grithin
Member
- Joined
- Jul 1, 2020
- Messages
- 120
A bit ago, when I read the studies about MB and ETC, the model I came up with was:
In thinking about it now, there's another possible model/application of MB:
In perhaps over 5 years of testing with MB, I've found:
- 15mg high concentration dose (just below the burning threshold) on back of tongue useful pre-gym to improve workout by reducing perceived exertion for about 1-2hrs (expected consequent to MAO inhibition)
- 0.25-1mg dose, taken ~ every 3hr, improves overall energy
I've also noticed, however, that MB, at low concentration, seems to promote some microbes.
Some relevant studies..
[From Mitochondrial Function to Neuroprotection-an Emerging Role for Methylene Blue](https://pubmed.ncbi.nlm.nih.gov/28840449/)
- `MB can reroute electrons in the mitochondrial electron transfer chain directly from NADH to cytochrome c, increasing the activity of complex IV and effectively promoting mitochondrial activity while mitigating oxidative stress`
[Methylene blue improves mitochondrial respiration and decreases oxidative stress in a substrate-dependent manner in diabetic rat hearts](https://pubmed.ncbi.nlm.nih.gov/28738167/)
- `methylene blue elicited a significant increase in H2O2 release in the presence of complex I substrates (glutamate and malate), but had an opposite effect in mitochondria energized with complex II substrate (succinate)`
febs.onlinelibrary.wiley.com
- `Our data suggest that the acceptor of electrons from MB is a Qo ubiquinol‐binding site of Complex III; `
- MBH2 donates electrons to complex IV. This is particular useful in some cases where complex I and complex II are impaired (which can occur with hydrazine and efavirenz Bypassing the compromised mitochondrial electron transport with methylene blue alleviates efavirenz/isoniazid-induced oxidant stress and mitochondria-mediated cell death in mouse hepatocytes)
[Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue](https://pubmed.ncbi.nlm.nih.gov/22067440/)
`MB hormesis can be explained by the pharmacokinetics of MB in mitochondria, which is determined by the mitochondrial membrane potential and the relative local concentration of MB. Higher membrane potentials induce higher MB accumulation (i.e. binding to mitochondrial proteins) which in turn promotes higher MB aggregation (i.e. dimerization of MB molecules). However, MB aggregation is also affected by the proportion of MB molecules to binding sites, with less aggregation at very high, and very low binding site concentrations. Production of radicals has been shown to increase in the presence of MB monomers and be minimal in the presence of MB dimers [[@{:mb_dimers}@{[gabrielli2004.pdf]}]] (Gabrielli et al., 2004). Thus, in the presence of an optimal mitochondrial membrane potential, low MB concentrations favor dimerization and reduction, whereas high concentrations promote oxidation and reaction with endogenous electron donors such as nicotine adenine dinucleotide (NADH) and nicotine adenine dinucleotide phosphate (NADPH). Therefore, it is expected that low MB doses or concentrations will be, in general, more effective than large ones at facilitating physiological effects within mitochondria. In fact, at high local concentrations, MB can potentially “steal” electrons away from the electron transport chain complexes, disrupting the redox balance and acting as a pro-oxidant (Vutskits et al., 2008). Consistent with this, cell cultures exposed to high (micromolar range) but not to low (nanomolar range) concentrations of MB induce high levels of oxidants, and show a compensatory up regulation of antioxidant enzymes with decreased heme expression and iron uptake by 50% (Atamna et al., 2008). Several detrimental effects of MB on neural structure or function have been reported in vivo, including humans. These effects have been associated with administration of large doses of the compound, contact with connective tissue or concomitant use of psychotropic drugs (Arieff and Pyzik, 1960; Poppers et al., 1970; Blass and Fung, 1976; Martindale and Stedeford, 2003; Sweet and Standiford, 2007; Vutskits et al., 2008).`
In thinking about it now, there's another possible model/application of MB:
In perhaps over 5 years of testing with MB, I've found:
- 15mg high concentration dose (just below the burning threshold) on back of tongue useful pre-gym to improve workout by reducing perceived exertion for about 1-2hrs (expected consequent to MAO inhibition)
- 0.25-1mg dose, taken ~ every 3hr, improves overall energy
I've also noticed, however, that MB, at low concentration, seems to promote some microbes.
Some relevant studies..
[From Mitochondrial Function to Neuroprotection-an Emerging Role for Methylene Blue](https://pubmed.ncbi.nlm.nih.gov/28840449/)
- `MB can reroute electrons in the mitochondrial electron transfer chain directly from NADH to cytochrome c, increasing the activity of complex IV and effectively promoting mitochondrial activity while mitigating oxidative stress`
[Methylene blue improves mitochondrial respiration and decreases oxidative stress in a substrate-dependent manner in diabetic rat hearts](https://pubmed.ncbi.nlm.nih.gov/28738167/)
- `methylene blue elicited a significant increase in H2O2 release in the presence of complex I substrates (glutamate and malate), but had an opposite effect in mitochondria energized with complex II substrate (succinate)`
FEBS Press
- MBH2 donates electrons to complex IV. This is particular useful in some cases where complex I and complex II are impaired (which can occur with hydrazine and efavirenz Bypassing the compromised mitochondrial electron transport with methylene blue alleviates efavirenz/isoniazid-induced oxidant stress and mitochondria-mediated cell death in mouse hepatocytes)
[Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue](https://pubmed.ncbi.nlm.nih.gov/22067440/)
`MB hormesis can be explained by the pharmacokinetics of MB in mitochondria, which is determined by the mitochondrial membrane potential and the relative local concentration of MB. Higher membrane potentials induce higher MB accumulation (i.e. binding to mitochondrial proteins) which in turn promotes higher MB aggregation (i.e. dimerization of MB molecules). However, MB aggregation is also affected by the proportion of MB molecules to binding sites, with less aggregation at very high, and very low binding site concentrations. Production of radicals has been shown to increase in the presence of MB monomers and be minimal in the presence of MB dimers [[@{:mb_dimers}@{[gabrielli2004.pdf]}]] (Gabrielli et al., 2004). Thus, in the presence of an optimal mitochondrial membrane potential, low MB concentrations favor dimerization and reduction, whereas high concentrations promote oxidation and reaction with endogenous electron donors such as nicotine adenine dinucleotide (NADH) and nicotine adenine dinucleotide phosphate (NADPH). Therefore, it is expected that low MB doses or concentrations will be, in general, more effective than large ones at facilitating physiological effects within mitochondria. In fact, at high local concentrations, MB can potentially “steal” electrons away from the electron transport chain complexes, disrupting the redox balance and acting as a pro-oxidant (Vutskits et al., 2008). Consistent with this, cell cultures exposed to high (micromolar range) but not to low (nanomolar range) concentrations of MB induce high levels of oxidants, and show a compensatory up regulation of antioxidant enzymes with decreased heme expression and iron uptake by 50% (Atamna et al., 2008). Several detrimental effects of MB on neural structure or function have been reported in vivo, including humans. These effects have been associated with administration of large doses of the compound, contact with connective tissue or concomitant use of psychotropic drugs (Arieff and Pyzik, 1960; Poppers et al., 1970; Blass and Fung, 1976; Martindale and Stedeford, 2003; Sweet and Standiford, 2007; Vutskits et al., 2008).`
LOL here I am doing sort of the same thing...
