Stable isotopes: their use and safety in human nutrition studies


Stable isotopes have been used as tracers in human nutritional studies for many years. A number of isotopes have been used frequently to assess body composition, energy expenditure, protein turnover and metabolic studies in general, such as deuterium (2Hydrogen), 18Oxygen, 13Carbon and 15Nitrogen. Nevertheless, there is still occasional confusion and concern over their safety, which can hinder the appropriate use of these isotopes in human studies. This mini review aims, therefore, to consider the safety of the four stable isotopes mentioned above, and to reiterate and reaffirm their safety once again. It is hoped that these data will be of use to new researchers in the field, as well as those considering the ethical or other implications of using these stable isotopes in nutritional research. Undoubtedly some of the confusion arises as deuterium, especially, is associated with the nuclear industry. However, as their name implies, of course, none of these stable isotopes are radioactive, and no adverse biological or physiological effects have been reported at the very low levels of enrichment that are used in human studies. There are ample data to reaffirm the safety of stable isotopes at the levels used in nutritional research, and unnecessary concerns and/or confusion should not be a block to continued use of these important tracers.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    Wong WW, Abrams SA. Production of stable isotopes for Nutrition related research. In: Abrams SA, Wong W, editors. Stable isotopes in human nutrition. Laboratory methods and research applications. New York: Oxford University Press, Cabi publications; 2003

  2. 2.

    Roberts SB, Coward WA, Schlingenseipn KH, Nohria V, Lucas A. Comparison of the doubly labelled water (2H2 18O) method and indirect calorimetry and a nutrient balance study for simultaneous determination of energy expenditure, water intake and metabolizable energy intake in preterm infants. Am J Clin Nutr. 1986;44:315–22.

    CAS  Article  Google Scholar 

  3. 3.

    Hoover JD, Wong WW, Adachi I, Brandt P, Jeewa A. Energy intake and expenditure in children with heart failure. Pediatr Crit Care Med. 2018;19:E627–30.

    Article  Google Scholar 

  4. 4.

    Al-Mokbel A, Courtney-Martin G, Elango R, Ball RO, Pencharz PB, Tomlinson C. Tryptophan requirement in school age children determined by the indicator amino acid oxidation method is similar to current recommendations. J Nutr. 2019;149:280–5.

    Article  Google Scholar 

  5. 5.

    Desneves KJ, Panisset MG, Rafferty J, Rodi H, Ward LC, Nunn A, et al. Comparison of estimated energy requirements using predictive equations with total energy expenditure measured by the doubly labelled water method in acute spinal cord injury. Spinal Cord. 2019.

  6. 6.

    Koletzko B, Sauerwald T, Demmelmair H. Safety of stable isotope use. Eur J Pediatr. 1997;156(Suppl 1):S12–7.

    CAS  Article  Google Scholar 

  7. 7.

    Klein PD, Klein ER. Stable isotopes: origins and safety. J Clin Pharm. 1986;26:378–82.

    CAS  Article  Google Scholar 

  8. 8.

    Jones PJ, Leatherdale ST. Stable isotopes in clinical research: safety reaffirmed. Clin Sci (Lond). 1991;80:277–80.

    CAS  Article  Google Scholar 

  9. 9.

    Urey HC, Brickwedde FG, Murphy GM. A hydrogen isotope of mass 2. Phys Rev. 1932;39:164.

    CAS  Article  Google Scholar 

  10. 10.

    Schoenheimer R, Rittenberg R. Deuterium as indicator in the study of intermediary metabolism. Science. 1935;82:156–7.

    CAS  Article  Google Scholar 

  11. 11.

    Jones PJH, Scanu AM, Schoeller DA. Plasma cholesterol synthesis using deuterated water in humans: effects of short term food restriction. J Lab Clin Med. 1988;111:627–33.

    CAS  PubMed  Google Scholar 

  12. 12.

    Coward WA. Deuterium method for measuring milk intake in babies. Response to Baum D, Dobbing. J Lancet. 1979;314:309.

    Google Scholar 

  13. 13.

    Racette SB, Schoeller DA, Luke AH, Shay K, Hnilicka J, Kushner RF. Relative dilution spaces of 2H- and 18O-labelled water in humans. Am J Phys. 1994;267:E585–90.

    CAS  Google Scholar 

  14. 14.

    Spielman H, Nau H. Embryotoxiciy of stable isotopes and the use of stable isotopes in studies of teratogenic mechanisms. J Clin Pharm. 1986;26:474–80.360.

    Article  Google Scholar 

  15. 15.

    Wolf D, Cohen H, Meshorer A, Wasserman I, Samual D. The effect of 18O on the growth and reproduction in mice. In: Klein ER, Klein PD, editors. Stable isotopes: proceedings of the Third International Conference. New York: Academic Press, 1978:353–60.

  16. 16.

    Trowbridge FL, Graham GG, Wong WW. Body water measurements in premature and older infants using H2 18O isotopic determinations. Ped Res. 1984;18:524–7.

    CAS  Article  Google Scholar 

  17. 17.

    Jones PJH, Schoeller DA. Validation of doubly labelled water for assessing energy expenditure in infants. Pediatr Res. 1987;21:242–5.

  18. 18.

    Speakman JR. Doubly labelled water: theory and Practice. London: Chapman and Hall; 1997.

  19. 19.

    Walczyk T, Coward WA, Schoeller DA, Preston T, Dainty J, Turnlund JR, et al. Stable isotope techniques in human nutrition research: concerted action is needed. Food Nutr Bull. 2002;23:69–75.

    Article  Google Scholar 

  20. 20.

    Gregg CT, Hutson JY, Prine JR, Ott DG, Furchner JE. Substantial replacement of mammalian body carbon with carbon-13. Life Sci. 1973;13:775–82.

  21. 21.

    Gregg CT. Some applications of stable isotopes in clinical pharmacology. Eur J Clin Pharm. 1974;7:315–9.

    CAS  Article  Google Scholar 

Download references


This paper was prepared with support from the International Atomic Energy Agency, Vienna.

Author information



Corresponding author

Correspondence to Peter S. W. Davies.

Ethics declarations

Conflict of interest

The author declares no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Davies, P.S.W. Stable isotopes: their use and safety in human nutrition studies. Eur J Clin Nutr 74, 362–365 (2020).

Download citation