I often focus on the bigger facets of the disease of civilization. Things like cardiovascular disease and cancer, which are major killers and the subject of intensive research. But the disease of civilization is a spectrum of disorders that affects the body in countless ways, large and small.
I recently read an interesting paper written by an all-star cast, including Loren Cordain, Staffan Lindeberg and Boyd Eaton. It's titled "Acne Vulgaris: A Disease of Western Civilization". The paper presents data from two different groups, the Kitavans of Papua New Guinea and the Ache hunter-gatherers of Paraguay. Both were systematically examined by doctors trained to diagnose acne. Out of 1,200 Kitavans and 115 Ache of all ages, not a single case of acne was observed. Hunter-gatherers and other healthy non-industrial cultures have nice skin. I dare you to find a pimple in Nutrition and Physical Degeneration.
In Western societies, acne is a fact of life. The paper states that 79 to 95% of modern adolescents suffer from some degree of acne, along with about 50% of young adults. That's an enormous difference.
The paper presents a very Cordain-esque hypothesis to explain the high incidence of acne in Western societies. In sum, they state that the Western diet causes hyperinsulinemia, which is thought to promote acne. This is due to insulin's effects on skin cell proliferation, its interference with the retinoid (vitamin A) signaling pathway, and its effect on sebum production.
They then proceed to point the finger at the glycemic index/load of the Western diet as the culprit behind hyperinsulinemia. It's an unsatisfying explanation because the Kitavans eat a diet that has a high glycemic load due to its high carbohydrate content, low fat content, and relatively high-glycemic index foods. I think the answer is more likely to reside in the specific types of carbohydrate (processed wheat) rather than their speed of digestion, with possible contributions from refined vegetable oil and an excessive sugar intake.
Monday, September 29, 2008
Thursday, September 25, 2008
Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is milder form of NASH, in which the liver becomes enlarged and accumulates fat. Ready for a shocker? The prevalence of NAFLD is thought to be between 20 and 30 percent in the Western world, and rising. It's typically associated with insulin resistance and often with the metabolic syndrome. This has lead some researchers to believe it's caused by insulin resistance. It's a chicken and egg question, but I believe it's the other way around if anything.
There are certain animal models of human disease that are so informative I keep coming back to them again and again. One of my favorites is the LIRKO mouse, or liver-specific insulin receptor knockout mouse. The LIRKO mouse is missing its insulin receptor in the liver only, so it is a model of severe insulin resistance of the liver. It accumulates a small amount of fat in its liver in old age, but nothing that resembles NAFLD. So liver insulin resistance doesn't lead to NAFLD or NASH, at least in this model.
What else happens to the LIRKO mouse? It develops severe whole-body insulin resistance, impaired glucose tolerance, high fasting blood glucose and hyperinsulinemia (chronically elevated insulin). So insulin resistance in the liver is sufficient to cause whole-body insulin resistance, hyperinsulinemia and certain other hallmarks of the metabolic syndrome, while liver and whole-body insulin resistance are not sufficient to cause NAFLD or NASH. This is consistent with the fact that nearly everyone with NAFLD is insulin resistant, while many who are insulin resistant do not have NAFLD.
In all fairness, there are reasons why NAFLD is believed to be caused by insulin resistance. For example, insulin-sensitizing drugs improve NAFLD. However, that doesn't mean the initial metabolic 'hit' wasn't in the liver. One could imagine a scenario in which liver insulin resistance leads to insulin resistance in other tissues, which creates a positive feedback that aggravates NAFLD. Or perhaps NAFLD requires two 'hits', one to peripheral insulin sensitivity and another directly to the liver.
In any case, I feel that the most plausible mechanism for NAFLD goes something like this: too much n-6 from polyunsaturated vegetable oil (along with insufficient n-3), plus too much fructose from sweeteners, combine to cause NAFLD. The liver becomes insulin resistant at this point, leading to whole-body insulin resistance, hyperinsulinemia, impaired glucose tolerance and general metabolic havoc.
There are certain animal models of human disease that are so informative I keep coming back to them again and again. One of my favorites is the LIRKO mouse, or liver-specific insulin receptor knockout mouse. The LIRKO mouse is missing its insulin receptor in the liver only, so it is a model of severe insulin resistance of the liver. It accumulates a small amount of fat in its liver in old age, but nothing that resembles NAFLD. So liver insulin resistance doesn't lead to NAFLD or NASH, at least in this model.
What else happens to the LIRKO mouse? It develops severe whole-body insulin resistance, impaired glucose tolerance, high fasting blood glucose and hyperinsulinemia (chronically elevated insulin). So insulin resistance in the liver is sufficient to cause whole-body insulin resistance, hyperinsulinemia and certain other hallmarks of the metabolic syndrome, while liver and whole-body insulin resistance are not sufficient to cause NAFLD or NASH. This is consistent with the fact that nearly everyone with NAFLD is insulin resistant, while many who are insulin resistant do not have NAFLD.
In all fairness, there are reasons why NAFLD is believed to be caused by insulin resistance. For example, insulin-sensitizing drugs improve NAFLD. However, that doesn't mean the initial metabolic 'hit' wasn't in the liver. One could imagine a scenario in which liver insulin resistance leads to insulin resistance in other tissues, which creates a positive feedback that aggravates NAFLD. Or perhaps NAFLD requires two 'hits', one to peripheral insulin sensitivity and another directly to the liver.
In any case, I feel that the most plausible mechanism for NAFLD goes something like this: too much n-6 from polyunsaturated vegetable oil (along with insufficient n-3), plus too much fructose from sweeteners, combine to cause NAFLD. The liver becomes insulin resistant at this point, leading to whole-body insulin resistance, hyperinsulinemia, impaired glucose tolerance and general metabolic havoc.
Tuesday, September 23, 2008
Agave Syrup
Anna brought up agave syrup in a comment on the last post, so I thought I'd put up a little mini-post so everyone can benefit from what she pointed out.
Agave syrup is made from the heart of the agave plant, which is pressed to release a juice rich in inulin. Inulin is a polymer made of fructose molecules. The inulin is then broken down either by heat or by enzymatic processing. The result is a sweet syrup that is rich in fructose.
Agave syrup is marketed as a healthy, alternative sweetener. In fact, it's probably as bad or worse than high-fructose corn syrup (HFCS). They are both a refined and processed plant extract. Both are high in fructose, with agave syrup leading HFCS (estimates of agave syrup range up to 92% fructose by calories). Finally, agave syrup is expensive and inefficient to produce.
The high fructose content gives agave syrup a low glycemic index, because fructose does not raise blood glucose. Unfortunately, as some diabetics learned the hard way, using fructose as a substitute for sucrose (cane sugar) has negative long-term effects on insulin sensitivity.
In my opinion, sweeteners come with risks and there is no free lunch. The only solution is moderation.
Agave syrup is made from the heart of the agave plant, which is pressed to release a juice rich in inulin. Inulin is a polymer made of fructose molecules. The inulin is then broken down either by heat or by enzymatic processing. The result is a sweet syrup that is rich in fructose.
Agave syrup is marketed as a healthy, alternative sweetener. In fact, it's probably as bad or worse than high-fructose corn syrup (HFCS). They are both a refined and processed plant extract. Both are high in fructose, with agave syrup leading HFCS (estimates of agave syrup range up to 92% fructose by calories). Finally, agave syrup is expensive and inefficient to produce.
The high fructose content gives agave syrup a low glycemic index, because fructose does not raise blood glucose. Unfortunately, as some diabetics learned the hard way, using fructose as a substitute for sucrose (cane sugar) has negative long-term effects on insulin sensitivity.
In my opinion, sweeteners come with risks and there is no free lunch. The only solution is moderation.
Monday, September 22, 2008
How to Fatten Your Liver
Steatohepatitis is a condition in which the liver becomes inflamed and accumulates fat. It was formerly found almost exclusively in alcoholics. In the 1980s, a new condition was described called nonalcoholic steatohepatitis (NASH), basically steatohepatitis without the alcoholism. Today, NASH is thought to affect more than 2% of the adult American population. The liver has many important functions. It's not an organ you want to break.
This week, I've been reading about how to fatten your liver. First up: industrial vegetable oil. The study that initially sent me on this nerd safari was recently published in the Journal of Nutrition. It's titled "Increased Apoptosis in High-Fat Diet–Induced Nonalcoholic Steatohepatitis in Rats Is Associated with c-Jun NH2-Terminal Kinase Activation and Elevated Proapoptotic Bax". Quite a mouthful. The important thing for the purpose of this post is that the investigators fed rats a high-fat diet, which induced NASH.
Anytime a study mentions a "high-fat diet", I immediately look to see what they were actually feeding the animals. To my utter amazement, there was no information on the composition of the high-fat diet in the methods section, only a reference to another paper. Apparently fat composition is irrelevant. Despite the fact that a high-fat diet from coconut oil or butter does not produce NASH in rats. Fortunately, I was able to track down the reference. The only difference between the standard diet and the high-fat diet was the addition of a large amount of corn oil and the subtraction of carbohydrate (dextrin maltose).
Corn oil is one of the worst vegetable oils. You've eaten corn so you know it's not an oily seed. To concentrate the oil and make it palatable, manufacturers use organic solvents, high heat, and several rounds of chemical treatment. It's also extremely rich in n-6 linoleic acid. The consumption of corn oil and other n-6 rich oils has risen dramatically in the US in the last 30 years, making them prime suspects in NASH. They have replaced the natural (more saturated) fats we once got from meat and milk.
Next up: fructose. Feeding rats an extreme amount of fructose (60% of calories) gives them nonalcoholic fatty liver disease (NAFLD), NASH's younger sibling, even when the fat in their chow is lard. Given the upward trend of US fructose consumption (mostly from high-fructose corn syrup), and the refined sugar consumed everywhere else (50% fructose), it's also high on my list of suspects.
Here's my prescription for homemade foie gras: take one serving of soybean oil fried french fries, a basket of corn oil fried chicken nuggets, a healthy salad drenched in cottonseed oil ranch dressing, and wash it all down with a tall cup of soda. It's worked for millions of Americans!
This week, I've been reading about how to fatten your liver. First up: industrial vegetable oil. The study that initially sent me on this nerd safari was recently published in the Journal of Nutrition. It's titled "Increased Apoptosis in High-Fat Diet–Induced Nonalcoholic Steatohepatitis in Rats Is Associated with c-Jun NH2-Terminal Kinase Activation and Elevated Proapoptotic Bax". Quite a mouthful. The important thing for the purpose of this post is that the investigators fed rats a high-fat diet, which induced NASH.
Anytime a study mentions a "high-fat diet", I immediately look to see what they were actually feeding the animals. To my utter amazement, there was no information on the composition of the high-fat diet in the methods section, only a reference to another paper. Apparently fat composition is irrelevant. Despite the fact that a high-fat diet from coconut oil or butter does not produce NASH in rats. Fortunately, I was able to track down the reference. The only difference between the standard diet and the high-fat diet was the addition of a large amount of corn oil and the subtraction of carbohydrate (dextrin maltose).
Corn oil is one of the worst vegetable oils. You've eaten corn so you know it's not an oily seed. To concentrate the oil and make it palatable, manufacturers use organic solvents, high heat, and several rounds of chemical treatment. It's also extremely rich in n-6 linoleic acid. The consumption of corn oil and other n-6 rich oils has risen dramatically in the US in the last 30 years, making them prime suspects in NASH. They have replaced the natural (more saturated) fats we once got from meat and milk.
Next up: fructose. Feeding rats an extreme amount of fructose (60% of calories) gives them nonalcoholic fatty liver disease (NAFLD), NASH's younger sibling, even when the fat in their chow is lard. Given the upward trend of US fructose consumption (mostly from high-fructose corn syrup), and the refined sugar consumed everywhere else (50% fructose), it's also high on my list of suspects.
Here's my prescription for homemade foie gras: take one serving of soybean oil fried french fries, a basket of corn oil fried chicken nuggets, a healthy salad drenched in cottonseed oil ranch dressing, and wash it all down with a tall cup of soda. It's worked for millions of Americans!
Thursday, September 18, 2008
A New Toy
I bought a new toy the other day: a blood glucose meter. I was curious about my post-meal blood glucose after my HbA1c reading came back higher than I was expecting. A blood glucose meter is the only way to know what your blood sugar is doing in your normal setting.
"Glucose intolerance" is the inability to effectively control blood glucose as it enters the bloodstream from the digestive system. It results in elevated blood sugar after eating carbohydrate, which is not a good thing. In someone with normal glucose tolerance, insulin is secreted in sufficient amounts, and the tissues are sufficiently sensitive to it, that blood glucose is kept within a fairly tight range of concentrations.
Glucose tolerance is typically the first thing to deteriorate in the process leading to type II diabetes. By the time fasting glucose is elevated, glucose intolerance is usually well established. Jenny Ruhl talks about this in her wonderful book Blood Sugar 101. Unfortunately, fasting glucose is the most commonly administered glucose test. That's because the more telling one, the oral glucose tolerance test (OGTT), is more involved and more expensive.
An OGTT involves drinking a concentrated solution of glucose and monitoring blood glucose at one and two hours. Values of >140 mg/dL at one hour and >120 mg/dL at two hours are considered "normal". If you have access to a blood glucose meter, you can give yourself a makeshift OGTT. You eat 60-70 grams of quickly-digesting carbohydrate with no fat to slow down absorption and monitor your glucose.
I gave myself an OGTT tonight. I ate a medium-sized boiled potato and a large slice of white bread, totaling about 60g of carbohydrate. Potatoes and bread digest very quickly, resulting in a blood glucose spike similar to drinking concentrated glucose! You can see that in the graph below. I ate at time zero. By 15 minutes, my blood glucose had reached its peak at 106 mg/dL.
My numbers were 97 mg/dL at one hour, and 80 mg/dL at two hours; far below the cutoff for impaired glucose tolerance. I completely cleared the glucose by an hour and 45 minutes. My maximum value was 106 mg/dL, also quite good. That's despite the fact that I used more carbohydrate for the OGTT than I would typically eat in a sitting. I hope you like the graph; I had to prick my fingers 10 times to make it! I thought it would look good with a lot of data points.
I'm going to have fun with this glucose meter. I've already gotten some valuable information. For example, just as I suspected, fast-digesting carbohydrate is not a problem for someone with a well-functioning pancreas and insulin-sensitive tissues. This is consistent with what we see in the Kitavans, who eat a high-carbohydrate, high glycemic load diet, yet are extremely healthy. Of course, for someone with impaired glucose tolerance (very common in industrial societies), fast-digesting carbohydrates could be the kiss of death. The big question is, what causes the pancreas to deteriorate and the tissues to become insulin resistant? Considering certain non-industrial societies were eating plenty of carbohydrate with no problems, it must be something about the modern lifestyle: industrially processed grains (particularly wheat), industrial vegetable oils, refined sugar, lack of fat-soluble vitamins, toxic pollutants and inactivity come to mind. One could make a case for any of those factors contributing to the problem.
"Glucose intolerance" is the inability to effectively control blood glucose as it enters the bloodstream from the digestive system. It results in elevated blood sugar after eating carbohydrate, which is not a good thing. In someone with normal glucose tolerance, insulin is secreted in sufficient amounts, and the tissues are sufficiently sensitive to it, that blood glucose is kept within a fairly tight range of concentrations.
Glucose tolerance is typically the first thing to deteriorate in the process leading to type II diabetes. By the time fasting glucose is elevated, glucose intolerance is usually well established. Jenny Ruhl talks about this in her wonderful book Blood Sugar 101. Unfortunately, fasting glucose is the most commonly administered glucose test. That's because the more telling one, the oral glucose tolerance test (OGTT), is more involved and more expensive.
An OGTT involves drinking a concentrated solution of glucose and monitoring blood glucose at one and two hours. Values of >140 mg/dL at one hour and >120 mg/dL at two hours are considered "normal". If you have access to a blood glucose meter, you can give yourself a makeshift OGTT. You eat 60-70 grams of quickly-digesting carbohydrate with no fat to slow down absorption and monitor your glucose.
I gave myself an OGTT tonight. I ate a medium-sized boiled potato and a large slice of white bread, totaling about 60g of carbohydrate. Potatoes and bread digest very quickly, resulting in a blood glucose spike similar to drinking concentrated glucose! You can see that in the graph below. I ate at time zero. By 15 minutes, my blood glucose had reached its peak at 106 mg/dL.
My numbers were 97 mg/dL at one hour, and 80 mg/dL at two hours; far below the cutoff for impaired glucose tolerance. I completely cleared the glucose by an hour and 45 minutes. My maximum value was 106 mg/dL, also quite good. That's despite the fact that I used more carbohydrate for the OGTT than I would typically eat in a sitting. I hope you like the graph; I had to prick my fingers 10 times to make it! I thought it would look good with a lot of data points.
I'm going to have fun with this glucose meter. I've already gotten some valuable information. For example, just as I suspected, fast-digesting carbohydrate is not a problem for someone with a well-functioning pancreas and insulin-sensitive tissues. This is consistent with what we see in the Kitavans, who eat a high-carbohydrate, high glycemic load diet, yet are extremely healthy. Of course, for someone with impaired glucose tolerance (very common in industrial societies), fast-digesting carbohydrates could be the kiss of death. The big question is, what causes the pancreas to deteriorate and the tissues to become insulin resistant? Considering certain non-industrial societies were eating plenty of carbohydrate with no problems, it must be something about the modern lifestyle: industrially processed grains (particularly wheat), industrial vegetable oils, refined sugar, lack of fat-soluble vitamins, toxic pollutants and inactivity come to mind. One could make a case for any of those factors contributing to the problem.
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