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. 

That’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).

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. Read more

This entry was nearly titled “Things That Might Not Kill You In Moderation But Certainly Won’t Make You Any Healthier Vol. I,” or “Hydrolyzed, Refined Sweeteners Masquerading as ‘Natural,’ Whole Foods,” but those seemed a little unwieldy. They do, however, capture the essence of the argument: agave is nutritionally no better than most other refined sweeteners, including high-fructose corn syrup (HFCS). If anything, it’s probably worse because it contains more fructose than table sugar or HFCS. It’s also no more or less “natural” than HFCS—it’s actually produced in a remarkably similar process that was first used on the fibrous pulp of the agave in the 1990s. While, as its proponents claim, the higher proportion of fructose has enabled people to call it a “low glycemic index sweetener,” sometimes alleged to be safer for diabetics and recommended by weight-loss programs like Weight Watchers, recent research suggests that large amounts of fructose aren’t healthy for anyone, diabetic or otherwise.

I mentioned agave nectar in passing in the HFCS post, but there’s enough conflicting information about it to merit its own post(s). A lot of the misinformation comes from agavevangelists, who can sometimes get a little sanctimonious about their avoidance of the demon HFCS and preference for “natural” sweeteners. Even this Vegfamily article that concludes “the physiological effects of all [caloric] sweeteners are similar” nonetheless claims:

Given the choice between sugar, HFCS, and agave nectar, I'll stick with organically-grown, unbleached cane sugar (evaporated cane juice) and organic raw agave nectar that are free of pesticides, herbicides, and chemical bleaching agents; not genetically engineered; and still retains some nutrients, as well as being vegan. Since HFCS is not available in organic form and is highly processed, I would never use it.

But agave nectar is just as processed as HFCS.

HFCS and Agave Nectar: One of These Things is Not Almost Exactly Like The Other

Like most starches, corn starch consists of large glucose polymers—70-80% the branched, non-water soluble amylopectin and 20-30% linear, soluble amylose. Normal or non-HFCS corn syrup, like Karo, is produced by breaking those polymers down into their constituent glucose molecules using acids, enzymes, and/or heat. For the history buffs: the acid hydrolysis of starch was first discovered because of the 1806 British blockade of the French West Indies. Napoleon I offered a cash reward for anyone who could come up with a replacement for cane sugar, and a Russian chemist named Konstantin Kirchhof found he could produce a sweet syrup from potato starch by adding sulfuric acid. The same process was first applied to corn in the mid-1860s, and gained popularity in the U.S. during the sugar shortages of WWI (source: The Oxford Encyclopedia of Food and Drink in America).

HFCS is produced by converting the glucose into fructose using an enzyme technology developed in Japan in the 1960s (detailed here). The resulting syrup, which contains up to 90% fructose, is then typically mixed with corn-based glucose syrup to produce HFCS-55 (the kind used in soft drinks, which has 55% fructose/45% glucose) or HFCS-45 (the kind used in baked goods, which has 45% fructose/55% glucose). Some people, like Cynthia commenting on Daily Candor, have suggested that the fructose and glucose in HFCS are absorbed into the bloodstream faster because they’re “free" instead of bound the way they are in the disacccharide sucrose, which is broken into glucose and fructose by the enzyme sucrase. Theoretically plausible, but apparently not true:

Sucrose is hydrolysed by brush-border sucrase into glucose and fructose.
The rate of absorption is identical, regardless of whether the sugar is presented to the mucosa as the disaccharide or the component monosaccharides (Gray & Ingelfinger, I 966, cited by H. B. McMichael in “Intestinal absorption of carbohydrates in man”).

Just like HFCS, agave nectar is produced by breaking down a plant-based polymer into its constituent sugars. In the case of agave, the relevant molecule is inulin, a fiber composed mostly of fructose units with a terminal glucose. Just like with corn and potato starch, there are different methods of hydrolyzing the sugars in inulin.  Blue Agave Nectar uses a thermic process. Madhava uses an enzyme process, just like HFCS.

Agavevangelists like to claim that agave nectar is a traditional sweetener used by native peoples, which appeals to the popular notion that the foodways of the past were generally healthier (e.g. Michael Pollan’s advice not to eat anything your great-grandmother wouldn’t recognize as food). Some, like Lynn Stephens of Shake Off the Sugar, merely note that the agave plant itself “has long been cultivated in hilly, semi-arid soils of Mexico.” That’s true, although it’s about as relevant as the long history of corn cultivation. Others claim that agave nectar itself has an ancient history. Flickr user Health Guy says of agave nectar: “It is 1-1/4 times sweeter than sugar, so you need less, and it has been consumed by ancient civilizations for over 5,000 years.”

Wrong. According to the website for Madhava Honey:

Agave nectar is a newly created sweetener, having been developed during the 1990's. Originally, the blue agave variety was used. This is the same plant used in the manufacture of tequila. During the late 90's, a shortage of blue agave resulted in huge increases in cost and a sweetener based on this plant became uneconomical. Further research was done and a method using wild agave was developed. Overcoming the language barrier between the Indians able to supply the nectar from the wild agave on their land and the Spanish speaking local manufacturer was the key that finally unlocked a supply of raw material and has led to our bringing this wonderful new product to market.

Still doing some native-washing (wild agave harvested by Indians who don’t speak Spanish—can’t you just feel the virtue?), but here’s what happens to the agave sap after harvesting, as described in the abstract of the 1998 patent issued for the production of fructose syrup from the agave plant:

A pulp of milled agave plant heads are liquified during centrifugation and a polyfructose solution is removed and then concentrated to produce a polyfructose concentrate. Small particulates are removed by centrifugation and/or filtration and colloids are removed using termic coagulation techniques to produce a partially purified polyfructose extract substantially free of suspended solids. The polyfructose extract is treated with activated charcoal and cationic and anionic resins to produce a demineralized, partially hydrolyzed polyfructose extract. This partially hydrolyzed polyfructose extract is then hydrolyzed with inulin enzymes to produce a hydrolyzed fructose extract. Concentration of the fructose extract yields a fructose syrup. (via Patentstorm)

It’s true that the corn used in HFCS is less likely than agave to be organically-grown, but you can get organic-certified corn syrup from the same manufacturer as the blue agave nectar pictured above and nutritionally, the main difference between that, the HFCS used in most processed foods, and agave nectar is the ratio of glucose: fructose. The regular corn syrup is 100% glucose, HFCS is usually 55/45 glucose/fructose, and agave nectar 56-90% fructose, depending on the plant and the process.

I’ve already talked a little about fructose vs. glucose here and here, but more coming soon in Agave-rant Part II concerning:

1) whether the fructose in agave is somehow better than, or indeed, different in any way from the fructose in HFCS

2) whether the fact that it’s sweeter than sugar makes it a lower-calorie alternative to sugar

3) whether its “low glycemic index” rating makes less likely to produce insulin resistance than table sugar and

4) whether it’s safer for diabetics

All of which people have claimed. I won’t keep you in suspense, especially given how long it may take me to put all of that together. The short answers are:

1) not in any nutritionally meaningful way

2) perhaps very slightly, but a <10 calorie/serving difference likely doesn’t make up for the increased risk of fatty liver syndrome and insulin resistance

3) no, it’s actually more likely to produce insulin resistance and

4) in miniscule amounts, perhaps, but recent trials involving diabetics and agave nectar were halted because of severe side effects.