Francesco Saverio Dioguardi

The Effects of Amino Acid Supplementation on Muscular Performance During Resistance Training Overreaching

The purpose of this study was to examine the effects of ami-no acid supplementation on muscular strength, power, and high-intensity endurance during short-term resistance training overreaching. Seventeen resistance-trained men were randomly assigned to either an amino acid (AA) or placebo (P) group and underwent 4 weeks of total-body resistance training consisting of two 2-week phases of overreaching (phase 1: 3 X 8–12 repetitions maximum [RM], 8 exercises; phase 2: 5 X 3–5RM, 5 exercises). Muscle strength, power, and high-intensity endurance were determined before (T1) and at the end of each training week (T2-T5). One repetition maximum squat and bench press decreased at T2 in P (5.2 and 3.4 kg, respectively) but not in AA, and significant increases in 1RM squat and bench press were observed at T3-T5 in both groups. A decrease in the ballistic bench press peak power was observed at T3 in P but not AA. The fatigue index during the 20-repetition jump squat assessment did not change in the P group at T3 and T5 (fatigue index = 18.6 and 18.3%, respectively) whereas a trend for reduction was observed in the AA group (p = 0.06) at T3 (12.8%) but not T5 (15.2%; p = 0.12). These results indicate that the initial impact of high-volume resistance training overreaching reduces muscle strength and power, and it appears that these reductions are attenuated with amino acid supplementation. In addition, an initial high-volume, moderate-intensity phase of overreaching followed by a higher intensity, moderate-volume phase appears to be very effective for enhancing muscle strength in resistance-trained men.

To Give or Not to Give? Lessons from the Arginine Paradox

Arginine is one of the 20 amino acids (AA) found in proteins and synthesized by human cells. However, arginine is also the substrate for a series of reactions leading to the synthesis of other AA and is an obligatory substrate for two enzymes with diverging actions, arginases and nitric oxide synthases (NOS), giving origin to urea and NO, respectively. NO is a very potent vasodilator when produced by endothelial NOS (eNOS). The ‘arginine paradox’ is the fact that, despite intracellular physiological concentration of arginine being several hundred micromoles per liter, far exceeding the ∼5 µM KM of eNOS, the acute provision of exogenous arginine still increases NO production. Clinically, an additional paradox is that the largest controlled study on chronic oral arginine supplementation in patients after myocardial infarction had to be interrupted for excess mortality in treated patients. Expression and activity of arginases, which produce urea and divert arginine from NOS, are positively related to exogenous arginine supplementation. Therefore, the more arginine is introduced, the more it is destroyed, eventually leading to impaired NO production. In this review, conditions influencing the low arginine concentrations found in plasma will be reviewed, revising the paradigm that simple replenishment of what is lacking will always produce beneficial consequences.

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.

Morphometric changes induced by amino acid supplementation in skeletal and cardiac muscles of old mice.

Aging is associated with progressive structural disorganization of muscular and cardiac fibers, decreasing functional capacity, and increased rates of disease and death. Aging is also characterized by disturbances in protein synthesis with impaired cellular organelle functions, particularly in the mitochondria. The availability of amino acids is a key factor for the overall metabolism of mammals and exogenous supplements of amino acid mixtures (AAm) could be a valid therapeutic strategy to improve quality of life, avoiding malnutrition and muscle wasting in the elderly. We investigated the morphoquantitative effects of long-term AAm supplementation on the mitochondria and sarcomeres (by electron microscope) and on collagen matrix deposition (by histologic techniques) in both skeletal and cardiac muscles of young and aged mice. Our data showed that old animals have fewer mitochondria and massive fibrosis in both muscles. Long-term AAm supplementation increased the number and volume of mitochondria and sarcomeres and decreased fibrosis in both skeletal muscle and hearts in old rats. These findings indicate that AAm restored muscular morphologic parameters and probably improved the mechanical performance of these organs.

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.

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.

Clinical use of amino acids as dietary supplement: pros and cons

Nitrogen supply is pivotal for the maintenance of life. Amino acids can be utilized to synthesize both glucose and lipids. The opposite, i.e., production of amino acids from either one of them, is not possible in the absence of other amino acids as donors of nitrogen. The quality of amino acid content in protein has been re-evaluated recently, and the relevance of essential amino acids has been repeatedly underlined. Essential amino acid requirements in different mammals are not identical, and ratios among them should be taken into account when projecting an efficient formulation. Recent research has demonstrated that genes respond to different qualities and quantities of nutritional supply, and increased provision of essential amino acids increases lifespan in animal experiments through mitochondriogenesis and maintenance of elevated rates of synthesis of anti-oxidant molecules. Moreover, genetic expression of key controllers of synthesis, like mTOR, may be particularly important for understanding skeletal muscle maintenance. Losses of muscle mass and impaired immune function are related to reduced protein supply, and there is increasing evidence that regular essential amino acid intake as part of an oral diet is effective in reversing muscle catabolism, promoting muscle anabolism, and restoring immunological function. Therefore, the use of amino acids as supplements to diet would be expanding in the near future. Is this safe? Few data are available on amino acid toxicity, and only one essential amino acid may be considered to have clinically relevant toxicity: methionine, because it is transformed into a toxic intermediate, homocysteine, when cysteine synthesis is required by metabolic needs. Matching of stoichiometric ratios between methionine and cysteine may solve the problem of supplying sufficient amounts of sulfur to the body. Arginine and glutamine are two non-essential amino acids than can become “conditionally essential” because of elevated needs during pathological conditions, and metabolism may not be able to maintain their concentrations at sufficient levels to match metabolic requirements. Chronic exogenous arginine supplementation has not proven to exert positive clinical effects in different trials, and sequential articulation of the knowledge of introduction of arginine-driven transcriptional, translational, and epigenetic adaptations may give us a key for interpreting those puzzling results.

Topical application of dressing with amino acids improves cutaneous wound healing in aged rats.

The principal goal in treating surgical and non-surgical wounds, in particular for aged skin, is the need for rapid closure of the lesion. Cutaneous wound healing processes involve four phases including an inflammatory response with the induction of pro-inflammatory cytokines. If inflammation develops in response to bacterial infection, it can create a problem for wound closure. Reduced inflammation accelerates wound closure with subsequent increased fibroblast function and collagen synthesis. On the contrary, prolonged chronic inflammation results in very limited wound healing. Using histological and immunohistochemical techniques, we investigated the effects of a new wound dressing called Vulnamin that contains four essential amino acids for collagen and elastin synthesis plus sodium ialuronate (Na-Ial), compared with Na-Ial alone, in closure of experimental cutaneous wounds of aged rats. Our results showed that the application of Vulnamin dressings modulated the inflammatory response with a reduction in the number of inflammatory cells and inducible nitric oxide synthase (iNOS) immunolocalisation, while increasing endothelial nitric oxide synthase (eNOS) and transforming growth factor-beta1 (TGF-beta1) immunolocalisation. Furthermore, the dressing increased the distribution density of fibroblasts and aided the synthesis of thin collagen fibers resulting in a reduction in healing time. The nutritive approach using this new wound dressing can provide an efficacious and safe strategy to accelerate wound healing in elderly subjects, simplifying therapeutic procedures and leading to an improved quality of life.

A Novel Amino Acids Oral Supplementation in Hemodialysis Patients: a Pilot Study

Background: Protein malnutrition and lowering serum albumin is frequent in hemodialysis patients. A special amino acid formulation has recently been used with favorable effects in elderly people but no data exist in renal patients. Aim: To assess the effects of this novel amino acid formulation in stable hemodialysis patients with reduced albumin levels. Methods: Thirty stable hemodialysis patients with serum albumin levels <3.5 g/dL, normalized protein nitrogen appearance (nPNA) <1.1 g/kg/d, and body mass index (BMI) >20 kg/m2 were selected: 15 patients were randomized to oral amino acid supplementation (4 g thrice a day) for 3 months and 15 patients comparable for age, gender, and dialysis durations formed the control group. Biochemistry and bioimpedentiometry parameters were measured at baseline and at the end of treatment. Results: No difference was observed between study group and control group at baseline. At the end of the study period, no change occurred in the studied parameters in the control group, whereas increase in serum albumin (3.1 ± 0.3 vs. 3.6 ± 0.2 g/dL, p < 0.001) and in total proteins (5.7 ± 0.4 vs. 6.4 ±0.7 g/dL, p < 0.001) occurred in the study group. Hemoglobin rose from 10.7 ± 0.9 to 11.7 ± 0.8 g/dL (p < 0.05) at the same erythropoiesis-stimulating agent (ESA) dosage. C-Reactive protein (CRP) levels decreased in the study group (8.7 ± 7.3 vs. 3.8 ± 3.1 mg/L, p < 0.01). Increase of body weight and of equilibrated protein catabolic rate (ePCR) was observed in the study group. Conclusions: Oral amino acids supplementation was able to improve albumin and total protein in hypoalbuminemia hemodialysis patients. This effect was associated with reduction of CRP levels that is with lowering of pro-inflammatory status and anemia improvement.