The Concept of Conditional Essentiality

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Snyderman (17) found that premature infants, in whom many enzymes of amino acid metabolism develop late during gestation, required cystine and tyrosine (which are dispensable for most full-term infants) to ensure nitrogen retention and maintain their normal plasma levels. Cystine and tyrosine were thus essential for premature infants. Rudman and associates (18, 19) subsequently proposed the term conditionally essential for nutrients not ordinarily required in the diet but which must be supplied exogenously to specific populations that do not synthesize them in adequate amounts. They applied the term initially to dispensable nutrients needed by seriously ill patients maintained on total parenteral nutrition (TPN). The term now is used for similar needs that result from developmental immaturity, pathologic states, or genetic defects.

Developmental Immaturity. Cystine and tyrosine, as mentioned above, are conditionally essential for premature infants ( 17). McCormick (3) has suggested that because preterm infants lack the enzymes for elongation and desaturation of linoleic and a-linolenic acids, elongated derivatives of these fatty acids, which are precursors of eicosanoids and membrane phospholipids, should be considered conditionally essential for them.

Damage to the cones of the eye and decline in weight gain of infant monkeys fed a taurine-free diet were prevented by supplements of taurine. In premature infants maintained on TPN without taurine, plasma taurine concentration declined, and the b-wave of the electroretinogram was attenuated. Gaull ( 20) suggests that taurine becomes conditionally essential for children maintained on TPN because they cannot synthesize enough to meet the body's need.

Plasma and tissue carnitine concentrations are lower in newborn infants than in adults, but this condition has not been associated with any physiologic defect. In infants maintained on TPN without carnitine, however, plasma and tissue carnitine levels are low, and in one study, this was associated with impaired fat metabolism and reduced nitrogen retention, both corrected by carnitine supplementation. Hoppel ( 21) concluded from a comprehensive review of the evidence that carnitine may be conditionally essential for premature infants maintained on TPN but is not conditionally essential for adults.

Pathologic States. Some patients with cirrhosis of the liver require supplements of cysteine and tyrosine to maintain nitrogen balance and normal plasma levels of these amino acids. Plasma taurine concentration also declines in adults with low plasma cystine levels. Insufficient synthesis of these nutrients in cirrhotic patients has been attributed to impairment of the synthetic pathway in the diseased liver. In some cancer patients, plasma choline concentrations declined by 50% when they were maintained on TPN. This was attributed to precursors of choline bypassing the liver during feeding by TPN ( 18).

In human subjects suffering severe illness, trauma, or infections, muscle and plasma glutamine concentrations decrease, generally in proportion to the severity of the illness or injury. In animals, decreased glutamine concentrations are associated with negative nitrogen balance, decreased tissue protein synthesis, and increased protein degradation. In clinical trials, nitrogen balance and clinical responses of surgical patients were improved by provision of glutamine in parenteral fluids following surgery. These findings support the conclusion that glutamine utilization exceeds its synthesis in patients in hypercatabolic states, and thus glutamine becomes conditionally essential for them (22).

Genetic Defects. Conditional essentiality of nutrients is also observed in individuals with genetic defects in pathways for synthesis of biologically essential but nutritionally dispensable substances. Genetic defects of carnitine synthesis result in myopathies that can be corrected by carnitine supplements ( 3). Genetic defects in the synthesis of tetrahydrobiopterin, the cofactor for aromatic amino acid hydroxylases, result in phenylketonuria and impaired synthesis of some of the neurotransmitters for which aromatic amino acids are precursors (3). Tetrahydrobiopterin is thus conditionally essential for such individuals.

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