Carbohydrate-Rich Diet Is The Likely Culprit For Insulin Resistance

Blame Hyperglycemia, But Not Hyperinsulinemia For Inflammation

I’ll defer to others on the fat storage point. I would doubt much fat would be stored in a low-insulin state. Probably depends on how low, or on the ratio with other hormones.

That insulin does not stimulate appetite is repeated often and is based on highly controlled experiments over short periods, many of them in animals. I am not sure these are applicable. In 2 of the most important treatment of diabetes RCTs (DCCT for Type 1 and UKPDS for Type 2 diabetes), weight gain was greater in the more intensive medically (much of it insulin or insulin secretagogue therapy) treated groups.

Myth 1 – who’s talking about healthy individuals? We’re trying to do something about the 1.1 billion overweight and obese people in the world and the fact that we have 171 million diabetics already confirms that there is nothing healthy about the workings of the pancreas of these people. Why would you want to elevate blood glucose levels if you do admit that they stop fat burning? Why do you want all those green spikes when you can have lots of blue?

Myth 2 – there are other things that can impact fat storage and fat burning, but all pale into insignificance compared with insulin. Insulin is the big daddy of fat storage so don’t worry about the minor players. If you think a calorie is a calorie (even Weight Watchers pro points have finally admitted that this is not the case) then you’ve just violated the second law of thermodynamics, you haven’t understood Fine and Feinman or Jequier and you should do the experiment with 2 groups of people – one on 3000 cals of fat/protein (zero carb) and the other on 3000 cals of carb (sugar will do fine as the only 100% carb) and see who loses and who gains.

Myth 3 – “dozens and dozens of experiments” – the link goes to one study! Can’t even be bothered to look at it. Insulin may well suppress appetite but the issue is what happens when insulin has cleared all the glucose in the blood stream (by turning it to glycogen and then fat if we don’t use the glycogen). If we don’t have a perfect functioning pancreas/insulin mechanism (and few people do because of our dreadful quantity and poor quality carb consumption) then we can release ‘too much’ insulin in response to the meal and our blood glucose levels then fall lower than they were before we ate the junk carb. That’s when we crave carbs – not when the insulin is sloshing around. Eat a confectionery bar and you will get the sugar high (and yes you’re not craving anything at that moment) but then the low soon comes and you want another confectionery bar. Eat an egg the first time round and you carry on merrily throughout the day.

Myth 4 is not separating protein from carbs. The study (one reference again) looked at HC/LP and HP/LC diets – but there was carb in both intakes. In all his milkshake examples – these still contain carb. The carb can be the thing raising the blood glucose levels in all circumstances. The only reference that didn’t make this mistake was the AJCN one. I looked at the reference for the claim that beef does the same as brown rice – the text says those words, but the data tables and the graphs show beef and brown rice being very different. I don’t know if the foods were overlapping and the experiment wasn’t controllable. Stress can trigger an insulin response, so things may be unrelated to the foods being tested. I have never seen anything suggest that red meat or fish requires insulin to be released (indeed this was how diabetics were kept alive before insulin – don’t eat anything that requires insulin!)

Second, if an insulin resistant person with hyperglycemia on a high carb diet switches to a well-formulated low carb diet, the hyperglycemia and hyper-insulinemia get much better or go away completely. So whatever the underlying cause, the dietary carbs were a de facto antecedent to the abnormal glucose and inulin values. The best published example of this is Guenther Boden’s 2005 paper (Ann Intern Med 142:403-11). When 10 type-2 diabetics were given free access to a low carb diet, they are a bit more protein and fat but a lot less carb, after which they had better dietary satisfaction (less ‘appetite’) in spite of falling insulin dosage and serum insulin levels.

Third, at the clinical level, it doesn’t really matter what the root cause of insulin resistance is – even if dietary carbs are not the criminal mastermind, they clearly are a major perp. If you handcuff them and frog-march them out of your diet, there is less metabolic crime being done to your body.

The reductionist approach to the problem of obesity and Type-2 diabetes has had 50 years in the driver’s seat, leaving behind it death and destruction. It is time we broaden our intellectual perspective, allowing a more cosmopolitan approach. In this mode, if we step back a bit, it is apparent that oxidative stress and inflammation (OS&I) are antecedents of insulin resistance and much of human obesity. Given that there are hundreds of genes that influence OS&I, as well of hundreds of nutrients that do the same (both positively and negatively), the idea that we could isolate one gene or one nutrient as the putative cause becomes patently ridiculous.

It’s true that the body can store fat even when it has low insulin levels when excess calories from a high carbohydrate low fat diet are stored as fat even if insulin levels are not high. Upwards of 85% of excess carbs turns to triglycerides or fat. The body is less likely to store fat if it is primarily burning fat for fuel

Insulin suppresses, doesn’t stimulate appetite. Insulin may make people feel less hungry if they eat and inject insulin to help balance blood sugar. If blood sugar is not balanced and someone is hungry they eat carbs and inject insulin so the nutrients gets into cells, this may reduce hunger and cause weight gain but it is expected as part of diabetes management. If insulin levels are high and food has been shuttled to its destination, you will be hungry because your blood sugar will be low and hunger is a symptom of low blood sugar. If you do not want to antagonize the pancreas to release insulin which is what happens as soon as your body recognizes a carb has been consumed.

Insulin is not bad, it is necessary for life. It just happens to be a natural physiologic response to the food, especially the carbs, we eat. Too much insulin secreted in response to too many carbs is the problem. Experts direct people to avoid fat and to eat low fat foods that are loaded with carbs, popcorn, non-fat yogurt, graham crackers etc. These will spike insulin released, they do not tell people to eat nuts, celery with hummus, half a tuna salad sandwich which will help balance appetite and insulin because the foods contain a balance of carbs protein and fat.

As for the insulin issue, high carb diets don’t lead to chronically high insulin levels in all people or under all conditions. If a diet is at maintenance level calories or lower, carbohydrate and energy needs will not be in excess. The body does not have to “handle” excess glucose/energy as it is easily cleared through non-insulin mediated glucose uptake and will not require a large release of insulin. The non-insulin dependent glucose uptake mechanisms in the body respond to increased blood glucose levels through increased glucose transport in a manner similar to the kinetics of enzyme-catalyzed reactions. GLUT1 (in erythrocytes) GLUT 2 (liver and pancreas), and GLUT3 (in neurons) transporters remove glucose from the blood through facilitated diffusion along a concentration gradient without the aid of insulin. In most tissues, hexokinase phosphorylates glucose to glucose 6 phosphate. Hexokinase has a low Km, but also a low Vmax, so although it does contribute to clearing glucose from the blood, its action is limited by energy use in the cell aiding in the disappearance of G6P (elevated levels of G6P inhibit hexokinase).

After a glucose challenge, glucokinase, found in the liver, would be the primary enzyme responsible for normalizing glucose levels. It has a high Km and functions only when glucose is elevated. It also has a high Vmax, which allows the liver to remove large amounts of glucose from the blood rapidly. When glucose levels in the blood (and hepatocyte—through the action of GLUT2) are elevated, glucose causes the release of glucokinase from its regulatory protein, the enzyme enters the cytosol, and phosphorylates glucose to glucose 6 phospate, thus maintaining the concentration gradient needed to keep glucose moving into the liver and out of the bloodstream. In this manner, the body is able to deal quickly with a flood of glucose even without the action of insulin-mediated glucose uptake.

The body may store fat when insulin levels are low–temporarily. The body can also release and utilize fat when insulin levels are low. The problem that occurs when insulin levels are elevated is that the former continues to be possible while the latter is no longer. Insulin levels maintained at or near basal levels will allow for fatty acid fuel cycling that is not possible when insulin levels are elevated. However, in cases where little or no insulin is produced, i.e. Type 1 diabetes, fat storage is not possible.

Insulin suppresses appetite–in the short term. It is true that for many years we have thought of insulin as an appetite suppressant. It does seem to be a fairly weak, short-term appetite suppressant. Emerging science, however, has demonstrated that in fact insulin contributes to a long-term “feed forward” mechanism (or addictive cycle) in humans. As our understanding of the interactions between hormones and transcription factors has developed, we’ve come to realize that it is not a simple matter of appetite being turned on or off. If we remember that food gives our bodies information about environmental conditions, we realize that there is more at stake in terms of regulating eating patterns than meal-related behavior.

Dr. Robert Lustig gave a terrific presentation on this at the 2010 November ASBP meeting called “Sugar, Hormones, and Addiction.” I’m still learning about the subject myself, but a revealing rodent study, done by none other than David Kessler of FDA fame, demonstrates that sucrose is much more reinforcing than flavor or fat. It goes beyond sweet taste too, as tasteless starches are also found to produce the same level of reinforcement as sweet tasting sugars.

The idea that protein stimulates insulin as much as carbohydrate comes from the fact amino acids do induce a transient rise in insulin, although glucose is unarguably the primary stimulus for insulin secretion. Insulin is anabolic in that regard (Don Layman refers to insulin as one of our “growth” hormones) and will stimulate protein synthesis, which is how amino acids will—for the most part—be utilized. Some may be turned into glucose or ketones and utilized for fuel if there is insufficient fuel otherwise.

In the context of a low-carbohydrate diet, some amino acids will enter the TCA cycle as intermediates and allow for the cycle to continue even in the absence of dietary glucose. But the most important thing to keep in mind is that under these low dietary glucose conditions, there is little excess glucose that needs to be converted to fat to be stored. For fat storage to occur from the insulin rise triggered by amino acids, quantities of protein that would overreach normal satiety signals would have to be consumed.

So here is an example where chronic insulin is reduced from Hernandez, et al. comparing low carbohydrate diets (“high fat” in their paper) and high carbohydrate diets in healthy obese adults. The figure clearly shows the decrease in insulin and corresponding increase in circulating fatty acids. Notice how the release of fatty acids is exactly out of phase with the insulin. The meal comes at a low point in the insulin levels and as the insulin starts to go up, free fatty acids starts to go down as the breakdown of fat is inhibited by insulin.

This is from Eckel’s lab and the title of the paper is “Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet” which is not accurate; it is really the failure to suppress the response to dietary fat. This is not surprising given that there is much more fat in the low carbohydrate diet and the additional release of free fatty acids is a good thing on a weight loss diet. It means that you are losing fat. The paper is also written as if this were a new effect rather than his particular eisegesis of a phenomenon that is in all the textbooks. So, there is no question that a low carbohydrate diet reduces insulin and lipolysis is increased.

This is not always seen, however, and it may well be because of the difference in amount and type of protein in the diet. For example, Gannon, et al. showed dramatic improvement in the control of blood glucose in people with diabetes. Under their conditions, which have substantially higher protein (30%) than Hernandez, et al. (15%), there is no reduction in insulin on carbohydrate restriction. This might be due to the protein but you can’t say for sure from these two studies because Gannon & Nuttal also had substantially higher carbohydrate (30%) whereas Hernandez was much lower (targeting <10% although amount consumed was not reported). The figure from their paper shows that there is also more limited release in fatty acids. Whether this is a good thing or not is hard to say but, again, you can see how the insulin and fatty acids are directly out of phase. So it is important to know the effect of both protein and carbohydrate and, probably most important, how they interact.

As for glucagon, this is less well studied. We know from in vitro studies that the hormone that hormone sensitive lipase is most directly sensitive to is glucagon. In Gannon, et al., glucagon did track fatty acid release and zdid increase (green) with time on the diet (10 wks) although it went down compared to earlier point (5 wks). The study cited by Weightology, Gravholt, et al. did not show any change in glucagon so, again, it is dependent on conditions.

The pertinent question for me, however, is this: once your metabolism has been damaged by fructose, can you consume rice and potatoes without causing elevated blood sugar? In my case, the answer is no. One small potato will send my blood sugar sky-high and keep it there for hours. The same thing happens for a small serving of pasta. If I’d never discovered Captain Crunch and Coca-Cola as a kid then that might not be the case, but that’s where I’m at, so I have to limit my starch intake now. When I was at my fattest, I was living on rice, potatoes and pasta. I didn’t drink fruit juice or sodas, so it wasn’t fructose making me fat.

Perhaps we can store a little fat with low insulin levels, but not enough to meet our metabolic needs. Before insulin shots were available, Type I diabetics would waste away and die no matter how much they ate. Teenage Type I diabetics will sometimes stop taking their insulin shots — despite the dangers — because they lose weight automatically. Clearly, insulin is required to store any significant amount of fat.

Insulin sweeps fat and sugar out of the blood. How that would suppress appetite is a mystery to me. If insulin suppresses appetite, somebody will have to explain to me why people can eat an entire box of cookies or an entire bag of potato chips, taking in more and more food even as insulin is skyrocketing. It’s been demonstrated several times that people on a low-carb diet spontaneously eat less, so something about limiting carbohydrates suppresses appetite, whether it’s by reducing insulin levels or some other biochemical process we don’t yet understand.

Discussing ASP and insulin and leptin and all the nitty-gritty details in the comment sections of blogs seems like second nature for many of us, but we run the risk of forgetting that it all looks like chemistry textbook gibberish to the average dude or lady who just wants to fit into the jeans they wore in high school. At this point, they don’t need to – nor, probably, could they effectively – worry about carb refeeds or boosting leptin or fine tuning macronutrient ratios in accordance with activity. It all gets to be way too much for the newbies. They want something as simple to understand as “eat less, move more,” except one that works. Even if “eat less, move more” is ineffective advice that rarely works over the long-term, it makes intuitive sense to someone who isn’t steeped in this stuff every day. We need simplicity.

That’s why I like focusing on insulin – because it simply works, and it’s easy to understand. If you’re trying to lose a lot of weight, eat fewer carbs to lower insulin spikes and mobilize fat stores. Exercise with intensity to improve insulin sensitivity, so that when you do refuel your glycogen stores with carbs, less insulin is required for the job. Get plenty of sleep, because mismanaged cortisol due to lack of sleep induces insulin resistance. You do those things to manage insulin, and you’ll lose weight. Then, once it works and the pounds start coming off, what usually happens is the formerly fat guy with only passing interest in nutrition becomes obsessed. He starts reading all the blogs, pouring over the archives, and learning about all the minutiae. He plays around with leptin, adds some post-workout carbs, and realizes that all these details do matter – but he didn’t get to that point by fretting over the small stuff. Paralysis by overanalysis is a real threat.

I’m not here to discover the hormonal seed of the obesity big bang that sets off the cascade of metabolic dysfunctions. I’m here to help people lose weight and get healthy. For the vast majority of people I come into contact with and who contact me or visit my site, reducing postprandial insulin spikes gets the job done. And for the vast majority of that vast majority, eating fewer carbs accomplishes that. If there’s a lull in the weight loss, or they’re looking to get to single digit body fat percentages, focusing on leptin refeeds and tinkering with the lesser-known, but still vitally important hormones can become the new focus. But for now? For the average obese person with chronic insulin resistance who just wants to live longer and walk the stairs without coughing up a lung? Dropping carbs, and therefore reducing insulin spikes simply works.

1. High-carb diets don’t lead to chronically high insulin levels

To support this contention, James makes the point that insulin is only elevated during and after meals, and not between meals. And since insulin levels come down between meals and during sleep, everything balances out. He illustrates this in the figure below, which I’ve excerpted from his blog. However, James’ characterization of the insulin response to meals underplays the fact that it can take 2-3 hours, or longer, after eating for insulin and glucose levels to return to baseline. So insulin levels won’t be at baseline for very long, except during sleep. And that’s only for individuals of normal weight who don’t snack. If you snack, those little blue “dips” in the first figure below totally disappear! For overweight people who have some degree of insulin resistance, it takes much more time for insulin levels to come down, and even the baseline level will be too high to lose much weight.This is all made very clear in the second figure, which I also took from James’ article. So fat burning and ketosis just won’t happen. It doesn’t take much carbohydrate to keep the insulin up. Technically, one can lose weight with a high carb diet, but only if you eat fewer and smaller meals and space them out. And that is hard to do for many people, because elevated insulin can induce hunger (more on this below).

This also undersells the real value of low carb diets — they do allow insulin levels to get low enough for lipolysis and ketosis to switch on. The only other way to get insulin levels very low, especially for the obese, is to give up snacks, fast, or exercise more.

2. Protein stimulates insulin just as much as carbohydrate.

First of all, everyone concedes that protein induces an insulin response. In Protein Power, the Eadeses put this at about 50% the insulin response as from an equivalent mass of carbohydrate. But James seems to go beyond that and suggest that proteins can be just as insulinogenic or more so. However all his evidence for it is based on studies using mixtures of protein and carbohydrate, where significant levels of carbohydrate are present. For example, he cites a study with a “low protein, high carbohydrate” meal (21 g protein, 125 g carbohydrate) and a “high protein, low carbohydrate” meal (75 grams each of protein and carbohydrate). The “high protein, low carbohydrate” meal was slightly more insulinogenic. But I don’t think anyone would consider 75 carbohydrate in a single meal as low carb! Similarly he cites studies where dairy (milk) was insulinogenic, attributing that to the protein. But the lactose sugar in dairy is significant! When I objected that there is too much carbohydrate in these protein containing meals to draw any conclusions, he retorted that in “normal” meals, nobody eats so little carbohydrate. I(Kind of circular I would say). And he asks: if carbohydrate is the cause, then why does the meal with MORE carbohydrate have a lower insulin response? The answer to this is that the insulin levels are similar within statistical variation, and that beyond a certain amount of carbohydrate, they just don’t increase any further. It could also have to do with the type of carbohydrate and protein present in the meals.

Similarly, from this study of mixed protein and carbohydrate, it is hard to draw any firm conclusions about appetite and satiety, since there is so much carbohydrate in both meals. Also, the statistical error bars are overlapping between the two meals, indicating no real difference. Nobody denies that appetite is suppressed during the meal – duh! What else would you expect, when glucose has not had a chance to drop back below baseline! The real question is what happens after the meal and between meals, and once the body gets inundated with carbohydrate over many years, raising basal insulin levels and leading to insulin resistance and a hypoglycemic response. This can only be answered by studying how obese, insulin resistant or hypoglycemic individuals response to high carb meals. Normal individuals aren’t the ones with the problem! There is a major flaw in focusing on single meal studies. What James does not address at all is which type of meal composition over the long term is more likely to lead to the insulin resistant pattern — the high carbohydrate meal, or the high fat, moderate protein, low carb meal. Eaten month after month — not just a single meal.

He also shows a comparison of the insulin producing effects of several different proteins in meals combining 51 grams protein with only 11 grams carbohydrate. Notice the insulin AUC scale, however. All of these protein meals produce less than 50 units of insulin (AUC = area under the curve). That’s far lower than any of the carbohydrate containing meals, which have AUC’s ranging from 1000 to 10,000 units!! (In the graph above, the higher carb meals had AUC around 5000 units). So who cares about these minor differences in insulin response, which are trivial and are dwarfed when more carbohydrate is added!

James also denies that protein has any counteracting effect due to glucagon. He cites some studies showing that glucagon does not lead to lipolysis (fat burning). However, in those studies, the glucagon was infused intravenously with simultaneous administration of insulin and growth hormone! I don’t know about you, but that’s not a very fair study. In a real physiological situation, the glucagon levels increase towards the end of the protein meal, as insulin is headed down. This helps the body to free up glucose from glycogen and fatty acids from fat tissue, in order to prevent a hypoglycemic response. But with low carb dieting and fasting, glucagon can remain high while insulin gets very low. The experiments that James cites overlook the realistic physiological context under which glucagon operates.

3. Insulin suppresses, doesn’t stimulate appetite

I think this is the single biggest mistake that James makes. And I see that a number of people posting on your forum make the same mistake. To support his contention, James cites studies in which insulin was directly injected (“central administration”) into the hypothalamus — the brain’s appetite center — and this caused suppression of appetite. However, the way this study was done was to simultaneously feed glucose intravenously to maintain constant blood glucose levels while the insulin was being injected. Under these highly artificial conditions, there was appetite suppression. And it is likely that insulin does have an an inhibitory effect at high levels and in particular parts of the brain. That is typical of most hormones and enzymes — they have different effects at different levels and locations in the body.

However, one should really look at how insulin acts on the body during the course of normal eating behavior. Insulin enters the tissues “peripherally” not “centrally.” And in that case, insulin acts to lower blood glucose. If the meal is small and not too high in carbs, the insulin response and glucose reponse are blunted, and there will be no hypoglycemic cravings. However, when eating high carbohydrate meals like doughnuts or orange juice, there is often both a blood sugar spike and an insulin spike that leads to a rebound effect with glucose dipping below normal baseline, giving rise to raveous hunger, tiredness, crankiness, and hypoglycemic symptoms. And this is even worse if you are insulin resistant, where the high insulin levels continue longer then needed, leading to intensified hunger. Gary Taubes (GCBC, Chapter 24) also cites studies by Jacques LeMagnen that demonstrated this effect in rats, that were induced to eat when insulin was administered. And James totally ignores this phenomenon, which is very common in the U.S. and Western countries, especially for the overweight. And it is a problem that is very well addressed with a low carb diet! When I brought this up to James, his reply was that this hunger was due to the low blood sugar, not the insulin. That’s like the lawyer of an accused murderer arguing that it was the gun and the bullet, not the accused, that was responsible for the killing. If A causes B, and B causes C….it follows that A was a cause of C.

4. The body can store fat even when it has low insulin levels.

Again, James is technically right on this point. He points out that glucose can passively diffuse into cells and be fixed into triglycerides (fat) even without the action of insulin. While that’s true, it happens at less than 20% of the rate that occurs when insulin is present! And it only happens when glucose levels are very high, whereas in the presence of insulin, even trace levels of glucose will be stored as glycogen or fat. It is also true that dietary fat can be stored as adipose tissue without the action of insulin. There is another enzyme, Acylation Stimulating Protein (ASP) which allows fatty acids to be taken up into fat cells, even when insulin levels are low and no carbohydrate is present. However, this is a highly reversible process, and the fat comes out of storage as easily as it goes into storage — whereas with insulin levels elevated even slightly above baseline, the release of fatty acids from adipose tissue is totally inhibited! So this is night and day. The only way to stay fat on a high fat diet is to continuously eat high amounts of fat with no break in the action. As soon as your meal is over, or you exercise, the fat starts coming off. Whereas with hi carbohydrate diets and high insulin, it probably takes 3-5 hours minimum to even get started with fat burning!

5. Insulin resistance causes high basal insulin levels, not the other way around

The one area where I agree with James Krieger is that insulin resistance is the problem, or at least one major problem, that underlies obesity. He does not think, however, that the insulin from high carbohydrate meals can lead to insulin resistance. Rather he contends that it is insulin resistance (from some other causes) that make the pancreas work harder to spit out insulin, leading to hyperinsulimia. My own view is that he is right about this second effect (IR causes hyperinsulinemia) , but he is wrong to deny the first effect (hyperinsulinemia is one cause of insulin resistance). It is just a fact that a high carbohydrate diet, eaten over many years, keeps insulin levels high, reducing fat burning and leading to fat accumulation. I think James’ studies focussing on single meals overlook the long term effects. Now I will agree that there are other factors that contribute to insulin resistance. It is true that fat accumulation leads to higher fat levels in the blood — which desensitizes glucose transport receptors and leads to insulin resistance. And high fructose in the diet and other inflammatory ingredients also lead to insulin resistance.

As a self-styled advocate of this hypothesis — I believe it is almost undoubtedly the most important idea of our time — I aim to challenge you on both the substance and the details. Obviously, the hypothesis is quite technical. Since I lack a degree in nutrition like you have, and since I haven’t immersed myself in the primary research on obesity and nutrition for ten years like Gary Taubes has, my response by default will focus on the big picture implications of what you’ve written.

Before we dive in, I wanted first to emphasize that I both respect your passion for these issues and believe that you care deeply about helping people live better and healthier. Although my rebuttal gets, at times, somewhat sarcastic (an expression of my passion for this stuff), please understand that I view you and others who believe as you do about calories as allies in the collective fight against obesity and disease.

Furthermore, I in no way hope to silence your criticism of the hypothesis. Any time people refuse to listen to their critics, problems erupt. I and other low carbers should be grateful for your scrutiny. As I mentioned to you in a post in the Obesity Forum months ago, I believe we are all on the same team. The basic issue, as I shall elucidate, is that we are operating out of different paradigms, and this leads to a kind of dissonance akin to the horrible sound that arises when two talented violinists play the same note, but not quite.
So with that prelude… let’s have at it!

The Core Argument — What Causes Obesity and What Cures It?

Before we wade into the weeds of the biochemistry of carbs, protein, insulin, glucagon, glyceroneogenesis, etc, etc, etc, we need to pull back. Examine what this thing is really about from a 30,000 foot perspective.

As far as I can make out from your website — when you cut through the graphs and technical discussions about things like fructose metabolism — you believe that CALORIES COUNT. You believe that what the pros in the field call a “positive energy balance” (too many food calories ingested) causes obesity; and a “negative energy balance” (eating less food and exercising more) cures it.

Simultaneously, you aim to smash the carb/insulin hypothesis about obesity.

This theory, at its essence, as far I as understand it, says that eating too many carbohydrates (in particular sugar and refined starches) makes you fat and sick. Having evolved for millions of years as hunter-gatherers, human beings get hurt by the chronic abuse of these new and biologically unusual foods. Among the many bad things carbs do, they chronically warp the body’s metabolism by spiking blood sugar and driving the pancreas to secrete way more insulin than it should. Over a long period of time, chronically elevated insulin levels wreak havoc throughout the body. In terms of the fat tissue, specifically, the long-term super-supply of insulin ultimately deforms adipose tissue regulation, leading to problems like obesity and, perhaps, anorexia.

The carb/insulin hypothesis is excruciatingly complicated. The “moving parts” involved no doubt number in the hundreds to thousands.

So if your overall point is that the carb/insulin hypothesis is not a complete and total description of reality… it is a fantastic point, and I am actually on board with you!

But James, that’s not the point you seek to make.

Your aim, as far as I can tell, is to drive people to embrace (or, rather, re-embrace) the calories-in-calories-out paradigm.

This idea was summarized as follows by researcher George Bray in a rebuttal to Gary Taubes’ Good Calories Bad Calories in the journal Obesity Reviews: Obesity is the result of a prolonged small positive energy surplus with fat storage as the result. An energy deficit produces weight loss and tips the balance in the opposite direction from overeating.

This idea certainly makes sense upon first inspection. I used to believe it. Indeed, even most heroes in the low carb world — including Atkins and Yudkin (who spoke of the inevitability of calories) — have assumed that this idea is somehow fundamentally correct. That it requires no justification. That it is akin to a religious truth.

The basic rejoinder is twofold:

1) Beating up on the carb/insulin hypothesis does nothing to prove that the Calories Count idea is correct.

2) The Bray assertion that Obesity is the result of a prolonged small positive energy surplus doesn’t follow from the laws of physics. Specifically, the 1st Law of Thermodynamics provides us with no causal information that’s of any use.

Gary Taubes actually published a response to Bray’s argument. He wrote:

“[Bray’s] inference of causality is logically indefensible. Vertical growth, too, if accompanied by increasing body mass, must be associated with positive energy balance. No one, however, (not even Bray, I presume) would state that children grow because they overeat or that their growth ‘is the result of prolonged small positive energy balance’. Rather, children overeat because they’re growing. The causality is reversed. Understanding the true causality is critical to understanding the phenomena. The underlying cause of this vertical growth and its accompanying positive energy balance is hormonal – the secretion of growth hormone.

The question posed in GCBC is why we rightfully focus on hormonal
regulation when discussing growth abnormalities – gigantism, for instance,
or dwarfism – but insist on discussing abnormalities of fat accumulation –
obesity and anorexia – as though fundamentally caused by eating behaviour without attending to the hormonal regulation of fat tissue.”

Robert McCleod, a whip smart Canadian blogger, also composed a rejoinder to the Bray thesis. I hope he doesn’t mind my quoting him at length, but he does an especially sharp job:

“Rebuttal: Conservation of Energy

One of Taubes’ chapters deals with the idea that energy balance in humans can be reduced to the First Law of Thermodynamics:

ΔE = Ein – Eout

I was somewhat confused to see this. Surely the nutritional scientists did not not really believe this, right? I mean, any idiot undergraduate students knows that the 1st Law is only useful in a closed system, and humans live on the planet Earth, not in an insulated box. Right?

Enter a rebuttal by G. Bray in the journal Obesity Reviews. Bray is a to be a major obesity researcher and one of the 2nd tier villains in the book. Taubes relates a story of Bray excising a section of a British report on obesity, where Bray removed the material pertaining to the relationship between insulin and obesity. He clearly has editorial support to make his case. Bray is one of the second-tier villains in Taubes’ book. Taubes has a footnote (p. 421), which suggests that Bray actively suppressed the carbohydrate-insulin hypothesis.

According to Novin, when he wrote up his presentation for the conference proceedings Bray removed the last four pages, all of which were on the link between carbohydrates, insulin, hunger, and weight gain. “I couldn’t believe he would make that kind of arbitrary decision,” Novin said.

Unfortunately, to a physicist this energy balance hypothesis looks like a silly hand-waving exercise, not a serious argument. Frankly I was flabbergasted when I first read this article. This conservation of energy argument is on the same scientific level as the ridiculous “drink cold water to lose weight” idiocy. A human organism is:

Not in thermal equilibrium with their environment. Last time I checked I have a body temperature around 38 °C and spend most of my time in 21 °C rooms.

Capable of significant mass flows (e.g. respiration).

Capable of sequestering entropy (e.g. protein synthesis).

Is wearing a sweater fattening (by insulating you from your environment)?

Here’s a quote from the rebuttal:

Let me make my position very clear. Obesity is the result of a prolonged small positive energy surplus with fat storage as the result. An energy deficit produces weight loss and tips the balance in the opposite direction from overeating.

According Bray’s thermodynamics argument, wearing sweaters makes you fat. This illustrates the greatest fallacy of trying to apply the 1st Law to a human: it makes the implication that living organisms consume kilocalories for the purpose of generating heat rather than perform useful work (i.e. breathing, contracting cardio and skeletal muscle, generating nervous action pulses, etc.). In reality heat is the waste product of basal metabolism. The first law does not distinguish between different types of energy. Heat, work are all equal under the First Law of Thermodynamics.



Applying the 1st Law to living organisms is Proof by Tautology. Yes, 1 + 1 = 2, but this tells us absolutely nothing about the underlying mechanics. The 1st Law does not (I repeat N-O-T) tell us whether you store excess energy in the form of fat, or bleed it off into the atmosphere by dilating blood vessels next to the skin, sweating, etc. To do so would require an accounting of entropy.

What would a semi-rigorous description of the thermodynamics of a human organism look like? Look at the title strip on the top of the page. See that equation in the background?



This type of equation would be a bare starting point for energy balance in a complex system like a living organism. Good luck actually accounting for all the terms. Those Σs are sums.”

So I throw down the gauntlet: what’s the rebuttal to this guy? How do you dismantle Robert McLeod’s debunking of Bray’s assertion?

Unfortunately, most people knee-deep in this debate — including you, me, Bray, and essentially every obesity expert — are not physicists. We lack a significant and deep understanding of the laws of thermodynamics and the math used to analyze these laws. I’d be willing to wager that Robert McCleod (among others) could take us all to school on the 1st Law of Thermodynamics.

I don’t mean to insult anyone. I actually majored in physics at Yale University, and the equation that McCleod asserts is “but a bare starting point for energy balance in a complex system like a living organism” reads like total gibberish to me.

Okay. Point made. So what flows from this? Well, first off, if the Bray position falls apart, then so does the idea that consuming excess calories causes obesity and creating a caloric deficit fixes it. Because those ideas flow directly from the calories-in-calories-out point of view.

But what about all the biochemistry? What about carbs and insulin and all that jazz?

Well… as I mentioned at the start, you raise some fascinating points. Any truly comprehensive theory of obesity, weight loss, and chronic disease must successfully explain all real world data, not merely some.

I cannot begin to comment on all you wrote because of my lack of space, time, and, frankly, expertise. But let’s touch on a few points…

I think we can all agree that the body has various complicated pathways by which it can convert all three macronutrients — carbs, protein and fat — into stored fat. This makes sense. After all, if this wasn’t true — if only carbs alone could drive fat storage — then people on ultra low carb diets would waste away and become emaciated. And that certainly doesn’t happen. Indeed, Wolfgang Lutz and Christian Allan describe treating anorexics with low carb diets in their book, Life without Bread. Here is their account:

“Usually thin people experience a loss of weight during the first few months on the diet. This eventually gives way to increased body mass as the production of growth hormone eventually increases, and the nutrients needed to build tissue (fat and protein) are consumed. Over a long period of time… they will eventually reach a larger body mass compared to when they began the low carbohydrate program. The new weight, however, will be in all the right places.”

How about that? Low carbing made these anorexics gain weight… but in all the right places. Interesting!

The reality is that the adipose tissue is a complex organ. It is a metabolically active organ, not an inert piggy bank to store excess calories, as Bray and you apparently insist.

So many factors can impact our fat tissue — alter it, disregulate it, perhaps fix it again. Think about all the hormones, enzymes, genetic factors, medications, exotic agents from outside the body, etc etc, that might influence its character and constitution. And, almost certainly, the relevant influence of these agents changes over time, varies from person to person, and, in general, generates a dynamism so dizzying complicated that I doubt even today’s biggest supercomputer, cranking on all cylinders, could model it for long.

So is it all as simple as, in the words of George Cahill (as quoted by Taubes in GCBC): “carbohydrate is driving insulin is driving fat”?

Likely this is an oversimplification.

As you point out, protein can stimulate insulin.

And people can put on fat when insulin is low (see the Life Without Bread example above).

And a low carb diet is not a magical cure for obesity that works every time, even with best compliance.

And there may be something to the idea that periodic and severe macronutrient restriction — so-called intermittent fasting — can jump start fat loss.

And if one is to assert that refined carbs makes you fat, you DO need to account for both people and populations who apparently eat significant carbs and generally manage to avoid obesity.

Varying up both the quantity and quality of macronutrients in the diet could, at least theoretically, lead to indirect manipulation of fat tissue metabolism, as could varying up both the quantity and quality of any exercise program.

And on and on. You can surely generate thousands of what appear to be attacks on the boiled down supposition that carbs -> insulin -> obesity. Basically you can say: your cause-and-effect chain is too darn simple!

The rebuttal is: sure, nuances abound. Granted! But the question is: how much does this oversimplification really matter?

The carb/insulin hypothesis appears to be a robust first approximation of reality. Much better, certainly, than the calories-in-calories-out hypothesis that most of the world insists is dogma.

Furthermore, in practical terms, an Atkins or Protein Power type diet should be the diet of choice — or at least the starting point for the diet of choice — not the American Heart Association diet that revolves solely around calorie counting and ignores the different effects that different quality nutrients have on the fat tissue.

Let me throw out a few more points:

1. You said the following: “In fact, if you truly wanted to keep insulin as low as possible, then you wouldn’t eat a high protein diet… you would eat a low protein, low carbohydrate, high fat diet.  However, I don’t see anybody recommending that.”

Many of the major LC plans recommend a low carb, moderate protein, high fat approach.

2. You wrote: “Your Body Can Synthesize and Store Fat Even When Insulin Is Low ”

True. As discussed above. And your point is…?

3. You wrote: “5000 calories of olive oil isn’t very palatable so of course I won’t get very far.  I wouldn’t get very far consuming 5,000 calories of pure table sugar either.”

I wouldn’t be so sure about the sugar part. As Taubes discusses in GCBC, Japanese sumo wrestlers fatten up by eating 10,000+ calories a day on a very low fat, very high carb diet.

4. You wrote the following:
“MYTH:  Since diabetics who inject insulin gain weight, this means that insulin is the reason for weight gain in non-diabetics. 
FACT:  Amylin is co-secreted with insulin in non-diabetics; amylin has appetite suppressant and lipolytic effects.”

So insulin is completely innocent? If you believe this is the case, then riddle me this. Explain the following evidence to me purely in terms of calories-in-calories-out. Fast forward to minute 7:00 of this clip from Taubes’ lecture series. There you will see a slide of a diabetic woman (Not Safe For Work, by the way — the woman is nude!) who gained enormous deposits of fat on her thighs after injecting insulin in her thighs for years.

Did that woman gain that fat in her thighs because she over-ate? Or because she didn’t exercise enough?

The consumption of excess calories clearly did not cause her to develop huge lobes of fat at the precise location of her insulin injection spots.

Those fat deposits were clearly caused by the insulin injections. She then “overate” enough food to supply the nutrients to nourish that new fat tissue. In at least this case, the “overeating” was clearly a consequence, not a cause, of the fat accumulation.

This is a very clear example of insulin acting as a lipogenic agent. In other words, INSULIN made that woman gain fat where she did.

Is insulin the ONLY lipogenic agent? No.

Is the science of fat regulation dazzlingly complex? Yes.

But insulin is INVOLVED. It is SIGNIFICANT. And it is significant not only when it comes to the cause/cure of obesity but also when it comes to the likely cause/cure of chronic diseases like Alzheimer’s, cancer, and so on.

In conclusion, to a first degree, two things almost certainly must be true about all of this:

1) Some form of the carb/insulin hypothesis of obesity and chronic disease should be our collective null hypothesis that we can shape and modify. I’m not saying we all hop on the carbs->insulin->obesity train and call it a day. But this hypothesis should be our home base. Our starting point. The new paradigm for thinking about obesity and disease.

2) The Bray interpretation of the 1st Law of Thermodynamics — the so-called calories-in-calories-out paradigm — has been decisively exposed as nonsense.