Roberto Aquilani

Is nutritional intake adequate in chronic heart failure patients

OBJECTIVES The goal of this study was to investigate the nutrition adequacy and energy availability for physical activity in free-living, clinically stable patients with chronic heart failure (CHF). BACKGROUND Little information exists regarding the nutrition adequacy and alimentary habits of patients with clinically stable CHF. We hypothesized that CHF patients have an inadequate intake of calories and protein, leading to a negative calorie and nitrogen balance, an expression of increased tissue breakdown. METHODS In 57 non-obese patients with CHF (52 males and 5 females; 52 +/- 3 years; body mass index <25 kg/m(2)) and in 49 healthy subjects (39 males and 10 females) matched for age, body mass index, and sedentary life style we evaluated total energy expenditure (TEE), calorie intake (kcal(I)), and nitrogen intake (N(I)) from a seven-day food diary, total nitrogen excretion (TNE), and energy availability (EA = kcal(I) - resting energy expenditure). A zero calorie balance (CB) occurred when kcal(I) = TEE; a nitrogen balance (NB) in equilibrium was set at NB (= N(I) - TNE) 0 +/- 1 g/day. RESULTS In patients and controls kcal(I) and N(I) were similar. However, in CHF patients the kcal(I) was <TEE with a consequent negative CB (-186 +/- 305 kcal/day vs. + 104.2 +/- 273 kcal/day of controls; p < 0.01). Nitrogen balance resulted negative in CHF (-1.7 +/- 3.2 g/24 h vs. + 2.2 +/- 3.6 g/24 h in controls; p < 0.01). Energy availability in CHF patients was 41% lower than in controls (p < 0.05). CONCLUSIONS Non-obese, free-living patients with clinically stable CHF have an inadequate intake of calories and protein and reduced energy availability for physical activity.

Mitochondrial Alterations, Oxidative Stress and Neuroinflammation in Alzheimer's Disease

Alzheimers disease (AD) is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The primary cause and sequence of its progression are only partially understood but abnormalities in folding and accumulation of insoluble proteins such as β-amyloid and Tau-protein are both associated with the pathogenesis of AD. Mitochondria play a crucial role in cell survival and death, and changes in mitochondrial structure and/or function are related to many human diseases. Increasing evidence suggests that compromised mitochondrial function contributes to the aging process and thus may increase the risk of AD. Dysfunctional mitochondria contribute to reactive oxygen species which can lead to extensive macromolecule oxidative damage and the progression of amyloid pathology. Oxidative stress and amyloid toxicity leave neurons chemically vulnerable. The mitochondrial toxicity induced by β-amyloid is still not clear but may include numerous mechanisms, such as the increased permeability of mitochondrial membranes, the disruption of calcium homeostasis, the alteration of oxidative phosphorylation with a consequent overproduction of reactive oxygen species. Other mechanisms have been associated with the pathophysiology of AD. Inflammatory changes are observed in AD brain overall, particularly at the amyloid deposits, which are rich in activated microglia. Once stimulated, the microglia release a wide variety of pro-inflammatory mediators including cytokines, complement components and free radicals, all of which potentially contribute to further neuronal dysfunction and eventually death. Clinically, novel approaches to visualize early neuroinflammation in the human brain are needed to improve the monitoring and control of therapeutic strategies that target inflammatory and other pathological mechanisms. Similarly, there is growing interest in developing agents that modulate mitochondrial function.

Adequate energy-protein intake is not enough to improve nutritional and metabolic status in muscle-depleted patients with chronic heart failure

An adequate energy‐protein intake (EPI) when combined with amino acid supplementation may have a positive impact nutritional and metabolic status in patients with chronic heart failure (CHF).

Oral Amino Acid Supplements Improve Exercise Capacities in Elderly Patients with Chronic Heart Failure

We investigated whether 30 days of oral supplementation with a special mixture of amino acids (AAs), together with conventional therapy, could improve exercise capacity in elderly outpatients with chronic heart failure (CHF). A group of 95 outpatients (12 women and 83 men; New York Heart Association class II-III) aged 65-74 years were studied. This was a randomized, double-blind, placebo-controlled study. The patients performed a basal exercise test and were then randomly assigned to a special oral nutritional mixture of AAs 4 g twice daily (n = 43) or placebo (n = 42). After 30 days we repeated the exercise test. In both tests we measured the following: oxygen consumption (VO2), CO2 production (VCO2), minute ventilation (VE), oxygen cost of ventilation (VO2/VE), CO2 elimination per liter of ventilation (VCO2/VE), respiratory exchange ratio (RER; calculated as VCO2/VO2), oxygen pulse (VO2/heart rate [HR]) and anaerobic metabolism during exercise (ANA-VO2). At day 30, exercise capacity in the AA group had improved (+11 +/- 8 W, p <0.01; +67.5 +/- 44 seconds, p <0.02). This improvement was associated with both reduced circulatory dysfunction and increased peripheral oxygen availability. Indeed, peak VO2 increased by 1.2 +/- 1.1 mL/kg per min (+12.7% +/- 13%; p<0.02) and VO2/HR improved by 1.5 +/- 1.4 mL O2 per heartbeat (p <0.05). ANA-VO2 was reduced by >50% in patients on AAs (from 20.2 +/- 10 mL/kg at day 0 to 10.9 +/- 5 mL/kg at day 30; p <0.02). These variables did not significantly change for patients who received placebo. In conclusion, the study showed that oral AA supplementation, in conjunction with standard pharmacologic therapy, appears to increase exercise capacity by improving circulatory function, muscle oxygen consumption, and aerobic production of energy in elderly outpatients with CHF.

Hypercatabolic Syndrome: Molecular Basis and Effects of Nutritional Supplements with Amino Acids

Hypercatabolic syndrome (HS) is a biochemical state characterized by increased circulating catabolic hormones (eg, cortisol, catecholamines) and inflammatory cytokines (eg, tumor necrosis factors, interleukin-1beta), and decreased anabolic insulin effects with consequent insulin resistance. The most important metabolic consequence of HS is the skeletal and cardiac muscle protein breakdown that releases amino acids (AAs), which in turn supports indispensable body energy requirements but also reduces skeletal and cardiac physiologic and metabolic functions. HS occurs in many diseases such as diabetes mellitus, chronic heart failure, chronic obstructive pulmonary disease, renal and liver failure, trauma, sepsis, and senescence. All of these conditions have predominant catabolic molecules with significant muscular wasting and metabolic impairment. Macronutrients such as AA supplements, taken together with conventional therapy, may maintain muscular protein metabolism and cell functions.

Pathogenic Gut Flora in Patients With Chronic Heart Failure

OBJECTIVES The goal of this study was to measure the presence of pathogenic gut flora and intestinal permeability (IP) and their correlations with disease severity, venous blood congestion, and inflammation in patients with chronic heart failure (CHF). BACKGROUND Evidence suggests that translocation of gut flora and/or their toxins from the intestine to the bloodstream is a possible trigger of systemic CHF inflammation. However, the relation between pathogenic gut flora and CHF severity, as well as IP, venous blood congestion as right atrial pressure (RAP), and/or systemic inflammation (C-reactive protein [CRP]), is still unknown. METHODS This study analyzed 60 well-nourished patients in stable condition with mild CHF (New York Heart Association [NYHA] functional class I to II; n = 30) and moderate to severe CHF (NYHA functional class III to IV; n = 30) and matched healthy control subjects (n = 20). In all subjects, the presence and development in the feces of bacteria and fungi (Candida species) were measured; IP according to cellobiose sugar test results was documented. The study data were then correlated with RAP (echocardiography) and systemic inflammation. RESULTS Compared with normal control subjects, the entire CHF population had massive quantities of pathogenic bacteria and Candida such as Campylobacter (85.3 ± 3.7 CFU/ml vs. 1.0 ± 0.3 CFU/ml; p < 0.001), Shigella (38.9 ± 12.3 CFU/ml vs. 1.6 ± 0.2 CFU/ml; p < 0.001), Salmonella (31.3 ± 9.1 CFU/ml vs 0 CFU/ml; p < 0.001), Yersinia enterocolitica (22.9 ± 6.3 CFU/ml vs. 0 CFU/ml; p < 0.0001), and Candida species (21.3 ± 1.6 CFU/ml vs. 0.8 ± 0.4 CFU/ml; p < 0.001); altered IP (10.2 ± 1.2 mg vs. 1.5 ± 0.8 mg; p < 0.001); and increased RAP (12.6 ± 0.6 mm Hg) and inflammation (12.5 ± 0.6 mg/dl). These variables were more pronounced in patients with moderate to severe NYHA functional classes than in patients with the mild NYHA functional class. Notably, IP, RAP, and CRP were mutually interrelated (IP vs. RAP, r = 0.55; p < 0.0001; IP vs. CRP, r = 0.78; p < 0.0001; and RAP vs. CRP, r = 0.78; p < 0.0001). CONCLUSIONS This study showed that patients with CHF may have intestinal overgrowth of pathogenic bacteria and Candida species and increased IP associated with clinical disease severity, venous blood congestion, and inflammation.

Fat-free mass change after nutritional rehabilitation in weight losing COPD: Role of insulin, C-reactive protein and tissue hypoxia

Background: Fat-free mass (FFM) depletion marks the imbalance between tissue protein synthesis and breakdown in chronic obstructive pulmonary disease (COPD). To date, the role of essential amino acid supplementation (EAAs) in FFM repletion has not been fully acknowledged. A pilot study was undertaken in patients attending pulmonary rehabilitation. Methods: 28 COPD patients with dynamic weight loss > 5% over the last 6 months were randomized to receive EAAs embedded in a 12-week rehabilitation program (EAAs group n = 14), or to the same program without supplementation (C group n = 14). Primary outcome measures were changes in body weight and FFM, using dual X-ray absorptiometry (DEXA). Results: At the 12th week, a body weight increment occurred in 92% and 15% of patients in the EAAs and C group, respectively, with an average increase of 3.8 ± 2.6 kg (P = 0.0002) and −0.1 ± 1.1 kg (P = 0.81), respectively. A FFM increment occurred in 69% and 15% of EAAs and C patients, respectively, with an average increase of 1.5 ± 2.6 kg (P = 0.05) and −0.1 ± 2.3 kg (P = 0.94), respectively. In the EAAs group, FFM change was significantly related to fasting insulin (r2 0.68, P < 0.0005), C-reactive protein (C-RP) (r2 = 0.46, P < 0.01), and oxygen extraction tension (PaO2x) (r2 = 0.46, P < 0.01) at end of treatment. These three variables were highly correlated in both groups (r > 0.7, P < 0.005 in all tests). Conclusions: Changes in FFM promoted by EAAs are related to cellular energy and tissue oxygen availability in depleted COPD. Insulin, C-RP, and PaO2x must be regarded as clinical markers of an amino acid-stimulated signaling to FFM accretion.

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.

Impairment in Walking Capacity and Myocardial Function in the Elderly: Is There a Role for Nonpharmacologic Therapy with Nutritional Amino Acid Supplements?

Elderly persons have reduced muscular mass, with consequent deterioration of their daily activities and reduced quality of life. This is more pronounced in elderly patients affected by chronic diseases such as chronic heart failure (CHF). It has been demonstrated that oral amino acid (AA) supplementation improves muscle protein metabolism. A recent study shows that use of oral supplements with a special mixture of AAs for 12 weeks increases (1) 6-minute walk distance (from 212.5 +/- 34 m to 268.8 +/- 34.9 m; p <0.001), (2) maximal isometric muscular strength (from 14.6 +/- 2.2 kg to 20.2 +/- 2 kg; p <0.001), and (3) peak exercise left ventricular ejection fraction (LVEF 0.55 + 0.4 vs 0.67 + 0.7) (0.558 vs 0.67 +/- 0.7; p <0.01). In a pilot observational study, we studied elderly patients with CHF who were clinically stable on standard therapy (age range, 68-76 years; New York Heart Association (NYHA) class II-III; LVEF <0.40; normal body mass index and arm muscle measurements; peak oxygen consumption <15 mL/kg per min). After basal assessment of (1) cardiac function (by 2-dimensional echocardiography), (2) 6-minute walk test, and (3) blood variables, an AA mixture (4 g x 2 die) was orally administered to the patients for 12 weeks in conjunction with standard therapies and a controlled diet. The AA supplements increased 6-minute walk distance significantly (201 +/- 12 m vs 226 +/- 9 m; p < 0.05). Interestingly, urea values were unchanged (31.3 +/- 10.5 mg/dL vs 32.4 +/- 8.1 mg/dL; p = NS). Our results suggest the potential role of a nonpharmacologic therapy with nutrients (ie, AAs) in an attempt to improve muscular metabolism and function in elderly subjects and in hypercatabolic syndromes such as CHF.

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 patients 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.