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Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers.

ABSTRACT: Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO) for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion.Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075) between July 2007 and August 2008. All subjects provided written consent to participate. Twelve subjects (5 males, 7 females; mean age, 38.8±9.2 years (range, 21-56 years)) were intravenously infused with increasing doses of sodium nitrite for 48 hours (starting dose at 4.2 µg/kg/hr; maximal dose of 533.8 µg/kg/hr). Clinical, physiologic and laboratory data before, during and after infusion were analyzed.The maximal tolerated dose for intravenous infusion of sodium nitrite was 267 µg/kg/hr. Dose limiting toxicity occurred at 446 µg/kg/hr. Toxicity included a transient asymptomatic decrease of mean arterial blood pressure (more than 15 mmHg) and/or an asymptomatic increase of methemoglobin level above 5%. Nitrite, nitrate, S-nitrosothiols concentrations in plasma and whole blood increased in all subjects and returned to preinfusion baseline values within 12 hours after cessation of the infusion. The mean half-life of nitrite estimated at maximal tolerated dose was 45.3 minutes for plasma and 51.4 minutes for whole blood.Sodium nitrite can be safely infused intravenously at defined concentrations for prolonged intervals. These results should be valuable for developing studies to investigate new NO treatment paradigms for a variety of clinical disorders, including cerebral vasospasm after subarachnoid hemorrhage, and ischemia of the heart, liver, kidney and brain, as well as organ transplants, blood-brain barrier modulation and pulmonary hypertension.http://www.clinicaltrials.gov; NCT00103025.

SUBMITTER: Pluta RM

PROVIDER: S-EPMC3018414 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers.

Pluta Ryszard M RM Oldfield Edward H EH Bakhtian Kamran D KD Fathi Ali Reza AR Smith René K RK Devroom Hetty L HL Nahavandi Masoud M Woo Sukyung S Figg William D WD Lonser Russell R RR

PloS one 20110110 1

<h4>Background</h4>Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO) for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion.<h4>Methodology</h4>Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075) between July 2007 and August 2008. All subjects provided wr ...[more]

PMID: 21249218

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Project description:BackgroundIntermittent fasting (IF) is defined as an eating pattern without calorie restrictions, alternating between periods of fasting and eating. In the past decades IF has not only become a popular weight-reducing diet but is thought to improve Quality of Life (QoL) and fatigue. However, very little evidence exists for the general population. Thus, we aimed to assess the impact of a 16-h fasting period per day over a three-month study period on QoL and especially fatigue in healthy people.MethodsWe conducted a prospective cohort study including healthy subjects. All participants fasted 16 h for at least five days a week while maintaining their normal lifestyle. In the study, we analysed blood samples as well as QoL through standardized questionnaires (WHO-5 questionnaire, Short Form Health 36). Furthermore, we measured the degree of fatigue with the Fatigue Assessment Scale (FAS) and Fatigue Severity Scale (FSS) as well as compliance, activity records, and weight alterations. All endpoints were evaluated at baseline, after two weeks, four weeks, and three months of IF.ResultsA total of 30 participants fasted for the entire study period. The results of the WHO-5 questionnaire (15.6 ± 4.6 vs. 18 ± 3.6, p < 0.0019) demonstrated a significant increase in QoL. For long-term QoL six out of eight domains measured by the Short Form Health 36 (SF-36) significantly improved (e.g., physical health: 92.3 ± 11.6 vs. 96.5 ± 6.3, p = 0.015; mental health: 75.5 ± 12.0 vs. 81.7 ± 9.0; p < 0.001 and body pain: 74.1 ± 31.8 vs. 89.5 ± 14.9; p = 0.008) after three months. Fatigue significantly decreased from 10.3 ± 3.2 to 8.4 ± 2.5; p = 0.002 for mental fatigue and from 12.6 ± 3.8 to 10.7 ± 3.3; p = 0.002 measured by the FAS. The mean FSS-Score at baseline was 3.5 ± 1.2 compared to 2.9 ± 1.1 (scale 1-7) after three months (p < 0.001). Notably, the proliferation marker IGF-1 was significantly reduced. No clinically significant changes in laboratory parameters were observed that would have endangered a participant's safety.ConclusionsIF according to the 16:8 regime over a fasting period of three months significantly improved several aspects of the QoL and decreased fatigue in healthy people, while maintaining a good safety profile. The practicability of this diet was also demonstrated for shift workers and people with a high percentage of active labour. Apart from the improvement in QoL and fatigue, the significant reduction in IGF-1, which can act as an accelerator of tumour development and progression, might be an indicator of the potential benefits of IF for patients with cancer.

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Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers.

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Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers.

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