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Rapid Responses: Rapid Responses published:
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Academic, my dear Watson
- David E Bratt (4 June 2001)
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Raw milk
- Cory Mermer (5 June 2001)
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Breast milk: nature's probiotic
- Carol M A Campbell, Carol MA Campbell (5 June 2001)
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Natural "probiotic"
- Virginia Thorley (10 June 2001)
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Was breastmilk forbidden?
- Rachel Myr (12 June 2001)
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probiotic milk: is there an adequate amount of Lactobacillus GG or just fresh water?
- Filippo Cremonini, Antonio Gasbarrini (22 June 2001)
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What about allergies?
- Adam Jacobs (22 June 2001)
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The effect of breast feeding on the incidence of infections
- Katja Hatakka (27 June 2001)
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Effective dose of Lactobacillus GG
- Maija Saxelin (27 June 2001)
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Let's be Realistic
- Jane Andrews (11 July 2001)
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David E Bratt, Paediatrician Private Practice
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This is fascinating academic news, the stuff of which grants are made (by food companies?) and of interest to those who cannot keep their children at home or breastfeed them. |
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Cory Mermer, Medical Researcher/Writer
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If non-pathogenic bacteria added to milk consumed by infants confers benefits, then might not "raw" or unpastuerized milk provide a similar benefit? Of course, fortification with certain deficient nutrients would most likely be warranted, especially if this were the primary source of nourishment for an infant. Does anyone have any information or thoughts about this? Would the risks be too great? Is there any published evidence, either positive or negative, on this subject? |
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Carol M A Campbell, CMO, Community Paediatrics Foyle H&SS Trust, Londonderry, Carol MA Campbell
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Editor, Breastfed infants have high intestinal levels of Lactobacillus bifidus, which promotes intestinal acidity and reduces growth of enteropathogens(1). Breastfed infants have been found to have, relative to artificially fed infants, a lower incidence of gastroenteritis, respiratory infection and otitis media(2). The children studied by Hatakka et al(3) included many who had been breastfed for long periods. This may account for the small differences they found: probiotic therapy is known to be more effective in non- breastfed children(4), who are deprived of the natural probiotic content of human milk. A more appropriate study design might compare groups of children with the duration and exclusivity of their breastfeeding (if any) carefully described. This could yield useful information both on optimum breastfeeding practice and on the true clinical usefulness of probiotic therapy. Meanwhile, perhaps we should simply encourage and support mothers to breastfeed their toddlers for longer, rather than devising yet another commercial substitute for breastmilk. Yours sincerely, Carol Campbell References 1. Riordan J, Auerbach KG (eds). Breastfeeding and human lactation. 2nd ed. Jones and Bartlett: Sudbury, 1999. 2. Campbell CMA. Breastfeeding and health in the western world. Brit J Gen Pract 1996;46:613-617. 3. Hatakka K et al. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ 2001;322:1327-9. 4. Oberhelman RA et al. A placebo-controlled trial of Lactobacillus GG to prevent diarrhoea in undernourished Peruvian children. J Pediatr 1999;134:15-20. |
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Virginia Thorley Brisbane, Queensland, Australia
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The paper by Hatakka et al(1) on effects of long-term consumption of probiotic milk of bovine origin on infections and days absent from day care is interesting, insofar as it goes. From a close reading of the paper, the study, involving day care children aged 1-6 years, makes no mention of a further relevant question, whether any of the younger children were continuing to receive breastmilk, a source of protective bacilli that costs nothing. I note that three of the study’s authors were either current or past employees of the manufacturer of the probiotic product, or had a past relationship. Health authorities are increasingly recommending that breastfeeding continue beyond the first year of extrauterine life,(2) yet the authors fail to state whether they had ascertained if any of the children were receiving breastfeeds, or whether all were non-breastfeeders. This is relevant because of the protective effects of breastmilk on the intestinal mucosa, a scenario in which Lactobacillus bifidus plays a role.(3) Indeed, breastmilk is protective against a wide range of digestive, respiratory and other ailments through a number of mechanisms.(4, 5) It is thus no wonder that in an earlier Peruvian study cited in the editorial by Wanke in the same issue,(6) it was the non-breasteeding children who showed the most improvement on the probiotic food. Perhaps we shall some day see the results of a study of the effects of breastfeeding into the second year on intestinal health and days absent from child care. Virginia Thorley, OAM, MA, IBCLC
REFERENCES (1) Hatakka K, Erkki S, Ponka A, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. Br Med J 2001;322(7298):1327-29. (2) American Academy of Pediatrics. Breastfeeding and the use of human milk. Pediatrics 1999;100(6):1035-39. (3)Riordan J, Auerbach KG. Breastfeeding and human lactation. Boston: Jones & Bartlett, 2nd edn., 1999, p. 141. (4) ibid, chapter 5. (5) Lawrence RA, Lawrence RM. Breastfeeding: a guide for the medical profession. St Louis: Mosby, 5th edn., 1999, chapter 5. (6)Wanke CA. Mr Med. J 2001;322(7298):1318. |
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Rachel Myr, editor Norwegian Association of Midwives
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I note that other respondents have mentioned that breastfeeding might give these children the same benefits as the probiotic used. In the article it is stated under the description of methods, that other probiotic-containing foods (than the milk with added probiotic) were 'forbidden'. Would the authors care to comment on whether that included breastmilk, and if so, whether there were any children who were weaned for the purpose of participating in this study? Again, it seems that we need to be reminded that breastfeeding is not something which is beneficial to the babes-in-arms and without impact once the child is over a year, or two, or three or more. Why, then, are we so stingy with this natural resource? For all we know, one reason we have two breasts can be to be able to continue to feed an older child even after the next baby is born. We really have no idea what is optimal breastfeeding duration. This study shows that at least one component of breastmilk has benefits for the child whose contact with surroundings has expanded. We already know that specific antibodies are distributed throughout the day's production of milk, so that a child getting breastmilk even once a day is getting a full quota of antibodies if the mother is only breastfeeding that child. |
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Filippo Cremonini, Resident, Professor Internal Medicine, UCSC Rome, Italy, Antonio Gasbarrini
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Dear Editor, Dr. Hatakka’s paper on the effect of probiotic milk supplementation on childhood respiratory tract infections is of great interest.(1) However, some concern is raised by the real amount of Lactobacillus GG actually delivered to the young patients. Lactobacillus GG has well-known positive effects on rotavirus diarrhoea, antibiotic-associated dirrhoea and several other conditions, and has been succesfully used specially in pediatric populations. (2,3) Rationale for probiotic effectiveness is based on the requirement of bowel wall colonisation. This may allow the local and systemic enhancement of the immune system which could explain the reduction of the incidence of infections at follow-up. Lactobacillus GG has, indeed, good properties of adhesion to the bowel wall, but supplementation should be performed with very high concentrations of bacterial Colony Forming Units (CFU). In almost all study performed CFU is in the range of billions. (4) In contrast, calculation of Lactobacillus GG supplemented by Hatakka and colleagues does not reach these figures, but is in terms of millions of CFU. This would not be adequate to achieve a colonization and a balancing effect over resident flora, whose entity is enormously much bigger. In this case a significant immunostimulation by relatively few Lactobacilli would be almost impossible. Moreover, the fecal assessment of Lactobacillus GG recovery, which is a possible tool to ascertain delivery of the probiotic to the colon, should have been performed before and after probiotic supplementation in the same subjects, to establish that recovery was really due to supplementation. The placebo design helps to indicate significant benefits between groups, but does not provide any direct evidence for a benefit specifically derived from the probiotic. This, despite producing interesting results, adds confusion to the debate on the optimum dose of probiotic (and the type of probiotic) needed to achieve a measurable effect. References 1. Hatakka K, Savilahti E, Ponka A, Meurman JH, Poussa T, Nase L, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centres : double blind, randomised trial. BMJ 2001;322:1-5 2. Vanderhoof JA, Young RJ. Use of probiotics in childhood gastrointetinal disorders. J Pediatr Gastroenterol Nutr 1998;27:323-32 3. Rolfe RD. The role of probiotic cultures in the control of gastrointestinal health. J Nutr 2000;130(suppl):S396-S402 4. Tuomola E, Crittenden R, Playne M, Isolauri E, Salminen S. Qualità assirance criteria for probiotic bacteria. Am J Clin Nutr 2001;73(suppl):S393-8 Filippo Cremonini, MD Antonio Gasbarrini, MD Medicina Interna, UCSC, Rome, Italy
Policlinico Gemelli, Largo Gemelli 8
00168 Roma, Italia
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Adam Jacobs, Director Dianthus Medical Limited
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Hatakka et al mention only in passing what is potentially one of the most interesting outcomes of this study, namely the effect of the treatment on the development of allergies. The hygiene hypothesis attributes the dramatic increase in the prevalence of asthma and other allergic diseases in recent years to a more sterile environment and a reduced incidence of childhood infections [1]. If it is true that infections in childhood protect against the development of allergy, then we might expect to see more of the children in the probiotic group going on to develop allergic diseases. On the other hand, high levels of gut lactobacilli are associated with a decreased prevalence of allergy [2]. Since the probiotic milk promotes colonisation of the gut with lactobacilli, we might therefore expect reduced incidence of allergy in the treated group. Unfortunately, the statement ‘There was no difference between the groups in abdominal pain or allergic symptoms’ does not really address this question. Was incident allergic disease specifically looked for? Was the sample size adequate to detect any effect on allergies? I am sure that the follow-up was not long enough to collect useful information on allergies. If Hatakka et al are planning any long-term follow-up of these children, I hope they will look at this question in more detail. If a simple intervention such as this can prevent the development of asthma, a disease with lifelong symptoms, need for medication, and effects on quality of life, I would consider this far more impressive than a small reduction in the incidence of some mild, self-limiting infections. References: 1. von Hertzen LC. The hygiene hypothesis in the development of atopy and asthma — still a matter of controversy? Q J Med 1998;91:767–771 2. Björkstén B, Naaber P, Sepp E, Mikelsaar M. The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy 1999;29:342–346 |
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Katja Hatakka, MSc, research nutritionist Valio Ltd, R&D, Finland
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Dear Readers, Dr Campbell, Thorley, and Myr raised a question concerning breast feeding and infections. We agree that breast milk is ideal food for infants, and also in Finland it is recommended that exclusive breast feeding should last 4-6 months and after that partial breast feeding until 6-12 months of age. Breast milk is known to contain different kinds of antibodies (1), and is known to support the growth of bifidobacteria in the intestine (2,3). In the beginning of our study we collected very extensive background data on children’s nutrition, including breast feeding. None of the children (aged 1-6 years) received breast milk during the study. There was no differences between the probiotic group and the placebo group in the mean duration of exclusive (2.8 vs 2.9 months; p=0.41) or total breast feeding (6.8 vs. 7.1 months; p=0.43). The mean time without breast feeding before the study was 47.7 months in the LGG group and 45.3 months in the placebo group (p=0.11), and the minimum time respectively was 2.5 vs. 3.1 months. We have now also adjusted the results by the duration of breast feeding, but this adjustment did not affect the results; the effect of probiotic milk was still apparent. Actually the duration of breast feeding seemed to have quite a small impact on the infections. Only gastrointestinal symptoms seemed to be negatively, but not significantly associated with breast feeding. We’d also like to stress, that milk containing probiotic Lactobacillus GG is cow’s milk and thus not a substitute for breast milk. Actually in Finland cow’s milk is not recommended to children under 12 months of age. What comes to raw milk, it may contain some beneficial bacteria but also many harmful bacteria. The safety aspects (4), in addition to ability to survive in the GI-tract and colonisation, are important characteristics of probiotic bacteria (5). To conclude, none of the children in our study were breast fed and breast feeding had been finished at least 2.5 months before the study, the mean time from the weaning being 3.9 years. Therefore we do not think that breast feeding has been a confounding factor or affected the incidence of infections in this intervention. Breast feeding is a very important factor in promoting children’s health. Colonic microflora also plays an important role in the development of immune response, and probiotics may be one possibility in enhancing immunity (6). Yours sincerely. Katja Hatakka References 1. Hanson LA. Breastfeeding provides passive and likely long-lasting active immunity. Ann Allergy Asthma Immunol 1998;81:523-533. 2. Wharton BA, Balmer SE, Scott PH. Faecal flora in the newborn. Effect of lactoferrin and related nutrients. Adv Exp Med Biol 1994;357:91-98. 3. Goldman AS. Modulation of the gastrointestinal tract of infants by human milk. Interfaces and interactions. An evolutionary perspectives. J Nutr 2000;130:426S-431S. 4. Salminen S, von Wright A, Morelli L, Marteau P, Brassart D, de Vos WM, Fonden R, Saxelin M, Collins K, Mogensen G, Birkeland SE, Mattila-Sandholm T. Demonstration of safety of probiotics - a review. Int J Food Microbiol 1998;44:93-106. 5. Tuomola E, Crittenden R, Playne M, Isolauri E, Salminen S. Quality assurance criteria for probiotic bacteria. Am J Clin Nutr 2001;73:393S- 398S. 6. Isolauri E, Sutas Y, Kankaanpaa P, Arvilommi H, Salminen S. Probiotics: effects on immunity. Am J Clin Nutr 2001;73:444S-450S. |
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Maija Saxelin, Ph.D., Senior Microbiologist Valio R&D
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Dr's Cremonini and Gasbarrini raised the question on the effective dose of the probiotics. It is an important and relevant question and we agree that when probiotic bacteria are given in dry form (in capsules, sachets etc), daily doses of billions may be needed. However, we have seen that milk (and maybe other buffering food substances) protect the bacteria very effectively in the intestine. In 1991 (1) we showed that about ten billion Lactobacillus GG bacteria (in powder form) were needed daily to be able to recover the strain in stools. Then we showed that when administered in fermented milk, one billion was high enough for faecal recovery (2). We did not study lower doses with fermented milk but later we studied the faecal recovery of LGG when administered in fresh milk. We found that 100 million cfu/day was high enough for faecal recovery (3). Another excellent vehicle is e.g. a ripened cheese. And the LGG level in faecal samples is higher when 10^8 cfu is administered in milk or cheese, compared to 10^10 in powder form (1, 3, 4). The compliance of the LGG administration was evaluated also in our study published recently in BMJ (5). It can be read in the electronic form of the article, unfortunately the printed version was shortened quite a lot. "Compliance was also measured by the faecal recovery of Lactobacillus (from 100 child before, in the middle and at the end the intervention). Initially 12% of children in the Lactobacillus group and 4% in the control group carried Lactobacillus GG type bacteria (P = 0.29). Recovery figures from the same children were 97% v 9% (P < 0.0001), respectively, in the middle of the study and 91% v 15% (P < 0.0001) at the end." There are still many open questions about probiotics and an effective dose is one of those. In our opinion there is not only one right answer to that, but it depends on the form of application. Recovery from faecal or biopsy samples (5) of the living probiotic strain is one tool to evaluate the effective dose, but the human intervention studies like our day care centre study are needed to confirm the health benefits. References 1. SAXELIN, M., ELO, S., SALMINEN, S., and VAPAATALO, H. 1991. Dose response colonization of faeces after oral administration of Lactobacillus casei strain GG. Microb. Ecol. Health Dis. 4: 209-214. 2. SAXELIN, M., AHOKAS, M., and SALMINEN, S. 1993. Dose response on the faecal colonization of Lactobacillus strain GG administered in two different formulations. Microb. Ecol. Health Dis. 6: 119-122. 3. SAXELIN, M. 1996. Colonization of the human gastrointestinal tract by probiotic bacteria. Nutrition Today 31 (6), Supplement 1: 5S-8S. 4. SAXELIN, M., PESSI, T., and SALMINEN, S. 1995. Fecal recovery following oral administration of Lactobacillus strain GG (ATCC 53103) in gelatine capsules to healthy volunteers. Int. J. Food Microb. 25: 199-203. 5. HATAKKA, K., SAVILAHTI, E., PÖNKÄ, A., MEURMAN, J.H., POUSSA, T., NÄSE, L., SAXELIN, M., and KORPELA, R. 2001. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. Br. Med. J. 322: 1327-1329. 6. ALANDER, M., SATOKARI, R., KORPELA, R., SAXELIN, M., VILPPONEN-SALMELA, T., MATTILA-SANDHOLM, T., and VON WRIGHT, A. 1999. Persistence of colonization of human colonic mucosa by a probiotic strain, Lactobacillus rhamnosus GG, after oral consumption. Appl. Environm. Microbiol. 65 (1): 351-354. |
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Jane Andrews, Senior Research Fellow University of Adelaide
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I note the flurry of responses this paper has generated, and was impressed with how unrealistic several of them are with regard to the practicality of extending breastfeeding beyond 12 months of age. Apart from the response the authors provided showing no difference between the breast & non-breast fed children in this study, it is also worth noting the practical reality that children are generally in childcare because their mothers are in paid work. Moreover, the majority of mothers do not have the luxury of on-site or co-located childcare facilities, which thus largely precludes ongoing breast feeding. Balancing work and childcare responsibilities are difficult enough for many mothers without an additional burden of guilt for failing to breastfeed beyond 12 months being applied without definite proof of its benefit. Declaration of competing interests: I am a mother of 3 children, who were breast fed to ~12 months of age, and have maintained work (and used childcare during this time). |
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