More response to my Gallon of Gas analogy to Calories Post ~ David Pendergrass PhD.

I was pleasantly surprised to receive a comment on my recent post -- More on Calories: A Gallon of Gas is NOT A Gallon of Gas? ... And Other Silly Thermodenyic Arguments -- from David Pendergrass, PhD.  Pendergrass has been a speaker at AHS, and last year his talk was:

The Physiology and Biochemistry of the Paleolithic Diet for Weight Reduction:  The physiology and biochemistry interactions of an individual using Paleolithic nutrition will be compared to an individual on the USDA recommended diet to demonstrate why Paleolithic Nutrition results in a success weight loss.

Bio: Director of Applied Science at the University of Kansas. He conducts a yearly seminar on appetite regulation. He is the author of the Smartest Loser program. He founded the Paleo Nutrition Foundation and a Paleo Nutrition Certification program online. 

Unfortunately, there does not appear to be a bootleg audio available for this presentation.   It's interesting, to me anyway, to get an idea of where the person I'm speaking with is "coming from".  As his book is no longer available on Amazon, there is no description beyond the title, nor a date of publication, there's nothing more to be had there.  As blogged on extensively here, I would find any discussion about some special physiological and/or biochemical interactions with "paleo nutrition" suspect as we'd have to clearly define what is meant by this.  As Pendergrass is defending fellow AHS speaker and low carb zealot (not normally comfortable with such words, but I do believe that is apt), and as he used the word *paradigm* in referring to CICO, I think it is safe to presume Pendergrass favors a VLC version of paleo.  Whether he is more in line with vintage Eaton, Konner, Cordain, DeVany, and Wolf's mass-media distributed diet books, and/or whether the fat content favors the low-to-very-low saturated fat content of Lindeberg, Ryberg, Frassetto, O'Dea, Jonnson, etc., is unknown.  Perhaps there is some information out there or Pendergrass has made his presentation available somewhere online.  (It is my understanding that AV issues occurred at AHS13 and the presentations were not of suitable quality to share.)

I am going to put Pendergrass' comment indented in dark blue and intersperse my responses in regular font.  Some find this changes the interpretation of the full comment, and if you are one of those people, by all means I encourage you to read his comment in full before proceeding.  Pendergrass begins his post by quoting from mine, beginning at "This does not change depending ..." in the screenshot below.

Dear Carb-Sane Asylum,

Please call me Evelyn.  :-)

You are correct that the energy in a gallon of gas is indeed the energy of a gallon on gas. The 1st Law is indeed immutable. And that in a "metabolic chamber with tightly monitored metabolic ward studies" you would have a calories out equilibration.  

You seem to be repeating this bizarre notion that somehow the human body functions differently in a metabolic chamber or even in a metabolic ward.   There is no reason to believe that substrate cycling or whatever is any different in either context.  The chamber is akin to "rest" only all gasseous and thermal with the environment inside the isolated chamber are measured along with bodily excretions.  I posted several links to the Atwater experiments in a prior post on  Calories (a browser search on Atwater will get you there faster).   I don't understand what you mean by "calories out equilibration", but if there is such a thing that alters the function of the human body in a metabolic chamber it most certainly is not applicable to a metabolic ward.  The major (huge) difference in ward vs. free-living studies being that calories in are monitored, verifiable and verified.  

However, you unfortunately do not discuss the rate of formation of such output which is directly tied to the basal metabolic rate. This, significantly, IS highly variable according to the dictates of the the brain-pituitary-gut-immune system. And importantly tied to satiation.

I'm confused here, because when you talk about" rate of formation of output" it sounds like you are speaking of kinetics.  Surely you are not suggesting that the chemical energy content of the food molecules is altered by the rate at which they are oxidized?    I think we can all agree that the BMR is a significant term on the CO side of the energy balance equation.   Many have tried valiantly to claim that various diets boost "fat burning" via increases in metabolic rate while you sleep!  I've yet to see convincing evidence that the macronutrient composition alters CO.  

As to satiation, this has nothing whatsoever to do with the thermodynamic argument.  Surely you aren't arguing that eating more food increases the CI of the food previously eaten?   I think rather that you are implying that certain diets may increase appetite and overall CI, but this is irrelevant to this discussion.

Using your own analogy of the (a) a motorcycle, (b) a car, (c) a truck or (d) my weed whacker, let's exam the efficiencies of work output for each of those machines. A gallon of gas for a motorcycle might well get a person 80 miles away, for a truck perhaps 20 miles away and for the weed wacker perhaps around the block. There is the same energy, but not the same work output. What happened to the extra energy? Answer, it left as either heat or conversion to another chemical bond formation unusable by that machine afterwards. In the case of the weed wacker, it left as smoke!  {bold emphasis mine}

You seem to be missing my point here so allow me to clarify.   Simply put, you are arguing that CO changes CI, or more specifically the partitioning of CO to different energy types changes CI.  I am specifically stating that this is not true!  First, I'm presuming that the engines in all of my devices are combustion engines and we have complete combustion. So hopefully we agree that 

Hydrocarbon + O2 → CO2 + H2O (and other possible products) + ENERGY 

is the same regardless of the how the combustion takes place.  Energy is, after all, a state function.  To save time, I'll cite this excellent discussion for the benefit of my readers who are unfamiliar with the concept.  Unfortunately no numbers are provided for their example, so rather than have to track down these values, I'll use letters for hypothetical compounds and make up some enthalpies to work with for a scenario analogous to reactions 1 through 3 at my link.  My hypothetical:

Reaction 1:  ∆H = [C+D] - [A+B] = [-100 + -150] - [100 + -50] = -300Reaction 2:  ∆H = [E+F] - [C] = [-200 + 50] - [-100] = -50Reaction 3:  ∆H = [D+E+F] - [A+B] = [-150 + -200 + 50] - [100 + -50] = -350

Whether the chemical reaction between A and B to form D, E and F occurs in a single step (reaction 3) or two steps (where a product of reaction 1 becomes a reactant in reaction 2) the net energy change in the transformation is -350 (let's just say kcal/mol for units).  

For glucose, I've shown the net reaction here.  (*The molecular weight of glucose is about 180 g/mol, and if we use the 4 Cal/gram average, each 180 grams of glucose metabolized to carbon dioxide and water provides about 720 "Calories In".)   Some of those calories go to generate ATP -- to eventually fuel the functions of every cell in our bodies including muscle contractions, nerve impulses, molecular synthesis and breakdown, etc. -- and some will be released as heat -- which as I've stated many times now, is not a waste product in a warm blooded human.

What Feinman seems to be suggesting is that substrate cycling between free glucose and stored glycogen somehow reduces the amount of energy that dietary glucose adds to the body.  I think the simple schematic above shows how this is not the case.  The glucose ↔ glycogen pathway is not part of the glucose metabolism (breakdown) pathway.  So if glucose is stored as glycogen, the body provides ATP "calories" to do so -- Calories Out.  The ~720 calories are still in that glucose bound up as glycogen, we didn't lose those Calories In.  The same would go, by the way, for the free fatty acid + glycerol ↔ triglyceride cycling that continually occurs in the body.  Such cycling is not part of the metabolism of fatty acids to carbon dioxide and water.  It bears repeating that the energy cost of gluconeogenesis would also be CO from the body, and when that glucose is eventually metabolized, if the substrate came from the diet, we have CI.  If the substrate came from the body (e.g. broken down protein), then it would be CO.  The energy cost of de novo lipogenesis would be CO, and since acetyl-CoA generally comes from the diet, thus the substrate was dietary in origin, when the fatty acids are metabolized the energy would be CI.  

The preceding discussion is easier to think of in the black box!  We "count" the calories when they are absorbed into the body CI.  They aren't really "calories" until the food molecules have been metabolized, but potential calories are just fine.  Then CO is the sum of any chemical, electrochemical or mechanical work done during the course of the living, breathing and moving about, plus whatever heat is generated in the process.    When potential CI exceeds CO, you gain mass because you store the unmetabolized molecules until needed (mostly as fat over the long term).  When fully metabolized CI do not meet CO needs, stored molecules (mostly from fat) are metabolized to do so and stored mass exits the body.

Whether most of it goes to mechanical work and a little to heat, whether you have a lot of friction and wind resistance, travel flat terrain or navigate the hills of San Fran, weed whack or power a generator, the amount of energy contained in the gasoline that is released in the (SAME) combustion remains the same. (BTW, I have a pure gas utilizing weed whacker, no oil mix, no more smoke than anything else :-) )

If you measured the environment that the machine is in, you would indeed measure the energy of that gasoline to be the same as it was going in. But the work output is completely different for each machine.

Exactly.  That is what I'm saying.

In the same line of thinking, the human body is capable of adjusting the basal metabolic rate through a series of hypothalamic circuits that alter cellular metabolism. For just a single example (and there are MANY), hypothalamic release of TRH (thyrotropin releasing hormone) to increase release of TSH in anterior pituitary increases thyroid hormones (T3/T4) which increases metabolism in every single cell especially in sympathetic neural circuitry. This effectively increases the BMR! Or to use your terms, an increase in CO.

Yes, the body will adjust CO to CI to some extent, but it doesn't change CI it changes the magnitude of the deficit or surplus. 

With low calorie diets the BMR is reduced through lowered basal release of TRH (again just a single example) . This is a conservation of energy in the face of decreased resources, an important evolutionary outcome for survival. Thus, the effect of simply lowering food intake by portion control for weight loss is blunted. The body responds correspondingly to a perceived loss of environmental resources by lowering the energy requirements.

Agreed, but this will happen if calories are reduced spontaneously or deliberately, and since carbohydrate restriction mimics starvation, it is possible that this "negative" adaptation of CO is seen with carb restriction even with caloric sufficiency.

Again, using your terms, the lowered CO results in lowered CI!

OK ... I think perhaps I see the issue here, but any confusion is cleared up by viewing calories in the way that the "paradigm" does.  In other words, although the calories aren't technically put "in" to our engine until they are required and released from their chemical bondage (see what I did there? :p ), but the calories are "in" our bodies.  To use the car analogy, the calories aren't "in" the engine to be able to do work when sitting as uncombusted fuel in the tank, but the potential calories in the gasoline are.  If we define CI as the chemical potential energy of absorbed food molecules, we can avoid any confusion.   

Thus, energy metabolism relative to food intake relative to satiety and feeding behaviors is altered as a calories out AND calories in. The body is far more dynamic than a mere weed wacker!

See, again here you are talking about irrelevant things.  Eating more increases CI because you add more.  How this supports any of Feinman's version of thermo is beyond me.    

The specific example given by Dr. Feinman is correct. The kcals conversion to ATP for a gram of glucose completely oxidized is indeed closer to 4 kcals and yielding 30 ATP per glucose. But if it gets converted to glycogen first, then for every glucose converted to glycogen there is a loss of one ATP, so those glucoses only generate 29 ATP per. This approximates a 3% loss of energy from the ATP cellular standpoint. The energy, however, is NOT lost, it leaves as unusable energy in the form of heat. This would have been measured nonetheless in an external metabolic chamber. I doubt, however, that the loss of energy to the cells (in the form of usable ATP) in that external chamber was counted.

I refer back to the discussion above.  Any ATP used for cycling is CO to the body, it does not alter the chemical potential energy added to the body (CI) when the glucose is ultimately metabolized.   Feinman's specific example is incorrect. 

Conversion of glucose to glycogen and glycogen to glucose is strongly under the influence of insulin, cortisol, and glucagon hormonal levels and glucose itself in response to blood glucose levels and neural input from brain. This aspect alone is enough to alter the basal metabolic rate and the CO. Since all of these ALSO impact satiety and feeding behavior, then the intake is also altered.

Again, that the body adapts and can alter CO is irrelevant here.  IF the BMR were altered significantly, especially to the degree some imply, and if this were altered by postprandial hormonal fluctuations, again to the extent some imply, we would see this in metabolic ward studies.  We do not.   

Part of my concern for not accounting for REFINED carbohydrates is the unusually high insulin resistance from consumption of such carbohydrates and the unusually high insulin response from lactose in dairy products.

Lactose is not particularly insulinogenic, the opposite actually.   It is the protein in dairy that appears to be responsible for dairy's insulinogenic effect.  I am not aware that refined carb is in and of itself at all related to insulin resistance, and we can add high GI carbs like potatoes and white rice to that as well.  Junky refined carbs consumed in the context of a relatively high fat (SAD is not low fat) hypercaloric diet seem to be problematic.  Context is everything.

I take no serious issue with carbohydrates found in whole foods such as fruit, but in a liquid or processed form (such as beer!) there is a high probability that insulin (and leptin resistance as well) result in problems with satiation from receptor downregulaiton in liver, brain, pancreas, muscle and immune tissues. Therefore a lower carbohydrate intake relative to other macronutrients seems prudent and indicated.

What diet is prudent and indicated is again irrelevant to this discussion.  That we tend to overeat highly palatable high carb and fat foods is CICO compliant.  But if we are looking for evidence of "quality" of calories and obesity, and since you're an ancestral guy ... I've blogged quite a bit about ancestral diets here -- what they were, not what is claimed by many in the community.

• Probably well over 95% of all of these cultures consume a high-to-very high carb, low-to-very low fat diet which is necessarily low in saturated fat.  
• The likely less than 5% of cultures that consume a high fat diet:
• Masai - Only the warrior class consume a whole milk dominated diet during this phase of their lives.  They do not consume a lot of meat, and women, children and elderly consume far less milk and meat vs. warriors.  There is significant evidence that serum cholesterol levels are mitigated due to genetic adaptation and consumption of saponins.
• Toukelou -- Consumed whole coconut which is 55% MCT and thus the diet is not nearly as high as a diet high in land herbivore meat and dairy.  (And Kitavan total fat is quite low).  Also vegetable fat with accompanying micronutrients in vegetable source, oligosaccharides, etc.
• Inuit -- Consumed a diet very high in protein and not nearly as high in fat as erroneously claimed (45P/55F).  Cold water mammal fat is some of the least saturated around, very high in PUFA especially O3 so no comparison to SAD or "paleo" fats.

This taken together with countless controlled experiments have demonstrated that a robust GSIS is not responsible for "insulin resistance", hyperglycemia, obesity or diabetes.  Feinman misrepresents this quite often as well, especially when he wrote that embarrassing letter to JAMA about the Bray overfeeding study.  So embarrasing, he has retracted the blog post about it after what can only be described as a humiliating defeat at the hands of Nigel Kinbrum on Fredrick Hahn's Facebook wall.  Sorry I'm too busy to track down links for all of the above, but this one I blogged on here if you're interested:  The First Law of Thermo still doesn't violate The Second Law.  

With all due respect, in a dynamic metabolic system such as that found in living systems, the calories in = calories out paradigm simply does not take into account all of the responses by the organism to its environment. It is in this dynamic system that a gallon of gas in ≠ gallon of gas out.

In a dynamic metabolic system, a pound of Fat (or carb or protein) In must equal a pound of Fat (or carb or protein) Out or we gain or lose weight (mostly fat especially when small differences exist over lengthy periods).   I hope this post has not been in vain and my rationale for this has been presented more clearly. 

Most sincerely,

David Pendergrass

I would like to thank you for your considered commentary, and most especially for engaging on the issues rather than resorting to Feinman-like tactics.  I had a fairly lengthy and time consuming email exchange with him four years ago, and came away from it realizing that he is not interested in explaining his ideas to someone such as myself who has both an extensive formal education on the subject (from multi-disciplinary angles I might add) and experience applying these concepts.  Your attempts were admirable and helped me to address the ideas in greater depth.  Thank you.

It quite frankly boggles the mind that a man of Feinman's education and stature could ever write the following, as he did in an email to Dr. Eades  (this is a screenshot from my post discussing this, warning these folks bring out the snark in me, from this post):

The concept of conservation of energy is integral to many applications of physics.  Work done by dissipative forces such as air resistance and surface friction, are analogous to First Law energy terms, not entropy, which appears to be Feinman's primary error in all of this.  In chemistry, heat evolved is a First Law energy term, not energy gone poof "because Second Law".   Just continues to baffle me that he is incapable of reconciling his ideas with the types of analyses done in engineering and science applying these laws all the time, not to mention that CICO holds up extremely well in practice.  (When it doesn't, it is almost always due to compliance/reporting, but measurement error may play more of a role than it is given attention.)

In this article [please make them stop! ... but HT CharlesG anyway :-) ]  Feinman is quoted as follows:

Feinman has looked at calories from the perspective of thermodynamics—or the laws that govern heat and energy. Like Ludwig, he says the idea that calories from different macronutrient sources would have the same effect on your body is silly. Put simply, it doesn’t make sense that “a calorie is a calorie” because your body uses the energy from different foods in a variety of ways, Feinman explains.

All metabolized food molecule CI basically have three fates:

• Generate ATP (and a few other ATP-like molecules) 
• Generate heat
• Excreted products of metabolism and/or very small molecules following substantial breakdown of the original food molecules

ATP is used by the body to fuel chemical reactions for "life" regardless of their source.  If something in a store costs $100, the store owner doesn't care if you got that Ben Franklin from getting lucky in the stock market, engaging in the world's oldest profession, or flipping burgers at McD's.  You give him $100, you walk out of the store the proud owner of a $100 Thingamajig.   Likewise if 100 MJ of heat is required to keep some space warm, it matters not if that is generated by an electric heater, a gas stove or a fireplace.  Heat is heat.  

What he is getting at is the likelihood of fat accumulation.  Insulin doesn't have the power to create mass out of thin air, so it is ultimately playing the role of traffic cop.  Insulin may influence the distribution of fat, and paradoxically, favor fat tissue over lean when low.  Hormones may alter CO to adapt to changes in CI, total energy expenditure on maintenance may differ with varied isocaloric diets, but neither of these has been demonstrated (and again would favor carbs over fat vis a vis obesity).  No, mostly what dictates fat accumulation is chronic energy excesses, and since fatty acids are:

• Already fatty acids and require almost no energy to store
• The most energy dense (e.g. most energy, least mass to move around) so there are virtually unlimited storage sites
• The last macronutrient to be burned for energy 

If you're really going to point fingers at a sole macronutrient, it's fat.  It's a paradigm that fits both scientific principles, epidemiological evidence and good old fashioned observation and common sense.  Thanks for reading :-)