Effect of Caloric Restriction and Protein Intake on Metabolism and Anabolic Sensitivity

Can Increased Dietary Protein Prevent the Suppression of Metabolism and Maintain Anabolic Sensitivity of Bone and Skeletal Muscle During Caloric Restriction?

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02945410

Enrollment

Registered

2016-10-26

Start date

2016-09-30

Completion date

2019-02-28

Last updated

2019-12-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Weight Loss, Starvation

Brief summary

The purpose of this study is to determine if an increased protein intake can attenuate the suppression of metabolic and anabolic hormones during caloric restriction

Detailed description

1. Preliminary testing Prior to the study start, participants will be weighed and body composition will be determined using calipermetry (7 sites) and bioelectrical impedance. Peak oxygen uptake (VO2peak) will be assessed using an incremental exercise test on a bicycle ergometer. 2. Randomization Participants will proceed through each of the following conditions lasting 5 days: CR-LP: Participants will be restricted to 30 kcal/kg FFM/day and protein intake will be low (0.8 g/kg BW/day). CR-HP: Participants will be restricted to 30 kcal/kg FFM/day and protein intake will be high (1.7 g/kg BW/day). CON: Participants will be in energy balance and consume 1.7 g protein/kg BW/day. 3. Diet Prescription Dietary energy intake will be controlled using clinical products and maltodextrin to meet target energy intakes. Participants will received calcium and Vitamin D supplementation throughout the study. 4. Exercise Prescription During all conditions, participants will conduct daily supervised exercise on a bicycle ergometer at an exercise intensity of 60% VO2peak. Exercise duration will be adjusted individually such that exercise energy expenditure will amount to 15 kcal/kg FFM/day. Additional exercise and intense physical activity will be prohibited. 5. Assessments The following assessments will be conducted prior to the start of each condition as well as upon completion of each condition: body weight and composition (impedance), fasting blood draw for assessment of metabolic and anabolic hormones, resting metabolic rate, aerobic fitness (VO2peak), and questionnaires. 6. Washout Once a participant has completed a study condition, participant will be allowed a washout of at least 14 days to allow protein balance to return to baseline (Hoffer & Forse, 1990). During this time, participants will resume their regular diet and physical activity.

Interventions

OTHERCaloric Restriction

Participants will consume 30 kcal/kg FFM/day.

OTHERProtein

Participants will consume 1.7 g protein/kg BW/day.

OTHERExercise

Participants will conduct aerobic exercise designed to expend 15 kcal/kg FFM/day

DIETARY_SUPPLEMENTCalcium and Vitamin D

Participants will be provided calcium and vitamin D supplement in order to maintain calcium and Vitamin D intake constant across all study arms

OTHERMaltodextrin

Participants will be provided with maltodextrin to supplement the liquid diet in order to meet caloric needs within each study arm

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

PREVENTION

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

MALE

Age

19 Years to 30 Years

Healthy volunteers

Yes

Inclusion criteria

* 4 hours/week of purposeful aerobic exercise over the last 3 months * Body mass index: 19-25 kg/m2 * \< 15% body fat

Exclusion criteria

* Cardiovascular disease risk factors that would result in greater than low risk * Smoking * Type I, type II diabetes, or history of high fasting glucose; * History of high blood pressure and/or use of medication for hypertension; * History of Dyslipidemia, or on lipid-lowering medication; * Underlying health condition and/or use of medication that could interfere with any of our study outcomes. * History or current diagnosis of a clinical eating disorder * Failure to adhere to study protocol

Design outcomes

Primary

Measure	Time frame
Change in Marker of Bone Resorption (CTx)	Baseline and day 6
Change in Resting Metabolic Rate	Baseline and day 6
Change in Circulating IGF-1	Baseline and day 6
Change in Marker of Bone Formation (P1NP)	Baseline and day 6

Secondary

Measure	Time frame	Description
Change in Body Weight	Baseline and day 6	—
Change in Body Fat Percentage	Baseline and day 6	—
Change in Aerobic Fitness (VO2peak)	Baseline and day 6	Analyzed in L/min rather than mL/kg/min to remove influence of weight loss.
Change in Perceived Hunger	Baseline and day 6	Perceived hunger will be assessed using 0-100 visual analog scales. In this case, 100 means maximum hunger while 0 means minimal hunger.

Countries

United States

Participant flow

Pre-assignment details

Participants Excluded prior to assignment: n = 4 did not meet inclusion criteria on preliminary questionnaires (n = 1 did not met the age requirements (reported a false age) n = 1 reported hyperthyroidism n = 2 reported insufficient levels of physical activity) n = 1 declined to participate in the study after enrolling

Participants by arm

Arm	Count
(1) CRHP (2) EB (3) CRNP In the Caloric Restriction and High Protein Intervention, participants will be calorie restricted to 30 kcal/kg FFM/day and consume 1.7 g protein/kg BW/day. In the Energy Balance Intervention, participants will consume 55 kcal/kg FFM/day and 1.7 g protein/kg BW/day. In the Caloric Restriction and Normal Protein Intervention, participants will be calorie restricted to 30 kcal/kg FFM/day and consume 0.8 g protein/kg BW/day. In all Interventions, participants will conduct aerobic exercise designed to expend 15 kcal/kg FFM/day. Participants will be provided calcium and vitamin D supplement in order to maintain calcium and Vitamin D intake constant across all study arms. Participants will be provided with maltodextrin to supplement the liquid diet in order to meet caloric needs within each study arm.	3
(1) CRHP (2) CRNP (3) EB In the Caloric Restriction and High Protein Intervention, participants will be calorie restricted to 30 kcal/kg FFM/day and consume 1.7 g protein/kg BW/day. In the Caloric Restriction and Normal Protein Intervention, participants will be calorie restricted to 30 kcal/kg FFM/day and consume 0.8 g protein/kg BW/day. In the Energy Balance Intervention, participants will consume 55 kcal/kg FFM/day and 1.7 g protein/kg BW/day. In all Interventions, participants will conduct aerobic exercise designed to expend 15 kcal/kg FFM/day. Participants will be provided calcium and vitamin D supplement in order to maintain calcium and Vitamin D intake constant across all study arms. Participants will be provided with maltodextrin to supplement the liquid diet in order to meet caloric needs within each study arm.	4
(1) CRNP (2) EB (3) CRHP In the Caloric Restriction and Normal Protein Intervention, participants will be calorie restricted to 30 kcal/kg FFM/day and consume 0.8 g protein/kg BW/day. In the Energy Balance Intervention, participants will consume 55 kcal/kg FFM/day and 1.7 g protein/kg BW/day. In the Caloric Restriction and High Protein Intervention, participants will be calorie restricted to 30 kcal/kg FFM/day and consume 1.7 g protein/kg BW/day. In all Interventions, participants will conduct aerobic exercise designed to expend 15 kcal/kg FFM/day. Participants will be provided calcium and vitamin D supplement in order to maintain calcium and Vitamin D intake constant across all study arms. Participants will be provided with maltodextrin to supplement the liquid diet in order to meet caloric needs within each study arm.	2
(1) CRNP (2) CRHP (3) EB In the Caloric Restriction and Normal Protein Intervention, participants will be calorie restricted to 30 kcal/kg FFM/day and consume 0.8 g protein/kg BW/day. In the Caloric Restriction and High Protein Intervention, participants will be calorie restricted to 30 kcal/kg FFM/day and consume 1.7 g protein/kg BW/day. In the Energy Balance Intervention, participants will consume 55 kcal/kg FFM/day and 1.7 g protein/kg BW/day. In all Interventions, participants will conduct aerobic exercise designed to expend 15 kcal/kg FFM/day. Participants will be provided calcium and vitamin D supplement in order to maintain calcium and Vitamin D intake constant across all study arms. Participants will be provided with maltodextrin to supplement the liquid diet in order to meet caloric needs within each study arm.	3
(1) EB (2) CRHP (3) CRNP In the Energy Balance Intervention, participants will consume 55 kcal/kg FFM/day and 1.7 g protein/kg BW/day. In the Caloric Restriction and High Protein Intervention, participants will be calorie restricted to 30 kcal/kg FFM/day and consume 1.7 g protein/kg BW/day. In the Caloric Restriction and Normal Protein Intervention, participants will be calorie restricted to 30 kcal/kg FFM/day and consume 0.8 g protein/kg BW/day. In all Interventions, participants will conduct aerobic exercise designed to expend 15 kcal/kg FFM/day. Participants will be provided calcium and vitamin D supplement in order to maintain calcium and Vitamin D intake constant across all study arms. Participants will be provided with maltodextrin to supplement the liquid diet in order to meet caloric needs within each study arm.	2
(1) EB (2) CRNP (3) CRHP In the Energy Balance Intervention, participants will consume 55 kcal/kg FFM/day and 1.7 g protein/kg BW/day. In the Caloric Restriction and Normal Protein Intervention, participants will be calorie restricted to 30 kcal/kg FFM/day and consume 0.8 g protein/kg BW/day. In the Caloric Restriction and High Protein Intervention, participants will be calorie restricted to 30 kcal/kg FFM/day and consume 1.7 g protein/kg BW/day. In all Interventions, participants will conduct aerobic exercise designed to expend 15 kcal/kg FFM/day. Participants will be provided calcium and vitamin D supplement in order to maintain calcium and Vitamin D intake constant across all study arms. Participants will be provided with maltodextrin to supplement the liquid diet in order to meet caloric needs within each study arm.	1
Total	15

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG004	FG005
Intervention 1 (5 Days)	Adverse Event	1	0	0	0	1
Intervention 1 (5 Days)	Withdrawal by Subject	0	3	0	0	0
Washout 1 (14 Days)	Withdrawal by Subject	0	0	2	1	0

Baseline characteristics

Characteristic	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) EB (3) CRHP	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP	(1) EB (2) CRNP (3) CRHP	Total
Aerobic Fitness (VO2max)	43.4 mL/kg/min STANDARD_DEVIATION 2.1	46.7 mL/kg/min STANDARD_DEVIATION 5.2	47.1 mL/kg/min STANDARD_DEVIATION 6.5	41.0 mL/kg/min STANDARD_DEVIATION 10.4	41.6 mL/kg/min STANDARD_DEVIATION 5	42.3 mL/kg/min STANDARD_DEVIATION 0	43.6 mL/kg/min STANDARD_DEVIATION 5.7
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	3 Participants	4 Participants	2 Participants	3 Participants	2 Participants	1 Participants	15 Participants
Age, Continuous	21.3 Years STANDARD_DEVIATION 3.2	19.5 Years STANDARD_DEVIATION 0.6	21 Years STANDARD_DEVIATION 0	25.3 Years STANDARD_DEVIATION 3.8	27 Years STANDARD_DEVIATION 1.4	21 Years STANDARD_DEVIATION 0	22.3 Years STANDARD_DEVIATION 3.4
Percentage Body Fat	17.9 % body fat STANDARD_DEVIATION 5.2	13.4 % body fat STANDARD_DEVIATION 4.4	12 % body fat STANDARD_DEVIATION 0.1	18 % body fat STANDARD_DEVIATION 1.7	19.2 % body fat STANDARD_DEVIATION 1.8	15 % body fat STANDARD_DEVIATION 0	15.9 % body fat STANDARD_DEVIATION 4
Race and Ethnicity Not Collected	—	—	—	—	—	—	0 Participants
Region of Enrollment United States	3 participants	4 participants	2 participants	3 participants	2 participants	1 participants	15 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	3 Participants	4 Participants	2 Participants	3 Participants	2 Participants	1 Participants	15 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 11	0 / 9	0 / 9
other Total, other adverse events	1 / 11	0 / 9	1 / 9
serious Total, serious adverse events	0 / 11	0 / 9	0 / 9