I read Gary Taubes’s new book The Case Against Sugar twice. First I read it in manuscript, then in galley proof. My intention was to write a review of it to be posted around the book’s publication date, but on or just before pub date a dozen other reviews hit the web. Consequently, some of the rush to get a review put up quickly kind of drained out of me. A couple of days ago, I received an email from a fellow blogger, Richard Nikoley of Free the Animal, linking to Stephan Guyenet’s case against The Case Against Sugar and asking me what I thought of it. I read the critique, and, since I had some time on my hands at that moment, dashed off my thoughts.
Richard wrote back and asked permission to publish my email to him on his blog. I was a little dumbstruck, because making the thing public wasn’t my intention when I wrote it. Plus, when I zapped it together, I was stuck in a lobby waiting for someone to show up, so I typed the frigging thing on my iPad. Consequently, it was crawling with typos. I reread it, and thought: Well, maybe it can kind of substitute for the review I was going to write. Especially since there are already so many other reviews out there right now. This one brings a little more personal touch and history since I know all the players involved.
Here is the email as I sent it to Richard:

One of my favorite quotes is from Bertrand Russell.

The stupid are cocksure while the intelligent are full of doubt.

I like it because we all are like atomic particles: we change states constantly.  In some aspects of our lives and on some subjects we are intelligent while in others we are stupid.  And, consequently, we are either cocksure or full of doubt, depending upon our state.
The older I get, the more I understand how potent the confirmation bias is.  And how it is almost impossible to overcome.  I’m suffused with it, as are you, and Taubes and Guyenet and just about anyone else either of us can point to.  As a result, I never know – for absolute certain – whether I am on the right side of any argument or not.  Whether I’m cocksure or full of doubt.
When I was in my middle thirties, I started gaining weight like crazy.  Before I knew it, I was 35-40 pounds overweight.  Like most doctors, I didn’t know shit about nutrition, so I went on the current fad diet at the time, which was in a book by a physician named Stuart Berger (who later died young and morbidly obese).  It was low-fat, and I did okay, but hated it.  I lost a bit, then regained.  I then went on Pritikin, which I really hated.  I think I tried one other diet, also low-fat (those were the only ones in vogue at that time), and it didn’t do me a lot of good.  Optifast, a hospital-based fasting program was all the rage then, and I discovered there was a similar program (Medifast) set up to be administered through physicians’ offices, so I sent off for the info with the idea of using it as a means to increase revenue in our clinic.  When I got the instructional materials, I read it through them and realized that it sounded suspiciously like a shake version of Atkins, whose book I had read years before and discounted, because the medical profession had badmouthed it. (At that time, I was as mainstream as mainstream can be.)  The packet contained a few scientific papers, so I read them.  The data they presented seemed convincing, so I decided to do the program myself before putting patients on it.  I lost effortlessly, wasn’t particularly hungry, and had no decrease in energy levels as I had experienced with the low-fat, low-cal diets I had tried. Which was interesting, because the shakes themselves were low-fat and low-calorie.  So the difference had to have been the carb restriction.
The problem I saw with the program was that the shakes worked great to effect weight loss, but when all the excess fat was lost, the company promoting the program had a low-fat, high-carb diet for maintenance.  That seemed strange to me because all the papers that came in the physician starter kit argued for the effectiveness of the program as being a consequence of the carb restriction.  If the papers were correct, I couldn’t figure out why the Medifast people thought adding a ton of carbs in for maintenance would do anything but bring about weight gain.  So, I redid the maintenance program and designed it low-carb.
My patients, many of whom were overweight, had observed my weight loss and asked me about it.  I decided that I would start running my own version of the fasting program and maintenance diet in the clinic.  It became a hugely successful operation.  I finally decided that if the fasting program worked so well, why wouldn’t a low-carb food program work just as well.  So, I tried it.  But since that diet contained a lot more fat, especially saturated fat (which was verboten in those days), I was worried about using it on anyone of heart attack age.  MD sent me a patient from her clinic and I had a few others that disabused me of that notion.
After my experience with these early patients, I overcame my fear of saturated fat and for the rest of the time I was in practice, I used low-carb diets that I fiddled with and refined to treat an enormous number of patients.  Most of those patients had tremendous success with it.  MD and I hired on to be one center of a major drug study for the drug that ultimately became Xenical.  It was a maintenance study, so we had to recruit patients and put them on a standardized, 6-month lead in weight loss diet which was the state-of-the-art low-fat, high-carb diet, designed by the drug company, to get them to lose enough to be accepted into the maintenance part of the program, during which they were to get the drug.  All they had to lose over the six months was four percent of their body weight to qualify for maintenance.  A 200 pound woman would have to lose eight pounds over six months to qualify.  And I can’t tell you how many of them didn’t qualify.  We got paid a fortune to do this study, but the payment schedule was skewed toward the end because the drug company (Hoffman LaRoche) obviously wanted patients to get to the maintenance phase to test their drug, so we did everything in our power short of horse whipping the patients to get them to stay on the program and lose.
One of the problems was that the drug-study patients came and waited in the same waiting room as our regular patients, all of whom were on low-carb diets.  They would talk among themselves, and when the low-fat, high-carb, drug-study patients heard how much the low-carb patients were losing (sometimes almost as much in a week as the drug study patients were losing over months), the former became discouraged and wanted to be regular clinic patients instead of drug-study patients.  It was a major pain in the ass.  But it was extremely informative to me, because I saw first hand the difference in outcome of patients who had extensive nutritional counseling, dietary guidance, a dietitian on call, and weekly office visits (the drug study patients) versus our regular clinic patients on low-carb diets who had a short session on what to eat and came into the clinic once every couple of weeks to weigh in.  There was no comparison.  The low-carb diet vastly outperformed the low-fat diet, hands down.  Better weight loss, better lab values, better sense of well being.  Virtually any parameter you want to measure, the low-carbers did better. (The FDA requires study centers to keep all the data for something like 12 years, and I still have it all.  I keep thinking someday that I can use it as the low-fat arm of a study or something.  It is extensive.)
The point of this long story is that I have many years of experience dealing with low-carb diets, so I have a difficult time believing it when people tell me that low-carb diets are just the same as any other diet.  My years of experience, both personally and professionally, tell me otherwise, irrespective of the findings of a few episodes of n=1 bro science here and there.  My confirmation bias is damn near set in stone.
So, with that intro, telling you upfront where my bias is and why, let me get to the Guyenet article.  Which I almost hesitate to do since I don’t think it really matters much.  A year or so ago, I read a paragraph in Scott Adams’s book that changed my mind about engaging in these kinds of things. I think it pretty much sums up the way things are:

If your view of the world is that people use reason for their important decisions, you are setting yourself up for a life of frustration and confusion.  You’ll find yourself continually debating people and never winning except in your own mind.  Few things are as destructive and limiting as a worldview that assumes people are mostly rational.

So, with that said, here I go:
I’m sure you’re aware of the big brouhaha that took place at AHS11 when Taubes questioned Guyenet during the Q&A after Stephan’s talk.  It was kind of chicken shit in that it wasn’t just a Q&A where Gary got in line to ask questions like everyone else.  Gary was speaking right after Guyenet (and Gary was the big star of the show) and he took the opportunity as he approached the podium to zing Stephan.
Later that night, Gary, Rob Lustig, and I (maybe you were there by then) were in the lobby of the hotel having a drink when Guyenet walked up.  The first words out of Gary’s mouth were, “Stephan, I’m sorry I was such an asshole today.”  Stephan blew it off as if there was nothing to it, and we all sat there chewing the fat.
After the conference, the internet went wild with the spat (if that’s what you want to call it) with all these people posting their iPhone versions of it and many of them, maybe most, taking Guyenet’s side.  I think it was only then that Stephan thought he had been ill used.
Whatever it was, Guyenet seem to have had it in for Gary since.  And it’s a shame since they were friends before.  I actually met Stephan though Gary.  I happened to be in Seattle, and Gary invited me to a dinner he threw there for Philippe Hujoel, who had invited him to speak at the University of Washington.  Gary also invited Stephan and a couple of other people I can’t remember. Now it’s blown up and Stephan has aligned himself with that troll Evie along with James Krieger, Alan Aragon and all the other Taubes haters.  So, it doesn’t surprise me that he wrote the review he did.
In my view, he took a lot of disingenuous shots at the book.  I’m assuming you’ve never read the book, but I have.  A couple of times, in fact.  Once in manuscript and again in galleys.  It’s like all of Gary’s books.  Informative, well-written, and fun to read.  Even if you don’t agree with all of it.  But I don’t see how you can take a hostile reviewer’s side without reading the book in question to see if the reviewer is on the mark or not.
Gary was straight up at the outset of the book in saying that he was making the case against sugar.  It’s even stated in the title: The Case Against Sugar. Not that he was being even handed.  Not that he was being unbiased.  But that he was gunning for sugar, much like a prosecutor in a trial.  He made the point that Big Sugar has a promotional arm that spends hundreds of millions of dollars to make its case – he is simply making the case for the other side.  And he basically ends the book by saying he hasn’t made the definitive case – all he has to go on are observational studies and poorly done, short RCTs.  To really determine if sugar is causative would require years of randomized controlled trials, which would be prohibitively expensive, and impossible to monitor.  The short term trials have been kind of bad for sugar, but that’s all they are: short term trials.  Gary admits as much.  Guyenet seems to be trying to make it out that Gary is definitively saying all the evidence is in and sugar is bad, when that’s really not the case.  He’s simply presenting the anti-sugar case.
(If you read anything that Big Sugar has put out in the last few years, they are making their case – such as it is – by saying that sugar is simply calories, nothing more, nothing less.  It’s a calorie just like an apple or a potato or a strip of bacon.  In their view, a 2,000 kcal diet of meat, squash, and blueberries would be equivalent to a 2,000 kcal diet of pure cane sugar.)
Gary starts by presenting a history of sugar and the sugar industry.  He discusses how the Dept of Agriculture was founded in large part to promote large ag industries, one of which was sugar beets.  He also points out how in the early days there was a revolving door between the Dept of Agriculture and Big Sugar, just like there is now between the FDA and Big Pharma.  And he describes many of the techniques Big Sugar used to increase the use of its product.
Recent internal documents from Big Sugar have come to light and were just published in the JAMA Internal Medicine (2016y Kearns Sugar Industry and Coronary Heart Disease Research A Historical Analysis of Internal Industry Documents) showing that the sugar industry did indeed influence and promote the idea that saturated fat was bad in an effort to deflect attention from themselves.  They spent a ton of money underwriting Frederick Stare, Hegsted, Keys and others to push the notion that saturated fat was the devil and deflect the attention from sugar. (The lead author on this study was one of Gary’s research assistants, whom he paid to travel to Boston to gather the documents.  After leaving Gary’s employ, she wrote the paper and went through the peer-review process to get it published.)
I’m not going to go down Guyenet’s list one by one, though I could, but there are a couple of areas I will mention in which I think he is stretching it more than a little to make his point.
One is in saying that restricting calories will reduce insulin levels.  Well, yes, sort of. But not by any stretch of the imagination to the extent reducing carbs will.  A metabolic ward study published in 1996 shows pretty clearly this isn’t the case.  Subjects in both arms went on 1,000 Kcal diets (low-calorie diets by anyone’s estimation) for 6 weeks.  One arm went on low-carb, the other on 45 percent carb (which compared to the ~55% carb in the typical American diet isn’t that high-carb).  Those on the calorie-restricted low-carb diet reduced insulin levels by about 50 percent, whereas the ones on the 45% carb diet slightly reduced insulin, but not to a statistically significant extent. (1996y Golay Reaven Similar weight loss with low- or hgh-carbohydrate diets)
As to the mentions of Kevin Hall, suffice it to say that that whole situation is mired in controversy, which won’t be resolved for a long time.  Even I wrote on it.  There is gotcha history there, and Gary probably shouldn’t have hired Hall in the first place.  We can discuss the whole affair over a brew sometime.
On the findings of metabolic ward studies, I had that go round with Colpo here and here.
And pointing the finger at the addictive qualities of sugar (should they exist – and Gary admits the jury is out on this) is not confirming the food reward theory.  There is a real but subtle difference.
One of the questions Gary proposes is this: Is there an amount of sugar the consumption of which becomes deleterious for health?  He reports on a number of researchers throughout the world who have asked this same question.  If you look at sugar consumption per capita, people seem to be okay as long as the per capita consumption doesn’t exceed a certain level.  I don’t have the book in front of me now, but, as I recall, these levels are in the 50-70 lbs/person/year, which is a helluva lot of sugar (I doubt that I consume five pounds per year, if that).  When the people in a country start to exceed those levels of intake, though, diabetes starts to appear and increase at rapid rates.  Gary didn’t make this up – he’s simply reporting the findings of other people.
One of the effects of the confirmation bias is that so many issues are never solved until the evidence on one side is so overwhelming that it has to be believed.  It takes a long time for the evidence to stack up to that extent, though, so it takes forever for people to finally come together.
It can happen individually, as in the case of Tim Noakes, who is an internationally renowned sports doc.  He wrote the early books on running and endurance exercise.  Was a big believer in carb loading and wrote about it extensively.  Until he developed diabetes.  Then he tried low-carb, and changed his life.
It takes a lot longer for the profession in general, but it is coming around.
Anyway, many of Stephan’s criticisms would be on point if Gary hadn’t already admitted to them in the book, so they’re not really valid criticisms. It’s not like Gary is trying to pull the wool over anyone’s eyes.

So, that was the email, which really wasn’t a review of Gary’s book as much as it was a defense of it. I’ve read many of the reviews circulating around out there, so let me give you my take on the book, which is a little different.

Does Sugar Damage Metabolic Flexibility?

Metabolic flexibility, in technical terms, is defined thus:

The concept of metabolic flexibility describes the ability of skeletal muscle to switch between the oxidation of lipid as a fuel during fasting periods to the oxidation of carbohydrate during insulin stimulated period.

More simply put, metabolic flexibility is a measure of the body’s ability to successfully deal with all incoming foods, irrespective of macronutrient composition. If you’ve got a lot of metabolic flexibility, you can pretty much chow down on whatever you want and not suffer any immediate consequences. If you eat fat, some is burned, most is stocked away till later. Same with carbs. You burn what you need, then store the rest as glycogen. What about both fat and carbs? Generally, you burn the carbs first, store the rest and store most of the fat. The point is, if you’ve got good metabolic flexibility, you can eat most anything and not suffer immediate consequences from it.
Unfortunately, unlike love and herpes, metabolic flexibility isn’t forever. Most of us experience a decline in metabolic flexibility as we age. But it takes a while, which is why children seem to be able to eat anything they want without paying the Piper (immediately, at least). Most of us adults aren’t so lucky. Sadly, many children aren’t either since rates of type II diabetes (formerly called adult-onset diabetes) are now increasing in children and adolescents.
Under normal metabolically flexible conditions, eating carbohydrate stimulates the pancreas to release a little insulin, which drives oxidation of the carbs needed for immediate energy and storage of the rest. When metabolic flexibility doesn’t work so well, the carb meal stimulates the release of insulin, which often isn’t enough to store away all the carb, and the blood sugar rises. The pancreas releases more insulin, which may or may not be enough to get the blood sugar down. Ultimately, someone who loses metabolic flexibility can find him/herself having both elevated insulin (hyperinsulinemia) and elevated blood sugar. We call this type II diabetes. It is often associated with obesity and the other disorders that are collectively called the metabolic syndrome.
There is a continuum running from mild glucose intolerance to full-blown diabetes and everything in between. The end result we diagnose as glucose intolerance, diabetes, metabolic syndrome or whatever. The cause is a decrease in metabolic flexibility.
No one really questions the idea of metabolic flexibility, or its decline with age. They do question why it happens. Why the decline? Why do some people have a minimal fall off with age, while others have a massive fall off and succumb to diabetes, obesity and all the rest. What makes people convert from being metabolically flexible to being metabolically INflexible?
Since the vast majority of people with metabolic inflexibility respond quickly and often completely to carbohydrate restriction, many, myself included, believe that carbohydrate overconsumption may be the cause.
Those of us who believe in this theory fall into one of three camps. One I call the Yudkin camp (after the British physician and nutritionist John Yudkin), the second the Cleave camp (named after Thomas L. Cleave, another British physician), and finally the all-carbs-are-bad camp that I don’t have a published Brit author to name it after.
Yudkin thought sugar was the initiating problem. Cleave thought refined carbs, mainly wheat and  sugar, were the initiating problem. Those in the third camp believe all carbs are bad.
The three camps differ in what they believe is the cause, the triggering event, so to speak, but they all agree that once the problem sets in and metabolic flexibility is lost, and the only way to successfully treat the problem is with a low-carb diet.
This is where Gary Taubes’s book, The Case Against Sugar, enters the picture. He is making the Yudkin case, although using a ton more research than Yudkin had available to him during his lifetime.
Gary musters a mountain of evidence that until various societies are exposed to sugar, diabetes, the signature feature of metabolic INflexibility, is rare. Once sugar is introduced into a society, nothing much happens at first, but as the amount of sugar eaten increases, cases of diabetes start popping up. Ultimately, when the sugar consumption is at high levels (in the US it peaked in 1999 at about 90 pounds of sugar per person per year and has fallen off slightly since), diabetes becomes epidemic.
(NB: Remember, the 90 pounds/person/year is an average. I doubt that I eat five pounds of sugar per year, which means someone else is eating 175 pounds per year to make the average work. It is those people who are doubtless the ones filling up the diabetic wards.)
Stephan Guyenet and others have attacked Gary because the data he musters comes from observational studies and short-term, often poorly done RCTs. The reason is that this is all the data that are available.
To truly nail this down, scientists would have to randomize people into two groups, the subjects in one of which would be expected to eat 100 pounds of sugar per year, while the subjects in the other group would eat almost no sugar (or a significantly lesser amount). The study would have to last for years to realize a significant outcome. Ethical issues aside, a study like this would be enormously expensive and would be impossible to accurately monitor. It’s one thing to randomize people into a study and have them not eat sugar for a month or six weeks – it’s entirely another to get them to forsake it or gorge on it for six years (or however long it would take for meaningful data to emerge).
You have to do it kind of like the studies on smoking were done. For ethical reasons, you couldn’t randomize non-smokers into a group and make them start smoking to compare outcomes with those who continued to smoke. Researchers had to rely on observational studies and animal studies, all of which strongly implicated smoking as a major driver of lung cancer.
As I mentioned in the email above, The Case Against Sugar is a standard Taubesian work. Compulsively readable and filled with all kinds of engaging and thought-provoking history. He veers off here and there to discuss the invention of ice cream and the origins of the candy and soft drink empires that exist today. And that’s not to mention the breakfast cereal industry, which, unfortunately, was the source of many of my own calories in my youth.
Can you guess the name of the first sugar-coated, pre-sweetened cereal? It was Ranger Joe, developed by a Philadelphia heating-equipment salesman, who got the idea from watching his own kids ladeling spoonful after spoonful of sugar onto their dry cereal. The founder could never get the clumping problems fixed, so he sold out in 1949 to the company that became Nabisco.

The Deadly Duo: Tobacco and Sugar

Another fascinating rabbit trail Gary takes us down is the unholy alliance between big sugar and big tobacco. By blending tobacco cured two different ways – both involving sugar – cigarette sales skyrocketed. The addition of sugar to tobacco made cigarette smoke easier to inhale and vastly more addictive.
Here is a short video of Gary explaining the process:

Taubes responds to Guyenet.

Before I wrote the email above that kicked this post off, Cato Unbound, a debate or discussion forum that is part of the Cato Institute, asked Gary to write an essay based on his findings on sugar. The editors of Cato Unbound then found three people to write responses. The three people were Yoni Freedhof, a Canadian physician (best known to readers of this blog as the physician who took the video of Kevin Hall and asked the fawning questions), Stephan Guyenet, whom we met in the email above, and Terence Kealy, whom I don’t know, but is a physician and biochemistry researcher.
After all the critiques were in, Gary was allowed to answer them all.
At the time of my email above, Gary’s lead essay along with the three responses were published. Since that time, Gary has responded. I’ll let the readers come to their own determination as to whether Gary adequately answered his critics, the main one of whom is Dr. Guyenet.
Here is Gary’s essay:
Unintended Consequences, Special Interests, and Our Problem with Sugar
Stephan Guyenet’s response:
Americans Eat Too Much Cake, but the Government Isn’t to Blame
Yoni Freedhof’s response:
Unintended Consequences, Special Interests, Sugar, and a View from the Clinical Trenches
Terrence Kealey’s response:
Putting Nutrition Claims to the Test
Gary’s response to the above:
The Case against Sugar Isn’t So Easily Dismissed
Since I started working on this blog post, two more responses have come in from the folks debating this issue. One more from Dr. Guyenet and one from Dr. Freedhoff. Here are the links to those. I’m assuming Gary will respond. When he does, I’ll post it.
Stephan Guyenet’s second response:
Extraordinary Claims Require Extraordinary Evidence
Yoni Freedhoff’s second response:
Complex Multi-Factorial Problems Tend not to Have Simple Singular Causes
My advice is to not sit on the sidelines as observers to this spat.  Read The Case Against Sugar yourself and come to your own conclusions based on how strong you believe the evidence to be.


  1. At a recent book talk, I asked Gary about your fascinating research on the ancient Egyptians. They were very kind to leave us a rich record of their culture, and even mummies we can put into scanners to see what happened to their health.
    If I understand correctly, they did not eat sugar, they did eat wheat, and they got the diseases of civilization, including diabetes and obesity. If this is true, ancient Egypt could be just the kind of counterexample, or black swan, Gary always looks for. Except in this case, a possible counterexample to his own thesis in the new book.
    Gary, true to form, took my question seriously and explained to the audience about black swans and the importance of never stopping the search for them. He wondered how much honey the Egyptians ate, though I do not see how they could have eaten enough to make the difference and, in any case, Gary’s thesis is about sugar, i.e., sucrose and HFCS.
    I’m very curious what you think. Could ancient Egypt suggest that Gary’s thesis is incorrect, or perhaps too simple, and if so how confident are you in the evidence we have about this case? To my knowledge, this is the only well documented case of a society that got our modern diseases without eating sugar, so a very important subject to understand fully.

    1. The ancient Egyptian data is what keeps me in the Cleave camp. They did eat refined grains, not as refined, of course, as we eat today, but they did eat a ton of wheat. It was the staple of their diet. Based on some other prehistoric data I plan to post about, I think it’s probably what we call ‘sticky’ carbs, i.e., carbs that are either highly refined or stick to your teeth. Also, re the Egyptians, they consumed a fair amount of seed oils along with their carbs, which could also be a factor. It’s all fascinating, that’s for sure.

      1. Thanks. I’m curious if you’ve had an opportunity to discuss this with Gary. I’d say your research could be the best current shot at assessing Gary’s thesis critically but fairly. He seems to be all in favor of that.
        In this case, it’s possible that Occam’s Razor may not be the perfect path through uncertainty. Sometimes it isn’t. As Einstein said, “It can scarcely be denied that the supreme goal of all theory is to make the irreducible basic elements as simple and as few as possible without having to surrender the adequate representation of a single datum of experience.” You may just have that datum.

        1. My formal research would be the low-fat, high-carb, low-cal arm of a study. To do the LCHF arm, we would have to age, sex, and weight match the subjects I have data for, which would be an expensive and lengthy task. And that’s not to mention actually carrying out the experiment once we got the subjects sorted.

          1. Sorry, I meant your research on the ancient Egyptians. It’s the only serious potential black swan for Gary’s sugar thesis I’m aware of. I’d love to see you and Gary bat that one around.

          2. I see. We have batted it around one on one a bit. Gary is not big, though, on accepting data from friendly debate. And I’m not sure he’s looked at the ancient Egyptian data closely. He needs to attend one of my talks. 🙂

      2. Along with The “DD,” we also found evidence of significant dental wear owing to their primitive milling techniques, thus introducing significant “sandpaper” into their diet, causing wear, decay, abscess, and the downstream heath effects of having rot in your mouth.
        I think WAP documented some of this adverse dental wear in his travels.

        1. There was extensive silica abrasion in the ancient Egyptian mummy evidence. They put sand in with their wheat to help grind it, but couldn’t get all the sand out. There are actually ads from the time where wheat millers would tout how their flour had less sand than a competitors. Made for ground down teeth, but not always tooth decay. I talk about this process starting at about 41:45 in this video filmed last Feb in Vail.

        2. It is also interesting to note that ancient Egyptians also loved their beer and wines! I wonder if this may also have contributed to excess carbs from both the grains and fruits utilized in their making? Things haven’t changed much lol! Mmmm mmmm!

          1. I’ve read a tongue in cheek theory that we originally grew grains to brew beer. Only when we had enough beer did someone think of eating them. And from then on it was downhill all the way.

      3. They did have booze, though. And as far as I can tell drank quite a lot of it – which isn’t surprising given that theirs was a hot climate and much of the water probably wasn’t potable.
        If the problem really does lie in the liver’s being overwhelmed, there’s a possible answer. Presumably AFLD will do just as well as NAFLD.
        Beer was widely drunk – by all classes it seems; and the rich seem to have drunk wine on top of that.
        “… one of the first kings of Egypt, Scorpion I, was buried … at Abydos on the middle Nile River. The German Institute of Archaeology in Cairo excavated Scorpion’s tomb … What was most astounding was that 700 jars containing some 4500 liters of resinated wine …”
        This seems telling, too:
        “In one particular [tomb mural] scene, a female guest says:
        ” ‘Give me eighteen cups of wine, for I want to drink until drunkenness, my inside is like straw.’ …”
        It’s also interesting to look at the diet of the diabetic and obese Chinese mummy Lady Dai:
        We know what she likely ate and drank, from what was buried with her for the afterlife, and it included a great deal of wine and fruit juice:
        “Quenching an eternal thirst, a variety of fruit juices and diverse cereal derived alcohols (distilled from millet, rice, and wheat) punctuated the subterranean landscape of Lady Dai’s tomb; yet, however copious the amount of alcoholic beverages unearthed at Changsha, nothing yet discovered rivals the anticipated afterlife liquor habit of Liu Sheng, Prince Jing of Zhongshan, who was buried with a staggering 5,000 kg of wine …”

    2. A black swan surely would be something that ruled out sugar consumption as explaining the cause of or rise in heart disease, cancer, etc., which is not done simply by saying here’s another cause.
      Or, put another way, is there a better explanation for the apparent correlation between the rise of sugar consumption and the increase in rates of diseases of civilization?
      What am I missing?

    3. Didn’t the ancient Egyptians have access to and eat a fair amount of dates and dried figs? Lots of sugar in those foods. Add those sugary foods to wheat, and it’s a major carb load.

    4. Would the Egyptians have eaten einkorn wheat? Is this lower in carb than modern wheat? Would it still be enough to induce diabetes? Thanks.

      1. The ancient Egyptians ate so much wheat that I doubt the carb difference in the old vs new wheat amounted to that much.

  2. Thanks for the thoughtful discussion. As a sort of technical question, you cited the definition of metabolic flexibility as the ability of skeletal muscle to switch fuels (presumably relatively seamlessly). Does this correctly imply that other tissues (organs) don’t switch? They have their preferred fuels and will by golly use them? Or perhaps they don’t switch so seamlessly?
    It seems a great part of basal metabolism for the sedentary person might be affected by this. I appreciate any response you can offer.

    1. Another useful definition was the first line in the body of the same paper I took the quote I used from:

      Metabolic flexibility describes the ability to adapt to substrate utilization to substrate availability.

      I think this is a better definition, but since the paper is behind a paywall, I used the one in the abstract, so I could link to it.
      Yes, all tissues are involved. Especially the liver.

  3. Thanks Mike, for a brilliant review/discussion/(seemingly needed) defense of Gary Taubes! I haven’t read or cared about Guyanet’s stance(s): I stopped ‘feeling good’ about his stuff back around 2011. (I was at the first AHS in LA and watched Gary ‘have at him.’ Having read “Good Cal, Bad Cal” twice by then, what Gary said made too much sense to me. And none of Guyanet’s stuff on his site or audio files struck me as … entirely reasonable.)
    This “review” comment isn’t directed at the substance of Gary’s book (I’m not done reading it yet…). I’m a (n old) technical editor by profession, so unconsciously ‘pay attention’ to whatever I read. (When reading fiction, I often observe, more than a bit sourly, that “the editorial eye never sleeps!”)
    I “pre-ordered” (not a real word) Gary’s book when it appeared on Amazon, and began reading it the minute it arrived. After a couple of chapters, I stopped and went: “Oh! Of course: It’s Gary Taubes! Just LYRICAL writing!!” I was not paying attention to HOW the book was written, and yet the grace and depth was just evident. Ye GODS: that man can write!!
    The way he puts a ton of information into your brain, and you don’t even notice the shovel going in, is astounding and rewarding. So, I urge everyone to get the book and learn!

  4. Years ago I read somewhere that research scientists knew that if you wanted to make an animal diabetic with drugs (streptozotocin, alloxan), the animals became diabetic faster if you fed them a high-carb diet. Unfortunately, I don’t know where I read that.

  5. I really appreciate this post. I think it’s intensely important for people to understand the power of Confirmation Bias. I honestly think it is one of the most powerful and destructive human behaviors of all time. And I’d like to understand the selective pressure which cause(d) our species to develop this. (I’m not saying other animals don’t have this, but how would we know?). Too bad “Mistakes Were Made” is so dated. It would be great to have a book about it that could transcend the time in which it was published.

    1. The confirmation bias is unbelievably powerful. Anyone who doesn’t believe it, wasn’t paying attention during the recent US election and presidential inauguration.
      I’m not sure I agree that Mistakes Were Made is all that dated, to tell you the truth. Some of the examples they use are older, but the premises are all still the same. It’s still one of my favorite books.

  6. Thank you for the informative email on the pit falls of sugar, I have read all the books written by the Dr Eades ,Protein Power , amazing truths about the affects of how high levels of carbs and sugar are destroying our lives. How very true,,,,(Few things are as destructive and limiting as a worldview that assumes people are mostly rational.)Two things I truly believe ,,GOD and Dr.Eades both save…..So very hard to convince love one.s and friends how easy it is to take back your live by reading and following the plan described in Protein Power,Thank You Again and GOD bless you all.. Please continue to email me,,,,

  7. This is an extremely useful and interesting post. The last time I looked, a secondhand paperback copy of Professor Yudkin’s original book on sugar was selling in the UK for about £100.

    1. I’m glad to hear the price is so high. I’ve got a couple of first editions of Pure, White and Deadly, which was the title as published in the UK in 1972 and a couple of first editions of Sweet and Dangerous, the title used for US publication, also in 1972. Bought them all for a song years ago when no one was thinking about the dangers of sugar.

      1. Yes, I have a 1972 edition of “Sweet and Dangerous,” complete with a nice dust jacket. I probably read about it in one of your blogs. Thanks! Besides Yudkin’s thoughts about sugar, I enjoy reading the book just for his nice compact writing style.

      1. Don’t know about the copyright issues, but I do know it took me forever to download, and I have pretty fast internet service.

  8. Dr. Eades,
    I want you to know your book and your blog has changed my life. And through you I learned of Gary Taubes.
    I have never understood Taubes bashers. I have read “Why We Get Fat” and “Good Calories, Bad Calories” . I consider them two of the most important books EVER written on human health. He didn’t write the books to sell a diet plan or a supplement. He is a pure science writer – combining investigative journalism with the mind of a scientist. He spent something like 5 years researching the material. His conclusion? Public health is full of poor science and poor scientists – men with hidden agendas and studies funded by food and drug companies. Often times both.
    Taubes ‘ exhaustive research uncovers compelling evidence – from the overlooked good science – that insulin and foods that raise it and keep it elevated seem to be the culprit behind obesity. In reading both books, I found Taubes to be extremely cautious (and long winded) in coming to this determination. Exactly as a sceintist should be.
    I have not yet read “The Case Against Sugar”. Now that I hear Gary writes the book like a prosecuting attorney attacking the defense, I want read it even more now.
    Dave B

  9. Interesting about the sugar in tobacco. I had read about that many years ago in “Sugar Blues.,” but hadn’t stumbled upon it anywhere else, and really didn’t know how it worked.
    Thanks for this blog. Guess I need to break down and buy this interesting book, even if I do know that sugar isn’t a health food.

  10. Thanks for this review/defense.
    In my view it’s an unfortunate mistake to think of this as “Taubes vs Guyenet” (as Guyenet seems to do), because they aren’t asking the same question.
    I suggest that readers who want to hear Taubes interviewed about his book go here:
    Russ Roberts, an economist who has been doing his podcast for ~10 years, is a fantastic interviewer. I haven’t listened yet but it should be very good.

  11. As a side note, do you think you’ll do (or have you done) a post on resistant starch? I read freetheanimal, and tried adding resistant starch to my low carb/paleo diet for three months in total. I used plantains, white potatoes at times, potato starch, plantain starch. I added probiotics in both pill form and fermented vegetables form. If there was a benefit to resistant starch, I couldn’t find it. If anything, it seemed to increase my blood sugar (even if just using the flours/pure starches and low carb and not paleo; for me, potatoes caused my blood sugar to fly through the roof, so I quit those after not too long), ceased weight loss, and caused or exacerbated IBS-like symptoms. As soon as I stopped using resistant starch, for instance, I lost 5 pounds in basically no time. I also cured any remaining IBS-like symptoms I had. I now follow a low fiber/low resistant starch diet, though I have been eating some fermented vegetables — mainly because I like the taste of them. And I’ve been cutting back on those and am going to start an experiment (once my remaining stock is done) where I eat no fermented vegetables. I’ve been experiencing such a benefit with no resistant starch/fiber, that I’ve transitioned to a ketogenic diet (for another reason, too)
    My thoughts are that if you’re eating a relatively high carb diet, probiotics/resistant starch are good. If you eat very few carbs, probiotics/resistant starch might not be good and might even be bad.
    It’d be interesting to see your take on it.
    By the way, freetheanimal has a lot of posts that seem to denigrate or hate low carb. And a lot of posters like that too.

    1. Back about eight or nine years ago, I wrote a post on resistant starch. I just checked, and the video doesn’t work, but other than that, the post pretty much reflects my current view on the subject. I know a lot of people think it’s great – I’m just not among their number. At least not yet. When I first started practicing medicine, I was an early adopter. Any new drug that came out, I was willing to give a try. To my patients. After a couple of bad experiences, I changed my ways and became a late adopter. I’m pretty much the same about any nutritional fads that come along. If they’re of lasting value, they’ll prove themselves out. Then I’ll jump on the train.

      1. Hey BobM:
        “By the way, freetheanimal has a lot of posts that seem to denigrate or hate low carb. And a lot of posters like that too.”
        I understand it might look that way to some. And, while I do have plenty of LC skeptics in my midst, there’s plenty of fans and plenty who still use it and tolerate my own skepticism.
        But let me clarify a bit. It’s not so much LC, per se that I’m skeptical of, but a certain version of it that was popularized by a well-know LC advocate about 4 years ago, that being a pure and chronic ketogenic diet. Not bouts of ketosis via episodic VLC eating or fasting, but full blown, under 30g per day if not near zero, combined with ~80% fat, and under ~15% protein. This, in combination with a rather obsessive need to measure blood ketone levels throughout the day.
        First, it ought come as no surprise that you would have loads of ketone bodies if 80% of what you eat is fat. Not a lot else for your body to burn.
        Second, that low of protein in the long term is likely not advantageous because a good portion of the micronutrition we obtain (vitamins and minerals) comes from awesome animal protein sources, animal protein is uniquely satiating in a “Protein Power” sort of way, and with very low carbs, essential glucose for brain function (~120g per day) has to come from somewhere, plus one needs to maintain muscle tone…so I just don’t see how 15% protein is enough.
        One need not search too had to find comparative pics of said chronic LC guy from four years ago, compared with current, where he appears to have lost significant upper-body muscle mass.
        Finally, recall that in classic Atkins, upwards of 120g carbs per day, according to individuals, was still LC by Atkins standards. I don’t count to much, but I’d guess on average, I myself am usually in the 100-150g per day range. I once knew a couple who were ardent LC fans for years. For him, he did best around 50 or less per day, but for her, through lots of experimentation, about 120 was best.
        Mileage varies by individual.

  12. You have to explain your reference to love and herpes. Think you may have intended to start the sentence with “Fortunately” though the joke is “unlike love, herpes is forever”. ?
    And since you brought it up, can one conclude that love causes herpes, or is that just correlation?
    On a more serious note, I am one with much doubt though I never thought it to mean intelligence. Quite the contrary, I always assumed it to mean I just wasn’t getting it. I am beginning to think science is irrational, not people. In fact people are too rational and maybe that gets in the way.
    Some thoughts: We know that not everyone with insulin resistance gets obese and/or diabetic. Conversely, not everyone who becomes diabetic is obese and has IR. Maybe with the onset of sugar and processed foods, a lot of chemicals were introduced in those foods such as preservatives, other food additives and dyes. There certainly were a lot more chemicals introduced in the environment around the same time as well. When were toxic tooth fillings with mercury introduced? When were contact lenses introduced, all with UV blocks and how does the blocking of light rays to our brain affect our metabolic state and health? What about psychiatric medications, prozac, xanax, ambien, all which became popular around the same time? What else causes oxidative stress and inflammation? Maybe that is the only precursor to metabolic syndrome. What about our bodies and minds under stress, and what about depression? Can we will and meditate ourselves to better health? Why do some people get sick and die after losing a loved one? Why can some people smoke and never get cancer? My mother smoked a lot since she was 13. She has a horrible existence now with many diseases none of which are cancer or related to the lungs. When centenarians are interviewed, they run the gamut from drinking booze every night to fried chicken. They always look giddy and stress free. Some exercise a lot, some don’t. True though that not one of them said they ate tons of sugar. And none were fat either.
    Also since you mentioned it, I also did the metagenics fasting diet a long time ago. I have previously mentioned in your blog Dr. Eades that when introduced to food I was told no protein, no fat at first. I was told the first foods to add were pasta, oatmeal and corn. Upon adding these foods I lost weight faster than while on the fast. The weight started coming back when introducing protein and fat although my caloric intake may have climbed quite a bit with these additions. To this day my I have more of an adverse BG reaction to fat than to just starch… for whatever its worth.

    1. Thanks for the interesting history. As Hamlet said to Horatio:

      There are more things in heaven and earth, Horatio, Than are dreamt of in your philosophy.

      And in another almost as famous quote, when Willy Sutton, after being arrested for bank robbery for the umpteenth, was asked why he kept robbing banks. His reply:

      Because that’s where the money is.

      Despite the vast number of possibilities you mentioned, I suspect that for the greatest number of people, the insulin-carb hypothesis is where the money is.
      I agree that there are many factors out there

    2. Hmm….”not everyone who becomes diabetic is obese and has IR”. Are you sure about this? I thought the definition of being diabetic (at least for type 2) was that you were insulin resistant? That is, you’re diabetic because you are insulin resistant. Now, a diabetic person might not be obese, that’s true.
      Also, there’s a theory that the number of repeats of a gene we have can determine how good we are at digesting carbs and also the insulin response created by such digestion. See, for instance, the following:
      So, you might have the ability to digest carbs without a radical insulin response, while someone like me may not be able to do the same. I hypothesize this is the reason why some people can lose weight on the “potato diet”, whereas I’d just have super high blood sugar on the same diet. It also could be the reason why certain authorities can’t understand why many people are obese while they (the authorities) can eat sugar and pasta and bread and it doesn’t affect them. It’s obviously that the obese lack “willpower”.

  13. Thanks Mike.
    You are a true gentleman, have taught me a thing or two about that, and are as well, an exemplary interlocutor.
    Let the debate continue.

  14. Thanks for your continued work, Dr. Mike. I have always loved your blog, you have done tremendous and fantastic work!! I believe that as long as one remains leptin and insulin sensitive, you will maintain your “Metabolic Flexibility”, I was a T2D at the age of 10, only undiagnosed. The work of Prof.. Unger has shown us that Leptin is the most powerful suppressant of glucagon in the pancreatic islets. If one remains leptin sensitive, insulin will not have a hard time to properly regulate glucagon in the pancreas. The correct insulin to glucagon ratio will be made directly in the pancreas, before it enters into the liver, under every condition.

  15. I’m sorry but I don’t understand why it requires a randomized controlled trial to determine what sugar does to health. If one Googles – fructose endocannabinoid system, this comes up.
    Although not all studies come to exactly the same conclusion, sufficient evidence has accumulated over the last 10?years to indicate that fructose, in certain concentrations and mainly in males has a significant impact on brain and cognitive functions. On the one hand, fructose intake affects appetite control by increasing ghrelin serum levels and hypothalamic CB1 mRNA, and decreasing the activation of brain satiety centers. On the other hand, it leads to brain insulin resistance, impaired learning and memory, and reduced neurogenesis.
    Primate obesity researcher Kevin L Grove notes that “…high-fructose corn syrup appears to accelerate the development of obesity and diabetes. Another researcher, Anthony G. Comuzzie reported that “It wasn’t until we added those carbs that we got all those other changes, including those changes in body fat.” http://www.nytimes.com/2011/02/20/health/20monkey.html
    My point is, scientists now have the tools to measure what sugar and fats do to the endocannabinoid system (ECS). There’s plenty of ECS research available at this point but very little interest in discovering what it all means. Google – endocannabionoid in conjunction with saturated fat, arachidonic acid, linoleic acid, NAFLD, T2 Diabetes, obesity, depression, or any other chronic inflammatory condition you can think of and perhpos you’ll see what I mean.
    Dave Brown

    1. I doesn’t require RCTs – those are just the only way to really remove all the variables.
      As I wrote, the idea that smoking is harmful was shown by observational studies. I agree with you that the studies you mention and others are convincing. But those who have other ideas won’t be satisfied with observational studies, and since long-term RCTs are virtually impossible to do, they’ll never be satisfied.

  16. It strikes me that, on this issue, both Guyenet and Taubes are off base. In his original essay, Taubes does emphasize sugar and that the dietary guidelines wording on sugar softened over time. He doesn’t consider a causal link to be established, so Guyenet is off base there, but Taubes makes himself vulnerable by ignoring all the other foods in the dietary guidelines to focus on sugar, allowing Guyenet to make valid arguments against this focus.
    However, Guyenet’s data isn’t saying what he says it says with respect to other foods. Let’s look at his list of the top sources of calories relative to Guyenet’s bullet points from the dietary guidelines.
    1. Grain based desserts like cake and cookies. These desserts do contain sugar, which the dietary bullet points counsel to minimize. However, they also contain even more starch, since they are grain based, which the dietary bullet points encourage. When you take both into account, these foods are neutral with respect to the dietary bullet points.
    2. Yeast breads. Bread contains little sugar, but plenty of starch. Eating lots of bread is directly in line with the dietary bullet points.
    3. Chicken and chicken dishes. The bullet points say nothing about meats. They do say to minimize fat. Chicken has been largely adopted based on its reputation as a low fat meat. The shift from beef to chicken is directly in line with the dietary bullet points.
    4. Soda and sugar drinks. The dietary bullet points do recommend against these due to their exclusive use of sugar for calories.
    5. Pizza. Pizza contains a variety of foods, which the bullet points recommend, and include starch, which the dietary bullet points also recommend. While pizza also contains fat, on balance, pizza is good if the dietary bullet points are your measure.
    6. Alcohol. This is actually pretty far down the list – it can’t represent more than 1/6 of calories, and probably represents less – so the bullet point on using alcohol “in moderation” seems to have been adopted by Americans.
    So basically, 3-4 of the top 6 sources of calories are in line with the dietary guideline bullet points, and only 1 is against them. That suggests that the bullet points, which are as far as most of the public gets with the guidelines, have indeed strongly influenced the American diet, contrary to Guyenet’s assertion.
    But Taubes, by focusing on sugar, is focusing on the one area where the guidelines have been ignored by the soft drink guzzling public. If Taubes really thinks that sugar is the only culprit, he should be saying the government did a great job with the guidelines, and the only problem is that the public ignored the sugar guideline.
    More likely, both Guyenet and, now, Taubes are wrong, and the problem with the guidelines isn’t so much their approach to sugar, but their approval of starch.
    And here’s the thing: even an experiment that told some people to eat lots of sugar, and others to eat a low carb diet, wouldn’t distinguish between the three low carb camps. To do that, you’d have to tell one group to eat sugar, another to eat white bread, and a third to eat forms of unrefined starch.
    The evidence for low carb is at this point pretty strong, in my view. The people who are pushing the idea that sugar is worse than other carbs – including Taubes – seem to be jumping to a conclusion with minimal support, though.

    1. I agree with you. Starches are often more problematic than sugar in a diet. It was my case, I always strictly limited sugar, cooked my food, ate vegetables, limited fat due to gallbladder issues. I couldn’t control my appetite and creping up weight till I eliminated starchy foods and strictly limited fruits. While I see a lot of people addicted to sugary foods, there are more addicted to any bread.

      1. I think it’s the volume. I also used to eat hordes of starches – Holy Health Grains – but not so much sugar, except for that equally “healthy” fruit juice.
        If I also drank the same kind of quantities of sugar-sweetened beverages as many people do I’d have arrived at he same place, only quicker.

  17. Enjoyed your article but couldn’t decide what you meant when you used the word “sugar”. Were you including starchy vegetables, beans, pasta, bread and sweet potatoes or did you just mean sugar – like what people put in their coffee and use for cake and candy? Maybe you meant anything that makes insulin spike.

    1. I meant sugar, as is table sugar, fructose, high-fructose corn syrup and combinations thereof. All the things we usually think of as caloric sweeteners. Not bread, beans, pasta, etc.

  18. I dont know about full of doubt making you intelligent, but to view anything outside of a probabilistic framework does make you a dummy. Life is uncertain and one needs to view any thing using probability(Bayes Theorem, the best). So as to the case against sugar i am glad that you have set some straight: Taubes is making a case; not concluding. As to my own probabilistic view i try to see what certain countries diets have in common, such as French, Japanese, etc. The one thing i see is far less sugar intake in these healthy populations than what we Americans add to our foods. So, i eat no added sugar; and only sugar i get is from some 85% cocoa in chocolate bar. My diet is devoid of simple carbs.
    As to confirmation bias Dr. Chris Gardner a vegetarian who did the A-Z study was honest enough to say that Atkins outperformed as to biomarkers his preferred diet. That is a rarity in society at large; someone who admits that what they thought would happen did not.
    As to diet and carb intake, i think he may be on to something with regard to his subsequent work where he saw people lose weight on both lo and hi carb, but it depended upon insulin sensitivity.
    It is sad that to many do not see things as probabilistic but only with certainty. As to diet people need to get it that you are not what you eat, but what and how you process what you eat: Different for different people.
    Excellent and well thought out review of Taubes book. Nice to see someone doing some thinking instead of towing a party line of say lo carb, or hi carb.

  19. Hi Dr. Eades
    Thanks for your work and this great and informative blog. My wife and I are about half way through our third year of a committed LCHF lifestyle and we’re both curious how you see the long term effects of the ketogenic diet; much has been written on “transitioning” or getting started on a LCHF or Paleo diet, but I really have not seen much in the way of serious studies on long term effects.
    I am a scientist myself (though not in the medical or health field) and did quite a bit of research on the LCHF topic before undertaking this diet. We cut out nearly all sugar, and almost all carbs ( <30 g/day) – and as expected, it produced profound positive changes in the first four to six months, after which the degree of change moderated somewhat. My cholesterol and other standard health indicators all improved significantly – they continue to slowly but steadily improve to this day; and I really have no specific health concerns at the age of 52.
    But I do see health professionals, nutritionists, MD's and others, who suggest that longer term "Keto" diets may be problematic. I have reviewed what I would consider both credible, and incredible arguments for both pro and con. I don't mind moderating my LCHF diet, but I cannot really conceive of going back to eating over 50 grams of carbs per day, or why that might possibly be advisable. Thanks. Scott

  20. Dr. Eades –
    What is your response to the critique that some cultures consumed a relatively large amount of sugars — e.g., honey and agave — as a percentage of daily energy? I don’t have the names of them in front of me, but I know you’re familiar with the claim. If true (which I tend to doubt), it would be a powerful argument against the hypothesis that sugar is a particularly noxious carbohydrate.
    Thank you for writing the best low-carb articles of any author out there.

    1. Some cultures do eat honey occasionaly, but it’s typically a seasonal occurrence. The data from the researchers Taubes presents in his book seem to show that it takes around 70 pounds of sugar (or honey) per person per year on average before a society starts to experience a surge in diabetes. I haven’t read all the literature on the subject, but I doubt that any of these cultures consume, on average, greater than 70 pounds of honey per person per year.

  21. For me, reading about these topics for the last six years or so, starting with the Pa.Nu blog of Dr. Kurt Harris, the issue is, as I see it, WHY eat sugar? Is it necessary for human survival? Because it is delicious? (For children?) And once we come to grips with that issue, WHY eat things that too rapidly turn into sugar? (Such as wheat flour and rice…)
    It is about the same for grass/seed oils: plainly “people” are not grain consumers (and therefore not as much adapted to such food sources) as birds and mice and other various rodents. Is there any doubt of that, really? And certainly it is obvious that early people did not have access to the required machinery to make seed and vegetable oils in any quantity.
    Clearly people, as omnivores, have an increased capacity to eat a variety of foods and stay alive and reproduce. That does not mean that all foods are equal or as equally required and healthful. And my view has been that the ability to consume carbohydrates is in the nature of an evolutionary “legacy” intended to allow for survival, somewhat like an emergency food source, when real food is scarce.
    Finally, it is more than plausible, it is simply realistic to admit that different people, both as groups and as individuals, have different responses (in terms of insulin reaction and production) to different diets. But it is still possible to make the general statement that eating carbohydrates and protein, to different degrees, trigger an insulin response in normal people, even though the blood sugar levels in all those various people may hit different peaks, at different times, etc. And a proper insulin response to sugar/carb consumption is a good thing, in terms of staying alive.
    None of that suggests anything like food “reward.” It just suggests that almost all “people” are adapted to a varied diet. I like to exploit that adaptation by occasionally having a pastry or cake at a birthday party, or having good sour dough bread with butter or olive oil, etc. There is no need to make a religion out of this. But keep an eye on reality. Primitive people had a diet where meals were sometimes irregular, and frequently far apart, and that may have been as much a factor as what was eaten.
    None of this argues in favor of anything except that people CAN eat sugar and carbohydrates, not that people should do that, or that there is no practical limit of such sugar consumption in terms of maintaining good health. Altogether it may suggest only that a small amount of sugar and carbohydrates in the diet in general is not grossly harmful.

  22. Fantastic blog – great to have a new one. Loved the Bertrand Russell quote and the bank robber quote too.
    Also, I’d like to take the opportunity to make an emotional thank you for your review of Dr Malcolm Kendrick’s “Cholesterol Con” book back in 2007 (?). This lead to his website/blogs and helped me to get me through my cardiac event last year.
    And also your interview/discussion with Ivor Cummins on CT – CAC scans and much more.

    1. Glad you profited from the post on Malcolm Kendrick’s book. And the discussion with Ivor on EBT, CT and CAC scans.

  23. Great post, Mike!
    Glad to see you back. I’ve missed your insight and droll wit. I’m finishing up Taubes’ book now and have found it fascinating and instructive.
    I’ve noticed most of Taubes’ strongest critics are young and slender with presumably excellent insulin sensitivity. They eat carbs and sugar without apparent harm. Does this result in a lack of imagination about how that changes via aging and metabolic derangement from poor food choices?
    It’s easy to ignore or misunderstand a disease you’ve not suffered yourself. Once you see the results of metabolic syndrome on your own body, figuring out a solution takes on new urgency. It’s personal.
    If you’re a dilettante sugar junkie, it’s just a bit of fun. But if it destroys your life from the inside out, suddenly the solution has a sharp edge to it.

  24. Mike, Allegedly, Einstein, Russel and Huxley after a meeting of the Royal Society of Britain in the 1950’s, stated that too much science was pre-occupied with dotting the ‘i’s and crossing the ‘t’s and that logic, common sense and imagination had suffered.
    Homosapiens underwent anatomic skeletal changes, metabolic changes shown in the histology, biochemistry and degenerative pathologies determined by atomic and other recent investigative tools, when the species anywhere adopted a nutrition and life practice we refer to as the Neolithic revolution and period. Your data on Egypt is consistent with this process.The insulin carbohydrate story started at the Neolithic period and has continued today.For 98% of our time on the planet our pancreas synthesis and production of insulin would have had a different morphology and glucagon likely sythesised more often.
    The increased load of carbohydrate and insulin production variously set a scene for insulin excess with insulin resistance, glycation, degrees of fat accumulation, endocrine type activity and inflammation.This is the crude simple template of changes with carbohydrate consumption.
    The sucrose, sugar contribution commenced in the last century, a disaccharide sugar, carbohydrate that digested in the gut to glucose and a near new sugar fructose. More recently, corn syrup is behaving similarly. Taubes, Lustig and yourself have made rational cases for avoiding the main stimulant for insulin production and so avoid the attendant pathologies of fat accumulation, diabetes and the ‘terminator’coronary heart disease, that kills 80-90% of those pathologies.
    Colonialism made grain carbohydrate extensively possible, aided by agrarian science and modified starvation such that a population explosion arose in the non affluent world. Starvation was reduced but a wide range of different types of malnutrition resulted, so that now the degenerative diseases are more common, than in the affluent world.
    There is enough historical evidence to eliminate sucrose and corn syrup from our diet. I would include any grain flour also. In medicine we work on percentages because our patients are humans.Remember for 98% of our time on this planet, we did not consume sugar, corn syrup, or grain flower or contract the degenerative diseases. The people of Tokelau and Kitava knew that.LAG.

    1. I’m with you. It would be great if sugar didn’t exist. I don’t think it’ll ever be banned, so we’ll just have to live with it and use education the same way the anti-tobacco forces have. It’s been pretty effective.

  25. Yay! Guyenet tweaks Michael Eades into posting so he can’t be all bad!
    “Science advances one funeral at a time” (Max Planck). Unfortunately the New Young Narcissists as I think of them – Freedhoff, Katz, Hall, Guyenet, Nunes etc. – are going to outlive me, as will their reinforcement of dogma vs. science. None of them are as brilliant as they believe they are, and their very income and social position depends on this. I used to enjoy reading Whole Health Source way back and long ago, up until Stephan became a Professional Researcher. When he deleted some of his previous posts, along with all the replies, I became suspicious. A Real Scientist would have left them be and added a convincing explanation as to why he had changed his opinion.
    “Food Reward” I never found convincing. In fact I never found it understandable. I just ate the most rewarding meal – rabbit casserole, with bacon, herbs and a bunch of low carb vegetables – and it was so rewarding I may not need to eat again until tomorrow. Oh wait, that’s satiating, not rewarding. Rewarding would be a meal that made me eat again soon. Which in my case would be carbs.
    Now Real Scientists like you and Taubes and a whole bunch of others would understand this – carbs spike my blood glucose, the insulin turns up late to the party and stays until all the glucose has gone home, my BG drops and the Hangry Hormones arrive – glucagon, cortisol, epinephrine, norepinephrine and I read recently also Neuropeptide Y. Undoubtedly other players will be revealed – and they will all be part of or related to the endocrine system. I’d read on SREBP and only recently discovered ChREBP for example.
    According to Guyenet this does not and cannot happen. He is not only calling me a liar, he is calling my GLUCOMETER a liar! If I had a pocket insulin meter (which I wish someone would invent) that would also be lying.
    Something a bit wrong there!
    He is employed (or was) to find ways for the Foodlike Substance Manufacturing Industry to make more addictive food, and to divert attention away from carbs (profitable!), insulin, endocrines in general back to a more sophisticated version of CICO and ELMM, ie. blame the patient. Meanwhile I expect you’ve seen Hall going after David Ludwig.
    Taubes doesn’t have all the answers – nor does anyone else – but he sure as hell ASKS ALL THE RIGHT QUESTIONS and backs his findings up with copious quantities of references. Such as he can dig out of the literature as it currently is. He missed out on a lot about Leptin in GCBC but wait, how much of what he missed was actually known at the time he was researching?
    Old farts like us are well aware of the time BEFORE there were “epidemics” of obesity, diabetes and other metabolic diseases. An increasing number of doctors and nurses and most dieticians have no personal experience that this was ever true. The New Young Lions in the “research community” likewise. Taubes, along with Teicholz, is looking at what changed between then and now. No, sugar isn’t the only player, but it’s a big one. I suspect Omega 6 oils too, look how much the consumption changed between then and now. Wheat is my personal bugbear (N=thousands) and this not only goes back to the Ancient Egyptians but has been grossly changed by breeding (not even GM) in the last few decades. Lots of other factors too. All power to Taubes for picking them off one factor at a time. He has several lifetimes of work ahead of him.

    1. I encourage people to go back and watch old movies. And not all that old. Even in movies made in the 1970s, all the actors look like stick people compared to the actors today. It’s really quite remarkable. Or look at old photos from Woodstock and compare them with photos of college kids today. You’re right that young folks today don’t have a clue as to what most people looked like just forty years ago. An amazing difference.

      1. It’s still noticeable here also. Lots of slim fit healthy old folks, lots of obese unhealthy young ones. If even the shopgirls in the supermarket have noticed the fat ones buying their Low Fat!!! foods and becoming inexorably fatter while the old folks are to be found in the butchers, veg shops and farm shops, one wonders if nutrition researchers are actually researching nutrition or doing marketing.
        Perhaps it’s time for Nutrition Research 2.0, which I suggest be carried out by physicists, engineers or journalists, all of whom seem better at linking data with the Real World.
        Some honourable exceptions of course, I wish more of Gerald Reaven’s work was unpaywalled, for example.

        1. When I was a child in a socialistic country, no kid at school was fat in 70-s, a general crowd consisted of not fat people. We ate traditionally cooked food with a bread at every meal, no one thought drinking tea with something sweet was wrong. However, that thinness didn’t get translated into a healthiness. People nowadays live longer while fatter.

  26. I’m still lost about what to do about my own obesity and high blood sugar. Last year, for 12 weeks, I tried “Protein Power” and gained weight, and then “Always Hungry?” for 12 weeks. I think I read about that program here. My HbA1c, which was 8.0 ticked up slightly to 8.1 and I gained some weight.
    Then I went on McDougall’s “Starch Solution” for 15 weeks. I lost 40 lb, and my HbA1c dropped to 6.1. My doctor was thrilled.
    For me, it seems HbA1c always is related to weight. If I lose weight my blood sugar goes down. If I gain weight it goes up. On the low-carb diets, even with mindful eating, my caloric intake tends to be higher. A tablespoon of oil here, a tablespoon of oil there – it adds up.
    On “Starch Solution” my total cholesterol ended up at 122, and LDL at 67. On “Protein Power” it remained in the normal range, but started creeping up.
    The problem, though, is that after 15 weeks on “Starch Solution” the high glycemic carbs seemed to trigger “hunger spikes” in me. And as much as I tried “mindful eating” I just got cravings after eating carbs – even “whole foods” like brown rice and potatoes. I’ve since regained 30 of the 40 lbs I lost.
    For the last week I tried recommitting myself to “Starch Solution” and tried my best to observe “mindful eating” – eating only when I was truly hungry. While my total caloric intake was less than on a low carb diet, doing it this way I was eating 2200 – 2300 calories day. I neither gained nor lost weight.
    So I’m not sure what to do exactly. All diets which actually result in weight loss (I’m currently about 110 kg) require long term deprivation it seems.
    I think one thing all diets seem to agree one, be they low carb or low fat, is that processed sugar is very unhelpful.

  27. I would love some more input into metabolic flexibility. I’ve lost 100+ lb following the principles outlined in Protein Power, and thanks to Staying Power and Atkins For Life, I’ve been in maintenance for over a year. If I remember correctly, you once wrote there’s a notion that living low-carb long enough might “heal” insulin resistance. I find that every six to eight weeks, I can have a treat day of whatever I want and it does not affect my weight. A friend of mine in maintenance can treat herself two to three times a month without detriment.
    Do you think this flexibility is perhaps something we’re born with? Is it possible carbohydrate tolerance might be a predisposition, so to speak? I understand that a lifetime of diet patterns has arguably the most influence, but what about genetics?

    1. I do think genetics is a big part of it. There are three components to the carb intolerance situation: genetics, activity level, and age. I call them the carb intolerance triad. And it is why people have more trouble losing weight when they age. Their genetics are the same, their activity level probably falls off a bit, and they are older. So, it requires more dietary diligence to maintain metabolic flexibility with age.

  28. Doc Eades- really enjoyed this post. I’ve been low carb for approximately 7 years. There is a weight lifter, John Kiefer, pushing a theory called carb backloading. Basically he states that by remaining low carb during the week and then loading up on simple carbs one night, the body can both grow muscle mass and burn fat. He sites a study that showed patients on a low carb diet plus a “cheat night” lost more body fat than those on an exclusively low carb diet. This seemed too good to be true but I was stuck about 20 lbs above my ideal weight and decided to try a night of controlled simple carb consumption. I drank a soda and eat a small chocolate bar. What followed was a night of tossing and turning while feeling as if I had a fever. In the morning, I was 3 lbs lighter than the weight I had been stuck at for months. I tried to repeat the effect with the same meal 4 days later without the restless night and without the weight loss. I worry that the effect, however small, may help in weight loss but drive up insulin resistance and therefore is not worth further experimentation. Curious as to your thoughts as to whether sugar in limited amounts at controlled times could increase metabolic rates and lead to weight loss?

    1. I wouldn’t really recommend sugar at any time. But I, myself, eat it on occasion. I’m not familiar with the program you mentioned, and I can’t really see physiologically how it would work. Taking carbs at night (at anytime, for that matter) will result in a release of insulin. Insulin is a growth and storage hormone, so it will increase muscle mass a bit. But at what cost? I don’t see how sugar at any time would lead to weight loss, but I’m always willing to be proven wrong.

  29. The fundamental technical error of Taubes (whom I greatly admire) and most other low-carb advocates (of which I am one) is in associating “insulin resistance” with T2DM. I am a monogenic (HNF1a) diabetic who has pored through the basic research literature for many years.
    Whole-body IR is a measurable parameter, and it DOES NOT progress at all in T2DM, even as insulin secretion degrades due to morphological derangement and apoptosis of beta cells.
    It is insulin deficiency that causes hyperglycemia in almost all forms of diabetes (excepting MODY2). This is because islet insulin is the primary regulator of alpha-cell secretion of glucagon. It is hyperglucagonemia, inducing excessive hepatic glucose output via glycogenolysis, that is the dominant cause of excess BG:
    Skeletal-muscle IR is a genetic characteristic, and is one of the factors controlling susceptibility to T2DM (the others are in the beta cell for the most part). Hepatic IR, meanwhile, is a misnomer and is “apparent” only via the above-described mechanism that actually occurs in the islets. Other insulin-mediated hepatic pathways such as de novo lipogenesis DO NOT exhibit IR behavior at all.
    Transcription factors (TFs) provide epigenetic responses to changes in diet (i.e. environment) and physiological status (e.g. adipose stores and cellular aging). As we age our maximum subcutaneous adipose storage capacity declines, nominally. When we “saturate” it, TFs (e.g. ChREBP) respond with de novo lipogenesis downregulation in adipocytes and upregulation in hepatocytes. This response is well-researched (K. Iizuka, Mark Herman et al), and completely overrides insulin/glucagon signaling.
    Fructose generates a measurably stronger TF response (but < 2x) than that of glucose. The problem is caused dominantly by all/total carb's.
    Taubes' own Nature article Prosperity's Plague details the subcutaneous adipose-saturation genesis of inflammation (i.e. metabolic syndrome and T2DM).
    IR is a grossly overextended and commonly incorrectly-applied concept — it has become a fatal error in understanding modern-diet-induced conditions of tissue degeneration.

  30. P.S. Why the apparently unique effect of dietary sucrose and HFCS vs. starches, one might ask. IMO the potency of fructose is mostly in its sweetness, 10x that of glucose, as Taubes observes in GCBC. Many, but not all, find it addictive.
    And also in its prevalence in almost all modern refined (shelf-stable) foods.
    The maltose-induced “beer belly”, as Cleaves observed, requires only this foodstuff to induce metabolic syndrome. Maltose is a disaccharide of glucose, containing no fructose. But many beer drinkers consume it in large quantites. Once normal adipose tissues are saturated and their de novo lipogenesis is downregulated, the liver takes over and the extra-high post-prandial portal (vein) hormone (i.e. insulin) levels induce added compensatory visceral adiposity with consequent immune response (e.g. macrophage invasion) and systemic inflammation.
    I think that the above-listed mechanisms can explain all of the historical observations cited by Taubes et al, associating sugar with modern metabolic conditions. But the problem is quantity of dietary carb’s overall — our evolutionary/genetic status is incompatible with the massive quantities present in the modern food supply and diet.

  31. Another incorrect low-carb concept IMO is the one associating insulin with degraded ability to burn fatty acids in insulin-regulated tissues (muscle, liver, etc.) — i.e. degraded metabolic flexibility. Lab measurements of hormone flux rates do not support this model.
    Rather, it is long-established “textbook” knowledge that ectopic intracellular fatty-acid metabolites appear with metabolic syndrome. And in skeletal muscle, for example, these interfere with beta oxidation, reducing it by 80% or more. Whereas they do not reduce any of the rate-limiting steps for burning glucose very much.
    This cellular pathology of MS is, IMO, the reason that those with excess visceral adiposity tend to get very hungry within a short time after each meal. We are evolved to burn fatty acids dominantly in the affected tissues that are some of the largest energy consumers in the body. When beta oxidation is grossly impaired there is over-reliance upon glucose supplied via the circulation, leading to the instability of BG in MS as well as early, abnormally strong hunger signaling because other tissues are “stealing” the BG supply that the brain requires (in the fed state, if not the fasted state).
    I believe that ectopic lipids are mostly a marker of MS, and not causal in any of the modern chronic pathology. They are disruptive in certain ways, but this is quickly and easily reversed with diet correction and decrease of adiposity, thus normalizing TFs and hormones.
    Cellular damage (accelerated aging, essentially) in T2DM (and even T1DM) and other metabolic conditions is most likely caused by dysregulation of normal cellular regulation of respiratory energy production (i.e. mitochondria) and its associated ROS and repair homeostasis, via chronic over-stimulation from modern diet. Chronic immune response (e.g. inflammation in T2DM and autoantibodies in T1DM) is almost always a consequence, and is involved.
    Insulin/glucagon are short-term response hormones. Glucagon keeps the brain supplied with fuel (either glucose or ketones) from second to second, and the islet hormones transition normally only to absorb meals. Insulin regulates glucagon (by suppression — it is counterregulatory inside the islets) and drives amino acids and glucose into the tissues when these nutrients are at high portal levels.
    The insulin-glucagon axis controls the liver, which in turn controls fuel and substrate supplies to the body. But insulin cannot explain chronic metabolic conditions — these are intracellular pathologies and epigenetic responses to environmental stresses outside of the “evolutionary context” of modern hominids.

  32. I left a comment a while back about a possible error on Page 150, but thought I’d found the correct info in the Notes. It was marked pending approval but never posted, or at least I’ve never found it. Did I do something wrong?

    1. No, you didn’t do anything wrong. For a time (like two years or so) I had limited time to spend on this blog. While I was away from it, comments stacked up until there were almost 1,300 awaiting moderation. They’re still there. I’m trying to keep up with the current comments while agonizing about the ones still in moderation. I’ve half a notion to just go in and approve them all and be done with it, but my more compulsive nature tells me I need to go through them all one by one. Consequently, I’ve been kind of paralyzed and haven’t done anything. Suggestions?

  33. Dr. Eades,
    I wonder if I might stimulate your interest with the following observation: Individuals with one of the three TCF gene mutations, like myself, for monogenic diabetes have been heavily studied. There has never been a single case of concurrent T2DM and MODY3 observed. And those with these TCF mutations ALL of have very high insulin sensitivity — this is universal. I am no exception.
    There is a strong statistical association with Nordic ancestry — I believe that these forms of monogenic diabetes were “conserved” in environments where no plant foods were consumed or available. In such environments the myocyte-protective (against excess glucose) insulin resistance (IR) that is achieved by most modern individuals roughly by time of maturity (i.e. full growth — say, age 18 or 20) in muscle tissue was less (or not) important, and greater insulin sensitivity was possibly even advantageous.
    I can provide many technical references upon request. But I am presently reading Taubes’ book, and I see (expectedly) the claim of sugar inducing IR. I just claim that this is wrong — muscle IR/IS is important in susceptibility to metabolic syndrome and T2DM because muscle is the largest by far of the body’s insulin-regulated blood-glucose clearance tissues. But IR does NOT progress with T2DM, nor does it do so in metabolic syndrome (other than, to a limited extent, coincidentally with increase of adiposity but this is independent of either pathological chronic condition).
    TCF-type monogenic diabetics never get T2DM, probably because of their high insulin sensitivity in muscle tissue. Clearance of glucose is always adequate to prevent overstress of the beta cells.
    Metabolic syndrome (MS) can definitely be observed in those like me, however, and I myself did have it in middle age before I understood any of my conditions.
    I could point to much more evidence that IR is NOT a causal factor in either MS or T2DM, and is largely genetic and added to in known proportions by obesity — I wish I could convey this evidence to Gary Taubes. I think that many of the obesity researchers DO understand this, and certainly islet researchers do — the field of measured data for all sorts of human cohorts (because of diabetes, mainly) is huge, and familiarity with these data belies the idea that IR is directly induced by any dietary component. And “hepatic IR” is a very unfortunately misleading term — the effect is in the islets as I explained earlier, and the phenomenon does not exist in the liver.
    I think that Taubes’ thesis that sugar is the primary cause of T2DM is probably correct, but that he has the mechanism completely wrong. I would love to help him and NuSI, but don’t know how to get through. Listened to Jimmy Moore’s recent interview of him and the unfortunate story of the NIH experiment gone wrong … I think I might be able to help overcome the impasse between NuSI and researchers like Eric Ravussin, for instance.

  34. A couple more thoughts as I read through Case Against Sugar:
    1. Taubes does give a nod, indirectly, to the importance of transcription factors by mentioning “hormones and enzymes” — the latter are ultimately driven, upregulated and downregulated, and so forth by transcription factors. Still, though, too much emphasis on hormones which regulate short-term perturbations and transients such as meals, and too little on the cell’s long-term regulatory mechanisms.
    2. As in GCBC, Taubes emphasizes the discovery of the radioimmunoassay for insulin. Very quickly afterward Unger (with assistance by Sol Berson that he credits) developed the analogous form of assay for glucagon, and following this the mechanisms of diabetes were discovered. They have never been SUCCESSFULLY challenged ever since. Taubes seems unaware of this story, as indeed most are. Unger’s work (followed by many others since, including Alan Cherrington for example) is vital to understanding the hormonal regulation of fuel in both non-diabetics and diabetics.
    3. Also as in GCBC, Taubes describes a widely observed but misleading characteristic of T2DM. He notes that in both obesity and T2DM the (average or total daily) levels/amounts of insulin are higher than in lean non-diabetics. This is true, but the key damaging defect in virtually all diabetics is deficient insulin secretion while absorbing meals — T2Ds are no exception at all to this.
    Basal homeostasis is disrupted in both metabolic syndrome and T2DM, and this is a very different thing than postprandial response. I believe that Taubes, like others who are not adequately steeped in the relevant physiology, has drawn the common incorrect conclusion that T2DM is caused by insulin resistance rather than by loss of beta-cell population and deranged morphology/function of the remaining beta cells.
    The proper/normal (non-diabetic) balance between alpha cells and beta cells in the islets, and the secretion of their respective hormones (glucagon and insulin being the primary ones), causes both the basal regulatory defects and the postprandial defects.
    The regulation within the islets is “paracrine”, because islet insulin regulates alpha-cell hormone secretion. When there is insufficient insulin, excessive glucagon secretion and many more cascading effects upon the liver result. All of these phenomena are well understood within the basic research community, but almost totally unrecognized outside these few people.

  35. In overly simplistic explanation of the basal hyperglycemia and hyperinsulinemia of T2DM (and the less advanced diabetic condition referred to as “pre-diabetes”), islet insulin deficiency generates hyperglucagonemia, resulting in excessive hepatic glucose production (over the cycle of a day, for instance). This both raises and destabilizes blood glucose (BG). If this is a chronic condition, a long-term hepatic adaptation upregulates gluconeogenesis to compensate for the extra hepatic glucose output (HGO) — this MUST happen (or the liver would quickly become depleted of glycogen), and it does (as confirmed by lab measurements).
    In T2DM, except in very advanced cases where almost all beta cells have been eliminated via apoptosis, there is still substantial endogenous insulin secretion. Due to increased basal HGO, BG is also abnormally high, and BG stimulates insulin secretion from the beta cells. The depleted and abnormal beta cells of the T2D are clearly deficient in glucose-stimulated insulin secretion (GSIS) during meal absorption. However, the much lower secretory rates required in the basal (or inter-meal) state can still be achieved by the damaged beta-cell population. Hence, the higher BG dominates in the basal state and there is basal hyperinsulinemia.
    The massive library of lab-measured data on T2Ds clearly demo’s all of this. None of this was available in Berson and Yalow’s time, of course, and they can be forgiven for incorrectly interpreting their early observations of hyperinsulinemia in T2Ds in the 1960s. Even well before Roger Unger, the correct hypotheses for paracrine islet endocrinology had already been roughly sketched out (Samols et al). Unger provided hard-core proof that these hypotheses were correct in the early 1970s with some truly outstanding work.
    The liver in T2DM is perfectly normal in its function, as far as I can tell. There is no “hepatic IR” — this is nonsense. The defect is in the islets, and the liver is responding normally to an abnormal islet-hormone balance, and all of the known phenomena of T2DM can be explained by mechanisms that are consistent with lab-measured hormone (and glucose and fatty acids and ketones, etc.) flux rates. Some of these have been done in humans, and also extensively in canine models.
    The opposite of the T2DM is the (generally obese) individual who eats a lot of carb’s and experiences reactive hypoglycemia. When the islets (from cadavres) of such individuals are examined there is a larger-than-normal beta-cell population — sometimes twice as many beta cells or more vs. normal. These people respond to large carb meals with abnormally high insulin response, but it tends to be delayed some. Insulin-regulated tissues will be adaptively more resistant as well. All of the abnormalities combine to create a hyperglycemic initial postprandial response followed by a steep decline in BG that stimulates adrenal (i.e. secondary, to islet) hormone secretion and is not pleasant. The brain recognizes this as a fuel crisis.
    As a lifelong diabetic, I have never (even once) experienced reactive hyperglycemia in my lifetime but I have non-diabetic blood relatives who do chronically.
    Plant-eating mammals such as mice have highly adaptive islets which respond over seasonal cycles to varying food supply by modulating beta-cell populations by factors of as much as five. Modern hominids have almost no capability to vary beta-cell population after age five or so — it is an evolutionary function that was probably lost after coming down from the trees many million years ago.

  36. In reading through the material on Cleave, Reaven and so forth, implicating the somewhat larger role of the liver in metabolizing fructose as compared to glucose, I spot another fatal error of assumption regarding diabetics.
    Most of the glycemic rise in response to portal blood glucose from a carb meal in the T2D is NOT from the meal-derived glucose itself. One needs only to know the portal hormone flux rates in response to bolus glucose, and do a few simple calculations, to recognize this.
    In a non-diabetic any substantial bolus glucose at all shuts down glucagon secretion to zero, via the paracrine suppressive action of local islet insulin on the alpha cells. This is really the only condition, interpreted indirectly by the liver as adequate meal-absorbed glucose to fuel the brain and other obligate neural tissues (that cannot access or metabolize fatty acids), that eliminates hepatic glycogenolytic output. It only occurs with very high portal BG levels only induced (normally, in absence of diabetes) by a carb-containing meal.
    Perversely, in the diabetic, glucagon secretion is amplified in response to the same meal-derived glucose bolus. In a typical T2D the postprandial glucagon secretion is 3 or 4 times that in the basal/inter-meal state. This “inverse” response is caused entirely by the relative deficiency of insulin secretion (by beta cells) in response to the bolus glucose.
    In T2DM both beta-cell function and number are diminished. In T1DM function is normal, but numbers are typically even more diminished except in the early years or if progress has been arrested (which is rare). In TCF monogenic diabetes the beta cells are normal but weaker and smaller than normal, due to the underexpression of many key functional insulin genes because of the autosomal dominant homeobox mutations.
    The three different forms of diabetes are radically different in physiological nature, but the effect upon the hyperglycemic response to bolus glucose is identical — this only depends upon the relative total deficiency of insulin secretion within the endocrine pancreas.
    So the notion that, due to the first response of the liver to fructose (or ethyl alcohol) and consequent delayed/diminished hepatic glucose metabolism, heightened demand (i.e. stress) upon the beta cells by possibly higher peak postprandial glucose is not plausible:
    1. It puts the cart before the horse. Very little, and brief, postprandial hyperglycemia occurs in non-diabetes while normal portal insulin/glucagon response is intact. Can the minor incremental postprandial glucose peaks due to high-flux hepatic fructose metabolism in a pre/non-T2D state really be driving most of the long-term decline in beta-cell function/numbers?
    2. Probably more importantly, the portal concentrations of both nutrients (e.g. glucose, amino acids) and islet hormones during meal absorption are much higher than in peripheral tissues, because the liver greatly dimishes these on “first pass-through”. The endocrine pancreas “sees” the postprandial nutrients first, even before the liver does. Portal hormone levels can be 40x peripheral levels, and islet hormone levels 400x during meal absorption.
    So even with high fructose metabolism in liver, portal glucose levels are dominated by the flux rate from the small intestine. Recirculated hepatic-artery glucose might be a bit higher (than without the fructose) for a while, but this will not significantly raise portal glucose concentrations by recirculation.

  37. If I could speak to Gary Taubes, I would mention a lot of research that seems unsupporting of the purported fructose role in causing T2DM:
    1. Before the days of many varieties of commercial rat chow that is typically doped with both fructose and dietary fat, much of which is used in rodent-model T2DM now, it was not uncommon practice in the basic research field to induce T2D with a simple pure glucose-only diet. This took one or two weeks typically as I recall. I think that Paul Robertson (cited in Taubes’ book) et al used this method, just for one example. And these rodents are herbivores (especially the mice) with highly adaptable endocrine pancreatic capacity, unlike humans who are pure and unusual carnivores with probably the least-adaptable islets in the mammal family (see research by Peter Butler et al in the field of human islet analysis — these are the people who obtain the carefully preserved, fresh pancreases of most motor-vehicle corpses who are organ donors).
    2. All of the systemic (i.e. post-absorptive) fructose-potentiated pathways (e.g. hepatic de novo lipogenesis and others associated with NAFLD, including hepatic transcription factors) that have ever been studied are similarly glucose-potentiated, I would claim. Fructose is typically about 50% stronger in its effect. Does this make it a unique metabolite, significantly different than glucose? I think not.
    There has been just an awful lot of earnest effort to ID a unique systemic role for fructose (as opposed to glucose) — I have tried to read all of the research literature on this. All experiments have been failures (including those of Robert Lustig’s colleagues at UC Davis) IMO, looking at the actual data no matter how the study results have been spun.
    I have an alternative model for the apparent “threshold effect” that comes upon so many of us in middle age, whereupon we start to develop excess visceral fat eating the same food that we kept super lean on when younger. I was one like this, and ate what most others simply were amazed at (huge quantities of food with lots of meat and carb’s) through my twenties or so, maintaining a 28-inch waist.

  38. Why do so few researchers focus upon the role of de novo lipogenesis in adipocytes (rather than hepatocytes)? I have several friends ranging in age from mid-sixties to late-eighties who are massively obese but basically very healthy otherwise. Their physical capacity (e.g. for brisk walking, heavy lifting) is intact and always has been. They have never had, nor have, any signs of metabolic syndrome. They have expansive capacity for subcutaneous adipose storage.
    Likewise I know a number in the same age range who eat massive amounts of carb’s (and anything else that they feel like, as I used to do and still can but do not because of my diabetes and also CVID) who are rail-thin and also strong and healthy.
    Anyone who does a simple calculation of the amount of carbohydrate energy in a very ordinary modern adult meal will realize that the vast majority of carb’s cannot possibly be burned during meal absorption. They dominantly go to adipose tissue, always, just as does dietary fat (by a radically different pathway that is very fast-acting — chylomicrons generated by small intestine — and bypasses the portal vein).
    I believe that the above-cited obese, older category do not require excessive hepatic de novo lipogenesis because their adipose DNL is intact and their capacity to increase subcutaneous adipose mass (by cell division, primarily) is effectively unlimited. They will have substantially increased IR in muscle tissue, for example, but nevertheless are healthy — i.e. they do not have ectopic fatty acid metabolite buildup in myocytes nor in hepatocytes, which is one of the signatures of metabolic syndrome and radically degrades fatty-acid metabolism.
    The above-cited lean, older category probably have high basal metabolic rates and do not need any excess adipose storage capacity. But where do their enormous boluses of glucose from the big meals go? They go directly to adipose tissue, wherein non-hepatic de novo lipogenesis converts them to triglycerides. And these people obviously burn fatty acids very efficiently — hence, they do not build up excess fat of any type.
    There are many different ways to arrive at whole-body homeostasis in different individuals under different conditions — some are healthy and some result in accelerated aging in specific tissues (hence, are unhealthy but not acutely so).
    Most basic researchers from many fields (some of whom were interviewed by Taubes for his article “Prosperity’s Plague”) believe that the threshold effect that can induce metabolic syndrome in most of us at some age is caused by a saturation of the adipose storage capacity — cell replication does respond by increasing cell mass above a certain threshold. This threshold is higher, typically, in youth when various growth-factor hormones and signaling molecules are high. These all gradually decline in middle age for most of us. And so does our basal metabolic rate, not least because growth processes are huge consumers of energy — the largest of all.
    I argue that there is a very large body of evidence pointing to subcutaneous “adipose saturation” as the tipping point, beyond which metabolic syndrome and (less frequently) T2DM can be “acquired” without significant reduction of total carbohydrate in the diet.
    One compelling indication, little recognized even by most basic researchers who have studied the adipose-related chronic disease states at molecular level, is the “bipolar” response of transcription factors regulating de novo lipogenesis (DNL) in liver and in adipose tissue. Once the tipping point is exceeded (i.e. carb intolerance) by the combination of diet and age (and also often menopause in women), hepatic DNL is upregulated and adipose DNL is downregulated. The latter response is probably an evolved, cell-protective adaptation to the overstress of continued excess fat-storage demand in the face of inadequate capacity of the adipocytes to replicate. The liver, on the other hand, is an extremely adaptable and capable organ — almost nothing does any permanent damage to it. NAFLD (except in extreme and rare cases) is transient and quickly eliminated with carb restriction.
    Back to Taubes and NuSI — it is my guess that a lot of the cause of impasse between NuSI and some of the experienced nutrition researchers derives from the NuSi overemphasis on insulin as being an explanation for almost everything in obesity-related specific-tissue degenerative conditions like T2DM. Some of these guys (whose research I have perused) are definitely aware of the above-described adipose role in MS and T2DM and CVD and other metabolic diet-induced chronic states.
    Insulin and carb’s are dominantly responsible for gain of adiposity in the healthy state — no question. But the evidence for a molecular basis for the degeneration of specific-tissue cells in common modern-diet chronic conditions is large. Taubes has a bias against these mechanisms which I do not fully understand the reasons for, and he has a bias for endocrinological mechanisms.
    Hormones participate, along with macronutrients themselves and other factors, in signaling cell-level stress conditions. Possibly more than anything else, mitochondrial signaling induces cellular stress responses. The signals drive transcription factors and other epigenetic long-term adaptation changes in cell metabolism. A common (to most or all modern metabolic maladies) mechanism is overstress upon the cells to produce energy by respiration, producing higher-than-normal ROS generation rates and inability of the cellular repair rates to keep pace with the ROS damage. The lack of significant time spent in the fully-fasted state with modern diet, wherein powerful repair mechanisms are initiated that are ALWAYS dormant in the fed state, is another anti-evolutionary environmental factor. The beta cells (of T2DM) are especially vulnerable to this problem, because it is the cellular energy-production cycle itself that regulates the insulin-secretion response to portal nutrients (AAs and glucose). For the glucose pathway, glucokinase is a rate-limiting early glycolytic step that is key to the regulatory response. Liver and endocrine-pancreatic cells (unlike other tissues) differentiate so that glucokinase is the dominant hexokinase — this gives these organs the ability to “sense” and respond to BG concentratation.
    However, for the same reason, as beta-cell researchers have long observed the islets lack most of the ROS repair mechanisms present in other cells because these would interfere with the basic sensitivty of the nutrient-driven energy-production hormone-manufacture-and-secretion loop in islet cells. A constantly excessive stimulus to the beta cells in particular, from modern diet, is a very plausible cause of T2DM. Damage to mitochondria and nucleus are implicated in the molecular research. Michael Brownlee seems to favor this theory for the cause of both T2DM and CVD (the latter due to similar cellular damage in endothelium as in beta cells with the former). So do I.

  39. In the context of “adipose saturation”, the calories-in/calories-out makes more sense for an individual who is at or beyond the tipping point (threshold of carb tolerance), I think. I wonder if Taubes might agree, however reluctantly.
    In the massive USA DPP study, and countless analogous studies in other major countries that followed, very moderate weight loss of ~7% in the diet-lifestyle cohort had much larger effect (reduction in diabetes risk markers and hyperglycemia) than in the metformin and control groups. This amount of weight loss in the overweight subjects would not have made them anything close to lean — just a bit less overweight or obese. Why the substantial result?
    Again, these people were likely at subcutaneous adipose saturation level, and most of the excess adiposity that they could expand was intra-abdominal (i.e. pot-belly, unhealthy, immune-response inducing). 7% was enough to greatly reduce the visceral fat or eliminate it. This reduces ectopic fat in various tissues, restores fatty-acid metabolism in those same tissues, reduces immune response involving macrophages and inflammatory cytokines and so forth, and restores a bit of excess buffering capacity in subcutaneous adipose tissue for fat storage fluctuations in responding to meals.
    These people should all ideally lean out completely by adequately restricting carb’s (rather than calories, as in the study of course) for the sake of their long-term health robustness (i.e. stability), rather than living on the razor’s edge where they can easily slip back into full-blown metabolic syndrome and pre-diabetes and then (clinically) overt diabetes. But the reason that the small adipose reduction was so effective is pretty clearly explained by the adipose-saturation model.
    Researchers such as Gerald Reaven, probably understanding much of this same model, have nevertheless been cowed into avoidance of endorsement of any kind of serious low-carb diet (even for a minority). Rather, they typically advocate very moderate weight loss by any means possible, and leave it at that. Clinicians, including GPs, typically do the same (if they are not explicit low-fat advocates).
    Excessive, abnormal hunger drives the eating of overweight people — no question. These are real physiological signals that are usually impossible to continuously overcome over the course of a year or more with a semi-starvation (low-calorie) diet. But insulin is more influential in getting to the stable overweight condition than it is in maintaining the excess adiposity and preventing weight loss by lesser food intake IMO. It is the severe degradation of fatty-acid metabolism induced by metabolic syndrome, in muscle and other large-mass tissues, that locks in the dependence upon constant carb feeding to maintain adequate blood-supplied glucose to these normally fat-burning tissues in addition to the normally glucose-burning brain. Not only is there much more need for glucose fuel overall, but also there is severely degraded buffering/storage capacity in adipose tissue, partially causing the blood-sugar instability of MS. The blood is a completely inadequate buffer, and various organs are endocrinologically driven into instability because the normal buffering stores of fuel (adipose tissues, liver, and even muscle via local glycogen) do not have normal function. Brain fuel crises are chronic and daily, triggering secondary responses (e.g. adrenal) because islet hormones cannot normally control the liver and whole-body fuel homeostasis. Steady and nimble (quickly adaptive) whole-body fuel supply REQUIRES normal buffering with adequate pools of energy-storing metabolites.

  40. Another allusion in Case Against Sugar is the idea that tissue glycogen buffers the carb’s in modern meals (in healthy individuals). And again, familiarity with the basic math makes this notion absurd IMO. Most body glycogen stores are in muscle tissue, but these are not part of buffer capacity because once stored this glycogen can only be burned by local cells, and cannot be returned to blood via glycogenolysis. Only the liver serves as a glycogen buffer, and its capacity in a man my size is ~100g.
    Most adults walk around every day in the fully-fed state — very few even get into the fully-fasted state once per year. In the fully-fasted state liver glycogen is reduced to 25% of that in the fed state, and the liver is fully converted to a glycogen-and-protein conserving mode. It does not burn glycogen to fuel its own processes, and instead burns fatty acids, throwing off huge amounts of ketones as fuel for the rest of the body (only the liver does this — muscle tissues do not). The remaining 25g of liver glycogen are fiercely defended, and cannot be significantly further reduced under any normal circumstances.
    In the modern diet 100g or more of carb’s is in an ordinary meal. There is just inadequate capacity in the liver to buffer any significant amount of this, especially since the liver is normally “topped up”, as are the muscle tissues. It is the adipose tissue that must be relied upon to deal with most of the carb’s of a modern meal, and these will be later “burned” as fatty acids by a healthy individual.
    I run 10 to 20 miles in the woods once per week, typically. At about the two-hour mark I have fully depleted all muscle and expendable liver glycogen. Normal (i.e. initial or start-of-run) power is lost (because no muscle glycogen, including heart glycogen, is left to ferment to lactate), and the steady, limited power left is fully aerobic. Breathing rate has gradually climbed to a maximum level for the same reason. When I finish the run and return home my blood glucose will be in the 50s or 60s (mg/dL — the same as it would be if I have fasted for 24 hours or more). If I have already been fasting for a day or more before a long run, my blood sugar will in the 30s or 40s typically. My ketones will be about 10mmol/L (insulin-producing diabetics have higher ketone production under all conditions, because of hyperglucagonemia — glucagon regulates and elevates hepatic ketone production at insulin levels which are normal for me in the fed state).
    If I am in the fully-fed state before the run, it will take about two days for my liver glycogen stores to be partially restored (I do eat a low-carb diet, but I eat some carb’s — dietary protein dominates my required insulin doses, though). Once liver glycogen has recovered to maybe 50% or 75% of normal fed-state capacity my fasting glucose levels will go back up by 30mg/dL or more. Since I measure BG once or twice per day as a diabetic, I have observed this transition many hundreds of times over the years. It is directly indicative of, and driven by, hepatic glycogen levels.
    I have read all of the hard research on liver metabolism and regulation that I could get my hands on, and find it very much consistent with my own personal case observations. There is just not much buffer capacity for dietary carb’s in modern man — the limited capacity in the liver is mainly for a guarantee of continuous fuel to the brain in the fed state, and storage in muscle is for “fight-or-flight” response primarily, when high-power (anaerobic) response is demanded.
    Stored glycogen, glycogenolysis and function in selected tissues are not a significant part of the evolved fuel-storage system in modern hominids — this purpose is almost exclusively fulfilled by adipose tissue. For a specialized carnivore with an oversized brain, evolved over the last 2 million years to select and kill and feed upon the largest and highest-fat animals in the environment, the role of the adipose organ should not be counterintuitive.
    Another well-known but little-recognized fact is that the typical half-life in blood of the chylomicron is ~ 5 minutes. It is many hours for VLDL in a healthy man. It is many days, and even weeks sometimes, in someone with metabolic syndrome.
    Chylomicrons deliver dietary fat to adipose (primarily) and other tissues. VLDL delivers dietary carb metabolized to fat in the liver to the same tissues. Is this not a clear indication that significant hepatic metabolism of carbohydrate is completely outside of evolutionary context?
    To me, it is surprising that some of us (mostly at young ages) have as much carb-metabolizing capacity as we do have. But I do believe this is all evolved since the dawn of agriculture by epigenetic change, which is one reason there is such a wide variation in carb tolerance amongst people with varying ancestry and modern/agricultural ancestral diets. Isolated peoples who have eaten whole-food diets, much less all animal-food diets, with very few generations of exposure to refined foods or plant foods respectively, develop T2DM and obesity at extremely young ages when the modern diet is adopted as Taubes has chronicled. The field of evolutionary biology has modeled and experimentally tested change in epigenetic status (in a single generation of organism) as one that reflects recent evolutionary environment in youth, and gradually walks back in evolutionary time with advancing age. To me, this helps explain all observed patterns associating diet and tissue-specific accelerated aging conditions in modern societies. Most of us by middle age reflect modern hominids of several hundreds of thousands of years ago — these animals ate dominantly large-prey diets, I think that Taubes would agree.

  41. Now having finished the recent Taubes book, I noticed that he complained in the beginning of the Epilogue of tautological reasoning. But his own use of the phrase “insulin resistance” is exactly this, I claim. He nevers defines it in the book. But being steeped in the literature of diabetes research, I do know where it comes from. IR as Taubes uses it really means metabolic syndrome (including its subclinic form, wherein fewer than three clinically testable traits are present). So writing “MS and IR”, as he constantly does, is redundant at best I claim.
    IR in this sense is a mere metaphor for a whole-body combination of “average” blood insulin and blood glucose that are both in excess of normal. This is really caused by the basal homeostasis rather than meal response.
    When one reads the research literature, the actual lab measurement methods are spec’d. DeFronzo and Reaven and all the other grand old men of diabetes research DO use the term IR, sometimes more loosely and often more precisely. But it really adds nothing to the discussion unless it is actually measured and isolated to individual organs. Whole-body IR can mean many different things and created many different ways, and it is in any case an analog value and not a digital condition — it is the inverse of IS (insulin sensitivity). It is impossible or at least arbitrary to define any particular maximum value of IR above which any individual can be considered in a pathological state. It is also possible to measure it many different ways in the same individual and the same time, arriving at much different values depending upon the laboratory measurement and “clamping” (e.g. insulin-clamping, glucose-clamping, etc.) conditions. Oral vs. IV delivery of glucose results in different outcomes, just to take one well-known example.
    Taubes is also very sloppy in the book, constantly referring to T2DM as simply “diabetes”. IR is NOT positively associated with either T1DM or most monogenic forms of diabetes. In fact, both of the latter categories predispose to markedly lower risk of metabolic syndrome than in the general population — this is well known. So the association is inverse for these two forms of diabetes. This is also true for obesity and these two forms of diabetes.
    Metabolic syndrome is significantly associated with T2DM, but also much more prevalent. The best research seems to indicate that at least half of the population of the USA is not susceptible to T2DM. This is primarily determined by beta-cell genes, research suggests — more of these T2DM-susceptibility genes have been ID’d for this one condition than for all other chronic maladies combined.
    It is also very well known that those who eventually acquire clinically overt T2DM do so roughly at the time when beta-cell funtion drops to 20% (this is measured in the research lab as the “disposition index”). This is also true of the other two categories of diabetes. When this threshold is crossed a key event occurs — there is total loss of insulin granulation, which is the stored form of insulin that is necessary for robust “acute GSIS”. So it is the response to a glucose bolus that really defines clinically overt diabetes in all its forms. This is also most important to causing the complications of diabetes (i.e. death of microvascular and neural tissues, renal damage, etc.).
    There are means in the research laboratory (if much less so using only clinical tools) to distinguish between individuals who only have metabolic syndrome but have no deterioration of beta-cell function. These individuals, who represent a large percentage of the adult population, will have nominally 100% beta-cell function but will have the mild “average” hyperglycemia and hyperinsulinemia of MS. As long as they maintain normal (or above-normal) beta-cell function they will NEVER develop complications of diabetes (the being true for MODY2 diabetics, who have normal insulin secretion but a BG “sensing” defect in glucokinase gene/function).
    Any study cohort that mixes potential pre-diabetics (who have measurably degraded beta-cell function) with pure MS will be fatally confounded. To my knowledge, no large study that has not done so has ever been performed, but the number of large studies that have done so is huge. Individual case studies, or ones on identical twins or very small cohorts with individualized data, have unfortunately fallen out of favor decades ago.
    So my suggestion to Gary Taubes and NuSI would be to design a small, practical (i.e. limited-cost) old-style study and to base its cohorts on individuals with MS but with 100% or greater (the latter being fairly common with MS and genetic non-susceptibilty to T2DM) beta-cell function.
    In this way, the problem of insulin-secretion deficiency in the beta cells can be separated from the phenomenon of MS — I claim that these two are independent, even though they often coexist (and chronic MS in genetically-susceptible individuals probably causes T2DM). My prediction would be that such experiments would yield results consistent with the hypothesis that MS is driven by subcutaneous adipose tissue saturation. I would predict the same even for rodent-model experiments, regardless of the means used to achieve the adipose saturation. And this can certainly be accomplished without any dietary fructose — one needs only to seriously look for such experiments in the literature that already exists. How’s that for application of Occam’s Razor, eh?

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