Dietary Protein Restriction and Health (LOWPRO)

Dietary Protein, FGF21 and Glucose Homeostasis

The incidence of type 2 diabetes worldwide has increased significantly over the past decades, which is associated with changing dietary habits and physical inactivity. According to the diet, so far there has been a great focus on the quality of carbohydrates and fat in relation to metabolic health, while the importance of protein has been neglected. The Danes' average protein intake is 1.5 g/kg/day, which is at the high end of the recommendations (0.8-1.5 g/kg/day) from the Nordic Nutrition Recommendations (NNR 2023). Recent studies in rodents have shown that protein restriction has positive effects on health, including improved glucose and insulin homeostasis and reduced fat mass, while a high intake of protein has a negative effect on insulin sensitivity. Previously the investigators have shown, in healthy young men, that consuming a diet low in protein (0.9 g/kg/day), compared to the participants usual diet (1.5 g/kg/day), over 7 days, resulted in an increased insulin sensitivity as well as a marked increase in the plasma fibroblast growth factor 21 (FGF21) concentration. The increased insulin sensitivity is thought to be mediated by the increase in plasma FGF21 concentration. However, the effect is not yet fully understood. It is also not clear whether the increase in plasma FGF21 concentration, as well as the mentioned metabolic effects on insulin and glucose homeostasis, will take place if the participants are kept weight stable on a eucaloric diet.

Study Overview

• Status: Completed
• Conditions: Healthy; Diet; Protein
• Intervention / Treatment: Other: Dietary protein restriction

Detailed Description

A three-arm protocol was performed. In protocol 1, participants ingested either a low-protein (LP) meal or a higher protein (HP) meal in a randomized order, separated by 72 h, followed by a 5-week low-protein, high-carbohydrate (LPHC) diet. In protocol 2 and 3, participants ingested either a LPHC diet or a low-protein, high-fat (LPHF) diet for 5 weeks followed by a higher protein diet (HPD) for another 5 weeks. All diets were eucaloric. Resting metabolic rate (RMR) was measured pre, during and post the protein-restricted interventions. A hyperinsulimic-euglycemic clamp was performed post the protein-restricted interventions and post the HPD interventions. A basal subcutaneous abdominal fat biopsy was obtained post the protein-restricted interventions and post the HPD interventions. In a run-in period over 14 days, the participant records the daily number of steps and physical activity, in order to determine their habitual activity level. During this period, a 4-day dietary record is performed, where all ingested food was weighed and recorded. During the experimental period the participant followed the supplied diet. All food consumed during the interventions was handed out to the subject at the institute. All food was packaged and weighed to 1 gram of accuracy. During the dietary intervention, a weekly test in the morning was performed, where the resting metabolic rate was measured and blood samples taken from the arm vein. At week 0, 5 and week 10 body composition was measured by dual energy x-ray absorptiometry scanning (DXA), and the fat biopsy was obtained . At all tests participants arrived fasting at the institute at 8:00 a.m. in the morning. The participant arrived by car or public transport.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • University of Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI≤25
• Maximal oxygen uptake ≤42-51 ml/kg/min) • non-smoking

Exclusion Criteria:

• The use of medicine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acute meal test; acute intake of a low protein, high carbohydrate diet. No drug intervention	Other: Dietary protein restriction; The consumption of different diets restricted in protein replaced by either carbohydrate or fat and an habitual diet.
Experimental: Chronic low protein, high carbohydrate diet; Low protein, high carbohydrate diet and habitual diet. No drug intervention	Other: Dietary protein restriction; The consumption of different diets restricted in protein replaced by either carbohydrate or fat and an habitual diet.
Experimental: Low protein , high fat diet; Low protein, high fat diet and habitual diet. No drug intervention	Other: Dietary protein restriction; The consumption of different diets restricted in protein replaced by either carbohydrate or fat and an habitual diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Energy balance	Energy balance was measured in an over-night fasted state via indirect calorimetry expressed in MJ/day prolonged eucaloric dietary protein restriction compared with a higher habitual protein intake	from week 0 to week 10.
Insulin sensitivity	Insulin sensitivity was measured by the hyperinsulinemic, euglycemic clamp procedure	Measured at week 5 (low protein, high carbohydrate diet) and week 5 on habitual diet and at week 5 (low protein high fat diet) and week 5 on habitual diet

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adipose tissue proteomics	Mass spectroscopy	After 5 weeks low protein, high carbohydrate and 5 weeks low protein, high fat. On the tenth week on habitual diet
Plasma FGF21	Measured by Elisa	Every week from week 0 to week 10

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Investigators: Principal Investigator: Bente Kiens, D.sci, PhD, University of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): January 31, 2020
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: February 7, 2024
• First Submitted That Met QC Criteria: February 18, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Energy; FGF21; Insulin action; Protein-restriction
• Other Study ID Numbers: lowprotein

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No