phosphocreatine and Cachexia

Weight loss and low BMI due to an underlying illness have been associated with increased mortality, reduced functional capacity, and diminished quality of life. There is a need for well tolerated, long-term approaches to maintain body weight in patients with cachexia or wasting. The purpose of this review is to highlight the scientific and clinical evidence derived from the recent literature investigating the rationale for and potential medical use of creatine supplementation in patients with cachexia or wasting.. Some studies have demonstrated that supplementation with creatine can increase creatine reserves in skeletal muscle and increase muscle mass and performance in various disease states that affect muscle size and function. The mechanisms underlying these effects are not clear. It has been suggested that creatine supplementation may increase intramuscular phosphocreatine stores and promote more rapid recovery of adenosine triphosphate levels following exercise, thus allowing users to exercise for longer periods or at higher intensity levels. Other hypothesized mechanisms include attenuation of proinflammatory cytokines, stimulation of satellite cell proliferation and upregulation of genes that promote protein synthesis and cell repair.. Creatine is a generally well tolerated, low-cost, over-the-counter nutritional supplement that shows potential in improving lean body mass and functionality in patients with wasting diseases. However, placebo-controlled studies have shown variable effects, with improvements in some and not in others. Additional studies with longer follow-up are required to identify the populations that might benefit most from creatine supplementation.

Topics: Adenosine Triphosphate; Body Composition; Cachexia; Creatine; Dietary Supplements; Exercise; Humans; Muscle, Skeletal; Muscular Atrophy; Phosphocreatine; Wasting Syndrome

Topics: Adenosine Triphosphate; Anatomy, Comparative; Animals; Blood Glucose; Brain Stem; Cachexia; Cats; Cerebral Ventricles; Electric Stimulation; Enteral Nutrition; Feedback; Feeding and Eating Disorders; Feeding Behavior; Globus Pallidus; Goats; Haplorhini; Humans; Hunger; Hypothalamus; Limbic System; Liver; Motor Cortex; Norepinephrine; Obesity; Phosphocreatine; Physiology, Comparative; Rabbits; Rats; Self Stimulation; Sheep; Starvation

Cancer-related cachexia is an obscure syndrome leading to muscle wasting, reduced physical fitness and quality of life. The aim of this study was to assess morphology, metabolism, and microcirculation in skeletal muscles of patients with cancer-related cachexia and to compare these data with matched healthy volunteers.. In 19 patients with cancer-induced cachexia and 19 age-, gender-, and body-height-matched healthy volunteers body composition and aerobic capacity (VO(2max)) were analyzed. Skeletal muscle fiber size and capillarization were evaluated in biopsies of the vastus lateralis muscle. The cross-sectional area (CSA) of the quadriceps femoris muscle was measured by magnetic resonance imaging as well as its isokinetic and isometric force. The energy and lipid metabolism of the vastus lateralis muscle was quantified by (31)P and (1)H spectroscopy and parameters of its microcirculation by contrast-enhanced ultrasonography (CEUS).. Morphologic parameters were about 30% lower in cachexia than in volunteers (body mass index: 20 +/- 3 vs. 27 +/- 4 kg m(-2), CSA: 45 +/- 13 vs. 67 +/- 14 cm(2), total fiber size: 2854 +/- 1112 vs. 4181 +/- 1461 microm(2)). VO(2max) was reduced in cachexia (23 +/- 9 vs. 32 +/- 7 ml min(-1) kg(-1), p=0.03), whereas histologically determined capillary density and microcirculation in vivo were not different. Both concentrations of muscular energy metabolites, pH, and trimethyl-ammonium-containing compounds were comparable in both groups. Absolute strength of quadriceps muscle was reduced in cachexia (isometric: 107 +/- 40 vs. 160 +/- 40 Nm, isokinetic: 101 +/- 46 vs. 167 +/- 50 Nm; p=0.03), but identical when normalized on CSA (isometric: 2.4 +/- 0.5 vs. 2.4 +/- 0.4 Nm cm(-2), isokinetic: 2.2 +/- 0.4 vs. 2.5 +/- 0.5 Nm cm(-2)).. Cancer-related cachexia is associated with a loss of muscle volume but not of functionality, which can be a rationale for muscle training.

Topics: Adenosine Triphosphate; Cachexia; Case-Control Studies; Female; Gastrointestinal Neoplasms; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Muscle, Skeletal; Nuclear Magnetic Resonance, Biomolecular; Oxygen; Phosphocreatine

Cancer cachexia is a syndrome manifested by a variety of metabolic abnormalities that include depletion of host energy stores. We studied liver and skeletal muscle high energy phosphate compounds, inorganic phosphorus (Pi), and the energy charge in tumor-bearing (TB), pair fed non-tumor-bearing (NTB), and tumor-bearing resected (RES) rats.. F344 rats were randomized into TB (n = 13), NTB (n = 13), and RES (n = 5) groups. On day 0, the flanks of the TB and RES animals were injected with 1 x 10(7)n methylcholanthrene (MCA)-induced sarcoma cells. On day 19, TB and NTB rat liver and skeletal muscle were analyzed for adenine nucleotides, phosphocreatine, and Pi, and RES animals underwent tumor resection followed by tissue analysis 10 days later.. Although the liver adenylate energy charge was maintained, the level of liver adenosine monophosphate was significantly increased and the liver adenosine diphosphate level was decreased in the TB animals (3.55 +/- 0.6, 3.70 +/- 0.3 mumoles/gm dry weight, p < 0.05, p = 0.05, respectively) when compared with the NTB animals (3.06 +/- 0.4, 4.00 +/- 0.5 mumoles/gm dry weight, respectively). Muscle adenosine diphosphate levels were significantly decreased in the TB animals (1.57 +/- 0.7 mumoles/gm dry weight) as compared with NTB animals (2.23 +/- 0.7 mumoles/gm dry weight, p < 0.05). In addition, muscle adenosine triphosphate, phosphocreatine, and phosphocreatine/adenosine triphosphate ratios were significantly decreased in TB animals (19.94 +/- 4.5, 81.51 +/- 12.8, and 4.20 +/- 0.8 mumoles/gm dry weight, respectively) as compared with NTB animals (24.44 +/- 1.9, 116.72 +/- 7.5, and 4.81 +/- 0.4 mumoles/gm dry weight, respectively, p < 0.05) and RES animals (24.08 +/- 3.3, 124.10 +/- 12.2, and 5.19 +/- 0.5 mumoles/gm dry weight, respectively, p < 0.05).. These alterations in high energy phosphate compounds in liver and skeletal muscle indicate that although the energy charge is maintained, energy depletion occurs early in the tumor-bearing state. These changes are tumor specific, not related to anorexia, and revert to non-tumor-bearing levels after tumor resection.

Topics: Adenosine Triphosphate; Animals; Cachexia; Male; Muscle, Skeletal; Neoplasms, Experimental; Phosphates; Phosphocreatine; Rats; Rats, Inbred F344