DSM Nutritional Products 0 LAFTI ® - new scientific efficacy data – Dec 2004

DSM Nutritional Products 1 Content The immune system in relation to infections “LAFTI L10 increases immunity” - Study in mice Clancy et al. Paper submitted - Study in humans Clancy et al. Manuscript in preparation

DSM Nutritional Products 2 T-helper cells (Th1 and Th2 cells) play an important role in the control and management of the immune system – in staying healthy produce cytokines (= signaling molecules) IFN-  (interferon-gamma) A cytokine that is involved in protection against viral and bacterial infection Low levels of IFN-  indicates a low Th1 activity and makes a person susceptible to infections Literature shows that probiotics can play a role in restoring type 1 activity related to IFN-  levels The immune system - parameters

DSM Nutritional Products 3 The intestinal micro flora is an important component of host defense 70% of the immune system is regulated in the small intestine Some probiotics can adhere to the gut mucosa and hereby positively affect the mucosal immune system By affecting the mucosal immune system it can effect the total immune system and therefore also positively affect health The immune system – role of probiotics

DSM Nutritional Products 4 Up-regulation of Th1 cells, by increasing their activity, is characterized by increasing IFN-  levels which can be measured Th2 cell Th1 cell Symplistic model illustrating a suppressed immune sytem which can lead to infection The immune system – balance is important + IFN-  levels

DSM Nutritional Products 5 Study about the effect of LAFTI L10 on the restoration of a suppressed immune system and the protection against Candida infection Infection prone mice (= mice with a reduced immune function) are studied Mice are treated with LAFTI L10; placebo and a control strain (L. fermentum) During treatment they are orally challenged with Candida At various time points IFN-  levels and the number of Candida (i.e. cheek, tongue and soft palate) is determined Study in mice – background

DSM Nutritional Products 6 Study in mice – results LAFTI L10 clears yeast (Candida) infection rapidly

DSM Nutritional Products 7 Study in mice – results LAFTI L10 restores secretion of IFN- 

DSM Nutritional Products 8 Conclusion Study in mice – conclusions Conclusions LAFTI L10 clears yeast (Candida) infection rapidly LAFTI L10 restores low levels of IFN-   Rapid clearance of Candida correlates with the increase of IFN-  LAFTI L10 may be used in restoration of a suppressed immune system and help with protection against Candida infection

DSM Nutritional Products 9 Study in humans – background EBV (Epstein Barr Virus) The presence of EBV in the saliva is a marker for infection EBV infection can lead to fatigue and impaired performance About 85% of adult Americans will test "positive" for EBV antibodies which means they have been exposed to the disease in the past All of the diseases in the Herpes family share the common element that the infection can occur multiple times. This process is called "reactivation." It happens because the body doesn’t really eliminate the virus; rather the virus becomes dormant in cells, only to re-emerge at a later date

DSM Nutritional Products 10 Study in humans – background Study about the effect of LAFTI L10 on the restoration of a suppressed immune system and the protection against virus infection Fatigued athletes suffering from a suppressed immune system are studied Especially endurance athletes frequently develop infections, particularly infections of the respiratory tract These infections lead to fatigue and impaired performance IFN-  levels are measured as a biomarker for the status of the immune system The infection with Epstein Barr Virus (EBV) is measured EBV infection is a disease of the herpes family.The virus can stay in the body without having symptoms. Infection (reactivation of the virus) will occur when the immunity is decreased.

DSM Nutritional Products 11 LAFTI L10 restores secretion IFN-  Study in humans – results

DSM Nutritional Products 12 Study in humans – conclusions Conclusions LAFTI L10 restores low levels of IFN-  There are strong indications that LAFTI L10 reduces EBV infection (further studies are needed to confirm reduction of EBV infection by LAFTI L10) LAFTI L10 may be used in restoration of a suppressed immune system. As a result LAFTI L10 may help in the protection against EBV infection and fatigue related to this infection.

DSM Nutritional Products 13 People with a suppressed immune system A suppressed immune system leading to yeast or viral infections and resulting in e.g. fatigue is common in: Endurance athletes People with a irregular/unhealthy lifestyle People with stress People taking antibiotics Pregnant women Elderly