Essential Amino Acid Supplements

The building blocks of protein are called amino acids. Proteins are composed of long chains of amino acids, with the chains folded in complex ways. Twenty different amino acids that are used in building proteins are known. Almost all of these 20 amino acids are found in almost all proteins, in differing sequences. These different sequences cause the chains to fold in different ways, bringing about myriad different functions. Of these 20 amino acids, 12 can be synthesized by the body from simpler constituents. The other 8 cannot; we must include them in our diet. For that reason these 8 are called essential amino acids. Just why the body cannot synthesize these amino acids remains a mystery. But all 8 of them are broken down at a slow rate.

In a series of experiments conducted over a 10-year period in the 1940s, Dr. William C. Rose determined the minimum requirements of each of the 8 essential amino acids by feeding subjects (students at the University of Illinois at Urbana) a protein-free diet supplemented by pure amino acids in varying quantities and measuring all nitrogen consumed (as food) and all nitrogen excreted (as urine plus stool). The difference between nitrogen intake and nitrogen output, called nitrogen balance, is a measure of change in total body protein. For each essential amino acid, intake below a certain amount led to negative nitrogen balance, indicating progressive loss of body protein stores, while intake above a certain amount led to positive nitrogen balance, showing that body protein stores were increasing. Just how Dr. Rose induced these students to consume what must have been a frightful diet, supplemented by unpleasant-tasting powders, remains a mystery, but this work stands as a landmark in the history of protein nutrition. Dr. Rose also demonstrated that most of the requirement for phenylalanine can be met by a closely related amino acid, tyrosine, and most of the requirement for methionine can be met by a closely related amino acid called cystine.

The quantities of each essential amino acid required for normal adults, in mg per kg per day, are held to be as follows, according to values given in Recommended Dietary Allowances, derived chiefly from Dr. Rose's work:

tryptophan

3.5

threonine

7

histidine

8 to 12

isoleucine

10

valine

10

lysine

12

methionine plus cystine

13

leucine

14

phenylalanine plus tyrosine

14

The total of these is 94 mg per kg per day, or 6.6 g per day (about W2 teaspoonfuls) for a 70 kg (154 lb) person. Substantial caloric intake was necessary to achieve these results, and also a small amount of non-essential nitrogen from another nitrogen source, such as ammonium or glycine.

Thus, nutrition can be maintained on zero protein and as little as 10 g of amino acids, if a mixture of these 9 essential amino acids is provided and if calories, vitamins, and minerals are also provided in adequate amounts. This is nearly the diet that Giordano and Giovannetti gave to their patients. This approach has been a very unpopular because of the severely limited diet. The very-low-protein diet, supplemented by essential amino acids, is, by contrast, relatively acceptable. It contains little meat, poultry, fish, eggs, milk, or cheese, foods high in protein. But, if foods high in protein are avoided, the choice of foods is unlimited. The total dose of essential amino acids provided is usually 10 g per day, to be taken in three doses with meals. The reason for this recommendation is that it has been reported that nitrogen balance is better when all of the required amino acids are provided with a meal rather than between meals. The optimum dose is less certain.

The mixture of amino acids can be taken as a powder, mixed (for example) in apple sauce, but the taste is very unpleasant. More commonly it is taken as capsules or tablets. These tablets contain about 700 mg each, so the total daily dose is about 15 tablets.

Recently chemists have developed a way to mask the unpleasant taste of amino acids. Thus essential amino acids are available in almost any flavor as a powder that can be made into an instant beverage or candies. (See Appendix 1.)

These preparations, as well as pure amino acids, are considered dietary supplements and are therefore not subject to regulation by the Food and Drug Administration. The advantage is that they are readily available; the big disadvantage is that most insurers won't reimburse you for the cost. However, reimbursement for these products by Medicaid has been granted in several states.

Supplements of essential amino acids also improve nutrition (as evidenced by an increase in serum albumin levels, which reflect protein nutrition) in patients on hemodialysis, even without dietary protein restriction. Since they already are eating substantial amounts of protein, this is hard to explain. A randomized double-blind comparison study was performed on 29 patients on hemodialysis who had subnormal levels of serum albumin at the start. After three months, those on the amino acid supplement showed a significant increase in serum albumin concentration. The problem with this treatment was compliance: Patients grew tired of taking so many pills, and as the study progressed, they skipped more and more doses, or stopped taking supplements altogether. A parallel comparison in 18 patients on peritoneal dialysis failed to establish a significant effect on serum albumin level, perhaps because there were too few patients enrolled. Additional studies are in progress. It is hoped that the powder with the taste of amino acids masked may improve people's willingness to stick with the supplements.

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