A diet rich in fruits and vegetables is associated with lowering of blood pressure (BP), but the nutrient(s) responsible for these effects remain unclear. Research suggests that inorganic nitrate present in leafy green vegetables is converted into NO in vivo to improve cardiovascular function. In this study, we evaluated the effect of leafy green vegetables on BP in subjects with elevated BP, with the aim of elucidating if any such effect is related to their high nitrate content. We enrolled 243 subjects, 50-70 y old, with a clinic systolic BP (SBP) of 130-159 mm Hg. After a 2-wk run-in period on a nitrate-restricted diet the subjects were randomly assigned to receive 1 of the following 3 interventions daily for 5 wk: low-nitrate vegetables + placebo pills, low-nitrate vegetables + nitrate pills (300 mg nitrate), or leafy green vegetables containing 300 mg nitrate + placebo pills. The primary end point measure was the difference in change in 24 h ambulatory SBP between the groups. A total of 231 subjects (95%) completed the study. The insignificant change in ambulatory SBP (mean ± standard deviation) was -0.6 ± 6.2 mm Hg in the placebo group, -1.2 ± 6.8 mm Hg in the potassium nitrate group, and -0.5 ± 6.6 mm Hg in the leafy green vegetable group. There was no significant difference in change between the 3 groups. A 5-wk dietary supplementation with leafy green vegetables or pills containing the same amount of inorganic nitrate does not decrease ambulatory SBP in subjects with elevated BP. This trial was registered at clinicaltrials.gov as NCT02916615.

Red blood cells (RBCs) mediate cardioprotection via nitric oxide–like bioactivity, but the signaling and the identity of any mediator released by the RBCs remains unknown. We investigated whether RBCs exposed to hypoxia release a cardioprotective mediator and explored the nature of this mediator. Perfusion of isolated hearts subjected to ischemia-reperfusion with extracellular supernatant from mouse RBCs exposed to hypoxia resulted in improved postischemic cardiac function and reduced infarct size. Hypoxia increased extracellular export of cyclic guanosine monophosphate (cGMP) from mouse RBCs, and exogenous cGMP mimicked the cardioprotection induced by the supernatant. The protection induced by hypoxic RBCs was dependent on RBC-soluble guanylate cyclase and cGMP transport and was sensitive to phosphodiesterase 5 and activated cardiomyocyte protein kinase G. Oral administration of nitrate to mice to increase nitric oxide bioactivity further enhanced the cardioprotective effect of hypoxic RBCs. In a placebo-controlled clinical trial, a clear cardioprotective, soluble guanylate cyclase–dependent effect was induced by RBCs collected from patients randomized to 5 weeks nitrate-rich diet. It is concluded that RBCs generate and export cGMP as a response to hypoxia, mediating cardioprotection via a paracrine effect. This effect can be further augmented by a simple dietary intervention, suggesting preventive and therapeutic opportunities in ischemic heart disease.

Aim: The inorganic anions nitrate and nitrite are oxidation products of nitric oxide (NO) that have often been used as an index of NO generation. More than just being surrogate markers of NO, nitrate/nitrite can recycle to bioactive NO again. Nitrate is predominantly eliminated via the kidneys; however, there is less knowledge regarding tubular handling. The aim of this study, as part of a large randomized controlled trial, was to explore potential sex differences in renal nitrate handling during low and high dietary nitrate intake. We hypothesized that renal clearance and excretion of nitrate are higher in men compared to women.Methods: In prehypertensive and hypertensive individuals (n = 231), nitrate and nitrite were measured in plasma and urine at low dietary nitrate intake (baseline) and after 5 weeks supplementation with nitrate (300 mg potassium nitrate/day) or placebo (300 mg potassium chloride/day). Twenty‐four hours ambulatory blood pressure recordings and urine collections were conducted.Results: At baseline, plasma nitrate and nitrite, as well as the downstream marker of NO signalling cyclic guanosine monophosphate, were similar in women and men. Approximately 80% of filtered nitrate was spared by the kidneys. Urinary nitrate concentration, amount of nitrate excreted, renal nitrate clearance (C_nitrate) and fractional excretion of nitrate (FE_nitrate) were lower in women compared to men. No association was observed between plasma nitrate concentrations and glomerular filtration rate (GFR), nor between FE_nitrate and GFR in either sex. After 5 weeks of nitrate supplementation plasma nitrate and nitrite increased significantly, but blood pressure remained unchanged. FE_nitrate increased significantly and the sex difference observed at baseline disappeared.Conclusion: Our findings demonstrate substantial nitrate sparing capacity of the kidneys, which is higher in women compared to men. This suggests higher tubular nitrate reabsorption in women but the underlying mechanism(s) warrants further investigation.

This non-randomized controlled trial aimed to compare the effect of the 5:2 diet on insulin levels as a primary outcome and markers of insulin secretion (connecting peptide (C-peptide) and insulin-like growth factor binding protein-1 (IGFBP-1)) and sensitivity (Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)), as well as body composition as secondary outcomes in overweight/obese individuals with and without type 2 diabetes (T2D). Ninety-seven participants (62% women), 35 with T2D and 62 BMI- and waist-matched controls without T2D, followed the 5:2 diet (two days per week of fasting) for six months with a 12-month follow-up. At six months, there was no loss to follow-up in the T2D group, whereas four controls discontinued this study. Overall, 82% attended the 12-month follow-up. After the intervention, insulin levels decreased in the control group and glucose decreased in the T2D group, while C-peptide, HOMA-IR, waist circumference, BMI, trunk, and total fat% decreased in both groups. Furthermore, low IGFBP-1, indicating hyperinsulinemia, improved in the T2D group. The changes in fasting glucose and waist measurement were significantly more improved in the T2D group than in the controls. Persistent positive effects were observed at the 12-month follow-up. The 5:2 diet for six months was feasible and efficient to reduce markers of insulin secretion and resistance and therefore holds promise as management of overweight/obesity in subjects with and without T2D.

Glucosinolate-rich broccoli sprouts combined with intense exercise training for 7 days have been shown to reduce blood lactate concentrations during exercise, attenuate hypoglycemic events, improve physical performance, and reduce markers of oxidative stress. This study aimed to investigate the acute, dose-dependent effects of glucosinolate-rich red kale sprouts (GRS) on blood lactate and blood glucose following the ingestion of three different doses. Fifteen healthy participants consumed 37.5 g or 75 g of GRS or an isocaloric placebo blended into a beverage on three separate occasions. The participants cycled on an ergometer at three submaximal work rates before and three hours after ingestion. Measurements of oxygen uptake, substrate-level oxidation, blood lactate, blood glucose, and ratings of perceived exertion were taken before and after each cycling interval. The intake of glucosinolate-rich sprouts acutely decreased blood lactate levels during submaximal cycling and increased blood glucose levels at rest. The largest reduction in blood lactate was observed at the 37.5 g dose compared to placebo, where the concentration was 0.4 ± 0.2 mM lower at work rate close to threshold (p = 0.003). For the 75 g dose, the reduction in blood lactate was 0.25 ± 0.1 mM (p = 0.02). No significant effects were seen in the lowest work rate. The mean resting glucose level was 3.9 ± 0.1 mM following placebo, compared to 4.3 ± 0.1 mM after intake of either 37.5 g or 75 g dose (p < 0.01, respectively). These findings suggest that glucosinolate-rich broccoli sprouts have a lactate-lowering effect during submaximal efforts, which may have important implications for supplementation for improving endurance performance.