Yogurt and yogurt-like fermented milks are well established and popular with children and parents. These products provide live cultures to the diet and nutrition in the form of protein, vitamins, and minerals. In addition, these products are relatively inexpensive, widely available, and easy to ingest. However, the value of the microbiological components of yogurts containing only traditional live cultures (S. thermophilus and L. bulgaricus) is generally limited to improving lactose digestion in lactose malabsorbers. These two active starter cultures do not survive intestinal transit in significant quantities and thus, have limited ability to positively impact intestinal health. This is the rationale behind many newer dairy products, which contain supplemental probiotic bacteria believed to survive the gastrointestinal tract. Unfortunately, validation of health effects of these products with meaningful patient-oriented, rather than surrogate, end points is often lacking.
Our aims in this study were to examine whether children who received a fermented milk containing the probiotic, L. casei
strain DN-114 001, and two traditional yogurt starters would have reduced overall illness and have less change in activity because of illness, as reported by their parents, than the children receiving control product. Although, we have mixed results, to our knowledge this is the largest probiotic clinical trial conducted in the United States and provides much needed data. One of the primary and most of the secondary outcome measures were negative, and although some of our positive findings are driven by a few individuals, the reduction of GITI (24% lower than control) is a robust outcome consistent with earlier probiotic research on this product. There are many potential hypotheses as to why we had mixed results in our study. Perhaps, it was easier for parents to determine whether a child had a runny nose, ear pain, or other symptom, but less clear if a young child's activity level was changed. Possibly, symptoms were sufficiently obvious to report, but insufficient in severity to result in a canceled activity. In addition, most of the positive earlier research on this product has been with gastrointestinal symptoms (Pedone et al., 1999
; Agarwal and Bhasin, 2002
; Giovannini et al., 2007
; Hickson et al., 2007
). Our results are similar in that the drink has its greatest impact in reducing GITI; however, this may impact overall health, but not activity levels of young children. A recently published manuscript examining the same intervention found a significantly decreased duration of CID (P
=0.009) in comparison with the control group in an elderly population (Guillemard et al., 2010
). Earlier conducted preclinical studies provide hypotheses on mechanisms of action and relevant information about the biological plausibility of the observed clinical effects on CIDs in human studies conducted with our intervention (Djouzi et al., 1997
; Guerin-Danan et al., 2001
; Freitas et al., 2003
; Ingrassia et al., 2005
; Medici et al., 2005
; Parassol et al., 2005
; Tien et al., 2006
; de Moreno de LeBlanc et al., 2008
; Baba et al., 2009
Similar to primary outcomes, secondary outcomes showed mixed results. The active group used statistically less medicine, but this was of questionable clinical significance as the absolute numbers were similar. In addition, there were no differences among groups in outcomes such as missed work or daycare/school. A study by Hatakka et al.
examined the effects of the probiotic Lactobacillus rhamnosus
GG on children in daycare centers. Children in the L. rhamnosus
GG group showed a 16% decrease in absences from daycare compared with control, and a significantly lower incidence of respiratory infection (relative reduction 17%, absolute reduction 9%) (Hatakka et al., 2001
). Weizman et al.
also studied probiotics in daycare centers. They fed infants either Bifidobacterium lactis
Bb-12, Lactobacillus reuteri
ATCC55730, or control formula containing no added probiotic. The control group had more days of febrile illness, increased episodes of diarrhea, and increased absences from daycare than the groups on the probiotic-fortified formulas (Weizman et al., 2005
). Our diary data did show participants in the active group had a statistically insignificant 24% decrease in daycare/school absences during the study period and parents had a statistically insignificant 33% less missed work in the active group compared with control during the 90-day trial. It is likely that the reason these major differences are not significant is due to the low number of completed diaries and a larger study may have found differences in activity levels. In addition, our study population was much more diverse than these two studies and many other more disease-oriented probiotic trials.
Our study has several limitations that need to be noted. We intentionally did not include independent examinations of children by physicians and instead relied on parental report. We studied a functional food, not a medicinal product; parents will thus feed their children without any physician input and we felt it was best to assess it under similar conditions. A limitation of this method is that some of these assessments are subjective and vary by evaluator. However, the large sample size and strict methodology should result in equal assessments per group. In addition, we enrolled generally healthy children from daycare/school settings. It is possible if our source population was not as healthy, we would have had different findings. Our overall illness rate was less than we anticipated from earlier literature and it was reported as a ‘mild' winter for illness in our recruitment area. Finally, compliance was measured by self-report. However, we analyzed through intention to treat, which is especially appropriate for a food product, which is unlikely to be consumed in real life everyday without missed servings.
Our randomized clinical trial shows that a fermented dairy drink with a characterized probiotic strain holds promise, but has limitations in promoting the health of children aged 3–6 years. The results of our clinical trial support the effectiveness of this product with an important patient-oriented outcome, CID, most specifically in gastrointestinal illness. It is important to recognize that this trial studied a specific probiotic strain, dose, and age group, and our findings cannot be extrapolated for other strains or outcomes. It is important that commercial products continue to be independently studied, important patient-oriented outcomes assessed, and subjected to high quality research techniques.