Obesity and the Brain

Nature Genetics just published a paper that caught my interest (1). Investigators reviewed the studies that have attempted to determine associations between genetic variants and common obesity (as judged by body mass index or BMI). In other words, they looked for "genes" that are suspected to make people fat.

There are a number of gene variants that associate with an increased or decreased risk of obesity. These fall into two categories: rare single-gene mutations that cause dramatic obesity, and common variants that are estimated to have a very small impact on body fatness. The former category cannot account for common obesity because it is far too rare, and the latter probably cannot account for it either because it has too little impact*. Genetics can't explain the fact that there were half as many obese people in the US 40 years ago. Here's a wise quote from the obesity researcher Dr. David L. Katz, quoted from an interview about the study (2):

Let us by all means study our genes, and their associations with our various shapes and sizes... But let's not let it distract us from the fact that our genes have not changed to account for the modern advent of epidemic obesity -- our environments and lifestyles have.

Exactly. So I don't usually pay much attention to "obesity genes", although I do think genetics contributes to how a body reacts to an unnatural diet/lifestyle. However, the first part of his statement is important too. Studying these types of associations can give us insights into the biological mechanisms of obesity when we ask the question "what do these genes do?" The processes these genes participate in should be the same processes that are most important in regulating fat mass.

So, what do the genes do? Of those that have a known function, nearly all of them act in the brain, and most act in known body fat regulation circuits in the hypothalamus (a brain region). The brain is the master regulator of body fat mass. It's also the master regulator of nearly all large-scale homeostatic systems in the body, including the endocrine (hormone) system. Now you know why I study the neurobiology of obesity.


* The authors estimated that "together, the 32 confirmed BMI loci explained 1.45% of the inter-individual variation in BMI." In other words, even if you were unlucky enough to inherit the 'fat' version of all 32 genes, which is exceedingly unlikely, you would only have a slightly higher risk of obesity than the general population.

Vacation

I'll be out of town until the beginning of November, so I won't be responding to comments or e-mails for a while. I'm going to set up a post or two to publish while I'm gone.

As an administrative note, I get a number of e-mails from blog readers each day. I apologize that I can't respond to all of them, as it would require more time than I currently have to spare. The more concise your message, the more likely I'll read it and respond. Thanks for your understanding.

Sleep Post Correction

An astute commenter pointed out that I misread the numbers in the paper on sleep and fat loss. I wrote that out of the total 3.0 kg lost, the high-sleep group lost 2.4 kg as fat, and the low-sleep group lost 1.4 kg of fat out of 2.9 kg total.

In fact, the high-sleep group lost 1.4 out of 2.9 kg as fat, and the low-sleep group lost 0.6 out of 3.0 kg as fat. So I got the numbers all mixed up. Sorry for the mistake. The main point of the post still stands though: sleep deprivation negatively influences body composition.

The correct numbers are even more interesting than the ones I made up. Even in the high-sleep group, nearly half the body weight lost by simple calorie restriction was lean mass. That doesn't make calorie restriction look very good!

In the sleep-deprived group, 80% of the weight lost by calorie restriction came out of lean mass. Ouch!

That illustrates one of the reasons why I'm skeptical of simple calorie restriction as a means of fat loss. When the body "wants" to be fat, it will sacrifice lean mass to preserve fat tissue. For example, the genetically obese Zucker rat cannot be starved thin. If you try to put it on a severe calorie-restricted diet, it will literally die fat because it will cannibalize its own lean mass (muscle, heart, brain, etc.) to spare the fat. That's an extreme example, but it illustrates the point.

The key is not only to balance energy intake with expenditure (which the brain does automatically when it's working correctly), but to allocate energy appropriately to lean and fat mass.

The Big Sleep

This blog usually focuses on diet, because that's my specialty. But if you want Whole Health, you need the whole package: a diet and lifestyle that is broadly consistent with our evolutionary heritage. I think we all know that on some level, but a recent paper has reminded me of it.

I somehow managed to get on the press list of the Annals of Internal Medicine. That means they send me embargoed papers before they're released to the general public. That journal publishes a lot of high-impact diet studies, so it's a great privilege for me. I get to write about the studies, and publish my analysis at the time of general release, which is the same time the news outlets publish their stories.

One of the papers they sent me recently is a fat loss trial with an interesting twist (1; see below). All participants were told to eat 10% fewer calories that usual for two weeks, however half of them were instructed to sleep for 8 and a half hours per night, and the other half were instructed to sleep for 5 and a half hours*. The actual recorded sleep times were 7:25 and 5:14, respectively.

Weight loss by calorie restriction causes a reduction of both fat and lean mass, which is what the investigators observed. Both groups lost the same amount of weight. However, 80% of the weight was lost as fat in the high-sleep group (2.4/3.0 kg lost as fat), while only 48% of it was lost as fat in the low-sleep group (1.4/2.9 kg lost as fat). Basically, the sleep-deprived group lost as much lean mass as they did fat mass, which is not good!

There are many observational studies showing associations between insufficient sleep, obesity and diabetes. However, I think studies like that are particularly vulnerable to confounding variables, so I've never known quite what to make of them. Furthermore, they often show that long sleep duration associates with poor health as well, which I find highly unlikely to reflect cause and effect. I discussed one of those studies in a post a couple of years ago (2). That's why I appreciate this controlled trial so much.

Another sleep restriction trial published in the Lancet in 1999 showed that restricting healthy young men to four hours of sleep per night caused them to temporarily develop glucose intolerance, or pre-diabetes (3).

Furthermore, their daily rhythm of the hormone cortisol became abnormal. Rather than the normal pattern of a peak in the morning and a dip in the evening, sleep deprivation blunted their morning cortisol level and enhanced it in the evening. Cortisol is a stress hormone, among other things, and its fluctuations may contribute to our ability to feel awake in the morning and ready for bed at night.

The term "adrenal fatigue", which refers to the aforementioned disturbance in cortisol rhythm, is characterized by general fatigue, difficulty waking up in the morning, and difficulty going to sleep at night. It's a term that's commonly used by alternative medical practitioners but not generally accepted by mainstream medicine, possibly because it's difficult to demonstrate and the symptoms are fairly general. Robb Wolf talks about it in his book The Paleo Solution.

The investigators concluded:

Sleep debt has a harmful impact on carbohydrate metabolism and endocrine function. The effects are similar to those seen in normal ageing and, therefore, sleep debt may increase the severity of age-related chronic disorders.

So there you have it. Besides making us miserable, lack of sleep appears to predispose to obesity and diabetes, and probably sets us up for the Big Sleep down the line. I can't say I'm surprised, given how awful I feel after even one night of six hour sleep. I feel best after 9 hours, and I probably average about 8.5. Does it cut into my free time? Sure. But it's worth it to me, because it allows me to enjoy my day much more.

Keep your room as dark as possible during sleep. It also helps to avoid bright light, particularly in the blue spectrum, before bed (4). "Soft white" bulbs are preferable to full spectrum in the evening. If you need to use your computer, dim the monitor and adjust it to favor warm over cool colors. For people who sleep poorly due to anxiety, meditation before bed can be highly effective. I posted a tutorial here.

1. Nedeltcheva, AV et al. "Insufficient Sleep Undermines Dietary Efforts to Reduce Adiposity." Annals of Internal Medicine. 2010. Advanced publication.


* The study was a randomized crossover design with a 3 month washout period, which I consider a rigorous design. I think the study overall was very clever. The investigators used calorie restriction to cause rapid changes in body composition so that they could see differences on a reasonable timescale, rather than trying to deprive people of sleep for months and look for more gradual body fat changes without dietary changes. The latter experiment would have been more interesting, but potentially impractical and unethical.

Potatoes and Human Health, Part III

Potato-eating Cultures: the Quechua

The potato is thought to have originated in what is now Peru, on the shores of lake Titicaca. Native Peruvians such as the Quechua have been highly dependent on the potato for thousands of years. A 1964 study of the Quechua inhabitants of Nuñoa showed that they obtained 74% of their calories from potatoes (fresh and chuños), 10% from grains, 10% from Chenopodia (quinoa and cañihua), and 4% from animal foods. Total energy intake was 3,170 calories per day (1).

In 2001, a medical study of rural Quechua men reported an average body fat percentage of 16.4% (2). The mean age of the volunteers was 38. Body fat did increase slowly with age in this population, and by age 65 it was predicted to be about 20% on average. That's below the threshold of overweight, so I conclude that most men in this population are fairly lean, although there were a few overweight individuals.

In 2004, a study in rural Quechua women reported a body fat percentage of 31.2% in volunteers with a mean age of 35 (3). Body fat percentage was higher in a group of Quechua immigrants to the Peruvian capital of Lima. Among rural women, average fasting insulin was 6.8 uIU/mL, and fasting glucose was 68.4 mg/dL, which together suggest good insulin sensitivity and glucose control (4). Insulin and glucose were considerably lower in the rural group than the urban group. Blood pressure was low in both groups. Overall, this suggests that some traditionally-living Quechua women are overweight by modern standards, however most of them are not.

Rural Quechua are characteristically short, with the average adult man standing no more than 5' 2" (2). One might be tempted to speculate that this reflects stunting due to a deficient diet. However, given the fact that nearly all non-industrial populations, including contemporary hunter-gatherers, are short by modern standards, I'm not convinced the Quechua are abnormal. A more likely explanation is that industrial foods cause excessive tissue growth in modern populations, perhaps by promoting overeating and excessive insulin and IGF-1 production, which are growth factors. I first encountered this hypothesis in Dr. Staffan Lindeberg's book Food and Western Disease.

I don't consider the Quechua diet to be optimal, but it does seem to support a reasonable level of metabolic health. It shows that a lifetime high-carbohydrate, high glycemic index, high glycemic load diet doesn't lead to obesity or insulin resistance in the context of a traditional diet and lifestyle. Unfortunately, I don't have more detailed data on other aspects of their health, such as digestion.

Potato-eating Cultures: the Aymara


The Aymara are another potato-dependent people of the Andes, who span Peru, Bolivia and Chile. The first paper I'll discuss is titled "Low Prevalence of Type II Diabetes Despite a High Body Mass Index in the Aymara Natives From Chile", by Dr. Jose Luis Santos and colleagues (5). In the paper, they show that the prevalence of diabetes in this population was 1.5%, and the prevalence of pre-diabetes was 3.6%. The prevalence of both remained low even in the elderly. Here's a comparison of those numbers with figures from the modern United States (6):

That's quite a difference! The prevalence of diabetes in this population is low, but not as low as in some cultures such as the Kitavans (7, 8).

Now to discuss the "high body mass index" referenced in the title of the paper. The body mass index (BMI) is the relation between height and weight, and often, but not always, reflects fatness. The average BMI of this population was 24.9, which is very close to the cutoff between normal and overweight (25).

Investigators were surprised to find such a low prevalence of diabetes in this population, despite their apparent high prevalence of overweight. Yet if you've seen pictures of rural native South Americans, you may have noticed they're built short and thick, with wide hips and big barrel chests. Could this be confounding the relationship between BMI and body fatness? To answer that question, I found another paper that estimated body fat using skinfold measurements (9). That study reported that both men and women remained relatively lean throughout life (ages 4-65), with only two of 23 subjects classified as overweight on the basis of body fat percentage, and none classified as obese.

Back to the first paper. In this Aymara group, blood pressure was on the high side. Serum cholesterol was also a bit high for a traditionally-living population, but still lower than most modern groups (~188 mg/dL). I find it very interesting that the cholesterol level in this population that eats virtually no fat was the same as on Tokelau, where nearly half of calories come from highly saturated coconut fat (10, 11). Fasting insulin is also on the high side in the Aymara, which is also interesting given their good glucose tolerance and low prevalence of diabetes.

Potato-eating Cultures: the Irish

Potatoes were introduced to Ireland in the 17th century. They were well suited to the cool, temperate climate, and more productive than any other local crop. By the early 18th century, potatoes were the main source of calories, particularly for the poor who ate practically nothing else. In 1839, the average Irish laborer obtained 87% of his calories from potatoes (12). In 1845, the potato blight Phytophthora infestans struck, decimating potato plantations nationwide and creating the Great Famine.

There isn't much reliable information on the health status of the Irish prior to the famine, besides reports of vitamin A deficiency symptoms (13). However, they had a very high fertility rate, and anecdotal reports described them as healthy and attractive (14):

As far as fecundity is concerned, the high nutritional value of the potato diet might have played a significant role, but little supportive evidence has been presented so far... What is known is that the Irish in general and Irish women in particular were widely described as healthy and good-looking. Adam Smith's famous remark that potatoes were "peculiarly suitable to the health of the human constitution" can be complemented with numerous observations from other contemporary observers to the same effect.

Controlled Feeding Studies

Starting nearly a century ago, a few scientists decided to feed volunteers potato-only diets to achieve various research objectives. The first such experiment was carried out by a Dr. M. Hindhede and published in 1913 (described in 15). Hindhede's goal was to explore the lower limit of the human protein requirement and the biological quality of potato protein. He fed three healthy adult men almost nothing but potatoes and margarine for 309 days (margarine was not made from hydrogenated seed oils at the time), all while making them do progressively more demanding physical labor. They apparently remained in good physical condition. Here's a description of one of his volunteers, a Mr. Madsen, from another book (described in 16; thanks to Matt Metzgar):

In order to test whether it was possible to perform heavy work on a strict potato diet, Mr. Madsen took a place as a farm laborer... His physical condition was excellent. In his book, Dr. Hindhede shows a photograph of Mr. Madsen taken on December 21st, 1912, after he had lived for almost a year entirely on potatoes. This photograph shows a strong, solid, athletic-looking figure, all of whose muscles are well-developed, and without excess fat. ...Hindhede had him examined by five physicians, including a diagnostician, a specialist in gastric and intestinal diseases, an X-ray specialist, and a blood specialist. They all pronounced him to be in a state of perfect health.

Dr. Hindhede discovered that potato protein is high quality, providing all essential amino acids and high digestibility. Potato protein alone is sufficient to sustain an athletic man (although that doesn't make it optimal). A subsequent potato feeding study published in 1927 confirmed this finding (17). Two volunteers, a man and a woman, ate almost nothing but potatoes, lard and butter for 5.5 months. The man was an athlete but the woman was sedentary. Body weight and nitrogen balance (reflecting protein gain/loss from the body) remained constant throughout the experiment, indicating that their muscles were not atrophying at any appreciable rate, and they were probably not putting on fat. The investigators remarked:

The digestion was excellent throughout the experiment and both subjects felt very well. They did not tire of the uniform potato diet and there was no craving for change.

In one of his Paleo Diet newsletters titled "Consumption of Nightshade Plants (Part 1)", Dr. Loren Cordain referenced two feeding studies showing that potatoes increase the serum level of the inflammatory cytokine interleukin-6 (22, 23). However, one study was not designed to determine the specific role of potato in the change (two dietary factors were altered simultaneously), and the other used potato chips as the source of potato. So I don't find these studies particularly relevant to the question at hand.

Just yesterday, Chris Voigt of the Washington State Potato Commission embarked on his own n=1 potato feeding experiment as a way to promote Washington state potatoes. He'll be eating nothing but potatoes and a little fat for two months, and getting a full physical at the end. Check out his website for more information and updates (18). Mr. Voigt has graciously agreed to a written interview with Whole Health Source at the end of his experiment. He pointed out to me that the Russet Burbank potato, the most popular variety in the United States, is over 135 years old. Stay tuned for more interesting facts from Mr. Voigt in early December.

Observational Studies

With the recent interest in the health effects of the glycemic index, a few studies have examined the association between potatoes and health in various populations. The results are all over the place, with some showing positive associations with health, and others showing negative associations (19, 20, 21). As a whole, I find these studies difficult to interpret and not very helpful.

Anecdotes

Some people feel good when they eat potatoes. Others find that potatoes and other members of the nightshade family give them digestive problems, exacerbate their arthritis, or cause fat gain. I haven't seen any solid data to substantiate claims that nightshades aggravate arthritis or other inflammatory conditions. However, that doesn't mean there aren't individuals who are sensitive. If potatoes don't agree with you, by all means avoid them.

The Bottom Line

You made it to the end! Give yourself a pat on the back. You deserve it.

In my opinion, the scientific literature as a whole, including animal and human studies, suggests rather consistently that potatoes can be a healthy part of a varied diet for most people, and they probably do not generally promote digestive problems, excessive fat gain or metabolic dysfunction.  Nevertheless, I wouldn't recommend eating nothing but potatoes for any length of time. If you do choose to eat potatoes, follow these simple guidelines:

• Don't eat potatoes that are green, sprouting, blemished or damaged
• Store them in a cool, dark place. They don't need to be refrigerated but it will extend their life
  
• Peel them before eating if you rely on them as a staple food
  

Enjoy your potatoes!