May 28, 2013

Nutritional biochemistry

Is sugar toxic?

Read Time 15 minutes

I remember one of my mentors in surgical residency made a very important distinction for me.  He said, “Peter, never forget what you are getting paid to do, and what you are doing for free.”  You see, there are some aspects of being a surgeon that are not particularly enjoyable.  The hours are long.  Sometimes you’re asked to intervene in a situation where there is no hope, and you feel you may only make things worse.  A lawsuit is just around the corner. But there are many aspects of surgery that are pure bliss.  Though I’m no longer a surgeon, some of my fondest memories in life stem from moments there.   Anastomosing a transplanted kidney into a patient (especially the renal vein anastomosis, which is the easiest to screw up).  Endartarectomizing a plaque-filled carotid artery.  Telling a patient and their family that you were able to remove the entire tumor in their colon, and that the lymph nodes were free of tumor.

What my mentor was saying to me was that those moments of pure bliss are not what we’re getting paid for.  In fact, we’d probably pay to do them!  What we’re getting paid for is the time we have to be away from our family.  The long hours, smelly call rooms, and bad hospital food.  The cost of medical malpractice insurance.

What does this have to do with the toxicity of sugar?  Well, nothing actually.  But I constantly remind myself of this when I feel my personal stress and anxiety mounting.  The past year has been a whirlwind of kinetic energy that makes my days in residency, 80 to 100 hours of work every week, seem tame and almost boring.  Most of what I do today is wonderful, but some is not.  I fly about 12,000 to 15,000 miles a month (in coach, no less) and spend about 8 to 10 nights a month in hotels.  Red-eyes are a regular part of my existence.  My day starts between 4:45 and 5:00 am and goes until 11 pm or later.  I can’t put in words how much I detest traveling and being away from my family.  So, I guess, that is exactly what I get paid to do.  (By the way, do not feel sorry for me.  I’m pretty sure all of this is self-imposed, but I still hate it.)

So, do you want to know what part of my role at NuSI gives me bliss that rivals the finest moments of surgery?  It’s exactly what I did a couple of weeks ago (and, fortunately, something I get to do often).  I spent a day with some of the best and most thoughtful scientists talking about their work and how we can make it better.

Can you imagine (assuming you’re as much a geek as I am) getting to pick the brains of the best scientists for hours on end?  Finding out why they are obsessed with the questions they ask? What keeps them up at night? What are the challenges they face?  What’s preventing them from resolving uncertainty?

I would pay to do this part of my job. This is the bliss described by Joseph Campbell.  And this meeting a few weeks ago was a great example of it.   This particular meeting focused on sugar research, specifically the metabolic impact of sucrose, high fructose corn syrup (HFCS), and fructose.  If you need a quick refresher on the distinctions, this should help. Spending so much time with this group got me thinking about a broader issue, which is actually the focus of this post:  Is sugar toxic?

What does ‘toxic’ mean?

Before we dive into the main focus of this post, we need to get crystal clear on our semantics.  Too much tomfoolery has already taken place for the simple reason that many people don’t understand the words they use.

For the purpose of rigor, let’s turn to the pharmacology literature for a clear understanding of toxicity.  Even though we all have an understanding of what “toxic” means, let’s be sure we’re understanding the nuance.  If you troll the medical textbooks you’ll eventually settle on a definition something like this (from Harrison’s Principles of Internal Medicine):

TOXICITY: The degree to which a substance can harm humans or animals. Acute toxicity involves harmful effects in an organism through a single or short-term exposure. Subchronic toxicity is the ability of a toxic substance to cause effects for more than one year but less than the lifetime of the exposed organism. Chronic toxicity is the ability of a substance or mixture of substances to cause harmful effects over an extended period, usually upon repeated or continuous exposure, sometimes lasting for the entire life of the exposed organism.

The first thing you may notice from this definition is that toxicity is actually subdivided into acute, subchronic, and chronic toxicity, based on how long it takes to progress from exposure to insult and the number of exposures necessary to cause insult.  This constitutes what I call:

Important point #1 – don’t confuse acute toxicity (what most people think of) with chronic toxicity.

Acute toxicity and the LD50

An example of acute toxicity is acetaminophen (abbreviated APAP, but commonly referred to by its trade name, Tylenol) overdose which, if significant enough, requires a liver transplant within days to prevent death from fulminant liver failure. (As an aside, this is particularly tragic because the liver, unlike the heart, lungs, and kidneys, can’t be supported extracorporeally; so if a person overdoses, and the liver is irreversibly damaged, they will need a liver transplant within days, or they will die.)

The question, of course, is what dose of APAP is toxic? (In this case, the toxicity is liver failure, which results in near-immediate death.)  Enter the LD50.  LD50 stands for “lethal dose required to kill 50% of the population.”  How is this quantified for a given substance, including APAP? Obviously, we don’t do randomized trials of increasing APAP doses in people until we definitively resolve this.  Instead, we (I’m using ‘we’ pretty liberally here – obviously I have never done this) do 3 things typically:

  1. Carry out the above experiment in animals to accurately estimate LD50 (in the animal);
  2. Mathematically model the best human data available and try to estimate LD50 (in humans);
  3. Compare the two estimates.

Not surprisingly, the answer to #1 is usually much higher than the answer to #2.  In the case of APAP, the LD50 in rats depends on age, but is probably somewhere between 800 and 1,500 mg/kg, suggesting a 75 kg human would expect toxicity (on average) between 60 and 110 gm (120 to 220 extra strength Tylenol tablets!).  Is this likely? Let’s go to step #2.  Below are data integrating known human toxicity with a mathematical model to estimate LD50, as a function of APAP dose (x-axis) and death versus survival over time (y-axis).  As you can see, this analysis suggests LD50 in humans is closer to 20 gm.  (These are data from humans who did not undergo liver transplant, except in the case of the yellow triangles.)

Acetaminophen Overdose Model

I’ve looked at several other models and they all appear to suggest about the same thing, The LD50 of APAP in humans is about 10 to 20 gm (10,000 to 20,000 mg or 20 to 40 Extra Strength Tylenol tablets), and most sources point to the lower end of that range.

So what’s my point of this?  My point is that there is a statistical distribution (see figure below) of the toxicity, which is why it’s called LD50 and not “LD” (which would imply everyone would experience toxicity from the same dose).  In other words (let’s simplify and ignore weight differences since this is in mg/kg and just assume I’m talking about a 75 kg human), some people will experience toxicity at 6 gm and others not until 16 gm. In the figure above, you can see one person lived, despite a dose of 40 gm (given that he received the antidote early enough) and another at 25 gm, without antidote.

Important point #2 – there is a spectrum of susceptibility to any toxin. 

LD50

What about chronic toxicity?

Sticking with APAP as our example, it turns out that much lower doses than the LD50, if taken day after day, are also toxic to the liver. How much lower?  As you’ll see below, the answer is highly dependent on the timing of these doses and other host factors.  In general, though, some authorities suggest repeated daily doses of more than 6 gm are toxic, while repeated doses below 4 gm daily are rarely toxic.  The point is that much smaller doses, if taken repeatedly, are still toxic.

Important point #3 – just because a dose does not result in acute toxicity does not mean it can’t or won’t cause chronic toxicity.

Complicating things a bit further…

There is no reason to expect physiology to be simple or binary, so adding one more layer of nuance to this already-longer-than-you-wanted-to-read-explanation is the following point. Factors such as alcohol consumption, underlying liver disease, viral infections, and genetic susceptibility are highly influential in both acute and chronic toxicity from APAP.  This shouldn’t be surprising, of course, though it complicates our discussion.  Since APAP taxes hepatocytes (liver cells), taking other drugs that do the same, consuming alcohol (uniquely metabolized by hepatocytes), or having underlying liver disease are invariably going to reduce hepatic reserve.  So, an individual’s ability to tolerate APAP is highly dependent on both measureable (e.g., cirrhosis) and idiosyncratic variations.

Important point #4 – host factors play a significant role in susceptibility to toxins.

Parting shot

I would be surprised if anyone reading this has not taken or used APAP (i.e., Tylenol or some generic equivalent).  In fact, most of us have experienced great relief from it.  That does not change any of the points above.

Important point #5 – the term “toxin” does not imply something is “bad” or universally harmful.

What does APAP have to do with sugar?

There must be some reason I’ve gone through all of this, right?  After all, the question of sugar’s toxicity is a somewhat polarizing one. On the one hand, folks like Dr. Rob Lustig have argued that fructose is harmful at the doses most people are consuming it today.  On the other hand, folks like Dr. James Rippe have argued the opposite.  Having read just about every paper and review article on this topic (I think) over the past year, I can say the debate has many facets, which I’ll outline briefly:

    1. The PRO sugar folks** argue that sugar, while void of any nutritional value, is no more or less harmful than a calorie of any other nature. In other words, it has no unique metabolically harmful consequence.
    2. Depending on affiliation, some of the PRO sugar folks debate back and forth about the advantages or disadvantages of sucrose (natural sugar from beets, cane, etc. composed of a linked glucose and fructose molecule) and HFCS (synthesized sugar composed of 55% fructose, 45% glucose mixture).   (There may be some merit to this discussion, though it would probably qualify as a “higher order” term. To a first or second order approximation, they are biochemically equivalent.) It appears this debate is a convenient way to avoid really confronting question/point #1.  The “natural sugar” producers can point at the corn growers, and vice versa, without really confronting the jugular question.  Both of these groups (sugar and corn) downplay research on pure fructose (which is pretty rare in nature and even our current environment), which is a valid point, though a distraction from the issue above.
    3. The ANTI sugar folks argue that sugar is indeed a “unique” macromolecule distinct from other carbohydrates.  Whether solely due to the fructose content, the combination of fructose and glucose, and/or the kinetics of the fructose (i.e., the speed with which the fructose requires hepatic attention when not accompanied by fiber) is a matter of debate and speculation, but those in this camp do agree that sugar is not “just” an empty calorie. The toxicity of sugar, they argue, is primarily related to its hepatic metabolism.  Specifically, “excess” (see below) ingestion of fructose increases VLDL production which increases apoB or LDL-P due to greater triglyceride load.  Additionally, at least at reasonable doses according to most literature, insulin resistance is worsened which amplifies the harm caused by other foods.
    4. Even among those who don’t subscribe to the idea that sugar is metabolically unique (and harmful), with or without a dose-effect, some argue that fructose consumption impacts subsequent food consumption in a way that glucose does not.  In other words, eating sugar may fail to satiate you and/or make you subsequently hungrier. These data are sometimes confounded, as are many data in this area, by the use of pure fructose, rather than the glucose-fructose mixture found in sugar.  Furthermore, evidence is emerging that sugar is addictive, much in the same way that a drug like heroin or cocaine might be, as suggested by functional MRI. So, while folks in this camp argue that sugar per se isn’t harmful, it does make you eat more (sugar and non-sugar, alike), and that is the harm.
    5. Perhaps the largest debate in this area stems from the dose issue.  The PRO sugar folks argue that at the doses most Americans consume sugar, there is no harm (even if there is a theoretical harm at very high doses).  The ANTI sugar folks argue that there is a dose-dependent (and probably a context-dependent – e.g., the insulin resistant person vs. the insulin sensitive person) deleterious impact of sugar, AND that current consumptive patients are indeed in this zone of toxicity. (This is probably the most comprehensive single review I’ve read on the entire topic, and I’ve discussed it point-by-point with 2 of the 3 authors.)
    6. Speaking of the dose issue, no area of this debate (in my opinion) has generated so much controversy.  How much sugar, defined as added sweetener (so this does not include the fructose found in fruit, for example) do Americans actually consume?  This is important, of course, if we want to know how applicable the above studies are to the question at hand.  Where to begin? (This topic alone is really a 3-part blog post.)  Estimating how much added sweeteners Americans consume is primarily done via two methods:
      1. Taking the difference between food availability data and waste data (ERS); or
      2. Using nutritional surveys (NHANES).

One of my colleagues, Clarke Read, looked into this recently.  Here is what he found (this was in response to a recent NY Times article suggesting sugar consumption is less than typically reported):

The adjustment to loss rates was done by RTI International in this report to the USDA Economic Research Service (ERS).  Section 4-1, which is an example calculation, is most useful.  RTI was asked to calculate estimates of loss, not estimates of consumption, and rather than working down from availability data, they in fact used NHANES 2003-2004 data to estimate consumption, then basically compared this to availability numbers (with a few adjustments) to find amounts of loss.  These loss percentages calculated from 2003-2004 then became the standard, and all other consumption data was calculated by applying this % loss to the availability data.

This means that all consumption numbers are effectively derived from NHANES data.  This is especially relevant for added sugars.  Since NHANES data tracks only consumption of foods, not ingredients, this availability-versus-consumption comparison initially leads to a 96% loss of cane and beet sugar (seen on page 95 of the 2011 USDA document — the “4 percent” referred to in the NY Times article), since NHANES data only reflects sugar added to foods directly, rather than used as an ingredient.  The judgment of a panel of experts was then used to determine the percentage of available sugar used as an ingredient, which led to their 34% loss estimate for sugars.  For HFCS, which is never consumed as a food and always as an ingredient, they simply gave it the same value as honey (15% loss between availability and consumption).  The ERS, however, overruled them (as described in the NY Times article — see the end of the Losses at Consumer Level section in the link for ERS evidence) and used the 34% loss estimate instead.

Page 10 of the 2011 USDA document shows who these 6 experts are.  The NY Times article asked 2 of these 6 about these sugar estimates, who don’t recall making them, though it’s implied that they simply don’t remember what happened back in 2008. In other words, while the overall trend in sugar data is determined by availability data (since % loss is assumed to be constant over time), the absolute amount consumed on any given year, as estimated by these loss-adjusted numbers, is entirely dependent on this RTI loss estimate which, for added sugars, is almost entirely dependent on an expert’s estimation.  All foods that are primarily consumed as foods rather than as ingredients have consumption levels that are based on an extrapolation of 2003-2004 NHANES data.

Translation: this is a complete cluster.  If you triangulate between the ERS and NHANES data, you wind up with an estimate of about 90 pounds of added sweetener per person, per year, or about 110 gm per day which, on average, works out to about 15% of total caloric intake.  Of course the actual consumption is much more nuanced (what isn’t?), since consumption varies a lot by age, gender, and socioeconomic status.  Furthermore, this estimate doesn’t include the fructose in fruit juice or fruit, though the latter probably isn’t nearly as high, or relevant, as the former.

Another very interesting point uncovered by colleague, Clarke, was that in a 2009 paper in The Journal of Nutrition, Dr. James Rippe (one of the leading proponents of sugar) noted the following:

“…fructose, as a component of the vast majority of caloric sweeteners, is seen to be particularly insidious.”

“It has also been shown to increase uric acid levels, which in turn promotes many of the abnormalities seen in the metabolic syndrome including hypertriglyceridemia.”

“There is considerable evidence of a detrimental effect on metabolic health of excess fructose consumption.”

Whether by accidental omission or otherwise, this paper is not listed on Dr. Rippe’s CV on his website.

**Sadly, it’s difficult to really interpret the data objectively from those in the PRO sugar camp because of the conflicts of interest.  Most of the PRO sugar scientists are heavily funded by the sugar industry.  For those interested in the historical context on science and the sugar industry, you’ll find this article particularly interesting.

Take home messages

What I find frustrating about this debate is that most people yelling and screaming don’t fully define the terms, perhaps because they don’t appreciate them (forgivable) or because they are trying to mislead others (unforgiveable).  The wrong question is being asked.  “Is sugar toxic?” is a silly question.  Why?  Because it lacks context.  Is water toxic? Is oxygen toxic? These are equally silly questions, I hope you’ll appreciate.  Both oxygen and water are essential for life (sugar, by the way, is not).  But both oxygen and water are toxic – yes, lethal – at high enough doses.

What did the APAP example teach us?  For starters, don’t confuse acute toxicity with chronic toxicity.  Let’s posit that no one has died from acute toxicity due to massive sugar ingestion.  But, what about chronic toxicity?  Can eating a lot of sugar, over a long enough period of time, kill you (presumably, through a metabolic disease like diabetes, Alzheimer’s disease, cancer, or heart disease)?

Even among a healthy population (i.e., people without overt liver disease), toxicity is a distribution function.  What’s toxic to one person may not be toxic to the next.  This is true of APAP and it’s true of sugar.  It’s true of most things I can think of, actually, including tobacco, alcohol, cocaine, and heroin. Ever wonder why “only” about one in six smokers dies of small cell lung cancer? Maybe it’s the same reason some people (e.g., me) get metabolically deranged from even modest doses of sugar, while others (e.g., Jill, my wife) can mainline the stuff and not appear to suffer many adverse effects.

I posit that Jill and I are both outliers on the distribution of susceptibility, probably driven mostly by genetic difference (rather than, say, exercise as we both exercise a lot).   So, I offer you a framework to consider this question.  I know some of you just want an answer to the question, Is sugar toxic or not? But I hope this slightly more nuanced response can help you figure out what you should be asking: Are you like me? Like Jill? Or like an Average Joe somewhere in between us?

This is what you will need to figure out on your own.  You could play it safe, assume you’re like me and eliminate all sugar from your diet (I eat no more than about 5 gm of sugar per day, almost exclusively in 85%+ dark chocolate – so less than 4 pounds per year).  But if you have Jill’s genes, maybe this is overkill.  (Though, I would argue, and may do so in a later post, that even Jill has noticed a change in her energy levels and a number of biomarkers by reducing her sugar content somewhat over the past 3 years.)

Sugar toxicity

It’s pretty easy (conceptually) to figure out where you are on this spectrum, but it does involve a few deliberate steps:

  1. Without making any adjustment in your current eating habits (i.e., fight like hell to avoid the Hawthorne effect), record everything you eat for a week and, using a database like this one (or something fancier like Nutritionist Pro), calculate exactly how much sugar you consume.
  2. Collect blood work (paying special attention to lipoproteins, triglycerides, glucose, and insulin among other things) and other measurements (e.g., DEXA if you want to assess body composition, waist measurement).
  3. Get intimately familiar with all the places sugar shows up that may seem counter-intuitive (e.g., “healthy” cereals, sauces, salad dressings, bread).  To do this experiment, you need not restrict your complex carbohydrate intake, but you’ll have to substitute products without added sugar.  For example, before I was in ketosis but beginning to discover my own susceptibility to sugar, I had to make my own spaghetti sauce from scratch rather than pour it out of jar.  I had to make steel cut oatmeal rather than eat Quaker oats.  I had to buy bread made with zero sugar (at $7 a loaf!) rather than my usual “whole wheat” bread.  You get the idea.  It takes time, and you should expect to spend a few extra dollars on food. But, it’s actually possible to find foods that contain minimal to zero added sugar.
  4. With this information in hand, begin the intervention: aim for a reduction of at least 50% from step #1. (In my first experiment I did 6 days per week of zero sugar, and one day of all I wanted.  Ultimately, this became too difficult, and it actually became easier to just go zero every single day.)
  5. Repeat the measurements (i.e., step #2) after about three months.  If you’ve seen minimal effect, assuming you were methodical and consistent, you’re probably in the Jill camp.  If you’ve lost fat, seen a reduction in your triglycerides, fasting glucose and insulin levels, increased your HDL-C, and decreased your apoB or LDL-P (assuming you were able to measure them), you’re probably in the Peter camp.

Last point I’ll make, as I suspect at least some of you are wondering.  How do two genetic outliers treat their genetic hybrid (i.e., our daughter)? I’ve written about this previously.  In short, we limit the sugar she eats in our house, but not so much outside of the house (e.g., birthday parties).  I estimate she eats about 25% of the sugar a “normal” kid does.  There is no doubt she loves it, and even a week ago when we went on a daddy-daughter date, I got her ice cream with sprinkles for dessert (the irony of me carrying a bowl of sprinkle- and Oreo-covered ice cream through a crowded restaurant was not lost on me).

What does amaze me is how it seems to override her senses.  That night, she had a big plate of salad, a bowl of soup, and even a large slice of pizza (if you’re wondering, I had 3 large plates of salad with chicken). She claimed to be absolutely full, and I believed it.  But when I brought that ice cream out, it was like she had never seen food in her life.  She simply devoured it.  The best part?  When she looked like she was done, I said, “OK sweetie, looks like you’re done, time to get going…” only to have her say, “No daddy!  I’m still finishing the chocolate broth!”  She literally left not one drop of melted ice cream (“chocolate broth”) or one single sprinkle or one single crumb of Oreo behind.

This does not seem “normal” to me, and for this reason I guess I refuse to accept, personally, that sugar is just a benign empty calorie.  But, one day our daughter will have to decide for herself where she lies on the distribution and how much she cares to do anything about it. Until then, we’ll save the chocolate broth for special (and not too common) treats.

Sarah's wedding

So, in response to the question, “Is sugar toxic?” it seems to me the answer is, “yes, sugar is probably chronically toxic to many people.”  And so is water. And so is oxygen.  My sincere hope, however, is that you now understand that this is probably the wrong question to be asking.  The better question is probably “What dose of sugar can I (or my child) safely tolerate to avoid chronic toxicity?”  The goal should be to figure out your toxic dose, then stay well below it.  (It’s probably not wise to consume 95% of the toxic dose of APAP just because you have a really bad headache.) What makes this important, of course, is that with water and oxygen, the toxic doses are so far out of the range of what we normally consume, it’s not really necessary to expend much mental energy worrying about the toxicity.  But with sugar, at least for many of us, the toxic dose is easy to consume, especially in world where sugar resides in almost everything we eat.

Photo by Joanna Kosinska on Unsplash

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323 Comments

  1. I’m new to your blog/web page but came across this post first. Regarding your daughter eating ice cream after being full. It seems pretty normal to me as far as what is typical with kids, even adults. Wouldn’t it have something to do with sensory specific satiety? Perhaps I’m understanding this term incorrectly, but it’s like eating at a potluck or a buffet. Because there are SO MANY enticing foods, it is easy to overeat because you’re not just eating ONE thing. I am not part of the low carb lifestyle. My family prefers oatmeal every single day. We add nuts and dried fruit to it, various milk options. But I get bored of it and can’t eat enough of just that to have it stick with me for more than a couple of hours. However, give me some savory foods and fruit and protein-rich items and I’m bound to eat more total calories because of the variety.
    The other thing that was brought to mind is a study I remember glancing at that showed that until children’s leg bones are done growing (or was it growth plates?) they have a huge tolerance and preference for sweet.
    When we serve dessert at our house, I tend to serve child-size portions WITH dinner, rather than at the end. The goal is to keep kids from learning that dessert is eaten on a full stomach. They often eat their dessert first and fill up til they are full from the rest of the offerings on the table. But then again, I sometimes let them eat as much as they want of a sweet (cookies for instance) during a snack time. I just make it a rule that they have to stay seated at the table. This way they feel like they have some control over portion and don’t feel unnecessarily deprived. But I don’t serve sweets frequently (more than you, probably).

  2. Like some of your other readers, Peter, I arrived here through your TedTalk:
    http://www.tedmed.com/speakers/show?id=18028

    I just wanted to tell you I really appreciate the way that you are going about your research: no “gut-feels”, no “knee-jerk-reactions”, and questioning each assumption and before researching your own conclusion. You are taking the long, hard route toward the answers we are looking for, but it’s far more trust-instilling than diet books and nutritionists who build their business on emotional responses and unproven, unfounded research.

    I come from a family of overweight sugar-holics, multiple stomach bypass surgeries (which ultimately did not solve the weight problem for ANY of the 6 of them), Type-2 diabetes, and lots of dietary assumptions. The end result for me is that I’ve decided I did not want to mess with any of it, so I’ve been eating whatever I wanted to including loads of sugar for the last ten years, and am now about 50lbs overweight.

    I look forward to hearing the conclusions you come to as a result of your research, and maybe losing some of the weight I’ve gained.

  3. Hi Peter

    I really enjoyed your video on TED. It’s something i have been mulling over for a while now. When we talk about cellular dysfunction we can see so many issues occuring. What are your thoughts on thyroid function and the implication on all of the problems that you are seeing and how simple sugar may enhance cellular function particularly when hypothyroidism is present. Sugar may also be the current target of nutritional hate but I found that this article provides an interesting balance to the arguement.

    Would be great to hear your thoughts. keep up the good work.

    Keith

  4. Finally!!! A critical look at the complex questions we should be asking about…well, everything! I’m so excited about discovering your blog and TED talk that I hardly know where to start…!
    First, I have often wondered why I can also “mainline” ‘sugar’ without gaining weight or becoming diabetic. I am concerned about my use/ “addiction” however, especially since having breast cancer in 2007 (NED now) and hearing about how ‘sugar’ “feeds” cancer. (Even the terms sugar, addiction, cancer-food need to be defined further, which brings me to my next point).
    Secondly, I love that terminology and hegemonic assumptions are being critically challenged and discussed, in both scientific and vernacular ways. When I wrote my MSW thesis about eating disorders in 1997, I almost drove myself crazy examining every possible assumption… language itself is so loaded! And the questions we ask, or don’t ask, also need to be carefully examined for biases.
    Thirdly, as a former nurse (NICU) I am delighted to see you addressing the diversity among patients with such compassion and curiosity. Why DO some people become obese, insulin resistant, diabetic, while others just don’t? Why do some smokers get lung cancer, while others don’t? Why do some people gain weight by eating relatively healthy foods, while others can ‘get away with’ eating a poor diet? What role, and how much of a role, does genetics play in all of this?
    There are so many more questions than answers! Keeping an open mind, questioning our assumptions, paying attention to nuances and discrepancies can open the door to so much more insight than trying to prove a vested interest or favoured theory. Thank you!
    Keep up the good work!

  5. Hi Peter,

    I also arrived here through your TED video and I’m glad that you are researching this topic, I believe it could have a large on our society, no pun intended. I also have encountered some questions that I think you would have the insight for. I agree with your stance and I would also hypothesize that one of the sugar side-effects could be “a” cause of bad dental development/health, and could be an indicator for people who don’t seem affected, like the Jill Camp.

    I have done some research regarding Nutrition and centered a diet plan around macronutrients (protein, fats, carbs), while striving to avoid unnecessary simple carbs (sugars) and “bad” fats. The only time I used sugar, more specifically Dextrose and MaltoDextrin (about 40-50 grams total), was after intense weightlifting. The reason I supplemented Dextrose and MaltoDextrin was to boost the metabolization of protein, improving the speed of delivery to muscles and jump starting the recovery phase. By using this simple sugar supplement, it would cause the body to react by increasing insulin levels which does two things: first it helps deliver the protein to the muscles by increasing uptake caused by the elevated insulin levels and secondly, mitigates the effects of cortisol, which is released during weight-training, further breaking down muscles and inhibiting the rebuilding phase. I have seen great results and no bad effects, although I am concerned about a few things.

    So here are my questions: Would/Could using Dextrose/Maltodextrin to boost Insulin levels be detrimental to overall health in the mid/long run? For example, causing an individual to be more insulin resistant? or despite the boost in muscle growth, could the sugar be causing harm to dental health via the bloodstream? is there “a time and place” for sugar in a peter’s camp individuals’ diet?

    Another concern of mine is consuming HFCS and other processed carbs, and I am disappointed because it is economically difficult for many to avoid HFCS or sugar substitues, perhaps there is an underlying effect that exacerbates the effects related to sugar consumption? I have read that particular sugar forms are metabolized in different ways physiologically and have different effects. Should I be concerned despite the claims stating that sugar is “chemically the same structure” etc.?

    I really appreciate your experiences and research, I hope that your findings are able to find their way into our culture for the health of many who suffer from dietary diseases.

    • Zack, I’ve never seen compelling evidence that sucrose and HFCS are biologically different, though I guess it’s possible in some settings. So if you’re worried about sucrose, be worried about HFCS, and vice versa. If not you’re not, nothing to worry about, enjoy the cheaper version (HFCS).

    • I would favor plain sugar (sucrose) and cane sugar over HFCS, since the latter can be contaminated during production and processing, such as when it was found that about half of all tested samples of HFCS in 2009 were contaminated with mercury.

      Besides, and I’m not sure how this is possible, but drinks sweetened with HFCS have a hint of “corn” in their flavor compared to drinks sweetened with white sugar. Not sure why, but I can definitely taste the difference. I remember sweet iced teas and sodas in the Middle East surprised me with their superior flavor; a more “sugary” taste if you will. It was hard for me to ignore the subtle corn flavor in U.S. sweet teas and sodas, especially with brands such as Arizona.

  6. Peter.

    Not sure how you’re able to do so much research and write many serious, thorough articles, but it’s welcomed and refreshing!

    You probably wrote the best series on cholesterol (The Straight Dope on Cholesterol) that I, or anyone, has ever come across.

    Again, thank you for all the work you do and information you share. It’s not in vain, that’s for sure! Just wanted to let you know.

  7. Peter – great blog and your TED talk was amazing. Beyond amazing. Should be required watching for everyone in the medical profession . . . including patients.

    Question (relating somewhat to this post): how would you handle a teacher (grade 2) who rewards all her students’ successes with candy. Or – how deal with a school that allows such an insane practice?

    Thanks – again – for all you do and for that brilliant talk.

    • Marcia, that’s a tough question and I guess at some point I’ll have to address it head on when it’s my child in that situation. I guess, and I may be overly naive here, I’d ask the teacher why he/she thinks candy is a great “reward” for a student?

    • Spoonfed blog has some resources on talking to teachers about food in the classroom: http://spoonfedblog.net/wp-content/uploads/2012/Spoonfed%20School%20and%20Junk%20Food%20Handout.pdf

      The link is not the one I was looking for but you could do a search on the blog. Also The Lunch Tray blog. One of those has another nice handout about food in schools. Ultimately if you can help your teacher see that food rewards (of any kind) are inappropriate at school that might help. Seems like most organizations that deal with children’s health state quite clearly that food rewards should not be given to children. Maybe print out some things like that.

    • As someone who has worked in school setting for many years, I would recommend following the excellent suggestion to find some credible written material about how inappropriate it is to use food for rewards and give it to the principal. I would ask the principal to bring this to the attention of the teachers but not say that a parent (or which parent) initiated it. This way your child is less likely to be identified by the teacher or other students as the person who made the candy go away.

  8. Hi Peter,

    I don’t know if this is the right place to share this (and you may well already be familiar with this); my husband and I have been discussion much of what you have written -with great interest!- and have been bouncing questions back and forth about the American/Western phenomena involved in context with the global (my husband is not American, so these types of discussion are the norm around our house). Anyway, a quick Google search pulled this up, and I thought to share it with you –on the off-chance you may not have already seen it. http://www.noorderlicht.com/en/projects/the-sweet-and-sour-story-of-sugar/ — in reading more about this project, the question of “toxicity” can (and does!) go beyond American consumption…WELL beyond it.

    Thank you SO much for all that you are doing. 🙂

    Cheers,
    Denise

  9. Peter – Thanks for the interesting article. Interesting that you begin with using APAP as the basis for your discussion. And I guess my question goes to both APAP and sugar. Is there a point of chronic toxicity that you will not end up with a chronic medical condition that can not be reparable. My concern is more on the lines of APAP. I had an anterior/posterior spine reconstruction with about 10 levels of fusion. After 2 weeks in the hospital I went home on Vicodin 10mg with 375mg APAP. For the first month I was taking 2 tablets every 4 hours. And then tapered to close to none after another 2 months. Lot of both, huh. I think I fell just under the LD50 for APAP for an extended time. Question is – after that amount is the liver able to repair itself? I know that Tylenol is in almost everything like sugar is, and I avoid lots of OTC meds like the plague. Just finished the Clean diet by Dr. Alejandro Junger hoping the detox would help. Incidentally I lost about 30 lbs. in that three weeks, and am going to continue with the diet, only adding a few more calories as it is very restrictive. Tim

    • Fortunately, Tim, the liver is one the few organs in the body that is completely able to regenerate after injury, provided the injury does not scar the hepatocytes or liver architecture. You doctors can definitely do a quick blood test to determine the health of your liver.

  10. Hi Peter.
    I came here after seeing your talk on TEDMED. My question is about sugar replacements. My theory is that while our bodies are built to deal with sugar to some extent (though not refined sugar, I concede). Is it plausible that the modern rise in obesity/insulin disorder could be in relation to the exponentially increased use of sugar replacement chemicals? What I mean to ask is, do you think that one cause of this damage to insulin receptors etc could be the unnatural/manufactured additive we have in todays diet?
    Anecdotally I notice a high number of people who have problems with health turn to sugar replacements, diet options, and “fat free” foods, and I wonder what the correlation/causation relation might actually be?
    I have often worried that, because we all “know” that sugars and fats are bad for us, and that the majority of the research we have focuses on those items, we overlook the damage that may be caused by the things that we replace them with. The packet says “80% less sugar!”, and that’s what sells. Nobody really notices the rest, or if they do, they place a smaller importance on it due to the public conception of sugars and fats…

    I was just curious to your thoughts and if you’ve come across similar theories in your research?

    Thanks!

  11. I listened to your TEDMED talk today and was greatly affected. Thank you so much for your compassion and understanding. I am a 67 year-old woman in excellent health, but 11 years ago I was headed in the wrong direction, weighing 262 lbs. and completely out of control with my eating. I have no idea what my glucose reading was at that time since I didn’t have the courage to see a doctor until many months later, after I had made major changes to my diet and lost a considerable amount of weight. I joined Overeaters Anonymous in August 2002, something I recommend with all my heart to anyone who is having difficulties with food. Since October of 2002 have not eaten anything containing sugar in any of its forms as an additive. Ditto for flour (the word can’t appear on an ingredient label). Today I weigh 137 lbs. on a 5’6″ frame. At a medical screening this morning my fasting glucose level was 77. The miracle for me is that since eliminating these foods from my diet I have not had a single compulsion to binge or even to overeat. I know this is a mere anecdote, but I believe my experience supports your theory, especially the part about hoping to make it possible for people to do the right thing. First we need to know what the right thing is, since I fear that many of us are getting bad advice from the nutrition experts. I am very familiar with the heartbreak and degradation which come as the result of obesity, and the contempt which many of us have experienced from members of the medical profession. My very best wishes for success in the work you are doing; I’d like to think we will see some results in my lifetime! Maybe you are too late to make amends to that woman in the ER, but I accept them gratefully on her behalf. You and she are both in my prayers today.

  12. Sugars, both glucose and fructose, are toxic. Their exposed oxygen atoms will react with protein if given the chance. It is our ability to convert sugar to glycogen or fat that keeps it from harming us. Sugar is not a natural nutrient, humans have to adapt to it. Two million years of evolution has given humans a fat based diet. So when glucose from grains became readily available ten thousand years ago, the human digestive system began to adapt to the increased glucose load. Ten thousand years is short in evolutionary terms but not insignificant. It should not be surprising that some people can thrive on a whole grain diet, but those people probably could also thrive on a fat based diet. But people who thrive on fat based diets, may not thrive on whole grain diets. We only had 40 years to adapt to fructose from a sugar based diet, so it is surprising, but not impossible, to find individuals who can thrive on sugar.

    Possibly an interesting experiment for NuSI would be to take advocates from the China Study and the Paleo schools and have them switch diets. It might even be funded by a television network looking for a new reality show.

    If both groups thrive, then Lustig was right; it is the sugar. If both groups get sick, then diet is genetically based. If one group thrives but not the other, then we can finally recommend a diet that is good for everybody.

  13. Hi Peter,
    I quit eating sugar ages ago after reading Dr Perricone say (in not these exact words) sugar makes you look OLD. I didn’t need any research, that did it for me…;) although I did finish his book and his research is compelling. I am wondering, is Stevia ok? Not the ones mixed with maltodextrin or anything like that but a high quality stevia with no additives. Does this count as “sugar” even thought it has no calories and is a plant? Green tea is a little strong without it! ;)….plus he recommends cinnamon to keep insulin levels in check, what is your opinion on that? As well as alpha lipoic acid to increase glutathione…I’d love to hear your take on these things.

    • I don’t really know, Dorothy, but I would guess stevia is less metabolically taxing than sucrose, if for no other reason that one consumes lower “doses” to get the same sweetness “effect.” Probably a similar argument for the typical non-nutritive sweeteners. This, of course, says nothing about the impact they may play on your brain.

  14. Great article – I just watched your TEDMED talk and was very impressed by your approach of questioning convention. In this same vein, what are your thoughts, or have you done any research into the role that synthetic chemicals play in the onset of insulin resistance. There are a number of chemicals (now classified as “obesogens”) which are linked to metabolic disease through various pathways (hormone disruption, suppression of leptin, altering production & development of fat cells, and even triggering insulin resistance).

    Many of the chemicals in our personal environment, from pesticides on our food, to chemicals in our cleaning products, household items, are “obesogens” and follow a totally different dose response curve than is found in traditional toxicological research. Obesogens are all endocrine disrupting chemicals, and are/can be bioactive at extraordinarily low levels in the body, resulting in a “non-monotonic dose response curve” rather than the monotonic one you’ve shown above… meaning very low levels of these chemicals, WELL below the LD50 tests, can me more toxic than larger exposures.

    I’m fascinated by the intersection of synthetic chemicals (and some natural ones) that are able to interfere with our bodies hormonal system, many pre-natally, that can result in insulin resistance leading to obesity, or other metabolic diseases, and the obesity epidemic.

    Would love to hear your thoughts on this side of the research!

    Thanks for all your work and helping to shift the conversation away from blame!

    • Lara, Unfortunately, I don’t have enough expertise on this topic to offer anything beyond a trite response. Hopefully there are folks doing the type of research on these chemicals that will be done on the food side in the coming decade.

  15. Hi Peter, thanks for the amazing work you are doing. I wonder if you could address why you supplement with magnesium and potassium. I have experienced cramping more often on a highly carb restricted diet but have never seen those supplements recommended. By what mechanism do you think the low carb diet depletes Potassium? Again, the website is incredible and I can’t wait to see what NUSI has in store for us.

  16. Thanks for this post. I stumbled across your TED talk tonight, which led me here. As a health/nutrition coach I am often posed the question about the impact of sugar on the body. It’s interesting, because so many people just want a yes/no answer. They don’t like the “it depends on your body” answer, whether it is about sugar or anything else health wise. Thanks again.!

  17. Dear Peter,
    thanks for your great blog and all the great job you are doing, i form part of the Spanish PCOS community a 6% of the women have this Syndrome which is believed to be generated by the insuline resistence, it is quite difficult to cope with it due to weight gain, androgin obesity, hirsustism and infertility, acanthosis nigricans, as you can see a whole miriad of symptons..We are carboaddicted but it seems doctors (at least in Spain) does not want to give us a low glycemic diet but the classic 1200 calories one which makes no effects on us, we only loose around 6 to 8 kilos at the beginning but then our bodies seem to stuck on this and despite our efforts no more weight loss, therefore we quit as we see no results. You are talking about kethosis, are you doing Dunkan diet? here is forbidden, endocrins say if the prescribe this type of diet they will be rejected from the Endocrine Association..
    In my oppinion a Dunkan diet is a bit strong for our bodies, we promote to avoid simple refine sugars and flours, eat more vegs and fiber which slows the glucose metabolism in our body, eat complex carbohidrates instead such as wholegrain bread and pasta (moderate) and what is more important to exercise.
    In the old times in my country people had no car or other vehicles and walk from their town to other towns, they ate heavy casseroles with legumes such as beans, cheackpeas, mixed with meat and they were lean and healthy. Nowaday with the stress of our daily lives we have no time to walk and also the stress is a key factor to eat, the more anxious we feel the more we eat , if you are a sugaradict the situation gets worse as you eat sugar to feel energetic but 3 hours later you feel down and tired and have to eat sugary things again to have energy.. it is a yo-yo situation¡¡
    i hope that one day you can find a good and healty dietary programme and we can have the great luck to try it¡¡
    many thanks for your great job¡¡

  18. Hi Peter,
    I came across your TED Talk and then this article. You mention eating chicken. What are your thoughts on the work of John and Ocean Robbins, Kathy Freston, Dr. T. Colin Campbell, Dr. Joel Furhmanm the documentary “Earthlings” regarding the many benefits of a plant-strong (vegan) diet – for weight-loss, disease-prevention and sustainability of our planet? Thanks in advance for any response. Warmly, Susanne Biro.

    • Susanne, sorry to ask this of you, but can you look through some of the comments in the blog (various posts), as I’ve addressed this several times. Too long to type out each out time. Sorry.

  19. I have often times wondered why we consider sugar a condiment and not a drug. Sugar is derived from the plant source as is heroin and cocaine and the end result is a white, crystalline substance. In the book, “Sugar Blues”, it was stated that sugar in the 17th and 18th centuries was taken through the nose; consider also that sugar has been used to cut more dangerous drugs. Yet, we pack the substance into processed foods and feed it to our babies. Could there be a correlation between sugar consumption and disease? I am pleased that you are looking in to the problem, Dr. Attia, and I leave it to you to find the answer.

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