Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure. Academic Article uri icon


  • To determine if age-associated vascular dysfunction in older adults with heart failure (HF) is due to insufficient synthesis of nitric oxide (NO), we performed two separate studies: 1) a kinetic study with a stable isotope tracer method to determine in vivo kinetics of NO metabolism, and 2) a vascular function study using a plethysmography method to determine reactive hyperemic forearm blood flow (RH-FBF) in older and young adults in the fasted state and in response to citrulline ingestion. In the fasted state, NO synthesis (per kg body wt) was 50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine. Citrulline ingestion (3 g) stimulated de novo arginine synthesis in both older [6.88 0.83 to 35.40 4.90 mol kg body wt(-1) h(-1)] and to a greater extent in young adults (12.02 1.01 to 66.26 4.79 mol kg body wt(-1) h(-1)). NO synthesis rate increased correspondingly in older (0.17 0.01 to 2.12 0.36 mol kg body wt(-1) h(-1)) and to a greater extent in young adults (0.36 0.04 to 3.57 0.47 mol kg body wt(-1) h(-1)). Consistent with the kinetic data, RH-FBF in the fasted state was 40% reduced in older vs. young adults. However, citrulline ingestion (10 g) failed to increase RH-FBF in either older or young adults. In conclusion, citrulline ingestion improved impaired NO synthesis in older HF adults but not RH-FBF, suggesting that factors other than NO synthesis play a role in the impaired RH-FBF in older HF adults, and/or it may require a longer duration of supplementation to be effective in improving RH-FBF.

published proceedings

  • Am J Physiol Endocrinol Metab

altmetric score

  • 17.1

author list (cited authors)

  • Kim, I., Schutzler, S. E., Schrader, A., Spencer, H. J., Azhar, G., Deutz, N., & Wolfe, R. R.

citation count

  • 45

complete list of authors

  • Kim, Il-Young||Schutzler, Scott E||Schrader, Amy||Spencer, Horace J||Azhar, Gohar||Deutz, Nicolaas EP||Wolfe, Robert R

publication date

  • December 2015