Thermodynamics and the metabolic advantage
There are a lot of disagreeable jobs out there. Dealing with Anthony Colpo is one of them. Trying to make sense of thermodynamics is another. Whereas dealing with AC is kind of like the job pictured at the left – distasteful but fairly simple – delving into the workings of the laws of thermodynamics is intellectually challenging but far from easy. Problem is, it appears kind of easy, and everyone, it seems, fancies himself to be an expert. (How many people have we heard blather on about how a calorie is a calorie is a calorie, thinking they are accurately stating the 1st law of thermodynamics?) But the truth is that the more you study thermodynamics and the more you seem to learn, the less you really understand.
I’ve had a family medical emergency that’s been occupying my time for the past week so I haven’t really had the consolidated time I’ve needed to finish off Part II of the AC book critique, but I haven’t forgotten about it. I should have it up in a day or two.
Until then, I’ll give you a little thermodynamics to chew on so you, too, can see that it is far from simple.
A commenter wrote the following in response to Part I of the AC critique:
Dear Dr. Eades,
I read the Feinman-Fine second-law article you cited above with interest, but found a mistake in the Figure 2 plot and the corresponding text. I didn’t notice any erratum either.
The figures in section “Efficiency and thermogenesis” should add up to 1825.5 kcal effective yield and not to the 1848 kcal given.
They seem to have interchanged the thermogenesis percentages of CHO (7%) and lipids (2.5%) in their calculation. The error source was perhaps the order in which they list the numbers: first percentages for F, C, and P from Jequier’s review, and then the diet C:F:P = 55:30:15. Go figure.
Nevertheless, it doesn’t affect the main result about metabolic advantage, weakens it a bit, though.
This came in while I was in the throes of dealing with the family problems, so I didn’t take the time to go back, pull the paper, figure out what the commenter was talking about and put my two cents worth in. I simply posted it as it was.
Thankfully, Dr. Feinman saw it and wrote a response on another website. I asked for permission, which he gave, to put it up here.
1. The approach taken by many that the idea of metabolic advantage has to be consistent with thermodynamics is correct. However, one has to understand and apply thermodynamics correctly, especially as it is used in bioenergetics.
2. People who get involved in this discussion have not followed the approach in biochemistry texts and traditional bioenergetics but have not explained why that approach is wrong. In the traditional approach from bioenergetics, for example, one usually looks at the Gibbs Free Energy, G rather than the internal energy, E. (G includes the effect of entropy from the second law).
3. What Figure 1 of the paper shows is that metabolic advantage must exist between systems that rely to different degrees on gluconeogenesis. You learn this in biochemistry: it costs you 6 ATP to obtain glucose from GNG but, of course nothing if you start with glucose. So, there is a built in metabolic advantage. Not could be. Not debatable. It is there. Period. That is an absolute biochemical fact. So just as people thought metabolic advantage was excluded by the “laws” of thermodynamics (by which they meant the first law), “a calorie is a calorie” is excluded by the combined first and second law. (To try to use the first law in the absence of the second law is like, actually exactly like, using gravity without considering friction).
4. Now whether you measure it [the metabolic advantage] in any particular experiment, whether the effect is great, whether it is compensated for by other processes (in low fat diets you make fatty acids which costs many ATP although the net effect may be to increase fat storage) is a different question than whether it is there or whether you want to ignore it.
5. Most of the time, as in Leibel’s experiment with the hospital patient, there is calorie balance but Leibel’s group have also done experiments with catch-up fat where there is not energy balance. But, again, application of the theory is different than what the theory says must be true. We have made the point that thermodynamics predicts a difference between high and low carbohydrate diets. It when it is not found that has to be explained. (The explanation lies in the specific homeostatic mechanisms of biological systems, not in physical law).
6. I personally believe a) Volek’s studies show the effect because the level of experimental error necessary to account for differences would be too large and, more important b) given the potential benefit in palpable metabolic advantage it would be worthwhile to try to find the conditions in which it can be seen and that this would be time better spent than in trying to disprove it with incompletely understood thermodynamics.
7. The other reason for looking for how the theory could be seen in a real weight loss experiment, is that it occurs unambiguously in numerous other biological systems: hypo- or hyper-thyroid conditions, catch-up fat in humans and animal models, animal knock-out or over-expression experiments.
8. I generally don’t pull rank on anybody and I don’t know that there is special criteria for being a scientist but you do have to understand the difference between an effect that is absolutely dictated by physical science (e.g. general theory of relativity) and the difficulty in demonstrating it experimentally (waiting for a solar eclipse and winding up with unreadable photographic plates).
9. Along these lines, like most chemists (or maybe most everybody), I have always found thermodynamics difficult and I am willing to learn from anybody who has an insight. However…
10. I grew up in Brooklyn so I am capable of a dialogue in the style favored by Colpo and Lyle McDonald but I mostly outgrew it and don’t want to debate at that level.
11. Relevant ideas to ponder: I once challenged Colpo to give me a definition of the nutritional calorie (because this makes clear what the issue is), that is, not the definition of the physical calorie (raises a gram of water 1 degree C ) but what we mean when we say carbohydrate has 4 kcal/g. His answer suggested that he had undergone spontaneous combustion but anybody else can answer the question. The other question is that in bioenergetics we talk about calories as the free energy, G, which is a potential, analogous to gravitational potential. When you throw the boulder off the cliff its potential energy is converted to kinetic energy and then goes to zero when it hits the bottom. Where does the energy go? The delta G (energy of reaction) for hydrolysis of a peptide bond is about 2 kcal. When it reaches equilibrium (amino acids) the energy is zero. In other words, thermodynamics talks about dissipation of energy, not conservation. How is that possible? Where does the energy go? Hope this helps.
Richard David Feinman
Professor of Cell BiologyTher
SUNY Downstate Medical Center
As a bit of lagniappe, here is a short video Dr. Feinman created on thermodynamics and irreversibility:
Richard Nikoley over at Free the Animal posted his take on the latest Colpo meltdown. As a part of his post, Richard dug out and put up one of my responses to a commenter from a post I wrote a couple of years ago. I had completely forgotten about it, but since it applies to the situation discussed above, I’m reprinting the comment by Ryan and my response below. A hat tip to Richard for ferreting this out:
I have a question that may be related to this.
On several low carb forums right now, there is a debate going on about what happens to the extra fat calories if carbs are kept extra low so that insulin is kept low. Some say it will be stored as fat anyway, others say it will be burned as heat and still others say it will be excreted. One member even did near-zero carbs and very high fat for a week (4500 calories instead of a normal 2500, with an average of about 80-90 g of protein). He lost a pound off of his already lean physique.
So, where does that extra fat go? Is it excreted? The detractors say that fat is completely digested before reaching the colon but I am not sure. If it is excreted, could you go ultra high fat, zero carb for a week or so and get the same detox results as the cosmic pizza grease?
Your comment raises an interesting question. Where does all the excess energy go?
I’ve had a number of patients and countless letters from readers who have had the same experience. They consume a ton of fat, but don’t gain weight…or even, as with the guy you described, lose a little. Mostly the letters we get are from people who complain that they are following our diet to the letter, yet not losing weight. When we investigate, we find that in virtually every case these people are consuming huge numbers of calories as primarily fat. We always ask them if it doesn’t strike them as strange that they’re eating as much as they are, yet not gaining.
In order to lose weight, one must create a caloric deficit. This can be done in a number of ways. People can burn more calories by increasing exercise; they can eat fewer calories; or they can increase their metabolic rate. Or they can do any combination of the above.
Most people going on a low-carb diet decrease their caloric intake. A low-carb diet is satiating, so most people eat much less than they think they are eating even though the foods they’re consuming are pretty high in fat. Some people, however, can eat a whole lot on a low-carb diet, and, can in fact, eat so much that they don’t create the caloric deficit and don’t lose weight. But the interesting thing is that they don’t gain weight either. They pretty much stay the same. They are eating huge numbers of calories and not gaining, so where do the calories go?
First, I don’t think they go out in the bowel. If they did, people would have cosmic pizza grease stools whenever they ate a lot of fat over a period of time, and they don’t. And a number of studies have shown that increasing fat in the diet doesn’t increase fat in the stool.
Eating a very-low-carbohydrate diet ensures that insulin levels stay low. Unless insulin levels are up, it’s almost impossible to store fat in the fat cells. With high insulin levels fat travels into the fat cell; with low insulin levels fat travels out. So, it’s pretty safe to say that the fat isn’t stored. So what happens to it?
The body requires about 200 grams of glucose per day to function properly. About 70 grams of this glucose can be replaced by ketone bodies, leaving around 130 grams that the body has to come up with, which it does by converting protein to glucose and by using some of the glycerol backbone of the triglyceride molecule (the form in which fat is stored) for glucose. If one eats carbs, the carbs are absorbed as glucose and it doesn’t take much energy for the body to come up with its 200 gram requirement; if, however, one isn’t eating any carbohydrates, the body has to spend energy to convert the protein and trigylceride to glucose. That’s one reason that the caloric requirements go up on a low-carb diet.
The other reason is that the body increases futile cycling. What are futile cycles? Futile cycles are what give us our body temperature of 98.6 degrees. Futile cycles are just what the name implies: a cycle that requires energy yet accomplishes nothing. It operates much like you would if you took rocks from one pile and piled them in another, then took them from that pile and piled them back where they were to start with. A lot of work would have been expended with no net end result.
The body has many systems that can cycle this way, and all of them require energy. Look up the malate-aspartate shuttle; that’s one that often cycles futilely.
Another way the body dumps calories is through the inner mitochondrial membrane. This gets a little complicated, but I’ll try to simplify it as much as possible. The body doesn’t use fat or glucose directly as fuel. These substances can be thought of as crude oil. You can’t burn crude oil in your car, but you can burn gasoline. The crude oil is converted via the refining process into the gasoline you can burn. It’s the same with fat, protein and glucose–they must be converted into the ‘gasoline’ for the body, which is a substance called adenosine triphosphate (ATP). How does this conversion take place? That’s the complicated part.
ATP is made from adenosine diphosphate (ADP) in an enzymatic structure called ATP synthase, which is a sort of turbine-like structure that is driven by the electromotive force created by the osmotic and electrical difference between the two sides of the inner mitochondrial membrane. One one side of the membrane are many more protons than on the other side. The turbine-like ATP synthase spans the membrane, and as the protons rush through from the high proton side to the low proton side (much like water rushing through a turbine in a dam from the high-water side to the low-water side) the turbine converts ADP to ATP.
The energy required to get the protons heavily concentrated on one side so that they will rush through the turbine comes from the food we eat. Food is ultimately broken down to high-energy electrons. These electrons are released into a series of complex molecules along the inner mitochondrial membrane. Each complex passes the electrons to the next in line (much like a bucket brigade), and at each pass along the way, the electrons give off energy. This energy is used to pump protons across the membrane to create the membrane electromotive force that drives the turbines. The electrons are handed off from one complex to the other until at the end of the chain they are attached to oxygen to form water. (If one of these electrons being passed along the chain of complexes somehow escapes before it reaches the end, it becomes a free radical. This is where most free radicals come from.)
There are two parts to the whole process. The process of converting ADP to ATP is called phosphorylation and the process of the electrons ultimately attaching to oxygen is called oxidation. The combined process is called oxidative phosphorylation. It is referred to as ‘uncoupling’ when, for whatever reason, the oxidation process doesn’t lead to the phosphorylation process. Anything that causes this uncoupling is called an ‘uncoupling agent.’
You can see that the whole process requires some means of regulation. If not, then the electromotive force (called the protonmotive force, since it’s an unequal concentration of protons causing the force) can build up to too great a level. If one overconsumes food and doesn’t need the ATP, then the protonmotive force would build up and not be discharged through the turbines because the body doesn’t need the ATP. The body has accounted for this problem with pores through the inner mitochondrial membrane where protons can drift through as the concentration builds too high and by proteins called uncoupling proteins that actually pump the protons back across. So we expend food energy to pump protons one way, then more energy to pump them back.
One of the things that happens on a high fat diet is that the body makes more uncoupling proteins. So, with carbs low and fat high, the body compensates, not by ditching fat in the stool, but by increasing futile cycling and by increasing the numbers of uncoupling proteins and even increasing the porosity of the inner mitochondrial membrane so that the protons that required energy to be moved across the membrane are then moved back. So, ultimately, just like the rocks in my example above, the protons are taken from one pile and moved to another then moved back to the original pile, requiring a lot of energy expenditure with nothing really accomplished.
This is probably all as clear as mud, but it is what happens to the excess calories on a low-carb, high-fat diet.