Insulin is an ancient hormone that influences many processes in the body. Its main role is to manage circulating concentrations of nutrients (principally glucose and fatty acids, the body's two main fuels), keeping them within a fairly narrow range*. It does this by encouraging the transport of nutrients into cells from the circulation, and discouraging the export of nutrients out of storage sites, in response to an increase in circulating nutrients (glucose or fatty acids). It therefore operates a negative feedback loop that constrains circulating nutrient concentrations. It also has many other functions that are tissue-specific.
Insulin resistance is a state in which cells lose sensitivity to the effects of insulin, eventually leading to a diminished ability to control circulating nutrients (glucose and fatty acids). It is a major contributor to diabetes risk, and probably a contributor to the risk of cardiovascular disease, certain cancers and a number of other disorders.
Why is it important to manage the concentration of circulating nutrients to keep them within a narrow range? The answer to that question is the crux of this post.
Read more »
Tampilkan postingan dengan label genetics. Tampilkan semua postingan
Tampilkan postingan dengan label genetics. Tampilkan semua postingan
Jumat, 11 November 2011
Kamis, 03 November 2011
Does High Circulating Insulin Drive Body Fat Accumulation? Answers from Genetically Modified Mice
The house mouse Mus musculus is an incredible research tool in the biomedical sciences, due to its ease of care and its ability to be genetically manipulated. Although mice aren't humans, they resemble us closely in many ways, including how insulin signaling works. Genetic manipulation of mice allows researchers to identify biological mechanisms and cause-effect relationships in a very precise manner. One way of doing this is to create "knockout" mice that lack a specific gene, in an attempt to determine that gene's importance in a particular process. Another way is to create transgenic mice that express a gene of interest, often modified in some way. A third method is to use an extraordinary (but now common) tool called "Cre-lox" recombination (1), which allows us to delete or add a single gene in a specific tissue or cell type.
Studying the relationship between obesity and insulin resistance is challenging, because the two typically travel together, confounding efforts to determine which is the cause and which is the effect of the other (or neither). Some have proposed the hypothesis that high levels of circulating insulin promote body fat accumulation*. To truly address this question, we need to consider targeted experiments that increase circulating insulin over long periods of time without altering a number of other factors throughout the body. This is where mice come in. Scientists are able to perform precise genetic interventions in mice that increase circulating insulin over a long period of time. These mice should gain fat mass if the hypothesis is correct.
Read more »
Studying the relationship between obesity and insulin resistance is challenging, because the two typically travel together, confounding efforts to determine which is the cause and which is the effect of the other (or neither). Some have proposed the hypothesis that high levels of circulating insulin promote body fat accumulation*. To truly address this question, we need to consider targeted experiments that increase circulating insulin over long periods of time without altering a number of other factors throughout the body. This is where mice come in. Scientists are able to perform precise genetic interventions in mice that increase circulating insulin over a long period of time. These mice should gain fat mass if the hypothesis is correct.
Read more »
Jumat, 07 Oktober 2011
The Case for the Food Reward Hypothesis of Obesity, Part II
In this post, I'll explore whether or not the scientific evidence is consistent with the predictions of the food reward hypothesis, as outlined in the last post.
Before diving in, I'd like to address the critique that the food reward concept is a tautology or relies on circular reasoning (or is not testable/falsifiable). This critique has no logical basis. The reward and palatability value of a food is not defined by its effect on energy intake or body fatness. In the research setting, food reward is measured by the ability of food or food-related stimuli to reinforce or motivate behavior (e.g., 1). In humans, palatability is measured by having a person taste a food and rate its pleasantness in a standardized, quantifiable manner, or sometimes by looking at brain activity by fMRI or related techniques (2). In rodents, it is measured by observing stereotyped facial responses to palatable and unpalatable foods, which are similar to those seen in human infants. It is not a tautology or circular reasoning to say that the reinforcing value or pleasantness of food influences food intake and body fatness. These are quantifiable concepts and as I will explain, their relationship with food intake and body fatness can be, and already has been, tested in a controlled manner.
1. Increasing the reward/palatability value of the diet should cause fat gain in animals and humans
Read more »
Before diving in, I'd like to address the critique that the food reward concept is a tautology or relies on circular reasoning (or is not testable/falsifiable). This critique has no logical basis. The reward and palatability value of a food is not defined by its effect on energy intake or body fatness. In the research setting, food reward is measured by the ability of food or food-related stimuli to reinforce or motivate behavior (e.g., 1). In humans, palatability is measured by having a person taste a food and rate its pleasantness in a standardized, quantifiable manner, or sometimes by looking at brain activity by fMRI or related techniques (2). In rodents, it is measured by observing stereotyped facial responses to palatable and unpalatable foods, which are similar to those seen in human infants. It is not a tautology or circular reasoning to say that the reinforcing value or pleasantness of food influences food intake and body fatness. These are quantifiable concepts and as I will explain, their relationship with food intake and body fatness can be, and already has been, tested in a controlled manner.
1. Increasing the reward/palatability value of the diet should cause fat gain in animals and humans
Read more »
Kamis, 25 Agustus 2011
A Roadmap to Obesity
In this post, I'll explain my current understanding of the factors that promote obesity in humans.
Heritability
To a large degree, obesity is a heritable condition. Various studies indicate that roughly two-thirds of the differences in body fatness between individuals is explained by heredity*, although estimates vary greatly (1). However, we also know that obesity is not genetically determined, because in the US, the obesity rate has more than doubled in the last 30 years, consistent with what has happened to many other cultures (2). How do we reconcile these two facts? By understanding that genetic variability determines the degree of susceptibility to obesity-promoting factors. In other words, in a natural environment with a natural diet, nearly everyone would be relatively lean, but when obesity-promoting factors are introduced, genetic makeup determines how resistant each person will be to fat gain. As with the diseases of civilization, obesity is caused by a mismatch between our genetic heritage and our current environment. This idea received experimental support from an interesting recent study (3).
Read more »
Heritability
To a large degree, obesity is a heritable condition. Various studies indicate that roughly two-thirds of the differences in body fatness between individuals is explained by heredity*, although estimates vary greatly (1). However, we also know that obesity is not genetically determined, because in the US, the obesity rate has more than doubled in the last 30 years, consistent with what has happened to many other cultures (2). How do we reconcile these two facts? By understanding that genetic variability determines the degree of susceptibility to obesity-promoting factors. In other words, in a natural environment with a natural diet, nearly everyone would be relatively lean, but when obesity-promoting factors are introduced, genetic makeup determines how resistant each person will be to fat gain. As with the diseases of civilization, obesity is caused by a mismatch between our genetic heritage and our current environment. This idea received experimental support from an interesting recent study (3).
Read more »
Rabu, 20 Oktober 2010
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):
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.
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.
Selasa, 29 September 2009
Malocclusion: Disease of Civilization
In his epic work Nutrition and Physical Degeneration, Dr. Weston Price documented the abnormal dental development and susceptibility to tooth decay that accompanied the adoption of modern foods in a number of different cultures throughout the world. Although he quantified changes in cavity prevalence (sometimes finding increases as large as 1,000-fold), all we have are Price's anecdotes describing the crooked teeth, narrow arches and "dished" faces these cultures developed as they modernized.
Price published the first edition of his book in 1939. Fortunately, Nutrition and Physical Degeneration wasn't the last word on the matter. Anthropologists and archaeologists have been extending Price's findings throughout the 20th century. My favorite is Dr. Robert S. Corruccini, currently a professor of anthropology at Southern Illinois University. He published a landmark paper in 1984 titled "An Epidemiologic Transition in Dental Occlusion in World Populations" that will be our starting point for a discussion of how diet and lifestyle factors affect the development of the teeth, skull and jaw (Am J. Orthod. 86(5):419)*.
First, some background. The word occlusion refers to the manner in which the top and bottom sets of teeth come together, determined in part by the alignment between the upper jaw (maxilla) and lower jaw (mandible). There are three general categories:
Over the course of the next several posts, I'll give an overview of the extensive literature showing that hunter-gatherers past and present have excellent occlusion, subsistence agriculturalists generally have good occlusion, and the adoption of modern foodways directly causes the crooked teeth, narrow arches and/or crowded third molars (wisdom teeth) that affect the majority of people in industrialized nations. I believe this process also affects the development of the rest of the skull, including the face and sinuses.
In his 1984 paper, Dr. Corruccini reviewed data from a number of cultures whose occlusion has been studied in detail. Most of these cultures were observed by Dr. Corruccini personally. He compared two sets of cultures: those that adhere to a traditional style of life and those that have adopted industrial foodways. For several of the cultures he studied, he compared it to another that was genetically similar. For example, the older generation of Pima indians vs. the younger generation, and rural vs. urban Punjabis. He also included data from archaeological sites and nonhuman primates. Wild animals, including nonhuman primates, almost invariably show perfect occlusion.
The last graph in the paper is the most telling. He compiled all the occlusion data into a single number called the "treatment priority index" (TPI). This is a number that represents the overall need for orthodontic treatment. A TPI of 4 or greater indicates malocclusion (the cutoff point is subjective and depends somewhat on aesthetic considerations). Here's the graph:
Every single urban/industrial culture has an average TPI of greater than 4, while all the non-industrial or less industrial cultures have an average TPI below 4. This means that in industrial cultures, the average person requires orthodontic treatment to achieve good occlusion, whereas most people in more traditionally-living cultures naturally have good occlusion.
The best occlusion was in the New Britain sample, a precontact Melanesian hunter-gatherer group studied from archaeological remains. The next best occlusion was in the Libben and Dickson groups, who were early Native American agriculturalists. The Pima represent the older generation of Native Americans that was raised on a somewhat traditional agricultural diet, vs. the younger generation raised on processed reservation foods. The Chinese samples are immigrants and their descendants in Liverpool. The Punjabis represent urban vs. rural youths in Northern India. The Kentucky samples represent a traditionally-living Appalachian community, older generation vs. processed food-eating offspring. The "early black" and "black youths" samples represent older and younger generations of African-Americans in the Cleveland and St. Louis area. The "white parents/youths" sample represents different generations of American Caucasians.
The point is clear: there's something about industrialization that causes malocclusion. It's not genetic; it's a result of changes in diet and/or lifestyle. A "disease of civilization". I use that phrase loosely, because malocclusion isn't really a disease, and some cultures that qualify as civilizations retain traditional foodways and relatively good teeth. Nevertheless, it's a time-honored phrase that encompasses the wide array of health problems that occur when humans stray too far from their ecological niche. I'm going to let Dr. Corruccini wrap this post up for me:
* This paper is worth reading if you get the chance. It should have been a seminal paper in the field of preventive orthodontics, which could have largely replaced conventional orthodontics by now. Dr. Corruccini is the clearest thinker on this subject I've encountered so far.
Price published the first edition of his book in 1939. Fortunately, Nutrition and Physical Degeneration wasn't the last word on the matter. Anthropologists and archaeologists have been extending Price's findings throughout the 20th century. My favorite is Dr. Robert S. Corruccini, currently a professor of anthropology at Southern Illinois University. He published a landmark paper in 1984 titled "An Epidemiologic Transition in Dental Occlusion in World Populations" that will be our starting point for a discussion of how diet and lifestyle factors affect the development of the teeth, skull and jaw (Am J. Orthod. 86(5):419)*.
First, some background. The word occlusion refers to the manner in which the top and bottom sets of teeth come together, determined in part by the alignment between the upper jaw (maxilla) and lower jaw (mandible). There are three general categories:
- Class I occlusion: considered "ideal". The bottom incisors (front teeth) fit just behind the top incisors.
- Class II occlusion: "overbite." The bottom incisors are too far behind the top incisors. The mandible may appear small.
- Class III occlusion: "underbite." The bottom incisors are beyond the top incisors. The mandible protrudes.
Over the course of the next several posts, I'll give an overview of the extensive literature showing that hunter-gatherers past and present have excellent occlusion, subsistence agriculturalists generally have good occlusion, and the adoption of modern foodways directly causes the crooked teeth, narrow arches and/or crowded third molars (wisdom teeth) that affect the majority of people in industrialized nations. I believe this process also affects the development of the rest of the skull, including the face and sinuses.
In his 1984 paper, Dr. Corruccini reviewed data from a number of cultures whose occlusion has been studied in detail. Most of these cultures were observed by Dr. Corruccini personally. He compared two sets of cultures: those that adhere to a traditional style of life and those that have adopted industrial foodways. For several of the cultures he studied, he compared it to another that was genetically similar. For example, the older generation of Pima indians vs. the younger generation, and rural vs. urban Punjabis. He also included data from archaeological sites and nonhuman primates. Wild animals, including nonhuman primates, almost invariably show perfect occlusion.
The last graph in the paper is the most telling. He compiled all the occlusion data into a single number called the "treatment priority index" (TPI). This is a number that represents the overall need for orthodontic treatment. A TPI of 4 or greater indicates malocclusion (the cutoff point is subjective and depends somewhat on aesthetic considerations). Here's the graph:
Every single urban/industrial culture has an average TPI of greater than 4, while all the non-industrial or less industrial cultures have an average TPI below 4. This means that in industrial cultures, the average person requires orthodontic treatment to achieve good occlusion, whereas most people in more traditionally-living cultures naturally have good occlusion.The best occlusion was in the New Britain sample, a precontact Melanesian hunter-gatherer group studied from archaeological remains. The next best occlusion was in the Libben and Dickson groups, who were early Native American agriculturalists. The Pima represent the older generation of Native Americans that was raised on a somewhat traditional agricultural diet, vs. the younger generation raised on processed reservation foods. The Chinese samples are immigrants and their descendants in Liverpool. The Punjabis represent urban vs. rural youths in Northern India. The Kentucky samples represent a traditionally-living Appalachian community, older generation vs. processed food-eating offspring. The "early black" and "black youths" samples represent older and younger generations of African-Americans in the Cleveland and St. Louis area. The "white parents/youths" sample represents different generations of American Caucasians.
The point is clear: there's something about industrialization that causes malocclusion. It's not genetic; it's a result of changes in diet and/or lifestyle. A "disease of civilization". I use that phrase loosely, because malocclusion isn't really a disease, and some cultures that qualify as civilizations retain traditional foodways and relatively good teeth. Nevertheless, it's a time-honored phrase that encompasses the wide array of health problems that occur when humans stray too far from their ecological niche. I'm going to let Dr. Corruccini wrap this post up for me:
I assert that these results serve to modify two widespread generalizations: that imperfect occlusion is not necessarily abnormal, and that prevalence of malocclusion is genetically controlled so that preventive therapy in the strict sense is not possible. Cross-cultural data dispel the notion that considerable occlusal variation [malocclusion] is inevitable or normal. Rather, it is an aberrancy of modern urbanized populations. Furthermore, the transition from predominantly good to predominantly bad occlusion repeatedly occurs within one or two generations' time in these (and other) populations, weakening arguments that explain high malocclusion prevalence genetically.
* This paper is worth reading if you get the chance. It should have been a seminal paper in the field of preventive orthodontics, which could have largely replaced conventional orthodontics by now. Dr. Corruccini is the clearest thinker on this subject I've encountered so far.
Sabtu, 15 Agustus 2009
Ischemic Heart Attacks: Disease of Civilization
Or, more precisely, disease of industrial civilization.
The scientific literature contains examples of cultures that don't suffer from the chronic non-communicable diseases that are so common in modern societies. Much of what I've read indicates that heart attacks are practically unique to cultures that have adopted industrial foodways and a modern lifestyle, being infrequent or entirely absent in those that have not.
I recently came across an incredible paper from 1964 in the American Journal of Cardiology, titled "Geographic Pathology of Myocardial Infarction", by lead author Dr. Kyu Taik Lee (Am. J. Cardiol. 13:30. 1964). This was published during a period of intense research into the cardiovascular health of non-industrial cultures, including Dr. George V. Mann's famous study of the Masai.
The first thing Lee and his colleagues did was collect autopsy statistics from San Francisco and Los Angeles hospitals. They analyzed the data by race, including categories for Caucasian-Americans (white), Japanese-Americans, Chinese-Americans, and Filipino-Americans. All races had a similar incidence of autopsy-proven myocardial infarction (MI = heart attack), including both silent (healed) and fatal MI. For comparison, they included a table with autopsy data from hospitals in Tokyo, South Japan and North Japan. I'm including the data from Tokyo in the graph because it's also an urban environment, but the finding was the same in all three regions. Here's what they found, by age group:
The Japanese had a very low rate of MI compared to both Caucasian-Americans and Japanese-Americans. The rate of MI in Caucasian-Americans and Japanese-Americans did not differ significantly. Thus, location but not race determined the susceptibility to MI.
Next, the investigators collected autopsy data from hospitals in New Orleans, again divided by race. This time they exained Caucasian-Americans and African-Americans. Both groups had a very high rate of MI, as expected, although the African-Americans had a lower rate than Caucasian-Americans. They also collected data from autopsies in Nigeria and Uganda for comparison. Here are the data for men:
And for women: 
Again, location but not race largely determined the incidence of MI. MI was extremely rare in the African autopsies. Here's what they had to say:
To satisfy the skeptics, Lee and colleagues imported hundreds of hearts from consecutive autopsies in Albany (USA), Africa, Korea and Japan. They had an American pathologist analyze them side-by side to eliminate any diagnostic bias. Here's what they found:
What do the traditional diets and lifestyles of Japan and Africa have in common? Not much. Even within Nigeria, the diet varies from heavily starch-based (root vegetables, soaked/fermented non-gluten grains, beans, plantains) to mostly reliant on high-fat dairy and meat. In fact, I believe it's the wrong question to ask. A better question is "what do we eat/do in the US that traditional Japanese, Koreans, Chinese, Polynesians, Melanesians and Africans don't"? For starters, none of them rely on industrial vegetable oils, sugar and wheat to nearly the same extent as modern America. Their food is generally prepared at home using wholesome ingredients and traditional methods.
They probably get more exercise than Americans, even if it's only walking in Tokyo or domestic tasks for women in parts of Africa. Traditional Africans surely get more sunlight and thus more vitamin D. I can't imagine life is less stressful in Tokyo than in San Francisco or Los Angeles.
I really like this study, and I think these graphs should be disseminated as much as possible. I've prepared high-resolution versions in JPEG, Powerpoint and PDF formats. E-mail me (click on my profile for the link) if you would like a copy. Let me know which format(s) you want.
The scientific literature contains examples of cultures that don't suffer from the chronic non-communicable diseases that are so common in modern societies. Much of what I've read indicates that heart attacks are practically unique to cultures that have adopted industrial foodways and a modern lifestyle, being infrequent or entirely absent in those that have not.
I recently came across an incredible paper from 1964 in the American Journal of Cardiology, titled "Geographic Pathology of Myocardial Infarction", by lead author Dr. Kyu Taik Lee (Am. J. Cardiol. 13:30. 1964). This was published during a period of intense research into the cardiovascular health of non-industrial cultures, including Dr. George V. Mann's famous study of the Masai.
The first thing Lee and his colleagues did was collect autopsy statistics from San Francisco and Los Angeles hospitals. They analyzed the data by race, including categories for Caucasian-Americans (white), Japanese-Americans, Chinese-Americans, and Filipino-Americans. All races had a similar incidence of autopsy-proven myocardial infarction (MI = heart attack), including both silent (healed) and fatal MI. For comparison, they included a table with autopsy data from hospitals in Tokyo, South Japan and North Japan. I'm including the data from Tokyo in the graph because it's also an urban environment, but the finding was the same in all three regions. Here's what they found, by age group:
The Japanese had a very low rate of MI compared to both Caucasian-Americans and Japanese-Americans. The rate of MI in Caucasian-Americans and Japanese-Americans did not differ significantly. Thus, location but not race determined the susceptibility to MI. Next, the investigators collected autopsy data from hospitals in New Orleans, again divided by race. This time they exained Caucasian-Americans and African-Americans. Both groups had a very high rate of MI, as expected, although the African-Americans had a lower rate than Caucasian-Americans. They also collected data from autopsies in Nigeria and Uganda for comparison. Here are the data for men:
And for women: 
Again, location but not race largely determined the incidence of MI. MI was extremely rare in the African autopsies. Here's what they had to say: There was only 1 case of healed myocardial infarction among over 4,000 adult autopsies in the Uganda series, and only 2 cases of healed myocardial infarction among over 500 adult autopsies in the Nigerian series. In the New Orleans Negro series the occurrence rate was far greater in every sex and age group than in either one of the Negro series in East and West Africa.Over 4,500 autopsies and not a single fatal MI. If this isn't worth studying, what is? These data should be part of first-year training in medicine and health programs.
To satisfy the skeptics, Lee and colleagues imported hundreds of hearts from consecutive autopsies in Albany (USA), Africa, Korea and Japan. They had an American pathologist analyze them side-by side to eliminate any diagnostic bias. Here's what they found:
In the African Negro series no infarct was found in any age group [out of 244 hearts, 39 over 60 years old]. In the Korean series there were only 2 cases of myocardial infarction [out of 106 hearts] and they were both women... In the Japanese series there were 8 cases of myocardial infarction in 259 hearts. All were men...In the American sample, nearly 40% of the hearts of men and women over 60 showed signs of MI. The findings of the American pathologist confirmed the international autopsy data, showing that diagnostic bias did not contribute to the results significantly. They also took measurements of the thickness of the coronary artery wall, an index of atherosclerosis. They found that the Americans had the most atherosclerosis, but all cultures had some degree of it and there was overlap in the amount of atherosclerosis between samples. This led the investigators to state:
Myocardial infarction and coronary thrombosis are almost nonexistent in Uganda and Nigeria, and the amount of coronary arteriosclerosis is significantly less in Africans than in whites. However, in the two groups there was some overlapping in the degree of arteriosclerosis. No Africans had infarcts, but some had the same or a greater degree of coronary arteriosclerosis as a few whites who had myocardial infarctions. One explanation for this may be that some difference in clotting or clot-lysis mechanisms is present in the two groups. In a previous study, we showed that the incidence of thromboembolic phenomena in the pulmonary circulation [blood clots in the lungs] was low in East Africans as compared with Americans.Now, the authors' conclusions:
These data strongly suggest that among the Orientals the environmental factor is playing a major role in the etiology of myocardial infarction and coronary thrombosis. If the genetic factor is an important one, those Orientals who moved to this country many years ago or who were born in this country should still maintain their low occurrence rate of myocardial infarction at least to some extent, and one would not expect to see similar occurrence rates of myocardial infarction in Orientals and whites as old as 50 to 59 years... As with the Orientals, this suggests that for Negroes in the United States environmental factors are more important than genetic factors in the etiology of myocardial infarction.Africans in Africa and Japanese in Japan = low incidence of MI. Africans, Japanese and Caucasians in the US = high and similar incidence of MI. Genes only influence a person's susceptibility to MI when they live in an environment that promotes MI. Otherwise, genes are basically irrelevant.
What do the traditional diets and lifestyles of Japan and Africa have in common? Not much. Even within Nigeria, the diet varies from heavily starch-based (root vegetables, soaked/fermented non-gluten grains, beans, plantains) to mostly reliant on high-fat dairy and meat. In fact, I believe it's the wrong question to ask. A better question is "what do we eat/do in the US that traditional Japanese, Koreans, Chinese, Polynesians, Melanesians and Africans don't"? For starters, none of them rely on industrial vegetable oils, sugar and wheat to nearly the same extent as modern America. Their food is generally prepared at home using wholesome ingredients and traditional methods.
They probably get more exercise than Americans, even if it's only walking in Tokyo or domestic tasks for women in parts of Africa. Traditional Africans surely get more sunlight and thus more vitamin D. I can't imagine life is less stressful in Tokyo than in San Francisco or Los Angeles.
I really like this study, and I think these graphs should be disseminated as much as possible. I've prepared high-resolution versions in JPEG, Powerpoint and PDF formats. E-mail me (click on my profile for the link) if you would like a copy. Let me know which format(s) you want.
Minggu, 15 Februari 2009
Paleolithic Diet Clinical Trials Part III
I'm happy to say, it's time for a new installment of the "Paleolithic Diet Clinical Trials" series. The latest study was recently published in the European Journal of Clinical Nutrition by Dr. Anthony Sebastian's group. Dr. Sebastian has collaborated with Drs. Loren Cordain and Boyd Eaton in the past.
This new trial has some major problems, but I believe it nevertheless adds to the weight of the evidence on "paleolithic"-type diets. The first problem is the lack of a control group. Participants were compared to themselves, before eating a paleolithic diet and after having eaten it for 10 days. Ideally, the paleolithic group would be compared to another group eating their typical diet during the same time period. This would control for effects due to getting poked and prodded in the hospital, weather, etc. The second major problem is the small sample size, only 9 participants. I suspect the investigators had a hard time finding enough funding to conduct a larger study, since the paleolithic approach is still on the fringe of nutrition science.
I think this study is best viewed as something intermediate between a clinical trial and 9 individual anecdotes.
Here's the study design: they recruited 9 sedentary, non-obese people with no known health problems. They were 6 males and 3 females, and they represented people of African, European and Asian descent. Participants ate their typical diets for three days while investigators collected baseline data. Then, they were put on a seven-day "ramp-up" diet higher in potassium and fiber, to prepare their digestive systems for the final phase. In the "paleolithic" phase, participants ate a diet of:
There are a couple of twists to this study that make it more interesting. One is that the diets were completely controlled. The only food participants ate came from the experimental kitchen, so investigators knew the exact calorie intake and nutrient composition of what everyone was eating.
The other twist is that the investigators wanted to take weight loss out of the picture. They wanted to know if a paleolithic-style diet is capable of improving health independent of weight loss. So they adjusted participants' calorie intake to make sure they didn't lose weight. This is an interesting point. Investigators had to increase the participants' calorie intake by an average of 329 calories a day just to get them to maintain their weight on the paleo diet. Their bodies naturally wanted to shed fat on the new diet, so they had to be overfed to maintain weight.
On to the results. Participants, on average, saw large improvements in nearly every meaningful measure of health in just 10 days on the "paleolithic" diet. Remember, these people were supposedly healthy to begin with. Total cholesterol and LDL dropped, if you care about that. Triglycerides decreased by 35%. Fasting insulin plummeted by 68%. HOMA-IR, a measure of insulin resistance, decreased by 72%. Blood pressure decreased and blood vessel distensibility (a measure of vessel elasticity) increased. It's interesting to note that measures of glucose metabolism improved dramatically despite no change in carbohydrate intake. Some of these results were statistically significant, but not all of them. However, the authors note that:
There's one last critical point I'll make about this study. In figure 2, the investigators graphed baseline insulin resistance vs. the change in insulin resistance during the course of the study for each participant. Participants who started with the most insulin resistance saw the largest improvements, while those with little insulin resistance to begin with changed less. There was a linear relationship between baseline IR and the change in IR, with a correlation of R=0.98, p less than 0.0001. In other words, to a highly significant degree, participants who needed the most improvement, saw the most improvement. Every participant with insulin resistance at the beginning of the study ended up with basically normal insulin sensitivity after 10 days. At the end of the study, all participants had a similar degree of insulin sensitivity. This is best illustrated by the standard deviation of the fasting insulin measurement, which decreased 9-fold over the course of the experiment.
Here's what this suggests: different people have different degrees of susceptibility to the damaging effects of the modern Western diet. This depends on genetic background, age, activity level and many other factors. When you remove damaging foods, peoples' metabolisms normalize, and most of the differences in health that were apparent under adverse conditions disappear. I believe our genetic differences apply more to how we react to adverse conditions than how we function optimally. The fundamental workings of our metabolisms are very similar, having been forged mostly in hunter-gatherer times. We're all the same species after all.
This study adds to the evidence that modern industrial food is behind our poor health, and that a return to time-honored foodways can have immense benefits for nearly anyone. A paleolithic-style diet is a very effective way to claim your genetic birthright to good health. Just remember to eat the organs and fat. And skip the canola oil and mayonnaise.
Paleolithic Diet Clinical Trials
Paleolithic Diet Clinical Trials Part II
One Last Thought
This new trial has some major problems, but I believe it nevertheless adds to the weight of the evidence on "paleolithic"-type diets. The first problem is the lack of a control group. Participants were compared to themselves, before eating a paleolithic diet and after having eaten it for 10 days. Ideally, the paleolithic group would be compared to another group eating their typical diet during the same time period. This would control for effects due to getting poked and prodded in the hospital, weather, etc. The second major problem is the small sample size, only 9 participants. I suspect the investigators had a hard time finding enough funding to conduct a larger study, since the paleolithic approach is still on the fringe of nutrition science.
I think this study is best viewed as something intermediate between a clinical trial and 9 individual anecdotes.
Here's the study design: they recruited 9 sedentary, non-obese people with no known health problems. They were 6 males and 3 females, and they represented people of African, European and Asian descent. Participants ate their typical diets for three days while investigators collected baseline data. Then, they were put on a seven-day "ramp-up" diet higher in potassium and fiber, to prepare their digestive systems for the final phase. In the "paleolithic" phase, participants ate a diet of:
Meat, fish, poultry, eggs, fruits, vegetables, tree nuts, canola oil, mayonnaise, and honey... We excluded dairy products, legumes, cereals, grains, potatoes and products containing potassium chloride...Mmm yes, canola oil and mayo were universally relished by hunter-gatherers. They liked to feed their animal fat and organs to the vultures, and slather mayo onto their lean muscle meats. Anyway, the paleo diet was higher in calories, protein and polyunsaturated fat (I assume with a better n-6 : n-3 ratio) than the participants' normal diet. It contained about the same amount of carbohydrate and less saturated fat.
There are a couple of twists to this study that make it more interesting. One is that the diets were completely controlled. The only food participants ate came from the experimental kitchen, so investigators knew the exact calorie intake and nutrient composition of what everyone was eating.
The other twist is that the investigators wanted to take weight loss out of the picture. They wanted to know if a paleolithic-style diet is capable of improving health independent of weight loss. So they adjusted participants' calorie intake to make sure they didn't lose weight. This is an interesting point. Investigators had to increase the participants' calorie intake by an average of 329 calories a day just to get them to maintain their weight on the paleo diet. Their bodies naturally wanted to shed fat on the new diet, so they had to be overfed to maintain weight.
On to the results. Participants, on average, saw large improvements in nearly every meaningful measure of health in just 10 days on the "paleolithic" diet. Remember, these people were supposedly healthy to begin with. Total cholesterol and LDL dropped, if you care about that. Triglycerides decreased by 35%. Fasting insulin plummeted by 68%. HOMA-IR, a measure of insulin resistance, decreased by 72%. Blood pressure decreased and blood vessel distensibility (a measure of vessel elasticity) increased. It's interesting to note that measures of glucose metabolism improved dramatically despite no change in carbohydrate intake. Some of these results were statistically significant, but not all of them. However, the authors note that:
In all these measured variables, either eight or all nine participants had identical directional responses when switched to paleolithic type diet, that is, near consistently improved status of circulatory, carbohydrate and lipid metabolism/physiology.Translation: everyone improved. That's a very meaningful point, because even if the average improves, in many studies a certain percentage of people get worse. This study adds to the evidence that no matter what your gender or genetic background, a diet roughly consistent with our evolutionary past can bring major health benefits. Here's another way to say it: ditching certain modern foods can be immensely beneficial to health, even in people who already appear healthy. This is true regardless of whether or not one loses weight.
There's one last critical point I'll make about this study. In figure 2, the investigators graphed baseline insulin resistance vs. the change in insulin resistance during the course of the study for each participant. Participants who started with the most insulin resistance saw the largest improvements, while those with little insulin resistance to begin with changed less. There was a linear relationship between baseline IR and the change in IR, with a correlation of R=0.98, p less than 0.0001. In other words, to a highly significant degree, participants who needed the most improvement, saw the most improvement. Every participant with insulin resistance at the beginning of the study ended up with basically normal insulin sensitivity after 10 days. At the end of the study, all participants had a similar degree of insulin sensitivity. This is best illustrated by the standard deviation of the fasting insulin measurement, which decreased 9-fold over the course of the experiment.
Here's what this suggests: different people have different degrees of susceptibility to the damaging effects of the modern Western diet. This depends on genetic background, age, activity level and many other factors. When you remove damaging foods, peoples' metabolisms normalize, and most of the differences in health that were apparent under adverse conditions disappear. I believe our genetic differences apply more to how we react to adverse conditions than how we function optimally. The fundamental workings of our metabolisms are very similar, having been forged mostly in hunter-gatherer times. We're all the same species after all.
This study adds to the evidence that modern industrial food is behind our poor health, and that a return to time-honored foodways can have immense benefits for nearly anyone. A paleolithic-style diet is a very effective way to claim your genetic birthright to good health. Just remember to eat the organs and fat. And skip the canola oil and mayonnaise.
Paleolithic Diet Clinical Trials
Paleolithic Diet Clinical Trials Part II
One Last Thought
Senin, 08 Desember 2008
Gluten Sensitivity: Celiac Disease is the Tip of the Iceberg
Celiac disease is a degeneration of the lining of the small intestine caused by a sensitivity to gluten. Gluten is the protein portion of wheat, rye, barley, and wheat relatives (spelt, kamut, emmer, einkorn and triticale). I found an interesting paper recently on the impact of celiac disease on nutrient status and bone density. Researchers compared 54 Northern Italian children with untreated celiac disease to 60 presumably healthy children. The celiac patients had extremely poor vitamin D status, with a deficiency rate of 35.18% compared to 5% in the control group. This was using the lenient cut-off point of 20 ng/mL. Average serum 25(OH)D3 in celiac patients was less than half the level of the control group. The celiac patients also had low serum calcium and magnesium, and elevated parathyroid hormone. Celiac children had lower bone mineral density. All parameters returned to normal after 6 months on a gluten-free diet.
This confirms what has been shown numerous times before: celiac disease interferes with nutrient status, including the all-important fat-soluble vitamins. It's not surprising, since it flattens the villi, finger-like structures necessary for efficient nutrient absorption in the small intestine. But wait, the overwhelming majority of our vitamin D comes from the effect of sunlight on our skin, not through our small intestine! So gluten sensitivity must be doing something besides just flattening villi. Perhaps it does. Feeding wheat bran to "healthy" volunteers caused them to burn through their vitamin D reserves at an accelerated rate. I think this underlines what I've come to believe about wheat: it's problematic for a large proportion of the population, perhaps the majority.
Approximately 12% of Americans can be diagnosed as gluten sensitive using blood antibody tests (anti-gliadin IgA or IgG). A subset of these have full-blown celiac disease. The vast, vast majority are undiagnosed. Gluten sensitivity associates with a dizzying array of diseases, including autoimmune disorders, cancer, and neurological problems. The problem with the blood tests is they aren't very sensitive. The most common blood tests for celiac disease look for a class of antibody called IgA. IgA is produced by the mucosa, including the gut. Unless gut damage is already extensive, the majority of IgA stays in the gut. This may cause the assay to overlook many cases of gluten sensitivity. A negative blood antibody test does not rule out gluten sensitivity!
I recently discovered the work of Dr. Kenneth Fine of EnteroLab. He has developed an assay that detects anti-gliadin IgA in stool. Gliadin is one of the problematic proteins in gluten that is implicated in gluten sensitivity. Dr. Fine has been conducting informal research using his fecal anti-gliadin IgA test (data here). He has found that:
This confirms what has been shown numerous times before: celiac disease interferes with nutrient status, including the all-important fat-soluble vitamins. It's not surprising, since it flattens the villi, finger-like structures necessary for efficient nutrient absorption in the small intestine. But wait, the overwhelming majority of our vitamin D comes from the effect of sunlight on our skin, not through our small intestine! So gluten sensitivity must be doing something besides just flattening villi. Perhaps it does. Feeding wheat bran to "healthy" volunteers caused them to burn through their vitamin D reserves at an accelerated rate. I think this underlines what I've come to believe about wheat: it's problematic for a large proportion of the population, perhaps the majority.
Approximately 12% of Americans can be diagnosed as gluten sensitive using blood antibody tests (anti-gliadin IgA or IgG). A subset of these have full-blown celiac disease. The vast, vast majority are undiagnosed. Gluten sensitivity associates with a dizzying array of diseases, including autoimmune disorders, cancer, and neurological problems. The problem with the blood tests is they aren't very sensitive. The most common blood tests for celiac disease look for a class of antibody called IgA. IgA is produced by the mucosa, including the gut. Unless gut damage is already extensive, the majority of IgA stays in the gut. This may cause the assay to overlook many cases of gluten sensitivity. A negative blood antibody test does not rule out gluten sensitivity!
I recently discovered the work of Dr. Kenneth Fine of EnteroLab. He has developed an assay that detects anti-gliadin IgA in stool. Gliadin is one of the problematic proteins in gluten that is implicated in gluten sensitivity. Dr. Fine has been conducting informal research using his fecal anti-gliadin IgA test (data here). He has found that:
- 100% of untreated celiac patients are antigliadin IgA positive by fecal test, compared to only 76% by blood (n= 17).
- 76% of microscopic colitis (a type of chronic diarrhea) patients are positive by the fecal test, compared to 9% by blood (n= 57).
- 57% of symptomatic people (digestive problems?) are positive by the fecal test, compared to 12% by blood (n= 58).
- 62% of people with autoimmune disease are positive by the fecal test.
- 29% of asymptomatic (healthy) people are positive by the fecal test, compared to 11-12% by blood (n= 240).
- Baby and cow feces are 0% positive by the stool assay.
It gets worse. Gluten sensitivity is determined in large part by genetics. A gene called HLA-DQ is intimately involved. It encodes a protein that is expressed on the surface of cells, that serves to activate immune cells when certain foreign substances are present. Different versions of the gene are activated by different substances. HLA-DQ2 and HLA-DQ8 are classically associated with celiac disease. Roughly 42% of the US population carries DQ2 or DQ8. According to Dr. Fine, every allele except DQ4 has some association with gluten-related problems! Only 0.4% of the U.S. population carries HLA-DQ4 and no other allele.
Not everyone who is genetically susceptible will end up developing health problems due to gluten, but it's impossible to estimate how many of the problems we attribute to other causes are in fact caused or exacerbated by gluten.
The immune system can be divided into two parts: innate and adaptive. The innate immune system is a nonspecific, first-line reaction to a perceived threat. The adaptive immune system is a more sophisticated, but slower system that produces a powerful response by particular cell types to a very specific threat. Antibody production is part of the adaptive immune system. Thus, if your gluten sensitivity test is looking for antibodies, it could still be missing an immune reaction to gluten mediated by the innate immune system!
This question has been addressed in a preliminary study. Researchers took gut biopsies from celiac patients and asymptomatic controls. Five out of six asymptomatic controls showed elevated interleukin-15, a marker of innate immune activation, upon exposure to gliadin. An activated innate immune system (commonly called 'inflammation') is associated with a wide array of chronic diseases, from obesity to cancer to cardiovascular disease. Inflammatory cytokines are elevated in celiac patients and may play a role in their bone pathology. What I would like to see is some negative controls-- would the gut biopsies have produced interleukin-15 in response to benign foods or is it truly specific to gluten?
I don't intend to imply that everyone has gluten sensitivity, but I do think the totality of the data are thought-provoking. They also include the association between the introduction of wheat to non-industrial populations and the development of widespread health problems. Another thing to keep in mind is that traditional sourdough fermentation breaks down a portion of gluten, possibly explaining the rise in gluten sensitivity that has paralleled a shift to quick-rise yeast breads. I believe that gluten sensitivity is behind many modern ills, and should be on the short list of suspects in the case of unexplained health problems. This is particularly true of digestive, autoimmune and neurological disorders. Gluten sensitivity is easy to address: stop eating gluten for a few weeks. See how you feel. Reintroduce gluten and see what happens. You might learn something about yourself.
Not everyone who is genetically susceptible will end up developing health problems due to gluten, but it's impossible to estimate how many of the problems we attribute to other causes are in fact caused or exacerbated by gluten.
The immune system can be divided into two parts: innate and adaptive. The innate immune system is a nonspecific, first-line reaction to a perceived threat. The adaptive immune system is a more sophisticated, but slower system that produces a powerful response by particular cell types to a very specific threat. Antibody production is part of the adaptive immune system. Thus, if your gluten sensitivity test is looking for antibodies, it could still be missing an immune reaction to gluten mediated by the innate immune system!
This question has been addressed in a preliminary study. Researchers took gut biopsies from celiac patients and asymptomatic controls. Five out of six asymptomatic controls showed elevated interleukin-15, a marker of innate immune activation, upon exposure to gliadin. An activated innate immune system (commonly called 'inflammation') is associated with a wide array of chronic diseases, from obesity to cancer to cardiovascular disease. Inflammatory cytokines are elevated in celiac patients and may play a role in their bone pathology. What I would like to see is some negative controls-- would the gut biopsies have produced interleukin-15 in response to benign foods or is it truly specific to gluten?
I don't intend to imply that everyone has gluten sensitivity, but I do think the totality of the data are thought-provoking. They also include the association between the introduction of wheat to non-industrial populations and the development of widespread health problems. Another thing to keep in mind is that traditional sourdough fermentation breaks down a portion of gluten, possibly explaining the rise in gluten sensitivity that has paralleled a shift to quick-rise yeast breads. I believe that gluten sensitivity is behind many modern ills, and should be on the short list of suspects in the case of unexplained health problems. This is particularly true of digestive, autoimmune and neurological disorders. Gluten sensitivity is easy to address: stop eating gluten for a few weeks. See how you feel. Reintroduce gluten and see what happens. You might learn something about yourself.
Jumat, 27 Juni 2008
Two Things that Get on My Nerves, Part I
The "Thrifty Gene" Hypothesis
The thrifty gene hypothesis is the darling of many obesity researchers. It was proposed in 1962 by the geneticist James V. Neel to explain the high rates of obesity in modern populations, particularly modernizing American Indians. It states that our species evolved under conditions of frequent starvation, so we're designed to store every available calorie. In today's world of food abundance, our bodies continue to be thrifty and that's why we're fat. You practically can't read a paper on overweight without seeing an obligatory nod to the thrifty gene hypothesis. The only problem is, it doesn't make much sense.
The assumption that hunter-gatherers and non-industrial agriculturalists lived under chronic calorie deprivation isn't well supported. The anthropological evidence indicates that most hunter-gatherers had abundant food, most of the time. They did have fluctuations in energy balance, but the majority of the time they had access to more calories than they needed. Yet they were not fat.
The Kitavans are a good example. They are a horticultural society that eats virtually no grains or processed food. In Dr. Staffan Lindeberg's studies, he has determined that overweight is virtually nonexistent among them, despite an abundant food supply.
The cause of obesity is not the availability of excess calories, it's the deregulation of the bodyweight homeostasis system. We have a very sophisticated set of feedback loops that "try" to maintain a healthy weight. It's composed of hormones (leptin, insulin, etc.), certain brain regions, and many other elements, known and unknown. These feedback loops influence what the body does with calories, as well as feeding behaviors. When you throw a wrench in the gears with a lifestyle that is unnatural to the human metabolism, you deregulate the system so that it no longer maintains an appropriate "set-point".
Here's what Neel had to say about the thrifty gene hypothesis in 1982 (excerpts from Good Calories, Bad Calories):
The thrifty gene hypothesis is the darling of many obesity researchers. It was proposed in 1962 by the geneticist James V. Neel to explain the high rates of obesity in modern populations, particularly modernizing American Indians. It states that our species evolved under conditions of frequent starvation, so we're designed to store every available calorie. In today's world of food abundance, our bodies continue to be thrifty and that's why we're fat. You practically can't read a paper on overweight without seeing an obligatory nod to the thrifty gene hypothesis. The only problem is, it doesn't make much sense.
The assumption that hunter-gatherers and non-industrial agriculturalists lived under chronic calorie deprivation isn't well supported. The anthropological evidence indicates that most hunter-gatherers had abundant food, most of the time. They did have fluctuations in energy balance, but the majority of the time they had access to more calories than they needed. Yet they were not fat.
The Kitavans are a good example. They are a horticultural society that eats virtually no grains or processed food. In Dr. Staffan Lindeberg's studies, he has determined that overweight is virtually nonexistent among them, despite an abundant food supply.
The cause of obesity is not the availability of excess calories, it's the deregulation of the bodyweight homeostasis system. We have a very sophisticated set of feedback loops that "try" to maintain a healthy weight. It's composed of hormones (leptin, insulin, etc.), certain brain regions, and many other elements, known and unknown. These feedback loops influence what the body does with calories, as well as feeding behaviors. When you throw a wrench in the gears with a lifestyle that is unnatural to the human metabolism, you deregulate the system so that it no longer maintains an appropriate "set-point".
Here's what Neel had to say about the thrifty gene hypothesis in 1982 (excerpts from Good Calories, Bad Calories):
The data on which that (rather soft) hypothesis was based has now largely collapsed.And what does he think causes overweight in American Indians now?
The composition of the diet, and more specifically the use of highly refined carbohydrates.RIP, thrifty gene.
Rabu, 11 Juni 2008
Masai and Atherosclerosis
I've been digging deeper into the health of the Masai lately. A commenter on Chris's blog pointed me to a 1972 paper showing that the Masai have atherosclerosis, or hardening of the arteries. This interested me so I got my hands on the full text, along with a few others from the same time period. What I found is nothing short of fascinating.
First, some background. Traditional Masai in Kenya and Tanzania are pastoralists, subsisting on fermented cow's milk, meat and blood, as well as traded food in modern times. They rarely eat fresh vegetables. Contrary to popular belief, they are a genetically diverse population, due to the custom of abducting women from neighboring tribes. Many of these tribes are agriculturalists. From Mann et al: "The genetic argument is worthless". This will be important to keep in mind as we interpret the data.
At approximately 14 years old, Masai men are inducted into the warrior class, and are called Muran. For the next 15-20 years, tradition dictates that they eat a diet composed exclusively of cow's milk, meat and blood. Milk is the primary food. Masai cows are not like wimpy American cows, however. Their milk contains almost twice the fat of American cows, more protein, more cholesterol and less lactose. Thus, Muran eat an estimated 3,000 calories per day, 2/3 of which comes from fat. Here is the reference for all this. Milk fat is about 50% saturated. That means the Muran gets 33% of his calories from saturated fat. This population eats more saturated fat than any other I'm aware of.
How's their cholesterol? Remarkably low. Their total serum cholesterol is about half the average American's. I haven't found any studies that broke it down further than total cholesterol. Their blood pressure is also low, and hypertension is rare. Overweight is practically nonexistent. Their electrocardiogram readings show no signs of heart disease. They have exceptionally good endurance, but their grip strength is significantly weaker than Americans of African descent. Two groups undertook autopsies of male Masai to look for artery disease.
The first study, published in 1970, examined 10 males, 7 of which were over 40 years old. They found very little evidence of atherosclerosis, even in individuals over 60. The second study, which is often used as evidence against a high-fat diet, was much more thorough and far more interesting. Mann et al. autopsied 50 Masai men, aged 10 to 65. The single most represented age group was 50-59 years old, at 13 individuals. They found no evidence of myocardial infarction (heart attack) in any of the 50 hearts. What they did find, however, was coronary artery disease. Here's a figure showing the prevalence of "aortic fibrosis", a type of atherosclerotic lesion:
It looks almost binary, doesn't it? What could be causing the dramatic jump in atherosclerosis at age 40? Here's another figure, of total cholesterol (top) and "sudanophilia" (fatty streaks in the arteries, bottom). Note that the Muran period is superimposed (top).
There appears to be a pattern here. Either the Masai men are eating nothing but milk, meat and blood and they're nearly free from atherosclerosis, or they're eating however they please and they have as much atherosclerosis as the average American. There doesn't seem to be much in between.
Here's a quote from the paper that I found interesting:
This may suggest that you can eat a wide variety of foods and be healthy, except industrial grain products (particularly white flour), sugar, industrial vegetable oil and other processed food. The Masai are just one more example of a group that's healthy when eating a traditional diet.
First, some background. Traditional Masai in Kenya and Tanzania are pastoralists, subsisting on fermented cow's milk, meat and blood, as well as traded food in modern times. They rarely eat fresh vegetables. Contrary to popular belief, they are a genetically diverse population, due to the custom of abducting women from neighboring tribes. Many of these tribes are agriculturalists. From Mann et al: "The genetic argument is worthless". This will be important to keep in mind as we interpret the data.
At approximately 14 years old, Masai men are inducted into the warrior class, and are called Muran. For the next 15-20 years, tradition dictates that they eat a diet composed exclusively of cow's milk, meat and blood. Milk is the primary food. Masai cows are not like wimpy American cows, however. Their milk contains almost twice the fat of American cows, more protein, more cholesterol and less lactose. Thus, Muran eat an estimated 3,000 calories per day, 2/3 of which comes from fat. Here is the reference for all this. Milk fat is about 50% saturated. That means the Muran gets 33% of his calories from saturated fat. This population eats more saturated fat than any other I'm aware of.
How's their cholesterol? Remarkably low. Their total serum cholesterol is about half the average American's. I haven't found any studies that broke it down further than total cholesterol. Their blood pressure is also low, and hypertension is rare. Overweight is practically nonexistent. Their electrocardiogram readings show no signs of heart disease. They have exceptionally good endurance, but their grip strength is significantly weaker than Americans of African descent. Two groups undertook autopsies of male Masai to look for artery disease.
The first study, published in 1970, examined 10 males, 7 of which were over 40 years old. They found very little evidence of atherosclerosis, even in individuals over 60. The second study, which is often used as evidence against a high-fat diet, was much more thorough and far more interesting. Mann et al. autopsied 50 Masai men, aged 10 to 65. The single most represented age group was 50-59 years old, at 13 individuals. They found no evidence of myocardial infarction (heart attack) in any of the 50 hearts. What they did find, however, was coronary artery disease. Here's a figure showing the prevalence of "aortic fibrosis", a type of atherosclerotic lesion:
It looks almost binary, doesn't it? What could be causing the dramatic jump in atherosclerosis at age 40? Here's another figure, of total cholesterol (top) and "sudanophilia" (fatty streaks in the arteries, bottom). Note that the Muran period is superimposed (top).
There appears to be a pattern here. Either the Masai men are eating nothing but milk, meat and blood and they're nearly free from atherosclerosis, or they're eating however they please and they have as much atherosclerosis as the average American. There doesn't seem to be much in between.
Here's a quote from the paper that I found interesting:
We believe... that the Muran escapes some noxious dietary agent for a time. Obviously, this is neither animal fat nor cholesterol. The old and the young Masai do have access to such processed staples as flour, sugar, confections and shortenings through the Indian dukas scattered about Masailand. These foods could carry the hypothetical agent."
This may suggest that you can eat a wide variety of foods and be healthy, except industrial grain products (particularly white flour), sugar, industrial vegetable oil and other processed food. The Masai are just one more example of a group that's healthy when eating a traditional diet.
Kamis, 24 April 2008
Scientist Discovers that Only Pills can Control Hypertension
I went to a presentation today by a prominent hypertension researcher. His talk began with a slide that had two pictures side-by-side: one of the late fitness advocate Jim Fixx, and the other of Winston Churchill. Fixx was a marathon runner, while Churchill was inactive, overweight and had a famous appetite. Fixx died of a sudden heart attack at 52, while Churchill lived to 90. The presenter went on to state that this is an example of how genes control CVD risk, implying that despite Fixx's exercise, his genes had condemned him to an early death.
I wanted to jump up and yell "I think you're leaving out the alternate hypothesis: running marathons and eating junk food isn't healthy!" But instead I suffered quietly through what ended up being an inane yet informative presentation.
His lab looks for gene variations that affect blood pressure (BP). There's a huge amount of money and research going into this. His lab and others have come up with two classes of mutations:
There is certainly a genetic component to hypertension, but it is only expressed in an unhealthy environment. Hypertension is tightly linked to lifestyle. It's a quintessential aspect of the "disease of civilization". It's highly responsive to carbohydrate restriction, as a number of clinical trials have shown. Remember the Kuna? They don't get hypertension when they live a non-industrial lifestyle (despite eating more salt than the average American), but as soon as they move to the city their hearts explode. It's been demonstrated in a number of other similar cases as well. Genetics are clearly not responsible.
Don't get me wrong, I do think genetics can modify a person's response to a poor lifestyle. But when the lifestyle is healthy, the vast majority of these differences fade away. I have a more thorough discussion of this point here.
If you give just the right dose of poison to a group of animals, 50% will die and 50% will survive (called the EC50 dose). You might then conclude that genetics had determined who lived and died. You wouldn't be wrong, but you'd be missing the point that what killed them was the poison.
The thing that really bothers me about this thinking is it's disempowering. The presenter suggested that the reason for the difference between Fixx and Churchill was their genes. If genes have us in such a tight grip, why bother trying to live well? The only logical solution is to pop hypertension pills and eat cake all day.
My guess is that if they had lived a more natural lifestyle, Fixx would have made it to 90 and Churchill would have been fit and lean.
I wanted to jump up and yell "I think you're leaving out the alternate hypothesis: running marathons and eating junk food isn't healthy!" But instead I suffered quietly through what ended up being an inane yet informative presentation.
His lab looks for gene variations that affect blood pressure (BP). There's a huge amount of money and research going into this. His lab and others have come up with two classes of mutations:
- Common allele variants that have an insignificant but measurable effect on blood pressure.
- Rare genetic mutations that have a significant effect on BP. The most common affects 1 in 2,000 people in the US.
There is certainly a genetic component to hypertension, but it is only expressed in an unhealthy environment. Hypertension is tightly linked to lifestyle. It's a quintessential aspect of the "disease of civilization". It's highly responsive to carbohydrate restriction, as a number of clinical trials have shown. Remember the Kuna? They don't get hypertension when they live a non-industrial lifestyle (despite eating more salt than the average American), but as soon as they move to the city their hearts explode. It's been demonstrated in a number of other similar cases as well. Genetics are clearly not responsible.
Don't get me wrong, I do think genetics can modify a person's response to a poor lifestyle. But when the lifestyle is healthy, the vast majority of these differences fade away. I have a more thorough discussion of this point here.
If you give just the right dose of poison to a group of animals, 50% will die and 50% will survive (called the EC50 dose). You might then conclude that genetics had determined who lived and died. You wouldn't be wrong, but you'd be missing the point that what killed them was the poison.
The thing that really bothers me about this thinking is it's disempowering. The presenter suggested that the reason for the difference between Fixx and Churchill was their genes. If genes have us in such a tight grip, why bother trying to live well? The only logical solution is to pop hypertension pills and eat cake all day.
My guess is that if they had lived a more natural lifestyle, Fixx would have made it to 90 and Churchill would have been fit and lean.
Senin, 03 Maret 2008
Genetics and Disease
There is a lot of confusion surrounding the role of genetics in health. It seems like every day the media have a new story about gene X or Y 'causing' obesity, diabetes or heart disease. There are some diseases that are strongly and clearly linked to a gene, such as the disease I study: spinocerebellar ataxia type 7. I do not believe that genetics are the cause of more than a slim minority of health problems however. Part of this is a semantic issue. How do you define the word 'cause'? It's a difficult question, but I'll give you an example of my reasoning and then we'll come back to it.
A classic and thoroughly studied example of genetic factors in disease can be found in the Pima indians of Arizona. Currently, this population eats a version of the American diet, high in refined and processed foods. It also has the highest prevalence of type II diabetes of any population on earth (much higher than the US average), and a very high rate of obesity. One viewpoint is that these people are genetically susceptible to obesity and diabetes, and thus their genes are the cause of their health problems.
However, if you walk across the national border to Mexico, you'll find another group of Pima indians. This population is genetically very similar to the Arizona Pima except they have low rates of obesity and diabetes. They eat a healthier, whole-foods, agriculture-based diet. Furthermore, 200 years ago, the Arizona Pima were healthy as well. So what's the cause of disease here? Strictly speaking, it's both genetics and lifestyle. Both of these factors are necessary for the health problems of the Arizona Pima. However, I think it's more helpful to think of lifestyle as the cause of disease, since that's the factor that changed.
The Pima are a useful analogy for the world in general. They are an extreme example of what has happened to many if not all modern societies. Thus, when we talk about the 'obesity gene' or the 'heart disease gene', it's misleading. It's only the 'obesity gene' in the context of a lifestyle to which we are not genetically adapted.
I do not believe that over half of paleolithic humans were overweight, or that 20% had serious blood glucose imbalances. In fact, studies of remaining populations living naturally and traditionally have shown that they are typically much healthier than industrialized humans. Yet here we are in the US, carrying the very same genes as our ancestors, sick as dogs. That's not all though: we're actually getting sicker. Obesity, diabetes, allergies and many other problems are on the rise, despite the fact that our genes haven't changed.
I conclude that genetics are only rarely the cause of disease, and that the vast majority of health problems in the US are lifestyle-related. Studies into the genetic factors that predispose us to common health problems are interesting, but they're a distraction from the real problems and the real solutions that are staring us in the face. These solutions are to promote a healthy diet, exercise, and effective stress management.
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