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Biomedical subjects

Alan A Jackson

Publications and source records attributed to Alan A Jackson.

At least 19 recordsLinked to original sources

Folate supplementation during pregnancy improves offspring cardiovascular dysfunction induced by protein restriction.

Dietary protein restriction in the rat compromises the maternal cardiovascular adaptations to pregnancy and leads to raised blood pressure and endothelial dysfunction in the offspring. In this study we have hypothesized that dietary folate supplementation of the low-protein diet will improve maternal vascular function and also restore offspring cardiovascular function. Pregnant Wistar rats were fed either a control (18% casein) or protein-restricted (9% casein) diet +/-5 mg/kg folate supplement. Function of isolated maternal uterine artery and small mesenteric arteries from adult male offspring was assessed, systolic blood pressure recorded, and offspring thoracic aorta levels of endothelial nitric oxide (NO) synthase mRNA measured. In the uterine artery of late pregnancy dams, vasodilatation to vascular endothelial growth factor was attenuated in the protein-restricted group but restored with folate supplementation, as was isoprenaline-induced vasodilatation (P<0.05). In male offspring, protein restriction during pregnancy led to raised systolic blood pressure (P<0.01), impaired acetylcholine-induced vasodilatation (P<0.01), and reduced levels of endothelial NO synthase mRNA (P<0.05). Maternal folate supplementation during pregnancy prevented this elevated systolic blood pressure associated with a protein restriction diet. With folate supplementation, endothelium-dependent vasodilatation and endothelial NO synthase mRNA levels were not significantly different from either the control or protein-restricted groups. Maternal folate supplementation of the control diet had no effect on blood pressure or vasodilatation. This study supports the hypothesis that folate status in pregnancy can influence fetal development and, thus, the risks of cardiovascular disease in the next generation. The concept of developmental origins of adult disease focuses predominately on fetal life but must also include a role for maternal cardiovascular function.

Animals↗

Substrate-energy metabolism and metabolic risk factors for cardiovascular disease in relation to fetal growth and adult body composition.

The effect of fetal programming on intermediary metabolism is uncertain. Therefore, we examined whether fetal programming affects oxidative and nonoxidative macronutrient metabolism and the prevalence of the metabolic syndrome in adult life. Healthy older men, aged 64-72 years, with either a lower birth weight (LBW, or=75th %ile; n = 13) had measurements of 1) net oxidative metabolism using indirect calorimetry before and for 6 h after a mixed meal (3,720 kJ) and 2) postprandial oxidation of exogenous [13C]palmitic acid. Body composition was measured using dual-energy X-ray absorptiometry. After adjustment for current weight and height, the LBW group had a lower resting energy expenditure (REE) in the preprandial (4.01 vs. 4.54 kJ/min, P = 0.015) and postprandial state (4.60 vs. 5.20 kJ/min, P = 0.004), and less fat-free mass than the HBW group. The BW category was a significant, independent, and better predictor of REE than weight plus height. There were no significant differences between groups in net oxidative and nonoxidative macronutrient (protein, fat, carbohydrate) metabolism (or of exogenous [13C]palmitate) or in the prevalence of the metabolic syndrome, which was present almost twice as commonly in the LBW than in the HBW group. The study suggests that fetal programming affects both pre- and postprandial EE in older life by mechanisms that are at least partly related to the mass of the fat-free body. BW was found to be a significant predictor of REE that was independent of adult weight plus height.

Aged↗

'Malnutrition Universal Screening Tool' predicts mortality and length of hospital stay in acutely ill elderly.

Malnutrition and its impact on clinical outcome may be underestimated in hospitalised elderly as many screening procedures require measurements of weight and height that cannot often be undertaken in sick elderly patients. The 'Malnutrition Universal Screening Tool' ('MUST') has been developed to screen all adults, even if weight and/or height cannot be measured, enabling more complete information on malnutrition prevalence and its impact on clinical outcome to be obtained. In the present study, 150 consecutively admitted elderly patients (age 85 (sd 5.5) years) were recruited prospectively, screened with 'MUST' and clinical outcome recorded. Although only 56 % of patients could be weighed, all (n 150) could be screened with 'MUST'; 58 % were at malnutrition risk and these individuals had greater mortality (in-hospital and post-discharge, P<0.01) and longer hospital stays (P=0.02) than those at low risk. Both 'MUST' categorisation and component scores (BMI, weight loss, acute disease) were significantly related to mortality (P<0.03). Those patients with no measured or recalled weight ('MUST' subjective criteria used) had a greater risk of malnutrition (P=0.01) and a poorer clinical outcome (P<0.002) than those who could be weighed and, within both groups, clinical outcome was worse in those at risk of malnutrition. The present study suggests that 'MUST' predicts clinical outcome in hospitalised elderly, in whom malnutrition is common (58 %). In those who cannot be weighed, a higher prevalence of malnutrition and associated poorer clinical outcome supports the importance of routine screening with a tool, like 'MUST', that can be used to screen all patients.

Acute Disease↗

Fetal programming of body composition: relation between birth weight and body composition measured with dual-energy X-ray absorptiometry and anthropometric methods in older Englishmen.

BACKGROUND: Reduced fetal growth is associated with differences in body composition in adult life that may predispose to cardiovascular disease and diabetes. Most published data are based on simple anthropometric measures, which incompletely describe body composition. OBJECTIVE: The objective was to assess body composition and fat distribution by using dual-energy X-ray absorptiometry (DXA). DESIGN: This was a case-control study of 64-72-y-old white men (n = 32) with a low (mean: 2.76 kg) or high (mean: 4.23 kg) birth weight. RESULTS: Compared with the high-birth-weight group, after adjustment for weight and height, the low-birth-weight group had a higher percentage body fat (29.31% compared with 25.33%; P = 0.029) and fat mass (P = 0.039) but a lower fat-free soft tissue (56.32 compared with 59.22 kg; P = 0.024), muscle mass (27.25 compared with 29.22 kg; P = 0.022), and muscle-to-fat ratio. Low birth weight was also associated with a higher trunk-to-limb fat ratio after control for total fat mass (1.42 compared with 1.16; P = 0.005) or percentage body fat (P = 0.041). The same body mass index predicted a greater percentage body fat (P = 0.019) in the low- than in the high-birth-weight group, and the same ratio of trunk-to-limb skinfold thickness (or waist-to-hip ratio) predicted a higher trunk-to-limb fat ratio (P < 0.01). CONCLUSION: Lifelong differences in adult body composition and fat distribution between the low- and high-birth-weight groups are consistent with programming in early life. The use of BMI to predict percentage body fat and the use of the trunk-to-limb skinfold thickness ratio (and waist-to-hip ratio) to predict the trunk-to-limb fat ratio measured by DXA can be misleading when low- and high-birth-weight groups are compared.

Absorptiometry, Photon↗

Integrating the ideas of life course across cellular, individual, and population levels in cancer causation.

Cells, individuals, and societies are complex systems in which the integrity of structure and function is protected through tight regulation and control. For each level of organization, health represents the ability to maintain integrity in response to the wider environment. Critical stages during growth and development act as checkpoints, where choice is exercised, and help determine future direction. Important among factors influencing the checkpoints include the availability of nutrients or foods within the immediate environment. At the cellular and whole-body levels, this information can be communicated to future generations. Recent work on the developmental origins of adult disease indicate specific factors that set limits on structure and function and potentially limit the capacity of the cell and individual to respond to environmental stressors that represent potential risk factors for neoplastic change. Epigenetic mechanisms modulate structure and function at the cellular and tissue levels, reflecting the potential for the growth and development of individuals, and reflect the food and nutrients available to the body as a whole and within the wider society. Understanding the nature and the interaction of the critical factors that determine and regulate variable stable and unstable gene expression will be increasingly important in characterizing abnormal cellular function and risk of disease for individuals and populations. This will require the ability to synthesize large data sets within and between different levels of organization to develop and refine a deeper understanding of how the systems are effectively integrated and regulated within and across generations and where this fails in the genesis of cancer.

Animals↗

Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring.

Environmental constraints during early life result in phenotypic changes that can be associated with increased disease risk in later life. This suggests persistent alteration of gene transcription. DNA methylation, which is largely established in utero, provides a causal mechanism by which unbalanced prenatal nutrition results in such altered gene expression. We investigated the effect of unbalanced maternal nutrition on the methylation status and expression of the glucocorticoid receptor (GR) and peroxisomal proliferator-activated receptor (PPAR) genes in rat offspring after weaning. Dams were fed a control protein (C; 180 g/kg protein plus 1 mg/kg folic acid), restricted protein (R; 90 g/kg casein plus 1 mg/kg folic acid), or restricted protein plus 5 mg/kg folic acid (RF) diet throughout pregnancy. Pups were killed 6 d after weaning (n = 10 per group). Gene methylation was determined by methylation-sensitive PCR and mRNA expression by semiquantitative RT-PCR. PPARalpha gene methylation was 20.6% lower (P < 0.001) and expression 10.5-fold higher in R compared with C pups. GR gene methylation was 22.8% lower (P < 0.05) and expression 200% higher (P < 0.01) in R pups than in C pups. The RF diet prevented these changes. PPARgamma methylation status and expression did not differ among the groups. Acyl-CoA oxidase expression followed that of PPARalpha. These results show that unbalanced prenatal nutrition induces persistent, gene-specific epigenetic changes that alter mRNA expression. Epigenetic regulation of gene transcription provides a strong candidate mechanism for fetal programming.

Acyl-CoA Oxidase↗

Low serine hydroxymethyltransferase activity in the human placenta has important implications for fetal glycine supply.

Glycine is essential for fetal development, but in both sheep and human pregnancy, little is transported directly from the mother to the fetus, indicating that fetal glycine is derived from other sources. In the sheep, placental conversion of maternal serine by serine hydroxymethyltransferase (SHMT) provides almost all the glycine transported to the fetus. Although mRNA for mitochondrial and cytoplasmic SHMT has been detected in human placenta, it is not known whether substantial placental conversion of serine to glycine occurs in species other than sheep. We determined SHMT activity in human, rat, and sheep placenta by measuring conversion of [3-(14)C]serine to (14)C-methylene tetrahydrofolate. Compared with term human placenta, SHMT activity per gram of placenta was 5.1-fold higher in term rat placenta and 24.1-fold higher in term sheep placenta. In sheep placenta, SHMT activity per gram of placenta increased 2.1-fold between mid-gestation and term. In human placenta, placental SHMT activity was similar 8 wk post conception and at term. The low activity of SHMT in the human and rat placenta suggests that, unlike in the sheep, placental conversion of serine to glycine is not a major source of fetal glycine in these species.

Animals↗

Protein/energy ratios of current diets in developed and developing countries compared with a safe protein/energy ratio: implications for recommended protein and amino acid intakes.

Revised estimates of protein and amino acid requirements are under discussion by the Food and Agriculture Organization (FAO)/World Health Organizaion (WHO), and have been proposed in a recent report on Dietary Reference Intakes (DRIs) from the USA. The nature and magnitude of these requirements are not entirely resolved, and no consideration has been given to the potential influence of metabolic adaptation on dietary requirements. We have examined the implications of these new values, and of the conceptual metabolic framework in which they are used, for defining the nutritional adequacy of protein intakes in developed and developing countries. We have expressed proposed values for protein requirements in relation to energy requirements, predicted for physical activity levels of 1.5, 1.75 and 2.0 times basal metabolic rate, in order to generate reference ratios for protein energy/total energy (reference P/E ratio) as a function of age, body weight, gender and physical activity level. Proposed values for amino acid requirements have been used to adjust the available digestible P/E ratio of foods and diets for protein quality. Focusing on the diets of UK omnivores and vegetarians and on diets in India, the risk of protein deficiency is evaluated from a comparison of P/E ratios of metabolic requirements with protein-quality-adjusted P/E ratios of intakes. A qualitative and conservative estimate of risk of deficiency is made by comparing the adjusted P/E ratio of the intake with a reference P/E ratio calculated for age, body weight, gender and physical activity according to FAO/WHO/United Nations University. A semi-quantitative estimate of risk of deficiency has also been made by the cut point approach, calculated as the proportion of the intake distribution below the mean P/E ratio of the requirement. Values for the quality-adjusted P/E ratio of the diet range from 0.126 for the UK omnivore diet to 0.054 for a rice-based diet of adults in West Bengal, which is lysine-limited, falling to 0.050 for 1-year-old children. The reference P/E ratio for men and women increases with age, is higher for females than males, is higher for small compared with large adults at any age and decreases with physical activity. Thus if a particular diet is potentially limiting in protein, protein deficiency is most likely in large, elderly sedentary women followed by the adolescent female and least likely in moderately active young children, the opposite of what has usually been assumed. Within the currently accepted framework, the diets do not meet the protein needs of the entire population of the UK, have a significant risk of deficiency throughout India for all except extremely active small adults, and are grossly inadequate for all population groups, apart from physically active young children in West Bengal, regardless of body weight or level of food intake. The lysine limitation of the cereal-based Indian diets is dependent on the choice of lysine requirement values from the published range. We consider that the value selected is too high, because of uncertainties and inconsistencies in the approaches used. A more appropriate choice from the lower end of the range would remove the lysine limitation of cereal-based diets, and reduce some of the perceived risk of deficiency. However, diets remain limited by the amount of digestible protein for many population groups, especially in West Bengal. In the context of risk management, one option would be to accept the current values and the conceptual metabolic framework within which they have been derived. This would have major implications for the supplies of high-quality protein to the developing countries. An alternative option would be to re-evaluate the currently proposed values for the requirements for protein and amino acids. We conclude that the choice of values for the adult lysine requirement should be re-evaluated and that serious consideration should be given to the extent to which adaptive mechanisms might enable the metabolic requirement for protein to be met from current intakes. This will entail a better understanding of the relationships between dietary protein and health.

Adolescent↗

Transfer of (15)N from oral lactose-ureide to lysine in normal adults.

The metabolic fate of salvaged urea-nitrogen was explored in normal adults who had consumed a diet that provided 36 g protein/day for 7 days. We hypothesised that the colonic microflora utilise nitrogen derived from urea salvage to synthesise lysine in functionally significant amounts for the host. Oral lactose-[(15)N(15)N]ureide is resistant to digestion but is fermented by the colonic microflora to release (15)NH3, which can be used for amino acid synthesis. Prime and intermittent oral doses of lactose-[(15)N(15)N]ureide were ingested for 18 h, urine was collected every 3 h and stools were collected for a further 2 days. Amino acids were isolated from urine and from faecal bacterial protein and the enrichment measured. Compared with baseline values, there was significant enrichment (atoms per cent excess) in faecal bacterial glycine (0.0526), alanine (0.117), lysine (0.0875) and histidine (0.0487), and in urinary glycine (0.016), alanine (0.0144) and lysine (0.0098), but not hisitidine. These data show that the gastrointestinal bacteria can utilise urea-nitrogen in the formation of essential and non-essential amino acids that are available to the host. We estimate that on this low protein diet the amount of lysine from bacterial synthesis and available to the host may be 30 mg/kg/day. These data have important implications for our current perceptions for the dietary requirements for essential amino acids.

Administration, Oral↗

Synthesis of erythrocyte glutathione in healthy adults consuming the safe amount of dietary protein.

BACKGROUND: The finding that plasma glutathione turnover decreases as dietary protein intake decreases suggests that the safe amount of dietary protein, although sufficient for maintenance of nitrogen balance, may be insufficient for maintenance of cellular glutathione. OBJECTIVE: Our objective was to determine the effect of the safe protein intake on the erythrocyte glutathione synthesis rate and its relation with urinary 5-L-oxoproline excretion. DESIGN: Erythrocyte glutathione synthesis and urinary 5-L-oxoproline excretion were measured in young adults (6 men and 6 women) by using an infusion of [(13)C(2)]glycine on 3 occasions: initially during the subjects' habitual protein intake (1.13 g.kg(-1).d(-1)) and on days 3 and 10 of consumption of a diet providing the safe protein intake (0.75 g.kg(-1).d(-1)). RESULTS: Compared with baseline values, the fractional synthesis rate of erythrocyte glutathione was significantly lower (P < 0.05) on days 3 and 10 of the diet with the safe protein intake. Urinary 5-L-oxoproline excretion increased significantly (P < 0.05) above baseline by the third day of the diet with the safe protein intake and remained elevated. Erythrocyte glutathione concentrations and absolute synthesis rates decreased by day 3 but recovered to baseline values by day 10. Erythrocyte concentrations of cysteine, methionine, and serine remained unchanged, whereas erythrocyte concentrations of glycine, glutamic acid, and glutamine increased significantly by day 10. CONCLUSION: During adaptation to the safe amount of dietary protein, there are changes in the concentration and kinetics of erythrocyte glutathione that suggest a reduced antioxidant capacity and possible increased susceptibility to oxidant stress.

Adaptation, Physiological↗

Response of hepatic proteins to the lowering of habitual dietary protein to the recommended safe level of intake.

The plasma concentrations of albumin, HDL apolipoprotein A1 (apoA1), retinol-binding protein (RBP), transthyretin (TTR), haptoglobulin, and fibrinogen were measured, and a stable isotope infusion protocol was used to determine the fractional and absolute synthesis rates of RBP, TTR, and fibrinogen in 12 young adults on three occasions during a reduction of their habitual protein intake from 1.13 to 0.75 g x kg(-1) x day(-1) for 10 days. This study was performed to determine whether healthy adults could maintain the rates of synthesis of selected nutrient transport and positive acute-phase proteins when consuming a protein intake of 0.75 g x kg(-1) x day(-1). During the lower protein intake, the plasma concentration of all the proteins, other than HDL-apoA1, remained unchanged. HDL-apoA1 concentration was significantly reduced (P < 0.05) after 3 days of the lower protein intake, but not at 10 days. The rates of synthesis of RBP and TTR declined significantly (P < 0.05), whereas the rate of synthesis of fibrinogen remained unchanged. The results indicate that, when normal adults consume the recommended safe level of protein, 0.75 g x kg(-1) x day(-1), there is a slower rate of turnover of nutrient transport proteins than on their habitual diet. Hence, healthy individuals consuming this amount of protein may be less able to mount an adequate metabolic response to a stressful stimulus.

Acute-Phase Proteins↗

Effect of reduced maternal protein intake in pregnancy in the rat on the fatty acid composition of brain, liver, plasma, heart and lung phospholipids of the offspring after weaning.

Reduced protein intake during pregnancy decreased maternal hepatic and plasma docosahexaenoic acid concentrations and impaired docosahexaenoic acid accumulation into fetal brain in the rat. The present study investigated whether restriction of maternal protein intake during pregnancy in the rat alters membrane phospholipid fatty acid composition in the offspring after weaning. Female rats (six per group) were mated and fed diets containing either 180 or 90 g protein/kg throughout pregnancy. Mothers were transferred to standard chow after delivery and the litters reduced to eight pups. Weaning was at 28 d and pups were killed 5 to 6 d later. Tissue weights or membrane total phosphatidylcholine (PC) and phosphatidylethanolamine (PE) concentrations in the offspring did not differ between dietary groups. There were significant differences between the 180 and 90 g/kg groups in liver, brain, lung and heart fatty acid composition that differed between tissues and phospholipid classes. For example, docosahexaenoic and arachidonic acid concentrations were 23 and 10 % lower respectively in hepatic PC, but not PE, in the 90 g/kg group. In brain, docosahexaenoic acid concentration was 17 % lower in PC, but not PE, while arachidonic acid content was 21 % greater in PE but unchanged in PC. The greatest differences were in unsaturated fatty acids, which suggests alterations to desaturase activities and/or the specificity of phospholipid biosynthesis. These results suggest that restricted maternal protein intake during pregnancy results in persistent alterations to membrane fatty acid content.

Animals↗

Effects of tuberculosis and HIV infection on whole-body protein metabolism during feeding, measured by the [15N]glycine method.

BACKGROUND: Tuberculosis (TB) and HIV infection are wasting diseases that frequently occur together and have severe consequences on nutritional status. OBJECTIVE: The objective was to determine the effects of TB and HIV, separately and together, on protein metabolism. DESIGN: Protein metabolism was determined in the fed state in 11 healthy control subjects, in 10 patients with HIV infection without TB or other active infection (HIV group), in 10 patients with active TB without HIV infection (TB group), and in 8 patients with HIV infection and active TB (HIVTB group) with the use of oral [(15)N]glycine and measurement of enrichment in urinary urea and ammonia. RESULTS: Whole-body protein flux and degradation were lower in the HIV group than in the control group (mean flux: 3.53 +/- 0.40 compared with 4.75 +/- 0.97 g. kg lean body mass(-1). 12 h(-1); P = 0.002). Protein flux, synthesis, and degradation were not significantly different between the control group and the TB and HIVTB groups. Net protein balance was strongly anabolic in the control, HIV, and TB groups but was neutral in the HIVTB group (P < 0.001 for comparison between groups). CONCLUSIONS: HIV infection was associated with a significant down-regulation of whole-body protein flux. TB alone was not associated with abnormal protein metabolism, but net anabolism in the fed state was impaired in the HIVTB group.

AIDS-Related Opportunistic Infections↗

Increased systolic blood pressure in rats induced by a maternal low-protein diet is reversed by dietary supplementation with glycine.

When rat dams consume a diet low in protein during pregnancy, their offspring develop high blood pressure. On a low-protein diet, the endogenous formation of the amino acid glycine is thought to become constrained. Glycine may become conditionally essential, as its rate of endogenous formation is inadequate to meet metabolic needs, and may be limiting for the normal development of the fetus. In the present study, five groups of Wistar rats were provided during pregnancy with one of five diets: a control diet containing 18% (w/w) casein (CON), a low-protein diet containing 9% casein (MLP), or the low-protein diet supplemented with 3% glycine (MLPG), alanine (MLPA) or urea (MLPU). The offspring were weaned on to standard laboratory chow, and blood pressure was measured at 4 weeks of age. Blood pressure was significantly increased in the MLP, MLPA and MLPU groups compared with the CON group, but for the MLPG group blood pressure was not significantly different from CON. Compared with the CON group, body weight was significantly reduced for the MLP, MLPA and MLPG groups, but for the MLPU group body weight was not different from CON. These data show that different forms of non-essential dietary nitrogen, when consumed during pregnancy, exert different effects upon the growth and function of the offspring. The availability of glycine appears to be of critical importance for normal cardiovascular development.

Animals↗

Effect of reduced dietary protein intake on hepatic and plasma essential fatty acid concentrations in the adult female rat: effect of pregnancy and consequences for accumulation of arachidonic and docosahexaenoic acids in fetal liver and brain.

During pregnancy, the accumulation of long-chain polyunsaturated fatty acids (LCPUFA) in fetal tissues places a substantial demand upon maternal lipid metabolism. As lipid metabolism is intimately linked to aspects of protein metabolism, a reduced protein intake in pregnancy may impair activities of enzymes and transport proteins responsible for supplying LCPUFA to the fetus, thereby compromising fetal development. We have investigated the effect of reduced protein intake on LCPUFA status in the non-pregnant rat and in the pregnant rat, and in fetus at day 20 of gestation. Female rats (n 5 per group) were either mated and fed the control diet (180 g protein/kg) or low-protein diet (90 g protein/kg, LPD) diet throughout pregnancy, or fed the control diet or LPD for 20 d (non-pregnant animals). The fatty acid compositions of maternal liver and plasma, and fetal liver and brain were determined by GC. Feeding the LPD did not lead to any gross changes either in adult or fetal growth, or in total lipid concentrations in adult rat liver. However, the LPD was associated specifically with lower liver (42.6 %) and plasma (19.4 %) phosphatidylcholine (PC), and plasma triacylglycerol (28.6 %) docosahexaenoic acid (DHA) concentrations in pregnant rats and reduced fetal brain PC- (26.1 %) and phosphatidylethanolamine- (25.6 %) DHA concentrations. Together, these results show that variations in maternal dietary protein consumption alter DHA status in pregnancy and modify DHA accumulation into the fetal brain. The present results suggest that lower maternal protein intakes reduce delivery of DHA from the mother to the fetus, which may impair development and function of the fetal brain.

Animals↗

Endogenous glycine and tyrosine production is maintained in adults consuming a marginal-protein diet.

BACKGROUND: The adequacy of indispensable amino acid supplies has received much attention in studies of protein requirements, but the availability of nitrogen for synthesis and maintenance of the supply of dispensable amino acids has been overlooked. OBJECTIVE: We aimed to determine whether nitrogen balance and the endogenous supply of the dispensable amino acids glycine and tyrosine can be maintained with a marginal protein intake. DESIGN: Phenylalanine, glycine, and tyrosine kinetics were measured in young adults (6 men, 6 women) on 4 occasions during a reduction in habitual protein intake (1.13 g x kg(-1) x d(-1)) to a marginal intake (0.75 g x kg(-1) x d(-1)) by using a multiple stable-isotope-infusion protocol. RESULTS: During the 10-d period of marginal protein intake, nitrogen excretion fell initially, then remained constant such that nitrogen balance was negative for the first 2 d and then positive or zero thereafter. Whole-body protein degradation and synthesis predicted from phenylalanine kinetics declined significantly (P < 0.05) over the period of marginal protein intake. Despite the reduction in the amount of glycine and tyrosine derived from whole-body proteolysis, the fluxes of glycine and tyrosine were maintained. CONCLUSIONS: The results show that adaptation to a marginal intake of dietary protein consisted of an overall reduction in whole-body protein turnover, net protein catabolism, and the rate of nitrogen excretion. The conserved nitrogen was sufficient to maintain the endogenous synthesis and hence the supply of glycine and tyrosine.

Adaptation, Physiological↗