Presentation on theme: "The effect of dietary nitrate on blood pressure in type 2 diabetes Dr Mark Gilchrist Peninsula Medical School 12 th September 2011."— Presentation transcript:
The effect of dietary nitrate on blood pressure in type 2 diabetes Dr Mark Gilchrist Peninsula Medical School 12 th September 2011
Health and vegetable rich diet Effects attributed to multiple factors: Carter et al BMJ 2010 Chlorophyll β-carotene Polyphenols Ascorbic acid Mg 2+
Inorganic nitrate and vegetables Green leafy vegetables (and beetroot) particularly rich in inorganic nitrate In mammals previously thought to be inert waste product
Organic vs inorganic nitrate Isosorbide mononitrateNitrate ion
Nitric oxide key regulator of vascular tone Palmer et al Nature 1987 Diminished production of NO in hypertension, hyperlipidemia, chronic kidney disease, type 2 diabetes Forte et al Lancet 1997 Scherrer et al Eur J Endocrinol 2000 Nitrate, nitrite, and nitric oxide
Nitrate involved in complex cycle with nitrite and nitric oxide NO 3 -NO 2 - NO Nitrate NitriteNitric oxide Nitrate, nitrite, and nitric oxide
Generate 1mmol nitrate/day from oxidation nitric oxide from L-arginine NOS pathway 1-2mmol nitrate per day typical Western diet Nitrate and nitrite may act as a storage pool of NO, delivering nitric oxide where it is required Lundberg et al Nat Rev Micro 2004
Simplified representation of the entero-salivary circulation of dietary nitrate Gilchrist et al Cardiovasc Res 2011 Duncan et al Nature Med 1995
Nitrate, nitrite, and blood pressure Reichart Am J Med Sci 1880 Stieglitz JAMA 1930
Larsen et al NEJM 2006 Nitrate, nitrite, and blood pressure
Effect of oral nitrate on plasma nitrite and BP Webb et al Hypertension 2008 Systolic Blood PressurePlasma Nitrite Time (hours)
Beneficial effects of dietary nitrate and nitrite Protection against IR injury (Webb et al Hypertension 2008) Improvement in exercise efficiency (Bailey et al JAP 2009) Reverse features of metabolic syndrome in eNOS KO mice (Carlstrom et al PNAS 2010)
2 weeks Placebo Active Study design Randomised, double blind, placebo controlled crossover design Active Placebo 4 weeks 24 hr ABPM
Placebo Beetroot juice treated with anion exchange resin Purolite A520e Selectively removes nitrate Active juice (250mls) nitrate dose 7.5mmol Placebo juice nitrate (250mls) dose 0.002mmol
Results 23 subjects, 15male, 8 female MeanSD Age (yrs) Duration of diabetes (yrs) Systolic BP (mmHg) Diastolic BP (mmHg) BMI HbA1c (%) Number antihypertensives
Dietary nitrate and BP (p=0.43) (95% CI: to 4.23).
Conclusion and discussion Dietary nitrate supplementation did not have a detectable effect on blood pressure in individuals with type 2 diabetes
Future work Is nitrate, nitrite and NO handling disordered in type 2 diabetes? Is this partly responsible for excess cardiovascular risk in type 2 diabetes?
Acknowledgements Supervisors –Prof Nigel Benjamin –Prof Angela Shore –Prof Paul Winyard CRF Nurses Christine Anning Claire Ball Linda Haynes Andrew Pitt Supported by: Peninsula NIHR Clinical Research Facility
WHO JEFCA 2003 Overall, the epidemiological studies showed no consistently increased risk for cancer with increasing consumption of nitrate. These data, combined with the results of the epidemiological studies considered by the Committee at its forty-fourth meeting, do not provide evidence that nitrate is carcinogenic to humans.