I knew the laser was way more powerful than sunlight, and I never said that retinas have no capacity to heal. Why do you think I wrote "Damage would probably be very slow to show up"? The indisputable facts are that
1. MB can generate ROS at nanomolar concentrations.
When hit with a powerful enough, proper wave length, light source - but not before then
. In fact, it's documented as an antioxidant under most cellular conditions. Like all antioxidants, too much of it becomes pro-oxidant. Here's yet another example of MB being a protector of neurons from oxidative damage
. Oh, and look, yet another example where MB attenuates super oxide production
. So no, MB is NOT a ROS producer at nanomolar levels without sufficient light energy stimulation, but a potent antioxidant. To reiterate once again: MB seems to be a pretty dang potent antioxidant within the ranges we're talking about using (100-1000nM) for mitochondria stimulation and increased brain function
, and even at the medicinal levels (which is 200 to 1000 times higher).
2. MB can generate ROS at solar intensities.
No. You have shown no proof of that, at all. I have seen no proof of that, at all. Rather, only counter proof. The crayfish paper used at least three times more energy than you can ever get from the sun (or they used 2,400 times that energy at MBs absorption spectrum according to Niner's calculation), even at noon at the equator, where sea level solar spectral energy maxes out at 137mW/cm^2. Now, the actual wavelengths that MB absorbs are the lowest energy wavelengths of visible light towards near infrared (590-690nm). And when MB was investigated directly with injections into the eyes of rabbits, at levels (in the eye, for all their doses) far beyond what you could get from taking 1mg a day, or even beyond at medical human dosages, they did not see any loss of retina function. There were signs of some toxicity at the higher dosages however.
3. Our antioxidant defenses and healing capacity are inadequate even without the added burden of MB, or else macular degeneration wouldn't be such a common problem.
Common problem? Age related macular degeneration is the highest cause leading to legal blindness with age, yes. However, it's estimated that only 10 percent of the population gets it over the age of 55, and up to 30 percent over the age of 75. The large majority of people do not get it. It would depend on what you classify as common if this is common or not. Furthermore, it is genetically caused predominately
, not related to oxidative stress (non-carriers of the risk gene only have a 22% chance of macular degeneration by age 95). So no, our antioxidant
systems are quite good enough for the vast majority of people.
It's reckless to quibble that the fraction of solar radiation that makes it into the eye might not cause MB to generate any ROS. Whatever happened to the principle of presumed guilty before proven innocent?
It is not reckless at all, but the very heart of the manner. MB isn't going to be generating ROS without sufficient light energy of the proper light spectrum getting to it - that is, it does not generate ANY ROS at all until it hits a certain light energy threshold, as a paper I already linked showed. That means that the proper amount of light has to filter through all the tissues and, if not directly entering the eye, bone. The only way to generate the highest amount of light energy onto the retina is by looking at a light source directly. This happens rarely (solar UV would do far more damage faster anyways), and we already have seen that actual sunlight doesn't carry the proper energy at all, even at high noon at the equator of the planet (where sunlight energy is its highest at sea level from anywhere on the planet).
On another note, MB can generate H2O2 ROS, but not super oxide, if you throw in a larger amount of it (mid micromols to low millimols), whereby it starts to interact with reductases
, far more specifically with malaria versions than human versions. But this is completely different than "photosensitization".
By the way, It is also possible to create a false dilemma by, and mascaraing as, being overly cautious.
An example. You said "our retinas are not prone to failure by any direct "sensitization" effect". That's exactly what lipofuscin does. You're obviously an intelligent person, so you're either not precisely conveying your ideas or are BSing us for some reason.
So far you haven't knocked down anything I said.
Erm, lipofuscin is a byproduct of the light reaction, not an exogenous "sensitizer" in the sense that we were talking about with MB.
To clarify, lipofuscin doesn't seem to directly absorb light and generate super oxide like MB can after a certain threshold. Rather, lipofuscin impairs the clearance and cycling of retinal
, and at the same time builds up retinyl palmitate that, once oxidized by light, becomes anhydroretinol, a signaling molecule which kicks on the apoptosis signaling cascade that then later goes on to generates ROS as part of its cascading signal
. That is, lipofuscin, generated by the normal vision cycle over time, acts to impair the recycling of vision cycle compounds (trans-retinal), and builds up photosensitive byproducts that become signalling molecules to induce apoptosis. This is different from MB directly generating ROS and being an exogenous factor, not a byproduct of the vision cycle.
So, I don't think these two are comparable at all. And what's more, is I said "not prone
to", not that it doesn't happen. Since around only 1/3rd of people ever get macular degeneration, and most of it is linked to certain genes, not "sensitization" for the generation of ROS and damage derived there in... I think I'm completely accurate in saying "not prone
to failure by any direct
On a personal note, I certainly haven't run around sounding pretentious and saying you are "BSing", even while proving some of your points unfounded and false.
Why are you assuming that we would have heard of a problem if it existed? Say you're a doctor and a MB-using patient of yours gets macular degeneration when he's old. Old people get that all the time. Why bother reporting it? It's best not to assume that absence of evidence is evidence of absence.
Even more interesting is those who take MB for genetic methylhemoglobinemia, they do have to take it over the long term. We don't hear of trouble with them, do we?
I believe that if their rates went up significantly, someone would have noticed that after all this time - as we've had plenty of time to notice such changed rates. Perhaps I just have more faith in medical and scientific observations. They got us this far, so far, after all.
Basically, what we have here is a finite risk for taking something that hasn't been documented to extend lifespan, or even square the curve. All I could find was this study on flies, which doesn't count because their antioxidant defenses suck.
I'm well aware of that study in flies, and they used a comparatively huge amount of MB, 1 mM in their food. Since the average person consumes around 4.7lb of food per day (according to the USDA
), or 2.13kg, to get 1mM (molality technically when dealing with dry weight, or mols per kg) of MB in the food would require consuming ~681mg. This is still lower than what the flies actually consumed, since a human eats less food per mass than a fly, and will have a much lower MB serum level even at this consumption. If you wanted 1mM in the blood, you'd need to take around 1.6 grams of MB, which is in line with the calculated LD 50 for MB.
MB only shows any signs of toxicity at calculated levels above 600mg in humans of standard weight (or about 10mg/kg - this is based on the rat data), and will get even more toxic as those levels rise. However, we're talking about a daily consumption of 1mg (or 0.01-0.02mg/kg!). That's, again, 200 to 1000 times LOWER than used in medicine over all these years. We've seen that any life enhancing effects, and even the brain and memory and learning enhancing effects, have to do with MB being in the correct proportion to cytochrome c. It's a narrow range between 10-1000nM, seeming to peak at 100nM (1mg for a standard person of my weight), non-existent at 10nM, and over halved by 1000nM. I highly doubt, with such minute amounts, that one has to worry about any of these dilemmas you are throwing out, since we are orders of magnitude below levels that have never been documented to cause them in the first place.
Common sense kinda prevails here. But if you can cough up the proof that can counter my proof (such as that MB is an antioxidant, not a ROS generator, in the nanomolar ranges outside of being properly energized by supra sunlight level red light) then of course I'll listen to it. But so far you've done no such thing.
Edited by geddarkstorm, 28 February 2009 - 12:28 AM.