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The effect of dietary nitrate on blood pressure in type 2 diabetes. Dr Mark Gilchrist Peninsula Medical School 12 th September 2011. Background. Health and vegetable rich diet. β-carotene. Polyphenols. Ascorbic acid. Mg 2+. Chlorophyll. Effects attributed to multiple factors:.
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The effect of dietary nitrate on blood pressure in type 2 diabetes Dr Mark Gilchrist Peninsula Medical School 12th September 2011
Health and vegetable rich diet β-carotene Polyphenols Ascorbic acid Mg2+ Chlorophyll • Effects attributed to multiple factors: Carter et al BMJ 2010
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 Isosorbidemononitrate Nitrate ion
Nitrate, nitrite, and nitric oxide • Nitric oxide key regulator of vascular tone Palmer et al Nature 1987 • Diminished production of NO in hypertension, hyperlipidemia, chronic kidney disease, type 2 diabetesForte 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 NO3- ⇌ NO2- ⇌ NO Nitrate Nitrite Nitric oxide
Nitrate, nitrite, and nitric oxide Lundberg et al Nat Rev Micro 2004 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
Simplified representation of the entero-salivary circulation of dietary nitrate Duncan et al Nature Med 1995 Gilchrist et al Cardiovasc Res 2011
Nitrate, nitrite, and blood pressure Reichart Am J Med Sci 1880 Stieglitz JAMA 1930
Nitrate, nitrite, and blood pressure Larsen et al NEJM 2006
Effect of oral nitrate on plasma nitrite and BP Systolic Blood Pressure Plasma Nitrite Time (hours) Time (hours) Webb et al Hypertension 2008
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)
Study design 2 weeks 4 weeks 2 weeks 24 hr ABPM 24 hr ABPM Randomised, double blind, placebo controlled crossover design
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
Dietary nitrate and BP 133.5 134.7 (p=0.43) (95% CI: -1.87 to 4.23). 95.6 94.7 77.6 75.6
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 Supported by: Peninsula NIHR Clinical Research Facility • CRF Nurses • Christine Anning • Claire Ball • Linda Haynes • Andrew Pitt • Supervisors • Prof Nigel Benjamin • Prof Angela Shore • Prof Paul Winyard
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.”
