[PART I – MYSTERIES]
[PART II – CURRENT THEORIES OF OBESITY ARE INADEQUATE]
[PART III – ENVIRONMENTAL CONTAMINANTS]
[INTERLUDE A – CICO KILLER, QU’EST-CE QUE C’EST?]
[PART IV – CRITERIA]
[PART V – LIVESTOCK ANTIBIOTICS]

In his book The Hungry Brain, neuroscientist Stephan Guyenet references a 1965 study in which volunteers received all their food from a “feeding machine” that pumped a “liquid formula diet” through a “dispensing syringe-type pump which delivers a predetermined volume of formula through the mouthpiece.” He devotes about three pages to the study, describing it like so:

What happens to food intake and adiposity when researchers dramatically restrict food reward? In 1965, the Annals of the New York Academy of Sciences published a very unusual study that unintentionally addressed this question. …

The “system” in question was a machine that dispensed liquid food through a straw at the press of a button—7.4 milliliters per press, to be exact (see figure 15). Volunteers were given access to the machine and allowed to consume as much of the liquid diet as they wanted, but no other food. Since they were in a hospital setting, the researchers could be confident that the volunteers ate nothing else. The liquid food supplied adequate levels of all nutrients, yet it was bland, completely lacking in variety, and almost totally devoid of all normal food cues.

The researchers first fed two lean people using the machine—one for sixteen days and the other for nine. Without requiring any guidance, both lean volunteers consumed their typical calorie intake and maintained a stable weight during this period.

Next, the researchers did the same experiment with two “grossly obese” volunteers weighing approximately four hundred pounds. Again, they were asked to “obtain food from the machine whenever hungry.” Over the course of the first eighteen days, the first (male) volunteer consumed a meager 275 calories per day—less than 10 percent of his usual calorie intake. The second (female) volunteer consumed a ridiculously low 144 calories per day over the course of twelve days, losing twenty-three pounds. The investigators remarked that an additional three volunteers with obesity “showed a similar inhibition of calorie intake when fed by machine.”

The first volunteer continued eating bland food from the machine for a total of seventy days, losing approximately seventy pounds. After that, he was sent home with the formula and instructed to drink 400 calories of it per day, which he did for an additional 185 days, after which he had lost two hundred pounds —precisely half his body weight. The researchers remarked that “during all this time weight was steadily lost and the patient never complained of hunger.” This is truly a starvation-level calorie intake, and to eat it continuously for 255 days without hunger suggests that something rather interesting was happening in this man’s body. Further studies from the same group and others supported the idea that a bland liquid diet leads people to eat fewer calories and lose excess fat.

This machine-feeding regimen was just about as close as one can get to a diet with zero reward value and zero variety. Although the food contained sugar, fat, and protein, it contained little odor or texture with which to associate them. In people with obesity, this diet caused an impressive spontaneous reduction of calorie intake and rapid fat loss, without hunger. Yet, strangely, lean people maintained weight on this regimen rather than becoming underweight. This suggests that people with obesity may be more sensitive to the impact of food reward on calorie intake.

In his review of the Hungry Brain, Scott Alexander provided a more concise description of the same study: 

In 1965, some scientists locked people in a room where they could only eat nutrient sludge dispensed from a machine. Even though the volunteers had no idea how many calories the nutrient sludge was, they ate exactly enough to maintain their normal weight, proving the existence of a “sixth sense” for food caloric content. Next, they locked morbidly obese people in the same room. They ended up eating only tiny amounts of the nutrient sludge, one or two hundred calories a day, without feeling any hunger. This proved that their bodies “wanted” to lose the excess weight and preferred to simply live off stored fat once removed from the overly-rewarding food environment. After six months on the sludge, a man who weighed 400 lbs at the start of the experiment was down to 200, without consciously trying to reduce his weight.

This study is especially meaningful for Guyenet because he favors a “food reward” explanation of the obesity epidemic, where obesity is at least partially the result of really delicious foods that make us want to eat a lot of them. He says that foods like “ice cream, brownies, french fries, chocolate, and bacon” have the ability to “powerfully drive cravings, overeating, and eventually, deeply ingrained unhealthy eating habits.” On the other hand, foods like “fruit, vegetables, potatoes, beans, oatmeal, eggs, plain yogurt, fresh meat, and seafood“ are “still enjoyable but they don’t have that intensely rewarding edge.” 

First of all, how dare he say that about potatoes. But second, while this study is not exactly the cornerstone of Guyenet’s argument, it does seem especially important evidence for the food reward perspective.

We wanted to review this study when we were writing A Chemical Hunger, but we couldn’t find the original paper, and since we couldn’t confirm the results for ourselves, we decided not to include it in the piece.

But now, reader Sam Marks (thank you Sam!) has found us a copy of the study! Finally able to review it, we offer this special interlude for your reading pleasure. (If you want to read the study for yourself, email us and we would be happy to send you a copy.)

Before we review, however, we want to offer our initial impressions. This study was performed in 1965, which means that it was decidedly pre-obesity-epidemic. In Part I, we review the evidence that obesity rates were stable until about 1980, when they suddenly started increasing. We think that this is evidence that modern obesity occurs for different reasons than historical obesity did. The people in this study probably were not obese for the same reason(s) people are obese today, so the same rules may not apply. 

In addition, studies from 1965 are not known for being super reliable. Back in 1965, sample sizes were small, teams had limited resources, and statistical analyses were more on the casual side.

STUDIES IN NORMAL AND OBESE SUBJECTS WITH A MONITORED FOOD DISPENSING DEVICE

Let’s take a look and see what we can learn about a diet of “homogeneous nutritionally adequate formula emulsion” (henceforth “nutrient sludge”). To give you the full experience, we will begin by covering the paper blow-by-blow. 

The authors begin by describing how they are jealous of experimental psychologists, who back in those days were still putting rats in Skinner boxes. These animal researchers could get “detailed and accurate information concerning rate of food ingestion, size of meals and intervals between feedings” by giving rats a lever which would dispense one food pellet when pushed, and using electronic monitoring equipment to record each time the lever is pressed.

To this end, the authors developed a device of their own, which dispenses food to human subjects at the press of a button, and secretly records the date and time of each “delivery” on a device “in a room remote from the subject who is kept unaware of its existence.”

The feeding machine … consists of a reservoir containing a liquid formula diet. The formula mixture is constantly mixed by a magnetic stirrer.

Yum.

Whenever the button is pressed, 7.4 ml. of formula are delivered directly into the mouth of the subject by the punp. [sic]

This is hilarious. 

They don’t say much about the nutrient sludge, only that it was “provided as ‘Nutrament’ through the courtesy of Warren M. Cox, Mead Johnson Research Laboratories, Evansville, Ind.” and that “carbohydrate contributed 50 per cent of the calories, protein 20 per cent and fat 30 per cent.“

Let’s meet the participants. In this study, they tested the feeding device (yikes) on both “normal-weight” and obese people.

The first normal-weight subject studied was well suited to the feeding machine because a severe deformity of his mouth made ingestion of normal food difficult. … His daily calorie intake did not vary appreciably, averaging 3075 ± 438 (S.D.) calories per day.

And:

A healthy 20 year-old volunteer subject also readily maintained his body weight during a nine-day period on the machine consuming an average of 4430 calories per day.  

And:

The results obtained in one individual, a 27-year-old man, are shown in FIGURE 4. Initially, he weighed 400 pounds. 

The response to feeding by machine of another obese subject, a woman aged 36, is shown in FIGURE 5. [Figure indicates that she was just under 400lbs at start]

So, first of all, these subjects do not seem like typical patients. One has “a severe deformity of his mouth” and ate 3075 calories of nutrient sludge every day for sixteen days. One is a 20-year-old who ate 4430 calories of nutrient sludge every day for nine days. And the two obese patients were both around 400lbs at the start — not typical cases by any measure!

If both these obese people were six feet tall (unlikely), their BMI at the start of the study would have been 54.2!!! Recall that obese is a BMI of 30, and extreme obesity / morbidly obese is a BMI of 40 or greater. This BMI chart we found from the NIH only goes up to 54. These people were literally off the charts, and again that’s assuming they are both six feet tall. If they were shorter, then their BMI would be even higher.

The sample size here is FOUR. If we only count the obese patients, the sample size is merely two. Except maybe not, because the discussion says, “The data show that the five obese subjects [emphasis added] ate only a small fraction of their daily calorie requirements by machine” (the end of p669 also suggests five obese subjects). We aren’t given any specifics about these “three additional obese subjects” except that they “showed a similar inhibition of calorie intake when fed by machine.” In any case, we’re given very little case information about any of the seven subjects, and at the end of the day this study has two control subjects and five obese subjects (though it’s not even an experiment).

We understand the benefits of case studies, but this one doesn’t seem particularly likely to generalize.

Making a long story short, both “normal-weight” participants maintained their healthy weight effortlessly on a diet of nutrient sludge. The obese participants ate only a couple hundred calories per day and effortlessly lost huge amounts of weight. Somewhat strangely, the treatment periods were very different. The obese male participant lost 200 lbs after 252 days on various forms of the nutrient sludge diet, while the obese female participant was there for only 24 days and lost 23 lbs. Both patients were very obese to start with, but this rate of weight loss still seems really extreme.

This study is from 1965, and realistically, the data are from a few years earlier. As mentioned above, we think that the abrupt increase in obesity rates starting in 1980 is evidence that modern obesity occurs for different reasons than historical obesity did. The aetiology of these cases of obesity is almost certainly different from the obesity we see today, and even today, very few people are 400lbs. 

Probably these people were obese for a different reason than your local bus driver with a BMI of 31. For example, they might have had a brain tumor that left their hunger response largely intact, but led them to compulsively overeat a particular food. This would explain why “the patient never complained of hunger or gastrointestinal discomfort” despite spending 26 days eating nothing but ~275 calories of nutrient sludge a day. 

Even if the aetiology were the same as modern obesity, there are a few huge problems, the biggest of which is THE CUPS!!!

About the obese male participant, they say:

To determine whether the bizarre feeding situation was by itself inhibiting his food intake, he was asked (after 18 days on the machine) to feed himself the same formula ad libitum using a pitcher and cup. In the third section of FIGURE 4 it can be seen that his calorie intake increased on this program to about 500 per day [from 275 ± 57 calories per day]. He was returned to machine feeding after another 26 days and, again, spontaneous food intake dropped to a lower level.

For the obese female participant:

Her spontaneous food intake over a 12-day period of observation also was extraordinarily low, 144 ± 91 calories per day. During this time she lost 23 pounds. When she took the same formula by cup, calorie intake increased to 442 ± 190.

(Also weird: on days 11 and 17, this participant appears to have eaten about zero calories?)

For one participant, calorie intake nearly doubled when he went from drinking from the syringe-pump to using a pitcher and cups. For the other, calorie intake tripled. This makes it pretty clear that the nutrient sludge itself was only driving part of the effect (or that the measurements are hopelessly imprecise). Contra Guyenet, the palatability of the sludge doesn’t seem to be the main force at play here. In addition, this is super weird. 

It’s also very strange that the healthy 20 year-old volunteer subject consumed 4430 calories of nutrient sludge per day (this was on average — one day, he consumed almost 5000 calories of the sludge). Their only explanation for this was, “the subject remained physically active throughout this period,” but this is still a LOT of calories! The FDA recommendation for an “Active” 20-year-old man is a mere 3,000 calories (same for “Very Active” from the NIH), and this guy was slurping down almost 48% more calories per day than the recommended amount, for nine days! The other “normal-weight” participant also consumed a lot of sludge, 3075 calories per day on average, and there’s no indication he was especially active.

This seems to argue against the idea that the sludge was all that unappetizing! The authors describe it as “bland”, but never suggest that it was intended to be unpalatable. The detail they give is, “carbohydrate contributed 50 per cent of the calories, protein 20 per cent and fat 30 per cent. The formula contained vitamins and minerals in amounts adequate for daily maintenance.” Maybe it was delicious, and the results from the two lean participants certainly seem to suggest that this is a possibility. Ask yourself this: would YOU eat 4430 calories of nutrient sludge per day if it were “bland”?

If the sludge truly was bland, this appears to be reasonably strong evidence against the food reward hypothesis! Taking this argument at face value, it seems like feeding healthy young men nothing but nutrient sludge is an extremely reliable way to make them overeat by 1000-2000 calories per day.

Alternately, the measurements could be way off for some reason. What seems more likely, that two normal-weight men decided to eat 3075 and 4430 calories of nutrient sludge every day for more than a week, and that five morbidly obese patients lost about 1 pound every day for up to 200 days, or that someone made a mistake and wrote down some of these numbers wrong? Even if the research team were 100% reliable, how good was the technology in 1965? How reliable were the pump and the printing timer? Small differences in the pump delivery doses could easily be responsible for the weird results we see. Not to sound paranoid, but was this guy really exactly 400 lbs to start, and did he really lose exactly 200 lbs over the course of the diet? Does eating 400 calories per day for 252 days pass a basic sanity check?

Also for comparison, Figure 4 (reproduced below) appears to show that the 400-lbs-obese man was eating only 2000 kcal/day of a “Regular Hospital Diet” for the eight days before going on a nutrient sludge diet. Was this how much he normally consumed? It seems weird. Guenet says that 275 calories was “less than 10 percent of his usual calorie intake”, suggesting the man’s normal diet was at least 2750 calories per day, but we don’t see where he’s getting that number from. If either of these numbers are right, that means that the 400 lb man had a normal calorie intake that was less than both of the lean subjects. 

In any case, another serious oddity is that he started losing weight as soon as he entered the hospital, at a rate of about one pound per day — eight days before he was put on the nutrient sludge diet! That kind of makes it seem like something else is causing the rapid weight loss. 

Other Studies

Of course, this is just one study. In fact, it’s merely the first of many! In the section we quoted at the beginning of this piece, Guyenet says, “further studies from the same group and others supported the idea that a bland liquid diet leads people to eat fewer calories and lose excess fat.” It would clearly be a big mistake for us to dismiss this early result without seeing the further studies, so let’s take a look.

Guyenet cites two further studies in The Hungry Brain, and we found a third with a little searching. This may not be the full literature on the subject, but it’s everything Guyenet cites plus one, so it seems like a good place to start.

The first was a study called An Automatically Monitored Food Dispensing Apparatus for the Study of Food Intake in Man. This study was from 1964, so it actually predates the study reviewed above. The abstract says that said apparatus was “tested on a patient for 17 successive days” and that “the pattern of energy intake reflected 3 identifiable meal-times in each 24-h period.”

As far as we can tell, this is simply the first test of the “automatically monitored food dispensing apparatus.” We can’t access the full article for some reason (if you can, please send it to us), but the abstract seems to specify that there was only one participant, and there’s no mention of weight loss or obesity at all.

The second is a paper from 1971 called Studies of Food-Intake Regulation in Man — Responses to Variations in Nutritive Density in Lean and Obese Subjects. This is one of the papers Guyenet cites in The Hungry Brain.

In this study, “dispensed liquid diet was studied in five lean and four obese young adults and two obese juvenile subjects.” The twist is that the researchers varied the “nutritive density” of the nutrient sludge over time without telling the research subjects. As before, subjects were (ideally) unaware that their food intake was being recorded. Also relevant is that the study was conducted in a metabolic research ward, which allows for a certain amount of control, and that participants were “maintained on light activity”, with the research team attempting to “prevent significant day-to-day variations in energy output”.

We see the same issues here that we highlighted in the original study. This is also before 1980, and so may not be informative about the current situation. The sample size is pretty small, but it’s bigger than before, and the subjects seem less idiosyncratic.

The lean participants were “five healthy male students 20 to 25 years of age”. The “grossly obese patients” came in two groups — four women between the ages of 25 and 30, and two adolescent boys ages 13 and 15. This isn’t an experiment, but it’s still kind of worrying how different the demographics are for the lean and the obese participants.

The results for the lean participants match the previous findings. “All the lean subjects,” they report, “were able to maintain weight within fairly narrow limits (0.6 to 2.3 per cent of initial body weight) by making appropriate adjustments in the calorie intake whenever the nutritive density was varied.” Thankfully, unlike the lean participants in the previous study, none of these fellows was consuming an insane amount of the sludge.

The obese adult female participants ingested only a few hundred calories of the sludge per day, and lost weight, though the weight loss doesn’t appear to be as extreme as in the first study. Of interest, however, “there was no increase of volume intake in response to formula dilution and no decrease in volume intake after formula concentration.” In fact, in two of the four obese women (that is, half), “there were paradoxical drops in volume intake when the nutritive density of the formula was decreased.”

This is very weird. It suggests that these women were controlling for the amount of nutrient studge they drank, rather than for calorie intake. Together with the results of the first study (and THE CUPS), the conclusion ends up looking less like “if obese people eat a bland diet, they return to a healthy weight” and more like “if you give obese people a diet through a food pump nozzle, they will suck the exact same tiny amount every day for some reason.” 

The story is further complicated by the fact that we get VERY different results for adolescent male participants. The 15-year-old was 101 kg and the 13-year-old was 135 kg at time of admission, and both of them maintained these weights by drinking thousands of calories of nutrient sludge. “During the periods in which caloric density was 1.0 kcal per milliliter,” they tell us, “energy intake was in excess of 3900 kcal per day.”

These participants really did seem to be controlling for calorie intake, because diluting the formula didn’t fool them. “When the formula was covertly diluted subject A.V. increased volume intake slightly, but not enough to maintain a caloric intake comparable to that achieved during intake of the more concentrated formula. In contrast, W.D. compensated for formula dilution with a striking increase in volume intake, thereby maintaining a near constant energy input.”

An examination of Table 2 reveals that at one point, one of the adolescents broke 4,000 calories of nutrient sludge per day, which is honestly impressive across a number of dimensions. In addition, “These two obese juvenile subjects differed from the obese adult subjects in that they either maintained or gained weight while receiving the machine-dispensed formula.” The magic bullet against obesity, this is not.

In fact, once again this seems like evidence against palatability as an explanation for obesity. If palatability were the driving force, then these teens wouldn’t be slurping down almost 4k calories of nutrient sludge to maintain their extreme weights. Indeed, it seems like palatability makes no difference at all. 

It’s especially concerning that this diet causes weight loss in only 2/3 of the participants. These six people may be obese for different reasons (i.e. obesity is a shared symptom but the result of a different underlying condition), but none of those reasons seem to be related to palatability. 

The other paper cited by Guyenet in his book was a 1976 piece titled Influence of a Monotonous Food on Body Weight Regulation in Humans. This study is not worth reviewing in depth because of its major departures from the original design. This is a two-author paper, and neither author was involved in any of the previous studies. Rather than the nutrient sludge being automatically recorded by a dispensing pump in the monitored environment of a hospital ward, subjects were sent home with “an ample stock” of Renutril®, a moderately sweet, vanilla flavored complete liquid diet that comes in 375 ml cans. For experimental control, “they were told to avoid as much as possible the odor, the sight, and even the thought of any other foods.”

Even if this design were above criticism, the results are unimpressive. The study lasted 3 weeks, and on the all-liquid bland diet, people’s weight decreased by only 3.13 kg. This is a far cry from the one pound per day reported in the 1965 study.

In addition, this study suffers from the same problems as all the studies above: the study was conducted before 1980, so it may not generalize, and the sample size was four.

Conclusions

Taken together, these studies do not provide much evidence in favor of palatability as a cause for obesity, or for the use of a bland diet in reversing it. The studies are all more than 40 years old, so the data predates the modern obesity epidemic. There are a number of bizarre observations and discrepancies (THE CUPS!!!) that don’t seem consistent with the palatability hypothesis. The total sample size across all four studies is 23.

In fact, these studies provide moderate evidence against the palatability hypothesis. Most participants lost weight on the nutrient sludge diet, but two patients not only ate heroic amounts, they actually gained weight. In the 1965 study, the nutrient sludge diet appears to have prompted two lean participants to overeat by something like 1000-2000 calories per day.

Finally, there is an external sanity check that makes us doubt the whole premise. If the nutrient sludge diet works, why hasn’t anyone done a real experiment on it? Why isn’t it being used to make 400 lbs men lose 200 lbs today? Either this is a huge missed opportunity, or these results are simply wrong. 

If this works, why hasn’t someone replicated it by now? It would be pretty easy to run a RCT where you fed more than five obese people nutrient sludge ad libitum for a couple weeks, so this means either it doesn’t work as described, or it does work and for some reason no one has tried it. Given how huge the rewards for this finding would be, we’re going to go with the “it doesn’t work” explanation. 

If you think palatable food is the relevant issue, an even better approach would be an experimental design where you develop two (or more) nutrient sludges, nutritionally identical but one more palatable than the other, and randomly assign a group of obese participants to eat either the palatable sludge or the unpalatable sludge. But we haven’t seen a design like this either.

If Guyenet — or anyone — believes this result is real, they should rush to do a metabolic ward study on a sample size of more than five people, and collect all the fame and fortune that comes with finding a diet that not only reliably works, but leads to weight loss of about one pound per day with no hunger or gastrointestinal discomfort.

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[Next Time: SUSPECT NUMBER TWO]

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