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A 180-calorie tax every day
The extra burn
The study compared people with one of two rare mitochondrial diseases against healthy controls, and the data so far come from only 20 people. The extra burn amounted to 15% more energy, a 180-calorie tax every day of life, about the equivalent of a slice of pizza.
The participants with mitochondrial disease also reported feeling more fatigued and stressed than the controls did. Their blood showed elevated levels of metabolic molecules such as lactate, which indicate faulty mitochondrial performance and correlate with anxiety.
Out in real life
A second part of the study followed participants through nine days of free living in their normal lives. Instead of an IV line, they drank special water labeled with isotopes, and the lab measured how quickly the isotopes left their bodies in urine samples, a well-established proxy for metabolic rate.
Out in the real world, the calorie gap between the two groups nearly closed. Healthy participants expended 16% more energy than they had in the chamber, compared with just 5% for those with mitochondrial disease. The chamber's restrictions amounted to a more typical day for people with a mitochondrial disease, who move less because they feel low in energy.
Why would faulty mitochondria raise energy use?
Cells with failing mitochondria switch on stress programs, and those programs cost energy of their own. Cells that cannot burn fuel fully lean more on glycolysis, which yields about 2 molecules of ATP per glucose, compared with roughly 30 to 32 when mitochondria finish the job. Making up the shortfall means moving more fuel through the system. Higher resting energy use in mitochondrial disease is called hypermetabolism, and earlier studies in cells and animals described it before this chamber work.
How does labeled water reveal energy use?
The method is called doubly labeled water, and it uses heavier forms of hydrogen and oxygen. Hydrogen leaves the body only as water, while oxygen leaves as both water and carbon dioxide. The gap between how fast the two isotopes disappear from urine shows how much carbon dioxide the body made, and carbon dioxide output converts to energy burned. The biologist Nathan Lifson developed the technique in the 1950s, working with mice.
Why does lactate rise when mitochondria struggle?
Glucose is broken down to pyruvate, and healthy mitochondria take the pyruvate and burn it for energy. When they cannot keep up, cells convert the pyruvate to lactate instead. The lactate spills into the blood, where it can be measured. Doctors use blood lactate, along with its ratio to pyruvate, as a standard marker when evaluating suspected mitochondrial disease.
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