experiments are devices of the imagination used to investigate the nature of
things…. The primary philosophical challenge of thought experiments is
simple: How can we learn about reality (if we can at all), just by thinking?
More precisely, are there thought experiments that enable us to acquire new
knowledge about the intended realm of investigation without new data?…
[T]hought experiments can disclose nature’s failure to conform to a
previously held set of expectations. In addition, they can suggest particular
ways in which both expectation and theory must henceforth be revised.
we announced the creation of the Nutrition Science Initiative (NuSI) in
September, I e-mailed information packets and press releases to many of my
colleagues in science and health journalism. I included a few who had
vehemently and even publicly disagreed with the arguments I’ve made in my books
and articles. I was hoping to see them embrace the idea that our conflicting
ideas should and could be tested, and any organization that could make this
happen would be a good thing and worthy of public support. They all expressed
their admiration for the effort in private, although none of them perceived it
as worth writing up publicly, at least not until we have experimental results
couple of these journalists took the opportunity to insist that we didn’t
really disagree all that much on what we had argued over the years, and they
explained why. Here’s how one put it in an e-mail back to me (and I’ve made a
few minor changes so that this writer can remain suitably anonymous):
think in our hearts we basically agree–I know you believe in calories because
you are a scientist. And I know you know that many cultures that consume large
amounts of carbohydrate but low fat and relatively low sugar are not fat.
(Japan, for example–and yes, I know they are not all slim, but we both know
they have a very low obesity rate.) Do I think some people get “hooked”
on sweets and simple carbs? Yes, I do. Do I think that can be a
problem for some people, hence steering clear of simple carbs is a good idea
for them? I do, and said so on national radio. Do I think there is
strong evidence that carbs per se (in absence of excess calories) will result
in excess weight gain? No I do not.
I wrote in […]–sugar ain’t great, nor is excess fat. Sugar and fat
infused foods packaged and “ready to eat” are what has made America
obese–sitting around doesn’t help, either. When you cut out carbs, you
cut out most of the fat–yes, you can eat pure whipped cream, but not the cake
or ice cream you’d normally put it on–so why bother? Yes, you can eat fried
pork-chops, but not breaded fried pork-chops–or clams or chicken–so that cuts
calories a bunch. You eat a lot less butter when you can’t eat the bread
or potato or pasta or cake or pie…etc, etc. There is only so much “whole
chicken and steak” and even full fat yogurt with berries that most of us can
stomach. So over time, on average we eat fewer calories when we cut out simple
and most complex carbs.”
thought a lot about this e-mail after I received it, for two reasons. One is
the tendency we all have (or at least I have and I do see it in others) to
assume that just because we’ve written something, other people have read it or
certainly should have read it. If only…
this case, I addressed the no-bread-no-butter, only-so-much-steak-you-can-eat
position at length in Good
Calories, Bad Calories (The
Diet Delusion, in the UK). I even quoted Jane Brody making
this point in the epigraph to Chapter 20 — “Unconventional Diets” — and set it
off against a quote from the DuPont physician Alfred Pennington to contrast how
the same observation — weight loss and absence of hunger on a diet unrestricted
in calories — could be perceived by one person, Pennington, as a “mighty
stimulant to thought on the matter,” and by another, Brody, as a triviality to
be dismissed without much conscious thought (as my friend did in the e-mail).
Pennington in 1954:
Here was a
treatment, that, in its encouragement to eat plentifully, to the full
satisfaction of the appetite, seemed to oppose not only the prevailing theory of
obesity but, in addition, principles basic to the biological sciences and other
sciences as well. It produced a sense of puzzlement that was a mighty stimulant
to thought on the matter.
Brody nearly half a century later:
help people lose weight? Of course it does. If you cannot eat bread, bagels,
cake, cookies, ice cream, candy, crackers, muffins, sugary soft drinks, pasta,
rice, most fruits and many vegetables, you will almost certainly consume fewer
calories. Any diet will result in weight loss if it eliminates calories that
previously were overconsumed.
than get upset at my journalist friend who either hadn’t bothered to read GC,BC after
years, or read it and found it thoroughly forgettable, I got to thinking about
the other point made in the e-mail: “I know you believe in calories because you
are a scientist.”
the possible mischaracterization of me as a scientist, this statement is a
little ambiguous. I obviously believe in calories as a measure of energy,
whatever that means to believe in such a thing. (It’s like believing in miles
as a measure of distance.) So that’s probably not what my friend meant. What I
don’t believe in is that discussions of caloric consumption and expenditure
tell us anything meaningful about why we get fat or why we lose fat, and I
believe that the mantra that ‘a calorie is a calorie is a calorie” serves only
to direct attention away from the meaningful characteristics of the
macronutrients in our diets.
arguing that the original sin in obesity research is this belief that our body
fat is regulated by the amount of energy we consume and expend. I think this is
simply the wrong way to think about obesity and the chronic diseases with which
it associates, and it’s because this is the fundamental assumption underlying
most obesity research, it’s the reason why we’ve made so little progress. (And
to those who think we have made real progress, I suggest they take a look
around at the people walking by and reconsider.)
to put this is that I think this energy balance hypothesis of obesity is an
incorrect paradigm and it has to be replaced with a correct paradigm before
progress will be made. Obviously my friend doesn’t understand this, so it got
me thinking about yet other ways to explain it that might get the point across.
This led me to a series of thought experiments, or gedankenexperiments as
learned to call them back in the days when I was writing about physics rather
than nutrition and health.
thing about thought experiments is that they come unfettered by financial,
ethical or real world constraints. We can do virtually anything in these
experiments and see what we think is likely to happen. And we can do it
quickly. So here goes.
imagine we have a pair of identical twins, unimaginatively named A and B.
They’re males, say, and 20-years-old. They’ve stopped growing and both are
weight stable when this experiment begins. (Remember we can do anything we like
in a thought experiment, so if we say they’re weight stable initially, then
they are.) Now we measure their daily energy expenditure. Let’s say they both
expend 3000 calories a day. Every day, day in and day out — 3000 calories.
Again, this is true of both of them because they’re identical in all respects.
experiment: We’re going to house A and B in our splendidly livable metabolic
ward and keep them there for the next 20 years. (Thought experiments also come
free of Institutional Review Boards. We don’t have to worry about whether
this is ethical or not. Our imaginary twins will be perfectly happy anyway
because we say so.) We’re going to feed themalmost identical
diets. Each one is going to get exactly 3000 calories a day so that their
intake matches their initial expenditure. If we believe in calories, as my
friend might have put it, the fact that we’re matching intake to expenditure
and both twins are getting the same intake suggests they will both maintain a
stable weight for the duration of the experiment.
here’s the experimental twist: the diets are not identical, they’re only almost identical.
They differ in the macronutrient content of ten percent of the calories. So
2700 calories of the two diets are identical. The other 300 calories of A’s
diet will come from sugar — sucrose, to be precise, molecules of glucose
bonded to molecules of fructose. In B’s diet, these 300 calories will come from
glucose alone. So A will get 150 calories of fructose that B won’t get, and B
will get 150 calories more glucose than A. Other than that the diets are indeed
identical with all the macro and micronutrients necessary for the twins to
we run the experiment for 20 years. What happens? Care to guess? Will A
and B still be identical after 20 years of A eating 300 calories of sugar every
day that B does not eat?
know sugar is metabolized differently from the glucose in starch because of the
fructose component. Glucose is metabolized by cells throughout the body;
fructose is metabolized primarily in the liver. We
know the liver will
turn some of this fructose into fat and if the fructose is delivered quickly
enough (say in liquid form as sugar water), it likely to cause insulin
resistance in the liver, which in turn might cause systemic insulin resistance.
The extra 150 calories of glucose in B’s diet will stimulate more insulin
secretion, although for B this will come in the absence of any fructose-induced
effects in the liver. One way or the other, A and B will experience different
metabolic and hormonal effects, despite eating precisely the same amount of
calories in diets that are otherwise 90 percent identical. Their fat cells, for
instance, will be on the receiving end of different hormonal and metabolic
signals. As Claude Bernard would say, the fat cells would be living in a
different milieu intérieur and
this will effect how they change over time.
way of asking what happens in this experiment is to ask whether this difference
in hormonal and metabolic responses to diets of equal caloric content will have
a meaningful effect on, say, fat accumulation and risk factors of chronic
disease. Indeed, why would we expect our twins to end up with identical body
compositions, weights, and chronic diseases risk factors, when their hormonal
and metabolic experiences over those 20 years are indeed different? The
question, of course, is are these differences meaningful.
we’re wedded to the energy balance way of thinking — if we believe in calories,
as my friend said — we’re supposed to predict that the twins will end up identical.
(That’s certainly what the sugar industry would like us to think. Although the
industry might even argue, based on observational studies from the 1980s, that
the twin eating sugar will end up leaner and healthier than the twin getting
only glucose.)But we’re also likely to maybe hedge a little bit. Okay, maybe
the twins will have slightly different body compositions after 20 years. Maybe
they’ll even have slightly different chronic disease risks, depending on how
this sugar-starch/fructose-glucose trade-off plays out. Surely, though, they’ll
weigh the same. After all, they’re consuming identical calories and these
calories are exactly matched to their initial expenditure. So they should end
up weighing what they weighed at the get-go and they should both weigh the
same. Yes? (And by the way, this thought experiment also negates any effects of
food reward or the addictive nature of sugars, because we’re limiting
consumption and so even if sugar is addictive and A wants to eat more of it,
he’s not getting the opportunity.)
the fact is even their weight’s can differ, because we’ve only fixed caloric
intake. We haven’t fixed their expenditure. Both will get exactly the same
number of calories. That’s a condition of the thought experiment. But the different
macronutrient composition of A’s diet vs. B’s, can have an effect on fat
accumulation and so weight despite caloric consumption being equivalent.
how: let’s assume two things for the sake of argument. First, the sugar in A’s
diet causes A to become insulin resistant. And second, insulin works to put fat
in fat tissue. There’s some evidence for our first assumption and the second
assumption is in the textbooks; there’s a lot of evidence for that.
as A becomes insulin resistant, his pancreas has to secrete more insulin than
B’s to handle the equivalent carbohydrate load. So A now might have higher
circulating levels of insulin than B. If he does, this means more calories
might be fixed in A’s fat tissue than in B’s. Put simply, A might now be
getting fatter than B. And as A gets fatter, his body has to compensate for the
calories that are being locked away in the fat tissue and for the greater
metabolic demands of a heavier body. What does A do?
A can’t do
is eat more, because we’ve fixed his caloric consumption at 3000 calories per
day. One option is he could cannibalize his lean mass to feed his growing fat
tissue. This can certainly be done without violating any thermodynamic laws.
Now A gets fatter while simultaneously losing muscle mass and his weight
remains more or less the same. A second option is that A’s body merely expends
less energy to make up for the calories being locked away in fat tissue and the
greater caloric requirement that comes from being heavier.
A gets fatter while his energy expenditure goes down. While B remains in energy
balance throughout the experiment — eating 3000 calories a day to match the
3000 calories he expends — A moves into positive energy balance. He’s still
consuming 3000 calories every day, but he’s expending less. And the reason he’s
in positive energy balance is because he’s amassing fat in his fat tissue and
getting heavier. (Although a naive observer, wedded to the energy balance,
might decide that A has become a couch potato and that’s why he’s getting
fatter. In this case, the direct effect of the sugar is to make A expend less
energy and this in turn causes the energy imbalance that makes A fat. The
causality is reversed.)
here’s a possible chain of events in our thought experiment that’s perfectly
consistent with the laws of thermodynamics but is inconsistent with the notion
that a calorie is a calorie is a calorie: first, the sugar causes A to be
insulin resistant; second, the insulin resistance serves to cause a
compensatory elevation of serum insulin levels; third, the elevated insulin
causes A to store calories in his fat tissue every day and grow fatter.
this effect is tiny, say, five calories worth of fat get trapped in A’s fat cells
every day, he’ll still put on ten pounds of fat over the 20 years of the
experiment and weigh 10 pounds more than his genetically-identical brother
eating his almost identical diet. If this fat-trapping amounts to 20 calories a
day — still less than one percent of the calories A is consuming — that would
amount to forty pounds of excess fat over the course of the experiment. It
would still be too subtle of an effect to be observable in the relatively
short-term experiments done to date on sucrose consumption.
assuming this did happen, or at least could happen, it would lead us to some
other interesting observations as well. For instance, if A puts on this fat
above the waist, it will increase his heart disease risk. The more fat he
gains, the greater his risk of diabetes. In fact, depending on the size of the
effect, he might become diabetic over the course of the study. His brother
might not. A’s cancer risk goes up, as well, with his adiposity. So does his
risk of getting Alzheimer’s. All without consuming a single calorie more than
his twin brother did. In fact, if we run the experiment long enough, the
brothers might die of different diseases and one might out live the other by a
you believe this scenario is a possibility, even a likely possibility, as I do,
you still believe in the laws of thermodynamics. You’re still thinking like a
scientist (as my friend might say). But now, I hope, you can see what I mean by
calories being the wrong paradigm. If we believe in calories,as my friend put
it, then we believe that the twins end up identical, just as they started,
because the quantity of calories consumed in the two diets was identical and
it’s quantity that matters, not quality. What do you believe?
started with identical twins, hence the very same genetic make-up. We’ve fed
them diets of identical calories. We’ve made a relatively subtle change in
macronutrient composition. Do we end up with twins that are still identical; or
do we end up with one twin fatter and perhaps sicker than the other? And, keep
in mind, as I said, that both twins are limited to 3000 calories a day, and
we’re making them eat all 3000, so any addictive effects of the sugar, say, are
not relevant. (And if food reward characteristics are meaningful, they have to
manifest themselves via the periphery — increasing fat mass, for instance,
through central nervous system stimulation of adipocytes — not merely by making
us want to eat more. )
we can do a host of variations on this experiment. For instance, we can start
off with two villages — A and B. Each village has one of each pair of 5000
identical twins. So each sibling pair is identical, but the 5000 sets of twins
are as genetically diverse as any 5000 individuals chosen at random. We put 5000
siblings in village A and their 5000 twins in village B. Now we do the
same experiment on this population scale. We measure their energy expenditures.
We match intake to expenditure for each pair of twins. Then the twins in
village A all get ten percent of their calories as a sucrose-sweetened
beverage. The twins in village B get ten percent of theirs as a beverage with
glucose, not the glucose-fructose mixture that village A is getting.
let’s run it out for 20 years. Do villages A and B end up with exactly the same
number of obese villagers, exactly the same incidence of diabetes? Heart
disease? Cancer? If we run it out for decades, do the two villages have the
same mortality rates? The only difference in their diets is the type of
carbohydrate that’s sweetening their daily drinks. (And remember, this is a
thought experiment: each villager is eating and drinking precisely what we say
they’re eating and drinking because they’re under our imaginary control. No
propositions need be voted on. We get perfect compliance to our interventions.)
you believe in the primacy of calories, or you’re a sugar industry
spokesperson, then you believe that the two villages start off identical and
they end up identical. (Or, for the sugar industry spokespeople, maybe Village
A ends up healthier.) If you believe that one village is going to end up fatter
and sicker than the other because they’re experiencing different metabolic and
hormonal experiences for 20 years, then you’re thinking as I now think and
Robert Lustig has argued so publicly. It’s not about the calories; it’s about
what those macronutrients do metabolically and hormonally. And who knows what
else, maybe the sucrose has an effect on gut biota that the glucose alone does
not,or vice versa, and if the two twins develop different bacterial populations
in their guts, then this might induce a whole host of other downstream
differences that could effect their weight and health.
can play these thought experiments all day long. That’s the joy of gedankenexperiments.
They’re ridiculously inexpensive and we can do them fast. Twenty years in a
gedankenexperiment can be instantaneous in reality.
about this one: instead of feeding twin B (or village B) glucose instead of
sucrose, what if he (or it) got dietary fat. So now twin A gets ten percent of
his calories as sugar water — pick your poison, so to speak, soda or fruit
juice. Now we’re accelerating the delivery method in this thought experiment by
making sure these calories are digested quickly. Twin B gets liquid fat, say
heavy cream. watered down so that the energy density is effectively identical
to the sugar water. So we control for energy density, a factor that the
authorities think is key to weight gain. But we dramatically change the
macronutrient content of these 300 calories — glucose and fructose calories for
A, fat calories for B. Now the hormonal and metabolic responses to these 300
calories are entirely different. Nothing subtle about it. What happens over 20
years? Same body composition, same disease status because the calories are
identical? Yes or no?
if we play more extreme variations with the diets. Rather than play with just
ten percent of the calories they consume, let’s play with 50 percent of them.
Twin A (or village A) gets his (or its) calories as a standard American
diet, replete with 50 percent carbohydrates, of which, say, a fourth is sugar
or high fructose corn syrup as is about the case today in the standard American
diet. Twin B (or village B) gets a paleo diet or even a ketogenic diet, same
amount of calories, far fewer to almost no carbohydrates, far more fat. What
happens? Both twins (or villages) eat precisely the same amount of calories
(each or per capita) every day for 20 years. Do they end up identical. Is
village A healthier and leaner or village B or neither?
let’s change it up entirely, and this will be the last experiment I’ll suggest
for the moment. Rather than start with genetically identical twins eating
different diets and so generating different hormonal/metabolic responses that
way, let’s start with subjects who are not genetically identical, and give them
the identical diet. So we can use fraternal twins or siblings, or total
strangers as our subjects, but now feed them the exact same diet. We’ll choose
our subjects so that they’re the same age, to the day, the same height
and weight and they expend the exact same amount of energy every day (at least
when the experiment begins). They’re both equally healthy. And now we feed them
the same diet — intake matched perfectly to expenditure — with 10 percent of
the calories coming as sucrose. What happens? How do they change over the
twenty years of the experiment, given the exact same diet, precisely the same
calories, precisely the same physical characteristics, but different genetic
differences in their DNA means they’ll almost assuredly have different hormonal
and metabolic responses to the diet. Maybe one does a slightly better job of
metabolizing fructose in the liver than the other does. Maybe one secretes a
little more insulin in response to the glucose, or is a little more sensitive
or resistant to the insulin secreted. Maybe the gut biota in one responds
differently. Maybe leptin resistance develops in one but not the other.
Anything can happen right, because genes ultimately determine all these
responses and their genes are different.
we’re feeding them exactly the same diet — same quality and quantity
— but the hormonal and metabolic responses are going to be different. Their milieu
intérieur is going to be different. Maybe a little different
as the years go by; maybe a lot. We don’t know. They may start out
relatively identical in relevant physical characteristics, but little by
little, they’re going to diverge. Why would we expect them to end up with with
the same weight, same fat mass, and even the same chronic disease risk profile?
if all these things do end up different, would our belief in calories have led
us to the same understanding of what happened and why?
we could do this experiment in real life, it wouldn’t really matter what we
believe. Right? We just do the experiment and see how it comes out. (And this
is what NuSI hopes
achieve, albeit in far more realistic experiments.) Because we can’t do the
experiments, we can do these thought experiments instead and inform our
understanding. Time permitting, more will be coming in later posts.
last note before I conclude here. Let’s go back to our original experiment with
twins A and B and their almost identical
diets. Imagine, now, as I suggested, that A gets fatter than B and even
heavier, because of the effect of the sugar in A’s diet on hepatic metabolism
and insulin sensitivity and so serum insulin levels and fat accumulation in fat
cells (and maybe all those other factors like gut biota). But A is never able
to eat more to compensate for this loss of calories into his fat tissue and his
increasing weight, because we don’t let him: we’ve fixed his caloric intake. As
a result it’s safe to assume that A would be hungrier than B is for the
entire 20 years. B can eat to satisfy the metabolic requirements of his body; A
cannot. How would that manifest itself? Would A at least feel like binging on
occasions? Could we create a binge eating disorder that never gets to manifest
itself in this particular thought experiment, just by changing the
macronutrient composition of the diet?
can see how thought experiments can lead us to all kinds of conclusions and (at
least hypothetical) observations that might not be intuitively obvious
could go on. I’m hoping the point is clear.
back to my friend’s e-mail: Yes, I believe that calories are a useful measure
of the energy contained in the foods we consume and a useful measure of the
energy our bodies expend. (Just as I believe miles are a useful measure of how
far I have to travel to get, say, from Oakland to Los Angeles.) Yes, I believe
in the laws of thermodynamics and I believe, as I say in both my books, they always hold
true. That’s why we call them
laws. But, no, I do not believe that we can learn anything useful about why
people get fat or why they get the diseases that associate with getting fat, by
focusing on the calories they consume and expend. It’s not about the calories.