Effect of L-arginine on Microcirculation, Myogenesis and Angiogenesis Associated With Aging, Sarcopenia and Diabetes

Effect of L-arginine Supplementation on Microcirculation, Endothelial Function and Vascular Smooth Muscle of Young, Elderly and Patients With Sarcopenia and Type 2 Diabetes Mellitus

This study aims was evaluated the effect of L-arginine on microcirculation, vasoreactivity / endothelial function and vascular smooth muscle of young and old women with Sarcopenia or Type 2 Diabetes Mellitus measured by Nailfold videocapillaroscopy and venous occlusion plethysmography before and after 14 days of consumption 5g oral L-arginine supplementation.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Sarcopenia; Aging; Microcirculation
• Intervention / Treatment: Dietary supplement: L-arginine; Dietary supplement: Maltodextrin

Detailed Description

Aging causes responsible endothelial changes, in part by a decrease in the blood flow of the skeletal muscles of the elderly. Reduction of muscle mass / function (Sarcopenia) and Diabetes Mellitus are frequent pathologies in the elderly. L-Arginine is a semi-essential amino acid precursor to nitric oxide synthesis (NO), an important vasodilator and protector cardiovascular.

Seventy-five women were allocated into three groups: twenty-five healthy young (HY) recruited among University students, and fifty women elderly, this was stratified in twenty-five healthy elderly (HE) control and twenty-five with hyperglycemia (HG) elderly from the ambulatories of the Geriatric and Diabetology at the State University of Rio de Janeiro (UERJ) and private supplementary health program. To control group was considered absence cardiovascular risk factor except advanced age. Participants were subjected to screening phase before being eligible for the study by telephone, which comprised of individual clinical history. All subjects signed the written Informed Consent Form enclosed in the protocol approved by Ethics Committee from the State University of Rio de Janeiro according to Helsinki Declaration.

The subjects elected for research made 4 visits to the Biovasc laboratory for data collection. First day: the protocol was explained and agreement from the voluntary obtained, followed and anamnesis and physical exam that included measure at-rest blood pressure, weight and height. Moreover, women examined after 6 hours fasting the microcirculation function using nailfold vidiocapilaroscopy (NVC), followed of the measure of forearm blood flow (FBF) and vascular reactivity by venous occlusion plethysmography (VOP). Second day: Venous blood sample collection after 12 hours fasting. In sequence, they realized whole-body dual-energy X-ray absorptiometry (DXA) to calculate the body composition main measure lean and fat mass. After, was delivered a box with 14 sachets content 5g L-arginine supplementation, and it was recommended to ingest with water 30 minutes before breakfast during 14 days. Third day: Return after the supplementation to realize measurement weight, and exams NVC and VOP. Fourth day: blood sample were taken after 12 hours fasting under effect of the L-arginine.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20550900
    • State University of Rio de Janeiro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• young women aged between 20 - 30 years, IMC < 24.9 kg/m2
• older women over 65 years healthy, BMI <35 kg/m2.
• Elderly women with or without a preexisting diagnosis of diabetes mellitus with fasting plasma glucose (FPG) > 100 mg/dL were classified into type 2 diabetes mellitus.

Exclusion Criteria:

• involved type 1 diabetes mellitus
• insulin use, cognitive impairment
• frailty
• disorders cardiometabolic
• liver and/or kidney dysfunction
• autoimmune diseases
• smoking
• rigorous exercise
• uncontrolled hypertension with pressure level > 140/90 mmHg, with up to two antihypertensive drugs of different classes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: L-arginine; L-arginine supplementation: 5g/sachet with water 30 minutes before breakfast for 14 days.	Dietary supplement: L-arginine; Handled powdered supplement to be mixed with water, has orange flavor for oral use.
Placebo Comparator: Maltodextrin; Maltodextrin supplementation: 5g/sachet with water 30 minutes before breakfast for 14 days.	Dietary supplement: Maltodextrin; hydrolysis of cornstarch or starch as a white powder to be mixed with water, has orange flavor for oral use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Microcirculation	Assessing microvascular changes in the peripheral circulation by microcirculatory image recordings were used Nailfold vidiocapilaroscopy.	before and after 14 days of intervention
Changes in Endothelium-dependent and endothelium-independent vasodilation	Changes in vasodilatation by endothelial reactivity and smooth muscle responsiveness were assessed by Venous occlusion plethysmography	before and after 14 days of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in metabolic markers	Metabolic markers associated with lipid profile (total cholesterol, triglycerides, Low Density Lipoproteins (HDLc) and High Density Lipoproteins (LDLc)); renal profile (urea and creatinine); Glycemic and insulin were analyzed to verify treatment response by comparing the results (mg/dL) before and after oral supplementation in the studied groups.	before and after 14 days of intervention
change in circulating muscle growth and degradation factors	Insulin-like growth factor-I (IGF-I) and follistatin (Fslt-I) growth-associated and (GDF-8 / Myostatin and interleukin 6 (IL-6)) degradation-associated were analyzed to verify response to treatment, comparing results (ng / ml) before and after oral supplementation in the study groups.	before and after 14 days of intervention
Body composition by DXA	The whole-body dual-energy X-ray absorptiometry (DXA) was used to measure appendicular skeletal muscle (ASM) composed lean body mass of arms and legs to calculated skeletal muscle mass index by following formula: ASM/height2.	before of intervention

Collaborators and Investigators

• Sponsor: Rio de Janeiro State University
• Collaborators: Laboratory for Clinical and Experimental Research on Vascular Biology
• Investigators: Principal Investigator: Daniel A Bottino, PhD, State University of Rio de Janeiro; Principal Investigator: Gerusa M Costa, MSc, State University of Rio de Janeiro

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: October 1, 2019
• First Posted (Actual): October 2, 2019

Study Record Updates

• Last Update Posted (Actual): October 2, 2019
• Last Update Submitted That Met QC Criteria: October 1, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus; Sarcopenia; Follistatin; L-arginine; endothelial function; Arginase; Asymmetric Dimethylarginine; Myostatin; Vascular smooth muscle
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Endocrine System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Sarcopenia
• Other Study ID Numbers: arginine

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: It is not yet known if there will be a plan to make IPD available.

Drug and device information, study documents

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