Impact of Nitrate Ingestion on Protein Synthesis (PRO-Nitrate)

The Impact of Dietary Nitrate Ingestion on Muscle Protein Synthesis in Elderly Type II Diabetics

A diet rich in leafy green vegetables has been shown to reduce the risk of developing chronic metabolic disease. The health benefits from these particular vegetables may be attributed to their high nitrate content. Recent work suggests that dietary nitrate triggers endogenous nitric oxide release, thereby stimulating vasodilation and improving muscle perfusion in an insulin-independent manner. We hypothesize that in an insulin-resistant state, nitrate co-ingestion will increase muscle perfusion, thereby improving post-prandial delivery of nutrients to skeletal muscle tissue. Specifically, a more efficient delivery of food derived amino acids will stimulate post-prandial muscle protein synthesis and, as such, compensate for a blunted muscle protein synthetic response to food intake in the elderly. This proposal will investigate the efficacy of nitrate co-ingestion as a means to augment muscle protein synthesis in elderly, type 2 diabetes patients and may lead to a novel therapy in the clinical care of type 2 diabetes patients.

Study Overview

• Status: Completed
• Conditions: Muscle Protein Synthesis
• Intervention / Treatment: Dietary supplement: Nitrate; Dietary supplement: Sodium chloride

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229ER
      • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years to 85 years (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male
• Aged between 70-85 years
• BMI < 30 kg/m2
• Non insulin-dependent diabetes mellitus type 2 patients (T2DM) ( >1 y since diagnoses)

Exclusion Criteria:

• Smoking
• Hypertension (according to WHO criteria)[29] and/or cardiovascular disease treated with medication containing nitrates and/or having vasodilatory effects
• Use of medication, except for oral blood glucose lowering medication
• Use of insulin
• All co-morbidities interacting with mobility and muscle metabolism of the lower limbs (e.g. arthritis, spasticity/rigidity, all neurological disorders and paralysis).
• HbA1c > 10.0% (86 mmol/mol)
• Donated blood in last 3 months
• Diagnosed impaired renal or liver function
• Myocardial infarction within the last 3 years
• Gastric acid inhibitors
• Use of anti-coagulants

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Nitrate; Sodium nitrate ingestion prior to ingesting intrinsically labeled protein	Dietary supplement: Nitrate; 0.15 mmol/kg body weight sodium nitrate (dissolved in 250 mL water)
PLACEBO_COMPARATOR: Sodium chloride; Sodium chloride placebo group	Dietary supplement: Sodium chloride; 0.15 mmol sodium chloride dissolved in 250 mL water.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle protein fractional synthetic rate	Muscle protein fractional synthetic rate assessed using the muscle biopsy technique.	-2, 0, +2, +5 h during the trial

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma amino acids	Blood sampling will occur through a catheter placed in an anticubital vein every 30 minutes throughout the test day. We will be using this plasma to measure plasma amino acids to determine the enrichment of labeled amino acids from both the IV tracer and the intrinsically-labeled casein protein. We wish to track the changes in amino acids from the intrinsically-labeled casein protein.	every 30 min (from -2 h to + 5 h during the test day)
Plasma nitrate	Plasma nitrate will be measured every 30 minutes during the test day through blood sampling from the catheter inserted into an antecubital vein. We want to measure the changes in plasma nitrate after consuming the nitrate or placebo beverage.	every 30 min (from -2 h to + 5 h during the test day)

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Study Director: Luc van Loon, PhD, Maastricht University

Publications and helpful links

General Publications

• Gorissen SHM, Trommelen J, Kouw IWK, Holwerda AM, Pennings B, Groen BBL, Wall BT, Churchward-Venne TA, Horstman AMH, Koopman R, Burd NA, Fuchs CJ, Dirks ML, Res PT, Senden JMG, Steijns JMJM, de Groot LCPGM, Verdijk LB, van Loon LJC. Protein Type, Protein Dose, and Age Modulate Dietary Protein Digestion and Phenylalanine Absorption Kinetics and Plasma Phenylalanine Availability in Humans. J Nutr. 2020 Aug 1;150(8):2041-2050. doi: 10.1093/jn/nxaa024.
• Kouw IW, Gorissen SH, Burd NA, Cermak NM, Gijsen AP, van Kranenburg J, van Loon LJ. Postprandial Protein Handling Is Not Impaired in Type 2 Diabetes Patients When Compared With Normoglycemic Controls. J Clin Endocrinol Metab. 2015 Aug;100(8):3103-11. doi: 10.1210/jc.2015-1234. Epub 2015 Jun 2.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (ACTUAL): July 1, 2012
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: November 3, 2011
• First Submitted That Met QC Criteria: November 14, 2011
• First Posted (ESTIMATE): November 17, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): April 15, 2016
• Last Update Submitted That Met QC Criteria: April 14, 2016
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: elderly; protein synthesis; type II diabetes; nitrate
• Other Study ID Numbers: 11-3-057

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO