Low Carb for Health

Carbohydrate Intake and Depression

2010-10-24T11:58:00.000-05:00

It's hard to know where to start on this one. Everywhere you look, if you look, you see surprisingly consistent correlations between carbohydrate intake and depression. Some studies draw a direct link. Others find strong correlations with certain long-term results of high carbohydrate consumption, such as insulin resistance (see here also), diabetes (and here), vitamin D deficiency (and here), obesity and so on. Some of these, and many others, make the leap to causation and successfully attempt to treat depression by correcting specific deficiencies or excesses. Still others observe a relationship between low-fat diets (independent of carbohydrate intake) and depression.

After a lot of searching, I managed to find a single study investigating the effects of a ketogenic diet on depression in humans. Its loneliness in the literature was not lost on its author:

It is surprising, after so much clinical experience spanning a period of two thousand years, that this paper is the first [and last] by a psychiatrist describing the applications of the ketogenic diet in the treatment of anxiety, depression, and dysperception. Meanwhile, throughout this most advanced society of ours, in every modern psychiatric facility patients are exposed to an overdose of carbohydrates... It is time that the application of available knowledge in this field should be the rule rather than the exception. Ignorance and fear of controversy are no longer an excuse to withhold this basic and physiologically-oriented treatment from our patients.

In addition, there is one other study, perhaps better designed and conducted than the one above, observing similar results from the same treatment, but in rats. The near-absence in medical literature of what looks like a pretty obvious conclusion, given the evidence, is disappointing and almost surprising. There's no shortage of informal discussion in online forums, blogs and so forth about this phenomenon, but serious treatment is conspicuously scarce in peer-reviewed medical journals.

All the available evidence seems to point to dietary carbohydrates as the major causal factor in endogenous depression, but the specific reasons are elusive. As you might expect, all this is really complicated. For example, reducing dietary carbohydrates almost necessarily means increasing intake of something else, usually fat. It also means reducing serum insulin levels, losing weight, and a pile of other things, any or all of which might be relevant to depression. So do carbohydrates directly cause depression? Is it the insulin secreted in response to elevated blood sugar from carby meals? Is it the lack of dietary fat in high-carbohydrate diets, as suggested here? The lack of vitamin D? Is it caused by insulin resistance, diabetes, obesity?

Some of these ideas can apparently be ruled out in at least some cases, but the entire body of available evidence speaks with a single voice: either directly or indirectly, increases in carbohydrate intake increase both the risk and severity of depression with remarkable consistency. Given that, we would expect - and we do find - that reducing carbohydrate intake has the opposite effect. Taken to its logical conclusion, these facts suggest that a ketogenic diet would be a fantastically effective treatment for depression. Very little research has been done to confirm this, but what is available appears to be a strong confirmation of everything else we know.

Conclusion: dietary carbohydrates are the major cause of clinical depression, and a ketogenic diet presents itself as an ideal treatment.

Top 10 Mistakes on a Low Carb Diet

2010-07-28T23:19:00.002-05:00

Generally this is a science blog, but I realize more and more that I came into this by a different path than most people, and it's hard to get everything across all at once when advocating a low carb diet. Some of these are mistakes I had to learn from along the way, and others are things I was able to "un-learn" before I got started. So, for those of you new to low-carb dieting, at least a few of these should steer you clear of some of the more common obstacles.

10. Jumping right in

If you've never eaten this way before, it can be hard. When I say don't jump right in, I don't mean "don't go cold turkey." I mean prepare first. Sit down and make a grocery list that will get you through a week, ideally. It should have enough meat, cheese, eggs and optionally green vegetables and sugar-free drinks for as many meals as you'll eat at home during that time. And don't skimp on the snacks. Lunch meat is one of my favorites. When you get back from the grocery store, put it all away and get rid of things you shouldn't have, all at once. That means cereal, pasta, chips... carbs! If it's available, it's likely to be a temptation. This can be a problem if the rest of the household isn't on board, so if you don't live alone, try to make that your first step.

9. Worrying about dietary cholesterol

A lot of people start a diet like this and avoid things like eggs. Eggs! I can't think of a more perfect food. Except maybe ribeyes. Anyway if you're still convinced that dietary cholesterol is harmful or risky, I won't be changing your mind in this post, but you absolutely must get down to the library or the book store and get your hands on this book. It will square you away. In the mean time, I'm comfortable asking you to take my word for it: you'll do more harm by avoiding cholesterol than by eating it, while you work on getting the book.

8. Giving up coffee

If you go to the Atkins website, you'll be admonished to keep your coffee intake down. They don't offer any explanation for that, and I have to disagree. Some people give up coffee because they're accustomed to drinking it with milk, which has lactose, a sugar. I take mine with heavy cream, which is very fatty and has almost zero carbohydrates. Whatever the reason, it's not uncommon for those giving up carbs and coffee at the same time to suffer needlessly. If you're already a coffee drinker, odds are you have a mild caffeine addiction, and you'll get headaches and experience other discomforts. As an added bonus, coffee works against gout, your risk of which may increase on a low carb diet.

7. Not going out

It may seem at first like it would be next to impossible to adhere to a diet like this at a typical restaurant, but it's just not true. More of them than you'd think have low-carb items on the menu, often labeled something like the "Atkins Special". But even those that don't, usually have plenty of dishes you can eat with small modifications. Burger? Skip the bun, and maybe add extra bacon and/or cheese. Does it come with fries? Try substituting broccoli or steamed vegetables. Fajitas? Pass on the tortillas and eat them with a fork - they're delicious that way. Just get a little creative, and restaurants can be quite nice.

6. Quitting too soon

The first few days can be rough. I've described this before, but it's worth saying again. Because you've been eating a high-carb diet, your blood is full of insulin. When you stop eating carbohydrates, the insulin in your blood doesn't dissipate immediately, and until it does, you'll mostly be unable to metabolize fat for fuel. So you'll be in a metabolic freakout while you're not eating the only fuel your cells can use, until your insulin levels fall and you start metabolizing fat. That is, until you enter ketosis. These few days are often pretty unpleasant. For me, the main symptom was a persistent headache, but your experience may be quite different. Most people are through it in about 3 days, but give it as long as a week if necessary. If you don't feel fantastic after a week, read this list again, because you're likely doing something wrong. If that's not the case, drop me an email and we'll see what we can come up with.

5. Drifting too far

I was guilty of this one more than once. Out of convenience or necessity, or just because, you eat something you shouldn't. You're out of ketosis, or think you might be. You say "Oh well, I messed it up, so I might as well do it right. Pour me a glass of Aunt Jemima, please." Don't do that. If you fall off the proverbial wagon, dust yourself off and hop right back on. Odds are you didn't do as much harm as you think, and it'll be a lot harder in a few days (or weeks, or worse) than it will be at your next meal.

4. Replacing too much

There's a low-carb or sugar-free version of just about everything. And far be it from me to condemn those things. But a lot of folks try to go low carb mostly by replacing cereal with low-carb cereal, bread with low-carb bread, sweets with sugar-free sweets, and so on. If you do this, you will not succeed, for several reasons. First, in most of these foods they don't replace the carbohydrates with anything you can even digest. Complex carbohydrates are typically replaced with fiber, an indigestible carbohydrate with no usable calories. Sugar is replaced by artificial sweeteners, including sugar alcohol. Many of these can give you gas and/or diarrhea, and none of them will satisfy you because they provide little or no energy. As much as possible, you should replace what you used to eat with foods high in fat and protein.

3. Fearing the cravings

By definition, half of all Americans eat a diet that is even worse than the average American diet. If you were one of these before the diet, it'll be a bit harder for you than for some other people at the beginning. I'm not talking about the first three days here. I'm talking about cravings. You'll feel intense cravings for carbohydrate-rich foods like pasta, or worse still, sugar. This is because carbohydrates are addictive. But fear not: this addiction can be beaten, and it's not as hard as, say, quitting smoking, if only because it doesn't take as long to rid yourself of the physical cravings. You may, of course, be in an even worse situation than this, and suffer from severe emotional cravings for carbohydrates. If you're in that position, I can't lie, this will be hard, but you need to realize the situation you're in. If you're not already diabetic, or morbidly obese, or both, you will be soon, and you cannot afford to succumb to your fear. And you - yes, even you - can beat it.

2. Not informing yourself

If you tell your doctor you're doing this, he or she will probably be pretty harsh with you. According to what's taught in medical school, this diet will kill you. That doesn't mean you shouldn't tell your doctor. That means you need to learn everything you can about why you're doing this, why conventional medical wisdom has it wrong, and so on. Learning all you can will help you avoid most of the mistakes on this list, not least of which is...

1. Not eating enough fat

I confess, the rest of the items on this list are in no particular order, but I saved this for number one. The most common and most harmful mistake you can make is to avoid fat. You must unlearn what you think you know about fat. See #2. Once you eliminate carbohydrates, you must have plenty of fat to maintain any semblance of health. Avoiding fat will not accelerate your weight loss - again, see #2. If you try to stay away from fatty foods, you will feel miserable, be unhealthy, and very likely fail. Eat all the bacon you want. The same goes for butter, steak, hamburger, eggs and so on. If what I'm about to say comes as a surprise, you probably haven't educated yourself enough to succeed on this diet: calories have nothing to do with obesity. Fat is very calorie-dense, which is just one of the reasons it's demonized in mainstream medicine and government dietary advice, but it is not the enemy. Eat it to your heart's content, and you are much more likely to experience the weight loss, the euphoria, the energy, the longevity, the health, the indescribable feeling of well-being that this diet has to offer.

Mosquito repellent?

2010-07-20T12:36:00.002-05:00

This one started out, for me, as a personal observation. Our family's currently camping (I'm sitting at a picnic table right now), and something curious happened last night. My wife, who had thoroughly doused herself with highly concentrated (25% DEET) OFF!®, was feasted upon just a foot or two from me, while I enjoyed a total but unexplained protection. This is our first major exposure to mosquitoes since starting the diet, now that I think of it, and this was not the normal state of affairs pre-diet. Mosquitoes positively loved me.

My wife, as it happens, is trying to get back on the proverbial wagon, but she is currently not in ketosis. Naturally, I thought of this as a possible factor, even if I couldn't explain how it would work. So I did some research.

It turns out that ketones (some of them more than others) are natural and effective mosquito repellents. According to some research, some of these compounds are considerably more effective (and less harmful) than DEET. Now they're trying to productize ketones as spray-on repellents.

As an experiment, I'm planning to go the rest of the camping trip without using any artificial repellents, and see how I fare. That's not exactly a rigorous double-blind, placebo-controlled trial, but it'll help me personally evaluate the voracity of this possibility.

Update 07/26/2010
As planned, I went the rest of the camping trip without the aid of artificial mosquito repellents, and I'm thrilled to report that I got not a single bite. This has led me to consider how primitive sub-Saharan tribes have managed to survive the scourge of Malaria that has plagued the rest of the African continent. I plan to keep looking into this.

Epilepsy

2010-05-31T20:49:00.001-05:00

I haven't written (much) about epilepsy until now because it's so, well, uncontroversial. But it's come to my attention that a lot of people who need to know about it, don't. So I'll start with a bit of history.

Around 400 BC, the physician Hippocrates (of Hippocratic Oath fame) wrote a book called On the Sacred Disease, about epilepsy. In it, he identifies the disease as a brain disorder rather than a demonic infestation, and recommends fasting as a treatment. Some centuries later, as recounted in the Bible, a man brought an epileptic child to Jesus for an exorcism, His disciples having failed. The child is miraculously cured on the spot, but Jesus takes a moment to point out that "this kind goeth not out but by prayer and fasting."

And so it goes until the 1920s, when the effectiveness of this treatment, combined with its long-term impracticality, led to a great deal of study of the biology of starvation, in hopes of discovering a treatment that could yield similar benefits in the long run. Enter the ketogenic diet, for a while. After 1939 and the development of phenytoin, the diet fell into disfavor until roughly the 1990s, which saw a resurgence of research on the matter that has continued unabated to this day.

Instead of linking to individual studies to back up my claim that dietary treatment is a mainstream approach to epilepsy, and especially pediatric epilepsy, I'll link to a whole pile of them and let you poke around. They all say more or less the same thing: the ketogenic diet is a very effective, but imperfect treatment for intractable epilepsy. Why the emphasis on "intractable"? I've yet to find a study that attempts the dietary therapy except as a last resort, after numerous drug therapies have failed. This is a problem.

First, I can't help but be cynical about the pharmaceutical profit motive behind the universality of this approach. But more importantly, and someone will correct me if I'm making an unjustified logical leap here, but the success rates must be artificially low, because it is only ever tried against the most difficult cases - those for which no other treatment works. And still it succeeds.

That's not the only reason to suspect that the (already impressive) success rates ought to be higher than those reported. For example, if the duration of the disease is a factor in its tenacity, then allowing it to persist long enough to vet half a dozen drug therapies puts the diet (and indeed, the patient) at an unfair disadvantage when it's kept on the bench until all else has failed. The possibility that duration plays a role is basically speculative, but weakly supported by the observation that the diet is somewhat less effective in treating adult epilepsy. Additionally, we can't afford to forget that these studies are generally published by epilepsy specialists, whose benefactors obviously include the manufacturers of antiepileptic drugs. So there exists a clear funding bias in favor of downplaying the efficacy of nonpharmaceutical treatments.

It may even be true - this is pure speculation but can't currently be ruled out - that drug therapies act on the disease or on the brain in such a way as to make it less susceptible to the effects of the diet. But enough of the weak arguments: I shall now break out the big guns and explain why the (amazing) success rates are as low as they are.

First, most of the so-called ketogenic diets administered range from 5:1 to 3:1 or even 2:1, meaning that 17% to as high as 33% of calories are from carbohydrates, assuming no patients are sneaking the occasional cupcake. Even on the best of these diets it will be a challenge to achieve and maintain a state of ketosis, and the rest don't deserve to be called ketogenic. If there are any carbohydrates at all in bacon or ribeyes, that's how many I consume on a typical day, and my only motivation is to stay generally healthy. I would think that an epilepsy patient, his parents and his doctor have a much stronger incentive to adhere as rigidly as possible to the treatment presented as the last best hope, but these studies suggest otherwise.

A better, but still imperfect, approach has been to use the Atkins diet, which at least in its initial stages is a ketogenic diet, and one with a more favorable ratio than any of the above. Observe the table on the second page of this paper on treating epilepsy with the Atkins diet, and notice the relationship between success and level of ketosis. Also noteworthy here are the relationships between success and age, and success and the number of antiepileptic drugs tried before attempting dietary treatment.

Yet another factor confounding the success rates is that many studies fail to even use what I would call food to administer the diet, then express disappointment and confusion at the dropout rate. Along with the other causes I've listed to be skeptical of the failure rate, this drives home a suspicion, at least to me, that a properly administered dietary therapy stands an excellent chance of reducing seizures in childhood epilepsy by 100%.

What would this therapy look like? It would be extremely low in carbohydrates, closer to 20:1 than 2:1. It would be administered at home by well-informed parents with some oversight from a doctor. It would consist of actual food - meat, eggs, dairy products etc. - and not powdered protein shakes. These well-informed parents might even lend support, if the child is old enough to justify it, by going on the diet themselves and removing any nonconforming foods from the house. They'd be surprised by their own results, unless they read this blog regularly.

Hashimoto's Hypothyroidism and Graves' Disease

2010-05-31T15:17:00.000-05:00

Most thyroid problems are caused by an underlying, often tissue-specific, autoimmune problem. The same trigger (an attack on thyroid cells by the immune system) can produce opposite clinical outcomes - either Graves' Disease (hyperthyroidism) or Hashimoto's Thyroiditis (hypothyroidism). Since they're both autoimmune disorders affecting the thyroid, I'm going to treat them as such, together.

First, I'll briefly cover autoimmune disorders in general for those who aren't familiar. The main job of your immune system is to get rid of things that don't belong in your body. To do that job without doing more harm than good, it's vitally important that it can distinguish self from nonself. When it gets that wrong, such as with pathogens that masquerade as healthy cells, massive failure ensues. Such is the case with autoimmune problems, where the immune system mistakenly identifies normal, healthy cells as nonself and attacks them. This can be systemic as in lupus or multiple sclerosis, or tissue-specific as in Graves' or Hashimoto's.

Many autoimmune problems are often comorbid with each other, and Hashimoto's and Graves' are no exception. Perhaps the most common disease found alongside autoimmune thyroid problems is celiac disease. This presents several interesting possibilities. One suggestion has been that celiac is itself an autoimmune disease. If so, its comorbidity with thyroid disease relative to other autoimmune diseases remains to be explained. Another, more intriguing possibility is the better established fact that celiac disease fosters malabsorption of several nutrients, especially vitamin D. This is all the more interesting because celiac itself may be caused by a deficiency in vitamin D, which protects the intestinal lining that's damaged in celiac cases.

So what's the link? What do vitamin D or celiac have to do with autoimmune thyroid disease? Vitamin D is crucial to the proper functioning of the immune system, and the volume of evidence that vitamin D deficiencies play a major role in autoimmune disease is overwhelming. Even very severe autoimmune diseases like lupus and multiple sclerosis can be completely reversed with intensive vitamin D supplementation therapy, but that can result in hypercalcemia. Vitamin D supplementation even completely prevents type 1 diabetes in rats bred to get the (autoimmune) disease.

Is vitamin D deficiency prevalent enough to explain the large numbers of autoimmune sufferers? That depends a lot on who's defining the deficiency. The FDA says that 200 IUs per day is adequate, and that's after raising it more than once. Many doctors, though, are pushing for it to be raised much further, to 1000 IUs per day or more, and insisting that very few people actually get sufficient vitamin D.

The next obvious question is how to fix a vitamin D deficiency. Assuming you're not absorption-impaired and you get enough dietary fat to make use of this fat-soluble vitamin/hormone, supplementation may suffice, but I prefer a more natural approach. Foods like meat, butter and eggs will go a long way, but if some of these researchers are right, even if you ate these things exclusively you may not be getting enough vitamin D for optimum health. For that, many of them say, you must also get plenty of exposure to sunlight. Be aware that sunlight, while catalyzing the conversion of cholesterol to vitamin D, also breaks down folate and thus increases your risk of melanoma if you're folate-deficient, but that's a topic for another article.

Conditioning and the Cephalic Phase Insulin Response

2010-04-11T23:29:00.000-05:00

It's well known that we secrete insulin in response to dietary carbohydrates. Specifically, we convert most non-fiber carbohydrates into glucose, whose presence in the blood is sensed by cells in the pancreas, which secrete insulin in response. But there's been a lot of work done in recent decades showing that the insulin response doesn't always match what we'd expect from this simple explanation.

For example, certain artificial non-nutritive sweeteners have been shown to elicit an insulin response. Certain fatty foods have a similar effect, including foods with little or no carbohydrate content, like butter. Why is this? What produces this response, if not the glucose-sensing islet β-cells in the pancreas? This study and others have posed the question, or at least acknowledged the gap in understanding: "the mechanism of the cephalic phase insulin response to meal ingestion has not been established in humans." This study, which looks at the subjects' metabolic responses to the taste of fat, rather than the ingestion of it, may give us a clue: it's your brain.

I have a testable hypothesis that fits what we know so far, and explains the positive correlation between reflexive insulin release and obesity. If you're on a typical American high-carbohydrate diet, your body is likely conditioned to expect a spike in blood sugar any time you eat a meal. If this conditioning is responsible for the "cephalic phase" insulin response, the stimuli I mentioned above should be expected to produce this result.

Insulin secretion can be conditioned in rats in response to arbitrary environmental cues, like site and sound, very much like Pavlov's salivating dog. There's a considerable body of work on the cephalic phase insulin response in humans, but I haven't seen any work that investigates whether it's a conditioned response. What I'd like to see is a similar test comparing the response in subjects on a typical diet versus subjects on a long term low carbohydrate diet. My prediction would be that the experimental group (the low-carbers), being deconditioned, would display little if any cephalic phase response.

How does a curious guy with an interest in this subject get a study like this done without spending his own money on it?

Athletic Performance on a Ketogenic Diet

2010-04-02T22:50:00.004-05:00

Bad blogger! It's been almost two months. I'm going to follow a suggestion I got in an encouraging email from a reader, and cover the effects of a ketogenic diet on athletic performance. "Athletic performance" covers a fairly broad range of activities, from high-intensity exercise like sprinting, to extreme endurance efforts like marathons. I'll try to be both brief and thorough.

Endurance Exercise

Most of the relevant research I've been able to find focuses on "submaximal exercise" or endurance training. Here the results are inconsistent, and the inconsistencies are themselves interesting to examine. In this study, titled "High fat diets and exercise performance", the author cites animal studies consistently showing significant performance enhancement after adaptation to high-fat diets. He then describes several human trials, some of which showed improved endurance and some of which did not. He proposes an interesting hypothesis to explain the disparity:

Part of the inconsistency between the animal and human results may be explained by differences in the percentage of calories from carbohydrate. The high fat diets given to animals contained little carbohydrate, usually 0-1% of total calories. The human diets on the other hand typically contained a moderate amount (10-20%) of their energy from carbohydrates.

A diet containing 10-20% carbohydrates is not likely to result in ketosis, unless the diet is also calorie-restricted. I assume they were trying not to kill the athletes, since as we all know dietary carbohydrates are absolutely necessary.

I mentioned adaptation. That's a recurring theme in modern research in this area. As most low-carbers are aware, the first few days or weeks of a ketogenic diet are a bit rough, and these scholarly efforts consistently demonstrate this. Many early experiments were too short, either by design or because unexpectedly poor results discouraged researchers or participants. Once the athlete adapts to the diet (enters ketosis and depletes his insulin levels), things turn around quickly and dramatically.

Adaptation is presented here as another potential resolution to the inconsistency of results among human studies, most of which only lasted one to two weeks. This is understandable, since locking participants in a metabolic ward for months at a time to ensure compliance is very expensive.

High-Intensity Exercise

All the material I've been able to find online suffers from the adaptation problem. One study published in 1994 compensated for this, and found "no difference" in performance between high-fat and high-carbohydrate diets. It's not available online (believe me, I tried) but it's well-summarized here. While it does account for adaptation, even this study provided 7% of calories from carbohydrate, so we don't know whether participants were in ketosis. Given a current lack of available time trial studies that meet the ideal criteria, let's discuss the results our theory would predict, and see if future research can confirm or falsify it.

Performance in high-intensity exercise like sprinting depends mainly on two factors that are significantly affected by diet: oxygen and fuel. Obviously on a ketogenic diet, the primary fuel will be fat rather than glucose (or glycogen, but I'll discuss that in a moment). In this context, the primary theoretical benefit of fat over glucose is its energy density - it yields more ATP and therefore energy per unit than glucose. This fact also affects the oxygen part of the equation. Since it's more energy-efficient, it's more oxygen-efficient, because more energy is produced per unit of oxygen.

That all seems pretty straightforward - fat wins! But it's complicated by the issue of availability. On a high-carbohydrate diet, glycogen is stored in the muscles, and it provides a very readily available fuel, delivered very quickly during high-intensity exercise. A ketogenic diet quickly depletes glycogen stores, so once the athlete has "adapted" to the diet, he likely has little to no intramuscular glycogen available for use as fuel. He does, however, have considerably more intramuscular triglycerides to replace it, and these are readily available as fuel. Trained athletes are able to metabolize (oxidize) these fat stores more effectively than non-athletes, so we would expect different results before and after the diet change, depending on the runner's level of fitness.

Another critical question is what happens when oxygen can no longer be delivered to the muscle cells quickly enough to keep up with demand. At the beginning of a sprint, this is no problem, but at some point that differs from runner to runner, an anaerobic system takes over which burns fuel without oxygen. If the fuel is glucose, cells use lactic acid fermentation to extract energy from the fuel without the benefit of oxygen. This results in a buildup of lactic acid in the muscles, which contributes to fatigue and the familiar burning and soreness associated with high-intensity exercise. So what happens when you're burning fat instead of glucose, and you run out of oxygen? If anyone knows the answer to that, I haven't found it. There's some reason to believe creatine is involved, but at this point it's not clear, at least to me. That dieters don't fall over from muscle failure is evidence that there's an anaerobic alternative to fatty acid metabolism, but I haven't been able to identify it.

So on the question of high-intensity exercise, the scholarly research is scarce and flawed, and the theory suffers from the unknown factor of anaerobic lipid metabolism. My prediction, then, is based largely on an anthropological idea:

As I've discussed more than once, carbohydrates as a substantial portion of the human diet are relatively new. Prior to the invention of agriculture, it seems that most humans spent most of their lives in ketosis, fed by meals whose acquisition likely involved a lot of sprinting. It stands to reason, then, that humans are well-suited to sprinting while in ketosis, and I'm prepared to allow this conclusion to fill in some of the blanks and predict that after a period of adaptation, a sprinter should outperform his non-ketogenic self.

Extreme Endurance Exercise

Here there seems to be no scholarly research at all. The closest thing I've found is an account of an arctic search and rescue expedition involving involuntary ketosis. Food supplies had been depleted, and food was only available from hunting and fishing. After several days of despair attributed to the adaptation period, things of course turned around for the rescue party. The leader of this expedition, Lt. Frederick Schwatka, describes it like so:

When first thrown wholly upon a diet of reindeer meat, it seems inadequate to properly nourish the system, and there is an apparent weakness and inability to perform severe exertive fatiguing journeys. But this soon passes away in the course of two or three weeks.

And the author of the paper shares his insight into the effect of this diet on men carrying a lot of heavy gear and encumbered by arctic-weather clothing:

That Schwatka was not impaired by his prolonged experience eating meat and fat is evidenced by his diary entry for the period 12–14 March 1880, during which he and an Inuit companion walked the last 65 miles in less than 48 hours to make a scheduled rendezvous with a whaling ship and complete his journey home.

Non-athletes, working under some of the least favorable conditions imaginable, presumably carrying a heavy load and wearing heavy, cumbersome clothing, covering 65 miles in less than two days is impressive.

However, I have my doubts that this translates very well into dietary recommendations for marathoners. Marathoners of course tend to be very lean, and eating a ketogenic diet won't change that. The amount of fat available for use as fuel is likely to be insufficient, though there's not a lot of evidence either way on that. The energy efficiency of fat metabolism may, thermodynamically speaking, allow for a large, fatty meal to see an athlete successfully through a marathon, but I'm not prepared to recommend that anyone try it.

10 Things to Look For in Diet Advice

2010-02-03T23:08:00.001-06:00

Weight loss is big money. So is health. So everywhere you go, especially on the Internet, you're constantly inundated with dietary advice. Somebody wants you to try the new superfood, herbal supplement, drug, or diet craze, and they promise amazing results. You'll get smarter, thinner or more energetic. You'll prevent cancer, the flu and heart disease. You'll live longer and have clear, wrinkle-free skin. All thanks to some super-special chemical or ingredient that's just been "proven" to confer these benefits.

I think it's unlikely that our bodies are optimized for an incomprehensible diet that was unknown six months ago, let alone six thousand years. I believe there is a natural solution to all these problems, and that excellent health is the natural state of man. But don't let my opinion on the matter sway you either. Bad advice tends to follow certain patterns. Good advice generally follows others. I'm going to try to help you sort through the mess of "information".

1. Citations
Does the article provide links to actual scientific literature, or just brief quotes from a researcher, which may well have been taken out of context? You'll notice here that when I start making claims about the effects of low-carb diets, I take great pains to provide references to original source material so you can read for yourself where the ideas are coming from. The rest is stringing the facts together with clear logic, and if I get that wrong you shouldn't believe me either.

2. Disclosure
A lot of "science" is funded by companies, governments, etc. with a vested interest in certain conclusions. That's not to say that scientists will always arrive at the conclusions their sponsors want to hear in hopes of securing future funding - but the temptation is undeniable. Research scientists depend on this funding for their livelihood, and the pressure is strong to keep the money coming. A good study or article will make it clear if there are any potential conflicts of interest. Take a look at this study, where the subtext on the bottom of the first page clearly states: "This study was funded by an unrestricted grant from the Atkins Center for Complementary Medicine." Does that mean the article should be dismissed as hopelessly tainted by its funding? That's for you to decide, so it's good information to have.

3. Incentive
This is strongly related to disclosure. What reason does the author of the advice have to make these claims? Is he, or the company he works for, selling something? Is he funded by someone who is? If the study is government-funded, do the results align with relevant government advice and policy? If so, you should suspect a bias in favor of government-friendly results. Or maybe it's not a study - it's a blog, an online newspaper article, or a website returned by a search engine. In this case incentive might be harder to work out, but that's why there are 10 things to look for!

4. Explanations
This one is a pet peeve of mine. Many purveyors of dietary advice are happy to simply make claims. Not only do they offer no citations, they can't even be bothered to explain why following their advice will produce the claimed effect. They just give you (for example) a list of foods to eat to "boost your brain power" with no supporting evidence or even logic - just a fluffy introduction, a list, and some fluffy closing remarks. Please don't give any such junk the time of day.

5. What's the law?
In the U.S., there's a lot of things drug companies can't say. For people selling foods and supplements, not so much. If you hear the words "no side effects!" you know right away it's not a drug, or not classified as one. The other thing you know right away is that the people selling it have not tested those claims in controlled studies. Some food companies are happy to make questionable claims with regard to health benefits, so watch out for those too. The point is, if you know what companies are and aren't allowed to tell you, you're better equipped to spot the marketing lies.

6. Fine Print
Some companies and individuals are so fly-by-night that they're happy to just vanish as soon as fraud charges are brought up, because they're so cheap to operate. If you caught some of the websites mentioned here while they were still up, you would have seen some little tiny text at the bottom explaining that contrary to everything else on the site, there's no real person named Karen Evans or Sarah Johnson or whatever - it's a fictional composite whipped up to blog about success stories with whatever they're selling. Takeaway lesson: if you're going to take somebody's word for something (don't do that), at least know enough about them to know if they exist.

7. Reputation
Try to distinguish this from fame. Some very famous advice-spewers have appalling reputations among their peers. Case in point: you've probably heard of Dr. Oz. Have you read what some other doctors have to say about him and his advice? Much of it is not flattering. But don't take their word for it either. I picked that link not because Dr. Eades is so unabashedly hostile toward Dr. Oz but because he so meticulously picks apart his advice, and doesn't just attack the man on a personal level. If you get advice, look for people who disagree and decide for yourself who has the more compelling argument.

8. Authority
OK, this is easy for me to say as a programmer blogging about physiology and heart disease, but status and authority often send exactly the wrong signals. Those who have either or both often have it because of a position they have a vested interest in maintaining, or they're afraid to lose it by siding with the underdog or the skeptic, regardless of which side is best supported by the available information. As soon as you find out that there's a group of people trying desperately to refute something you've always been told, do yourself a favor and see what they're all about. Often you'll find they're delusional, but when you find such a group that's really onto something, it can change your life. Those people will seldom have much status, authority, or impressive-sounding affiliations.

9. The Other Side
Most people who have done honest, thorough research to tell you something you didn't already know, or to try to convince the reader that a commonly held belief is flawed, will produce an honest presentation of the other side of the argument. They can do this because they're well-informed about those claims and still confident in their own. They will fairly describe, and then systematically dismantle, the opposing argument. Beware those who misrepresent the

The Politics of Low Carb

2010-01-28T23:19:00.002-06:00

For a long time it never occurred to me that politics - or, more properly, philosophy - might have anything to do with my own discovery of or interest in low-carb diets. But I spend a lot of time studying and thinking about both, and I've come to what I think are some interesting conclusions worth sharing.

There's a very interesting cross-section of libertarians and low-carbers, and I'm one of the many members of both camps. That observation led me to ponder what might be common to both sets of ideas that would lead to such a large intersection.

Libertarians, by definition, are staunch defenders of individual liberty and limited (if any) government. Low-carb dieters have necessarily shunned conventional medical wisdom and government dietary guidelines. That's a pretty weak correlation on its face, so I think we need to look up the chain to what I believe is the natural root of both intellectual pursuits.

Some people believe, whether they're conscious of it or not, that man is inherently evil. More specifically, man's desires are maligned as evil. Sexual desires are predatory and/or destructive, the desire for prosperity is synonymous with greed, our gastronomic tendencies are equated with gluttony, and our very desire for freedom from government interference is tantamount to shirking our duties to society. If you're nodding your head in agreement at these ideas, you believe that your natural desires are things to be resisted. That good can only be done through sacrifice, that to satisfy your desires requires something evil to be done.

What I believe, what libertarians believe, and what I suspect most low-carbers believe, is pretty much the opposite of all that. That we have succeeded as a species largely because we have desires that are good not only for us, but for society and humanity, and that to reject them harms the species as well as the individual. That altruistic behavior is best expressed among families and communities on a voluntary basis, that indiscriminate or compulsory charity ultimately does harm to everyone involved.

What in the world does this have to do with diet?

You love fat. If you don't think you do, ask yourself if you've trained yourself not to, because you've been told it will kill you. Ask yourself seriously how you feel about butter. Bacon. Ribeyes. You love them because your body loves them. If you're one of the first group of people I described, the people who look on their own wants and needs with disgust, the dietary recommendations you've heard for the last few decades ring true to you. If you could only deny yourself consistently enough, you'd be thin and live to see your hundredth birthday.

If you're not, there's a good chance you've always been skeptical of nutritionists. Their advice did not ring true. You love bacon, and there's got to be a biological driver for that. More than that, bacon makes you feel good. It energizes you without the crash that accompanies some other meals. You practically (or even literally) moan with a pleasure that emanates from something primal and natural. And, if this is you, you know exactly what I'm talking about and I need go no further...

Except to venture to predict that you also have libertarian leanings. As simple and right as the idea may seem to others, you're not so sure there's anything moral about the confiscation of the fruits of one man's labor to be handed out to another, however noble the goal. Left to his own devices, each man will pursue his own happiness, and the efforts of both are hampered by the punishment of achievement on one side and the subsidization of failure on the other. You may even go so far as to call this evil.

If I'm wrong about all this, I've probably just lost half (which is to say, 1.5) of my readers. But I don't think I am. I would love to hear your thoughts.

Top 10 Myths About the Ketogenic Diet

2010-01-24T02:46:00.006-06:00

I'm often surprised by the uninformed and/or misinformed comments I hear and read about low-carb or ketogenic diets. I want to address some of the things I hear most often.

It's a "fad diet"

Ketosis is dangerous and harmful!

ketoacidosis

ketones

You won't get the nutrients you need

entire post

more

vitamin C

All that fat will give you heart disease

written

single study

It only works (for weight loss) because you eat fewer calories

here

You'll feel terrible

and

You'll wreck your kidneys

kidney disease

anywhere

causes

kidney stones

uric acid

potassium citrate

Maybe it's good for some quick weight loss, but it's dangerous in the long term

FUD

has been done

This study shows the beneficial effects of ketogenic diet following its long term administration in obese subjects with a high level of total cholesterol. Moreover, this study demonstrates that low carbohydrate diet is safe to use for a longer period of time in obese subjects with a high total cholesterol level and those with normocholesterolemia.

It gives you bad breath

ketones

halitosis

I'll never be able to stick with it

have

expose yourself to

Aging: It's In the Cells

2010-01-23T16:46:00.004-06:00

We talk about a lot of diseases and other problems as if they're age-related. Alzheimer's, heart disease, cataracts and so on. In a sense they are age-related, but that sounds so... inevitable. It's helpful to be a little more specific.

Most of what we think of as the effects of aging occur at a cellular level, and are the result of an accumulation of damage over the cell's lifetime. That damage is primarily caused by "oxidative stress". You've probably heard of free oxygen radicals. They're created all the time in your body, and they wreak havoc on cells by reacting with proteins and other structures that are otherwise stable. Over time, this damage tends to pile up. The result, generally speaking, is aging.

You've heard of antioxidants, and you've probably heard that they're very good for you. The reason is that they help protect you against aging and certain diseases by preventing free oxygen radicals, or "reactive oxygen species" (ROS) from damaging your cells. Your body has some of its own antioxidant solutions, but most of the time you have more ROS than antioxidants, and that results in oxidative stress unless the cells are able to repair the damage faster than it accumulates.

Enter the ketogenic diet. There are several ways (see the section called "Antioxidant mechanisms") the diet lowers the production of ROS, which is extremely helpful in preventing the damage to begin with. But perhaps even more important is an effect I've talked about before and will talk about again: cellular autophagy.

"Autophagy" is Greek for "self eating", and in this context it describes the process of cells breaking down, metabolizing and replacing their own internal structures like proteins and organelles. This turnover helps keep oxidative damage from accumulating. That's important for protection against a lot of diseases, including cancer, atherosclerosis and Alzheimer's disease, but now we're here to talk about aging.

I can go a long way here by quoting from this article from Nature:

A common characteristic of all ageing cells is the accumulation of damaged proteins and organelles... [I]t is easy to infer that a gradual decrease in autophagic activity with age could play a major role in the functional deterioration of ageing organisms. Conversely, caloric restriction, the only intervention known to slow down ageing, seems to improve autophagy induction, possibly owing to lower levels of insulin, an autophagy inhibitor.

And this one put out by the Laboratories for the Biological Mechanisms of Aging at Harvard Medical School:

The dietary regimen of calorie restriction extends lifespan in diverse organisms ranging from yeast to mammals... but how calorie restriction works is not yet known. One of the changes associated with calorie restriction is a shift in the way in which energy is generated and used; that is, there is a shift from energy produced by glycolysis... towards energy produced by the breakdown of proteins and lipids.

Take note of the emphasis on caloric restriction. As this paper points out, "Calorie restriction and the ketogenic diet share two characteristics: reduced carbohydrate intake and a compensatory rise in ketone bodies." This statement omits, possibly because it goes without saying, that both diets also significantly reduce insulin levels. Insulin, as the first quote points out, inhibits autophagy.

The point is that the ketogenic diet has many, perhaps most, of the same effects as fasting and calorie restriction. The main difference, since they produce the same metabolic state (ketosis) is that the ketogenic diet doesn't resort to breaking down the proteins that make up your body, since they're abundant in the diet.

What this has to do with aging is hopefully clear by now. Autophagy is a significant anti-aging process that's inhibited by insulin, and insulin levels are kept very low on a ketogenic diet. This was well-understood by Dr. Atkins, whose low-carb weight loss program you've probably heard about. You may not have heard of his book on how the diet affects aging, which can be previewed here and purchased here, and which offers a much more in-depth but very readable treatment of the subject.

Weight Loss, Part 2 of 1 Zillion

2010-01-17T20:29:00.002-06:00

For a low-carb blog, there hasn't been much coverage to date of obesity and weight loss. Weight loss is definitely the foremost reason people try such a diet. A perception of adverse health effects is the main reason others don't try it, and debunking some of those myths is the main focus of the blog. It's definitely in-scope, though, to explain scientifically why the diet is an effective way to lose weight.

The prevailing - almost unquestioned - theory of obesity and weight loss is a simple thermodynamic equation: calories in equals calories out, the so-called "energy balance". It makes intuitive sense. Whatever your caloric intake, what you don't use, you store. If your output is more than your intake, you tap into your reserves, which are stored as fat, and weight loss is the result. If you do the opposite, you get fat. Even this study from 2008, whose conclusion is to confirm the effectiveness of a ketogenic diet, has this to say:

One hears all sorts of fads and fancies in diet suggested for reducing weight. No special article of food has any merit in this regard. Total calories must be reduced.

It's a good hypothesis, and on the surface, our observations might seem to confirm it. But a growing mountain of research continues to reinforce the success of another, slightly more complex theory involving the intricacies of human metabolism. I'm going to try to explain it in as much detail as you can digest, linking as always to scholarly literature along the way in case you'd like to dig deeper.

There are two primary fuels your cells can use to produce energy. The first is glucose, a very simple carbohydrate. Glucose is mainly produced by breaking down more complex carbohydrates, which are in your diet in the form of grains, potatoes, sugars and so on. Once your digestive system has extracted this usable fuel from what you've eaten, it enters the bloodstream.

Here, things get a bit more complicated. Nearly every cell in your body has everything it needs to take in glucose and get energy from it, but very few of them can do it without insulin. Your muscles, for example, are the main consumers of glucose in your body, and those cells require insulin to even allow glucose to penetrate the membrane to enter the cell. Fortunately, certain cells in your pancreas are able to sense glucose in your bloodstream and produce insulin in response. The more glucose in your blood, the more insulin is released. This is how your body manages blood sugar levels: blood glucose signals your pancreas to produce insulin, and insulin signals the rest of your cells to consume the glucose. More on this later.

If there's no glucose in the blood, there's little to no insulin either. And if there's no insulin, glucose can't be metabolized. People who can't produce insulin have type 1 diabetes and must inject insulin to manage their blood sugar. So, if there's no glucose and therefore no insulin in the blood, what do your cells use as fuel? The answer here is, basically, fat.

Before we get to fat metabolism, we need to talk about how and why fat is stored, since this is the essence of weight gain. Allowing your muscle cells to use glucose is only one of many functions of insulin. Another is signaling your fat cells to store fat. Since we know that there's no insulin in the blood if there's no glucose, and there's no glucose in the blood if you're not eating carbohydrates, it is impossible to store fat without eating carbohydrates. There are actually other reasons this is true, but I'll discuss those in another article.

As I said, if there's no insulin in the blood, your cells burn fat (usually in the form of ketones and fatty acids.) You always have some fat circulating in the blood in one form or another, but it cannot be used by most of your cells if there's so much insulin in the blood that they're busy working to get your blood sugar down. You see, high blood sugar is dangerous, which is why type 1 diabetes is so tricky to manage - the diabetic body is unable to manage it as a normal body would, and if the sugar is allowed to accumulate in the blood, well, things get bad.

Excess ketones in the blood are entirely different. You're able to simply excrete them in your breath, sweat and urine. And your cells don't need any special signals to metabolize them - that's the default, as long as there's no insulin forcing them to use glucose instead. So, if you're not eating carbohydrates, there's almost no glucose in the blood, therefore there's almost no insulin, therefore your cells burn fat, and any excess fat is simply excreted since (without insulin) it can't be stored.

I've explained now why it's impossible gain weight without eating carbohydrates, but how does such a diet help you lose weight? I've mentioned that insulin forces cells to use glucose as their exclusive fuel, overriding any other factors. Similarly, it forces fat cells to store fat, regardless of any other contradictory signals they might be getting. For example, the hormone epinephrine (also called adrenaline) tells your fat tissue to mobilize its fat stores, because you're probably about to need a lot of energy. Insulin tends to override this. In fact, there is a large number of hormones that stimulate the release of fat stores (without insulin), and you can learn a lot about that here.

Exercise causes a complex and interesting cascade of hormonal responses, many of which play important roles in the release of fat from the fat tissue. One of these responses is that your insulin levels are lowered almost immediately, which is necessary for the other hormonal responses to work. If you're on a ketogenic diet, though, you don't have the insulin obstacle to overcome: your fat cells immediately start releasing fat into the bloodstream to be burned as fuel, and if you don't use it all up, you simply excrete the excess - since, again, you can't store it.

So by eating a ketogenic diet, you have guaranteed that you at least can't put on weight. Any exercise you do is now far more effective, because fat is released more quickly and can't be re-stored if you fail to use it up. And whether you know it or not, you're already doing enough exercise to lose weight by changing nothing but your diet. I'm a programmer of all things, and on top of that I work from home, often from my bed, and I still lost 30 lbs. in the first six weeks of the diet, doing no more exercise than going about my daily, mostly sedentary, routine.

And here's the kicker. Calories don't matter. You eat as much as you want, and as long as you don't eat carbohydrates, your body literally throws away whatever it doesn't burn for fuel. And your fat tissue leaps at the slightest excuse to unload stored fat, because there's no insulin telling it not to.

At this point I can think of exactly three reasonable excuses not to be considering a low carb, ketogenic diet. The first one is, you get diet advice everywhere you look, and this is just another gimmick or "fad diet". To that I would say, do your research. Nothing I've said in this article is controversial other than my unabashed recommendation of the diet. I've oversimplified here and there, but human metabolism is pretty well understood, and all the physiology in this post is easy to confirm on your own, if you don't believe me or the resources I've (painstakingly) linked to.

Another perfectly understandable excuse is that you're concerned about adverse health effects. Well, that's what most of the rest of my blog is dedicated to, and in those articles you'll find even more links, to even more peer-reviewed scientific literature to back up my claims.

The last is that you just don't think you can do without carbs. You love pasta, or bread, or cheesecake, or all the above. Look, I'm Italian! If I can live without pasta, so can you. OK, that's a simplistic answer, and I'm mostly kidding. The real answer is that you are addicted to carbohydrates, and the good news is that it's a surprisingly easy habit to kick. The first few days are rough, but you'll find that your cravings just go away after a short time.

I'll close with some bonus citations of medical literature for further research:

Migraines: Are They Preventable?

2010-01-16T02:15:00.001-06:00

A link between migraine headaches and epilepsy has been known or suspected (depending on who's asked) for a long time. For the last century or so, a ketogenic diet has been used with a lot of success to treat epileptic patients. We'd like to know if that suggests anything about its efficacy in the treatment of migraines.

This would probably be a lot easier if we knew more about the causes and physiologies of epilepsy and migraines, but we should be able to get some hints from what we do know. For example, migraines seem to correspond with an unusually alkaline blood pH and to respond favorably to lowering it (making it more acidic). On a very-low-carb diet, the blood is very acidic because the ketone bodies themselves are acidic. This may account for the success of the diet in treating urinary tract infections.

Another place doctors are looking for the cause of migraines is GABA, an important neurotransmitter. Ketosis has significant effects on GABA metabolism, which is specifically targeted by lots of migraine and epilepsy medications with great success. Ketosis, in many important ways, mimics the effects of these drugs. Or to put it another way, the drugs mimic the effects of ketosis!

Another very important neurotransmitter is glutamate. It's also a chemical precursor to GABA, so there's a lot of interplay between the two in the brain. Impairments in the metabolism of either chemical, and in the conversion of glutamate to GABA, have been implicated in a number of neurological problems, including epilepsy and migraines. The ketogenic diet increases the rate of conversion of glutamate to GABA, which would tend to protect against these problems according to our current understanding of them. The article I'm going to use to back up these claims is positively dense with great information, and if you can handle scientific literature written for scientists you might want to check it out: The Neuropharmacology of the Ketogenic Diet.

All this is mostly theoretical, of course. A few rigorous studies that have been done to figure out if migraines can be effectively treated with a ketogenic diet, but unfortunately their full texts aren't freely available online. This one has some of the results available, and they're interesting enough that I almost want to purchase the article.

What I did find with little trouble is quite a bit of anecdotal evidence of people treating their own symptoms with the diet. Some tried the diet to lose weight and realized they stopped having migraines. Some of them remained migraine-free even after stopping the diet, which matches up with some of the published results. If any of you migraine sufferers feel like experimenting on yourselves, or if you already have, I would really love to hear about it.

Gout

2010-01-13T21:59:00.002-06:00

I hate to admit it, but there are some potential downsides to the low-carb diet. One of them is an increased risk of gout. Gout is not life-threatening, but I'm here to tell you, it's painful. I first got it many years ago, long before I had even heard of low-carb diets, but once you get it you're far more prone to it thereafter.

It's caused by a buildup of uric acid crystals in the joints. These things hurt. The joint becomes stiff and swollen, probably due to tissue damage caused by the crystals. This might explain why it has such a strong tendency to return once you've had it: to oversimplify, you now have uric-acid-crystal-shaped holes in the tissues where the crystals can easily reform under the right conditions.

The traditional treatment is a diet low in purines (a class of organic compound of which our reviled uric acid is a member), which by definition is a diet high in carbohydrates. This is also effective at preventing it in the first place. The "perfect storm" created by the low-carb diet is a consequence of first being very high in purines, and second, diminishing the ability of your kidneys to eliminate uric acid, leading to buildup and crystalization under some circumstances.

It's been known for a long time that it's not the ketosis that sets this up, but the large amount of fat in the diet. Now, while eating a low-carb, high-fat diet does increase your risk of experiencing this unpleasantness, it's still relatively uncommon. That's because other contributing factors seem to be required, and there are a lot of things that help protect against it. For example, if you're getting plenty of fluids, your kidneys are generally active enough to get rid of the excess uric acid produced by your diet. And if you're getting plenty of exercise, the crystals likely won't have a chance to form in the joints in the first place.

There also seem to be some specific foods you can consume to lower your risk. Dairy products, for example, tend to decrease the amount of uric acid in your blood. Coffee has been shown to decrease your risk of getting gout in the first place, but no one seems to know why. Anecdotally, I'm pretty sure I can vouch for coffee as an effective treatment and preventative even after getting it, and this is possibly explained by the effects of caffeine on uric acid levels.

And still other foods further increase your risk. These include organ meats such as liver and kidneys, which are very high in purines, and alcohol. The flare-up I'm presently suffering from happened to occur after an expense-account night at the bar, but I'm sure that's completely unrelated.

This is the first of a short list of "gotchas" that I'll be covering. The takeaway lesson? More dairy products, more coffee, less alcohol. Milk, by the way, has lactose, a sugar that's not compatible with a low-carb diet in high doses, so I recommend regular coffee with lots of heavy cream for two powerful nearly-carb-free preventatives at once.

Are You Addicted to Carbs?

2010-01-10T15:31:00.001-06:00

Thanks to the prevalence of obesity, and the resulting profitability of the weight-loss industry, you're bombarded with advice everywhere you look. You've tried following some of it, and maybe it worked for a while, but not for long. I'm dispensing some here too, though this blog isn't primarily about weight loss. A lot of the advice is remarkably consistent - exercise and watch your calories. But that doesn't work for you. Why?

The prevailing theory is simple: you don't have enough willpower. Me, I get skeptical when I hear about willpower. It suggests that your body is telling you what it needs, and you need willpower to shut it up or ignore it. With the important exception of addiction, I think this is a bad idea.

My favorite psychologist likes to say "trust the organism." You are an amazing organism, and your body is very good at knowing what it needs and letting you know. Hunger is no exception, and its messages should be heeded. It's there for a reason. And, importantly, eating when you're hungry isn't what's making you fat. It's what you're eating. And this is where addiction comes in.

You eat a high-carb meal, possibly full of sugar. This spikes your insulin levels, which signals your body to use all the glucose that's now in your blood. If you've eaten this way for a long time, odds are your insulin signaling is somewhat impaired. So eventually your blood sugar levels return to normal, but your blood is still full of insulin.

Now, insulin tells your cells to consume glucose exclusively. It shuts down fat metabolism in order to regulate your blood sugar levels, but since your blood glucose has already been consumed, you have a problem. You've become hypoglycemic. This is only a problem in the presence of insulin, which is only in your blood because you ate the carbohydrates in the first place, or possibly because you put it there with a needle. You probably have fat (which can normally be used for fuel) circulating in your blood as well, but thanks to the insulin it's doing you no good, so your cells have no usable fuel at all, and your body starts freaking out.

One of the symptoms of mild hypoglycemia is a craving for carbohydrates. Caving in to this solves the problem by giving your cells more glucose, but it also perpetuates the problem: your pancreas still responds by secreting more insulin.

On and on it goes until you're fat, fully insulin resistant, and finally diabetic. And the root cause could accurately be described as carbohydrate addiction. The good news is, it's not as hard to beat as most other addictions. If you give them up completely, as on a ketogenic diet, you'll have a few rough days. Not nearly as bad as if you were, say, quitting smoking, but you'll feel it. After those (usually) 3-5 days, you're free! As one of my surprised friends put it after a week or two on the diet, when she saw a fabulous chocolate cake, "I felt nothing!"

"Ketogenic"

2010-01-08T17:27:00.003-06:00

When I talk about a low-carb diet, I don't just mean a diet that cuts down on carbs. I mean one that cuts them as close to zero as you can tolerate. A ketogenic diet. So let me explain what that means.

Its name refers to the process in the liver and elsewhere of converting fatty acids into ketone bodies, which can be used as fuel (directly or indirectly) in place of glucose by most of your cells. Unlike glucose, unused ketones are excreted in your breath and urine, rather than stored as fat. A lot of low-carbers use "Ketostix" test strips to ensure that they have entered, or are still in, the state of ketosis. They work by reacting with acetone, one of the three ketone bodies produced on the diet. And that works because unlike the other ketones, acetone can't be converted to acetyl-CoA, which is necessary ketones' use as fuel in the citric acid cycle.

I've said a lot already about some of the nasty effects of glucose metabolism and insulin. And I'll say a lot more. But there's a flip side, too. By eating a ketogenic diet, not only are you protecting yourself from those effects, but the ketones themselves offer many benefits of their own. For one, they are a much more efficient fuel source than glucose, in terms of energy vs. oxygen consumption. That's all nice and chemical, and the real-world effects are somewhat muted by the complexity of metabolism, but overall ketones offer about a 28% increase in your heart's hydraulic efficiency (see that last link.)

Largely because of this, the ketogenic diet has been shown to increase exercise capacity and endurance. And if you've ever tried the diet, you know from first-hand experience that you have much more energy than before, once your body has adapted to it, which typically takes three or four days.

Another very interesting effect comes from one of the other ketone bodies, called beta hydroxybutyrate. It's long been known that this ketone has a protective effect in neurons with respect to Alzheimer's disease. And on the ketogenic diet, beta hydroxybutyrate replaces glucose as the brain's primary fuel source. Too bad the "high-fat ketogenic diet ... may not be suitable for use in adults because of its atherogenic potential," eh? I guess we'll have to toss it out. Or not.

Wouldn't it be great if there was a diet out there somewhere that didn't leave you hungry, that let you eat delicious food, that didn't give you heart disease, and maybe just maybe protected you from all sorts of other chronic diseases? Let me suggest that we are amazing organisms, and that our health is not so precarious that we have to follow some insane diet of exotic "superfoods", or abstain from the foods we as a species "grew up on", or subject ourselves to drug regimens, to stay happy, healthy and thin. And if you think that's wishful thinking, research for yourself where decades of increasing conformance to government-recommended diets has gotten us in terms of obesity, chronic disease and overall health.

A Historical Perspective

2010-01-07T23:26:00.005-06:00

I'm a big fan of simplicity. Occam's Razor and all that. Maybe that comes from being a programmer, or maybe I'm a programmer because I appreciate simplicity. And maybe that's why I was so receptive to the low-carb ideas. The more I listened to dietary recommendations from the government, the American Heart Association and so on, the more I wondered how the human species lasted long enough to even invent these ideas, if our dietary requirements are so complicated and counterintuitive.

Not that long ago, we hadn't even invented agriculture. We lived on whatever we could get wherever we lived, and that was mostly meat anywhere you care to look. Eskimos ate huge amounts of seal meat, so their diet was unbelievably fatty. They ate almost no plant matter. Aboriginal Australians ate mostly lean kangaroo meat and were similarly healthy (nutritionists love this one). Early humans are thought to have subsisted almost entirely on large game. That such a diet was successful enough for the species to survive and even flourish is often explained away by the assumption that their lives were "nasty, brutish and short" and so chronic disease was not a factor. People who make this claim are nutritionists - not anthropologists, who know better.

Thousands of studies have observed the sharp decline in the health and life expectancies of traditional hunter-gatherer populations when they either migrate to "civilization" or are encroached upon by it. Most of them offer tortured explanations, are amazed by "paradoxes" or, more honestly, suggest that we need to take a closer look at our own assumptions.

There is a long list of so-called "diseases of civilization", which are unknown or very rare among hunter-gatherer populations. These appear to include heart disease, type 2 diabetes, Alzheimer's disease, obesity and high blood pressure, as well as lesser problems such as acne, early onset puberty, nearsightedness, skin tags, acanthosis nigricans, polycystic ovary syndrome and male pattern baldness. All of these are potentially caused (as explained in the linked paper) by insulin resistance or hyperinsulinemia, and I suspect that's just the beginning of the list. And if this is your first time here, that means they're caused by high-carbohydrate diets.

Autophagy: Self-Eating

2010-01-06T18:43:00.003-06:00

No, this isn't some radical new kind of low-carb diet. It's a cellular process I touched on in a previous article, and I'll be talking about it again soon, so I thought it'd be useful to cover it on its own.

Cells age, like everything else. Their internal structures, membranes, nuclei and even their DNA suffer damage over time, largely from free oxygen radicals. Cells have several solutions available to them for dealing with this damage. The first line of defense appears to be autophagy, which describes several different processes for handling just the damaged bits, rather than self-destruction, or apoptosis.

This process is crucial for the prevention of cancer, heart disease, various neurological disorders, and other diseases, and most effects of aging can be blamed on its failure. Consider the opening statement of this introduction: "Protein quality-control, especially the removal of proteins with aberrant structures, has an important role in maintaining the homeostasis of non-dividing neural cells." The paper is about neurology, but the same statement is true of other cells.

What does all this have to do with a low-carb diet? The process is regulated by a protein called mTOR, which in turn is regulated by our old friend insulin. Take a moment to consider this, from the list of insulin's effects from that Wikipedia article: "Decreased autophagy - decreased level of degradation of damaged organelles. Postprandial levels inhibit autophagy completely." I had to look up "postprandial". I figured it meant some crazy-high insulin level only seen in hospitals, but it means "after a meal". That can only mean after a typical meal, since a low-carb meal by design doesn't spike your insulin levels.

What this means is that when you eat carbohydrates, at least in quantities that constitute a meal, this critical process is completely shut down. After years of doing this habitually, you become insulin-resistant as we discussed before, and in all likelihood you have postprandial-looking insulin levels for all your waking hours. You almost entirely lose its protection against the diseases I listed earlier and almost certainly many more that haven't yet been identified. You age much more quickly. This last tidbit was identified, with brief commercial success, some time ago, but odds are this is the first time you've heard about it, much less had it explained. And I haven't even gotten started - there's a lot more to cover on the subject of aging.

Which reminds me, I'm going to be talking about autophagy a lot in the future, so I wanted to cover the basics in an article I could link back to, instead of trying to explain the same complicated issue each time it comes up. I'll be doing more of that kind of thing, partly to try to cut down on the length of my posts. Let me know in the comments how I'm doing on the balance of good info vs. readability and I'll keep tweaking accordingly.

Low-Carb and Nutrition

2010-01-06T01:11:00.002-06:00

I hear it all the time. "Well you have to eat some carbs." Really? Why? What did people do for the zillion-plus years before agriculture was invented? What have hunter-gatherer populations done since then, including modern meat-eating tribes?

Is there some specific nutrient we're going to miss out on? Vitamin C comes up now and then, as it's found only in trace quantities in most foods permissible on this kind of diet, but there are theories to explain the anecdotal evidence of hundreds of thousands of low-carbers that there's no problem there. Maybe one of you readers can tell me what disease of deficiency I'm going to be afflicted with. Or maybe both of you!

Fact is, a diet consisting entirely of meat, dairy and eggs (not that most low-carb diets look quite like this) is very rich in all essential nutrients except vitamin C, which we've just covered: we meat-eating landlubbers don't get scurvy. Or any other nutritional deficiencies. Some of us, just to be on the safe side, take some multivitamins, but I suspect they haven't done their homework.

I think the most well-informed criticism available for the diet is not about what it's missing, but what it has: fat. I touched on it when I talked about "heart healthy", but it deserves some extra attention so I'll be talking more about it in the near future. Mean time, what do you want to hear about?

Alzheimer's Disease: Type 3 Diabetes?

2010-01-04T20:09:00.007-06:00

The idea is starting to get popular among Alzheimer's researchers. Other studies link Alzheimer's disease (AD) to neuronal insulin resistance, and still others postulate the cause and effect in the opposite direction. But a considerable and growing amount of research is beginning to identify the disease with diabetes itself, even calling for it to be renamed to "type 3 diabetes".

I'll let this research stand on its own if you want to read some of it, which I highly recommend, and I'm going to move on to some specific details of interest here. First, one of the hallmark features of AD is evidence of "chronic oxidative stress" in and around affected neurons. I've mentioned before, and I'll cover it in more detail later, that the free oxygen radicals that cause this damage are produced as byproducts of glucose metabolism, and that without dietary carbohydrates, the problem is avoided. From the same article:

[I]mpairments in cerebral glucose utilization and energy metabolism represent very early abnormalities that precede or accompany the initial stages of cognitive impairment. This concept truly warrants revisiting, particularly in light of the emerging evidence that impaired insulin signaling may have an important role in the pathogenesis of AD.

This sounds a lot like stuff we've talked about before, doesn't it? We then learn, from the this article, that "high concentrations of insulin affect the function and survival of neurons in culture by sensitizing them to toxin and stress-induced insults."

Perhaps the most important bit, and I'm still quoting from the same article but the information is easily found elsewhere, is:

Physiological insulin levels promote Aβ clearance by peptide degradation, a mechanism that involves insulin degrading enzyme (IDE) activity. A low level of insulin in brain reduces Aβ release from intracellular to extracellular compartments and high levels reduce Aβ degradation in the extracellular compartment.

That Aβ business is amyloid beta, what amyloid plaques are made of in the brains of Alzheimer's patients. Read it again if you need to. Insulin appears to be responsible for regulating the cleanup of amyloid plaques, which practically are Alzheimer's disease. Too much insulin (generally a consequence of too much blood glucose, a dietary problem) reduces degradation of the plaque. Low levels of insulin downregulate the removal of Aβ from the neurons' interiors, but this is (likely) because low insulin levels reflect low glucose levels, and we've seen that glucose and/or insulin are responsible for much of the cellular damage in the first place.

We then have a clinical observation from the same paper:

[A] growing body of evidence has been developed suggesting that glucose metabolism is associated with the pathogenesis of AD, age-related cognitive decline and neuroinflamation. Intravenous insulin infusion in healthy, eugylcemic older subjects induces a facilitation of memory while it increases cerebrospinal fluid levels of Aβ. (emphasis mine)

The picture gets clearer and clearer the more we look at it. We have physiological models of AD as an insulin resistant brain state, a mechanical model implicating insulin in the failure to rid the brain of amyloid plaques, a well-established epidemiological "link" between AD and type 2 diabetes and insulin resistance, clinical observations confirming the theories...

And we have other articles in this blog setting this up as a pixel in an even bigger picture about the role of refined dietary carbohydrates in other chronic conditions. And we still have a long way to go.

Type 2 Diabetes: The Last Phase of Insulin Resistance

2010-01-04T17:04:00.001-06:00

I've covered insulin resistance (IR) and mentioned its relationship to type 2 diabetes, but I need to discuss diabetes in a bit more depth, if only to establish a background for future posts.

A central and controversial thesis behind this blog and many of the ideas behind low-carb diets is that tissues become insulin resistant after prolonged exposure to elevated insulin levels, caused by a diet high in carbohydrates. That's a bit of an oversimplification, but that's the gist. I'll go into greater depth shortly to back up that assertion. Central to this post in particular is the idea that type 2 diabetes is nothing more than the final (insert pregnant question mark here, and anticipate a future post) phase of IR, in which all major tissue groups have become insulin resistant.

Both conditions are well-known to correlate with metabolic syndrome or syndrome X, and as seen here and elsewhere it's all been long thought to be caused by obesity. As far as I can tell from currently available research, that assumption is still the state of the art, though some research is finally beginning to stumble on a more sensible explanation. That is, that diet is the root cause of this cluster of diseases, including obesity.

Unfortunately, most studies don't isolate the component of diet that's to blame, because they combine high fat (which we like around here) with refined carbohydrates (which we assert are the enemy) and (correctly) blame the diet for IR. Other studies start with IR and find it to be the cause of metabolic syndrome. All that's left is to test high fat and refined carbohydrate diets separately to (inevitably) arrive at carbohydrates as the root cause, and for someone to connect the dots from dietary carbohydrates (especially refined carbohydrates) all the way to the endpoints of metabolic syndrome, and today's topic, type 2 diabetes.

As for that final step, establishing type 2 diabetes as a manifestation of insulin resistance, we're getting so close! But still a bit backward, it seems, no matter how consistently we witness the order in which they occur, even in a controlled study (the only one I could find even making the attempt, and the full text is not freely available, which may be contributing to its failure to make a significant impact on the field.)

The complete (if somewhat simplified) picture goes like this. Your skeletal muscle is your body's main consumer of insulin and glucose, and your adipose (fat) tissue is #2. So it's usually (but not always) in that order that the tissues become insulin resistant, given the high-carbohydrate diet and perhaps a genetic predisposition to IR. Once the two major consumers of glucose and insulin begin failing to respond, and perhaps the third, your liver, your capacity to manage your blood sugar levels by secreting ever-increasing amounts of insulin is greatly impaired, and you are diabetic. In other words, your adipose tissue can't pick up the slack from your insulin-resistant muscles (making you fat in the process) because it too has become resistant, and either your liver can't handle the load on it's met the same fate, and you now have diabetes.

The hypothesis I'm proposing in this blog, the one so ably elucidated in the book I keep mentioning, the one partially described and defended in this post, predicts that type 2 diabetes is treatable without insulin, and likely even reversible using the same treatment: you guessed it, the low-carb diet. Without carbohydrates in the diet, your ability to produce or make use of insulin is largely irrelevant, because it's not necessary for your new mode of metabolism. Thus depriving your tissues of both glucose and insulin over time via diet, insulin sensitivity should eventually be restored to normal or near-normal levels, and by definition you will no longer have type 2 diabetes.

I look forward to seeing the research that bears this out (or refutes it, if that's how things work out). Have you or someone in your family ever tried treating type 2 diabetes with diet alone? I'd love to hear about your experience.

Cancer: Not as Hard as We Think

2010-01-04T02:37:00.005-06:00

I'm going to start with a bold claim: cancer has the same cause, and should be treated with the same measures, as obesity. I didn't say breast cancer, or skin cancer. Different cancers have different properties that make it useful to study them separately, but all cancers have certain important things in common that make it possible to study cancer as a whole.

Before I go on, let me disclaim myself: I'm not a doctor, and this analysis is not intended as medical advice. If you have cancer, or want to prevent it, see your doctor, but do so armed with as much information as you can get.

Now that I've made this ludicrous claim, I'd better back it up with some science. You might first want to cover some cancer basics, which I'm going to skip... possibly here.

I'm going to talk about some things that all cancer cells have in common. One is called the Warburg Effect after its discoverer. Warburg described a feature common to all forms of cancer - they carry out all their metabolism anaerobically. This is important for a number of reasons. For one, on a low-carbohydrate diet, the only source of fuel available in the bloodstream in any quantity is ketone bodies, which cannot be metabolized without oxygen. Cancer cells are thus unable to make metabolic use of ketones. To my knowledge, there's no research available that confirms or refutes this statement, but it's a logical conclusion of the discovery of cancer's exclusively anaerobic metabolism, and should probably be studied closely.

Another, related feature of cancer cells is that insulin receptors are overexpressed. This means that cancer cells are avid glucose consumers, giving them a competitive advantage over surrounding healthy tissue. On a low-carb diet, of course, there's hardly any blood glucose to consume, so this critical feature of cancer cells confers no advantage whatsoever, and may well be a distinct disadvantage. Together with the inability to metabolize other fuels, this means that theoretically cancer cells cannot survive in a human on a low-carb diet.

Possibly the most important feature common to all cancer cells is their ability to avoid apoptosis, or programmed cell death, which in healthy cells is triggered by certain types of damage or DNA transcription errors. Without this feature, cancer cells would destroy themselves. There is another process by which cells deal with damage: autophagy. We don't know as much as we'd like about this process, but we do know that it allows cells to recycle aging and damaged organelles and that it's inhibited by insulin. This insulin-induced failure of cells to "take out the garbage" via autophagy may, according to many studies (and let me emphasize this one), may be a primary pathway to cancer development. From the article:

Malignant transformation is frequently associated with suppression of autophagy. The recent implication of tumor suppressors ... in autophagic pathways indicates a causative role for autophagy deficiencies in cancer formation.

Given this and the fact that "[i]nsulin and its downstream molecules such as mTOR/ S6K1 are well-known inhibitors of autophagy", let it not go without saying that on a low-carb diet, cellular autophagy occurs far more frequently than on a traditional diet, and in theory should reliably prevent the development of cancer according to this model.

There's also considerable epidemiological evidence for the role of dietary carbohydrates in cancer development. Vilhjalmur Stefansson, a Canadian anthropologist, published a book entitled Cancer: disease of civilization?, where he says:

"Stanislaw Tanchou .... gave the first formula for predicting cancer risk. It was based on grain consumption and was found to accurately calculate cancer rates in major European cities. The more grain consumed, the greater the rate of cancer." Tanchou made the claim in 1843, to the Paris Medical Society. He also postulated that cancer would likewise never be found in hunter-gatherer populations. This began a search among the populations of hunter-gatherers known to missionary doctors and explorers. This search continued until WWII when the last wild humans were "civilized" in the Arctic and Australia. No cases of cancer were ever found within these populations, although after they adopted the diet of civilization, it became common.

Modern study of hunter-gatherer populations and their risk of cancer has become difficult because, well, the ones we know about have mostly been destroyed or "civilized" and now consume high-carbohydrate diets. For a very thorough epidemiological examination of cancer and other "diseases of civilization" among hunter-gatherer populations, check out Good Calories, Bad Calories: Fats, Carbs, and the Controversial Science of Diet by Gary Taubes. I've linked to this book before, and I will again. If there's a must-read book for the low-carber or the skeptic, this is currently the one.

I'm sure I'll be writing more about cancer. I've touched on some some physiological and epidemiological evidence that carbohydrate consumption plays a causative role in cancer development, and later I'll dig a bit deeper and cover other lines of reasoning.

Rethinking "Heart Healthy"

2010-01-03T17:43:00.001-06:00

"Heart healthy" has become synonymous with "low fat". The number one killer of Americans is variously called atherosclerosis, heart disease, cardiovascular disease, or coronary artery disease, but these refer to the same condition or its symptoms and complications: the accumulation of plaque in the arteries, causing a loss of elasticity (hardening) and eventually blockage.

Conventional wisdom holds that LDL cholesterol, by its very presence, causes a buildup in certain parts of the arterial walls, leading to this condition, and that the best way to prevent and treat it is with a low-fat diet, or cholesterol-lowering drugs. If this is correct, then a low-carb, high-fat diet is dangerous indeed. My aim here is to discredit that hypothesis and present an alternative.

The hypothesis itself was sound and worth pursuing. It arose from the Framingham Study (thoroughly debunked in this book), the original canonical work on the matter, and the discovery that statin drugs, which lower LDL cholesterol levels, also tend to protect against heart disease. The assumption is that these drugs achieve the latter by means of the former, which if correct means that heart disease is primarily caused by high levels of LDL cholesterol. It turns out, however, that cholesterol levels are a poor predictor of heart disease, so we must question this assumption.

Early in the development of the hypothesis, it was believed that total cholesterol levels, including HDL, were the culprit. As the theory evolved, LDL was implicated, and ultimately the ratio of HDL to LDL, with HDL earning a reputation as "good" cholesterol, and LDL as "bad". LDL is, after all, the type of cholesterol responsible for arterial plaque deposits, and HDL is how the body packages cholesterol for destruction in the liver. Thus, the current state of the art as I understand it is that LDL levels correspond to cholesterol on its way to wreak havok, such as in the arteries, and HDL is the reverse of the process. This is seen not just as an indicator, but as an almost-root cause of heart disease, with the real root of the problem being dietary fat that raises LDL levels.

When you get your cholesterol checked at the doctor's office, the results are a reasonably complete "lipid profile", including HDL, LDL, VLDL and triglycerides, all of which have been shown in various studies as independent risk factors for heart disease. The conclusion, again, is that one or more of these numbers, or a combination, is the cause of heart disease, and that any treatment regimen should target those numbers. One thing they don't tell you is that the standard test doesn't even count LDL, what many doctors (including mine, quite vociferously) consider to be the most important number. It's estimated based on total cholesterol and HDL, with the assumption (sometimes justified) that HDL molecules are about 5 times the molecular weight of LDL molecules. This leads to the current technique for estimating heart disease risk from cholesterol: if your LDL to HDL ratio is less than 5:1, you must have more cholesterol leaving problem sites than being delivered to it, and your risk decreases. If it's greater than 5:1, you have a problem.

All well and good, but as I mentioned (and linked) the evidence does not quite bear this out. One reason for this may be the misleading numbers that result from the estimation of LDL. LDL refers to a relative density of lipids in each molecule, and there's a large degree of variance within the classification of LDL. If you are on a low-carb, high-fat diet, your lipid profile will likely show a "favorable" HDL figure, a high (unfavorable) LDL figure, very low triglycerides and very low VLDL. This pattern has been shown to be a favorable lipid profile, as it suggests a lower concentration of what appear to be the harmful, higher-density subcategory of LDL molecules. This in turn suggests a predominance of larger, less-dense, "fluffy" LDL molecules, which is unexpected and will not correlate with the 5:1 ratio assumed for the difference in molecular weight between LDL and HDL. Thus your doctor will be unnecessarily alarmed, especially if he didn't graduate from medical school in the last 5-10 years.

We now know that heart disease is strongly correlated to insulin resistance, Syndrome X or metabolic syndrome, and type 2 diabetes, which I'm trying to show are all manifestations of the same root problem. We're advised to consume a low-fat diet to reduce our risk of heart disease, but no one seems to have any success with that. We seem to be perpetuating a dogma that can't be penetrated by science.

There is another hypothesis available, implicating chronic inflammation as the cause of heart disease. A number of recent studies have established the link from inflammation to one or more of these interrelated conditions. Other studies suggest the link from insulin and/or insulin resistance to this inflammation, and even more directly to heart disease itself. Insulin promotes the proliferation of smooth muscle cells in the arterial walls, and these cells produce inflammatory agents such as C-reactive protein. From the article:

[I]t might be... that the insulin resistance itself [rather than the inslulin], by production of proinflammatory cytokines, induces atherogenesis and that the hyperinsulinaemia could be the body's compensatory attempts to suppress the inflammation and overcome insulin resistance... A vicious circle can also develop: decreased insulin sensitivity in organs such as skeletal muscle, adipose tissue, and liver leads to increased inflammatory activity, which in turn leads to further reductions of insulin sensitivity. Moreover, glucose has proinflammatory effects: it increases synthesis of reactive oxygen species and accentuates several inflammatory markers in vitro.

I'm going to be talking a lot about that last bit, how glucose itself promotes the production of "reactive oxygen species", and how all the movie stars keep talking about the health benefits of antioxidants, and how it all relates to the low-carb diet, in the near future. Stay tuned!

Insulin Resistance: The Root of All Evil

2010-01-03T16:05:00.003-06:00

Central to the theme of this blog is the concept of insulin resistance, which along with insulin itself, I'll identify as the cause of a great many problems. I'll start with the basics.

As I mentioned before, insulin is secreted by cells in your pancreas in response to elevated blood glucose levels, which in turn are caused by dietary carbohydrates. Your body converts digestible carbohydrates into glucose, which is what stimulates the release of insulin, and that insulin is necessary for your body to make use of the glucose and manage your blood sugar levels. When tissues become insulin resistant, their ability to make use of blood glucose is impaired, leading to a whole range of problems.

There appears to be a very influential genetic component to the risk of developing insulin resistance (IR), but no specific cause has yet been identified to everyone's satisfaction. A great deal of evidence exists to support the (intuitive) hypothesis that it's caused by chronically elevated blood insulin levels, which in turn can only be caused by a high-carbohydrate diet. This hypothesis stipulates that many conditions, including obesity, type 2 diabetes, and even heart disease are symptoms of the problem.

This idea is also consistent with the etiology of these conditions, and their correlations with each other. We know that IR is tissue-specific, and that different tissue types become insulin resistant at different rates and in different orders, apparently determined by genetic factors. One common scenario described by the hypothesis (and frequently observed) is as follows. After some years of chronically elevated insulin levels, skeletal muscle tissues become insulin resistant. This has negative effects of its own, but for our purposes it largely removes the main consumer of glucose from the glucose "economy" in the body. The second-biggest consumer is your adipose (fat) tissue.

When your adipose tissue becomes the main consumer of glucose, because your muscles have begun to fail to make use of it, you start putting on weight rather quickly, because that's how fat tissue responds to glucose and insulin. At some point, even your adipose tissue will probably become insulin resistant. At this point, you'll stop gaining weight, or at least slow down, and if your muscle tissues are already resistant, you are now diabetic.

The last two paragraphs do not represent current medical thought. It's currently believed that IR is caused by obesity, and that it correlates with diabetes for unknown reasons. So what I'm trying to present is a bit of logic that puts the high-carbohydrate diet squarely at the beginning of the cause-and-effect chain. This diet leads to chronically elevated blood glucose levels, which necessarily lead to high insulin levels. Prolonged exposure to elevated insulin levels causes insulin resistance (in one tissue type after another) and, once the major consumers of insulin have become resistant, the result is diabetes. The hypothesis that proposes this chain of events successfully and simply explains a great many observations and answers many outstanding questions.

For example, obesity is strongly correlated with type 2 diabetes, but why aren't all diabetics obese? Our answer is that in some individuals, adipose tissue becomes insulin resistant (making weight gain effectively impossible) before the skeletal muscles do. Why do diets high in fiber, a carbohydrate, seem to be beneficial with regard to obesity, IR and diabetes? Fiber can't be digested (converted into glucose, like other carbohydrates) by humans, so it doesn't raise blood sugar levels or stimulate an insulin response. Some kinds of dietary fiber may also trap otherwise digestible carbohydrates in the digestive tract and prevent their metabolism.

Insulin itself has a long list of undesirable effects, many of which I'll cover later. But insulin resistance, caused by prolonged exposure to insulin, is at the heart of type 2 diabetes, obesity, and a long and fascinating list of other chronic diseases that I'll be covering in the blog.

Obesity Is a Disorder, Not a Character Flaw

2010-01-02T17:25:00.002-06:00

Obesity, technically speaking, is a disorder of excess fat accumulation. How your body stores and accumulates fat is reasonably well-understood. How is it, then, that there's so much confusion about what makes you fat?

First, the basics. You eat a meal containing carbohydrates, such as bread, pasta, corn, potatoes, etc. Your digestive system breaks down these carbohydrate molecules into glucose. Your pancreas senses the glucose in the bloodstream and releases insulin in response. In your muscle cells, this insulin binds to receptors that (indirectly) allow the glucose to pass through the cell membrane to be metabolized for energy. In other words, glucose in the blood is required for insulin, and insulin is required to make use of the glucose.

One of the many effects of insulin is to signal your adipose tissue (your fat cells) to store fat, in the form of triglycerides. There are many other hormones that signal these cells to release or mobilize the stored fat for energy, but these do not work in the presence of insulin. It should already be clear that insulin levels are largely responsible for fat storage. Another important fact is what triglycerides are made of, and how they are assembled. First, the triglycerides in your fat cells are put together inside those cells. Individual fat molecules (fatty acids) are able to penetrate the cell membrane, and they pass back and forth more or less freely. Given the insulin signal, your adipose cells will assemble a triglyceride out of three (the "tri" part) fatty acids and one glycerol (the "glyceride" part) molecule. This new, much larger molecule cannot penetrate the cell membrane, so it is trapped or stored in the fat tissue until the cell receives a signal to disassemble the molecule to release the individual fatty acid and glycerol molecules into the bloodstream.

If we're fighting obesity, that last bit is obviously what we want. Once released, the fatty acids can be used directly for fuel by your cells (but again, not in the presence of insulin!) and the glycerol can be converted to glucose in the liver. Note, too, that glycerol is created during glucose metabolism. This is important because triglycerides cannot be manufactured without glucose. So, without carbohydrates in your diet, it is doubly impossible to store fat, since both glucose and insulin are required for fat storage, and with no carbohydrates in your diet, none (or almost none) of either will be available.

This is where the "thermodynamic" theory of fat storage comes from. In this cycle, any glucose not used by your muscle cells, or to a lesser degree your other cells, will be used to store fat, with the help of the insulin that was released in response to the meal. "Calories in = calories out" makes intuitive sense, after all, but it is not the whole truth. In fact, it's out the window entirely when you remove carbohydrates from the equation, because there's an entirely different metabolic process at work.

If you're on a low-carb diet, there is very little glucose in your blood stream. There is some, because your liver will manufacture it for the few cells, mostly neurons, that still require it, but the levels are negligible. The same is therefore true of insulin, which will be released in trace amounts by your pancreas, but the levels are nothing like those seen on a typical, government-recommended, diet. So there is not nearly enough of either to meet your body's metabolic needs. This is where the dietary fat comes in. If your diet is very low in carbs, it must be very high in fat, or you're starving. Starving is not good. And - commit this to memory - fat is not bad. That is the most important message of this blog, so I'm not going to leave it at that.

Basics again. You eat a fatty meal, very low in carbohydrates. A ribeye steak, let's say. Soon, it's all in your small intestine, which tries to absorb nutrients from it through the intestinal walls. Only water-soluble nutrients can penetrate these walls, though, so your gall bladder releases bile, produced by your liver, into the small intestine to allow absorption though a rather complex chemical process. The result of this is availability of fat in the bloodstream, for use as cellular fuel. Now, insulin signals muscle cells to use glucose exclusively as fuel, in part to manage your bloodsugar levels. But since there's almost no insulin in your blood at this point, it's free to use fat instead.

This has certain benefits. The most relevant here is that without insulin and glucose in the blood, this fat cannot be stored. Any fat that you don't metabolize will be excreted instead, in your breath, sweat and urine. This is where the thermodynamic theory of metabolism breaks down, because you simply get rid of what you don't use. Eventually, you will have used or excreted all the fat in your bloodstream, unless you eat another fatty meal. This situation stimulates your fat cells to release stored fat into the bloodstream for use as fuel. If this happens on a large scale, of course, you lose weight, and this mode of metabolism is called ketosis.

This is a basic overview of the theory behind low-carb weight loss. Nothing I've said here about how it works is terribly controversial. The processes are pretty well understood, though there are still pockets of dissent in the medical community. Ketosis is often referred to as an undesirable state. I think this is mostly due to confusion with ketoacidosis, a dangerous condition suffered mostly by diabetics and alcoholics. Others consider ketosis to be the body's emergency condition in response to starvation, which is correct, but most low-carbers consider it to be the body's preferred state. I plan to defend this position in later posts.

The main source of controversy surrounding low-carb weight loss solutions is the prevalent idea that dietary fat is harmful, even if the diet is an effective weight loss solution. Since this post is about obesity, I won't be addressing those concerns here, but rest assured they'll be well covered later.

So on one hand we have the popular weight loss dogma, which is all about calories and the insistence that obesity is caused by sin: gluttony and sloth. To combat it, they say, we must reject what our bodies tell us and abstain from eating, and simultaneously exercise for its own sake to balance out the thermodynamic equation. On the other, we have the low-carb theory, which tells us that we're not eating too much, we are very simply eating the wrong stuff. According to this theory, it's ridiculous to cast a judgmental eye on obesity, especially considering our constant bombardment with bad information. It's also a simple problem to solve, by eating delicious food in whatever quantities will satisfy your hunger.

Most other posts will be dedicated to examining the conventional beliefs about the harmful effects of low-carb, high-fat diets, and the many possible beneficial effects that you may be unaware of. I've already got dozens of articles piled up in my head, so expect a rapid-fire burst in the coming weeks and months, and don't hesitate to tell me what you think I should write about next. Expect copious references to scholarly literature, and give me what for if I try to make a claim without backing it up. Thanks for reading!