be attacking the probiotics. After withdrawal of the probiotics, the immune reaction tapers off until any subsequent exposure. This is not a bad thing and can be used efficaciously by pulsing the probiotics. Also, a variation on that theme can be employed. That is to say, instead of withdrawing all probiotics for any period of time, a substitution of another product, which contains different organisms would seem the logical next step. For instance, if a product that just L rhamnosus is being used and the above condition presents, a product of just Bifidobacterium could be employed. If a single strain of Bifidobacterium is used, and again the same situation occurs, then a third product with several strains could be administered. It most certainly is going to have to go on a case-by-case basis, according to the physician's observations. In the foreseeable future, there will be products designed specifically to address the issue in this way. This "probiotic rotation" will be applicable in a variety of situations. As can be seen, the area of probiotics is still in its infancy. This neonate is soon to grow-up, however, as major pharmaceutical companies enter this exciting and efficacious area of healthcare. As clinical data from the application of probiotics to conditions such as autism, down syndrome, cancer, lactose intolerance, etc, comes to light, consumer/patient demand awareness of the importance of these organisms will concomitantly increase. With that, we can expect better products, tailored to specific conditions to also be developed.
References: 1. Havenaar & Huis in 't Veld, 1992. 2. Mitsuoka, T. 1978Intestinal Bacteria and Health.Iwanami Shoten. Tokyo. Japan. 3. Brudnak, MA 2001 Probiotics and Autism. Townsend Letter for Doctors & Patients.April. 4 Wieder Nutrition International. Personal Communication. 5. Schiffrin et al, 1995. Journal of Dairy Science, 78: 491-497. 7. Deguchi, Y. et al 1994.Microbial Ecology In Health and Disease Vol. 6:85-94. 8. Brudnak, MA. High-dose Probiotics for Detoxification Townsend Letter for Doctors & Patients. Submitted. 6. Presented at The Seventh International Symposium on Infections in the Immunocompromised host. June 21-24, 1992, Boulder, Colorado, USA 9. Hove H, Nordgaard-Andersen I, Mortensen PB. Effect of lactic acid bacteria on the intestinal production of lactate and short-chain fatty acids, and the absorption of lactose. Am J Clin Nutr. 1994 Jan;59(1):74-9. 10. Gaon, D., et al. Lactose digestion by milk fermented with human strains of Lactobacillus acidophilus and Lactobacillus casei. 1995. Medicina (Buenos Aires), 55:237-242. 10. Kirkman Laboratories, Wilsonville OR. USA. Personal Communication. 12. Klaire Laboratories, Solana Beach CA. USA. Personal Communicatoin. 13. Mangiante G, Colucci G, Canepari P, Bassi C, Nicoli N, Casaril A, Marinello P, Signoretto C, Bengmark S. Lactobacillus plantarum Reduces Infection of Pancreatic Necrosis in Experimental Acute Pancreatitis. Dig Surg. 2001;18(1):47-50. 14. Philippe R Marteau, Michael de Vrese, Christophe J Cellier, and Jürgen Schrezenmeir Protection from gastrointestinal diseases with the use of probiotics . Am J Clin Nutr 2001 73: 430S-436S. [Abstract] [Full Text] 15. Gregor Reid Probiotic agents to protect the urogenital
tract against infection Am J Clin Nutr 2001 73: 437S-443S. 17. Badou A, Savignac M, Moreau M, Leclerc C, Pasquier R Druet P, Pelletier L. HgCl2-induced interleukin-4 gene expression in T cells involves a protein kinase C-dependent calcium influx throughL-type calcium channels. J Biol Chem. 1997 Dec 19;272(51):32411-8.
Please feel free to contact me. Mark A. Brudnak PhD, ND
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