If diet composition causes hyperphagia, we should be able to see it in animals. I just came across a great study from the lab of Dr. Neil Stickland that explored this in rats. They took two groups of pregnant rats and fed them two different diets ad libitum, meaning the rats could eat as much as they wanted. Here's what the diets looked like:The animals were fed two types of diet throughout the study. They were fed either RM3 rodent chow alone ad libitum (SDS Ltd, Betchworth, Surrey, UK) or with a junk food diet, also known as cafeteria diet, which consisted of eight different types of palatable foods, purchased from a British supermarket. The palatable food included biscuits, marshmallows, cheese, jam doughnuts, chocolate chip muffins, butter flapjacks, potato crisps and caramel/chocolate bars.
It's important to note that the junk food-fed rats had access to rat chow as well. Now here's where it gets interesting. Rats with access to junk food in addition to rat chow ate 56% more calories than the chow-only group! Here's what they had to say about it:These results clearly show that pregnant rats, given ad libitum access to junk food, exhibited hyperphagia characterised by a marked preference for foods rich in fat, sucrose and salt at the expense of protein-rich foods, when compared with rats that only had access to rodent chow. Although the body mass of dams was comparable among all groups at the start of the experiment, the increased energy intake in the junk food group throughout gestation was accompanied by an increase in body mass at G20 [gestational day 20] with the junk food-fed dams being 13 % heavier than those fed chow alone.
Hmm, this is remarkably reminiscent of what's happening to a certain group of humans in North America right now: give them access to food made mostly of refined grains, sugar, and industrially processed vegetable oil. They will prefer it to healthier food, to the point of overeating. The junk food then drives hyperphagia by interfering with the body's feedback loops that normally keep feeding behaviors and body fat within the optimal range. These data support the hypothesis that metabolic damage is the cause of, not the result of, "super-sized" food portions and other similar cultural phenomena. The rest of the paper is interesting as well. Pups born to mothers who ate junk food while pregnant and lactating had a greater tendency to eat junk than pups born to mothers who ate rat chow during the same period. This underscores the idea that poor nutrition can set a child up for a lifetime of problems.
One of the things I didn't mention in the last post is that Americans are eating more calories than ever before. According to Centers for Disease Control NHANES data, in 2000, men ate about 160 more calories per day, and women ate about 340 more than in 1971. That's a change of 7% and 22%, respectively. The extra calories come almost exclusively from refined grains, with the largest single contribution coming from white wheat flour (correction: the largest single contribution comes from corn sweeteners, followed by white wheat flour).Some people will see those data and decide the increase in calories is the explanation for the expanding American waistline. I don't think that's incorrect, but I do think it misses the point. The relevant question is "why are we eating more calories now than we were in 1971?"We weren't exactly starving in 1971. And average energy expenditure, if anything, has actually increased. So why are we eating more? I believe that our increased food intake, or hyperphagia, is the result of metabolic disturbances, rather than the cause of them.Humans, like all animals, have a sophisticated system of hormones and brain regions whose function is to maintain a proper energy balance. Part of the system's job is to keep fat mass at an appropriate level. With a properly functioning system, feedback loops inhibit hunger once fat mass has reached a certain level, and also increase resting metabolic rate to burn excess calories. If the system is working properly, it's very difficult to gain weight. There have been a number of overfeeding studies in which subjects have consumed huge amounts of excess calories. Some people gain weight, many don't.The fact that fat mass is hormonally regulated can be easily seen in other mammals. When was the last time you saw a fat squirrel in the springtime? When was the last time you saw a thin squirrel in the fall? These events are regulated by hormones. A squirrel in captivity will put on weight in the fall, even if its daily food intake is not changed.A key hormone in this process is leptin. Leptin levels are proportional to fat mass, and serve to inhibit hunger and eating behaviors. Under normal conditions, the more fat tissue a person has, the more leptin they will produce, and the less they will eat until the fat mass has reached the body's preferred 'set-point'. The problem is that overweight Westerners are almost invariably leptin-resistant, meaning their body doesn't respond to the signal to stop eating!Leptin resistance leads to hyperphagia, overweight and the metabolic syndrome (a common cluster of symptoms that implies profound metabolic disturbance). It typically precedes insulin resistance during the downward slide towards metabolic syndrome.I suspect that wheat, sugar and perhaps other processed foods cause hyperphagia. I believe hyperphagia is at least partially secondary to a disturbed metabolism. There's something about industrial foods that reached a critical mass in the mid-70s. The shift in diet sent us into a tailspin of excessive eating and unprecedented weight gain.
The New York Times just published an article called "The Overflowing American Dinner Plate", in which they describe changes in the American diet since 1970, the period during which the obesity rate doubled. Bill Marsh used USDA estimates of food consumption from 1970 to 2006. Predictably, he focuses on fat consumption, and writes that it has increased by 59% in the same time period. The problem is, we aren't eating any more fat than we were in 1970. The US Centers for Disease Control NHANES surveys show that total fat consumption has remained the same since 1971, and has decreased as a percentage of calories. I've been playing around with the USDA data for months now, and I can tell you that Marsh misinterpreted it in a bad way. Here are the raw data, for anyone who's interested. They're in easy-to-use Excel spreadsheets. I highly recommend poking around them if you're interested.The reason Marsh was confused by the USDA data is that he confused "added fats" with "total fat". While total fat intake has remained stable over this time period, added fats have increased by 59%. The increase is almost exclusively due to industrially processed seed oils (butter and lard have decreased). Total fat has remained the same because we now eat low-fat cuts of meat and low-fat dairy products to make up for it! Another problem with the article is it only shows percent changes in consumption of different foods, rather than absolute amounts. This obscures some really meaningful information. For example, grain consumption is up a whopping 42%. That is the largest single food group change if you exclude the misinterpreted fat data. Corn is up 188%, rice 170%, wheat 21%. But in absolute amounts, the increase in wheat consumption is larger than corn or rice! That's because baseline wheat consumption dwarfed corn and rice. We don't get that information from the data presented in the article, due to the format. So now that I've deconstructed the data, let's see what the three biggest changes in the American diet from 1970 to 2006 actually are:- We're eating more grains, especially white wheat flour
- We're eating more added sweeteners, especially high-fructose corn syrup
- Animal fats from milk and meat have been replaced by processed seed oils
Wheat + sugar + processed vegetable oil = fat and unhealthy. Sounds familiar, doesn't it?
A final note about the Chinese study in the previous post: the overweight vegetable-eaters (read: wheat eaters) exercised more than their non-vegetable-eating, thin neighbors. So although their average calorie intake was a bit higher, their expenditure was as well. Although I speculated in the last post that affluent people might be eating more wheat and fresh vegetables, the data don't support that. Participants with the highest income level actually adhered to the wheat and vegetable-rich pattern the least, while low-income participants were most likely to eat this way. Interestingly, education showed a (weaker) trend in the opposite direction. More educated participants were more likely to eat the wheat-vegetable pattern, while the opposite was true of less educated participants. Thus, it looks like wheat makes people more educated. Just kidding, that's exactly the logic we have to avoid when interpreting this type of study!
Dr. Michael Eades linked to an interesting study yesterday on his Health and Nutrition blog. It's entitled "Vegetable-Rich Food Pattern is Related to Obesity in China." It's one of these epidemiological studies where they try to divide subjects into different categories of eating patterns and see how health problems associate with each one. They identified four patterns: the 'macho' diet high in meat and alcohol; the 'traditional' diet high in rice and vegetables; the 'sweet tooth' pattern high in cake, dairy and various drinks; and the 'vegetable rich' diet high in wheat, vegetables, fruit and tofu. The only pattern that associated with obesity was the vegetable-rich diet. The 25% of people eating closest to the vegetable-rich pattern were more than twice as likely to be obese as the 25% adhering the least.The authors of the paper try to blame the increased obesity on a higher intake of vegetable oil from stir-frying the vegetables, but that explanation is misleading. A cursory glance at table 3 reveals that the vegetable-eaters weren't eating any more fat than their thinner neighbors. Dr. Eades suggests that their higher carbohydrate intake (+10%) was partially responsible for the weight gain, but I wasn't satisfied with that explanation so I took a closer look. Dr. Eades also pointed to their higher calorie intake (+120 kcal/day), which makes sense to me. One of the most striking elements of the 'vegetable-rich' food pattern is its replacement of rice with wheat flour. The 25% of the study population that adhered the least to the vegetable-rich food pattern ate 7.3 times more rice than wheat, whereas the 25% sticking most closely to the vegetable-rich pattern ate 1.2 times more wheat than rice! In other words, wheat flour rather than rice was their single largest source of calories. This association was much stronger than the increase in vegetable consumption itself! All of a sudden, the data make more sense. Wheat seems to associate with health problems in many contexts. Perhaps the reason we don't see the same type of association in American epidemiological studies is that everyone eats wheat. Only in a culture that has a true diversity of diet can you find a robust association like this. The replacement of rice with wheat may have caused the increase in calorie intake as well. Clinical trials of low-carbohydrate diets as well as 'paleolithic diets' have shown good metabolic outcomes from wheat avoidance, although one can't be sure what role wheat plays from those data. I don't think the vegetables had anything to do with the weight gain, they were just incidentally associated with wheat consumption. But I do think these data are difficult to reconcile with the idea that vegetables protect against overweight.
I left out one of the juicier tidbits from the last post because it was getting long. Investigators Kang-Jey Ho et al. wanted an explanation for why the Masai didn't have high serum cholesterol despite their high dietary cholesterol intake (up to 2,000 mg per day-- 6.7 times the US FDA recommended daily allowance).
They took 23 male Masai subjects aged 19 to 24 and divided them into two groups. The first group of 11 was the control group, which received a small amount of radioactive cholesterol in addition to a cholesterol-free diet that I will describe below. The second group of 12 was the experimental group, which they fed 2,000 mg cholesterol per day, a small amount of radioactive cholesterol as a tracer, and the exact same cholesterol-free diet as the control group. For the duration of the 24-week trial, the subjects ate the experimental diet exclusively. Here's what it was (in order of calories, descending): - Nondairy coffee creamer (made of corn syrup solids and vegetable oil)
- Beans
- Sugar
- Corn
- Corn oil
- A vitamin pill
Not a healthy diet by most peoples' standards, but those items are nevertheless widely eaten in the US. Over the course of the 24-week study, the investigators found no difference in serum cholesterol between the control and experimental groups. This isn't really surprising. The body has mechanisms for regulating blood cholesterol, and if you aren't eating any it just synthesizes more to stay at its preferred level.
The really interesting thing is that serum cholesterol increased dramatically in both groups. It went from 125 mg/100 mL to over 170 mg/100 mL, despite a large decrease in the saturated fat they were eating. The change took about two weeks to occur, and remained fairly stable for the remainder of the trial.
Both groups also gained weight. In the first week, they gained an average of 3 pounds each. To be fair, the initial gain was probably most water, which is what happens when a person increases their carbohydrate and salt intake. The investigators freaked out and cut their calorie intake by 400 kcal, only allowing them 3,600 kcal per day. Initially, they were voluntarily consuming 4,000 kcal per day. I find that interesting as well. Something tells me they weren't chugging non-dairy creamer because it was so delicious, but because their confused hormones were telling them to EAT.
Even after putting the subjects on calorie restriction (not letting them eat as much as they wanted, by an average of 400 kcal/day), they continued gaining weight. By the end of the study, the 23 subjects had gained an average of 7.8 lbs per person.
To summarize, this is what the investigators saw when they put 23 unfortunate Masai men on a bottom-rung industrially processed diet: elevated cholesterol, hyperphagia (excessive eating), and weight gain. Sounds familiar, doesn't it?
One of the surprising things I noticed when I was poring over data from the NHANES survey (US CDC National Health and Nutrition Examination Survey) from 1975 to 2006 is that the number of inactive people has diminished in that same time period from 50% to 24%. This is shocking to most people. We have this romanticized idea that in the 1970s people were more active, as if everyone chopped wood and walked 15 miles to work in the morning. The reality is, there were office jobs, housewives and cars without the large numbers of runners and gym-goers we have today. Granted, NHANES data are self-reported and should be taken with a grain of salt. However, Chris at Conditioning Research pointed me to a study looking at changes in energy expenditure from the 1980s to the present in North America and Europe. It doesn't suffer from the same biases because it's based on direct measurement rather than self-reporting. Here's the executive summary: we're expending slightly more energy than we used to, partly because we exercise more and partly because it takes more energy to move our heavier bodies around. I'm certainly not blaming the obesity problem on an increase in physical activity, but I do think we can safely rule out inactivity as the reason we've gotten fatter. In my mind, this only leaves one major possible cause for the obesity epidemic: changes in diet. Don't get me wrong, I think exercise is good. It has numerous positive effects on physical and mental health. But it's not as powerful of a tool for fat loss and general health as diet.Anecdotally, I do know several people who lose fat when they exercise regularly. I also know some who don't lose fat when they exercise. Exercise and a healthy diet converge on some of the same metabolic pathways, such as sensitivity to insulin. But diet changes are far more effective than exercise at correcting metabolic problems. The reason is simple: the problems a person corrects with a good diet are caused by a poor diet to begin with.
Lentils are a healthy food that comes with a few caveats. They have more protein and less carbohydrate than any other legume besides soybeans and peanuts, and they contain a remarkable array of vitamins and minerals, particularly B vitamins. One cup delivers 90% of your RDA of folate, so between lentils and liver there's no need for those sketchy prenatal vitamins.
Lentils must be properly prepared to be digestible and nutritious! I can't emphasize this enough. We did not evolve eating legumes, so we have to take certain steps to be able to digest them adequately. As with all beans and grains, proper soaking is essential to neutralize their naturally occurring toxins and anti-nutrients. Anti-nutrients are substances that interfere with the absorption of nutrients. Soaking activates enzymes in the seeds themselves that degrade these substances. It also cuts down substantially on cooking time and reduces flatulence.
Phytic acid is an anti-nutrient that's abundant in beans, grains and nuts. It can dramatically reduce the absorption of important minerals such as iron, calcium, magnesium and zinc, leading to deficiencies over time. It may be one of the main reasons human stature decreased after the adoption of agriculture, and it probably continues to contribute to short stature and health problems around the world.
Lentils and other seeds also contain trypsin inhibitors. Trypsin is one of the digestive system's main protein-digesting enzymes, and seeds probably inhibit it as a defense against predators. Another class of toxins are the lectins. Certain lectins are able to bind to and damage the digestive tract, and even pass into the circulation and possibly wreak havoc. This is a short list of a few of the toxins found in beans and grains. Fortunately, all of these toxins can be reduced or eliminated by proper soaking. I like to soak all legumes for a full 24 hours, adding warm water halfway through. This increases the activity of the toxin-degrading enzymes.
Here's a method for preparing lentils that I've found to be effective. You will actually save time by doing it this way rather than cooking them without soaking, because they cook so much more quickly: - 24 hours before cooking, place dry lentils in a large bowl and cover with 2" of water or more.
- After 12 hours or so, drain and cover the lentils with very warm water (not hot tap water).
- Drain and rinse before cooking.
- To cook, simply cover the soaked lentils with fresh water and boil until tender. I like to add a 2-inch piece of the seaweed kombu to increase mineral content and digestibility.
many thanks to *clarity* for the CC photo
As you may have noticed, I suspect fructose is involved in overweight and other health problems. It seems to have adverse effects on fat deposition in the liver and insulin sensitivity that could be related to its association with weight gain. I looked through USDA estimated per capita consumption of different sweeteners to get an idea of how fructose consumption has changed in the US in the time since adult obesity rates have doubled.
In 1970, we ate an estimated 72.5 lb/year of cane and beet sugar (sucrose) per person, which is 50% fructose and 50% glucose. We also ate 0.4 lb/year of corn syrup, which is most commonly 55% fructose, 45% glucose. Consumption of other unspecified sweeteners was 12.0 lb/year, for a total intake of 84.9 lb/year of added sweeteners.
In 2007, we ate an estimated 44.2 lb/year of sucrose, 40.1 lb/year of corn syrup, and 12.9 lb/year of other unspecified sweeteners, for a total added sweetener intake of 97.2 lb/year. Doing the math, and generously assuming that the "other" sweeteners are 100% honey (~50% fructose), here are the results: - 1970: 42.5 lb/year of added fructose.
- 2007: 50.6 lb/year of added fructose.
At 19%, it's not a staggering increase, but it's definitely significant. I also think it's an underestimate, because it doesn't include fruit juice or total fruit consumption, both of which have increased. Other notable findings: grain intake has increased 41% between 1970 and 2005, due chiefly to rising consumption of processed wheat products. Added fats and oils have increased 63% in the same time period, with the increase coming exclusively from vegetable fats. The use of hydrogenated shortening has more than doubled.
What has caused the dramatic expansion of American waistlines in the last 30 years? No one knows for sure, but I think it's probably related to diet since the percentage of people who exercise has actually increased in the same time period. My money is on the wheat and sugar, with possible contributions from hydrogenated oil, polyunsaturated vegetable oils and chemical pollutants. The reason is that wheat and sugar seem to have devastating metabolic effects on populations throughout the world, such as the Pima.
At 38% and climbing in 2006, the Pima indians (Akimel O'odham) of Arizona have the highest rate of diabetes of any population in the world. They also have staggering rates of obesity (~70%) and hypertension. Things were very different for them before 1539, when the Spanish first made contact. They lived on an agricultural diet of beans, corn and squash, with wild fish, game meat and plants. As with most native people, they were thin and healthy while on their traditional diet. In 1859, the Pima were restricted to a small fraction of their original land along the Gila river, the Pima Reservation. In 1866, settlers began arriving in the region and diverting the Gila river upstream of the reservation for their own agriculture. In 1869, the river went dry for the first time. 1886 was the last year any water flowed to the Pima Reservation in the Gila river. The Pima had no way to obtain water, and no way to grow crops. Their once productive subsistence economy ground to a halt. Famine ensued for 40 desperate years. The Pima cut down their extensive mesquite forests to sell for food and water. Eventually, after public outcry, uncle Sam stepped in.The government provided the Pima with subsidized "food": white flour, sugar, partially hydrogenated lard, and canned goods. They promptly became diabetic and overweight, and have remained that way ever since. The Pima are poster children for mainstream nutrition researchers in the US for several reasons. First of all, their pre-contact diet was probably fairly low in fat, and researchers love to point out that they now eat more fat (comparable to the average American diet). Another reason is that there's another group of Pima in Mexico who still live on a relatively traditional diet and are much healthier. They are genetically very similar, supporting the idea that it's the lifestyle of the American Pima that's causing their problems. The third reason is that the Mexican Pima exercise more than the Arizona Pima and eat a bit less. I of course agree with the conclusion that their lifestyle is behind their problems; that's pretty obvious. I think most Pima know it too. If they got their water back, maybe things would be different for them.
However, the focus on macronutrients sometimes obscures the fact that the modern Pima diet is pure crap. It's mostly processed food with a low nutrient density. It also contains the two biggest destroyers of indigenous health: white flour and sugar. There are numerous examples of cultures going from a high-fat diet to a lower-fat "reservation food" diet and suffering the same fate: the Inuit of Alaska, the Maasai and Samburu of Kenya, tribes in the Pacific Northwestern US and Canada, certain Aboriginal groups, and more. What do they all have in common? White flour, sugar and other processed food. The exercise thing is somewhat questionable as well. True, Mexican Pima exercise 2.5 times more than Arizona Pima, but the Arizona Pima still exercise much more than the average American! Women clock in at 3.1 hours a week, while men come in at a whopping 12.1 hours a week! I am a bike commuter and weight lifter, and even I don't exercise that much. So forgive me if I'm a little skeptical of the idea that they aren't exercising enough to keep the weight off. The history of the Pima is a heart-wrenching story that has been repeated hundreds, perhaps thousands of times all over the world. Europeans bring in white flour, sugar and other processed food, it destroys a native populations' health, and then researchers either act like they don't understand why it happened, or give unsatisfying explanations for it. The Pima are canaries in the coal mine, and we can learn a lot from them. Their health problems resemble those of other poor Americans (and wealthier ones also, to a lesser extent). This is because they are both eating similar types of things. The problem is creeping into society at large, however, as we rely more and more on processed wheat, corn, soy and sugar, and less on wholesome food. Obesity in the US has doubled in the past 30 years, and childhood obesity has tripled. Diabetes is following suit. Life expectancy has begun to diminish in some (poor) parts of the country. Meanwhile, our diet is looking increasingly like Pima reservation food. It's time to learn a lesson from their tragedy.
I've been puzzled by an interesting question lately. Why is it that certain cultures are able to eat large amounts of carbohydrate and remain healthy, while others suffer from overweight and disease? How do the pre-industrial Kuna and Kitavans maintain their insulin sensitivity while their bodies are being bombarded by an amount of carbohydrate that makes the average American look like a bowling ball?I read a very interesting post on the Modern Forager yesterday that sent me on a nerd safari through the scientific literature. The paper that inspired the Modern Forager post is a review by Dr. Staffan Lindeberg. In it, he attempts to draw a link between compounds called lectins, found in grains (among other things), and resistance to the hormone leptin. Let's take a step back and go over some background.One of the most-studied animal models of obesity is called the "Zucker" rat. This rat has a missense mutation in its leptin receptor gene, causing it to be nonfunctional. Leptin is a hormone that signals satiety, or fullness. It's secreted by fat tissue. The more fat tissue an animal has, the more leptin it secretes. Normally, this creates negative feedback that causes it to eat less when fat begins to accumulate, keeping its weight within a narrow range.
Zucker rats secrete leptin just fine, but they lack leptin receptors in their brain. Their blood leptin is high but their brain isn't listening. Thus, the signal to stop eating never gets through and they eat themselves to morbid obesity. Cardiovascular disease and diabetes follow shortly thereafter, unless you remove their visceral fat surgically.The reason Zucker rats are so interesting is they faithfully reproduce so many features of the disease of civilization in humans. They become obese, hypometabolic, develop insulin resistance, impaired glucose tolerance, dyslipidemia, diabetes, and cardiovascular disease. Basically, severe metabolic syndrome. So here's a rat that shows that leptin resistance can cause something that looks a whole heck of a lot like the disease of civilization in humans.
For this model to be relevant to us, we'd expect that humans with metabolic syndrome should be leptin-resistant. Well what do you know, administering leptin to obese people doesn't cause satiety like it does in thin people. Furthermore, elevated leptin predicts the onset of obesity and metabolic syndrome. It also predicts insulin resistance. Yes, you read that right, leptin resistance may come before insulin resistance. Interestingly enough, the carbohydrate-loving Kitavans don't get elevated leptin like europeans do, and they don't become overweight, develop insulin dysfunction or the metabolic syndrome either. This all suggests that leptin may be the keystone in the whole disease process, but what accounts for the differences in leptin levels between populations?
This study was released today, demonstrating in 6,583 patients that visceral fat mass in the 40s predicts the risk of dementia in old age. Patients in the highest quintile (20% with the most visceral fat mass) had an almost three-fold higher risk of dementia than patients in the lowest quintile. Overall fat mass was less strongly correlated with dementia. This study is so timely, they must have heard about my blog post.They used a measure of visceral fat called the "sagittal abdominal diameter", basically the distance from the back to the belly button. In other words, the beer belly.What we're looking at is another facet of the pervasive "disease of civilization" that rolls into town on the same truck as sugar and white flour. Weston Price described it in 14 different cultures throughout the world in Nutrition and Physical Degeneration. Diabetes, cardiovascular disease, obesity, cancer and dementia all seem to come hand-in-hand. It's hard to say exactly what the root cause is, but the chain of causality seems to pass through visceral fat in many people.
This week, I stumbled upon a very interesting series of articles from the lab of Dr. Nir Barzilai.The first article I came across showed that surgical removal of the visceral fat deposit of rats increased their lifespan. Visceral fat (VF) is the "beer belly", and consists of the perinephratic fat around the kidneys and the omental fat in front of the intestines. It doesn't include subcutaneous fat, the fat layer under the skin.VF is tightly associated with the metabolic syndrome, the quintessential "disease of civilization" that affects 24% of Americans (NHANES III). It's defined by three or more of the following criteria: high blood pressure, large waist circumference, low HDL cholesterol, high triglycerides, and high fasting glucose. The metabolic syndrome is associated with a 3-4-fold increase in the risk of death from cardiovascular disease, and a 6-fold increase in the risk of developing type II diabetes. From a review on the metabolic syndrome (parentheses mine):
The most common alteration related to the impaired glucose metabolism with aging is the progressively increased fasting and postprandial [post-meal] plasma insulin levels, suggesting an insulin-resistant state.
This is all well and good, but who cares? What's to say VF plays any role other than as a simple marker for overweight?The longevity paper led me to Dr. Barzilai's previous papers, which answered this question rather thoroughly. Rats raised on standard rat chow, which is a sad little compressed pellet made of grains and added nutrients, develop elevated insulin and insulin resistance with age, just like humans. Unless they don't have VF. Rats that had their VF surgically removed did not develop insulin resistance or elevated insulin with age, despite rebounding to their original total fat mass rather quickly (VF accounts for ~18% of total fat in these rats). These parameters are unaffected by removing an equal amount of subcutaneous fat, which has been shown in human liposuction patients as well.Removing VF also improved diabetes-prone Zucker rats, which are profoundly insulin-resistant (leptin receptor loss-of-function). It kept wild-type rats just as insulin-sensitive as calorically restricted controls, which had a small amount of VF. This shows that VF isn't just a passive player; it's essential for the development of insulin resistance. It also shows, along with human studies, that insulin resistance is not an inevitable consequence of aging.Adipose (fat) tissue is being increasingly recognized as an important endocrine (hormone-secreting) organ. It produces many different hormones that affect insulin sensitivity and appetite regulation, among other things. These hormones are collectively known as fat-derived peptides (FDPs). At least one of these FDPs, TNF-alpha, promotes insulin resistance.Dr. Barzilai's group went on to explore the mechanism of VF contributing to insulin resistance. They increased the rate of glucose flux into the fat tissue of rats by infusing either glucose or insulin into the bloodstream. These treatments both cause increased glucose uptake by fat cells. What they saw when they dissected the rats was striking. The VF had ramped up its production of FDPs from 2- to 15-fold, while the subcutaneous fat had barely changed. Incidentally, insulin increased glucose uptake by VF twice as much as subcutaneous fat.I'll say this again, because it's important. They forced glucose into VF cells, and those cells dramatically upregulated FDP production. And again, no visceral fat, no FDPs.In earlier papers, he also showed that the removal of VF dramatically reduces the expression of TNF-alpha and leptin (two FDPs) in subcutaneous fat on a longer timescale, showing that VF and subcutaneous fat communicate to alter the metabolism. Again, TNF-alpha promotes insulin resistance, making it a possible link between the fat tissue and peripheral effects. VF removal had no effect on triglycerides, suggesting that they're only a marker of insulin dysfunction rather than a cause.Now to take this research to its logical conclusion. Here's a plausible sequence of events leading up to the metabolic syndrome:- A meal high in quickly digested carbohydrate elevates blood glucose. OR, excessive fructose causes insulin resistance in the liver which leads to high fasting glucose.
- Visceral fat responds by increasing production of FDPs.
- FDPs, directly and/or indirectly, cause insulin resistance in the liver, muscle and other tissue. Liver insulin resistance causes alterations in lipoprotein ("cholesterol") profile (more on this in another post). Fat tissue remains insulin-sensitive.
- The vicious cycle continues, with increased visceral fat size and glucose uptake increasing FDP production, which makes the liver more insulin resistant, which increases glucose production by the liver, etc.
From the US Centers for Disease Control website:
Since the mid-seventies, the prevalence of overweight and obesity has increased sharply for both adults and children. Data from two NHANES surveys show that among adults aged 20–74 years the prevalence of obesity increased from 15.0% (in the 1976–1980 survey) to 32.9% (in the 2003–2004 survey).
In hunter-gatherer and some semi-agricultural societies, obesity is rare. In most, it's nonexistent. Wild animals typically do not accumulate enough fat to interfere with vigorous exercise, and when they do, it's because they're about to hibernate or migrate. Wild animals also tend to have similar amounts of body fat between individuals (at a given age and sex), unlike industrialized humans. This makes me think that obesity is an unnatural effect of our current lifestyle. Whatever the cause, it's getting progressively more common.
According to certain nutrition experts, we know exactly what causes overweight. It's a character flaw known as overeating. Calories in, calories out. And the cure is to eat less. The problem is, this treatment has a poor record of efficacy.
Restricting calories is also fraught with problems. Each person's metabolism has a preference for a specific body composition within the context of a particular lifestyle. If total calories are restricted without changing diet composition, the body reacts vigorously to maintain homeostasis. Energy expenditure is reduced; muscle and organ mass diminish. The psychological effects are particularly bad, as anyone can tell you who has been on a low-calorie diet. In 1944, Ancel Keys undertook a calorie restriction trial in conscientious objector "volunteers" in Minnesota. They remained on a 1,570-calorie diet that was low in fat and protein and high in carbohydrate, for 24 weeks. Hardly a draconian calorie count. Here's a quote from the study:
As starvation progressed, fewer and fewer things could stimulate the men to overt action. They described their increasing weakness, loss of ambition, narrowing of interests, depression, irritability, and loss of libido as a pattern characteristic of "growing old".
Some of the men ended up suffering from neurosis and borderline psychosis before the end of the study, one culminating in self-mutilation. This is what we're being prescribed for weight loss?
There are some diet trends that have associated with rising obesity in the US. Per capita calorie consumption has increased. This increase is due to a higher consumption of carbohydrate. Total protein and fat consumption have been almost identical for the past 30 years. This period also saw increases in the consumption of unsaturated vegetable oils, hydrogenated vegetable oils and high-fructose corn syrup. It's hard to say from this association which of these factors (if any) has caused us to gain weight in the last 30 years, but it certainly isn't total fat or protein. Fortunately, we have other clues.
If diet composition causes hyperphagia, we should be able to see it in animals. I just came across a great study from the lab of Dr. Neil Stickland that explored this in rats. They took two groups of pregnant rats and fed them two different diets ad libitum, meaning the rats could eat as much as they wanted. Here's what the diets looked like:The animals were fed two types of diet throughout the study. They were fed either RM3 rodent chow alone ad libitum (SDS Ltd, Betchworth, Surrey, UK) or with a junk food diet, also known as cafeteria diet, which consisted of eight different types of palatable foods, purchased from a British supermarket. The palatable food included biscuits, marshmallows, cheese, jam doughnuts, chocolate chip muffins, butter flapjacks, potato crisps and caramel/chocolate bars.
It's important to note that the junk food-fed rats had access to rat chow as well. Now here's where it gets interesting. Rats with access to junk food in addition to rat chow ate 56% more calories than the chow-only group! Here's what they had to say about it:These results clearly show that pregnant rats, given ad libitum access to junk food, exhibited hyperphagia characterised by a marked preference for foods rich in fat, sucrose and salt at the expense of protein-rich foods, when compared with rats that only had access to rodent chow. Although the body mass of dams was comparable among all groups at the start of the experiment, the increased energy intake in the junk food group throughout gestation was accompanied by an increase in body mass at G20 [gestational day 20] with the junk food-fed dams being 13 % heavier than those fed chow alone.
Hmm, this is remarkably reminiscent of what's happening to a certain group of humans in North America right now: give them access to food made mostly of refined grains, sugar, and industrially processed vegetable oil. They will prefer it to healthier food, to the point of overeating. The junk food then drives hyperphagia by interfering with the body's feedback loops that normally keep feeding behaviors and body fat within the optimal range. These data support the hypothesis that metabolic damage is the cause of, not the result of, "super-sized" food portions and other similar cultural phenomena. The rest of the paper is interesting as well. Pups born to mothers who ate junk food while pregnant and lactating had a greater tendency to eat junk than pups born to mothers who ate rat chow during the same period. This underscores the idea that poor nutrition can set a child up for a lifetime of problems.
One of the things I didn't mention in the last post is that Americans are eating more calories than ever before. According to Centers for Disease Control NHANES data, in 2000, men ate about 160 more calories per day, and women ate about 340 more than in 1971. That's a change of 7% and 22%, respectively. The extra calories come almost exclusively from refined grains, with the largest single contribution coming from white wheat flour (correction: the largest single contribution comes from corn sweeteners, followed by white wheat flour).Some people will see those data and decide the increase in calories is the explanation for the expanding American waistline. I don't think that's incorrect, but I do think it misses the point. The relevant question is "why are we eating more calories now than we were in 1971?"We weren't exactly starving in 1971. And average energy expenditure, if anything, has actually increased. So why are we eating more? I believe that our increased food intake, or hyperphagia, is the result of metabolic disturbances, rather than the cause of them.Humans, like all animals, have a sophisticated system of hormones and brain regions whose function is to maintain a proper energy balance. Part of the system's job is to keep fat mass at an appropriate level. With a properly functioning system, feedback loops inhibit hunger once fat mass has reached a certain level, and also increase resting metabolic rate to burn excess calories. If the system is working properly, it's very difficult to gain weight. There have been a number of overfeeding studies in which subjects have consumed huge amounts of excess calories. Some people gain weight, many don't.The fact that fat mass is hormonally regulated can be easily seen in other mammals. When was the last time you saw a fat squirrel in the springtime? When was the last time you saw a thin squirrel in the fall? These events are regulated by hormones. A squirrel in captivity will put on weight in the fall, even if its daily food intake is not changed.A key hormone in this process is leptin. Leptin levels are proportional to fat mass, and serve to inhibit hunger and eating behaviors. Under normal conditions, the more fat tissue a person has, the more leptin they will produce, and the less they will eat until the fat mass has reached the body's preferred 'set-point'. The problem is that overweight Westerners are almost invariably leptin-resistant, meaning their body doesn't respond to the signal to stop eating!Leptin resistance leads to hyperphagia, overweight and the metabolic syndrome (a common cluster of symptoms that implies profound metabolic disturbance). It typically precedes insulin resistance during the downward slide towards metabolic syndrome.I suspect that wheat, sugar and perhaps other processed foods cause hyperphagia. I believe hyperphagia is at least partially secondary to a disturbed metabolism. There's something about industrial foods that reached a critical mass in the mid-70s. The shift in diet sent us into a tailspin of excessive eating and unprecedented weight gain.
The New York Times just published an article called "The Overflowing American Dinner Plate", in which they describe changes in the American diet since 1970, the period during which the obesity rate doubled. Bill Marsh used USDA estimates of food consumption from 1970 to 2006. Predictably, he focuses on fat consumption, and writes that it has increased by 59% in the same time period. The problem is, we aren't eating any more fat than we were in 1970. The US Centers for Disease Control NHANES surveys show that total fat consumption has remained the same since 1971, and has decreased as a percentage of calories. I've been playing around with the USDA data for months now, and I can tell you that Marsh misinterpreted it in a bad way. Here are the raw data, for anyone who's interested. They're in easy-to-use Excel spreadsheets. I highly recommend poking around them if you're interested.The reason Marsh was confused by the USDA data is that he confused "added fats" with "total fat". While total fat intake has remained stable over this time period, added fats have increased by 59%. The increase is almost exclusively due to industrially processed seed oils (butter and lard have decreased). Total fat has remained the same because we now eat low-fat cuts of meat and low-fat dairy products to make up for it! Another problem with the article is it only shows percent changes in consumption of different foods, rather than absolute amounts. This obscures some really meaningful information. For example, grain consumption is up a whopping 42%. That is the largest single food group change if you exclude the misinterpreted fat data. Corn is up 188%, rice 170%, wheat 21%. But in absolute amounts, the increase in wheat consumption is larger than corn or rice! That's because baseline wheat consumption dwarfed corn and rice. We don't get that information from the data presented in the article, due to the format. So now that I've deconstructed the data, let's see what the three biggest changes in the American diet from 1970 to 2006 actually are:- We're eating more grains, especially white wheat flour
- We're eating more added sweeteners, especially high-fructose corn syrup
- Animal fats from milk and meat have been replaced by processed seed oils
Wheat + sugar + processed vegetable oil = fat and unhealthy. Sounds familiar, doesn't it?
A final note about the Chinese study in the previous post: the overweight vegetable-eaters (read: wheat eaters) exercised more than their non-vegetable-eating, thin neighbors. So although their average calorie intake was a bit higher, their expenditure was as well. Although I speculated in the last post that affluent people might be eating more wheat and fresh vegetables, the data don't support that. Participants with the highest income level actually adhered to the wheat and vegetable-rich pattern the least, while low-income participants were most likely to eat this way. Interestingly, education showed a (weaker) trend in the opposite direction. More educated participants were more likely to eat the wheat-vegetable pattern, while the opposite was true of less educated participants. Thus, it looks like wheat makes people more educated. Just kidding, that's exactly the logic we have to avoid when interpreting this type of study!
Dr. Michael Eades linked to an interesting study yesterday on his Health and Nutrition blog. It's entitled "Vegetable-Rich Food Pattern is Related to Obesity in China." It's one of these epidemiological studies where they try to divide subjects into different categories of eating patterns and see how health problems associate with each one. They identified four patterns: the 'macho' diet high in meat and alcohol; the 'traditional' diet high in rice and vegetables; the 'sweet tooth' pattern high in cake, dairy and various drinks; and the 'vegetable rich' diet high in wheat, vegetables, fruit and tofu. The only pattern that associated with obesity was the vegetable-rich diet. The 25% of people eating closest to the vegetable-rich pattern were more than twice as likely to be obese as the 25% adhering the least.The authors of the paper try to blame the increased obesity on a higher intake of vegetable oil from stir-frying the vegetables, but that explanation is misleading. A cursory glance at table 3 reveals that the vegetable-eaters weren't eating any more fat than their thinner neighbors. Dr. Eades suggests that their higher carbohydrate intake (+10%) was partially responsible for the weight gain, but I wasn't satisfied with that explanation so I took a closer look. Dr. Eades also pointed to their higher calorie intake (+120 kcal/day), which makes sense to me. One of the most striking elements of the 'vegetable-rich' food pattern is its replacement of rice with wheat flour. The 25% of the study population that adhered the least to the vegetable-rich food pattern ate 7.3 times more rice than wheat, whereas the 25% sticking most closely to the vegetable-rich pattern ate 1.2 times more wheat than rice! In other words, wheat flour rather than rice was their single largest source of calories. This association was much stronger than the increase in vegetable consumption itself! All of a sudden, the data make more sense. Wheat seems to associate with health problems in many contexts. Perhaps the reason we don't see the same type of association in American epidemiological studies is that everyone eats wheat. Only in a culture that has a true diversity of diet can you find a robust association like this. The replacement of rice with wheat may have caused the increase in calorie intake as well. Clinical trials of low-carbohydrate diets as well as 'paleolithic diets' have shown good metabolic outcomes from wheat avoidance, although one can't be sure what role wheat plays from those data. I don't think the vegetables had anything to do with the weight gain, they were just incidentally associated with wheat consumption. But I do think these data are difficult to reconcile with the idea that vegetables protect against overweight.
I left out one of the juicier tidbits from the last post because it was getting long. Investigators Kang-Jey Ho et al. wanted an explanation for why the Masai didn't have high serum cholesterol despite their high dietary cholesterol intake (up to 2,000 mg per day-- 6.7 times the US FDA recommended daily allowance).
They took 23 male Masai subjects aged 19 to 24 and divided them into two groups. The first group of 11 was the control group, which received a small amount of radioactive cholesterol in addition to a cholesterol-free diet that I will describe below. The second group of 12 was the experimental group, which they fed 2,000 mg cholesterol per day, a small amount of radioactive cholesterol as a tracer, and the exact same cholesterol-free diet as the control group. For the duration of the 24-week trial, the subjects ate the experimental diet exclusively. Here's what it was (in order of calories, descending): - Nondairy coffee creamer (made of corn syrup solids and vegetable oil)
- Beans
- Sugar
- Corn
- Corn oil
- A vitamin pill
Not a healthy diet by most peoples' standards, but those items are nevertheless widely eaten in the US. Over the course of the 24-week study, the investigators found no difference in serum cholesterol between the control and experimental groups. This isn't really surprising. The body has mechanisms for regulating blood cholesterol, and if you aren't eating any it just synthesizes more to stay at its preferred level.
The really interesting thing is that serum cholesterol increased dramatically in both groups. It went from 125 mg/100 mL to over 170 mg/100 mL, despite a large decrease in the saturated fat they were eating. The change took about two weeks to occur, and remained fairly stable for the remainder of the trial.
Both groups also gained weight. In the first week, they gained an average of 3 pounds each. To be fair, the initial gain was probably most water, which is what happens when a person increases their carbohydrate and salt intake. The investigators freaked out and cut their calorie intake by 400 kcal, only allowing them 3,600 kcal per day. Initially, they were voluntarily consuming 4,000 kcal per day. I find that interesting as well. Something tells me they weren't chugging non-dairy creamer because it was so delicious, but because their confused hormones were telling them to EAT.
Even after putting the subjects on calorie restriction (not letting them eat as much as they wanted, by an average of 400 kcal/day), they continued gaining weight. By the end of the study, the 23 subjects had gained an average of 7.8 lbs per person.
To summarize, this is what the investigators saw when they put 23 unfortunate Masai men on a bottom-rung industrially processed diet: elevated cholesterol, hyperphagia (excessive eating), and weight gain. Sounds familiar, doesn't it?
