Rationale: The immune system in the ageing population becomes compromised with age (termed "Immunosenescence"). Therefore, elderly people have a decreased ability to respond to infection and vaccination. Furthermore, many of the health issues associated with ageing are linked to inflammation ("Inflammaging"). It has been suggested that this compromised immune function is in part due to reduced Toll-like receptor (TLR) function, which is part of the innate immune system. Milk and dairy based products have been shown to have beneficial effects on inflammation and immunity. This effect may be mediated via support of the innate immune response and promotes TLR7 signaling in in vitro assays (unpublished observation). Also prebiotics have been suggested to influence markers of innate immune function. Furthermore, TLR function has been suggested to be correlated to vitamin D status. Therefore, in the current pilot study, the potential of milk protein, prebiotics and vitamin D to support innate immune function in elderly will be investigated.

Objective: Aim of the current study is to evaluate the effect of milk protein on the innate immune response in elderly in a pilot study. Furthermore, support of this effect by prebiotics and Vitamin D will be studied.

Study design: The study will be a double-blind placebo-controlled pilot study. Study population: Healthy female elderly subjects of 65-85 years of age. Intervention: Period 1: Milk protein or placebo. Period 2: Milk protein + prebiotics or placebo. Period 3: Milk protein + prebiotics + Vitamin D or placebo.

Inclusion Criteria:

• Female
• Age 65-85 years
• BMI 20-30 kg/m2
• Non-smoking
• Generally healthy
• Regular and normal Dutch eating habits
• Veins suitable for cannulation (blood sampling)
• Voluntary participation
• Having given written informed consent
• Willing to comply with study procedures
• Accept use of all encoded data, including publication, and the confidential use and storage of all data for 15 years.
• Accept disclosure of the financial benefit of participation in the study to the authorities concerned

Exclusion Criteria:

• Having chronic inflammatory or autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease
• Disease of GI tract (including major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, known or suspected gastrointestinal disorders, colon or GI tract cancer), liver, gall bladder, kidneys, thyroid gland
• Immune-compromised
• Use of vitamin supplements containing vitamin D and not willing to discontinue this during the study
• Use of anti-inflammatory drugs (for corticosteroids and NSAIDs : frequency >1 per week)
• Use of immunosuppressive drugs
• Excessive alcohol usage (>3 consumptions/day or >15 consumptions/week)
• Participation in any clinical trial including blood sampling and/or administration of substances within 60 days before inclusion in this study
• Use of hormonal replacement therapy
• Mental status that is incompatible with the proper conduct of the study
• A self-reported milk allergy or sensitivity to dairy ingredients
• Unexplained weight loss or weight gain of > 3 kg in the 3 months prior to pre-study screening
• First and second degree relatives of personnel of NIZO food research or Wageningen University, department of Cell Biology and Immunology or Human Nutrition
• Not having a general practitioner
• Not willing to accept information-transfer concerning participation in the study, or information regarding his health, like laboratory results and eventual adverse events to and from his general practitioner
• Holiday to a sunny country during the study, starting from inclusion
• Light therapy during the study, starting from inclusion
• Use of prebiotic supplements during 2 months before study start, and during the study