Thursday, May 28, 2015

How Bad is Fructose? David Despain Interviews Dr. John Sievenpiper

In my article "Is Sugar Fattening?", I discussed a recent review paper on fructose, by Dr. John Sievenpiper and colleagues (1).  It was the most recent of several review papers to conclude that fructose is probably not inherently fattening in humans, but that it can be fattening if it's consumed to excess, due to the added calories.  Dr. Sievenpiper and colleagues have also written other papers addressing the metabolic effects of fructose, which appear to be fairly minor unless it's consumed to excess (2, 3, 4, 5).  The senior author on these studies is Dr. David Jenkins at McMaster University.  David Despain, a science and health writer who publishes a nice blog called Evolving Health, recently interviewed Dr. Sievenpiper about his work.

It's an interesting interview and very timely, due to the recent attention paid to fructose in the popular media. This has mostly been driven by a couple of high-profile individuals-- an issue they discuss in the interview.  The interview, recent papers, and sessions at scientific conferences are part of an effort by researchers to push back against some of the less well founded claims that have received widespread attention lately.

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Tuesday, May 26, 2015

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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Sunday, May 24, 2015

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!

Friday, May 22, 2015

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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Thursday, May 21, 2015

Lower Blood Pressure Naturally

Recently, Chris Kresser published a series on dietary salt (sodium chloride) and health (1).  One of the issues he covered is the effect of salt on blood pressure.  Most studies have shown a relatively weak relationship between salt intake and blood pressure.  My position overall is that we're currently eating a lot more salt than at almost any point in our evolutionary history as a species, so I tend to favor a moderately low salt intake.  However, there may be more important factors than salt when it comes to blood pressure, at least in the short term. 

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Monday, May 18, 2015

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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Sunday, May 17, 2015

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. 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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Beyond Ötzi: European Evolutionary History and its Relevance to Diet. Part III

In previous posts, I reviewed some of the evidence suggesting that human evolution has accelerated rapidly since the development of agriculture (and to some degree, before it).  Europeans (and other lineages with a long history of agriculture)  carry known genetic adaptations to the Neolithic diet, and there are probably many adaptations that have not yet been identified.  In my final post in this series, I'll argue that although we've adapted, the adaptation is probably not complete, and we're left in a sort of genetic limbo between the Paleolithic and Neolithic state. 

Recent Genetic Adaptations are Often Crude

It may at first seem strange, but many genes responsible for common genetic disorders show evidence of positive selection.  In other words, the genes that cause these disorders were favored by evolution at some point because they presumably provided a survival advantage.  For example, the sickle cell anemia gene protects against malaria, but if you inherit two copies of it, you end up with a serious and life-threatening disorder (1).  The cystic fibrosis gene may have been selected to protect against one or more infectious diseases, but again if you get two copies of it, quality of life and lifespan are greatly curtailed (2, 3).  Familial Mediterranean fever is a very common disorder in Mediterranean populations, involving painful inflammatory attacks of the digestive tract, and sometimes a deadly condition called amyloidosis.  It shows evidence of positive selection and probably protected against intestinal disease due to the heightened inflammatory state it confers to the digestive tract (4, 5).  Celiac disease, a severe autoimmune reaction to gluten found in some grains, may be a by-product of selection for protection against bacterial infection (6).  Phenylketonuria also shows evidence of positive selection (7), and the list goes on.  It's clear that a lot of our recent evolution was in response to new disease pressures, likely from increased population density, sendentism, and contact with domestic animals.

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Wednesday, May 13, 2015

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.

Read more »

Friday, May 8, 2015

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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Thursday, May 7, 2015

Beyond Ötzi: European Evolutionary History and its Relevance to Diet. Part II

In previous posts, I described how Otzi was (at least in large part) a genetic descendant of Middle Eastern agriculturalists, rather than being purely descended from local hunter-gatherers who adopted agriculture in situ.  I also reviewed evidence showing that modern Europeans are a genetic mixture of local European hunter-gatherers, incoming agricultural populations from the Middle East, neanderthals, and perhaps other groups.  In this post, I'll describe the evidence for rapid human evolution since the end of the Paleolithic period, and research indicating that some of these changes are adaptations to the Neolithic (agricultural/horticultural/pastoral) diet.

Humans have Evolved Significantly Since the End of the Paleolithic

Evolution by natural selection leaves a distinct signature in the genome, and geneticists can detect this signature tens of thousands of years after the fact by comparing many genomes to one another.  A landmark paper published in 2007 by Dr. John Hawks and colleagues showed that humans have been undergoing "extraordinarily rapid recent genetic evolution" over the last 40,000 years (1).  Furthermore:
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The Neurobiology of the Obesity Epidemic

I recently read an interesting review paper by Dr. Edmund T. Rolls titled "Taste, olfactory and food texture reward processing in the brain and the control of appetite" that I'll discuss in this post (1).  Dr. Rolls is a prolific neuroscience researcher at Oxford who focuses on "the brain mechanisms of perception, memory, emotion and feeding, and thus of perceptual, memory, emotional and appetite disorders."  His website is here.

The first half of the paper is technical and discusses some of Dr. Rolls' findings on how specific brain areas process sensory and reward information, and how individual neurons can integrate multiple sensory signals during this process.  I recommend reading it if you have the background and interest, but I'm not going to cover it here.  The second half of the paper is an attempt to explain the obesity epidemic based on what he knows about the brain and other aspects of human biology.

Read more »

Wednesday, May 6, 2015

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 H
uman 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 leaner 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.

Tuesday, May 5, 2015

Media Appearances

Last October, I participated in a panel discussion organized by the Harvard Food Law Society in Boston.  The panel included Drs. Walter Willett, David Ludwig, Robert Lustig, and myself, with Corby Kummer as moderator.  Dr. Willett is the chair of the Harvard Department of Nutrition; Dr. Ludwig is a professor of nutrition and pediatrics at Harvard; Dr. Lustig is a professor of clinical pediatrics at UCSF; and Kummer is a food writer and senior editor for The Atlantic
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Saturday, May 2, 2015

Speaking at AHS13

The 2015 Ancestral Health Symposium will be held in Atlanta, GA, August 14-17.  Last year was a great conference, and I look forward to more informative talks and networking.  Tickets go fast, so reserve yours now if you plan to attend!

This year, I'll be speaking on insulin and obesity.  My talk will be titled "Insulin and Obesity: Reconciling Conflicting Evidence".  In this talk, I'll present the evidence for and against the idea that elevated insulin contributes to the development of obesity.  One hypothesis states that elevated insulin contributes to obesity, while the other states that elevated insulin is caused by obesity and does not contribute to it.  Both sides of the debate present evidence that appears compelling, and it often seems like each side is talking past the other rather than trying to incorporate all of the evidence into a larger, more powerful model.

There's a lot evidence that can be brought to bear on this question, but much of it hasn't reached the public yet.  I'll explore a broad swath of evidence from clinical case studies, observational studies, controlled trials, animal research, physiology, and cell biology to test the two competing hypotheses and outline a model that can explain all of the seemingly conflicting data.  Much of this information hasn't appeared on this blog.  My goal is to put together a talk that will be informative to a researcher but also accessible to an informed layperson.

On a separate note, my AHS12 talk "Digestive Health, Inflammation and the Metabolic Syndrome" has not been posted online because the video recording of my talk has mysteriously disappeared.  I think many WHS readers would be interested in the talk, since it covers research on the important and interdependent influence of gut health, inflammation, and psychological stress on the metabolic syndrome (the quintessential modern metabolic disorder).  I'm going to try to find time to make a narrated slideshow so I can post it on YouTube.