Related Experiment Video
Updated: Aug 7, 2026

Assessing Endothelial Vasodilator Function with the Endo-PAT 2000
Published on: October 15, 2010
Folate and vitamin B6 rapidly normalize endothelial dysfunction in children with type 1 diabetes mellitus
Karen E MacKenzie1, Esko J Wiltshire, Roger Gent
1Department of Diabetes and Endocrinology, Children, Youth, and Women's Health Service, Adelaide, Australia. karen.mackenzie@adelaide.edu.au
Insights
High-dose folate and vitamin B6 significantly improved endothelial dysfunction in children with type 1 diabetes, with effects sustained for 8 weeks. These vitamins normalized vascular function, independent of other metabolic markers.
Area of Science:
- Vascular Biology
- Pediatric Endocrinology
- Nutritional Science
Background:
- Endothelial dysfunction is an early complication in type 1 diabetes mellitus, preceding overt vascular disease.
- Folate status is implicated in the development of endothelial dysfunction in diabetic patients.
Purpose of the Study:
- To investigate the effects of high-dose folate and vitamin B6 on endothelial function in children with type 1 diabetes.
- To determine the immediate and sustained effects of folate and vitamin B6, alone and in combination, on vascular health.
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving 124 children with type 1 diabetes.
- Vitamins (folate 5 mg/day, vitamin B6 100 mg/day) were administered alone or combined, with endothelial function assessed via brachial artery ultrasound (flow-mediated and glyceryltrinitrate-induced dilation).
- Measurements were taken at baseline, 2-4 hours post-dose, and at 4 and 8 weeks of treatment.
Main Results:
- Flow-mediated dilation (FMD) normalized in all treatment groups, improving significantly from baseline to 8 weeks with folate, vitamin B6, and combination therapy.
- Improvements in FMD were observed within 2 hours and maintained for 8 weeks; placebo and glyceryltrinitrate-induced dilation showed no significant changes.
- Increased serum folate, red cell folate, and vitamin B6 levels correlated with FMD improvements, independent of homocysteine, glucose, HbA1c, or CRP levels.
Conclusions:
- High-dose folate and vitamin B6 effectively normalized endothelial dysfunction in children with type 1 diabetes.
- The positive effects on endothelial function were sustained over 8 weeks.
- Combination therapy offered no additional benefit over monotherapy with either folate or vitamin B6.
Background:
Endothelial dysfunction, a precursor of vascular disease, begins early in type 1 diabetes mellitus and is associated with folate status.
Methods:
A randomized, double-blind, placebo-controlled study of folate (5 mg daily) and vitamin B6 (100 mg daily) in 124 children with type 1 diabetes determined the immediate and 8-week effects of these vitamins, alone and in combination, on endothelial function. Endothelial function, assessed as flow-mediated dilation and glyceryltrinitrate-induced dilation with high-resolution ultrasound of the brachial artery, was measured at baseline, at 2 and 4 hours after the first dose (n = 35), and at 4 and 8 weeks of treatment (n = 122).
Results:
Flow-mediated dilation normalized in all treatment groups. From baseline to 8 weeks, flow-mediated dilation improved with folate from 2.6% +/- 4.3% (mean +/- SD) to 9.7% +/- 6.0%, with vitamin B6 from 3.5% +/- 4.0% to 8.3% +/- 4.2%, and with folate/vitamin B6 from 2.8% +/- 3.5% to 10.5% +/- 4.4%. This improvement in flow-mediated dilation occurred within 2 hours and was maintained at 8 weeks for each treatment. Flow-mediated dilation in the placebo group, and glyceryltrinitrate-induced dilation in all groups, did not change. Increases in serum folate, red cell folate, and serum vitamin B6 levels related to increases in flow-mediated dilation. Improvement in flow-mediated dilation was independent of changes in total plasma homocyst(e)ine, glucose, hemoglobin A1c, and high-sensitivity C-reactive protein levels. Baseline red cell folate levels and baseline diastolic blood pressure were related inversely to improvement in flow-mediated dilation. Serum triglyceride and low-density lipoprotein cholesterol inversely related to baseline flow-mediated dilation.
Conclusions:
High-dose folate and vitamin B6 normalized endothelial dysfunction in children with type 1 diabetes. This effect was maintained over 8 weeks, with no additional benefit from combination treatment.
Related Concept Videos
Type I Diabetes II: Pathophysiology
Type II Diabetes II: Pathophysiology
Type I Diabetes III: Clinical Manifestations
Diabetes Mellitus: Overview and Type I Subtype
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Type I Diabetes I: Introduction
Diabetes Mellitus: Type 2 and Gestational
