Tuesday, May 17, 2011
Why Do Low-Carb?
If you have done much reading about the low-carb lifestyle, you have heard about insulin. Insulin is a hormone secreted by the pancreas after we eat carbohydrate or to a lesser extent when we eat protein. Insulin is important because it binds to the insulin receptor, which is found on the surface of most of the cells in the body. The figure above shows the surface of a cell with a molecule of insulin bound to its receptor.
The insulin receptor is made of four protein subunits. The two beta subunits pass from the exterior through the cell wall and into the interior of the cell. When insulin binds to its receptor, the receptor auto-activates and begins to affect a large number of signaling proteins that reside within the cell. As illustrated on the left side of the drawing, some of these proteins propagate growth signals to the nucleus of the cell. We’ll deal with those later. The proteins shown on the right side of the drawing transmit metabolic signals into the cell. Depending on the type of cell, this signaling cascade can cause the uptake of glucose and amino acids into the cell, the synthesis of glycogen in the cell, the synthesis of protein in the cell, the cessation of lipolysis in the cell and the inhibition of de novo glucose synthesis in the cell.
So far so good. Insulin is such a powerful hormone and it has so many effects that its absence is incompatible with life. However, an excess of insulin is not particularly good either. When too much insulin is present, the metabolic signaling cascade becomes too strong. The cells defend against excessive signaling by degrading some of their insulin receptors and by making fewer receptors to replace the ones that have been destroyed. Some of the intermediate signaling proteins are also downregulated in various ways. The cell is said to have become “insulin resistant.”
Normally insulin resistance is not a problem. As insulin levels fall, the synthesis and/or activation of signaling intermediates resumes and the cell becomes ready for the next onset of insulin release. In native cultures like the Inuit, where carbohydrate intake is low, the levels of blood insulin only rise a modest amount in response to ingested protein. In non-Westernized cultures like the Kitavans of Papua New Guinea, a large amount of carbohydrate is consumed, but it comes in the form of sweet potatoes, cassava, taro and yams. These people have a low fasting insulin that decreases with age.  Kitavans also have low obesity, low diastolic blood pressure, and low-to-no incidence of stroke or ischemic heart disease. If Kitavans can maintain insulin sensitivity and good health while eating a high carbohydrate diet, why should we even consider the challenges of attempting a low-carb diet?
What kinds of carbs?
The answer probably involves the types of carbohydrates we consume rather than the absolute percentage of carbohydrates in our diet. Post-800 AD, the Aztec consumed maize as their most important staple. They were known to suffer from dental problems, obesity and heart disease.[4, Comments] The ancient Egyptians ate bread and porridge made from wheat and used barley to make beer. They suffered from periodontal disease, and atherosclerosis was found in 60% of those who lived past age 40. In Good Calories Bad Calories (pp 89-97), Gary Taubes gives numerous examples of native peoples (Gabonese, South Africans, Native Americans, Melanesians) who did not experience chronic diseases such as obesity, diabetes and heart disease until after well-meaning explorers and settlers, beginning in about the middle of the nineteenth century, brought them large quantities of white flour and sugar.
Permanent insulin resistance
Although the proof is only inferential, it appears that carbohydrates such as refined grains, beer and sugar may have the ability to cause permanent insulin resistance in susceptible individuals who consume them. The effect is not immediate. For some reason, after years of eating these types of food, some people progressively lose the ability to reset their metabolic insulin response system. Muscle cells require more insulin to take up glucose. Liver cells require more insulin before they will stop making glucose through gluconeogenesis. It becomes harder to shut down lipolysis and it becomes more difficult to maintain muscle mass. On the other hand, the action of insulin as a growth signal is not impaired (see the left side of the figure above). A steady, high level of insulin produces proliferation and migration of vascular smooth muscle cells, and these in turn play an important role in diseases such as hypertension, atherosclerosis and cardiovascular disease.
It appears that once the metabolic insulin signaling system is broken, it cannot be repaired. It can be treated with drugs, or it can be managed by eating foods that minimize the release of insulin. For those who spend their lives eating the types of carbohydrates that indigenous peoples do, insulin is a good and faithful servant. It helps them metabolize and store their food for later use and performs a myriad of functions without causing insulin resistance. But for those who have spent too many years indulging in sugar, high-fructose corn syrup, refined grains, beer and other easily digestible carbohydrates, it may be necessary to switch to a diet that keeps insulin secretion at a minimum, i.e., a diet low in all kinds of carbs, in order to achieve and maintain a healthy lifestyle.
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Excellent summary of the problem.
The only place where I would raise a question is regarding "It appears that once the metabolic insulin signaling system is broken, it cannot be repaired."
I haven't really seen this studied with any great specificity. Certainly exercise can increase insulin sensitivity, but I haven't seen anything on whether in the intracellular signalling systems change in parallel.
In any case, if w are talking about metabolic damage done over 20-30 years or more of poor diet, I find it entirely feasible that the repair processes might be slow. They might even be as slow as the rate at which the damage was incurred. But I haven't seen anything that attempted to measure this sort of thing.
The Glucose Teolerance Test is sometimes cited, but it has obvious problems when applied to someone who has been on a low-carb diet (whose enzymatic systems are totally unprepared for an onslaught of glucose). I do know that many people following the TNT diet, which is very low-carb at first but after weight loss adds a couple of high-carb days a week to increase muscle building, seem to cope reasonably well with carbs--at least when compared to their obese, pre-low-carb state.
In any case, it would be nice to see some research on the cell biology of repair to metabolic damage rather than gross measures like GTT. But I've never come across any. Cn you point me to some?
Hi, David. Unfortunately I'm relying on anecdotal information when I refer to a permanently broken insulin signaling system. People will go on a low-carb diet and say their diabetes has been "cured" (for example, Dr. William Davis in the comments, here. But if they go back to the carbs, their symptoms come back as well. (And I was able to get Dr. Davis to admit that later on in the comments.)
Nor do I know what a broken metabolism means on a molecular basis (Nobel prize territory?), but experientially in those who are vulnerable to the condition, it seems to start happening after about 20 years of eating refined carbohydrates.
That's not hard science, and I'm the first to admit it. I could be wrong, of course, but perhaps somebody will eventually be able to figure out what happens to specific insulin signaling intermediates in response to decades of human consumption of refined carbohydrates. Rat studies wouldn't do it, and the career risks involved in pursuing something so nebulous would be considerable.
I'm enjoying the conversation over at Stephan's blog.
What do you make of the studies that Mirrorball threw up in defense of the IR begins in adipose tissue? Chris then followed up his agreement with Stephan concerning the obese and high circulating FFA levels in the blood. What does this tell us?
I would think that if IR began with adipose tissue, other body cells would remain sensitive and continue to prefer glucose. Couple this with the possibility that the high FFA levels may only be detected in the obese after they have reached adipose equilibrium - not the same (maybe) for those gaining, or lean, but about to gain.
I ask also because I began to gain body fat at 6 years old - at a time when no one else was (70's). Fast food, candy, and crap was not yet ubiquitous, and Mom made fresh whole foods. I gained weight first, then began to eat more - I distinctly remember this. My adolescent years were hell, with yo-yo dieting; trying to reduce intake, move more, blah, blah.
In my 20's, and on my own, I discovered that a high meat diet (no-carb) kept me satisfied and controlled my weight. Now a coach and (almost) an exercise scientist, I am trying to find out why this also works in dozens and dozens of folks that I have worked with.
Taubes' theory fits; and those cats at Stephan's blog maybe onto to something, but does it really change what I would prescribe in practice to my patients? Of course, I do give individualized attention once they adapt.
Welcome to the blog, berto! You've raised some interesting questions. I try to give more careful thought to answers here than I do out in the blogosphere, so give me some time and I'll see what I can come up with.
Sorry for the delay. Blogger kicked me out of my own blog, but I'm back in again. Here goes.
CarbSane and Mirrorball come to the discussion with the belief that insulin resistance happens first in adipose cells. This is based on the writings of Keith Frayn. One of Frayn's quotes is, "NEFA release per unit fat mass is actually less in obese subjects than in lean subjects (effectively, it is down regulated by the fasting hyperinsulinaemia). However, because of the increased fat mass, total NEFA delivery to the circulation is increased in obesity."
As I tried to explain over at Stephan's blog, because of the fact that NEFA (free fatty acid) release is less per unit mass in obese subjects, this indicates that their adipose tissue is still insulin-responsive.
Mirrorball's link about ectopic fat formation is another indication of the insulin responsiveness of adipose tissue. If the adipose cells were not insulin-responsive, how could they store all that fat? Wouldn't insulin resistance cause unregulated lipolysis and just release it into circulation again?
As far as the article about knocking out GLUT4 in mouse adipocytes, that's a rather specific defect. When you knock out the insulin receptor in mouse adipocytes (the FIRKO mouse) you have complete insulin resistance in adipocytes. Guess what? According to an article about extended longevity in FIRKO mice the authors note that these mice are healthy, have no lipodystrophy, no deterioration of glucose tolerance, and low body fat in spite of a normal food intake. If that's the case, starting off with adipocyte insulin resistance would seem to be a good thing rather than a bad one.
As for your experience of starting to gain body fat at six years of age, is that the age when you began to eat school lunches? Back in the day, school lunches had some meat, a starch, a couple slices of bread, a vegetable like peas or carrots, and most definitely a dessert. With milk to wash it down. And you probably had Rice Krispies with sugar and milk for breakfast. And milk and a couple of cookies after school. At least that was standard when I was growing up. It doesn't take much of a carb-tooth to turn that sort of food into extra pounds, even when you're a little kid.
Thanks for your quick response.
I had logically worked out in my head exactly what you describe, but (a) I probably lack the language to express it well enough for communication; And (b) I wanted to make sure I wasn't blind by Taubes' theory. I've been reading about it for so long that, and it fits everything that I have seen for results (in many) that I get afraid it may become dogma for me.
Although, both Chris Masterjohn and Stephan, it seems, are on this kick as well - and they are somewhat intelligent thinkers so I'm not sure where this will go.
The bottom line is, for me as a health care provider, what works in the trenches, whether it be for IR leptin resistance, adipose resistance, are what have you, low-no carb works very well for most, if not all (some do need a little tweaking).
Thanks again for your quick response. I not exactly new here, I mostly lurk and study. If I contribute at all it is usually over at Richards blog. But I'm getting better at speaking up lately.
Interesting post and comment above regarding FIRKO mice.
GH increase in humans tends to also lead to adipocyte IR.
Over time, that invariably leads to increased insulin sensitivity:
Not exactly the same thing, but somewhat similar end results.
Concerning gaining weight just about the time of consuming school lunches...
You're definitely onto something there, however I also had another thought after reading a post elsewhere: it also coincided with a rise in McDonalds and pizza consumption along with a more prosperous familial bottom line.
And there ya go....
But I was the only one in my family to suffer: oh well.
Thanks for the insight, Stargazey.
Hi, Ned. My problem with understanding specific aspects of insulin resistance is that it is usually measured on a whole-body level. It's hard to tell if you're measuring reluctance of muscle cells to take up glucose, reluctance of the liver to stop making glucose or reluctance of fat cells to take up glucose. Anyway, thanks for the information on GH and insulin sensitivity. I didn't know it would come back after several months of increased GH.
Hi, berto! That's interesting about the McDonalds and pizza connection. It's possible that you secreted more insulin (or were more sensitive to it) than the rest of your family. But you did finally discover low-carb and that's a good thing!
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