Centurelli M.A.; Abate M.A.
M.A. Centurelli, Department of Pharmacy, New England Medical Center, Box 420, 750 Washington St., Boston, MA 02111 United States
Annals of Pharmacotherapy (United States) 1997, 31/5 (639-642)

The use of DHEA for the treatment of AIDS shows some promise, although controlled trials have not been performed to evaluate its efficacy. Low serum concentrations of DHEA have been correlated with states of decreased immune function in humans, since concentrations are lowest in early childhood, late adulthood, and as HIV disease progresses. DHEA appears to possess immunomodulating effects, perhaps by enhancing the secretion of IL-2 from activated T cells as demonstrated in a murine model. A decline in DHEA concentrations, particularly when initially less than 2.01 mug/L, might also prove to be a predictor of HIV disease progression. It is also plausible that a decrease in DHEA concentrations can be used to predict a decline in overall health status. Although the role of DHEA in the treatment of AIDS has not yet been determined, the drug appears to show potential for clinical benefit that should be evaluated in large, randomized, controlled trials.

Yen S.S.C.; Morales A.J.; Khorram O.
Dept of Reproductive Medicine, University of California, San Diego,La Jolla, CA 92093 U S
Annals of the New York Academy of Sciences (United States) 1995, 774/- (128-142)

DHEA in appropriate replacement doses appears to have remedial effects with respect to its ability to induce an anabolic growth factor, increase muscle strength and lean body mass, activate immune function, and enhance quality of life in aging men and women, with no significant adverse effects. Further studies are needed to confirm and extend our current results, particularly the gender differences.

Chen RS; Huang CC; Chu NS
Dept of Neurology, Chang Gung Medical College and Memorial Hospital, Taipei, Taiwan
Eur Neurol (Switzerland) 1997, 37 (4) p212-8

We report a short-term double-blind, crossover study of CoQ10 in 8 patients with mitochondrial encephalomyopathies. Four patients had myoclonus epilepsy with ragged-red fibers syndrome, 3 had mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome, and 1 had chronic progressive external ophthalmoplegia with myopathy. A trend of effectiveness of CoQ10 in several parameters was noted. Fatigability of daily activities was alleviated. The endurance to muscle exercise was augmented. Global muscle strength scored by Medical Research Council scale was increased. The extent of elevation in serum lactate and pyruvate levels after exercise was decreased. However, only the global MRC index score had a statistical significance (p < 0.05). There were no side effects during therapy. The serum CoQ10 levels were significantly lower in patients than in normal controls before CoQ10 treatment and increased significantly after treatment.

Arenas J; Huertas R; Campos Y; Diaz AE; Villalon JM; Vilas E
Centro de Investigacion, Hospital 12 de Octubre, Madrid, Spain.
FEBS Lett (Netherlands) Mar 14 1994, 341 (1) p91-3

The effects of L-carnitine on the pyruvate dehydrogenase (PDH) complex and carnitine palmitoyl transferase (CPT) were studied in muscle of 16 long-distance runners (LDR). These subjects received placebo or L-carnitine (2 g orally) during a 4-week period of training. Athletes receiving L-carnitine showed a dramatic increase (P < 0.001) in the PDH complex activities. By contrast, the levels of CPT, both 1 and 2, were unchanged. No significant changes were observed after placebo administration. We previously reported [Huertas R. et al., Biochem. Biophys. Res. Commun. 188 (1992) 102-107] that L-carnitine induces an increase in the activities of complexes I, III and IV of the respiratory chain in muscle of LDR. Taken together, our data suggest that the improvement in (maximal oxygen consumption) VO2max observed in LDR after L-carnitine administration is based on these biochemical findings.

Stanko RT; Reynolds HR; Lonchar KD; Arch JE
Clinical Nutrition Unit, Montefiore University Hospital, Pittsburgh, PA 15213.
Am J Clin Nutr (United States) Nov 1992, 56 (5) p950-4

We evaluated the effects of a three-carbon compound, pyruvate, on plasma lipid concentrations in hyperlipidemic patients consuming a high-cholesterol (560-620 mg), high-fat (45-47% of energy; 18-20% of energy as saturated fatty acid), anabolic diet (0.11-0.12 MJ/kg body wt) for 6 wk. Forty subjects consumed the diet, randomly supplemented with 36-53 g pyruvate (n = 19) or 21-37 g polyglucose (placebo, Polycose, n = 21) as a portion of carbohydrate energy. Plasma cholesterol and LDL-cholesterol concentrations were unchanged in the placebo group, but decreased by 4% and 5%, respectively, in the pyruvate group (P < 0.05 vs placebo). Plasma HDL-cholesterol, HDL3-cholesterol, and triglyceride concentrations were similar in both groups. Resting heart rate, diastolic blood pressure, and rate-pressure product were unchanged after 6 wk of therapy in the placebo group, but decreased by 9%, 6%, and 12%, respectively with pyruvate supplementation (P < 0.05 vs placebo). We conclude that pyruvate supplementation of a high-fat, high-cholesterol, anabolic diet will decrease plasma cholesterol and LDL-cholesterol concentrations without affecting the HDL-cholesterol concentration.

Stanko RT; Robertson RJ; Galbreath RW; Reilly JJ Jr; Greenawalt KD; Goss FL
Department of Medicine, Montefiore University Hospital, Pittsburgh, Pennsylvania.
J Appl Physiol (United States) Nov 1990, 69 (5) p1651-6

The effects of dietary supplementation of dihydroxyacetone and pyruvate (DHAP) on metabolic responses and endurance capacity during leg exercise were determined in eight untrained males (20-30 yr). During the 7 days before exercise, a high-carbohydrate diet was consumed (70% carbohydrate, 18% protein, 12% fat; 35 kcal/kg body weight). One hundred grams of either Polycose (placebo) or dihydroxyacetone and pyruvate (treatment, 3:1) were substituted for a portion of carbohydrate. Dietary conditions were randomized, and subjects consumed each diet separated by 7-14 days. After each diet, cycle ergometer exercise (70% of peak oxygen consumption) was performed to exhaustion. Biopsy of the vastus lateralis muscle was obtained before and after exercise. Blood samples were drawn through radial artery and femoral vein catheters at rest, after 30 min of exercise, and at exercise termination. Leg endurance was 66 +/- 4 and 79 +/- 2 min after placebo and DHAP, respectively (P less than 0.01). Muscle glycogen at rest and exhaustion did not differ between diets. Whole leg arteriovenous glucose difference was greater (P less than 0.05) for DHAP than for placebo at rest (0.36 +/- 0.05 vs. 0.19 +/- 0.07 mM) and after 30 min of exercise (1.06 +/- 0.14 vs. 0.65 +/- 0.10 mM) but did not differ at exhaustion. Plasma free fatty acids, glycerol, and beta-hydroxybutyrate were similar during rest and exercise for both diets. Estimated total glucose oxidation during exercise was 165 +/- 17 and 203 +/- 15 g after placebo and DHAP, respectively (P less than 0.05). It is concluded that feeding of DHAP for 7 days in conjunction with a high carbohydrate diet enhances leg exercise endurance capacity by increasing glucose extraction by muscle.

Wolfe R.R.
R.R. Wolfe, Univ. of Texas Med. Branch Galveston, Shriners Bums Institute, Metabolism Unit, 815 Market Street, Galveston, TX 77550 United States
Advances in Experimental Medicine and Biology (United States) 1998, 441/- (147-156)

Fatty acids are the most abundant source of endogenous energy substrate. They can be mobilized from peripheral adipose tissue and transported via the blood to active muscle. During higher intensity exercise, triglyceride within the muscle can also be hydrolyzed to release fatty acids for subsequent direct oxidation. Control of fatty acid oxidation in exercise can potentially occur via changes in availability, or via changes in the ability of the muscle to oxidize fatty acids. We have performed a series of experiments to distinguish the relative importance of these potential sites of control. The process of lipolysis normally provides free fatty acids (FFA) at a rate in excess of that required to supply resting energy requirements. At the start of low intensity exercise, lipolysis increases further, thereby providing sufficient FFA to provide energy substrates in excess of requirements. However, lipolysis does not increase further as exercise intensity increases, and fatty acid oxidation becomes approximately equal to the total amount of fatty acids available at 65% of VOinf 2 max. When plasma FFA concentration is increased by lipid infusion during exercise at 85% VOinf 2 max, fat oxidation is significantly increased. Taken together, these observations indicate that fatty acid availability can be a determinant of the rate of their oxidation during exercise. However, even when lipid is infused well in excess of requirements during high-intensity exercise, less than half the energy is derived from fat. This is because the muscle itself is a major site of control of the rate of fat oxidation during exercise. We have demonstrated that the mechanism of control of fatty acid oxidation in the muscle is the rate of entry into the mitochondria. We hypothesize that the rate of glycolysis is the predominant regulator of the rate of carbohydrate metabolism in muscle, and that a rapid rate of carbohydrate oxidation caused by mobilization of muscle glycogen during high intensity exercise inhibits fatty acid oxidation by limiting transport into the mitochondria. During low intensity exercise, glycogen breakdown and thus glycolysis is not markedly stimulated, so the increased availability of fatty acids allows their oxidation to serve as the predominant energy source. At higher intensity exercise, stimulation of glycogen breakdown and glycolysis cause increased pyruvate entry into the TCA cycle for oxidation, and as a consequence the inhibition of fatty acid oxidation by limiting their transport into the mitochondria.

Chen R.-S.; Huang C.-C.; Chu N.-S.
C.-C. Huang, Department of Neurology, Chang Gung Memorial Hospital, 199 Tung Hwa North Road, Taipei Taiwan
European Neurology (Switzerland) 1997, 37/4 (212-218)

We report a short-term double-blind, crossover study of CoQinf 1inf 0 in 8 patients with mitochondrial encephalomyopathies. Four patients had myoclonus epilepsy with ragged-red fibers syndrome, 3 had mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome, and 1 had chronic progressive external ophthalmoplegia with myopathy. A trend of effectiveness of CoQinf 1inf 0 in several parameters was noted. Fatigability of daily activities was alleviated. The endurance to muscle exercise was augmented. Global muscle strength scored by Medical Research Council scale was increased. The extent of elevation in serum lactate and pyruvate levels after exercise was decreased. However, only the global MRC index score had a statistical significance (p < 0.05). There were no side effects during therapy. The serum CoQinf 1inf 0 levels were significantly lower in patients than in normal controls before CoQinf 1inf 0 treatment and increased significantly after treatment.

Kinscherf R; Hack V; Fischbach T; Friedmann B; Weiss C; Edler L; Bartsch P; Droge W
Division of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
J Mol Med (Germany) Jul 1996, 74 (7) p393-400

Skeletal muscle catabolism, low plasma glutamine, and high venous glutamate levels are common among patients with cancer or human immunodeficiency virus infection. In addition, a high glycolytic activity is commonly found in muscle tissue of cachectic cancer patients, suggesting insufficient mitochondrial energy metabolism. We therefore investigated (a) whether an "an-aerobic physical exercise" program causes similar changes in plasma amino acid levels, and (b) whether low plasma glutamine or high glutamate levels are risk factors for loss of body cell mass (BCM) in healthy human subjects, i.e., in the absence of a tumor or virus infection. Longitudinal measurements from healthy subjects over longer periods suggest that the age-related loss of BCM occur mainly during episodes with high venous glutamate levels, indicative of decreased muscular transport activity for glutamate. A significant increase in venous glutamate levels from 25 to about 40 microM was seen after a program of "anaerobic physical exercise." This was associated with changes in T lymphocyte numbers. Under these conditions persons with low baseline levels of plasma glutamine, arginine, and cystine levels also showed a loss of BCM. This loss of BCM was correlated not only with the amino acid levels at baseline examination, but also with an increase in plasma glutamine, arginine, and cystine levels during the observation period, suggesting that a loss of BCM in healthy individuals terminates itself by adjusting these amino acids to higher levels that stabilize BCM. To test a possible regulatory role of cysteine in this context we determined the effect of N-acetyl-cysteine on BCM in a group of subjects with relatively low glutamine levels. The placebo group of this study showed a loss of BCM and an increase in body fat, suggesting that body protein had been converted into other forms of chemical energy. The decrease in mean BCM/body fat ratios was prevented by N-acetyl-cysteine, indicating that cysteine indeed plays a regulatory role in the physiological control of BCM.

Rennie MJ; Ahmed A; Khogali SE; Low SY; Hundal HS; Taylor PM
Department of Anatomy and Physiology, University of Dundee, Scotland, United Kingdom.
J Nutr (United States) Apr 1996, 126 (4 Suppl) p1142S-9S

The glutamine and glutamate transporters in skeletal muscle and heart appear to play a role in control of the steady-state concentration of amino acids in the intracellular space and, in the case of skeletal muscle at least, in the rate of loss of glutamine to the plasma and to other organs and tissues. This article reviews what is currently known about transporter characteristics and mechanisms in skeletal muscle and heart, the alterations in transport activity in pathophysiological conditions and the implications for anabolic processes and cardiac function of altering the availability of glutamine . The possibilities that glutamine pool size is part of an osmotic signaling mechanism to regulate whole body protein metabolism is discussed and evidence is shown from work on cultured muscle cells. The possible uses of glutamine in maintaining cardiac function perioperatively and in promoting glycogen metabolism are discussed. (33 Refs.)

Herskowitz K; Plumley DA; Martin TD; Hautamaki RD; Copeland EM 3d; Souba WW
Department of Surgery, University of Florida College of Medicine, Gainesville 32601.
J Surg Res (United States) Jul 1991, 51 (1) p82-6

Despite the attenuated skeletal muscle proteolysis that occurs following hypothermic anesthesia and open heart surgery, blood amino acid levels are maintained, suggesting enhanced amino acid release by another organ. To investigate the role of the lung in this response, we determined the release of glutamine (Gln) and alanine by the lung, since these two amino acids transport two-thirds of circulating amino acid nitrogen. Three groups of patients were studied: (a) preoperative non-stressed controls; (b) postoperative general surgical patients; and (c) postoperative cardiac surgical patients studied on Postoperative Day 1 following open heart surgery requiring cardiopulmonary bypass and hypothermic anesthesia. In preoperative controls the lung was an organ of glutamine and alanine balance. These exchange rates were unaffected by the stress of an abdominal surgical procedure despite a mild increase in pulmonary blood flow. However, lung Gln release in the cardiac surgical patients was significantly increased (-0.6 +/- 1.2 mumole/kg/min in controls vs -6.5 +/- 1.3 mumole/kg/min in postoperative hearts, P less than 0.05) and was due exclusively to an increase in the pulmonary artery-systemic arterial concentration difference. Alanine release by the lungs was also increased in the postoperative cardiac surgical patients. The mechanism by which this augmented pulmonary glutamine release occurs following open heart surgery is unclear, but the lungs appear to play a central role in maintaining amino acid homeostasis. This metabolic role of the lungs following hypothermic anesthesia and cardiopulmonary bypass has not been previously described.

Dechelotte P; Darmaun D; Rongier M; Hecketsweiler B; Rigal O; Desjeux JF
Inst.Nat. de la Sante et de la Recherche Medicale Unite 290, Hopital Saint-Lazare, Paris, France.
Am J Physiol (United States) May 1991, 260 (5 Pt 1) pG677-82

To assess absorption and metabolic effects of enterally delivered glutamine, a total of 10 healthy subjects received perfusions of natural L- glutamine at graded infusion rates (ranging from 0 to 126 mmol/h; n = 2-8 subjects at each rate) along with a nonabsorbable marker (polyethylene glycol) through a double-lumen nasojejunal tube. Perfusions were administered after an overnight fast during three consecutive 1- or 2.5-h periods and in a randomized order. In eight subjects, continuous intravenous infusion of D-[6,6-2H2]glucose, L-[1-13C]leucine, and L-[15N]alanine was simultaneously performed. Glutamine was nearly quantitatively absorbed over the 30-cm study segment; estimated Km and Vmax of glutamine absorption were 2.48 and 2.32 mmol/min over the 30-cm study segment. Enteral glutamine administration induced 1) a dose-dependent increase in plasma glutamine level; 2) a rise in the plasma level and appearance rate (Ra) of alanine (from 191 +/- 42 to 213 +/- 51 mumols.kg-1.h-1, P less than 0.05, for 0 and 46.8-mmol/h glutamine infusion rates, respectively) and in plasma levels of glutamate, citrulline, aspartate, and urea; 3) a decline in plasma free fatty acid and glycerol levels; and 4) no change in leucine or glucose Ra. We conclude that glutamine is efficiently absorbed by human jejunum in vivo and may directly inhibit lipolysis, whereas it neither affects proteolysis nor glucose production in healthy postabsorptive humans.

Vinnars E; Hammarqvist F; von der Decken A; Wernerman J
Department of Anesthesiology, St Goran's Hospital, Stockholm, Sweden.
J Parenter Enteral Nutr (U S) Jul-Aug 1990, 14 (4 Suppl) p125S-129S

Skeletal muscle protein catabolism following trauma has until recently not been possible to counteract by intravenous nutritional means. The obligatory loss of nitrogen with concomitant reduction of skeletal muscle protein synthesis is also accompanied by a decrease of muscle free glutamine, the extent of which is proportional to the muscle protein catabolism. Serving as a human model of surgical trauma, patients undergoing elective cholecystectomy were given total parenteral nutrition including additions of either glutamine or its analogs (ornithine-alpha-ketoglutarate, alpha-ketoglutarate, or alanylglutamine) during 3 postoperative days. The polyribosome concentration and the intracellular glutamine concentration in skeletal muscle, as well as nitrogen balance, showed a less pronounced skeletal muscle catabolism in these groups than when conventional total parenteral nutrition was given. It is concluded that a support of either glutamine or its carbon skeleton, alpha-ketoglutarate, counteracts the postoperative fall of muscle free glutamine and of muscle protein synthesis. Furthermore, statistical correlations could be shown between the changes of muscle glutamine and muscle protein synthesis and the postoperative nitrogen losses.

Fong YM; Tracey KJ; Hesse DG; Albert JD; Barie PS; Lowry SF
Department of Surgery, New York Hospital-Cornell Medical Center, New York 10021.
Surgery (United States) Mar 1990, 107 (3) p321-6

Glutamine and alanine are dominant nitrogen carriers from skeletal muscle stores to splanchnic organs. In addition, these amino acids may also serve as a primary energy source for the gastrointestinal tract during injury. To investigate these contributions, we studied extremity amino acid efflux during hypocaloric dextrose feedings and during total parenteral nutrition in a population of normal volunteers (NL VOL) (n = 9), a group of patients with sepsis who had undergone laparotomy without bowel resection and were in the intensive care unit (ICU) (n = 7), and patients with sepsis after laparotomy (PT) (n = 2) who had recently undergone greater than 80% bowel resection. Circulating alanine and glutamine levels were significantly lower in the patients compared with NL VOL under both feeding conditions. The peripheral output of alanine was higher in the ICU group than in the NL VOL during hypocaloric feedings. Glutamine efflux, however, was independent of either the counterregulatory hormone or substrate background. By contrast, enterectomy was associated with a marked decrease of extremity glutamine efflux compared with NL VOL or the ICU patients who did not undergo enterectomy (-62 +/- 9 nmol/min/dl tissue in the PT vs -265 +/- 32 nmol/min/dl tissue in the NL VOL and -311 +/- 58 nmol/min/dl tissue in the ICU group) during the dextrose feedings; this difference persisted during subsequent total parenteral nutrition (+12 +/- 13 nmol/min/dl tissue in PT vs -178 +/- 56 nmol/min/dl tissue in the NL VOL and -287 +/- 81 nmol/min/dl tissue in the ICU group). These data suggest that distinct mechanisms regulate peripheral alanine and glutamine balance and that the gastrointestinal tract provides a feedback signal to peripheral tissues to maintain glutamine mobilization under both nonstressed and stressed conditions.

Hammarqvist F; Wernerman J; Ali R; von der Decken A; Vinnars E
Department of Surgery, St. Goran's Hospital, Stockholm, Sweden.
Ann Surg (United States) Apr 1989, 209 (4) p455-61

Twenty-two patients undergoing elective abdominal surgery were given total parenteral nutrition (TPN) after the operation. The TPN contained either a conventional amino acid solution supplemented with glutamine or a conventional amino acid solution without supplementation. To study amino acid and protein metabolism, muscle biopsy specimens were taken before surgery and on the third postoperative day. The postoperative decrease in the intracellular concentration of free glutamine was less pronounced in the glutamine group (21.8 +/- 5.5%) than in the control group (38.7 +/- 5.1%; p less than 0.05). The protein synthesis was reflected in the concentration and size distribution of ribosomes. No significant changes in these parameters were seen in the glutamine group after the operation. In the control group, the total concentration of ribosomes fell by 27.2 +/- 8.5% (p less than 0.05), and the relative proportion of polyribosomes fell by 10.6 +/- 2.9% (p less than 0.01). Although there were significant changes in the control group, no significant differences in the changes of these parameters between the two groups were detected. The cumulative nitrogen loss was significantly less in the glutamine group as compared to the control group during the period studied--2.3 +/- 1.4 g versus 8.5 +/- 1.5 g, respectively (p less than 0.01). Administration of glutamine to catabolic patients is advocated.

Zielke HR; Zielke CL; Ozand PT
Fed Proc (United States) Jan 1984, 43 (1) p121-5

Cultured mammalian cells have two primary mechanisms for obtaining energy necessary for growth: carbohydrate metabolism to lactate and glutamine oxidation to CO2. In tissue culture medium containing both glucose and glutamine, the contribution of glutamine oxidation to the energy requirement ranges between 30 and 50%. As the glucose concentration is decreased, or when glucose is replaced by other carbohydrates, the rate of glutamine oxidation increases and glutamine becomes the sole energy source for cultured cells. The rate of glutamine oxidation is regulated by the presence of glucose. The apparent absolute requirement for glucose or other carbohydrates in tissue culture medium is related to its role in anabolic reactions rather than in energy production. Oxidation of glucose, fatty acids, or ketone bodies does not contribute significantly to the energy needs of cultured mammalian cells. The data also suggest that consideration should be given to glutamine as an important energy source in vivo.

Roth E.; Spittler A.; Oehler R.
Chirurgisches Forschungslabor, Universitatsklinik fur Chirurgie, Allgemeines Krankenhaus, Wahringer Gurtel 18-20,A-1090 Wien Austria
Wiener Klinische Wochenschrift (Austria)1996,108/21 (669-676)

Glutamine is the most abundant free amino acid of the human body. In catabolic stress situations such as after operations, trauma and during sepsis the enhanced transport of glutamine to splanchnic organs and to blood cells results in an intracellular depletion of glutamine in skeletal muscle . Glutamine is an important metabolic substrate for cells cultivated under in vitro conditions and is a precursor for purines, pyrimidines and phospholipids. Increasing evidence suggests that glutamine is a crucial substrate for immunocompetent cells. Glutamine depletion in the cultivation medium decreases the mitogen-inducible proliferation of lymphocytes, possibly by arresting the cells in the Ginf 0-Ginf 1 phase of the cell cycle. Glutamine depletion in lymphocytes prevents the formation of signals necessary for late activation. In monocytes glutamine deprivation downregulates surface antigens responsible for antigen preservation and phagocytosis. Glutamine is a precursor for the synthesis of glutathionine and stimulates the formation of heat-shock proteins. Moreover, there are suggestions that glutamine plays a crucial role in osmotic regulation of cell volume and causes phosphorylation of proteins, both of which may stimulate intracellular protein synthesis. Experimental studies revealed that glutamine deficiency causes a necrotising enterocolitis and increases the mortality of animals subjected to bacterial stress. First clinical studies have demonstrated a decrease in the incidence of infections and a shortening of the hospital stay in patients after bone marrow transplantation by supplementation with glutamine . In critically ill patients parenteral glutamine reduced nitrogen loss and caused a reduction of the mortality rate. In surgical patients glutamine evoked an improvement of several immunological parameters. Moreover, glutamine exerted a trophic effect on the intestinal mucosa, decreased the intestinal permeability and thus may prevent the translocation of bacteria. In conclusion, glutamine is an important metabolic substrate of rapidly proliferating cells, influences the cellular hydration state and has multiple effects on the immune system, on intestinal function and on protein metabolism. In several disease states glutamine may consequently, become an in dispensable nutrient, which should be provided exogenously during artificial nutrition.

Darmaun D.
Nemours Children's Clinic, 807 Nira Street,Jacksonville, FL 32207 United States
Nutrition Clinique et Metabolisme (France) 1994, 8/4 (231-240)

Glutamine is synthetized in most tissue and accounts for two-thirds of the free amino acid pool in skeletal muscle . Glutamine is not only an interorgan nitrogen shuttle but a precursor of urinary ammonium, and a favorite fuel of the immune system and the gut (which uses ~ 17 g of glutamine per day). Because they were designed at a time when glutamine was considered both unstable and non-essential, 'traditional' parenteral nutrition (PN) solutions are devoid of glutamine . Although 'classic' PN is able to maintain normal rates of glutamine turnover in healthy subjects or unstressed patients, classic PN solutions are unable to correct the precipitous depletion of glutamine pool that accompanies catabolic illness. Glutamine becomes a 'conditionally essential' amino acid in these situations. Replenishment of glutamine pool seems to stimulate protein synthesis, and improves nitrogen balance in catabolic patients. Supplementation of PN with glutamine -containing dipeptides or alpha-ketoglutarate (at doses of 15-50 g/d) is as effective as glutamine itself. The enteral route represents an attractive alternative for the supply of glutamine since: 1) glutamine is efficiently absorbed; 2) nearly 50% of enterally infused glutamine reaches systemic blood; 3) glutamine residues present in a bound form in peptides seem to be bioavailable; and 4) in addition to its protein anabolic effect, glutamine affects intestinal absorption and trophicity.

Wilmore D.W.
Laboratory for Surgical Metabolism, Brigham and Women's Hospital, Department of Surgery, 75 Francis Street,Boston, MA 02115 United States
Rivista Italiana di Nutrizione Parenterale ed Enterale (Italy) 1992, 10/1 (1-6)

Glutamine is an abundant amino acid in the body, but is absent from most enteral and parenteral formulas. A variety of studies have demonstrated that catabolic states initiate breakdown of skeletal-muscle protein and glutamine is formed. A large proportion of the glutamine is transported to the gastrointestinal tract and used as a primary fuel source and incorporated as a substrate in cell synthesis. Administering glutamine by the enteral or parenteral route enhances enterocyte proliferation, attenuates atrophy of the pancreas and prevents hepatic steatosis. Incorporation of glutamine in nutrient formulations should enhance recovery and function of the gastrointestinal/tract in our critically ill patients.

Souba W.W.; Smith R.J.; Wilmore D.W.
Department of Surgery, University of Texas Medical School, Houston, TX 77030 United States
Journal of Parenteral and Enteral Nutrition (United States) 1985, 9/5 (608-617)

Selective metabolism of glutamine by the gut may have adaptive value. As previously noted, glutamine (and glutamate) are abundant amino acids that together comprise nearly one-third of the amino acid nitrogen in meat. Skeletal muscle proteolysis yields a similar profile of amino acids. The enzymatic machinery for metabolizing circulating or luminal glutamine and glutamate in the intestinal epithelium not only provides energy to the enterocytes, but also may prevent the delivery of excessive quantities of glutamate into the systemic circulation where it may have toxic effects. Because of its anatomical relationship with the liver, it may be possible for the gut to process glutamine nitrogens in a unique way. Unlike other tissues which must capture and transport ammonia by utilizing a carbon carrier, the gut can harmlessly release this potentially toxic compound into the portal blood with ammonia trapping mechanisms in the liver assuring its conversion into urea or back to glutamine . The increased gut consumption of glutamine in catabolic states may be related to the ability of this amino acid to displace glucose as a fuel. During glucocorticoid administration, which accelerates gut glutamine uptake, the bowel became an organ of slight glucose release. Thus, glutamine may be preferentially consumed and oxidized by the gut in place of glucose during catabolic states. These adaptations may spare glucose for reparative tissues and inflammatory cells. The concept that the intestinal tract becomes physiologically quiescent during illness may merit reconsideration. The data on glutamine handling by the intestine discussed in this review suggest an important role for increased intestinal amino acid metabolism during stress states. The interorgan transfer of glutamine from muscle to the intestine exemplifies the complex metabolic cooperation between tissues that is necessary for survival during a critical illness.

Krishnamoorthy R.V.; Radha E.
Dept. Zool., Bangalore Univ., Bangalore India
Enzyme 1974, 18/3-4 (253-256)

Glutamine activates and histamine inhibits the activity of a crystalline lysozyme preparation as well as natural secretions like tears and nasal mucus.

Sousa MF; Abumrad NN; Martins C; Nissen S; Riella MC
Department of Medicine, Evangelic School of Medicine, Curitiba, Brazil.
Nephron (Switzerland) 1996, 72 (3) p391-4

The binding capacity of calcium beta -hydroxy -beta -methylbutyrate (calcium HMB), compared to other binders, was investigated in an in vitro study. Fifty milliequivalents of either calcium HMB, calcium acetate, calcium carbonate, aluminum hydroxide gel or non-gel aluminum hydroxide was added to a phosphate solution, titrated (HCl or NaOH), shaken and centrifuged to four different pH levels at 37 degrees C (simulating the gastrointestinal milieu). The difference in phosphate concentration between that of the initial and that of the supernatant represented from the bound phosphate in the precipitate. After 4 h at a pH of 6 (representing the intestinal condition after a meal), the binding percentage was: calcium acetate = 95.6%, calcium HMB = 92.6%, calcium carbonate = 46.4%, aluminum hydroxide gel = 33.4% and non-gel aluminum hydroxide = 17.8%. There was no significant difference (p > 0.05) between calcium HMB and calcium acetate. These results suggest that calcium HMB is an efficient phosphate binder in vitro, which may predict its effective role in vivo.

Nissen S.L.; Abumrad N.N.
Dr. S. Nissen, Iowa State University, Ames, IA 50011 United States
Journal of Nutritional Biochemistry (United States) 1997, 8/6 (300-311)

This review develops the hypothesis that a metabolite of leucine termed beta -hydroxy beta -methylbutyrate (HMB) plays a key role in animal metabolism and that in certain circumstances insufficient amounts of HMB are either consumed in the diet or produced endogenously to supply tissue needs. The origin and metabolism of HMB is reviewed including the role of HMB in cholesterol biosynthesis. HMB feeding studies in animals are reviewed, which indicate that dietary supplementation of HMB can improve immune function and health and can increase the fat content of milk in lactating animals. Seven human studies are reviewed where HMB wasted. The results of both animal and human studies indicate that dietary supplementation of HMB is safe, as evidenced by lack of physical adverse effects and a lack of effect on blood hematology and chemistry. The only consistent change in blood chemistry was a decrease in LDL cholesterol, which changed 7% (P < .01). In humans undergoing resistance training, HMB supplementation increased lean mass gains from 50 to 200%, with similar percentage increases in strength when compared with unsupplemented subjects. The effects of HMB on muscle size and function seems to result from a diminution of exercise-related muscle damage and muscle protein breakdown. A general hypothesis is proposed that HMB is metabolized to HMG-CoA in tissues such as muscle, mammary tissue, and certain immune cells and is used for de novo cholesterol synthesis. In times of stimulated growth and/or differentiation, HMG-CoA may be rate-limiting for cholesterol synthesis, which could limit cell growth or function. It is proposed that feeding HMB can provide a saturating source of cytosolic HMG-CoA for cholesterol synthesis and in turn allow for maximal cell growth and function

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