The effects of plant stanols on the immune function of asthma patients

Plant stanols are well known for their effects on lowering intestinal
cholesterol absorption ultimately resulting in 10-15% reduced serum LDL
cholesterol concentrations in humans. In addition we have also shown that serum
triacylglycerol (TG) concentrations may be lowered in subjects with elevated
baseline concentrations. Till now, there is little evidence for plant stanol
effects other than improving lipid profiles. However, we have very recently
found strong indications in ex vivo models using isolated human peripheral
mononuclear blood cells (PBMCs) from healthy volunteers that plant stanols have
the capacity to improve immune function. More into detail, plant stanols
shifted the differentiation of naive T-cells into the Th1 direction by
activating a specific receptor present on the Antigen presenting cells (APCs)
and T-cells. This effect might ultimately be helpful in situations in which the
Th1/Th2 cell balance is disturbed into a Th2 over-responsiveness. By activating
the Th1 response, the disturbed balance may be restored. This is for example a
possibility in the treatment or prevention of asthma, food allergies or HIV in
susceptible subjects. In addition, very recently (MEC 08-3-051) we also showed
these ex vivo Th1 stimulating effects of plant stanols specifically in PBMCs
isolated from asthma patients, as said, a condition characterized by a Th2
dominant immune response.

The major research objective is to prove that the consumption of plant stanol
ester enriched yogurts can improve immune function in vivo in asthma patients

A double-blind randomized placebo-controlled human intervention study in which
90 patients with clinically proven asthma will participate: 45 in the
intervention group receiving plant stanol yoghurt and 45 in the control group
receiving a control yoghurt without added plant stanols. At the end of the
run-in period as well as at the end of the experimental period blood will be
sampled to isolate PBMCs. These cells are used to evaluate effects on cytokine
production, phagocytic capacity of neutrophils, and the activity of NK cells.
In addition, during the experimental period all subjects receive a vaccination
against Hepatitis A Virus. After 1, 2, 3, and 4 weeks blood will be sampled to
monitor specific immunoglobulin titers to HAV.

During the first two weeks of the study (the run-in period) all participants
receive control yoghurts without added plant stanol esters. Directly after
these two weeks, the intervention period starts, which lasts eight weeks.
During this period 45 participants continue to use the control yoghurts, and 45
participants switch to the consumption of plant stanol ester enriched yoghurts.

During the study, 9 blood samples (each 20 or 50 mL) will be taken. Total time
investment for the subjects will be 160 min. Occasionally, a heamatoma or
bruise can occur during venipuncture. After the vaccination a heamatoma or a
sore arm can occur. These side effects should disappear within 4-5 days. Other
common side effects are headache, loss of appetite, and fatigue, which usually
will disappear within 24 hours. The results of this study will show whether
consumption of plant stanol enriched yogurts is able to restore the disturbed
th1/Th2 balance in asthma patients. This is expected to reduce asthmatic
exacerbations, as the Th2 dominant immune response seems causal to asthmatic
symptoms.