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. 


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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  1. I might be in a good position to contribute to this discussion. I stopped eating added sugar on March 01, 2010. Not for medical reason, just to gain control over my life. So I became my own experiment. I only went low carbs on November 01, 2011, so spent 20 months with only sugar reduction. In the fall of 2011, I realized I was no longer getting sick. A cold would be half a day of very slight sore throat, and a flu would be aches and slight chill for two days. I have 3 young children, so in the winter one of those hits the house every 3 weeks. My wife would still feel the full impacts of those infections. My only sources of sugar were vegetables, fruits and dairy products. I would still drink an occasional diet soft drink or chew sugar free gum.

    On a side note, researching the reason for this effect, is how I discovered Gary Taubes in October 2011. 130 lbs lighter by the summer of 2012 and running triathlons.

    In the last few months, around the 3 years mark, a very strong transformation has happened. This from someone who was obviously highly resistant to insulin, although not yet diabetic. Someone who love sweet to the point of skipping a meal to get to desert faster.

    – I no longer have any craving for sweet food.
    – I can no longer drink diet sodas or chew sugar free gum – too sweet.
    – I can no longer eat fruits – also too sweet.
    – The smell of something sweet cooking, actually makes me slightly nauseous.
    – My immune system is still much stronger than it used to be (Did not see any more changes after I went Low carbs).

    I eat a lot of vegetables, and no problems with those, although I really taste the sugar in onions and sweet peppers. I always loved fruits, but am quite happy to let them go, if it means no more addiction or craving.

    Is sugar toxic? If my immune system received a major boost to fight viruses and bacteria, what chance would it have had to fight something like cancer.

    So in my case, yes, sugar is very toxic.

    • David, see EA FB page. I posted 2 links to very good assessments of these papers, one by Chris Kresser, the other by Chris Masterjohn. NY Times, unfortunately, not so thoughtful on this topic.

  2. Much of what I have read on this subject is confusing and contradictory. This article is one of the few I have read that is frank and well-reasoned. It troubles me when science is hijacked for whatever reason and it appears to me that the sugar industry has corrupted the field. In any event, I doubt the average person can sort through the debate on sugar even if they have the time to learn the biochemistry.

    I prefer any argument that can be put to the test and that is what you suggest. Use your body as a laboratory and find out if ingesting sugar/carbs makes any difference. It sure did in my case.

    Thanks for a beautiful piece. I look forward to the rest of it.

    • Read, I’m glad this was helpful. Though I didn’t go into it in this post, there are a lot of experiments out there that need doing which can shed much more light on this topic and resolve much of the ambiguity.

  3. Thanks for another wonderful post, Peter. Just some anecdotal (n=1) observations. Like your wife, I don’t seem to be especially carb-sensitive. I used to always have a sweet tooth. Then, about 15 years ago, at age 33, I put on about 12 pounds in about three months. At first I panicked–clothes didn’t fit; for the first time ever I wasn’t “Hollywood thin,” etc. But then I realized that I felt better overall. Whereas before I would get headaches that lasted for days, those had disappeared, my mood swings disappeared, and my sweet tooth was greatly reduced. (I was eating more food of all kinds in general, not more sweets.) Bottom line: before, I literally wasn’t eating enough to support my metabolism. I felt better at 145 pounds than at 132 pounds. I came to believe that, for some people, thinner doesn’t necessarily equal better health. Also, my sweet tooth has proven to be about habituation. Before I got involved with my now husband, I was a fairly accomplished baker. But he’s a lifelong diabetic (type-1, diagnosed at age four). He didn’t care about my skills as a pastry chef. I stopped keeping sweets around, and, over time, my sweet tooth kind of faded. Now most times, I’d rather have a few extra bites of dinner than “save room” for dessert. Don’t get me wrong: if sweets are around I will probably indulge–one of my favorite things about Thanksgiving weekend is pie for breakfast on Friday morning. But I don’t feel compelled to seek sweets out or to buy them when I’m shopping, etc. Plus, when I eat something sweet for breakfast, I don’t feel great for the rest of the day, so I only do so very rarely, and I’ve learned to throw away “special-occasion” sweets after a couple of days. It has taken time (like everything, right?). But, in my case, the sweet tooth faded once it wasn’t being indulged.

  4. Thank you for another great post. I get so tired of the masses of uneducated and unqualified who espouse the use of a certain supplement to rid the body of “toxins” or who are antagonistic towards certain foods because they are “toxic” to the body. Undoubtedly some of these claims are true, but even a blind squirrel find a nut occasionally. Your thorough, reasoned approach and sound science are a rare commodity these days. Even better, I like how you break down the prognosis for certain segments of population. Rarely does one size fit all and the medical community is way behind the times on this point.

  5. If I intellectually don’t want sugar, yet can’t seem to keep away from it if ever I once start, then the answer for me is a resounding “yes!” That, and the fact that I feel so horrible after having any, then yes again, it must be toxic for this body.

  6. OK, this is asking for rampant speculation, but…what do you think the effect would be of switching from HFCS/sucrose to glucose as a sweetener, across the board? It’s still not likely to be a great thing to eat huge amounts of. However, there have been societies that ate lots of high-GI starches but had far lower diebetes, obesity, etc., than we do, and there’s little chemical difference there. As a straight substitution you’d use more of it to get the equivalent sweetness, but if it really is more satiating, perhaps not all that much more.

    • For starters, glucose isn’t really that sweet, so there are at least 2 variables that are changing, one in the brain, and the other in the body, based on site of metabolism. Look at the work of Kimber Stanhope, who has done this experiment. There does indeed appear to be a significant difference, at least at the doses she looked at.

    • Thanks for the pointer to Kimber Stanhope! For others who are interested, here are a few links to relevant papers:

      Consumption of Fructose and High Fructose Corn Syrup Increase Postprandial Triglycerides, LDL-Cholesterol, and Apolipoprotein-B in Young Men and Women

      Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans with easy-to-read translation at which also talks about a subsequent study.

    • An anecdote from a friend who tried swapping in glucose for sucrose: he found that it worked great for homemade jam, which he usually finds too sweet anyway. However, for dessert-type things, they just never seemed sweet enough for him, no matter how much glucose he added. So it might not work for everyone, but given how little sugar I eat, I may try it for occasional treats. Or I might try glucose + some high-intensity noncaloric sweetener.

  7. Thanks for a great article! I have been in ketosis for the past two years and it feels really great. I have a brain tumor that has totally been shrinking. I wanted to know if you knew anything about the psychological aspects of sugar. I like you have children and while I do try to limit their sugar intake it is impossible to try and eliminate it. So I know of all of the physical aspects of sugar consumption but what about what it does to the mind. How my child’s behavior will change from eating some fructose, in terms of some fruit. It’s interesting but his sense of his limitations totally changes and he becomes down right naughty. Might it have to do something with the gut-brain connection?

    • Christine, this seems (purely based on experience, as I’m not familiar with this literature) highly variable by individual. For what it’s worth (probably not much…), even when my daughter gorges on sugar, she’s still behaviorally fine. Conversely, I have friends who report the opposite with their children. So I suspect it’s more complex than a binary issue.

    • I have 4 daughters and 1 son. All of my daughters can eat as much sugar as they want and have no effects. My son on the other hand used to have severe behavioral issues when he ate too much sugar. When I used to drink Coca Cola I would be ok for a week or so then get massive headaches. It wasn’t always this way but seemed to get worse as I got older. I’ve never heard of meat headaches, so I’m not worried about too much fat or protein.


    • Christine, I have a background in functional neurology and functional medicine and although the gut-brain connection plays a role, that’s only 1 piece to the puzzle. I work with children with neurobehavioral disorders and in my experience, they not only have a reduced level of cognitive, motor, and sensory abilities, but also a reduced level of autonomic and immune regulation abilities. Coincidence? Absolutely not. The desynchronization and ineffective interhemispheric communication (ability for the right and left hemispheres of the brain to communicate) is the bigger picture that explains all of the abnormalities. For instance, a child with an underactive right hemisphere of the brain may present with social deficits since the right side of the brain is primarily responsible for the development of social skills but that child may also present with decreased gut motility, decreased barrier functions, increased heart rate, decreased insulin sensitivity, and increased insulin surges, etc. The right hemisphere of the brain plays a role in all of those functions, too. Of course it’s more complicated than that but it’s important to understand the influence the brain has on our body.

      Give 5 children the same amount of fructose, and you can get 5 very different responses. Apart of that reason is the gut-brain connection as you mentioned…how effective the gut is in processing the fructose. However, if the brain has some type of deficit, (even if it’s not major enough to have the traditional symptoms of a child with a neurobehavioral disorder) it can influence the gut, insulin sensitivity, etc. (all the things mentioned above). We all have a threshold…give anybody enough sugar and they will react to it in some way. The question is: how can we heighten that threshold so that we aren’t as easily affected by sugar or any other substance for that matter? (That’s my personal goal to figure that out).

    • Hi Chris (it’s Ali from Bee’s group). I have thought long and hard about this one. My grandsons both turn into Tasmanian Devils if they get too much sugar.

      Every food in nature comes packaged with a complete array of nutritional elements. Not only do they distinguish the foods from each other, but they also provide elements that help the body digest the food, and support the body in general. Processed sugar is lacking these elements. It has nothing in it to tell the body what to do with it. That I believe is where the toxicity lies. Because the body then has to call on its own resources to try to process it, that means those elements are diverted from other important processes, including neurological.

      So, that may be the case with sugar but if fruit comes with an array of nutritional elements, why would that affect your son? There are many factors that unbalance the ecology of the gut. Even one course of antibiotics can apparently deplete 50% or more of the gut flora. High sugars in general can change gut flora favouring yeasts over other more beneficial microbes. Eventually it may get to the point where it just becomes one huge fermentation tank! The fermentation process involving sugars produces alcohol.

      Is your son’s – and my grandson’s reaction, whether fruit or processed sugar just a response to a form of intoxication?

      When I was riddled with Candida, because it triggered constant fermentation in the food I ate, my body could not process alcohol at all (and I do wonder if this phenomenon could well explain the existence of NAFLD – as my body readjusted and the Candida went away I had several weeks of my liver clearing out debris and very probably fat globules!). I avoided it for years. Now, after being relatively low carb for over 5 years I can consume a little without any problem (i’m not a lover of alcohol anyway).

  8. Hi Peter,
    This is one of the best blog posts I’ve read about sugar. Thanks for putting this together.

    Slightly off topic, with all the traveling you do, do you have any advice on how you maintain a decent diet? I often travel for work and wonder off the reservation with my diet. Apart from all the sugar lots of restaurants put in their dishes and salad dressings, I also have trouble finding real cream for coffee, getting enough saturated (as opposed to polysaturated) fats, etc. How do you do it with all the traveling you do?

  9. Thanks – what you write confirm my observational findings. I am heaviy overweight but claim not to be sensitive to sugar (I am fat on “cream and butter”) which always gets me into a lot of arguments with the LCHF people who refuses to believe my experience. Candy and chocolate do not trigger my cravings – I do binge on icecream but more on salty, fat foods. I am diagnosed with BED but it is not sugar that is my downfall. You put that discussion in perspective for me, thanks again (and I am swedish, hence the maybe weird language)

  10. I have 2 kids: 3.5 y.o. and barely 2.y.o. My youngest never experienced added sucrose in anything and she is very fond of meaty stuff (she might actually be addicted to salty food – but we only eat so-called “primal” foods). My oldest kid had experienced added sucrose at times before we removed most processed foods from our eating habits. Even though he has not had extra sucrose (i.e. added in foods) for a long time, he still talks about it. I explain to him that even if it tastes good in the mouth, it is not necessarily good in the belly. It seems to sink in. When grand-ma forgets that we don’t eat sweetened stuff and proposes something with added sucrose, he refuses it. I am not naive enough to think it will last but my kids won’t get it at home as long as they live with me. I do use xylitol once in a while when I bake for them, which seems to be non-addictive.

  11. Peter, you are spot-on with your blog, as I have come to expect. Coming from the world of pharmacy and chemistry, I often say that everything is toxic. Every drug is a potential toxin. The only question should be: “How toxic is the drug (or chemical compound) and under what conditions?”

    At first glance that might seem to undermine the meaning of the word “toxic,” but I don’t believe so. People in the US are told this is safe and that is unsafe, when there is always a degree of danger associated with everything. Toxic is not a black and white term. Some toxins have a large dosage range that will make you sick long before it kills you. With others, a small error in dosage is enough to kill. Some people will have a sensitivity to a drug that other people do not. Some toxins are eliminated quickly and others slowly. These are the nuances that the average person fails to grasp when the term “toxic” is used.

    Kings and other VIPs during the middle ages took small doses of arsenic, in increasing amounts, to build up their tolerance to arsenic. Indeed it worked, or at least until they increased their dosage one time too many and exceeded their absolutely lethal threshold. So our bodies can be quite forgiving of toxins under the right circumstances.

    I understand Robert Lustig’s reasons for declaring sugar toxic, but his usage comes across as extreme and exaggerated. His argument is soundly based upon the metabolic pathway, and as you so eloquently argue, much like the toxicity of Tylenol. Yes, both are toxic, but people will have varying degrees of response to the toxic effects of each chemical.

    So the problem with sugar is that:
    A) it is toxic to many people (but probably not everyone),
    B) the dosage for toxicity varies greatly, and
    C) the toxicity can be manifested in a number of ways with a multitude of symptoms, most of which are not obvious to people in the short term.

    Until we can find a way to quantitate an individual patient’s toxicity to sugar, and provide them with a dosage threshold, the term toxic is meaningless to them.

    People who know I have been in pharmaceutical research (although not a pharmacist myself) often ask me if some drug they are taking is safe. I give them both a yes and no answer. Every drug is safe, but every drug is toxic. Every drug will show bad reactions for some individuals, even if only rarely. So patients should contact a doctor or pharmacist if they have any misgivings about their reaction to a drug. However, every drug is considered safe, for most people, when taken as directed and in the proper dosage.

    Then real questions for a physician are…
    “What dosage regiment for sugar would you feel comfortable telling people they could follow without being at risk for toxic effects?” and “If there is no generally safe dosage that you could recommend with a clear conscience, should this drug (sugar) be declared toxic and withdrawn from the market?”
    Normally, withdrawal would be the FDA’s reaction to a serious toxic drug response. Viewing sugar in this manner would certainly validate Lustig’s utilization of the term “toxic.”

    Perhaps we should label sugar as a “drug”, before we label it as “toxic”. Referring to sugar as a nutrient is a meaningless argument. It is not an essential nutrient. Some people argue that sugars are essential, since our bodies use them in biological pathways, but we can make what we require and do not need to consume it. Any chemical that is not essential to our diet can just as validly be called a drug instead of a nutrient. Moreover, unlike basic, essential nutrients, sugar stimulates the same brain receptors as opiate drugs.

    I say we begin by referring to sugar as a drug. Then we can judge it by the same criteria as other drugs, including it’s toxic effects, addiction, etc.

    … Bill Vincent

    • Bill, very well said. Thanks very much for sharing your experiences and insights with us. You’re obviously much more expert on this topic than I am. I think your idea of “drug” versus “toxin” is very interesting.

  12. Another fantastic article. Your blog has increased my understanding of metabolism and physiology exponentially. Hardly a day goes by where I don’t use it in my office with our weight loss patients. I do have a question? I am much like you with my sugar reaction ( my fasting insulin is 10), i have lost 75 pounds on a low carb, adequate protein diet but now I am crossfitting 4-5 times a week and following the wendler 5-3-1 program 2-3 x a week. I fuel my workouts with superstarch (amazing stuff), I want to lose another 10% body fat which would bring me down to 15%. I know my protein and carb numbers per day and plan to fill the rest of my daily calories with fat. My question is can i best alter my body comp by eating total calories at a significant (1000 cal) deficit of my total daily expenidiiture and perhaps impacting athletic performance or by eating at my TDEE and building more muscle and allow the fat percentage to reduce that way.

    • Ron, I’m a big Wendler guy, too, so I’m glad to hear there is at least one other weight lifting geek out there who is into that nuance. In “theory,” yes the caloric deficit would ideally come from reducing fat to what might be termed a “hypocaloric KD,” thought the semantics can be misleading, because it’s really only referring to exogenous calories. IF might be another technique to experiment with.

  13. Peter,great discussion as usual. My understanding is that Dr. Lustig’s thesis is actually that fructose ( alone or as a component of sucrose) is effectively toxic due to its specific metabolism (which he explains in exquisite detail) . And he acknowledges it’s not acute; rather chronic and dose dependent similar to alchohol. I think he’s been making the toxicity argument to call attention to the problem, not to generate a debate over use of the word toxic.

    • Correct, Larry. Most of the discussiona round sugar pertains, specifically, so the fructose component and its unique metabolic requirements in the liver (similar to alchol). In fact, I think Rob suggests an “ideal” limit of the total alchol + fructose in a 24 hour period to minimize the effect of chronic toxicity. I suspect this threshold varies for all the reasons I discussed, but I do think there is really something to idea of NOT mixing sugar and alchohol. Simply too much for the liver to process.

  14. Thank you. I was particularly interested in your observations about your genetic hybrid. I had gestational diabetes with both my sons and I often wonder how this has affected them and what their futures hold. The first time, the diabetes was not controlled [the screening test was high normal] and I had a 12 lb son by c-section. He had uric acid crystals in his urine (but normal blood work) for at least a year. The second time, I controlled with a VLC diet and then insulin, and delivered a very healthy 7.5 lb son. The older boy (now a young adult) is a “fruit bat” – loves sweets and takes a dim view of green vegetables. The younger boy loves savory food and salad. He won’t finish a slice a birthday cake since it’s too sweet. But he does love (full fat) ice cream.

    Life is interesting.

    • Chris, thanks so much for sharing this experience with everyone. I guess, for you and your family, the most important thing to think about is what you can do now, moving forward (vs. worrying about what you have no control over). I continue to see emerging evidence that what a mother eats and doesn’t eat during pregnancy has a significant impact on the life and metabolism of her child. What I don’t know is if this epigenetic overlay is greater than the genetic component. I suspect the answer is, “it depends…”

    • This aspect interests me. The old adage used to be ‘eat for two’ when a woman was pregnant, but then the ‘establishment’ decided that was just an old wives tale. Well, believe it or not, the old wives were right.

      As a foetus is forming in the womb, the growth is driven by nutritional elements. If the mother doesn’t have enough of one or a few different elements for the two of them then where would the baby get them from? I think Weston Price adequately illustrated this when he related the ‘pigs and vitamin A’ experiment that he came across. We only need to be deficient in a small amount of any given element and it can have a profound effect on the growing foetus.

      The establishment does understand this in a limited way – they do furnish pregnant women with folic acid to prevent Spina Bifida, and some get extra iron, but that’s about as far as it goes. Maybe what we eat doesn’t affect the baby radically, but perhaps it won’t develop quite as many neurons in the brain, or nephrons in the kidneys. Maybe it may be more vulnerable to a particular health problem in the future. Maybe it won’t process certain elements as well as another person. So much about disease is put down to ‘genetics’, but what if these are familial issues driven more by nutritional deficiencies rather than genetic mutations?

      As Curtis H Wood wrote back in the 1950s, we are overfed but undernourished. There is a glut of nutritionally empty food out there that provides virtually nothing but calories. That isn’t good for us, and it certainly isn’t good for building strong, healthy children.

  15. Hello Peter an all,

    I am surprised you did not mention the area under the curve of total sugar (and glucose too) consumption in connection with the causation of metabolic syndrome, insulin resistance, carbohydrate intolerance, sugar addiction, carbohydrate addiction, however you want to characterize the problems.
    Many of us are not encountering this problem until later in life and need help with alerting our children to the risks of their chronic exposure to sucrose. I read that Jane Brody article downplaying the sugar risks Taubes mentioned when my kids were little, ans even used her cookbook. The area under the curve of total sugars consumption would be helpful part of an explanation.
    Despite knowing that at least one grandfather who had diabetes requiring insulin, and despite knowing that I had spilled sugar during my second pregnancy (not diabetes though), and despite two of three children who weighed more than 9 pounds at birth, . . . I failed to grasp the risks with enough sense of urgency to try to change my way of eating.
    In retrospect, perhaps I should have been more alert, but understanding the chronic effects seems to have eluded even most physicians, apparently. Certainly none has ever mentioned them to me, despite the gradual onset of the signs of metabolic syndrome — never including obesity or too high tryglycerides, or even waist measurement!
    Now it is not at all clear to me that any of the chronic damage is reversible. It is not even clear that I can get intoketosis, or that I wantto, considering this zone of misery problem!

    Perhaps you could post a graph illustrating an example of lifetime consumption of sugars?

    • Good point, Jane. I don’t really know the answer, but the AUC might be a helpful model of chronic risk. It is almost certainly the case for most people that aging increases susceptibility to this particular molecule. Is it this the result of something else (i.e., an independent change in insulin sensitivity)? Or a direct result of some change in hepatic processing? Not sure…

  16. Peter, I started reading your blog about a week ago and find it fascinating. I think my wife is actually starting to get annoyed with me talking about it so much. What initially drew me in is your analytical approach to nutrition. I like to think of it as the moneyball approach to nutrition. I just started trying to eat similarly to how you’ve described and it is going well so far.

    My question though is this; when I start to describe what you eat to people, they usually say make the comparison to Atkins. I don’t actually know much about Atkins though. Can you highlight some of the differences in philosophy between your approach and the Atkins approach?

    • Atkins is all about calling to the appeal for fat loss whilst also being able to indulge our acculturation.

      90+% of the online discussions to do with Atkins/ketogenic are like whining kids going “mummy can I have a cookie?” and struggling with the social eating culture they were raised with, in this way Atkins provides a framework which is essentially a coping mechanism that you can fall back on – a “diet” that is both effective and maintainable in the long run.

      The way to internalise “healthy” eating is to forget about food as an energy source, and remember that it’s really a hormone stimulant/suppressant – what you want to do is minimise the (detrimental) hormonal fluctuations which are at the root of every modern disease.

      All we need is a bit of protein, some trace vitamins/minerals, and energy. The big stupid nutrition war is on where to get the energy, and people will go to enormous lengths to justify getting it from poor sources (which mess with your hormones on the way to becoming energy).

    • Well, one difference is that Peter started with cutting sugar, then . . Refined flour, then fruit? I do not recall the details that he mentioned. I would describe his approach as working his way down the carb ladder as Westman calls it in the newest edition of the Atkins book, instead of immediately severely restricting carbohydrates to 20 g by eating only protein and low carb vegetables.
      Peter also supplements with lots of fish oil and MCT oil,which are not mentioned by Westman, but not a multivitamin. At least that is what I recall. I also do not recall him mentioning salt requirements or eating broth on a daiy basis.

      My question for Peter is why do you believe that you can get by without vitamin supplements, such as B vitamins, without plant sources? I worry about folate for women of child bearing age, for example,

  17. Is exercise toxic?

    When Exercise Is Too Much of a Good Thing

    None of the younger athletes or the older nonathletes had fibrosis in their hearts. But half of the older lifelong athletes showed some heart muscle scarring. The affected men were, in each case, those who’d trained the longest and hardest. Spending more years exercising strenuously or completing more marathon or ultramarathon races was, in this study, associated with a greater likelihood of heart damage.


    • I’m pretty familiar with this literature, and I desperately want to believe it’s wrong! James O’Keefe has been discussing this for a while, and we’ve had a number of discussions about it. In humans most of the data are observational, so we need to be careful not to over-interpret. But the mechanism of action makes sense, as far as atrial stretch and atrial arrhythmia.

  18. Hi Peter.
    Thank you for the great posts. My own story is as a dietitian whose understanding and approach to nutrition completely changed over 10 years ago because of the personal experience of having a child with quite a severe weight problem. Two of my children as youngsters could eat what they liked and stay lean, whereas my middle daughter always carried weight around the middle. She was less active, more interested in food, didn’t like meals to be delayed and at times could eat quite large amounts of food in a sitting. She gained a lot of weight at around 12 years of age and even with 20 years experience in nutrition, I found it difficult to explain why this was happening. Luckily I met a GP who suggested she be tested for insulin resistance, which she was found to have. But that was just the start of it. I knew little about IR and how to treat it, so had to go back to study. We trialled different eating plans and found a lower carb plan that she has followed for the last 6-7 years. She is very sensitive to all carbs, not just sugars but knows how much she can tolerate. My clinical practice has changed because of this. I now explain to clients with IR/Met Syn how the way they process carbs can result in excessive hunger, cravings, snoring, high BP, low energy, high Tgs, fatty liver, anxiety, low moods etc. Often after a week’s trial of lower carb they feel different and that’s a huge motivator for change. A major problem for me is undoing peoples’ beliefs about diet and health. 30 years of Aust Dietary Guidelines promoting a diet based on carbs has a lot to answer for!

    • Ash,

      Great comment! Clearly that is a very helpful way to think about it.

      I am reminded that Peter has a very good short list of recommended books.

      The Atkins book by Westman et al is a very helpful step-by-step guide losing fat, but I learned more about the hormonal effects of food choices from Taubes’s books, and from Lustig’s book and online talks.
      Now, this website seems to be an excellent resource for better understanding the effects on our lipoprotein markers.

      The quality of the commentary here is quite a draw.

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