Monday, June 3, 2013

Dr. Jekyll dieted and became Mr. Hyde

One of the most fascinating topics for an independent health researcher is the dichotomy between short- and long-term responses in successful dieters. In the short term, dieters that manage to lose a significant amount of fat mass, tend to feel quite well. Many report that their energy levels go through the roof.

A significant loss of fat mass could be considered one of 30 lbs, or 13.6 kg. This is the threshold for weight loss used in the National Weight Control Registry. Ideally you want to lose body fat, not lean mass, both of which contribute to weight loss.

So, in the short term, significant body fat loss feels pretty good for the dieters. In the long term, however, successful dieters tend to experience the symptoms of chronic stress. This should be no surprise because some of the same hormones that induce a sense of elation and high energy are the ones associated with chronic stress. These are generally referred to as “stress hormones”, of which the most prominent seem to be cortisol, epinephrine (adrenaline), and norepinephrine (noradrenaline).

Stress hormones display acute elevations during intense exercise as well ().

This is all consistent with evolution, and with the idea that our hominid ancestors would not go hungry for too long, at least not on a regular basis. High energy levels, combined with hunger, would make them succeed at hunting-gathering activities, leading to a period of feast before a certain threshold of sustained caloric restriction (with or without full fasting) would be reached. This would translate into a regular and cyclical hunger-feast process, with certain caloric costs having to be met for successful hunting-gathering.

After a certain period of time under sustained caloric restriction, it would probably be adaptive among our ancestors to experience significant mental and physical discomfort. That would compel our hominid ancestors to more urgently engaged in hunting-gathering activities.

And here is a big difference between those ancestors and modern urbanites: our ancestors would actually be working towards getting food for a feast, not restraining themselves from eating what they have easily available at home or from a grocery store nearby. There are major psychological differences here. Dieting, in the sense of not eating when food is easily available, is as unnatural as obesity, if not more.

So what are some of the mechanisms by which the body dials up stress, leading to the resulting mental and physical discomfort? Here is one that seems to play a key role: hypoglycemia.

Of the different types of hypoglycemia, there is one that is quite interesting in this type of context, because it refers to hypoglycemia in response to intake of any food item that raises insulin levels; that is, food that contains protein and/or carbohydrates. More specifically, we are referring here to reactive hypoglycemia, of the same general type as that experienced by those on their way to type II diabetes.

But reactive hypoglycemia in successful dieters is often different from that of prediabetics, as it is caused by something that would sound surprising to many: successful dieters appear to become too insulin sensitive for their own good!

There is ongoing debate as to what is considered a blood glucose level that is low enough to characterize hypoglycemia. Several factors influence that, including measurement method and age. One important factor related to measurement method is this: commercial fingerstick glucose meters tend to grossly underestimate low glucose levels (e.g., 50 mg/dl shows as 30 mg/dl).

Having said that, glucose levels below 60 mg/dl are generally considered low.

Luyckx and Lefebvre selected 47 cases of reactive hypoglycemia for a study, from a total of 663 standard four-hour oral glucose tolerance tests (OGTT). They classified these 47 cases as follows, with the number of cases in each class within parentheses: obesity (11), obesity with chemical diabetes (9), postgastrectomy syndrome (3), chemical diabetes without obesity (1), renal glycosuria (7), and isolated reactive hypoglycemia (16).

Postgastrectomy is the period following a gastrectomy, which is removal of part of one’s stomach. The modern term for this stomach amputation procedure is “bariatric surgery”; admittedly a broader term, which many people say they would do as if they were referring to a walk in the park!

In the cases of isolated reactive hypoglycemia, the individuals had normal weight, normal glucose tolerance, and no glycosuria (excretion of glucose in the urine). As you can see in the paragraph above, this, isolated reactive hypoglycemia, was the category with the largest number of individuals. The figure below illustrates what happened in these cases.

The cases in question are represented in the left part of the graph with dashed lines (the full lines are for normal controls). There a reasonably normal insulin response, lower in fact in terms of area under the curve (AUC) than for the controls, leads to an abnormal reduction in blood glucose levels. They are 9 out of 16, the majority of the isolated reactive hypoglycemia cases. In those 9 individuals, insulin became “more potent”, so to speak.

Reactive hypoglycemia is frequently associated with obesity, in which case it is also associated with hyperinsulinemia, and caused by an exaggerated insulin response. About 40 percent of the reactive hypoglycemia cases in the study were classified as happening in obese individuals.

This study suggests that, if you are not obese, and you are diagnosed with reactive hypoglycemia following an OGTT, chances are that the diagnosis is due to high insulin sensitivity – as opposed to low insulin sensitivity, coupled with hyperinsulinemia. A follow-up test should focus on insulin levels, to see if they are elevated; i.e., to try to detect hyperinsulinemia.

I have been blogging here long enough to hear from people who have gone the full fat2fit2fat cycle, sometimes more than once. They start dieting, go from obese to lean, feel good at first but then miserable, drop the diet, become obese or almost obese again, then start dieting again …

Quite a few are folks who do things like ditching industrial foods, regularly eating organ meats, and doing resistance exercise. How can you go wrong doing all of these, generally healthy, things? Well, they all increase your insulin sensitivity. If you don’t build in plateaus to slow down your progress, you may not give your body enough time to adapt.

You may become too lean, too fast, for your own good. The more successful the diet, the bigger is the risk. No wonder the paleo diet is being targeted lately as a “bad” diet. How can you go wrong on a diet of whole foods; “real” whole foods, not “whole wheat”? Well, here is how you can go wrong. The diet, if not managed properly, may be too successful for your own good; too much of a good thing can be a problem, you know!

See the graph below, from a previous post on a related topic (). I intend to discuss a method to identify the point at which weight loss should stop, in a future post. This method builds on the calculation of a simple index, which is unique to each individual. Let me just say now that I suspect that, with exceptions, frequently people are hurting their health by trying to have six pack abs.

But what does all this have to do with stress hormones? The connection is this. Hypoglycemia is only “felt”, as something unpleasant, due to the body’s frequent acute stress hormone response to it. Elevated levels of stress hormones also increase blood glucose levels, countering hypoglycemia. Our body’s priority is preventing hypoglycemia, not hyperglycemia ().

And here is an interesting pattern, based on anecdotal evidence from HCE () users. It seems that folks who have abnormally high insulin sensitivity, also have medium-to-high HbA1c (a measure of glycation) and fasting blood glucose levels. By medium-to-high HbA1c levels I mean 5.7 to even as high as 6.2.

Since cortisol is elevated, one would expect higher fasting blood glucose levels – the “dawn phenomenon”. But higher HbA1c, how? I am not sure, but I believe that HbA1c will be found in the future to be something a bit more complicated than what it is believed to be: a measure of average blood glucose over a period of time. I am not talking here about cases of anemia.

One indication of this complicated nature of the HbA1c is the fact that blood glucose levels in birds are high yet HbA1c levels are low, and birds live much longer than mammals of comparable size (). Some birds have extremely high glucose levels, even carnivorous birds who consume no or very small amounts of carbohydrate (e.g. hawks), with fairly low HbA1c levels.

The title of this post is inspired in the classic short novel “Strange Case of Dr. Jekyll and Mr. Hyde” by the Scottish author Robert Louis Stevenson; who also authored another famous novel, “Treasure Island”. In “Dr. Jekyll and Mr. Hyde”, gentle Dr. Jekyll becomes nasty Mr. Hyde (see poster below, from Wikipedia).

Mr. Hyde had a bad temper, impaired judgment, and was prone to criminal behavior. Hypoglycemia has long been associated with bad temper, impaired judgment, and criminal behavior (, ).


penis buyutme said...

this is a very Nice Post,

David Isaak said...

Hi, Ned--

Very interesting indeed.

As far as the idea that hormones help us in searching for a feast, I think you are probably right.

I am also coming to believe that the most unnatural thing we do is to consume roughly the same quantity of calories and roughly the same qualities of foods day after day.

If people really wanted to go "paleo" I suspect they would mix it up more: feast and fast, huge protein volumes one day, a ton of berries the next, maybe nothing at all on the third day...

As the Greeks failed to say, immoderation in all things.

Anonymous said...

This does only apply to people who diet down more than 30lbs? What about someone who was fairly lean all his life and wants a six pack, dieting for no more than 10lbs?

Kindke said...

"Dieting, in the sense of not eating when food is easily available, is as unnatural as obesity, if not more"

Thats the key point and something im sure everyone has noticed. When your sitting there, feeling very hungry, and restraining yourself from eating, you generally find yourself completely unmotivated to do ANYTHING ( except, acquire food ).

IF your employed you may be sitting there feeling completely unmotivated to do your job, but as soon as lunchtime comes around, and you think about going to the supermarket, SUDDENLY you feel motivated and full of energy. This is what sapolsky talks about when he says "dopamine" is about pursuit of reward and motivation. I.E. dopamine makes you "do" stuff. When your sitting there at your desk, and hungry, thinking about doing your work doesnt elicit a dopamine response, but thinking about going to the supermarket probably does elicit a massive dopamine response, suddenly making your motivated and energetic.

Theres another interesting paper by Kathleen D. Vohs that looks at how self-control changes your perception of time and I can relate to this fully. When your sitting there, hungry, trying to stop yourself from eating because your "dieting", time feels to move especially slowly. Constantly your looking at the clock. On my nightshifts at work I have noticed that when ordering a large takeaway meal the nights tend to feel like they go quickly, as compared to those nights where I just have a whey protein shake and some nuts.

Self-Regulation and the Extended Now: Controlling the Self Alters the
Subjective Experience of Time

Mordecai said...


After losing 110 pounds in 16 months on a LCHF ad libitum diet I still have 95 pounds to lose. But I ran into a wall in the last 4 months, even with the addition of calorie restriction and more exercise.

Kindke's writing suggests that this plateau may be the result of completing the reversal of adipocyte hypertrophy, and I may now be stuck with the wages of adipocyte hyperplasia, reversable only by apoptosis (i.e. deus ex machina) if at all.

This post however, seems to suggest that my plateau could be the result of a long term excess of stress hormones.

Does this mean that there's still hope of continued weight loss for someone like me, but that calorie restriction and large quantities of exercise are now the wrong approach? I should just stick with ad libitum LCHF indefinitely, and hope?

Thanks much ...

Nigel Kinbrum said...

This is interesting. During an insulin stress test (10U of fast insulin) on my pituitary gland, my serum glucose fell to 2mmol/L (36mg/dL). I felt sweaty & shaky but otherwise O.K. I lost intellectual function, of which I was completely unaware.

Steve Cooksey over-exercised while on a VLC diet and had a fainting spell. I blogged about it in "Funny turns": What they aren't and what they might be.

For the last six years, while mum was ill with Lewy Body Dementia, I was quite irritable. Since mum passed away, I have become less irritable and I also temporarily wee'ed rather a lot! I think that I probably had high serum cortisol due to chronic stress/low-grade depression while mum was ill and that went away when she died.

J. Stanton - said...

The study I referenced in this article contains graphs of glucose, insulin, and epinephrine release over time in response to three different meals of varying composition.

Note the negative blood glucose excursion and the huge epinephrine spike resulting from the quickest-digesting meal ("high-GI")...and the subjects weren't even weight-reduced!


Ned Kock said...

Hi Anon. Has that person been trying and having problems getting the six-pack abs? If yes, I’d like to know more.

Ned Kock said...

Hi Mordecai. How do you know that you have more 95 lbs to lose?

Ned Kock said...

Interesting JS. And not shown in the graphs is the resulting change in blood glucose due to the adrenaline spike. Since presumably the acute increase in adrenaline is in part an attempt to raise blood glucose levels, we should see a sharp increase in blood glucose as well after those adrenaline spikes. This is illustrated in this graph, for some individuals at least:

Here may be the reason for the high HbA1c levels seen in some of these folks. Blood glucose spikes, happening multiple times, may lead to more glycation – causing a widening gap between HbA1c levels and average blood glucose over a period of time.

Anonymous said...

Hi Ned, i had one ill informed attempt at reducing my weight from "skinny with some subcutaneous fat in the belly region", using the diet and training regime you get if you ask popular media what one should eat and do. No consistency in macro and micro-nutrients, too much empty calories, jogging for sports. Gave up due to hunger issues.

Now, several years later, after doing my research (here and on similar blogs and info sites) which led to a diet roughly in the paleo vein, doing IF as well as proper weight training, hunger is way less of an issue.

Since doing this, i added some muscle (did a bulk of roughly 10kg over the last year), while my subcutaneous fat stayed subjectively the same. Now i feel like going for an attempt at reducing it - up to a point thats comfortable and healthy. If that includes six packs, all the better.

Mordecai said...


> Hi Mordecai. How do you know that you have more 95 lbs to lose?

I'm a life-long yo-yo dieter and I've been down to my (minus 95lbs from here) goal weight twice in my adult life before gaining back all plus more.

It felt wonderful to be at that weight. Long hikes that are a death march when I'm fat felt like I was just floating over the earth when near goal. For me that's about 17% body fat. The only drawback was somewhat more cold sensitivity.

My still big belly and the fact that I can only now fit into the largest of Walmart clothes are other indications.

I'm very happy with my results up to now of course, and with LCHF I feel much less inclined to start binging again. But still it's disappointing to hit the wall.

Cross country hiking is my thing and I've arranged my life to make it a daily habit, working remotely as a programmer from a rural lot on the edge of a huge public forest. Now I can walk maybe 4 miles over rough ground before exhaustion. At goal I could do 20 miles day after day. I'm greedy and want some more of those miles back.

Thanks again for your very valuable blog.

Ned Kock said...

Anon, Mordecai: This is an issue that I am still thinking about, but it seems wise to reduce one’s weight until the following ratio is minimized, and no further: (waist circumference) / (total body weight).

This ratio should follow a U-curve pattern, going down as one loses body fat, and going up again at some point when one starts having difficulty retaining lean body mass.

Going beyond this may be unhealthy, predisposing one to infections, regardless of whether one is ripped or not.

Most sedentary folks would probably not have six-pack abs at this point.

Tread said...

I'm really looking forward to the post about finging a set point for "ideal" bodyfat for each individual.

I've been skinny/slim all my life, but gained quite a bit of weight over a few years in my mid-30s when my metabolism slowed down and had a broken bone. I became the dreaded skinny-fat guy, 94kg at 183cm.

I then dieted back down to below 12% bodyfat, lost 25kg and 25cm from my waist, and now have almost a six pack. I did it with IF, paleo, weightlifting (minimal volume maximal intensity Reverse Pyramid Training) and LeanGains, and took 1.5 years to do it.

Now I'm 38, 3 months after the cut. I have kept everything the same, but increased my weighlifting volume and intensity (Starting Strength) calories above maintenance levels (-10% TDEE on off-days, +40% or higher on workout days). My muscle mass has increased a bit, strength quite a bit, and my bf% has remained steady.

So, I am now clean bulking, and don't see any issues in maintaining 12% bf. This is possibly because my (skinny) fat period was relatively short (3-4 years), I didn't crash diet, I'm naturally skinny/slim with fast metabolism, and have poor appetite. Or perhaps the worst is yet to come, and I will relapse :P

I have considered dieting down to below 10% bodyfat, but I'm not entirely convinced that it is a healthy and sustainable bf level.

Patrick Snook said...
This comment has been removed by the author.
Patrick Snook said...

Hi Ned,

I see you're still thinking about it, but could you please elaborate on this, explain the cause-and-effect, from your reply to Mordecai/Anon:

"This ratio should follow a U-curve pattern, going down as one loses body fat, and going up again at some point when one starts having difficulty retaining lean body mass."

Many thanks,


Anonymous said...

Hi Ned,

i would love to add to Patricks question with a related one:

Why would the body feel the need to metabolise its muscle before its fat reserves? Is it the lack of a strong enough stimulus in the form of training, or can that happen even with resistance taining?


Ned Kock said...

Hi Patrick. That will require a full post in the future. The idea is simple though. Let us say you lose only body fat when you lose weight. Your waist then will shrink up to a point, and so will your waist/weight ratio. Beyond that point, you’ll start losing lean mass and your waist will no longer shrink, at which point your waist/weight ratio will go up again.

In reality people don’t lose only body fat when they lose weight, and different people will start losing lean mass at different levels of body fat. The waist/weight ratio could be useful in the identification of that optimal point, which would also be influenced by diet and lifestyle.

This needs a future post. Two foundational posts are linked below, with additional links to other reference posts within them:

Ned Kock said...

Anon, our body consumes about 5 g of glucose per hour; mostly our brain. For someone who has undergone adaptation to low glucose availability, this will go down a bit, but not much.

These 5 g have to come from somewhere. While one is fasting, the 5 g will come from one’s liver glycogen stores. These stores grow as one adapts to intermittent fasting, with 100 g being a reasonable estimate of their capacity, in my opinion.

When one is under stress, this consumption seems to go up, possibly due to loss from increased re-cycling. Stress hormones increase blood glucose levels by stimulating liver secretion, excess glucose is re-stored as glycogen in the liver, later it is secreted again, and so on.

Muscle glycogen stores, a much larger “tank”, are “locked” until one does glycogen-depleting exercise. But during exercise those stores are recycled, so muscle can be seen as a one-way consumer of glycogen, not a giver. This of course as long as one is using muscle on a regular basis, otherwise atrophy ensues.

If you are under caloric deficit, and combine that deficit with glycogen-depleting exercise, you end up losing muscle – not muscle cells, but amino acid content. Low amino acid content stimulates replenishment, but the body also likes to use amino acids as a source of energy. In fact, if amino acids and glucose are available, amino acids will be prioritized as a source of energy, but not exclusively (it will always be a mix of what is available, including FFAs and fat from VLDL particles).

Among all of the macronutrients, the one with the greatest protein-sparing capacity is not even protein, it is fat. Why is that? The reason is that protein is prioritized for energy generation when it is in circulation. If you are in caloric deficit, you’ll experience a loss of amino acids.

A side note. Most successful approaches to building muscle and losing fat rely on cycling between caloric deficits and surpluses. Building muscle and losing fat, in combination, are necessary in competitive bodybuilding and in many weight-class sports that require strength.

Another side note. You might have noticed that in weight-class sports that require strength usually the most “ripped” athletes (ripped = low body fat percentage) are in the categories below heavyweight. Interesting eh? You may want to take a look at this post:

Abhi said...

Regarding NEd's comment:

(waist circumference) / (total body weight).

This ratio should follow a U-curve pattern, going down as one loses body fat, and going up again at some point when one starts having difficulty retaining lean body mass.

This is a very accurate and practical observation, from my own experience. I used Paleo to lose weight from 89 KGs (waist 41inches) to about 73 KGs (waist 35 inches) over 15 months. I kept accurate measurements of waist/arm circumference and body weight.

I observed that after I reached 77 kgs, i did not reduce much of my waist circumference and started losing muscle mass after that to the extent that i looked very skinny at 73 kgs height 5 ft 10 in.
(I was aiming for a 6 pack and almost got there... but i was too skinny and even started losing hair on my head) I guess the combination of VLC and massive weight loss was too stressful for my body...

I am back to 87kgs now 2 years later, and am planning to reduce my weight gradually by trying to maintain as much muscle mass as possible.

Unknown said...

Wow. This is one of your most interesting articles Ned.

I totally agree with these two statements:

"If you don’t build in plateaus to slow down your progress, you may not give your body enough time to adapt."

"You may become too lean, too fast, for your own good. The more successful the diet, the bigger is the risk."

I'm looking forward to reading your post about the method to identify the point at which weight loss should stop.

ProudDaddy said...

My comment didn't get published, and I won't try to duplicate the whole thing. Suffice it to say that Figure 2B in "Normal Weight Obesity...", Romero-Corral, et al., European Heart Journal 2010, if correct, is an astounding statement on the effect of waist size.