Hormonal & Appetite Response to Macronutrients

I came across this paper recently and thought I would share it here on my blog.  I think it is rather eye-opening as to the postprandial hormone responses to meals rich in each of the macros (and alcohol) and the ultimate effect on satiety.

This study was done in normal weight healthy humans (9 women, 10 men) in their early 20's.  They fed them a meal containing the same calories, but high in one of each nutrient.  Each subject was given each diet with a 4-8 week "washout" in between, a standard diet the day before each test day, and subjects fasted 10 hour overnight before testing.   Hormones, etc. were measured for 5 hours postprandially, and then were provided an ad libitum meal.   Here are the diets tested:

Unfortunately it would be impossible to keep all things constant varying so many parameters, but the high protein meal contained roughly 2.5X the 12% for all of the other meals.  The high carb v. high fat meals were relatively isoprotein with fat/carb percents flipping between the two meals at 65% for the enriched macro.  In the alcohol meal they essentially exchanged 23% of carb calories for alcohol.  

Below are some subjective assessments related to appetite and satiety.  Interesting, eh?  Apparently none of the differences reached statistical significance, but *if anything* they trended in favor of protein and carbs over fat.  It's interesting as well that the ad libitum intake was significantly different between men and women.  If anything, both fat and carb reduced future intake in the women but increased it in the men (not stat.sig., just trends folks).  

This next graphic at left is for blood glucose and lactate along with insulin and glucagon profiles.   At right of each are the "AUC's" indicating total 5 hour exposure.  The glucose profiles are predictable with mostly carb raising levels.  Lactate is increased by carb and alcohol to statistically similar degree.  Since these were mixed meals, albeit enriched in one macro or another, the insulin responses were not as pronounced as one might presume.  I think most often misunderstood or not well characterized is the glucagon response.  Glucagon is actually suppressed by the high carb meal, but it is increased considerably by protein, fat and alcohol.  A common "out" given to protein for it's insulinogenic properties is the fact that it stimulates glucagon while carbs do not.  Clearly it does, but so, too, do fat and alcohol. 

Next up we have the energy expenditure and oxidation rates of glucose and fatty acids.  Note that DIT = Dietary Induced Thermogenesis.  As reported in Nutrient Fates, alcohol is highly thermogenic!  In this study exceeding protein.  However at the same time, alcohol suppresses fatty acid oxidation moreso than even carb.  The DIT for carb and fats were essentially the same, which differs slightly from Jequier's factors as in Nutrient Fates.  This illustrates that except at extremes, manipulation of carb:fat ratios are unlikely to alter total energy expenditure.  I note that fat oxidation rates are suppressed (albeit to a negligible degree for protein and fat) following all meals!  So much for eating fat stimulating fat burning...  Comparing the carb and alcohol meals we see that DIT for carb is less than that for alcohol, and yet the alcohol consumers virtually shut down fat oxidation (as would be expected because of obligate hepatic alcohol metabolism).  So ... does fatty acid oxidation rate necessarily correlate with energy expenditure?  It would appear not.   Meanwhile, only carbohydrate stimulated its own oxidation considerably, and since all meals contained some carbs, we see that carb oxidation is increased after all meals.  

And what of the mastermind hormone leptin?   I don't see any "spiking" going on ... unless you consider the alcohol-induced anti-spike!  Maybe there's something to this Spiked Leptinade after all ;-) ... or perhaps the "hard stuff" is the anti-Leptinade!

Clearly leptin is not a postprandially stimulated hormone in this study.  Yeah, carbs seem to suppress it the least in the postprandial period, but mostly it's carbs for which the leptin-to-FAoxidation correlation falls apart.  

Lastly, let's look at postprandial lipids.  Despite the alcohol meal containing ~38% of the fat of the fat meal, the postprandial AUC for circulating triglycerides is almost equal to that of the high fat meal and vastly exceeds both the carb and protein meals containing roughly equal and slightly more fat respectively.   Moral?  Don't drink and eat fat!  How about that all important availability of NEFA?  You know, the stuff your insulin is starving your mitochondria of causing your metabolism to be so effed up?  Well, we note that all meals ultimately lower NEFA levels.  Somewhat surprisingly (though apparently not significantly) protein seems to lock away your fat the most (and we know how fattening protein is!).  Sure carbs play the role of metabolic bully (bad, bad carbs!!) and, as might be expected so does alcohol.  But it is worth noting that even the fat meal reduces NEFA somewhat.  But fear not peeps, as you can see, the fats are released by hour 5.  And cheers!!  If you've had alcohol, you're on the way to fat burning in hour 6!!  I note that I've omitted the incretin data (GLP-1, GLP-2, GIP) , please feel free to check it out!

Yes, I realize there's not much original or groundbreaking in this post.  But I thought it might be helpful to share it and put the graphics out there.  As a Ricky Martin fan once said "pictures are worth more than a thousand words".  The next time you read claims about what this or that macro does to this or that hormone level or your metabolism, remember these images!


Anonymous said…
'Moral? Don't drink and eat fat!'

NOW you tell me...
oh dear, won't Leptin Man (Neurosurgeon! by day) be disappointed
Swede said…
That's neat to hear about the alcohol being the highest in dietary induced thermogenesis. It certainly meshes with my experience!

Now that it's football season, on Sunday's I usually eat a decent breakfast and then anywhere from 15 to 20 beers for the rest of the day. Even at 150 calories a pop, as long as I don't eat anything after breakfast I always weigh less on Monday than I did on Sunday.

Beer is often blamed as blamed as a diet saboteur, but I suspect that is because it is usually accompanied by fat and calorie rich foods (nachos, chips and dip, hot wings, etc...).
Lerner said…
The advice I always see out on the web is to have that wine with food so as to kind of cushion the flood of alcohol into the system. Yet it did seem to me that TAG elevation would be most enhanced with food. Besides having it with fat, I'd suppose the same would be true for the 'massive' carb feeding a' la that of the Acheson study. The calories in this study were ~ 600 and 700 respectively for women and men.

I supposed everybody learned after Tim Russert that alcohol raises TAG. But since alcohol breaks down to CO2 and water, how does it raise TAG? Does the same effect occur with alcohol only?

ethanol-> acetaldehyde-> acetic acid-> AcetylCoA-> H2O and CO2
Lerner said…
There is an Oprah-ish doctor advice tv show called "The Doctors". Today was a segment in which the ER doc (Travis) who is a host explained how insulin works: it attaches to blood glucose and then is able to thereby usher the glucose into cells. There was even an animation of that. Really.


...then click "Type 1 vs Type 2 Diabetes". It's only a few short minutes, and might be gone by tomorrow.

To be fair, to a clinician the MOA really doesn't matter. Even so, I'd like to nominate him for a Taubesey Award, for being muddled about mechanisms.
P2ZR said…
Hi Evelyn,

Thanks for the tidy breakdown of the data (and attaching most of the graphs)! As a young person, I wish I could have Swede's experience (15-20 beers and weigh less the next day?!), but there's only so much a petite female can wish for ;)

With these recent examinations of macro fates and mitochondria, have you seen this: http://www.marksdailyapple.com/managing-your-mitochondria/ ? I think the newfound zeal for "[beastly] fat-burning" may require a good dose of Carbsanity....
Quarrel said…

without knowing anything about Swede, I think it's a fair bet that they aren't a petite female. You may get very similar results (intoxication wise) on 7-10 and a similar result weight wise :)

(Swede, despite the name, may also be American where the beer is weak as piss - as they say :)

More on-topic, while I agree that Mark's latest is interesting, his diet recommendations in general (and the PHD for that matter), both seem to gel pretty well with Evelyn's 'sanity' to me. Low-carb compared to a SAD is pretty similar to high-carb (ie 50g of carbs!) to the LLVLC crowd. They're mostly voices of moderation like Evelyn.

Mitochondria posts do seem to be sweeping the paleo-sphere though :)

CarbSane said…
Welcome to the Asylum Sarah! I just now realized you posted here once before ... twas a busy time, but still how I missed your hilarious comments I'll never know!

I just read Mark's piece. Hmmm.... The obese are amazing fat burners. Somehow I don't think that's what he's getting at! >:) So many mitochondriacs these days, so little time. Sisson seems to have somewhat moderated his starch carb stance over time. Back in 2009-2010 I could have sworn Grok foraged only for non-nutritive fiber containing non-animal foods! I still think he needs to change that over 150g/day leads to insidious weight loss nonsense though!
CarbSane said…
@Swede: From my younger drinking and dieting days, the "wisdom" was always it's not the booze that's fattening, it's what you eat (drink) along with it. It may not be the healthiest approach overall, but eating as little as possible when someone is going to imbibe is probably a good idea metabolically. 15-20 eh? Wow! I thought I had a high tolerance! LOL
Sanjeev said…
> So many mitochondriacs these days, so little time


"managing your mitochondria"

yeah, fire up that iPod app, right after you invent fire, then the wheel, then club your future mate on the head to drag back to the primal lair.

Why, oh WHY do I smell a Tony Robbins / Brian Tracy / Mark Sisson crossover? "One Minute Mitochondria", or "who moved my mito-cheese". I'd buy one of those. Or at least point & laugh.

Mark could teach those guys a thing about logo design though ... that caveman doing jazzdance/ballet/Riverdance/Bangra fusion is growing on me.
Sanjeev said…
Reading Sisson's fish oil post reminded me of a thought I've been working on ... I'm getting suspicious about this "eat whole food" thing.

I've been reading more and more about how observational studies pointed to some agent (say fish, or garlic) that supposedly had health benefits. Some fraction's isolated from the agent, tested via intervention studies that work, then later with bigger and more carefully controlled intervention studies and these fail, and the fallback position is "eat the whole foods (fish or garlic), not the fraction.

Am I missing something? The suspected beneficial food has NOT been studied using carefully controlled intervention studies.

So what's the thinking here? The "cofactors are needed for the oil or garlic fraction" thing is JUST A GUESS until the whole food is tested. Isn't it just as likely that some other un-noticed difference between the populations in the original observational studies (something other than the fish or the garlic) was "culprit" ?

This one form of "whole foodism" is beginning to smell fishy[0] to me ... like supernaturalism (magical thinking) in drag.

[0] and, yes, garlick-y
@ Sanjeev "that caveman doing jazzdance/ballet/Riverdance/Bangra fusion" ...if jazz hands are involved, I'm in!
Sanjeev said…
I'll join you


If you like arrhythmic[0], flailing dance partners and your feet can survive being frequently trod upon ...

[0] not to be confused with oy-rhythmic (spelt eurhythmic)
CarbSane said…
Love it!

How about dancing to "All you Zombies" ... Yeah, they were the Mitochondrialites!!
qw said…
Do you think the outcome could have been different if the subjects had followed the diets for some time before they were tested?
qw said…
I meant that if the subjects had followed diets with the same macronutrient distribution as a test meals for some time before the tests, do you think the outcome could have been different then?