I wish I knew how, but this study definitely shares a theme with the remarkable effects of a bland diet and spontaneously reduced caloric intake in obese but not lean subjects, (from the first post in this series, found here).
In brief, there were 3 groups of rats in this study: 1) diet-induced obese (“sham”); 2) diet-induced obese rats that underwent gastric bypass surgery (“RYGB”); 3) chow-fed lean controls (“lean”). The dietary regimen was a kerfuffle, but that wasn’t really the point of the study; to make the rats obese, they were given standard chow, a purified high sugar high fat diet, and chocolate-flavoured Ensureall at once… and we have no idea how much of each they were consuming :/ But here’s the nutrient breakdown of each anyway, by calories:
and here is a rough ingredient list:
HFD, high fat high sugar diet
They performed a battery of psychological evaluations designed to empirically measure how much an animal “wants” or “likes” a rewarding food. Call me simple, but I would’ve rather just seen how much of each of the above diets the rats consumed when presented with all 3 simultaneously. If most of their calories came from the sweet chocolate-flavored Ensure, then I’d say they still liked rewarding foods. If on the other hand they selected more of the sugar-free chow, then they probably don’t care as much for rewarding food. Maybe this wouldn’t fly in psychonutrition circles, but I don’t really think such circles exist. Alternatively, would RYGB rats have lost more weight if they were fed exclusively chow compared to those given Ensure? Fortunately, this question was addressed in an earlier manuscript by Zheng (Meal patterns, satiety, and food choice in a rat model of Roux-en-Y gastric bypass surgery [Zheng, Berthoud, et al., 2009 AJP])
When given the sugar-free chow diet, the control rats eat less. When given a high sugar high fat diet, the control rats eat more. RYGB rats don’t seem to care. But that’s kind of exactly what Shin showed by complicated psychological tests:
Lean and sham (obese) rats like a very sweet beverage (1.0 M sucrose) significantly more than a more bland solution (0.01 M sucrose). RYGB rats don’t seem to care. This was repeated to a tee in another group of “obesity-prone” rats suggesting it might be a true product of the gastric bypass surgery:
And oddly enough, human subjects that have undergone roux-en-Y gastric bypass surgery seem to be able to detect much lower concentrations of sucrose but not like it as much (they can “taste” it more, but might not “like” it more) (they are satisfied with less-sweet foods) (Changes in patients’ taste acuity after Roux-en-Y gastric bypass for clinically severe obesity [Burge et al., 1995 JADA])
Are these findings related to obese humans who spontaneously consume significantly less of a bland diet? (recall obese but not lean human subjects lost weight on the bland diet). Similarly, rats consume significantly more of a tasty junk-food cafeteria diet. There is definitely something magical about roux-en-Y gastric bypass surgery; it is the single most effective treatment [cure] for obesity. Obese humans eat less of a bland diet, roux-en-Y gastric bypass surgery decreases the “liking” of a sugar-rich beverage (but enhances one’s ability to detect sucrose)… RYGB and that bland diet caused massive weight loss in their respective [obese] subjects… These things just have to be related, my spidey-sense is going wild
Sometime in the late ‘90’s I thought a bland diet would cure obesity. If meals consisted of baked chicken and plain rice, or hard-boiled eggs and oatmeal, for example, then soon people wouldn’t look forward to eating and mealtimes would be unpleasant. Eventually, food intake would revert to being governed properly by hunger as opposed to the rewarding or hedonistic aspects of delicious [junk] foods. Furthermore, food intake might even be less than energy expenditure because the reduced caloric intake would be supplemented with stored energy from fat tissue until a normal body weight was regained (an early version of the set point theory?).
I still think this is true, but completely impractical. Suggesting the removal of tasty junk food is generally considered militaristic and is often countered with loaded [and relatively meaningless] phrases like “everything in moderation.”
There are a ton of complicated studies involving lean and obese subjects, given bland or sweet foods while electroencephelograms measure brain electrical activity in attempt to determine if obesity affects a person’s response to or liking of sweets….
this study is way cooler.
The abstract, in its entirety [sic]:
This is possibly one of the best controlled human dietary intervention studies of all time.
In brief, this study used a human-sized Skinner box to measure consumption of a bland yet nutritionally complete food-like liquid substance (“It’s a single cell protein combined with synthetic aminos, vitamins, and minerals. Everything the body needs.” –Dozer, The Matrix). 50% carb, 20% protein, 30% fat (strictly in terms of macronutrients, not too different from the modern Western diet [~60% carb, 15% protein, 25% fat])
the actual device:
Whenever a subject was hungry, they would put the straw in their mouth and press a lever to dispense exactly 7.6 mL of Nutrament. Intake was monitored by a microwave-sized computer, and the only instruction was to feed exclusively from the machine, ad libitum, i.e., with no restrictions whatsoever.
Experiment #1: a lean man, 60 years of age, studied for 16 days.
This subject quickly adapted to the diet and was able to maintain body weight for the entire duration of the intervention. Similar results were obtained from another male subject, 20 years of age, studied for 9 days.
Interpretation: 1) the machine works equally well for young and old [lean] subjects, and 2) switching from a normal diet to the bland Nutrament didn’t appreciably affect food intake or energy expenditure because calorie intake and body weight were unchanged.
Here is where it gets interesting. Next they tested a 400-lb [obese] man, 27 years of age. His caloric intake and body weight dropped markedly for 70 days straight despite being encouraged to eat whenever hungry. After 70 days, he was switched to a similarly bland meal-replacement beverage for another 6 months, during which time body weight continued to rapidly decline. “ … the patient never complained of hunger or gastrointestinal discomfort.”
Body weight (top half), calorie intake (bottom half). Red dot, baseline; orange dot, machine feeding period; green dot, switched to drinking from a cup instead of from the machine; blue dot, feeding from the machine and the cup; purple dot, given a liquid formula to consume at home with instructions to restrict physical activity. The last part of the study was the only time when food intake was restricted, and given the consistent reduction in body weight, adherence was likely 100%.
They switched him to drinking from a cup to determine if there was something about “the bizarre feeding situation,” i.e., feeding exclusively from the machine, which inhibited food intake. Calories increased a little, but not much. NB when he was sent home, they instructed him to restrict physical activity (probably to reduce excess stimulation of hunger). Overall, he lost 200 pounds. Similar results were obtained with a 390-pound woman, 36 years of age, who over the course of 23 days lost 23 pounds. In all of these cases, food intake spontaneously decreased to an extremely low level if the subject was obese.
The authors thought it was important that 1) the liquid was bland, 2) the subjects didn’t know how many calories they were ingesting, and 3) they were no longer eating in a social atmosphere. “In other words, [the subject] is guided principally by subjective hunger.” couldn’t have said it better myself.
These researchers carried out a similar intervention, subjects were provided a bland liquid supplement “Renutril” as their sole source of calories, of which they were instructed to consume ad libitum while avoiding “as much as possible the odor, the sight, and even the thought of any other foods.” Alliesthesia, or the “liking” of sweet foods with a full or empty belly, was also assessed before and after weight loss. These subjects ingested significantly more calories than those in Hashim’s study (> 1000 vs. < 500 kcal) but they still lost a lot of weight (similar bland liquid calories: “Renutril”).
Alliesthesis (see figure below): Normally, a sucrose-sweetened beverage is perceived to be sweeter as sucrose concentration increased, and this is blunted after a 50-gram bolus of glucose is delivered directly into the stomach (via naso-gastric tube) (top left in figure below). IOW, with a belly full of calories, food tastes less delicious (hunger IS the best spice). Similar results were obtained after weight loss with ad lib Renutril (bottom left), but not with a calorically-restricted, flavorful “mixed” diet (top right [pre-weight loss] vs. bottom right [post-weight loss]).
Interpretation? Caloric restriction-induced weight loss on a flavorful “mixed” diet must induce somewhat of a starvation response (since it tastes good, your “wanting more of it” overpowers the signal from the calories in your belly). Importantly, this is not the case with ad libitum Renutril-induced weight loss; these subjects were honestly not hungry. They weren’t sad or depressed about the new liquid diet; they just simply weren’t hungry.
Apparently, cravings were not a problem in Hashim’s or Cabanac’s studies. It’s a weird paradigm, but I like Cabanac’s final figure:
translation: body weight set point on a bland diet is lower than on a flavorful diet
Furthermore: sounds like torture!
From Hashim we saw that a bland diet could promote the loss of excess fat mass by reducing hunger. Starvation does not ensue because the subjects have excess fat mass (by definition, as this only works in obese people) to supply energy for the body. One important point here is that these effects seem to be dependent on the presence excess fat mass; caloric intake was normal and body weight maintained in lean subjects. The second important point, garnered from Cabanac, is that the diet must be bland to prevent the rebound ravenous hunger experienced by most dieters. Subjects who lost weight by a calorie-restricted mixed diet were not adequately satiated even when they had a belly full of calories (hypocaloric flavorful diet –> impaired alliesthesis). IOW it’s not “calories” because they were reduced in both cases; it is the diet. (yes this is further confirmation that the type of calories matters)
I applaud these researchers for their extremely meticulous and detailed food intake data, which was particularly difficult and labor-intensive because the “cafeteria diet” was employed. The cafeteria diet provides rodents with their usual chow, but also includes a rotating selection of bona fide human junk foods like Fruit Loops, Hostess Blueberry Muffins, Cheez-it crackers, Frito’s, etc., etc. So measuring food intake isn’t as simple as collecting the leftover pellets, they have to really dig around to get all the crumbs, etc., and separate them to know exactly how much of each food was consumed.
A sample menu:
At the end of the day, when all of the hard work is done, we get this neat little table:
Divide and conquer
Note to nutrition researchers: this is a great way to present food intake data. The only thing missing is one or two more columns stating the primary source of the fat and proteins (could actually get rid of the “Fat kcal” column because it’s redundant).
The cafeteria diet is a wide variety of junk food (a double whammy: variety & junk). And as seen below, the cafeteria diet hijacks food intake homeostasis. On either the low-fat (open squares, “LFD), high-fat (closed squares, “HFD”), or standard chow (open circles, “SC”) diets, rats ate about the same number of calories.
But they go crazy for the cafeteria diet (closed circles, “CAF”). NB the 3 “control” diets (LFD, HFD, & SC) represent a wide variety of macronutrient ratios, and none of them are consumed as much as CAF. That’s because of one simple reason: the cafeteria diet is delicious. A bland diet will promote the loss of excess fat mass (Hashim & Cabanac), and a delicious junk food diet will promote the accumulation of excess fat mass:
Cafeteria rats gained almost twice as much weight as chow, who gained the least amount of weight (probably because standard rodent chow has the least sugar of all the diets). So palatability plays a big role in determining hunger and food intake in humans (Hashim & Cabanac) AND rodents (Sampey). Macronutrient composition is important, as it will determine how the ingested calories are partitioned (see figure e, above). Sugar makes everything taste better; Crisco is gross, but if you add some sugar the resulting ‘icing’ is delicious. disclaimer, I don’t condone the consumption of straight sugar, Crisco, or any combination therein.
Lastly, think about the bland diet / weight loss connection. think it would work? (the difference between obese and lean subjects was quite robust, much more so than anything that has come from an electroencephalogram)… If the patients really didn’t feel hungry, is it such a bad idea? eating delicious food is “rewarding,” but it’s not like they’re being asked to avoid all rewarding activities (e.g., sex).
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Time for the second edition of our ketosis series. Some background: physiological ketosis occurs when the body is burning fat very rapidly, like after an overnight fast or during low carb high fat dieting (e.g., Atkins induction phase). NB this is not the same as pathological diabetic ketoacidosis or alcoholic ketoacidosis. In humans, ketotic diets work like a drug for fat loss. In rodents, there are a variety of responses which although they vary widely between studies, they all provide insight into this “unique” state.
This study included four! diet groups. Although the dietary interventions were poorly designed from a nutrition perspective, the fact that there were four of them means that we should be able to learn something from this paper.
The fourth group is 66% calorie restricted (CR) chow.
As a brief aside, although the diets could have been designed better, at least their KD was a bona fide ketogenic diet (in contrast to the first paper in the ketosis series, where the ketogenic diet group was only mildly ketotic [bHB was only 50% greater in KD relative to control). As seen in the table above, b-hydroxybutyrate, the major circulating ketone body, was markedly elevated in KD compared to the other groups.
Caloric intake was similar among the groups (except CR [open circles], who ingested 33% fewer calories [by design])
One minor point: the HF diet is high in fat and sugar; KD is only high in fat, chow is low in fat, and neither KD nor chow have any sugar. Does palatability affect food intake in mice? If so, we might expect mice to eat more HF than KD (HF = cake icing; KD = Crisco). And by “more,” do we mean “more calories” or “more food?” Palatability probably doesn’t affect food intake [in the mice in this study] because although HF mice were eating just as many calories as KD and chow, they were eating much less food (higher calorie density etc.).
Interestingly, however, body weight differed markedly between the groups … [i sense a diatribe on the laws of energy balance… ]
HF (closed squares, top line) gained the most weight, followed by chow (open diamonds), then CR (open circles) and KD (closed triangles). That last part is pretty amazing; mice on the ketogenic diet (KD, closed triangles) were eating half more calories than CR but they weighed just as much. Alternatively, CR mice were eating 33% fewer calories than KD but they weighed just as much! Either KD increases energy expenditure, or CR reduces it.
…err… or both. Looks like KD (closed triangles) was always a little higher while CR (open circles) was always a little lower. The figure above is showing total metabolic rate. FTR, the units are kcal/hr which in this instance is the appropriate metric. It is not uncommon for researchers to present these data as kcal/kg*hr, which corrects for differences in body weight. Even though there were differences in body weight, “kcal/hr” is still the proper way to present these data because absolute, not relative, differences in metabolic rate produce changes in body weight that can be compared across groups. Relative differences in metabolic rate, such as those that are normalized for body mass (kcal/kg*hr), are interesting and informative, but they don’t describe a variable that directly impacts body weight and can be compared across groups, which is what we are looking for in this case.
One more point needs to emphasized at this … point.
Mice fed chow, HF, and KD all ingested the same kcal/d (~15, as per figure 1.) Since we know the composition of the diets, the amount consumed of each macronutrient can be calculated:
KD mice ate >2x more fat than HF (1599 mg vs. 757 mg). HF mice ate the most sugar, while KD ate the least sugar. Thus, HF mice (who were also eating a high sugar diet) diet weighed 50% more than those on the ketogenic diet, despite eating only half as much fat (and equal calories)! Why? *
CR mice lost weight, but their metabolic rate declined significantly (think: sluggishness, fatigue, etc.). KD mice ate 50% more calories than CR mice but weighed exactly the same and had a higher metabolic rate (think: lots of energy, high activity level, etc.). *
Well, actually, in terms of body composition, chow guys did the best:
HF mice accumulated the most fat mass (the product of a carb-rich high fat diet). They also had as much lean mass as the chow group. If we were to transcribe these data to percent body fat, chow would have the lowest (they weigh more than KD & CR, but have the same amount of fat mass; the numerator [fat mass] is the same but the denominator [body weight] is higher in the chow group).
Chow-fed mice ate the most protein and had the highest lean mass. Coincidence? By this you might argue that KD ate the least protein therefore they should have less lean mass than CR. *You’re forgetting that the ketogenic diet is 0% carbs and 50% magic.
KD & CR had the lowest lean mass. A few points about this: for starters, the ultra-low protein intake caused this in KD mice (muscle wasting), while in CR mice it was more likely due to a combination of deficient calories and suboptimal protein intake. When calorie intake goes down, the amount of protein required to maintain nitrogen balance increases. So if you reduce calories, lean mass will decline unless protein intake is increased. In CR, calories and protein intake declined.
WRT the KD mice, they exhibited reduced lean mass but their relative metabolic rate was the highest out of all 4 groups. Usually a loss of lean mass is accompanied by (or causes) a reduced metabolic rate, but the opposite happened. I find this interesting. Very interesting.
The researchers did a few more experiments*, and further confirmed that the ketogenic diet increases the absolute energy expenditure and markedly increases relative energy expenditure which allows the animals to eat just as much food while losing weight.
*actually, they did a ton more experiments, this paper was a bear. Kudos.
They also tested “overall well-being” by measuring how much the mice explored a novel environment. They found no difference between KD & chow, but HF mice exhibited “reduced exploratory activity.” Translation: a high fat (ketogenic) diet is good (e.g., KD), but a high fat high carb diet is bad (e.g., HF).
For the inquiring minds, the mechanism of KD’s anti-obesity effects were most likely due to elevated heat dissipation via brown adipose tissue . This is in contrast to which what was alluded above; although “exploratory behavior” was similar in KD mice, physical activity was not measured directly so it can’t be concluded that KD mice ran around and played more than the other mice. Given the brown fat data, it is possible that basal metabolic rate (total heat production) was increased due to the ketogenic diet. This could be good news for some; on a ketogenic diet, weight loss is not dependent on increased physical activity, the fat mass would simply (almost literally) melt away, no need to exercise.
This study is another example of how “eat less and move more” is wrong. KD mice didn’t “eat less,” they ate differently; and the composition of the diet alone accomplished the “move more” part without requiring any type of exercise by increasing basal metabolic rate. The diet did all the hard work for them. And these mice were eating ad libitum, which means they were never hungry in contrast to the CR mice that were eating 33% fewer calories. Calorie restricted diets are optimal for neither fat loss nor well-being.
We interrupt your regularly scheduled program for this urgent message: the National Health and Nutrition Examination Survey (NHANES) has issued a declaration of war.
OK, jk, the title of this manuscript is certainly eye-catching, but after a few days of brooding, plotting, and scheming, and some sleepless nights, I’ve come to the conclusion that while it may be “eye-catching,” it’s really not saying very much.
NHANES is a government run program that has been going on forever and is basically an enormous database of diet, health, disease, etc., risk factors, and is used to make nutrition or health recommendations. There have probably been a million publications using data from NHANES.
This study included roughly 15,000 people over 18 years of age and had a follow-up period of 5 years. They divided participants into 6 groups: people who ate candy and chocolate, those who ate only candy, those who ate only chocolate, and the people who did the opposite (e.g., those who didn’t eat only candy).
Sugar candy was defined as flavored/colored, crystalline/semisolid, sugar (e.g., peppermint, lollipops, licorice, gum drops, etc.). Chocolate candy was defined as a mixture of cacao, cocoa butter, sugar and some extra’s (nuts, milk, fruit, caramel, etc.).
Reason #1 why this study isn’t saying very much: we are not talking about a Halloween pillow case or Easter basket full of candy. Not even close. More like 4 Hershey Kisses, or 1 Reese’s Peanut Butter Cup (not even the whole package). On average, everyone in the total population eats less than one serving per day which means that on most days no candy or chocolate is eaten at all. This seems like a very low threshold for deeming someone to be a candy consumer, but it still includes about 10 – 20 % of their population. Think of 10 people you know personally (friends, family, co-workers), how many of them have eaten candy in the past 48 hours? If your answer includes more than 1 person, then these data don’t apply because the study population is not representative of the population from whence you hail. phew! Without going any further, I think this one point disqualifies the applicability of these results for about 95% of internet-accessing people.
If it looks like a duck, quacks like a duck, and you’re still not sure, send me the link.
Other anomalies in their data:
(divide and conquer)
Of course it’s perfectly plausible for one subgroup of people to eat significantly more yet weigh less than another subgroup selected from the same population, but how likely is that to occur in all 6 subgroups above?
More simply, here is a graph of calorie intake vs. body weight:
In each case, the blue symbols (nonconsumers) eat less but weigh more than the red symbols (consumers). The only “normal” outcome, i.e., where those who eat more also weigh more, is comparing the red circle (people who eat both candy and chocolate) to the red square (people who eat chocolate but not candy). I’m not saying these data are incorrect or were falsified, I’m just saying they are unique. And when graphed this way, it is easy to see that consumers are eating over 150 more kilocalories per day than nonconsumers despite weighing ~2 pounds less.
Given the old (outdated) relationship between the amount of additional kilocalories required to gain one pound of fat mass, a difference of 150 kilocalories per should result in an additional pound of fat gained every 24 days… (which could theoretically be prevented by running an additional 1.5 miles every day) … yet those people are 2 pounds lighter
Furthermore, the candy consumers weigh significantly less and are more active, so their risk for a variety of metabolic disorders should be reduced, right? Nope:
Candy: 0
Nutrition: 1
Will eating a piece of candy every day make you fat? No. Will stressing out about food or abandoning indulgences improve your health or quality of life? Certainly not. Do I feel all preachy now? yes, a little.
My current running hypothesis, based on a few rodent-diet studies, is that leptin resistance is mediated entirely by sugar and is not influenced by dietary fat. The relationship between leptin resistance and obesity is somewhat less clear (does leptin resistance cause hyperphagia and obesity? does hyperphagia and obesity cause leptin resistance? The latter example seems odd, but it would imply that leptin resistance develops after the onset of obesity… which would be supported by the observation of leptin sensitive obesity (e.g., here)
The study discussed below is another example of obesity sans leptin resistance. To review, leptin resistance can occur without obesity on a high fructose diet, but it does not occur on a sugar free high fat diet.
Unfortunately, this was a pretty bad “diet” study from a nutrition perspective because there are way too many variables. Are the results due to increased dietary fat? lower protein? lower carbs? Aargh. We will never know because they were all manipulated and uncontrolled. (psychologists and neuroscientists should NOT be allowed to design nutrition experiments). Even the types of protein and fat were different between the groups.
This study in a nutshell: leptin sensitivity and various other metabolic parameters were measured in rats fed chow or a ketogenic diet.
Divide and conquer.
What is a ketogenic diet?
exhibit A:
A ketogenic diet is insulinopenic = low carb, high fat. The biochemical signature is elevated serum ketone bodies. ?-hydroxybutyrate (red box in the table above) is the most abundant, and its elevation in the ketogenic diet-fed rats (KD) confirms that indeed, this was a ketogenic diet (note, b-Hb @ 0.33 mM is a very mild ketosis).
Unfortunately, these authors quantified fat mass by tissue excision and weighing, which is an inferior and inaccurate technique. However, since the fat mass and leptin data* concur, we can infer KD rats were probably a little fatter by the end of the study.
*Leptin increases when fat mass increases.
Leptin sensitivity was measured by injecting leptin i.p. and measuring food intake for the next 24 hours. Higher leptin sensitivity results in a greater reduction in food intake. As seen in the figures below, chow-fed rats (figure a, on the right) were more leptin resistant than KD rats (figure b, on the right).
In fact, KD rats responded to 100 ug of leptin whereas it took almost 6 times more (2 mg/kg = ~600ug) to achieve a similar reduction in chow-fed rats.
One minor critique: the authors believed that a key novel finding of their study was that KD rats were more leptin sensitive despite being fatter… Given that adiposity was such a critical factor in their conclusion, they should have used something better than the worst way to measure fat mass. Thus, a weak point of this study is that the validity of the conclusion (which is also in the title of the paper) is based on a notoriously inaccurate technique.
Interestingly, despite exhibiting resistance to peripherally administered leptin (above), chow-fed (below, figure a) rats were equally sensitive to KD rats (figure b) when leptin was centrally administered (i.c.v.):
The authors proceeded to speculate that leptin is less able to cross the blood-brain barrier in chow fed rats compared to KD. It’s possible. One theory on the mechanism of leptin resistance states that elevated triacylglycerols impair leptin’s ability to cross the BBB. This is probably not true, as KD rats were more leptin sensitive despite having higher triacylglycerols. $
One more minor critique, which I only mention because this issue arises frequently and is often ignored. although I still don’t know what it means:
1) If KD rats were significantly more sensitive to leptin, why was their 24h food consumption similar to chow-fed rats? (see saline injections in any of the figures above and here)
2) Leptin levels in KD rats were significantly higher than those in chow-fed rats (8.65 vs. 2.99 ng/mL). If they were indeed more leptin sensitive, then shouldn’t their food intake been lower than chow-fed rats?
3) KD rats had significantly higher leptin levels (8.65 vs. 2.99 ng/mL). So injecting KD rats with 100ug leptin increased their leptin from 8.65 ng/mL to 8.65 + X. Whereas injecting chow rats with 100ug leptin increased their leptin from 2.99 to 2.99 + X. Since “8.65 + X” will always be mathematically greater than “2.99 + X,” circulating leptin in the KD rats injected with 100ug of leptin should have been significantly greater than circulating leptin in chow-fed rats injected with 100ug leptin, so KD rats would have ingested less than chow-fed rats even if they were equally leptin sensitive. As such, I don’t think it’s proper to conclude, from those experiments alone, that KD rats were more leptin sensitive. $$
3.5) Is there a difference between endogenous and exogenous leptin? I.e., is exogenous leptin stronger than endogenous leptin? If so, this is very important. Food for thought.
HFD, high fat high sugar diet
