2.1. Odporność organizmu (ID 733)

The claimed effect is “immune health”. The Panel assumes that the target population is sportsmen and sportswomen, and other members of the general population engaged in strenuous physical activities.
“Immune health” is not sufficiently defined. In the context of the proposed wording, the Panel assumes that the claimed effect refers to “support of the immune system” and “contribution to the immune function/response to exercise”.
The Panel considers that the claimed effects are general and non-specific and do not refer to any specific health claim as required by Regulation (EC) No 1924/2006.

2.2. Integralność i przepuszczalność błony śluzowej jelit (ID 1602)

The claimed effect is “intestinal health”. The Panel assumes that the target population is the general population.
“Intestinal health” is not sufficiently defined. In the context of the proposed wording, the Panel assumes that the claimed effect refers to the aspects of “promoting/maintaining integrity of the intestinal lining, preventing (increased) intestinal permeability”.
Maintenance of a normal epithelial barrier in the intestines and avoidance of excess intestinal permeability is required for normal intestinal function.
The Panel considers that maintaining integrity of the intestinal lining and normal intestinal permeability is beneficial to human health.

3.1. Odporność organizmu (ID 733)

Among the 55 references cited to substantiate the claimed effect, 38 were either general reviews or did report on outcomes other than immune function or immune system-related laboratory parameters (e.g. metabolic or muscle performance). The Panel notes that these references did not provide scientific data that could be used to substantiate the claimed effect. Of the remaining 17 studies on L-glutamine with immune system-related outcomes, nine are human interventions and eight are cross-sectional studies.
Human intervention studies
Castell et al. (1996) studied infections in men and women participating in various sport activities (marathon, ultra-marathon, mid-distance running and rowing) shown to be associated with increased incidence of infections after competition. Castell and Newsholme (1997) report on the same studies. On a double-blind basis, in altogether 8 separate series, athletes were either given 5 g L-glutamine (72 subjects) or placebo (maltodextrin, 79 participants) in two drinks immediately after and 2 hrs after strenuous exercise. In the glutamine group, 80.8±4.2% of subjects reported no infections during the next seven days, whereas in the placebo group only 48.8±7.4% of participants did (p<0.001). The Panel notes that the criteria for self-reported infections were not specified. Further, it is not clear from the papers whether the reporting was complete or whether there were any drop-outs.
Castell and Newsholme (1997) and Castell et al. (1997) also report on various immune cell and soluble mediator parameters. Whereas a significant difference in the CD4+/CD8+ (helper/suppressor) ratio was observed in one study between the glutamine and placebo groups (n=12), no differences were observed with regard to a number of cellular and soluble mediator parameters in the other study (n= 18).
Hiscock et al. (2003) studied eight healthy, highly trained men in a randomised, double-blind, crossover study and found that the normal increase in post-exercise IL-6 levels was further enhanced by glutamine supplementation. Krieger et al. (2004) studied 13 healthy runners given oral glutamine supplementation (0.1 g/kg) or placebo. Salivary IgA concentration and output were found to be unchanged by training and glutamine supplementation. In contrast, mean nasal IgA across the study period was significantly higher in runners receiving glutamine than in those receiving placebo. Krzywkowski et al. (2001) studied ten male athletes in a randomised, placebo-controlled, double-blind crossover study. Glutamine supplementation had no effect on a number of cellular parameters, except for a small reduction in exercise-induced neutrocytosis. Rohde et al. (1998a, 1998b) in two placebo- controlled intervention studies (16 runners and 8 cyclists, respectively) found no effect of glutamine supplementation on a number of lymphocyte subpopulations and functional parameters. Walsh et al. (2000) studied seven well-trained men who performed exercise in what appears to have been a placebo-controlled, crossover study. Glutamine supplementation had no effect on post-exercise leukocytosis or neutrophil function.
The Panel notes that, although glutamine supplementation generally prevented the fall in plasma glutamine concentrations during exercise, consistent effects on the immune system-related laboratory parameters measured were not observed. The Panel also notes that no scientific conclusions can be drawn for the substantiation of the claimed effect from the other five studies that used interventions other than glutamine, such as branched-chain amino acids (Bassit et al., 2000, 2002) and carbohydrate diet (Bacurau et al., 2002; Gleeson et al., 1998; Mitchell et al., 1998).
Cross-sectional studies
Bailey et al. (2003) reported on 55 high-altitude mountain climbers, and observed an association between severity of mountain sickness symptoms (n=10), symptoms of infection and plasma concentrations of glutamine. Hack et al. (1997) investigated healthy untrained subjects performing either aerobic or anaerobic exercise training programs for 8 weeks; the decrease in plasma concentrations of glutamine showed a strong positive correlation to the exercise-induced reduction in CD4+ T cells. Robson et al. (1999) studied 18 healthy cycling males and concluded that reductions in neutrophil function observed after exercise appear unrelated to the plasma glutamine concentration.
The Panel notes that human cross-sectional studies provide only limited evidence for a causal role of glutamine on the outcomes measured (co-variation).
In weighing the evidence, the Panel took into account that the claimed effects are general and do not refer to any specific health claim as required by Regulation (EC) No 1924/2006; that the only intervention study on glutamine in relation to a clinical immune-related outcome, which indicated an effect of glutamine supplementation on reduced occurrence of infections post-exercise, had several methodological weaknesses i.e. self-reported infections and lack of clarity regarding completeness of reporting; that other intervention studies showed no or minor effects on laboratory parameters only, and that the cross-sectional data provides only limited evidence for a causal role of glutamine on the outcomes measured .
The Panel concludes that a cause and effect relationship has not been established between the consumption of L-glutamine and “support of the immune system” and “contribution to the immune function/response to exercise”.

3.2. Integralność i przepuszczalność błony śluzowej jelit (ID 1602)

Six references were cited to substantiate the claimed effect.
Two randomised placebo-controlled intervention trials in breast cancer patients receiving chemotherapy (Li et al., 2006) and in patients after portal hypertension surgery (Tang et al., 2007), respectively, were provided. The Panel notes that the evidence provided does not establish that the results of these studies can be extrapolated to the general population.
One reference reports on an experimental study in rats receiving total parenteral nutrition (Li et al., 1994), and one reference describes an in vitro study on proliferation and protein kinases in intestinal epithelial cell lines (Rhoads et al., 1997). The Panel considers that the evidence provided in the animal and in vitro studies does not predict an effect of glutamine consumption on the claimed effect in humans.
One general review of L-glutamine and a second review on glutamine and the intestinal tract were cited. The Panel notes that no scientific conclusions can be drawn from these references for the substantiation of the claimed effect.
In weighing the evidence the Panel took into account that the rat and the in vitro studies provide limited evidence to support the claimed effect in humans, and that the results of two studies in patient populations cannot be extrapolated to the general population.
The Panel concludes that a cause and effect relationship has not been established between the consumption of L-glutamine and maintaining integrity of the intestinal lining and normal intestinal permeability.