Impact of Nitrate Ingestion on Protein Synthesis

Maastricht University Medical Center25 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

DOUBLE

Enrollment

Conditions

Muscle Protein Synthesis

Interventions

Eligibility

Sex: MALEMin age: 70 YearsMax age: 85 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Muscle protein fractional synthetic rate

Muscle protein fractional synthetic rate assessed using the muscle biopsy technique.

Time frame: -2, 0, +2, +5 h during the trial

Secondary Outcomes

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.

Time frame: 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.