Food Reward: a Dominant Factor in Obesity, Part IV

What is Food Reward?

After reading comments on my recent posts, I realized I need to do a better job of defining the term "food reward".  I'm going to take a moment to do that here.  Reward is a psychology term with a specific definition: "a process that reinforces behavior" (1).  Rewarding food is not the same thing as food that tastes good, although they often occur together. 

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Healthy Skeptic Podcast

Chris Kresser has just posted our recent interview/discussion on his blog The Healthy Skeptic.  You can listen to it on Chris's blog here.  The discussion mostly centered around body fat and food reward.  I also answered a few reader questions.  Here are some highlights:

• How does the food reward system work? Why did it evolve?
• Why do certain flavors we don’t initially like become appealing over time?
• How does industrially processed food affect the food reward system?
• What’s the most effective diet used to make rats obese in a research setting? What does this tell us about human diet and weight regulation?
• Do we know why highly rewarding food increases the set point in some people but not in others?
• How does the food reward theory explain the effectiveness of popular fat loss diets?
• Does the food reward theory tell us anything about why traditional cultures are generally lean?
• What does cooking temperature have to do with health?
• Reader question: How does one lose fat?
• Reader question: What do I (Stephan) eat?
• Reader question: Why do many people gain fat with age, especially postmenopausal women?

The podcast is a sneak preview of some of the things I'll be discussing in the near future.  Enjoy!

Fast Food, Weight Gain and Insulin Resistance

CarbSane just posted an interesting new study that fits in nicely with what we're discussing here.  It's part of the US Coronary Artery Risk Development in Young Adults (CARDIA) study, which is a long-term observational study that is publishing many interesting findings.  The new study is titled "Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis" (1).  The results speak for themselves, loud and clear (I've edited some numbers out of the quote for clarity):
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Food Reward: a Dominant Factor in Obesity, Part III

Low-Fat Diets

In 2000, the International Journal of Obesity published a nice review article of low-fat diet trials.  It included data from 16 controlled trials lasting from 2-12 months and enrolling 1,910 participants (1).  What sets this review apart is it only covered studies that did not include instructions to restrict calorie intake (ad libitum diets).  On average, low-fat dieters reduced their fat intake from 37.7 to 27.5 percent of calories.  Here's what they found:
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Clarifications About Carbohydrate and Insulin

My statements about carbohydrate and insulin in the previous post seem to have kicked up some dust!  Some people are even suggesting I've gone low-fat!  I'm going to take this opportunity to be more specific about my positions.

I do not think that post-meal insulin spikes contribute to obesity, and they may even oppose it.  I'm not aware of anyone who researches metabolism for a living who thinks post-meal insulin spikes contribute to obesity, and after having looked into it, I understand why.  It's not a controversial issue in my field as far as I can tell. Elevated fasting insulin is a separate issue-- that's a marker of insulin resistance.  It's important not to confuse the two.  Does insulin resistance contribute to obesity?  I don't know, but it's hypothetically possible since insulin acts like leptin's kid brother in some ways.  As far as I can tell, starch per se and post-meal insulin spikes do not lead to insulin resistance.
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Healthy Skeptic Podcast and Reader Questions

Chris Kresser, Danny Roddy and I just finished recording the podcast that will be released on May 24th.  It went really well, and we think you'll find it informative and maybe even practical!

Unfortunately, we only got around to answering three of the questions I had selected:

1. How does one lose fat?
2. What do I (Stephan) eat?
3. Why do many people gain fat with age, especially postmenopausal women?

I feel guilty about that, so I'm going to answer three more right now.

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DO NOT USE OBSERVATION FOR PROSTATE CANCER PATIENTS YOUNGER THAN 65 YEARS OF AGE

Radical prostatectomy appears to be a wise choice for men with early-stage prostate cancer who are younger than 65 years, according to new data from a Swedish randomized clinical trial that compares surgery with "watchful waiting."
The study shows that, at 15 years, the cumulative incidence of death from prostate cancer was 14.6% among 347 men randomized to prostatectomy and 20.7% among 348 men being observed without treatment.
However, the survival benefit was confined to men younger than 65 years of age, according to the study authors, led by Anna Bill-Axelson, MD PhD, from the University Hospital in Uppsala, Sweden.
For men older than 65 years, survival was highly similar in the 2 groups.
The new data from the ongoing Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) appear in the May 5 issue of the New England Journal of Medicine.
It has been conducted in men with predominantly symptom-detected early prostate cancer. All the men had clinical stage T1 or T2 disease, well or moderately well differentiated histologic findings, and a prostate-specific antigen (PSA) level of below 50 ng/mL.
"This is the best information we have to date on the extent to which treatment will influence outcomes in men with early prostate cancer," said H. Ballentine Carter, MD, from Johns Hopkins University in Baltimore, Maryland. Dr. Carter was not involved with the study and was approached for comment by Medscape Medical News.
However, the results do not rule out the value of watchful waiting or active surveillance, said Dr. Carter.
"The study strongly supports the role of treatment and the role of surveillance," he said.
The results from this study indicate that a patient's age — and related life expectancy — are apparently pivotal to receiving benefit from watchful waiting in early prostate cancer, Dr. Carter explained.
He interpreted the study findings for clinicians and patients.
"If you are young and have a long life expectancy — 15 years or more — then you need to be treated for prostate cancer," he said, adding that this even applies to men with very-low- or low-risk prostate cancer.
"If you are an older man — 65 to 70 years old — and you have low- or very-low-risk disease, your first consideration should be whether or not treatment is necessary," he pointed out. Such men should "consider being monitored."
Dr. Carter described the randomized controlled trial as a "very, very important paper," saying it was "very carefully done" research.
The fact that Dr. Carter advocates for possible surveillance among certain older men is in keeping with what he knows from his own experience.
He is the senior author of a recently published study of 769 men enrolled initially in active surveillance in which there have been no known prostate-cancer-specific deaths after an average follow-up of about 3 years.
"This study offers the most conclusive evidence to date that active surveillance may be the preferred option for the vast majority of older men diagnosed with a very low-grade or small-volume form of prostate cancer," he said about his study.
Men With Low-Risk Disease Also Benefited From Treatment
SPCG-4 enrolled men from 1989 to 1999; they now have a median follow-up of 12.8 years, which allowed the authors to make 15-year estimates.
The study authors had previously shown that radical prostatectomy provided a survival benefit as well as a reduction in the risk for metastases (J Natl Cancer Inst. 2008;100:1144-1154). The updated data continue to show these benefits, but over a longer period of time.
The "most important new finding" from SPCG-4 is that a subgroup of men with low-risk disease received a survival benefit from radical prostatectomy, said Matthew Smith, MD, PhD, in an editorial accompanying the study. Dr. Smith is a radiation oncologist at the Massachusetts General Hospital Cancer Center in Boston.
Low risk was defined as a PSA level of less than 10 ng/mL and a tumor with a Gleason score of less than 7 or a World Health Organization grade of 1 in the preoperative biopsy specimens. There were a total of 124 men in the radical-prostatectomy group and 139 in the watchful-waiting group who qualified as low risk.
With respect to death from prostate cancer among these low-risk men, the absolute between-group difference at 15 years was 4.2% points (6.8% for the radical-prostatectomy group vs 11.0% for the watchful-waiting group). This corresponds to a relative risk of 0.53 (95% confidence interval, 0.24 to 1.14; P = .14), according to the authors.
This survival benefit for the low-risk men who received surgery might, however, not be "relevant" for many men who have low-risk prostate cancer detected today, Dr. Smith points out.
That is because most of the men in SPCG-4 had cancers detected on the basis of symptoms rather than by elevated PSA levels.
To illustrate what differences can arise out of these varying methods of detection, Dr. Smith notes that, in SPCG-4, the number needed to treat with prostatectomy to prevent 1 death at 15 years was 15. "The predicted number needed to treat is substantially greater for contemporary men with low-risk prostate cancers detected by PSA screening because the rates of death from prostate cancer are lower in this group," he writes.
Surgery Benefit Only in Younger Men: Novelty Questioned
The study authors say that their finding that only younger men benefited from surgery is novel in the literature. "The finding that the effect of radical prostatectomy is modified by age has not been confirmed in other studies of radical prostatectomy or external-beam radiation" they point out.
They suspect that, contrary to their findings to date, surgery might have some survival benefit for some older men.
"The apparent lack of effect in men older than 65 years of age should be interpreted with caution because, owing to a lack of power, the subgroup analyses may falsely dismiss differences," they write.
The data have hints that surgery has a positive effect in at least some older men, they say.
"At 15 years, there was a trend toward a difference between the 2 groups in the development of metastases," they write about the watchful-waiting and surgery groups.
The study stipulated that men treated with surgery who progressed should receive hormonal therapy (as opposed to observed men who progressed — they received surgery). That might have allowed some men to die from other diseases, say the authors. "Therefore, competing risks of death may blur the long-term effects of treatment," they write.
This study was supported by grants from the Swedish Cancer Society and the National Institutes of Health. One of the coauthors reports serving on the advisory board of Pfizer and receiving lecture fees from Astellas. The other authors have disclosed no relevant financial relationships.

Administrative Note

My blog is being mercilessly ripped off by cheesy feed aggregators that are using my material for commercial gain, often without attribution.  I was able to ignore them when there were only one or two, and when they appeared far down the list on Google searches.  But at this point, there are 20+ rip-off sites that ride my coattails under questionable circumstances, and are getting decent Google rankings, so I've had enough.  I'm changing my feed settings so that I only partially syndicate my posts, and I'm adding a short plagiarism warning to each post.

What that means is that if you're using an RSS reader, you'll have to click through to my blog to read my material in full.  I apologize for the inconvenience, but I don't see any other solution.

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Ask Me a Question

On May 13th, I'll be recording a podcast with Chris Kresser of The Healthy Skeptic. Chris interviewed me about a year ago, and I thought it went well. Chris is a good host and asks interesting questions.

This time around, we're going to do things a bit differently. I'll start with a little overview of my current thoughts on obesity, then we'll answer reader questions. The show is going to be mostly about obesity and related matters, but I may answer a couple of questions that aren't related to obesity if they're especially interesting. There are two ways to leave questions: either in the comments section of this post, or the comments section of Chris's post. The show will air on May 24th.
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Food Reward: a Dominant Factor in Obesity, Part II

How to Make a Rat Obese

Rodents are an important model organism for the study of human obesity. To study obesity in rodents, you have to make them fat first. There are many ways to do this, from genetic mutations, to brain lesions, to various diets. However, the most rapid and effective way to make a normal (non-mutant, non-lesioned) rodent obese is the "cafeteria diet." The cafeteria diet first appeared in the medical literature in 1976 (1), and was quickly adopted by other investigators. Here's a description from a recent paper (2):

In this model, animals are allowed free access to standard chow and water while concurrently offered highly palatable, energy dense, unhealthy human foods ad libitum.

In other words, they're given an unlimited amount of human junk food in addition to their whole food-based "standard chow." In this particular paper, the junk foods included Froot Loops, Cocoa Puffs, peanut butter cookies, Reese's Pieces, Hostess Blueberry MiniMuffins, Cheez-its, nacho cheese Doritos, hot dogs, cheese, wedding cake, pork rinds, pepperoni slices and other industrial delicacies. Rats exposed to this food almost completely ignored their healthier, more nutritious and less palatable chow, instead gorging on junk food and rapidly attaining an obese state.

Investigators have known for decades that the cafeteria diet is a highly effective way of producing obesity in rodents, but what was interesting about this particular study from my perspective is that it compared the cafeteria diet to three other commonly used rodent diets: 1) standard, unpurified chow; 2) a purified/refined high-fat diet; 3) a purified/refined low-fat diet designed as a comparator for the high-fat diet. All three of these diets were given as homogeneous pellets, and the textures range from hard and fibrous (chow) to soft and oily like cookie dough (high-fat). The low-fat diet contains a lot of sugar, the high-fat diet contains a modest amount of sugar, and the chow diet contains virtually none. The particular high-fat diet in this paper (Research Diets D12451, 45% fat, which is high for a rat) is commonly used to produce obesity in rats, although it's not always very effective. The 60% fat version is more effective.

Consistent with previous findings, rats on every diet consumed the same number of calories over time... except the cafeteria diet-fed rats, which ate 30% more than any of the other groups. Rats on every diet gained fat compared to the unpurified chow group, but the cafeteria diet group gained much more than any of the others. There was no difference in fat gain between the purified high-fat and low-fat diets.

So in this paper, they compared two refined diets with vastly different carb:fat ratios and different sugar contents, and yet neither equaled the cafeteria diet in its ability to increase food intake and cause fat gain. The fat, starch and sugar content of the cafeteria diet was not able to fully explain its effect on fat gain. However, each diets' ability to cause fat gain correlated with its respective food reward qualities. Refined diets high in fat or sugar caused fat gain in rats relative to unpurified chow, but were surpassed by a diet containing a combination of fat, sugar, starch, salt, free glutamate (umami), interesting textures and pleasant and invariant aromas.

Although the cafeteria diet is the most effective at causing obesity in rodents, it's not commonly used because it's a lot more work than feeding pellets, and it introduces a lot of variability into experiments because each rat eats a different combination of foods.

How to Make an Obese Human Lean

In 1965, the Annals of the New York Academy of Sciences published a very unusual paper (3). Here is the stated goal of the investigators:

The study of food intake in man is fraught with difficulties which result from the enormously complex nature of human eating behavior. In man, in contrast to lower animals, the eating process involves an intricate mixture of physiologic, psychologic, cultural and esthetic considerations. People eat not only to assuage hunger, but because of the enjoyment of the meal ceremony, the pleasures of the palate and often to gratify unconscious needs that are hard to identify. Because of inherent difficulties in studying human food intake in the usual setting, we have attempted to develop a system that would minimize the variables involved and thereby improve the chances of obtaining more reliable and reproducible data.

Here's a photo of their "system":
It's a machine that dispenses bland liquid food through a straw, at the push of a button. They don't give any information on the composition of the liquid diet, beyond remarking that "carbohydrate supplied 50 per cent of the calories, protein 20 per cent and fat 30 per cent. the formula contained vitamins and minerals in amount adequate for daily maintenance."

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 investigators could be confident that the volunteers ate nothing else.

The first thing they report is what happened when they fed two lean people using the machine, for 16 or 9 days. Both of them maintained their typical calorie intake (~3,075 and ~4,430 kcal per day) and maintained a very stable weight during this period.

Next, the investigators did the same experiment using two "grossly obese" volunteers. Again, they were asked to "obtain food from the machine whenever hungry." Over the course of the first 18 days, the first (male) volunteer consumed a meager 275 calories per day. The second (female) volunteer consumed a ridiculously low 144 calories per day over the course of 12 days, losing 23 pounds. Without showing data, the investigators remarked that an additional three obese volunteers "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 70 days, losing approximately 70 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 his total weight loss was 200 lbs. The investigators remarked that "during all this time weight was steadily lost and the patient never complained of hunger or gastrointestinal discomfort." This is truly a starvation-level calorie intake, and to eat it continually for 255 days without hunger suggests that something rather interesting was happening in this man's body.

This machine-feeding regimen was nearly as close as one can get to a diet with no rewarding properties whatsoever. Although it contained carbohydrate and fat, it did not contain any flavor or texture to associate them with, and thus the reward value of the diet was minimized. As one would expect if food reward influences the body fat setpoint, lean volunteers maintained starting weight and a normal calorie intake, while their obese counterparts rapidly lost a massive amount of fat and reduced calorie intake dramatically without hunger. This suggests that obesity is not entirely due to a "broken" metabolism (although that may still contribute), but also at least in part to a heightened sensitivity to food reward in susceptible people. This also implies that obesity may not be a disorder, but rather a normal response to the prevailing dietary environment in affluent nations.

A second study by Dr. Michel Cabanac in 1976 confirmed that reducing food reward (by feeding bland food) lowers the fat mass setpoint in humans, using a clever method that I won't discuss for the sake of brevity (4). I learned about both of these studies through the writing of Dr. Seth Roberts, author of The Shangri-La Diet. I'd also like to thank Dr. Stephen Benoit, a researcher in the food reward field, for talking through these ideas with me to make sure I wasn't misinterpreting them.

I'd like to briefly remark that there's an anatomical basis for the idea of two-way communication between brain regions that determine reward and those that control body fatness. It's well known that the latter influence the former (think about your drive to obtain food after you've just eaten a big meal vs. after you've skipped a meal), but there are also connections from the former to the latter via a brain region called the lateral hypothalamus. The point is that it's anatomically plausible that food reward determines in part the amount of body fat a person carries.

Some people may be inclined to think "well, if food tastes bad, you eat less of it; so what!" Although that may be true to some extent, I don't think it can explain the fact that bland diets affect the calorie intake of lean and obese people differently. To me, that implies that highly rewarding food increases the body fat setpoint in susceptible people, and that food with few rewarding properties allows them to return to a lean state.

In the next few posts, I'll describe how food reward explains the effectiveness of many popular fat loss diets, I'll describe how this hypothesis fits in with the diets and health of non-industrial cultures, and I'll outline new dietary strategies for preventing and treating obesity and certain forms of metabolic dysfunction.