Fat Futile Cycling from Carb Excess - A more lay-person friendly version

I think I misunderstood the confusion many seemed to have over this recent post:

One of my readers posted a link to that post over at Mark Sisson's forum ... the responses were ... erm ... interesting.  Perhaps I'm not worthy of "writting" (<- commenter spelling, not mine) on this subject, but I can tell y'all that I'm definitely not some "poser" with an agenda to oppose low carb.  I'm not sure my diet these days qualifies as low carb in the VLC circles, but it certainly fits in with Sisson's 80/20% primal plan.  And I did lose most of my weight eating VLC most of the time.  

In any case, apparently I presumed a bit more background on this topic than I should have.  So, here goes the laymen's terms explanation.

In LC circles, there are many proponents of a so-called "Metabolic Advantage" of low carb dieting.  According to this theory, people lose more weight eating more LC calories compared to an LF diet.  When carefully controlled studies either disprove this, and perhaps give a slight edge to the carbs, the debate is predictably shifted to the notion of "but you won't gain weight on LC".

Taubes has stated this, Atkins implied this, and in their recent book, the Drs. Eades basically stated this as fact.   Before I get to the study here, I think it is worth stating for the record that, whatever our metabolic behavior in the context of OVERFEEDING (in most studies, gross, sustained overfeeding), it has little relevance to metabolic behavior in the context of underfeeding (which is what any weight loss regime ultimately is).  When we overfeed 3500 calories it doesn't translate into exactly a full pound increase in fat mass, this much is pretty clear, and to be expected.  But we WILL gain weight.

Our bodies defend rather strongly against starvation, less strongly against surplus/excess.  Perhaps this is because early humans didn't have to worry about excesses?  A logical evolutionary explanation.  But we do possess a hormonal regulatory system that tries to adapt and maintain homeostasis.  Two that are often mentioned are futile cycling and uncoupling (two mechanisms often confused with one another).  Let's define them:

1.  A futile (metabolic) cycle is one that occurs with no apparent reason to "do work", IOW harness the energy for some "meaningful" purpose.  I'm not a big fan of the "futile" designation, because these cycles do serve an important function -- maintaining body temperature -- but I'm not the one who coined that term.  You can think of futile cycling as riding a stationary bike, you're pedaling away, but not going anywhere.

2.  Uncoupling:  Our mitochondria can be loosely analogized to a rechargeable battery.  The chemical energy produced from the metabolic reaction "charges up" the battery.  However it is conceivable that we could over-charge a battery (yes, most devices these days have built in protection mechanisms to prevent this).  Uncoupling proteins are our metabolic protection.  If our mitochondrial batteries are overcharging because of too much energy used to charge them up, uncoupling proteins essentially open channels to discharge them.  This would be like having a rechargeable battery plugged in but having some sort of shorting device across the terminals at the same time dissipating part of the charge.    In thermogenic fat -- aka brown fat, or brown adipose tissue, BAT -- uncoupling is part of the normal operation to generate heat.  This type of fat represents a significantly greater proportion of total fat mass in small animals like the rats and mice used in metabolic studies.

Both of these mechanisms have been demonstrated to exist to SOME degree as an adaptive mechanism to temporary "flooding" of the metabolic works, e.g. in cases of overfeeding.   They both "waste" energy.  From an evolutionary POV, there would seem to be no advantage to such mechanisms kicking in with modest excesses.

In rats and mice, these apparently kick in to a greater degree than has been shown in humans.  Evidence of futile cycling would be an increase in body temperature.  In one human study, subjects eating around 600g fat/day became sweaty ... that's a lot of fat overfeeding.  (FWIW my math on this demonstrates the limits ~ if it's wrong I welcome comments correcting it.  A calorie is the amount of energy required to raise 1 g water 1 degree C.  We're mostly water so it's not a bad approximation.  Food calories are actually kilocalories so burning 1 food calorie will raise 1 kg of your body 1 degree C.  Let's say you weigh 100 kg, this means if you convert an excess 100 cal, your temp goes up from 37 to 38C (98.6 to 100.4 F).  Just another 100 cal and you're up to 102.2 F and 100 more than that (300 total) and you're in danger zone!)

In any case, it is generally asserted in LC circles that both (1) and (2) occur for low carb excesses (e.g. excess fat in the absence of carbs).  What was surprising about this study was that it demonstrated a futile cycle that is initiated by CARB excesses.  The cycle itself is a "fat cycle" -- lipogenesis (synthesis of fatty acids) and lipid oxidation (burning of the fatty acids) -- but it is not initiated by or "wasting" excess dietary fat, but rather dietary carbs. 

This simply pokes yet another hole in the theories of some metabolic advantage of low carb diets as well as further demonstrates what Jequier summarized in Nutrient Fates:  excess carbs do NOT add significantly to fat STORES.  This futile cycle goes a long way to explaining why.

A somewhat related final note regarding the uncoupling:  This occurs in the mitochondria well after the point of Acetyl CoA is fed into the Krebs cycle.  As I've mentioned many times in discussions about "fat burning" vs. "carb burning" for energy, we're talking a small amount of the energy obtained from either macronutrients via fatty acid oxidation and glycolysis.  The majority of the energy (ATP) comes after this through Krebs and even more from the electron transport chain.  I have yet to find scientific support for the claims that uncoupling is enhanced with LC diets vs. HC diets. 


David Isaak said…
This isn't about futile cycles or overfeeding, but it does touch on the metabolic advantage issue:


If I've done my math correctly, I think they are saying that on average a low-carb regime tight enough to demand gluconeogenesis burns an extra 81 Calories a day as compared to an isocaloric diet including ample carbs.

Not huge. But as large as that proverbial "extra slice of bread a day" that supposedly packs on 8-10 pounds a year.
CarbSane said…
Yes Feinman and Eades often bring up the metabolic cost of gluconeogenesis. Thing is other processes are down regulated, like de novo lipogenesis which, many forget or ignore, is also an energy requiring process. There are likely a myriad of adaptations. I've not seen the math, but I've also heard statements that certain cells use ketones more efficiently than glucose. That means they use less!

It would be interesting to measure RMR before and several years after someone goes hard core low carb for several people in some sort of controlled verifiable manner. Not likely feasible.