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Structure
A nucleotide consists of a base (either a purine, such as adenine, or a pyrimidine, such as cytosine) linked to a sugar (either ribose or deoxyribose) and one, two or three phosphates.
Functions
Nucleotides form the basis of DNA and RNA, are important in tissues with rapid turnover (for example, gut and immune system) and are metabolic regulators (involved in energy transfer, ‘acid’ handling, synthesis and breakdown of large molecules.)
Sources
There are three sources of nucleotides:
- Dietary
- Manufactured from various amino acids
- Salvaged as they are liberated from cells
Nucleotides and their bases are not considered ‘essential’ because they can be synthesised from simpler substances. At certain times, however, the processes of synthesis may not be able to meet demand, for example, during periods of rapid cell turnover as in normal growth or in gut disease. At these times, the body relies more heavily on dietary sources of nucleotides. Therefore, nucleotides are regarded as ‘conditionally essential nutrients’, especially in certain conditions when they must be provided in the diet.
There is wide variation in reports of the amount of nucleotides found in breast milk. The variation depends on analytical methods, the individual nucleotides measured, the inclusion of nucleic acids and nucleosides along with the nucleotides, and whether the nucleotides present in the cells in the milk are included. At birth, colostrum provides the highest concentration of nucleotides and during the first four weeks of lactation, the nucleotide concentration falls by about a half. Mature human breast milk contains at least 10 mg/litre of nucleotides, depending on the methods used, and may contain more if the nucleotides present in the cells in the milk are included in the analysis.
Cow’s milk contains considerably lower amounts of nucleotides and their exact chemical composition differs from those in human milk. Due to degradation during heat treatment, many infant formulas contain low concentrations of nucleotides so that supplements are added during the manufacture of some infant formulas. European regulations permit a maximum concentration of 5 mg/100kcal of nucleotides to be added to infant feeds (with variable amounts for each specific nucleotide) while recommendations from The USA Life Sciences Research Office (LSRO) allow up to 16 mg/ 100 kcal.
As a result, it is likely that infants receiving nucleotides from breast milk or a supplemented formula rely less on new synthesis of nucleotides from amino acids or their salvage from other cells to meet their requirements.
At weaning, good sources of dietary nucleotides are fish, poultry and meat. Some peas and pulses provide nucleotides, but, generally, milk products and vegetables are poor sources.
The effects of nucleotide supplementation
The results of many investigations show the effects, in vitro and in animals, of nucleotides on the gut, immune function, the liver, metabolism and the brain.
Far fewer studies have been done with human babies and some have been criticised because they are not randomly assigned, double blind trials; the amount of nucleotide received is unclear; or there have been so many observers that ‘standardisation’ is difficult. However, a few studies have shown some benefits of supplemental nucleotides including the growth enhancement of babies born light for gestational age, fewer episodes of diarrhoea, improved immunological functions in babies’ blood with greater antibody responses to diphtheria and haemophilus influenzae immunisations, and changes in lipid metabolism.
Views differ on whether nucleotides should be added to all infant formulas. Some experts argue that since nucleotides are present in human milk and may have positive effects, they should be added to formulas unless there is good evidence to the contrary. Others wish to see more research to critically assess the benefits and appropriate level of nucleotide supplementation.
References
Two major symposia were published in 1994 (1., 2. below.) Recent reviews below are by Carver (3.), Cosgrove (4.), Jagadeesan (5.), Levy (6.), and Yu (7.)
Walker WA. Symposium: nucleotides and nutrition. J Nutr. 1994;124:121 S–164S.
Rudolph FB. Symposium: Dietary nucleotides. J Nutr. 1994;124:143S–144S.
Carver JD. Dietary nucleotides: effects on the immune and gastrointestinal systems. Acta Paediatr Suppl. 1999;88: (430): 83–8.
Cosgrove M. Perinatal and infant nutrition: Nucleotides. Nutrition. 1998; 14 :748– 51.
Jagadeesam V. Nucleotides in nutrition. Nutrition in disease management. Update Series. Nutrition Foundation of India 2000; 7: 7–16.
Levy J. Immunonutrition: the pediatric experience. Nutrition. 1998; 14:643–77.
Yu, VY. The role of dietary nucleotides in neonatal and infant nutrition. Singapore Med J. 1998;39: 145–50.
May 2003
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