June 9, 2009

Good Science: Dr. Leibel Explains Metabolic Slowdown with Weight Loss

I first learned about Dr. Rudolf Leibel's groundbreaking work in obesity studies when I read the book, Fat : Fighting the Obesity Epidemic back in the 1990s.

Dr. Leibel and Dr. Jules Hirsch research obesity at Rockefeller University. In a field where 99% of the published research would not earn a grade of "A" in a 9th grade science class, these researchers stand out. They use rigor and carefully applied scientific techniques and it is very hard to find flaws in their research.

Where other nutritional researchers based their studies of food intake on infamously inaccurate nutritional questionnaires filled with questions of appalling vagueness, like "How many times in the last month did you eat cheese", these researchers study subjects who live at their lab for months at a time where every bite that goes into their mouth is measured and tracked.

And not just what goes in. Because their focus is on the metabolic changes that occur with various food intakes, they also measure a lot more.

Rather than summarizing, I'll give you a quote from Dr. Leibel, which appeared in a wonderful interview published in Scientific American. The whole interview is well worth reading. You'll find it HERE.

In that interview, Dr. Leibel explains how he determines calorie expenditure when tracking metabolic changes in his subjects. What follows is a lengthy excerpt, but it is impossible to communcate the rigor of his research without quoting the whole thing:
... We use heavy isotopes of water. Here we give the patient two isotopes of water to drink... We give them deuterated water [also known as heavy water] and O18 water. So one is tagged on the hydrogen and one is tagged on the oxygen.

The interesting thing is that when you give somebody water like this, the deuterium comes out of the body which is determined by water turnover in the individual. The O18 is in equilibrium with carbon dioxide, so the O18 comes out by two mechanisms: first with normal water by transpiration, perspiration and urine, but also in the breath. The difference between those two decay curves (the O18 comes out faster), which we obtain by getting urine from these patients every day for 10 days-that gap is proportional to carbon dioxide production in that individual. By doing this, we can figure out how much carbon dioxide this person made over a period of 10 days. Knowing that, and knowing what the so-called diet quotient is-in other words, what the ratio of carbohydrates to fat in their diet is-you can back-calculate the amount of oxygen used to produce that amount of carbon dioxide. So by some simple algebra using the rate of carbon dioxide excretion, you can actually calculate how much oxygen their body used in the process of oxidative metabolism. That is a very critical number because it tells you how much energy they burned. Oxygen consumption can be immediately converted into calories.

Then we take the individual and we measure their body composition-how much fat is in the body-by different techniques. We weigh them in air, then weigh them in water, using Archimedes' principle. We do a scan of the body with low-energy x-rays. And we also do it by isotope distribution, since when we administer the doped water, it gets distributed in the body's water space, not in the fat. So by looking at the partitioning of that water we can get another measure of body composition. So we very carefully document the amount of body fat in these people at the end of these periods of weight stability.

Then we put them through a series of metabolic studies: looking at how they metabolize glucose, how much insulin the pancreas produces, what thyroid hormone is doing, what the catecholamines are doing-in other words, how much epinephrine and norepinephrine they're producing-and how much dopamine they're producing.

... We use a technique called spectral analysis, in which you deconvolute the heart rate and also by drug blockade techniques, where we give doses of atropine and esminol sufficient to totally lyse the activity of one limb of the autonomic nervous system. By then studying heart rate in these people we can actually tell whether either their sympathetic or parasympathetic nervous system has been cranked up or cranked down as a result of changing their body weight.

Finally, these people are put through a series of measures of exercise physiology. We look at how skeletal muscle converts energy into work.... This is done by bicycle odometers and treadmills and also by putting one the of the large muscles into a nuclear magnetic resonance (NMR) device.

...we also measure the energy expenditure of the patient at rest. We put a hood over their head and measure the rate of oxygen consumption while they are resting. We measure the energy expenditure that occurs when they ingest a fixed number of calories-this is called the thermic effect of feeding.
Quite a step from giving a questionnaire with the question, "How many hours did you exercise in the past month" which is the usual way nutritional research papers attempt to answer the question of how many calories were burned.

One of the most intriguing findings of Dr. Leibel's exceedingly technical research has been that normal people appear to have a very powerful weight "set point." When they eat more than needed to maintain their weight at that set point, their body becomes 15% more efficient in burning off the excess calories. When they eat less than they need for maintenance, which is what happens with intentional weight loss dieting, their bodies become 15% LESS efficient.

Here's Dr. Leibel again, explaining this:
When you do these studies you find that when you force an individual's weight up 10 percent, they require more energy to maintain that higher body than you would predict based on their requirements at usual body weight.

There is some degree of heterogeneity. It is not that great, although you do occasionally see people who have very little increase in energy expenditure when they gain weight [emphasis mine] . Why somebody who has this change in body weight doesn't increase is a very interesting question.

...When a person goes down 10 percent in body weight, lean or obese their reduction in energy expenditure is in the 15 percent range. If you take them down by 20 percent, it doesn't get any more. So it appears that whatever this defense mechanism is, if you want to look at it teleologically like that, it kicks in quite early: 10 percent is enough to bring it out. We don't know whether five percent is, because we've never tested that small an increase in weight.

A fraction is due to changes in resting energy expenditure. But the majority of the change occurs in the energy cost of physical activity.... We're trying to figure out the mechanism by which a change in body weight not only would cause an alteration in resting energy expenditure but also in the energy cost of physical activity. Is something happening in muscle or in the autonomic nervous supply to skeletal muscle, which influences blood flow?
What I like about Dr. Leibel is his truly scientific objectivity. He doesn't speculate. He looks at the evidence and when the evidence does not explain his findings, he does more research. If everyone researching diet would do this, rather than doing idiotically designed studies intended only to prove their preesisting beliefs, we might actually understand what happens in a broken metabolism that causes people to adjust their setpoint ever upward, in contrast to what is observed to happen in a normal person.

Having reviewed the 1990s research, I did some Googling to see what Dr. Leibert was up to now, and I was rewarded with a wonderfully insightful study published last year.

Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. Rosenbaum M, Hirsch J, Gallagher DA, Leibel RL. Am J Clin Nutr. 2008 Oct;88(4):906-12.

In this study, the researchers took 21 people all of the same weight into their lab for the kind of "every molecule measured" study of their energy metabolism you read about above. Seven subjects had not lost weight. Seven had dieted down to that weight--a 10% loss from their starting weight in the past two months. Seven had dieted down to that weight--also a 10% loss from their starting weight at least a year before.

All subjects were fed precisely titrated nutritional formulas which matched their observed nutritional and caloric needs.
Twenty-four-hour total energy expenditure (TEE) was assessed by precise titration of fed calories of a liquid formula diet necessary to maintain body weight. Resting energy expenditure (REE) and the thermic effect of feeding (TEF) were measured by indirect calorimetry. Nonresting energy expenditure (NREE) was calculated as NREE = TEE - (REE +TEF).
When the last drop of urine and sweat had been accounted for here's what they found:

"Declines in energy expenditure favoring the regain of lost weight persist well beyond the period of dynamic weight loss."

Even a whole year after losing weight, people's metabolisms remained depressed.
TEE [total energy expenditure}, NREE [nonresting energy expenditure], and (to a lesser extent) REE [resting energy expenditure] were significantly lower in the Wt(loss-sustained) and Wt(loss-recent) groups than in the Wt(initial) group. Differences from the Wt(initial) group in energy expenditure were qualitatively and quantitatively similar after recent and sustained weight loss.
Now it's important to keep in mind that these are metabolically normal people--they don't have to contend with autoimmune attacked thyroids, flaky adrenals, or failing beta cells. Those of us who have diabetes who have embarked on intense stints of dieting and emerged with little to show for it may find in the experience of these normal people, some hint of what we are up against.

This research suggests very strongly, and Dr. Leibel stresses that everyone can lose weight by cutting back on calories. But after the set point is attained, the body will fight back against further weight loss by decreasing how much it burns even when we are sleeping.

In considering this research, it's worth noting that the study subjects were eating so called "balanced" diets, high in carbohydrates. One can only dream of seeing studies that look at what happens, metabolically to people on long term low carb diets subjected to this kind of study.

Because of what we see with leptin studies, my guess is that there is still a significant, persistent metabolic slowdown no matter what nutrient mix a person eats. But my own observations and the data I have collected--through feeble questionnaires of course, since no one is entrusting me with their precious bodily fluids--suggest that low carb dieting may give us another 5-10% worth of leeway before the inevitable metabolic slowdown kicks in.

That might explain why so many people who responded to my low carb diet questionnaire report stalling at 20% of initial weight lost and regaining when they get below that figure. My own maintainable set point appears to be at 15% of initial weight lost. Below that and regain is inevitable.

OTOH, most people eating carb controlled diets or using strategies that keep their blood sugars normal do report that they are able to maintain their 15-20% weight loss long term. Many more than the statistics on weight loss maintenance drawn from studies of people on standard diets would predict. I weighed in at 142 lbs this morning which represents complete maintenance of my 2002-2003 weight loss coming from a high of 170 lbs.

I do have to restrict calories to maintain and it takes effort. But it can be done. Metformin REALLY helps. I am starting to think that whatever it does to liver and muscles may fight the metabolic slowdown that Dr. Leibel has so brilliantly discovered and described.

20 comments:

Anonymous said...

Interesting article. It may offer a means by which heavy exercise has been noted to help some people keep fat off. Maintaining 20 pounds of excess muscle may be metabolically expensive. If you slow down the exercise program (as I did last year after an undiagnosed neurological/fatigue session) muscles go, and fat comes back. Taubes maintained exercise does not help in weight loss, and while I understand his reasoning those of us over at jpfitness have observed otherwise. RobLL

Jenny said...

Rob,

Somewhere else in the Leibel interview, he points out that obese people end up with 30% more lean muscle than normal people which makes the loss of metabolic burn all that more puzzling since they don't necessarily lose all that muscle with short term weight loss.

My guess with the studies that Taubes cites is that they are looking at averages. Using averages rather than medians is the explanation for why a lot of research turns out to be useless.

On average, exercise doesn't appear to help prevent regain, but if you look at how data is collected and analyzed, the quality is so poor (That "How many hours did you exercise in the past month" questionnaire) that the studies are probably not worth poring over.

If exercise helps, go for it. It never did anything for me as far as weight loss though I did a lot of it through the years. But then I'm not IR and I have my share of weird metabolic things going on.

ItsTheWooo said...

I have maintained a loss of 160 pounds (present weight 124ish) and I have had resting metabolic studies. My RMR is roughly 1000 calories, which is actually 80% of expected. In my case, the drop in RMR is greater than 16%.

If anything, I think low carb diet actually DECREASE RMR more than do carb diets, because very low carb dieting suppresses the sympathetic nervous system. If I eat carbs I can expect an increase in sympathetic nervous system activity, thus changes like increased blood pressure and a higher metabolic rate.


However, and this is an important point, there is more to "calories out" than the metabolic rate. A substantial amount of calories are actually wasted in terms of heat, and this is NOT measured by a resting metabolic/oxidative metabolism test.
This is where low carb diets really shine. It is shown in studies that hyperinsulinemic, hyperglycemic, obese individuals have depressed levels of thermogenesis while they are maintained on carbohydrate diets... but eating low carb diets dramatically increase the amount of food calories wasted as heat particularly in those with metabolic problems (the obese, hyperinsulinemic).


So even though my resting metabolic rate is roughly 1000 calories, and I do very little exercise, I am able to eat about 1600-1700 food calories per day and still maintain my weight. Which is approximately a normal intake for a woman of my size, perhaps a little less. The reason I am able to eat so much is that even though the low carb diet suppresses resting metabolic rate/oxidative metabolism ("energy") ... so much of food is wasted as pure heat when eating a high protein/high fat/low carbohydrate diet.


The irony is, even though my metabolism and body temperature can be expected to increase when eating a high carbohydrate diet, I actually am able to eat substantially less calories (about 1500) before I start gaining weight. This is directly because high carb diets suppress dietary thermogenesis and uncoupling proteins in metabolically atypical people (e.g. the obesity prone, the hyperinsulinemic).

Kathy W. said...

Thanks for posting this excerpt, and the links.

For me, diabetes + menopause has made it incredibly difficult to lose weight. (Compared to this, weight loss was effortless in my 30s!) From 2001 to 2005, I lost 22% from my starting weight -- incredibly slowly, about 6 to 10 pounds a year. When I hit 22% lost (which was still 20+ pounds from my goal weight), I started slowly regaining (faster than I lost, of course!). Like trying to turn an ocean liner, I managed to stop the regain after putting back on more than half the weight lost, which put me at a 10% net loss.

It feels like an epic battle.

Jenny said...

ItsTheWoo,

Thanks for posting the very insightful comment! That about LC depressing the sympathetic nervous system fits in with somethings I've read elsewhere.

Interestingly, when I take metformin, my blood pressure and pulse stay very low. When I don't they both go up and I have to take Diovan whether or not I'm eating a lot of carbs.

That's also very interesting about the increased thermogenesis. I am having an ongoing problem with being freezing all the time, despite every thyroid test being normal. I often feel very cold when the thermometer is at 75. It's worse since I went on the metformin, and I have read this is often a problem for people who are taking Byetta, too.

Donn said...

Seth Roberts who wrote the Shagri-La Diet describes how he believes you can change your set point. His basic premise is that calories associated with flavor cause your set point to raise, and calories not associated with flavor causes your set point to lower.

His blog is at:
http://www.blog.sethroberts.net/

A long but interesting article is at:
http://sethroberts.net/about/whatmakesfoodfattening.pdf

In this article he used sugar flavored water, in his book he recommends flavorless oils which have the same affect, but are heather (especially for those with glucose issues).

Jonah said...

Well, this study definitely does not describe my experience- I can't keep my weight up. But then, I'm a 20 year old male with hyperthyroidism, diabetes, and IBS.

So here's a question about those studies: you said the subjects were healthy. What age range were they in? Would you expect that weight gain and loss dynamics would be the same in people in their 80s, 60s, 40s, and 20s?

Jenny said...

That Seth Roberts claim sounds extremely silly to me and the kind of thing people come up with who are selling diets.

If you can find any objective evidence to back this up, let me know. But it sounds like pure snake oil.

===
Jonah,

Follow the link and you can read the study yourself and see if it answers your questions. That's why I provide the links.

Donn said...

Dr. Davis from the heart scan blog is where I read about the diet. The following is a quote from him on thier form:
2) Weight loss. Although my experience is preliminary, the bland oil between meals idea articulated in another thread on this Forum, the idea promoted by Seth Roberts in his awfully-named Shangri La diet, works (to my great surprise). 1-2 tbsp between meals, nothing to eat one hour before or after the oil. If you follow what Roberts articulates, extra-light olive oil, canola, walnut, or flaxseed (my preference) works. Although he believes it is the lack of taste that is important, I'm not so sure. Nonetheless, to my surprise, it appears to work, particularly if undertaken along with a wheat-free, cornstarch-free diet.

Trinkwasser said...

Agreed, it would be fascinating to see the results of such research on diabetics, hypothyroid etc. and other "outliers": I'd volunteer as a member of a family many of whom can easily attain the blood glucose, blood pressure, insulin resistance and lipids of an obese person without gaining weight.

Being locked in the lab might give me time to research leptin

Jim, the Guacamole Diet guy said...

"most people eating carb controlled diets or using strategies that keep their blood sugars normal do report that they are able to maintain their 15-20% weight loss long term."

At least that's encouraging. I wonder if an extremely low carb diet would do even better.

Jenny said...

Jim,

It has been my observation over almost 11 years of reading low carb and diabetes diet boards, that almost no people who eat very low carb diets are able to stick with them for more than three years.

The strength of the moderate low carb diet is that people are able to stick to it much longer. But with the VLCD people go through a religious conversion, are excited for a few years, get bored, often their energy starts to flag after a few years, too, and they end up going off the diet, often intensely, and even oftener regaining everything they lost and more.

That's why I advocate for a more restrained approach to LC for controlling diabetes. People with diabetes have to maintain control for many decades to come.

Jim, the Guacamole Diet guy said...

I have read Seth Roberts' book, and it sounded nutty to me at first. However, I know someone who knows Seth Roberts, and I understand that Seth keeps very meticulous records of his self-experimentation. That often leads him to some surprising conclusions. I wouldn't just automatically reject anything he says. However, I suspect the extra-light olive oil works because it has lots of fat, not because it has little taste.

Trinkwasser said...

Some people report a degree of adrenal suppression from metformin.

I know your principal problem isn't IR or metabolic syndrome but I have been poring over this

http://www.nutritionandmetabolism.com/content/2/1/3

really need to borrow someone else's brain to fully grasp it, but glucocortisoids may conceivably be involved in your and ItsTheWoo's reponses

billye said...

I have been on a low carb diet for 8 months. I am also a former type 2 diabetic. I dare say that I am cured due to my last two HBA1C tests, 4.9 and now 4.7. I started out at 240 pounds and I am now 192 pounds. This is exactly the 20% figure that you say is max for weight loss. I hope you are wrong. My doctor who treats CKD with low carb-high fat lifestyle change along with high dose vitamin D3 and fish oil put me on this program. He says that I will continue to lose weight past the 20%. www.nephropal.blogspot.com is his very interesting site. What in g-ds name would make me go off this life style when I have such great control over my diabetes without any medication what so ever. I love the food and for the first time in my life I have complete control of my hunger drive.

Jenny said...

Billye,

The critical point to understand is this: You already have got all the health benefits you need and you will continue to experience them whether or not you lose more weight.

If you get too centered on weight loss, over time the frustration of not getting to goal can derail the diet and you lose those health benefits.

You are early in the process--this problem usually kicks in after a few years when the early enthusiasm wanes and the effort of eating differently from everyone around you can become more onerous.

But if you focus on the health benefit rather than a weight goal, you do have that continual reinforcement and over time, continual good health.

lightcan said...

Hi Jenny,

I don't agree with Woo saying that low carb increases thermogenesis. Losing weight (with low carb) might decrease T3, as in my case, and I feel cold all the time. I lost 36 out of 96 kg, that's roughly 30%.

Jenny said...

A decline in T3 is a known effect of low carb diets on some people. The Eades used to discuss it on their web page a decade ago, then they removed it, and when asked about it, said they had never said it. I double checked at the time , and found the old version page on The Wayback Machine web site where they reported treating some of their low carb diet patietns with T3.

Dr. Bernstein reports the slowing of thyroid function too, but insists it is from autoimmune thyroid disease, however as I have no autoimmune disease and definitely experienced a metabolic slowdown after 3 years of very low carb dieting, my money is on it being an effect of the body perceiving the ketogenic state as being starvation.

Lyle Macdonald calls the effect "euthyroid syndrome" in his book, The Ketogenic Diet.

lightcan said...

Thanks, Jenny,
I remember dr.Eades saying he treated somebody with T3

Honey Razwell said...

Lyle McDonald is a fraud and a salesmen. Dr. Leibel has clearly stated that with regard to body weight- the body completely has a mind of its own.