Exercise training and muscle energy efficiency


I am always encouraging people to exercise for the general and brain health. Research has demonstrated that exercise obviously improves muscle function and your performance. Additionally, while exercising a trained individual is more efficient biomechanically and biochemically (including increased fat oxidation and number of mitochondria).

However, an unanswered question is the difference between trained and untrained sedentary individuals while at rest (in vivo).

Befroy et. al., PNAS, 2008 (open access) examined this question and the result have some interesting implications. They had 8 control subjects and 7 athletes of similar age (26), weight and BMI. The athletic group had to be performing 4 or more hours of running, or running based sports, per week. The peak VO2 max in the trained group averaged 60.9 which is considerably higher than normal sedentary peak of 30-40 (though they don’t report the exact numbers for the control group).

They measured mitochondrial oxidative function by examining the flux through the tri-carboxylic acid (TCA) cycle using magnetic resonance spectroscopy (MRS). They also importantly measured the rate of muscle ATP synthesis using MRS.


At rest (important distinction compared to more active) substrate oxidation via the TCA cycle was 54% higher in the muscles of the trained group. So with a 54% increase in substrate (fat and carbohydrates) oxidation what do you think would happen with muscle energy (ATP)?

Interesting part:

Muscle ATP synthesis at rest were not different between the trained and untrained group – despite the 54% increase in mitochondrial oxidation rate in the TCA cycle. Hence, it appears as if the trained group have a reduced muscle energy efficiency compared to the untrained.

The authors conclude that:

… there is an uncoupling of oxidation from energy production in endurance-trained muscle at rest.

Of course in the discussion they are trying to explain the lack of enhanced ATP in the trained group at rest – but in reality the body doesn’t need the extra energy. Sure the trained body has a greater number of engines (mitochondria) – but at rest there is relatively little need for all these energy producers. The authors suggest that, somewhat paradoxically, at rest the trained mitochondria become less efficient and go into a greater uncoupling state.

The results are consistent with the general literature of increased mitochondrial numbers, which would allow a higher rate of flux of the TCA cycle. These overall changes would allow a higher capacity for fatty acid oxidation and ATP production under high demand (e.g. running). Since the trained group has more mitochondria but at rest the muscle requires the same amount of energy (ATP) as the untrained group each mitochondria in the trained group is producing less energy per unit compared to the untrained. Hence, in the trained energy production at rest is less efficient. The decrease in energy efficiency results in an increase in basal TCA cycle flux and oxygen consumption.

Wow ! – that doesn’t sound good. Exercise and become less efficient – use more substrate (carbohydrates and fats) and a greater amount of oxygen but get the same amount of energy.

However, the elevation of TCA flux may also be a benefit when starting an exercise bout as one could more quickly ramp up ATP production. And from previous research we know that once you get beyond the resting state the trained system kicks in and will easily outperform the untrained one.

Other considerations:

But these results might also explain how we hear so many stories of overweight people not eating much but still gaining weight (or at least not losing weight) compared to lighter, more in shape individuals who can eat a ton and not gain weight. The overweight out of shape individual would have a more efficient mitochondria – extracting a higher percentage of energy per food unit compared to the trained individual.

Additionally, the uncoupling in the trained individual would result in high heat production from the uncoupling process. Looking at this evolutionary heat production was very important as we migrated to cooler climates. So the ‘wasted’ energy of inefficient trained muscles wouldn’t really be such a waste since it would be a possible benefit. In our modern world of climate controlled houses this is not a concern.

Many of you might have observed that on a cool fall day it is the ‘less trained’ individuals wearing warmer clothes including hats, gloves etc – while you can spy these slim runner types walking around in a t-shirt. The above at rest muscle energy inefficiency and subsequent increased excess heat production could be an explanation.

I would even offer the hypothesis that the individual can tell their level of fitness by the changes they notice in level of clothing they require during the cool/cold season.

Take home message:

Exercise can make your at rest energy production less efficient (compared to untrained) – due to the fact the muscles don’t require much energy in this state. And while being less efficient sounds bad – once you ramp up energy need (as required to do physical work – and for survival in our past) the trained system outperforms the untrained. As an added bonus – that was probably vital to survival in the past – the inefficient energy system produced by training (or trying to live in the past) results in extra heat production  at rest.

Additionally, the results from the paper might help explain why it is easy to keep lean if you exercise (more wasted energy in the form of heat) and hard to reduce weight if you are in an untrained state. So to lose weight start exercising so you become less energy efficient – I know that sounds weird.

How much clothing are you wearing walking around outside this fall?