Can Obesity Be Predicted? Does Inactivity Cause It? And What About Corn Syrup?

The latest nutrition news tells us more about the state of the science (and the reporting) than it does what we need to know.

Today’s quiz. Three of the questions are based on the latest nutrition news. The 4th (for paid subscribers) is about a bigger issue.

1. If your doctor told you they had a genetic test that could predict your children’s adult obesity risk, would you have them take it?

2. Does inactivity make us (too) fat and, well, how long have we known the answer to that question?

3. Is the world a less obesogenic place if we can drink our Cokes sweetened by cane sugar rather than high fructose corn syrup?

4. If someone has been funded by industry, can we trust their science?

The short answers: 1) I certainly wouldn’t; 2) no and, well, for at least a century; 3) not in my book (literally), and 4) depends on the person, doesn’t it?

Now let’s get to the longer answers, beginning (as usual) with a preamble.

Every once in a while, I find myself feeling profound sympathy for reporters on the nutrition, obesity, and chronic disease beat. They have a supply and demand problem.

They’re hired because these subjects are catnip for readers. Eating Healthy. Losing Weight. The demand for nutrition news is high. The reporter’s job is to fill that demand, even as the supply of legitimate news is invariably, hopelessly low.

This isn’t sports, after all, or politics or crime, beats in which something new happens daily. It’s science, progressing, as it does, like a stock market, with daily fluctuations around long-term trends, punctuated every few dozen blue moons by unpredictable shifts to new baselines. Whatever prompts those shifts would be real news, but only in rare exceptions (new drugs like the GLP-1 drugs for weight loss, the results of major clinical trials, etc.) can a reporter even suspect that in advance.

So the reporters on the health beat have embraced what may be their only option: rather than write about what is legitimately new and noteworthy, they cover what the journals publish. The endless supply of new articles solves the supply and demand problem, so long as they don’t think too critically about the implications of the articles. If your job is to report weekly on nutrition and obesity, then you have to assume that at least one article published weekly is newsworthy.

Another critical issue in this supply-and-demand problem is also on the supply side: The researchers, too, have an obligation to publish new research. That is, after all, their job, and they have graduate students who need publications to complete their degrees and secure their own jobs. So, on some level, much of academic research becomes indistinguishable from a paper mill. While the ideal is that the papers represent meaningful science, the papers themselves are the product.

There will always be exceptions—real, meaningful research—which is why the scientific community tolerates this kind of situation, but that meaningful research is the stuff that is few and far between.

Along these lines, one of the memories that I cannot shake from my long career as a journalist is from a 2008 symposium on medical and health reporting. The audience was young journalists on the health beat, and their publications had sent them to this symposium so they could be taught how to think more critically about the subjects they’d be tackling. This was shortly after Good Calories, Bad Calories was published, and I was one of the speakers, as was an editor high on the masthead of the New England Journal of Medicine. Between presentations, this editor and I were discussing the supply and demand issue.

What she said to me was that her journal, the NEJM, had a surprisingly difficult time getting enough good papers to fill its pages every week, even though the NEJM was the single most prestigious and influential biomedical journal in the world.

“Imagine,” she added, “the shit the other journals must be publishing.”

The latest news: obesity prediction and the value of exercise

Ok, with that preamble out of the way, here’s the latest news. First, the New York Times with a story that the Washington Post didn’t bother to cover:

And then the Washington Post, with a “major new” study that the Times didn’t see fit to cover:

Let’s start with the Times and the idea that we might prevent obesity by predicting it in childhood. This study was published in Nature Medicine. The reporter is my old friend Gina Kolata (i.e., we have clashed publicly in the past), and here’s her lede:

Researchers have known for decades that genetics may be more powerful than environment in predicting who will develop obesity. Identical twins tend to have the same body mass index, even if they are reared apart. Adopted children tend to have a degree of obesity similar to their birth parents rather than their adoptive ones.

Identifying the genetic roots of obesity could aid with prevention starting in childhood. But finding a genetic footprint for obesity has proved challenging. With rare exceptions, there’s not one gene or even a few that are the culprits. Instead, obesity is spurred by thousands of gene variants acting in concert. Each variant exerts a tiny effect.

….“There is definitely predictive value in genetics,” Dr. [Joel] Hirschhorn [an author of the paper and a professor of pediatrics and genetics at Boston Children’s Hospital] said. And, he added, with the new study, “we are now a lot closer to being able to use genetics in a potentially meaningful predictive way.”

This was the kind of huge collaborative study that’s a fixture of modern medical science. The researchers used genetic data from over 5 million people, which means multiple large datasets collected by researchers around the globe. The result is hundreds of authors from hundreds of institutions funded by dozens, if not hundreds, of funding agencies.¹

The databases include not just the sequenced DNA from the individuals but also their body mass index. That allowed the researchers to look for particular gene variants that associate with body weight, and then combine different variants, weighted to reflect the size of the association, into a polygenic score, PGS, that could, in theory, predict whether or not other lean individuals were likely to someday become obese. An important point here is that the researchers doing this kind of exercise learn nothing about what these genes do, the mechanism of the “tiny effect” they exert, only how different variants of that gene associate with body weight.

Once the researchers had their candidate PGS, they honed the predictive power in other datasets—now including kids and adults of different ethic and national backgrounds—and finally on the participants from two major clinical trials. This was all very impressive. The numbers involved were huge, and I could imagine why Kolata and the Times would think of this as newsworthy. But we haven’t gotten yet to what we learned and the implications.

The end result, the polygenic score, can be thought of as a test that can someday be given to children to predict some of their future obesity risk. The score only accounts for a third of the genetic risk, says Hirschorn in The Times, but they are now “a lot closer to being able to use genetics in a potentially meaningful predictive way.”

What does Hirschorn mean by a “potentially meaningful predictive way?” Well, if your child’s PGS is high, say in the top 10%, then that means your child would have roughly a 50-50 chance of becoming obese in adulthood. A coin toss. If it’s low or very low, that chance might be one in ten.

Now, here’s a reasonable question to ask: What would we do with that information?

Maybe it’s my lack of imagination, or my lack of medical training, but I don’t see the value. Most of us know if we struggle with our weight, without the help of a genetic test. I’d bet that those parents who bother to think about it know whether their children do. If immediate members of the family do, that will be pretty telling.

Kolata is mostly right when she says we have known for decades “that genetics may be more powerful than environment in predicting who will develop obesity.” We have known that since the late 1800s, when European physicians writing about obesity would observe that some very large proportion of their obese patients had obese, diabetic, or gouty family members.

That obesity runs in families and so has a large genetic component—today considered equivalent to that of height—is one of the oldest observations in the business. This is from an 1891 article in a British medical journal: “In endeavouring to ascertain the reason why some people are corpulent and others not, we must realise at once that the condition is markedly hereditary. As one breed of pigs is noted for the ease with which it fattens, so with men.”² So here’s another reasonable question: Would a polygenic score do a better job at predicting obesity than a look around the immediate family?

For the sake of argument, let’s imagine we had a PSG that told us with absolute certainty whether a child was going to be lean or obese as an adult—not a 50-50 chance, but absolute certainty—what should the parents do about it?

I cannot foresee a world in which we start our children on drug therapy while they’re still lean because their polygenic risk score predicts they’re going to someday become obese. (If they’re not lean or no longer lean, we don’t need the PSG test.) I hope to never see a world in which parents put their still-lean kids on calorie-restricted diets because their PGS is grim. As for the more benign treatment of teaching the kids to eat healthy or avoid unhealthy foods—however we define those, which is the subject of many of my posts—I would hope the parents are doing that regardless of the PGS.

What about sedentary behavior? Surely that makes us fatter?

The Washington Post says no, and credits that “major new study,” published in the Proceedings of the National Academy of Sciences, with finally clarifying the issue.

For decades, common wisdom and public health messaging have assumed that people in highly developed nations, like the United States, are relatively sedentary and burn far fewer daily calories than people in less-industrialized countries, greatly increasing the risk for obesity.

But the new study says no. Instead, it finds that Americans, Europeans and people living in other developed nations expend about the same number of total calories most days as hunter-gatherers, herders, subsistence farmers, foragers and anyone else living in less-industrialized nations.

The first critical point about this study is that the authors—led by Herman Pontzer, a professor of evolutionary anthropology at Duke—are energy balance people. They study energy expenditure because they think it might explain why we get fat, and they think it might because they believe, as Pontzer and his co-authors state unequivocally [albeit with my italics], that “[f]undamentally, weight gain results from consuming and absorbing more calories than are expended.”

These researchers do not see their job as explaining the biological mechanisms that induce some of us to fatten and others not, because they believe that the energy imbalance concept already explains that. Some of us consume and absorb more calories than we expend, and some don’t. With that settled, they see their job as determining how the imbalance plays itself out: i.e., what role the consuming and absorbing play, and what role the expending.

“Public health organizations typically attribute this imbalance to both reduced physical activity energy expenditure (AEE) and dietary changes promoting overconsumption,” Pontzer et al tell us. And they add that “daily physical activity has declined within industrialized populations over the past few decades as economic development increased.”

But can that explain the coincident increases in obesity?

So Pontzer and his colleagues dipped into their databases, in this case those that had data on both daily energy expenditure (measured by a technique called doubly-labeled) and body mass. In total, they had the necessary data from over 4200 individuals, from 34 populations around the world representing “a wide spectrum of economic development, including hunter-gatherers, pastoralists, farmers, and people in industrialized countries.” And then they could compare the numbers for the different populations to see what it told them.

Their conclusion: individuals from the industrialized populations were indeed bigger, fatter, and heavier than those from the non-industrialized societies—the farmers, pastoralists, hunter-gatherers—but they expended essentially the same amount of energy, at least when the expenditure was corrected for the bigger bodies. According to Pontzer and his colleagues, hunter-gatherers and agropastoralists in equatorial Africa had “size-adjusted” daily energy expenditures equivalent to folks in Norway and the U.S.. Agropastoralists in Siberia had size-adjusted TEEs “ on par with cohorts from the Gambia, Australia, and Switzerland.”

In short, this idea that populations get fatter—the U.S., for instance—because our livelihoods require no physical activity doesn’t hold up. I’m not surprised.

One way to look at this is to consider the possibility that energy balance thinking has led us down a blind alley, as I believe it has. But this perspective is not exactly in fashion, and it’s certainly not embraced by Pontzer and his co-authors.

They take the easier way out. If energy expenditure can’t explain why industrialized nations tend toward obesity and the non-industrialized societies don’t, then it must be how much we’re eating. If it’s not expenditure, it must be intake. Here’s Pontzer et al:

Our analyses suggest that increased energy intake has been roughly 10 times more important than declining total energy expenditure in driving the modern obesity crisis.

Or as the Post summarizes it:

In other words, we’re eating too much.³

To their credit, Pontzer et al do discuss the conspicuous limitation of their analysis: these are all associations. They say nothing about causality:

The data in this study are cross-sectional and we lack detailed dietary data for most of the populations in this dataset. We therefore cannot establish causality in the relationships between economic development, body fat percentage, and dietary intake. We also cannot resolve the environmental, societal, and physiological factors promoting increased caloric intake and absorption.

And to the Post’s credit, the article concludes with quotes from influential public health authorities saying, in effect, “we knew this all along,” which we did.

“It’s clear from this important new research and other studies that changes to our food, not our activity, are the dominant drivers of obesity,” said Dariush Mozaffarian, director of the Food is Medicine Institute at Tufts University…

But Mozaffarian is being a bit disengenuous here. Obesity researchers have known this, too, for over a century. No important new research or major studies were necessary to confirm it. The problem is that the energy balance thinking always implied it, and so the authorities kept ignoring the actual evidence.

Much of the progress in obesity research from 1900 through 1930 was establishing that no matter how they measured energy expenditure, obese individuals, because of their bigger bodies, burned off at least as many calories as lean individuals did. These researchers (again, mostly European) measured all the various facets of energy expenditure that researchers still measure today (albeit without the advantages of the doubly-labeled water technique) and concluded that none provided meaningful information about why some people struggled with their weight and others didn’t.

In this case, we didn’t have to rely on studies like Pontzer’s to observe associations between sedentary behavior and body weight regulation because we had clinical trials. By the 1990s, it was clear that if physical activity had any effect on body fat accumulation, it was trivial. (You can see the numbers circa 2019 in this Cochrane Collaboration review, although the authors do add a wildly optimistic spin to them.)

My favorite example was a Danish trial published in 1989. The Danes went through the considerable effort of training couch potatoes to run marathons. After 18 months of training and after actually running a marathon, the eighteen men in the study had lost an average of five pounds of body fat. As for the nine women subjects, the Danes reported, “no change in body composition was observed.” Why not? As the trainees became physically active, they also became hungrier. Back in the era of common sense, we would have said that they worked up an appetite. So they ate more to compensate for the energy expended in the workout.⁴

I admit that criticizing a study like Pontzer’s or the Post’s coverage of it on the basis that we’ve known all this for a century is not particularly fair, because most obesity researchers (and journalists) don’t know this history. Moreover, the world is, indeed, still full of influencers (many of them physical trainers) who insist that exercise is the key to body weight control and that sedentary behavior drives obesity (because, well, it’s calories-in minus calories-out). So maybe the Washington Post is right that this is still a commonly held belief. If the editors think that debunking it, though, on a population-wide level is going to change this thinking any more than a century of common sense or clinical trials did, they’re far more optimistic than I have ever been.

How about actual news? MAHA takes on high fructose corn syrup.

Deferring to The New York Times:

With one Truth Social message from President Trump, high-fructose corn syrup became the most talked-about ingredient of the summer.

The president surprised nearly everyone last week — including executives at the Coca-Cola Company — when he announced that Coke would start using cane sugar. “You’ll see,” he wrote. “It’s just better!” In the United States, almost all Coke is made with high-fructose corn syrup.

As a result, Coca-Cola is reintroducing Coke sweetened with cane sugar rather than high fructose corn syrup (HFCS). This move prompted Robert F. Kennedy Jr. to proclaim on X: “MAHA is winning.”

But are they? And what did Trump mean by “better”? Taste better? Is he one of these people who has always preferred Mexican Coke because it’s made with cane sugar? Or did he mean it’s healthier, which is what put this story in the MAHA wheelhouse?

The Times headline on this story does reflect an encouraging shift in perspective. It does not ask if sugar is healthier than HFCS. It asks if HFCS is “worse for you than sugar?” The former implies one might be benign and the other not, which was the (sort of) thinking of 20 years ago. The latter implies neither is benign, and asks which is worse. That aligns with my thinking (and my writing in the Times).

The answer to either question, though, is that it’s hard to imagine it makes the slightest difference.

To make a long story very short, cane and beet sugar are both sucrose, a molecule of fructose bonded to a molecule of glucose. High fructose corn syrup, as it’s used most commonly in beverages, is known as HFCS-55 because it’s supposed to be 55% fructose and 42% glucose, with the other 3 percent being various other sugars (maltose, for instance).

As I wrote in my 2016 book The Case Against Sugar, the corn refiners settled on this balance of fructose and glucose because it came closest to tasting like sugar/sucrose when used in, well, Coca-Cola. Beginning in the mid-1980s, the beverage industry switched over to using HFCS rather than sugar because it was reliably cheaper and would stay that way. Here’s how that story played out:

Because the introduction of HFCS-55 roughly coincided with the beginning of the obesity epidemic in the U.S., researchers and journalists later suggested that HFCS was the cause, implying that it was somehow distinct from sugar itself. HFCS was promptly demonized as a particularly pernicious aspect of the diet—“the flashpoint for everybody’s distrust of processed foods,” as the New York University nutritionist Marion Nestle has described it—and that’s often still considered to be the case. This is why cans of Pepsi sweetened by sucrose rather than high fructose corn syrup proudly proclaim that they contain “natural sugar.” Paul Newman’s lemonade, sweetened with sucrose (“cane sugar,” as the label says), proclaims prominently on the carton that it contains “no high fructose corn syrup.”…

All of this controversy, however, while it may benefit the sugar (sucrose) industry in particular, serves only to obfuscate the key point… Our bodies appear to respond the same way to both sucrose and HFCS. In a 2010 review of the relevant science, Luc Tappy, a researcher at the University of Lausanne in Switzerland who is considered by biochemists who study fructose to be among the world’s foremost authorities on the subject, said there was “not the single hint” that HFCS was more deleterious than other sources of sugar.

This is why I tend toward pessimism about how Trump and the MAHA movement are approaching the chronic disease epidemics in America. Like the MAHA front against food dyes, there’s always a possibility that getting rid of these industrial ingredients will make our diets incrementally healthier. But what happens when Coca-Cola follows in the footsteps of Pepsi and Paul Newman’s lemonade and implies that their product is benign because it’s HFCS-free? I’ve said the same about food-dye-free Fruit Loops. Should we consider these cereals benign because they’re absent the troublesome dyes but still contain relatively massive amounts of sugar?

At some point, Trump and the MAHA folks will have to take on the heavy lifting to both promote and fund the science necessary to establish what is causing the obesity and diabetes epidemics. Is it just calories, as Marion Nestle, grand dame of nutrition policy, suggests to the Times (yet again) in this HFCS article? (“The thing that counts is the amount of calories sugar adds,” she is quoted as saying. “But nobody talks about calories.”) Is sugar poison, as RFK Jr has said. (I wish he’d said “sugar may be poison,” implying the need for research to determine unambiguously whether it is.) Is it the glycemic index of the carbs? The seed oils? Environmental contaminants? Food dyes!? The world is full of hypotheses, and they need to be tested.

Can we trust a scientist who takes money from industry?

Now, for paid subscribers or those who want to support my work and become paid subscribers, my brief take on industry-funded researchers. This is a critically important subject, and it cries out for lengthy discussion. I’ll get to that in a future post, but first, I wanted to share a recent discovery: the single best conflict of interest statement I’ve ever seen in the peer-reviewed medical literature