Metabolic Syndrome, Non Alcoholic Fatty Liver Disease, Obese, Overweight
Conditions
Keywords
high protein diet, meal replacements, low calorie diet, intra hepatocellular lipid
Brief summary
Obesity is a major problem worldwide and current dietary interventions are not proving to be enough to cease the increase in levels of obesity and its detrimental side effects, such as nonalcoholic fatty liver disease (NAFLD). Existing data suggests that adjustments in the macronutrient composition of the diet, more specifically the protein content, may have beneficial effects on body composition and an antiobesegenic effect on appetite. This may be important in terms of controlling body weight and reducing the amount of fatty tissue within our bodies and organs, and therefore preventing obesity and its health related side effects. The investigators will perform a study to investigate whether a high protein low energy diet compared to a normal protein low energy diet, in overweight adults can modify appetite and aid loss of weight and fat mass. Subjects will receive either a high protein low energy diet (1.34g protein/kg body weight) or a normal protein low energy diet (0.8g protein/kg body weight) in the form of 2 meal replacements and one conventional meal per day with 2 snacks for 12 weeks. HYPOTHESIS In overweight subjects with the metabolic syndrome, a 12 week dietary intervention with a high protein low energy diet will lead to a reduced appetite, body weight and fat mass, more specifically to a greater fall in levels of fat in the liver and pancreas than a low energy normal protein diet.
Interventions
DIETARY_SUPPLEMENTHigh Protein, low calorie meal replacement
The high protein group will have meal replacements with added protein powder (to achieve 1.34g protein/kg body weight) and the control group will have standard meal replacements (0.8g protein/kg body weight). Meal replacements have been used in hundreds of previous human studies and are generally not found to be linked to any serious adverse effects.
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Overweight and obese people as classified by BMI 27-35kg/ m2 (inclusive) * A Finnish Diabetes Risk Score (FINDRISC) \>8 \[22\] * Waist circumference measurement of ≥102cm in males or ≥88cm in females * Assessed as appropriate for inclusion, based on a prestudy screening (see section 3.4) * Willingness and ability to give written informed consent and willingness and ability to understand, to participate and to comply with the study requirements
Exclusion criteria
* Claustrophobia * Pacemaker, metal implant, clips, implanted device, shrapnel or bullets, metal in eyes that precludes magnetic resonance imaging * Treatment with any medication that might affect the study outcome (e.g., medication that is affecting appetite regulation and/or blood flow) * Current pregnancy or breast feeding * Delivery within the last year * Bariatric surgery * History of any disease with unknown outcome * Significant intercurrent disease or history of clinically significant disease of any type, in particular liver, kidney, or heart disease, any form of diabetes mellitus or psychiatric illness (including Depression as defined by BDIII score above 28) * History of cancer, excluding skin cancer * History of severe or multiple allergies, severe adverse drug reaction or leucopenia * Smokers * Regular drinkers of more than three units of alcohol daily (1 unit = 300 ml beer, 1 glass wine, 1 measure spirit) * Subjects who have had a fluctuation of body weight \>5% in the 3 months prior to entering into the study * History of, or current evidence of, abuse of alcohol or any drug substance, licit or illicit * Regular intake of overthecounter (OTC) medication (other than the occasional paracetamol/aspirin) * Poor compliers or subjects unlikely to attend * Blood donation within the 12 week period before the initial study dose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Lipid Content of the Liver (Intrahepatocellular Lipid) | Change from Baseline at 12 weeks | Changes in body weight and body composition, more specifically visceral, muscle, liver and pancreas fat content will be measured using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Individual's data will be compared at baseline and at 12 weeks of following the diet and also to that of the participants given normal protein low energy diets. This data may therefore support our hypothesis that high protein intakes may help to aid weight loss and reduce fat mass and would therefore be a viable option in the treatment of obesity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Appetite Regulation, Measured by VAS and Food Intake. | Baseline and 12 weeks | It has also been suggested that highprotein diets are more beneficial in the regulation of appetite. We therefore aim to measure any changes in appetite whilst on a highprotein lowenergy diet compared to a normalprotein lowenergy diet. Changes in appetite will be measured using validated questionnaires assessing subjects feeling of hunger, pleasantness and volume able to eat as well as fullness. This data may support our hypothesis that highprotein intakes may alter appetite regulation and therefore be a useful in the treatment of obesity. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Composite Appetite Score AUC (Area Under Curve) | Baseline and 12 weeks | A composite appetite score was calculated combing all four appetite measures to give a summary measure of appetite. Each appetite measure was assessed using validated 100 mm visual analogue scales (VAS) for hunger, fullness, desire to eat, and prospective food consumption (PFC) with the most positive and most negative sensations anchoring opposite ends of the line, from 'Not at all' or 'Nothing' to 'Extremely' or 'A large amount'. Participants were asked to mark the line at the point corresponding to their perceived appetite at that time. There is no score which is better or worse. Composite Appetite score (mm min) = \[desire to eat + hunger + (100 - fullness) + prospective consumption\]/4, as described by (Anderson et al, 2002). This reflects the four appetite related VAS (visual analogue scale) questions and was used as a summary measure of appetite. Area Under the Curve (AUC) was calculated for composite appetites score using the trapezoidal rule. AUC scores range from 0-9000mm\*min |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Protein Low Calorie Meal Replacements Meal replacements with added protein powder(1.34g pro/kg).
High Protein, low calorie meal replacement: The high protein group will have meal replacements with added protein powder (to achieve 1.34g protein/kg body weight) and the control group will have standard meal replacements (0.8g protein/kg body weight). Meal replacements have been used in hundreds of previous human studies and are generally not found to be linked to any serious adverse effects. | 21 |
| Normal Protein, Low Calorie Meal Replacement Group The control group will have standard meal replacements (0.8g protein/kg body weight).
High Protein, low calorie meal replacement: The high protein group will have meal replacements with added protein powder (to achieve 1.34g protein/kg body weight) and the control group will have standard meal replacements (0.8g protein/kg body weight). Meal replacements have been used in hundreds of previous human studies and are generally not found to be linked to any serious adverse effects. | 18 |
| Total | 39 |
Baseline characteristics
| Characteristic | High Protein Low Calorie Meal Replacements | Normal Protein, Low Calorie Meal Replacement Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 18 Participants | 39 Participants |
| Age, Continuous | 46 years STANDARD_DEVIATION 9 | 44 years STANDARD_DEVIATION 14 | 45 years STANDARD_DEVIATION 11 |
| BMI | 30.6 kg/m2 STANDARD_DEVIATION 3 | 30.8 kg/m2 STANDARD_DEVIATION 2.4 | 30.7 kg/m2 STANDARD_DEVIATION 2.7 |
| Race/Ethnicity, Customized Asian | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Mixed | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 12 Participants | 23 Participants |
| Region of Enrollment United Kingdom | 21 participants | 18 participants | 39 participants |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Change in Lipid Content of the Liver (Intrahepatocellular Lipid)
Changes in body weight and body composition, more specifically visceral, muscle, liver and pancreas fat content will be measured using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Individual's data will be compared at baseline and at 12 weeks of following the diet and also to that of the participants given normal protein low energy diets. This data may therefore support our hypothesis that high protein intakes may help to aid weight loss and reduce fat mass and would therefore be a viable option in the treatment of obesity.
Time frame: Change from Baseline at 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Protein Low Calorie Meal Replacements | Change in Lipid Content of the Liver (Intrahepatocellular Lipid) | IHCL Baseline | 27.9 % IHCL | Standard Error 26.8 |
| High Protein Low Calorie Meal Replacements | Change in Lipid Content of the Liver (Intrahepatocellular Lipid) | IHCL 12 weeks | 21.4 % IHCL | Standard Error 23.2 |
| Normal Protein, Low Calorie Meal Replacement Group | Change in Lipid Content of the Liver (Intrahepatocellular Lipid) | IHCL 12 weeks | 5.9 % IHCL | Standard Error 5 |
| Normal Protein, Low Calorie Meal Replacement Group | Change in Lipid Content of the Liver (Intrahepatocellular Lipid) | IHCL Baseline | 9.3 % IHCL | Standard Error 5.6 |
p-value: <0.05ANOVA
Secondary
Change in Appetite Regulation, Measured by VAS and Food Intake.
It has also been suggested that highprotein diets are more beneficial in the regulation of appetite. We therefore aim to measure any changes in appetite whilst on a highprotein lowenergy diet compared to a normalprotein lowenergy diet. Changes in appetite will be measured using validated questionnaires assessing subjects feeling of hunger, pleasantness and volume able to eat as well as fullness. This data may support our hypothesis that highprotein intakes may alter appetite regulation and therefore be a useful in the treatment of obesity.
Time frame: Baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Protein Low Calorie Meal Replacements | Change in Appetite Regulation, Measured by VAS and Food Intake. | Energy Intake Baseline | 1769 kcal Energy | Standard Error 205 |
| High Protein Low Calorie Meal Replacements | Change in Appetite Regulation, Measured by VAS and Food Intake. | Energy Intake 12 weeks | 1369 kcal Energy | Standard Error 125 |
| Normal Protein, Low Calorie Meal Replacement Group | Change in Appetite Regulation, Measured by VAS and Food Intake. | Energy Intake 12 weeks | 1528 kcal Energy | Standard Error 114 |
| Normal Protein, Low Calorie Meal Replacement Group | Change in Appetite Regulation, Measured by VAS and Food Intake. | Energy Intake Baseline | 1864 kcal Energy | Standard Error 156 |
Other Pre-specified
Composite Appetite Score AUC (Area Under Curve)
A composite appetite score was calculated combing all four appetite measures to give a summary measure of appetite. Each appetite measure was assessed using validated 100 mm visual analogue scales (VAS) for hunger, fullness, desire to eat, and prospective food consumption (PFC) with the most positive and most negative sensations anchoring opposite ends of the line, from 'Not at all' or 'Nothing' to 'Extremely' or 'A large amount'. Participants were asked to mark the line at the point corresponding to their perceived appetite at that time. There is no score which is better or worse. Composite Appetite score (mm min) = \[desire to eat + hunger + (100 - fullness) + prospective consumption\]/4, as described by (Anderson et al, 2002). This reflects the four appetite related VAS (visual analogue scale) questions and was used as a summary measure of appetite. Area Under the Curve (AUC) was calculated for composite appetites score using the trapezoidal rule. AUC scores range from 0-9000mm\*min
Time frame: Baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Protein Low Calorie Meal Replacements | Composite Appetite Score AUC (Area Under Curve) | Composite Appetite Score (VAS) Baseline | 4063 mm*min | Standard Deviation 372 |
| High Protein Low Calorie Meal Replacements | Composite Appetite Score AUC (Area Under Curve) | Composite Appetite Score (VAS) 12 weeks | 3728 mm*min | Standard Deviation 428 |
| Normal Protein, Low Calorie Meal Replacement Group | Composite Appetite Score AUC (Area Under Curve) | Composite Appetite Score (VAS) Baseline | 3376 mm*min | Standard Deviation 372 |
| Normal Protein, Low Calorie Meal Replacement Group | Composite Appetite Score AUC (Area Under Curve) | Composite Appetite Score (VAS) 12 weeks | 3370 mm*min | Standard Deviation 428 |