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Title: The effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes mellitus
Author: Gilchrist, Mark
Awarding Body: Exeter and Plymouth Peninsula Medical School
Current Institution: Exeter and Plymouth Peninsula Medical School
Date of Award: 2011
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Introduction Diets rich in green leafy vegetables have been shown to lower blood pressure and lower the risk of cardiovascular disease. Green leafy vegetables are particularly rich in inorganic nitrate. Dietary nitrate supplementation, via sequential reduction to nitrite and nitric oxide, has previously been shown to lower blood pressure and improve endothelial function in healthy humans. Aims To develop a nitrate-depleted beetroot juice placebo in order to conduct a randomised double blind control trial. To determine if supplementing dietary nitrate with beetroot juice, a rich source of nitrate, will lower BP, improve endothelial function and insulin sensitivity in individuals with type 2 diabetes (T2DM). To determine if supplementing dietary nitrate will lower BP in healthy older adults. Methods The beetroot juice nitrate concentration was lowered using an ion exchange resin. The nitrate content of 250 ml of active juice was 7.5 mmol, whilst nitrate- depleted juice had 0.002 mmol of nitrate in 250ml. Twenty-seven patients, age 67.2 +/-4.9 years, (18 male) were recruited for a double blind, randomised, placebo-controlled crossover trial. Participants were randomised to begin in either order a 2 week period of supplementation with 250 ml beetroot juice daily (active, 7.5 mmol of nitrate) or 250 ml nitrate-depleted beetroot juice (placebo 0.002 mmol of nitrate) followed by a 4 week washout period before entering the second arm of the study. At the conclusion of each intervention period 24 hour ambulatory blood pressure monitoring, vascular tests and a hyperinsulinaemic euglycaemic clamp were performed. Seventeen healthy controls, age 60.5 ± 3.6 (11 male) were recruited to a more limited protocol examining the effect of dietary nitrate supplementation on blood pressure. Results The mean systolic BP was unchanged: 134.6 ± 8.4 mm Hg vs 135.1 ± 7.8 mm Hg (mean±SD) placebo vs active - mean difference of -0.5 mm Hg (placebo- active) p=0.737 (95% Cl -3.9 to 2.8) in the T2DM group. The plasma nitrate concentration was 31IJM (median, IOR; 19.8-41.6) vs 150IJM (122.7, 200), p<0.001. The plasma nitrite concentration was 232 nM (200, 265) vs 390nM (312, 537), p<0.001, for placebo vs active. There were no differences in endothelial function or insulin sensitivity between supplementation arms. The healthy control group mean systolic BP was unchanged at 129.2 ± 9.8 mm Hg vs 131.0 ± 13.1 mm Hg, with a mean difference of -1.8 mm Hg, p=0.320 (95% CI-5.4 to 1.9). The plasma nitrate concentration was 19.81JM (10.6, 37.7) vs 116.6 IJM (91.9, 158.9), p<0.001, and the plasma nitrite concentration 285 nM (245,348) vs 335 nM (296, 357), p=0.127. Conclusion Supplementation of the diet with 7.5 mmol of nitrate per day caused an increase in the plasma nitrite concentration, but did not lower blood pressure, improve endothelial function or improve insulin sensitivity in individuals with T2DM in this study. Dietary nitrate supplementation did not lower BP in healthy older adults in this study.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available