National Institute on Aging, a federal government agency, has been doing CR and CR with 2DG (a CR mimetic) study for well over a dozen years. The findings are consistently positive relating to health and life expansion.
The 2DG function:
2-deoxy-d-glucose is a glucose that do not generate ATP, like the usual glucose converted from food intake, therefore reducing the calorie generation.
In other words, when one eats potato chip, the label on the bag says 4 servings at 200 calories each. One of course eats the whole bag, which is 800 calories.
When a certain quantity of 2DG is taken along with the bag of potato chips, a portion of the 800 calories is not generated, therefore say only 200 or 400 calories are generated, thereby creating CR effect.
The other benefit is in CRON itself - Caloric Restriction with Optimal Nutrition. A real CR diet will limit the food intake, depriving the body of the nutrients that come with the food. With 2DG supplement, one eat normally, absorbing all the nutrients in the food (the whole bag of chips instead of 1/4 of the bag) while only retard the generating of calorie.
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However, 2DG proves to be toxic in large dosage, therefore unfit for human consumption.
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My question is, is there anyway, a non-toxic 2DG can be made, since it has so many benefits and seems to be the only wholesome candidate for CR effect (glucophage seems to be of some CR benefits, too but it is a drug which may have side effects).
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cj123: National Institute on Aging, a federal government agency, has been doing CR and CR with 2DG (a CR mimetic) study for well over a dozen years. The findings are consistently positive relating to health and life expansion.
Umm ... except for that minor issue of killing the little bastards ...
Regrettably, however, 2DG has a fatal flaw preventing it from being the 'magic pill' we were hoping for. Though safe at certain low levels, it apparently becomes toxic for some animals when the amount delivered is raised just a bit or given over long periods. The narrowness of the safety zone separating helpful and toxic doses would bar it from human use. We hope this is not a general feature of CR mimetics.
Ingram confirmed that 2DG was toxic in the long term even at low doses at IABG 10:
... and also in personal communication with me.
cj123: The 2DG function: 2-deoxy-d-glucose is a glucose that do not generate ATP, like the usual glucose converted from food intake, therefore reducing the calorie generation. In other words, when one eats potato chip, the label on the bag says 4 servings at 200 calories each. One of course eats the whole bag, which is 800 calories. When a certain quantity of 2DG is taken along with the bag of potato chips, a portion of the 800 calories is not generated, therefore say only 200 or 400 calories are generated, thereby creating CR effect. The other benefit is in CRON itself - Caloric Restriction with Optimal Nutrition. A real CR diet will limit the food intake, depriving the body of the nutrients that come with the food. With 2DG supplement, one eat normally, absorbing all the nutrients in the food (the whole bag of chips instead of 1/4 of the bag) while only retard the generating of calorie.
No, that is not what it does. 2DG does not block nutrient absorption, but throws a wrench in glycolysis, 'starving' the cell for fuel even as you digest all of your food. Again from the _Scientific American_ piece:
The compound structurally resembles glucose, so it enters cells readily. It is also altered by an enzyme that usually acts on glucose itself. But the enzyme that completes the next of several steps involved in glucose processing essentially chokes on the intermediate produced from 2DG. When it tries to act on this intermediate, it fails; in addition, its ability to act on the normal glucose intermediate becomes impaired.
The net result is that cells make smaller amounts of glucose's by-products, just as occurs when caloric restriction limits the amount of glucose going into cells. Certain of these products serve as the raw material for the ATP-making machinery ... in ... mitochondria. Deprived of this raw material, the machinery makes less ATP. In essence, 2DG tricks the cell into a metabolic state similar to that seen during caloric restriction, even though the body is taking in normal amounts of food. As long as the amount of ATP made meets the minimum requirements of cells, this diminished operation of the ATP-making machinery is apparently beneficial.
Why might reduced functioning of the ATP-producing machinery help combat aging? We can't say with certainty, but we have some ideas. A long-standing theory of aging blames the production of molecules called free radicals. The lion's share of free radicals in the body are emitted as the ATP-making machinery operates. ... Perhaps by reducing the rate of ATP production, 2DG and caloric restriction slow the rate at which free radicals form and disrupt cells.
The lack of glucose's by-products might retard aging in another way as well. Certain of those substances help to induce cells in the pancreas to secrete insulin after an organism eats. Reductions in the amount of those by-products would presumably limit insulin secretion and thereby minimize insulin's unwanted actions in the body. Aside from indirectly promoting excessive operation of the ATP-making machinery and thus boosting free-radical production, insulin can contribute to heart disease and to undesirable cell proliferation.
We also suspect that cells interpret reduced levels of raw materials for the ATP-making machinery as a signal that food supplies are scarce. Cells may well respond to that message by switching to a self-protective mode, inhibiting activities not needed for cell maintenance and repair -- such as reproduction -- and pouring most of their energy into preserving the integrity of their parts. ... This adoption of a self-preservation mode would mirror changes that have been proposed to occur on an organismic level in times of food scarcity.
cj123: However, 2DG proves to be toxic in large dosage, therefore unfit for human consumption.
Ingram confirmed that 2DG was toxic in the long term even at low doses at IABG 10:
... and also in personal communication with me. CF the op cit quote from _Sci Am_ above: 'it apparently becomes toxic for some animals when the amount delivered is raised just a bit *or given over long periods.*'
cj123: My question is, is there anyway, a non-toxic 2DG can be made, since it has so many benefits and seems to be the only wholesome candidate for CR effect (glucophage seems to be of some CR benefits, too but it is a drug which may have side effects). ========
shpongled: Artificial sweeteners. None of them are completely safe, but better than your health than a lot of sugar.
As should be clear at this point, that isn't the same thing at all, at all. I use sucralose (an artificial sweetener: 'splenda' is sucralose 'cut' with maltodextrin and filler) to make assorted CR goodies, such as Sherm's Bingeing Brownies:
... without adding heaps of empty Calories, which makes it IMO a good CR lifestyle tool. But that is quite different from an actual Luddite attack on the glycolytic machinery using 2DG as a 'sabot.'
Anyway, 'cj123's' opinion is apparently 'yes, there a way that a non-toxic 2DG can be made,' since he has approached the CR society about selling it to us; see also his offer on sci.life-extension:
cj123: our team on the project has successfully re-engineered the production process and now we have a completely safe non-toxic 2DG, which we call P-2DG. All 60 mice survived and living well after being administered up to 10g/kg via I.G., and 2g/kg via I.V. The acute toxicity study is done by a third party university lab.
If you are interested to learn more, let me know.
This is nonsense. I have seen these peoples' study: it only covers acute toxicity -- one big dose. Useless! There was no acute toxicity to 2DG in Ingram's or Mattson's studies either: that's why they were able t put out glowing reports on the stuff for years, until a lifespan study finally fell apart under the influence of subtle, long-term toxicity.
Contrary to what he seems to think, it is totally implausible that the problem with the 2DG was a contaminant. If it were otherwise, Ingram et al -- who were at one time very hot on the stuff, & tried both higher and lower doses which were not acutely toxic -- would've secured a pharma-grade source instead of reagent-grade material.
It's an effect of 2DG itself. You can't (apparently) keep putting the stuff into the cell and keep only partially metabolizing the stuff via glycolysis forever: perhaps a breakdown product is subtly toxic, or perhaps some negative long-term effect on the glycolytic machinery occurs.
cj123: It is a dietary supplement produced from organic matter.
Oh, it’s a DIETARY SUPPLEMENT! And it’s produced from 'ORGANIC MATTER'! Well, then, it MUST be safe.
He's a charlatan and would apparently gladly poison us to make a quick buck.
Scientific facts are to be discussed and learned. Pre-emptive strike sometimes doesn't work. If one is not patient enough to discuss, how can he learn. If he doesn't learn, or only choose selectively what he wants to learn, like you limit your food to potato chips only, how can you know that potato can be fried, baked, or even served smashed?
When one thinks he knows everything, he is ................
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