Citation

The consumption of raw cow’s milk as an allergy-preventive measure is promising, but the risk
of infections hampers usability. As an alternative to raw milk, specific raw milk components
for supplementing processed milk may be interesting. Since bioactive whey proteins are
often implied to be responsible for the allergy-preventive potential of raw cow’s milk, the
present study assessed whether alkaline phosphatase (ALP), lactoferrin (LF), osteopontin
(OPN), and IgG could restore the allergy-protective effect lost upon milk processing. Female
C3H/HeOuJ were orally treated with PBS, raw milk, processed milk, processed milk spiked
with ALP, with LF, with OPN, with IgG, or with a combination of these four whey proteins for
eight consecutive days prior to sensitization and challenge with ovalbumin (OVA). Effects on
acute allergic symptoms, basophil activation, and immunoglobulin levels were subsequently
assessed. Raw milk-treated mice showed a reduced OVA-induced allergic response compared
to processed milk-treated mice. Of the four individual whey proteins tested, only the addition
of LF to processed milk was able to reduce the acute allergic skin response compared to
processed milk alone, although all four whey proteins reduced anaphylactic shock symptoms.
OPN-treated mice furthermore showed a reduction in both basal and OVA-specific basophil
activation. Spiking processed milk with the combination of ALP, LF, OPN, and IgG reduced the
acute allergic skin response, anaphylactic shock symptoms, and basophil activation compared
to processed milk alone. In addition, a tendency towards a reduction in OVA-IgE levels was
observed in this group. Due to the lack of a strong allergic response in the positive control
group, the obtained results require careful interpretation. Processed milk spiked with the
combination of the four bioactive whey proteins most closely resembled the allergy-protective
raw milk effect. Of the individual whey proteins tested, LF was most effective in restoring the
allergy-protective effect lost upon milk processing, although ALP, OPN, and IgG also showed
promising effects. This study thereby provides preliminary evidence that spiking processed
milk with bioactive whey proteins, a