The Influence of a Meal Replacement Formula on Leptin Regulation in Obese Adults

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*Corresponding author email: aloys.berg@klinikum.uni-reiburg.de
Symbiosis Group
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

12345
6 7*
1Zentrum für Prävention und Sportmedizin, Technische Universität München, Germany
2NIHR Clinical Research Network: Diabetes, Metabolic & Endocrine and Renal Disorders, Imperial College, London
3Department of Epidemiology & Prevention, Wake Forest University Health Sciences, Winston-Salem, North Carolina, US
4Department of Health and Human Sciences, London Metropolitan University, London, UK
5Institut für Bewegungs- und Arbeitsmedizin, Universitätsklinikum Freiburg, Germany
6Department of Nutrition, Institut für Sport und Sportwissenschaft, Universität Freiburg, Germany
7Medizinische Fakultät der Universität Freiburg, Germany
 Open Access
Research Article

*Corresponding author: Prof. Dr. med. Aloys Berg, Medizinische Fakultät der Universität Freiburg, E-mail: aloys.berg@klinikum.uni-reiburg.de

Yrs: Years; BMI: Body Mass Index; kg/m2: Kilogram/
Meter2; LS: Lifestyle group; MR: Standardized meal replacement
group; MRPT: Standardized meal replacement accompanied by
supervised physical training; ng/ml: Nanogram/millilitre; kg:
Kilogram; h-CRP: High-sensitivity C-reactive protein; IL6: Human
Interleukin 6; SD: standard deviations; SPSS: Analytical Software;
BW: Body Weight; G: Gramm

Obesity levels have dramatically increased in the United
States (US) and in the majority of European countries during the
past few decades [1-3]. A study in 2001 [4] revealed increases in
obesity among US adults for both sexes and across all ages, ethnic
backgrounds, educational levels and smoking levels. A chronic
imbalance between energy intake and energy expenditure
appears to play a role in the development of obesity [5, 6].
Serum leptin levels may have a potential role in the prediction
of weight loss and weight-loss maintenance [7]. Serum leptin
       
through lifestyle changes in overweight adults [8, 9]. Leptin, as a
circulating adipokine, is a regulatory factor for food intake, energy
expenditure and body fat distribution. Leptin also participates
in a signalling system regulating the amount of adipose energy
stored in the brain [5]. In addition, leptin resistance may be
responsible, in part, for the development of obesity among the
aging population [10].
Appropriate intervention strategies to reverse body weight
gain and elevated body fat, respectively, are still a matter of
debate because additional metabolic and endocrine effects may
         
[11]. According to several studies, a high-protein, low-glycaemic

   The increasing prevalence of
overweight and obese adults warrants improved dietary strategies
for weight management and metabolic control. Hence, the objective
of this study was to investigate the effects of a high-protein diet on
leptin regulation.
This study was a secondary analysis of data collected
from a randomized controlled trial, conducted in 90 overweight adults
(age: 47.5 ± 7.5 yrs.; BMI: 31.5 ± 2.3 kg/m2) who were followed over
         
         
weight loss and intervention type. Participants were randomized
into 3 interventions groups: 1) therapeutic lifestyle changes, (LS);
2) standardized meal replacement (Almased®) (MR); and 3)
standardized meal replacement accompanied by supervised physical
training (MRPT). For the analyses, both diet groups (MR, MRPT) were
pooled into one common group and compared to the LS group in a
parallel two-group study design with endpoint assessment after 24
weeks of intervention.
 In total, 83 participants completed the 24-week study.
      
regulation occurred in all intervention participants regardless of
their group assignment (LS; MR, MRPT). Participants’ consumption

effect on serum leptin levels (-15.5 ± 7.5 and -12.5 ± 7.8 vs. -8.7 ± 6.1
ng/ml). Greater body weight reductions were also observed in the
diet groups (-8.9 ± 3.9 kg) compared to the LS group (-6.2 ± 4.2 kg).
Conclusions



 Leptin; Meal Replacement; Energy Metabolism; High
Protein Diet; Weight Regulation;

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 Koohkan S, Golesorkhi M, Vitolins MZ, McCarthy DH, Berg A, et al. (2016) The Influence of a Meal Replacement
Formula on Leptin Regulation in Obese Adults. J Nutrition Health Food Sci 4(4): 1-5. DOI: http://dx.doi.org/10.15226/
jnhfs.2016.00169


© 

13]. For this reason, a subgroup analysis was performed on the
data collected from an intervention study to examine the effects
of a protein-rich meal replacement on the body composition and
metabolic conditions of overweight adults.

For the secondary data analyses, we used data collected from
a randomized controlled three-arm study including 90 men and
women. All volunteers were overweight middle-aged adults
(31.5 ± 2.3 kg/m2; 47.5 ± 7.5 yrs.); non-smokers; free from known
food allergies, metabolic diseases; and none regularly used any
medications.
For the main trial, participants were randomized into 3
intervention groups: 1) therapeutic lifestyle changes: LS; 2)
standardized meal replacement (Almased ®), MR; and 3)
standardized meal replacement accompanied with supervised
exercise/physical training (MRPT). All participants completed
a comprehensive medical examination before and after the
intervention, including body composition analysis by air
displacement plethysmography (Bod Pod®) [14] and laboratory
investigations, i.e., blood glucose, insulin, plasma lipids,

For this investigation, we analysed leptin and insulin
changes to determine the effects of age, gender, baseline level,
weight loss, and intervention type. In this analysis, the effects
of the therapeutic lifestyle vs. diet with and without supervised
exercise interventions on the selected laboratory criteria were
evaluated. We also evaluated the change from baseline to the end
of intervention at the 24-week visit.
All volunteers were interviewed and screened before
participating in this study at the Department of Sports Medicine
of the Freiburg University hospital. The study was conducted
in accordance with the Declaration of Helsinki guidelines. All
procedures involving human subjects were approved by the
Ethics Commission of Freiburg University (EK-Freiburg No.
230/01) and registered as a controlled clinical trial (ClinicalTrials.

informed consent. The clinical trial was designed and performed
according to an approved, published protocol [11].

For the secondary data analysis, both meal replacement
groups were merged into a single group (MR/MRPT) due to the
similarity of their outcomes (Table 1). The meal replacement
groups were compared to the lifestyle group (LS) in a parallel
two-group evaluation. The endpoint assessment occurred 24
weeks after the interventions.
The results are expressed as the means ± Standard Deviations
[SD] for all parameters. Descriptive, multivariable analyses were
performed to evaluate the changes from baseline using the exact
Mann-Whitney test and the ANOVA test. For each participant,
complete data sets were available in Microsoft® Excel XP
        
All analyses were performed using SPSS version 18.02.



and MRPT (p > 0.1) (Table 1).
Therefore, for this secondary data analysis, both
meal replacement groups using the meal replacement
formula were merged into a single group (MR/MRPT)
and compared to the lifestyle group (LS) with endpoint
assessment after 24 weeks of intervention (Table 2).
At baseline, all demographic, clinical and laboratory variables
were not different between groups. Independent of the
intervention (LS vs. MR/MRPT), the 83 patients who completed
       
and metabolic regulation (Table 2). The MR and MRPT groups
experienced changes in body weight (BW -8.9 ± 3.9 kg)
       
reductions compared to the LS group (-6.2 ± 4.2 kg).
    
mass, serum leptin levels, and insulin between the interventions
(Table 2). Even after adjusting for weight loss differences,
  
reductions in serum leptin levels (-13.9 ng/ml) compared with
participants in the LS group (-9.8 ng/ml) post-intervention. This
effect was not observed for insulin.

In this study, we compared the effects of different weight-
management interventions, including therapeutic lifestyle
changes and the use of a meal replacement product with or
without supervised exercise training. Overall weight and fat
        
This group also demonstrated greater improvements in blood
markers of metabolic health.
          
       
yoghurt-honey-based meal replacement product (Almased®) on
weight reduction and the regulation of insulin and leptin [11].
According to this randomized controlled trial, insulin and leptin
levels decreased more in participants using the meal replacement
compared to participants receiving lifestyle group counselling.
In the current study, we conducted a secondary analysis of the

         
        
formula on reductions in leptin and insulin levels. These results

When the leptin results were adjusted for age, gender,
baseline leptin level, body weight change, and intervention
type (LS vs. MR/MRPT), the meal replacement approach
clearly had an independent effect on plasma leptin levels and
improved the effects on leptin reduction caused by weight loss.
Therefore, the results suggest a relationship between protein
intake and leptin regulation in the overweight adults examined.
Several studies have demonstrated that an increase in the

Page 3 of 5
 Koohkan S, Golesorkhi M, Vitolins MZ, McCarthy DH, Berg A, et al. (2016) The Influence of a Meal Replacement
Formula on Leptin Regulation in Obese Adults. J Nutrition Health Food Sci 4(4): 1-5. DOI: http://dx.doi.org/10.15226/
jnhfs.2016.00169


© 

     
 
Total cholesterol (mg/dl) 225 ±30.4 196±23.1 0.000 221±34.8 198±32.6 0.000 0.396
HDL-cholesterol (mg/dl) 59±14.1 52±10.4 0.003 59±14.0 54±15.6 0.002 0.763
LDL-cholesterol (mg/dl) 128±25.6 114±15.2 0.003 127±29.2 112±26.3 0.000 0.897
Apo B (mg/dl) 119±20.9 101±16.2 0.000 115±27.4 92.5±25.5 0.000 0.085
Leptin (ng/dl) 37.9±26.7 22.5±13.9 0.000 33.9±24.2 21.3±16.3 0.000 0.226
Insulin (µU/ml) 11.7±8.92 6.3±3.97 0.003 13.8±11.35 7.8±5.90 0.001 0.139
Glucose (mg/dl) 92±9.4 90.0±9.1 0.226 98±14.4 91.0±10.5 0.000 0.260
Data comparison between the MR and MRPT groups [11].
aFor changes before–after
bFor differences in changes between the groups
proportion of dietary protein from 15% to 30% of energy
intake with a constant level of carbohydrate intake produces a
sustained decrease in ad libitum energy intake, which may be
mediated by increased central nervous system leptin sensitivity
       
protein loss and enhancing glycaemic control [7, 11-12, 15-16].
Participants consuming a diet high in protein with a low
glycaemic index continue to lose weight after the initial weight
loss [13]. In fact, higher dietary protein intake was achieved by
reducing carbohydrate intake, which adds further support to
        
carbohydrate content (g) multiplied by glycaemic index) is
important for controlling body weight in obese patients [17-19].

found in soy protein isolates) may also contribute to the weight
loss produced by low-carbohydrate diets [7, 20]. Moreover, weight
loss interventions using meal replacement approaches together
with dietary counselling and increased physical activity lead
to substantial, favourable changes in both anthropometric and
metabolic risk factors, while preserving lean muscle mass [12, 21].
Recent studies have shown that meal replacement regimens are
safe and associated with greater weight loss than individualized
diet plans [22, 23]. A meal replacement regimen high in soy
protein may be more effective at improving body weight and body
composition and reducing associated cardio-metabolic risk factors,
such as insulin, leptin, endothelial function and anthropometric
measures compared to lifestyle interventions (e.g., fat restricting
low calorie diets and increased physical activity) [11, 24, 25].
      
      
(compared to baseline). As a soy and milk protein-based product,
the meal replacement used in this study had an energy-sparing

Soy proteins have been noted to improve receptor-mediated
transport of insulin and leptin through the blood brain barrier
                   










Body Weight
(kg)
91.2±11.6 90.2±11.3 84.9±10.8
c / y
81.8±11.7
c / y
Fat Mass
(kg)
36.9±6.27 36.2±6.38 30.4±7.60
c / x
26.8±7.80
c / x
Triglyceride
(mg/dl)
127±68.4 143±66.0 137±55.2
-
133±71.9
-
Apolipoprotein B
(mg/dl)
115±20.3 117±23.9 105±20.9
- /c
97±21.6
c / x
Fasting Blood
Sugar (mg/dl)
95±14.1 95±12.2 90±9.9
a / -
90±9.8
c / -
Insulin
(µU/ml)
8.8±3.92 12.7±10.1 7.4±3.98
- / y
7.1±5.02
c / y
HOMA- Index
(U)
2.2±1.26 3.1±2.65 1.7±1.00
- / y
1.6±1.17
c / y
Leptin
(ng/ml)
37±29.2 36±25.4 28±20.7
b / y
22±15.0
c / y
Interleukin-6
(pg/ml)
1.8±1.25 2.2±2.05 1.8±2.30
-
1.7±1.29
A
hs-CRP
(mg/dl)
0.27±0.22 0.30±0.28 0.23±0.16
-
0.19±0.17
C

Page 4 of 5
 Koohkan S, Golesorkhi M, Vitolins MZ, McCarthy DH, Berg A, et al. (2016) The Influence of a Meal Replacement
Formula on Leptin Regulation in Obese Adults. J Nutrition Health Food Sci 4(4): 1-5. DOI: http://dx.doi.org/10.15226/
jnhfs.2016.00169


© 
and are responsible for an increased effect of these hormones
in the hypothalamus. This effect not only impacts appetite
regulation but may also impact peripheral insulin and leptin
resistance in obese participants [27-30]. These effects may
       
exhibit a variety of biological and molecular activities [20,25].
         
proteins important for lipid metabolism [31, 32]. The effects
of soy protein on gene expression or the regulation of nuclear
transcription factors might also, at least in part, be able to
account for the alterations observed in insulin and leptin [33,
       
this meal replacement product [20] may account for some of the

a reduction in body fat mass and hepatic fat accumulation, in
addition to improved fatty acid metabolism, which led to lower
       
insulin resistance [33].

In summary, the meal replacement strategy utilized
for weight reduction in this trial may provide therapeutic
    
including impaired glucose tolerance and leptin resistance.
      
       
milieus that are responsible for weight stabilization. Moreover,
the meal replacement product can safely and effectively produce

leptin.

We thank the technical staff of the Department of
Rehabilitative und Präventive Sportmedizin, Medizinische
Universitätsklinik Freiburg – renamed the Institut für
Bewegungs- und Arbeitsmedizin - for their assistance in input
operations. We also thank all general practitioners who were
engaged in supervising the lifestyle program. Last, we thank the
Almased Wellness Company (Bienenbüttel, Germany) for their
support in performing this study.

This research was funded by Almased Wellness GmbH,
Bienenbüttel, Germany. A. Berg has written “The Almased Well-
ness Concept” outlining the effects of a soy-enriched diet in ealth
and disease.
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