Low Dose β-carotene Supplementation Diminishes Oxidative Stress in Type 2 Diabetics and Healthy Individuals

This study has been completed.
Sponsor:
Collaborators:
Seguros Caracas Foundation
National Fund for Science and Technology, Science Mission
Information provided by (Responsible Party):
Maria Nieves Garcia-Casal, Instituto Venezolano de Investigaciones Cientificas
ClinicalTrials.gov Identifier:
NCT01477112
First received: November 15, 2011
Last updated: November 18, 2011
Last verified: November 2011
  Purpose

Since diabetes has multiple etiologies and oxidative stress one of the proposed mechanisms, the objective is to determine the effect of supplementation with β-carotene to type 2 diabetics and healthy individuals, on iron metabolism, oxidative balance, and antioxidant plasma capacity, using doses similar to the daily nutritional requirement.


Condition Intervention
Diabetes Mellitus
Oxidative Stress
Iron Metabolism Disorders
Dietary Supplement: Betacarotene
Dietary Supplement: Controls. No treatment

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effect of the Supplementation With β-carotene to Type 2 Diabetic Patients and Healthy Controls on the Iron Status and Antioxidant Capacity of Plasma

Resource links provided by NLM:


Further study details as provided by Instituto Venezolano de Investigaciones Cientificas:

Primary Outcome Measures:
  • Changes in oxidative status [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hemoglobin and hematocrit [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
  • Ferritin [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    Enzyme linked immunosorbent assay (ELISA) with monoclonal antibodies

  • Iron metabolism markers [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    Serum iron, total iron binding capacity (TIBC) and unsaturated iron binding capacity (UIBC) were determined by the methods proposed by the International Committee of Standardization of Hematology.

  • Blood Chemistry [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    Glycemia, triglycerides, total cholesterol, LDL, and HDL were determined automatically in a Ciba Corning 550 Express autoanalizer, using classic enzymatic methods for the determination of these variables.

  • Glycosylated Hemoglobin [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    It was determined using a commercial kit (Bioscience, Caracas, Venezuela),

  • Oxidized LDL [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    Analyzed by a solid phase two-site enzyme immunoassay from Mercodia (Sweden), which contains 2 monoclonal antibodies directed against separated antigenic determinants on the oxidized apolipoprotein B molecule.

  • Thiobarbituric Acid Reactive substances (TBARS) [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    Were detected by the quantification of malondialdehyde present in the sample, by reacting 2 molecules of thiobarbituric acid with 1 molecule of malondialdehyde, which produces an abduct that is detected at 535 mn.

  • Ferric Reducing ability of Plasma (FRAP). [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    Measured after 4 and 10 min incubation, was used to determine the ability of plasma to reduce iron from ferric to ferrous state, based on the formation of a triazine-Fe+3 complex, that when reduced to Fe+2, generate a change in color that is measured at 593 nm.

  • Activities of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    Determined by commercial kits (Cayman Chemicals, Pittsburg) following the recommended protocols

  • Serum zinc and copper. [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    By flame atomic absorption spectrophotometry

  • β-carotene. [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    It was determined by HPLC, with a reverse fase C18 column.

  • Serum retinol [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    It was determined by HPLC, with a reverse fase C18 column, as an indirect measure of betacarotene metabolism.

  • Serum nitrites [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    Were determined as an indirect measure of the concentration of nitric oxide, since nitrites are the stable end products of its degradation. Nitrates were reduced to nitrites by activated cadmium. Then sulfanilamide and nitrites generate a chromophore that reacts with naftilethylenediamine, to generate a product visible at 540 nm.

  • Serum and erythrocyte folates. [ Time Frame: Time 0, 45 days and 75 days after supplementation ] [ Designated as safety issue: No ]
    The method is based in the folate-dependent controlled growth of a Lactobacillus strain that is measured spectrophotometrically and quantified against a standard curve.


Enrollment: 117
Study Start Date: January 2010
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Supplemented Diabetics (DB)
Diabetics supplemented with betacarotene for 45 days
Dietary Supplement: Betacarotene
6 mg betacarotene in caplets for 45 days (daily)and reevaluate parameters 30 days after finishing supplementation
Other Name: β-carotene as a soft gel capsule (GNC, Pennsylvania-USA)
Experimental: Unsupplemented Diabetics (DS)
Diabetics without betacarotene supplementation
Dietary Supplement: Controls. No treatment
Evaluate at time 0, 45 days and 75 days, but without receiving betacarotene supplements
Other Name: No supplements
Active Comparator: Supplemented Controls (CB)
Controls supplemented with betacarotene for 45 days
Dietary Supplement: Betacarotene
6 mg betacarotene in caplets for 45 days (daily)and reevaluate parameters 30 days after finishing supplementation
Other Name: β-carotene as a soft gel capsule (GNC, Pennsylvania-USA)
Active Comparator: Unsupplemented Controls (CS)
Controls without betacarotene supplementation
Dietary Supplement: Controls. No treatment
Evaluate at time 0, 45 days and 75 days, but without receiving betacarotene supplements
Other Name: No supplements

Detailed Description:

Type 2 diabetes is a chronic, multifactorial disease, and oxidative stress one of the pathophysiological mechanisms associated with its appearance and development. The objective was to determine the effect of supplementation with β-carotene to type 2 diabetics and healthy individuals, on iron metabolism, oxidative balance, and antioxidant plasma capacity, using doses similar to the daily nutritional requirement.

A total of 117 volunteers participated in the study. Type 2 diabetics (34) and healthy individuals (24), received 6 mg β-carotene for 45 d, and were compared to similar non-supplemented diabetic (33) and control (26) groups. Blood samples were taken at the beginning, end and 30 days after finishing supplementation, to determine hemoglobin, hematocrit unsaturated iron binding capacity, total iron binding capacity, transferrin saturation, ferritin, glycemia, glycosylated hemoglobin, cholesterol, triglycerides, HDL, LDL, oxidized LDL, copper, zinc, TBARS, FRAP, nitrites, GPx, SOD, folates, retinol and β-carotene.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Patients with a diagnose of Type 2 diabetes mellitus of at least 5 years of diagnosis, in treatment with oral hypoglycemics Patients in regular control (once a month) in the Hospital

Exclusion Criteria:

  • Hospitalized patient
  • Diabetic patient with diabetes related acute complications (ketoacidosis, hyperosmolar coma)in the 3 months previous to the study.
  • Individuals with infections that required antibiotics in the 3 weeks previous to the study.
  • Individuals with antibodies anti-insulin, autoimmune diseases or in treatment with immunosuppressive drugs.
  • Individuals with viral infections such as hepatitis B, hematological, renal or hepatic diseases.
  • Pregnancy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01477112

Locations
Venezuela
Hospital Baudilio Lara
Barquisimeto, Lara, Venezuela
Sponsors and Collaborators
Instituto Venezolano de Investigaciones Cientificas
Seguros Caracas Foundation
National Fund for Science and Technology, Science Mission
Investigators
Study Director: Maria N Garcia-Casal, PhD Instituto Venezolano de Investigaciones Cientificas
Principal Investigator: Jose M Moreno, PhD Instituto Venezolanode Investigaciones cientificas
  More Information

Additional Information:
Publications:
Responsible Party: Maria Nieves Garcia-Casal, Director of Pathophysiology Laboratory, Instituto Venezolano de Investigaciones Cientificas
ClinicalTrials.gov Identifier: NCT01477112     History of Changes
Other Study ID Numbers: IVIC-HUMNUT-001
Study First Received: November 15, 2011
Last Updated: November 18, 2011
Health Authority: Venezuela: Instituto Venezolano de Investigaciones Cientificas

Keywords provided by Instituto Venezolano de Investigaciones Cientificas:
Type 2 diabetes
β-carotene
Oxidative balance
Oxidants
Antioxidants

Additional relevant MeSH terms:
Diabetes Mellitus
Iron Metabolism Disorders
Metabolic Diseases
Glucose Metabolism Disorders
Endocrine System Diseases
Antioxidants
Carotenoids
Beta Carotene
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 23, 2014