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Abstracts

Life Extension Magazine November 2010
Abstracts

Plant protein

Role of dietary protein in the sarcopenia of aging.

Sarcopenia is a complex, multifactorial process facilitated by a combination of factors including the adoption of a more sedentary lifestyle and a less than optimal diet. Increasing evidence points to a blunted anabolic response after a mixed nutrient meal as a likely explanation for chronic age-related muscle loss. There is currently insufficient longer-term research with defined health outcomes to specify an optimal value for protein ingestion in elderly individuals. However, there is general agreement that moderately increasing daily protein intake beyond 0.8 g x kg(-1) x d(-1) may enhance muscle protein anabolism and provide a means of reducing the progressive loss of muscle mass with age. The beneficial effects of resistance exercise in aging populations are unequivocal. However, research has not identified a synergistic effect of protein supplementation and resistance exercise in aging populations. There is little evidence that links high protein intakes to increased risk for impaired kidney function in healthy individuals. However, renal function decreases with age, and high protein intake is contraindicated in individuals with renal disease. Assessment of renal function is recommended for older individuals before they adopt a higher-protein diet.

Am J Clin Nutr. 2008 May;87(5):1562S-1566S

Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein.

To counteract the debilitating progression of sarcopenia, a protein supplement should provide an energetically efficient anabolic stimulus. We quantified net muscle protein synthesis in healthy elderly individuals (65-79 yrs) following ingestion of an isocaloric intact whey protein supplement (WY; n=8) or an essential amino acid supplement (EAA; n=7). Femoral arterio-venous blood samples and vastus lateralis muscle biopsy samples were obtained during a primed, constant infusion of L-[ring-2H5]phenylalanine. Net phenylalanine uptake and mixed muscle fractional synthetic rate (FSR) were calculated during the post-absorptive period and for 3.5 h following ingestion of 15 g EAA or 15 g whey. After accounting for the residual increase in the intracellular phenylalanine pool, net post-prandial phenylalanine uptake was 53.4+/-9.7 mg phe leg-1 (EAA) and 21.7+/-4.6 mg phe leg-1 (WY), (P<0.05). Postabsorptive FSR values were 0.056+/-0.004% h-1 (EAA) and 0.049+/-0.006% h-1 (WY), (P>0.05). Both supplements stimulated FSR (P<0.05), but the increase was greatest in the EAA group with values of 0.088+/-0.011% h-1 (EAA) and 0.066+/-0.004% h-1 (WY), (P<0.05). While both EAA and WY supplements stimulated muscle protein synthesis, EAAs may provide a more energetically efficient nutritional supplement for elderly individuals.

Exp Gerontol. 2006 Feb;41(2):215-9

Amino acid ingestion improves muscle protein synthesis in the young and elderly.

We recently demonstrated that muscle protein synthesis was stimulated to a similar extent in young and elderly subjects during a 3-h amino acid infusion. We sought to determine if a more practical bolus oral ingestion would also produce a similar response in young (34 +/- 4 yr) and elderly (67 +/- 2 yr) individuals. Arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 micromol/kg) constant infusion (0.05 micromol.kg(-1).min(-1)) of L-[ring-2H5]phenylalanine. Muscle protein kinetics and mixed muscle fractional synthetic rate (FSR) were calculated before and after the bolus ingestion of 15 g of essential amino acids (EAA) in young (n = 6) and elderly (n = 7) subjects. After EAA ingestion, the rate of increase in femoral artery phenylalanine concentration was slower in elderly subjects but remained elevated for a longer period. EAA ingestion increased FSR in both age groups by approximately 0.04%/h (P < 0.05). However, muscle intracellular (IC) phenylalanine concentration remained significantly higher in elderly subjects at the completion of the study (young: 115.6 +/- 5.4 nmol/ml; elderly: 150.2 +/- 19.4 nmol/ml). Correction for the free phenylalanine retained in the muscle IC pool resulted in similar net phenylalanine uptake values in the young and elderly. EAA ingestion increased plasma insulin levels in young (6.1 +/- 1.2 to 21.3 +/- 3.1 microIU/ml) but not in elderly subjects (3.0 +/- 0.6 to 4.3 +/- 0.4 microIU/ml). Despite differences in the time course of plasma phenylalanine kinetics and a greater residual IC phenylalanine concentration, amino acid supplementation acutely stimulated muscle protein synthesis in both young and elderly individuals.

Am J Physiol Endocrinol Metab. 2004 Mar;286(3):E321-8

Increased protein requirements in elderly people: new data and retrospective reassessments.

Dietary protein requirements of elderly people were determined by short-term nitrogen-balance techniques and using calculations recommended by the 1985 Joint FAO/WHO/UNU Expert Consultation. Twelve men and women aged 56-80 y were randomly assigned to groups that consumed either 0.80 +/- 0.01 or 1.62 +/- 0.02 g protein.kg-1.d-1 (mean +/- SEM). Net nitrogen balance was negative for the lower-protein group (-4.6 +/- 3.4 mg N.kg-1.d-1) and positive for the higher-protein group (13.6 +/- 1.0 mg N.kg-1.d-1); the intake required for nitrogen equilibrium was estimated to be 1.00 g.kg-1.d-1. Nitrogen-balance data from three previous protein requirement studies in elderly people were recalculated by using the same balance formula and combined with the current study data to provide an overall weighted mean protein requirement estimate of 0.91 +/- 0.043 g.kg-1.d-1. Together, the current and retrospective nitrogen-balance data suggest that the mean protein requirement in elderly adults is considerably greater than the 0.60 g.kg-1.d-1 established by the 1985 Joint FAO/WHO/UNU Expert Consultation. A safe protein intake for elderly adults would be 1.0-1.25 g.kg-1.d-1 of high-quality protein.

Am J Clin Nutr. 1994 Oct;60(4):501-9

Amino acids and proteins in relation to the nutrition of elderly people.

In this short review some aspects of body protein and amino acid metabolism during ageing in human subjects have been explored. The picture that emerges is a progressive diminution of total body protein with ageing, due largely to a decline in the size of the skeletal muscle mass. These changes are accompanied by a shift in the overall pattern of whole body protein synthesis and breakdown, with muscle mass estimated to account for about 30% of whole body protein turnover in the young adult, as compared with a lower value of 20% or less in the elderly subject. The metabolic significance and possible functional implications of this alteration in the quantitative contribution by muscle to whole body amino acid and protein dynamics have been considered. The determination of requirements for individual essential amino acids and for total protein has been discussed, and it is evident that the data are limited and often contradictory. However, elderly individuals are more likely to be influenced by various biological, environmental and social factors, the effects of which would be generally to increase protein needs above those for younger adults. Thus, in practice, the protein needs of elderly people are probably higher than for the young. The decline in energy intake, together with its possible consequences for reduced dietary protein utilization, will also tend to increase the protein need of elderly subjects, compared with that for physically more active young adults. Until more data become available, it is recommended for food planning purposes that an appropriate protein allowance could be 12-14% of the total energy intake, for mixed protein sources characteristic of the diets of industrialized countries or the more affluent sectors of populations in developing countries. Energy intake should be at a level that meets the estimates proposed by FAO/WHO/UNU for older persons. Tentative recommendations are made herein that intakes of specific indispensable (essential) amino acids, per unit of protein need, should be similar to those for the young school-age child and they should be higher than those currently judged by international authorities (i.e. FAO/WHO/UNU) to be sufficient for maintenance of protein nutritional status in the adult. In view of (i) the increasing proportion of older individuals within technically advanced populations together with the need of this group for health care and (ii) the important role played by diet and food habits in health maintenance, and in the aetiology or progression of degenerative disease, it is vitally necessary to improve upon the current state of knowledge concerning protein and amino acid metabolism and nutrition during the later phases of our lives.

Age Ageing. 1990 Jul;19(4):S10-24

Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study.

BACKGROUND: Dietary surveys suggest that many older, community-dwelling adults consume insufficient dietary protein, which may contribute to the age-related loss of lean mass (LM). OBJECTIVE: The objective of the study was to determine the association between dietary protein and changes in total LM and nonbone appendicular LM (aLM) in older, community-dwelling men and women. DESIGN: Dietary protein intake was assessed by using an interviewer-administered 108-item food-frequency questionnaire in men and women aged 70-79 y who were participating in the Health, Aging, and Body Composition study (n=2066). Changes in LM and aLM over 3 y were measured by using dual-energy X-ray absorptiometry. The association between protein intake and 3-y changes in LM and aLM was examined by using multiple linear regression analysis adjusted for potential confounders. RESULTS: After adjustment for potential confounders, energy-adjusted protein intake was associated with 3-y changes in LM [beta (SE): 8.76 (3.00), P=0.004] and aLM [beta (SE): 5.31 (1.64), P=0.001]. Participants in the highest quintile of protein intake lost approximately 40% less LM and aLM than did those in the lowest quintile of protein intake (x+/-SE: -0.501+/-0.106 kg compared with -0.883+/-0.104 kg for LM; -0.400+/-0.058 kg compared with -0.661+/-0.057 kg for aLM; P for trend<0.01). The associations were attenuated slightly after adjustment for change in fat mass, but the results remained significant. CONCLUSION: Dietary protein may be a modifiable risk factor for sarcopenia in older adults and should be studied further to determine its effects on preserving LM in this population.

Am J Clin Nutr. 2008 Jan;87(1):150-5

Protein turnover and requirements in the healthy and frail elderly.

There are as yet no definitive data that warrant the establishment of evidence-based dietary protein recommendations for the elderly. We reviewed the relevance of the new 2002 recommended protein intake of 0.80 g/kg body weight.d for adults to healthy and frail elderly persons. We found that data from published nitrogen balance studies indicate that, a higher protein intake of 1.0 - 1.3 g/k.d is required to maintain nitrogen balance in the healthy elderly, which may be explained by their lower energy intake and impaired insulin action during feeding compared with young persons. Although it needs to be confirmed, a decrease in efficiency of protein utilization with aging may also dictate a higher protein-intake recommendation. Measures of the dynamic aspects of protein metabolism done in the postabsorptive state have shown no change in whole body protein turnover per unit of active metabolic tissue with aging. However, the contribution of muscle protein to wholebody protein metabolism was significantly reduced in the elderly, and explained by their reduced muscle mass and lower rates of myofibrillar protein turnover. Consequently, the contribution of nonmuscle protein, especially that of visceral tissue whose rates of protein turnover are known to be more rapid was proportionally greater with aging. It is conceivable that higher protein consumption rates could compensate for the decrease in availability of muscle amino acids and spare the muscle mass. Despite a paucity of data on the frail elderly population, we present a rationale to justify a greater protein intake of at least equivalent to that of their healthy counterparts. We propose that higher protein intakes for the elderly, and especially the frail population, than those presently recommended may minimize the sarcopenia of aging and thereby protect against some of the health risks of aging.

J Nutr Health Aging. 2006 Jul-Aug;10(4):272-83

Protein requirement of elderly women: nitrogen balance responses to three levels of protein intake.

BACKGROUND: For elderly women, insufficient data exist to assess the accuracy of the assumed mean protein requirement of 0.6 g of protein x kg(-1) x day(-1), and the adequacy of the current Recommended Dietary Allowance (RDA) of 0.8 g of protein x kg(-1) x day(-1). The aims of this study were to assess the mean protein requirement and suggested safe and adequate protein intake (protein allowance) of elderly women using a shorter-term nitrogen balance protocol. METHODS: During three separate 18-day trials, 11 elderly women (age range, 70-81 years) were randomly fed eucaloric diets designed to provide either 0.50, 0.75, or 1.00 g of protein x kg(-1) x day(-1). Nitrogen balance was determined at Weeks 2 and 3 (Days 7-10 and 14-17, respectively) of each trial using data from total nitrogen analyses of duplicate food composites, 24-hour urine collections, and stool collections. The mean protein requirement was calculated using linear regression of individual women’s data from all three trials and inverse prediction. RESULTS: At protein intakes of 0.53 +/- 0.02, 0.76 +/- 0.02, or 1.06 +/- 0.05 g of protein x kg(-1) x day(-1), net nitrogen balances during Week 2 were -14.5 +/- 3.1, 3.8 +/- 2.5 and 23.4 +/- 3.3 mg of nitrogen x kg(-1) x day(-1), respectively, for these body weight- and body composition-stable women. At Week 3, the net nitrogen balances were -0.1 +/- 2.7, 8.5 +/- 3.6 and 42.0 +/- 3.0 mg of nitrogen x kg(-1) x day(-1). From Week 2 to Week 3, shifts to more positive nitrogen balances occurred due to decreases in urinary nitrogen excretion. The mean protein requirement at Week 2 was calculated to be 0.70 +/- 0.09 g of protein. kg(-1) x day(-1) (coefficient of variation [CV] = 13%) and at Week 3 was calculated to be 0.56 +/- 0.09 g of protein x kg(-1) x day(-1) (CV = 17%). From these data, an adequate protein allowance was estimated to be greater than the RDA at Week 2 (0.90 g of protein x kg(-1) x day [d](-1)), and not different than the RDA at Week 3 (0.76 g of protein x kg(-1) x d(-1)). CONCLUSIONS: The decrease over time in urinary nitrogen excretion from Week 2 to Week 3 suggests that these elderly women did not achieve a metabolic steady state during this shorter-term nitrogen balance study. Collectively, these data suggest that the total protein needs of elderly women are at or above the current RDA for protein. However, the results of this study indicate that shorter-term nitrogen balance protocols are insufficient to firmly establish the RDA for protein of elderly women, and further research is required using alternative criteria measures.

J Gerontol A Biol Sci Med Sci. 2001 Nov;56(11):M724-30

The protein digestibility-corrected amino acid score.

The protein digestibility-corrected amino acid score (PDCAAS) has been adopted by FAO/WHO as the preferred method for the measurement of the protein value in human nutrition. The method is based on comparison of the concentration of the first limiting essential amino acid in the test protein with the concentration of that amino acid in a reference (scoring) pattern. This scoring pattern is derived from the essential amino acid requirements of the preschool-age child. The chemical score obtained in this way is corrected for true fecal digestibility of the test protein. PDCAAS values higher than 100% are not accepted as such but are truncated to 100%. Although the principle of the PDCAAS method has been widely accepted, critical questions have been raised in the scientific community about a number of issues. These questions relate to 1) the validity of the preschool-age child amino acid requirement values, 2) the validity of correction for fecal instead of ileal digestibility and 3) the truncation of PDCAAS values to 100%. At the time of the adoption of the PDCAAS method, only a few studies had been performed on the amino acid requirements of the preschool-age child, and there is still a need for validation of the scoring pattern. Also, the scoring pattern does not include conditionally indispensable amino acids. These amino acids also contribute to the nutrition value of a protein. There is strong evidence that ileal, and not fecal, digestibility is the right parameter for correction of the amino acid score. The use of fecal digestibility overestimates the nutritional value of a protein, because amino acid nitrogen entering the colon is lost for protein synthesis in the body and is, at least in part, excreted in urine as ammonia. The truncation of PDCAAS values to 100% can be defended only for the limited number of situations in which the protein is to be used as the sole source of protein in the diet. For evaluation of the nutritional significance of proteins as part of mixed diets, the truncated value should not be used. In those cases, a more detailed evaluation of the contribution of the protein to the amino acid composition of the mixed diet is required. From such an evaluation, it appears that milk proteins are superior to plant proteins in cereal-based diets.

J Nutri. 2000 Jul;130(7):18655-75

Amino acid supplementation increases lean body mass, basal muscle protein synthesis, and insulin-like growth factor-I expression in older women.

CONTEXT: Inadequate dietary protein intake has been implicated in sarcopenia. OBJECTIVE AND DESIGN: The objectives of this study were to determine whether: 1) chronic essential amino acid (EAA) supplementation improves postabsorptive muscle protein fractional synthesis rate (FSR), lean body mass (LBM), and one-repetition maximum muscle strength, and androgen receptor and IGF-I muscle protein expression; and 2) the acute anabolic response to EAA ingestion is preserved after a 3-month supplementation period. Using a randomized, double-blinded, placebo-controlled design, older women (68 +/- 2 yr) were assigned to receive either placebo (n = 7), or 15 g EAA/d [supplemented treatment group (SUP)] (n = 7) for 3 months. Metabolic outcomes were assessed in association with stable isotope studies conducted at 0 and 3 months. SETTING: The study was performed at The University of Texas Medical Branch General Clinical Research Center. RESULTS: Ingestion of 7.5 g EAA acutely stimulated FSR in both groups at 0 months (P < 0.05). Basal FSR at 3 months was increased in SUP only. The magnitude of the acute response to EAA was unaltered after 3 months in SUP. LBM increased in SUP only (P < 0.05). One-repetition maximum strength remained unchanged in both groups. Basal IGF-I protein expression increased in SUP after 3 months (P = 0.05), with no changes in androgen receptor or total and phosphorylated Akt, mammalian target of rapamycin, S6 kinase, and 4E-binding protein.

CONCLUSIONS: EAA improved LBM and basal muscle protein synthesis in older individuals. The acute anabolic response to EAA supplementation is maintained over time and can improve LBM, possibly offsetting the debilitating effects of sarcopenia.

J Clin Endocrinol Metab. 2009 May;94(5):1630-7

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