Nucleotides as immunomodulators in clinical nutrition

Dietary nucleotides, like glutamine, have attracted attention as a key ingredient missing from nutritional formulae for many years. They are the building blocks of tissue RNA and DNA and of ATP and their presence in breast milk has stimulated research in babies which has indicated that supplementation of infant formula milk leads to improved growth and reduced susceptibility to infection. Animal studies have confirmed some of these data. In particular, dietary nucleotides modulate immune function, promote faster intestinal healing and have trophic effects on the intestine of parenterally-fed rats which are similar to those resulting from glutamine supplementation, but at much lower intakes. Nucleotide supplementation has also been shown to improve some aspects of tissue recovery from ischaemia/reperfusion injury or radical resection. There is, however, a fundamental paradox. The intestine and liver possess powerful homeostatic mechanisms which degrade intake of purines and pyrimidines (i.e. salvage) and replace it with de novo synthesised output. It is possible that peripheral tissues receive only small amounts of nucleotides of dietary origin. Previously, nucleotides have been proposed as being conditionally-essential nutrients that provide an adequate supply of purines and pyrimidines for nucleic acid synthesis in neonates or in the stressed patient. This review explores this puzzle in the light of recent data from nutritional studies and from research into purinergic signalling in the intestine, heart and cells of the immune system. We propose that dietary nucleotides should be considered within a pharmacological and metabolic framework.