• Your life and health are your own responsibility.
• Your decisions to act (or not act) based on information or advice anyone provides you—including me—are your own responsibility.


Calorie Cage Match! Sugar (Sucrose) Vs. Protein And Honey (There Is No Such Thing As A “Calorie”, Part VI)

Caution: contains SCIENCE!

We’ve already proven the following in Part II, Part III, and Part IV:

  • A calorie is not a calorie when you eat it at a different time of day.
  • A calorie is not a calorie when you eat it in a differently processed form.
  • A calorie is not a calorie when you eat it as a wholly different food.
  • A calorie is not a calorie when you eat it as protein, instead of carbohydrate or fat.
  • Controlled weight-loss studies do not produce results consistent with “calorie math”.

Next, we’ve proven the following in Part V:

  • Calorie counts on food eaten away from home are off by over 10%, with the lowest-calorie and most “healthy” items most likely to be underreported.
  • Even when cooking at home, our estimates of portion size and calorie content, both immediate and retrospective, are wildly inaccurate: the average error exceeds 50%.
  • Therefore, even if all calories were equal (and we’ve proven they’re not), the errors in estimating our true “calorie” intake exceed the changes calculated by the 3500-calorie rule (“calorie math”) by approximately two orders of magnitude.

And we’re not done yet!

Empirical Evidence: A Calorie Is Not A Calorie When You Substitute Protein For Sugar

(Hat tip to George Henderson for the next three studies. They’re fascinating, and there’s far more to discuss than the side effect of dismantling CICO and “calorie math”—but for now I’ll stick to the subject at hand.)

J Biol Chem. 2008 Mar 14;283(11):7196-205. Epub 2007 Dec 10.
cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids.
Madsen L, Pedersen LM, Liaset B, Ma T, Petersen RK, van den Berg S, Pan J, Müller-Decker K, Dülsner ED, Kleemann R, Kooistra T, Døskeland SO, Kristiansen K.
(Full text)

“We show that n-6 PUFAs were pro-adipogenic when combined with a high carbohydrate diet, but non-adipogenic when combined with a high protein diet in mice.”

Both diets were purified lab chemicals, containing 25% corn and soybean oil by weight, and both were exactly the same, with one exception: the “high-carbohydrate” diet contained 20% casein (milk protein) and 43% sucrose (sugar) by weight, whereas the “high-protein” diet contained 54% protein and 9% sugar by weight.

Note that the mice were pair-fed by weight, not calories—so the high protein+corn oil group was eating 10% more “calories” than the high sucrose+corn oil group…and 33% more “calories” than the chow diet group. Therefore, according to the self-appointed “guardians of science”, they should have gained 33% more weight.

Figure 2B, Madsen 2008

Meanwhile, back in reality, the high-sucrose group gained over six times as much weight as the high-protein group, despite consuming fewer “calories”…

…and the chow group gained exactly the same amount of weight as the high-protein group, despite consuming 1/3 fewer “calories”.

“The mice fed corn oil in combination with sucrose gained an average of 11.3 g of body weight and became visibly obese (Fig. 2, B and C, and Table 1). The mice fed corn oil in combination with protein gained on average less than 1.8 g of body weight during the 56 days of feeding and had small amounts of white adipose tissue (Table 2 and Fig. 2, B and C). In fact, the weight gain and amount of body fat in mice fed a high corn oil diet supplemented with protein was comparable with the body weight gain and adipose tissue mass in mice fed an energy-restricted low fat chow diet (Fig. 2, B and C, and Table 1). “

Fortunately, this study also addressed a couple common canards. The authors measured the digestibility of each diet, which didn’t vary significantly. (It was slightly larger in the high-protein group.) And apparently high-protein diets don’t cause mice to exercise, either: the study measured both energy expenditure (which was actually smaller in the high-protein group) and oxygen consumption (roughly equal).

Conclusion: A calorie is not a calorie when you substitute protein for sugar.

Empirical Evidence: A Calorie Is Not A Calorie When You Substitute Protein For Sugar (Again)

Here’s a similar experiment, again done by the Madsen group:

PLoS ONE 6(6): e21647 (2011)
Sucrose Counteracts the Anti-Inflammatory Effect of Fish Oil in Adipose Tissue and Increases Obesity Development in Mice
Tao Ma, Bjørn Liaset, Qin Hao, Rasmus Koefoed Petersen, Even Fjære, Ha Thi Ngo, Haldis Haukås Lillefosse, Stine Ringholm, Si Brask Sonne, Jonas Thue Treebak, Henriette Pilegaard, Livar Frøyland, Karsten Kristiansen, Lise Madsen

I’ll skip to the punchline. In this case, the pair-fed diets were isocaloric (contained the same number of “calories”):

Figure 4, Ma 2011

Yet the fish oil+sucrose group gained about five times as much weight as the fish oil+protein group.

As a bonus, when fed ad libitum (science-ese for “food was freely available 24/7”):

Mice fed a fish oil-enriched diet in combination with sucrose had markedly higher feed efficiency and required less than 50% of the calories to achieve the same weight gain as mice fed a fish oil-enriched diet in combination with protein. (Hao 2012, referencing Ma 2011)

Conclusion: A calorie is not a calorie when you substitute protein for sugar (again).

Empirical Evidence: A Calorie Is Not A Calorie When You Change The Type Of Fat Or Substitute It For Sugar

Here’s yet another paper exploring the relationships between linoleic acid, EPA and DHA, and carbohydrate content:

Obesity (Silver Spring). 2012 Oct;20(10):1984-94. doi: 10.1038/oby.2012.38. Epub 2012 Feb 15.
Dietary linoleic acid elevates endogenous 2-AG and anandamide and induces obesity.
Alvheim AR, Malde MK, Osei-Hyiaman D, Lin YH, Pawlosky RJ, Madsen L, Kristiansen K, Frøyland L, Hibbeln JR.
(Full text)

This time, all diets contained 20% protein by calories. “Medium-fat” diets contained 35% fat and 45% carbohydrate: “high-fat” diets contained 60% fat and 20% carbohydrate…and though this study (like the others) contains much fascinating data, I’ll skip straight to the graphs.

“Feed efficiency” is the amount of weight gained per mouse, per dietary “calorie” consumed. Note that it varies by over 30%, depending on the total fat percentage (higher fat diets were, on average, less efficient) and the proportion of linoleic acid (higher LA diets were, on average, more efficient).

Figure 2B, Alvheim 2012

Conclusion: A calorie is not a calorie when you change the type of fat, or when you substitute it for sugar.

Empirical Evidence: A Calorie Is Not A Calorie When You Substitute Protein For Sugar (Yet Again)

Am J Physiol Endocrinol Metab. 2012 May 15;302(9):E1097-112. doi: 10.1152/ajpendo.00524.2011. Epub 2012 Feb 14.
High-glycemic index carbohydrates abrogate the antiobesity effect of fish oil in mice.
Hao Q, Lillefosse HH, Fjaere E, Myrmel LS, Midtbø LK, Jarlsby RH, Ma T, Jia B, Petersen RK, Sonne SB, Chwalibog A, Frøyland L, Liaset B, Kristiansen
(Full text)

“…Increasing amounts of sucrose in the diets dose-dependently increased energy efficiency and white adipose tissue (WAT) mass.”

Again, these are isocalorically pair-fed mice:

Figure 1A, Hao 2012

“…An increase in insulin secretion alone was insufficient to promote obesity development because mice receiving glybenclamide in combination with proteins and fish oil did not become obese. This finding is in keeping with the observation that a high-fat diet is unable to increase adipose tissue mass in the absence of carbohydrates (47, 50).

“Obviously, increased adipose tissue mass is related to energy intake. However, macronutrient composition can influence energy efficiency in such a way that mice consuming the same amount of calories end up with quite different amounts of adipose tissue. Thus, increasing the amount of sucrose in the feed from 13 to 43% led to approximately fivefold higher energy efficiency.”

Conclusion: A calorie is not a calorie when you substitute protein for sugar (yet again).

Empirical Evidence: A Calorie Is Not A Calorie When You Substitute Honey For Table Sugar

This one speaks for itself:

J Food Sci. 2007 Apr;72(3):S224-9.
The effect of honey compared to sucrose, mixed sugars, and a sugar-free diet on weight gain in young rats.
Chepulis LM.

“Overall percentage weight gain was significantly lower in honey-fed rats than those fed sucrose or mixed sugars, despite a similar food intake.”


“Weight gains were comparable for rats fed honey and a sugar free diet although food intake was significantly higher in honey-fed rats.”

Conclusion: A calorie is not a calorie when…you know the rest.

Conclusion: Protein and Honey Beat Sucrose

In this article, we’ve demonstrated the following:

  • A calorie is not a calorie when you substitute protein for sugar.
  • A calorie is not a calorie when you change the type of fat, or when you substitute it for sugar.
  • A calorie is not a calorie when you substitute honey for sugar.

The weight of the evidence points towards the following hypothesis: adding refined sucrose (“table sugar”) to a diet in exchange for protein, or even honey, makes it more fattening—per calorie. (There is also evidence for sucrose making a high-fat diet more fattening per calorie, but I need to do more reading first.)

This effect is in addition to the usual effect of refined sucrose causing greater food consumption…and since the experiments used purified ingredient diets, it’s not a matter of unprocessed food vs. refined sugar.

Note that I’m not going to defend this hypothesis too strongly, because these experiments involve mice and rats, not people…but it’s worth further investigation.

Continue to Part VII, “Carbohydrates Matter, At Least At The Low End.”

(Or, you can refresh your memory by going back to Part I, Part II, Part III, Part IV, or Part V.

Live in freedom, live in beauty.


Protein Matters: Yet More Peer-Reviewed Evidence That There Is No Such Thing As A “Calorie” To Your Body (Part IV)

(This is a multi-part series. Go back to Part I, Part II, or Part III.)

Empirical Evidence: Greater Weight Loss And Fat Loss On Isocaloric High Protein Diets

Dozens of studies have demonstrated that high-protein diets result in greater loss of bodyweight and fat mass than isocaloric lower-protein diets. (Isocaloric = containing the same number of “calories”.)

Instead of bombarding you with citations, I’ll point you to references 11 through 44 (and 2) of this excellent paper:

Nutr Metab (Lond). 2012 Sep 12;9(1):81. doi: 10.1186/1743-7075-9-81.
Dietary protein in weight management: a review proposing protein spread and change theories.
Bosse JD, Dixon BM.
(Fulltext available here.)

While some will critique that the satiating effect of higher dietary protein sometimes results in voluntary hypophagia [11], leading to an energy intake discrepancy between groups, there is evidence that increased dietary protein leads to improved body composition and anthropometrics under iso-, hypo-, and hyper-caloric conditions [2, 11-44]. Thus, the traditional dogma of “energy in versus energy out” explaining weight and body compositional change is not entirely accurate.

Now, it’s quite possible to pick a fight by cherry-Googling a few studies that show no advantage to high-protein diets. CITATION WAR!!11!!!1 Who’s right?

Rule Of Thumb: When there is a wide spread of outcomes, it’s likely that other factors, besides the one being studied, are influencing the results.

For instance, there are studies showing that calcium supplementation increases weight loss, and studies showing it does not. Instead of arguing that the studies opposing one’s hypothesis must all be flawed or fabricated, it’s more productive to look for other factors…

…and indeed, we find that calcium supplementation only increases weight loss if one is calcium-deficient to begin with.

Br J Nutr. 2009 Mar;101(5):659-63.
Calcium plus vitamin D supplementation and fat mass loss in female very low-calcium consumers: potential link with a calcium-specific appetite control.
Major GC, Alarie FP, Doré J, Tremblay A.

The application to such controversies as “Is there a metabolic advantage to low-carb diets?” should be obvious.

First, we know that a host of factors besides protein intake influence weight and fat mass (some of which I discussed in Part II and Part III). Furthermore, the dozens of studies in question prescribed a wide range of diets—anything from nutrient shakes to nuts to protein supplements to prepared meals to “we give you dietary advice; you keep dietary records and we’ll analyze them for compliance”—so we would rightly expect some of these changes to influence study outcomes. Unfortunately, it’s difficult to discern patterns across such a wide range of variables.

However, Bosse and Dixon have found two factors that can easily be compared between studies: protein spread and protein change.

Protein spread is the difference in protein content between low- and high-protein diets; protein change is the difference in protein content between a test subject’s habitual diet and the high-protein diet.

“In studies where a higher protein intervention was deemed successful there was, on average, a 58.4% g/kg/day between group protein intake spread versus a 38.8% g/kg/day spread in studies where a higher protein diet was no more effective than control. The average change in habitual protein intake in studies showing higher protein to be more effective than control was +28.6% compared to +4.9% when additional protein was no more effective than control. Providing a sufficient deviation from habitual intake [“protein change” -JS] appears to be an important factor in determining the success of additional protein in weight management interventions.” (Ibid.)

Even more striking, when the authors excluded studies in which the protein content of the low-protein diet was insufficient to meet the RDA, the mean difference in spread increased from 19.6% to 21.7%, and the mean difference in change increased from 23.7% to 37%!

Figure 2, Protein spread

Figure 3, Protein change

For those skeptical about the ranges in the above graphs: “…There appeared to be plausible explanations for nearly all outliers.” (Ibid.) Read the Discussion section if you’re interested in the details.

For instance: “A flaw in previous trials was that at times higher protein groups consumed more protein than control, yet less than their habitual intake, and saw no difference in anthropometrics [33, 52, 57, 61]. Thus, the “intervention” diet was really not an intervention to their metabolism. […] In some cases, increasing the % of kcals from protein during energy restriction can actually result in less protein being consumed during intervention than habitual intake as a simple function of energy deficit.” (Ibid.)

For example, if you design a 1000-“calorie” diet for someone whose habitual intake is 1900 “calories” with 15% protein, you’ll have to include 28.5% protein just to give them the same amount of protein they were getting before.

“What is the protein spread on this study?” and “What is the protein change in this study?” are common-sense questions to ask. If protein spread is too small, the diets will be too similar to cause significantly different outcomes. If protein change is too small, the “high-protein” diet won’t be different enough from a subject’s habitual diet to cause a significantly different outcome. So while other factors are very likely to influence the outcome, it’s clear that protein change (and, to a lesser extent, protein spread) account for most of the difference between outcomes in high-protein dietary interventions.

Conclusion: A calorie is not a calorie when you consume it as protein instead of fat or carbohydrate.

Our Story So Far

  • A calorie is not a calorie when you eat it at a different time of day.
  • A calorie is not a calorie when you eat it in a differently processed form.
  • A calorie is not a calorie when you eat it as a wholly different food.
  • A calorie is not a calorie when you eat it as protein, instead of carbohydrate or fat.
  • Controlled weight-loss studies do not produce results consistent with “calorie math”.
  • And, therefore:

  • Calorie math doesn’t work for weight gain or weight loss.

What happens if we decide to “count calories” anyway? Continue to Part V, “Can You Really Count Calories?”.

(This is a multi-part series. Go back to Part I, Part II, or Part III.)

Live in freedom, live in beauty.


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…Evokes a direct and total engagement with life, and explains why hyenas laugh. READ IT!!!”

Yes, this is a review of The Gnoll Credo.

If you haven’t yet read it, ask yourself: what value might I place on such an experience? I suspect it exceeds $10.95 US…so click here and buy one.

Thank you.

Dietary Protein 101: What Is Protein, And Why Do We Need To Eat It Every Day?

Different schools of nutrition argue endlessly about protein. Vegans swear it destroys our kidneys and we’re eating far too much. Strength athletes and leangains devotees can’t get enough. The government claims 56 grams/day is more than enough for anyone—yet even the most conservative and fat-friendly paleo templates recommend closer to 90 grams. Paleo eaters and omnivores enjoy pointing out that animal protein is “complete”, unlike most grain and vegetable proteins, while vegetarians and vegans swear by “protein combining”. And just about everyone gets confused when acronyms like BV, NPU, and PDCAAS enter the picture.

What Is Protein, Anyway?

Talking about “protein” is like talking about “buildings”. Just as “building” can mean a single-family home, a chemical factory, a mud-and-straw hut, a skyscraper, or the Taj Mahal, “protein” can mean anything from tiny di- and tri-peptides containing perhaps a few dozen atoms, to the giant linked chains of keratin that make up our hair and fingernails.

As such, it turns out that “protein” is a term so broad as to be nearly useless when applied to nutrition. When we’re asking the question “How much protein should we eat?” what we’re really asking is “Which amino acids do we require, what relative proportions to we require them in, and to what degree are the foods containing them digestible, bioavailable, and not otherwise poisonous or disruptive to our metabolism when ingested?”

If that sentence wasn’t immediately comprehensible to you, fear not—the purpose of this article is to explain it!

What is Protein Made Of?

Proteins are molecules made up of amino acids stuck together by peptide bonds.

Amino acids are so named because they contain both an amine group (-NH2) and a carboxyl group (-COOH). In the renderings below, we can see the carboxyl groups (the two red balls with one white ball attached) and the amine groups (the blue ball with two white balls attached). The alpha carbon, to which they’re both attached, is colored black. Here are a few examples:





Click here to see the 2D and 3D structure of all 21 standard amino acids.

A peptide bond occurs when the carboxyl from one amino acid bonds covalently to the amine of another—releasing a molecule of water in the process. Result: we can make just about any shape and size of protein we want by stringing together the right amino acids in a single-file chain, carboxyl to amine.

Strictly speaking, all the biologically important amino acids are alpha-amino acids, in which the amine and the carboxyl are both attached to the first carbon atom. The term “amino acid” usually refers only to the alpha-amino acids.

What Can Proteins Do?

It turns out that proteins are extremely versatile molecules. They are the basic machinery of all cells: DNA is, quite literally, just instructions for building proteins out of amino acids. They catalyze chemical reactions (“enzymes”), they signal metabolic and immune events (e.g. insulin, leptin, growth hormone, antibodies), they transport oxygen (hemoglobin and myoglobin), and they’re structural components of everything from the cytoskeleton and mitochondria of every cell to our tendons, ligaments, hair, nails, and connective tissue. Even the parts of a cell which are made from other molecules, such as phospholipids and polysaccharides, are ‘built’ by their interaction with proteins!

The average human cell is approximately 65% water, 20% protein, 12% lipid (fat), 1% RNA and DNA, and 2% “other” by mass. (Freitas 1998)

Why Do We Need To Eat Protein?

Of the 21 amino acids coded for by the DNA of multicellular organisms, adult humans can only synthesize 12 of them. The other nine must be consumed in the diet, so we call them essential amino acids.

Essential Nonessential
Histidine Alanine
Isoleucine Arginine*
Leucine Aspartate
Lysine Cysteine*
Methionine Glutamate
Phenylalanine Glutamine*
Threonine Glycine*
Tryptophan Proline*
Valine Serine*

* = conditionally essential – see below

It’s actually far more complicated than “essential” or “non-essential”. Some amino acids can be converted to each other, but not created from scratch. Some amino acids can be synthesized, but not rapidly enough to meet all our metabolic needs. And children can’t synthesize some of the amino acids that adults can.

Further reading:

J. Nutr. July 1, 2000 vol. 130 no. 7 1835S-1840S
Dispensable and Indispensable Amino Acids for Humans
Peter J. Reeds

Result: humans have a non-negotiable requirement for dietary amino acids in order to sustain the basic processes of life.

Why Do We Need To Eat Protein Every Day?

Some nutrients, like vitamin B12, are stored within the body and released when needed—so though we must consume a certain amount on average, we don’t have to do so every day in order to keep ourselves healthy.

Unfortunately, we have no way to store amino acids. We have a tremendous capacity to store fat in fat cells, and a very limited capacity to store glucose (as glycogen in our muscles and liver)—but we must either use amino acids to synthesize proteins, burn them for energy, convert them to glucose, or (very rarely, and if all else fails) excrete them.

Therefore, humans have a daily requirement for each one of the amino acids necessary to life, in the quantities required by whatever proteins the trillions of cells in our bodies are making (minus our ability to synthesize some of them).

Why “Complete Protein” Is Important

Imagine a factory that assembles cars. Let’s say you have 400 wheels and tires in inventory, 200 headlights, 100 chassis, 100 engines…but only ten steering wheels. It doesn’t matter that you’ve got almost enough parts to build 100 cars: ten steering wheels means you can build ten cars. Whichever part you have the fewest of limits how many cars you can build.

Our bodies have the same problem when building proteins. For instance, lysine is an essential amino acid—so if we haven’t consumed any lysine, we can’t build any proteins that contain lysine, no matter how many of the other amino acids are available. This leaves us with two options:

  • Don’t build that protein. This is not usually a viable option, as it results in signals not reaching the intended recipient, damaged cells and tissues not being repaired, pathogens not being attacked…in other words, the failure of basic metabolic processes.
  • Disassemble existing tissues in order to get the amino acid(s) we need. This is known as catabolysis or ‘going catabolic’, and is what actually occurs. Muscles are the first tissues to be catabolized, as becoming slightly weaker is usually less harmful than impairing the function of other organs.

Our Summary (so far)

  • Proteins form the basic machinery of all cells.
  • Proteins are made out of amino acids.
  • Amino acids are not interchangeable: to synthesize a protein, each one of its constituent amino acids must be available.
  • Many amino acids are essential—we cannot synthesize them, and therefore must ingest them as part of our diet. Many others are conditionally essential, and cannot be synthesized or converted at the rate we require them.
  • Since we have no way to store amino acids for later use, our bodies have a daily requirement for them.
  • Therefore, we must ingest each amino acid, roughly in the proportion we require it, every day.


Our biological needs are for specific amino acids in specific proportions, but “protein” can mean any combination of one or more amino acids. Therefore, the amount of “protein” in food is, by itself, a nearly meaningless number.

I’ll discuss measures of protein quality, and much more, next week!

Live in freedom, live in beauty.


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