Applied Trophology, Vol. 9, No. 5
(May 1965)

Amino Acid Content; U.S. Healthy?

Contents in this issue:

  • “Amino Acid Content,”
  • “U.S. Healthy?”

The following is a transcription of the May 1965 issue of Dr. Royal Lee’s Applied Trophology newsletter, originally published by Standard Process Laboratories.

Amino Acid Content

Taken in part from “Evaluation of Protein Quality.” Report of an International Conference Committee on Protein Malnutrition, Food and Nutrition Board, National Academy of Sciences. National Research Council, Publication 1100, March 1963.

B. Effects of Excessive Intakes of Amino Acids

If a diet contains a surplus of amino acids which cannot be used for protein synthesis, the efficiency with which the dietary protein is used will be low. Also, if the unbalance is large enough, the requirement of the animal for the amino acid in greatest deficit in the diet may be increased. The extent to which the amino acid pattern of a diet may be unbalanced without affecting amino acid requirements has not been adequately studied, and it is difficult, except when the quantity of dietary protein is inadequate to support maximal growth, to assess accurately whether the amino acid needs of an animal have been slightly increased.

1. Amino Acid Imbalance and Chemical Score

The results of amino acid imbalance studies indicate that even a small increase in the concentrations of certain amino acids can sometimes increase the amounts of others needed to maintain a given rate of growth when the total protein intake is low.100 In most of the studies in which an effect of dietary level of protein on amino acid requirements has been demonstrated, the requirements have been expressed as a percentage of the diet; hence, it is not always clear whether the absolute amount of amino acid required to support a given rate of growth is increased. In a two-week study101 in which wheat gluten was used, the requirement for lysine as a percentage of the diet and the total amount of lysine to support maximum growth were both increased. There is an analogy between experiments on the effect of dietary level of protein on amino acid requirements and experiments on amino acid imbalance. When a mixture of amino acids lacking one amino acid is added to a diet, especially a low-protein diet, and an imbalance is created, the total amino acid (protein) content of the diet is increased and more of the limiting amino acid, expressed as a percentage of the diet, is required to prevent a depression in growth rate. The absolute amount of amino acid required to overcome the depression may also be increased.100,102

The accepted relationship between the Chemical Score (amino acid balance) of a protein and its nutritional value may be affected by an amino acid imbalance. In experiments on protein mixtures having a wide range of Chemical Scores, prepared from combinations of casein and gelatin, the rat tolerated a protein mixture with a “Chemical Score” (based on the amount of tryptophan per 16 gm of nitrogen, assuming that methionine-supplemented casein has a Chemical Score of 100) of 50 without any apparent ill effects. If the Chemical Score fell below 50, food intake and growth were depressed. Further work is needed to check this observation with other protein combinations. This effect apparently is not detected if Biological Value is determined by the classical paired-feeding technique with mature animals.103,104

No adverse effect of poor amino acid balance would be detected in comparisons involving paired feeding if the food intake of an animal fed a diet with a poorly balanced pattern of amino acids fell to the point at which it consumed only as much protein as it could metabolize efficiently. Measurements of growth and efficiency of nitrogen utilization in experiments in which nitrogen balance and paired-feeding techniques were used to study the effects of an amino acid imbalance support this conclusion.105,106 However, when food consumption and growth are used as criteria, the performance of an animal fed a diet in which there is an imbalance of amino acids may be much below that predicted from the amino acid pattern of the diet or its Chemical Score.

2. Effects of Excesses of Individual Amino Acids

Also arising from the concept of amino acid balance is the question of how large an excess of an individual amino acid an organism can tolerate. Over the years many observations have indicated that there is a definite limit of tolerance for most amino acids, and that this limit depends upon the level of protein in the diet, the levels of certain vitamins such as pyridoxine and niacin, and the age of the animal.107 The quantities of individual amino acids shown to exert toxic effects have been well beyond those that could logically be used as dietary supplements.

a. Toxic effects from excesses of amino acids

The term toxicity as applied to amino acids has been rather loosely used. The evidence of toxicity has been obtained from animal experiments. Besides increased mortality, and lesions of the eyes, skin, liver, and pancreas, depressed growth rate has in many experiments also been taken as evidence of toxicity. Amino acid toxicities may be reduced in severity by improving the quality of low-protein diets with supplements of the limiting amino acid, but a growth depression is not completely prevented by this procedure. With an amino acid imbalance, improving the quality of a low-protein diet with a supplement of the most limiting amino acid completely prevents the growth depression, and usually stimulates growth.

The quantity required to cause toxicity varies greatly among the individual amino acids,108,109 indicating as Russell, et al.110 suggested that the basis for the effect is probably dependent on the structure and metabolism of the particular amino acid. Methionine, cystine, tyrosine, tryptophan, and histidine, which enter into many metabolic pathways, appear to be most toxic. Isoleucine and valine, which are readily oxidized completely and are not metabolized by a wide variety of pathways, are less toxic.111 The others fall variously in between, roughly in the sequence leucine, phenylalanine, arginine, lysine, and threonine, although there is not complete agreement about this.108, 109

In general, the toxic effect of a given quantity of an individual amino acid is less when the diet is adequate than when it is inadequate, probably because the well-nourished animal is better able to metabolize an excess of many of the individual amino acids than an animal on a deficient diet. There appears, however, to be a definite limit to the amount of several of the amino acids that can be metabolized efficiently even by an animal fed an adequate diet.

The growth depression due to an excess of an individual amino acid is greater when the diet is low in protein, indicating that the organism can tolerate an excess of one better when it has an adequate supply of all of the others.109,112–116 However, there have been few studies of amino acid toxicity in which the dietary level of protein and the toxic level of the amino acid have been increased proportionally. In one such study, when the proportion of tyrosine to fibrin was kept constant, toxicity occurred with each level of protein (Stucki, W.P., and Harper, A.E., unpublished). Also, severe growth depressions due to excesses of methionine and tryptophan have been observed in animals fed a 30–40 percent protein diet.112

b. Amino acid antagonism

Two examples of adverse effects of dietary excesses of individual amino acids appear to be unique. These are effects of an excess of leucine113 and an excess of lysine.117 These are classified as amino acid antagonisms because excess leucine depresses the utilization of the structurally similar isoleucine and of valine when the latter two are not limiting for growth,119 and excess lysine depresses the utilization of arginine. An amino acid antagonism differs from an imbalance in that the growth depression caused by an imbalance is prevented by a supplement of the most limiting amino acid, whereas the growth depression due to an antagonism is not prevented by a supplement of the most limiting amino acid unless this is one of the antagonistic amino acids. The distinction between amino acid antagonism and toxicity is that the former is alleviated by structurally similar amino acids, whereas the latter is not. Addition of 2 percent of L-leucine to an isoleucine deficient diet increased the requirement of the rat for isoleucine,113 and addition of 2 percent of lysine to a diet marginal in arginine increased the requirement of the chick for arginine.117 Further, the growth of rats fed diets high in leucine and low in isoleucine was stimulated (DeMuelenaere, H.J.H., and Harper, A.E., unpublished) when the leucine content of the diets was reduced.118 Since an amino acid antagonism, like an imbalance, depresses food intake, the growth of an animal fed a diet in which there is enough of an excess of an ammo acid to cause an antagonism may be less at the same level of protein than would be predicted from the Chemical Score of the diet.118

The bases for the adverse effects attributed to amino acid imbalances, antagonisms, and toxicities have not been established. A consistent finding is that alterations of the free amino acid pattern of the blood and body fluids are frequently more pronounced than would be expected from the amino acid pattern of the protein ingested.120,121,122 Food intake is rapidly depressed by all of these conditions, so it is difficult to distinguish clearly between direct metabolic effects of imbalances and antagonisms and the indirect effects of low food intake.

U.S. Healthy?

Back in June 1957, in Milwaukee, Dr. Paul Dudley White stated in an address before the Wisconsin Heart Association, “The present ‘epidemic’ of coronary thrombosis and atherosclerosis has made the United States ‘the most unhealthy country in the world.’”

This statement should bear weight as Dr. White was known worldwide as a heart disease specialist long before he attended President Eisenhower for his coronary attack. Since then, nothing has changed for the better or refuted Dr. White’s statement in its application today, as statistics show cardiovascular conditions continue to lead all causes of death in this country.

From a recent report by the American Heart Association, we learn the United States continues to lead the world in deaths from cardiovascular disease. The report shows South Carolina has the highest death rate and New Mexico the lowest. Washington D.C. leads all of our cities in deaths from heart disease.

“They that give up essential freedom for the sake of a little liberty, deserve neither one.”

—Benjamin Franklin




Heather Wilkinson

Heather Wilkinson is the Archives Editor for Selene River Press.

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