Category Archives: marion nestle

HFCS Follow-up: What the Rats at Princeton Can and Can’t Tell Us

Ed called my attention to last week’s press release about the study at Princeton currently getting some mass media attention. The press release claims:

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. 

i know it's a squirrel, not a rat. apparently no one's gotten a rat to do this and then circulated it with the right keywords to match my google search. this image likely not original to: http://ybfat101.com/notyourfault.shtmlThat’s pretty surprising, given that other studies have suggested that there is no difference between HFCS and sucrose. The Princeton study doesn’t offer a definitive explanation for the difference they found, but they suggest that it may have something to do with the slightly greater proportion of fructose in the HFCS.

As I noted in the first post on high-fructose corn syrup, HFCS-55, which is the kind used in soft drinks and the Princeton study, has roughly the same proportions of fructose and glucose as table sugar. Table sugar, or sucrose, is composed of fructose bonded to glucose so it’s a perfect 50-50 split. HFCS-55 contains 55% fructose, 42% glucose, and 3% larger sugar molecules. There’s a lot of evidence that fructose is metabolized differently than glucose, and may promote the accumulation of fat, especially in the liver and abdomen. Indeed, that’s why I believe that agave nectar is probably nutritionally worse than table sugar. Still, I’d be pretty shocked if a 5% increase in fructose could produce a statistically significant difference in weight gain, unless the rats were eating nothing but sugar-water. And they weren’t—in both of the experiments reported in the original study, the rats had access to unlimited “standard rat chow,”

Experiment 1: Rats Who Binge?

In the first experiment, 40 male rats were divided into four groups of ten. All of them had 24-hour access to rat chow and water. Group 1 was the control, so they just had chow and water. Group 2 had 24-access to an 8% solution of HFCS (.24 kcal/mL), which the press release claims is “half as concentrated as most sodas”. Group 3 had 12-hr access to the same HFCS solution. And Group 4 had 12-hr access to a 10% solution of sugar dissolved in water (.4 kcal/mL), which the press release claims is “the same as is found in some commercial soft drinks.” The two things of note so far are that none of the rats had 24-hr access to sucrose-sweetened water, and that the concentration of the sucrose was nearly 2x that of the HFCS syrup.*

Why the 24 hr vs 12 hr groups? According to the study:

We selected these schedules to allow comparison of intermittent and continuous access, as our previous publications show limited (12 h) access to sucrose precipitates binge-eating behavior (Avena et al., 2006).

In other words, they fed the sucrose group on a schedule that they already knew would cause binging. And they didn’t include a 24-hr sucrose group to control for that.

That helps to explain the results: the rats that had 24-hr access to HFCS-water gained less weight than either the rats who had 12-hr access to sucrose-water or the rats that had 12-hr access to HFCS-water. So according to the experiment, it’s better to consume some HFCS than it is to binge on sugar (not, obviously, how they chose to frame it in either the formal write-up or the press release).

Princeton rats

The only difference between the four groups in the first experiment that was statistically significant at a p<0.05 was between the rats who got chow only and the rats who got 12-hr HFCS. There was no statistically significant difference between the rats who had 12-hr access to sucrose-water and the rats who had 12-hr access to HFCS-water. There wasn’t even a significant difference between the rats who had 24-hr access to HFCS-water and the chow-only rats. So the only basis for the claim in the press release that HFCS is worse than sucrose is the fact that the rats with 12-hr HFCS got a “significant” amount fatter while the 12-hr sucrose rats didn’t. Even though the 24-hr HFCS rats didn’t either.

I am not the only one who’s picked up on this—both Marion Nestle (a vocal critic of the food industry) and Karen Kaplan (not, as far as I can tell, a shill for the Corn Refiners Association) also dispute the claim that this research demonstrates anything conclusive about HFCS vs. sucrose. The lead researcher replied to Nestle’s post, and rather than addressing the discrepancy between the 12-hr and 24-hr HFCS groups, he merely corrects her assumption that the 24-hr rats should be fatter:

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. –Bart Hoebel

Which just makes it all the more baffling why they didn’t include a 24-hr sucrose group. Additionally, according to their results, binging or “consuming more” doesn’t explain the results, because:

There was no overall difference in total caloric intake (sugar plus chow) among the sucrose group and two HFCS groups. Further, no difference was found in HFCS intake and total overall caloric intake in the groups given 12-h access versus 24-h access. Both groups consumed the same amount of HFCS on average (21.3±2.0 kcal HFCS in 12-h versus 20.1±1.6 kcal HFCS in 24 h), even though only the 12-h group showed a significant difference in body weight when compared with the control groups.

The only explanation they offer for these results is the slight difference in the amount of fructose the rats in the HFCS and sucrose groups consumed. But even that relies on the idea that the HFCS rats did not feel as satisfied by their sugar water and compensated by eating more:

…fructose intake might not result in the degree of satiety that would normally ensue with a meal of glucose or sucrose, and this could contribute to increased body weight.

Unless satisfaction itself makes rats thinner.

Experiment 2 (Males): Wait, Where’s the Sucrose?

In the first part of the second experiment, 24 male rats were divided into three groups of eight. Again, all three had unlimited chow and water. Group 1 had 24-hr access to the HFCS-solution, Group 2 had 12-hr access to the HFCS-solution, and Group 3 was the chow-only control. Sucrose, you’ll note, drops out entirely. According to the study:

Since we did not see effects of sucrose on body weight in Experiment 1 with males, we did not include sucrose groups in this long-term analysis in males.

But there were no effects of HFCS on body weight on the 24-hr schedule! The omission of sucrose from this experiment makes as much sense as the omission of a 24-hr sucrose group in the first one. The lead researcher’s reply to Marion Nestle’s criticisms offered no further clarification about this choice. 

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.

This study went on for 6 months instead of 2 months and, as the table above shows, the groups with both 24-hr and 12-hr access to HFCS-water gained a significantly greater amount of weight than the chow-only rats. This time, the 24-hr HFCS rats gained more weight than the 12-hr HFCS rats.

Experiment 2 (Females): Sucrose is back (still only 12-hr)! But chow is limited.

In order to “determine if the findings applied to both sexes,” they also ran a slightly different version of the second experiment on some female rats (n unknown). The control group, as usual, got unlimited chow and food. Group 1 got 24-hr access to HFCS-water. The remaining two groups got 12-hr access to chow (“to determine if limited access to chow, in the presence of HFCS or sucrose, could affect body weight”) and either 12-hr access to HFCS-water or 12-hr access to sucrose-water. Yeesh. How about testing one thing at a time, guys?**

So this time, only the rats with 24-hr access to HFCS gained a significantly greater amount of weight than the chow-only rats, which flies in the face of the claim that rats with limited access to a palatable food eat more. And the 12-hr sucrose rats actually gained slightly more weight (though not a statistically significant amount) than the 12-hr HFCS rats.

In other words, the findings in the three studies were completely inconsistent. For male rats in the short term, 12-hr access to HFCS induces significant weight gain but 24-hr access to HFCS does not. For male rats in the long term, both 12-hr or 24-hr access to HFCS induces significant weight gain, but they didn’t test sucrose. For female rats in the long term, only 24-hr access to HFCS with unlimited chow induces significant weight gain and limited chow, HFCS, and sucrose do not. And yet, based on this, they claim:

In Experiment 2 (long-term study, 6–7 months), HFCS caused an increase in body weight greater than that of sucrose in both male and female rats. This increase in body weight was accompanied by an increase in fat accrual and circulating levels of TG, shows that this increase in body weight is reflective of obesity.

Despite the fact that Experiment 2 didn’t even test the long-term effects of sucrose consumption on male rats, and 12-hr HFCS (albeit with limited chow) didn’t cause significant weight gain in female rats.

As Usual: Needs More Research

Based on the results of all three experiments, they conclude:

Rats maintained on a diet rich in HFCS for 6 or 7 months show abnormal weight gain, increased circulating TG and augmented fat deposition. All of these factors indicate obesity. Thus, over-consumption of HFCS could very well be a major factor in the
“obesity epidemic,” which correlates with the upsurge in the use of HFCS.

Despite the fact that obesity has also increased in many countries where HFCS is virtually never used, like Australia. According to a 2008 USDA paper:

Australia and the United States have a high and rising prevalence of obesity. They have opposite sugar policies: virtually no distortions affect Australia’s use of sugar, whereas sugar policy in the United States taxes sugar use. Sugar consumption per capita in Australia has been flat from 1980 to 2001, after which it increased by 10%-15%. Sugar is the major sweetener consumed in Australia.

The fact that the experiment doesn’t seem to show that HFCS is necessarily worse than sucrose doesn’t mean the findings aren’t intriguing. I really do want to know, for example, why rats with 12-hr access to HFCS gain more weight in the short term than rats with 24-hr access to HFCS, but the 24-hr HFCS rats gain more in the long term. And if, as they claim, the rats in all the groups consumed the same number of calories—which Nestle doubts because, "measuring the caloric intake of lab rats is notoriously difficult to do (they are messy)”—why were there any differences at all at the end of the trials? If none of the rats are eating more (and indeed, it seems that in some cases the HFCS rats were eating slightly less), what is the mechanism causing them to gain more weight, at least on some feeding schedules?

Does the concentration of the sugar have anything to do with it? In his reply to Nestle, Hoebel says:

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.

I want to know if that’s true for HFCS as well. And did the difference in the concentrations of the HFCS and sucrose drinks have anything to do with the difference in the rats’ weight in this study?

Or does it maybe have something to do with sucrase, the enzyme that splits the fructose and glucose in table sugar? From what I’ve read, sucrase is present in the human digestive tract in sufficient amounts that it doesn’t rate-limit the absorption of those sugars in sucrose compared to the consumption of free fructose and glucose. But is it somehow involved in metabolism or appetite-regulation?

So rather than answering any questions about HFCS vs. table sugar, this really just raises a lot of new ones.

*It’s also not clear why they gave them different concentrations of sweetener. You’d think they would make them both soda-strength, or at least calorically equivalent.

**The failure to control for multiple variables does, in fact, complicate their ability to make any conclusions about gender difference:

In the present study, male rats maintained on 12-h access to HFCS also gained significantly more weight than chow-fed controls, while female rats maintained on 12-h access did not. It is possible that this can be accounted for by the fact that these males had ad libitum chow, while the females had 12-h access to chow. It is possible that the lack of chow for 12 h daily suppressed weight gain and TG levels
that might have otherwise been elevated in the female 12-h HFCS access group. This would indicate an effect of diet rather than a gender difference.

Things that won’t kill you Vol. 2: Fruit juice

This may seem like a strange thing to argue about, because the popular consensus still seems to be that juice is healthy. Jamba Juice markets itself as "the category-defining leader in healthy blended beverages, juices, and good-for-you snacks." They even use Jamba as an adjective to mean the opposite of high fructose corn syrup and trans-fats (adding those things to juice ""just wouldn’t be Jamba"), which again, constructs the brand as healthy vs. the demon poisons that make people fat. Even if it’s foolish to go looking for truths in advertising, I don’t think Jamba Juice’s branding generally occurs to people as a massive irony or lie. Advocates of banning or restricting soda vending machines in schools often claim that the soda should be replaced with 100% fruit juice with no added sugars, and for many people, a glass of orange juice still represents "part of a nutritious breakfast" strongly with desirable nutrients like Vitamin C.

The Case Against Juice

But a number of health trends have begun cast suspicion on juice, especially the (impartial and incomplete) shift from primarily low-fat to primarily low-calorie and low-carb dieting in mainstream weight-loss culture, and the growing concern about the role sugars (especially fructose) play in personal and national obesity.

On the low-calorie front, people who believe that losing weight or maintaining a healthy weight is all about the basic algebra of calories-in vs. calories-out often end up axing all caloric beverages from their diets because they have a bad satiety-to-calorie ratio—I mean, obviously, right? Fruit juice is just fruit with some or all of the filling fiber removed. If the goal is maximum satiety on minimum calories, you’re better off eating whole fruit and drinking water or artificially sweetened beverages.

On the low-carb front, people who believe that what’s important is not how many calories you eat but what kind are also going to see juice (and sometimes most fruits and vegetables as well) as "unhealthy." It does seem to be true that diets high in carbohydrates drive up insulin levels, slowing metabolism and encouraging the body to store fat. And the overwhelming majority of the calories in most fruit juices are in the form of carbohydrates. Some green vegetable juices have protein content approaching 50% of the carbohydrate content, but that just makes it 75% bad rather than 100% bad, at least as true carbophobes are concerned.

And finally, there are some non-carbophobes who might avoid juice because they’re wary of sugar qua sugar, rather than sugar qua carbohydrate. The carbohydrates in fruit juice primarily take the form of fructose—wikipedia has a handy chart of the kinds of sugars in common plant foods. It doesn’t seem like there’s a true consensus yet about whether or not fructose is especially bad—despite recent studies linking fructose to obesity, even within the medical community, some people still advocate fructose as a "low glycemic" sugar that’s better for diabetics. It basically all comes down to whether you think the fact that fructose is digested in the liver and doesn’t trigger insulin production is a good thing or a bad thing. To link it to other sugar purveyors: pro-agave nectar people should also think that fruit juice is healthy and people who think hfcs is bad because they think it’s "high fructose" compared to other sugars are, well, a) wrong, but b) should also be advocating hfcs-sweetened sodas over fruit juices, which are even richer in sugar.

Personally, I think the evidence that fructose in large amounts causes equivalent blood sugar spikes to other sugar, increased "bad" cholesterol and triglycerides and signs of insulin resistance compared to glucose, and can cause non-alcoholic fatty liver disease consumed in vast quantities suggests that it is certainly no better and possibly much worse for human health than glucose or sucrose. But "worse for human health" is relative, not absolute, and depends a lot on amount, kind, and context. 

What is health?

I’m generally convinced by the argument made by people like Gary Taubes that a diet composed of almost-exclusively proteins and fats might better represent the pre-agricultural, hunter-gatherer diet (as would cyclical feast and famine) and prevent carbohydrate-induced insulin resistance and fat storage. Jared Diamond makes some of the same points in Guns, Germs, and Steel. But the benefits of agriculture ultimately outweighed the costs—both for the species as a whole and measured by individual health metrics. In the immediate aftermath of the transition to agriculture, lifespans and average height decreased, but after a few thousand years, people depending on rice, corn, and wheat began to get healthier again

Does that mean carbohydrates are a healthier basis for a diet than proteins and fats? No. But it does mean that people can (and do) live very long lives uninterrupted by diet-based disease during which they are strong and energetic enough to physically do anything they want to do while eating a diet consisting substantially of carbohydrates. And I think that’s not a bad working definition of "healthy."

It seems to me that the debate comes down to a difference between ideas about nutritional "health" based on what might be theoretically optimal (for a very limited set of criteria), ideas about health based on potential pathology, and ideas about health based on actual health outcomes

Fear of juice is based on the first two—the idea that either people should eat as few carbohydrates as possible in pursuit of some sort of optimal diet, or that the fructose in juice will cause fatness (an aesthetic problem, not a medical problem) or disease and eventually death. Based on actual health outcomes, I think it would be almost impossible to make a case for the claim that drinking fruit juice—occasionally or regularly—is categorically unhealthy or the direct cause of disease or death.

In fact, things like fruit juice and hamburgers and Doritos, which can each be constructed as "unhealthy" are hard to entirely rule out of a "healthy diet." Even proponents of a soda tax generally agree that the only reason soda is a reasonable target is because it has no identified nutrients (what would happen if they fortified them, I wonder?).

The nutrient-density of juice is the primary reason for the long tradition of juice being regarded as a health food. If your concern is about essential vitamins and minerals (like many older models of nutrition, which people like Marion Nestle stand by) or consuming carbohydrates for fuel, which many physically active people still do, it’s hard to argue with the healthfulness of juice. I agree with Michael Pollan’s claim that popular beliefs about health often fall prey to "nutritionism," or the attempt to reduce food and nutrition to scientifically-identified nutrients and vitamins. At the same time, I don’t think you have to be brainwashed by the continued prevalence of nutritionism to believe there’s good evidence that many of the nutrients that scientists have identified are actually valuable or promote health and well-being (even if they’re not the only valuable aspects of food).

All juices are not created equal

The person who requested this entry was concerned specifically about fresh juices being portrayed as unhealthy, because they seem to have been smeared by concerns about packaged juices being just other source of dietary sugar.

While not all fruits lend themselves as readily to the production of refined sugars as sugar beets, some like apples, pears, and grapes can be turned into a nutrient-poor sweetener without most of the fruits’ color, flavor, or minerals and many fruit juices marketed as 100% natural fruit juices, like Juicy Juice, are sweetened with fruit juice that’s basically been turned into a sugar syrup. The nutritional distinction between those drinks and hfcs-sweetened soda is probably negligible regardless of whether your primary concern is calories, carbohydrates, sugar, or vitamins.

But the reason packaged juices often combined with fruit-based sugar is that many fruit juices aren’t actually that sweet on their own, or their sweetness is offset by the intensity of the flavor, as anyone who’s ever tried 100% cranberry or concord grape or cherry or blueberry juice knows. The fresh juices you can get at juice bars or make at home are calorie-dense, but they’re also extraordinarily nutrient dense and not likely to be consumed in quantity or alongside meals. They’re more often enjoyed on their own, like a snack, particularly after a workout—basically just like fruit. When you leave in some of the pulp, it becomes even less nutritionally distinct from fruit, and when you include vegetable juices or the juices of things like wheatgrass and ginger which are difficult or unpleasant to eat raw, you may be enjoying something that could, by some criteria, be healthier than a piece of fresh fruit.

Some juices even have pretty well-established medicinal uses. Cranberry juice, for example, can help prevent and cure urinary tract infections (that study notes the existence of "diet" cranberry juice, which I’d never heard of, but now that I have I wonder why there aren’t more "diet" juices sweetened with artificial sweeteners rather than pear or grape juice-sugar. Not that those would necessarily be "healthy" by everyone’s standards, especially given the links between saccharin and cancer and suspicions about the healthfulness of aspartame and sucralose…)

Ultimately, while I don’t think even the occasional hfcs-sweetened Capri Sun is incompatible with a "healthy" diet and life, I think it’s unreasonable to conflate fresh juice without added sweeteners with juices sweetened with refined juice-sugar. I guess people trying to eat an "optimal" diet a la Gary Taubes should avoid all juices, fresh or no, but I don’t envy them their carbohydrate-less life, nor am I convinced that the total deprivation of many foods that have aesthetic, gustatory, social and/or cultural value is necessarily "healthy" or "optimal" either. For the vast majority of people who think fruit and vegetables are part of a healthy diet, fruit juice and especially fresh fruit juice should also pass muster as a "healthy" choice especially when consumed in moderation, which I suspect fresh fruit juices usually are.