Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04773132 |
| Other study ID # |
2014/01182 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 19, 2015 |
| Est. completion date |
December 11, 2017 |
Study information
| Verified date |
February 2021 |
| Source |
Clinical Nutrition Research Centre, Singapore |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Obesity is commonly described as a consequence of excess calorie intake. Conventionally, the
physiological variables that have been of extensive interest are food intake and energy
expenditure. Despite decades of research on factors influencing intake and expenditure, to
date, no compelling theory has been promulgated to explain why certain humans are more
susceptible to weight gain than others. The investigators hypothesize that the measure of an
individual's fraction of energy mobilized or deposited as protein (P-ratio), contributes
towards an obese morphology and may essentially form a novel approach in understanding the
etiology, management and treatment of obesity. In addition, there is a general perception
that the consumption of sugar sweetened foods and beverages are one of the major causes of
obesity. This study aims to understand metabolic flexibility and the glycemic index of diets
in the etiology of obesity. Individual metabolic flexibility may be the key factor that
predisposes an individual to obesity. This study is carried out to determine the P-ratio in
human subjects.
Description:
Obesity is commonly described as a consequence of excess calorie intake. Conventionally, the
physiological variables that have been of extensive interest are food intake and energy
expenditure. Despite decades of research on factors influencing intake and expenditure, to
date, no compelling theory has been promulgated to explain why certain humans are more
susceptible to weight gain than others. The investigators believe that a measure of an
individual's metabolic flexibility towards an obese morphology is essential and forms a novel
approach in understanding the etiology, management and treatment of obesity. Payne and
Dugdale developed a simple model of energy balance, based on dividing the human body into
four compartments, namely "fast" lean tissue (protein), "slow" lean tissue (protein),
structural fat, and tissue fat. Notionally, these are considered to act as four separate
compartments which interconnect with each other. Body weight is thus simply the sum of the
four weights, and metabolic rate is the sum of the separate compartment rates. Any energy
deficit in the "balancing compartment" is met by withdrawing tissues from the neighboring fat
and lean (muscle) compartments in a proportion which is fixed for any individual. The
observed human variability in both the susceptibility to gain weight or to lose weight
efficiently on a calorie surplus or restricted diet is thus afforded by using the model
developed by Payne and Dugdale for energy balance. P-ratio is calculated on the assumption
that body protein is 16% nitrogen and has a metabolizable energy value of 16.7 kJ/g. Thus
P-ratio can be calculated as: P- ratio= urinary nitrogen excretion x 6.25 x 16.7 / total
energy expenditure. The regulatory control of energy-partitioning between protein and fat is
highly variable between individuals, but constant within the same subject. It is this
variability in tissue partitioning between lean (protein) and fat that is central to the
regulation of body weight. This implies that for a given individual, there is a fixed
partitioning of energy between lean (protein) and fat tissue when excess calories are
consumed. Using the results of the classical study of human semi-starvation by Keys et al,
Dugdale and Payne calculated the individual pattern of tissue mobilization (P-ratio) in these
subjects. The P-ratio ranged from 0.03 to 0.60. On the basis of these data, they classified
individuals into "metabolically lean" and "metabolically fat". A P-ratio of 0.03 means
approximately 3% of the energy loss from this subject's body tissues was derived from protein
catabolism and 97% from fat. Thus during excess calorie consumption, 3% of the calories will
be deposited as protein and 97% as fat ("metabolically fat"). Similarly a subject with a
P-ratio of 0.60 will deposit 60% calories as protein and only 40% as fat ("metabolically
lean"). This stratification of "metabolic type" is a novel approach in obesity research,
treatment and its management. The current method for the determination of P-ratio is based on
subjects undergoing total starvation/fasting, e.g. complete food restriction, ad libitum
water intake. This is a highly impractical approach. The investigator's proposal is to
develop a more convenient and practical methodology to determine the P-ratio. An individual's
Basal Metabolic Rate after a 10 hour overnight fast will approximate the denominator of the
P-ratio. Henry et al reported a quantitative relationship between a fasting urine nitrogen
loss (FUNL) and obligatory urinary nitrogen loss (OUNL), the ratio FUNL: OUNL remained close
to 1.5. OUNL can be measured in urine when a subject is fed a protein free diet. With these
two measures, the P-ratio of an individual can be estimated. OUNL is the protein lost in the
urine when fed a zero or non-protein diet and fasting urinary loss is the nitrogen lost
during starvation/ fasting (FUNL). The investigator's proposed study will be the first
real-time study that will utilize the obligatory urine nitrogen loss and BMR to quantitate
human P-ratio.
