Effectiveness of protein supplementatIon combined with resistance exercise training to counteract disproportional fat-free mass loss following metabolic-bariatric surgery: the ENRICHED study.

There is a worldwide increase in both prevalence and severity of obesity with
currently over 153,000 individuals with severe obesity (i.e., body mass index
>40 kg/m2) in the Netherlands. Obesity is a chronic disease and a risk factor
for cardiovascular disease, type 2 diabetes mellitus and various cancers and
negatively impacts both physical and psychological aspects of quality of life.
For these individuals, metabolic-bariatric surgery (MBS) is the most effective
approach to achieve long-term weight loss and substantial reduction in
comorbidities. Therefore, the number of patients undergoing MBS has
exponentially increased up to 12,000 procedures annually in the Netherlands.
Previous studies have repeatedly shown that MBS is a cost-effective procedure
in terms of disease prevention and related future health care costs. However,
long-term health in these patients clearly leaves room for improvement.
Post-MBS weight loss consists of both fat mass (FM) and fat-free mass (FFM).
Skeletal muscle tissue is the largest component of FFM and is essential for
functional capacity, metabolic health, thermoregulation and bone strength.
Excessive FM and insufficient FFM, i.e. sarcopenic obesity, have negative
health consequences, therefore optimal weight loss strives for FFM maintenance
while maximizing FM loss. Our research group showed that the ratio between FM
loss and FFM loss varies largely between patients who underwent MBS, with an
average percentage of FFM loss of total weight loss (=FFML/WL) of 20-25% [range
6-54%] at 12 months post-surgery. Our recent data showed that a FFML/WL >=25%
was associated with a 1.56 times higher risk for major adverse cardiovascular
events and all-cause mortality in middle-aged and older patients. This study
highlights that a disproportional composition of weight loss with a relatively
high FFM loss could be detrimental for future health. Furthermore, 28-34% of
the patients showed a FFML/WL >=25%, underscoring that disproportional FFML/WL
is highly prevalent among individuals who underwent MBS. Therefore, MBS care
should strive for a more balanced weight loss and strategies that counteract
FFM loss during MBS-induced weight loss are required, thereby also improving
metabolic health. Interventions with additional protein and resistance exercise
are successful in increasing or maintaining muscle mass in other clinical
populations. However, studies that examined the impact of additional protein
and exercise on FFM in patients who underwent MBS remain inconclusive,
presumably due to feasibility issues. Feasibility issues may arise from
impaired protein intake, digestion and absorption following the alterations to
the gastro-intestinal tract, and/or population-specific barriers towards
exercise and diet. These population-specific limitations should be incorporated
into new, feasible intervention protocols.

To compare the effect of a 6-month of enriched care consisting of additional
protein intake and regular resistance exercise on the prevalence of
disproportional fat-free mass loss (defined as a FFML/WL >30% as main outcome
parameter) in patients who underwent MBS compared to standard care.

This is a multicenter randomized controlled trial that includes four clinical
centers of the NOK. Each center will be allocated to either control (standard
care) or intervention location (providing enriched care). Participants and
researchers could not be blinded due to practical considerations. Patients will
be informed and recruited during the preoperative care program. An initial
screening is performed by the standard care team to determine eligibility based
on in- and exclusion criteria. Informed consent will be collected prior to any
measurements.

During the 6-month intervention period, the control group follows standard care
protocols, while standard care is complemented by additional protein intake,
resistance training and counseling sessions with dieticians and
physiotherapists for the enriched care group. Patients in the enriched care
group will be provided with powdered whey protein supplements for the first
twelve postoperative weeks. To enhance tolerability and, consequently,
compliance, patients are instructed to follow a gradually increasing protein
supplementation protocol. This protocol includes 15-20 grams of whey
supplementation daily for 4 weeks, followed by 15-20 grams twice daily for the
next 4 weeks, and finally 15-20 grams thrice daily for an additional 4 weeks.
After twelve weeks, patients are enrolled in counseling sessions with NOK
dieticians, which focuses on the transition from protein supplements to
protein-rich food products, and implementing these products into the daily
intake pattern. Furthermore, these patients will be invited to join supervised
group sessions of resistance exercise at their NOK center once a week. Next to
these sessions, patients are instructed to perform resistance exercises in
their home environment on a daily base. They will be guided through this
process with the help of additional counseling sessions with a physiotherapist.
Given the gastrointestinal and physical post-operative limitations, the protein
and resistance training interventions will commence 2 and 6 weeks after the
surgical procedure, respectively. During the 6-month follow-up, all patients
are assigned to standard care. Measurements are performed before MBS, at 3, 6,
and 12 months follow-up post-baseline.

Participating in this study brings negligible risks. The products will be
produced according to the HACCP/ISO22000 regulations in certified facilities
and using approved and commercially available ingredients. Resistance training
is performed with regular supervision of trained physiotherapists and adjusted
to the participant*s needs and ability. Subject with an elevated risk related
to this study will be excluded of participation. Measures related to this study
are blood samples, body composition analysis, muscle strength/function tests,
submaximal exercise tests, physical activity and dietary intake assessments and
questionnaires/diaries. These measures are minimally invasive and can be graded
as *negligible risk*.*