Monday, January 30, 2012

Kleiber's law and its possible implications for obesity

Kleiber's law () is one of those “laws” of nature that is both derived from, and seems to fit quite well with, empirical data. It applies to most animals, including humans. The law is roughly summarized through the equation below, where E = energy expenditure at rest per day, and M = body weight in kilograms.


Because of various assumptions made in the original formulation of the law, the values of E do not translate very well to calories as measured today. What is important is the exponent, and what it means in terms of relative increases in weight. Since the exponent in the equation is 3/4, which is lower than 1, the law essentially states that as body weight increases animals become more efficient from an energy expenditure perspective. For example, the energy expenditure at rest of an elephant, per unit of body weight, is significantly lower than that of a mouse.

The difference in weight does not have to be as large as that between an elephant and a mouse for a clear difference in energy expenditure to be noticed. Moreover, the increase in energy efficiency predicted by the law is independent of what makes up the weight; whether it is more or less lean body mass, for example. And the law is very generic, also applying to different animals of the same species, and even the same animal at different developmental stages.

Extrapolating the law to humans is quite interesting. Let us consider a person weighing 68 kg (about 150 lbs). According to Kleiber's law, and using a constant multiplied to M to make it consistent with current calorie measurement assumptions (see Notes at the end of this post), this person’s energy expenditure at rest per day would be about 1,847 calories.

A person weighing 95 kg (about 210 lbs) would spend 2,374 calories at rest per day according to Kleiber's law. However, if we were to assume a linear increase based on the daily calorie expenditure at a weight of 68 kg, this person weighing 95 kg would spend 2,508 calories per day at rest. The difference of approximately 206 calories per day is a reflection of Kleiber's law.

This difference of 206 calories per day would translate into about 23 g of extra body fat being stored per day. Per month this would be about 688 g, a little more than 1.5 lbs. Not a negligible amount. So, as you become obese, your body becomes even more efficient on a weight-adjusted basis, from an energy expenditure perspective.

One more roadblock to go from obese to lean.

Now, here is the interesting part. It is unreasonable to assume that the extra mass itself has a significantly lower metabolic rate, with this fully accounting for the relative increase in efficiency. It makes more sense to think that the extra mass leads to systemic adaptations, which in turn lead to whole-body economies of scale (). In existing bodies, these adaptations should happen over time, as long-term compensatory adaptations ().

The implications are fascinating. One implication is that, if the compensatory adaptations that lead to a lower metabolic rate are long term, they should also take some time to undo. This is what some call having a “broken metabolism”; which may turn out not to be “broken”, but having some inertia to overcome before it comes back to a former state. Thus, lower metabolic rates should generally be observed in the formerly obese, with reductions compatible with Kleiber's law. Those reductions themselves should be positively correlated with the ratio of time spent in the obese and lean states.

Someone who was obese at 95 kg should have a metabolic rate approximately 5.6 percent lower than a never obese person, soon after reaching a weight of 68 kg (5.6 percent = [2,508 – 2,374] / 2,374). If the compensatory adaptation can be reversed, as I believe it can, we should see slightly lower percentage reductions in studies including formerly obese participants who had been lean for a while. This expectation is consistent with empirical evidence. For example, a study by Astrup and colleagues () concluded that: “Formerly obese subjects had a 3–5% lower mean relative RMR than control subjects”.

Another implication, which is related to the one above, is that someone who becomes obese and goes right back to lean should not see that kind of inertia. That is, that person should go right back to his or her lean resting metabolic rate. Perhaps Drew Manning’s Fit-2-Fat-2-Fit experiment () will shed some light on this possible implication.

A person becoming obese and going right back to lean is not a very common occurrence. Sometimes this is done on purpose, for professional reasons, such as before and after photos for diet products. Believed it or not, there is a market for this!

Notes

- Calorie expenditure estimation varies a lot depending on the equation used. The multiplier used here was 78,  based on Cunningham’s equation, and assuming 10 percent body fat. The calorie expenditure for the same 68 kg person using Katch-McArdle’s equation, also assuming 10 percent body fat, would be about 1,692 calories. That would lead to a different multiplier.

- The really important thing to keep in mind, for the purposes of the discussion presented here, is the relative decrease in energy expenditure at rest, per unit of weight, as weight goes up. So we stuck with the 78 multiplier for illustration purposes.

- There is a lot of variation across individuals in energy expenditure at rest due to other factors such as nonexercise activity thermogenesis ().