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Conjugated linoleic acid reduces body fat mass in overweight and obese humans.
Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O. Scandinavian Clinical Research AS, N-2027 Kjeller, Norway.
J Nutr 2000 Dec;130(12):2943-8
Conjugated linoleic acid (CLA) has been shown to reduce body fat mass (BFM) in animals. To investigate the dose-response relationships of conjugated linoleic acid with regard to BFM in humans, a randomized, double-blind study including 60 overweight or obese volunteers (body mass index 25-35 kg/m(2)) was performed. The subjects were divided into five groups receiving placebo (9 g olive oil), 1.7, 3.4, 5.1 or 6.8 g conjugated linoleic acid per day for 12 wk, respectively. Dual-energy X-ray absorptiometry was used to measure body composition [measurements at wk 0 (baseline), 6 and 12]. Of the 60 subjects, 47 completed the study. Eight subjects withdrew from the study due to adverse events; however, no differences among treatment groups were found regarding adverse events. Repeated-measures analysis showed that a significantly higher reduction in BFM was found in the conjugated linoleic acid groups compared with the placebo group (P: = 0.03). The reduction of body fat within the groups was significant for the 3.4 and 6.8 g CLA groups (P: = 0.05 and P: = 0.02, respectively). No significant differences among the groups were observed in lean body mass, body mass index, blood safety variables or blood lipids. The data suggest that conjugated linoleic acid may reduce BFM in humans and that no additional effect on BFM is achieved with doses > 3.4 g CLA/d.
Effect of oral creatine supplementation on jumping and running performance.
Bosco C; Tihanyi J; Pucspk J; Kovacs I; Gabossy A; Colli R; Pulvirenti G; Tranquilli C; Foti C; Viru M; Viru A University of Rome-Tor Vergata, Fondazione Don Gnocchi, Italy.
Int J Sports Med (Germany) Jul 1997, 18 (5) p369-72
The study was designed to investigate the effect of creatine monohydrate ingestion (20 g daily for 5 days) on performance in 45 s maximal continuous jumping and in all-out treadmill running at 20 km x h(-1), (inclination 5 degrees, duration approximately 60s). The participants were qualified sprinters and jumpers. The effect of creatine was compared with placebo in a double-blind design. Creatine (Cr) supplementation led to a significant enhancement of performance capacity in the jumping test by 7% during the first 15 s and by 12% during the second 15 s of the exercise. The positive effect of Cr supplementation was not observed in the last third of the continuous jumping exercise, when the contribution of anaerobic metabolism was decreasing. The time of intensive running up to exhaustion improved by 13%. The results show that Cr supplementation helps to prolong the time during which the maximal rate of power output could be maintained.
Androgen replacement in menopause.
Burd ID, Bachmann GA. Women's Health Institute, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Curr Womens Health Rep. 2001 Dec;1(3):202-5.
Menopause and the years leading to the menopausal transition are associated with significant decline in sex steroid levels. In contrast to the abrupt decline in estrogens at the time of menopause, a fall in the circulating testosterone and the adrenal preandrogens most closely parallel increasing age. Their accelerated decrease occurs in the years preceding menopause. It is now recognized that the decline in androgens plays a significant role in affecting perimenopausal and menopausal symptomatology and quality of life. Loss of circulating levels of androgens affects libido, vasomotor symptoms, mood and well-being, bone structure, muscle mass. Also, it influences cardiovascular profile. In the menopausal female (in whom these symptoms are clearly linked to low levels of bioavailable testosterone levels), hormone replacement therapy may be of benefit. Recently, interest is increasing in the use of androgen replacement not only for women who have undergone premature or surgical menopause but also for those who experience natural menopause and premenopausal loss of libido from diminished free testosterone.
Aromatase, adiposity, aging and disease. The hypogonadal-metabolic-atherogenic-disease and aging connection.
Cohen PG. 2480 Windy Hill Road SE Suite 200, Marietta, GA 30067, USA.
Med Hypotheses 2001Jun;56(6):702-8
In males, aging, health and disease are processes that occur over physiologic time and involve a cascade of hormonal, biochemical and physiological changes that accompany the down-regulation of the hypothalamic-anterior pituitary-testicular axis. As aging progresses there are relative increases of body fat and decreases in muscle mass. The increased adipose tissue mass is associated with the production of a number of newly generated factors. These include aromatase, leptin, PAI-1, insulin resistance, and the dyslipidemias, all of which can lead to tissue damage. Fatty tissue becomes the focal point for study as it represents the intersection between energy storage and mobilization. The increase in adipose tissue is associated with an increase in the enzyme aromatase that converts testosterone to estradiol and leads to diminished testosterone levels that favor the preferential deposition of visceral fat. As the total body fat mass increases, hormone resistance develops for leptin and insulin. Increasing leptin fails to prevent weight gain and the hypogonadal-obesity cycle ensues causing further visceral obesity and insulin resistance. The progressive insulin resistance leads to a high triglyceride-low HDL pattern of dyslipidemia and increased cardiovascular risk. All of these factors eventually contribute to the CHAOS Complex: coronary disease, hypertension, adult-onset diabetes mellitus, obesity and/or stroke as permanent changes unfold. Other consequences of the chronic hypogonadal state include osteopenia, extreme fatigue, depression, insomnia, loss of aggressiveness and erectile dysfunction all of which develop over variable periods of time. Copyright 2001 Harcourt Publishers Ltd.
Bioavailability of glutamine and effects of glutamine on protein metabolism
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.
Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid/thioctic acid: participation of elements of the insulin signaling pathway.
Estrada DE, Ewart HS, Tsakiridis T, Volchuk A, Ramlal T, Tritschler H, Klip A. Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Diabetes 1996 Dec;45(12):1798-1804
Thioctic acid (alpha-lipoic acid), a natural cofactor in dehydrogenase complexes, is used in Germany in the treatment of symptoms of diabetic neuropathy. Thioctic acid improves insulin-responsive glucose utilization in rat muscle preparations and during insulin clamp studies performed in diabetic individuals. The aim of this study was to determine the direct effect of thioctic acid on glucose uptake and glucose transporters. In L6 muscle cells and 3T3-L1 adipocytes in culture, glucose uptake was rapidly increased by (R)-thioctic acid. The increment was higher than that elicited by the (S)-isomer or the racemic mixture and was comparable with that caused by insulin. In parallel to insulin action, the stimulation of glucose uptake by thioctic acid was abolished by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, in both cell lines. Thioctic acid provoked an upward shift of the glucose-uptake insulin dose-response curve. The molar content of GLUT1 and GLUT4 transporters was measured in both cell lines. 3T3-L1 adipocytes were shown to have >10 times more glucose transporters but similar ratios of GLUT4:GLUT1 than L6 myotubes. The effect of (R)-thioctic acid on glucose transporters was studied in the L6 myotubes. Its stimulatory effect on glucose uptake was associated with an intracellular redistribution of GLUT1 and GLUT4 glucose transporters, similar to that caused by insulin, with minimal effects on GLUT3 transporters. In conclusion, thioctic acid stimulates basal glucose transport and has a positive effect on insulin-stimulated glucose uptake. The stimulatory effect is dependent on phosphatidylinositol 3-kinase activity and may be explained by a redistribution of glucose transporters. This is evidence that a physiologically relevant compound can stimulate glucose transport via the insulin signaling pathway.
Efficacy of dietary CLA and CLA+Guarana (ADIPILL) on body adiposity, and adipocytes cell number and size.
Experimental Biology Meeting,
FASEB.
New Orleans, Louisiana, April 20-24, 2002.
Carbohydrate ingestion augments creatine retention during creatine feeding in humans.
Green AL; Simpson EJ; Littlewood JJ; Macdonald IA; Greenhaff PL Department of Physiology and Pharmacology, University Medical School, Queen's Medical Centre, Nottingham, UK.
Acta Physiol Scand, 158(2):195-202 1996 Oct
Blood and urine samples were obtained from four groups of healthy male subjects (A-D, total n = 22) before, during and after ingesting the following: group A, 5 g of creatine in solution; groups B and C, 5 g of creatine and 93 g of simple carbohydrate in solution: group D, a creatine- and carbohydrate-free solution. Subjects ingested the above preparations every 4 h for the remainder of the day and throughout the next day (total daily creatine dose = 20 g), and reported back to the laboratory on day 3 to undergo the same procedures as on day 1. Throughout this time, subjects weighed and recorded all dietary intake, and those in groups B and C ingested a prescribed isoenergetic high carbohydrate diet. Subjects in group C also performed 1 h of cycling exercise at 70% of their maximal oxygen consumption on the morning of each day. On both days 1 and 3, peak plasma creatine concentration, the area under the plasma creatine concentration/time curve and urinary creatine concentration were lower in groups B and C than in group A. Conversely, serum insulin concentration was higher in groups B and C than in A. No differences were evident when comparing groups B and C. These data suggest carbohydrate ingestion augmented creatine retention during creatine feeding and that creatine retention was not further increased when exercise was performed prior to ingestion.
The nutritional biochemistry of creatine
Greenhaff P.L. Dr. P.L. Greenhaff, Department of Physiology, University Medical School, Queen's Medical Centre, Nottingham NG7 United Kingdom
Journal of Nutritional Biochemistry (United States) 1997, 8/11 (610-618)
Creatine is a naturally occurring compound that is synthesized endogenously and is present in a meat eaters diet. It is stored in abundance in skeletal muscle, where it exists in free and phosphorylated forms and plays a pivotal role in maintaining a high adenosine triphosphate:adenosine diphosphate ratio during intense contraction. Fatigue development during short-term maximal exercise has been associated with the inability of skeletal muscle to maintain this ratio, at least partly because of phosphocreatine depletion. Ingestion of creatine monohydrate in solution at a rate of 20 g/day for 5 to 6 days has been shown to increase muscle total creatine concentration by approximately 25 mmol/kg dry mass in man, but the variation between subjects is large. After this initial loading phase, muscle stores can be maintained by ingesting 2 g/day. A positive relationship has since been demonstrated between muscle creatine uptake and improvements in performance during repeated bouts;of maximal exercise and rates of phosphocreatine resynthesis during recovery from maximal exercise. The mechanism by which improvements in maximal exercise performance are achieved following creatine ingestion possibly relates to an increase in phosphocreatine concentration. Specifically in Type II muscle fibres, maintaining adenosine triphosphate resynthesis during exercise. Recently, muscle creatine accumulation has been shown to be substantially increased by combining creatine supplementation with carbohydrate ingestion; elevating muscle creatine concentration in all subjects close to the upper limit of 160 mmol/kg dm. Creatine supplementation should be viewed as a significant development in sports-related nutrition.
Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers.
Grindstaff PD; Kreider R; Bishop R; Wilson M; Wood L; Alexander C; Almada A Dept of Human Movement Sciences and Education, Univ of Memphis, Memphis, TN 38152
Int J Sport Nutr (United States) Dec 1997, 7 (4) p330-46
In a double-blind and randomized manner, 18 male and female junior competitive swimmers supplemented their diets with 21 g.day-1 of creatine monohydrate (Cr) or a maltodextrin placebo (P) for 9 days during training. Prior to and following supplementation, subjects performed three 100-m freestyle sprint swims (long course) with 60 s rest/recovery between heats. In addition, subjects performed three 20-s arm ergometer maximal-effort sprint tests in the prone position with 60 s rest/recovery between sprint tests. Significant differences were observed among swim times, with Cr subjects swimming significantly faster than P subjects following supplementation in Heat 1 and significantly decreasing swim time in the second 100-m sprint. There was also some evidence that cumulative time to perform the three 100-m swims was decreased in the Cr group. Results indicate that 9 days of Cr supplementation during swim training may provide some ergogenic value to competitive junior swimmers during repetitive sprint performance.
Reasons for the degeneration of ageing skeletal muscle: a central role for IGF-1 signalling.
Grounds MD. Department of Anatomy and Human Biology, The University of Western Australia, Crawley, Australia. mgrounds@anhb.uwa.edu.au
Biogerontology 2002;3(1-2):19-24
This paper examines two major possibilities for the striking loss of skeletal muscle mass and strength that occurs in very old animals and humans. It is concluded that muscle regeneration is not significantly impaired with age. Instead, it seems that individual myofibres undergo atrophy, with selective death of the fast type 2B myofibres, due to the combined effects of many age-related changes the main causes being: nutrition (under-nutrition and lack of vitamin D), decreased hormone levels (e.g growth hormone, testosterone), reduced physical activity, and a loss of nerves that innervate the muscles. The discussion focusses on the central role of a local muscle form of insulin-like growth factor-I (IGF-I) in muscle hypertrophy, atrophy and motorneurone loss. Reduced IGF-I signalling is involved in muscle atrophy and results from decreased muscle exercise, reduced growth hormone and insulin levels, reduced vitamin D, and treatment with drugs like corticosteroids, dexamethasone, and cyclosporin. In addition, elevated levels of inflammatory cytokines like TNF-alpha and IL-6 can cause muscle wasting (cachexia) although this is usually associated with disease, and TNF-alpha may also act (at least in part) by inhibiting IGF-I signalling. The possible clinical prevention of age-related muscle wasting (and associated motorneurone loss) by the locally acting muscle isoform of IGF-I is discussed.
Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis and improves nitrogen balance.
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.
Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation.
Harris RC; S¨oderlund K; Hultman E Department of Clinical Chemistry II, Karolinska Institute, Huddinge University Hospital,Sweden.
Clin Sci (Colch), 83(3):367-74 1992 Sep
1. The present study was undertaken to test whether creatine given as a supplement to normal subjects was absorbed, and if continued resulted in an increase in the total creatine pool in muscle. An additional effect of exercise upon uptake into muscle was also investigated.
2. Low doses (1g of creatine monohydrate or less in water) produced only a modest rise in the plasma creatine concentration, whereas 5g resulted in a mean peak after 1h of 795 (SD 104) mumol/l in three subjects weighing 76-87 kg. Repeated dosing with 5g every 2h sustained the plasma concentration at around 1000 mumol/l. A single 5g dose corresponds to the creatine content of 1.1 kg of fresh, uncooked steak.
3. Supplementation with 5g of creatine monohydrate, four or six times a day for 2 or more days resulted in a significant increase in the total creatine content of the quadriceps femoris muscle measured in 17 subjects. This was greatest in subjects with a low initial total creatine content and the effect was to raise the content in these subjects closer to the upper limit of the normal range. In some the increase was as much as 50%.
4. Uptake into muscle was greatest during the first 2 days of supplementation accounting for 32% of the dose administered in three subjects receiving 6 x 5g of creatine monohydrate/day. In these subjects renal excretion was 40, 61 and 68% of the creatine dose over the first 3 days. Approximately 20% or more of the creatine taken up was measured as phosphocreatine. No changes were apparent in the muscle ATP content.(ABSTRACT TRUNCATED AT 250 WORDS) Creatine ingestion increases anaerobic capacity and maximum accumulated oxygen deficit.
Jacobs I; Bleue S; Goodman J Defence and Civil Institute of Environmental Medicine, North York, ON.
Can J Appl Physiol (United States) Jun 1997, 22 (3) p231-43
The purpose of this study was to test the hypothesis that ingestion of creatine monohydrate increases anaerobic exercise capacity, as reflected by the maximal accumulated oxygen deficit (MAOD). Subjects were assigned, double-blind, to placebo (PL, n = 12) or creatine (CR, n = 14) groups and ingested 5-g doses 4 times daily of artificial sweetener or artificially sweetened creatine monohydrate, respectively, for 5 days. On a separate day subjects exercised to exhaustion at 125% VO2max. After two familiarization trials, MAOD was again determined before treatment, after 5 days of PL or CR treatment, and 7 days later. MAOD increased after CR treatment from 4.04 +/- 0.31 to 4.41 +/- 0.34 L (p < .001) and remained elevated for another 7 days (4.31 +/- 0.33, p < .001). Time to exhaustion also increased in CR from 130 +/- 7 to 141 +/- 7 s (p < .01) and remained increased for another 7 days (139 +/- 8 s, p < .01). These data demonstrate that ingesting creatine monohydrate for 5 days increases the MAOD, and is likely to have an ergogenic effect on supramaximal exercise performance that persists for at least a week after treatment.
Effects of creatine supplementation on body composition, strength, and sprint performance.
Kreider RB; Ferreira M; Wilson M; Grindstaff P; Plisk S; Reinardy J; Cantler E; Almada AL Department of Human Movement Sciences & Education, The University of Memphis, TN 38152, USA. kreider.richard@coe.memphis.edu
Med Sci Sports Exerc (United States) Jan 1998, 30 (1) p73-82
PURPOSE: To determine the effects of 28 d of creatine supplementation during training on body composition, strength, sprint performance, and hematological profiles.
METHODS: In a double-blind and randomized manner, 25 NCAA division IA football players were matched-paired and assigned to supplement their diet for 28 d during resistance/agility training (8 h x wk[-1]) with a Phosphagen HP (Experimental and Applied Sciences, Golden, CO) placebo (P) containing 99 g x d(-1) of glucose, 3 g x d(-1) of taurine, 1.1 g x d(-1) of disodium phosphate, and 1.2 g x d(-1) of potassium phosphate (P) or Phosphagen HP containing the P with 15.75 g x d(-1) of HPCE pure creatine monohydrate (HP). Before and after supplementation, fasting blood samples were obtained; total body weight, total body water, and body composition were determined; subjects performed a maximal repetition test on the isotonic bench press, squat, and power clean; and subjects performed a cycle ergometer sprint test (12 x 6-s sprints with 30-s rest recovery).
RESULTS: Hematological parameters remained within normal clinical limits for active individuals with no side effects reported. Total body weight significantly increased (P <0.05) in the HP group (P 0.85 +/- 2.2; HP 2.42 +/- 1.4 kg) while no differences were observed in the percentage of total body water. DEXA scanned body mass (P 0.77 +/- 1.8; HP 2.22 +/- 1.5 kg) and fat/bone-free mass (P 1.33 +/- 1.1; HP 2.43 +/- 1.4 kg) were significantly increased in the HP group. Gains in bench press lifting volume (P -5 +/- 134; HP 225 +/- 246 kg), the sum of bench press, squat, and power clean lifting volume (P 1,105 +/- 429; HP 1,558 +/- 645 kg), and total work performed during the first five 6-s sprints was significantly greater in the HP group.
CONCLUSION: The addition of creatine to the glucose/taurine/electrolyte supplement promoted greater gains in fat/bone-free mass, isotonic lifting volume, and sprint performance during intense resistance/agility training.
The effects of creatine supplementation on high-intensity exercise performance in elite performers.
McNaughton LR; Dalton B; Tarr J Kingston University, Kingston upon Thames, Survey, UK.
Eur J Appl Physiol (Germany) Aug 1998, 78 (3) p236-40
The aim of this research was to determine whether creatine supplementation at a dose of 20 g x day(-1), given in 4 x 6-g doses (5 g creatine monohydrate and 1 g glucose) for 5 days, was effective in improving kayak ergometer performances of different durations. Sixteen male subjects with the following characteristics [mean (SEM)]: age 21 (1.2) years, height 170.2 (1.7) cm, weight 75.3 (2.3) kg, sigma8 skinfolds 59.3 (2.6) mm, and maximal oxygen consumption 67.1 +/- (4.3) ml x kg x min(-1), undertook three maximal kayak ergometer tests of 90, 150 and 300 s duration on a wind-braked kayak ergometer (CON). Two groups were then randomly formed, with one group taking the supplement (SUP) while the other took a placebo (PLAC). No pre-test differences existed between the SUP and the PLAC groups in any of the variables measured. After supplementation each group then repeated the same kayak ergometer tests as performed previously and after a 4-week "washout period" the groups took either the PLAC or SUP for another 5 days and then completed the final tests. The SUP group completed significantly more work than either the CON or PLAC groups in all of the tests (90 s, P < 0.01; 150 s, P < 0.001; 300 s, P < 0.05). Body mass remained stable throughout the test period in both the CON and PLAC groups, but both were significantly less than the SUP body mass of 77.3 (1.0) kg (P < 0.01). The results of this work indicate that creatine supplementation can significantly increase the amount of work accomplished during kayak ergometer performance at durations ranging from 90 to 300 s.
Feeding conjugated linoleic acid to animals partially overcomes catabolic responses due to endotoxin injection.
Miller CC, Park Y, Pariza MW, Cook ME. Poultry Science Dept., U.W. Madison 53706.
Biochem Biophys Res Commun 1994 Feb 15;198(3):1107-1112
The ability of conjugated linoleic acid to prevent endotoxin-induced growth suppression was examined. Mice fed a basal diet or diet with 0.5% fish oil lost twice as much body weight after endotoxin injection than mice fed conjugated linoleic acid. By 72 hours post injection, mice fed conjugated linoleic acid had body weights similar to vehicle injected controls; however, body weights of basal and fish oil fed mice injected with endotoxin were reduced. Conjugated linoleic acid prevented anorexia from endotoxin injection. Splenocyte blastogenesis was increased by conjugated linoleic acid.
Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans.
Monteleone P; Beinat L; Tanzillo C; Maj M; Kemali D Institute of Medical Psychology and Psychiatry, First Medical School, University of Naples, Italy.
Neuroendocrinology, 52(3):243-8 1990 Sep
The activity of brain cortex-derived phosphatidylserine (BC-PS) on the neuroendocrine and neurovegetative responses to physical stress was tested in 8 healthy men who underwent three experiments with a bicycle ergometer. According to a double-blind design, before starting the exercise, each subject received intravenously, within 10 min, 50 or 75 mg of BC-PS or a volume-matched placebo diluted in 100 ml of saline. Blood samples were collected before and after the exercise for plasma epinephrine (E), norepinephrine (NE), dopamine (DA), adrenocorticotropin (ACTH), cortisol, growth hormone (GH), prolactin (PRL) and glucose determinations. Blood pressure and heart rate were also recorded. Physical stress induced a clear-cut increase in plasma E, NE, ACTH, cortisol, GH and PRL, whereas no significant change was observed in plasma DA and glucose. Pretreatment with both 50 and 75 mg BC-PS significantly blunted the ACTH and cortisol responses to physical stress.
Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men.
Monteleone P; Maj M; Beinat L; Natale M; Kemali D Institute of Psychiatry, First Medical School, University of Naples, Italy.
Eur J Clin Pharmacol, 42(4):385-8 1992
The effect of chronic administration of phosphatidylserine derived from brain cortex on the neuroendocrine responses to physical stress has been examined in a placebo-controlled study in 9 healthy men. Phosphatidylserine 800 mg/d for 10 days significantly blunted the ACTH and cortisol responses to physical exercise (P = 0.003 and P = 0.03, respectively), without affecting the rise in plasma GH and PRL. Physical exercise significantly increased the plasma lactate concentration both after placebo and phosphatidylserine. The results suggest that chronic oral administration of phosphatidylserine may counteract stress-induced activation of the hypothalamo-pituitary-adrenal axis in man.
Effects of dietary chromium picolinate supplementation on growth, carcass characteristics, and accretion rates of carcass tissues in growing-finishing swine.
Mooney KW; Cromwell GL Department of Animal Sciences, University of Kentucky, Lexington 40546, USA.
J Anim Sci 1995 Nov;73(11):3351-7
An experiment was conducted to evaluate the effects of chromium picolinate (CrP) on growth performance, carcass composition, and tissue accretion rates in pigs from 27 to 109 kg BW. Seven littermate sets of Yorkshire-Hampshire barrows, individually penned, were fed a fortified, corn-soybean meal basal diet (.95% lysine from 27 to 55 kg; .80% lysine from 55 to 109 kg) supplemented with 0 or 200 micrograms/kg of Cr from CrP. Addition of CrP increased (P < .09) ADG but did not affect ADFI or feed:gain ratio. Average and 10th rib backfat and longissimus muscle area were not affected by Cr supplementation. The right side of the carcass was physically dissected into muscle, fat, bone, and skin. Additionally, five pigs were killed for determination of initial body composition. Dietary CrP addition increased (P < .02) the percentage of muscle and decreased (P < .06) the percentage of fat. Total gain of dissected bone and skin were not different between treatments, but CrP increased (P < .06) the total gain of dissected muscle and decreased (P < .02) the total gain of dissected fat. Also, CrP increased the daily accretion rates of muscle (P < .05) and bone (P < .03) and decreased the daily accretion rate of fat (P < .05). The left side of the carcass was ground for determination of water, protein, lipid, and ash. The addition of CrP to the diet increased the percentage (P < .09) and accretion rate (P < .09) of water and increased the percentage (P < .004), total gain (P < .02), and accretion rate (P < .02) of protein while decreasing (P < .04) the percentage of lipid. Pigs fed CrP also had a decreased (P < .004) percentage of lipid in the dissected carcass muscle. Water, protein, and ash from the dissected muscle were not different between treatments. These results suggest that CrP supplementation throughout the entire growing-finishing phase increases the total gain and accretion rate of muscle while decreasing the total gain and accretion rate of fat. This results in carcasses with an increased percentage of muscle and decreased percentage of fat.
The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women.
Morales AJ, Haubrich RH, Hwang JY, Asakura H, Yen SS. Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, USA.
Clin Endocrinol (Oxf) 1998 Oct;49(4):421-32
OBJECTIVE: The biological role of the adrenal sex steroid precursors--DHEA and DHEA sulphate (DS) and their decline with ageing remains undefined. We observed previously that administration of a 50 daily dose of DHEA for 3 months to age-advanced men and women resulted in an elevation (10%) of serum levels of insulin-like growth factor-I (IGF-I) accompanied by improvement of self-reported physical and psychological well-being. These findings led us to assess the effect of a larger dose (100 mg) of DHEA for a longer duration (6 months) on circulating sex steroids, body composition (DEXA) and muscle strength (MedX).
SUBJECTS AND DESIGN: Healthy non-obese age-advanced (50-65 yrs of age) men (n = 9) and women (n = 10) were randomized into a double-blind placebo-controlled cross-over trial. Sixteen subjects completed the one-year study of six months of placebo and six months of 100 mg oral DHEA daily.
MEASUREMENTS: Fasting early morning blood samples were obtained. Serum DHEA, DS, sex steroids, IGF-I, IGFBP-1, IGFBP-3, growth hormone binding protein (GHBP) levels and lipid profiles as well as body composition (by DEXA) and muscle strength (by MedX testing) were measured at baseline and after each treatment.
RESULTS: Basal serum levels of DHEA, DS, androsternedione (A), testosterone (T) and dihydrotestosterone (DHT) were at or below the lower range of young adult levels. In both sexes, a 100 mg daily dose of DHEA restored serum DHEA levels to those of young adults and serum DS to levels at or slightly above the young adult range. Serum cortisol levels were unaltered, consequently the DS/cortisol ratio was increased to pubertal (10:1) levels. In women, but not in men, serum A, T and DHT were increased to levels above gender-specific young adult ranges. Basal SHBG levels were in the normal range for men and elevated in women, of whom 7 of 8 were on oestrogen replacement therapy. While on DHEA, serum SHBG levels declined with a greater (P < 0.02) response in women (-40 +/- 8%; P = 0.002) than in men (-5 +/- 4%; P = 0.02). Relative to baseline, DHEA administration resulted in an elevation of serum IGF-I levels in men (16 +/- 6%, P = 0.04) and in women (31 +/- 12%, P = 0.02). Serum levels of IGFBP-1 and IGFBP-3 were unaltered but GHBP levels declined in women (28 +/- 6%; P = 0.02) not in men. In men, but not in women, fat body mass decreased 1.0 +/- 0.4 kg (6.1 +/- 2.6%, P = 0.02) and knee muscle strength 15.0 +/- 3.3% (P = 0.02) as well as lumbar back strength 13.9 +/- 5.4% (P = 0.01) increased. In women, but not in men, an increase in total body mass of 1.4 +/- 0.4 kg (2.1 +/- 0.7%; P = 0.02) was noted. Neither gender had changes in basal metabolic rate, bone mineral density, urinary pyridinoline cross-links, fasting insulin, glucose, cortisol levels or lipid profiles. No significant adverse effects were observed.
CONCLUSIONS: A daily oral 100 mg dose of DHEA for 6 months resulted in elevation of circulating DHEA and DS concentrations and the DS/cortisol ratio. Biotransformation to potent androgens near and slightly above the range of their younger counterparts occurred in women with no detectable change in men. Given this hormonal milieu, an increase in serum IGF-I levels was observed in both genders but dimorphic responses were evident in fat body mass and muscle strength in favour of men. These differences in response to DHEA administration may reflect a gender specific response to DHEA and/or the presence of confounding factor(s) in women such as oestrogen replacement therapy.
Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men.
Nestler JE; Barlascini CO; Clore JN; Blackard WG Division of Endocrinology and Metabolism, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
J Clin Endocrinol Metab (United States) Jan 1988, 66 (1) p57-61
To assess the effects of dehydroepiandrosterone (DHEA) on body fat mass, serum lipid levels, and tissue sensitivity to insulin, five normal men were given placebo and five normal men were given oral DHEA [1600 mg/day (554.7 mmol/day)] for 28 days in a randomized, double blind study. In the DHEA group serum DHEA-S levels rose 2.5- to 3.5-fold, and mean (+/- SEM) serum androstenedione rose from 4.3 +/- 0.6 to 8.6 +/- 1.2 nmol/L (P less than 0.004, by paired t test), but serum total testosterone, free testosterone, sex hormone-binding globulin, estradiol, and estrone levels did not change. In the DHEA group the mean percent body fat decreased by 31%, with no change in weight. This suggests that the reduction in fat mass was coupled with an increase in muscle mass. DHEA administration also resulted in a fall in mean serum total cholesterol concentration (4.82 +/- 0.21 vs. 4.48 +/- 0.29 nmol/L; P less than 0.05), which was due almost entirely to a fall of 7.5% in mean serum low density lipoprotein cholesterol (3.21 +/- 0.11 vs. 2.97 +/- 0.14 nmol/L; P less than 0.01). No changes in anthropometric parameters or serum lipid levels occurred in the placebo group. Tissue sensitivity to insulin, assessed by the hyperinsulinemic-euglycemic clamp technique, did not change in either the placebo or DHEA groups. These results suggest that in normal men DHEA administration reduces body fat, increases muscle mass, and reduces serum low density lipoprotein cholesterol levels. Tissue sensitivity to insulin was unaffected by short term DHEA administration.
Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training.
Nissen S; Sharp R; Ray M; Rathmacher JA; Rice D; Fuller JC Jr; Connelly AS; Abumrad N Iowa State University, Ames 50011, USA.
J Appl Physiol, 81(5):2095-104 1996 Nov
The effects of dietary supplementation with the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) were studied in two experiments. In study 1, subjects (n = 41) were randomized among three levels of HMB supplementation (0, 1.5 or 3.0 g HMB/day) and two protein levels (normal, 117 g/day, or high, 175 g/day) and weight lifted for 1.5 h 3 days/wk for 3 wk. In study 2, subjects (n = 28) were fed either 0 or 3.0 g HMB/day and weight lifted for 2-3 h 6 days/wk for 7 wk. In study 1, HMB significantly decreased the exercise-induced rise in muscle proteolysis as measured by urine 3-methylhistidine during the first 2 wk of exercise (linear decrease, P < 0.04). Plasma creatine phosphokinase was also decreased with HMB supplementation (week 3, linear decrease, P < 0.05). Weight lifted was increased by HMB supplementation when compared with the unsupplemented subjects during each week of the study (linear increase, P < 0.02). In study 2, fat-free mass was significantly increased in HMB-supplemented subjects compared with the unsupplemented group at 2 and 4-6 wk of the study (P < 0.05). In conclusion, supplementation with either 1.5 or 3 g HMB/day can partly prevent exercise-induced proteolysis and/or muscle damage and result in larger gains in muscle function associated with resistance training.
Nutritional role of the leucine metabolite beta-hydroxy beta- methylbutyrate (HMB)
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
Dietary conjugated linoleic acids increase lean tissue and decrease fat deposition in growing pigs.
Ostrowska E, Muralitharan M, Cross RF, Bauman DE, Dunshea FR. Agriculture Victoria, Victorian Institute of Animal Science, Werribee, VIC 3030, Australia.
J Nutr 1999 Nov;129(11):2037-42
Conjugated linoleic acids (CLA) decrease the body fat content of rodents; the aim of this study was to determine whether dietary CLA altered carcass composition of pigs. Female Large White x Landrace pigs (n = 66) were used in this study. To obtain initial body composition, six pigs were slaughtered at 57 kg live weight, whereas the remaining pigs were allocated to one of six dietary treatments (0, 1.25, 2.5, 5.0, 7.5 and 10.0 g/kg CLA, containing 55% of CLA isomers). The diets, containing 14.3 MJ digestible energy (DE) and 9. 3 g available lysine per kg, were fed ad libitum for 8 wk. Dietary CLA had no significant effect on average daily gain (861 vs. 911 g/d for pigs fed diets with and without CLA, P = 0.15) or feed intake (2. 83 vs. 2.80 kg/d, P = 0.74). The gain to feed ratio was increased by dietary CLA by 6.3% (0.328 vs. 0.348, P = 0.009). Fat deposition decreased linearly (-8.2 +/- 2.09 g/d for each gram per kilogram increase in CLA concentration; P < 0.001) with increasing inclusion of CLA. At the highest level of CLA inclusion, fat deposition was decreased by 88 g/d (-31%). Similarly, the ratio of fat to lean tissue deposition decreased linearly (-0.093 +/- 0.0216 for each gram per kilogram increase in CLA concentration; P < 0.001) with increasing dietary CLA. The carcass lean tissue deposition response to dietary CLA was quadratic in nature and was maximized (+25%) at 5. 0 g/kg dietary CLA. Overall, dietary CLA increased the gain to feed ratio and lean tissue deposition and decreased fat deposition in finisher pigs.
Effect of conjugated linoleic acid on body composition in mice.
Park Y, Albright KJ, Liu W, Storkson JM, Cook ME, Pariza MW. Department of Food Microbiology and Toxicology, University of Wisconsin-Madison 53706, USA.
Lipids 1997 Aug;32(8):853-8
The effects of conjugated linoleic acid (CLA) on body composition were investigated. ICR mice were fed a control diet containing 5.5% corn oil or a CLA-supplemented diet (5.0% corn oil plus 0.5% CLA). Mice fed CLA-supplemented diet exhibited 57% and 60% lower body fat and 5% and 14% increased lean body mass relative to controls (P < 0.05). Total carnitine palmitoyltransferase activity was increased by dietary CLA supplementation in both fat pad and skeletal muscle; the differences were significant for fat pad of fed mice and skeletal muscle of fasted mice. In cultured 3T3-L1 adipocytes CLA treatment (1 x 10(-4)M) significantly reduced heparin-releasable lipoprotein lipase activity (-66%) and the intracellular concentrations of triacylglyceride (-8%) and glycerol (-15%), but significantly increased free glycerol in the culture medium (+22%) compared to control (P < 0.05). The effects of CLA on body composition appear to be due in part to reduced fat deposition and increased lipolysis in adipocytes, possibly coupled with enhanced fatty acid oxidation in both muscle cells and adipocytes.
[Physical exercise in the aged].[Article in French]
Petermans J. Service de Geriatrie, CHR Citadelle.
Rev Med Liege 2001 Apr;56(4):223-227
In the future, physical activities should be more frequent in the elderly population, because of free time and better quality of life. Muscular exercise is very useful; muscular strength and effort ability are preserved in conditioned aged people. It reduces loss of muscle mass, so called sarcopenia; it improves deconditioning and quality of life. In healthy elderly, exercise improves postural status, bone mass and broken risk, cognitive function. However, the impact on falls and immunosenescence is not well known. In ill elderly, quality of life seems better in cardiac and Alzheimer disease, if a control physical activity is performed. Exercise should be adapted and rehabilitation should be done every time it's possible. Social contact and relationships also have good effects, which must be encouraged.
Explaining How Creatine Throws Off Body's Balance 2000.
Powers, M.
Study funded by the National Athletic Trainers Association Research and Education Foundation. Gainesville, FL: University of Florida.
Creatine supplementation enhances intermittent work performance.
Prevost MC; Nelson AG; Morris GS Marine Corps Air Station, EI Toro, USA.
Res Q Exerc Sport (United States) Sep 1997, 68 (3) p233-40
To determine the impact of creatine supplementation on high-intensity, intermittent work, 18 participants each performed 2 sets of 4 different work bouts to exhaustion. For 5 days prior to the first set of work bouts, all participants received a placebo (5 g of calcium chloride daily). For the second set of work bouts, 9 participants again received the placebo, while the other 9 received creatine supplementation (18.75 g creatine monohydrate daily for 5 days prior to and 2.25 g creatine daily during testing). The four work bouts in each set consisted of cycling to exhaustion at 150% peak oxygen uptake (VO2peak) either nonstop (A), intermittently for either 60-s work/120-s rest periods (B), 20-s work/40-s rest (C), or 10-s work/20-s rest (D). Creatine supplementation significantly increased (p < .01) the total work time of all bouts. Protocol D showed the greatest increase (> 100%); C increased 61.9%; B increased 61.0%; and A increased 23.5%. These results demonstrate that creatine supplementation significantly extends one's capacity to maintain a specific level of high-intensity, intermittent exercise.
Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial.
Riserus U, Berglund L, Vessby B. Clinical Nutrition Research Unit, Department of Public Health and Caring Sciences/Geriatrics, Faculty of Medicine, Uppsala University, Uppsala, Sweden. ulf.riserus@geriatrik.uu.se
Int J Obes Relat Metab Disord 2001 Aug;25(8):1129-35
BACKGROUND: Abdominal obesity is strongly related to metabolic disorders. Recent research suggests that dietary conjugated linoleic acid (CLA) reduces body fat and may improve metabolic variables in animals. The metabolic effects of CLA in abdominally obese humans have not yet been tested.
OBJECTIVE: To investigate the short-term effect of CLA on abdominal fat and cardiovascular risk factors in middle-aged men with metabolic disorders.
METHODS: Twenty-five abdominally obese men (waist-to-hip ratio (WHR), 1.05+/-0.05; body mass index (BMI), 32+/-2.7 kg/m(2) (mean+/-s.d.)) who were between 39 and 64-y-old participated in a double-blind randomised controlled trial for 4 weeks. Fourteen men received 4.2 g CLA/day and 10 men received a placebo. The main endpoints were differences between the two groups in sagittal abdominal diameter (SAD), serum cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, free fatty acids, glucose and insulin.
RESULTS: At baseline, there were no significant differences between groups in anthropometric or metabolic variables. After 4 weeks there was a significant decrease in SAD (cm) in the CLA group compared to placebo (P=0.04, 95% CI; -1.12, -0.02). Other measurements of anthropometry or metabolism showed no significant differences between the groups.
CONCLUSIONS: These results indicate that CLA supplementation for 4 weeks in obese men with the metabolic syndrome may decrease abdominal fat, without concomitant effects on overall obesity or other cardiovascular risk factors. Because of the limited sample size, the effects of CLA in abdominal obesity need to be further investigated in larger trials with longer duration.
Glutamine: Effects on the immune system, protein metabolism and intestinal function
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.
Dietary conjugated linoleic acid reduces adiposity in lean but not obese Zucker rats.
Sisk MB, Hausman DB, Martin RJ, Azain MJ. Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602, USA.
J Nutr 2001 Jun;131(6):1668-1674
Recent studies have demonstrated a reduction in body fat in growing animals fed conjugated linoleic acid (CLA). Two experiments were conducted to extend these observations to obese rats so that the mechanism of the actions of CLA might be more easily elucidated. In experiment 1, male lean and obese Zucker rats were fed diets containing either 0 or 0.5% CLA for 5 wk. There was no effect of diet on growth rate or food intake. Dietary CLA reduced retroperitoneal and inguinal fat pad weights in the lean rats but increased fat pad weights in the obese genotype (diet x genotype interaction; P < 0.05). Determination of fat pad cellularity indicated that these changes in fat pad weight were due to a reduction or increase in average fat cell size for the lean and obese Zucker rats, respectively. In experiment 2, we sought to reproduce these effects on fat pad size, as well as to determine the effect of dietary CLA on the catabolic response to bacterial endotoxin injection in obese Zucker rats. Growing female lean and obese Zucker rats were fed diets containing 0 or 0.5% CLA for 8 wk. On d 28, each rat was injected intraperitoneally with lipopolysaccharide from Escherichia coli serotype 055:B5 (1 mg/kg body weight) and body weight was determined over the next 96 h. There was a diet x genotype interaction (P < 0.05) for the body weight response to lipopolysaccharide 24 h postinjection. Lean rats fed CLA lost less weight than did lean controls, but obese rats fed CLA lost more weight than did obese controls. As in the first experiment, there was a diet x genotype (P < 0.05) for the effect of treatment on retroperitoneal fat pad weights determined at the end of the experiment. Lean rats fed CLA had smaller RP fat pads than did lean controls, but obese rats fed CLA once again had heavier RP fat pads than did obese controls. These results indicate that CLA reduces body fat and catabolic response to endotoxin injection in lean Zucker rats but not in the obese genotype. The observed interaction between diet and genotype warrants additional investigation into the specific mechanism(s) of the biological activities of CLA.
A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies.
Tarnopolsky MA; Roy BD; MacDonald JR Department of Neurology, McMaster University Medical Center, Hamilton, Ontario, Canada.
Muscle Nerve (United States) Dec 1997, 20 (12) p1502-9
Fatigue in patients with mitochondrial cytopathies is associated with decreased basal and postactivity muscle phosphocreatine (PCr). Creatine monohydrate supplementation has been shown to increase muscle PCr and high-intensity power output in healthy subjects. We studied the effects of creatine monohydrate administration (5 g PO b.i.d. x 14 days --> 2 g PO b.i.d. x 7 days) in 7 mitochondrial cytopathy patients using a randomized, crossover design. Measurements included: activities of daily living (visual analog scale); ischemic isometric handgrip strength (1 min); basal and postischemic exercise lactate; evoked and voluntary contraction strength of the dorsiflexors; nonischemic, isometric, dorsiflexion torque (NIDFT, 2 min); and aerobic cycle ergometry with pre- and post-lactate measurements. Creatine treatment resulted in significantly (P < 0.05) increased handgrip strength, NIDFT, and postexercise lactate, with no changes in the other measured variables. We concluded that creatine monohydrate increased the strength of high-intensity anaerobic and aerobic type activities in patients with mitochondrial cytopathies but had no apparent effects upon lower intensity aerobic activities.
Role of glutamine and its analogs in posttraumatic muscle protein and amino acid metabolism.
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.
Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study.
Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, Nevitt M, Harris TB. Institute for Research in Extramural Medicine, VU University Medical Center, Amsterdam, The Netherlands. m.visser.emgo@med.vu.nl
J Gerontol A Biol Sci Med Sci 2002 May;57(5):M326-32
BACKGROUND: A decline in muscle mass and muscle strength characterizes normal aging. As clinical and animal studies show a relationship between higher cytokine levels and low muscle mass, the aim of this study was to investigate whether markers of inflammation are associated with muscle mass and strength in well-functioning elderly persons.
METHODS: We used baseline data (1997-1998) of the Health, Aging, and Body Composition (Health ABC) Study on 3075 black and white men and women aged 70-79 years. Midthigh muscle cross-sectional area (computed tomography), appendicular muscle mass (dual-energy x-ray absorptiometry), isokinetic knee extensor strength (KinCom), and isometric grip strength were measured. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by enzyme-linked immunosorbent assay (ELISA).
RESULTS: Higher cytokine levels were generally associated with lower muscle mass and lower muscle strength. The most consistent relationship across the gender and race groups was observed for IL-6 and grip strength: per SD increase in IL-6, grip strength was 1.1 to 2.4 kg lower (p <.05) after adjustment for age, clinic site, health status, medications, physical activity, smoking, height, and body fat. An overall measure of elevated cytokine level was created by combining the levels of IL-6 and TNF-alpha. With the exception of white men, elderly persons having high levels of IL-6 (>1.80 pg/ml) as well as high levels of TNF-alpha (>3.20 pg/ml) had a smaller muscle area, less appendicular muscle mass, a lower knee extensor strength, and a lower grip strength compared to those with low levels of both cytokines.
CONCLUSIONS: Higher plasma concentrations of IL-6 and TNF-alpha are associated with lower muscle mass and lower muscle strength in well-functioning older men and women. Higher cytokine levels, as often observed in healthy older persons, may contribute to the loss of muscle mass and strength that accompanies aging.
Creatine supplementation enhances muscular performance during high-intensity resistance exercise.
Volek JS; Kraemer WJ; Bush JA; Boetes M; Incledon T; Clark KL; Lynch JM Center for Sports Medicine, Pennsylvania State University, University Park 16802, USA.
J Am Diet Assoc (United States) Jul 1997, 97 (7) p765-70
OBJECTIVE: This study was undertaken to investigate the influence of oral supplementation with creatine monohydrate on muscular performance during repeated sets of high-intensity resistance exercise.
SUBJECTS/DESIGN: Fourteen active men were randomly assigned in a double-blind fashion to either a creatine group (n = 7) or a placebo group (n = 7). Both groups performed a bench press exercise protocol (5 sets to failure using each subject's predetermined 10-repetition maximum) and a jump squat exercise protocol (5 sets of 10 repetitions using 30% of each subject's 1-repetition maximum squat) on three different occasions (T1, T2, and T3) separated by 6 days.
INTERVENTION: Before T1, both groups received no supplementation. From T1 to T2, both groups ingested placebo capsules. From T2 to T3, the creatine group ingested 25 g creatine monohydrate per day, and the placebo group ingested an equivalent amount of placebo.
MAIN OUTCOME MEASURES: Total repetitions for each set of bench presses and peak power output for each set of jump squats were determined. Other measures included assessment of diet, body mass, skinfold thickness, and preexercise and 5-minute postexercise lactate concentrations.
RESULTS: Lifting performance was not altered for either exercise protocol after ingestion of the placebos. Creatine supplementation resulted in a significant improvement in peak power output during all 5 sets of jump squats and a significant improvement in repetitions during all 5 sets of bench presses. After creatine supplementation, postexercise lactate concentrations were significantly higher after the bench press but not the jump squat. A significant increase in body mass of 1.4 kg (range = 0.0 to 2.7 kg) was observed after creatine ingestion.
CONCLUSION: One week of creatine supplementation (25 g/day) enhances muscular performance during repeated sets of bench press and jump squat exercise.
Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse.
West DB, Delany JP, Camet PM, Blohm F, Truett AA, Scimeca J. Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808, USA.
Am J Physiol 1998 Sep;275(3 Pt 2):R667-72
Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in the fat of beef and other ruminants. CLA is reported to have effects on both tumor development and body fat in animal models. To further characterize the metabolic effects of CLA, male AKR/J mice were fed a high-fat (45 kcal%) or low-fat (15 kcal%) diet with or without CLA (2.46 mg/kcal; 1.2 and 1.0% by weight in high- and low-fat diets, respectively) for 6 wk. CLA significantly reduced energy intake, growth rate, adipose depot weight, and carcass lipid and protein content independent of diet composition. Overall, the reduction of adipose depot weight ranged from 43 to 88%, with the retroperitoneal depot most sensitive to CLA. CLA significantly increased metabolic rate and decreased the nighttime respiratory quotient. These findings demonstrate that CLA reduces body fat by several mechanisms, including a reduced energy intake, increased metabolic rate, and a shift in the nocturnal fuel mix.
Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by alpha-lipoic acid in 3T3-L1 adipocytes.
Yaworsky K, Somwar R, Ramlal T, Tritschler HJ, Klip A. Hospital for Sick Children, Toronto, Ontario, Canada.
Diabetologia 2000 Mar;43(3):294-303
AIMS/HYPOTHESIS: A natural cofactor of mitochondrial dehydrogenase complexes and a potent antioxidant, alpha-lipoic acid improves glucose metabolism in people with Type II (non-insulin-dependent) diabetes mellitus and in animal models of diabetes. In this study we investigated the cellular mechanism of action of alpha-lipoic acid in 3T3-L1 adipocytes.
METHODS: We treated 3T3-L1 adipocytes with 2.5 mmol/l R (+) alpha-lipoic acid for 2 to 60 min, followed by assays of: 2-deoxyglucose uptake; glucose transporter 1 and 4 (GLUT1 and GLUT4) subcellular localization; tyrosine phosphorylation of the insulin receptor or of the insulin receptor substrate-1 in cell lysates; association of phosphatidylinositol 3-kinase activity with immunoprecipitates of proteins containing phosphotyrosine or of insulin receptor substrate-1 using a in vitro kinase assay; association of the p85 subunit of phosphatidylinositol 3-kinase with phosphotyrosine proteins or with insulin receptor substrate-1; and in vitro activity of immunoprecipitated Akt1. The effect of R (+) alpha-lipoic acid was also compared with that of S(-) alpha-lipoic acid.
RESULTS: Short-term treatment of 3T3-L1 adipocytes with R (+) alpha-lipoic acid rapidly stimulated glucose uptake in a wortmannin-sensitive manner, induced a redistribution of GLUT1 and GLUT4 to the plasma membrane, caused tyrosine phosphorylation of insulin receptor substrate-1 and of the insulin receptor, increased the antiphosphotyrosine-associated and insulin receptor substrate-1 associated phosphatidylinositol 3-kinase activity and stimulated Akt activity.
CONCLUSION/INTERPRETATION: These results indicate that R (+) alpha-lipoic acid directly activates lipid, tyrosine and serine/threonine kinases in target cells, which could lead to the stimulation of glucose uptake induced by this natural cofactor. These properties are unique among all agents currently used to lower glycaemia in animals and humans with diabetes.
Replacement of DHEA in aging men and women. Potential remedial effects
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.
Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPAR gamma-dependent mechanism.
Yu Y, Correll PH, Vanden Heuvel JP. Department of Veterinary Science and Center for Molecular Toxicology and Carcinogenesis, 226 Fenske Laboratories, Penn State University, University Park, PA 16802, USA.
Biochim Biophys Acta 2002 Apr 15;1581(3):89-99
Conjugated linoleic acid (CLA) is a dietary fatty acid that has received considerable attention due to its unique properties in rodent models including anti-cancer, anti-atherogenic and anti-diabetic effects. The effects of CLA are similar to those seen with ligands for peroxisome proliferator-activated receptor (PPARs), most notably of the PPAR gamma subtype. With the recent observation of a role for PPAR gamma in regulation of immune responses, we suspected that CLA could affect immune function, in particular macrophage activity. The goal of our study was to examine whether this dietary fatty acid has anti-inflammatory properties similar to those reported for PPAR gamma activators such as 15-deoxy prostaglandin J(2) (PGJ(2)). In reporter assays, various CLA isomers activated PPAR gamma in RAW264.7 mouse macrophage (RAW) cells. CLA decreased the interferon-gamma (IFN gamma)-induced mRNA expression of mediators of inflammation including cyclooxygenase 2 (COX2), inducible NOS (iNOS), and tumor necrosis factor alpha (TNFalpha). Reporter assays also demonstrated reduced IFN gamma-stimulated transcriptional activity of the iNOS and COX2 promoters by CLA. Consequently, CLA decreased the production of PGE(2), TNFalpha and the inflammatory agent nitric oxide (NO) in RAW cells treated with IFN gamma. Other pro-inflammatory cytokines such as IL-1 beta and IL-6 were similarly decreased by CLA treatment of RAW cells. In addition, various CLA isomers induced HL60 cell differentiation along the monocytic lineage as assessed by measuring expression of the cell surface marker CD14. This differentiation process, as well as the regulation of iNOS and COX2 by 15dPGJ(2), is believed to involve PPAR gamma. Mutations of Leu(468) and Glu(471) to alanine in helix 12 of the ligand-binding domain of PPAR gamma resulted in a protein with strong dominant-negative activity (dnPPAR gamma). Transfecting dnPPAR gamma into RAW cells eliminated the ability of various CLA isomers to regulate the iNOS reporter construct. Taken together, these results suggest that CLA has anti-inflammatory properties that are mediated, at least in part, by the nuclear hormone receptor PPAR gamma. |