Double-blind controlled dietary cross-over intervention with differentially fertilised intact lettuce leaves shows acute reduction in blood pressure in young adults, associated with faster uptake of nitrate than of phenolics.

PURPOSE: To compare acute effects on blood pressure (BP) of ingestion of visually similar lettuce with controlled high and low content of either nitrate or phenolic compounds. METHODS: In a randomised cross-over design, 19 healthy participants (22-31 years) received 50 g of lettuce containing either 530 mg (8.4 mmol) nitrate + 11 mg (0.03 mmol) phenolic compounds (HNLP); or 3 mg nitrate (0.05 mmol) + 77 mg (0.2 mmol) phenolic compounds (LNHP), obtained by differential fertilisation. Ambulatory BP was recorded along with plasma, salivary and urinary nitrate and nitrite and plasma concentrations of cyclic guanosine monophosphate (cGMP), phenolic metabolites, Trolox equivalent antioxidant capacity (TEAC) and ferric reducing antioxidant power (FRAP). RESULTS: Compared with LNHP, 3 h post ingestion of HNLP, plasma nitrate increased 0.31 ± (95%CI) 0.12 mM (+ 240%), and salivary nitrate 5.5 ± 1.4 mM (+ 910%); accumulated urinary nitrate excretion increased 188 ± 72 mg (+ 296%) (all P < 0.001). Systolic BP was reduced 4.9 ± 4.2 mmHg (P = 0.031) between 3 and 6 h after ingestion of HNLP compared with LNHP; systolic BP differences were negatively correlated (P = 0.004) with differences in saliva nitrate concentrations. LNHP increased plasma phenolics at 6 h, predominantly 3'-methoxycinnamic acid-4'-glucuronide (ferulic acid-4'-glucuronide), 116%, 204 ± 138 nM more than HNLP (P = 0.001); increased cGMP 14% (P = 0.019); and reduced FRAP 3.1% (P = 0.009). CONCLUSION: The acute BP difference within 6 h of consumption matched the plasma/saliva nitrate peak, not the slower changes of plasma phenolics. This is the first double-blind controlled dietary intervention demonstrating differential effects on human physiology by consumption of an intact plant food, where compositional differences were obtained by controlling growing conditions, indicating potential opportunities for health claims relating to precision/vertical farming. CLINICAL TRIAL REGISTRATION: The trial was retrospectively registered on ClinicalTrials.gov, with identifier NCT02701959, on March 8, 2016.

Inorganic Nitrate Supplementation in Young and Old Obese Adults Does Not Affect Acute Glucose and Insulin Responses but Lowers Oxidative Stress.

BACKGROUND: Aging and obesity are associated with raised oxidative stress and a reduction of nitric oxide (NO) bioavailability, with subsequent decline in insulin sensitivity and endothelial function. Inorganic nitrate is converted into NO via a 2-step reduction process and may be an effective nutritional intervention to modify vascular and metabolic functions. OBJECTIVES: This study tested whether inorganic nitrate supplementation improved glucose disposal and attenuated the acute effects of hyperglycemia on oxidative stress, inflammation, and vascular function in young and old obese participants. METHODS: Ten young (aged 18-44 y) and 10 old (aged 55-70 y) obese participants consumed 75 g glucose followed by either potassium nitrate (7 mg/kg body weight) or potassium chloride (placebo) in a randomized, double-blind crossover design. Resting blood pressure (BP), endothelial function, and blood biomarkers were measured for 3 h postintervention. Biomarkers included plasma nitrate/nitrite (NOx), glucose, insulin, cyclic GMP, interleukin 6, 3-nitrotyrosine, E- and P-selectins, intercellular adhesion molecule 3 (ICAM-3), and thrombomodulin, as well as superoxide in freshly isolated peripheral blood mononuclear cells (PBMCs). RESULTS: Inorganic nitrate supplementation did not affect plasma glucose (P = 0.18) or insulin (P = 0.26) responses. The increase in plasma NOx concentrations 3 h after the administration of inorganic nitrate was significantly higher in young than in old participants (234% increase compared with 149% increase, respectively, P < 0.001). Plasma 3-nitrotyrosine concentrations declined significantly after inorganic nitrate supplementation compared with placebo (3 h postdose, 46% decrease compared with 27% increase, respectively, P = 0.04), and a similar nonsignificant trend was observed for superoxide concentrations (3 h postdose, 16% decrease compared with 23% increase, respectively, P = 0.06). Plasma cyclic GMP, ICAM-3, and thrombomodulin concentrations differed between young and old participants (P < 0.01). Inorganic nitrate supplementation did not improve BP or endothelial function. CONCLUSIONS: Oral supplementation with inorganic nitrate did not improve glucose and insulin responses but reduced oxidative stress in old individuals during acute hyperglycemia. This trial was registered at www.controlled-trials.com as ISRCTN42776917.

Patient with myelodysplastic syndrome presented with recurrent pericardial effusion diagnosed as epicardial hemangioma; Case report of a rare diagnosis with rare presentation.

Primary cardiac tumors are extremely rare and cardiac hemangiomas comprise less than 3% of them. Presentation of such disease with recurrent pericardial effusion is even rarer. Our patient is known case of myelodysplastic syndrome and up to our knowledge there are no reported case in which cardiac hemangioma was diagnosed in a patient with myelodysplastic syndrome. This 64 years male patient presented to our department with recurrent pericardial effusion, diagnosis was a query after extensive work he was found to suffer from a cardiac tumor based on the pulmonary artery and right ventricle. We performed surgery for him on cardiopulmonary bypass and did complete resection of the mass for him and result of biopsy showed mixed hemangioma. Recurrent pericardial effusion is most commonly a sign of a malignancy. Even with advancement of medical technology diagnoses of cardiac hemangiomas are still difficult. Treatment and definitive diagnosis is still complete surgical resection and histopathological examination.

Manipulation of Contents of Nitrate, Phenolic Acids, Chlorophylls, and Carotenoids in Lettuce (Lactuca sativa L.) via Contrasting Responses to Nitrogen Fertilizer When Grown in a Controlled Environment.

This study aimed to use different nitrogen fertilizer regimes to produce Butterhead lettuce with such large differences in nitrate content that they could be used as treatment and placebo to study the effect of inorganic nitrate on human health. Plants were grown under controlled conditions at 27/23 °C day/night with a relatively low photosynthetically active radiation (PAR) of 150 µmol m-2 s-1 for 14 h day-1 and nitrogen supplies ranging from 26 to 154 ppm of N as ammonium nitrate in the fertigation solution. This resulted in contrasting high (∼1078 mg nitrate 100 g-1 FW) or low (∼6 mg 100 g-1) nitrate contents in the leaves. Contents of carotenoids and chlorophylls in fresh weight did not differ significantly between the highest and the lowest N-supply levels. However, increased nitrogen supply reduced contents of phenolic compounds from 154 to 22 mg 100 g-1 FW, dry matter content from 8.9% to 4.6%, and fresh weight per plant from 108.52 to 47.57 g/plant FW (all P < 0.001). Thus, while fertilizer treatments can provide lettuce with substantially different nitrate contents, maintaining similar pigment contents (color), they also strongly influence the contents of phenolic acids and flavones.

Effects of handgrip exercise or inorganic nitrate supplementation on 24-h ambulatory blood pressure and peripheral arterial function in overweight and obese middle age and older adults: A pilot RCT.

INTRODUCTION: Hypertension is a major contributor to the global burden of cardiovascular diseases and its prevalence increases progressively with ageing. Therefore the identification of effective, age-friendly exercise and nutritional interventions which lower blood pressure (BP) is a research priority. OBJECTIVE: To undertake a pilot RCT examining the efficacy of isometric handgrip exercise (IHGE) and beetroot juice (a rich source of inorganic nitrate) consumption in modifying clinic and 24-h ambulatory BP (24-h ABP), peripheral arterial function and plasma asymmetric dimethylarginine (ADMA) in older overweight and obese adults. DESIGN: Thirty middle age and older adults (62±5 years) were randomised to: (a) bilateral IHGE at 50% of maximal voluntary contraction (8 min/day), (b) 140 ml/day of concentrated beetroot juice, or (c) no-intervention (control group), for 7 days. All groups followed a standardised diet to control nitrate intake. Clinic and 24-h ABP, peripheral arterial function quantified by pulse wave velocity (PWV) and arterial volume distensibility were assessed before and after intervention. SETTING: Clinical ageing research unit, Newcastle University. RESULTS: At baseline, there were no between-group differences in age, handgrip strength, clinic or 24-h ABP, BMI, waist circumference, fat mass, physical activity level, energy intake or urinary and plasma nitrate concentrations. After intervention, there were no significant effects on clinic systolic and diastolic BP or 24-h ABP, PWV (p=0.54), arterial volume distensibility (p=0.89), or ADMA (p=0.45). CONCLUSIONS: IHGE or beetroot juice consumption for 7 days did not affect BP or peripheral arterial function in overweight and obese middle age and older adults. Ageing may reduce the effects of these interventions on vascular function and studies are needed to test this hypothesis.