The Merck-y waters of Amino Acids: 9 Inherent Difficulties in Defining Amino Acids | The National Academies Press

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img excerpt, The Journal of Biological Chemistry 2002. The American Society of Biochemistry and Molecular Biology

The enclosed and attached determination, put forward by D.Joe Millward in 1999, describes the inherent difficulties encountered in the act of defining amino acids.

Throughout this depiction, the author covers many integral areas relating to the substandard values and testing anomalies conveyed by prior biological chemistry experts. One which has been divulged on by is the testing and subsequent establishment of the basis for essentiality of amino acids by Dr.Rose and Associates in 1942. The study, as depicted above, states that “the “Subjects” were fed a diet consisting of corn starch, sucrose (sugar), butter fat without protein, corn oil, inorganic salts, the known vitamins and mixtures of highly purified amino acids”.

With testing of any type, especially one as important as this, it would be essential to feed the “Subjects” controlled healthy foods; closer to what they would ‘normally’ eat.

By not controlling the habitual adaptation quandary, as broached by D.Joe Millward below, the results are basically anomalous; further affected by the intake of food that each Subject was provided. As it is apparent that the study favored corn-based products for its Subjects, without providing any indication to the types of chemicals used in growing the corn or in converting the corn to oil, this would also affect the differing residual amino acids located in the Subjects urine.

Bryan Stralow

Protein and Amino Acids, 1999

Pp. 169-216. Washington, D.C.

National Academy Press

Inherent Difficulties in Defining Amino Acid Requirements

D. Joe Millward1


To address the role of protein and amino acids in performance, this chapter is based on the premise that it is an inherently difficult problem to define the dietary requirements of human adults for indispensable amino acids and to assess the nutritional value (protein quality) of different food protein sources to provide for those needs. There are three major reasons for this difficulty. The first is adaptation, that is, a variable metabolic demand for amino acids set by the habitual intake. Thus, the extent to which any intake appears to be adequate will depend on the completeness of adaptation to that intake. The second is methodology, with no entirely satisfactory practical nitrogen or amino acid balance method or other measure of dietary adequacy. The third is lack of quantifiable, unequivocal metabolic indicators of adequacy that can validate balance measurements. The questions posed in this review cannot currently be answered because of the absence of studies of outcome in terms of physical performance in long-term, controlled feeding trials.


In 1985, the Food and Agriculture Organization (FAO) report on protein and energy requirements was published (FAO/WHO/UNU, 1985), a feature of which was the recommendation that protein quality should be evaluated by the PDCAAS method (protein-digestibility corrected amine acid score), making use of age-specific amine acid scoring patterns. Because the indispensable amine acid (IAA) requirement values used to calculate the scoring patterns fell markedly with age, from over 50 percent of total protein requirement in infants to only 16 percent in adults (see Table 9-1), the quality of any protein would now be assessed as higher when used for adults than for children. Furthermore the low requirement level of IAA in adults meant that all natural diets and food proteins would be adequate. Thus, apart from digestibility, protein quality ceased to be an issue in the nutrition of adults.

Considerable disquiet arose about the 1985 report. Young (1986) argued that the adult IAA requirement values were seriously flawed because of the way Rose (1957) conducted his nitrogen (N) balance studies (mainly excess energy and no account for miscellaneous N losses). Millward and Rivers (1988) reviewed the subject, paying particular attention to the adaptive changes in amine acid oxidation that can occur and that will influence requirement values. They argued that the marked fall with age in the requirement values was mainly a reflection of the methodologies used in their assessment. Thus, the infant values were largely patterned on the composition of breast milk, while the adult values, measured in balance studies with excess nonessential nitrogen and low levels of indispensable amine acid, would have identified minimum requirement values. They concluded that IAA requirements are complex, include an adaptive component, and can only be defined under specific artificial conditions that would allow definition of a minimum value and that ”current estimates of adult requirements may be close to this level.” To identify which IAA might be rate limiting for the obligatory N losses (ONL), they calculated the obligatory oxidative amine acid losses (OOL) as estimates of the losses of tissue IAAs that would give rise to the ONL, as discussed in detail below.

Young et al. (1989) then published a paper entitled “A Theoretical Basis for Increasing Current Estimates of the Amine Acid Requirements in Adult Man with Experimental Support.” This paper reproduced the table of eel values from Millward and Rivers (1988). After making some small adjustments in lysine, threenine, and valine values derived from their stable isotope studies and increasing all values assuming a 70 percent efficiency of utilization, Young and colleagues proposed that this pattern, the “MIT” (Massachusetts Institute of Technology) scoring pattern, should be used as the basis for protein quality evaluation in adults and in children given the similarity between their pattern and that of the FAO preschool child pattern.

In 1989, FAO/WHO convened a meeting to consider protein quality evaluation and to endorse the PDCAAS method recommended by FAO in 1985. However the report (FAO/WHO, 1991) rejected both the 1985 adult and older school child IAA requirement values as flawed, was unable to identify any other appropriate adult scoring pattern, and proposed that the scoring pattern for the preschool child be utilized for older children and for adults as a strict interim measure. It was argued that (a) the preschool child data were reliable, (b) in the absence of any other data, some pattern was needed for older children and adults, and (c) the slow growth of children compared with adults means that a major change in the requirement pattern with age was unlikely.

Although Young and colleagues broadly agreed with this conclusion in that the MIT and preschool patterns were similar, Millward (1994) argued that the report was flawed. In fact, the data that formed the basis of the preschool child pattern had never been published and were not available for scrutiny except for some “typical” data for lysine published in a book review (Pineda et al., 1981). The data, which were derived from study of preschool children who had recovered from protein energy malnutrition (PEM), show that the N balances were so large in the children studied that they would have been exhibiting catchup growth as far as lean tissue was concerned (growth rates and N retentions of 3 times the expected values). This growth would markedly increase the need for indispensable amine acids compared with that of normal preschool children, older children, and especially adults. Millward (1994) also argued against acceptance of the MIT scoring pattern on the grounds that amine acid requirements for maintenance cannot be predicted from the amine acid composition of body proteins.

Fuller and Garlick (1994) have reviewed the controversy, and while they did not endorse the MIT pattern, they did conclude that the FAO values were likely to be underestimates, having failed to include miscellaneous N losses in the original balance studies. They reported adjusted higher values, taking into account estimated miscellaneous N losses. They also raised concern that the tracer studies may also suffer from an underestimate of losses and that neither N nor tracer studies are inherently better than the other. These issues are considered in more detail below. Waterlow (1996) made a detailed analysis of the tracer studies and came to conclusions similar to Fuller and Garlick, that is, they did not accept the theoretical basis of the MIT pattern but recognized that the 13C leucine studies do point to a higher leucine requirement than does the FAO value. The issue was considered at an international meeting of an expert group in London in 1994. However, contrary to what was published (Clugston et al., 1996), the MIT pattern was not endorsed at this meeting since, as subsequently reported by Millward and Waterlow (1996), the published statement “a large majority of the group accepted as an interim operational

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