Limits...
New insights on effects of a dietary supplement on oxidative and nitrosative stress in humans.

Nemzer BV, Fink N, Fink B - Food Sci Nutr (2014)

Bottom Line: In this clinical study, we demonstrated that administration of SPECTRA™ resulted in statistically significant long-term inhibition of mitochondrial and cellular ROS generation by as much as 17% as well as 3.5-times inhibition in extracellular NADPH system-dependent generation of O2 (-), and nearly complete inhibition of extracellular H2O2 formation.For the first time, we have measured synergetic, biological effects of a natural supplement on changes in OSM and cellular metabolic activity.The unique design and activity of the plant-based natural supplement, in combination with the newly developed and extended Vitality test, demonstrates the potential of using dietary supplements to modulate OSM and also opens the door to future research into the use of natural supplements for supporting optimal health.

View Article: PubMed Central - PubMed

Affiliation: VDF FutureCeuticals Inc. 2692 N State Rt. 1-17, Momence, Illinois, 60954 ; University of Illinois at Urbana-Champaign 1201 W. Gregory Dr, Urbana, Illinois, 61801.

ABSTRACT
The research community is generally agreed that maintenance of healthy levels of free radicals and related oxidants are important for good health. However, utilization of the "redox stress hypothesis" can provide us with concrete nutritional targets in order to better support and maintain "optimal health." Following this hypothesis we performed a crossover, double-blind, placebo-controlled, single-dose study on the effects of SPECTRA™, a dietary supplement, on oxidative stress markers (OSM) in human participants (n = 22). The measurement of OSM (ex vivo intra- and extracellular formation of reactive oxygen species (ROS, O2 (-), H2O2, OH(-)) in whole blood, respiratory activity of blood cells, as well as mitochondrial-dependent ROS formation, and respiratory activity), was performed using EPR spectrometer nOxyscan, spin probe CMH, and oxygen label NOX-15.1, respectively. Furthermore, we investigated the ability of SPECTRA™ to modulate ex vivo cellular inflammatory responses induced by stimulation with exogenous TNF-α and also followed changes in bioavailable NO concentrations. In this clinical study, we demonstrated that administration of SPECTRA™ resulted in statistically significant long-term inhibition of mitochondrial and cellular ROS generation by as much as 17% as well as 3.5-times inhibition in extracellular NADPH system-dependent generation of O2 (-), and nearly complete inhibition of extracellular H2O2 formation. This was reflected in more than two times inhibition of ex vivo cellular inflammatory response and also increases in bioavailable NO concentration. For the first time, we have measured synergetic, biological effects of a natural supplement on changes in OSM and cellular metabolic activity. The unique design and activity of the plant-based natural supplement, in combination with the newly developed and extended Vitality test, demonstrates the potential of using dietary supplements to modulate OSM and also opens the door to future research into the use of natural supplements for supporting optimal health.

No MeSH data available.


Related in: MedlinePlus

Effect of SPECTRA™ on “mitochondrial” ROS generation in blood cells collected from human volunteers. Detection of mitochondrial ROS generation was performed using spin probe CMH (200 μmol/L) and bench-top EPR spectrometer nOxyscan after addition of Antimycin A (10 μmol/L) in the blood samples taken prior to and at 60, 120, 180 min after consumption of standard breakfast (bread roll with glass of water). Blue columns (control): prior to and 60, 120, 180 min after consumption of standard breakfast (bread roll with glass of water); red columns (placebo): after consumption of standard breakfast and placebo capsule; and green columns (SPECTRA™): after consumption of standard breakfast and SPECTRA™ capsule. The values of ROS generation were calculated as delta value between “total” and “Antimycin A” sample. Data are mean ± SEM (n = 22), *P < 0.05 versus value “before.” CMH, 1-hydroxy-3-methoxycarbonyl-2.2.5.5-tetramethylpyrrolidine; EPR, elec-tron paramagnetic resonance; ROS, reactive oxygen species.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4256589&req=5

fig04: Effect of SPECTRA™ on “mitochondrial” ROS generation in blood cells collected from human volunteers. Detection of mitochondrial ROS generation was performed using spin probe CMH (200 μmol/L) and bench-top EPR spectrometer nOxyscan after addition of Antimycin A (10 μmol/L) in the blood samples taken prior to and at 60, 120, 180 min after consumption of standard breakfast (bread roll with glass of water). Blue columns (control): prior to and 60, 120, 180 min after consumption of standard breakfast (bread roll with glass of water); red columns (placebo): after consumption of standard breakfast and placebo capsule; and green columns (SPECTRA™): after consumption of standard breakfast and SPECTRA™ capsule. The values of ROS generation were calculated as delta value between “total” and “Antimycin A” sample. Data are mean ± SEM (n = 22), *P < 0.05 versus value “before.” CMH, 1-hydroxy-3-methoxycarbonyl-2.2.5.5-tetramethylpyrrolidine; EPR, elec-tron paramagnetic resonance; ROS, reactive oxygen species.

Mentions: As Figure1 immediately below demonstrates, at 60 min after 100 mg single-dose SPECTRA™ administration we observed a significant decrease in total generation of ROS/metabolic activity of blood cells in human volunteers. These effects persisted for another 2 h followed by a significant trend toward baseline 3 h after administration. Under pathological conditions, increased oxidative stress itself can alter oxygen levels. Changes in oxygen levels may subsequently affect mitochondrial oxygen consumption. In order to circumvent this problem, EPR method has been developed for measuring superoxide and oxygen consumption in mitochondrial respiratory complexes using the oxygen labels such as NOX-15.1 (Mariappan et al. 2009). By using a gas controller and nontoxic spin label NOX-15.1, we were able to measure oxygen consumption simultaneously during detection of ROS. The merit of this method is that it allows us to measure superoxide production and oxygen consumption in parallel using the same incubation medium and substrate concentration in each blood sample. Simultaneously to changes in levels of ROS, we observed a significant increase in cellular oxygen consumption (Fig.2) as well as mitochondrial oxygen consumption (Fig.3) after 1 h of SPECTRA™ ingestion. These levels continued to be slightly elevated during the next 2 h. These findings suggest optimization of redox balances and optimization of respiratory activity of mitochondria factors that are important for healthy aging (Dikalova et al. 2010; Nazarewicz et al. 2013). The same pattern as cellular ROS generation was recognized in the mitochondrial generation of ROS after SPECTRA™ administration. It decreased significantly after 1 h and continued to decrease for the next 2 h (Fig.4). Although generation of ROS in the control and placebo group showed nonsignificant tendencies toward depletion of ROS formation, this is consistent with previous observations collected from nonathletically trained participants (B. Fink, unpubl. data). In addition to the decrease in “total” ROS generation and oxygen consumption, the administration of a single dose of SPECTRA™ significantly inhibited generation of extracellular NADPH oxidase-dependent superoxide (O2−, Fig.5) and peroxidase-dependent hydrogen peroxide (H2O2, Fig.6). The possibility for such regulatory effects on NADPH-oxidases activity suggests that SPECTRA™ may help support cardiovascular health in healthy aged subjects (Wyche et al. 2004; Dikalov et al. 2012). Compared to the “total” ROS generation, the values of both superoxide and hydrogen peroxide generation in the control as well as in the placebo group showed nonsignificant depletion tendencies over the observation period.


New insights on effects of a dietary supplement on oxidative and nitrosative stress in humans.

Nemzer BV, Fink N, Fink B - Food Sci Nutr (2014)

Effect of SPECTRA™ on “mitochondrial” ROS generation in blood cells collected from human volunteers. Detection of mitochondrial ROS generation was performed using spin probe CMH (200 μmol/L) and bench-top EPR spectrometer nOxyscan after addition of Antimycin A (10 μmol/L) in the blood samples taken prior to and at 60, 120, 180 min after consumption of standard breakfast (bread roll with glass of water). Blue columns (control): prior to and 60, 120, 180 min after consumption of standard breakfast (bread roll with glass of water); red columns (placebo): after consumption of standard breakfast and placebo capsule; and green columns (SPECTRA™): after consumption of standard breakfast and SPECTRA™ capsule. The values of ROS generation were calculated as delta value between “total” and “Antimycin A” sample. Data are mean ± SEM (n = 22), *P < 0.05 versus value “before.” CMH, 1-hydroxy-3-methoxycarbonyl-2.2.5.5-tetramethylpyrrolidine; EPR, elec-tron paramagnetic resonance; ROS, reactive oxygen species.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4256589&req=5

fig04: Effect of SPECTRA™ on “mitochondrial” ROS generation in blood cells collected from human volunteers. Detection of mitochondrial ROS generation was performed using spin probe CMH (200 μmol/L) and bench-top EPR spectrometer nOxyscan after addition of Antimycin A (10 μmol/L) in the blood samples taken prior to and at 60, 120, 180 min after consumption of standard breakfast (bread roll with glass of water). Blue columns (control): prior to and 60, 120, 180 min after consumption of standard breakfast (bread roll with glass of water); red columns (placebo): after consumption of standard breakfast and placebo capsule; and green columns (SPECTRA™): after consumption of standard breakfast and SPECTRA™ capsule. The values of ROS generation were calculated as delta value between “total” and “Antimycin A” sample. Data are mean ± SEM (n = 22), *P < 0.05 versus value “before.” CMH, 1-hydroxy-3-methoxycarbonyl-2.2.5.5-tetramethylpyrrolidine; EPR, elec-tron paramagnetic resonance; ROS, reactive oxygen species.
Mentions: As Figure1 immediately below demonstrates, at 60 min after 100 mg single-dose SPECTRA™ administration we observed a significant decrease in total generation of ROS/metabolic activity of blood cells in human volunteers. These effects persisted for another 2 h followed by a significant trend toward baseline 3 h after administration. Under pathological conditions, increased oxidative stress itself can alter oxygen levels. Changes in oxygen levels may subsequently affect mitochondrial oxygen consumption. In order to circumvent this problem, EPR method has been developed for measuring superoxide and oxygen consumption in mitochondrial respiratory complexes using the oxygen labels such as NOX-15.1 (Mariappan et al. 2009). By using a gas controller and nontoxic spin label NOX-15.1, we were able to measure oxygen consumption simultaneously during detection of ROS. The merit of this method is that it allows us to measure superoxide production and oxygen consumption in parallel using the same incubation medium and substrate concentration in each blood sample. Simultaneously to changes in levels of ROS, we observed a significant increase in cellular oxygen consumption (Fig.2) as well as mitochondrial oxygen consumption (Fig.3) after 1 h of SPECTRA™ ingestion. These levels continued to be slightly elevated during the next 2 h. These findings suggest optimization of redox balances and optimization of respiratory activity of mitochondria factors that are important for healthy aging (Dikalova et al. 2010; Nazarewicz et al. 2013). The same pattern as cellular ROS generation was recognized in the mitochondrial generation of ROS after SPECTRA™ administration. It decreased significantly after 1 h and continued to decrease for the next 2 h (Fig.4). Although generation of ROS in the control and placebo group showed nonsignificant tendencies toward depletion of ROS formation, this is consistent with previous observations collected from nonathletically trained participants (B. Fink, unpubl. data). In addition to the decrease in “total” ROS generation and oxygen consumption, the administration of a single dose of SPECTRA™ significantly inhibited generation of extracellular NADPH oxidase-dependent superoxide (O2−, Fig.5) and peroxidase-dependent hydrogen peroxide (H2O2, Fig.6). The possibility for such regulatory effects on NADPH-oxidases activity suggests that SPECTRA™ may help support cardiovascular health in healthy aged subjects (Wyche et al. 2004; Dikalov et al. 2012). Compared to the “total” ROS generation, the values of both superoxide and hydrogen peroxide generation in the control as well as in the placebo group showed nonsignificant depletion tendencies over the observation period.

Bottom Line: In this clinical study, we demonstrated that administration of SPECTRA™ resulted in statistically significant long-term inhibition of mitochondrial and cellular ROS generation by as much as 17% as well as 3.5-times inhibition in extracellular NADPH system-dependent generation of O2 (-), and nearly complete inhibition of extracellular H2O2 formation.For the first time, we have measured synergetic, biological effects of a natural supplement on changes in OSM and cellular metabolic activity.The unique design and activity of the plant-based natural supplement, in combination with the newly developed and extended Vitality test, demonstrates the potential of using dietary supplements to modulate OSM and also opens the door to future research into the use of natural supplements for supporting optimal health.

View Article: PubMed Central - PubMed

Affiliation: VDF FutureCeuticals Inc. 2692 N State Rt. 1-17, Momence, Illinois, 60954 ; University of Illinois at Urbana-Champaign 1201 W. Gregory Dr, Urbana, Illinois, 61801.

ABSTRACT
The research community is generally agreed that maintenance of healthy levels of free radicals and related oxidants are important for good health. However, utilization of the "redox stress hypothesis" can provide us with concrete nutritional targets in order to better support and maintain "optimal health." Following this hypothesis we performed a crossover, double-blind, placebo-controlled, single-dose study on the effects of SPECTRA™, a dietary supplement, on oxidative stress markers (OSM) in human participants (n = 22). The measurement of OSM (ex vivo intra- and extracellular formation of reactive oxygen species (ROS, O2 (-), H2O2, OH(-)) in whole blood, respiratory activity of blood cells, as well as mitochondrial-dependent ROS formation, and respiratory activity), was performed using EPR spectrometer nOxyscan, spin probe CMH, and oxygen label NOX-15.1, respectively. Furthermore, we investigated the ability of SPECTRA™ to modulate ex vivo cellular inflammatory responses induced by stimulation with exogenous TNF-α and also followed changes in bioavailable NO concentrations. In this clinical study, we demonstrated that administration of SPECTRA™ resulted in statistically significant long-term inhibition of mitochondrial and cellular ROS generation by as much as 17% as well as 3.5-times inhibition in extracellular NADPH system-dependent generation of O2 (-), and nearly complete inhibition of extracellular H2O2 formation. This was reflected in more than two times inhibition of ex vivo cellular inflammatory response and also increases in bioavailable NO concentration. For the first time, we have measured synergetic, biological effects of a natural supplement on changes in OSM and cellular metabolic activity. The unique design and activity of the plant-based natural supplement, in combination with the newly developed and extended Vitality test, demonstrates the potential of using dietary supplements to modulate OSM and also opens the door to future research into the use of natural supplements for supporting optimal health.

No MeSH data available.


Related in: MedlinePlus