Essential amino acid supplementation is associated with reduced serum C-reactive protein levels and improved circulating lymphocytes in post-acute inflamed elderly patients.

BACKGROUND: Persistent systemic inflammation leads to multidistrectual body dysfunctions. Attenuation of inflammation may improve patients' functional and life prognoses. We hypothesized that essential amino acids (EAAs) given to elderly patients in rehabilitation after acute diseases may be associated with a reduced inflammatory state. Therefore, this retrospective study investigated whether the supplementation of EAAs - modulators of immune competence - was associated with a reduced inflammation rate in elderly patients. METHODS: The medical records of 282 patients admitted to the rehabilitation (rehab) institute after acute index events (surgery or medical diseases) (age: 81.18 ± 8.58 years; females: 67.9%) were analyzed. RESULTS: 46 patients (16.3% of the entire population) had received EAA supplements (S), whereas the remaining 236 patients had not (N-S). Systemic inflammation (I) (serum C-reactive protein (CRP) > 0.5 mg/dL) was present in 67.4% of the I-S group and 57.2% of the I-N-S group. During rehab, the I-S group (but not the I-N-S group) showed a reduction in CRP levels (p = 0.03) and an increase in circulating lymphocytes (p = 0.035), immune cells of the adaptive immune system. C-reactive protein levels remained virtually unchanged in non-inflamed patients who received supplements but increased in non-inflamed patients who did not receive supplements (p = 0.05). Stratified for developed infections, CRP levels reduced in S patients (p = 0.008) but did not in N-S patients. CONCLUSION: EAA supplementation was associated with reduced inflammation in both inflamed and infected patients. In addition, EAA supplementation was associated with increased circulating lymphocytes in inflamed patients.

Supplemented amino acids may enhance the walking recovery of elderly subjects after hip fracture surgery.

The purpose of this study was to investigate whether supplemented essential amino acids (EAAs) could enhance rehabilitation therapy (Rehab) for recovery of walking capacity in subjects after hip fracture surgery (HFS). Eighty-three elderly subjects with HFS (20 ± 11 days after acute trauma) were eligible for the study and randomized to receive Rehab only (Rehab; n = 27), Rehab + placebo (RP; n = 28) or Rehab + EAAs (RE 8 g/day; n = 28). The patients' walking capacity (m) was measured by 6-min walking distance (6MWD) at admission and at discharge (median 66 days after admission). All patient groups were treated with the same Rehab (2 sessions/day × 5 days/week). The results showed that the gain in 6MWD was higher in RE than in Rehab and RP (p = 0.034; p = 0.024). The study shows that EAA supplementation can enhance walking recovery rate in subjects with HFS.

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.

The Hip Functional Retrieval after Elective Surgery May Be Enhanced by Supplemented Essential Amino Acids.

It is not known whether postsurgery systemic inflammation and plasma amino acid abnormalities are still present during rehabilitation of individuals after elective hip arthroplasty (EHA). Sixty subjects (36 females; age 66.58 ± 8.37 years) were randomized to receive 14-day oral EAAs (8 g/day) or a placebo (maltodextrin). At admission to and discharge from the rehabilitation center, serum C-reactive protein (CRP) and venous plasma amino acid concentrations were determined. Post-EHA hip function was evaluated by Harris hip score (HHS) test. Ten matched healthy subjects served as controls. At baseline, all patients had high CRP levels, considerable reduction in several amino acids, and severely reduced hip function (HHS 40.78 ± 2.70 scores). After treatment, inflammation decreased both in the EAA group and in the placebo group. Only EAA patients significantly improved their levels of glycine, alanine, tyrosine, and total amino acids. In addition, they enhanced the rate of hip function recovery (HHS) (from baseline 41.8 ± 1.15 to 76.37 ± 6.6 versus baseline 39.78 ± 4.89 to 70.0 ± 7.1 in placebo one; p = 0.006). The study documents the persistence of inflammation and plasma amino acid abnormalities in post-EHA rehabilitation phase. EAAs enhance hip function retrieval and improve plasma amino acid abnormalities.

Unaffected arm muscle hypercatabolism in dysphagic subacute stroke patients: the effects of essential amino acid supplementation.

Alterations in muscle protein turnover of the unaffected side of stroke patients could contribute to physical disability. We investigated whether hypercatabolic activity occurred in unaffected arm muscle and whether supplemented essential amino acids (EAAs) could limit muscle hypercatabolism (MH). Thirty-eight dysphagic subacute stroke subjects (<3 months after acute event) (29 males+9 females; 69.7±11.4 yrs) were enrolled and randomized to receive 8 g/day EAAs (n=19; EAA group) or isocaloric placebo (maltodextrin; n=19, Plac group). Before randomization, all patients had their arterial (A) and venous (V) amino acids measured and muscle (A-V) differences calculated in the unaffected arm. Eight matched and healthy subjects served as controls. When compared to healthy controls, the entire stroke population showed significant muscle release (=negative value A-V) of the amino acid phenylalanine (phenyl-) indicating a prevalence of MH. Moreover, randomized EAA and Plac groups had similar rates of MH. After 38 days from the start of the protocol, the EAA group but not the Plac group had MH converted to balanced protein turnover or anabolic activity. We concluded that muscle protein metabolism of the unaffected arm of dysphagic subacute stroke individuals could be characterized by MH which can be corrected by supplemented EAAs.

Essential amino acids and exercise tolerance in elderly muscle-depleted subjects with chronic diseases: a rehabilitation without rehabilitation?

Exercise intolerance remains problematic in subjects with chronic heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD). Recent studies show that supplemented essential amino acids (EAAs) may exert beneficial effects on CHF/COPD physical capacity. The results from 3 investigations (2 conducted on CHF and 1 on COPD subjects) served as the basis for this paper. The 3 studies consistently showed that elderly CHF and COPD improved exercise intolerance after 1-3 months of EAA supplementation (8 g/d). In CHF exercise capacity increased 18.7% to 23% (watts; bicycle test), and 12% to 22% (meters) in 6 min walking test. Moreover, patients reduced their resting plasma lactate levels (by 25%) and improved tissue insulin sensitivity by 16% (HOMA index). COPD subjects enjoyed similar benefits as CHF ones. They increased physical autonomy by 78.6% steps/day and decreased resting plasma lactate concentrations by 23%. EAA mechanisms explaining improved exercise intolerance could be increases in muscle aerobic metabolism, mass and function, and improvement of tissue insulin sensitivity (the latter only for the CHF population). These mechanisms could be accounted for by EAA's intrinsic physiological activity which increases myofibrils and mitochondria genesis in skeletal muscle and myocardium and glucose control. Supplemented EAAs can improve the physical autonomy of subjects with CHF/COPD.

Supplementation of essential amino acids may reduce the occurrence of infections in rehabilitation patients with brain injury.

BACKGROUND: 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). METHODS: 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). RESULTS: 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). CONCLUSION: 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.

BACKGROUND & AIMS: 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. METHODS: Forty-one patients (58.5% women; mean age 79.8 yrs) 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. RESULTS: 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). CONCLUSIONS: 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.

Nutrition for brain recovery after ischemic stroke: an added value to rehabilitation.

In patients who undergo rehabilitation after ischemic stroke, nutrition strategies are adopted to provide tube-fed individuals with adequate nutrition and/or to avoid the body wasting responsible for poor functional outcome and prolonged stay in the hospital. Investigations have documented that nutrition interventions can enhance the recovery of neurocognitive function in individuals with ischemic stroke. Experimental studies have shown that protein synthesis is suppressed in the ischemic penumbra. In clinical studies on rehabilitation patients designed to study the effects of counteracting or limiting this reduction of protein synthesis by providing protein supplementation, patients receiving such supplementation had enhanced recovery of neurocognitive function. Cellular damage in cerebral ischemia is also partly caused by oxidative damage secondary to free radical formation and lipid peroxidation. Increased oxidative stress negatively affects a patient's life and functional prognosis. Some studies have documented that nutrition supplementation with B-group vitamins may mitigate oxidative damage after acute ischemic stroke. Experimental investigations have also shown that cerebral ischemia changes synaptic zinc release and that acute ischemia increases zinc release, aggravating neuronal injury. In clinical practice, patients with ischemic stroke were found to have a lower than recommended dietary intake of zinc. Patients in whom daily zinc intake was normalized had better recovery of neurological deficits than subjects given a placebo. The aim of this review is to highlight those brain metabolic alterations susceptible to nutrition correction in clinical practice. The mechanisms underlying the relationship between cerebral ischemia and nutrition metabolic conditions are discussed.

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.

Normalization of zinc intake enhances neurological retrieval of patients suffering from ischemic strokes.

INTRODUCTION: The objective of this study was to investigate whether zinc (Zn2+) supplementation could contribute to neurological retrieval of patients suffering from strokes and low Zn2+ intake. PATIENTS AND METHODS: Twenty-six patients with subacute stroke, having adequate daily energy (> or = 24 kcal/kg/day) and protein (> or = 0.8 g/kg/day) intake (EPI) and Zn2+ ingestion lower than two-thirds of the recommended allowance of 10 mg/day, were randomly allocated either to a control group (n = 13) or Zn2+ group (n = 13) where Zn2+ supplementation consisted of 10 mg Zn2+/day. Neurological gravity was tested with the NIH stroke scale (NIHSS) at patient admission and after 30 days of protocol commencement. RESULTS: At day 30, the improvement in NIHSS was higher in the zinc group than in the placebo (-4.7 +/- 1.3 points versus -3.3 +/- 1.1 points; P < 0.02). NIHSS and Zn2+ intake were negatively correlated (r = -0.46; P < 0.02). CONCLUSION: The normalization of Zn2+ intake in stroke patients with low mineral intake may enhance neurological recovery.

Protein supplementation may enhance the spontaneous recovery of neurological alterations in patients with ischaemic stroke.

OBJECTIVE: To determine whether protein supplementation could enhance neurological recovery in subacute patients with ischaemic stroke. DESIGN: Alimentation-independent patients with ischaemic stroke were randomly allocated to either 21 days of protein supplementation (protein-supplemented group; n=20) or to a spontaneous diet only (control group; n=21) in order to investigate the recovery of neurological changes (measured using the National Institute of Health (NIH) Stroke Scale). SETTING: Tertiary care rehabilitation in Italy. PARTICIPANTS: Forty-two patients (27 male and 15 female; 66.4 +/- 11 years) 16 +/-2 days after the acute event. INTERVENTION: Supplementation with a hyperproteic nutritional formula (10% protein). MAIN OUTCOME MEASURES: NIH Stroke Scale and protein intake. RESULTS: At admission to rehabilitation, both groups of patients were homogeneous for demographic, clinical and functional characteristics. After 21 days from the start of the protocol, the NIH Stroke Scale was found to be enhanced in the group with supplemental proteins (-4.4 +/- 1.5 score versus -3 +/- 1.4 of control group; P<0.01). When expressed as difference (triangle up) between baseline and 21 days, the NIH Stroke Scale correlated negatively with change in protein intake (g/day) (r=-0.50, P= 0.001) and positively with change in carbohydrate/protein ratio (r = +0.40, P=0.01) CONCLUSIONS: Protein supplementation may enhance neurological recovery in subacute patients with ischaemic stroke.

Branched-chain amino acids may improve recovery from a vegetative or minimally conscious state in patients with traumatic brain injury: a pilot study.

OBJECTIVE: To investigate whether supplementation with branched-chain amino acids (BCAAs) may improve recovery of patients with a posttraumatic vegetative or minimally conscious state. DESIGN: Patients were randomly assigned to 15 days of intravenous BCAA supplementation (n=22; 19.6g/d) or an isonitrogenous placebo (n=19). SETTING: Tertiary care rehabilitation setting. PARTICIPANTS: Patients (N=41; 29 men, 12 women; mean age, 49.5+/-21 y) with a posttraumatic vegetative or minimally conscious state, 47+/-24 days after the index traumatic event. INTERVENTION: Supplementation with BCAAs. MAIN OUTCOME MEASURE: Disability Rating Scale (DRS) as log(10)DRS. RESULTS: Fifteen days after admission to the rehabilitation department, the log(10)DRS score improved significantly only in patients who had received BCAAs (log(10)DRS score, 1.365+/-0.08 to 1.294+/-0.05; P<.001), while the log(10)DRS score in the placebo recipients remained virtually unchanged (log(10)DRS score, 1.373+/-0.03 to 1.37+/-0.03; P not significant). The difference in improvement of log(10)DRS score between the 2 groups was highly significant (P<.000). Moreover, 68.2% (n=15) of treated patients achieved a log(10)DRS point score of .477 or higher (3 as geometric mean) that allowed them to exit the vegetative or minimally conscious state. CONCLUSIONS: Supplemented BCAAs may improve the recovery from a vegetative or minimally conscious state in patients with posttraumatic vegetative or minimally conscious state.

Branched-chain amino acids enhance the cognitive recovery of patients with severe traumatic brain injury.

OBJECTIVE: To investigate whether supplementation with branched-chain amino acids (BCAAs) in patients with severe traumatic brain injury (TBI) improves recovery of cognition and influences plasma concentrations of tyrosine and tryptophan, which are precursors of, respectively, catecholamine and serotonin neurotransmitters in the brain. DESIGN: Forty patients with TBI were randomly assigned to 15 days of intravenous BCAA supplementation (19.6g/d) (n=20) or an isonitrogenous placebo (n=20). SETTING: Tertiary care rehabilitation setting in Italy. PARTICIPANTS: Forty men (mean age, 32+/-15 y) with TBI and 20 healthy subjects (controls) matched for age, sex, and sedentary lifestyle. INTERVENTION: Supplementation with BCAAs. MAIN OUTCOME MEASURES: Disability Rating Scale (DRS) and plasma concentrations of BCAAs, tyrosine, and tryptophan. RESULTS: Fifteen days after admission to the rehabilitation department, the DRS score had improved significantly in both the placebo group (P<.05 vs baseline) and in the BCAA-supplemented group (P<.01 vs baseline). The difference between the 2 groups was significant (P<.004). Plasma tyrosine concentration improved in the group given BCAA supplementation, and tryptophan concentration increased in patients receiving placebo. CONCLUSIONS: Supplemental BCAAs enhance the retrieval of DRS without causing negative effects on tyrosine and tryptophan concentration.