Dates of funding 2017-2019
Impact of dietary nitrate supplementation via beetroot juice on skeletal muscle metabolic control and exercise tolerance in sickle cell anemia
Sickle Cell Disease results in severely compromised exercise capacity, and thus the quality of life, for those afflicted. This is due to both central cardiopulmonary and peripheral vascular factors which conspire to reduce maximal oxygen uptake (VO₂max) and instill premature fatigue during exercise. SCD results in high rates of hemolysis and the resulting release of free-hemoglobin (HB) rapidly scavenges nitric oxide (NO) resulting in impaired cardiovascular control. Our work focuses on the impact of Hb on skeletal muscle vascular and metabolic control as this is likely a primary mechanism of peripheral vasculopathy and exercise decrement in SCD.

Over the past decade, a plethora of investigations have demonstrated the robust efficacy of dietary nitrate supplementation in the treatment of many prevalent diseases related to loss of NO bioavailability; accordingly, it has been hailed as an “unrecognized nutrient.” Previous investigations in humans and animals have demonstrated that NO₃^–, when consumed, serves as a powerful controller of muscle O₂perfusion, presumably following its reduction to nitrite (NO₂^–) and NO in vivo. Collectively, these results strongly support the premise that dietary NO₃^– as a nutritional therapeutic will ameliorate Hb-mediated NO depletion for patients with SCD, and therefore evoke improved exercise tolerance and quality of life. Thus, this project is aimed at uncovering the mechanistic basis for skeletal muscle dysfunction in SCD and the therapeutic potential of dietary NO₃^– in preclinical models of this disease. Results from these investigations will directly impact the design of future clinical studies at the University of Colorado, Denver in the coming years.

Dates of funding 2017-2019
Impact of dietary nitrate supplementation via beetroot juice on skeletal muscle metabolic control and exercise tolerance in sickle cell anemia
Sickle Cell Disease results in severely compromised exercise capacity, and thus the quality of life, for those afflicted. This is due to both central cardiopulmonary and peripheral vascular factors which conspire to reduce maximal oxygen uptake (VO₂max) and instill premature fatigue during exercise. SCD results in high rates of hemolysis and the resulting release of free-hemoglobin (HB) rapidly scavenges nitric oxide (NO) resulting in impaired cardiovascular control. Our work focuses on the impact of Hb on skeletal muscle vascular and metabolic control as this is likely a primary mechanism of peripheral vasculopathy and exercise decrement in SCD.

Over the past decade, a plethora of investigations have demonstrated the robust efficacy of dietary nitrate supplementation in the treatment of many prevalent diseases related to loss of NO bioavailability; accordingly, it has been hailed as an “unrecognized nutrient.” Previous investigations in humans and animals have demonstrated that NO₃^–, when consumed, serves as a powerful controller of muscle O₂perfusion, presumably following its reduction to nitrite (NO₂^–) and NO in vivo. Collectively, these results strongly support the premise that dietary NO₃^– as a nutritional therapeutic will ameliorate Hb-mediated NO depletion for patients with SCD, and therefore evoke improved exercise tolerance and quality of life. Thus, this project is aimed at uncovering the mechanistic basis for skeletal muscle dysfunction in SCD and the therapeutic potential of dietary NO₃^– in preclinical models of this disease. Results from these investigations will directly impact the design of future clinical studies at the University of Colorado, Denver in the coming years.

Dates of funding 2017-2019
Impact of dietary nitrate supplementation via beetroot juice on skeletal muscle metabolic control and exercise tolerance in sickle cell anemia
Sickle Cell Disease results in severely compromised exercise capacity, and thus the quality of life, for those afflicted. This is due to both central cardiopulmonary and peripheral vascular factors which conspire to reduce maximal oxygen uptake (VO₂max) and instill premature fatigue during exercise. SCD results in high rates of hemolysis and the resulting release of free-hemoglobin (HB) rapidly scavenges nitric oxide (NO) resulting in impaired cardiovascular control. Our work focuses on the impact of Hb on skeletal muscle vascular and metabolic control as this is likely a primary mechanism of peripheral vasculopathy and exercise decrement in SCD.

Over the past decade, a plethora of investigations have demonstrated the robust efficacy of dietary nitrate supplementation in the treatment of many prevalent diseases related to loss of NO bioavailability; accordingly, it has been hailed as an “unrecognized nutrient.” Previous investigations in humans and animals have demonstrated that NO₃^–, when consumed, serves as a powerful controller of muscle O₂perfusion, presumably following its reduction to nitrite (NO₂^–) and NO in vivo. Collectively, these results strongly support the premise that dietary NO₃^– as a nutritional therapeutic will ameliorate Hb-mediated NO depletion for patients with SCD, and therefore evoke improved exercise tolerance and quality of life. Thus, this project is aimed at uncovering the mechanistic basis for skeletal muscle dysfunction in SCD and the therapeutic potential of dietary NO₃^– in preclinical models of this disease. Results from these investigations will directly impact the design of future clinical studies at the University of Colorado, Denver in the coming years.

Dates of funding 2017-2019
Impact of dietary nitrate supplementation via beetroot juice on skeletal muscle metabolic control and exercise tolerance in sickle cell anemia
Sickle Cell Disease results in severely compromised exercise capacity, and thus the quality of life, for those afflicted. This is due to both central cardiopulmonary and peripheral vascular factors which conspire to reduce maximal oxygen uptake (VO₂max) and instill premature fatigue during exercise. SCD results in high rates of hemolysis and the resulting release of free-hemoglobin (HB) rapidly scavenges nitric oxide (NO) resulting in impaired cardiovascular control. Our work focuses on the impact of Hb on skeletal muscle vascular and metabolic control as this is likely a primary mechanism of peripheral vasculopathy and exercise decrement in SCD.

Over the past decade, a plethora of investigations have demonstrated the robust efficacy of dietary nitrate supplementation in the treatment of many prevalent diseases related to loss of NO bioavailability; accordingly, it has been hailed as an “unrecognized nutrient.” Previous investigations in humans and animals have demonstrated that NO₃^–, when consumed, serves as a powerful controller of muscle O₂perfusion, presumably following its reduction to nitrite (NO₂^–) and NO in vivo. Collectively, these results strongly support the premise that dietary NO₃^– as a nutritional therapeutic will ameliorate Hb-mediated NO depletion for patients with SCD, and therefore evoke improved exercise tolerance and quality of life. Thus, this project is aimed at uncovering the mechanistic basis for skeletal muscle dysfunction in SCD and the therapeutic potential of dietary NO₃^– in preclinical models of this disease. Results from these investigations will directly impact the design of future clinical studies at the University of Colorado, Denver in the coming years.

Dates of funding 2017-2019
Impact of dietary nitrate supplementation via beetroot juice on skeletal muscle metabolic control and exercise tolerance in sickle cell anemia
Sickle Cell Disease results in severely compromised exercise capacity, and thus the quality of life, for those afflicted. This is due to both central cardiopulmonary and peripheral vascular factors which conspire to reduce maximal oxygen uptake (VO₂max) and instill premature fatigue during exercise. SCD results in high rates of hemolysis and the resulting release of free-hemoglobin (HB) rapidly scavenges nitric oxide (NO) resulting in impaired cardiovascular control. Our work focuses on the impact of Hb on skeletal muscle vascular and metabolic control as this is likely a primary mechanism of peripheral vasculopathy and exercise decrement in SCD.

Over the past decade, a plethora of investigations have demonstrated the robust efficacy of dietary nitrate supplementation in the treatment of many prevalent diseases related to loss of NO bioavailability; accordingly, it has been hailed as an “unrecognized nutrient.” Previous investigations in humans and animals have demonstrated that NO₃^–, when consumed, serves as a powerful controller of muscle O₂perfusion, presumably following its reduction to nitrite (NO₂^–) and NO in vivo. Collectively, these results strongly support the premise that dietary NO₃^– as a nutritional therapeutic will ameliorate Hb-mediated NO depletion for patients with SCD, and therefore evoke improved exercise tolerance and quality of life. Thus, this project is aimed at uncovering the mechanistic basis for skeletal muscle dysfunction in SCD and the therapeutic potential of dietary NO₃^– in preclinical models of this disease. Results from these investigations will directly impact the design of future clinical studies at the University of Colorado, Denver in the coming years.

Dates of funding 2017-2019
Impact of dietary nitrate supplementation via beetroot juice on skeletal muscle metabolic control and exercise tolerance in sickle cell anemia
Sickle Cell Disease results in severely compromised exercise capacity, and thus the quality of life, for those afflicted. This is due to both central cardiopulmonary and peripheral vascular factors which conspire to reduce maximal oxygen uptake (VO₂max) and instill premature fatigue during exercise. SCD results in high rates of hemolysis and the resulting release of free-hemoglobin (HB) rapidly scavenges nitric oxide (NO) resulting in impaired cardiovascular control. Our work focuses on the impact of Hb on skeletal muscle vascular and metabolic control as this is likely a primary mechanism of peripheral vasculopathy and exercise decrement in SCD.

Over the past decade, a plethora of investigations have demonstrated the robust efficacy of dietary nitrate supplementation in the treatment of many prevalent diseases related to loss of NO bioavailability; accordingly, it has been hailed as an “unrecognized nutrient.” Previous investigations in humans and animals have demonstrated that NO₃^–, when consumed, serves as a powerful controller of muscle O₂perfusion, presumably following its reduction to nitrite (NO₂^–) and NO in vivo. Collectively, these results strongly support the premise that dietary NO₃^– as a nutritional therapeutic will ameliorate Hb-mediated NO depletion for patients with SCD, and therefore evoke improved exercise tolerance and quality of life. Thus, this project is aimed at uncovering the mechanistic basis for skeletal muscle dysfunction in SCD and the therapeutic potential of dietary NO₃^– in preclinical models of this disease. Results from these investigations will directly impact the design of future clinical studies at the University of Colorado, Denver in the coming years.

Dates of funding 2017-2019
Impact of dietary nitrate supplementation via beetroot juice on skeletal muscle metabolic control and exercise tolerance in sickle cell anemia
Sickle Cell Disease results in severely compromised exercise capacity, and thus the quality of life, for those afflicted. This is due to both central cardiopulmonary and peripheral vascular factors which conspire to reduce maximal oxygen uptake (VO₂max) and instill premature fatigue during exercise. SCD results in high rates of hemolysis and the resulting release of free-hemoglobin (HB) rapidly scavenges nitric oxide (NO) resulting in impaired cardiovascular control. Our work focuses on the impact of Hb on skeletal muscle vascular and metabolic control as this is likely a primary mechanism of peripheral vasculopathy and exercise decrement in SCD.

Over the past decade, a plethora of investigations have demonstrated the robust efficacy of dietary nitrate supplementation in the treatment of many prevalent diseases related to loss of NO bioavailability; accordingly, it has been hailed as an “unrecognized nutrient.” Previous investigations in humans and animals have demonstrated that NO₃^–, when consumed, serves as a powerful controller of muscle O₂perfusion, presumably following its reduction to nitrite (NO₂^–) and NO in vivo. Collectively, these results strongly support the premise that dietary NO₃^– as a nutritional therapeutic will ameliorate Hb-mediated NO depletion for patients with SCD, and therefore evoke improved exercise tolerance and quality of life. Thus, this project is aimed at uncovering the mechanistic basis for skeletal muscle dysfunction in SCD and the therapeutic potential of dietary NO₃^– in preclinical models of this disease. Results from these investigations will directly impact the design of future clinical studies at the University of Colorado, Denver in the coming years.

Dates of funding 2017-2019
Impact of dietary nitrate supplementation via beetroot juice on skeletal muscle metabolic control and exercise tolerance in sickle cell anemia
Sickle Cell Disease results in severely compromised exercise capacity, and thus the quality of life, for those afflicted. This is due to both central cardiopulmonary and peripheral vascular factors which conspire to reduce maximal oxygen uptake (VO₂max) and instill premature fatigue during exercise. SCD results in high rates of hemolysis and the resulting release of free-hemoglobin (HB) rapidly scavenges nitric oxide (NO) resulting in impaired cardiovascular control. Our work focuses on the impact of Hb on skeletal muscle vascular and metabolic control as this is likely a primary mechanism of peripheral vasculopathy and exercise decrement in SCD.

Over the past decade, a plethora of investigations have demonstrated the robust efficacy of dietary nitrate supplementation in the treatment of many prevalent diseases related to loss of NO bioavailability; accordingly, it has been hailed as an “unrecognized nutrient.” Previous investigations in humans and animals have demonstrated that NO₃^–, when consumed, serves as a powerful controller of muscle O₂perfusion, presumably following its reduction to nitrite (NO₂^–) and NO in vivo. Collectively, these results strongly support the premise that dietary NO₃^– as a nutritional therapeutic will ameliorate Hb-mediated NO depletion for patients with SCD, and therefore evoke improved exercise tolerance and quality of life. Thus, this project is aimed at uncovering the mechanistic basis for skeletal muscle dysfunction in SCD and the therapeutic potential of dietary NO₃^– in preclinical models of this disease. Results from these investigations will directly impact the design of future clinical studies at the University of Colorado, Denver in the coming years.

Dates of funding 2017-2019
Impact of dietary nitrate supplementation via beetroot juice on skeletal muscle metabolic control and exercise tolerance in sickle cell anemia
Sickle Cell Disease results in severely compromised exercise capacity, and thus the quality of life, for those afflicted. This is due to both central cardiopulmonary and peripheral vascular factors which conspire to reduce maximal oxygen uptake (VO₂max) and instill premature fatigue during exercise. SCD results in high rates of hemolysis and the resulting release of free-hemoglobin (HB) rapidly scavenges nitric oxide (NO) resulting in impaired cardiovascular control. Our work focuses on the impact of Hb on skeletal muscle vascular and metabolic control as this is likely a primary mechanism of peripheral vasculopathy and exercise decrement in SCD.

Over the past decade, a plethora of investigations have demonstrated the robust efficacy of dietary nitrate supplementation in the treatment of many prevalent diseases related to loss of NO bioavailability; accordingly, it has been hailed as an “unrecognized nutrient.” Previous investigations in humans and animals have demonstrated that NO₃^–, when consumed, serves as a powerful controller of muscle O₂perfusion, presumably following its reduction to nitrite (NO₂^–) and NO in vivo. Collectively, these results strongly support the premise that dietary NO₃^– as a nutritional therapeutic will ameliorate Hb-mediated NO depletion for patients with SCD, and therefore evoke improved exercise tolerance and quality of life. Thus, this project is aimed at uncovering the mechanistic basis for skeletal muscle dysfunction in SCD and the therapeutic potential of dietary NO₃^– in preclinical models of this disease. Results from these investigations will directly impact the design of future clinical studies at the University of Colorado, Denver in the coming years.

Dates of funding 2017-2019
Impact of dietary nitrate supplementation via beetroot juice on skeletal muscle metabolic control and exercise tolerance in sickle cell anemia
Sickle Cell Disease results in severely compromised exercise capacity, and thus the quality of life, for those afflicted. This is due to both central cardiopulmonary and peripheral vascular factors which conspire to reduce maximal oxygen uptake (VO₂max) and instill premature fatigue during exercise. SCD results in high rates of hemolysis and the resulting release of free-hemoglobin (HB) rapidly scavenges nitric oxide (NO) resulting in impaired cardiovascular control. Our work focuses on the impact of Hb on skeletal muscle vascular and metabolic control as this is likely a primary mechanism of peripheral vasculopathy and exercise decrement in SCD.

Over the past decade, a plethora of investigations have demonstrated the robust efficacy of dietary nitrate supplementation in the treatment of many prevalent diseases related to loss of NO bioavailability; accordingly, it has been hailed as an “unrecognized nutrient.” Previous investigations in humans and animals have demonstrated that NO₃^–, when consumed, serves as a powerful controller of muscle O₂perfusion, presumably following its reduction to nitrite (NO₂^–) and NO in vivo. Collectively, these results strongly support the premise that dietary NO₃^– as a nutritional therapeutic will ameliorate Hb-mediated NO depletion for patients with SCD, and therefore evoke improved exercise tolerance and quality of life. Thus, this project is aimed at uncovering the mechanistic basis for skeletal muscle dysfunction in SCD and the therapeutic potential of dietary NO₃^– in preclinical models of this disease. Results from these investigations will directly impact the design of future clinical studies at the University of Colorado, Denver in the coming years.