Science of Nutrition Podcast

I recently did an interview with Seth Yoder, who has a master's degree in nutrition science and writes the blog The Science of Nutrition.  Seth caught my attention recently with his withering review of The Big Fat Surprise, the latest book to claim that ideological/incompetent scientists and public policy makers got the science of nutrition backward and we should all be eating low-carb, high-fat, high-meat diets.  I was impressed by how deeply Seth dug into the reference list, and how well he picked up on subtle but troubling misrepresentations of the evidence.

Last week, Seth and I got together at a local brewpub to do an interview.  We were joined by Carrie Dennett, an MPH/RDN who has a nutrition blog and writes for the Seattle Times.  I'd probably do a lot more interviews if I could ride my bike to them and have my interviewer buy me a drink.

Speaking of drinks, by the end of the interview I had a little buzz-- you might hear it in my voice if you listen closely.  As usual, I had plenty to say about body fat regulation, food reward, and other topics, with plenty of side trips to discuss particularly fascinating studies.  Also, the word of the day was 'compelling'.

Enjoy the interview!

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Can Hypothalamic Inflammation and Leptin Resistance be Reversed?

A new study by yours truly begins to address the key question: can hypothalamic inflammation and leptin resistance be reversed?

Leptin is the primary hormonal regulator of body fatness in the human body (1).  Secreted by fat tissue, it acts in many places in the body, but its most important effects on body weight occur via the brain, and particularly a brain region called the hypothalamus.  The hypothalamus is responsible for keeping certain physiological variables within the optimal range, including blood pressure, body temperature, and body fatness.

In obesity, the brain loses its sensitivity to leptin, and this causes the body to begin 'defending' a higher level of body fatness, analogous to how a person with a fever 'defends' a higher body temperature (1).  Once a person has become obese, it's difficult to return to true leanness because this system vigorously opposes major fat loss.  Leptin resistance makes fat loss more difficult.

In rodent models, leptin resistance is caused at least in part by inflammatory signaling in the hypothalamus.  We can observe this in multiple ways, but one common way is to look at the appearance of specific cells in the brain that change number, size, and shape when inflammation is present (2).  These cells are called microglia and astrocytes.  In addition to the work in rodents, we've published preliminary evidence that these same inflammatory changes occur in the hypothalamus of obese humans (2).

A key question is whether or not these inflammatory changes can be reversed.  Is a person with leptin resistance doomed to have it forever, undermining fat loss efforts for the rest of his or her life?  Or can it be corrected, possibly allowing easier and more sustainable fat loss?  We just published a study in Endocrinology that begins to answer this question, using a mouse model of dietary obesity (3).  I'm co-first author of this study along with my colleague Kathryn Berkseth, MD.  My former mentor Mike Schwartz, MD is senior author.

The Study

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Food Reward Friday

This week's lucky "winner"...  Cheesecake Factory Bruleed French Toast!

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Help Fund High-Quality Research on Diet and Health

University of California, San Francisco researcher Dr. Ashley Mason has asked me to spread the word about a diet-health study she's preparing to conduct in collaboration with Dr. Lynda Frassetto.  Dr. Frassetto is a widely recognized expert on mineral metabolism and bone health, and also one of the few researchers who has managed to wrangle funding to study the health impacts of a Paleolithic-style diet.  Her findings have been quite provocative.  

Together with their collaborators, Drs. Mason and Frassetto are preparing another diet-health trial to study the impact of two different diets on polycystic ovary syndrome, or PCOS.  PCOS is a common hormonal disorder among reproductive-age women, and its signs and symptoms include ovarian cysts, excess hair growth, menstrual irregularity or absence, infertility, and obesity.  Its causes are unknown, but insulin resistance is a core characteristic of it and is thought to play an important role.  PCOS is thought to be influenced by diet and lifestyle. 

A research team including Drs. Frassetto and Mason, as well as Drs. Umesh Masharani, Heather Huddleston, and Michael Cohn will test a Paleolithic-style diet and an American Diabetes Asssociation diet to see if either or both improves insulin resistance and menstrual cycle regularity for women with PCOS.  Each diet will likely have beneficial effects, however it remains unknown which will be more effective at treating PCOS.

Currently, it's exceedingly difficult for researchers to land funding from the National Institutes of Health (NIH) to do nutrition-related research in the context of disease treatment or management, particularly if it involves a Paleo diet. Recognizing the important potential of fleshing out the relationship between diet and health, researchers are looking for other ways to fund their work.  This study will give them the early data they need to start large, truly definitive studies of the links between diet and insulin resistance, and you can help make it happen.

Please check out their crowdfunding website to learn more about the study, the researchers, and make tax-deductible donations to support their work. And, if you're attending the Ancestral Health Symposium, one of the "backer" rewards is having lunch with the researchers.

Click here to see their crowdfunding site! 


This post was prepared in part using content provided by Dr. Mason.

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Fat and Carbohydrate: Clarifications and Details

The last two posts on fat and carbohydrate were written to answer a few important, but relatively narrow, questions that I feel are particularly pertinent at the moment:

• Was the US obesity epidemic caused by an increase in calorie intake?
• Could it have been caused by an increase in carbohydrate intake, independent of the increase in calorie intake?
• Does an unrestricted high-carbohydrate diet lead to a higher calorie intake and body fatness than an unrestricted high-fat diet, or vice versa?
• Could the US government's advice to eat a low-fat diet have caused the obesity epidemic by causing a dietary shift toward carbohydrate?

However, those posts left a few loose ends that I'd like to tie up in this post.  Here, I'll lay out my opinions on the relationship between macronutrient intake and obesity in more detail.  I'll give my opinions on the following questions:

• What dietary macronutrient composition is the least likely to cause obesity over a lifetime?
• What dietary macronutrient composition is best for a person who is already overweight or obese?
• Is fat inherently fattening and/or unhealthy?

From the beginning

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Food Reward Friday

This week's lucky "winner"... kettle corn!

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Has Obesity Research Failed?

I frequently encounter the argument that obesity research has failed because it hasn't stopped the global increase in obesity rates.  According to this argument, we need to re-think our approach to obesity research because the current approach just isn't working.

Grant funding for obesity research keeps increasing in the US, and the prevalence of obesity also keeps increasing*.  What gives?  Maybe if we just scrapped the whole endeavor we'd be better off.

Let's take a closer look at this argument and see how it holds up.

Why Do Research?

There are two fundamental reasons why we do research:

1. To gather accurate information about the natural world.  This information is intrinsically valuable because we like knowing how the world works, and it may eventually have practical value that's not immediately obvious.
2. Practical applications.  We want to solve problems and improve our lives.

If we want to determine whether or not obesity research has failed, we should evaluate it using those two metrics.

Has Obesity Research Gathered Accurate Information?

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Food Reward Friday

This week's lucky "winner"... Lay's milk chocolate-dipped potato chips!!

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A New Understanding of an Old "Obesity Gene"

As you know if you've been following this blog for a while, obesity risk has a strong genetic component.  Genome-wide association studies (GWAS) attempt to identify the specific locations of genetic differences (single-nucleotide polymorphisms or SNPs) that are associated with a particular trait.  In the case of obesity, GWAS studies have had limited success in identifying obesity-associated genes.  However, one cluster of SNPs consistently show up at the top of the list in these studies: those that are near the gene FTO.

As with many of the genes in our genome, different people carry different versions of FTO.  People with two copies of the "fat" version of the FTO SNPs average about 7 pounds (3 kg) heavier than people with two copies of the "thin" version, and they also tend to eat more calories (1, 2).  

Despite being the most consistent hit in these genetic studies, FTO has remained a mystery.  As with most obesity-associated genes, it's expressed in the brain and it seems to respond somewhat to nutritional status.  Yet its function is difficult to reconcile with a role in weight regulation: 

• It's an enzyme that removes methyl groups from RNA, which doesn't immediately suggest a weight-specific function.
• It's not primarily expressed in the brain or in body fat, but in all tissues.
• Most importantly, as far as we know, the different versions of the gene do not result in different tissue levels of FTO, or different activity of the FTO enzyme, so it's hard to understand how they would impact anything at all.  

An important thing to keep in mind is that GWAS studies don't usually pinpoint specific genes.  Typically, they tell us that obesity risk is associated with variability in a particular region of the genome.  If the region corresponds to the location of a single gene, it's a pretty good guess that the gene is the culprit.  However, that's not always the case...

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Fat vs. Carbohydrate Overeating: Which Causes More Fat Gain?

Two human studies, published in 1995 and 2000, tested the effect of carbohydrate vs. fat overfeeding on body fat gain in humans.  What did they find, and why is it important?

We know that daily calorie intake has increased the US, in parallel with the dramatic increase in body fatness.  These excess calories appear to have come from fat, carbohydrate, and protein all at the same time (although carbohydrate increased the most).  Since the increase in calories, carbohydrate, fat, and protein all happened at the same time, how do we know that the obesity epidemic was due to increased calorie intake and not just increased carbohydrate or fat intake?  If our calorie intake had increased solely by the addition of carbohydrate or fat, would we be in the midst of an obesity epidemic?

The best way to answer this question is to examine the controlled studies that have compared carbohydrate and fat overfeeding in humans.

Horton et al.

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Garden Update: A Banner Year

Things are warming up here in Seattle and the flowers are blooming.  I just planted my first crops of the year-- potatoes and strawberries.

2013 was a banner year for my 500-square-foot urban vegetable garden, including my first experience growing and processing a grain.  I never got around to posting about it last year-- so here it is.

Interbay mulch technique

The bed on the right has been mulched with leaves, spent coffee
grounds, and burlap sacks ($1/sack at the local hardware store).
The beds on the left were planted with a rye-clover-vetch-pea
cover crop.  Paths are mulched with wood chips.

In the fall of 2012, I tried a new technique for improving the soil called "Interbay mulching".  This is a variation on sheet mulching, which involves placing uncomposted organic matter directly onto the garden soil in fall and letting it compost until the next growing season.  To Interbay mulch, you simply cover your sheet mulch with burlap.  This keeps everything moist, protects earthworms from bird predation so they can munch freely, and suppresses weeds.  I used leaves (carbon) and spent coffee grounds from a local coffee shop (nitrogen) for my organic matter.

When I pulled back the burlap last spring, I was initially disappointed.  The coffee grounds had disappeared completely, but there was still a lot of leaf matter left on the soil, indicating that it had only partially composted.  However, I later decided that it had worked well, because the soil structure underneath was improved and it seemed to be enriched with significant organic matter as well as a large population of fat earthworms.  The mulch suppressed weeds remarkably well, and the beds remained mostly clean for the rest of the season.

Those observations, combined with huge yields from the mulched beds, convinced me that it was worthwhile.

New tools
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More Graphs of Calorie Intake vs. BMI

In the last post, a reader commented that the correlation would be more convincing if I graphed calories vs. average BMI rather than the prevalence of obesity.  It was a valid point, so I went searching for average BMI values from NHANES surveys.  I dug up a CDC document that contains data from surveys between 1960 and 2002 (1).  Because these data only cover five survey periods, we only get five data points to analyze, as opposed to the eight used in the last post.  The document contains BMI values for men and women separately, so I averaged the two to approximate average BMI in the general adult population.  It's also worth noting that I use the approximate midpoint of the survey period as the year.

First, a graph of average BMI over time.  It went up:

Now, let's see how well average BMI correlates with calorie intake:

The correlation between calorie intake and obesity prevalence was remarkable, but this correlation is simply incredible.  An R-squared value of 0.98 indicates that daily calorie intake and average BMI are almost perfectly correlated.

We can further deduce that each 100-calorie increase in daily food intake is associated with an 0.62-point increase in average BMI among US adults.  

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Calorie Intake and the US Obesity Epidemic

Between 1960 and 2008, the prevalence of obesity in US adults increased from 13 to 34 percent, and the prevalence of extreme obesity increased from 0.9 to 6 percent (NHANES surveys).  This major shift in population fatness is called the "obesity epidemic".

What caused the obesity epidemic?  As I've noted in my writing and talks, the obesity epidemic was paralleled by an increase in daily calorie intake that was sufficiently large to fully account for it.  There are two main sources of data for US calorie intake.  The first is NHANES surveys conducted by the Centers for Disease Control.  They periodically collect data on food intake using questionnaires, and these surveys confirm that calorie intake has increased.  The problem with the NHANES food intake data is that they're self-reported and therefore subject to major reporting errors.  However, NHANES surveys provide the best quality (objectively measured) data on obesity prevalence since 1960, which we'll be using in this post.

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