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

Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01477112
• Other study ID #: IVIC-HUMNUT-001
• Status: Completed
• Phase: N/A
• First received: November 15, 2011
• Last updated: November 18, 2011
• Start date: January 2010
• Est. completion date: December 2010

Study information

• Verified date: November 2011
• Source: Instituto Venezolano de Investigaciones Cientificas
• Contact: n/a
• Is FDA regulated: No
• Health authority: Venezuela: Instituto Venezolano de Investigaciones Cientificas
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 117
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Iron Metabolism Disorders
• Metabolic Diseases
• Oxidative Stress

Intervention

Dietary Supplement:
• Betacarotene
6 mg betacarotene in caplets for 45 days (daily)and reevaluate parameters 30 days after finishing supplementation
• Controls. No treatment
Evaluate at time 0, 45 days and 75 days, but without receiving betacarotene supplements

Locations

Country	Name	City	State
Venezuela	Hospital Baudilio Lara	Barquisimeto	Lara

Sponsors (3)

Lead Sponsor	Collaborator
Instituto Venezolano de Investigaciones Cientificas	National Fund for Science and Technology, Science Mission, Seguros Caracas Foundation

Country where clinical trial is conducted

Venezuela, 

References & Publications (4)

Ford ES, Cogswell ME. Diabetes and serum ferritin concentration among U.S. adults. Diabetes Care. 1999 Dec;22(12):1978-83. — View Citation

Ford ES, Mokdad AH, Giles WH, Brown DW. The metabolic syndrome and antioxidant concentrations: findings from the Third National Health and Nutrition Examination Survey. Diabetes. 2003 Sep;52(9):2346-52. — View Citation

Song Y, Cook NR, Albert CM, Van Denburgh M, Manson JE. Effects of vitamins C and E and beta-carotene on the risk of type 2 diabetes in women at high risk of cardiovascular disease: a randomized controlled trial. Am J Clin Nutr. 2009 Aug;90(2):429-37. doi: 10.3945/ajcn.2009.27491. Epub 2009 Jun 2. — View Citation

Sugiura M, Nakamura M, Ikoma Y, Yano M, Ogawa K, Matsumoto H, Kato M, Ohshima M, Nagao A. The homeostasis model assessment-insulin resistance index is inversely associated with serum carotenoids in non-diabetic subjects. J Epidemiol. 2006 Mar;16(2):71-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in oxidative status		Time 0, 45 days and 75 days after supplementation	No
Secondary	Hemoglobin and hematocrit		Time 0, 45 days and 75 days after supplementation	No
Secondary	Ferritin	Enzyme linked immunosorbent assay (ELISA) with monoclonal antibodies	Time 0, 45 days and 75 days after supplementation	No
Secondary	Iron metabolism markers	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.	Time 0, 45 days and 75 days after supplementation	No
Secondary	Blood Chemistry	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.	Time 0, 45 days and 75 days after supplementation	No
Secondary	Glycosylated Hemoglobin	It was determined using a commercial kit (Bioscience, Caracas, Venezuela),	Time 0, 45 days and 75 days after supplementation	No
Secondary	Oxidized LDL	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.	Time 0, 45 days and 75 days after supplementation	No
Secondary	Thiobarbituric Acid Reactive substances (TBARS)	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.	Time 0, 45 days and 75 days after supplementation	No
Secondary	Ferric Reducing ability of Plasma (FRAP).	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.	Time 0, 45 days and 75 days after supplementation	No
Secondary	Activities of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx).	Determined by commercial kits (Cayman Chemicals, Pittsburg) following the recommended protocols	Time 0, 45 days and 75 days after supplementation	No
Secondary	Serum zinc and copper.	By flame atomic absorption spectrophotometry	Time 0, 45 days and 75 days after supplementation	No
Secondary	ß-carotene.	It was determined by HPLC, with a reverse fase C18 column.	Time 0, 45 days and 75 days after supplementation	No
Secondary	Serum retinol	It was determined by HPLC, with a reverse fase C18 column, as an indirect measure of betacarotene metabolism.	Time 0, 45 days and 75 days after supplementation	No
Secondary	Serum nitrites	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.	Time 0, 45 days and 75 days after supplementation	No
Secondary	Serum and erythrocyte folates.	The method is based in the folate-dependent controlled growth of a Lactobacillus strain that is measured spectrophotometrically and quantified against a standard curve.	Time 0, 45 days and 75 days after supplementation	No

External Links

•   American Diabetes Association
•   Instituto Venezolano de Investigaciones Cientificas