Monday, June 25, 2012

The Flatline Days

Almost done with insulin infusions, thankfully. This post follows on from the initial post here.

It's time to discuss the discussion and then leave this paper for ever. Here's your starter for 10, and I quote:

"These three studies suggest the following: (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."

and at the end of the discussion:

" seems probable that our prolonged, modest elevations of insulin resemble the elevated basal plasma insulin induced by prolonged overfeeding and perhaps, obesity."

Let's combine suggestions (1) and (2) and drop down to our local McMuffin restaurant to watch the people eat. I've never tried this, so you have to realise I'm making all of this up, in its entirety.

In comes Jo Blob at 400kg, fasting plasma insulin at 100microIU/ml. Obviously this fasting hyperinsulinaemia blunts his appetite and he turns down the "you wanna supersize that?" offer, sits picking at his fries and soda for half an hour and eventually pushes the burger-in-a-bun away after three mouthfuls as his satiety hormone has kicked in, to even higher levels than it was when he was fasting.

Across the aisle sits Dr Guyvernment at 55kg with a fasting insulin of 5microIU/ml. Where is his satiety? Obviously he is ravenous and after the double baked potato with a baked potato on the side and three baked potatoes to follow, he's still ravenous because he is so insulin sensitive that he can't get his satiety hormone level over diddly squat.

It's the age old story. Skinny people overeat because their insulin levels are low and and fat people are chronically over sated so refuse food. Have you noticed anything along these lines? No? Somewhere along the line we do have to have a reality check!

The next statement from the discussion which caught my attention was this one:

"As pointed out earlier, some animals which received the higher dosage of insulin showed hyperphagia, as has been reported in numerous other studies [3. 8, 9, 11, 15]. It is probable that animals which became hyperphagic were more insulin sensitive and perhaps increased food intake to counteract hypoglycemia."

Okaaaay. This suggests that the animals on 6iu/24h over-ate. On average. I hate to query the obvious but does this imply the animals on 1iu/24h didn't overeat? So of course this means that the 6iu/24h animals must have gained more weight due to their hyperphagia. So did the 6iu/24h group really gain extra weight compared to the 1iu/24h group? Go look at Fig 1. Here it is again if you've forgotten:

Duuuuh. The 1iu/24h group gained more weight than the (partially hyperphagic) 6iu/24h group, even if p never got below 0.05. The people who wrote the quoted text are the same people who drew the graph... They have the daily food intakes and weight gains for each individual rat...

And finally, before I leave this execrable paper for ever, are the animals on insulin pumps just ill from their insulin infusion? Let's quote the authors again:

"We realize that a simpler explanation for our results might be that the animals become sick following the release of the insulin, however, we offer two arguments against this. First, water intakes were not decreased by insulin infusions from the Minipumps but were elevated by an average of 47.3% during the first 2 days following pump implantation and then returned to normal. Following this initial elevation, water intakes were not significantly different from controls (0 U/day animals) and the pump-implanted animals’ own baselines..."

Never mind the second argument. Let's think about polydipsia (and presumably polyuria because weight didn't increase) as markers of robust good health in a patient, any patient. I'll use a make-believe, utter fantasy, clinical setting:

Dr Insulin: Ah, hello Mrs Ratty, how are you since I implanted your insulin infusor pump two days ago, to help control your appetite?

Mrs R: I can't seem to stop drinking. I've always got to have a bottle of Evian by my side and I'm spending 47.3% more on the stuff. I wake up in the night to have a drink and I always seem to be spending a penny.

Dr I: Excellent, a good thirst is always my first maker of robust health.

Mrs R: Oh, so you won't need this urine sample I've brought?

Dr I: Oh no, no need to check your urine if you have a healthy thirst.

Mrs R: So I can throw it away?

Dr I: Of course. By the way, is that your sample in the five litre container? Could I oblige you by assisting with its disposal?

Mrs R: Thank you so much, it is quite heavy. You are so helpful. Goodbye.

Dr I: Goodbye (and after Mrs R has left): Igor, IGOR! Come, never mind the LIRKO mice, we have jam a-plenty tonight. Boil down this sample at once...

Okay. If a rat on a pump giving a constant rate infusion of insulin gets Somogyi overswing, how long does it take for the overswing to correct itself, while ever insulin levels are held constant?

I would guess two, at the most three, days. The Flatline Days. When glucose is high and appetite is consequently low. Pure speculation. It would have taken 30 seconds on a urine glucose test stick to check this. They had the sticks.



Stipetic said...

On first read, I read "excretable paper" instead of "execrable paper." Turns out the meaning is synonymous either way.

Thanks for the accompaniment to my morning coffee (rich in fat, low in potatoes), Peter. Enlightening, as always.

blogblog said...

Dr G has quoted a paper based on reading the facial expressions of rats (I'm not making this up!) that (he claims) proves beyond all doubt that palatability controls appetite

Jane said...


You need to read Dr G's post more carefully. What he says makes sense. Palatability is known to release beta-endorphin in the hypothalamus, and beta-endorphin inhibits the sympathetic nervous system which innervates adipose tissue and activates lipolysis and thermogenesis.

FrankG said...

Yes indeed Jane... I strongly suggest that if you still do read Dr G's musings, you are well advised to read them VERY carefully. ;-) Watch out for appeals to authority and specious arguments that do not stand up to even superficial scrutiny.

Jenny said...

It isn't high insulin, per se that drive appetite, but the blood sugar drops that insulin causes. A person with very high circulating insulin levels will not have that raging appetite if their blood sugar stays stable, but in real life, it rarely does since the insulin does, eventually, lower the blood sugar, sometimes very swiftly. The faster the drop, the more intense the hunger, even within the normal blood sugar range. I have documented some of the reasons for this in my book Diet 101: The Truth about Low Carb Diets.

karl said...

Who funded this abomination? The money path is important to know.

Peter said...

Karl, "This work was supported by grant AM 17259 (DAVW), center grant AM 17624 (DAVW & FXPS), grant NS 7687 (DN) and research development funds from Occidental College."

Not sure that people where so good at manipulating data to support funding in those days. It looks more like blind faith to me, coupled with cognitive dissonance and groupthink. It's the degree of selectivity in data selection and reporting that makes me gasp.

There should be a joke along the lines of "What do you get when you mix a surgeon, 3 psychologists and some obesity funding...." Can't think of a worthy punchline!


Andrew S said...

"[T]his decrease in meal size is not compensated for by an increase in meal frequency" is a shameful statement. And for a scientist to blindly accept the stated conclusions without looking at the data is inexcusable, and also makes a mockery of peer review.

From Wikipedia: "[Polydipsia] is characteristically found in diabetics, often as one of the initial symptoms".

Gonna hafta have a think about these first three days; I'm still wrapping my brain around it.

Andrew S said...

ok, summary and theory here:

Rats eat CIAB, so despite getting the calories they need they're not getting proper nutrition and hence over-eat, hoping that next bite contains something other than sugar. Their cells have adapted to blood glucose levels and endogenous insulin generation.

Now give the rats a continuous insulin injection. All that BG rushes in to cells due to heightened GLUT4 expression. After immediate metabolic needs are met, the rest builds up as glycogen, and then when that's full the excess starts causing superoxide production. Cells shut down, becoming intensely IR, to take care of the superoxide problem.

As digestion continues, BG rises. Cells don't care. Hunger disappears, and rats consume excess water mayhap to thin out the glucose concentration in the blood and/or to slow digestion. Any time the Simogyi effect diminishes, there's BG and insulin to fill cells back up again.

After about three days, cells have adapted to the new insulin regime. With a constant insulin drip, lipolysis is arrested and weight gain ensues.

tess said...

"What do you get when you mix a surgeon, 3 psychologists and some obesity funding...."

how about, an obesity-researcher whose brain has been excised?

Exceptionally Brash said...

"What do you get when you mix a surgeon, 3 psychologists and some obesity funding...." I am not sure, but I am certain that it is endergonic.

karl said...

RE: Dr. G and palatability

For some reason he has ignored the research of Dr Wurtman at MIT - Serotonin levels go up with carb intake - thus comfort food. Serotonin Receptors in the brain actually down-regulate and thus carbohydrates are a real addiction. ( As are the SSRI that are only trialed for 6 weeks ).

To re-normalize these receptors might take weeks. In the mean time, every crash in BG causes a crash in serotonin which reinforces a destructive life style.

I wonder if there is any research that compares glucose and fructose for their effect on serotonin?

Stan Bleszynski said...

I will leave discussing Dr. Guyvernment's "theories" aside, and will use this thread as an opportunity to ask some off topic question regarding leptin. I am trying to work out an engineering model of the human metabolism involving glucose and fat as energy inputs, and insulin and leptin as control circuits operating two intertwined negative feedback loops.


- Is it a good approximation to assume that leptin level is proportional to the amount of adipose tissue in the body?

- Is leptin regulating the transport of fatty acids into the non-adipose cells directly (locally in the cells), and out of the adipose cells directly, or only through the hypothalamus/brain?

- Is fat metabolism self-regulated only within the cells (by malonate feedback/clamp as per Masterjohn's article?), or is leptin also involved locally as well. Is it correct to assume that the local malonate clamp is operating in addition to the global regulation of fat burn through leptin acting through brain, in a similar fashion as GLUT1 works for glucose locally by itself and GLUT4 controls glucose uptake globally through insulin?

- Can one assume that consumption of dietary fat stimulates the release of leptin in a similar fashion (proportionally) as consumption of carbohydrates stimulates insulin?

Stan (Heretic)

blogblog said...

people who have ZERO sense of taste still eat more or less normally (and can get fat).

ItsTheWooo said...

@Jane Guyenet has denied palatability has anything to do with reward.

Guyenet does not believe there is a metabolic defect causing obesity (e.g. inhibited lipolysis/thermogenesis via beta endorphin).

Guyenet believes obesity is a problem of fat slobs putting food in their gullets because their brain is like DOPAMINE DOPAMINE DOPAMINE I CAN FLY ON CHEETOS rather similar to a crackhead. It is no more complex than too many calories consumed due to an excessive dopamine response to certain foods, and those foods are "rewarding".

I agree w. frank, if you must read Guyenet pay close attention, he is rather fond of contradicting himself and quoting super ridiculous references to bolster his ridiculously simplistic TOE of obesity. (You ate too many mars bars. Problem solved.)

@Jenny I also believe insulin resistance in the brain and a loss of sympathetic response is part of some obesities.

Guyenet will inform you only severe diabetic hypoglycemia causes hunger. Guyenet will inform me that when my sugar went from 140->45 I may be a bit hungry. However, I must be imagining the numerous times I went from like 110->70 in a few minutes and felt shaky and hungry as well.

ItsTheWooo said...

@Karl technically if we are gonna start with food addiction/comfort eating it should be noted comfort foods are typically high fat, and the goal is to make endorphin NOT to make serotonin.

No one comfort eats pretzels or sugar. They eat cookies and ice cream and brownies... fat, and dairy, along with the sugar. Comfort eating is an attempt to get at endorphin, not serotonin.... but IMO the whole food addiction/comfort eating thing has been mischaracterized as addiction to food when it is more accurately described as a stress management technique.
Stress hormones are regulated by central opiates; taking opiates or raising endorphin suppresses the stress response, people feel calm and contented. People are driven to eat and seek food when stressed because 1) stress hormones fuck up your blood sugar and insulin and powerfully increase appetite... 2) food exerts negative feedback control over central stress responses.
Eating helps people stay sane in shitty circumstances, basically. This is probably because stress, throughout our evolution, was a reiable indicator of active or likely future nutrient deprivation. If your cortisol is increasing, and this is going on for many days, it's a good sign that perhaps in the future you are about to starve to death and die. Better get to eating.

Insulin says the same thing, as insulin pretty much follows cortisol, as stress hormones clearly make you a glucose intolerant diabetic fat blimp, you overproduce insulin to all those healthy paleo potatoes you shovel in the hole. I've often thought that hyperinsulinemia promotes resistance and weight gain specifically because hyperinsulinemia is typically redundant with stress. I mean, in healthcare, you'll see this combo pretty commonly: dexamethasone and basal insulin. Give the dexamethasone in the am, inject the lantus in the pM. This is just how things work.

If you increase your "HELP WE'RE GOING TO STARVE TO DEATH AND DIE!" (cortisol) hormone, you need to increasE youre "QUICK STORE FAT ASAP" (insulin) hormone. The body does this naturally, unless of course you are really unhealthy, then I need to inject you with it.

There's a pretty good relationship between fat tissue and both cortisol/stress hormones/insulin. Cortisol is pretty important in adipogenesis, along with insulin; stress hormones regulate the fat tissue, literally shutting down growth of lean tissues, bone, skin, muscle, BRAIN, in favor of adipose hypertrophy/plasia.

Steroids increase the appetite. Progesterone is an adrenal gland hormone, and a substrate for cortisol. We give dying patients who are cachexic progesterone, which increases cortisol, which makes them think nothing is better than eating food. Gee what do progesterone and cortisol have in common, other than gland of origin? How about the fact they are both high in anticaptory nutrient stress?

Opiates are like the anti-stress chemical. Run into a bag of sugar and dairy and you've hit the garden of eden jackpot as far as your brain is concerned. It's like "Hey, why so serious? Calm down, rest, sleep. Let's turn off that stress production shall we?" Look at your average doper. Emaciated under a pile of rags, blissed out and nodding off. Usually ended up on dope after years of depression/stress, which the found magically resolved with dope.

Myopia is pretty cool. People think food addiction is because "big food" (god I hate that phrase) has engineered irresistibly delicious food. In reality modern life has engineered unmanageably horrific and unnatural living circumstances which may drive certain people (not all fat asses, but some of them) to find comfort in brownies to manage their otherwise brain rotting mental illness and disease inducing levels of stress.

If this is addiction, that one partakes in moderate over consumption of baked goods to deal with a horribly deprivational environment, I guess people with bum legs are also emotional walkers because they tend to start limping to get around.

Jane said...




No, that is not what Guyenet believes.

Jane said...


'Yes indeed Jane... I strongly suggest that if you still do read Dr G's musings, you are well advised to read them VERY carefully. ;-) Watch out for appeals to authority and specious arguments that do not stand up to even superficial scrutiny.'

Please could you give me an example of such an argument?

Elliot said...


"Please could you give me an example of such an argument?"

Jane said...


' about, an obesity-researcher whose brain has been excised?'

Do you mean Stephan Guyenet?

Jane said...


Thanks. The point Stephan was making was valid. I think he could have used less extreme language, but it was actually quite restrained compared to the language others use about him.

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


He writes...
"In the first study, published in 1980 by Dr. Dennis A. Vanderweele and colleagues, rats were implanted with mini-pumps delivering insulin at a steady rate throughout the day and night for 7 days (4). They tested four different doses: 0, 1, 2 and 6 units per day, and measured food intake and body weight. This is a model of chronically elevated insulin reminiscent of what is seen in insulin-resistant people."
my bold emphasis


This was offered as a "Final Nail" in the coffin of the CIH. And while some may consider infusing insulin into a dozen otherwise healthy rats for A WEEK, to be "a model of chronically elevated insulin reminiscent of what is seen in insulin-resistant people." are you really so easily fooled?

I can accept that this study may have some validity at some level but when someone who claims to have access to an overwhelming body of evidence AND frequently speaks as if he has the voice of the entire "research community" -- when such a person offers such a weak study as a "final nail" to an opposing hypothesis I have to pause and think how far I can trust this person's word anymore.

Someone who frequently tries to bolster their position by reminding us that they are a "real scientist" (not like the others) suggest to me that they feel unsure about their position. Real science stands on its own without appeals to authority.

Furthermore, anyone who dismisses Type 2 Diabetics or those with Metabolic Syndrome as "outliers" or otherwise not pertinent to the discussion of obesity, are so far off the mark that they are not worthy of my respect.

Elliot said...


"Thanks. The point Stephan was making was valid. I think he could have used less extreme language, but it was actually quite restrained compared to the language others use about him."

Huh? He produced not one, not two, but three studies supposedly in support of his claims against Peter's, and exactly none of them actually did support them.

As far as "the language other use about him," commenters aside, I think you'll find that Peter was actually quite mild and polite toward Dr. Guyenet for a long time-- but once somebody calls you "utterly confused" and full of "cognitive dissonance" then I think no one would argue that turnabout is fair play.

Puddleg said...

Here is where the food reward hypothesis and the insulin hypothesis come together:
Stephan found a paper on the fattening effects of these taste receptors that didn't mention insulin. Here's one that includes it:

Sci. Signal., 28 February 2012
Vol. 5, Issue 213, p. ec64
[DOI: 10.1126/scisignal.2002999]


How Sweet It Is

Wei Wong

Science Signaling, AAAS, Washington, DC 20005, USA

Fructose is the sweetest natural sugar. It is detected by a heterodimer of the sweet taste G protein–coupled receptors T1R2 and T1R3, which are present not only on the tongue but also in other organs, including the intestine and the pancreas. Kyriazis et al. found that fructose potentiated insulin release from isolated mouse islets when added in combination with a concentration of glucose expected to induce insulin release (8.3 mM) but not with a concentration that would not be expected to induce insulin release (3 mM). In β cells from wild-type mice, the increase in intracellular calcium concentration (which is required for insulin release) elicited by 8.3 mM glucose was potentiated by fructose, an effect that was not seen in β cells from T1R2–/– mice. In islets isolated from wild-type or T1R2–/– mice, increasing the glucose concentration from 8.3 to 16.7 mM induced a substantial increase in insulin release (a phenomenon called glucose-stimulated insulin secretion). This increase was further enhanced by adding fructose in combination with the higher glucose concentration to islets from wild-type mice but not those from T1R2–/– mice. Similarly, when administered in vivo, fructose potentiated glucose-induced insulin secretion in wild-type mice but not in T1R2–/– mice. The ability of fructose to potentiate glucose-induced increases in intracellular calcium required phospholipase C (PLC) β2 and the cation channel TRPM5. Fructose potentiated glucose-stimulated insulin secretion in human islets, an effect that was blocked by pharmacological inhibition of T1R3. The authors note that sweet taste receptors in the intestine stimulate the absorption of ingested glucose and the release of glucagon-like peptide, a hormone that promotes glucose-induced insulin secretion. They speculate that sweet taste receptors in the intestine and pancreas could be activated by dietary fructose, including that found in high-fructose corn syrup, a sweetener widely used by food manufacturers that has been controversially linked to metabolic diseases.

G. A. Kyriazis, M. M. Soundarapandian, B. Tyrberg, Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. Proc. Natl. Acad. Sci. U.S.A. 109, E524–E532 (2012). [Abstract] [Full Text]

karl said...


I would disagree - While the term "comfort food" does not have a precise definition - there is no shortage of papers written on the connection between carbohydrate cravings and depression.

ItsTheWooo said...

@Jenny In fashion of Nigel and others you seem to be randomly making your own definition up of food reward and putting words in Guyenet's mouth. I have been following him along trying to get a clear picture of what exactly he believes. He's contradicted himself numerous times, but the dust has clearly settled here:

-Palatability is not reward, some palatable foods iwll not lead to dopamine disinhibitoin and addiction, which is the definition of food reward.

-Reward is a dopamine mediated phenomenon, certain foods typically those modernly engineered produce excessive dopamine and lead people to compulsively eat them.

-Fat people are not hungry, their eating behavior is similar to drug seeking, it is a compulsion which isn't related to true hunger for calories/biological appetite.

-All metabolic problems in obesity are secondary to their obesity; fat cell overdistention is leading to insulin resistance and high insulin levels. The fat cell is over distended because they keep eating too many calories, because of food reward.

-Insulin is neutral/passive/facilitative of obesity. Insulin does not cause glucose problems and insulin is always reactive to nutrition in obesity. Hypoglycemia is not real.

When you come in here with your "palatability causes obesity" stuff you must understand this is purely your own belief and guyenet doesn't share it at all. He does not believe palatability is reward, and he certainly doesn't believe palatability causes metabolic defects.

ItsTheWooo said...

@karl first you must understand a lot of research is bullshit. Many so called "carbohydrate foods" are more accurately described as high fat/sugar/starch combination foods.

Second, carbohydrate craving is a sign of atypical depression (which I have) and again, people in atypical depression are not sitting down with a bag of pretzels or potato chips. They're generally stuffing their faces with excessive food calories, energy dense food, which contains lots of carbs but also good heaping of fat. It should be noted measures of carbohydrate craving (which is really calorie craving) improve when chromium is supplemented, a mineral that helps regulate insulin use in the body and is considered related to the atypical depression syndrome.

The atypical depression syndrome most intimately is related to defective HPA axis with supersensitive suppression of CRH. This is only exacerbated by chronic hyperglycemia/carb eating, which furthers suppresses stress responses.

PS, abnormally deficient central stress response (redundant with your atypical depressive syndrome) will also lead to low endorphin levels, which is probably the real cause of the depressive symptoms in atypical depression (the fatigue, on the other hand, is mediated differently by low central stress response). Google proopiomelanocortin for more infoz.

Third and finally, serotonin is forever linked with endorphin anyway... serotonin increase leads to more endorphin being produced, as well as more CRH. The efficacy of SSRIs in depression is possibly related to the fact serotonin boosts a low endorphin, the real cause of most non-severe depression. So this is all redundant anyway.

ItsTheWooo said...

*low fat potato chips, sorry.

Peter said...

George and Woo and all,

Thanks for your input. I'm very hindered in this discussion as I simply never read Guyenet beyond the comment he made on Hyperlipid and the link from Frank. When I look at his extraordinarily misleading partial quotes from bent papers on metabolism I'm gobsmacked at the arrogance intrinsic in describing myself as being confused and having cognitive dissonance.

To those of us who have the stomach to track what he really (at the moment) thinks (if that is not an overstatement) I'm grateful. To see the selectivity in his reporting of taste receptor k/o mice studies is very nice and utterly predictable.

I am open to the bizarre concept that some of his ideas may be correct, in an utterly hypothetical way of course. The fact that they will be rooted in metabolism and will only be presented in a fashion which obscures this is my prediction.

Or that it's all bollocks, of course.


Makro said...

OT: It appears as if the low reward value of low-carbohyrate fare (compared to a hyperrewarding low-fat diet) boosts TEE by 300 kcal / day.

Makro said...

(During weight loss maintenance, that is)

Jane said...

Peter, Stephan was VERY rude to you, no doubt about it. 'Confused' and 'cognitive dissonance' were unforgivable and incorrect. However, if you are honest you must admit that things Wooo has said about Stephan, and continues to say, are at least as bad. You encourage her to do it, I imagine because you know what will happen if you dare to disagree with her.

Jane said...


'Huh? He [Stephan] produced not one, not two, but three studies supposedly in support of his claims against Peter's, and exactly none of them actually did support them.'

Yes, they did. Which is not to say Peter is wrong, he isn't, not to my mind anyway. You need to understand the whole history of this debate.

gallier2 said...


thank you for that link. I feel that we will have a lot of hand waving and rationalising coming from the CICO (Colpo, Carbinsane, Krieger) and FR crowd. That study is the first one I've seen that comes close to proving a metabolic advantage for low-carb. The funny thing they won't be able to dismiss it because it is neither sponsored by the Atkins Foundation, nor is nutrition&metabolism involved and WestonAPrice Foundation is also absent. It was done by David Ludwig, someone that I knew only as a purveyor of CW until now.
Another prediction: there will ne a lot discussion about the dangers of cortisol and thyroid hormones from the usual suspects.

Makro said...

Gallier: Mostly cortisol, as CRP was nonsignificant. (I guess they could do da trend).

Jane: I've repeatedly reccommended Woo to cut the bile, with limited results, but it's not as if she reacted adversely to the mere suggestion.

Again though, for good measure: Spite in empirical debate leads to autolobotomy. (Some genteel ribbing is fine though, imho).

gallier2 said...

Oh, absolutely Makro. I only predicted that they will harp on that relentlessly because those were the only parameters that were somewhat negative on the low-carb arm.

Jane said...


If you really have tried to get a clear picture of what exactly Stephan believes, as you told Jenny, you have failed. I do not recognise ANYTHING you said. Have you forgotten I read everything Stephan writes?

Jane said...

Makro, spite in empirical debate leads to autolobotomy! Hahaha

I think Wooo should be restricted to 20 lines a day. Or maybe 10. I would hate to see her go, but she needs to be made to think before she writes, because it really is mostly incomprehensible.

tess said...

"I think Wooo should be restricted to 20 lines a day. Or maybe 10. I would hate to see her go, but she needs to be made to think before she writes, because it really is mostly incomprehensible."

who do you think you are? this is not your blog, and i see you dictating elementary and/or mistaken statements over and over -- far more than 20 lines a day! those of us who have been treated disrespectfully by SG are entitled to our poor opinions of him. don't delude yourself that we "don't understand" -- some of us believe it's YOU who don't.

FrankG said...

@Jane "...she needs to be made to think before she writes..."

This is me being very glad that this is Peter's blog and not yours ;-)

I read that: by claiming to have read everything Stephan writes this makes you the authoritative judge of how it should be interpreted? Please see my comments earlier about appeals to authority.

I notice that you offer no counter points but are simply dismissive of others.

On that note I was expecting a response to my example of his specious argument style above.

In case there is any confusion: Specious -- having a false look of truth or genuineness.

To claim a 7 day (yes just one week) trial of infusing otherwise healthy rats with insulin, as a model for a condition which in humans takes many months, years or even decades to develop, may fool some but do you really think it valid... just because an accredited obesity researcher SAYS it is so?

This is but one example of the many I noticed before (like Peter) I chose to no longer read his blog.

And while you feel free to pass personal judgment on Wooo... the fact that you claim to continue to read Stephan's blog and clearly have respect for his work suggest to me as one commenter put it (or something similar) at WHS "the intelligence level on this blog has just gone down again"

Anonymous said...


I think Wooo should be restricted to 20 lines a day. Or maybe 10. I would hate to see her go, but she needs to be made to think before she writes, because it really is mostly incomprehensible.


Shocking rudeness right there coming from someone who claims Guyenet has been treated unfairly. This is Peter's blog; he decides who gets to comment on it, not you. I personally find Woo's comments perfectly comprehensible and in fact incredibly helpful in my personal struggle against obesity. It would be a shame if she stopped blogging/commenting because of people like you or Guyenet who offer nothing clinically useful in this debate, nothing whatsoever, just pointless speculation and theorising which has thus far sent no one's obesity into remission as far as I can see. I see, because you and Guyenet have PhDs and are "real scientists", that gives you the right to talk (crap mostly), but Woo can't say what she thinks.

You spam other people's blogs with your kooky grand theory of micronutrient imbalances causing every disease known to man for which you, by the way, haven't produced a shred of evidence. Some may find you just as annoying as you find Woo, yet I don't see anyone telling you to shut up.

ItsTheWooo said...

When I wrote @Jenny I meant @Jane, I do apologize, as Jenny was not mischaracterizing Stephen and randomly making up a definition for the FR hypothesis... Jane was doing this.

Re: Jane, no offense, but who crowned you moderator of the internet? You keep telling us about how rude this person is or that person, as if you are some kind of internet judge judy. Frankly I don't think anyone has been overly rude. Rudeness is part of argument and discussion, at times, and no one has crossed the line (lately anyway haaa).
If it helps, I am going to take your queen of internet crown for a few seconds to let you know I have found many many things you have said to be EXTREMELY rude, both to me and others... so you should probably consider being less rude. Thanks.

Galina L. said...

Sorry, Jane, but I am afraid more people would hate to restrict Wooo to 10 lines and/or see her go than to side with you. There is always an option to skip reading what is annoying, I am sure there are some who skip mine comments or , after seeing your name, promptly assume it is about a copper deficiency again and skip the comment because they read it already several times. BTW, I always read your comments and respect your opinion about micro-nutrient deficiency, but not about shutting the Wooo off.

I noticed that Wooo cut her bile a lot especially while commenting on other people blogs, which is great because it allows her to participate in discussions and not being dismissed just on grounds of inappropriate behavior. I guess on own blog a person is free to say basically whatever. She left numerous comments on the Carbsane blog about several blog-posts and never said anything disrespectful or hostile to Evelyn (as far as I noticed).

Galina L. said...

I think it is not necessary for Peter to shat Wooo now as a necessary protection in order to be safe in case if he decides to join safe starches movement in a future. It doesn't look like he is an easily offended gentleman with a particularly thin skin (may be he has a wish to have a Kevlar skin in order to deal with his toothy patients) and an ability to be easily pissed off and to stay pissed-of forever.

Puddleg said...

"I am open to the bizarre concept that some of his ideas may be correct, in an utterly hypothetical way of course. The fact that they will be rooted in metabolism and will only be presented in a fashion which obscures this is my prediction."

Well said Peter.
These are the tables from the fructose-glucose-taste receptor paper:

Consume fructose after fries, and you're all set for an insulin spike. The ratios were Fructose 10.0 mM plus 8.3 mM glucose.

Eating a piece of fruit might not elevate glucose to this tipping point; the glucose has to be high enough to elevate insulin by itself for the boosting effect of fructose to be seen.
This can explain why fruit juice might be fattening and fruit not, for example.

Jane said...

'..who do you think you are? this is not your blog, and i see you dictating elementary and/or mistaken statements over and over -- far more than 20 lines a day..'

No, it's not my blog. It's Peter's. If he thinks I have made mistaken statements, which would be very serious, he can tell me.

'..On that note, I was expecting a response to my example of his specious argument style above..'

For you, Stephan's argument style is specious. For me, it isn't. How are we to agree about this? WHS gives me a clear and concise summary of current research in obesity and related topics, and this is why I value it.

'..You spam other people's blogs with your kooky grand theory of micronutrient imbalances causing every disease known to man for which you, by the way, haven't produced a shred of evidence..'

I have produced a lot of evidence, which you may not have followed up. If you have evidence against micronutrient deficiency being a major cause of disease, let's hear it.

If as you say, Stephan has offered nothing clinically useful in this debate, it's because he has not yet integrated micronutrient deficiency into his theory. Neither food reward, nor insulin, nor genes nor anything else can explain obesity without consideration of micronutrient deficiencies. I can give you all the evidence you like about this. If I do, will you listen?

Jane said...

BTW Wooo, I think you took my entirely unjustified and very rude attack on you very well indeed.

FrankG said...

@Jane: "For you, Stephan's argument style is specious. For me, it isn't..."

I suspect that I am wasting my time and I'm already rapidly forming my own opinion as to your credibility and reliability as a source of anything useful in this discussion, but I'll offer you one last chance to directly answer my question rather than sidestepping it as you have above...

Stephan -- armed with a wealth of evidence to back him up -- claims that a 7 day (one week) trial of infusing otherwise healthy rats with insulin, serves as a model for a condition which in humans takes many months, years or even decades to develop. In this context where Stephan -- a credentialed "scientist" -- is trying to systematically build a case against the Carbohydrate Insulin Hypothesis and offering this study as a final nail in its coffin do you really think it is valid evidence?

Or do you think (as I do) that he relies on many of his "lay" readers to simply take his word for it and bask in his ability to post lots of links? Trusting that most won't actually scrutinize the studies he offers, or (god forbid) critique them... well they couldn't be expected to really... not being scientists 'n all.

I am hoping for a proper answer rather that this childlike stance of "yes you did!" "no I didn't!!" that I am so far hearing from you.

You may be surprised to hear that I remain open-minded which is why I took the time to read Stephans' blog in the first place.. hoping to learn something. Heck I even gave that shrieking harpy Crabinsane the benefit of the doubt at first... we live and learn I guess.

Jane said...

I cannot accept your offer of 'one last chance'. If you ask me a specific question about the science, rather than trying to set a trap for me, I will answer it if I can.

bopes said...

"do you really think . . . [SG's 'coffin nail' study] is valid evidence?"

looks like a pretty specific question there . . .

Ned Kock said...

Insulin is co-secreted with a number of other hormones. One of those, like insulin also secreted by the beta-cells in the pancreas, is amylin – a powerful appetite suppressor:

Unknown said...

Peter--love to see your thoughts on this one.

Peter said...

Teresa (and Liz), at a glance it's quite interesting. I look at the urinary cortisol and the TSH/T3 levels and wonder quite what is going on there... But the basic metabolic rate data are pretty much what you'd expect. Life is ultimately logically self consistent.

It also makes me think of Jenny's comments to Jimmy Moore. Us long timers are waaaaaay beyond the ken of any hard data. Short term is not always a truncated version of long term!


Richard Nikoley said...

I already exchanged an email about this w Peter earlier, but for those interested in that JAMA paper, I emailed Dr. Ludwig with some questions and got an almost immediate response. The text of my email and his response, here:

Puddleg said...

Thanks Richard.
I actually like the way Ludwig's study was done, despite his predetermined bias. Yes, the duration is much too short to show weightloss (or improvement in CRP) from VLC, but the method is (from the abstracts and discussion) about as good as it gets with human diet studies, kudos to him.

"The theoretical energy yield (as ATP) from one molecule of palmitic acid is 2340 kcal (sic), so that the efficiency of conversion is 980/2340, or 42%, with the remainder of the energy being produced as heat" (old textbook)
Every possible energy source has its own theoretical efficiency, real efficiency may vary, and inter-conversions and storage cycles must also eat into efficiency, as well as CYP450 conversions (as with some alcohol and PUFA calories).
No wonder a calorie isn't a calorie any more.

Dr Guyenet is the Zen master of metabolism; he provides resistance training for the mind.

Peter said...

"Dr Guyenet is the Zen master of metabolism; he provides resistance training for the mind."

OMG, that is so funny... and true! Made my day and it's only 6.30am here!



Peter said...

Richard, Ta too, makes sense.


Stipetic said...

FrankG, generally accepted guideline for rodent studies are categorized in this fashion:

Acute can range from a single dose to one week administration. Historically, these are mainly single dose studies.

Sub-chronic range from 7 days to 6 months. Historically, the 28-day study is probably the most often used.

Chronic studies from 6 months to 2 years (with some saying there is no need to go beyond half the expected lifespan). Historically, these go all over the board, with 1 year being the most often used.

So, to say that 7 days mimics a chronic situation in humans is amusing.

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

Since the Ludwig study is a short-term experiment, urinary cortisol levels cannot predict long-term sequelae--what shows up in your pee is not an indication with what's hanging out in your crimson juice (think ketones). If they'd take their head out of their dogass (according to Webster: combo of dogma and ass), they'd know it is likely a marker of GFR, where GFR is merely tracking protein intake ( Pubmednonites can find numerous papers on this. Insulin AUC and Cmax can explain the difference between low-fat and low-GI (kinda curious they have a low-GI group but they didn't measure insulin, hmmmmm).

Bottom line, urinary cortisol levels obtained from short-term experimentation is not a "hormonal measure of stress" or predictor of "increased risk of cardiovascular mortality."

The "apparent" down-regulation of thyroid function can just as easily be explained by the energy dynamics involved.

The study is great. I could have done without the comment section as the results speak for themselves.

FrankG said...

@Stipetic : "... So, to say that 7 days mimics a chronic situation in humans is amusing."

It is indeed laughable but also in the context of someone who has set himself up as an expert, explaining science to us poor uneducated lay-people; it is misleading and dare I say dishonest. Reading comments at WHS there are clearly many who simply take him at his word. I wonder what it is like to have someone else tell you what to think?

For Jane to then say "WHS gives me a clear and concise summary of current research in obesity and related topics" even when faced with this glaring distortion of the facts, leads me to conclude that she is also not worth listening to. There is a great deal on offer out here on the interweb and in my opinion it pays to be critically selective.

I also agree about Stephan's arrogance and I find this most off-putting: the idea that in order to be a "real" scientist one must have a University Degree in a scientific field. I dare say that a great many of our biggest discoveries were made by "amateur" scientists -- for example Charles Darwin was not even initially hired for the Beagle voyage as a naturalist but as a companion (of equal class-status) to the Captain, after dropping out from his studies to become a village vicar -- and I see no reason why any intelligent, enthusiastic, open-minded and critical-thinking person cannot make their own interpretation of data and observations.

In my experience the best scientists show humility and awe when faced with the grandeur of the natural World -- E. O. (Ed) Wilson, described by many as a Giant on the stage of Science, instead calls himself "a student of the ants"! And I recall an example that Richard Dawkins gives: of an elderly Oxford Professor who attends a lecture given by a young researcher who sets out convincing evidence disproving the theory that has been the life's work of the elder. At the end of the lecture the older man goes down to the younger, shakes his hand and thanks him! That to me is what science is all about.

FrankG said...

I missed one crucial characteristic of a scientist: an enquiring and imaginative mind... a childlike wonder about the World, which I think Einstein (as a great example) maintained throughout his life.

I've also heard it said that science progresses one funeral at a time -- perhaps this why I find Stephan so disheartening... he seems unable to move beyond the constraints of his mentor and so we get another generation of the same old same old story. I've no doubt he will do well in his chosen field -- just so long as he keeps saying the right things an doesn't rock the boat.

Makro said...


The hyperprofessionalization of science is indeed a problem, for several reasons, especially when combined with ever-increasing specialization.

- People easily get "locked in" to one approach / conclusion early on in the process (Their "Schtick"). Switching tracks (or views) hence becomes kind of hard.

- People rapidly become part of a "corps", or a "team", that is not only a social grouping, but also holds their career in its collective hands. Conformism is just objectively the best approach in this environment, with few exceptions.

Peter said...

Makro and Frank,

Groupthink is the word which keeps coming to mind re Guyenet. Subjugation of thought to group conformity, to the point of self destruction if needs be...

Fascinating to watch


Makro said...

@Richard Cool, will give it a read!

Sam Knox said...

@Peter, Stipetic

Differences in T3 in the Ludwig study should be expected, although someone will likely seize on this as a "danger" of low-carb diets.

Andrew S said...

In order to study advanced physics, one cannot simply be a technical bureaucrat like a patent clerk. To study evolution, one can't simply be a naturalist-minded village vicar. To lead a billion-dollar company would be impossible without graduating college and obtaining an MBA. It's foolish to think a musician could compose a notable work without years of study and training under the masters. To think that an amateur upstart could possibly challenge the research of credentialed scientists is absurd.

Sam Knox said...

@Andrew S

For a minute, I thought you were serious...

Peter said...

Sam, that will, no doubt, make Andrew smile. Neat!