from this study, image from this post
It occurred to me as I was thinking again about LIRKO, that this little mouse not only countered TWICHOO 1.0, but it pretty much puts the lid on TWICHOO X.0.  This profoundly hyperglycemic and hyperinsulinemic liver insulin-receptor knockout mouse, is not fat.  Though not statistically significant, the trend is to eat a tad less, be a tad smaller, and pack on fewer fat grams  than controls.  But let's just call it a wash.

For any newer readers, TWICHOO stands for Taubes Wrong Insulin-Carbohydrate Hypothesis Of Obesity.  Version 1.0 was that which was put forth in Good Calories Bad Calories.  In this version, Taubes put forth four ways by which the carbohydrate could promote obesity:
1.  Carbohydrates stimulate insulin which stimulates fat storage and/or traps fats in our fat cells so fat accumulates.
This was pretty much the "lead singer" of his Barbershop Quartet singing the TWICHOO jingle.  Carbs stimulating insulin basically led to chronically elevated insulin levels.  The other three are:
2.  Excess carbohydrates are converted to fats by de novo lipogenesis, and these fats accumulate in our fat cells.   
Tenor hitting the high notes?  Then
3.  Carbohydrates stimulated insulin spikes lead to chronically elevated insulin (hyperinsulinemia) that leads to the development of insulin resistance.  This IR begins in the muscles (accelerating process 2 and enhancing process 1 for more fat accumulation) until the adipocytes eventually become IR themselves. 
The harmonizing baritone it is!  And who can forget the fourth singer, the bass in my mind,
4.  Carbohydrates provide the backbone molecule, alpha glycerol phosphate (aka G3P), for the process by which fats are "fixed" or "trapped" in the fat cells.  Dietary carb is required for G3P and the more carb, the more G3P, the more fat is "fixed" and  accumulates.  
If one listens to Taubes' lectures over the years, it becomes obvious that the tenor left the group first.  Not around the nutrition blogosphere, mind you, but from Taubes' lectures.  You'll hear the voice go down as he says it wasn't as much as he initially was led to believe (from his cherry picking).  Folks like Eades, Sisson and most especially Gedgaudas never got the memo on the departure of Denny L. Gee from the group.   Rumors started circulating in 2009 that the bass, Al Phageepee was disenchanted with his role in the group.  But Taubes fought mightily cutting deal after deal with Al to keep him hanging on until summer of 2010 rolled around.  Rumor has it Al left for a weekly gig singing solo in The Asylum Bar & Lounge.

This left the duo of G. Diddy Lucose and the singer who insisted on being called "The Resistance".  It got contentious who was singing melody and who was singing harmony.  For a year or more, Taubes tried different roles for his remaining duet.   He tried to replace Denny and Al too, to no avail.  Finally, sometime earlier this year, Gary appeared to have decided on his final form for his Butchershop Quartet.  It would be "The Resistance" singing a different tune in the lead, with G.Diddy harmonizing, and the replacements Taubes finally found for Denny and Al.   Rumor has it that G.Diddy is not so happy in the supporting role, but he's got a book to sell and some undisclosed stock options in UCAN have also been rumored to be part of the deal.  The new TWICHOO X.0 goes something like this:
1.  Carbs still spike insulin, and insulin still traps fat in fat cells, and scientists are all still idiots operating at sub-optimal intelligence and all that.  Such is a given, but now:
2.  The antics of carbs and insulin from #1 are likely not the cause of obesity after all so long as the body remains sensitive to that insulin.  The Japanese eat white rice after all.
3.  Fructose, conveniently another carbohydrate, causes insulin resistance in the liver.  This insulin resistance now leads to hyperinsulinemia and exacerbates both glucose and insulin spikes from consuming glucose. 
4.   Hyperinsulinemia causes fat to not only accumulate in the fat cells, but this locking away of this fuel source causes the rest of the body to suffer a state of "internal starvation" leading to out of control appetite and consumption of excess calories.
Singing tenor we now have Hy Perinsulin and on bass, in a nod to the Hall & Chow foundation of reality, a lucrative but much hushed contract was entered  into with Cal O. Riezcount.

But Houston, we have a problem with the Butchershop Quartet.  It hangs together even less cohesively than did the original group.  And LIRKO, more of a minor pestilence to TWICHOO 1.0, proves to carry the bulogic plague that should go down in the history books for bringing about the extinction of the Gen X TWICHOOB.  Why do I say that?  Well because v. X.0 hinges entirely on hepatic insulin resistance.  While one could weave scenarios for the cognitive dissonance that LIRKO posed to v. 1.0, there's no getting around this specific in the reincarnation.

If TWICHOO X.0 is correct, then LIRKO should be a porker.  LIRKO is a mouse genetically given (poor things) the ultimate hepatic insulin resistance -- it has no insulin receptors in its liver.  What happens is that insulin fails to do the major thing it is tasked with in the liver -- suppress gluconeogenesis.  This mouse is genetically engineered to be the model what TWICHOO X.0 claims is diet induced.  Yet it doesn't fatten.  And it's not because of some cross-signaling preventing adipocytes from taking up glucose or retaining fatty acids.  Indeed NEFA are suppressed by around 40%, and yet this mouse doesn't resort to overeating to get compensate for its "internal starvation".  

I'll leave you with a quote from GCBC:
But the greatest single change in the American diet was in fact the spectacular increase in sugar consumption from the mid-nineteenth century onward, from less than 15 pounds a person yearly in the 1830s to 100 pounds by the 1920s and 150 pounds (including high-fructose corn syrup) by the end of the century. In effect, Americans replaced a good portion of the whole grains they ate in the nineteenth century with refined carbohydrates.
And here I thought they replaced lard with sugar ... but I digress.....  

My question is this.  Where's the missing obesity epidemic that began in the mid-19th century?   The grand PhD thesis does not support TWICHOO 1.0, X.0 or any of  the nuanced versions in between.  A good scientist ditches hypotheses when evidence fails to support them.  Well, a good scientist formulates hypotheses based on observations ....


kb said…
This comment has been removed by the author.
kb said…
Why no mention of hydrogenated vegetable oils? That was a major new introduction into the American diet around the same time. It was made from cottonseed oil, a byproduct of the cotton farming industry, which was originally used to make soap, and apparently in its unrefined state is pretty nasty, toxic and said to cause organ failure.

When this country's health starting declining with heart disease, obesity and cancer, soon after Crisco's introduction, it was alleged that attention was diverted by the manufacturer, P&G, by hiring a scientist who went around claiming that the said diseases were caused by animal fats, and therefore the new hydrogenated vegetable oil was the healthy alternative.

After some googling, I notice that P&G has a presence in the lc community. They have sponsored at least one favorable lc study, have paid lc proponents as consultants, supported talk radio shows that have hosted lc promoters, and even made a large push - no pun intended - promoting Metamusil to the lc community after the success of the Atkins and South Beach diets, stating that they noticed many lc dieters complained of constipation. Apparently this proved quite advantageous for them.

P&G sold Crisco a decade ago, however before they did, they were being blamed for this country's declining health, and it was even implied by many they took us there knowingly. Now they are out of the Crisco business and out of the cereal business, so they can righteously support the lc community in blaming cereal for our declining health.

Is this a bizzaro world or what?
blogblog said…
Bring on the conspiracy theories!

In Australia the intake of HVO (and HFCS) has always been negligible - but we have levels of obesity and CHD nearly as high as the USA.
CarbSane said…
Quite interesting kb. Rod Taylor (who put together that LC Down Under tour near as I can tell) thinks it's fruit.
kb said…
As long as the spotlight is no longer on P&G, I'm sure they are happy and now obviously busy rebuilding their reputation. Is their interest in lc strictly a marketing opportunity... or deliberate manipulation to divert attention away from the Crisco backlash? I have no idea, but feel the distinction is an important one.

I was not intending to suggest conspiracy, rather that big business has way too much power and influence, and look how they can influence our health doctrines. Other point was, what happened to trans fats issue?

Then again, I guess I do have to question the agenda if the trans fat issue is completely overlooked, and fruit is being blamed for obesity and disease. We have to stop being sheep, start using common sense and think for ourselves. Sadly, it is such an effort sometimes to find the truth.
kb said…
Another trivia for you- P&G is not in the food business any longer for people, but I believe they still manufacture dog food with their cottonseed oil. Why do dogs get obesity and cancer? I don't know that it is an epidemic with pets, but it always strikes me weird that they do at all. Ok so many are not as active as they should be and they don't drink alcohol, do drugs, eat fruit, sugar, HFCS, butter, or at McDonalds.... But their food is highly processed with cottonseed oil, grain and some animal byproducts. Interesting to note what we can rule out... for dogs anyway.
kb said…
PS My dog has been eating same diet as I for almost a decade. She is 14 and very healthy, hasn't been to the vet in years, no vaccines or flea medications which btw, she never had less with the medication anyway... another pharmaceutical scam. She has never had fleas and gotten less and less ticks over the years. This past summer and fall she had none. No stomach issues ever. Previous dog was on dog food almost his whole life. In later years, had tumors everywhere, very bad arthritis, and was incontinent.
CarbSane said…
Don't get me started on the pet food industry! But also don't get me started on the Catkins people either ;-) Cats ARE carnivores!

Diana said…
"Catkins" - you stole the words right out of my starch-metabolizing mouth, Evie! Cats are meant to eat a protein/fat diet, with a teeny bit of carbs in the form of stuff that cleans their teeth. Before I understood this stuff my cat died of diabetes. I'll never get over the guilt because I inadvertently facilitated his death.

Re: "Lirko" - since we're playing games with names, Lirko sounds like an Eastern European weightlifting mouse. A mighty mouse indeed.

I do have a serious question. "Carbs stimulating insulin basically led to chronically elevated insulin levels."

Maybe what is leading to chronically elevated insulin levels is chronic eating. If you eat 2000 calories a day distributed amongst those "eat six small meals" (and snacks....) might this not stimulate weight gain more than two 1000 calorie meals in a 4-hour window? Yes, that's the basic IF philosophy.

Or is it just calories and REE?
an3drew said…
Is Kruse losing it even further? I just went by his site for the first time in a long time and he was talking about going into a mile-deep hole and other assorted weirdness.
Anonymous said…
Yep, it's a bizarre world. Every time I read mention of how X food ingredient is used for Y horrible use, I try to remember what food it was that shares its composition with NAPALM! Yeah, I can't remember what the devil that food was, but apparently people don't realize that when they eat that food, they are eating something akin to NAPALM! Whoa!

Please. The horrible histories of food and the nefarious producers of food... I mean, shouldn't we all be pickled or fried or dead from what has been around for years?

(BTW, I read an article that suggested heroin users live with something like 'pickled' insides, but youthful outsides - a ringing endorsement of heroin usage if ever I read one...)
Unknown said…
The only significant benefit in terms of weight loss for intermittent fasting--as I understand it--is better adherence to energy intake restriction for those who tend to overeat whenever it is 'meal time'.

Now if we want to talk about insulin and glucose tolerance, that is another story. I've seen situations where it does help with glucose tolerance. I have also seen situations where it can worsen glucose tolerance by stressing the system.
Unknown said…
Youthful outsides? Okay, I can comment extensively on the matter.

If looking gaunt, emaciated with an overwhelmingly polarised state of mood and alertness is youth, then bang on with heroin. I don't know about youth, but if being youthful requires one to be the spitting image of a tripping version of Skeletor--mainly over the Skeletor part--then sure. Outside of that, I really don't see how someone could arrive to that conclusion about heroin users.

I am curious to read the article myself. Got a link?
Galina L. said…
You don't understand or underestimate that a diet has to be as easy to execute as it is possible. I got an impression that you don't have a need to lose weight at the moment. I guess you are eating reasonable portions, do not overeat, exercise, something like that. Now imagine somebody who does pretty much the same thing - eats generally healthy without stuffing herself, do other things right, but there are lbs to loose, or even worse, weight gain is creapping up. Not only lazy gluttons have weight problem. What that person has to do? Where to cut the food without getting hungrier? In order not to get into the macro-nutrients thing again, I guess I can say - limiting amount of meals and narrowing the eating window is not a bad option.It is easier to follow some general rule that agonizing several times a day over food choices. I think that eating food that keeps you not hungry for hours is the pre-requirement for IF. It is possible that IF is not perfect for some personal situations , but for many it is the way to go, especially when other strategies do not work efficient enough..
CarbSane said…
I cannot be bothered as he just makes my head hurt. As far as I'm concerned unless he experiences some sort of re-birth in the community, he's past history. At this point anyone considering paying his fees would be adequately forewarned were they to do a quick search before sending along their money.
CarbSane said…
@Kade- this is what human studies tend to show. Some do well to eat a little here and there. Others do better eating 1000 cal all in one sitting. Pilon's Eat Stop Eat is macro agnostic as far as I recall. I did Fast 5, also macro agnostic and I did many carb days at the time.

The one thing I think I like about the fasting buzz is perhaps the end to this 3 meals a day + snacks notion. That works for some, but I've never really been such a person only the diet folks make you think you'll die if you ever skip a meal. Breakfast isn't the most important meal of the day for many of us who just aren't hungry. If you're not hungry, don't eat!

Ash Simmonds said…
@blogblog: Aussie here, where do you get the idea that HVO consumption is negligible here?

I grew up in a family that cooked real food - meat n veg - for the most part, however we always used margarine and various frankenoils with everything. As far as I can tell most people still do, and are completely unaware of the damage - indeed are still stuck in blue pill land acquiescing to the veggie oil is healthier than real fat dogma.
Anonymous said…
Here's that link...
Galina L. said…
I wonder, how close is oxycodone to heroin? It is prescribed routinely.
blogblog said…
there is far more trans fat in butter than in table margarine. Table margarines are made with non-hydrogenated vegetable oils.

Trans fats in Australia.
blogblog said…
Eating three meals a day plus snacks only dates back to the Industrial Revolution. People were forced to eat at scheduled times rather than when they were hungry. Most hunter-gatherers eat one large evening meal and the occasional small snack.
Unknown said…

I am going to make a request.

Please don't jump to conclusions about my posts because it's becoming rather tiresome having to compose an entire barrage of text to clarify something that most people--who aren't dogmatic or defensive--would fully comprehend.

Read again, please:

"I've seen situations where it *does help with glucose tolerance*. I have also seen situations where it can worsen glucose tolerance by stressing the system."

And. . .

"The only significant benefit in terms of weight loss for intermittent fasting--as I understand it--is better adherence to energy intake restriction for those who tend to overeat whenever it is 'meal time'."

Now where or when have I said that it doesn't work in terms of helping people with calorie restriction? Where have I said that it doesn't work for no one? Where have I generalised? Short answer: No where. Applied to each of those questions.

Should I start dumping peer-reviewed journal links on how high cortisol is NOT always a good thing and how some people do develop this problem of glucose tolerance despite a good diet, depending on other life style factors? Also, should I mention how I can sympathise with the idea when a person is dropping weight, their cortisol levels will rise since weight loss? That despite being long-term healthy, most weight loss strategies to come with a short term (and acceptable) stress?

Of course you can eat all the food you want that prevents hunger, but that doesn't mean that everyone else doing the same is not going to have a hormonal feedback response to such a treatment. Need I bring up all those people over at Matt Stone's website? No one's condemning intermittent fasting or low carbohydrate. I actually brought up valid points about it up there, but acknowledging the potential pitfalls and trade-off points is important as well since you don't represent everyone else, don't you think?

I am afraid, I am not the one generalising, you are.


"Breakfast isn't the most important meal of the day for many of us who just aren't hungry. If you're not hungry, don't eat!" - Evelyn

Exactly. I think they've just taken something that works for a certain, very general situation and applied it to the overall populace. Now I wish the IF-admirers stop generalising the same thing towards their counterparts. You'd think that the contrarians, having worked from the sidelines against mainstream prejudice, would have a more rational and even-handed attitude. But the moment someone says, "X works, but--" it's virtually the end of times; same level of resistance, snapping and jumping the gun.
Unknown said…
Thanks for the link, Eulerandothers.

The following quote from the article was interesting.

“Heroin is not magical, not irresistible. Withdrawal is like having a cold or the flu for a few days. A lot of what we perceive as classic withdrawal symptoms are there from the start. As your body becomes more skilled at processing heroin, it goes through you more quickly. At first you don’t feel so great the morning after taking it, then only six hours after, then an hour or two. Following this path leads to a narrowing focus and a demeaning obsession with your immediate physical state, which is one reason heroin addicts can be so tiresome to be around. It’s not a fit focus for an intelligent person."

I actually knew someone--in a similar predicament--who said almost the exact same thing.
Jane said…
Kade, does Matt Stone talk about autophagy? This seems to be what intermittent fasting is all about. Autophagy breaks down damaged mitochondria (and other things) so new ones can be made. It's a relatively new field and scientists are getting very excited about it. As well they might, because it looks like failure of autophagy might explain everything from Alzheimer's to obesity. If your mitochondria aren't working properly you can't really do anything.

Autophagy can also be triggered by exercise. If you're interested, look up 'exercise-induced autophagy'. For obesity, look up 'POMC autophagy'. Several recent papers have reported that POMC neurons in the hypothalamus need autophagy to function properly, and if it doesn't work the animals get fat.

Unknown said…
I think Matt Stone may have spoken of autophagy, but it's not like I visit his site regularly or keep tabs on these things.

Needless to say, I doubt that autophagy is all that IF is about for quite a few people who use IF for cutting and weight-loss purposes. Nevertheless, autophagy is another topic that I find very interesting. From my reading, there's also the protein--more specifically, methionine--restriction connection, which has been used to explain autophagy in both the calorie restricted and those engaged in intermittent fasting.

I also read some conjecture in some places that IF--for autophagy purposes--seems most effective in intermittent bouts; that is, intermittent intermittent fasting. I can't comment further on that point.
Galina L. said…
Sorry for annoying, your request is taken.
Unknown said…
Thank you and please do understand that I regretfully took the tone that I had to take because the response made it seem like I have something against these strategies when personally, I might even be an advocate or practitioner on some levels. I am certainly interested in more work--less gimmicks--on high-fat/moderate-protein quasi-ketogenic diets in terms of brain health and longevity.

It's just that belonging to the industry that I belong to, I feel very out of place not playing Devil's advocate on these topics, even when I'm in favour. A friend of mine was doing research for an article on the subject of intermittent fasting for a local magazine and I was consulted on parts and we had to consider the negative evidence as well before arriving to a confident, defensible opinion. On the whole though, there's always good merit to these approaches when done right, just as there's downsides when done wrong.
CarbSane said…
@Kade or anyone -- I'm thinking about that study or series of studies that came out about performance in school/attention span/all that jazz that spurned this whole "breakfast is the most important meal of the day" meme. It was all about poor children being sent to school w/ empty bellies and this was put forth as a reason why they performed poorly academically. I want to say this was mid80's as I think I was already in and perhaps out of college when this was getting a lot of attention, but perhaps it even predates it. It's the reason for the *creepy* shredded wheat commercials about keeping kids "full and focused" for the day (I say creepy b/c the shredded wheat biscuit narrating is going to be eaten!!).

We have now developed into a nation with a wholly distorted view of what hunger is. "Food insecurity" is purportedly rampant and yet its definition is not even having to go 24 hrs between meals. I'm not saying that wouldn't be a problem, but if it's not a chronic situation, it's not reality in terms of undernutrition.

I note that school food programs have not improved academic performance ...
kb said…
@blogblog - Trans fat usually refers to hydrogenated vegetable oil and there is none in butter but according to Wiki, there are trace amounts of an omega 7 fatty acid called Vaccenic acid in butter.
CarbSane said…
Oops, forgot question in first paragraph. Anyone know the exact timeframe of those studies?
Galina L. said…
Growing up in 60-s and 70-s in Russia, I heard everywhere about the breakfast being the most important meal of the day, and supper being the most dangerous one, and it is still the same popular "meme" there,most revered and recommended breakfast foods are and were hot cereals(even cream of wheat), country cheese, yogurt. Healthy food needed to be warm. I have no idea, was it based on some research or what else. I am still reluctant to eat in late evening, it is so engraved on my brain surface. My son has a wonderfully regulated appetite, sometimes he overeats, then doesn't eat for a while. I remember with regret how I tried to make him eat at regular intervals because I used to think (because I was raised on such believes) he may develop an inflammation of stomach or some GI disorder without regular meals.
Diana said…
Autophagy sounds like another diet weirdo hobbyhorse that someone is flogging, the point of which is to distract us from CICO.
Diana said…
"Food insecurity." It's also a good fund raising meme. The fact is, with food stamps and surfeits of food, you probably have to be on a remote Indian reservation to go hungry in the US. If worse comes to worse, you can dumpster dive. Not saying that's an ideal way of life, but it's possible.

In my area, food is expensive. Everything that comes into Manhattan has that last transportation premium. And there's loads of cheap food around.

I saw a Nova documentary about hungry kids in America, and forgive me for sounding callous, but it was propaganda. The kids weren't absolutely poor: they were low-status and had stressed out parents. I could go on about this but I'll be brief: they had access to loads of calories. One boy who made some extra bucks after school mowing lawns complained that he didn't have enough money to gas up his motorized lawn mower. He was a bit plump. Why couldn't he use a push lawn mower? We've totally lost the idea of what a body is meant for. And what hunger really is.
Galina L. said…
Some time ago my husband got intrigued by "fight the hunger" commercials while watching "Tour de France", and started to look into who organised the advertisement. He told me later it was the Kraft company.
People in the low income bracket are more often plump then in affluent parts of our society. It is possible to slice and dice that fact in several ways. Probably, that boy illustrates also another fact of life that priorities matter. It looks like making more money with more efficient mover was higher priority for him than getting into the single digit fat percentage number. Being concerned about fitness became the luxury of our time.People with extra money or extra time and fewer responsibilities can afford it. The quality of food or even the concern of getting food could belong to the same category.
Diana said…
Galina, I'm well aware of the fact that priorities matter. I mean, duh. My point is that that THE KID wasn't aware of that fact and the reason why is because until now, he didn't have to be. I also realize that the poor, however defined, do not have the luxury of worrying about fitness. My point was that even a poor person in our society doesn't have to use their body the way a poor person in India does - they drive, and use gas powered lawn mowers. OK? Is there anything about that you'd like to argue with?
Anonymous said…

Breakfast in 1910 Great Britain. Not the studies you're looking for, but what a revelation that gluten is a miracle food and Grape Nuts were on the table!
Galina L. said…
Am not arguing at the moment,I agree with your comment that it is hard to luck food in US. I just remarked that in US being poor often means being fat. In India lean people have to work very hard and under-eat, while here physical activity often is a luxury, and the most time saving way and efficient way to do things excludes physical activity .
Jane said…
Thanks Kade, that's just what I wanted.
Diana said…
"Following this path leads to a narrowing focus and a demeaning obsession with your immediate physical state, which is one reason heroin addicts can be so tiresome to be around. It’s not a fit focus for an intelligent person."

Hah, it reminds me of Low Carb dieters. Or any obsessive dieters. It reminds me of.....oh, I won't say the name, but a certain famous yo-yo dieter, who is obsessively concerned with taking his vitals every day, and who, like the worst junkie, keeps going back to his dope.

Guess who.
Diana said…
" In India lean people have to work very hard and under-eat, while here physical activity often is a luxury, and the most time saving way and efficient way to do things excludes physical activity ."

Exactly. You've just solved the obesity epidemic. And guess what, low carb ain't got a thing to do with it.
blogblog said…

don't rely on Wikipedia for facts.

"Trans fats" is shorthand for trans-esterified fatty acids. They can be a byproduct of bacterial fermentation in the rumen. As a result TEFA can occur naturally in animal fats including milk and beef tallow.

Partially hydrogenated vegetable oils contain some trans fats. However FULLY hydrogenated vegetable oils such as copha contain (almost) ZERO trans fats.
blogblog said…
when I was studying food scince back in the 1980s we had a textbook called 'Food and Nutrition in Australia'. It tells us all about the Australia diet of the early 20th century as well as modern diets.

One hundred years ago the Australian diet was arguably WORSE than today. People were eating a lot of fried foods. Salt intake was very high. All bread was white bread. Processed breakfast cereals were common. Very little fresh fruit or vegetables were eaten.
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