by Marion Nestle
Mar 24 2010

HFCS makes rats fat?

I can hardly believe that Princeton sent out a press release yesterday announcing the results of this rat study.  The press release says: “Rats with access to high-fructose corn syrup gained significantly more weight than those with access to table sugar, even when their overall caloric intake was the same.”

How they came to these conclusions is beyond me. Here’s the original paper.

It has long been known that feeding sugars to rats makes them eat more and gain weight.  But, as summarized in Table 1 in the paper, the researchers did only two experiments that actually compared the effects of HFCS to sucrose on weight gain, and these gave inconsistent results.  Their other experiments compared HFCS to chow alone.

The study is extremely complicated and confusingly described.  As best as I can tell, here’s what they found:

1.  The first study used 10 male rats in each group and observed them for 8 weeks.  At the end of the study, the rats fed chow alone weighed 462 grams.  The rats fed sucrose plus chow weighed 477±9 grams.   The rats fed HFCS plus chow weighed 502±11 grams.   The authors say the difference between 477 and 502 grams is statistically significant.  But these rats were offered the sugars for 12 hours per day.  The rats fed HFCS for 24 hours per day, which should be expected to be fatter, were not.  They weighed less (470 grams) than the rats fed sucrose for 12 hours per day.  So these results are inconsistent.

2.  The second study did not compare rats eating HFCS to rats eating sucrose.  It just looked at the effects of HFCS in groups of 8 male rats.

3.  The third study used female rats (number not given) and observed them for 7 months.  At the end of the study period, female rats fed HFCS plus chow for 12 hours a day weighed 323±9 grams.  Female rats fed sucrose plus chow under the same conditions weighed 333±10 grams.   This result is not statistically significant.

Although the authors say calorie intake was the same, they do not report calories consumed nor do they discuss how they determined  that calorie intake was the same.  This is an important oversight because measuring the caloric intake of lab rats is notoriously difficult to do (they are messy).

So, I’m skeptical.  I don’t think the study produces convincing evidence of a difference between the effects of HFCS and sucrose on the body weight of rats.  I’m afraid I have to agree with the Corn Refiners on this one.

So does HFCS make rats fat?  Sure if you feed them too many calories altogether.  Sucrose will do that too.

NOTE 3/26: see point-by-point response to this post by Bart Hoebel, one of the authors of the study, in the Comments below.

Addition, November 23: Thanks to Jeff Walker, professor of Biology at the University of Southern Maine, Portland, for doing a detailed critique of the study, most thoughtful and well worth a look.

  • Emily

    What do you make of the study claiming HFCS can cause liver damage? I didn’t hear much of the story because I was dashing out the door, but I was curious about whether the study was a scientifically valid one. I have to admit that I have always had misgivings about HFCS because it’s a purely manufactured product.

  • JPL

    Fructose takes its toll on the liver just like alcohol. People do get fatty liver disease from eating too much fructose. I haven’t seen any convincing evidence that there is much of a difference whether the fructose comes from HFCS or sucrose though.
    Try it for yourself. Check the labels. No sugar for a couple of weeks. See the difference.

  • I am head of the laboratory that did the Princeton high-fructose corn syrup study (B.H.) and would like to address the points made by Marion Nestle (M.N.)
    M.N. I can hardly believe that Princeton sent out a press release yesterday announcing the results of this rat study. The press release says: “Rats with access to high-fructose corn syrup gained significantly more weight than those with access to table sugar, even when their overall caloric intake was the same.” It has long been known that feeding sugars to rats makes them eat more and gain weight. But, as summarized in Table 1 in the paper, the researchers did only two experiments that actually compared the effects of HFCS to sucrose on weight gain, and these gave inconsistent results.
    B.H. Eating sucrose does not necessarily increase body weight in rats, although it has been shown to do so in some studies, usually employing high concentrations of sucrose, such as 32%. Our previously published work, has found no effect of 10% sucrose on mean body weight. At this concentration, rats seem to compensate for the sucrose calories by eating less chow. You are correct that we twice compared HFCS to sucrose in the present article. There were statistically significant effects on body weight, triglycerides level and fat accrual in both male and female rats.
    M.N. The first study used 10 male rats in each group and observed them for 8 weeks. At the end of the study, the rats fed chow alone weighed 462 grams. The rats fed sucrose plus chow weighed 477±9 grams. The rats fed HFCS plus chow weighed 502±11 grams. The authors say the difference between 477 and 502 grams is statistically significant. But these rats were offered the sugars for 12 hours per day. The rats fed HFCS for 24 hours per day, which should be expected to be fatter, were not. They weighed less (470 grams) than the rats fed sucrose for 12 hours per day. So these results are inconsistent.
    B.H. Actually, it is well known that limited access to foods potentiates intake. There have been several studies showing that when rats are offered a palatable food on a limited basis, they consume as much or more of it than rats offered the same diet ad libitum, and in some cases this can produce an increase in body weight. So, it is incorrect to expect that just because the rats have a food available ad libitum, they should gain more weight than rats with food available on a limited basis.
    M.N. The second study did not compare rats eating HFCS to rats eating sucrose. It just looked at the effects of HFCS in groups of 8 male rats.
    B.H. In Experiment 2, the long-term study, we did compare HFCS to sucrose in female rats; the schedules of availability were different as explained in the article, because we were interested in assessing the effects of limited vs. continuous access, and males vs. females, in addition to comparing HFCS to sucrose. We also explored body fat accrual and triglyceride levels in both male and female rats. We explain in the article that we purposefully did not compare HFCS to sucrose in Experiment 2 in males, because we did not see an effect of sucrose on body weight in males in Experiment 1 (see Method section).
    M.N. The third study used female rats (number not given) and observed them for 7 months. At the end of the study period, female rats fed HFCS plus chow for 12 hours a day weighed 323±9 grams. Female rats fed sucrose plus chow under the same conditions weighed 333±10 grams. This result is not statistically significant.
    B.H. Our finding with female rats was statistically significant, as reported in the paper for Experiment 2. The data you highlight are selected, and they do not portray all of the groups and the findings of this experiment. The main findings of this part of the study are that, with long-term access, female rats with ad libitum access to HFCS weighed the most after 7 months (end point body weight was 355 g), and this was statistically different than the 12-hour sucrose and chow-fed control groups. In no place in the article do we say that the groups that you highlight are statistically different.
    M.N. Although the authors say calorie intake was the same, they do not report calories consumed, nor do they discuss how they determined that calorie intake was the same. This is an important oversight because measuring the caloric intake of lab rats is notoriously difficult to do (they are messy).
    B.H. Caloric intake for the sugars was reported in the Results section for Experiment 1. As commonly done, we did not present the overall caloric intake since there was no difference between groups. In the Methods section we explain that we measured HFCS, sucrose and chow intake daily. We computed the calories consumed as described in the Methods section. We followed standard laboratory protocol for collecting data on food consumption. The drinking tubes used in the study to administer sucrose and HFCS solutions had an anti-drip devices built in, and we collected food spillage for accuracy. Our laboratory has an extensive history of accurately collecting data on these measures. We reported the caloric intake and the standard error of sugar consumption, which illustrates the variability in intake for a given group.
    M.N. So does HFCS make rats fat? Sure if you feed them too many calories altogether. Sucrose will do that too.
    B.H. We agree that sucrose can also increase body weight, and in our article we cite studies showing weight gain using higher concentrations than the one tested in the present study. However, in our studies published in the last six years, we do not see rats becoming obese when offered a 10% sucrose solution. In the present study we report finding that 8% HFCS does cause obesity, and it does not appear to be due to increased calorie intake. This leads to an interesting scientific question that warrants further exploration. We plan on conducting new research that could provide additional information to help address this important and interesting topic of research.
    Our study in laboratory rats complements the growing body of literature suggesting that HFCS affects body weight and some obesogenic parameters. We cite in our paper additional evidence reported by other groups that supports our findings, and also acknowledge studies that suggest that HFCS does not affect body weight in ways different than that of sucrose. We acknowledge in the paper that at higher concentrations (i.e., 32%) sucrose have been shown to increase body weight. We are claiming, however, that at the concentrations we compared in this study, HFCS causes characteristics of obesity. The data show that both male and female rats are (1) overweight, (2) have heavier fat pads, particularly in the abdominal area and (3) have elevated circulating triglyceride levels.
    For more information and references on this topic, see a recent review published this year by Dr. George Bray, Curr Opin Lipidol. 2010 Feb;21(1):51-7.”Soft drink consumption and obesity: it is all about fructose”.

  • Here’s an example of a study that totally doesn’t matter. Does anyone really think that HFCS is harmless?

  • Samiam888

    Interesting choice not to simply duplicate the feeding timing. Why expose your study to these doubts? Are rats that expensive these days?

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  • Bagalagalaga

    The original paper also only mentions that in the short-term male rat experiment is when they observed the “less calories from HFSC gives more weight gain than the sucrose fed rats” effect, but they do not seem to keep track of total calories for the long term studies. Did they just assume that this held true for the male and female long term studies too? I think knowing the total calories becomes a big concern in the interpretation of Figure 4, which shows females with unlimited access to HFSC gain significant weight, but those with 12 hrs of sucrose OR HFSC do not.

    Overall I’d say it’s decently convincing that unlimited access to HFSC can lead to obesity, but I wouldn’t make the conclusion that it’s worse than sucrose from this, especially since the female rats had no change in ANY of the three categories , weight, body fat, or TG levels between the 12h sucrose and 12h corn syrup groups.

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  • It would be interesting if invert sugar was offered as a complement to sucrose and HFCS.

  • david tran

    seems like a poorly designed study to me.

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  • Jeff

    As I read the study, the rats were given full access to regular water in addition to sweetened water. I see no mention of the possibility that the lower concentration of the fructose made the HFCS solution more palatable to a thirsty rat, and therefore more likely to be a substitute to the regular water.

    I would be less likely to drink a syrupy drink when thirsty than pure water, but probably more likely to drink a diluted sweetened drink when thirsty.

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  • What about Dr. Lustig’s lecture explaining the physiology of HFCS ? Lots of PhD’s and experts working on this one. Long video but well worth the investment… I’ve watched it twice already. http://www.youtube.com/watch?v=dBnniua6-oM

  • So what about Dr. Lustig’s lecture explaining the physiology of HFCS ? Lots of PhD’s and experts working on this one. This is a long video about 90 mins, but well worth the investment… I’ve watched it twice already. http://www.youtube.com/watch?v=dBnniua6-oM

  • Unfortunately, I feel the bias, whether intentional of not, is the most likely source of disagreement over HFCS. People in the food industry have a huge financial stake in protecting HFCS, and I suspect an enormous amount of data would be necessary to’ persuade’ them that HFCS is contributing to our raising rate of obesity.
    On the other hand, I can see no reasons for bias on the part of the Princeton researchers…for the sake of our national health, please keep up the good work…

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  • JP

    “Unfortunately, I feel the bias, whether intentional of not, is the most likely source of disagreement over HFCS. People in the food industry have a huge financial stake in protecting HFCS, and I suspect an enormous amount of data would be necessary to’ persuade’ them that HFCS is contributing to our raising rate of obesity.
    On the other hand, I can see no reasons for bias on the part of the Princeton researchers…for the sake of our national health, please keep up the good work”

    Mark, while I am no proponent of over-sugared foods, I think this post is a bit naieve.

    A reason for bias on behalf of the Princeton researchers — future funding.

    Obesity is one of the pre-eminent medical issues of our day, and a major risk factor in so-many diseases and illnesses it is silly.

    A study establishing a link between a ultra-common sweetener and increased levels of obesity and other obesogenic factors would be a springboard for a plethora of future studies. Being the Phd and lab that established such a link would certainly give you a legup in very competitive grant applications.

    This is especially true in a down-economy, a First Lady committed to reducing obesity in America and a government searching for scientific solutions to America’s health and debt problems (which reducing obesity is a major factor in).

    I’m not accusing the authors of the study of any malfeasance. But, on the surface, there is plenty of reason for bias in interpreting the data, and in the very structure of such an experiment.

    And in the end, its the same reason as the food industry’s rote denials of such a link — money!

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