Amino acid excess and imbalances
The primary worth to the body of the proteins consumed in the diet is for the amino acids made available following digestion and absorption. The responses to higher intakes of protein and amino acid imbalances in rat and other animal studies have been fully discussed. Some forty to fifty years ago Harper and his colleagues drew attention to the possible toxic effects of either excess or imbalanced intakes of amino acids upon the metabolic behavior of the body(Harper et al, 1970). Although they stated that they were unable to develop a simple rule to be applied across the board, there are a limited number of general principles, which can be used to guide the approach to the human situation.
`It is important to distinguish clearly between deficiencies and imbalances of amino acids… Investigations of imbalances are concerned with the effects of surpluses of indispensable amino acids other than the one that is limiting for growth or maintenance … Again, it must be emphasized that the term amino acid imbalance is also de®ned operationally’.
There are a number of points of importance, which derive from this work:
1. The molar requirement by the metabolism of the body for non-essential amino acids (NEAA) is substantially greater than that for essential amino acids (EAA).
2. EAA are toxic in excess, when they are presented to the body at a rate which exceeds the rate at which they can be effectively disposed. Any toxic excess can have profound metabolic consequences.
3. One of the toxic effects of EAA is that they interfere with the normal metabolism of NEAA, and increased intakes of NEAA might ameliorate the toxic effects of some EAA.
4. The relative toxicity of any diet which contains excess, or an unbalanced mixture of amino acids, will depend upon the overall metabolic state of the animal, or the extent to which there are alternative routes for disposal(net protein deposition during growth), or the availability of critical NEAA for effective detoxification.
These observations are of direct relevance to the present considerations. The important issues in the determination of dietary protein requirements are the lower limit of intake, which ensures adequate availability of each EAA and NEAA, and the upper limit of intake before the toxic effect of one or other amino acid becomes manifest. Here we need to take care about how we de®ne the upper limit of intake for an amino acid, or determine when the capacity for metabolising an individual amino acid has been exceeded. We have become used to accepting toxic manifestations of an excess of a dietary intake of an amino acid as requiring rather extreme metabolic responses and have not been suf®ciently critical in identifying the normal limits of metabolic capacity within and between individuals in the population, and the need to identify the limits of adaptation within the `normal’ range of intakes. Animal studies show that the ability to tolerate a relatively small excess of one or the other amino acid is determined by the overall pattern of the diet in general and other amino acids in particular. The conclusion to be drawn from these observations is that the ability to tolerate an increase in protein, or amino acids, is related to the capacity of the body to meet its requirements for endogenously formed amino acids, and to effectively excrete any excess.