Proteins are macro-molecules crucial for cell life, which are made up of amino acids (AAs). In healthy people, protein synthesis and degradation are well balanced. However, in the presence of hypercatabolic stimulation (i.e., inflammation), protein breakdown increases as the resulting AAs are consumed for metabolic proposes. Indeed, AAs are biochemical totipotent molecules which, when deaminated, can be transformed into energy, lipids, carbohydrates, and/or biochemical intermediates of fundamental cycles, such as the Krebs’ cycle. The biochemical consequence of hyper-catabolism is protein disarrangement, clinically evident with signs such as sarcopenia, hypalbuminemia, anaemia, infection, and altered fluid compartmentation, etc. Hypercatabolic protein disarrangement (HPD) is often underestimated by clinicians, despite correlating with increased mortality, hospitalization, and morbidity quite independent of the primary disease. Simple, cheap, repeatable measurements can be used to identify HPD. Therefore, identification and treatment of proteins’ metabolic impairment with appropriate measurements and therapy is a clinical strategy that could improve the prognosis of patients with acute/chronic hypercatabolic inflammatory disease. Here, we describe the metabolism of protein and AAs in hypercatabolic syndrome, illustrating the clinical impact of protein disarrangement. We also illustrate simple, cheap, repeatable, and worldwide available measurements to identify these conditions. Finally, we provide scientific evidence for HPD nutritional treatment.

The goal of this study was to measure arterial amino acid levels in patients with chronic heart failure (CHF), and relate them to left ventricular function and disease severity. Amino acids (AAs) play a crucial role for heart protein-energy metabolism. In heart failure, arterial AAs, which are the major determinant of AA uptake by the myocardium, are rarely measured. Forty-one subjects with clinically stable CHF (New York Heart Association (NYHA) class II to IV) were analyzed. After overnight fasting, blood samples from the radial artery were taken to measure AA concentrations. Calorie (Kcal_I), protein-, fat-, carbohydrate-intake, resting energy expenditure (REE), total daily energy expenditure (REE × 1.3), and cardiac right catheterization variables were all measured. Eight matched controls were compared for all measurements, with the exception of cardiac catheterization. Compared with controls, CHF patients had reduced arterial AA levels, of which both their number and reduced rates are related to Heart Failure (HF) severity. Arterial aspartic acid correlated with stroke volume index (r = 0.6263; p < 0.0001) and cardiac index (r = 0.4243; p = 0.0028). The value of arterial aspartic acid (µmol/L) multiplied by the cardiac index was associated with left ventricular ejection fraction (r = 0.3765; p = 0.0076). All NYHA groups had adequate protein intake (≥1.1 g/kg/day) and inadequate calorie intake (Kcal_I < REE × 1.3) was found only in class IV patients. This study showed that CHF patients had reduced arterial AA levels directly related to clinical disease severity and left ventricular dysfunction.

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.

Conflicting results about alterations of plasma amino acid (AA) levels are reported in subjects with Alzheimer’s disease (AD). The current study aimed to provide more homogeneous AA profiles and correlations between AAs and cognitive tests. Venous plasma AAs were measured in 54 fasting patients with AD (37 males, 17 females; 74.63 ± 8.03 yrs; 3.2 ± 1.9 yrs from symptom onset). Seventeen matched subjects without neurodegenerative symptoms (NNDS) served as a control group (C-NNDS). Patients were tested for short-term verbal memory and attention capacity and stratified for nutritional state (Mini Nutritional Assessment, MNA). Compared to C-NNDS, patients exhibited lower plasma levels of aspartic acid and taurine (p < 0.0001) and higher 3-methylhistidine (p < 0.0001), which were independent of patients’ MNA. In comparison to normonourished AD, the patients at risk of and with malnutrition showed a tendency towards lower ratios of Essential AAs/Total AAs, Branched-chain AAs/Total AAs, and Branched-chain AAs/Essential AAs. Serine and histidine were positively correlated with verbal memory and attention capacity deficits, respectively. Total AAs negatively correlated with attention capacity deficits. Stratifying patients with AD for MNA may identify a dual pattern of altered AAs, one due to AD per se and the other linked to nutritional state. Significant correlations were observed between several AAs and cognitive tests.

Chronic diseases are characterised by altered autophagy and protein metabolism disarrangement, resulting in sarcopenia, hypoalbuminemia and hypo-haemoglobinaemia. Hypo-haemoglobinaemia is linked to a worse prognosis independent of the target organ affected by the disease. Currently, the cornerstone of the therapy of anaemia is iron supplementation, with or without erythropoietin for the stimulation of haematopoiesis. However, treatment strategies should incorporate the promotion of the synthesis of heme, the principal constituent of haemoglobin (Hb) and of many other fundamental enzymes for human metabolism. Heme synthesis is controlled by a complex biochemical pathway. The limiting step of heme synthesis is D-amino-levulinic acid (D-ALA), whose availability and synthesis require glycine and succinil-coenzyme A (CoA) as precursor substrates. Consequently, the treatment of anaemia should not be based only on the sufficiency of iron but, also, on the availability of all precursor molecules fundamental for heme synthesis. Therefore, an adequate clinical therapeutic strategy should integrate a standard iron infusion and a supply of essential amino acids and vitamins involved in heme synthesis. We reported preliminary data in a select population of aged anaemic patients affected by congestive heart failure (CHF) and catabolic disarrangement, who, in addition to the standard iron therapy, were treated by reinforced therapeutic schedules also providing essential animo acids (AAs) and vitamins involved in the maintenance of heme. Notably, such individualised therapy resulted in a significantly faster increase in the blood concentration of haemoglobin after 30 days of treatment when compared to the nonsupplemented standard iron therapy.