Impact of Nitrate Ingestion on Protein Synthesis

NCT01473576 | Completed

• 1 other identifier: 11-3-057
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Muscle Protein Synthesis

Keywords

type II diabetes; protein synthesis; nitrate; elderly

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Plasma amino acids

  every 30 min (from -2 h to + 5 h during the test day)

• Plasma nitrate

  every 30 min (from -2 h to + 5 h during the test day)

Study Arms (2)

Nitrate

EXPERIMENTAL

Sodium nitrate ingestion prior to ingesting intrinsically labeled protein

Dietary Supplement: Nitrate

Sodium chloride

PLACEBO COMPARATOR

Sodium chloride placebo group

Dietary Supplement: Sodium chloride

Interventions

Nitrate DIETARY_SUPPLEMENT

0.15 mmol/kg body weight sodium nitrate (dissolved in 250 mL water)

Nitrate

Sodium chloride DIETARY_SUPPLEMENT

0.15 mmol sodium chloride dissolved in 250 mL water.

Sodium chloride

Eligibility Criteria

• Age: 70 Years - 85 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University

Maastricht, Limburg, 6229ER, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 32069356 DERIVED

• 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.

  PMID: 26037513 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Nitrates; Sodium Chloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Anions; Ions; Electrolytes; Inorganic Chemicals; Nitric Acid; Nitrogen Compounds; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Sodium Compounds

Study Officials

• Luc van Loon, PhD

  Maastricht University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2011
• First Posted: November 17, 2011
• Study Start: August 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: December 1, 2013
• Last Updated: April 15, 2016

Record last verified: 2012-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)