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High Fructose Corn Syrup: Much Maligned? Or the Devil’s Food Cake?

The views expressed are those of the author and are not necessarily those of Scientific American.

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I did a post back in 2009 on High Fructose Corn Syrup (HFCS). In researching that post I dug hard into the chemistry of HFCS, the similarities and differences from sugar, and the current literature on whether it’s coming for your waistline. At the time, I concluded that, while I know fructose on it’s own isn’t good for you, the data isn’t yet convincing, and I as yet couldn’t distinguish between the effects of HFCS, and the massive increase in our diets of sugars in general.

And now I’ve found this paper, and have been asked to cover the topic again. And…I could be convinced. But I’m not convinced yet and I’ll tell you why.


Bocarsly, et al. “‘High fructose corn syrup causes characteristics of obesity in rats: increased body weight, body fat and triglyceride levels”. Pharmacology, Biochemistry, and Behavior, 2010.

This paper came out in 2010, and when it did, it generated a minor buzz. Everyone loves to hate on HFCS, and while many studies have shown that there is relatively little difference between HFCS and regular sugar (though there are some differences in metabolism, which I will get back to), the only real data we have so far to link to is that Americans as a whole are getting fatter, and we’re all eating a lot of HFCS (except for those of us who don’t, some Americans who can afford it are now opting out due to the very fears we are discussing).

And then, out came this paper. Some lauded it real proof of the evils of HFCS. Others (particularly people in the HFCS industry) criticized it as poor science with no real indications. Me? Well, I think it could be a bit of both.

So, what is HFCS? Well, table sugar is a combination of two monosaccharides, which are single molecule sugars, glucose and fructose. When you bring them together, they bond into a disaccharide, known and loved the world over as sucrose.

(Source. The O in the middle there is the linkage you’re looking for)

HFCS is…basically sucrose. Except it’s not. The most common formulation of HFCS is 55% fructose and 42% glucose (yes, that does not add up to 100%, there’s a small amount of other stuff in there). This means that, while the fructose and glucose bond all they can, there is some fructose left over and floating about. And fructose is SWEETER than glucose. So a higher proportion of fructose to glucose makes for more free fructose and a sweeter drink. In theory. The reality is that the percentages aren’t that different, and the sweetness of HFCS is pretty comparable. The big difference here is PRICE. HFCS is a heck of a lot cheaper than sucrose due to corn subsidies in the US from the government. This has made it much easier over time for companies producing processed foods to produce lower cost versions of those foods made with HFCS instead of sugar (I’m looking at you, Coca-Cola), and this means their profit margins can be higher. If you were a company, the siren song of HFCS would be hard to deny. And so it’s become hard to avoid HFCS in some foods, especially foods that are prepared (HFCS is in your peanut butter, your jelly, and even your bread), and particularly so for those who can’t afford the more expensive alternatives.

But of course, there might be a problem with HFCS. You see, Americans have this obesity epidemic going on. Our weights have increased a great deal in the last few years, and we want to know why, and preferably we want something nice and easy to make go away that we can point our fingers at. HFCS makes a good candidate for this, it became popular around the same time that Americans started getting fatter, it’s all “unnatural” sounding, and it’s something that would be relatively easy to make go away, definitely easier than changes to lifestyle and infrastructure.

But just because HFCS came out around the time Americans started getting larger doesn’t mean HFCS is to blame. And HFCS is not the only thing that has increased recently, our entire world has become a lot sweeter, and a lot saltier, than it ever has before. It could be general changes in diet and habits. Correlation is not causation, after all. While it’s easy to point fingers, people need actual PROOF that ingestion of HFCS causes increased weight gain.

And then along came this study. In this study, the authors looked at three conditions in which rats got to eat HFCS.

1) Male rats got 2 months of four different conditions. 12 hour or 24 hour access to HFCS with their chow, 12 hour sucrose with their chow, and just chow.

2) Male rats for 6 months of three different conditions. 12 hour or 24 hour access to HFCS with their chow, or just chow.

3) FEMALE rats got 7 months of four different conditions. 12 hour or 24 hour access to HFCS with their chow, 12 hour sucrose with their chow, and just chow.

They then looked at how much the rats weighed at the end, how much sweet stuff they consumed, and, in some cases, blood levels of triglycerides.

They found that male and female rats exposed to 24 hour HFCS with their chow gained more weight compared to chow alone, and after 6-7 months, male and female rats with 24 hour HFCS access had elevated levels of triglycerides. Finally, males and females after 6-7 months of 24 hour HFCS had heavier fat pad weights in their abdomens than those with access to chow.


Or at least, that’s one interpretation.

While some immediately hailed this as the real proof we needed that HFCS and the corn industry were evil, others immediately called the results into question. I think both sides have something to be said for them. While the study DOES show increased weight gain, it’s poorly grouped, all groups received different treatments (why six months for males and seven months for females?), and the results…are not very consistent. In their eight week treatment group, the 12 hour HFCS weight gain was HIGHER than the 24 hour HFCS weight gain, in the 6 month males the 12 AND 24 hour groups were higher, and in the 7 month females only the 24 hour group was higher. The 6 month males and the 7 month females had similar inconsistencies in fat pad levels, with males showing bigger fat pads after 12 hour access, and females only showing bigger fat pads after 24 hour access. Now, this could be the result of a sex difference between males and females, but I really think you can’t parse that out without having similar treatment times and conditions, which they didn’t have. Results continued to be really inconsistent for the triglycerides group.

Finally, the biggest criticism others made of the study (to my mind). The authors measured how much HFCS and sucrose were consumed in the first group, and found that the rats drinking sucrose were actually getting more calories from the drinks. BUT. They never measured total calorie intake. At all. And they never measured the HFCS and sucrose consumption in their long term animal trials at all. Now, it’s not hard to see why, rats are messy eaters and it can be hard to determine how much chow is hitting the belly vs hitting the floor, but I think this is a pretty big issue. Some studies have shown that, as rats eat more sucrose, they compensate by eating less chow. Is this still true here? What about for HFCS? Were the rats consuming more or less calories TOTAL?

Now, I note up there that this is the biggest criticism others have made of the study. Me? I’ve got more. They looked at blood glucose levels for the first group, and not for the second two. I have to wonder why (especially since blood glucose levels are ridiculous easy to take). And secondly, I do believe that the rats eating the HFCS gained more weight. I definitely do. But the consistent results are only between the 24 hour HFCS condition and chow. When they looked a sucrose, they only looked at 12 hour access. Where IS that 24 hour sucrose condition? Would rats gain just as much weight? Inquiring minds want to know.

And finally, here’s my biggest criticism. What is the mechanism. WHY does HFCS cause more weight gain? The authors of this study did not address this (the data is a little preliminary in that respect). The idea from other studies is that HFCS doesn’t active feeding hormones such as leptin in the same way as sucrose does, and this means that you don’t feel as full and you eat more (this is usually in studies with rats using just fructose, not really the same conditions, as fructose alone is rough in humans. Like diarrhea rough. They also got similar results with sucrose which the authors did not see here). But I don’t see leptin levels here…and even if I did, WHY? HOW is this promoting abdominal obesity?

So basically, I do believe the rats gained more weight. I think it’s clear enough. But I want to know if that’s the HFCS, or high caloric consumption (by comparing it to the same sucrose access, a condition they didn’t have). And I want to know HOW it’s working. Do people (or rats) who have this HFCS condition have higher leptin resistance? Higher insulin resistance? What is the mechanism? Because a mechanism could really convince me that HFCS is TEH EVILZ. Until then, I believe what I have believed, that our world is just too sweet in general and our portion sizes too large, and that your Coca-Cola is too many calories, whether those calories are from HFCS, or from sugar.

But I’m willing to be convinced.

Bocarsly, M., Powell, E., Avena, N., & Hoebel, B. (2010). High-fructose corn syrup causes characteristics of obesity in rats: Increased body weight, body fat and triglyceride levels Pharmacology Biochemistry and Behavior, 97 (1), 101-106 DOI: 10.1016/j.pbb.2010.02.012

Scicurious About the Author: Scicurious is a PhD in Physiology, and is currently a postdoc in biomedical research. She loves the brain. And so should you. Follow on Twitter @Scicurious.

The views expressed are those of the author and are not necessarily those of Scientific American.

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  1. 1. matthartings 9:06 am 08/23/2011

    Great post Sci!
    The one thing I’ve always wondered with any of these HFCS studies is: HFCS tastes sweeter than regular sucrose. So, manufacturers don’t have to use as much when making their products. Shouldn’t any experiment try to do this baseline correction? Or at least study it? Even if HFCS makes us gain more weight versus sucrose (on a per molecule basis), we’re not getting as many molecules of total sugar with HFCS in our products. It doesn’t seem like anyone is studying this “real-life” comparison. Have you seen anyone addressing this?

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  2. 2. scicurious 9:11 am 08/23/2011

    Hi matthartings,

    You know, this is one of the things that really surprised me when I started looking in to HFCS. See, the popular wisdom is that, as fructose is sweeter than glucose, HFCS must be sweeter because it has more fructose floating around. ACTUALLY, HFCS 55 is about as sweet as sucrose by weight! My guess is that it’s because the percentages are not different enough for us to detect a difference. We ARE in fact getting just as many molecules of sweetener with HFCS as we are with sucrose. I think this is where people kind of mix up things like HFCS and aspartame, which is so much sweeter than sucrose that you need very little of it. What makes HFCS more popular is not that it’s sweeter, it’s that it’s cheaper.

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  3. 3. kclancy 9:57 am 08/23/2011

    Very interesting post, Sci. I still avoid HFCS, but understand that there is a lot of privilege going into my ability to do that.

    I do wish the experiments you describe had been performed — the groups were very odd. Let’s hope someone does a follow-up so we can try and understand this more.

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  4. 4. matthartings 10:28 am 08/23/2011

    Hmm … the misinformation of me has been thorough! Thanks for clearing that up, Sci!

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  5. 5. ejwillingham 12:19 pm 08/23/2011

    Had my students look into claims about HCFS as part of their critical thinking project in my sci class, and we didn’t find much in the way of convincing evidence that it’s teh evilz, although that was before this study came out. The criticisms you cite are important.

    We (our family) try to avoid HFCS simply because we try to avoid highly processed foods in favor of things we make ourselves (not always successfully). But more than that, we try to avoid eating (and drinking) too much. I’m at a loss as to why we keep looking for these relatively obscure causative agents in obesity before looking at what those of us who have been alive since the 1960s already know: Before Obesity (B.O.), there weren’t Big Gulps. B.O., *all* portion sizes were much smaller. B.O., there weren’t “super sizes,” etc. B.O., there weren’t nearly as many options for sedentary pursuits as there are today. B.O., we had to, you know, go to the bank, the post office, the store, the 5 ‘n’ 10, etc., *in person*. Everyday living was perforce much more active while we were also still being programmed for lower portion sizes. Nothing was as easy or sedentary as it is today, and I *still* take home about 3/4 of every meal I have in a restaurant because they simply give you too much food nowadays.

    I trace the division between B.O. and D.O. (during obesity) to a commercial I still remember (from late ’70s/early ’80s?) for a chain trumpeting its oversized soda offerings, in which a law enforcement officer stands holding what used to be a “large” soda container–20 oz, maybe?–and saying in a low, threatening voice, “You call this a *large*?” The message was, YOU NEED LARGER CONTAINERS OF SODA. Thereafter, that’s exactly what we have had. I’ve frequently seen very young children–toddlers–with cola in their baby bottles.

    I once tweeted a question that didn’t get much of a response, but it’s based on an observation I’ve made in comparing children in school districts serving populations of differing socioeconomic status. My observation was that in the wealthy district, there were literally no obese children and very few even overweight adults–teachers, parents, administration. In the district/schools serving a population from a lower socioeconomic status, obesity was/is much more prevalent across all age groups and statuses. Is that a HFCS difference, an access difference (like the privilege that Dr. Clancy mentions), an education difference, what? That was my question. Why this disparity?

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  6. 6. ktkeith 5:36 pm 08/23/2011

    As you note, it’s quantity, more than the particular type of carbohydrate, that matters. But that does not mean HFCS is not a problem. It is so ubiquitous that it is a major source of the vast amounts of empty calories that foul the US diet. And, its production is hugely wasteful and environmentally destructive.

    The dose makes the poison, and HFCS is poisoning us.

    Link to this
  7. 7. Quantumburrito 9:01 am 08/24/2011

    Nice post. What do you think of the molecular level explanation, namely that HFCS contributes to weight gain because fructose (unlike glucose) is shunted through the pathway involving fructose-1-phosphate (instead of fructose-6-phosphate) which is broken down into trigylcerides much more easily and is also subject to less control?

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  8. 8. scicurious 9:32 am 08/24/2011

    Quantumburrito: I find the molecular method to be plausible, but I still wonder whether HFCS has a high enough percentage to make a material difference outside of other factors. I DO think they gained weight in this study (though there was no 24 hour sucrose condition to compare them to and I think that would be interesting), and that may be why, it may also be that the HFCS rats took in more calories total due to differences in satiety, or even through another mechanism, but I want to see those differences in intake and the mechanisms behind them (or the differences, say in triglyceride values that can be directly derived from the HFCS, which I bet you could do with labeling) before I really call it. It’s the current lack of mechanism that makes me wonder if it’s just an increase in food intake in general that is to blame. We humans eat a LOT more than we used to, and we eat a lot more of saccharides in general than we used to, and even if HFCS turns out to be a culprit, I’m not sure elimination of HFCS entirely would make us any skinnier.

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  9. 9. SquintMom 1:26 pm 09/26/2011

    I have three comments here. First, with regard to your statement “[HFCS] would be relatively easy to make go away, definitely easier than changes to lifestyle and infrastructure.” I have to say I disagree. While SOME consumers could make HFCS “go away” from their dietary repertoire if they were suitably convinced it was a problem, the poorest members of society (who are coincidentally those most at risk for obesity and type 2 diabetes) would have a hard time doing so because of corn subsidies. As you point out in your blog, HFCS is extremely inexpensive. This is partly because of the process used to produce it, but mostly because of the import taxes on sugar and the incredible subsidies given to corn growers. The net result of all this subsidizing and taxing is that if a woman goes to the grocery store with $2 in cash or food stamps to feed her family, she’s going to get the most calories for the least money if she chooses processed (read: HFCS-containing) foods. The politics associated with HFCS make it INCREDIBLY difficult to make it go away.

    Second, yes, there are questions this study raises. One of these, of course, is why the 12-hour HFCS rats gained more than the 24-hour HFCS rats. However, I would like to introduce the notion that when dealing with living creatures, there’s a behavioral component that one must consider in addition to the biochemical component. Who knows…maybe the 12-hour HFCS rats learned over time that their access to sweet water would be removed away periodically, so they gorged on it when it was available (reasonable to suppose, given that the 12-hour rats drank essentially the same number of calories of sweetened water as the 24-hour rats). This could then affect eating patterns. To be clear, I’m just speculating here – there may or may not be any scientific truth behind my pure speculation, but I wish to make the point that the “odd” results don’t indicate experimental invalidity; rather, they indicate that there’s something more going on here. Regardless, to explain the result of the 12-hour rats being fattest requires delving into behavior, not simply into biochemistry. Which leads me to my final point…

    The notion that this paper “proved” anything about HFCS is ludicrous, and in defense of the researchers, was not what they were trying to claim. The media has a distressing habit of making much hay of single-study results, when if the researchers themselves were interviewed, they’d likely say nothing more than, “Yes, well, that was interesting.” The Bocarsly paper isn’t PROOF that HFCS is bad. No single scientific publication, in its own right, is PROOF of anything. Further, we can’t expect researchers to be Renaissance men (or women); it’s not the job of biochemists/physiologists to explain behavior, so it’s not a failure of the paper that they neglected to delve into the myriad possible reasons that the results came out as they did. I suspect that over many years, a picture of HFCS and its effects on the human body will begin to emerge and will include many facets, including influence on metabolism and on behavior. That the researchers didn’t propose a mechanism for HFCS’s effects isn’t a failure of their research; it’s an acknowledgement (and an appropriate one!) that they hadn’t determined, or even attempted to determine, the mechanism behind HFCS’s effects. Rather, they’d simply demonstrated something, which was that HFCS (for whatever reason) made some rats porky. Isn’t that interesting? Let’s not make it out to be anything more than that, shall we?

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