Isotopic measurements of energy metabolism

In the past, determining an individual’s total daily expenditure depended on recording food intake over several days and measuring body composition changes during that period. This method, although widely used, is limited by the individual’s ability to keep accurate records and by the ability to match the individual’s activities to accurate energy costs.

Fortunately, the use of isotopes has expanded our ability to investigate energy metabolism. Isotopes are elements with an atypical atomic weight. They can be either radioactive(radioisotopes) or nonradioactive(stabile isotopes).  As an example, carbon-12 (¹²C) has a molecular weight of 12, is the most common natural form of carbon, and is nonradioactive. In contrast, carbon-14(¹⁴C) has two more neutrons than ¹²C, giving it an atomic weight of 14. ¹⁴C is created in the laboratory and is radioactive.

Carbon-13 (¹³C) constitutes about 1% of the carbon in nature and is used frequently for studying energy metabolism. Because ¹³C is nonradioactive, it is less easily traced within the body than ¹⁴C. But although radioactive isotopes are easily detected in the body, they pose a hazard to body tissues and thus are used infrequently in human research.

¹³C and other isotopes such as hydrogen 2(deuterium, or ²H) are used as tracers, meaning that they can be selectively followed in the body. Tracer techniques involve infusing isotopes into an individual and then following their distribution and movement.

Although the method was first described in the 1940s, studies that used doubly labeled water for monitoring energy expenditure during normal daily living in humans were not conducted until the 1980s. The subject ingests a known amount of water labeled with two isotopes(²H₂¹⁸O), hence the term doubly labeled water. The deuterium(²H) diffuses throughout the body’s water, and the oxygen-18(¹⁸O) diffuses throughout both the water and the bicarbonate stores(where much of the CO₂ derived from metabolism is stored). The rate at which the two isotopes leave the body can be determined by analysis of their presence in a series of urine, saliva, or blood samples. These turnover rates then can be used to calculate how much CO₂ is produced, and that value can be converted to energy expenditure through the use of calorimetric equations.

Because isotope turnover is relatively slow, energy metabolism must be measured for several weeks. Thus, this method is not well suited for measurements of acute exercise metabolism. However, its accuracy(more than 98%) and low risk make it well suited for determining day-to-day energy expenditure. Nutritionists have hailed the doubly labeled water method as the most significant technical advance of the past century in the field of energy metabolism.