Glucagon, Dietary Protein, and Low-Carbohydrate Diets

Glucagon is a hormone that plays an important role in blood glucose control. Like insulin, it's secreted by the pancreas, though it's secreted by a different cell population than insulin (alpha vs. beta cells). In some ways, glucagon opposes insulin. However, the role of glucagon in metabolism is frequently misunderstood in diet-health circles.

The liver normally stores glucose in the form of glycogen and releases it into the bloodstream as needed. It can also manufacture glucose from glycerol, lactate, and certain amino acids. Glucagon's main job is to keep blood glucose from dipping too low by making sure the liver releases enough glucose. There are a few situations where this is particularly important:

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Dogs Eating Carbs

Five years ago, I had an interesting conversation with a veterinarian friend about dog food. We were talking about diabetes in one of the dogs she was treating, and I remarked "that's what happens when you feed a carnivore carbohydrate". She gave me a funny look. At the time, I was seeing the world through the low-carb lens, and I remember thinking how bizarre it was that she didn't yield to my impeccable logic. As they say, live and learn.

The journal Nature published a fascinating paper on the evolution of the domestic dog today (1). Researchers compared the genome of wolves and domestic dogs to see what genetic changes accompanied domestication.

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The Potato Diet

In 2010, I wrote a series of blog posts on the health properties of potatoes (1, 2, 3). The evidence showed that potatoes are non-toxic, filling per calorie, remarkably nutritious, and can be eaten as almost the sole source of nutrition for extended periods of time (though I'm not recommending this). Traditional South American cultures such as the Quechua and Aymara have eaten potatoes as the major source of calories for generations without any apparent ill effects (3). This is particularly interesting since potatoes are one of the highest glycemic and most insulin-stimulating foods known.

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Nutrition Science Initiative (NuSI)

Some of you may have heard of an ambitious new nutrition research foundation called the Nutrition Science Initiative (NuSI). In this post, I'll explain what it is, why it matters, and how I feel about it-- from the perspective of an obesity researcher.

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Ancestral Health Symposium 2012

I recently returned from AHS12 and a little side trip to visit family. The conference was hosted at Harvard University through the Harvard Food Law Society. Many thanks to all the organizers who made it happen. By and large, it went smoothly.

The science as expected ranged from outstanding to mediocre, but I was really encouraged by the presence and enthusiastic participation of a number of quality researchers and clinicians. The basic concept of ancestral health is something almost anyone can get behind: many of our modern health problems are due to a mismatch between the modern environment and what our bodies "expect". The basic idea is really just common sense, but of course the devil is in the details when you start trying to figure out what exactly our bodies expect, and how best to give it to them. I think our perspective as a community is moving in the right direction.

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Interview with Aitor Calero of Directo al Paladar

Aitor Calero writes for the popular Spanish cooking and nutrition blog, Directo al Paladar ("straight to the palate"). We did a written interview a while back, and he agreed to let me post the English version on my blog. The Spanish version is here and here.

Without further ado, here it is:

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Why Did Energy Expenditure Differ Between Diets in the Recent Study by Dr. Ludwig's Group?

As discussed in the previous post, a recent study by Dr. David Ludwig's group suggested that during weight maintenance following fat loss, eating a very low carbohydrate (VLC) diet led to a higher metabolic rate (energy expenditure) than eating a low-fat (LF) diet, with a low glycemic index (LGI) diet falling in between the two (1). The VLC diet was 30 percent protein, while the other two were 20 percent. It's important to note that these were three dietary patterns that differed in many ways, and contrary to claims that are being made in the popular media, the study was not designed to isolate the specific influence of protein, carbohydrate or fat on energy expenditure in this context.

Not only did the VLC diet lead to a higher total energy expenditure than the LF and LGI diets, the most remarkable finding is that it led to a higher resting energy expenditure. Basically, people on the VLC diet woke up in the morning burning more energy than people on the LGI diet, and people on the LGI diet woke up burning more than people on the LF diet. The VLC dieters burned 326 more calories than the LF dieters, and 200 more than the LGI dieters.

It's always tempting to view each new study in isolation, without considering the numerous studies that came before it, but in this case it's essential to see this study through a skeptical lens that places it into the proper scientific context. Previous studies have suggested that:

1. The carbohydrate:fat ratio of the diet has little or no detectable impact on energy expenditure in people who are not trying to lose weight (2, 3).
2. The carbohydrate:fat ratio of the diet has little or no detectable impact on energy expenditure in people who are being experimentally overfed, and if anything carbohydrate increases energy expenditure more than fat (4, 5).
3. The carbohydrate:fat ratio of the diet has little or no detectable impact on energy expenditure during weight loss (6, 7, 8), and does not influence the rate of fat loss when calories are precisely controlled.

This new study does not erase or invalidate any of these previous findings. It fills a knowledge gap about the effect of diet composition on energy expenditure specifically in people who have lost weight and are trying to maintain the reduced weight.

With that, let's see what could have accounted for the differences observed in Dr. Ludwig's study.
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New Study: Is a Calorie a Calorie?

A new study in JAMA led by Dr. Cara B. Ebbeling and colleagues purports to challenge the idea that all calories are equally fattening (1). Let's have a look. When thinking about the role of calorie intake in body fatness, there are basically three camps:

1. Calories don�t matter at all, only diet composition matters.
2. Calories are the only thing that matters, and diet composition is irrelevant.
3. Calories matter, but diet composition may also play a role.

The first one is an odd position that is not very well populated. The second one has a lot of adherents in the research world, and there�s enough evidence to make a good case for it. It�s represented by the phrase �a calorie is a calorie�, i.e. all calories are equally fattening. #1 and #2 are both extreme positions, and as such they get a lot of attention. But the third group, although less vocal, may be closest to the truth.
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What Causes Insulin Resistance? Part V

Previously in this series, we've discussed the role of cellular energy excess, inflammation, brain insulin resistance, and micronutrient status in insulin resistance. In this post, I'll explore the role of macronutrients and sugar in insulin sensitivity.

Carbohydrate and Fat

There are a number of studies on the effect of carbohydrate:fat ratios on insulin sensitivity, but many of them are confounded by fat loss (e.g., low-carbohydrate and low-fat weight loss studies), which almost invariably improves insulin sensitivity. What interests me the most is to understand what effect different carbohydrate:fat ratios have on insulin sensitivity in healthy, weight stable people. This will get at what causes insulin resistance in someone who does not already have it.

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I Got Boinged, and Other News

The reaction to my post "The Carbohydrate Hypothesis of Obesity: a Critical Examination" has been overwhelmingly positive, particularly among the scientists I've heard from. 

On Saturday, the inimitable maker and writer Mark Frauenfelder posted a link to my post on the variety blog BoingBoing.  BoingBoing has been on my sidebar for three years, and it's the place I go when I need a break.  It's a fun assortment of science, news, technology and entertainment.  BoingBoing was originally a zine started by Frauenfelder and his wife in 1988, and it has been on the web since 1995.  Today, it has multiple contributing authors and it draws several hundred thousand hits per day.  I'm thrilled that Frauenfelder posted my article there.  Apparently he likes my blog.  Thanks!

I added a new section (IIB) to my original post.  It discusses what human genetics can teach us about the mechanisms of common obesity.  It is consistent with the rest of the evidence suggesting that body fatness is primarily regulated by the brain, not by fat tissue, and that leptin signaling plays a dominant role in this process. 

The Carbohydrate Hypothesis of Obesity: a Critical Examination

Introduction

I'd like to begin by emphasizing that carbohydrate restriction has helped many people lose body fat and improve their metabolic health. Although it doesn't work for everyone, there is no doubt that carbohydrate restriction causes fat loss in many, perhaps even most obese people. For a subset of people, the results can be very impressive. I consider that to be a fact at this point, but that's not what I'll be discussing here.

What I want to discuss is a hypothesis. It's the idea, championed by Gary Taubes, that carbohydrate (particularly refined carbohydrate) is the primary cause of common obesity due to its ability to elevate insulin, thereby causing increased fat storage in fat cells. To demonstrate that I'm representing this hypothesis accurately, here is a quote from his book Good Calories, Bad Calories:

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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!

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. 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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Interview with Chris Voigt of 20 Potatoes a Day

Introduction

Chris Voigt is the executive director of the Washington State Potato Commission, which supports and promotes the Washington state potato industry (1). On October 1st, Mr. Voigt began a two month, potato-only diet to raise awareness about the health properties of potatoes. It was partially in response to the recent decision by the federal WIC (Women, Infants and Children) low-income assistance program to remove potatoes from the list of vegetables it will pay for. Mr. Voigt's potato diet has been a media sensation, leading to widespread coverage in several countries. He maintains a website and blog called 20 Potatoes a Day.


Diet Facts

For 60 days, Mr Voigt's diet consisted of nothing but potatoes and a small amount of cooking oil (canola and olive), with no added nutritional supplements. Based on what he has told me, I estimate that 10-15% of his calories came from fat, 10% from protein and 75-80% from high-glycemic carbohydrate. His calorie intake ranged from 1,600 kcal (first 3 weeks) to 2,200 kcal (remaining 5.5 weeks) per day. Prior to the diet, he estimated that his calorie requirement was 2,200 kcal, so he attempted to stay as close to that as possible.

Health Markers

Mr. Voigt has posted the results of physical examinations, including bloodwork, from the beginning, middle and end of the diet. The change he experienced during that time is nothing short of remarkable. He shed 21 pounds, his fasting glucose decreased by 10 mg/dL (104 to 94 mg/dL), his serum triglycerides dropped by nearly 50%, his HDL cholesterol increased slightly, and his calculated LDL cholesterol dropped by a stunning 41% (142 to 84 mg/dL). The changes in his HDL, triglycerides and fasting glucose are consistent with improved insulin sensitivity (2, 3), and are not consistent with a shift of LDL particle size to the dangerous "small, dense" variety (4).

Interview

What was your diet like prior to the potato diet?

My best estimate is that it was probably a little better than the average US citizen only because of a high rate of produce consumption. I generally would eat about 10 servings of fruits and vegetables a day. But I ate everything else too. I would eat a wide range of food, a little bit of everything, including foods that aren�t considered �healthy�.

You essentially ate nothing but potatoes, fat and flavorings for two months. Can you give us an idea of how much fat you were eating? What kind of fat was it?

I averaged about 2 tablespoons of cooking oil a day over the span of the 60 days. Canola oil was used for frying and olive oil was used for roasting.

How was your digestion?

Potatoes are pretty easy on the digestive system. I actually got a lot of emails from people who suffer from severe digestive disorders and literally, potatoes are the only thing they can eat. My 60 days of potatoes was nothing compared to some folks with these digestive disorders. I was getting a lot of fiber so things were pretty regular, but not too regular :)

You lost 21 pounds during your two months of eating only potatoes. Do you have a sense of whether it came out of fat, muscle or both? For example, did your pants become looser?

Pants definitely became looser. I also noticed it in my neck size for shirts. I�m assuming most all of it was due to fat loss.

Do you think you were able to meet your calorie goal of 2,200 calories per day? Were you hungry during the diet?

I was not meeting the goal of 2,200 calories a day during the first 3 weeks of the diet. During the first three weeks of the diet I only ate until I was full. I didn�t realize that potatoes would give me such a high sense of fullness after each meal. So for those first 3 weeks, I was only consuming about 1,600 calories a day. After the third week I had lost 12 pounds and realized that I needed to change strategy. I then began to eat more potatoes despite the sense of fullness I was experiencing. So for the remaining 5 � weeks I was very diligent about eating the 2,200 calories. I continued to lose weight but at a slower place. I lost an additional 9 pounds over the course of those remaining 5 1/2 weeks. At the start of my diet I estimated, via a couple different on line calorie calculators, that I burn about 2,200 calories a day. Since I continued to lose weight, I�m assuming I actually burn closer to 2,800 calories a day. Something that may have also played a role in continued weight loss was the amount of resistant starch I was getting from potatoes. I ate a lot of cooked potatoes that had been refrigerated. These are generally higher in resistant starch. If I were to do the diet again, I would like to set up an experiment to gauge the effect of resistant starch.

What foods did you crave the most?

I craved mostly foods that had a �juicy crunch�, like an apple, or cucumbers, or carrots, or celery. I never acquired a taste for raw potatoes so virtually all the potatoes I consumed were cooked. No matter how you cook your potatoes, you always get that same soft cooked texture. I craved foods with a crisper texture.

How was your energy level?

My energy level was very good the entire time of the diet. I really didn�t notice a change in energy at the start of the diet so I assumed that the potato diet didn�t have a positive or negative effect on my energy level. It wasn�t until I finished the diet and started to consume other foods that I noticed my energy level has seemed to drop a bit.

How did you feel overall? Were there any unexpected effects of the diet?

I felt really good on the diet. I had lots of energy, slept good at night, and seemed to avoid the cold viruses that circulated at home and work.

The only unusual thing that occurred is what my wife told me. I�m a habitual snorer. The day I started eating only potatoes, my snoring stopped. It restarted the day I started to include other foods in my diet. I�m assuming it was just some weird coincidence but that�s what she tells me.

My doctor and I expected my cholesterol to drop but not at the level we saw. I�ve had borderline high cholesterol for the past decade. I started the diet at 214 and saw it drop to 147 at the end of 60 days. We anticipated a drop of maybe 10-25 points. It was a huge surprise to see a 67 point drop.

Your fasting glucose went from 104 mg/dL, which I consider high, to 94 mg/dL, which is on the high side for someone eating a high-carbohydrate diet, but within the clinically normal range. Do you have a family history of diabetes?

No history of diabetes. My parents are in their early eighties and their parents lived to their 70�s and 80�s with no history of type one or two diabetes.

Reading your blog posts, it seemed like you were having a hard time with the diet at first, but after a while you complained less and even seemed to enjoy it at times. Did you get used to it?

I would say that week 2 and 3 were probably the hardest. The first week was easy probably because of the novelty of the diet. Then reality set in for week 2 and 3. After that, I found my groove and it got easier. During the work week was easy but weekends, particularly Sunday�s, were the hardest. During the work week I did most of my eating at my desk so I wasn�t around a lot of other people eating or surrounded by other foods. Weekends were more difficult because I was around other people every meal and always had other foods in front of me at home.

What kinds of potatoes did you eat?

I literally ate every kind of potato I could get my hands on. I ate yellow skin/yellow flesh potatoes, red skin/white flesh, red skin/red flesh, purple skin/white flesh, purple skin/purple flesh, russet potatoes with white flesh, russet potatoes with yellow flesh, white potatoes, yellow potatoes with white flesh, purple fingerlings, yellow fingerlings, red fingerlings and numerous experimental varieties.

Did you peel them or eat the skin?

I ate the skin at least 90% of the time if not more. There is a myth that all the nutrition in a potato is in the skin or right under the skin. That�s not true, there are nutrients spread throughout the potato but most of the fiber is located in the skin.

What variety of potato is your favorite?

It really depended on the cooking method. For frying, I preferred russet potatoes. For baking, I preferred red potatoes. For mashed, I preferred yellow potatoes. For roasting, a toss-up between russets and reds.

How long did it take you after the diet ended to eat another potato?

As strange as it sounds, potatoes were my first two meals after my diet ended. I was saving my first non-potato meal for a special event that was planned at the local Head Start facility. The beef, dairy, apple, and potato producers put together a nice dinner event and nutrition workshop for all the kids and their parents at the Head Start center in Moses Lake. I still eat potatoes pretty regularly, but most of the time now I�m eating them with more than just seasonings.

Are there any other facts about potatoes you think Whole Health Source readers might find interesting?

Just a reminder that I�m not encouraging anyone to follow in my footsteps and eat just potatoes. This diet is not intended to be the next �fad� diet but was simply a bold statement to remind people that there is a tremendous amount of nutrition in a potato. There is no one food product that can meet all of your nutritional needs. I fully support a well balanced healthy diet, which potatoes can be a part of.

In 2008, the United Nations declared it to be the �Year of the Potato�. This was done to bring attention to the fact that the potato is one of the most efficient crops for developing nations to grow, as a way of delivery a high level of nutrition to growing populations, with fewer needed resources than other traditional crops. In the summer of 2010, China approved new government policies that positioned the potato as the key crop to feed its growing population. The Chinese government formed a partnership with the International Potato Center in Peru to help them facilitate this new emphasis on the potato.

Thanks Chris, for doing your experiment and taking the time to share these details with us!

In the next post, I'll give my interpretation of all this.

Dr. Mellanby's Tooth Decay Reversal Diet

I have a lot of admiration for Drs. Edward and May Mellanby. A husband-and-wife team, they discovered vitamin D, and determined that rickets is caused by poor calcium (or phosphorus) status, typically due to vitamin D deficiency. They believed that an ideal diet is omnivorous, based on whole foods, and offers an adequate supply of fat-soluble vitamins and easily absorbed minerals. They also felt that grain intake should be modest, as their research showed that unsoaked whole grains antagonize the effect of vitamins D and A.

Not only did the Mellanbys discover vitamin D and end the rickets epidemic that was devastating Western cities at the time, they also discovered a cure for early-stage tooth decay that has been gathering dust in medical libraries throughout the world since 1924.

It was in that year that Dr. May Mellanby published a summary of the results of the Mellanby tooth decay reversal studies in the British Medical Journal, titled "Remarks on the Influence of a Cereal-free Diet Rich in Vitamin D and Calcium on Dental Caries in Children". Last year, I had to specially request this article from the basement of the University of Washington medical library (1). Thanks to the magic of the internet, the full version of the paper is now freely available online (2).

You don't need my help to read the study, but in this post I offer a little background, a summary and my interpretation.

In previous studies, the Mellanbys used dogs to define the dietary factors that influence tooth development and repair. They identified three, which together made the difference between excellent and poor dental health (from Nutrition and Disease):

1. The diet's mineral content, particularly calcium and phosphorus
2. The diet's fat-soluble vitamin content, chiefly vitamin D
3. The diet's content of inhibitors of mineral absorption, primarily phytic acid

Once they had defined these factors, they set about testing their hypotheses in humans. They performed eight trials, each one in children in an institutionalized setting where diet could be completely controlled. The number of cavities in each child's mouth was noted at the beginning and end of the period. I'll only discuss the three most informative, and only the most successful in detail. First, the results:

I'll start with diet 1. Children on this diet ate the typical fare, plus extra oatmeal. Oatmeal is typically eaten as an unsoaked whole grain (and soaking it isn't very effective in any case), and so it is high in phytic acid, which effectively inhibits the absorption of a number of minerals including calcium. These children formed 5.8 cavities each and healed virtually none-- not good!

Diet number 2 was similar to diet 1, except there was no extra oatmeal and the children received a large supplemental dose of vitamin D. Over 28 weeks, only 1 cavity per child developed or worsened, while 3.9 healed. Thus, simply adding vitamin D to a reasonable diet allowed most of their cavities to heal.

Diet number 3 was the most effective. This was a grain-free diet plus supplemental vitamin D. Over 26 weeks, children in this group saw an average of only 0.4 cavities form or worsen, while 4.7 healed. The Mellanbys considered that they had essentially found a cure for this disorder in its early stages.

What exactly was this diet? Here's how it was described in the paper (note: cereals = grains):

...instead of cereals- for example, bread, oatmeal, rice, and tapioca- an increased allowance of potatoes and other vegetables, milk, fat, meat, and eggs was given. The total sugar, jam, and syrup intake was the same as before. Vitamin D was present in abundance in either cod-liver oil or irradiated ergosterol, and in egg yolk, butter, milk, etc. The diet of these children was thus rich in those factors, especially vitamin D and calcium, which experimental evidence has shown to assist calcification, and was devoid of those factors- namely, cereals- which interfere with the process.

Carbohydrate intake was reduced by almost half. Bread and oatmeal were replaced by potatoes, milk, meat, fish, eggs, butter and vegetables. The diet is reminiscent of what Dr. Weston Price used to reverse tooth decay in his dental clinic in Cleveland, although Price's diet did include rolls made from freshly ground whole wheat. Price also identified the fat-soluble vitamin K2 MK-4 as another important factor in tooth decay reversal, which would have been abundant in Mellanby's studies due to the dairy. The Mellanbys and Price were contemporaries and had parallel and complementary findings. The Mellanbys did not understand the role of vitamin K2 in mineral metabolism, and Price did not seem to appreciate the role of phytic acid from unsoaked whole grains in preventing mineral absorption.

Here are two sample meals provided in Dr. Mellanby's paper. I believe the word "dinner" refers to the noon meal, and "supper" refers to the evening meal:

Breakfast- Omelette, cocoa, with milk.
Lunch- Milk.
Dinner- Potatoes, steamed minced meat, carrots, stewed fruit, milk.
Tea- Fresh fruit salad, cocoa made with milk.
Supper- Fish and potatoes fried in dripping, milk.

Breakfast- Scrambled egg, milk, fresh salad.
Dinner- Irish stew, potatoes, cabbage, stewed fruit, milk.
Tea- Minced meat warmed with bovril, green salad, milk.
Supper- Thick potato soup made with milk.

In addition, children received vitamin D daily. Here's Dr. Mellanby's summary of their findings:

The tests do not indicate that in order to prevent dental caries children must live on a cereal-free diet, but in association with the results of the other investigations on animals and children they do indicate that the amount of cereal eaten should be reduced, particularly during infancy and in the earlier years of life, and should be replaced by an increased consumption of milk, eggs, butter, potatoes, and other vegetables. They also indicate that a sufficiency of vitamin D and calcium should be given from birth, and before birth, by supplying a suitable diet to the pregnant mother. The teeth of the children would be well formed and more resistant to dental caries instead of being hypoplastic and badly calcified, as were those in this investigation.

If I could add something to this program, I would recommend daily tooth brushing and flossing, avoiding sugar, and rinsing the mouth with water after each meal.

This diet is capable of reversing early stage tooth decay. It will not reverse advanced decay, which requires professional dental treatment as soon as possible. It is not a substitute for dental care in general, and if you try using diet to reverse your own tooth decay, please do it under the supervision of a dentist. And while you're there, tell her about Edward and May Mellanby!

Preventing Tooth Decay
Reversing Tooth Decay
Images of Tooth Decay Healing due to an Improved Diet
Dental Anecdotes

Glucose Tolerance in Non-industrial Cultures

Background

Glucose is the predominant blood sugar and one of the body's two main fuel sources (the other is fatty acids). Glucose, in one form or another, is also the main form of digestible dietary carbohydrate in nearly all human diets. Starch is made of long chains of glucose molecules, which are rapidly liberated and absorbed during digestion. Sucrose, or table sugar, is made of one glucose and one fructose molecule, which are separated before absorption.

Blood glucose is essential for life, but it can also be damaging if there is too much of it. Therefore, the body tries to keep it within a relatively tight range. Normal fasting glucose is roughly between 70 and 90 mg/dL*, but in the same individual it's usually within about 5 mg/dL on any given day. Sustained glucose above 160 mg/dL or so causes damage to multiple organ systems. Some people would put that number closer to 140 mg/dL.

The amount of glucose contained in a potato far exceeds the amount contained in the blood, so if all that glucose were to enter the blood at once, it would lead to a highly damaging blood glucose level. Fortunately, the body has a hormone designed to keep this from happening: insulin. Insulin tells cells to internalize glucose from the blood, and suppresses glucose release by the liver. It's released by the pancreas in response to eating carbohydrate, and protein to a lesser extent. The amount of insulin released is proportional to the amount of carbohydrate ingested, so that glucose entering the blood is cleared before it can accumulate.

Insulin doesn't clear all the glucose as it enters the bloodstream, however. Some of it does accumulate, leading to a spike in blood glucose. This usually doesn't exceed 130 mg/dL in a truly healthy person, and even if it approaches that level it's only briefly. However, diabetics have reduced insulin signaling, and eating a typical meal can cause their glucose to exceed 300 mg/dL due to reduced insulin action and/or insulin secretion. In affluent nations, this is typically due to type II diabetes, which begins as insulin resistance, a condition in which insulin is actually higher than normal but cells fail to respond to it.  The next step is the failure of insulin-secreting beta cells, which is what generally precipitates actual diabetes.

The precursor to diabetes is called glucose intolerance, or pre-diabetes. In someone with glucose intolerance, blood glucose after a typical meal will exceed that of a healthy person, but will not reach the diabetic range (a common definition of diabetes is 200 mg/dL or higher, 2 hours after ingesting 75g of glucose). Glucose tolerance refers to a person's ability to control blood glucose when challenged with dietary glucose, and can be used in some contexts as a useful predictor of diabetes risk and general metabolic health. Doctors use the oral glucose tolerance test (OGTT), which involves drinking 60-100g glucose and measuring blood glucose after one or two hours, to determine glucose tolerance.

Why do we care about glucose tolerance in non-industrial cultures?

One of the problems with modern medical research is that so many people in our culture are metabolically sick that it can be difficult to know if what we consider "normal" is really normal or healthy in the broader sense. Non-industrial cultures allow us to examine what the human metabolism is like in the absence of metabolic disease. I admit this rests on certain assumptions, particularly that these people aren't sick themselves. I don't think all non-industrial cultures are necessarily healthy, but I'm going to stick with those that research has shown have an exceptionally low prevalence of diabetes (by Western standards) and other "diseases of civilization" for the purposes of this post.

Here's the question I really want to answer in this post: do healthy non-industrial cultures with a very high carbohydrate intake have an excellent glucose tolerance, such that their blood glucose doesn't rise to a high level, or are they simply resistant to the damaging effects of high blood glucose?

The data

I'm going to start with an extreme example. In the 1960s, when it was fashionable to study non-industrial cultures, researchers investigated the diet and health of a culture in Tukisenta, in the highlands of Papua New Guinea. The eat practically nothing but sweet potatoes, and their typical daily fare is 94.6 percent carbohydrate. Whether or not you believe that exact number, their diet was clearly extraordinarily high in carbohydrate. They administered 100g OGTTs and measured blood glucose at one hour, which is a very stringent OGTT. They compared the results to those obtained in the 1965 Tecumseh study (US) obtained by the same method. Here's what they found (1):
Compared to Americans, in Tukisenta they had an extraordinary glucose tolerance at all ages. At one hour, their blood glucose was scarcely above normal fasting values, and glucose tolerance only decreased modestly with age. In contrast, in Americans over 50 years old, the average one-hour value was around 180 mg/dL!

Now let's take a look at the African Bantu in the Lobaye region of the Central African Republic. The Bantu are a large ethnic group who primarily subsist on a diverse array of starchy foods including grains, beans, plantains and root crops. One hour after a 100g OGTT, their blood glucose was 113 mg/dL, compared to 139 mg/dL in American controls (2). Those numbers are comparable to what investigators found in Tukisenta, and indicate an excellent glucose tolerance in the Bantu.

In South America, different investigators studied a group of native Americans in central Brazil that subsist primarily on cassava (a starchy root crop) and freshwater fish. Average blood glucose one hour after a 100g OGTT was 94 mg/dl, and only 2 out of 106 people tested had a reading over 160 mg/dL (both were older women) (Western Diseases: Their Emergence and Prevention, p. 149). Again, that indicates a phenomenal glucose tolerance by Western standards.

I have to conclude that high-carbohydrate non-industrial cultures probably don't experience damaging high blood glucose levels, because their glucose tolerance is up to the task of shuttling a huge amount of glucose out of the bloodstream before that happens.

Not so fast...

Now let's turn our attention to another study that may throw a wrench in the gears. A while back, I found a paper containing OGTT data for the !Kung San (also called the Bushmen), a hunter-gatherer group living in the Kalahari desert of Africa. I reported in an earlier post that they had a good glucose tolerance. When I revisited the paper recently, I realized I had misread it and in fact, their glucose tolerance was actually pretty poor.

Investigators administered a 50g OGTT, half what the other studies used. At one hour, the San had blood glucose readings of 169 mg/dL, compared to 142 mg/dL in Caucasian controls (3)! I suspect a 100g OGTT would have put them close to the diabetic range.

Wait a minute, these guys are hunter-gatherers living the ancestral lifestyle; aren't they supposed to be super healthy?? First of all, like many hunter-gatherer groups the San are very small people: the men in this study were only 46 kg (101 lbs).  The smaller you are, the more a given amount of carbohydrate will raise your blood glucose.  Also, while I was mulling this over, I recalled a discussion where non-diabetic people were discussing their 'diabetic' OGTT values while on a low-carbohydrate diet. Apparently, carbohydrate refeeding for a few days generally reverses this and allows a normal OGTT in most people. It turns out this effect has been known for the better part of a century.

So what were the San eating? The study was conducted in October of 1970. The San diet changes seasonally, however their main staple food is the mongongo nut, which is mostly fat and which is available year-round (according to The !Kung San: Men, Women and Work in a Foraging Society). Their carbohydrate intake is generally low by Western standards, and at times of the year it is very low. This varies by the availability of other foods, but they generally don't seem to relish the fibrous starchy root crops that are available in the area, as they mostly eat them when other food is scarce. Jean-Louis Tu has posted a nice analysis of the San diet on BeyondVeg (4). Here's a photo of a San man collecting mongongo nuts from The !Kung San: Men, Women and Work in a Foraging Society:

What did the authors of the OGTT study have to say about their diet? Acknowledging that prior carbohydrate intake may have played a role in the OGTT results of the San, they made the following remark:

a retrospective dietary history (M. J. Konner, personal communication, 1971) indicated that the [San], in fact, consumed fairly large amounts of carbohydrate-rich vegetable food during the week before testing.

However, the dietary history was not provided, nor has it been published, so we have no way to assess the statement's accuracy or what was meant by "fairly large amounts of carbohydrate-rich vegetable food." Given the fact that the San diet typically ranges from moderately low to very low in carbohydrate, I suspect they were not getting much carbohydrate as a percentage of calories. Looking at the nutritional value of the starchy root foods they typically eat in appendix D of The !Kung San: Men, Women and Work in a Foraging Society, they are fibrous and most contain a low concentration of starch compared to a potato for example. The investigators may have been misled by the volume of these foods eaten, not realizing that they are not as rich in carbohydrate as the starchy root crops they are more familiar with.

You can draw your own conclusions, but I think the high OGTT result of the San probably reflect a low habitual carbohydrate intake, and not pre-diabetes. I have a very hard time believing that this culture wasn't able to handle the moderate amount of carbohydrate in their diet effectively, as observers have never described diabetic complications among them.

Putting it all together

This brings me to my hypothesis. I think a healthy human body is extraordinarily flexible in its ability to adapt to a very broad range of carbohydrate intakes, and adjusts glucose tolerance accordingly to maintain carbohydrate handling in a healthy range. In the context of a healthy diet and lifestyle (from birth), I suspect that nearly anyone can adjust to a very high carbohydrate intake without getting dangerous blood glucose spikes. A low carbohydrate intake leads to impaired glucose handling and better fat handling, as one would expect. This can show up as impaired glucose tolerance or even 'diabetes' on an OGTT, but that does not necessarily reflect a pathological state in my opinion.

Every person is different based on lifestyle, diet, personal history and genetics. Not everyone in affluent nations has a good glucose tolerance, and some people will never be able to handle starch effectively under any circumstances. The best way to know how your body reacts to carbohydrate is to test your own post-meal blood glucose using a glucose meter. They are inexpensive and work well. For the most informative result, eat a relatively consistent amount of carbohydrate for a week to allow your body to adapt, then take a glucose measurement 1 and 2 hours after a meal. If you don't eat much carbohydrate, eating a potato might make you think you're diabetic, whereas after a week of adaptation you may find that a large potato does not spike your blood glucose beyond the healthy range.

Exercise is a powerful tool for combating glucose intolerance, as it increases the muscles' demand for glucose, causing them to transport it out of the blood greedily after a meal. Any exercise that depletes muscle glycogen should be effective.


* Assuming a typical carbohydrate intake. Chris Kresser recently argued, based on several studies, that true normal fasting glucose for a person eating a typical amount of carbohydrate is below 83 mg/dL. Low-carbohydrate eating may raise this number, but that doesn't necessarily indicate a pathological change. High-carbohydrate cultures such as the Kitavans, Aymara and New Guineans tend to have fasting values in the low 60s to low 70s. I suspect that a very high carbohydrate intake generally lowers fasting glucose in healthy people. That seems to be the case so far for Chris Voigt, on his diet of 20 potatoes a day. Stay tuned for an interview with Mr. Voigt in early December.

Interview with Jimmy Moore

About two months ago, I did an interview with Jimmy Moore of the Livin' la Vida Low Carb internet empire. I hardly remember what we talked about, but I think it went well. I enjoyed Jimmy's pleasant and open-minded attitude. Head over to Jimmy's website and listen to the interview here.

I do recall making at least one mistake. When discussing heart attacks,I said "atrial fibrillation" when I meant "ventricular fibrillation".

Intervew with Chris Kresser of The Healthy Skeptic

Last week, I did an audio interview with Chris Kresser of The Healthy Skeptic, on the topic of obesity. We put some preparation into it, and I think it's my best interview yet. Chris was a gracious host. We covered some interesting ground, including (list copied from Chris's post):

• The little known causes of the obesity epidemic
• Why the common weight loss advice to �eat less and exercise more� isn�t effective
• The long-term results of various weight loss diets (low-carb, low-fat, etc.)
• The body-fat setpoint and its relevance to weight regulation
• The importance of gut flora in weight regulation
• The role of industrial seed oils in the obesity epidemic
• Obesity as immunological and inflammatory disease
• Strategies for preventing weight gain and promoting weight loss

Some of the information we discussed is not yet available on my blog. You can listen to the interview through Chris's post here.