Clinical trial NCT01473576: Impact of Nitrate Ingestion on Protein Synthesis
Official title: The Impact of Dietary Nitrate Ingestion on Muscle Protein Synthesis in Elderly Type II Diabetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Muscle Protein Synthesis
Keywords: type II diabetes
protein synthesis
nitrate
elderly
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2011-11-17
Enrollment: 25
Sex: MALE
Minimum age (years): 70
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


Eligibility criteria: 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

Primary outcomes:
measure: Muscle protein fractional synthetic rate
timeFrame: -2, 0, +2, +5 h during the trial
Secondary outcomes:
measure: Plasma amino acids
timeFrame: every 30 min (from -2 h to + 5 h during the test day)
measure: Plasma nitrate
timeFrame: every 30 min (from -2 h to + 5 h during the test day)
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
state: Limburg
Study officials:
affiliation: Maastricht University
name: Luc van Loon, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.