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.