Impact of A2 milk versus conventional milk on intestinal health: a proof-of-concept study in Irritable Bowel Syndrome patients

Dairy products such as cow*s milk are widely produced and an important
component of the human diet. Beta-casein is a major protein component of cow*s
milk, includes A1 and/or A2 β-casein, and is composed of important amino acids
that contribute to functions such as muscle growth. Most cows produce a mixture
of A1 and A2 β-casein (conventional milk), whereas some cows produce only A2 β-
casein (A2 milk). By differences in one specific amino acid at position 67
being histidine or proline, respectively, it is suggested that A2 milk will
induce less gastrointestinal (GI) symptoms compared with conventional milk.
Previous studies in China, Australia and New Zealand indeed showed this indeed
lower GI symptoms after A2 milk vs conventional milk intake in healthy
indivuals. However, further studies are needed on the comparison between A2
milk and conventional milk on prevalent GI symptoms in various geographical
populations, and especially in relevant subgroups, such as irritable bowel
syndrome (IBS) patients. In Western populations, IBS is a prevalent (i.e. 10%)
functional bowel disorder characterized by abdominal pain and altered bowel
habits. According to the Rome IV criteria, IBS subtypes include IBS with
constipation (IBS-C), IBS with diarrhea (IBS-D) and mixed IBS with both
constipation and diarrhea (IBS-M). Although the pathophysiology is incompletely
understood, it is generally regarded as a multifactorial disorder involving
host factors such as low-grade immune activation and defense. Diet has also
suggested to play a role in inducing GI symptoms in IBS patients. Therefore we
aim to study GI symptoms in IBS-C and IBS-D patients.

This study will be done to gain insights in the effects of A2 milk on GI
symptoms, and immune and defense parameters, in IBS patients. The information
will gain more insights in the working mechanism of different types of
beta-casein in individuals which indicate that nutritional components trigger
GI symptoms. In case study results will be positive, this may lead to the
development of new food products such as A2 milk, to improve intestinal health.

The study conforms to a randomized, double-blind and placebo-controlled design
including two cross-over intervention periods

One 1-day intervention period subjects will ingest 200 mL A2 milk two times
that day. In the other 1-day period intervention period, subjects will ingest
200 mL conventional milk two times that day. Which product will be ingested in
which period (first or second) will be determined by randomization.

There are small burdens volunteers can experience during this study. After
screening, participants will have to visit the Maastricht Universitair Medisch
Centrum+ two times. In total, a participant will spend approximately eighteen
hours at the university facility. They will have to take A2 milk or
conventional milk two times during two 1-day intervention days; the products
used have been proven to be safe for human use. During two visits and spread
over 19 days, a total of 28 mL blood will be sampled by venepuncture via an
evacuated tube system, which may lead to minor discomfort and/or a small
hematoma at the site of puncture. During the both intervention days, body
weight will be determined and subjects will bring a fecal sample to each
intervention day which is collected at home. Moreover, daily questionnaires
will have to be filled out at several occasions during this study. Besides we
ask subjects to fill out a three-day food diary two times.