The NUTRIOME study: Precision nutrition and postprandial immune response

Suboptimal diet is an important risk factor for the development of
non-communicable diseases, such as stroke, diabetes or colon cancer (conditions
often related to metabolic disturbance and low-grade inflammation) which are
major drivers of mortality and morbidity, thus contributing to the global
burden of disease. Precision nutrition - i.e. tailoring diet to the right
individual at the right time, based on individual factors (e.g., genes,
metabolic profile, environmental factors or gut microbiota) - could potentially
lead to the development of more effective diet-based disease prevention
strategies. Although nutrition and lifestyle factors play a critical role in
disease prevention, individuals do not necessarily respond in the same way to
dietary or lifestyle changes. This highlights the need for better understanding
of the determinants of inter-individual differences in response to food.

Since humans spend a substantial portion of each day in a postprandial state,
individual metabolic and inflammatory responses to meals are likely to play a
role in the pathophysiology of diet-related diseases. Although there are data
on postprandial glucose response to meals, there is limited data on
postprandial inflammatory responses and to what extent diet can be tailored to
individuals for long-term health benefits, depending on their postprandial
metabolic and inflammatory responses. Further, studies that reported on
differential individual responses to intervention foods often utilised drinks
or single foods high in fat or sugar that would not fit into the framework of a
*healthy and sustainable food system* and the response to such foods may be
different compared to foods that are more similar to what people consume in
their daily life.

To acquire metabolic health data from three dietary challenge meals for the
development of an algorithm for personalised dietary advice, and subsequently
test the effectiveness of this personalised dietary advice compared to a
general healthy diet based on national dietary guidelines on cardiometabolic
health. Secondarily, determinants of individual dietary responses will be
investigated.

The study is a multi-centre study, conducted in Gothenburg (Sweden), Oslo
(Norway) and Wageningen (Netherlands). The study will be conducted in two
phases that are separated by approximately 7-9 months. In Phase 1 of the study,
participants will undergo three meal challenges in a crossover design, that are
each separated by at least five days. The order of the meals will be set
randomly according to a Latin square design. In Phase 2, the participants will
be randomised into receiving either personalised nutrition advice or general
dietary advice. The algorithm will be developed using the response pattern to
the three different test meals in Phase 1 and current knowledge about the
impact of specific foods on such responses. All participants in the general
dietary advice group will receive dietary advice based on official dietary
guidelines in the three countries. Dietary advice will largely be within the
normal range of official dietary guidelines. Prior to the start of the
intervention, several measurements, including glucose and haemoglobin capillary
blood tests and anthropometrics, will be performed.

During Phase 1, participants will be provided with three intervention meals.
They will consume one study meal each week at the clinic in the morning. The
three different intervention meals are isocaloric, but based on different food
sources (plant-based, fish-based, and meat-based) and differ in nutrient
composition. The plant-based meal is a carbohydrate-rich meal and the fish -and
meat-based meals differ in fat quality. All meal compositions are within the
range of a normal diet. The foods used in the study are commercially available
foods and do not confer any risks.

During Phase 2, all participants are randomly assigned to one of two diets,
which will be either personalised dietary advice or a control diet, based on
healthy dietary guidelines across the three participating countries. The
personalised dietary advice will be based on an algorithm considering the
individuals* postprandial glucose, triglycerides and inflammation markers in
response (low, medium, high response group) to each of the three study meals in
Phase 1, matched with established knowledge about the effects of specific foods
on such metabolic parameters. There will be no specific meals provided for the
intervention during Phase 2.

Burdens that the participants may experience include the time they need to
invest in the study and the dietary/lifestyle restrictions during the two
intervention periods. The total study duration for a participant will be
approximately 10 months, including a 7-month break. The total time that needs
to be invested by participants in this study during visits is approximately 38
hours, of which 24 hours during Phase 1 and 14 hours during Phase 2.

While participating in the study, participants will be required to eat
standardised meals for a total of eight days during the study (standardised
dinner meal before each of the meal test -and HFMM visits; the three meal tests
themselves) as well as limit their physical activity for three days around each
meal test. This can cause limited inconvenience to the participants.
All study meals provided in this study are prepared from commercially available
foods and should not cause any major gastrointestinal or other symptoms. In
Phase 2, the participants will be required to make changes to their habitual
diet, depending on the dietary advice that was allocated to them.

The following burdens or risks may be associated with participation:

- Participants will have to wear a continuous glucose monitor (CGM) at two
occasions. The placement of the CGM, though minimally invasive, could be
considered a burden for the participants. The adhesive from the CGM sensor
could cause light skin irrita-tion but no other discomfort is to be expected.
The sensor is waterproof, thus, no sani-tary restrictions or restrictions to
recreational activities are necessary (with the excep-tion of situations that
would expose the sensor to very high temperatures, e.g., sauna, which should be
avoided during the study). We minimise this burden by using a con-tinuous
glucose monitor that does not need regular calibration by finger pricks. The
placement of the Freestyle Libre will be done by experienced researchers.
- At three occasions during the study, participants will also wear an activity
monitor; an accelerometer. The ActiGraph placement is not invasive and has an
adjustable band to make wearing it as comfortable as possible.
- During test days, blood will be collected via a venous catheter.
Venipunctures can oc-casionally result in a local hematoma or bruise. Some
participants in previous studies report pain during venepuncture. The blood
collection will be done by experienced nurses. A total of ~900 mL of blood will
be drawn over the entire RCT (> 10 month pe-riod), divided in approximately 560
mL during Phase 1 (including baseline) and 340 mL in Phase 2. For conventional
blood donations, men donate ~500 mL blood every 2.5 months and women every 4
months.
- The collection and storage of faecal and urine samples can be experienced as
a burden. However, based on previous experience, this procedure is quite
feasible.
- Throughout the study, questionnaires will be completed and food intake will
be recorded periodically by means of an app or computer during daily life,
which requires additional time investment.
- The self-administered dry blood-spot samples can cause some discomfort and
potentially irritate or bruise the skin around the puncture location.
- The total radiation dose participants will be exposed to during the DXA scan
is approximately 0.002 mSv. Since the average annual radiation exposure per
person in the Netherlands is ~2.5 mSv per year, the amount of radiation
exposure during DXA scans is negligible. Any contraindications for the DXA scan
will be checked at screening as well as immediately before the participant
undergoes the scan.
- The blue coloured pastries are made from commercially available ingredients,
including a food-grade blue dye. No discomfort is to be expected from consuming
them, only small temporary staining of the tongue, which will not last >1 hour.
- No risks are known about the OGTT and HFMM test. These measurements are
routinely applied in human metabolic research, and SOPs are available in the
database of the Human Nutrition department.

Since the prevalence of overweight and cardio-metabolic disorders is continuing
to rise, study outcomes could provide future health benefits for the general
public. Participants will receive useful information about their health status
and the intervention diets that the participants will follow may be
advantageous to overall health.