Reader Mallory has asked some questions, which I will use as a framework for talking about the metabolic need for carbohydrates.
In response to "what are the Triglyceride/fatty acid/Krebs cycle and the Randle cycle and can you comment on Taubes description of these in GCBC?"
For starters, the triglyceride/ fatty acid cycle (not really a metabolic cycle in the sense of metabolism of substrates, just a feedback mechanism really) as described by Taubes has nothing whatever to do with the Krebs cycle. That is just his term for the equilibrium between esterification and lipolysis and the transport of Triglycerides back to adipocytes from the liver.
The Kreb's cycle is totally different, occurring inside mitochondria and is the keystone of aerobic respiration. That is what you are using when you burn fat or glucose aerobically and amino acids and ketone bodies can feed into it as well. The Kreb's cycle is very efficient, and is employed as long as there are enough substrates and oxygen available in most circumstances. It is not determined by diet, really, it is like your furnace if you live in wisconsin in the winter. It is always on to some degree when it has substrates in a functioning cell with mitochondria.
The Randle cycle also is not really a cycle of metabolic substrates the way the TCA or Krebs cycle is. The Randle cycle is just mutual feedback between glucose and NEFA (non-esterified fatty acids) or ffa (free fatty acids, same thing) that determines which is the predominant energy substrate. When glucose in the blood is high, glucose is the preferred energy substrate and glycerol phosphate, a metabolite of glucose, rises in the cell. This is the backbone of triglyceride (fat) and fat storage is thereby stimulated and lipolysis inhibited. Glycolysis is stimulated so more glucose can be burned (Usually in the Kreb's cycle)
(Important: note that inhibited does not mean stopped! It means the balance is towards fat storage but there is always lioplysis and esterification happening at the same time! Think of patrons passing by a crowded bar. Some enter and some leave. The change over time in the number of patrons in the bar is determined by the net difference between those leaving and those entering over time. That's integral calculus, basically. The point is, you don't have to stop people from leaving to get a bigger crowd, just shift the balance so more come in than go. )
Conversely, when NEFAs are high, the balance between lipolysis and esterification is shifted so there is net release of NEFA for use a substrate (usually burned in the Kreb's cycle again) and glycolysis is inhibited (again, not stopped, but inhibited) Part of this mutual feedback is being mediated by insulin, which is responding to glucose levels, among other things.
So the Randle cycle is just the mechanism whereby your body "knows" how to shift fuel sources based on fuel availability. Makes sense, as multicellular life was founded first on metabolism of glucose. The ability to store and burn fat (much more efficient than glucose) evolved later. You need mitochondria to bun fat. Almost any living cell can burn glucose, with our without mitochondria. It makes perfect sense that we are evolved to be able to use either glucose or fat for fuel.
PaNu dogma is that we are healthier when spending more time in fat-burning mode. This dogma does not, however require us to fantasize that we are somehow unable to metabolize glucose or that glucose is useless as an internal fuel source. It is adaptative that humans can survive well for long periods, especially when calorie restricted, with carbohydrate as the predominant fuel source. It is entirely consistent that fatty acids are the best fuel when available for most processes, but that glucose remains a backup fuel both on a dietary and internal metabolic basis. How long would our ancestors have survived if they were unable to eat plants?
Let's stipulate that there is no absolute dietary need for carbohydrate. Is there a metabolic need?
Definitely.
As most of you know, fatty acids cannot cross the blood/brain barrier. Neurons can shift about half their metabolism to ketone bodies, but still require a gradient of glucose that can diffuse into the brain. If your blood glucose level drops too low, you are in a coma. Also, red blood cells require glucose.
Finally, apart from these special situations, there is another very significant situation in which it makes perfect sense that we have retained the ability to burn glucose generally.
That is called anaerobic glycolysis.
When you need to perform a lot of work very quickly, like running from a predator, or spending twenty minutes lifting weights, you are not burning fatty acids. Aerobic glycolysis and lipolysis are very efficient but too slow for very high intensity tasks.
Any time you need high intensity work done by muscles faster than can be accommodated by aerobic respiration, you are absolutely, positively, using glucose for anaerobic glycolysis.
I don't care if you have not eaten of the plant world in eons, that is what is happening.
The question was asked: "does low insulin keep muscles from burning glucose"
For as long as there is aerobic work, with low insulin levels, fatty acids will be preferred. However, the instant anaerobic work is done, you are absolutely using glucose to do it because you cannot burn NEFAs anaerobically. If I lift weights or sprint on a 15 hour fast, my insulin levels are very low, yet I can instantaneously burn glucose anaerobically.
How about: "When insulin is low the liver does not give up the glucose."
Generally False. It's just the opposite. When fasting or just between meals, you are constantly burning a small amount of glucose in your brain (hopefully) and you need to constantly maintain your serum BG level. If you did not replenish your serum BG from somewhere, it would drop to dangerous levels. In order to make up for the glucose consumed, and in response to falling glucose, hormones like glucagon and epinephrine are released, which promote gycolysis of liver glycogen, which is then released into the blood.
Good thing, too, or I would quickly be in a coma with my daily 15 hour fasts.
Finally, I need to make sure everyone understands what is happening with glycogen in the liver if you eat no carbohydrates (or less than replacement levels, like I often do on VLC) .
It is still there. Really. You have lots of glycogen stored in your liver as the glucose storage depot to keep your blood glucose stable. If you don't eat enough carbohydrate, this is where gluconeogenisis comes in. GNG is induced when your liver glycogen has been depleted to a certain critical level. As discussed in my previous post, amino acids will be used to make new glucose (hence, gluco- neo-genesis) and the glycogen will be restocked.
The big difference between VLC and high carb eaters is in the turnover of liver glycogen. Th high carb eater is using it as his main fuel, so his "gas tank" is being both filled and emptied simultaneously at a higher rate.
Everyone has glycogen in their liver, and everyone uses it.
The Final Question asked: "Is excess protein just peed out?"
No. Unless your kidneys are diseased, there are no protein or amino acids in your urine. Excess protein not used for new protein synthesis may be burned (efficiently or inefficiently) or stored as fat. If metabolised, urea shows up in the urine as a byproduct, but amino acids are not just spilling out like your body doesn't know what to do with them.
To repeat from my prior post, there is no particular fate for any macronutrient in your diet, and any excess substrate with caloric value can be stored as fat or burned. If you can eat excess protein or fat or for that matter carbohydrate and not gain weight, that is only proving that your diet has not deviated from favorable insulin levels, your caloric intake is low, or whatever. It is not because that macronutrient "can't be" turned into fat.
Reader Mallory has asked some questions, which I will use as a framework for talking about the metabolic need for carbohydrates.
In response to "what are the Triglyceride/fatty acid/Krebs cycle and the Randle cycle and can you comment on Taubes description of these in GCBC?"
For starters, the triglyceride/ fatty acid cycle (not really a metabolic cycle in the sense of metabolism of substrates, just a feedback mechanism really) as described by Taubes has nothing whatever to do with the Krebs cycle. That is just his term for the equilibrium between esterification and lipolysis and the transport of Triglycerides back to adipocytes from the liver.
The Kreb's cycle is totally different, occurring inside mitochondria and is the keystone of aerobic respiration. That is what you are using when you burn fat or glucose aerobically and amino acids and ketone bodies can feed into it as well. The Kreb's cycle is very efficient, and is employed as long as there are enough substrates and oxygen available in most circumstances. It is not determined by diet, really, it is like your furnace if you live in wisconsin in the winter. It is always on to some degree when it has substrates in a functioning cell with mitochondria.
The Randle cycle also is not really a cycle of metabolic substrates the way the TCA or Krebs cycle is. The Randle cycle is just mutual feedback between glucose and NEFA (non-esterified fatty acids) or ffa (free fatty acids, same thing) that determines which is the predominant energy substrate. When glucose in the blood is high, glucose is the preferred energy substrate and glycerol phosphate, a metabolite of glucose, rises in the cell. This is the backbone of triglyceride (fat) and fat storage is thereby stimulated and lipolysis inhibited. Glycolysis is stimulated so more glucose can be burned (Usually in the Kreb's cycle)
(Important: note that inhibited does not mean stopped! It means the balance is towards fat storage but there is always lioplysis and esterification happening at the same time! Think of patrons passing by a crowded bar. Some enter and some leave. The change over time in the number of patrons in the bar is determined by the net difference between those leaving and those entering over time. That's integral calculus, basically. The point is, you don't have to stop people from leaving to get a bigger crowd, just shift the balance so more come in than go. )
Conversely, when NEFAs are high, the balance between lipolysis and esterification is shifted so there is net release of NEFA for use a substrate (usually burned in the Kreb's cycle again) and glycolysis is inhibited (again, not stopped, but inhibited) Part of this mutual feedback is being mediated by insulin, which is responding to glucose levels, among other things.
So the Randle cycle is just the mechanism whereby your body "knows" how to shift fuel sources based on fuel availability. Makes sense, as multicellular life was founded first on metabolism of glucose. The ability to store and burn fat (much more efficient than glucose) evolved later. You need mitochondria to bun fat. Almost any living cell can burn glucose, with our without mitochondria. It makes perfect sense that we are evolved to be able to use either glucose or fat for fuel.
PaNu dogma is that we are healthier when spending more time in fat-burning mode. This dogma does not, however require us to fantasize that we are somehow unable to metabolize glucose or that glucose is useless as an internal fuel source. It is adaptative that humans can survive well for long periods, especially when calorie restricted, with carbohydrate as the predominant fuel source. It is entirely consistent that fatty acids are the best fuel when available for most processes, but that glucose remains a backup fuel both on a dietary and internal metabolic basis. How long would our ancestors have survived if they were unable to eat plants?
Let's stipulate that there is no absolute dietary need for carbohydrate. Is there a metabolic need?
Definitely.
As most of you know, fatty acids cannot cross the blood/brain barrier. Neurons can shift about half their metabolism to ketone bodies, but still require a gradient of glucose that can diffuse into the brain. If your blood glucose level drops too low, you are in a coma. Also, red blood cells require glucose.
Finally, apart from these special situations, there is another very significant situation in which it makes perfect sense that we have retained the ability to burn glucose generally.
That is called anaerobic glycolysis.
When you need to perform a lot of work very quickly, like running from a predator, or spending twenty minutes lifting weights, you are not burning fatty acids. Aerobic glycolysis and lipolysis are very efficient but too slow for very high intensity tasks.
Any time you need high intensity work done by muscles faster than can be accommodated by aerobic respiration, you are absolutely, positively, using glucose for anaerobic glycolysis.
I don't care if you have not eaten of the plant world in eons, that is what is happening.
The question was asked: "does low insulin keep muscles from burning glucose"
For as long as there is aerobic work, with low insulin levels, fatty acids will be preferred. However, the instant anaerobic work is done, you are absolutely using glucose to do it because you cannot burn NEFAs anaerobically. If I lift weights or sprint on a 15 hour fast, my insulin levels are very low, yet I can instantaneously burn glucose anaerobically.
How about: "When insulin is low the liver does not give up the glucose."
Generally False. It's just the opposite. When fasting or just between meals, you are constantly burning a small amount of glucose in your brain (hopefully) and you need to constantly maintain your serum BG level. If you did not replenish your serum BG from somewhere, it would drop to dangerous levels. In order to make up for the glucose consumed, and in response to falling glucose, hormones like glucagon and epinephrine are released, which promote gycolysis of liver glycogen, which is then released into the blood.
Good thing, too, or I would quickly be in a coma with my daily 15 hour fasts.
Finally, I need to make sure everyone understands what is happening with glycogen in the liver if you eat no carbohydrates (or less than replacement levels, like I often do on VLC) .
It is still there. Really. You have lots of glycogen stored in your liver as the glucose storage depot to keep your blood glucose stable. If you don't eat enough carbohydrate, this is where gluconeogenisis comes in. GNG is induced when your liver glycogen has been depleted to a certain critical level. As discussed in my previous post, amino acids will be used to make new glucose (hence, gluco- neo-genesis) and the glycogen will be restocked.
The big difference between VLC and high carb eaters is in the turnover of liver glycogen. Th high carb eater is using it as his main fuel, so his "gas tank" is being both filled and emptied simultaneously at a higher rate.
Everyone has glycogen in their liver, and everyone uses it.
The Final Question asked: "Is excess protein just peed out?"
No. Unless your kidneys are diseased, there are no protein or amino acids in your urine. Excess protein not used for new protein synthesis may be burned (efficiently or inefficiently) or stored as fat. If metabolised, urea shows up in the urine as a byproduct, but amino acids are not just spilling out like your body doesn't know what to do with them.
To repeat from my prior post, there is no particular fate for any macronutrient in your diet, and any excess substrate with caloric value can be stored as fat or burned. If you can eat excess protein or fat or for that matter carbohydrate and not gain weight, that is only proving that your diet has not deviated from favorable insulin levels, your caloric intake is low, or whatever. It is not because that macronutrient "can't be" turned into fat.