Glutamine, Leucine, Valine, Isoleucine, Papain, Bromelain, Beta-sitosterol, Bioflavonoid extract (30-50% polyphenols)

Transcription

1 Recover-Ease Formula: Glutamine, Leucine, Valine, Isoleucine, Papain, Bromelain, Beta-sitosterol, Bioflavonoid extract (30-50% polyphenols) BRANCHED CHAIN AMINO ACIDS (BCAAs = Leucine / Valine / Isoleucine) 1. De Palo EF, Gatti R, Cappellin E, Schiraldi C, De Palo CB, Spinella P. Plasma lactate, GH and GHbinding protein levels in exercise following BCAA supplementation in athletes. Amino Acids. 2001;20(1): MacLean DA, Graham TE, Saltin B. Branched-chain amino acids augment ammonia metabolism while attenuating protein breakdown during exercise. Am J Physiol Dec;267(6 Pt 1):E Calders P, Pannier JL, Matthys DM, Lacroix EM. Pre-exercise branched-chain amino acid administration increases endurance performance in rats. Med Sci Sports Exerc Sep;29(9): MacLean DA, Graham TE. Branched-chain amino acid supplementation augments plasma ammonia responses during exercise in humans. J Appl Physiol Jun;74(6): Blomstrand E, Andersson S, Hassmen P, Ekblom B, Newsholme EA. Effect of branched-chain amino acid and carbohydrate supplementation on the exercise-induced change in plasma and muscle concentration of amino acids in human subjects. Acta Physiol Scand Feb;153(2): MacLean DA, Graham TE, Saltin B. Stimulation of muscle ammonia production during exercise following branched-chain amino acid supplementation in humans. J Physiol Jun 15;493 ( Pt 3): Carli G, Bonifazi M, Lodi L, Lupo C, Martelli G, Viti A. Changes in the exercise-induced hormone response to branched chain amino acid administration. Eur J Appl Physiol Occup Physiol. 1992;64(3): Blomstrand E, Ek S, Newsholme EA. Influence of ingesting a solution of branched-chain amino acids on plasma and muscle concentrations of amino acids during prolonged submaximal exercise. Nutrition Jul-Aug;12(7-8): Mittleman KD, Ricci MR, Bailey SP. Branched-chain amino acids prolong exercise during heat stress in men and women. Med Sci Sports Exerc Jan;30(1): Blomstrand E, Hassmen P, Ekblom B, Newsholme EA. Administration of branched-chain amino acids during sustained exercise--effects on performance and on plasma concentration of some amino acids. Eur J Appl Physiol Occup Physiol. 1991;63(2): Coombes JS, McNaughton LR. Effects of branched-chain amino acid supplementation on serum creatine kinase and lactate dehydrogenase after prolonged exercise. J Sports Med Phys Fitness Sep;40(3): Bassit RA, Sawada LA, Bacurau RF, Navarro F, Costa Rosa LF. The effect of BCAA supplementation upon the immune response of triathletes. Med Sci Sports Exerc Jul;32(7): Parry-Billings M, Budgett R, Koutedakis Y, Blomstrand E, Brooks S, Williams C, Calder PC, Pilling S, Baigrie R, Newsholme EA. Plasma amino acid concentrations in the overtraining syndrome: possible effects on the immune system. Med Sci Sports Exerc Dec;24(12):

2 De Palo. Sezione di Biochimica Clinica, Dipartimento di Scienze Medico Diagnostiche, Universita degli Studi, Padova, Italy. BCAAs stimulate protein synthesis Triathletes who took BCAAs had lower lactic acid levels following exercise Growth hormone levels were increased following supplementation Branched chain amino acids (BCAA) stimulate protein synthesis, and growth hormone (GH) is a mediator in this process. A preexercise BCAA ingestion increases muscle BCAA uptake and use. Therefore after one month of chronic BCAA treatment (0.2 gkg(-1) of body weight), the effects of a pre-exercise oral supplementation of BCAA (9.64 g) on the plasma lactate (La) were examined in triathletes, before and after 60 min of physical exercise (75% of VO2 max). The plasma levels of GH (pgh) and of growth hormone binding protein (pghbp) were also studied. The end-exercise La of each athlete was higher than basal. Furthermore, after the chronic BCAA treatment, these end-exercise levels were lower than before this treatment (8.6+/-0.8 mmol L(-1) after vs 12.8+/-1.0 mmol L(- 1) before treatment; p < 0.05 [mean +/- std. err.]). The end-exercise pgh of each athlete was higher than basal (p < 0.05). Furthermore, after the chronic treatment, this end-exercise pgh was higher (but not significantly, p = 0.08) than before this treatment (12.2+/-2.0 ng ml(-1) before vs 33.8+/-13.6 ngml(-1) after treatment). The end-exercise pghbp was higher than basal (p < 0.05); and after the BCAA chronic treatment, this end-exercise pghbp was 738+/-85 pmol L(-1) before vs 1691+/-555 pmol L(-1) after. pgh/pghbp ratio was unchanged in each athlete and between the groups, but a tendency to increase was observed at end-exercise. The lower La at the end of an intense muscular exercise may reflect an improvement of BCAA use, due to the BCAA chronic treatment. The chronic BCAA effects on pgh and pghbp might suggest an improvement of muscle activity through protein synthesis. MacLean DA. School of Human Biology, University of Guelph, Ontario, Canada. BCAA supplementation reduced muscle breakdown during exercise In this study, five men exercised the knee extensor muscles of one leg for 60 min (71 +/- 2% maximal work capacity) with and without (control) an oral supplement (77 mg/kg) of branched-chain amino acids (BCAA). BCAA supplementation resulted in a doubling (P < 0.05) of the arterial BCAA levels before exercise (339 +/- 15 vs /- 86 microm). During the 60 min of exercise, the total release of BCAA was 68 +/- 93 vs /- 198 mumol/kg (P < 0.05) for the BCAA and control trials, respectively. The intramuscular BCAA concentrations were higher (P < 0.05) for the BCAA trial and remained higher (P < 0.05) throughout exercise. In both trials, substantial quantities of NH3 were released, and when NH3 production equivalent to IMP accumulation was subtracted the net NH3 production was 1,112 +/- 279 and 1,670 +/- 245 mumol/kg (P < 0.05) for the control and BCAA trials, respectively. In contrast, the release of the essential amino acids (EAA) was much lower for the BCAA than the control trial (P < 0.05). When the BCAA were subtracted from the EAA (EAA-BCAA), the total release of EAA minus BCAA was lower (P < 0.05) for the BCAA (531 +/- 70 mumol/kg) than the control (924 +/- 148 mumol/kg) trial. These data suggest that BCAA supplementation results in significantly greater muscle NH3 production during exercise. Furthermore, the increased intramuscular and arterial BCAA levels before and during exercise result in a suppression of endogenous muscle protein breakdown during exercise.

3 Calders P. Laboratory of Normal and Pathological Physiology, University of Gent, Belgium. BCAA supplementation increased running time by 25% (in rats) This study investigated the effects of pre-exercise branched-chain amino acid (BCAA) administration on blood ammonia levels and on time to exhaustion during treadmill exercise in rats. Adult female Wistar rats were trained on a motor driven treadmill. After a 24-h fast, rats were injected intraperitoneally (i.p.) with 1 ml of placebo or BCAA (30 mg), 5 min before performing 30 min of submaximal exercise (N = 18) or running to exhaustion (N = 12). In both cases, rats were sacrificed immediately following exercise, and blood was collected for the measurement of glucose, nonesterified fatty acid (NEFA), lactic acid, BCAA, ammonia, and freetryptophan (free-trp) levels. Control values were obtained from sedentary rats that were subjected to identical treatments and procedures (N = 30). Plasma BCAA levels increased threefold within 5 min after BCAA administration. Mean run time to exhaustion was significantly longer (P < 0.01) after BCAA administration (99 +/- 9 min) compared with placebo (76 +/- 4 min). During exercise, blood ammonia levels were significantly higher (P < 0.01) in the BCAA treated compared with those in the placebo treated rats both in the 30-min exercise bout (113 +/- 25 mumol.l-1 (BCAA) vs 89 +/- 16 mumol.l-1) and following exercise to exhaustion (186 +/- 44 mumol.l-1 (BCAA) vs 123 +/- 19 mumol.l-1). These data demonstrate that BCAA administration in rats results in enhanced endurance performance and an increase in blood ammonia during exercise. MacLean DA, Graham TE. School of Human Biology, University of Guelph, Ontario, Canada. BCAA supplementation increased plasma glutamine levels This study examined the effects of branched-chain amino acid (BCAA) supplementation on amino acid and ammonia (NH3) responses during prolonged exercise in humans. Seven men cycled for 60 min at 75% of maximal O2 uptake after 45 min of either placebo (dextrose, 77 mg/kg) or BCAA (leucine + isoleucine + valine, 77 mg/kg) supplementation. Plasma samples (antecubital vein) were collected at rest and during exercise and analyzed for plasma NH3 and amino acids, whole blood glucose and lactate, and serum free fatty acids and glycerol. After BCAA administration, plasma BCAA levels increased from 375 +/- 22 to 760 +/- 80 microm (P < 0.05) by the onset of exercise and remained elevated throughout the experiment. Plasma NH3 concentrations increased continually during exercise for both trials and were higher (P < 0.05) after BCAA supplementation than after placebo administration. The mean plasma NH3 increase from rest to 60 min was 79 +/- 10 and 53 +/- 4 microm for BCAA and placebo trials, respectively. Plasma alanine and glutamine concentrations were elevated (P < 0.05) during exercise for both treatments. However, only glutamine concentrations were greater (P < 0.05) for BCAA trial than for placebo trial during exercise. There were no significant differences between treatments for glucose, lactate, free fatty acids, and glycerol or any other plasma amino acid. These data suggest that increased BCAA availability before exercise, when initial muscle glycogen is normal, results in significantly greater plasma NH3 responses during exercise than does placebo administration.

4 Blomstrand E. Research Laboratories, Pripps Bryggerier, Bromma, Sweden. BCAA supplementation increases plasma BCAA concentration during exercise (compared to a drop when only carbohydrate is given) Plasma glutamine levels are maintained by BCAA supplementation Five male endurance-trained subjects performed exhaustive exercise on a cycle ergometer at a work rate corresponding to 75% of their VO2max after reduction of their muscle glycogen stores. During exercise the subjects were given in random order a 6% carbohydrate solution continuing 7 g L-1 of branched-chain amino acids (BCAA), a 6% CHO solution and flavoured water. The physical performance was lowered in four of the five subjects when they were given flavoured water during exercise as compared with the two conditions when CHO was supplied. No difference in performance was found when the subjects were given CHO + BCAA or only CHO during exercise. When CHO + BCAA was supplied the plasma and muscle (vastus lateralis) concentrations of BCAA increased during exercise by 120 and 35%, respectively. In the other conditions there was no change or a slight decrease in the plasma concentrations of BCAA, but the muscle concentrations of BCAA were decreased after exercise. The plasma concentration of glutamine over the whole exercise period and 5 min after exercise was higher when CHO + BCAA were supplied during exercise compared with a supply of CHO alone or water. However, exercise caused no change in the muscle concentration of glutamine, whereas that of glutamate decreased in all three conditions. A supply of CHO + BCAA or CHO alone did not affect the exerciseinduced increase in the plasma and muscle concentration of aromatic amino acids, indicating that neither BCAA nor CHO influenced the net protein degradation during exercise. MacLean DA. Copenhagen Muscle Research Center, Rigshospitalet, Denmark. BCAA supplementation reduced plasma lactic acid accumulation and increased levels of glutamine and alanine. This study examined the effects of a large (308 mg kg-1) oral dose of branched-chain amino acids (BCAAs) on muscle amino acid and ammonia (NH3) metabolism during 90 min of dynamic knee extensor exercise (64 +/- 2% of maximum workload). 2. BCAA supplementation resulted in a 4-fold increase in the arterial BCAA level (from 373 to 1537 microm, P < 0.05) and a 1.5-fold increase in the intramuscular BCAA level (from 3.4 +/- 0.2 to 5.2 +/- 0.5 mmol (kg dry weight)-1, P < 0.05) by the onset of exercise. Over the 90 min exercise period, the exercising muscle removed a total of / mumol kg-1 of BCAAs. In contrast, in the control trial, there was a total release of 588 +/- 86 mumol kg-1 (P < 0.05) of BCAAs. 3. The total release of NH3 over the 90 min exercise period was /- 317 mumol kg-1 (P < 0.05) in the control trial and /- 552 mumol kg-1 (P 0.05) in the BCAA trial. Similarly, the total release of alanine and glutamine was /- 153 and /- 270 mumol kg-1, respectively, for the control trial and /- 178 and /- 217 mumol kg-1, respectively, for the BCAA trial. 4. The lactate release and arterial lactate values were all consistently lower in the BCAA trial than in the control trial. The net production of lactate (intramuscular shifts + total release) was lower (P < 0.05) in the BCAA trial (49.9 +/ mmol kg-1) than in the control trial (64.0 +/ mmol kg-1). 5. It is concluded that: (1) the administration of BCAAs can greatly increase their concentration in plasma and subsequently their uptake by muscle during exercise, and (2) long-term exercise following BCAA administration results in significantly greater muscle NH3, alanine and glutamine production, as well as lower lactate production, than is observed during exercise without BCAA supplementation. These data strongly suggest that BCAAs are an important source of NH3 during submaximal exercise and that their contribution to NH3, alanine and glutamine production can be significantly altered by changes in BCAA availability.

5 Carli G. Istituto di Fisiologia Umana, Universita di Siena, Italy. In distance runners, 1-hour of running increases cortisol and decreases testosterone levels. BCAA supplements prevented the drop in testosterone levels following exercise It was the aim of the present experiment to detect possible effects of branched-chain amino acids (BCAA) on the endocrine response to 1 h of continuous running. Blood samples were collected from 14 long-distance runners (age years) in two different trials performed at 1-week intervals. In both trials (E and P) blood samples were collected at the following times: 9 a.m. (basal values sample), a.m. (sample 90), a.m. (sample 150), p.m. (sample 210); the athletes performed 1 h of running at a constant predetermined speed between samples 90 and 150. Following the basal sample a mixture containing BCAA (E trial), or not containing BCAA (P trial) was ingested. In both trials no hormone basal concentrations, except insulin, were changed before exercise. In P trial, following exercise (sample 150), human growth hormone (HGH), prolactin (PRL), adrenocorticotropic hormone (ACTH) and cortisol (C) increased, while testosterone (T) decreased. In sample 210, after 1 h of rest, while ACTH, PRL and HGH had recovered to basal concentrations, C remained elevated and T displayed a further decrease. In the E trial a similar pattern of change was observed in sample 150 for HGH, PRL, ACTH and C; in sample 210 HGH and PRL displayed significantly lower values than in the corresponding P trial samples. The T was not modified by the running exercise and increased during the recovery period. It is, therefore, suggested that BCAA administration before exercise affects the response of some anabolic hormones, mainly HGH and T. Blomstrand E. Pripps Bryggerier, Research Laboratories, Bromma, Sweden. Endurance cyclists taking BCAA supplements showed a better maintenance of muscle glycogen levels during exercise ( glycogen-sparing effect). On two occasions, seven male endurance-trained cyclists performed sustained exhaustive exercise with reduced muscle glycogen stores. During exercise, the subjects were supplied in random order with an aqueous solution of branched-chain amino acids (BCAA) or flavored water (placebo). Ingestion of BCAA caused the concentration of these amino acids to increase by 135% in the plasma and by 57% in muscle tissue during exercise, whereas in the placebo trial there was no change or a slight decrease in the concentration in plasma and a decrease of 18% in the muscle. The plasma concentration of alanine increased by 48% during exercise when BCAA were ingested, and the increase in the muscle concentration of alanine during exercise was larger (70% versus 31% in the placebo trial), suggesting an increased rate of alanine production. Also, the plasma concentration of arginine increased by 14% during exercise when BCAA were ingested, whereas there was no change during exercise in the placebo trial. There was a smaller decrease in the muscle glutamate concentration during exercise in the BCAA trial (32% versus 47% in the placebo trial; p < 0.05), but, for the remaining amino acids, there was no difference between the BCAA and placebo trials. There was a significant decrease in the muscle glycogen concentration during exercise in the placebo trial, whereas only a small decrease was found in the BCAA trial (28 and 9 mmol/kg wet wt [p < 0.05] in the placebo and BCAA trial, respectively). This might indicate that an increased supply of BCAA has a sparing effect on muscle glycogen degradation during exercise.

6 Mittleman KD. Department of Exercise Science, Rutgers University, New Brunswick, NJ 08903, USA. BCAA supplements increased endurance performance in the heat (cycle time to exhaustion) To assess the effect of branched-chain amino acids (BCAA) supplementation on endurance performance in the heat, six women and seven men participated in two trials of rest in the heat (Ta = /- 1.8 degrees C; rh = 39 +/- 14%), followed by 40% VO2peak exercise to exhaustion. Subjects ingested 5 ml x kg(-1) of a placebo (PLAC) or BCAA drink every 30 min. Cycle time to exhaustion increased during BCAA ( / vs / min, P < 0.05) for men and women. Plasma glucose was maintained at baseline values for both drinks; however, women had significantly higher concentrations (5.9 +/- 0.6 vs 4.0 +/- 0.2 mm, P < 0.05). Plasma free fatty acids and ammonia were not influenced by drink or gender but increased over time. BCAA resulted in a significant (P < 0.05) increase in plasma BCAA (1209 +/- 119 vs 496 +/- 44 microm), while F-TRP (9.6 +/- 0.9 vs /- 1.3 microm) and F- TRP:BCAA were decreased ( / vs / ND) in both men and women. Cardiovascular and thermoregulatory data were similar between treatments for all subjects. Psychological data were not influenced by BCAA. These results indicate BCAA supplementation prolongs moderate exercise performance in the heat. Blomstrand E. Pripps Bryggerier, Research Laboratories, Bromma, Sweden. BCAA supplements improved mental performance in marathoners and crosscountry runners following a race BCAA supplements improved marathon running performance Previous studies have shown that sustained exercise in human subjects causes an increase in the plasma concentration ratio of free tryptophan: other large neutral amino acids [including the branched-chain amino acids (BCAA)]. This should favour the transport of tryptophan into the brain and also the synthesis of 5-hydroxytryptamine, which is thought to contribute to fatigue during prolonged exercise. A mixture of the three BCAA was given to subjects during a 30-km cross-country race or a marathon (42.2 km) and the effects on mental and physical performances were measured. The mental performance, measured as the performance in the Stroop Colour and Word Test (CWT), was improved after, as compared to before the 30-km cross-country race when a BCAA supplement was given during the race, whereas the CWT scores were similar before and after in the placebo group. The running performance in the marathon was improved for the "slower" runners (3.05 h-3.30 h) when BCAA was taken during the race; however, there was no significant effect on the performance in the "faster" runners (less than 3.05 h). The results showed that both mental and physical performance was improved by an intake of BCAA during exercise. In addition, the effects of exercise on the plasma concentration of the aromatic amino acids were altered when a BCAA supplement was given during the marathon.

7 Coombes JS. Centre for Human Movement, University of Tasmania, Launceston, Australia. BCAA supplementation reduced muscles damage following 2 hours of cycling exercise BACKGROUND: The aim of this study was to examine the effects of branched-chain amino acid (BCAA) supplementation on serum indicators of muscle damage after prolonged exercise. We hypothesized that BCAA supplementation would reduce the serum activities of intramuscular enzymes associated with muscle damage. METHODS: To test this hypothesis, sixteen male subjects were assigned to one of two groups: the supplemental group (consuming 12 g x d(-1) BCAA for 14 d in addition to their normal diet) or the control group (normal diet only). Baseline serum creatine kinase (CK) and lactate dehydrogenase (LDH), shown to be accurate indicators of muscle damage, were determined during the week before the exercise test. The exercise test was administered on day seven and required the subjects to cycle for 120 min on an ergometer at approximately 70% VO2max. Blood samples were taken prior to and immediately following exercise and at 1 hr, 2 hrs, 3 hrs, 4 hrs, 1 d, 3 d, 5 d and 7 d postexercise. All subjects were required have their diets analyzed daily during the 14 d. RESULTS: Dietary analyses indicated that all subjects consumed the recommended daily intake of BCAA (0.64 g x kg(-1)) in their normal diets. Baseline serum values for CK and LDH were not different between groups in the 7 d prior to the test (p>0.05). However there were significant increases (p<0.05) between the pre-exercise and postexercise values for LDH and CK until 5 d postexercise test. Importantly, the BCAA supplementation significantly reduced this change in LDH from 2hrs to 5 d posttest, and CK from 4 hrs to 5 d post-test (p<0.05). CONCLUSIONS: These results indicate that supplementary BCAA decreased serum concentrations of the intramuscular enzymes CK and LDH following prolonged exercise, even when the recommended intake of BCAA was being consumed. This observation suggests that BCAA supplementation may reduce the muscle damage associated with endurance exercise. Bassit RA. Dept of Physiology & Biophysics, Inst Biomedical Sciences, Univ Sao Paulo, Brazil. Elite triathletes consuming BCAA supplements showed no reduction in plasma glutamine levels (compared to a 23% drop in placebo group) Following an Olympic distance triathlon, immune system parameters were reduced 22% in placebo group, but were maintained by BCAA supplementation Triatletes consuming BCAA supplements experienced 34% fewer infections INTRODUCTION: Intense long-duration exercise could lead to immune suppression through a decrease in the circulating level of plasma glutamine. The decrease in plasma glutamine concentration as a consequence of intense long-duration exercise was reversed, in some cases, by supplementing the diet of the athletes with branched-chain amino acids (BCAA). To better address this question, we have evaluated some blood parameters (lymphocyte proliferation, the level of plasma cytokines, plasma glutamine concentration, and in vitro production of cytokines by peripheral blood lymphocytes) before and after the Sao Paulo International Triathlon, as well as the incidence of symptoms of infections between the groups. METHODS: Twelve elite male triathletes of mean age /- 3.2 yr (ranging from 21.4 to 30.1 yr), weighing /- 3.9 kg, swam 1.5 km, cycled 40 km, and ran 10 km (Olympic triathlon) in the Sao Paulo International Triathlon held in April 1997 and April In both events, six athletes received BCAA and the others, placebo. RESULTs: Athletes from the BCAA group (BG) presented the same levels of plasma glutamine, before and after the trial, whereas those from the placebo group showed a reduction of 22.8% in plasma glutamine concentration after the competition. Changes in the proliferative response of peripheral blood lymphocytes were accompanied by a reduction in IL-1 production after exercise (22.2%), which was reversed by BCAA supplementation (20.3%), without changes in IL-2 production. DISCUSSION: The data obtained show that BCAA supplementation can reverse the reduction in serum glutamine concentration observed after prolonged intense exercise such as an Olympic triathlon. The decrease in plasma glutamine concentration is paralleled by an increased incidence of symptoms of infections that results in augmented proliferative response of lymphocytes cultivated in the absence of mitogens. The prevention of the lowering of plasma glutamine concentration allows an increased response of lymphocytes to ConA and LPS, as well as an increased production of IL-1 and 2, TNF-alpha, and IFN-gamma, possibly linked to the lower incidence of symptoms of infection (33.84%) reported by the supplemented athletes.

8 Parry-Billings M. Department of Biochemistry, University of Oxford, U.K. Plasma glutamine concentration was decreased in overtrained athletes and after long-term exercise (marathon race) and was increased after short-term, high intensity exercise (sprinting) BCAA supplementation was shown to prevent the decrease in plasma glutamine and is theorized to help prevent the immune suppression observed during strenuous training and following competition Overtraining and long-term exercise are associated with an impairment of immune function. We provide evidence in support of the hypothesis that the supply of glutamine, a key fuel for cells of the immune system, is impaired in these conditions and that this may contribute to immunosuppression. Plasma glutamine concentration was decreased in overtrained athletes and after long-term exercise (marathon race) and was increased after short-term, high intensity exercise (sprinting). Branched chain amino acid supplementation during long-term exercise was shown to prevent this decrease in the plasma glutamine level. Overtraining was without effect on the rate of T-lymphocyte proliferation in vitro or on the plasma levels of interleukin-1 and -6, suggesting that immune function is not impaired in this condition. Given the proposed importance of glutamine for cells of the immune system, it is concluded that the decrease in plasma glutamine concentration in overtraining and following long-term exercise, and not an intrinsic defect in T lymphocyte function, may contribute to the immune deficiency reported in these conditions.

9 GLUTAMINE 1. Pedersen BK, Toft AD. Effects of exercise on lymphocytes and cytokines. Br J Sports Med Aug;34(4): Bassit RA, Sawada LA, Bacurau RF, Navarro F, Costa Rosa LF. The effect of BCAA supplementation upon the immune response of triathletes. Med Sci Sports Exerc Jul;32(7): Nieman DC. Is infection risk linked to exercise workload? Med Sci Sports Exerc Jul;32(7 Suppl):S Field CJ, Johnson I, Pratt VC. Glutamine and arginine: immunonutrients for improved health. Med Sci Sports Exerc Jul;32(7 Suppl):S Mackinnon LT. Chronic exercise training effects on immune function. Med Sci Sports Exerc Jul;32(7 Suppl):S Smith DJ, Norris SR. Changes in glutamine and glutamate concentrations for tracking training tolerance. Med Sci Sports Exerc Mar;32(3): Antonio J, Street C. Glutamine: a potentially useful supplement for athletes. Can J Appl Physiol Feb;24(1): Castell LM, Newsholme EA. Glutamine and the effects of exhaustive exercise upon the immune response. Can J Physiol Pharmacol May;76(5): Walsh NP, Blannin AK, Robson PJ, Gleeson M. Glutamine, exercise and immune function. Links and possible mechanisms. Sports Med Sep;26(3): Castell LM, Newsholme EA. The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition Jul-Aug;13(7-8): Kingsbury KJ, Kay L, Hjelm M. Contrasting plasma free amino acid patterns in elite athletes: association with fatigue and infection. Br J Sports Med Mar;32(1): Rohde T, Krzywkowski K, Pedersen BK. Glutamine, exercise, and the immune system--is there a link? Exerc Immunol Rev. 1998;4: Rowbottom DG, Keast D, Morton AR. The emerging role of glutamine as an indicator of exercise stress and overtraining. Sports Med Feb;21(2): Castell LM, Poortmans JR, Newsholme EA. Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol. 1996;73(5): Rowbottom DG, Keast D, Goodman C, Morton AR. The haematological, biochemical and immunological profile of athletes suffering from the overtraining syndrome. Eur J Appl Physiol Occup Physiol. 1995;70(6): Newsholme EA. Biochemical mechanisms to explain immunosuppression in well-trained and overtrained athletes. Int J Sports Med Oct;15 Suppl 3:S142-7.

10 Pedersen BK. Copenhagen Muscle Research Centre, Univ of Copenhagen, Denmark. Repeated strenuous exercise is associated with suppressed immune function OBJECTIVES: To review results on exercise induced changes in the immune system following strenuous and moderate exercise. METHODS: A literature search over the past 15 years was conducted using Medline and selected papers. RESULTS: After intense long term exercise, the immune system is characterised by concomitant impairment of the cellular immune system and increased inflammation. Thus low concentrations of lymphocytes, suppressed natural immunity, suppressed lymphocyte proliferation, and suppressed levels of secretory IgA in saliva are found simultaneously with high levels of circulating proinflammatory and antiinflammatory cytokines. The underlying mechanisms are multifactorial and include neuroendocrinological and metabolic factors. The clinical consequences of the exercise induced immune changes have not formally been identified, but the exercise effect on lymphocyte dynamics and immune function may be linked to the exercise effects on resistance to infections and malignancy and the cytokine response may be linked to muscle damage or muscle cell growth. CONCLUSIONS: Moderate exercise across the life span seems to increase resistance to upper respiratory tract infections, whereas repeated strenuous exercise suppresses immune function. It is premature to offer advice on nutrition to athletes in order to alter the exercise induced immunosuppression found after exercise. Bassit RA, Sawada LA, Bacurau RF, Navarro F, Costa Rosa LF. Dept of Physiology and Biophysics, Inst Biomedical Sci, Univ Sao Paulo, Brazil. Endurance competition reduces plasma glutamine levels and increase risk of infection (upper respiratory tract infections / URTIs / colds and flu) BCAA supplementation of triathletes prevents the drop in glutamine levels and reduces the incidence of upper respiratory tract infections following races INTRODUCTION: Intense long-duration exercise could lead to immune suppression through a decrease in the circulating level of plasma glutamine. The decrease in plasma glutamine concentration as a consequence of intense long-duration exercise was reversed, in some cases, by supplementing the diet of the athletes with branched-chain amino acids (BCAA). To better address this question, we have evaluated some blood parameters (lymphocyte proliferation, the level of plasma cytokines, plasma glutamine concentration, and in vitro production of cytokines by peripheral blood lymphocytes) before and after the Sao Paulo International Triathlon, as well as the incidence of symptoms of infections between the groups. METHODS: Twelve elite male triathletes of mean age /- 3.2 yr (ranging from 21.4 to 30.1 yr), weighing /- 3.9 kg, swam 1.5 km, cycled 40 km, and ran 10 km (Olympic triathlon) in the Sao Paulo International Triathlon held in April 1997 and April In both events, six athletes received BCAA and the others, placebo. RESULTs: Athletes from the BCAA group (BG) presented the same levels of plasma glutamine, before and after the trial, whereas those from the placebo group showed a reduction of 22.8% in plasma glutamine concentration after the competition. Changes in the proliferative response of peripheral blood lymphocytes were accompanied by a reduction in IL-1 production after exercise (22.2%), which was reversed by BCAA supplementation (20.3%), without changes in IL-2 production. DISCUSSION: The data obtained show that BCAA supplementation can reverse the reduction in serum glutamine concentration observed after prolonged intense exercise such as an Olympic triathlon. The decrease in plasma glutamine concentration is paralleled by an increased incidence of symptoms of infections that results in augmented proliferative response of lymphocytes cultivated in the absence of mitogens. The prevention of the lowering of plasma glutamine concentration allows an increased response of lymphocytes to ConA and LPS, as well as an increased production of IL-1 and 2, TNF-alpha, and IFN-gamma, possibly linked to the lower incidence of symptoms of infection (33.84%) reported by the supplemented athletes.

11 Nieman DC. Dept of Health, Leisure, & Exercise Science, Appalachian State University. Various data suggest that endurance athletes are at increased risk for upper respiratory tract infections (URTIs) during heavy periods of training and for the 1-2 weeks following competition Glutamine supplementation may be associated with a reduced risk of infections during training and competition Anecdotal, survey, and epidemiological data suggest that endurance athletes are at an increased risk for upper respiratory tract infection (URTI) during periods of heavy training and the 1 - to 2-wk period after race events. The majority of athletes, however, who participate in endurance race events do not experience illness. Of greater public health importance is the consistent finding of a reduction in URTI risk reported by fitness enthusiasts and athletes who engage in regular exercise training while avoiding overreaching/overtraining. There is growing evidence that for several hours subsequent to heavy exertion, several components of both the innate and adaptive immune system exhibit suppressed function. The immune response to heavy exertion is transient, however, and further research on the mechanisms underlying the immune response to prolonged and intensive endurance exercise is necessary before meaningful clinical applications can be drawn. Field CJ. Dept of Agricultural, Food & Nutrition, University of Alberta, Edmonton, Canada. Numerous clinical studies support the use of glutamine supplements as a way to modulate the immune response during strenuous training Glutamine can be considered an essential amino acid for supporting immune function in athletes engaged in strenuous training and competition There is considerable literature demonstrating that specific nutrients can influence immune function in health and disease. This review will examine the literature and the rational for classifying two amino acids, glutamine (gln) and arginine (arg), as "immunonutrients" during infections. An understanding of immune defenses during infections (virus, parasite, bacteria, protozoa) and metabolism of gln and arg by immune cells is necessary to understand how these nutrients can influence specific functions of the immune system. This review focuses on several key clinical studies in immunosuppressed individuals (burn patients, individuals with cancer and HIV infection, and those undergoing surgery or who have experienced major traumas) that have tested the hypothesis that the provision of gln and/or arg is beneficial to immune function and clinical outcome. These clinical studies support the dietary "essentiality" of these two nutrients for improving immune responses in most immunosuppressive states associated with high rates of infection. However, the role of these nutrients in modulating the immune changes that occur with exercise in healthy athletes demands additional experiments.

12 Mackinnon LT. School of Human Movement Studies, The University of Queensland, Brisbane, Australia. Intense exercise suppresses the body s resistance to upper respiratory tract infections (URTIs) Prolonged periods of intense training can lead to impairment in immune parameters PURPOSE: This paper reviews the recent literature on the chronic effects of exercise training on immune function in humans. There is a general perception by athletes and other physically active individuals that regular moderate activity enhances, whereas intense exercise suppresses, resistance to minor illnesses such as upper respiratory tract infection (URTI). This perception is supported by epidemiological data in endurance athletes and limited data from intervention studies using moderate exercise in previously untrained individuals. The apparently high incidence of URTI among endurance athletes has prompted interest the relationship between chronic exercise training and immune function. Whereas immune cell number is generally normal during intense exercise training, recent evidence suggests that prolonged periods of intense training may lead to slight impairment in immune parameters such as neutrophil function, serum and mucosal immunoglobulin levels, plasma glutamine concentration, and possibly natural killer cell cytotoxic activity. In contrast. moderate exercise training has either no effect on, or may stimulate, these immune parameters. CONCLUSION: Whereas athletes are not clinically immune deficient, it is possible that the combined effects of small changes in several immune parameters may compromise resistance to minor illnesses such as URTI. Strategies to prevent URTI in athletes include avoiding overtraining, providing adequate rest and recovery during the training cycle and after competition, limiting exposure to sources of infection, ensuring adequate nutrition, and possibly vitamin C supplementation. It is uncertain at present whether moderate exercise training is helpful in preventing infectious illness among the wider population. Smith DJ, Norris SR. University of Calgary & National Sports Centre, Alberta, Canada. Heavy training is associated with a reduction in plasma glutamine levels Reduced plasma glutamine levels were associated with over-training in highperformance athletes undergoing intense training PURPOSE: The purpose was to monitor high-performance athletes throughout training macrocycles and competitions and examine the changes in plasma glutamine (Gm) and glutamate (Ga) concentrations in order to develop a model of tolerance to training. METHODS: Plasma glutamine and glutamate concentrations of 52 National team athletes (31 male and 21 female) divided into male and female groups of speed skating, swimming, and cross-country skiing were measured in an early season rested condition to determine highest Gm and lowest Ga concentrations and over 2-4 macrocycles, which included heavy training to establish lowest Gm and highest Ga concentrations. RESULTS: In the rested condition, there were no differences within and between the male and female groups, excluding five athletes (OTA) who became overtrained in heavy training. The mean (+/-SD) Gm concentration was 585 +/- 54 micromol x L(-1), Ga concentration 101 +/- 16 micromol x L(-1), and Gm/Ga ratio / micromol x L(-1). The OTA had a significantly higher Ga concentration of 128 +/- 16 micromol x L(-1) and lower Gm/Ga ratio of / micromol x L(-1) than all the other groups. In heavy training, there was a significant decrease (P < 0.05) in Gm concentration to 522 +/- 53 micromol x L(-1), significant increase in Ga concentration to 128 +/- 19 micromol x L(-1) and significant decrease in Gm/Ga ratio to / micromol x L(-1). The OTA Gm concentration of 488 +/- 31 micromol x L(-1) was significant lower than only the male speed skating and swimming groups. However, the Ga concentration of 171 +/- 17 micromol x L(-1) and Gm/Ga ratio of / micromol x L(-1) were significantly higher and lower respectively than all other groups. CONCLUSIONS: Based on the changes in Gm and Ga concentration under different training conditions, we propose an athlete tolerance to training model where glutamine concentration reflects tolerance to volume of work and glutamate concentration reflects tolerance to high intensity training. We suggest that the Gm/Ga ratio may globally represent overall tolerance to training.

13 Antonio J. Human Performance Laboratory, University of Nebraska-Kearney. Glutamine has potential utility as a dietary supplement for athletes engaged in heavy exercise training especially for maintenance of muscle protein mass and immune system function The role of glutamine as a possible ergogenic aid has not been posited in the scientific literature. Although there is an abundance of clinical evidence supporting the need for exogenous glutamine in the maintenance of muscle protein mass and immune system function in critically ill patients, little work has been done that examines the potential utility of glutamine for athletes engaged in heavy exercise training. This brief review will describe a number of studies on the effects of glutamine supplementation on muscle protein mass, immune system function, and glucose regulation. Based on the available clinical evidence, we would speculate that glutamine has potential utility as a dietary supplement for athletes engaged in heavy exercise training. Castell LM. Department of Biochemistry, Oxford University, U.K. Glutamine supplements have a beneficial effect on reducing the incidence of upper respiratory tract infections (URTIs) in runners following a marathon Prolonged exercise can reduce plasma levels of glutamine Glutamine is an important fuel for cells of the immune system There is a high incidence of infections in athletes undergoing intense, prolonged training or participating in endurance races (e.g., the marathon), in particular, upper respiratory tract infections. Prolonged, exhaustive exercise can lower the plasma level of the amino acid, glutamine, which is an important fuel for some cells of the immune system and may have specific immunostimulatory effects. This could therefore be an important factor in the event of an impaired response of immune cells to opportunistic infections. The effects of feeding glutamine to sedentary individuals and to marathon and ultramarathon runners before and after prolonged, exhaustive exercise has been investigated in a series of studies that monitored the incidence of infections and some acute-phase response markers. Oral glutamine, compared with a placebo, appeared to have a beneficial effect on the incidence of infections reported by runners after a marathon.

14 Walsh NP. Sport Health Dept, Trinity and All Saints University College, Leeds, England. Prolonged exercise reduces plasma glutamine levels and stresses the immune system Over-trained athletes exhibit lower plasma glutamine levels than healthy active non-athletes Glutamine is the most abundant free amino acid in human muscle and plasma and is utilised at high rates by rapidly dividing cells, including leucocytes, to provide energy and optimal conditions for nucleotide biosynthesis. As such, it is considered to be essential for proper immune function. During various catabolic states including surgical trauma, infection, starvation and prolonged exercise, glutamine homeostasis is placed under stress. Falls in the plasma glutamine level (normal range 500 to 750 mumol/l after an overnight fast) have been reported following endurance events and prolonged exercise. These levels remain unchanged or temporarily elevated after short term, high intensity exercise. Plasma glutamine has also been reported to fall in patients with untreated diabetes mellitus, in diet-induced metabolic acidosis and in the recovery period following high intensity intermittent exercise. Common factors among all these stress states are rises in the plasma concentrations of cortisol and glucagon and an increased tissue requirement for glutamine for gluconeogenesis. It is suggested that increased gluconeogenesis and associated increases in hepatic, gut and renal glutamine uptake account for the depletion of plasma glutamine in catabolic stress states, including prolonged exercise. The short term effects of exercise on the plasma glutamine level may be cumulative, since heavy training has been shown to result in low plasma glutamine levels (< 500 mumol/l) requiring long periods of recovery. Furthermore, athletes experiencing discomfort from the overtraining syndrome exhibit lower resting levels of plasma glutamine than active healthy controls. Therefore, physical activity directly affects the availability of glutamine to the leucocytes and thus may influence immune function. The utility of plasma glutamine level as a marker of overtraining has recently been highlighted, but a consensus has not yet been reached concerning the best method of determining the level. Since injury, infection, nutritional status and acute exercise can all influence plasma glutamine level, these factors must be controlled and/or taken into consideration if plasma glutamine is to prove a useful marker of impending overtraining. Castell LM. University Department of Biochemistry, Oxford, United Kingdom. Marathon running decreases plasma glutamine levels by 20% Post-exercise infection rates are elevated for at least 1-week following intense competitions such as marathon, ultra-marathon and rowing. The provision of oral glutamine after exercise appeared to have a beneficial effect on the level of subsequent infections Athletes undergoing intense, prolonged training or participating in endurance races suffer an increased risk of infection due to apparent immunosuppression. Glutamine is an important fuel for some cells of the immune system and may have specific immunostimulatory effects. The plasma glutamine concentration is lower after prolonged, exhaustive exercise: this may contribute to impairment of the immune system at a time when the athlete may be exposed to opportunistic infections. The effects of feeding glutamine was investigated both at rest in sedentary controls and after exhaustive exercise in middle-distance, marathon and ultramarathon runners, and elite rowers, in training and competition. Questionnaires established the incidence of infection for 7 d after exercise: infection levels were highest in marathon and ultra-marathon runners, and in elite male rowers after intensive training. Plasma glutamine levels were decreased by approximately 20% 1 h after marathon running. A marked increase in numbers of white blood cells occurred immediately after exhaustive exercise, followed by a decrease in the numbers of lymphocytes. The provision of oral glutamine after exercise appeared to have a beneficial effect on the level of subsequent infections. In addition, the ratio of T- helper/t-suppressor cells appeared to be increased in samples from those who received glutamine, compared with placebo.

15 Kingsbury KJ. MDL Laboratory, London, United Kingdom. In three groups of Olympic athletes, low glutamine levels were associated with chronic fatigue, over-training, suppressed immune function and increased infections AIM: There is little information on the plasma free amino acid patterns of elite athletes against which fatigue and nutrition can be considered. Therefore the aim was to include analysis of this pattern in the medical screening of elite athletes during both especially intense and light training periods. METHODS: Plasma amino acid analysis was undertaken in three situations. (1) A medical screening service was offered to elite athletes during an intense training period before the 1992 Olympics. Screening included a blood haematological/biochemical profile and a microbial screen in athletes who presented with infection. The athletes were divided into three groups who differed in training fatigue and were considered separately. Group A (21 track and field athletes) had no lasting fatigue; group B (12 judo competitors) reported heavy fatigue at night but recovered overnight to continue training; group C (18 track and field athletes, one rower) had chronic fatigue and had been unable to train normally for at least several weeks. (2) Athletes from each group were further screened during a post-olympic light training period. (3) Athletes who still had low amino acid levels during the light training period were reanalysed after three weeks of additional protein intake. RESULTS: (1) The pre-olympics amino acid patterns were as follows. Group A had a normal amino acid pattern (glutamine 554 (25.2) micromol/l, histidine 79 (6.1) micromol/l, total amino acids 2839 (92.1) micromol/l); all results are means (SEM). By comparison, both groups B and C had decreased plasma glutamine (average 33%; p<0.001) with, especially in group B, decreased histidine, glucogenic, ketogenic, and branched chain amino acids (p<0.05 to p<0.001). None in group A, one in group B, but ten athletes in group C presented with infection: all 11 athletes had plasma glutamine levels of less than 450 micromol/l. No intergroup differences in haematological or other blood biochemical parameters, apart from a lower plasma creatine kinase activity in group C than in group B (p<0.05) and a low neutrophil to lymphocyte ratio in the athletes with viral infections (1.2 (0.17)), were found. (2) During post-olympic light training, group A showed no significant amino acid changes. In contrast, group B recovered normal amino acid levels (glutamine 528 (41.4) micromol/l, histidine 76 (5.3) micromol/l, and total amino acids 2772 (165) micromol/l) (p<0.05 to p<0.001) to give a pattern comparable with that of group A, whereas, in group C, valine and threonine had increased (p<0.05), but glutamine (441 (24.5) micromol/l) and histidine (58 (5.3) micromol/l) remained low. Thus none in group A, two in group B, but ten (53%) in group C still had plasma glutamine levels below 450 micromol/l, including eight of the 11 athletes who had presented with infection. (3) With the additional protein intake, virtually all persisting low glutamine levels increased to above 500 micromol/l. Plasma glutamine rose to 592 (35.1) micromol/l and histidine to 86 (6.0) micromol/l. Total amino acids increased to 2761 (128) micromol/l (p<0.05 to p<0.001) and the amino acid pattern normalised. Six of the ten athletes on this protein intake returned to increased training within the three weeks. CONCLUSION: Analysis of these results provided contrasting plasma amino acid patterns: (a) a normal pattern in those without lasting fatigue; (b) marked but temporary changes in those with acute fatigue; (c) a persistent decrease in plasma amino acids, mainly glutamine, in those with chronic fatigue and infection, for which an inadequate protein intake appeared to be a factor. Rohde T. Copenhagen Muscle Research Center, Rigshospitalet, Denmark. The decrease in plasma glutamine level following strenuous exercise has been associated with the observed suppression of immune function and increase in post-exercise illness Glutamine is known to be important for cells replicating in culture. It has been proposed that the decrease in plasma glutamine concentration in relation to catabolic conditions, including strenuous exercise, resulting in a lack of glutamine for cells of the immune system, is responsible for the transient postexercise immunosuppression. This review discusses the potential role of glutamine on the postexercise in-vitro changes in immune parameters. Furthermore, the value of glutamine as a nutritional supplement to athletes and the possible influence on these parameters is reviewed.

16 Rowbottom DG. Department of Microbiology, University of Western Australia, Perth. During various catabolic states, such as extreme levels of exercise, muscle glutamine stores become depleted Inadequate recovery from exercise leads to rapid drops on plasma and muscle levels of glutamine Athletes suffering from overtraining are known to exhibit low plasma glutamine levels for months or years Immune system function is likely to be compromised in athletes suffering from overtraining and inadequate recovery from exercise Glutamine is an amino acid essential for many important homeostatic functions and for the optimal functioning of a number of tissues in the body, particularly the immune system and the gut. However, during various catabolic states, such as infection, surgery, trauma and acidosis, glutamine homeostasis is placed under stress, and glutamine reserves, particularly in the skeletal muscle, are depleted. With regard to glutamine metabolism, exercise stress may be viewed in a similar light to other catabolic stresses. Plasma glutamine responses to both prolonged and high intensity exercise are characterised by increased levels during exercise followed by significant decreases during the post-exercise recovery period, with several hours of recovery required for restoration of pre-exercise levels, depending on the intensity and duration of exercise. If recovery between exercise bouts is inadequate, the acute effects of exercise on plasma glutamine level may be cumulative, since overload training has been shown to result in low plasma glutamine levels requiring prolonged recovery. Athletes suffering from the overtraining syndrome (OTS) appear to maintain low plasma glutamine levels for months or years. All these observations have important implications for organ functions in these athletes, particularly with regard to the gut and the cells of the immune system, which may be adversely affected. In conclusion, if methodological issues are carefully considered, plasma glutamine level may be useful as an indicator of an overtrained state. Castell LM. University Department of Biochemistry, Oxford, UK. Athletes (runners and rowers) receiving glutamine supplements experienced significantly fewer upper respiratory tract infections (URTIs) during the 7-days following competition compared to those given a placebo There is an increased risk of infections in athletes undertaking prolonged, strenuous exercise. There is also some evidence that cells of the immune system are less able to mount a defence against infections after such exercise. The level of plasma glutamine, an important fuel for cells of the immune system, is decreased in athletes after endurance exercise; this may be partly responsible for the apparent immunosuppression which occurs in these individuals. We monitored levels of infection in more than 200 runners and rowers. The levels of infection were lowest in middle-distance runners, and highest in runners after a full or ultramarathon and in elite rowers after intensive training. In the present study, athletes participating in different types of exercise consumed two drinks, containing either glutamine (Group G) or placebo (Group P) immediately after and 2 h after exercise. They subsequently completed questionnaires (n = 151) about the incidence of infections during the 7 days following the exercise. The percentage of athletes reporting no infections was considerably higher in Group G (81%, n = 72) than in Group P (49%, n = 79, p < 0.001).

17 Rowbottom DG. Dept of Microbiology, Univ of Western Australia, QE II Medical Centre, Nedlands. A reduced plasma level of glutamine was associated with the over-training syndrome (fatigue, infection, reduced performance) in a group of 10 athletes To help clarify the overtraining syndrome (OTS), a combination of parameters were measured in ten athletes who were suffering from OTS. Blood samples were obtained at rest and a range of haematological, biochemical and immunological tests were carried out on the samples. For each parameter, the mean value for the group was compared to an established normal range amongst age-matched controls. The subjects were also asked to complete a questionnaire to establish the severity of their condition. The data indicated that the debilitating fatigue experienced by the OTS sufferers was not related to any of the blood parameters traditionally associated with chronic exercise stress, since levels were normal in OTS. The only parameter measured which deviated significantly from the normal range for both the sedentary controls and the athletes was the plasma concentration of glutamine. Although the data in this study would suggest that plasma glutamine concentrations represented an objective, measurable difference between OTS subjects and normal controls, it remains to be shown that there is any correlation between glutamine concentrations and other clinical symptoms of OTS such as physical capability. Newsholme EA. Department of Biochemistry, University of Oxford. Sustained endurance training and overtraining are known to reduce body stores of glutamine and may lead to increased glutamine requirements for support of immune system function Glutamine is utilized at a high rate by some cells of the immune system (including lymphocytes and macrophages) and is essential for the viability and normal functioning of these cells. Experiments on lymphocytes in vitro showed that the proliferative response of these cells was dependent on the concentration of glutamine and this suggests that a decrease in plasma glutamine concentration could be responsible, at least in part, for the reported impairment of immune function in various conditions. Much of the glutamine that enters the body is utilized by cells of the small intestine, so that muscle is an important source for the plasma glutamine, Hence, the plasma concentration of glutamine represents a "metabolic link" between skeletal muscle and cells of the immune system. Indeed, the flux-generating step of glutamino metabolism in cells of the immune system is considered to be located in skeletal muscle which synthesizes and stores glutamine. The flux generating step is probably the outward transport of glutamine across the plasma membrane. The rate of this transport process and therefore glutamine release from muscle is decreased in conditions associated with a reduction in immune function or activity in the rat such as sustained exercise. The plasma glutamine concentration in man is decreased in a number of pathological conditions, with the largest decrease recorded following major burns. It is also decreased after prolonged exercise (e.g. marathon run) and in the overtrained state. It is suggested, therefore, that sustained physical activity could damage the glutamine release process so that it does not respond adequately to increased glutamine requirement by the immune system.

18 BETA-SITOSTEROL 1. Plant sterols and sterolins - Monograph. Altern Med Rev Apr;6(2): Bouic PJ, Lamprecht JH. Plant sterols and sterolins: a review of their immune-modulating properties. Altern Med Rev Jun;4(3): Bouic PJ, Clark A, Lamprecht J, Freestone M, Pool EJ, Liebenberg RW, Kotze D, van Jaarsveld PP. The effects of B-sitosterol (BSS) and B-sitosterol glucoside (BSSG) mixture on selected immune parameters of marathon runners: inhibition of post marathon immune suppression and inflammation. Int J Sports Med. Plant sterols and sterolins - Monograph. Altern Med Rev 2001 Apr;6(2): A variety of animal and human studies have shown beta-sitosterol to possess antiinflammatory and immune-modulating properties Beta-sitosterol may also normalize DHEA:Cortisol ratio following stressful events such as exhaustive exercise Beta-sitosterol supplements may provide therapeutic benefit in disease processes related to stress-induced immune suppression and the over-training syndrome Sterols and sterolins, also known as phytosterols, are fats present in all plants, including fruits and vegetables. Although they are chemically similar to the animal fat, cholesterol, they have been shown to exert significant unique biochemical effects in both animals and humans. Because they are bound to the fibers of the plant, they are difficult to absorb during the transit of digested food through the gut, particularly in individuals with impaired digestive function. For this reason, and because much of the modern diet is overprocessed and low in fresh plant materials, sterols and sterolins appear in the serum and tissue of healthy humans at times lower concentrations than that of cholesterol. Beta-sitosterol (BSS) is the major phytosterol in higher plants along with its glycoside, beta-sitosterolin (BSSG). Animal studies have demonstrated BSS and BSSG possess anti-inflammatory, antipyretic, antineoplastic, and immune-modulating properties. In other in vitro, animal, and human studies, a proprietary BSS:BSSG mixture has shown promise in normalizing T-cell function, dampening overactive antibody responses, and normalizing DHEA:cortisol ratios. Research has shown plant oils contain the highest concentration of phytosterols, nuts and seeds contain moderate amounts, and fruits and vegetables generally contain the lowest phytosterol concentrations. Because only low levels of these substances are found in humans, increased dietary intake of unprocessed fruits and vegetables or supplementation with commercial phytosterols may be of benefit in reestablishing optimal immune parameters. Restoring balance to the immune system may be of therapeutic benefit in disease processes such as chronic viral infections, stress-induced immune suppression, tuberculosis, allergies, cancer, and rheumatoid arthritis and other autoimmune conditions.

19 Bouic PJ. Dept of Medical Microbiology, University of Stellenbosch. Tygerberg, South Africa. Beta-sitosterol exhibits anti-inflammatory and immune-modulating properties probably via its effects on targeting specific T-helper lymphocytes, the Th1 and Th2 cells, which helps to normalize their functioning and improve T-lymphocyte and natural killer cell activity Beta-sitosterol (BSS) and its glycoside (BSSG) are sterol molecules which are synthesized by plants. When humans eat plant foods phytosterols are ingested, and are found in the serum and tissues of healthy individuals, but at concentrations orders of magnitude lower than endogenous cholesterol. Epidemiological studies have correlated a reduced risk of numerous diseases with a diet high in fruits and vegetables, and have concluded that specific molecules, including b-carotene, tocopherols, vitamin C, and flavonoids, confer some of this protective benefit. However, these epidemiologic studies have not examined the potential effect that phytosterols ingested with fruits and vegetables might have on disease risk reduction. In animals, BSS and BSSG have been shown to exhibit antiinflammatory, anti-neoplastic, anti-pyretic, and immune-modulating activity. A proprietary BSS:BSSG mixture has demonstrated promising results in a number of studies, including in vitro studies, animal models, and human clinical trials. This phytosterol complex seems to target specific T-helper lymphocytes, the Th1 and Th2 cells, helping normalize their functioning and resulting in improved T-lymphocyte and natural killer cell activity. A dampening effect on overactive antibody responses has also been seen, as well as normalization of the DHEA:cortisol ratio. The re-establishment of these immune parameters may be of help in numerous disease processes relating to chronic immune-mediated abnormalities, including chronic viral infections, tuberculosis, rheumatoid arthritis, allergies, cancer, and auto-immune diseases. Bouic PJ. Dept. Medical Microbiology, Tygerberg, South Africa. Ultra-marathon runners taking beta-sitosterol supplements showed a maintenance of immune system function, reduced inflammation and a lower Cortisol:DHEA ratio following competition compared to athletes receiving placebo Athletes receiving beta-sitosterol experienced less immune system suppression during the post-marathon recovery period A pilot study was undertaken to investigate the effects of the intake of capsules containing the plant sterols and sterolins (BSS:BSSG mixture) on selected immune parameters of volunteers participating in an ultra-marathon in Cape Town, South Africa. Those runners having received active capsules (n=9) showed less neutrophilia, lymphopenia and leukocytosis when compared to their counterparts having received placebo capsules (n=8): the placebo treated individuals showed significant increases in their total white blood cell numbers as well as in their neutrophils (p=0.03 and 0.03 respectively). Furthermore, statistically significant increases within lymphocyte subsets were observed in the runners having received the active capsules: CD3+ cells increased (p=0.02) as did CD4+ cells (p=0.03). In parallel, the BSS:BSSG capsules decreased the plasma level of IL6 in the runners using the active capsules (p=0.08) and significantly decreased the cortisol: DHEA ratio (p=0.03), suggesting that these volunteers had less of an inflammatory response and were less immune suppressed during the post-marathon recovery period. These findings justify further investigations into the use of the phytosterols to prevent the subtle immunosuppression associated with excessive physical stress.

20 PROTEOLYTIC ENZYMES (Papain and Bromelain) 1. Neverov VA, Klimov AV. The pathogenetic basis for and clinical use of systemic enzyme therapy in traumatology and orthopedics. Vestn Khir Im I I Grek. 1999;158(1): Gal P, Tecl F, Skotakova J, Mach V. Systemic enzyme therapy in the treatment of supracondylar fractures of the humerus in children. Rozhl Chir Dec;77(12): Duskova M, Wald M. Orally administered proteases in aesthetic surgery. Aesthetic Plast Surg Jan-Feb;23(1): Singer F, Oberleitner H. Drug therapy of activated arthrosis. On the effectiveness of an enzyme mixture versus diclofenac. Wien Med Wochenschr. 1996;146(3): Hoernecke R, Doenicke A. Perioperative enzyme therapy. A significant supplement to postoperative pain therapy? Anaesthesist Dec;42(12): Zh Mikrobiol Epidemiol Immunobiol 1999 Sep- Oct;(5): Neverov VA. Research Institute of Physical Training, Moscow, Russia. Proteolytic enzymes are shown to reduce pain and inflammation in patients recovering from injuries such as soft tissue trauma and orthopedic surgery The use of the experimental model of the development of acute secondary immunodeficiency, accompanied by the redistribution of immunoglobulins from plasma to blood cells, for evaluating the effect of immunomodulation is substantiated. The preparation of proteolytic enzymes has been shown to produce significant and dose-dependent decrease the sorption of immunoglobulins on mouse cells in the process of swimming. The authors have generalized their experiences in 140 patients where schemes of the effective systemic enzyme therapy are proposed for patients of the orthopedic-traumatological profile. Gal P. Clinical Centre for Trauma Research (traumatologie-klinika), Brno, Germany. Proteolytic enzyme blends were shown to reduce pain and inflammation, while increasing circulation in patients recovering from bone fractures Patients receiving the enzymes experienced faster healing compared to those who did not receive the supplements The authors present their experience with enzyme therapy for the treatment of supracondylar fractures of the humerus in children. On monitoring the condition of the extremity by Doppler ultrasound, where the flow through the radial artery was quantified they obtained better results in the group of patients treated by systemic enzyme therapy than in the control group. Systemic enzyme therapy is recommended as a suitable supplement in comprehensive treatment where the most important part is played by correct and early treatment along with precise monitoring of the extremity during the postoperative course.