Friday, December 28, 2012

Insulin: Are you hungry? Part 2

Well, over the years I have made the occasional serious blooper on Hyperlipid.

Perhaps the worst of these, to my intense shame, is the acceptance of insulin as a satiety hormone. This is complete bollocks and, thankfully, some deleted-expletive person in obesity research has finally opened my eyes to this. The gift was from Dr Guyenet of course. This is how he convinced me that insulin is not a satiety hormone:

Let's feed some rats standard crapinabag and inject one group with nothing much, one with glargine insulin and another with detemir insulin. But here's the trick. Because we know that hypoglycaemia triggers overeating and the overeating causes weight gain, let's limit the insulin dose to one which does not cause hypoglycaemia... No overeating, active satiety hormone, weight loss...

Because we have been (mis)informed that insulin is a satiety hormone we would expect the insulin-injected rats should eat less, weigh less blah blah blah. What really happens? This does:

I've seen this paper cited as showing insulin can reduce weight gain. By Dr Guyenet no less. Who didn't mention the graphs. Which are core to the paper.

Technically this shows that insulin does bugger all to food intake and fat storage. This is hardly surprising as giving a sub hypoglycaemic dose of insulin will simply attempt to lower blood glucose which will be avoided by reduction of endogenously produced insulin. Total insulin will stay the same. There will be subtleties of peripheral administration vs portal secretion but I guess these are a bit too subtle for this study. There are also fascinating differences in duration of binding of detemir insulin to the insulin receptor vs other insulins. Not surprising as it has a socking great fatty acid tagged on one end but that's another set of stories.

Ah, but what about the effect of detemir insulin on limiting fat gain of rats fed toffeefudgecheescake, aka D12492?

We are talking Fig 3 parts b and e here:

Okay, we're now utterly convinced that insulin limits weight gain. Well, detemir insulin does. Of course glargine insulin doesn't, as Dr Guyenet forgot to mention when citing this paper. It produces a non significant increase in weight over vehicle treated controls.

Just for a giggle, consider changing the grams to kgs on graph e and imagine these rats as humans. Given a group size of 6-8 leading to statistically ns changes in fat mass, would you consider 5kg fat mass gain (a ns change) on glargine, without eating any extra, non significant? Biologically? In dress size? Tee hee.

Now let's look at section e in a little more detail.

The study is very, very carefully set up. The insulin and the D12492 were both started on the same day. It is utterly convincing (to me) that detemir insulin limits weight gain IN THE FIRST 7-10 DAYS of D12492 feeding. From day 10 onwards the fat mass does not change in the control, the detemir or the glargine groups. Not even a trend. A bit like the crapinabag groups demonstrated throughout. In fact, identical to the crapinabag groups. Where's your satiety Guyenet?

Now here's a thought experiment. Let's pretend that all rats were fed D12492 from day 0 to day 10 without injected insulin, so became equally obese with a fat mass of 65 grams, same as the controls on day 10. From day 10 onwards all groups then received their respective insulin or vehicle for four weeks.

Would the fat mass have changed from the 65g starting weight? Of course not, look at the last weeks on graph e. These people are not stupid, though they do like to give that impression.

From this study the follow on question has to be: What is the difference between detemir insulin and either endogenous insulin or glargine insulin during the first 7 days of feeding D12492 to rats?

We all recall from the paper from the Schwartz lab featuring the world's greatest mis-citation expert, that the first few days of sucrose/fat feeding produces an acute inflammatory lesion in the hypothalamus of rats which get fat on D12492. If I had to guess I would suggest detemir insulin limits this injury. How and why cannot be guessed at from this paper but needless to say groups working with gold thioglucose injury have considered what factors influenced hypothalamic injuries. That leads to far out speculation, so I'll limit this post to what Guyenet's citations really do show.

They show that physiological insulin does NOT suppress appetite. Are you surprised? Me neither.

Of course an increased dose of insulin might suppress appetite. But this would need a glucose infusion to maintain life, which would promote DNL in adipocytes and inhibit lipolysis. No hunger while you gain fat. You have to wonder what the point of the above study was, excepting it supports a grant maintaining position and is a self justification for a bizarre mindset.

I also notice Guyenet re-cited this crap. Doesn't he read Hyperlipid????? Giggle... That was a rhetorical question!

Less rhetorical is to ask whether he has actually read the Vanderweele paper at all, particularly Fig 4 of the paper and whether he has reverse engineered said Fig 4 to see the problems with the conclusions of the paper!

Finally he has cited a drug study using an insulin mimetic, not insulin. Well, bully for insulin mimetics. With an insulin mimetic you can mimic lethal doses of insulin without all that inconvenient death. The body does not produce lethal doses of insulin under physiological conditions. If you want to know about physiological doses of insulin within the CNS I can just quote this paper. I feel the authors are being just a teensy weensy bit over the top in their deprecatory attitude to the "centralinsulinisasatietyhormone" brigade. But I can understand why! Here's my fav quote:

"To reduce the likelihood of pharmacological effects of the insulin doses administered, we choose a dose of insulin that is more than 15,000–fold lower than those commonly used for ICV [third ventricle, CSF] insulin infusions"

That's about as rude as you get in Cell Metabolism! You can't use the word "pillock". Drug doses (pharmacologic) of insulin produce drug effects. If you give only physiological dose rates you get physiological effects! Now isn't that amazing?

Oh btw, at physiological levels brain insulin increases peripheral lipogenesis and decreases lipolysis. Did you think insulin would do the opposite through the brain compared to what it does in the periphery?


A more believable scenario is that ATP generation within the brain using glucose metabolism, facilitated by insulin in those areas responsible for energy sensing, does occur. But this combination of glucose and insulin will also store fat, as it should, when it occurs post prandially. Which is exactly what excess energy sensing should signal. Insulin without the glucose is pharmacology, unless you suffer from reactive hypoglycaemia.


BTW I notice over on Woo's blog that there has been some discussion as to whether Dr Guyenet is just dumb or being very deliberately misleading, ie conspiring to mislead. I don't do orchestrated conspiracy theories. I don't really do the financial drive thing either, not for some body who is still as wet behind the ears as Dr Guyenet certainly is. No, for a junior post-doc it has to be:


He has the whole of the knowledge base of the Schwartz lab at his beck and call and the above three citations are the best dross that the Good Doctor can come up with... But still he believes! Stupid.


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Bill said...

iesnabo19I hate meeces to pieces.

As a layman I can't understand why mice are dragged up to analyse dietary issues ad infinitum.

Surely unless you have serious metabolic issues, just eliminating grains, minimising sugar and making sure that grass fed saturated fat is abundant in your diet, that's the holy grail.
Why are prison volunteers not used in dietary studies with incentives for participating?
Let's have some practical innovative trials involving human beings, instead of lab rats and mice. Please.....??

Beth said...

Who is Woo (as in " I notice over on Woo's blog"). I'd like to go read what he says.

Thanks, Beth

Sidereal said...

Thank you for taking the time to read the fake references and dissect them for us. Frankly, I don't bother with anything Guyenet writes anymore; way too much deliberate misrepresentation/lying and/or lack of understanding of primary sources going on over there. I just find out from the Woo when he has said something particularly egregious; she's usually on his case pronto. ;)

Just goes to show you how these days a PhD is a worthless qualification. I have known people even stupider than Guyenet who managed to obtain PhDs. Granted, mine is a discipline lacking any intellectual rigour (psychiatry) but still, a PhD is a PhD and you should be up to scratch. Unfortunately, graduate schools now exist for the sole purpose of providing free or very cheap (below minimum wage) labour for the universities. Because of this, science has become very technical/bureaucratised so people like Guyenet thrive in it (conscientious, high trait anxiety, mediocre intellectually but good at ass kissing so all good). Why pay for research assistants when you can hire students to do the same job for free? It means no real progress has been made in medicine since, oh, the discovery of antibiotics and painkillers but hey, there's always another garbage "me too" drug in the horizon like another statin, PPI or SSRI which needs a fucking meta-analysis to show its efficacy due to having a most wonderful NNT of 300.

Another problem is the peculiar academic culture that develops in these labs. You must fall in line with whatever the principal investigator believes, no matter how stupid, as he/she is the grant holder. In this instance, daddy Schwartz believes that insulin keeps you thin so his lackeys do too or must at least publicly defend this position. Sometimes people just tow the line, in other cases a sort of a folie a deux develops where the PI's beliefs are actually internalised by the minions. I have seen this happen so many times and it's really funny/sad to watch the religious conversion happening in real time. More rarely, some nutjob like me shows up who doesn't give a shit but they are given the "you're gifted but..." speech.

Super Quad Damage said...


Bill has it right, though:
Say A Big NoNoNo! to ANY seeds and seed oils as a sure way to to get your health in order once (if) you're insulin sensitive again following a VLC diet.
DoDoDo! add intense strength training and frequent intermittent fasting if you want your body fat as low as possible for your genetic heritage.

Craig said...
This comment has been removed by the author.
Kindke said...

Peter there is also this study on insulin therapy causing weight gain 12 Nov 20. [Epub ahead of print]

However, there was no effect of insulin treatment on total food intake, although it did increase fat mass. Although in this study the author blames the hypoglycaemia as causing the problems.

Stephan Guyenet said...

Hi Peter,

This blog keeps getting funnier and funnier. For someone who claims not to read my blog, you sure do follow it closely! Every time I write something about insulin, you get your knickers in a bunch about it.

The funniest part about this post is that I never even claimed insulin is a satiety hormone. Satiety hormones are substances like CCK, amylin and PYY-- hormones that regulate food intake on a meal-to-meal basis. Insulin, on the other hand, plays a role in long-term energy balance, which is why it is not generally considered a satiety hormone.

I think a good principle for blogging is that you should start at least with a Wikipedia level of knowledge about the subject at hand. Understanding the meaning of basic terms like "satiety hormone" is a good starting place. I think you can get there.

Here is the typical formula for your posts: Stephan is misinterpreting paper X [insert joke/insult]. The authors also misunderstood their own data [insert joke/insult]. Let me tell you how it really is [insert bizarre interpretation that happens to support Peter's personal beliefs]

Peter, if your ideas are so hot, why don't you write them up and publish them in a peer-reviewed journal instead of toying around on the Internet? Or write a grant? Oh that's right, because researchers are such idiots they wouldn't recognize Peter's genius. Best to keep preaching to the choir from your armchair.

The more agitated you become, the deeper you sink into the pseudoscience quicksand Peter.

Purposelessness said...

Wow, ANOTHER argument from authority. When will it ever end.

Elliot said...


Virtually every time I've chased one of your references, I've found that you left out important aspects or simply forgot/misrepresented what was actually in it. You realize that a PhD does not entitle you to do this, right?

Similarly, when you posted about scientific method/philosophy of science (something about which I know a bit) what you wrote was complete gobbledegook, and in your concrete example you made an obvious logical mistake.

It is nevertheless such a shame that poor lil' Stephan is not getting the respect he thinks he deserves, though :(

Exceptionally Brash said...

Wow!, Dr. G. Hey, the reason there is so much joking around is due to the utter desperation many of us feel, that our experiences have been so discounted by the supposed "experts". Maybe I haven't read all that carefully, but I can't find anything here in Peter's blog that refutes my own experience. Sorry to break it to you, but my reality doesn't mesh with your theories, and my reality won't melt away just because you are a "peer".

Exceptionally Brash said...

Yes, in the software test field, there is this favorite saying, "There are 10 kinds of people...." There are the designers that prance over and declare "my-s-don't-stink" when a bug has been found by an "underling" and then there is this other kind of developer who runs over and says, "how'd you do that? do it again! Now! Lemme see!" Folks can decide if they want to be the 10th kind of scientist, but I can pretty much guarantee that their work will be notorious (and not in a good way) if they fail to look at the data.

Gadfly said...

So, Dr. Guyenet's response is to quibble over the semantics of "satiety hormone", do a little arguing from authority and not address a single one of the issues raised in Peter's argument. Throw in a couple of ad hominems (pseudoscience) and "that's a wrap!" And he wonders why so many think he's a weasel?

FrankG said...

Stephan Guyenet said: "...I never even claimed insulin is a satiety hormone"

A very quick search using "insulin +satiety" over at Whole Heap 'O Shit

Turns up "... If anything, insulin constrains food intake and body fatness, and research indicates that this action occurs via the brain. Insulin infused into the brains of baboons causes a suppression of appetite and fat loss, which is consistent with the fact that insulin and leptin have overlapping functions in the brain (10, 11). Knocking out insulin receptors in the brain leads to increased fat mass in rodents, suggesting that its normal function involves constraining fat mass (12). Insulin is also co-secreted with amylin, which suppresses food intake and body weight (13). This is why insulin is viewed by some obesity researchers as an anti-obesity hormone. ..."

No doubt there are many other quotable quotes along the same theme but I prefer to spend as little time over there as possible these days :-)

Gadfly said...

Of course, only a little digging reveals that the Dr. is playing games with words. Perhaps he didn't call insulin a "satiety hormone", but he used the following conclusion from a paper to support his purported destruction of the Insulin Hypothesis:

"3) this effect [of insulin - EDIT ] appears to be a heightening of satiety rather than an induction of illness."

I suppose we can quibble over just how much satiety a hormone needs to induce before it's officially a "satiety hormone", but the implication is clear enough. Interestingly, if one reads the comments/discussion of that post, one sees that a good number of the posters understood the Dr. to be arguing precisely that insulin induces satiety.

Gadfly said...

A few more instances of Stephan's thoughts on insulin and satiety, in his own words:

"Experiments in which investigators feed volunteers protein foods that stimulate insulin to different degrees show that the amount of satiety is positively correlated with the degree of insulin release"

""If calories and protein are kept the same, high-carbohydrate meals cause equal or greater satiety than high-fat meals, and equal or less subsequent food intake, despite a much larger insulin response (4, 5, 6, 7). Due to the insulin-stimulating effect of protein, low-carbohydrate high-protein meals can sometimes stimulate insulin to an equal or greater degree than high-carbohydrate meals, yet even in these cases higher insulin release is associated with increased satiety (8)"

Sure, there's a distance between "association" and labelling insulin a "satiety hormone", but there's also a great distance between making that red herring your central point and addressing the criticisms of your citations. The Dr. has heroically demonstrated both in this case.

Gadfly said...

Oh snap! Frank beat me to it....

FrankG said...

No worries Gadfly... it really didn't take a lot of digging to find out what I already knew... the good doctor's word is not worthy of my trust.

Yes there is a nauseating pile of weaselling occurring where he may not have used the precise words "insulin is a satiety hormone" but that is clearly the meaning of so much of what he does write and as you pointed out "if one reads the comments/discussion of that post, one sees that a good number of the posters understood the Dr. to be arguing precisely that insulin induces satiety." I don't see the good doctor rushing to disavow anyone of that notion, which others put about on his behalf.

DLS PABLO said...

o snap! i just realized 2 things. 1) i dont give a fuk bout his 2) not all low carbers look like ass?! - that woo girl is HOT (!) now continue arguing bout teh inzulinz boyz im going to read (?) dat woo blog. i have my popcorn infused ice cream ready. lets do this like a boss or maybe a Greek god

Peter said...

Hee hee


karl said...

I think we should just move on and ignore Guyenet. Here is why:

He has more than once either misconstrued or grossly misunderstood the results of papers he has cited to me and just recently, an author of a paper he was citing corrected him on his blog:

See what JJ posts.

What I notice is he fails to concisely state what his hypothesis is on his blog. I once got him to state it in an email to me:

"The bottom line is that (in normal healthy people) long-term fat mass is guided centrally by the brain, not locally by insulin. Insulin does contribute to that, but by acting in the brain and in the opposite direction of what is often claimed."

So now he must have changed his mind about insulin decreasing appetite?

He says on his site, that the reason low-carb works is it restricts food intake by limiting choices - somehow he can't see that other diets don't work where low carb does and I for one don't stop eating because of food choices - I have a lower appetite and I don't eat as often on low carb.

For me to accept his take I would have to think that the established adipose science does not exist or is wrong. ( I think that If FA flux into adipose is inappropriately high - in the end it is just like a calorie deficit - which does effect the brain ).

He apparently thinks that the brain is the ultimate/only regulator. (There is quite a bit of evidence that contradicts this and biology almost always has several over-laping feedback loops - not just one. )

Very tasty foods have been around longer than the T2D pandemic. (my current hypothesis is that insulin may not be as important as insulin sensitivity - and that the huge increase of PUFA in the diet has shifted the FA flux balance - making obese people hungry )

There have been many people that want to make this all about will-power or morally degenerate food choices. IMO that is a discredited puritanical take.

Lionel said...
This comment has been removed by the author.
Gabriella Kadar said...

Back in 1985 I had a 'Triple Bolus' test done for anterior pituitary function. The following were injected: insulin,
gonadotropin-releasing hormone (GnRH)and
thyrotropin-releasing hormone (TRH).

In mg/100ml my blood glucose was 70 at the beginning. I was told the insulin would only drive the glucose down to about 35. It went to 8. I was blacking out so the resident utilized a 'dextrose push' to raise the blood glucose via intravenous.

Sure it went up a bit, but the insulin made me starving hungry for the rest of the day. I ate all day long after getting home from the hospital.

My experience is that insulin is anything but a satiety hormone.

JJ said...

Actually, no one really knows what the function of insulin in satiety is because we don't know where the relevant insulin is coming from - i.e. from the pancreas or from the brain itself. An important aspect of our recent study (Mehran et al Cell Metabolism) is that small amounts of insulin are produced in the brain. The Seattle group really hates this idea, but the data are the data. We won't know what this insulin does until we delete it and see what happens to food intake and body mass.

As one of the comments pointed out, the injections of super-high levels of insulin may or may not tell us what the role of endogenous insulin is, but they certainly can't tell us about the effects of insulin coming in from the periphery which never exceeds the picomolar range.

I think the best data we have at the moment is from the brain region-specific knockouts that are coming from the Bruning group.

There is much more work to be done.

Oh, Bill, the reason researchers study mice is because we can delete specific genes at specific times and in specific tissues, and then extract tissues whenever we want. Can't do that to people, ethically or technically. The human studies are nice, but almost always just correlations. If you want answers, you need to do loss-of-function genetic physiology. And, yes, your core physiology is more like that of a mouse than you would probably want to know. Sorry.

Galina L. said...

Am I remember properly from long time ago reading that anorexic are given insulin in order to make them eat? Or it is a legend of some sort?

JJ said...


Not a legend. Insulin was used to put on weight.

Kitty said...
This comment has been removed by the author.
Kitty said...

I'd have more respect for Guyenet if he manned up and admitted he is wrong, because to continue to deny that Peter and Wooo pwned him is just getting ridiculous and exposes himself to further embarassment, like his last post.

For my money, (and many more regulars here I suspect) a gram of clinical experience is worth a kilo of theoretical mental masturabtion.
Guyenet has none of the former, and far too much of the latter. Its time he faced up to the facts.

Gadfly said...

"I'd have more respect for Guyenet if he manned up and admitted he is wrong"

And give up the soothing sensation of Sanjeev polishing his gonads day and night?

Wolfstriked said...

Nooooo Peter Nooo.I look to you as the one blogger that does not get involved in this "Paleo wars" bullshit.We need at least one person to stay sane so we don't all resort to acting like Nikoley's.

TL:DR......Peter keep the blog stating facts and stay away from the name calling please.;)

Unknown said...

Peter is stating facts. You're interpreting them as attacks simply because you can understand what he wrote this time. Peter typically writes at an extremely high scientific level, but he's still taking the piss out of Guyenet -- you just miss his meaning during those posts.

I think that laymen can follow this post is why it flushed Stephan from his lair; the "Goof Doctor" Guyenet understood how damaging Peter is when he includes non-biochemists in the discussion.

(I guess there aren't any real biochemists on Stephan's tenure committee.)

In any event, Peter is showing how relevant papers are being ignored for cherry-picked ones, and how relevant data in other papers is ignored to deceive readers. Those are facts, and extremely relevant ones.

It blows my mind how an off-hand remark by Taubes two years ago resulted in Stephan's climing so far up his silly tree.

Call the fire department! Save the kitty!

Unknown said...

er, climbing

Simon Carter said...

"And give up the soothing sensation of Sanjeev polishing his gonads day and night?"
Goddamn it, Gadfly, my tea shot out my nose and messed up up my laptop!

Sam Knox said...

Dr. Guyenet has apparently never heard the expression, "If you're in a hole, stop digging."

Stephan Guyenet said...

Ah, I see Peter's loyal followers are trying to defend him. As I said, I never referred to insulin as a satiety hormone, no matter how much you try to stretch what I wrote. "Satiety hormone" is a term with a specific scientific meaning, and I never applied it to insulin.

Furthermore, I accurately cited the insulin detemir/glargine paper, which by the way is titled "Insulin detemir attenuates food intake, body weight gain and fat mass gain in diet-induced obese Sprague–Dawley rats". I think this whole post was a reaction to a tweet I made weeks ago that read "long-acting insulin attenuates diet-induced obesity in rats" with citation. Sorry for not getting into the nuances of insulin detemir and glargine (long-acting insulins), it was a tweet... If someone can show me where I inaccurately cited that paper, I'd certainly like to see it-- as usual Peter seems to have made this up out of thin air.

Peter, have you come clean to your readers yet about fabricating the "fact" that liver-specific insulin receptor knockout (LIRKO) mice have glycosuria (sugar in the urine)? This was a very convenient "fact" for you, but you cited no reference, and it isn't true:

After all your flailing around, you still haven't explained convincingly why a mouse with 10X hyperinsulinemia and no glycosuria isn't fat. Keep making things up Peter, no one will notice.

Also, have you explained to your readers the real reason why the Look AHEAD study was terminated early? You speculated conveniently that the low-fat diet must have been killing people. In fact, it was terminated early because it was statistically underpowered-- they had a much lower than expected event (i.e. death or heart attack) rate both in the experimental and control groups. It was all over the press releases. Keep making things up Peter, no one will notice.

I find it remarkable that a person with a wife and young child thinks it's a good use of his time to spend hours on the Internet whining on and on about statements that some obesity researcher never even made. Keep making things up Peter, no one will notice.

This blog is an absolute parade of fabrications, one after another. But as long as you can defend your "Optimal Diet" religion against reality, that's all that matters.

Sam Knox said...

Still digging...

Anon said...

There must be a pony in there somewhere. :-)

O Numnos said...

It feels rude to comment on the nature of the content of an individuals blog. It's their space, sure it's in the public domain, but just because you read and/or comment on it doesn't give you the right.

Hyperlipid is my "go to" blog for LCHF - I know, "no guru's" another reason I like it so much.

The recent "protons" series - WOW! beautiful, seductive reasoning - a real joy to read - MORE!!

The odd indulgent well-judged insult - LOL - makes me smile.

There are "enough" angry, ranty name-calling blogs - this hasn't been one.

Still, this post seemed "out of style" - I don't know, one out of hundreds?

I agree with Wolfstriked, my initial thoughts were "Nooo..."

But like I said, I aint earned the right.

Love, peace & happy new year.

blogblog said...
This comment has been removed by the author.
blogblog said...


" Can't do that to people, ethically or technically. The human studies are nice, but almost always just correlations. If you want answers, you need to do loss-of-function genetic physiology. And, yes, your core physiology is more like that of a mouse than you would probably want to know. Sorry."

A lovely justification - unfortunately it is almost totally false. Mice are REALLY used because they are small and only live for two years. This makes them the ideal for short term studies - eg a PhD thesis.

Modern science is about publication - not gaining useful knowledge.

Realistic studies should use dogs or pigs with a transplanted human microbiome. Unfortunately dogs and pigs are large and long-lived.

Stephan Guyenet said...

Hi O Numnos and Wolfstriked,

There will be no blog war. Why? For the same reason why the scientists Peter criticizes almost never show up on this blog to defend themselves. Who wants to waste time arguing with ignorant knuckleheads on the Internet?

Peter goes on and on with no opposition because it simply isn't worth the effort for knowledgeable people to point out how absurd his arguments are. I will not waste blog space arguing with Peter-- therefore there will be no blog war.

However, since Peter is getting personal with his fact-fabrication, I am going to make a minor exception just this once in the comments section of this post.

So Peter, why don't you explain to us where you got the information that LIRKO mice have glycosuria? What exactly is the reference supporting that claim, because you seem to have forgotten to include it in your posts?

C57BL/6 mice don't excrete glucose into the urine until their blood glucose exceeds 400 mg/dL:

LIRKO mice have a fasting glucose of 132 mg/dL and fed glucose of 363 mg/dL, suggesting that they have little or no glycosuria, as supported by the second paper.

So please explain to your dear readers the origins of that claim.

Stephan Guyenet said...

And while you're at it Peter, why don't you explain why a 9-word tweet, which described the paper I cited as accurately as a tweet can, caused you to lose your cool and write the above post?

Again, the paper was titled "Insulin detemir attenuates food intake, body weight gain and fat mass gain in diet-induced obese Sprague–Dawley rats", and my tweet read "long-acting insulin attenuates diet-induced obesity in rats". Insulin detemir is a type of long-acting insulin. If you don't like the results of the paper, you can take it up with the authors.

Purposelessness said...

U mad bro?

I envy people who have the time to read blogs they professed a dislike in and then go on to spew attempted insults in the comments. While complaining that the author wastes his time (?)

But i guess when your boss polices what you can and can't write on the internet, it makes a certain kind of people want to do the same to others.

DLS PABLO said...

don't you get it? he is making a exception! ... how cute, that pic begs for a mustache and single eyeglass! how old is this guy-net ? lol

Sidereal said...

And give up the soothing sensation of Sanjeev polishing his gonads day and night?


xxxxxxxxxxxx said...

Mr. Guyenet, you so very thin and frail. Its worrisome. You need more grassfed butter. Really, not trying to a smartass ok? Forget the conveluted studies and have some extra meat and fat from time to time. You'll feel better. From a concerned observer.

gunther gatherer said...

I'm sorry everyone, but Stephan's right. Once you start checking the actual studies Peter cites for yourself, you see the stuff he conveniently left out.

Here is some de-programming for all of you, if any of you have the courage to admit you are wrong some day:

Even though this guy is a vegan, he actually CHECKED the studies you all cite, and has consequently left a mushroom cloud where Taubes and your stupid insulin-obesity theory used to be.

I don't know what you're up to Peter. After so many years blogging and working as a medical professional, you'd think you'd know how to read studies and be objective. Are you just innocently naive, extremely arrogant, or stuck with a Polish bias for Dr. Kwasniewski?

Or are you just a wacko who likes to get attention on the internet by styling himself as some kind of "maverick" fighting against an imagined dogma in the "establishment"?

melchiormeijer said...

G(h)unther, what the h*ll has happened to you??? You are kidding, aren't you?

Happy New Year, anyway!

Peter, thanks for the work you do. I wish you and your loved ones all the best in 2013. I'm silently hoping for a thought exchange between you and Dr James Johnson, who apparently doesn't think you are particularly stupid ;-).

Cheers from a stupid, still highly insulinocentric Dutchman,


mintyweaver said...

Thank you Peter.
After living many decades with a body producing massive amounts of insulin, your blog has saved my life.
Mainstream medical wisdom did its ignorant and arrogant best to kill me.

This blog is the only place I have found, which resonates with my experience over many years.
It is the only place I have found with useful and practical answers which have greatly enhanced my health and happiness.

May I suggest to Dr. G, who obviously has far too much time on his hands, that he give up his ego attachments to his previous concepts and start working towards reality.
If that is, he wishes to be seen as a scientist. He is starting to make himself look a right prat.
May I remind him that for a long, long time many people considered the world to be flat, some still do!
Please Dr.G don't bother attacking me, I'm nobody important, so if you attack me, you will only prove my points.

I do almost agree with you on one point though Dr.G!

Peter, could you please consider distilling your knowledge, into an idiots guide!
Who cares about peer review it is no longer reliable, if your research is applicable and effective, we are interested.
I would be very happy to contribute in any way you would appreciate.

I can't thank you enough Peter, may I wish you, your family and all your contributors a heartfelt thank you and a very Happy New Year :)))

Purposelessness said...

I happen to know that at least some of the pro-obesity-research- and pro-unmentionable-C commenters are actually long-term-trolls, trying to test out the limits of Poe's law. I won't tell you which though, that would ruin the fun :)

"The core of Poe's law is that a parody of something extreme by nature becomes impossible to differentiate from sincere extremism. A corollary of Poe's law is the reverse phenomenon: sincere fundamentalist beliefs being mistaken for a parody of that belief."

What is strange to me are the people going on blogs they don't like and continuing to tell everyone that only their conclusions are correct. (That reminds me, I haven't seen Nigel in a while - were are you bro?) I mean, I enjoy looking through studies mainstream obesity researches and she-who-will-not-be-mentioned dig up, but I tend to reach entirely different conclusions than them. Still, I don't post on their blogs starting fights with everyone and everything.

Also, happy new year!

Neil Timms said...


Sorry, but as soon as I'm listening to a you tube presentation that supports the 7 nation study or china study I know that objectivity, context and science have already left any possible discussion. The only mushroom I could see was a somewhat sagging and rotting unpalatable example. I have spent much time looking at both sides regarding the above studies.

Context: the human body has evolved to make Cholesterol - so why hundreds of thousands of years after our species differentiated should it now be a bad thing for us? If the environment has changed, might that not be a better target for our research?

@Peter, you are not my guru (best to avoid those) but I deeply appreciate your time and effort in presenting health and diet material on your blog - Really makes me think even if my lack of formal medical education means I can't follow all the detail without extra work. All the best for 2013 and - don't ever stop. stop. (caps left out for sake of politeness (a black adder reference for sake of humor and those who don't know the scenes by heart)). My own cream recipe (pre finding your blog) is to make Creme Fraiche - current frankenstein version is goat cream inoculated with st ivel cultured cow buttercream - sets solid in the fridge and is IMHO yummy. I often consume with raw honey and berries.

I don't expect we can all be right all the time. From what I can see the very poor work labelled science by many in the health and diet field so far has given us a very confused position to work from. It amazes me that people get paid to do such a terrible job of research.

I cannot see that any discussion on human diet (as in what to eat or not eat as opposed to simply loosing weight) is possible without context - personally I consider a good general starting point is the human species in the environment in which it evolved. Detailed examination of tiny parts of our biology in an environment arguably significantly different from our evolutionary origins may not be of full use to our understanding as we have lost context.

All the best to all for 2013.

(I duck - donning flak jacket and tin helmet).

Jane said...

Wow! Peter and Stephan talking to each other! Nice fireworks, boys.

Stephan Guyenet said...

Look folks, no amount of squirming and comebacks will get around the fact that this entire post is based on a 9-word tweet I wrote on Nov 13, reading exactly as follows:

"Long-acting insulin attenuates diet-induced obesity in rats"

As far as I recall, that is the one and only time I've ever cited that paper. The paper in question is titled "Insulin detemir attenuates food intake, body weight gain and fat mass gain in diet-induced obese Sprague–Dawley rats". The paper just so happened to show... that insulin detemir (a long-acting insulin) attenuates diet-induced obesity in rats-- exactly what I stated, and exactly what is shown in the graph Peter posted. I did not mention satiety in relation to that paper.

This 9-word tweet caused Peter to fly into a juvenile rage and write the above post, in which he invented a position for me, criticized the fabricated position, and used the opportunity to hurl a number of gratuitous insults.

I understand that this is Peter fan-land, but does no one else find this a little bit strange?

No one thinks it's strange that Peter never actually pointed us to the place where I supposedly discussed this paper, and supposedly took the position he's attributing to me? Where is the link? Where are the quotes?

gunther gatherer said...

Hi Neil,

"Sorry, but as soon as I'm listening to a you tube presentation that supports the 7 nation study or china study I know that objectivity, context and science have already left any possible discussion."

Are you implying that you are somehow objective and interested in the real context and science, when you just stated the above? You just admitted your own prejudice and bias, the very thing you accuse the clip poster of having.

Here is more explanation on the China Study, from the same channel:

And Purposelessness, I've been reading this blog since it's inception, when I myself was VLC, after being LC-paleo for years before that. But unlike many LCers, I actually read OTHER opinions on OTHER blogs dealing with nutritional studies. Then I go back and actually look at the data sources for these opinions and decide if the writer was correct for MYSELF.

I urge VLCers and anyone taking Gary Taubes simply at his word to do the same.

Gadfly said...

Apparently the Dr. can read Peter's mind from across a continent and an ocean. Is there anything he cannot do?

Sam Knox said...

I can't be the only one who is struck by the breathtaking irony of Dr. Guyenet accusing someone else of "fly(ing) into a juvenile rage".

Simon Carter said...

Dr. Guyenet, a lot of people think you are a bullshit artist. Peter thinks you are stupid. Coming here and whining like this is not helping your cause. If Peter is as wrong as you state you have nothing to worry about. The academic world you are part of will surely see the soundness of your positions, won't they?

Lionel said...

I think it has all gone a bit Spanish Inquisition now!

Neil Timms said...


Having read from and about the two studies I formed an opinion - just my own - that I did not agree with the methods or conclusions of the studies - and that other explanations for the results were just as plausible or indeed more probable. I could of course be wrong and in time change my views based on new evidence, argument, or discussion.

I did not accuse anyone of bias - not a word I used. I do not agree with them.

I fully accept that other people may form different opinions from the same studies. So I said "I know......" in my post - that means to me that I believe that I know in my own mind what I think about that subject - it does not mean that I think everyone or indeed anyone else needs to believe the same as me - if you think that the 7 nation and china studies were objective, in context, science then I have no problem with that. Differing opinions assist informed discussion.

I actually came to paleo/VLC/whatever material via various ways of eating (including raw vegan for a while LOL) - I have not yet found a way of eating that fits (again to my mind) our probable evolutionary past as well as something close to paleo/VLC/whatever.



Stargazey said...

Peter, if your ideas are so hot, why don't you write them up and publish them in a peer-reviewed journal instead of toying around on the Internet? Or write a grant? Oh that's right, because researchers are such idiots they wouldn't recognize Peter's genius. Best to keep preaching to the choir from your armchair.

You may have noticed that Peter already has a day job. And he doesn't have a research lab. Normally grants are not awarded for writing review articles.

Again, the paper was titled "Insulin detemir attenuates food intake, body weight gain and fat mass gain in diet-induced obese Sprague–Dawley rats", and my tweet read "long-acting insulin attenuates diet-induced obesity in rats".

The operative word here is "gain." Insulin detemir affects diet-induced weight and fat gain, but does not affect obesity once obesity has occurred.

"Satiety hormone" is a term with a specific scientific meaning, and I never applied it to insulin.

I don't think Peter and the commenters here realized that "satiety hormone" is a term of art. From the above-cited references, however, you have repeatedly referred to insulin as a substance that induces satiety. Or is that wrong as well?

Peter, have you come clean to your readers yet about fabricating the "fact" that liver-specific insulin receptor knockout (LIRKO) mice have glycosuria (sugar in the urine)?

Can you please provide a link to where Peter did this? Are you implying that if Peter did make this egregious error, it invalidates everything else he has said?

Johnny said...

Stargazey, he knows that. "go put it in a peer-reviewed journal if you're so smart" is the un- or under-accomplished scientist's battle-cry. He can ignore the amateurs, or crush them by knowing more, or whinge about peer-review. Option 3 isn't a great one, but it's made me laugh so far!

Son, when your plan A is to suggest to an accomplished anesthesiologist that he read wikipedia about hormones, you should go straight to plan B. Accusing Peter of just being a liar is a much better tack.

"keep preaching to the choir from his armchair" -- what a bizarre church! lol.

"If we hit that bullseye, the rest of the dominoes should fall like a house of cards. Checkmate."

JJ said...

Hi Blogblog,

You wrote "A lovely justification - unfortunately it is almost totally false. Mice are REALLY used because they are small and only live for two years. This makes them the ideal for short term studies - eg a PhD thesis."
Sorry, but you are incorrect on many levels. Mice live up to 4 years in the lab. PhD thesis are 4-6 years. Of course mice are more convenient than pigs, but to not believe that they are good mammalian models is to not understand evolution. The main reason scientists like myself use them is that we can manipulate their genome with ease, and this allows use to do loss-of-function genetic experiments. This type of genetic experiment is the only way to know if a specific gene is essential for a physiological function. This is what we showed when we deleted have of the insulin alleles and prevented weight gain.

"Modern science is about publication - not gaining useful knowledge."
Again, incorrect on many levels. These are not mutually exclusive. If we gain useful knowledge, how do you suggest we convey it? Randomly tell people on the bus?

"Realistic studies should use dogs or pigs with a transplanted human microbiome. Unfortunately dogs and pigs are large and long-lived."
Thanks for the zoology lesson. Of course pigs are closer to humans physiological. A knockout pig study, like the one we did in mice, would cost 10 million dollars and take 10-15 years. As it was our study was almost 1 million dollars over 7 years.

JJ said...

LIRKO mice are hypoglycemic in most papers. That is why they don't gain weight - way TOO much insulin. Well outside the physiological range.

v/vmary said...

i don't get it- the detemir insulin still leaves the mice with less fat mass in the end. does this result mean anything in the real world? can detemir insulin be used as a weight loss drug??? i get that after 10 days all 3 groups don't gain or lose, but the detemir group still ends up with less fat mass and that is where i want to be.

Stephan Guyenet said...

To all:

It's remarkable how this community unconditionally accepts everything Peter feeds it. Peter fabricated my position on the paper he discussed, provided no evidence to support his fabrication, not even a link, and no one has the balls to question Peter's story. Or at least, those who have the balls are keeping silent (except Gunther).

When I point this out, the only thing I have received is a stream of insults and adolescent comebacks. No one, including Peter, has provided any evidence whatsoever that I made the claims about this paper that Peter attributes to me. Are you really so brainwashed that Peter no longer has to support his claims?

By the way, here is one example of Peter's fabricated claim that LIRKO mice have glycosuria:

"What Stephan does not tell you (amongst a million other relevant snippets) is what the "calories out" through glycosuria are. BG is 400mg/dl, urinary calorie loss is not mentioned."

Another example appears in the following post:

Again, this claim is fabricated out of thin air. He repeats it over and over, but never provides a reference for it, because there is no reference. Young LIRKO mice have a fasted glucose of 131 mg/dL, and a fed glucose of 363 mg/dL (not 400 as Peter keeps repeating-- this appears to be another exaggeration), and a fasted glucose of 131 mg/dL, both of which are below the threshold of glycosuria for C57BL/6 mice. Older LIRKO mice have NORMAL glucose. Plus, the only paper that ever measured glucose in the urine of LIRKO mice found that they have none (noted at the end of the methods section).

Another example: Peter attempted to discuss our recent JCI paper on hypothalamic injury, and besides misrepresenting the paper's findings, the whole time he referred to the VMH when the paper was actually about the arcuate nucleus. If you're going to mangle my papers, at least get your neuroanatomy right. The liberal use of humor does not make up for a failure to understand fundamentals.

Wake up people: Peter is suckering you with pseudoscientific nonsense, and you're gobbling it right up without any critical thought. The only reason he gets away with this garbage is that knowledgeable people don't generally waste their time correcting Internet ideologues. Peter will say whatever it takes, and insult anyone who he feels threatened by, to protect his ideology.

Well folks, I think I made my point, so I'm going to call it a day.

xxxxxxxxxxxx said...

Its a cart before the horse thing Mr. G. Those of us who've found health and (ahem) vitality with low carb or keto eating arent being fooled into hallucinating our own recoveries. Maybe some have eaten foods that harm their bodies due to some mouthy smuck and a long list of pub med articles, but thats not most of us. When high fat , insulin controlled eating works , it just works. Not sure what planet you're from implying we're being brainwashed by some maniacal blogger who's hypnotized us into an illusion of health and strength.

DLS PABLO said...

Peter saves animals. Eats animals. Has a beard... Stephan dooms animals. Eats plain potatoes. Shaves. Peter acted as a good MAN. Stephan(y)? acted as a cruel woman. Period. Now how can you argue with this conclusive facts of LIFE ! begone and seek proper nutrition and or medical attention, hurry!
edit, that sounded kinda gay... or misogynist -gay? there is nothing wrong with females! (unless they are ugly and or mean to animals)

DLS PABLO said...

edit also nothin wrong been gay! (ok maybe if you are really gay, like sweet potato crash diet fagyty fag.

Stargazey said...

Stephan, thank you for the links. The note at the end of the methods section does suggest that LIRKO mice did not experience glycosuria in that study.

However, please consider the following. In this blogpost ( ), Peter says:

But the LIRKO mouse, with insulin levels 8-20 times those of a control mouse, never becomes hypoglycaemic. It's ONLY hyperinsulinaemic BECAUSE it can't mop up dietary glucose.

So perhaps we are actually seeing the anorexic effect of insulin in this mouse model. The levels might be high enough.

In other words, the constant insulin excess in the LIRKO mouse's brain may be able to regulate its appetite to calories in=calories out. Which may explain why the LIRKO mouse doesn't get fat, even though it also develops profound muscle insulin resistance. (MIRKO mice do get fat.)

However, in humans without the LIRKO mutation, a prolonged systemic insulin excess will produce severe hypoglycemia and resultant irresistible hunger. High insulin in the brain may shut down hunger initially, but if nutrients have been stored and insulin remains high, falling blood sugar will ensure that the person goes back to the pantry looking for more food. And if this happens continually, the person will eventually gain weight.

Sam Knox said...

Pablo, see previous comment re: Holes and digging. ;-)

Sam Knox said...

Speaking of rodents and insulin, this is interesting:

Rats intermittently injected with insulin to produce hypoglycemia gained weight compared to controls in spite of identical food intake, apparently because both basal metabolism and activity were drastically reduced.

Sam Knox said...

Now, I guess I'll go look for my balls...

ItsTheWooo said...

The internet is so full of drama lately. Its unfortunate I have a full time job and was not able to enter the fray earlier!

First, it must be pointed out that STEPHAN IS SO MAD. Furious! Foaming at the mouth. Why? Peter has at best exhibited passive aggressive snark toward while criticizing your ridiculously arrogant boastful ideas and conclusions...the level of disinhibited aggression observed here is grounds for a comforting pat on the back containing transdermal ativan, no questions. This is OVER THE LINE/CROSSED THE LIMIT.

If peter ever had free time or arrogance enough to behave this way on your blog you would have banned him instantly, because you love to ban people, so its just YOU AND YOUR ECHO CHAMBER. At least Peter gives a stage to contradictory opinions... you will pretend to allow debate only to ban or warn or dismiss anyone either immediately or after a few back and fourth exchanges.

Second, it must be an effect of toxins in potato skins but the paleo cult is FULL OF LIE lately. First JM lying through his ketone breathed teeth about not knowing what a neonazi is, and now STEPHAN lying about never making the claim that insulin is a satiety hormone.

Whether or not the phrase "satiety hormone" has a specific definition is IRRELEVANT and you know it. You have argued for months that insulin promotes satiety, it's effect on food intake is exclusively that of inhibition/appetite suppression outside of hypoglycemic events.

THIS IS SEMANTICS, and that is an act of desperation + appeal to authority, which is basically the majority of your arguments. "But we all think this, so it's right" <-no, actually, the fact the majority of researchers think something does not make it true and this is the fatal flaw in your worker bee uncreative, linear way of looking at anything.

There are numerous historical examples where the direction of research has been terribly wrong, most recently/relatedly the idea that saturated fat is evil and disease causing, and transfats would be a superior choice. This notion, once practically championed as truth, is now an embarrassing artifact quietly forgotten. THIS, TOO, WILL BE THE FATE OF YOUR STUPID IDEA THAT hedonism makes people have hypoglycemic reactions, lethargic, and accumulate hundreds of pounsd of body fat. IT IS AN IRRATIONAL STUPID IDEA, only possible to ever manifest by a group of people who have never studied real patients, and it will be forgotten as embarrassing and wasteful and detrimental to human progress.

Everything you do (what little significance it has already) will fade into obscurity as a bad joke, in time. Sorry to tell you that. It's not too late to change, but I suspect you will continue parroting the party line and merely building on of what was done before you, because you lack the creative/novel thinking required for ingenuity and success. It's too bad you choose a field where the research is doomed and wrong.

ItsTheWooo said...

Third, I have no formal scientific or research training and the few times I have investigated your references they were overtly fabricated, fraudulent.
Your article on sugar was a terrible joke, for example.

You don't like being pointed out when you exaggerate your reference, fabricate the conclusions, or other acts of deception. To fucking bad, then, I suggest you stay on your echo chamber blog or the blogs of those who are hopelessly biased in your favor, such as that nut carbsane.

Oh, BTW, you have time enough for carbsane (a remedial math teacher in junior college, self professed eating disorder case who refuses to believe anything but laziness/apathy or weakness causes obesity, even though she herself is quite obese)... but you don't have time for Peter? LOL.

What you probably meant to say was "I have time for people who are too ignorant to understand my arguments, too dim to conceive of an alternative hypothesis or see the opposite of my arguments as being possibly valid... I ONLY HAVE TIME FOR SYCOOOPHAAAANTS BECAUSE ITS KIND OF LIKE BEING SUCCESSFUL WITHOUT HAVING TO THINK/DO/SAY ANYTHING IMPORTANT TO HUMANITY".

Oh and you're wrong that we never contradict Peter. There have been many occasions I disagreed with Peter's conclusions or ideas. He's overwhelmingly right almost all the time but I do not mindlessly agree with him. Perhaps that's true of some people, but this is no different than your brain dead cult of people like gunther gatherer .... fools who are incapable of thought and the best they can come up with is "I found a guru better than you, so I'm leaving you for my new guru" rather similar to a prostitute leaving their pimp for a stronger pimp offering better protection/drugs.

ItsTheWooo said...


Elliot said...


Virtually every time I've chased one of your references, I've found that you left out important aspects or simply forgot/misrepresented what was actually in it. You realize that a PhD does not entitle you to do this, right?

YOU LIE, STEPHAN. You lie all the time. Whether this is because you are so arrogantly sure you are right, even being wrong can't stop your rightness... or if you are merely out to deceive, that remains to be seen. However, you have committed at best brazen misrepresentations or at worst deceit and fraud.

The evidence is all over your blog. Most of your sycophants don't read your references, and thats the way you like it. They just wait for you to regurgitate the ideas into their brains like a momma bird throwing up into the mouths of hatchlings.

This is where Peter is different from you. Peters formula is typically to take the findings of a paper, BEGIN his post by describing the observations, and then he hypothesizes why they occur.

When peter contradicts, it's always the researchers' conclusions, never the data / outcome.

You do the reverse, because you're desperately trying to substantiate your idea.

ItsTheWooo said...

ANOTHER truth quote!

mintyweaver said...

Thank you Peter.
After living many decades with a body producing massive amounts of insulin, your blog has saved my life.
Mainstream medical wisdom did its ignorant and arrogant best to kill me.

This blog is the only place I have found, which resonates with my experience over many year

Need to keep this double visible, because when it comes down to it variations of the insulin/endocrine hypothesis of obesity are saving people, NO ONE is improving from variations of the hedonism hypothesis.

Stephan, have you ever had someone who was truly crippled by obesity, lethargy, blood sugar swings ever write you a thank you letter?

Sure you have vanity pound morons saying "thank you when I stopped eating twix bars all day I felt a little more full eating only potatoes". What about people like myself, or mintyweaver, who have histories of being debilitated with pathological obesity and attending symptoms of an energy use disorder?

I'm just honestly curious. Has even ONE person wrote you a thank you / success letter? Not the dieting vanity pound freaks. People who are like "Every 2 hours I would feel faint and shaky and my life was horrible because my body could not make energy normally".

ItsTheWooo said...

One more comment.

(SRRY I can't help myself)

I just want to point out Stephan focusing on 'LIRKO MICE NOT BEING EXHIBITED TO GLYCOSURIA" is a great example of his thinking. This is an utterly irrelevant point. It doesn't much at all affect the argument Peter makes, other than to say it invalidates the potential for urinary loss of energy, Peter acknowledges the mice eat less.

BTW, 393 and 400 are the same and you know that. 400 is easier to grasp, and is actually a lot more accurate in that sense. For example I don't say "I weigh 123.1 pounds" I would be more likely to say "I weigh 120-125 pounds".

The more relevant points Peter makes regarding LIRKO is that the liver cannot make fats from glucose (so how on earth can the LIRKO store fat on a mouse chow diet) and secondarily the adipocytes are severely IR, which inhibits fat accumulation (along with depressed ability to store dietary glucose as fat).

You are really fixated with urinary loss of calories, Stephan. Why is that? Is it part of your control problems? I've observed this in anorexic little girls, they will not drink water because they are afraid of the out of control feeling when they have to use the bathroom... they restrict both fluid and food to master their body and its impulses. We've already seen ample evidence you are preoccupied with loss of control over food, so I have to assume your obsession with urination and loss of calories in urine is maybe related to that.

It seems you frequently blog about glycosuria and often use this as a convenient excuse when describing diabetic weight gains on insulin (they stopped peeing out glucose!@!!!!!!!of course they're fat now all their hedonism is coming to roost in fat tissue!)

Even if Peter (is human!) and made an error here it doesn't invalidate teh rest of his argument. Yourself and carbsane and glad handing each other "LOL LIRKO IS HIGH INSULINZ BUT NO FATS" simply don't care regarding the actual pathophysiological reason that occurs, as long as you have SOME KIND of example of high insulin + no weight gain you're good to go.

I would also argue there is a reason you and carbsane need to cherry pick these animal models of hyperinsulinemia without obesity: they almost NEVER OCCUR, and they only occur in the context of severe adipocyte insulin resistance. THAT IS THE ONLY TIME it is generally observed hyperinsulinemia with body fat wasting/loss/normalization.
A similar naturally occuring example would be "donohue syndrome", which I blogged about many times; infants born without any functional insulin receptors in virtually every tissue of their bodies. They exhibit all expected signs of an insulin deficiency even though they are profoundly hyperinsulinemic.

Their presentation is remarkable in many ways, but most specifically their body fat IS ESPECIALLY wasted. They are very small from growth hormone deficiency, and their subcutaneous fat is paper thin.

Jane said...


'It's remarkable how this community unconditionally accepts everything Peter feeds it.'

No, it doesn't. I am part of this community and I question everything Peter says. Often I find things that aren't quite right, but I know Peter hasn't the time to discuss it with me so I let it go. He will correct it in time himself if it really is wrong. Maybe it's me that's wrong.

Likewise, I sometimes find things on your own blog that aren't quite right - like wheat being toxic, for instance - but I let them go or make a minor comment because I know your thinking is progressing and eventually you will come round, all the faster if I don't hassle you.

BTW, Peter thinks wheat is toxic too. This whole community seems to think wheat is toxic. Now there's a thing. I eat enormous quantities of wheat so I should be dead.

Stargazey said...

Wooo, I believe LIRKO mice are able to use glucose to synthesize fatty acids in their adipocytes. (Read here about DNL in fat cells .)

And according to this article , although the muscles of LIRKO mice are profoundly insulin resistant, their adipocytes are not.

...the markedly impaired glucose utilization in LIRKO mice, as compared with control mice, reflects profound skeletal-muscle insulin resistance. Interestingly, this extrahepatic insulin resistance may be specific for muscle, based on the following observations. Normal basal FFA levels in LIRKO mice suggest normal whole-body rates of lipid turnover, and the similar suppression of FFA levels in response to insulin suggests normal insulin sensitivity with respect to antilipolytic actions on adipocytes in LIRKO mice. Therefore, in addition to primary tissue-specific (hepatic) insulin resistance in LIRKO mice, the secondary insulin resistance caused in part by hyperinsulinemia may also be tissue-selective, with a much greater effect in muscle than in fat.

Exceptionally Brash said...

it is also well known in the T1DM community that if you want to keep your weight down, just go ahead and eat the carbs and then go sparingly on the insulin. Using the correct amount of insulin is considered the healthy way, but it makes you fat.

Exceptionally Brash said...

Wow again, Dr. G on the interpretation of the lookahead study. Studies just don't get designed out of the blue without looking at the power, and the fact that it went on for years and years and YEARS, and then near the end, concluding that it was "underpowered". Well, that's just a bunch of weasel activity for sure. When they designed the study around the idea that they would detect a certain difference, and then they didn't. EVERY SINGLE TEST IN THE WORLD IS UNDERPOWERED TO DETECT A DIFFERENCE THAT IS IS NOT THERE! Now, I am not a biochemist, either a real one, an internet one, or a published one, but I do know statistics, and when I see it being mashed up like this, it sure is annoying.

Gadfly said...

"Foods that spike insulin the most in humans lead to the greatest satiety and lowest food intake at subsequent meals".

Dr. Ego.

"I didn't say 'satiety hormone', I said 'hormone associated with satiety!' Neener, neener!"

Dr. Ego.

Now, perhaps this sort of thing passes with the squints the Dr. goes to all the best faculty parties with, but for us laypeople possessed only of common sense (and impressive MENSA phallus') it's hard to swallow. Perhaps it's not rewarding enough.

Peter gets some of it right and some wrong. Dr. Phd finds a couple of nuts now and again despite the mote in his eye and a hamartia obvious to all but himself. But, what Peter doesn't ask me to do is to take his word for it because he has some letters behind his name signifying little more than extensive institutionalisation. Incidentally, in a field that has been more cause than cure for the very thing it purports to be expert in. The pluck of some folks.

Perhaps most comical is Dr. Ego's insistence on the soundness Food Reward Theory because it is accepted by the scientific establishment. Of course, he doesn't mention that there are significant countervailing theories propounded by folks with just as many letters behind their names who probably think his supervisor is a dough head. Essentially, the volume of Stephan's message is amplified in this sphere because of the absence of opposing voices. Of course, we all saw the mess the Dr. did make when actually faced with one of those researchers in the case of JJ.

lian johnston said...

I'm seriously amazed at the "low-carb works for me so I subscribe to or at least condone everything Peter says" mentality openly displayed here.

Galina L. said...

So far it looks like that the people who have clinical experience (Peter, Wooo, Siderail) disagree with the person who does a scientific research (Stephan Guyenet) about what causes obesity. Is it possible to have the same level of disagreement about interpretation of clinical experience as about interpretation of the data of scientific research?I am interested, are there people with clinical experience who would side with Dr.Guyenet?

blogblog said...


I suggest you read Gulliver's Travels. Jonathon Swifty skewered pseudo-scientists who literally spent their time distilling moonbeams from cowshit.

Knockout mice (dogs, pigs etc) are pseudoscientific versions of human diseases. They tell us nothing of real use.

Mammals may have virtually identical physiology at the hormonal level but this tells us absolutely NOTHING about what a species should eat.

Pandas and Polar bears have virtually identical anatomy and physiology. Theory would suggest that they are both broadly omnivorous. Yet observation shows one is a bamboo eater and the other is an extreme carnivore. The only obvious distinguishing factor regarding diet is their gut microbiota.

blogblog said...

A couple of years ago a leading Australian medical researcher made a the following cynical observation:

"The main purpose of medical research is to produce PhD candidates not cure diseases."

Jane said...

You are missing a trick here. JJ has some extremely interesting things to say and nobody is listening.

He has evidence for something people think is impossible, the reprogramming of white fat into something resembling brown fat. If you have 'brown' fat you can burn off calories that would otherwise be making you obese. This reprogramming needs insulin to be low, which on the face of it means insulin = obesity. However, it turns out that periodic low insulin works just as well as constant low insulin. In other words, it's absence of low insulin that = obesity.

This shouldn't really be surprising because we've known for years that insulin secretion oscillates and bad stuff happens if it doesn't.

Jane said...

Here's a paper about oscillatory insulin secretion. You can't tell who's going to get diabetes with the usual tests but you can if you analyse oscillations.

'Routine screening procedures for insulin secretion yield little predictive value for later development of diabetes but more sophisticated methods using time-series analysis of diurnal, ultradian and rapid oscillatory insulin secretion reveal the presence of profound defects in glucose-intolerant individuals. Furthermore, studies of rapid pulsatile insulin secretion have revealed defects in glucose-tolerant first-degree relatives of patients with Type 2 diabetes. ..'

Peter said...

@ Dr Guyenet

Mis-citation. You kindly dropped by in to the comments of my blog some time ago and you said this:

"If you look at studies where overfeeding produced greater fat gains, you see a consistent increase in fasting insulin that corresponds with fat gain, just as those silly obesity researchers would predict: "

The actual data from all three links are summarised here.

Did you read the studies before posting the links? None of them support your contention. All are compatible with Knudsen's results, these are shown as the top line of the image. Link one never measured the hyperinsulinaemia noted by Knudsen. Ot will have been there. That's your only let out for citing this study.

You knew the data = mis-citation
You didn't read the studies = stupid

Any other explanations?

Next, this is you again:

"If you give insulin-sensitive animals large doses of insulin, as in the paper you cited, they gain fat because it causes hypoglycemia, which is a powerful trigger for food intake. But if you give them smaller doses of insulin that do not cause hypoglycemia, they do not gain fat, and often they actually lose fat. See these three papers for example: "

Okay. have you read these papers? In the first only the 2iu/d group reached p<0.05 after 7 days on insulin, looking at depressed weight gain, sustained in to the post insulin period. This single significant finding could not be duplicated, especially the post pump depression of weight gain, in the second part of the paper, best data in Fig 4. No mice lost any weight EVER and any delayed weight gain from the first 3 days was made up in the post pump period. The post pump food intake per day of the part two 2iu/d mice was the highest cited in the whole study. It was the lowest in part one. Huh?

Link two has nothing to do with insulin. Huh again. But from the abstract: "Oral administration of a mimetic in a mouse model of high-fat diet-induced obesity reduced body weight gain, adiposity and insulin resistance". Zero suggestion of weight LOSS at any time point. The needle in the brain drug does cause weight loss. There's the queue, fatty.

Link three, sorry if you forgot, is about insulin detemir vs insulin glargine. No animals lost ANY fat at ANY time point in this study. The weight gain with glargine was ns greater, at the group size used, in the D12492 fed rats. Insulin detemir is clearly interesting during the early phases of D12492 feeding to rats.

I don't see any evidence for the statement "often they actually lose fat". Oops. Maybe you thought no one would look up the refs. Maybe you never read them yourself.

You read the studies = deliberate mis citation
You didn't read the studies = stupid

Any other explanations?

Your TNFa and muscle iNOS knockout links are classic Guyenet. You have a model with a discordant weight to insulin level. Pay dirt. Cite them and the number. But do you understand them? That's tricky. If you understand them you are mis-citing again. If you don't understand them, you're stupid.

Any other explanation?

Personally I think stupid is a complement cf deliberate mis-citation.

The science is quite straight forward. You need to think them through. This is easy enough while doing the washing up. If you want to understand, that is. Getting the time to write it down is the challenge.

You absolutely have me on the glycosuria threshold of rats. Touche. I hope you didn't waste too much time trying to make the LIRKO jam. Better get on with your grant applications.


Peter said...

oops, typo; compliment, nothing too filling meant.

Purposelessness said...

Hey Jane!

I never came across people who thought turning white to brown fat was impossible. No matter.

Have you read about the "exercise hormone" (horrible name) Irisin? One of its effects is "browning" white fat:

And, funnily enough, exercise is not the only stimulus for Irisin production, a high fat diet is too:

Lots and lots of interesting research coming out right now :)

FrankG said...

I don't consider myself to be part of any "community" here. I read this blog (among several others) as a free-thinking individual. I may rub-shoulders on-line with several of the same individuals from time to time (at least those who don't troll using constantly changing aliases) but that is as far as it goes and I feel free to disagree with any of them.

In that same vein I do not consider myself to be a "follower". I read from multiple sources, I apply critical thinking to ALL of them and I make up my *own* mind as to what I find convincing, or not.

The mere fact that Stephan throws around these epithets as if they are insults, I think underlines the patronising attitude he has about his own readership.

Over time I will of course favour some sources as more reliable than others and possibly even prefer certain writing styles.

Peter has once again just pointed out something which became apparent to me by my own application of scrutiny to Stephan's claims and links... they don't hold up.

Even in the recent discourse here I see blatant misrepresentation of the truth with weasel-words and squirming. For Stephan to bare-faced continue to claim he does not say insulin (a hormone) causes satiety when his own quotes are here for everyone to read ("...If anything, insulin constrains food intake...") defies all rational thinking and is one of the reasons I no longer read his blog. I appreciate Peter's take on this but I didn't need hm to tell me that Stephan's claims do not stand up to scrutiny.

The funny thing is as Dr Lustig (and as I understand JJ) have also stated" Insulin CAN lead to satiety in the short-term... it makes sense to tell the body that we are busy digesting food and don't need any more just now thank-you. This is the problem facing black & white thinkers who can only see that insulin is either "good" or "bad"... no room for any shades of grey in-between.

As for quibbling over the difference between a Blood Glucose level of 363mg/dl vs. 400mg/dl I suggest you try both levels on yourself Stephan and see how insignificant that difference really is... they are BOTH very unhealthy and damaging levels of Glucose... and THAT is no exaggeration.

Jane said...

I wish you would state things more clearly. Here I am trying to judge whether Stephan really has made unsubstantiated statements and I can't because I don't understand what you're saying.

I can't imagine anyone reading your blog has more time than I do to try and untangle things, which means if I don't understand it nobody will.

I have a horrible suspicion that those of your readers who are nastiest about Stephan are the ones who think they understand what you are saying but don't.

Sam Knox said...


I can't speak for anyone else, but as a non-scientist with a good grasp of English, I understand exactly what Peter is saying, and it didn't take any time at all:

The Good Doctor's conclusions are not supported by his citations, which means that he either misrepresented or misunderstood them. If he misrepresented them, he's a "bullshit artist". If he misunderstood them, he's "stupid".

I hope this helps, and thank you for a stunning display of condescension.

john said...

What is Stephan thinking? ...He comes to Hyperlipid and makes a condescending comment about publishing in a respected journal. Then he insults the commenters about eating up Peter's "pseudoscience."

Hyperlipid's collection of followers is at the top in terms of independent critical thinking: people constantly ask questions and have interesting conversations. But oh, Gunther is the intelligent open-minded one, because when his former guru Peter didn't come through for him, his new guru Stephan lived up to the task, but just temporarily; now he's into the China study clan; soon it'll be Ray Peat.

So there is no reference for LIRKO sugar-pee, and blood glucose doesn't quite reach 400mg/dl; good lord, throw Hyperlipid in the trash...immediately!

gunther gatherer said...

John, are 3 kidney stones and cholesterol of 320 your definition of "didn't come through for me"? LOL.

Not taking your childish bait: First of all I was addressing Peter and not his cult of personality here. Secondly, no one is saying you should be like me or like anyone else, only to look up the data he presents here (and Stephan's too!) and interpret it yourselves.

The real question, and one only you can answer, is: why does the idea of thinking for yourself make you, Woo and others here so defensive and angry?

xxxxxxxxxxxx said...

I've never seen such a big muscled up guy with such a serious case of little man syndrome. Sad really. Sorry Peter.

Stephan Guyenet said...

Haha, you are really something Peter. Are you telling me this entire post was about an error I made in a hasty comment on one of my own posts-- the very same post in which I CORRECTLY described the papers?

If you read the post itself, I CORRECTLY cited the papers as "reducing body weight gain" and "opposing weight gain".

I made a small error in the comment, in which I said it "reduced" fat gain rather than "opposing" or "attenuating" it. Sometimes my comments are hastily written, but obviously I understood and correctly represented the papers if you read the actual post (as well as the tweet I wrote about the insulin detemir paper, in which I used the word "attenuate"). You decided to cherry pick the hasty comment instead of the (correctly cited) post right above it, using it to fuel your angry insulting writing. What is wrong with you Peter? (by the way, "what is wrong with him?" was the subject line of a message I received about this very post)

Just admit it Peter, you are digging for any excuse to insult me and make me look bad, no matter how ridiculous, because you feel threatened by me. Why else would you write about me so much, and make up any excuse possible to throw insults my way? Ever since I criticized the carb-insulin hypothesis, you've been on a petty war path. Fabrication, ad hominem attacks, whatever it takes to discount Stephan's arguments. No worry, he'll never show up here to defend himself.

I'm glad you admitted to fabricating the LIRKO glycosuria data, it is a good first step. Now, you should admit to not having the foggiest understanding of our JCI paper, repeatedly referring to the VMH when the paper was about the arcuate.

john said...


I don't know what you ate or did, so I can't comment, which is sort of the point: your "faith" in Peter shouldn't follow your personal experience, and even though you claim you make your own decisions, evidence would maybe indicate otherwise. If you have health problems, try to understand why. But all the study results you've ever interpreted shouldn't change overnight; that would be pulling a Matesz.

Regarding minutiae that Peter or anyone may or may not reference or be wrong about, I just don't care and don't judge based on that. I read those I can learn from. It's the guru, dogmatic, or disingenuous mentality that causes people to give a crap about such things. Jack Kruse can come off as a manic weirdo, but I've learned from him; Art Ayers never references anything, but it's still a great blog.

The idea of thinking for myself doesn't make me angry...? It's the accusation that I don't. Look through the comment sections, and it is obvious that there are plenty of disagreements and insightful discussions. Most people here eat or support high fat. That's not enough to warrant the religious label, given by the occasional venturing CarbSane or WHS fanatic.

IcedCoffee said...

Sigh, I normally enjoy Hyperlipid comment sections, but this is discouraging.

Stephan Guyenet said...

Correction: the comment Peter cited was from the following post, rather than the "nail in the coffin" post:

In this hastily written comment, I said insulin causes fat loss rather than attenuating fat gain-- a rather minor error that does not change the overall point-- increasing insulin in this context does not cause fat gain. Again, I correctly described the first two papers in a post here:

And correctly described the insulin detemir paper in my tweet (using the word "attenuate"), which is the only time I have ever individually referred to that paper.

If the readers of Peter's blog want to see who is right here, please go to my post:

And see for yourself whether I said insulin causes fat loss, or insulin prevents fat gain. I have not altered my post since Peter wrote the above post.

By the way, Peter's interpretation of the Vandeweele paper is nonsense. If anyone wants to see the paper and decide for themselves who described it most faithfully, send me an e-mail and I'll provide you with the full text. There you will see what the authors thought of their own finding:

"1) insulin limits meal size when blood levels are modestly elevated for prolonged periods of time in the rat, 2) this decrease in meal size is not compensated for by an increase in meal frequency and, hence, total daily food ingestion and body weight gain are reduced, and 3) this effect appears to be a heightening of satiety rather than an induction of illness."

But I'm sure Peter's interpretation is right-- with all his experience in physiology research, he knows better than the people who actually did the experiment...

Galina L. said...

About kidney stones. Fortunately, most of the time, it is a rare event (or events), it is difficult to draw conclusions exactly why it happened. I myself had couple kidney stones passing after several months in a diet when I limited red mead and fats the most. I can't be sure it was connected. I am speculating, that because of more frequent migraines I was dehydrated more often (I usually experience a lot of vomiting during attacks, can't eat and even drink for long periods of time). However, I had way more infections, migraines, more prominent allergies on a low fat than a low carb diet, and I can tell it for sure because numbers are more prominent to draw a conclusion. I noticed no positive correlation between low total cholesterol numbers and my health.

Ketosis makes significant difference for people who need it to normalize existing troubles with processing carbs. People who don't have a need for such normalization can just practice eating so called "real food" and be fine. It doesn't make them into witnesses to testify that carb content in a diet doesn't make any difference.

gunther gatherer said...

Stephan, since you're seeing clearly with regards to the insulin-obesity argument, I think you should also spend some time checking the facts of these same folks when they try to disqualify the diet-heart research, especially with regards to saturated fat and cholesterol.

If they can misrepresent or misinterpret one set of data, they can certainly do it with another. Please make your stance on dietary cholesterol clear on WHS, since "saturated fat good, PUFAs bad" is a central tenet of blogs like these and in fact LC/paleo dogma can't survive without it.

Have your thoughts on SF/cholesterol changed at all since you realized how ridiculous these tin-foil hat bloggers are?

JJ said...

OK Blogblog,

I’ll give this one more try, for the benefit of the other readers, before giving up on you.

Where to start… I’m trying to think of a way of saying that you obviously don’t know who you are trying to lecture, without coming across as too arrogant. I’m not a pseudo-scientist. I’m a real science professor with a real track record of real science. My google scholar page is here -
I wrote the recent paper that reports, for the first time in any mammal, that a specific reduction in insulin prevents diet-induced weight gain. I ventured out into blogland and twitter to see how the paper was being discussed and used by lay people. Many people have take the time to read it carefully, like Jane. I have always made myself available to answer the public’s questions about it and I’m not trying to convince people about what to eat.

I don’t need advice from some random person on internet about what books to read.

For the record, myself, my team and my colleagues around the world do medical research to try to understand the root causes of diseases. I’m sure there are a few with different motives, but I don’t know any personally. We also receive funds from charities composed of patients and families of patients who are desperate for answers to life and death questions. They fund a mix of observational human studies and mechanistic model system studies for a reason, because they both give key and complementary answers. Do you think insulin was discovered with human research? I can give hundreds of examples.

You stating that “They tell us nothing of real use” doesn’t make it so, so I hope no one who reads that takes you seriously.

Same goes for your ridiculous comment about polar bears and pandas. I can tell you that they are adapted to different environments (My Ph.D. is in comparative physiology but a Ph.D. is certainly not required to figure that out). Their gut microbial has nothing to do with the relative lack of vegetation on seasonal ice flows, when compared to say… a bamboo forest. Bears, like humans, are highly flexible omnivores.

Finally, quoting a cynical but unnamed “leading” Australian medical researcher isn’t really helpful either. I’m a “leading medical research” who thinks the opposite. Why don’t you start a poll. I have lots of “leading” colleagues in Australia and elsewhere who do medical research for the right reasons. Also, since when is training the next generation of Ph.D.s mutually exclusive to doing research and finding cures? I’m quite proud of the Ph.D.s I have trained and they have gone on to make important contributions.

john said...


You must know that your argument here will be unproductive. Hyperlipid and Whole Health Source have many of the same readers, or at least they did at some point.

I can't speak for others, but what I find annoying about your arguments is the implication that "we" think low/high measured insulin is sufficient for leanness/fatness, which is false. To me it comes off as a tricky strawmen, where you are choosing your words carefully in order to gain acceptance instead of furthering physiology knowledge.

You have provided a few examples of knockouts that would perhaps conflict with some of Taubes' statements (not others' like Peter's), but I am not interested in Taubes debunkings or the debunking of the "mainstream" "carbohydrate-insulin hypothesis;" I, like many others, just want to learn.

Adipocyte insulin resistance is a key factor in fat storage, as shown by examples like FIRKO and rats that drink glutamine solutions. Also, all else equal, it seems that inhibition of insulin secretion is a good way to reduce fat storage, like with rats that eat oxidized fats.

You continually bring up food reward, etc and calorie intake as meaningful itself, but that is not insightful. Calories do not equal adipose tissue; there is no set threshhold after which calories become adipose tissue; calories are merely facilitative. Even if you realize this, it's not what you suggest.

Fat is apparently the least thermogenic macro, so why do ketogenic mice display (relative to weight) up to ~twice the metabolic rate? When the only explanation is, "The brain lowered/raised the setpoint," people move on.

Again, I don't know if others here have similar problems with your somewhat recent ideas, but those are some things I've noticed.

Stephan Guyenet said...

Hi Dr. Johnson,

Please do not waste your time in this viper's nest. The only reason I'm here is that Peter has gotten increasingly personal in his angry flailing at me.

Remember the exchange we had on my blog, in which we disagreed but maintained a polite rapport? That's not the coin of the realm here. Peter is a UK veterinarian with no research training or experience as far as I know, who is an adherent of a diet called the "Optimal Diet", promoted by a Polish guru called Jan Kwasniewski. The diet is a very low-carb, low-protein, high animal fat diet that he believes is the optimal diet for humans. He has his wife and young child eating this diet so he is heavily invested. This blog is mostly an attempt to justify Peter's diet by whatever means necessary. Ever since I critically examined Gary Taubes's carb-insulin hypothesis, Peter has been flailing around at me.

Consequently, this blog tends to attract people who are of the same mindset as Peter.

Hi Gunther,

Please send me a personal e-mail if you want to discuss your question-- it is off topic here.

xxxxxxxxxxxx said...

Peter , I'd like to express my admiration of you, that your character is strong enough to allow those of different views to come and debate and even insult, and still you never ban. The most ironic thing about that is allowing those who pop up in your vipers nest who are known to ban challengers on thier own blogs. I guess banning is deemed a "gentlemans" out.

DLS PABLO said...

another failed generalization. ex i think the op diet is mostly bollocks, but this place introduced me to the power of teh awesome egg yolk , im grateful for that everyday.... whats your contribution to society guynet? food reward? give me a fkn break! cuack. cuak

gunther gatherer said...

XXX, how would you even know if Peter banned commenters or not?? Do you know how a blog works?

I assume you're eating tons of saturated fat and avoiding vegetables because Peter just said so as well? Or because he seems like a really cool, easygoing guy, who's really witty and smug? Come on, man. This is your health you're playing with.

This is the kind of blind, cultish admiration that needs to be called out.

xxxxxxxxxxxx said...

Shit, Im busted. I do everything dietarily possible to follow the exact eating plans layed out by my beloved leader, Peter. Ill let my veins harden, my heart blow up, and my fat cells bloat to unrecognizable proportions just cuz Peter says too, Damn straight! Havent you heard? We're a religion, not a loosely knit group of interested readers/knowledge seekers who happen to get what Peter says. Nooooo, its much more nefarious and frightening than that.........guy, calm down and get real.

Gadfly said...

"We're a religion"

I've just finished saying my 'Hail Petros' for all the irredeemably PUFA-laden fish, salacious salad, sugary-sweet potato and downright Evil rice I ate today.

xxxxxxxxxxxx said...


gunther gatherer said...

That was actually funny Gadfly, so good on you.

Gadfly said...

I'm off to flagellate with a stick of Kerry Gold.

gunther gatherer said...

NOOO, you flagellate with fiber on this blog. Then spread antioxidants on the open wound for extra penance...

v/vmary said...

Hi Jane, if you just read Peter's post, the study is difficult to sort out. the link to the article in peter's post wouldn't come up for me, so i googled the title of the article and here is the full text plus graphs.

karl said...

I think part of the problem is papers that start out misleading.

We have a new paper Adaptations in brain reward circuitry underlie palatable food cravings and anxiety induced by high-fat diet withdrawal

Where the so called high-fat diet (actually hydrogenated goop once again ) also changes the carbohydrate source from corn starch to sucrose - a fact that requires digging. We already know from other papers that sugar withdrawal causes symptoms.

When I was in grade school we learned that real science experiment change only one variable at a time - how do we get junk science like this from folks with PhDs?

Why do we have folks with Phd's that appear to be trying to stack-the-deck?


It is clear to me that insulin is not the only controlling signal that modulates FA flux via adipose tissue. But it clearly is a major one. Insulin sensitivity, autonomic, leptin are also involved and I can't follow Guyenet's logic that the longterm flux balance is independent of insulin's relative levels ( if we have high insulin sensitivity, the level of insulin does not need to be as high to have net FA going into adipose tissue - thus looking at one signal at a time is not so enlightening ).

The other confounder is short term studies - the body changes over the course of weeks - receptors up-regulate and down regulate and papers that only look at 8 hour, or a few days can be counter productive. It is possible to see positive effects turn negative and visa-versa.

Short turn PUFA's look good - lower BG, but long term, if we are inappropriately increasing insulin sensitivity, it is quite possible that we are changing the FA flux and thus the Homeostasis set point.

If we send FA (think calories ) to adipose tissue, there is less to fuel metabolic activity - less energetic states are associated with increased hunger.

At some point, it is the brain directing us to seek food, but that does not separate us from the underlying metabolic balance.

Insulin may not directly induce hunger, I've not seen enough to say we know that definitively, but to imply that it reduces hunger is more than I can swallow.

tess said...

Dr. Guyenet, it's highly ironic that you should list references to your blog archives when your record for going back and CHANGING THEM without notifying readers is so strong. that's why i stopped reading you in the first place.

nor can i fathom why you're going on and on here -- surely you're not expecting to impress any of us?

kilton said...

People and their extreme dieting tendencies are so adorable. Gunther goes from VLC to veganism, and brags about it as if it means he knows something. His idol Don is the same way, bouncing back and forth between extremes like it's cool. Anything to avoid boredom I guess. :-)

Exceptionally Brash said...

Hail Peter, my guru! Wow, I get to be a viper? It feels so inclusionary, after being passed over for inclusion in the 3-c club, too cheep for the kruse-klub. I don't care if you are a front for the chocolate industry, I love you herr Peter! P.S. Do we get uniforms?

blogblog said...


Peter has published far more peer-reviewed papers (at least 11 according to Google Scholar) than you have.

Anyone research scientist in his 30s who has such a pathetic publication record and made as little career progress as yourself can't afford to criticise anyones academic or intellectual prowess..

gunther gatherer said...

Kilton, if you think I'm telling you to be a vegan, you have serious reading comprehension problems. Read before you tap.

Stipetic said...

Stephan Guyenet said: “Also, have you explained to your readers the real reason why the Look AHEAD study was terminated early? You speculated conveniently that the low-fat diet must have been killing people. In fact, it was terminated early because it was statistically underpowered-- they had a much lower than expected event (i.e. death or heart attack) rate both in the experimental and control groups. It was all over the press releases. Keep making things up Peter, no one will notice.”

As pointed out, Peter was speculating. When it comes to this, Peter is quite upfront when his speculations hat is on. And that’s one of the attractive traits of this site (thinking ahead). Peter uses know facts to speculate into the unknown. He’s the Captain Kirk of the Paleo/Nutrition blog world.

However, Stephan's view, I believe, exposes an inexperience with clinical trials.

Here’s Prof Russell V. Lenth’s take--you can Google him--on retrospective power anaylsis (the supposed reason for abandoning the Look AHEAD study): The fact that retrospective power adds no new information is harmless in its own right. However, in typical practice, it is used to exaggerate the validity of a significant result (“not only is it significant, but the test is really powerful”) or to make excuses for a non-significant one (“well, P is 0.38, but that’s only because the test isn’t very powerful”). The latter case is like blaming the messenger.

Since I work for BigPharma as a clinical expert of sorts (I’m like the Wolf character in Pulp Fiction—I’m called in to clean up messes, which is a sexed up way of saying I answer deficiency letters from authorities like the FDA, EMA, TGA, etc, about our clinical studies), I’d like to give my own take on the Look AHEAD study. As quoted by Stephan, the press suggested that the study was underpowered (reread Lenth reference above). In order to know this, an interim analysis had to have be conducted on the data. BTW, an interim report is as detailed as a final report. You have access to all the data concerning your primary and secondary endpoints, not just the rate of adverse events (mentioning only the rate of adverse events as a reason to abandon ship is deceiving—-although it is used in the sample size estimation, it is actually the total number of adverse events that is important; that are used the final calculations). Therefore, the authors had full access to what their data was pointing to. They could easily see if they stayed on course and reached the number of subjects to adequately power the study whether they would get the results they wanted (ie. low-fat was indeed better). When a clinician/researcher is in such a position (as I have on several occasions), one has to make decisions.

Stipetic said...

Continuation from above:

If the data are good—-the interim report shows a trend in your favor (ie. low-fat arm displays favorable results that will become statistically significant should the study be extended to its conclusion), then you damn well finish the study. Should you have underestimated the adverse events rate (which is a grave error and why one tends to overestimate this criterion when doing sample size estimations: if one wants to be a bit cynical, it can also be seen as a gambling move--it's playing with the producer's risk, trying to get a positive result without having to invest in a full sample size), then you either extend the study until you’ve recruited the appropriate number of subjects based on the new adverse events rate or you add study sites that can add to your current pool of subjects (all well-written up protocols have contingency plans to account for this). Bottom line, if the interim results are in your favor, you will finish the study. Period.

If the data are not good—-it doesn’t seem from the interim report like you’ll meet your primary endpoints even if you continue the study to its end (ie. low-fat diet shows no benefits or contains more adverse events than the comparator/control group), you cut your losses. You stop the study and make up an excuse for doing so. A favorite: we underestimated the rate of adverse events. It’s uncommon for anyone to question the researchers as to why they didn’t just recruit more subjects if the interim report showed that the treatment arm was performing better than the comparator.

My experience tells me that it's well within reason for Peter to speculate the way he did. I find it troubling, actually, the you took the authors at their word. Inquisitive minds want to know.

Stipetic said...

Dr. Johnson, thank you for making an appearance and congratulations on a well-conducted and informative study. I've been reading your posts here with great attention. Please continue to contribute where you see fit. We are here to learn.

Although I have a similar take on rodent trials as blogblog, I'll try not to bore you with platitudes. But you made a point I commonly make--the reason rodents are used is mainly because of the cost (money talks).

Speaking of money, Peter's proton series is priceless. A gem. A must read.

Exceptionally Brash said...

hey Stipetic, I read somewhere that these researchers attributed the failure of the lookahead study to the fact that the control side didn't die fast enough like they were supposed to. This apparently makes the treatment side not look as good as planned when compared. One might think that the something that affected the mortality rate of the control also affected the treatment side, so a comparison is valid (and in this case, showing a non-significant difference). Of course, one never really knows.

ItsTheWooo said...

@Gadfly your post at 8:44pm was like heroin.
You win the internets for today.

Thank you for the extreme reward value; I no longer feel compelled to dramatically and frantically pour a box of double stuff oreos down hatch for the time being.

@Lian I know, I'm shocked + appled.

We should be stomping on him & kicking him in teh face like a furious mob for not converting to potatoism with Nikeoly and Robb Wolf and even the 5 minutes Jimmy tried it (until he remembered his extreme fatness problem and he realized taters ain't gonna work).

Everyone knows these days if you don't immediately denounce heathens , modern waste and gluttony exemplified by the obese, particularly obese carnivores, you'll end up on PALEODRAMA. What worse fate is there, then ending up on McEwens paleodrama? It's like meangirls but for geeks.

Besides, A righteous person fasts until they're pale + anemic, eats moderate amounts of unsalted boiled potatoes, and shivers in disgust when observing a fat person, or someone enjoying a steak, or arguing that obesity is only possible via endocrine signalling in fat tissue. Peter is beyond hope, truly an evil menace, almost as bad as TEH JEW according to prevailing paleo authorities such as KKK Grand Wizard David Duke.

I've understood DNL in adipocytes is responsible for small amounts of fat gain, the liver playing the overwhelming role of converting dietary glucose into fat for storage in adipocytes. This is why high cholesterol and blood lipid abnormalities are hallmark of severe insulin resistance (i.e. adipocytes resisting further growth). For example, in lipodystrophy, patients have triglyceride levels in the thousands. They are also intensely hyperglycemic. They have no adipocytes, which is basically the same as having extreme adipocyte insulin resistance. the main difference being they look emaciated wehreas fat people look overfat and we think "that hedonistic glutton". Both are experiencing severe IR, with hyperglycemia and elevated lipids in blood.

Metabolically healthy obesity with insulin hypersecretion from a likely nervous system defect (i.e. the kind of obesity I have) features all signs of negative IR; relatively low BP, low cholesterol, low blood sugar/frequent hyperglycemia in spite of needing a wheel barrow to cart your massive fat ass around. Imagine being 300 pounds and having a BP of like 120/80 and normal blood sugar and low cholesterol. I had it!

Signs of hyperinsulinemia however are quite positive (cutaneous changes from insulin overexposure, frequent blood nutrient erratic/instability) and indeed I had significant signs of hyperinsulinemia.

The LIRKO model is very fascinating, I would like to know more about it, because ultimately there is a physical reason WHY it has severe hyperinsulinemia but does not gain fat, as this should never occur. If the adipocytes are normally insulin sensitive, and it is not *intensely* diabetic... perhaps there is more to the liver and insulin signalling in fat gain and obesity than that which is superficially apparent (constraining glucose production, stimulating fat/glycogen synthesis).

Or perhaps this anomalous effect is isolated to this genetic freak animal model and doesn't really suggest anything more! That's possible too.

ItsTheWooo said...

U r wasting your time!
Gunther gather gets all of his information from 10 minute youtube videos made by skull faced emaciated vegan extremists.

Unless it is in youtube format, <20 minutes with pictures & music, and says something like "MILK CONTAINS BUGS & PUS!!!!!!!!!" in the title... well, frankly, gunther gatherer DONT CARE, gunther don't give a SHIT, rather much like the crazy nasty ass honeybadger.

"Fat is apparently the least thermogenic macro, so why do ketogenic mice display (relative to weight) up to ~twice the metabolic rate? When the only explanation is, "The brain lowered/raised the setpoint," people move on."




Peter OMG GUYENET IS TALKING ABOUT U, IN EMAILS. He got an email, and someone said "what is wrong with him", him being you, peter. THEY ARE TALKING ABOUT YOU.
Who can it be? carbsane, diana, melissa, sanjeev? Who was our mysterious critic? Will we ever know?

*comforts* I'm so sorry Peter. Here's a kleenex. It's going to be okay.

Jane said...

Sam Knox
You're not a scientist? Well, I am. I have a first-class degree from Oxford and a PhD from Cambridge. I was runner-up to the Oxford prize in zoology in 1976, and the lab where I did my PhD is the MRC Laboratory of Molecular Biology where Francis Crick worked. I was thrown out of my Oxford college fellowship in 1985 because my research had led me to believe that modern disease is caused by nutritional deficiencies and not by genes. Francis Crick & co thought it was genes, and I was a heretic.

I have now spent nearly 30 years studying the scientific literature full time. Do you know what that means? Evenings, weekends and Christmas, and zero social life. This is what it takes, because the literature is unimaginably vast.

I have many friends among the top Oxford scientists. They thought genetics and biotechnology would 'cure half our diseases and prevent the other half' (quote from Tony Blair) and it hasn't happened.

BTW, Peter knows my history, and knows exactly what I'm talking about. So does Stephan. If you think I am an enemy, you can think again.

gunther gatherer said...

Woo, do you realize you are quite sick? Are we supposed to believe a bipolar high-fat apologist with a history of eating disorders is the go-to expert for health advice? Take a look at yourself.

Normally I'd scroll over your hysterical rants like everyone else does, but this time it needs to be said: get some help, honey.

ItsTheWooo said...

Gunther, do you have a vegan propaganda youtube video I can watch that can instruct me on how to get help? Preferably one that is 10 minutes in length with music and pictures.

gunther gatherer said...

The first step is admitting your problem, so glad you asked, Woo:

Gadfly said...

Hi Jane,

Impressive resume. Someone with such obvious intelligence can probably guess why some would rankle at the suggestion that our criticism of Dr. Ego is because we don't really grock the conversation.

It's not that, I'm just immature and crass and harbour a deep -- probably irrational -- derision for academic functionaries who overestimate their IQs and relative significance, groomed during years of working with them. I rank Stephan's successes in gardening higher than his academic resume on my list of skills that matter.

And, no, I'm not anti-intellectual, I simply recognise that other than in the realm of infectious disease control, our technological medicine has done very little to extend the potential lifespan of humans. We lived just as long without eggheads telling us how to walk, eat and think. Our purposes as a species - whatever they may be - were carried out every bit as well without a million Stephan Guyenet's trumpeting their meagre accomplishments and telling us to eat our greens. It seems that the greater the interference in the food supply from these scienters, the greater our collective metabolic troubles have become. They should beg for anyone of any intelligence to listen to them for more than a moment, rather than parading about as though they hold some arcane knowledge unknown to we benighted morons.

And to be more crass still, I'll put my MENSA score up against Stephan's any day of the week.

ItsTheWooo said...

Thanks gunther that was helpful! Do you think they'll let me eat marscapone cream and chocolate and macadamia nuts in ana recovery? Or do you think they'll force feed ensure down a nasogastric tube like that poor girl in the video? Yck! I'll just do my at home ana recovery involving eating lots of food and sitting on my ass. It's working pretty well.

PS look at my profile! Thanks I love this title! It makes me feel like a political rebel or dissident, I'm the che guevara of carbing.

First I was elected court jester of carbing (right after Duke knighted Sir Moore as a Grand Wizard of carbing, I ran up afterward and was titled the Low Carb Court Jester) and now I'm a bipolar high fat apologist.

Sidereal said...

Gadfly wins the thread. We may as well all go home.

I'm not john, but I wish to answer Gunther's question directed at him:

The real question, and one only you can answer, is: why does the idea of thinking for yourself make you, Woo and others here so defensive and angry?

Maybe because we have been cursed with this endocrine disease which the medico-scientific establishment refuses to treat as a real disease but instead as some kind of a behavioural/emotional/addiction (i.e., psychiatric) problem, a recent-onset epidemic of mass gluttony and sloth, inexplicably beginning around 1980. Somebody like you who, I'm guessing, was likely a young fit male maybe 10 lbs overweight tops before discovering glucose-restricted insulin-suppressing diets can't understand why these diets are literally life-saving for some of us whereas for you it's a stupid fad and a totally optional neurotic lifestyle choice because clearly your body runs well on any substrate (for now, but do get back to us when you hit 40).

Peter is not a guru and no one here subscribes to the Hyperlipid religion. Most of us here do not eat to Kwasniewski's ratios, I don't think, although I have no idea why Guyenet thinks this is a dangerous diet to be feeding one's wife and children, perhaps he could show us some data or at least argumentation behind his faux-concerned statement. The reason why a lot of us respect Peter greatly is because here is an actual person with no vested interest (financial, career or otherwise) and a BMI of 20 who GETS IT and has a very unique and insightful way of looking at the data. The Proton series he has written alone shits all over all Guyenet's intellectual accomplishments.

What have mainstream medicine, "real professors of science" and neurobiology researchers done for us? Nothing but harm, actually. Most recently, there was a concerted attempt (which thankfully failed) to include obesity in the DSM-5, the upcoming revision of the diagnostic bible of psychiatry. What evidence was offered for this attempt to psychologise a clearly medical problem? Oh well, SOME people with obesity have binge-eating disorder and display behavioural patterns analogous to addiction, plus we have a lot of rat research carried out by people like Guyenet where rats enthusiastically press levers to self-administer more sucrose to get the dopamine hit (invariably called "a high-fat diet" in both the title, abstract, and the discussion of the published paper ;) ), therefore all obesity must be caused by an addiction and so it should be in the DSM.

Those of you who are neither fat nor clinicians may not understand why I'm getting so exercised over this but this would have enormous clinical implications on the way we conceptualise treatment for obesity and now suddenly you would have justification for inpatient admissions on psych wards to treat fat people with useless harmful therapies like forced exercise, cognitive behavioural therapy, antidepressants. If you are emotionally neutral about this, have a look at the "success" of these psychological approaches for the treatment of chronic fatigue syndrome (another mitochondrial disorder like obesity) in the United Kingdom where the Simon Wessely "they are crazy" school of thought won.

gunther gatherer said...

"...eating lots of food and sitting on my ass."

Yeah, that's because eating disorders and compulsive lying are part of the same disorder:

"It's working pretty well."

Mmmm yep we can all see that.

Sidereal said...
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Sidereal said...

Additonally, remind yourself that the aetiology of every medical condition looks really multifactorial and complicated until somebody discovers the actual cause / final common pathway which invariably turns out to be quite simple at the end of the day. Go to the library and pull up any standard text of gastroenterology from 1970 written by real professors of gastroenterology and you will find reams and reams of bullshit written about the complex pathophysiological mechanims leading to ulcer formation, including of course STRESS and the neurotic, anxious, hysterical, hypochondriacal personality.

As Woo said in one of her comments, nobody has ever clinically benefitted from the hedonism hypothesis of obesity whereas people are regaining their lives every day after reading much-maligned Gary Taubes' or Peter D's work.

gunther gatherer said...

Sidereal, I appreciate your comment. I'm actually 42 and that pic needs to be changed. My focus is not on the emotional aspects of this research we're all doing here, it's on the data.

And just because someone loses weight and feels better after a lifetime on the SAD does not mean VLC or LC is good for you long term.

Your other points are valid but if we're to arrive at some answers in the world of health and nutrition, we need non-biased approaches to reading and interpreting these studies. I'm not saying Stephan or anyone else is the last word in science, weight loss or health, just that I checked Taubes' research and he omits a LOT of data and then claims it doesn't exist.

If he really cared about public health as much as he claims to, he would admit he's wrong so we could all learn something. Instead we're mired in discussions like this about stuff that's been put to rest a long time ago (like cholesterol-heart, like insulin, etc.) Biases by bloggers aren't helping us move foreward, they are just confusing us more.

Gadfly said...

"Instead we're mired in discussions like this about stuff that's been put to rest a long time ago (like cholesterol-heart, like insulin, etc.)"

If these subjects were put to rest, as you allege, why is there so much current, ongoing research into them? Just in this thread we have Dr. Johnson who has been involved in some startling new research regarding insulin.

As for cholesterol/heart, there's more opinions than you can shake a stick of Kerry Gold at even amongst mainstream researchers.

Mmmm...Kerry Gold.

FrankG said...

Yes I noticed in a earlier comment some whining about a [total] cholesterol of 320?

I'd love someone to explain how total cholesterol can be in anyway a meaningful marker for poor health when it includes the HDL-C?

The logic goes something like this...

HDL-C is the "good" cholesterol so "more is better!" :-)

Higher HDL-C means an higher Total-C... :-)

BUT an higher Total-C is bad?!? :-(

... . . . . . . .

It's at this point that James T. Kirk will usually have convinced the rogue computer to self-destruct... except it seems that we are dealing with paradox absorbing crumple zones à la Futurama's Robot Santa Claus

xxxxxxxxxxxx said...

Perplexing to me the conflicting message of how insignificant Peter and his work is, and yet a few hot headed people who disagree with Peter have spent the better part of thier new years holiday camped out here on his blog comments?? Granted Im a simple minded person, but these things seem very contadictory. Either the work is important and profund enough to raise a threat to the status quo, or we've got some extemely bored "professions" with nothing more to than hang out being jerks to bloggers and thier viper commenters who don't even matter. ???????

gunther gatherer said...

Here's a primer on understanding cholesterol, Frank:

First hit on Google. Sorry if the whining woke you up.

FrankG said...

I'm also interested in discussing "what makes a person a scientist?"

As a profession I can appreciate that the appropriate aptitude, education and credentials (plus opportunities, I guess) can pave the way to a successful career but are these always prerequisites for someone to be considered a "scientist"?

I didn't choose that career path, or profession but I did start out in a clinical health profession and now work on computer software design, development etc...

Can I not think like a scientist, apply the scientific method of scrutiny to observations, reach conclusions and re-test them? I can certainly read and interpret scientific papers for myself. For me the key is to keep asking questions rather than assume I have all the answers.

I'd go so far as to suggest that with my own fresh perspective, I might even see something in the observations that was overlooked by the experts.

Don't get me wrong: I have respect for those who work hard and make this their profession but that does not automatically make their opinion somehow superior to mine, or by default "right".

Earning a PhD I have no doubt, requires a massive effort but I would suggest it is a passport to start the real learning rather than a certificate of absolute knowledge.

One of my favourite scientists is E.O. Wilson who could readily be described as a world-authority on ants but describes himself as "a student of the ants" :-)

Stipetic said...

hey Stipetic, I read somewhere that these researchers attributed the failure of the lookahead study to the fact that the control side didn't die fast enough like they were supposed to. This apparently makes the treatment side not look as good as planned when compared. One might think that the something that affected the mortality rate of the control also affected the treatment side, so a comparison is valid (and in this case, showing a non-significant difference). Of course, one never really knows.

Howdy, EB. I'm sure you know, but it's worth mentioning, the study endpoints (primary or otherwise) should be applied equally for treatment and comparator/control arms (ie. if death was the primary endpoint, then the estimates are based on death for each arm; if it’s non-fatal MI/hospitalized angina/non-fatal stroke, or a composite of these, then the number of events in each arm is compared, etc). In this study, and as you point out, the authors expected a rate of adverse events—death due to cardiovascular event—to be higher for the La-Z-Boy plus all-you-can-eat buffet group. Based on this difference in estimated death rate (Jillian Micheals-by-your-side lifestyle plus low-hedonic bleh-this-is-awful diet versus La-Z-Boy plus all-you-can-eat buffet), and selection of a comparability margin and confidence intervals (I deal with equivalencey/non-inferiority/superiority trials, so I’m not sure what margins and intervals were selected in this study), they estimated a sample size applying acceptable power (1-beta) and significance values (alpha). Then they went on with the study for eleven years until a data and safety review board had pity on the low-palatability folks and decided to pull the plug. It wasn’t that the study was underpowered or that the rate of adverse events was low (and as you point out, since this is a comparative trial in nature the rate becomes largely irrelevant as it was equally low in both arms), it’s just that no matter how hard the review board massaged the data it was never going to show a difference between the bleh-this-is-awful and all-you-can-eat arms based on the study objectives. Not in 10 more years; not in 50. Like I said in my previous post, whatever claims have been made for stopping the trial other than stating that the intervention showed no benefits over the buffet arm are attempts to save face.

We may find out eventually what really happened as the researchers are already trying to tease out some good out of the data. This of course is not good science, but is common. But in the process, we might be able to get a peak at the number of adverse events for each group.

My front page take: Mega-study shows benefits of exercise on heart disease bankrupted by low-fat diet in folks with Type II diabetes.

Gadfly said...

"Can I not think like a scientist, apply the scientific method of scrutiny to observations, reach conclusions and re-test them? I can certainly read and interpret scientific papers for myself. For me the key is to keep asking questions rather than assume I have all the answers."

Science is organized common sense where many a beautiful
theory was killed by an ugly fact.

- Thomas Huxley

FrankG said...
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FrankG said...

"Here's a primer on understanding cholesterol, Frank:"

So I have spent the last several years deeply researching cholesterol, reading everything that I can from all sides of the controversy, self-experimenting and documenting my own efforts... umpteen (often heated) discussions with my family Doctor, Endocrinologists and even a Lipidologist...

BUT GG thinks it would be helpful for me to read a primer written anonymously on WebMD, which contains such basic mis-informtaion as "LDL cholesterol can build up on the walls of your arteries..."

Gimme a break..!

AND this is the guy who keeps urging us to "think for ourselves!" ... "It's for your own good man!" LOL

Gadfly said...
This comment has been removed by the author.
gunther gatherer said...

"(often heated) discussions"

You getting angry and defensive when faced with a scientific consensus based on a huge body of international investigation compiled over the last 50 years that goes against what you'd like to believe?

Who'da thunkit, Frank.

You just want to be anti-something Frank. It's not gonna be me though, so piss off.

Gadfly said...

"We may find out eventually what really happened as the researchers are already trying to tease out some good out of the data. This of course is not good science, but is common."

In a faculty lounge somewhere...

"So Bob, the bloody facts won't conform to our will."

"Nope. Funny thing, my teenage daughter was just suggesting that I might tone down the omniscience thing the other day."

"My ex-wife said the same to me. So, we got all this data and still have a couple of grad students on contract, I suppose we better find something quick."

"Only way anyone will pony up for another 10-year ride for us. I'm gonna miss expensing those "lunches" at the •special• Vietnamese place."

"Hardest part of all this..."

"So what do we tell them in the meantime?"

"That it took us 10 years to figure out that we didn't have a big enough sample."

Think that'll fly?

Some fool is bound to believe it.

FrankG said...

Soooo.... we SHOULDN'T think for ourselves at all..?!?

...instead we should mindlessly bow to the authority of "scientific consensus based on a huge body of international investigation compiled over the last 50 years"

Hypocrite much, or just confused?

BTW I am still here :-)

Gadfly said...
This comment has been removed by the author.
Gadfly said...

xxxxxxxxxxxx said...

Frank, just stick to the google searches ok? Some might be willing to go all mano a mano over the macro. While they smite you for being against things during their third day of arguing over diet theories. Lol!

gunther gatherer said...

Frank, I'll help you with the big words, 'cause you seem to need special assistance:

Think for yourself, AFTER READING the data and checking it for yourself. Just thinking for yourself, because you think that's cool, doesn't work if you actually don't know anything to begin with.

If the data overwhelmingly goes against what you believe, guess what: you're wrong.

FrankG said...

"So I have spent the last several years deeply researching cholesterol, reading everything that I can from all sides of the controversy, self-experimenting and documenting my own efforts... umpteen (often heated) discussions with my family Doctor, Endocrinologists and even a Lipidologist..."

BUT it seems I am wrong because GG says so... a man who apparently believes LDL builds up ON the artery walls (because "the consensus" says that)... better get the I/V Draino ready :-)

gunther gatherer said...

Once again Frank, reading comprehension:

I didn't say you were wrong, I said an overwhelming body of data says so. But of course, you seem to know better, so don't let facts get in your way.

Gadfly said...

Is that like the consensus that the universe was static and unchanging before a Jesuit priest suggested something like the "Big Bang?"

FrankG said...

As I recall there was a "consensus" that the Earth was the centre of the Universe, and that it was stationary -- makes perfect sense if you just go outside and look around you.

I daresay there was a "consensus" at some stage that it would be so much safer to stay in the cave, where it is safe and warm; rather than venturing out to see what might be over the next hill...

As was mentioned earlier "the consensus" had stomach ulcers pegged as due to stress and diet -- high pressure job, missed meals, too much coffee and smoking. Until a lone scientist questioned this and spoke out against the consensus, having discovered that H. Pylori bacteria was the major cause.

Science is NOT supposed to be about consensus, or appeals to authority. These are things to be questioned and scrutinised, rather than mindlessly accepted as fact.

LeonRover said...
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LeonRover said...

"If the data overwhelmingly goes against what you believe, guess what: you're wrong."

The data so far provided has been consistently UNDERwhelming - except for those who wish to promote statin taking. It is THEIR belief, nay, their CONJECTURE that is underwhelmed by (lack of) data.

Even Tom Dayspring, when recently chatting to Dear Jimmy, has NOT suggested that Jimmy ought to take medication MERELY because his LDL-P is in the top quintile of the distribution.

gunther gatherer said...

I love how you guys think you're a modern-day Copernicus. This is the cult of personality in action here.

But you've taken it so far, you're willing to bet your hearts. That's a shame.

Apparently ego is more important than health here. If you want facts, the research is there for you to read someday when you can think straight. Cheers.

FrankG said...

I notice how that seems to be your only comeback GG... a variation of the theme "you need to read the data and think for yourselves"... is that really all you got?
'cos so far as I can tell from myself and other comments here, that is EXACTLY what we are already doing... which basically means you got NOTHING man! What a waste of time!

xxxxxxxxxxxx said...


LeonRover said...

It seems the longer Gunther keeps banging his Tin Drum, the more FranG & Others have listened.

I know that I have looked at a lot of data, have also examined the methodology of examining the data and have concluded that results are mediocre.

The results of studies, as shown on the insert labels of statins descrbes an NNT of 250.

And, yes, I am willing to "bet my heart" that I am in 249 out 250 upon whom no adverse effect will fall (prospectively).

It seems others are not - hey, that is their decision. I've had such conversations with physicians over the past 18 years and none is willing to stake money on counter-position.

Exceptionally Brash said...

Oh Gadfly, your account of this sausage-making methodology is funny. What I find interesting about the lookahead explanation is how it seems to have been scrubbed a bit since the initial splash. All the media blurbs emphasize that the treatment group lost weight, never the important comparison with the control group. Oh, that pesky control group, how dare they improve without any professional intervention? Then again, this whole study may just point to the success of the low-fat/exercise media campaign that we are all exposed to on a daily basis. Maybe there was no control. Maybe all that diet advice seeped in anyway. Personally, I would love to see how the diet and behaviors of the control group changed over the years. Personally, if I was assigned to a control group of something like this, I'd probably change my diet and exercise pattern, too, without prompting by professionals and the constant contests they held for the treatment group.

Exceptionally Brash said...

Stipetic, thank you for your explanation.

Stephan Guyenet said...

Now that we've figured out exactly where Peter got his inspiration for the above post, let's review what we've established:

1) The above post, ad hominem attacks and all, was a reaction to a single sentence I wrote in the comments section of one of my own posts:

"But if you give them smaller doses of insulin that do not cause hypoglycemia, they do not gain fat, and often they actually lose fat."

In this single sentence of my comment, hastily composed, I mistakenly said that insulin causes fat loss, rather than prevents fat gain. This made no difference to my point, which was that low-dose insulin does not cause fat gain in non-diabetic animals. I had previously made my position on two of those papers abundantly clear in a blog post, which Peter is well aware of because he spent several of his own posts flailing around at it:

In my post, which Peter has read, and which is the only post in which I have described the papers in detail, I correctly described low-dose insulin as limiting fat gain rather than causing fat loss. Yet Peter chose instead to focus on the single sentence in my hastily written comment, using it as the basis of his whole insulting post (above), claiming I misrepresented the papers, even though he was quite aware of my actual position on the papers. Peter did not provide a reference to my statement in his post because he knew how ridiculous it would look.

This was a misleading tactic and can only be described as trolling.

2) By his own admission (above), Peter fabricated data about LIRKO mice in an effort to undermine my credibility, and undermine the relevance of LIRKO mice to the insulin-obesity question. Not only did he invent the idea that they have glycosuria, he even repeatedly used specific fabricated numbers for their blood glucose levels ("400 mg/dL") when the actual data are plain to see in table 1 of the paper he has referenced himself.

Peter has been flailing around at me in whatever way he can, including fabrication, misrepresentation, ad hominem attacks, and adolescent jokes, for more than a year.

Peter, this "debate" is over, and you owe me an apology.

Stephan Guyenet said...

Now that this matter is settled, I'm going to open up a bit for my last comment.

I realize I said some insulting things about the people who read this blog. To those who didn't deserve it, I apologize.

The reason Peter's posts anger me is that ad hominem attacks like the ones in this post literally have the potential to endanger my personal safety and that of my family and friends. I'm not a particularly paranoid person, but there are some extremely intense zealots on the Internet, and some of them frequent Peter's blog. I won't exaggerate my own importance, but my picture is on the Internet and I am somewhat of a public figure, and it's not that hard to figure out where I work and where I live.

Folks like Peter and "ItsTheWoo" take particular pleasure in whipping others into a frenzy over my work. As a result you get extremely angry people accusing me of being a "bullshit artist" (above) etc. For example, here's one of the many ad hominem attacks Peter flung at me in the post above:

"BTW I notice over on Woo's blog that there has been some discussion as to whether Dr Guyenet is just dumb or being very deliberately misleading, ie conspiring to mislead. I don't do orchestrated conspiracy theories. I don't really do the financial drive thing either, not for some body who is still as wet behind the ears as Dr Guyenet certainly is."

Look, disagree with my views if you want, but my ideas get NIH grants, peer-reviewed publications, and presentations at professional conferences. I do make mistakes sometimes, but I am not a bullshit artist, nor am I dumb or attempting to mislead. With 11 years of full-time research experience under my belt, I am certainly less "wet behind the ears" than Peter who (as far as I know) has no research experience at all.

People post all sorts of nonsense on the Internet, and it isn't my concern. What is my concern is when people fire up the crazies and point them in my direction. I am literally concerned that someone is going to come to my door one of these days and hurt me or my friends/family because someone like Peter went beyond politely disagreeing and into ad hominem territory for his own personal amusement and/or ego defense. I am literally concerned that someone is going to try to stick a knife in my back at AHS while in a Hyperlipid- or "Woo"-fueled rage. It won't be Peter (might be Woo though), but as I said there are a lot of disturbed people out there.

To anticipate my critics, I realize that I went into ad hominem territory in my comments above, but please consider that 1) I do not make ad hominem attacks against Peter in my blog posts, nor do I plan to, and 2) Peter has been provoking me with ad hominem attacks, misleading claims, and fabrications for over a year. As Melissa McEwen said recently, "Sometimes it’s hard to tell if Peter is serious or just trolling". So yes, I was angry, and Peter got what he had coming for a long time.

So please, what I am asking this entire community with all candor, is that you feel free to disagree with me (including on my blog if you choose-- I welcome respectful debate), but stop the ad hominem stuff. It is irresponsible because it literally has the potential to put me and my friends and family in danger, and these kinds of attacks are not constructive and not necessary to make your point.

Stargazey said...

By his own admission (above), Peter fabricated data about LIRKO mice in an effort to undermine my credibility, and undermine the relevance of LIRKO mice to the insulin-obesity question.

Not exactly. Peter admitted that the mice were not glycosuric. Because that bit of information was obscurely referenced in the materials and methods, he missed it and inferred a totally logical explanation for lack of fat gain in LIRKO mice. He was wrong about glycosuria. Period.

The question remains. LIRKO mice are insulin resistant in the liver and become profoundly insulin resistant in skeletal muscle as well. They have about 10x the insulin levels of a normal mouse. Why don't they become fat? My hypothesis is that in this one unique instance, systemic insulin is able to remain high because hypoglycemia does not occur. Ever. And in this one unique instance, the concentration of insulin stays high enough in the brain that insulin's satiety effect can be maintained over time. That's it. That's all. And that's why the data are the data, but have no clinical relevance to human beings who do not have the LIRKO mutation and who suffer hypoglycemia when their systemic insulin reaches 10x its normal level.

Sidereal said...

I am literally concerned that someone is going to try to stick a knife in my back at AHS while in a Hyperlipid- or "Woo"-fueled rage. It won't be Peter (might be Woo though), but as I said there are a lot of disturbed people out there.

I am deeply perturbed by this comment.

xxxxxxxxxxxx said...

The internet is about intellectual freedom. No one can shut anyone down by mislabeling their words. Now you can make a jackass out of yourself by trying to pretend you have the authority to police others on their own blogs. Silly. But too many people have suffered untimely deaths at the hands of doctors following false science. I dont think debating and calling out bad science will ever end. The skin has to become thicker if you want to maintain a public internet presence.

Anon said...

i am literally concerned that someone is going to try to stick a knife in my back at AHS while in a Hyperlipid- or "Woo"-fueled rage. It won't be Peter (might be Woo though), but as I said there are a lot of disturbed people out there.

Really? You seriously believe that someone would be willing to spend the rest of their life locked in a cage, merely to silence you?

You are a complete lunatic.

xxxxxxxxxxxx said...

With true compassion Stephan, I think you should consider psychiatric help. Im not being funny. That is in no way a joke.

gallier2 said...

And while your at it, check in a dictionary the difference between insult and ad hominem. Neither Peter nor Woo used an ad hominem argument against you, they used insults, no doubt, but they addressed the substance of your posts and your theories. Appeal to authority as you constantly do (obesity researcher this, obesity researcher that, bla bla) can be seen as a form of ad hominem.

I'm not a particularly paranoid person,

Yes, you are, it's proven by your last comment.

Stargazey said...

I am literally concerned that someone is going to try to stick a knife in my back at AHS while in a Hyperlipid- or "Woo"-fueled rage. It won't be Peter (might be Woo though), but as I said there are a lot of disturbed people out there.

Right. This happens all the time. Wooo is going to drive across the country or lie in wait at AHS in order to knife you in the back. Seriously? Self-centered, much?

Sidereal said...

I do hope that Dr. Guyenet is just "taking the piss" as we say over on this side of the pond or that someone has hacked into account. Or perhaps he thinks that by emotionally escalating this discussion to absurd levels he will silence debate / opposition to his ideas. If, however, he really does hold the beliefs he described in his latest comment, I would strongly recommend relating them to his GP who will be able to refer him for suitable specialist care.

FrankG said...

If I had serious concerns about the safety of my loved ones as a result of my internet presence, then I would question how important that continued internet presence were to me? Is it worth it?

I am not trying to silence you, as I can just as (usually) easily achieve that for myself by ignoring your blog... which I generally do these days after previous failed attempts to reason with you.

As the saying goes "if you can't stand the heat, get out of the kitchen."

Unfortunately out here in the real world, you are dealing with pesky, unpredictable humans; as opposed to easily controlled, genetically modified mice... sorry if we don't play along as you might think we ought to. You don't make the rules.

It seems to me that Gary Taubes started looking into obesity research in the first place, after witnessing the polite round of applause usually expected at the end of an obesity researcher's presentation; as compared to the third degree grilling he was more used to seeing with physicists!

STG said...

You need to recover some peace of mind, emotional balance and dignity. Do not engage, defend, explain or rationalize. You are in an emotional whirlpool and are appearing to be very pathetic and fearful!Calm down: Turn off your computer, take a walk/go for a run/listen to some classical music/meditate/take a deep breath and think about what your objective is?

Exceptionally Brash said...

Dr G, I accept your apology. But I also hope that others on the other side of things will take your words seriously and quit attacking people like me who find the most success on a low carb diet and did not do well on the plan you promote.
And I am so glad that you took down some of your earlier posts, and especially the nasty comments from several readers of your blog. Your blog was one of the first paleo-type blogs I followed, and it was shocking to me to read those comments by your fans, to the point where I quit reading and participating at all. Too bad you couldn't take down some of the comments on Paleohacks as well.
If you want to clean up the town and weed out the bad apples, it might be helpful to do that within your own bin as well.
Personally, I think the only one who has been materially damaged from the "paleo cesspool" has been Jack Kruse, who was physically removed from the cruise. Let's hope that that is as bad as it gets.

Galina L. said...

Why do we discuss cholesterol at all? The post is about hunger, insulin,satiety , fat gain, and how it all connected. You want us to consider your life experience and the fact that you lost some small amount of weight and significantly lowered your total cholesterol level, while ignoring what Frank's diet did to him - he lost 60 lb, needs now 10 times less injected insulin (he is D2) and avoids health complication typical for diabetic, but, big OOPS!, his total cholesterol went up. If you really think that in a such situation it is reasonable for you to lecture him about dangers of higher blood cholesterol levels, than you could be totally dismissed in future conversations.Or thinking for yourself means ignoring others? Don't you see how stupid your position looks like?

FrankG said...

Thanks Galina but at this stage I don't see any point in trying to engage GG in reasoned discussion.

Although you are broadly correct: I lost well over 100lbs and have maintained that (easily) for going on 4 years now AND my lipids (and all other regularly measured health markers) are just fine thanks :-)

Galina L. said...

@Dear Stephan,
I am sorry to learn that you feel yourself in a physical danger as a result of some posts and comments on internet. Probably my opinion doesn't matter much for you, but as a careful observer of all discussions you mentioned, I completely sure that your concerns are not valid, no one out of all who participated in the discussions leaves any impression as a person who may have a desire to harm you physically. Wooo just strongly disagrees with you, that is all. I regularly read her blog, she never ever expressed any desire of any harm being done to you. Please, just calm down. I am sure tomorrow you will see everything in more realistic light.

gunther gatherer said...

Galina, get a grip. And learn to read.

This has got to be the fourth time I've explained that I am talking about checking the facts and the data. Not lecturing anyone, and I wasn't even addressing Frank until he got defensive and aggressive as he always does when anyone challenges his belief system.

And BTW, you can lose 100 lbs on any diet if you are coming from a crappy diet to begin with. Doesn't make LC right. Do I even have to tell you this?

karl said...

@Guyenet said
"was a reaction to a single sentence I wrote in the comments section of one of my own posts:"

"But if you give them smaller doses of insulin that do not cause hypoglycemia, they do not gain fat, and often they actually lose fat."

Actually, you didn't make this claim just once. You have implied it several times.

Now moving away from the boring politics and back to science:

If we look at appetite and insulin, if we try to see this objectively, I can see that it is possible that insulin does not increase 'appetite' directly. But that is a long way from saying it does not influence long-term appetite via indirect feedbacks.

Lets see if we can all agree that insulin is central in setting the direction and magnitude of the FA flux over time?


If insulin is increased, it AND there are no compensating feedbacks the amount of calories available to run the body are reduced.


But biological systems don't work that way - there are several overlapping feedbacks - that could result in things like:

* Less movement - slowed metabolism - (thus less calories burned ).

* Catabolism - fat mass increases while protein is converted to glucose - fat gain without weight gain.

* Modulation of adipose tissue by autonomic system

* Shifts in insulin sensitivity. etc.

* Shifts in appetite and thus calorie intake - directly from insulin, fats, sugars are all possibilities.

What is going on is complex and it is very important to keep in mind what is a hypotheses and what we know with some confidence.

That being said, I have no doubt, having lived for years on a low-fat diet and then switching for 5 years now to a low-carb diet, (both diets cause food restrictions ) that low-carb reduced appetite while low-fat made me constantly hungry.

It is important that when we talk about possibilities we make it clear that we say that these are possibilities. Quoting cherry picked papers ( particularly correlative info ) and papers that seek to keep grant money flowing rather than actually test a hypothesis (such as the paper I cited above) is not helpful. It is also important to look for counter examples in the literature - and be aware that there are lots of poor quality papers and an increasing torrent of purposely misleading papers and out-and-out fraud.

Real science requires something different than lab-coats and degrees - Richard Feynman's writings about science - his Cargo Cult address and his work on education are a great place to learn what real science is.


Food choice in the end is a factor - but I'm unconvinced that this pandemic is due to moral decay - I'm much more interested in what has changed in the industrialization of our foods.

When fructose spikes of trygly that apparently blocks leptin's effect on the brain. Triglycerides Induce Leptin Resistance at the Blood-Brain Barrier is interesting - probably a real effect, except I don't think it explains the whole story - I can come up with counter examples where populations ate lots of sucrose and did not get as obese as the west is now.

It is only when we add PUFA generated inappropriate insulin sensitivity to the hypotheses that the long term picture appears clearer (and this is where Petro insight shines - all is good until we stop getting fatter).

There is a problem with lowcarb diets that would be explained by the PUFA effect hypothesis. Many obese people have great success losing weight via LC, but end up 15% overweight in the end. Reducing insulin's effect by cutting carbs may not be enough if the fats have too many PUFAs.

Sam Knox said...

I'm just looking forward to a getting a good night's sleep now that we've got that LIRKO/glycosuria thing settled.

Purposelessness said...

What I learned today:

1.) Obesity research is a highly emotionally charged field.

2.) Obesity researchers don't need to know their fallacies. Ad hominem = You are wrong because you are X.
Calling someone a name because he lacks intelligence or misrepresented stuff might be unfriendly, but it is not an ad hominem argument.

3.) Being paranoid doesn't seem to hamper the career of an obesity researcher.

4.) Spending more time on an "pseudoscience" blog than the blog author himself suggests that obesity researchers work VERY reasonable hours.

5.) Experience in research doesn't seem to correlate with the abilities of the researcher.

6.) While a low carb diet seems to, anecdotally, produce even tempered individuals, a diet low in "food reward" seems to produce cranky individuals prone to child-like tantrums. (I know Woo might seem contradict this, but think about it. Maybe Woo would be even more ranty on a high carb diet, we don't know.)

7.) Obesity researchers seem to think ranting and arguing on the internet = violent behaviour.

Overall, if I were an armchair psychoanalist, I might say a certain PhD seems to project an awful lot on bloggers and commenters who haven't said even remotely enough to justify his judgements. Half of what he said, though, seems to be wonderfully applicable to himself.

I just hope everyone reads this comments and will judge for one self. The comments here paint a pretty clear picture about most people involved.

Disclaimer: This comment is a work of fiction, written solely for the amusement of myself and a few others. Similarities between fictional characters and real people is unintentional and regretted.

Galina L. said...

You are right , you not only talking about cholesterol, China Study, dangerous sat fats, but busy moderating blog advising people type carefully, learn to read, go and watch some vegans on youtube in order to finally find right facts.
Another Yes, I hear it all the time that the most important thing for a weight loss is to drop the crappy diet. Usually such hint is shared by people who eat a crappy diet themselves and think that everybody is doing the same. Like couple days ago one lady without any health problems (and avid crusader against LC "dogma") on another blog said that she experienced weight gains only if she eats a whole loaf of bread with butter in one sitting, but one roll was fine. So , the hedonism is an issue.

Sidereal said...

Researchers fighting with us internet crackpots during working hours is apparently what your tax dollars (NIH grants) are being spent on, ladies and gentlemen.

gunther gatherer said...

Galina, and you are busy making me scroll more. You usually have zero content to your comments, but this one was particularly educating just for the fact that now we can see you can't read. Shouldn't you be telling some pointless story about your husband and what LC things he chooses for lunch?

xxxxxxxxxxxx said...

Sid, you're going to get 5 demerits from the blogger police for that shameless display of .......of.......truth?

Galina L. said...

True, I usually base my comments on my own experience, not on what some gurus said. Probably because I am thinking for myself, as you advise, and not taking somebody's word as a final truth.
BTW, my husband doesn't eat a LC diet.

gunther gatherer said...

Sorry Galina, guess I scroll too fast when I see your name now. But I should have remembered that since you repeatedly mention it...

Galina L. said...

You are most welcome to scroll, Ganther.

LeonRover said...

"Four hounds gone south,
one has your liver in his mouth.
Poor Actaeon.
. . . .
The female hate
of things too female to relate
Poor Actaeon.
. . . .
Four hounds went south,
one had your liver in his mouth.
Poor Actaeon."

- Michael Hartnett.

Gob said...

Boy, veganism sure makes people angry and miserable. Anyone have any ideas how Gunther can pull himself out of his funk? Maybe some meditation?

gunther gatherer said...

What a fitting name you've chosen Gob. You just can't shut it I guess, even long after the horse is dead and buried on this thread. Yawn...

LeonRover said...

Gunther could try the 200 days Orthodox fasting being currently advocated by The Primal Don.

gunther gatherer said...

My feeling about fasting is that if you have to do it to maintain weight or health, your diet doesn't really work.

Would anyone else like to pop in with some obnoxious, glib comments just to taunt me and extend this thread even longer or are we done here?

If anyone is angry and miserable, it seems like you guys. Not a sign of vibrant health to me. Jus' sayin'.

ItsTheWooo said...

@SG: No offense, but you sound really crazy. Like, you're going to have a nervous breakdown type crazy.

If you are imminently away from mental colapse, I'm sorry if my mockery has contributed!
Otherwise I have to assume this is just manipulation/retaliation; if so, plz do not accuse me of trying to murder you IRL as that's neither witty nor scathing nor mocking, it's just kinda creepy/icky. Call me a bipolar high fat apologist with anorexia and bulimia if you must mock me.
Truly feel creeped out right now!

I really don't think it's fair at all you make the comparison between me mocking your work and your ideas, and occasionally you, to me trying to have you murdered or actually attempting to murder you. Again, are you serious, or are you in the midst of a nervous breakdown?

I've made less than zero attempt to contact you and I have an extremely small readership. But really, if what I've written is this distressing to you, you almost put me in a position where I have no choice but to withdraw... even if for no other reason than you seem mentally unstable enough not to handle it.

One of the reasons I've (jokingly, not seriously) mocked you so is because I read you as a very unemotional stable person but your comments here make me totally reconsider my assumption and lay on a nice heaping of teh guilts.

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