Oral Essential Amino Acids Research Articles

Acceptability, Compliance, and Safety of Non-small Cell Lung Cancer Cachectic Participants Continuing Compassionate Access in the ACCeRT Clinical Study

Objective: Cancer cachexia is defined as: a ‘multifactorial syndrome’, and it has been suggested that a multitargeted approach is required in its management. High prevalence is seen within non-small cell lung cancer, and patients may continue to experience cachexia post end of anti-cancer treatment, and in the late/end stage.Material and Methods: Participants who had completed week 20/End of Trial visit in the main Auckland’s Cancer Cachexia evaluating Resistance Training (ACCeRT) study were invited to continue with treatment under compassionate use. Participants could continue with 2.09 g of eicosapentaenoic acid (EPA), 300 mg COX-2 inhibitor (celecoxib), once daily; plus two sessions per week of progressive resistance training (PRT), and 20 g oral essential amino acids (EAA); high in leucine, in a split dose over three days post each session. Data was collected on the acceptability, compliance and adherence to medication/PRT sessions. Secondary endpoints included: change in body weight and fat free mass, handgrip and leg strength, the Functional Assessment of Anorexia/Cachexia Therapy, Multidimensional Fatigue Symptom Inventory-Short Form, World Health Organization Quality of Life — BREF, Glasgow prognostic score, and pro-inflammatory cytokines.Results: All six participants, who completed the main ACCeRT study, opted to continue with compassionate use. Acceptability remained high, with overall compliance to last study/PRT visit of 81.0% for EPA, 98.8% for celecoxib, 78.9% for PRT and 77.2% for EAA. Participants continued to lose body weight and Fat-Free Mass, along with reduced albumin and increased C-Reactive protein levels. Mean time on compassionate study treatment was 78 days, and with a mean overall survival of 257 days (140 + 117).Conclusion: Non-small cell lung cancer (NSCLC) cachectic patients are willing to be enrolled onto a multi-targeted treatment regimen, and may benefit from cachexia symptom management even during their late/refractory stage.

Effects of Different Doses of Oral Essential Amino Acid Supplementation in the Patients Aged over 80 Years on Chronic Hemodialysis

The prevalence of malnutrition especially of essential amino acid (EAA) is a significant concern in end-stage renal disease (ESRD) and hemodialysis (HD) patients. The present study evaluates the efficacy of Amiyu® Granule (AG), a pharmaceutically manufactured oral EAA and histidine supplement, in the improvement of the nutritional indices of the ESRD and HD elderly patients (> 80-year-old).

A multi‐targeted treatment approach to cancer cachexia: Auckland's Cancer Cachexia evaluating Resistance Training (ACCeRT) trial

AbstractBackgroundCancer cachexia is a condition often seen at diagnosis, throughout anti‐cancer treatments and in end‐stage non‐small‐cell lung cancer patients.Methods and resultsParticipants with late‐stage non‐small‐cell lung cancer and cachexia (defined as ≥5% weight loss within 12 months) were randomly assigned 1:2 to 2.09 g of eicosapentaenoic acid (EPA) and 300 mg of cyclo‐oxygenase‐2 inhibitor celecoxib orally once daily vs. same dosing of EPA, celecoxib, plus two sessions per week of progressive resistance training and 20 g of oral essential amino acids high in leucine in a split dose over 3 days, after each session. Primary endpoint was the acceptability of the earlier multi‐targeted approach. Main secondary endpoints included change in body weight and fat‐free mass, by bioelectric impedance analysis and total quadriceps muscle volume by magnetic resonance imaging over 20 weeks. Sixty‐nine patients were screened resulting in 20 patients being enrolled. Acceptability scored high, with 4.5/5 (Arm A) and 5/5 (Arm B) for EPA and 5/5 for celecoxib within both arms and 4.8/5 for progressive resistance training sessions and 4.5/5 for essential amino acids within Arm B, all at Week 20. Results showed a net gain in bioelectric impedance analysis fat‐free mass of +1.3 kg, n = 2 (Arm A), compared with +0.7 kg, n = 7 (Arm B) at Week 12, and —1.5 kg, n = 2 (Arm A), compared with —1.7 kg, n = 4 (Arm B) at Week 20. Trends in efficacy in terms of improvement and/or stability in cachexia markers were seen within magnetic resonance imaging muscle volume, albumin, and C‐reactive protein levels within both arms. There were no exercise‐related adverse events, with one possible related adverse event of asymptomatic atrial fibrillation in one participant within Arm A.ConclusionsNon‐small‐cell lung cancer cachectic patients are willing to be enrolled onto a multi‐targeted treatment regimen and may benefit from cachexia symptom management even during the late/refractory stage.

The effect of oral essential amino acids on incretin hormone production in youth and ageing.

BackgroundThe effect of substantive doses of essential amino acids (EAA) on incretin and insulin production, and the impact of age upon this effect, is ill‐defined.MethodsA 15‐g oral EAA drink was administered to young (N = 8; 26 ± 4.4 years) and older (N = 8; 69 ± 3.8 years) healthy volunteers. Another group of younger volunteers (N = 9; 21 ± 1.9 years) was given IV infusions to achieve equivalent plasma amino acids (AA) profiles. Plasma AA, insulin, glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic peptide (GIP) were quantified over 2 hours.ResultsIn younger recruits, EAA‐induced rapid insulinaemia and aminoacidaemia with total amino acids(AA), EAA and branched chain amino acids (BCAA) matched between oral and IV groups. Insulin peaked at 39 ± 29 pmol L−1 at 30 minutes following oral feeding compared to 22 ± 9 pmol L−1 at 60 minutes following IV feeding (P: NS). EAA peaked at 3395 μmol L−1 at 45 minutes during IV infusion compared to 2892 μmol L−1 following oral intake (Feeding effect: P < 0.0001. Oral vs IV feeding: P: NS). There was an 11% greater increase in insulin levels in the 120 minutes duration of the study in response to oral EAA as opposed to IV EAA. GIP increased following oral EAA (452 pmol L−1 vs 232 pmol L−1, P < 0.05). Age did not impact insulin or incretins production.ConclusionPostprandial rises in EAA levels lead to rapid insulinaemia which is higher with oral compared with IV EAA, that is attributed more to GIP and unaffected by age. This finding supports EAA, on their own or as part of high‐protein meal, as nutritive therapeutics in impaired glycaemia and ageing.

The Effects of Electrical Acupuncture and Essential Amino Acid Supplementation on Sarcopenic Obesity in Male Older Adults: A Randomized Control Study

Objective: Aging which is accompanied by loss of skeletal muscle and increase of body fat in some adults older than 60 years does not only result in remarkable influences on daily life function but also increases the risk of cardiovascular events. This study used electrical acupuncture together with essential amino acid supplementation to treat sarcopenic obesity (SO) in male older adults. Methods: A total of 48 male participants with SO (>60 years old) were randomized to electrical acupuncture with oral essential amino acids (EA + AA) or oral essential amino acids alone (AA). Acupuncture points on the limbs were punctured and stimulated electrically once every 3 days for 12 weeks. All participants received essential amino acids orally, twice per day for 28 weeks. Body fat percentage (BFP) and appendicular skeletal muscle index (ASM/H²) was determined by bioelectrical impedance analysis. Results: Both groups exhibited significant changes in BFP after 12, 20, and 28 weeks compared with baseline values; for ASM/H², there were significant differences to baseline values after 12, 20, and 28 weeks in the EA + AA group, but only after 28 weeks in the AA group. Between the two groups, there were significant differences in BFP after 12, 20, and 28 weeks, and in ASM/H² after 20 and 28 weeks. Conclusion: Both methods decrease BFP and increase ASM/H². In male older adults, electrical acupuncture with oral essential amino acids is more effective and can increase muscle mass in a shorter time than oral essential amino acids alone.

Human skeletal muscle is refractory to the anabolic effects of leucine during the postprandial muscle-full period in older men

Leucine modulates muscle protein synthesis (MPS), with potential to facilitate accrual/maintenance of muscle mass. Animal models suggest that leucine boluses shortly after meals may prolong MPS and delay onset of a “muscle-full” state. However, the effects of nutrient “top-ups” in humans, and particularly older adults where deficits exist, have not been explored. We determined the effects of a leucine top-up after essential amino acid (EAA) feeding on anabolic signaling, MPS, and muscle energy metabolism in older men. During 13C6-phenylalanine infusion, 16 men (∼70 years) consumed 15 g of EAA with (n=8, FED + LEU) or without (n=8, FED) 3 g of leucine top-up 90 min later. Repeated blood and muscle sampling permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling including mTOR complex 1 (mTORC1) substrates, cellular ATP and phosphorylocreatine, and MPS. Oral EAA achieved rapid insulinemia (12.5 iU·ml−1 25 min post-feed), essential aminoacidemia (3000 μM, 45–65 min post-feed), and activation of mTORC1 signaling. Leucine top-up prolonged plasma EAA (2800 μM, 135 min) and leucine availability (1050 μM, 135 min post-feed). Fasting FSRs of 0.046 and 0.056%·h-1 (FED and FED + LEU respectively) increased to 0.085 and 0.085%·h-1 90–180 min post-feed and returned to basal rates after 180 min in both groups. Phosphorylation of mTORC1 substrates returned to fasting levels 240 min post-feed in both groups. Feeding had limited effect on muscle high-energy phosphates, but did induce eukaryotic elongation factor 2 (eEF2) phosphorylation. We demonstrate the refractoriness of muscle to nutrient-led anabolic stimulation in the postprandial period; thus, leucine supplements should be taken outside of meals, or with meals containing suboptimal protein in terms of either amount or EAA composition.

Despite Inflammation, Supplemented Essential Amino Acids May Improve Circulating Levels of Albumin and Haemoglobin in Patients after Hip Fractures

Essential amino acids (EAAs) are nutritional substrates that promote body protein synthesis; thus we hypothesised that their supplementation may improve circulating albumin (Alb) and haemoglobin (Hb) in rehabilitative elderly patients following hip fractures (HF). Out of the 145 HF patients originally enrolled in our study, 112 completed the protocol. These subjects were divided into two randomised groups, each containing 56 patients. For a period of two months, one group (age 81.4 ± 8.1 years; male/female 27/29) received a placebo, and the other (age 83.1 ± 7.5 years; male/female 25/31) received 4 + 4 g/day oral EAAs. At admission, the prevalence of both hypoAlb (<3.5 g/dL) and hypoHb (<13 g/dL male, <12 g/dL female) was similar in the placebo group (64.3% hypoAlb, 66% hypoHb) and the treated group of patients (73.2% hypoAlb, 67.8% hypoHb). At discharge, however, the prevalence of hypoAlb had reduced more in EAAs than in placebo subjects (31.7% in EAAs vs. 77.8% in placebo; p < 0.001). There was a 34.2% reduction of anaemia in hypoHb in EAA subjects and 18.9% in placebo subjects, but the difference was not statistically significant. Oral supplementation of EAAs improves hypoAlb and, to a lesser extent, Hb in elderly rehabilitative subjects with hip fractures. Anaemia was reduced in more than one third of patients, which, despite not being statistically significant, may be clinically relevant.

血液透析患者に対する腎不全用必須アミノ酸製剤のアミノグラムおよび血清アルブミンへの効果

血液透析患者に対する腎不全用必須アミノ酸製剤のアミノグラムおよび血清アルブミンへの効果

A Dose- rather than Delivery Profile–Dependent Mechanism Regulates the “Muscle-Full” Effect in Response to Oral Essential Amino Acid Intake in Young Men ,

Background: The anabolic response of skeletal muscle to essential amino acids (EAAs) is dose dependent, maximal at modest doses, and short lived, even with continued EAA availability, a phenomenon termed “muscle-full.” However, the effect of EAA ingestion profile on muscle metabolism remains undefined.Objective: We determined the effect of Bolus vs. Spread EAA feeding in young men and hypothesized that muscle-full is regulated by a dose-, not delivery profile–, dependent mechanism.Methods: We provided 16 young healthy men with 15 g mixed-EAA, either as a single dose (“Bolus”; n = 8) or in 4 fractions at 45-min intervals (“Spread”; n = 8). Plasma insulin and EAA concentrations were assayed by ELISA and ion-exchange chromatography, respectively. Limb blood flow by was determined by Doppler ultrasound, muscle microvascular flow by Sonovue (Bracco) contrast-enhanced ultrasound, and phosphorylation of mammalian target of rapamycin complex 1 substrates by immunoblotting. Intermittent muscle biopsies were taken to quantify myofibrillar-bound 13C6-phenylalanine to determine muscle protein synthesis (MPS).Results: Bolus feeding achieved rapid insulinemia (13.6 μIU · mL−1, 25 min after commencement of feeding), aminoacidemia (∼2500 μM at 45 min), and capillary recruitment (+45% at 45 min), whereas Spread feeding achieved attenuated insulin responses, gradual low-amplitude aminoacidemia (peak: ∼1500 μM at 135 min), and no detectable capillary recruitment (all P < 0.01 vs. Bolus). Despite these differences, identical anabolic responses were observed; fasting fractional synthetic rates of 0.054% · h−1 (Bolus) and 0.066% · h−1 (Spread) increased to 0.095% and 0.104% · h−1 (no difference in increment or final values between regimens). With both Spread and Bolus feeding strategies, a latency of at least 90 min was observed before an upswing in MPS was evident. Similarly with both feeding strategies, MPS returned to fasting rates by 180 min despite elevated circulating EAAs.Conclusion: These data do not support EAA delivery profile as an important determinant of anabolism in young men at rest, nor rapid aminoacidemia/leucinemia as being a key factor in maximizing MPS. This trial was registered at clinicaltrials.gov as NCT01735539.

The effectiveness of oral essential aminoacids and aminoacids containing dialysate in peritoneal dialysis

Background/Aim: Oral essential amino acids (AAs) containing supplements (EAS) and AA containing dialysate (ACD) are frequently used in peritoneal dialysis (PD) patients with malnutrition. The present study was conducted to investigate two strategies and compare their effects on the malnutrition status of PD patients. Materials and Methods: A total of 31 EAS, 14 ACD patients were enrolled in this study. Serum albumin levels were lower than 3.5 g/dL in all subjects. EAS group patients took five pills containing AAs three times a day with meals. In the other, 2.000 cc of 1.1% ACD was given to patients daily during the study. Demographic and laboratory parameters were analyzed and compared at baseline and 6th month. Results: Significant increases in BMI, albumin, and protein in both groups. Mean albumin levels increased significantly by 0.54 g/dL in ACD group (p < 0.005) and 0.49 g/dL in EAS group (p < 0.001) following 6 months. Mean albumin and delta albumin levels did not differ between two groups. Conclusion: These strategies may play an important role in increasing albumin levels and improving the nutritional status of PD patients.

Supplementation of Essential Amino Acids May Reduce the Occurrence of Infections in Rehabilitation Patients With Brain Injury

To investigate whether supplementation with oral essential amino acids (EAAs) may reduce the occurrence of nosocomial infection among patients with brain injury (BI: stroke, trauma, anoxic coma). Patients (n = 125; 77 men, 48 women; mean age 63 ± 15 years) with stroke (68.8%), subarachnoid hemorrhage (17.6%), traumatic BI (7.2%), and anoxic BI (6.4%) 88 ± 15 days after the index event. Patients were randomly assigned to 2 months of oral EAAs (n = 63; 8 g/d) or placebo (n = 62). Over the first month of rehabilitation, there were 60 infections in the whole population of 125 patients (48%); however, the rate was 23.2% lower in the EAA group (23 episodes/63 patients; 36.5%) than in the placebo group (37 episodes/62 patients; 59.7%) (P < .01). The types of infection were similarly distributed between the 2 groups. Serum levels of prealbumin <20 mg/dL and C-reactive protein (CRP) >0.3 mg/dL were the best predictors of future infection (prealbumin: odds ratio [OR] = 4.17, confidence interval [CI] 1.84-9.45, P < .001; CRP: OR = 3.8, CI 1.71-8.44, P < .001). Supplementary EAAs may reduce the occurrence of nosocomial infections in rehabilitation patients with BI. Prealbumin and CRP are the best predictors of future infections.

Effect of essential amino acid supplementation on quality of life, Amino acid profile and strength in institutionalized elderly patients

This study assessed the efficacy of supplemented essential amino acids on depressive symptoms, nutrition, muscle function, daily physical activity, and health-related quality of life (HRQoL) of institutionalized elderly patients. Forty-one patients (58.5% women; mean age 79.8yrs) with sequelae of coronary artery disease (73%), femoral fracture (34%), were randomly assigned to receive oral essential amino acids 4 gr 2 times a day for 8 weeks or isocaloric placebo. Before randomization and 8 weeks after the protocol started, the following variables were measured: depressive symptoms (Geriatric Depression Scale, GDS), nutritional panel (Mini Nutritional Assessment, MNA; serum albumin and prealbumin levels), muscle strength (Hand Grip, HG), Activity Daily Life (ADL), Quality of Life (SF-36, HRQoL) and amino acid profile. Compared with the placebo group, EAA patients improved nutrition (MNA score 22.6±1.5 post vs 21.8±1.6 pre; p<0. 04, albumin g/dl 4.04±0.35 post vs 3.88±0.3 pre; p<0.01), GDS(score 10.3±1.75 post vs 13.85±3.37 pre; p<0.001), HG (Kg 19.75±1.7 post vs 18.68±1.36 pre; p=0.001), ADL (p<0.04) and both physical and mental components of SF-36 (p<0.002). Oral supplementation with essential amino acids improved several determinants of quality of life in institutionalized elderly patients, including depressive symptoms, nutrition, muscle function and daily life activity.

Effects of oral amino acid supplementation on long-term-care-acquired infections in elderly patients

The very high general infection rate (IRI) observed in our Geriatric Intensive Rehabilitation Center (GIRC) led us to investigate whether patient supplementation with essential amino acids (EAAs), modulators of immuno-competence, could reduce IRI. Eighty elderly patients admitted to our GIRC ( n = 40; age 79.5 ± 7.71; male/female 14/26) or placebo ( n = 40; age 82.13 ± 6.15; male/female 13/27) were allocated to an 8 g/day oral EAAs group and were surveyed for infections (>48 h from admission) over the first month of their hospital stay. The IRI was 67% for the entire population of patients, 82.5% (33/40 patients) in the placebo group and 52% (21/40 patients) in the EAA group ( p < 0.02). When patients were divided into infection group (IG) and without-infection group (WIG), independently of post randomization allocation, the WIG had higher levels of serum albumin ( p < 0.001), blood hemoglobin (Hb) concentration ( p = 0.01), dietary protein ( p = 0.008) calorie intakes ( p = 0.05) but lower serum C-reactive protein (CRP) ( p < 0.001). The factor of CRP > 0.8 mg/dl and Hb ≤ 12 in females, ≤13 in males was associated 4 times and 3.6 times risk of infection, respectively, by sex. EAAs supplementation may lower the risk of infection by 30% in the rehabilitative elderly population. CRP and blood hemoglobin levels can be considered risk markers of future infection.

Successful treatment of hypoalbuminemic hemodialysis patients with a modified regimen of oral essential amino acids

Objective: To evaluate compliance and the change in serum albumin associated with essential amino acid (EAA) therapy in hypoalbuminemic hemodialysis subjects. Design and Setting: Open label, single intervention, pilot study conducted at 2 outpatient hemodialysis centers located in Baltimore, Maryland. Subjects: Eighteen patients with a mean 3-month prestudy serum albumin of <3.8 g/dL and a mean Kt/V of ≥1.0, without any recent hospitalizations or infections, who provided informed consent, and who demonstrated ≥90% compliance rate during a 2 week run-in period, were enrolled in the study. The mean age was 61.3 years, 44% were male, 78% were black, and 50% were diabetic. Intervention: Subjects were instructed to take 3 Aminess N tablets (Recip AB, Stockholm, Sweden) 3 times each day with meals (total of 6.8 g of EAA per day) for 4 months. Main outcome measure: Median 4-month compliance and the change in mean follow-up serum albumin levels (mean of the serum albumin levels at day 30, day 60, day 90, and day 120 after the start of therapy) compared with mean baseline serum albumin levels (mean of the serum albumin levels at day −90, day −60, day −30, and day 0 before therapy). Secondary outcomes included changes in grip strength and body weight. Data was also collected on C-reactive protein levels, dialysis adequacy (Kt/V), and serum bicarbonate. A 2-day dietary recall was obtained at both the start and finish of the study. Results: Monthly compliance with EAA tablets remained relatively stable over the study period, with median compliance rates of 86%, 88%, 82%, and 82% at months 1 through 4, and an overall median compliance of 82%. Seventy-eight percent of patients had an overall compliance rate of 70% or greater. Serum albumin improved from baseline to follow-up by a mean (95% confidence interval) of 0.20 g/dL (95% confidence interval, 0.04 to 0.30; P = .001). Lowest postdialysis weight increased from a mean of 74.5 kg to 77.1 kg ( P = .05), and there was a nonsignificant increase in grip strength. C-reactive protein levels increased in 33%, remained constant in 11%, and decreased in 56% of subjects, and there was no significant correlation between change in C-reactive protein levels and improvement in serum albumin. Dietary recalls did not show any significant change in the spontaneous protein or caloric intakes in association with the use of the EAA tablets. Conclusion: Although uncontrolled, these results support the feasibility and benefits of moderate dose oral EAA supplementation in hypoalbuminemic hemodialysis subjects. © 2001 by the National Kidney Foundation, Inc.

Successful treatment of hypoalbuminemic hemodialysis patients with a modified regimen of oral essential amino acids

Successful treatment of hypoalbuminemic hemodialysis patients with a modified regimen of oral essential amino acids

Oral and Parenteral Essential Amino Acid Therapy in Malnourished Hemodialysis Patients

Background/Aims: Malnutrition has been encountered more frequently than expected and is associated with increased morbidity and mortality in hemodialysis (HD) patients. Until the last few years, only oral and enteral nutritional supplies have been used in the treatment of malnutrition in HD patients. However, intradialytic parenteral essential amino acid (EAA) nutrition has recently been introduced to treat these patients. The present study was conducted to compare both methods of EAA nutrition, oral and parenteral, in malnourished HD patients. Methods: Half of the 20 malnourished HD patients in this study received 0.9 g/kg/week of oral EAA (oral group), while the other half of the patients were treated with the same dose of parenteral EAA (parenteral group) for 4 months. However, at the very beginning of the study, 4 patients from the oral group were transferred to the parenteral group because of complaints such as nausea and vomiting. Therefore, this study was completed with 6 patients in the oral group and 14 patients in the parenteral group. Some biochemical parameters, including blood lymphocyte counts and anthropometric measurements as indicators of the nutritional status, were obtained from both of the groups in the pre- and posttreatment periods. Results: Following the treatment, there were no statistically significant differences between the groups with respect to anthropometric measurements. However, statistically significant increases were observed in serum albumin (p = 0.048) and creatinine (p = 0.006) levels and blood lymphocyte counts (p = 0.006) in the parenteral group, while there were statistically significant increases only in serum calcium (p = 0.028) levels and blood lymphocyte counts (p = 0.038) in the oral group following the treatment when compared to pretreatment values. Conclusion: These results show that parenteral EAA therapy is more comfortable and effective than oral EAA therapy in the treatment of malnourished HD patients.

Randomized double-blind trial of oral essential amino acids for dialysis-associated hypoalbuminemia

Hypoalbuminemia is associated with substantial morbidity and mortality in dialysis patients. Subjects with a mean three-month prestudy serum albumin of 3.8 g/dL or less and who demonstrated >/=90% compliance during a two-week run-in period were randomized to 3.6 g of essential amino acids (EAAs) or placebo three times daily with meals for three months. Randomization was stratified by dialysis modality and by severity of the hypoalbuminemia. The primary study outcome was change in the average of three monthly serum albumin measurements between baseline and follow-up. Fifty-two patients were randomized; 47 patients (29 hemodialysis and 18 peritoneal dialysis) met the predetermined primary analysis criteria. The mean compliance rates averaged 75, 70, and 50% at months 1, 2, and 3, respectively, and were similar for EAAs and placebo. Serum albumin in the hemodialysis patients, EAA versus placebo, improved [(mean +/- SE) 0.22 +/- 0.09 g/dL, P = 0.02]. Changes in peritoneal dialysis patients were not significant (0.01 +/- 0.15 g/dL), but approached significance for the total study group (0.14 +/- 0.08 g/dL, P = 0.08). Patients in the very low albumin strata (<3.5 g/dL) improved more than those in the low albumin strata (3.5 to 3.8 g/dL, P < 0.01). There was a significant correlation (r = 0.83, P = 0.001) within the hemodialysis EAA group between the baseline C-reactive protein level and improvement in serum albumin. Improvements were also seen in grip strength and SF-12 mental health score, but not in serum amino acid levels, SF-12 physical health score, or anthropometric measurements. Oral EAAs induce a significant improvement in the serum albumin concentration in hemodialysis but not peritoneal dialysis subjects. Further study of their long-term effects on morbidity and mortality is warranted.

Loss of Amino Acids during Hemodialysis: Effect of Oral Essential Amino Acid Supplementation

The aim of this study was to investigate the effect of amino acid (AA) supplementation on the loss and its time course of free AA, during hemodialysis. 2 uremic patients on regular hemodialysis received an increasing number of essential AA tablets during the dialysis. The loss and its time course of 6 essential and 7 nonessential free AA during dialysis was assayed in the dialysate. The loss per dialysis treatment of the administered essential AA increased almost proportionally with the doses of AA tablets. For the nonessential AA, no definite relationship between doses of AA tablets and losses was observed. At all levels of supplementation, methionine was retained best: 90% of the amount present in the tablets. Threonine showed the lowest retention: 15-55%.

THE EFFECTS OF KETOACID ANALOGUES ON GROWTH, BODY COMPOSITION AND METABOLISM IN CHILDREN WITH ADVANCED CHRONIC RENAL FAILURE

A 10 year old girl with advanced chronic renal failure (GFR 11ml/min/1.73m2) and subnormal growth was treated with a protein restricted diet supplemented with oral essential amino acids and the ketoacid analogues (KAA) of valine, leucine, isoleucine, phenylalanine and methionine. Blood urea fell from 20 to 6 mmol/l and nitrogen balance improved from +1.5 to +2.1 GN/day. Growth velocity during 0.8 yrs treatment increased from 4.6 to 10.5cm/year, growth velocity standard deviation score for bone age from -0.79 to +4.36, height standard deviation score for bone age from -1.56 to -0.57. Skinfold thickness increased from the 10th to 75th percentile, weight for height from 84 to 99%. The diet was well tolerated and no complications except mild hypercalcaemia were seen. These results suggest that the anabolic effect of KAA may be beneficial to growth in uraemic children. Eight further children are currently on treatment. The effects of KAA on their growth, body composition, plasma amino and ketoacid levels, and hormonal and metabolic status, will be presented.

Oral essential amino acid supplements in children with advanced chronic renal failure

The effects on growth, nitrogen balance, and body composition of a protein-restricted diet supplemented with oral essential amino acids (EAA) were studied in seven children with advanced chronic renal failure. The diet was designed to provide minimum protein requirements for height-age, half in unselected form and half as an EAA supplement. Energy from carbohydrate and fat were increased to give a protein/energy ratio of 1.25 G:100 kcal. Nitrogen balance, studied in five children before and after 6 to 8 months of EAA treatment, was improved in each case. intracellular water (total body water minus bromide space) increased in four children but fell in three children during treatment. No significant improvement in growth, expressed as height or height velocity standard deviation scores in relation to bone age, was observed. Serum urea and urea/creatinine ratio fell after institution of EAA treatment, but the fall was not sustained. Although the EAA preparation proved acceptable to the children, dietary assessments indicated that the desired dietary aims were rarely achieved. It is concluded that, in this pediatric age group, the long-term application of a protein restricted diet with EAA supplements is of limited value.