please don't flame me! I am just going to present a thought I suddenly had (and admittedly one on which I did only superficial research). What if we conjured up a medicine that would inhibit an enzyme that is critical for muscle breakdown? Then in the fasted state the body would use more fatty acid oxidation to obtain energy. Granted, we'd be hungrier, but stronger as well. Any ideas? I'm sure this idea has been considered before and there's a detailed resolution out there.
just a thought but ..
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Um, your body doesn't usually use your muscles for energy. It does prefer fat.
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Yea I am pretty sure besides your brain...muscle is the last resort the body will use for energy. My $.02 would be that those enzymes aren't just used when your starving but also during muscle building and remodeling.
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ETC uncouplers are pretty good at dissipating metabolic energy. Just don't wear a sweater...
http://www3.interscience.wiley.com/journal/120750652/abstract?CRETRY=1&SRETRY=0
http://www3.interscience.wiley.com/journal/120750652/abstract?CRETRY=1&SRETRY=0
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What he said . . . .
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I loled at this
I think it would probably be abused by bodybuilders trying to get cut without losing muscle mass. It would clinically be useful for weight loss in general though particularly during the first few days of a diet when the body is using gluconeogenesis more often before it switches to relying more heavily on fatty acids for most tissues and ketone bodies for the nervous system...
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From Lippincott's Biochem review:
"During the first few days of fasting, there is a rapid breakdown of
muscle protein, providing amino acids that are used by the liver for
gluconeogenesis (see Figure 24.14, 0). [Note: Alanine and glutamine
are quantitatively the most important gluconeogenic amino
acids released from muscle.] After several weeks of fasting, the rate
of muscle proteolysis decreases because there is a decline in the
need for glucose as a fuel for brain, which has begun using ketone
bodies as a source of energy."
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The OP asked about the fasting state, in which case your body does usually use muscle proteins for energy.
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It still wouldn't fix the real problem, which is what happens once you stop fasting.
If it were really getting rid of the fat that were the problem, lipo would have taken over the world.
I think dentists should invent a retainer that makes it really annoying to chew and swallow, and can't be removed by the pt, so that we could do something less extreme than gastric bypass.
If it were really getting rid of the fat that were the problem, lipo would have taken over the world.
I think dentists should invent a retainer that makes it really annoying to chew and swallow, and can't be removed by the pt, so that we could do something less extreme than gastric bypass.
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Agreed. Or being able to take a month off of training without losing any ground. You'd no longer see all those football players show up to training camp out of shape from the winter.
thanks scotty for these interesting references.
As to the other posters who thought muscle isn't involved in energy production, I'm pretty sure that muscle is a major source of energy (along with TGs from adipose tissue) in the fasted state.
I think ETC uncouplers would be a bad idea, and the fact that 2,4-dinitrophenol is a toxin corroborates my suggestion. DNP is an ETC uncoupler, so that complex V won't work even though complexes I-IV continue. The result is that you don't produce ATP even though you re-oxidize NADH and continue the TCA cycle. You will probably die. Even if you inject the uncoupler into the muscle directly, you won't be able to produce the ATP to for muscle fiber movement (by kinesin?). So, it'll paralyze the target tissue.
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Isoprop, is that what I think your avatar is?
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You wouldn't be any stronger though, which was the OP's other comment. I missed the fasting state comment though in the first post.
DNP is only fatal in large doses, it use to be sold as a weight loss supplement until people started thinking more is better. Some BBs still use it as a quick way to lose fat but from what I've heard it's a pretty awful experience and there are better alternatives. And ya'll call ATP synthase complex V? I've never heard it called that.
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insulin growth factor 1. google search it. its currently for sale as a workout "supplement". activates satellite cells to stimulate muscle growth.
hey thanks for pointing that out to me. I also feel that a high protein diet could really help because it would act as an alternative source of substrate (a competitive inhibitor, if you will, in the sense that a diet-derived amino acid competes for a muscle-derived amino acid to bind the active site of some enzyme) for the enzymes that utilize broken down amino acids (e.g. urea production, TCA cycle anaplerotic reactions, etc.). If the body is getting its amino acids from another source (diet), then muscle breakdown probably would slow. I know this sounds really obvious, but the notion of dietary glutamate as a competitive inhibitor of, say, glutamate dehydrogenase, is not (to me, at least 😳). Maybe this is why L-glutamine, which breaks down to form L-glutamate, is commercially sold as a product for body-builders.
For the record, I think ATP synthase is a commonly used term, but I personally prefer complex V.
mmmcdowe
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Maybe I'm wrong, but isn't muscle in a state of break down and recreation like bone is? If this is true, then it would seem to me that even if you weren't fasting you might get some moderate muscle build up by using inhibitors. I, for one, would be nervous about using that. The body breaks down muscle for a reason, I'd rather not interfere too much!
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I realize your question is in regards to the fasting state, but if you want to target weight loss, wouldn't it make more sense to market a drug that applies to people who are overweight? I don't think most of them even get to the fasting state--that takes days!
My understanding is that your body uses the following as it's primary energy source, in order:
carbs
fat
protein
ketones (or something like that)
So, if your goal is to burn fat, wouldn't you want to prevent the burning of carbs, not protein? The Atkins diet isn't healthy, because you still need carbs (otherwise you'd be severely dehydrated and have no good, quick back-up fuel); you just don't want to burn them.
So I like your idea, but I'd target it to an enzyme in carbohydrate metabolism if I were designing it, forcing the body to use fats instead. I guess a side effect could be burning muscle once you got through most of your fat, or screwing around with cell membranes since you're depleting the body of phospholipids and cholesterol.
My understanding is that your body uses the following as it's primary energy source, in order:
carbs
fat
protein
ketones (or something like that)
So, if your goal is to burn fat, wouldn't you want to prevent the burning of carbs, not protein? The Atkins diet isn't healthy, because you still need carbs (otherwise you'd be severely dehydrated and have no good, quick back-up fuel); you just don't want to burn them.
So I like your idea, but I'd target it to an enzyme in carbohydrate metabolism if I were designing it, forcing the body to use fats instead. I guess a side effect could be burning muscle once you got through most of your fat, or screwing around with cell membranes since you're depleting the body of phospholipids and cholesterol.
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Fasting is defined as 12 hours of not eating.
Best way to burn fat is doing cardio exercise.
i'd like to point out to Dr. Bubbles that I'm looking for a way to strengthen muscle using medicine (and obviously a combination of a healthy diet and exercise). I agree to Dr. Chad's comment regarding burning fat: cardio exercise is the way to go because it forces you to enter the fasting state more quickly.
Also, you won't starve in the fasting state, you'll starve in the starvation state, which occurs when you begin to starve (~2-3 days after last intake).
and mmmcdowe, when you get to medical school (or perhaps before, if you like to read ahead) you'll learn all about how and why the body breaks down the energy fuels it does. You'll also come to realize that muscle breakdown isn't a necessity for energy as there are multiple alternative routes to provide you the energy you need, including eating. For instance, individuals who lack myostantin actually live amazingly healthy lives (ex. story of the five year old who can do the iron cross already wtf?).
i appreciate everyone's thoughtful replies and interesting reference links. You all make this place a valuable resource to push the envelope of knowledge!
Also, you won't starve in the fasting state, you'll starve in the starvation state, which occurs when you begin to starve (~2-3 days after last intake).
and mmmcdowe, when you get to medical school (or perhaps before, if you like to read ahead) you'll learn all about how and why the body breaks down the energy fuels it does. You'll also come to realize that muscle breakdown isn't a necessity for energy as there are multiple alternative routes to provide you the energy you need, including eating. For instance, individuals who lack myostantin actually live amazingly healthy lives (ex. story of the five year old who can do the iron cross already wtf?).
i appreciate everyone's thoughtful replies and interesting reference links. You all make this place a valuable resource to push the envelope of knowledge!
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I apologize--I misunderstood your ultimate goal for this pharm agent. Also, I did confuse fasting with starvation. Even in this light, I still feel like to fat-burn in the fasting state, you still have to fast for 12 hours. I did that last year during a research project--it sucked. I can't imagine how people who overeat are going to get there.
But, since the idea here is to not breakdown muscle mass, there are certainly some wonderful ideas posted. Best of luck!
But, since the idea here is to not breakdown muscle mass, there are certainly some wonderful ideas posted. Best of luck!
it's really very simple to arrive at the fasting state .. just go to sleep after eating dinner .. often you wake up in the fasted state, hence the commonly used phrase "overnight fast." A lot of our problems we dealt with were the changes in glucagon/insulin in an overnight fast, etc. etc.
