Nutrient Requirements and Interactions
Pattern of Amino Acid Requirements in Humans: An Interspecies Comparison Using Published Amino Acid Requirement Recommendations1'2
M. J. McLARNEY, P. L PELLETT AND V. R. YOUHG*3 Department of Nutrition, university of Massachusetts, Amherst, MA 01003 and *Clinical Research Center and Laboratory of Human Nutrition, School of Science, Massachusetts Institute
of Technology, Cambridge, MA 02142 Downloaded from https://academic.oup.com/jn/article/126/7/1871/4723627 by guest on 25 September 2021
been the subject of various reviews (Irwin and Hegsted ABSTRACT We undertook an interspecies compari 1971, Munro 1972). National (Williams et al. 1974) and son of essential (indispensable) amino acid require international expert consultations (FAO/WHO 1973 ments, in relation to those for total protein, to examine and 1991, FAO/WHO/UNU 1985) have used the avail whether the current, internationally proposed human amino acid requirement patterns are significantly dif able data to arrive at proposed, or tentative, amino acid ferent from those of other animals. Data were compiled requirements [usually expressed as mg(kg •d)] and pat in their original form and then expressed as mg amino terns [usually expressed as mg amino acid/g crude pro acid/g total dietary protein (N x 6.25) required (amino tein (N X 6.25) required] for practical application in acid requirement pattern). Patterns of requirements human nutrition. We have questioned the validity of within the various species were organized according to four, arbitrary age-developmental groupings (very the current national (Williams et al. 1974) and interna young, early growth, growth and mature), and these tional (FAO/WHO/UNU 1985) values for indispensable were compared with the requirements for (a) human amino acid requirements in healthy human adults infants, (b) 2-5 year old children, (c) 10-12 year old (Marchini et al. 1993, Young 1991, 1992a and 1992b, children and (c) adults, respectively. Statistical com parisons determined if significant differences existed Young and Pellett 1990, Young et al. 1989). Further, between humans and other species, at apparently sim we have proposed a tentative new set of amino acid ilar age-development stages, for both the total and for requirements and a new amino acid requirement pat individual indispensable amino acids. The sum of the tern (Young and Pellett 1990) for the adult age group, specific indispensable amino acid requirements for hu mans was significantly different than that for other which differ markedly from those proposed in 1981 for species at infancy, growth and adulthood; the greatest adults by FAO/WHO/UNU (1985). Our tentative (MIT) differences, however, were for the amino acid require amino acid requirement pattern is comparable to the ment pattern in adulthood. The change between the preschool child amino acid requirement pattern (FAO/ very young and adult was the greatest for humans. WHO 1991, FAO/WHO/UNU 1985); we based our pro Some of this difference might be due to experimental posal on data generated from 13C-labeled amino acid factors, including the biological status of a species within the arbitrary groupings described and the crite tracer studies, as well as on considerations of the amino ria used to determine "requirements." nevertheless, acid composition of body mixed proteins (Young and it is difficult to escape the conclusion that the current El-Khoury 1995, Young et al. 1989). If our newly pro international human amino acid requirements, for adults in particular, appear to be anomalous when posed amino acid requirement pattern (mg amino acid/ judged against data for other animal species. J. Nutr. g protein required) is a better, quantitative approxima 126: 1871-1882, 1996. tion of the dietary needs in adult humans than is the pattern proposed by FAO/WHO/UNU (1985), this INDEXING KEY WORDS: could have important implications for the nutritional •humans •essential amino acids •indispensable amino acids •amino acid requirements 1Supported in part by National Institutes of Health grant DK •interspecies comparison 42101. 2The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 The requirements for the individual indispensable solely to indicate this fact. amino acids in human subjects of various ages have 3To whom correspondence should be addressed.
0022-3166/96 $3.00 ©1996 American Institute of Nutrition. Manuscript received 22 December 1994. Initial review completed 5 April 1995. Revision accepted 20 March 1996. 1871 1872 McLARNEY ET AL. evaluation of dietary protein in this age group and for previously some concerns about extrapolating specific the design and nutritional assessment of diets for adults animal amino acid requirement data to humans, the in health and disease. Experimental studies are under following analysis would seem to be reasonable in the way in our laboratories (El-Khoury et al. 1994a and present context. 1994b, Hiramatsu et al. 1994, Marchini et al. 1993 and Previously, few attempts have been made to com 1994) to further evaluate the merits of our hypothesis pare, in some detail, the human indispensable amino and the quantitative reliability of our tentative new acid requirements with those of other species (Smith requirement values (Young 1991 and 1992b, Young and 1980). Hence, the present study is a cross-species El-Khoury 1995, Young and Pellett 1990). amino acid requirement comparison designed to exam The determination of protein quality and the estab ine whether the human requirement pattern is signifi lishment of human amino acid requirements (FAO/ cantly different than that for other animals. We have WHO 1991) also have important public health and eco depended largely upon the requirement values pro nomic (Young and Pellett 1991) ramifications and rele posed by various expert groups because these figures Downloaded from https://academic.oup.com/jn/article/126/7/1871/4723627 by guest on 25 September 2021 vance for the establishment of sound national and in presumably reflect the best collective judgment of the ternational food and nutrition policies (Young and Pel relevant, published data for the various species exam lett 1990). The 1989 FAO/WHO committee on protein ined here. These values may well differ from those pro quality evaluation determined that the primary criteria posed by individual investigators. Thus, for example, for judging any food protein or mixture of food proteins the estimates made by Benevenga et al. (1994) of the should be its digestibility and its indispensable amino amino acid requirements for growth of laboratory rats acid content, relative to the pattern of amino acid hu differ substantially from those proposed by NRC man requirements (FAO/WHO 1991). (1978), and these more recent data may represent better An approach that might help to evaluate the practi estimates of the requirements for young, rapidly grow cal importance of human nutrient requirement data is ing rats. However, it seems appropriate to use the pub to relate these to comparable data obtained in other lished sets of requirement values that have emerged experimental animal species, to the extent that this is from the National Research Council (see below), be possible. In support of this suggestion, animals such as cause they are probably the most widely accepted fig hamsters, rabbits, rats, pigs and avian species have been ures and, therefore, useful for the present purpose. Fur used to help interpret, or predict, human metabolic thermore, had we used the data of Benevenga et al. responses to changes in the dietary protein and/or in (1994), our conclusions would remain as described dispensable amino acid supply, and this is particularly below. so with respect to an assessment of dietary protein quality (Pellett and Young 1980, Porter and Rolls 1973). Fuller and Garlick (1994) recently made extensive use of data obtained from experiments in pigs to evaluate MATERIALS AMD METHODS current estimates of the amino acid requirements in human adults. Therefore, we considered it potentially Database selection. Values for indispensable amino useful to make an extensive comparison of current hu acid requirements were obtained via an extensive li man amino acid requirement data with those for vari brary and computer-aided bibliographic search (Table ous experimental species. While all of the species ex 1 for source references); we have used, in particular, amined herein require the same minimal, qualitative the requirement estimates published by authoritative mix of indispensable amino acids as do human sub groups, especially NRC-National Academy of Sciences. jects, we recognize that different species exhibit unique With reference to the requirements for poultry, we used metabolic/nutritional characteristics. For example, the NRC (1984) requirement profile, which differs there are differences in the response in cats and dogs somewhat from the recently published NRC (1994) re to an arginine-free diet relative to that seen in humans port and also from that proposed by Baker and Han (Baker and Czarnecki-Maulden 1991, Carey et al. 1987) (1994) for chicks. However, these differences also and also in the sulfur amino acid metabolism (Mac- would not affect significantly the comparisons that we Donald et al. 1984) of these pets, compared with that have made below and the conclusions drawn from in humans. Furthermore, a major factor affecting them. amino acid requirements in the young is the postnatal All of the requirement data were compiled first in growth rate (Lewis 1992), which differs markedly their original form, using a spreadsheet software pro among species (Blaxter 1978, Brody 1945, Peters 1988, gram (LOTUS 123 3.1, Lotus, Cambridge, MA). The Taylor 1965), with the rate being relatively slow in requirement values for the species included in the pres humans. However, in partial support of the approach ent analysis were then converted to milligrams amino that we take below, Reeds (1988) has concluded that acid per protein requirement, or allowance. Our justi few fundamental differences in protein metabolism ex fication for this procedure is given below and the values ist between humans and other mammals. Although we obtained are presented in Table 1. For the animal spe (Young 1991, Young and El-Khoury 1995) have raised cies, requirements were calculated relative to the pub- COMPARATIVE AMINO ACID REQUIREMENT PATTERNS 1873
TABLE 1 birdsAge/development Amino acid requirements of mammals and development!Saaamino42334050382831213490.272533353736312738403540.1222333433263240.12173317551931170.56AaaThrTrpto age and
Protein groupVery indiet182312282424152160.3015221218242116131850.26121718151530.17129412940.39His26141525211515271950.281915211715131419161630.1719142114141630.211621131912164.0.27He46333642393241594090.232833393435212938323360.1728333933293440.13133828742541220.55Leu935659636842709364160.246655675659503969565690.17445668563955120.22194249432540100.26Lysmg664752585758548058100.185840584950335341324490.2144385347464660.1416422926363370.21accordingValTotalReferenceacid/g
protein72565867644875556090.1563556368593543693253150.2722566356425490.16196750433849130.2543383542363343473950.133438364437293138323650.1428313638313430.109332643253280.2617 youngHuman y)Chick infant (0-1 559 wk)Broilergrowth |0-6 3410 wk)Rat growth (0-3 3613 (weanling)^Turkeygrowth 509 wk|Swinegrowth (0-4 438
kg)Quail(105 339 Downloaded from https://academic.oup.com/jn/article/126/7/1871/4723627 by guest on 25 September 2021 growth)Hamster(start 4023 (weanling)3Mean 6112 human)so(excluding 425 7)CVEarly(n = 150.44 0.2411 growthHuman y)Chick (2-5 359 wk)Turkey(6-14 359 wk)Dog |4-8 4214 kg)Broiler(3 379 wk)Cat (3-6 366 wk)Swine(10 258 kg)Rabbit(10-20 3113 kg)MiceMean(1 448 4010 human)SD(excluding 363 8)CVGrowthHuman(n = 60.27 0.179
y)Chick (10- 12 259 wk)Turkey(14-20 349 wk)Broiler(11-14 429 wk)Swine(6-8 348 kg)Mean(50- 110 319 human)so(excluding 351 8)CVMatureHuman(n = 50.08 0.135
adultTurkey 138 holdingDog 428 adultRat2Swine, 3512 557 boarMeanadult 279 human)SD(excluding 402 4)CV%(n = 120.25 0.30460321340408375296378465369570.15339314370356336244275366288319460.15241304366321266314410.13127325253369214290700.24U)(2)(2)(4)(2)(5)(2)(4)(1)(2)(2)(3)(2)16)(5)(7)(4)U)(2)(2)(2)|5|HI(2)13)(4)(5)
1Total = (His, He, Leu, Lys, Saa, Aaa, Thr, Try, Val); Saa = methionine and cystine; Aaa = phenylalanine and tyrosine. 2 Value used is for methionine only. 3 Value is for phenylalanine only. References: 1, FAO/WHO/UNU (1985); 2, National Research Council (1984) (Nutrient Requirements of Poultry); 3, National Research Council (1985) (Nutrient Requirements of Dogs); 4, National Research Council (1978) (Nutrient Requirements of Laboratory Animals); 5, National Research Council (1988) (Nutrient Requirements of Swine); 6, National Research Council (1986) (Nutrient Requirements of Cats); 7, National Research Council (1977) (Nutrient Requirements of Rabbits). lished estimate of the required protein content of the metabolic/physiological characteristics shared by hu dry diet (listed in the first column of Table 1) and then mans. Hence, we reviewed, but did not include data assembled into one of four groups based on an arbitrary for fish and insect categories and the available data grouping for age/developmental stage (see below). for "breeding" and "lactation" groups were eliminated The data presented in Table 1 were selected from from this analysis, because direct determinations of the published requirement values for those species that indispensable amino acid requirements for these latter might be considered to have, in a broad sense, protein physiological conditions have not been undertaken in 1874 McLARNEY ET AL. human subjects. Additionally, if for any species there The present method of expression of requirements was not a complete requirement pattern for all of the is the same, therefore, as that used for evaluating the indispensable amino acids of interest, we eliminated relative capacity of food proteins to meet indispensable the data from further consideration. Arginine was not amino acid requirements. FAO/WHO/UNU (1985) ap included here because it appears to be a dispensable plies the term "pattern of requirement" to this form of amino acid, as judged by growth and nitrogen balance expression and here we are interested principally in criteria, in the nutrition of healthy humans. how this pattern for human subjects, at differing devel Expressions of requirements and use of groupings: opmental stages of life, compares with that for various assumptions and justification. Potential limitations other species. It should be noted that our use of this and criticisms of our inquiry are related to the follow form of expression of an amino acid requirement pat ing major considerations. First, requirements among tern differs from that of the so-called, ideal amino acid the various species studies have been established using "pattern," "profile" or "ratio," in which the require different criteria and diets, and this could well give rise ments for the individual indispensable amino acids are Downloaded from https://academic.oup.com/jn/article/126/7/1871/4723627 by guest on 25 September 2021 to differences among species due solely to methodolog expressed as a ratio of the requirement for a specific ical rather than to biological or species-specific factors. indispensable amino acid to that for a reference amino Thus, the requirements for the pig (NRC 1988), for acid such as lysine or tryptophan (Baker 1993, Baker example, are defined as the amounts required to and Han 1994). We will, therefore, also give some brief achieve the accepted level of growth and feed efficienc consideration below to this latter mode of expressing ies when pigs are fed corn-soybean meal diets. On the amino acid needs. other hand, the requirements for indispensable amino Third, it has been necessary to make some arbitrary acids in the rat (NRC 1978) represent a pattern that choices regarding the four age/developmental stage cat has been used successfully in studies with purified egories that we have used to summarize the available diets; those for humans have been based, in pre-school, data and in drawing our comparisons between humans school-age, and adults largely, but not solely, on nitro and the various species included in this analysis. Be gen balance criteria; for infants, the current amino acid cause we are interested primarily in an evaluation of requirements are derived simply from the amino acid human amino acid requirements, and how these composition of the mixed proteins in human breast change in relation to the total protein requirement, we milk (FAO/WHO/UNU 1985). We will refer again to were restricted to the use of four age groups for which this matter of the requirements in human infants in amino acid requirement values have been assembled the Discussion. by the most recent international, expert consultation We accept that this diversity in the approach for (FAO/WHO/UNU 1985); these are infants (0-1 y), pre estimating amino acid requirements limits our ability school children (2-5 y), school-age children (10-12 y) to draw precise, quantitative conclusions. Neverthe and adults (assumed to be 17 + y). Thus, it was neces less, because of the broad similarity of the pattern of sary to attempt to use requirement data for the various requirements among the various nonhuman species in species that could be considered to be a reasonable, cluded here, which contrasts, as outlined below with albeit gross, age/developmental match with these hu that for humans, this "requirement estimation" issue man groups. Hence, we have designated the four com would seem to us not to be sufficiently overriding as parative groups as "very young," "early growth," to invalidate our approach or our general conclusions. "growth" and "mature" and we indicate the age, or Second, it is necessary to establish, for our specific body weight, for the various species included within purposes, a suitable definition of, and basis for compar these categories. We accept that there may be other ing, the amino acid requirements of the different spe choices of subcategories, but we find the present ones cies included here. This is important because, as indi to be useful for our purposes. Furthermore, it should cated above, published values for requirements are ex be appreciated that in our category of "mature" we pressed in various ways and comparisons are include data for swine and turkeys. We realize that meaningful only when using a uniform basis of expres farm animals raised for production are usually mar sion. Thus, the requirement for total protein (nitrogen) keted before reaching full adult size, but this does not which differs among the species, would be expected to appear to us to be a major problem or of great impor be paralleled by the requirement level for the total, and tance. The mature group for animals included here re probably the specific, indispensable amino acids. We flects a physiologic stage well beyond sexual matura are unaware of, or could not point to, a situation in tion and it must be recognized also that in young adult which a higher or lower requirement for total dietary humans, body weight (and lean body mass) has not yet protein is not paralleled by a higher or lower require reached its maximum (Forbes and Reina 1970); how ment, respectively, for the indispensable amino acids. ever, it is the data from such individuals that are in Hence, for comparison purposes, we have chosen to cluded in the mature category. express the indispensable amino acid requirements for Statistical evaluation. The four age-developmental the various species in reference to the stated require groups were examined individually to determine if any ment for protein (mg amino acid/g protein). major differences existed between the proposed human COMPARATIVE AMINO ACID REQUIREMENT PATTERNS 1875 amino acid requirement patterns (FAO/WHO/UNU (expressed as amino acid required per gram protein re 1985) and those for the various species included. De quired) give values that are ~ one-half to one-third of scriptive statistics were calculated to determine the the values for the other species. mean requirement, standard deviation (so) and coeffi Figure 3 illustrates the relatively steeper decline in cient of variation (CV) for each individual amino acid the requirements (ratio of amino acid requirement pat in all species within the particular group excluding hu tern in mature to that in the very young) for specific mans. indispensable amino acids between infancy and adult The Friedman two-way ANOVA by ranks was per hood for the human, compared with a lesser fall for the formed on each of the four age groups to determine amino acid requirements for the average of the various whether any significant difference existed in the over species. Finally, as presented in Table 1 and depicted all pattern of amino acid requirements between species in Figure 4, the total indispensable amino acid require within the group. The Friedman test is a nonparametric ment pattern at infancy in humans is 460 mg amino analog to the two-way ANOVA and is employed when acid/g protein,- the adult value is 127 mg/g protein or Downloaded from https://academic.oup.com/jn/article/126/7/1871/4723627 by guest on 25 September 2021 it is not known if the data are normally distributed and 28% of the infant figure. In contrast, the comparable the assumptions necessary for parametric analysis are average for the species included in Table 1 is 369 mg/ not met (Daniel 1991). This test is appropriate when g protein in the very young (also see Fig. 4) and 290 ever the data are measured on an ordinal scale and mg/g protein in mature, or 79% of the former value. can be meaningfully arranged according to a two-way Comparison of amino acid requirements in relation classification. The assumption we make is that the ob to tryptophan. In Table 2 the requirements for specific servations appearing in any given block are indepen amino acids are expressed in relation to that for trypto dent of the observations appearing in the other blocks phan. From the detailed data shown here, it appears (Daniel 1991). Each species within an age-develop that there are no striking differences among the various mental category was taken to be an independent group, species and/or between these and humans. It should and then amino acid requirements were ranked for each be pointed out, nevertheless, that there is substantial species, with a ranking of 1 being given to that amino variation within the data set. When the amino acid acid showing the lowest requirement value, expressed requirement values were expressed in relation to ly as mg amino acid/g protein. The data were analyzed sine, or leucine, the comparisons that emerged were with the aid of a software statistical package (BMDP3S- quite similar to the findings with tryptophan. Hence, Nonparametric Statistics BMDP Statistical Software, these results are not reported here. 1990, DEC/ULTRIX, Los Angeles, CA). Comparison using freidman's two-way ANOVA. Freidman's two-way ANOVA was used to determine whether any significant differences existed in the amino acid requirement pattern between species for a specific RESULTS age-developmental group. This test identifies significant differences by ranking the values in ascending order Comparison of mean requirements. A graphical from lowest to highest value. The range of values for representation of the human requirement for specific individual amino acids was ranked between species indispensable amino acids in relation to the mean of within one group, and the procedure provided a total the requirements for all species combined, and for each rank which was used for comparison. These results are age-developmental category, is given in Figure 1, based shown in Table 3. They demonstrate that the require on the data summarized in Table 1. The human re ment pattern in the human infant is the highest and quirement values used in these comparisons are those that in the adult (mature) it is the lowest, in relation to proposed by FAO/WHO/UNU (1985). Values used here the other species compared in this analysis. In early for the other species were taken from Table 1, and it growth, the preschool child ranked in about the middle can be seen (compare Fig. la and Id] that the quantita of the nine other species considered. The growth cate tive fall in the human amino acid requirement pattern, gory shows the human moving to the lowest total rank, as defined in Materials and Methods, with increasing although the specific values were variable, ranging range age and development is much greater than that for the from 1 to 3 out of a possible ranking of 1 to 5. For the average of the values for the other species. The human mature group, the human values consistently rank the amino acid requirement at infancy (based on the com lowest for all amino acids, except for histidine and the position of human breast milk; see Discussion) appears sulphur amino acids, when compared with the require to represent one of the highest requirement patterns; ments for the dog, rat, swine and turkey. in contrast, the human adult shows the lowest require ment pattern of any of these species. In Figure 2, we compare the specific amino acid re DISCUSSION quirements among the mature of the various species included in our survey,- this shows that for these vari Very young. The human infant's indispensable ous amino acids, the human adult requirement pattern amino acid requirements have been estimated by 1876 McLARNEY ET AL.
lUU90 JQHumanB= = Non-Human Species
801
7°
B.0) 60 ^'8 50
0 140|>
30 Downloaded from https://academic.oup.com/jn/article/126/7/1871/4723627 by guest on 25 September 2021
20
10
0(b) His lie Leu Lys Saa Aaa Thr Trp Val His lie Leu Lys Saa Aaa Thr Trp Val
Humans = Non-Human Species Q = Humans = Non-Humans
His lie Leu Lys Saa Aaa Thr Trp Val His lie Leu Lys Saa Aaa Thr Trp Val
FIGURE 1 The specific indispensable amino acid requirements, per gram of protein required, for humans in comparison with the mean for "nonhuman species" requirements, according to age/developmental groups (a) very young; (b) early growth; (c) growth; (d) mature. Based on data summarized in Table 1. Saa = sulfur amino acids jmethionine plus cystine); Aaa = aromatic amino acids (phenylalanine plus tyrosine). growth and nitrogen balance studies or from the intake accretion/growth responses. However, we should point of cow's milk formulas that supported satisfactory out that the differences between the levels of amino growth (Fomon 1993, FAO/WHO 1973). Earlier, a com acids required per gram of protein by the human infant posite of the lower estimate from either of the two and those for the rat were less dramatic for leucine and sets of requirements was taken to represent the best lysine when comparisons were made against the newer estimate of requirement in this age group (FAO/WHO estimates proposed by Benevenga et al. (1994), rather 1973). Because this set of estimated requirements than those given in NRC (1978). Interestingly, when closely resembled the amino acid composition pattern the total requirement of 373 mg amino acids/g protein, of human breast milk, the latter was recommended as as determined directly via experimental studies (FAO/ the requirement pattern for infants. We have used this WHO 1973), is compared with the average of the spe breast milk pattern (FAO/WHO/UNU 1985) here for cies requirement, the values became quite similar. It our interspecies, comparative purposes. is also worth mentioning that Davis et al. (1994) found Use of the amino acid composition of human breast a "remarkable commonality in the general amino acid milk as an index of the requirements for amino acids pattern of milk . . . ," and they believe that there is a by the infant may possibly explain why the require likely commonality in the pattern of amino acid re ments in the very young were greater for the human quirements of the young of the species that were in compared with the average of the species requirements cluded in their survey, involving both primates and (Table 1 and Fig. la). In the latter case, the require nonprimates. ments were determined by nitrogen balance or nitrogen The various species of birds included in the very COMPARATIVE AMINO ACID REQUIREMENT PATTERNS 1877
Human Non-Human Species Downloaded from https://academic.oup.com/jn/article/126/7/1871/4723627 by guest on 25 September 2021
Very Young Early Growth Growth Mature Leu Lys Saa Thr FIGURE 4 The total indispensable amino acid require FIGURE 2 Comparison of the requirements for specific ment pattern in humans compared with the mean value for indispensable amino acids between human adults and those total indispensable amino acids in "nonhuman" species for in mature category for four other species (see Table 1). Saa = four age/development groups. total sulfur amino acids (methionine plus cystine). young category had similar requirements for both indi the breast milk amino acid pattern for comparison pur vidual amino acids and total requirements, whereas poses. those for the mammals (pigs, rats and hamsters) Early growth. The amino acid requirement pattern showed an apparent greater interspecies difference. In proposed for the preschool child is based on various clusion of the hamster, with the most extreme values criteria of amino acid adequacy (FAO/WHO/UNU for requirements, elevated the average species require 1985). It was considered by (FAO/WHO 1991) that this ment by 16 points. Thus, if hamsters had not been requirement pattern was robustly determined, and thus included in this survey, the distinction between the it should serve as the tentative estimate of the amino human infant amino acid requirement pattern and that acid requirement pattern for all ages, with the excep for the other species would be even greater, when using tion of infancy. Further, from our analysis of this age/ developmental group, it turned out to be the only pat tern in which the human amino total acid requirement was not apparently different from the average of the o—3b>tKaKn-»
TABLE 2 Amino acid requirements of mammals and birds when tryptophan =
Age/development group His He Leu Lys Saa Aaa Thr Trp Val Totali
mg amino acid/g protein VeryyoungHuman y)Chick infant (0-1 wk)Broiler(0-6 wk)Rat (0-3 (weanling)3Turkey wk)Swine(0-4 |l-5jcg)Quail growth]Hamster(start Downloaded from https://academic.oup.com/jn/article/126/7/1871/4723627 by guest on 25 September 2021 (weanling)4Mean human)so(excluding 7)Early(n = growthHuman y)Chick (2-5 wk)Turkey(6- 14 wk)Dog (4-8 kg)Broiler(3 wk)Cat(lOwk)Swine(3-6
kg)RabbitMiceMean(10-20
human)so(excluding 8)GrowthHuman(n =
y)Chick (10- 12 wk)Turkey(14-20 wk)Broiler(11-14 wk)Swine(6-8 kg)Mean(50- 110 human)SD(excluding 4)MatureHuman(n =
adultTurkey holdingDog adultRat maintenance3Swine, boarMeanadult human)SD(excluding (n = 4)1.51.51.51.52.21.91.61.21.61.01.71.6231.21.62.01.81.52.01.71.02.11.52.21.51.81.8033.22.51.71.61.71.90.42.73.53.63.34.24.04.52.63.51.82.53.64.22.43.73.33.63.04.03.42.23.13.64.23.53.63.70.32.64.53.76.23.64.51.25.55.95.95.07.35.37.74.15.53.16.05.97.33.96.38.04.95.57.05.93.64.96.17.25.94.96.01.03.85.06.53.63.64.71.43.95.05.24.76.27.35.93.55.02.05.34.3633.45.35.36.63.34.04.63.64.94.15.65.05.85.10.83.25.03.82.25.14.01.42.53.54.04.04.03.53.40.93.01.8233.63.82.63.85.03.43.05.03.61.62.43.63.63.53.33.50.23.44.02.34.62.73.41.14.25.95.85.36.95.98.22.45.21.85.75.96.94.86.35.75.45.54.05.55.62.46.16.75.95.36.00.63.88.06.63.65.45.91.92.54.03.53.33.84.14.62.13.41.03.14.13.93.13.94.73.93.04.03.71.93.13.43.84.03.93.8031.84.03.43.63.63.60.31.01.01.01.01.01.0.0.0.0.0.0.0.01.01.01.01.01.0.0.0.0.0.0.0.0.0.00.01.01.01.01.01.01.00.03.23.63.64.04.64.14.32.73.72.03.23.74.62.63.84.03.93.55.03.82.42.83.74.53.63.93.90.42.65.04.64.63.94.50.527.134.034.032.740.337.041.220.531.911.230.833.740.224.935.639.034.429.336.033.117.826.833.238.934.033.334.82.725.439.033.631.030.633.63.9
1The values are derived from Table 1 by dividing the requirement (mg amino acid/g protein) for a specific amino acid (e.g., histidine) by the requirement for tryptophan (mg/g protein). 2 Total = (His, Ile, Leu, Lys, Saa, Aaa, Thr, Try, Val). 3 Value used is for methionine only. 4 Value is for phenylalanine only. ertheless, the amino acid requirement values (mg ments in adult swine, made by Baker et al. (1966a and amino acid/g protein) for adult humans were about 1966b), show large differences depending upon whether 60% lower than those for adult pigs (127 mg/g vs. 214 body nitrogen equilibrium or a small positive balance mg/g protein) (Table 1). Swine consistently had one of is used as a criterion for evaluation. These values also the lowest total amino acid requirement patterns for differ substantially from the "maintenance require all species throughout the different stages of growth ment" estimates proposed by Fuller et al. (1989). Thus, and development, while also exhibiting only an appar considerable insecurity is to be attached to the specific ently relative modest decline (18%) from infancy (296 values that we have used here for mature pigs. mg/g protein) to maturity (214 mg/g protein). However, Estimates of amino acid requirements for dogs (bea a note of caution ought to be made here because the gles) include only data for the early stage of growth and NRC requirement pattern is based on limited data and for maturity. The requirement for total indispensable derived largely by extrapolation and assumption. Fur amino acids declined from 356 mg/g protein in early ther, the direct estimates of the amino acid require growth to 253 mg/g protein in adulthood, a modest COMPARATIVE AMINO ACID REQUIREMENT PATTERNS 1879
TABLE3 Amino acid requirements of mammals and birds expressed according to Freidman's rank sum test1
Age/developmentgroupVery
amino146538173294167581244S23245Aaaacid/gprotein134586272314758691244512453Thr142375871238469581335412345Trp135336871335759584144412445Val123546871274456891244512345Totali16.522.031.039.041.552.558.563.014.024.537.038.547.049.560.563.570.516.517.526.532.042.511.520.028.037.538.0 youngSwine kg)Chick(1-5 wk)Broilergrowth (0-6 wk)Turkeygrowing (0-3 wk)Quailgrowth (0-4 growth)Rat(start (weanling)3Hamstergrowth
wk)4Human(6 Downloaded from https://academic.oup.com/jn/article/126/7/1871/4723627 by guest on 25 September 2021 y)Early infant (0-1 growthCat wk)Swinegrowth (10 kg)Mice(10-20 growthChick wk)Humangrowth (6-14 y)Broiler (2-5 wk)Doggrowing (6-8 kg)Turkeygrowth (3 wk)Rabbitgrowth (8-11 kg)GrowthHumangrowth (1
y)Swine (10- 12 kg)Chick(50- 110 wk)Broilergrowth (14-20 wk)Turkey(6-8 wk)MatureHumangrowth (14-17
adultSwine adultDog adultTurkey holdingRat maintenance3His313536871254846984222531254He123456871345276981244512345Leu123564882153765892144512534Lys612436872713965942314514352Saamg
1 Requirements are ranked in order with lowest requirement value = 1. 2 Total = rank for sum of amino acids. 3 Value is for methionine only. 4 Value is for phenylalanine only. decrease of 29%. Again, this is much lower than the percentage decline from 375 mg/g protein at birth, to changes between infancy or early growth and the adult 325 mg/g protein at maturity, a 14% reduction. How human requirement values. Wannemacher and McCoy ever, the values for lysine and the sulfur amino acids (1966) have suggested that amino acid requirements of were experimentally determined, and they too exhib adult dogs may actually increase from maturity to old ited only relatively small decreases (19 and 16%, re age, but there is little definitive evidence to support spectively) through the latter stages of growth and mat that this might also be the case in humans (Young uration. 1992a; for review). Rats had the highest total amino acid requirement of The turkey showed one of the highest essential all of the mature species (369 mg/g protein) and showed amino acid requirement patterns throughout life. For only a 10% decline between the very young and mature this species, only the requirements for infancy, and groups. The indispensable amino acid requirements for those at all stages of growth for lysine and sulfur amino maintenance of adult rats are based on metabolic body acids, have been derived directly via feeding experi size (mg/kg°7S)and are the average results of three dif ments. Estimations and interpolations have been used ferent studies conducted by Benditt et al. (1950), Said to determine the requirements for the remaining amino and Hegsted (1970) and Smith and Johnson (1967). acids through the various stages of growth and develop Comparison in relation to tryptophan. Use of an ment (NRC 1984). All of the amino acid requirement amino acid requirement pattern, expressed in relation values for the "holding" stage are predicted estimates. to the most limiting amino acid, has possible utility, This might be the basic reason why the total amino and in this context some investigators have promoted acid requirements for this species shows the smallest the concept of an "ideal protein" (Baker 1993, Baker 1880 McLARNEY ET AL. and Czarnecki 1991, Baker and Han 1994, NRC 1988). FAO/WHO/UNU (1985) used for the present compara This concept attempts to establish the ideal ratio tive analysis (see Mature in Table 1). Hence, whether among the different indispensable amino acids (setting the difference in the degree of change in the amino acid a limiting amino such as lysine or tryptophan equal to requirement pattern between infancy and adulthood in 1).The comparisons in the present study illustrate that humans, on the one hand, and that for the other species when requirements were expressed in relation to tryp included here, on the other, reflects major underlying tophan (or lysine or leucine), the "ideal protein" is sim differences in the biology of and metabolic needs for ilar within all age categories to that for the average of amino acids among the species or whether it reflects the nonhuman species (Table 2). the different criteria and/or methods and interpretation Overall evaluation. A consistent trend that emerged of the data, cannot be judged precisely from the present from this analysis was the difference between the hu analysis. However, considering the relatively slow man indispensable (essential) amino acid requirement postnatal growth of humans, in comparison with that pattern and that established in other species. Humans of the other species (Brody 1945, Blaxter 1978),it seems Downloaded from https://academic.oup.com/jn/article/126/7/1871/4723627 by guest on 25 September 2021 had the second highest pattern for total indispensable more likely to us that the distinction noted here is due, amino acid requirements in infancy (exceeded only by importantly, to experimental rather than underlying the golden hamster) when values were expressed as mg biological factors. The principal issue, we believe, is amino acid/g protein. In addition, the human showed the inadequacy of the nitrogen balance technique, ex the lowest absolute pattern by the time maturity had perimental design and assessment criteria as they have been reached. No other species for which more than one been applied in the earlier human experiments, espe age-development phase, amino acid requirement pattern cially those concerning determination of adult amino was available for scrutiny exhibited such a dramatic acid requirements (Young and Marchini 1990; for re change in total or individual amino acid requirements view). If, for comparison purposes, we had used instead as a result of increasing age and developmental stage. our tentative, new amino acid requirement pattern This dramatic change for humans may actually be (Young and Pellett 1990), the differences between hu somewhat less if the 1973 FAO/WHO amino acid re mans and the other species would have been far less quirement values are accepted as being a more appro profound; indeed, the general similarity in age/develop priate set of estimates. Thus, in this case, the amino ment amino acid requirement patterns among the vari acid requirement pattern would amount to 400 mg to ous species, including humans, have been striking! tal indispensable amino acids/g protein, compared with Thus, we are left with a sense of insecurity concern the value of 460 mg/g protein for human breast milk, ing the adequacy of the international and nationally which is the figure we have used in this paper. Never defined amino acid requirement values for human theless, in either case, the amino acid pattern for hu adults. Indeed, they seem to be anomalous if, according man infants exceeds that for all the other species except to Lightman and Gingerich (1991), it is accepted that for rats and golden hamsters (Table 1).Hence, our gen an "anomaly in science is an observed fact that is diffi eral conclusions are independent of which of the two cult to explain in terms of the existing conceptual human amino acid "requirement" data sets are used in framework." The fact that our tentative, new amino the analysis. Finally, we are aware that in their position acid requirement pattern (Young and Pellett, 1990) paper prepared for a meeting of the International Di brings the human data more closely in line with the etary Energy Consultancy Group, Dewey et al. (1996) amino acid requirement patterns and their rates of estimated, using a factorial method, that the amino change with development as in the other species acid requirements of 3- to 6-mo-old infants are much should not be ignored. This observation implies that lower than those summarized by FAO/WHO (1973)and the MIT amino acid requirement pattern (mg amino FAO/WHO/UNU (1985). Nevertheless, it does not acid/g protein) might better reflect the quantitative re seem appropriate for us to use the values proposed by quirements for amino acids in humans than does the Dewey et al. (1996) until a further validation of their 1985 FAO/WHO/UNU pattern. Furthermore, as indi approach and values has been made. Again, however, cated earlier, in 1989, FAO/WHO (1991)recommended, even if their estimates of the amino acid requirements for interim purposes, use of the amino acid require of the infant are eventually found to be reasonable, they ment pattern for the preschool child as the basis for would not weaken the general strength of the argu assessing dietary protein quality across all age groups ments that we have made in the present assessment of beyond infancy. This pattern is similar to our proposed human amino acid needs, especially with reference to requirement pattern (Young and Pellett 1990). adults. Additional, direct studies, aimed at a careful reas As pointed out earlier, we have raised questions sessment of human amino acid requirements, using about the validity of the amino acid requirement values new criteria and novel and improved methods, are re for healthy human adults and we developed (Youngand quired to establish the validity of our conclusions. Ap Pellett 1990) a tentative new amino acid requirement propriately, Fuller and Garlick (1994) make a compara pattern. This pattern is distinctly different from the ble recommendation. adult amino acid requirement pattern proposed by Finally, we recognize that an alternative hypothesis COMPARATIVE AMINO ACID REQUIREMENT PATTERNS 1881 could be that humans are exceptional, as Blaxter (1978) nous tracer studies with L-[l-13C]leucine and |'5N,15N]urea. Am. has proposed to be the case for total protein and cal J. Clin. Nutr. 59: 1000-1011. cium, but he explains this to be related to "the fact El-Khoury, A. E., Fukagawa, N. K., Sánchez,M., Tsay, R. H., Gleason, R. E., Chapman, T. E. &.Young, V. R. (1994b) The 24-h pattern that man is a slow-growing mammal throughout life and rate of leucine oxidation, with particular reference to tracer accreting little per unit time." Hence, the present find estimates of leucine requirements in healthy adults. Am. J. Clin. ings are not explained by his view. Therefore, until Nutr. 59: 1012-1020. more definitive amino acid requirement data become FAO/WHO (1973) Energy and Protein Requirements. Report of a available for the "mature" of various primate and non- joint FAO/WHO ad hoc Expert Committee. Tech. Rep. Ser. No. 522. WHO, Geneva, Switzerland. primate mammalian species, we conclude that the in FAO/WHO (1991) Protein Quality Evaluation. Report of the joint ternationally proposed amino acid requirement values FAO/WHO Expert Consultation. FAO Food and Nutrition Paper for the human adult (FAO/WHO/UNU 1985) are of No. 51. Food and Agriculture Organization of the United Nations, questionable validity, with reference to their use in Rome, Italy. FAO/WHO/UNU (1985) Energy and Protein Requirements. Re practical human nutrition. We recommend, in the in Downloaded from https://academic.oup.com/jn/article/126/7/1871/4723627 by guest on 25 September 2021 port of a joint FAO/WHO/UNU Expert Consultation. Tech. Rep. terim, our proposed MIT amino acid requirement pat Ser. No. 724. WHO, Geneva, Switzerland. tern (Young and El-Khoury 1995) for this purpose. Fomon, S. f. (1993) Nutrition of Normal Infants, ch. 8, pp. 121- 146. Mosby Year Book, Inc., St. Louis, MO. Forbes, G. B. & Reina, J. C. (1970) Adult lean body mass declines with age: some longitudinal observations. Metabolism 19: 653-663. Fuller, M. F. & Garlick, P. J. 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