Let's play Concentration!

While I was writing the Essential Carbohydrate post, I got to thinking about another canard often bantied about in low carb circles.  That being that our circulating blood glucose amounts to only about a teaspoon of sugar.  Here's how that calculation goes:

Another way of looking at this is that for a normal person, a "glucose spike" to 125 mg/dL amounts to an increase in dissolved circulating glucose of perhaps 2g (85 mg/dL - 125 mg/dL) and a glucose intolerant person might see 10g dissolved glucose in circulation (200 mg/dL)  following a meal.  This small amount compared to the "large amounts" of carbohydrate in even a small serving of pasta or rice is often seized on by low carb advocates to foster carbophobia.

Now, nobody would argue against the fact that glucose is a signalling molecule in human metabolism.  But there are other circulating signalling molecules such as amino acids, but I'll not be dealing with them in this post.  The third class of nutrient signalling molecules are the free fatty acids, aka non-esterified fatty acids, NEFA.  

So let's do that calculation for NEFA.  The calculation is a little more complicated as usually NEFA are reported in molar concentrations and NEFA are a mixture of different fatty acids, but we can get a rough idea here using palmitic acid as our fatty acid.  Typical fasting levels are 400 µmol/L and palmitic acid has a molar mass of 256 g/mol (I'm going to use 250 to make my math a bit nicer).  Here's the math:

I can hear the clamoring in the audience ... but CS, CS!! ... NEFA is not from dietary fat, you know that!  And indeed I do.  However, you have only a half a gram of non-esterified fatty acids flowing in your blood in the fasted state.  This is the level that contributes to the stimulation of basal insulin secretion.   It is conceivable for dietary fatty acids that escape the esterification process to directly add to the circulating NEFA concentration.

Behold the PB&C shake from Cold Stone Creamery:  And I'm going to use the "Like It" smallest size that weighs in at only 1322 cals* (the largest size tops 2000!!).  This shake contains 82g of fat and 119g carb (104g sugar) ... oh, and a whopping 27g protein!  FWIW, this works out to 56% fat, 36% carb, 8% protein.   (* site claims 1280 cal but using macro grams and the 9/4/4 common values I get 1322)  
So you get one of these concoctions.  What happens in a normal person?  Well, you're certainly covering those carbs with enough fat ;-) .  One can presume that the 15 "non-sugar" carbs are actually a sugar after all, lactose, but even if we count those and 1/2 the sugar grams, you've ingested 67g glucose carb, and your Lustigometer registers just into the fructox zone at 52g.  The whopping fat load gets packed up into chylo and hopefully whisked out of plasma in relatively short order thanks to both insulin and ASP.  The insulin also suppresses NEFA release from adipocytes.  BG stays normal, NEFA stays normal.   In this study on normal post-menopausal women (I note the rather higher fasting NEFA) we see what happens to insulin, glucose and NEFA following a large breakfast  (78g carb, 41g fat, 17g protein, about 750 cal), and a cheeze pizza lunch five hours later (68g carb, 6g fat,  21g protein , just over 400 cal).  Of note, it is quite possible that the relatively low carb high fat PB&C might not elicit the appropriate trapping as seen in this case.  (Note: the various curves are for different test oils 40g consumed in morning meal).

Note how the NEFA is shut down appropriately here despite the morning meal containing 41g fat.

But how about the metabolically damaged person consuming the PB&C?  For an obese person with insulin resistance, insulin pours out of the pancreas and depending on the degree of compensation and IR, glucose gets cleared from the blood.  The fat and fructose will elicit a transient IR that exacerbates that already existing.  But the 52g fructose is not likely to overtax the liver, but perhaps it makes a couple of grams of additional fat from it.   What of all that fat?  This person's plasma is bound to be cloudier than Carly Simon's coffee and surely the adipocytes would love to get their grubby hands on those fatty acids.  The scenario at right (from Frayn) is set in motion -- just as it would be for the metabolically normal person -- but impaired "trapping" in insulin resistant adipocytes leads to more NEFA "escapees" into circulation via the path on lower right of the diagram.   Further, the insulin resistant fat cells do not answer the suppression call insulin is making on HSL.  This results in inappropriate NEFA release from the fat cells.   Thus, such a person would be starting out with slightly elevated glucose levels and NEFA levels, and it is likely that the NEFA are elevated to a greater extent than the glucose.  Now add to that the inappropriate amounts of NEFA released from the fat and you're "starting out" even higher in terms of the level of signaling molecules before we consider the added NEFA from the esterification escapees.  

In other words, if this same person had chosen a slim smoothie instead of this caloric abomination, they would likely still have the elevated postprandial NEFA, but with less sugar, perhaps avoid any pp hyperglycemia.  But assaulting their body with the PB&C -- if even 1% of the fatty acids from the 82g ingested escape, that's 0.8g NEFA.  Now ... yes, this doesn't all happen in an instant, but glucose spikes and is cleared rather rapidly whereas dietary fats last much longer.  Indeed what doesn't get taken up the first time around (chylo remnants) is repacked by the liver and sent back out (VLDL).  The levels remain elevated longer, including perturbations in NEFA.  

As Frayn stated in this study, blogged on here, the obese experienced a slightly muted NEFA suppression after the first meal.  But the real problem was that:
adipose tissue fat storage after meals was substantially depressed in the obese men. This was especially so for chylomicron-derived fatty acids,
It's also been demonstrated that low carbohydrate meals exacerbate this problem.

So ...  You have a deranged carbohydrate metabolism.  Even Taubesians attribute this, ultimately, to a deranged fat metabolism and dysfunctional fat cells.  So you go on a low carb diet and get the blood glucose levels under control.  But at what "signalling" and metabolic expense?  If you're obese and IR, you already don't properly suppress NEFA release from fat cells after a meal, and you've got a problem with chylomicron clearance!  But it's worse from a signaling POV.  With glucose the clearance of the signal is slowed.  With fats, the impaired clearance is akin to converting chylo to signalling molecules (NEFA) --> metabolic mahem. Whatever the problem for the obese/IR, it can only be made worse, IMO, on a VLC diet if caloric reduction and weight loss does not result.

So ...

The teaspoon of sugar in the blood thing is interesting, but unless one becomes a diabetic, their BG isn't likely to be influenced in a chronic fashion that much from consuming many times that amount.  But normal dietary fat consumption will certainly impact NEFA (and likely BG) considerably well before a diabetic state develops if it ever does.  When fixing/treading lightly on one metabolic signalling molecule, it's worth remembering not to do so by making the other worse.


MM said…
Wow, only 0.5g of fat is circulating at one time? That's only 1/8 tsp of olive oil for example. Even if you double it you get a whole quarter of a tsp. How do we ever managed to burn pounds of fat??
CarbSane said…
Hi MM, well we do have more fat in the form of triglycerides - that get broken down by lipases associated with various cells and taken up -- but even that is not a lot. The 0.5g is for 400 micromolar NEFA - and even that is not totally "free" as it is attached to albumin. How do we lose pounds? Well this is constant in the non-fed state and they flow into the cells constantly. The trig/FA cycle releases them all the time from adipose and much is taken up and esterified (temp storage) in the cells while the rest goes back to adipose.

It tis a number to boggle the mind, however, eh? That low sustains fasting metabolism.
bentleyj74 said…
That's kind of scary if there is indeed anything to either of them [tsp of sug or 1/8 tsp of fat]

If I were strictly looking at ratios I'd say it favors carb metabolism.
Duffy Pratt said…
MM said "How do we ever manage to burn pounds of fat?"

It helps me to think about the actual mechanisms by which we gain and lose weight. The Calorie In/Calorie Out explanation is derivative, and contains several hidden assumptions. The law of conservation of energy, taken by itself, has nothing to do with weight. Outside of atomic reactions, the law of conservation of mass and the law of conservation of energy are distinct from each other. Atomic fission does not occur with any regularity in the human body, so there is no conversion of matter to energy.

How do we gain weight in our bodies? By eating, drinking, and inhaling and perhaps in some other minor ways. How do we lose weight? By pissing, shitting, sweating, breathing and some other minor ways as well. The main thing to remember is that the major mechanism for weight loss is exhaling. Every time one inhales, the body takes in a quantity of O2 molecules. Every time one exhales, the body gets rid of a similar quantity of C02 molecules. It's the difference in weight of the carbon dioxide that is the primary driver of weight loss.

The weight of the free oxygen in the body cannot be very much. How much do you think one inhales over the course of 5-6 minutes? I don't know the answer, but it's got to be very small, and thats basically all that we can store.

The amount of burnable stuff in the blood doesn't have to be much greater than the amount that that 5-6 minute supply of oxygen can burn. The miracle is how well balanced things must be to keep the supply of burnable stuff available for the amount of oxygen thats taken in. At any one time, its all very small and extremely finely tuned, but over time it adds up.

Finally, the other miracle is how amazingly well a functioning body does at eliminating the burned and thus useless waste that it produces. The reason the calorie in/ calorie out works is primarily a function of how efficiently we eliminate waste through breathing, and how relentless the body is at storing potential heat energy as fat molecules.
Tonus said…
As an aside, medium or large ice cream cups from Cold Stone have been my don't-give-a-damn "cheat treat" this summer. If anyone has ever wondered whether you could make something taste more "sugary" than pure sugar, visit a Cold Stone Creamery.
Anonymous said…
There was a post on LLVLC that I read a while ago that I can't find now but the crux of it was that there is 5g of dissolved glucose circulating at any given time in the bloodstream. When you are low carbing your brain can function on ketones for 40% percent of its energy needs but there is still an essential requirement for glucose which can be obtained by glucogenesis. As I remeber in the post when you are low carbing how does the body stop this 5g of glucose from being used by the muscles and other tissue instead of the brain. Before the glucose reaches the brain in the low carb state it could be used by other tissue/muscles depriving the brain of this essentail glucose. There was a way that this doesn't happen and it was to do with receptors or valves in muscles or cells which block the absorption of glucose in the low carb state and ensure it goes to the brain, what mechanism would this work by? I am trying to find the origanal post on LLVLC
CarbSane said…
Welcome saima! This is what is often called "physiological insulin resistance" which is the body's glucose sparing mechanism during fasting/starvation. VLC mimics the metabolic state of starvation (glycogen depletion, increased ketone production, gluconeogenesis, glyceroneogenesis) and would set the physio IR in motion so to speak so that glucose produced is mostly reserved for the brain.

I've seen this type of IR described as "the good kind" -- a term and description folks seem to have made up and I've seen little or no evidence for such in the literature. Insulin plays roles in the body besides glucose homeostasis and IR is IR no matter the underlying mechanism. Physio IR is intended to be transient, or to ensure survival during times of famine.
Diana said…

One of the perverse attractions of LC for me were the words "mimic" and "starvation."

I didn't want to starve - having shudderingly remembered my binge and starve days of college. But I did want to mimic its effects.

There was something undeniably attractive about the word "starvation."

Is that effed, or what?
CarbSane said…
@Tonus: Hubby laughed at your comment. So true!

One summer I used to pass by Baskin Robbins on my way home every day. Stopped a lot for peanut butter and chocolate ice cream more days than not. A single scoop (OK, sometimes a double) cone. I was thin that summer :D
CarbSane said…
Outside of atomic reactions, the law of conservation of mass and the law of conservation of energy are distinct from each other.

What do you mean by this?
Duffy Pratt said…
I mean that matter converts to energy only in an atomic reaction. In Newtonian physics, the laws of conservation of matter and conservation of energy were distinct from each other. Einstein changed that insight, and merged the two laws into one.

You can increase or decrease the energy or potential energy of something without changing its mass. Weight, at the first level, is a question of mass. The consequences of energy balance for weight loss is derivative. We gain or lose weight because the net mass of our bodies change. That change happens to accompany a change in energy balance. But the weight loss results from the loss of mass, and not directly from the conversion of potential energy into heat. (A colon cleanse will lead to weight loss, and that weight loss may have very little to do with the number of calories lost as a result. Same goes for an amputation or surgical procedure. My dog lost almost 4 pounds when she got spayed -- almost 20 percent of her body weight. That certainly had almost nothing to do with calories. Similarly, I can imagine an organism that failed to excrete its waste and just grew with it, kind of like the Blob in the terrible Steve McQueen movie. For such an organism, calorie in calorie out would say exactly nothing. It works because we are so efficient at eliminating waste and storing fat.)
CarbSane said…
This is a very strange post Duffy. Sorry.

Weight = mass x acceleration due to gravity ... so weight is essentially mass on the planet earth.

I am also careful to distinguish true "weight loss" as being actual body mass that must be "burnt off" or "broken down" to exit the body ... as opposed to water weight that can fluctuate irrespective of energy status but within limits. Indeed that is what mostly comprises the "outperformance" by LC diets in early stages. Perhaps the obese person or someone suffering from edema can gain or lose 10-20 lbs of water, but for most of us it's more like a couple of pounds up or down. Too much down and you're dehydrated and perhaps dead.

So please, let's not cloud the issue by talking weight in this manner.

CICO is the same as MIMO for chemical energy containing molecules.
Duffy Pratt said…
I agree with the conclusions. I brought it up in the first place because I wanted to make clear that we mainly lose weight by breathing. That makes it easier for me to grasp why it can be such a seemingly slow, steady flow. And also that it can happen with such seemingly low supplies of fuel in the blood.
Duffy Pratt said…
Oh, and your water weight loss estimates are a little conservative. Even when not obese, I've lost 10 pounds or more of water weight sometimes. I've observed this by weighing myself before and after a long bicycle ride (70 miles +), or after a really hot Bikram Yoga class. And this is without either obesity or edema. Sheer size also matters. I can probably hold 4 pounds of water in my stomach with little difficulty.
Diana said…
"I brought it up in the first place because I wanted to make clear that we mainly lose weight by breathing. "

You mean, as in breathing hard? Like when you exercise? Expend calories?

Please elaborate.
Duffy Pratt said…
Yes, in part. When we exercise, we increase the rate of fuel consumption. This simultaneously creates the need for increasing the flow of oxygen, and for getting rid of the carbon dioxide that the burning of the fuel creates. Exercise thus increases the rate of the mass deficit that comes from breathing.

But its not just exercise. As I understand it, basal metabolism measurements primarily involve getting a person to stay at rest, and then monitoring their breath. What I'm saying about O2 and CO2 is a pretty gross oversimplification. But it does make the point.

Here is an article about basal metabolic rate and pulmonary function:

Diana said…
So I'd better get my azz in gear and move. And get my muscles bigger & toned so I can do this more efficiently.

Sounds right to me, Duffy. Glad we agree that expending calories is a good way to burn fat. CICO. ELMM. Gotcha.
Sue said…
CS, so do I have this right?
The fat is locked into the fat cells but escapes more readily out of the chylomicrons?
Quarrel said…

(yes, I'm very late to this, but oh well)

"The law of conservation of energy, taken by itself, has nothing to do with weight. Outside of atomic reactions, the law of conservation of mass and the law of conservation of energy are distinct from each other. Atomic fission does not occur with any regularity in the human body, so there is no conversion of matter to energy."

This just isn't true, and is why CS is confused.

You do not need atomic fission to convert mass to energy.

There are a bazillion (I counted) chemical reactions in the body that are either endothermic or exothermic. This essentially sees us converting matter to energy (heat, basically) or vice-versa all the time. Want to keep your body warm? You'll find an exothermic reaction as the cause.

So many reactions in the body see us break molecular bonds and/or form them, with energy out/in as appropriate.

Other than that, yes, we all have a BMR and it really matters. Because of this, for most people, weight loss is a matter of energy (calorie) restriction, rather than energy expenditure (exercise).

(Pet peeve- you'll see so many people say you burn X calories exercising for Y minutes. They rarely tell you the number net of your BMR, because then you'd discover that your muffin just cancelled our all your exercise, and you could have just sat on the couch for most of your "burn".)

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