EDITORIAL COMMENTS 553

Lack of a correlation in hospitalized patients with AIDS. Nutrition 1996; 12:511.

17. Kimmel PL, Umana WO, Bosch JP. Abnormal urinary protein excretion in HIV-infected patients. Clin Nephrol 1993; 39: 17

18. Ingulli E, Tejani A, Fikrig S, et al. Nephrotic syndrome associated with acquired immunodeficiency syndrome in children. J Pediatr 1991; 119:710

19. Beisel WR. Trace elements in infectious processes. Med Clin N Am 1976;60:831

20. Powanda MC, Cockerell GL, Pekarek RS. Amino acid and zinc movement in relation to protein synthesis early in inflammation. Am J Physiol 1973;225:399

21. Odeh M. The role of tumor necrosis factor-a in acquired immuno- deficiency syndrome. J Intern Med 1990; 228:549

22. Abrams A, Duncan D, Hertz-Picciotto I. A prospective study of dietary intake and acquired immune deficiency syndrome in HIV- seropositive homosexual men. J Acquir Immune Defic Syndr 1993;6:949

23. Caselli M, Bicocchi R. Serum zinc levels in patients with acquired immunodeficiency syndrome. La Presse Med 1986; 15: 1877

24. Odeh M. The effects of HIV on hematopoiesis. Eur J Hematol 1992;49:277

25. Flieger D, Riethmuller G, Ziegler-Heitbrock HWL. Zn+’ inhibits both tumor necrosis factor-mediated DNA fragmentation and cytol- ysis. Int J Cancer 1989;44:315

26. Obeid LM, Linardic CM, Karolak LA, et al. Programmed cell death induced by ceramide. Science 1993; 259: 1769

27. L’age-Stehr J. AIDS research. Immunol Today 1989; lo:541 28. Dowd PS, Kelleher J, Guillou PJ. T-lymphocyte subsets and in-

terleukin-2 production in zinc deficient rats. Br J Nutr 1986;55:59 29. Winchurch RA, Togo J, Adler WH. Supplemental zinc (Zn”)

restores antibody formation in cultures of aged spleen cells. II. Effects on mediator production. Eur J Immunol 1987; 17: 127

30. Pawelic GP, Rehbein A, Schaudt K, et al. IL-4 responsive human helper T-cell clones are resistant to growth inhibition by tumor necrosis factor. J Immunol 1989; 143:902

31. Hart PH, Vitti GF. Burgess DR, et al. Potential anti-inflammatory effects of interleukin 4: Suppression of human monocyte tumor necrosis factor (Y, interleukin 1, and prostaglandin EZ. Proc Nat1 Acad Sci USA 1989;86:3803

32. Zhang Z-Y, Reardon IM, Hui JO, et al. Zinc inhibition of renin and the protease from human immunodeficiency virus type 1. Bio- chemistry 1991;30:8717

33. Mitsuya H, Yarchoan R, Broden S. Molecular targets for AIDS therapy. Science 1990;249:1533

34. Tang AM, Graham NM, Kirby AJ, et al. Dietary micronutrient intake and risk of progression to acquired immunodeficiency syn- drome (AIDS) in human immunodeficiency virus type 1 (HIV-l )- induced homosexual men. Am J Epidemiol 1993; 138:937

35. Broun ER, Greist A, Tricot G, et al. Excessive zinc ingestion: A reversible cause of sideroblastic anemia and bone marrow depres- sion. JAMA 1990;264:1441

36. Chandra RK. Excessive intake of zinc impairs immune responses. JAMA 1984; 252: 1443

Fatigue During Prolonged Exercise

The cause ( s ) of fatigue during prolonged submaximum exercise has been a research interest of exercise scientists for over half a century. Christensen and Hansen ’ were among the first to report that increasing the carbohydrate content of the diet improved endurance capacity during prolonged cycling. In the early l!XOs, the rein& duction of a percutaneous needle biopsy technique provided the means by which we could study metabolic events in muscle during exercise in general and the influence of diet on exercise capacity in particular. 23 Subsequent studies confirmed a strong association between the depletion of muscle glycogen stores and the onset of fatigue. More recent studies have also confirmed that during pm- longed running glycogen depletion occurs in both type I and type II muscle? During very heavy exercise that lasts several minutes rather than hours, fatigue is associated not with glycogen depletion but with the accumulation of glycolytic metabolites, of which hydro- gen ions are the most prominent?

Ingesting a carbohydrate solution during prolonged submaximal exercise delays the onset of fatigue6 and improves endurance perfor- mance.’ The mechanism(s) responsible for the improvement in endurance capacity is linked to glycogen sparing during exercise’ as a consequence of the metabolism of the exogenous supply of carbohydrate. Although most attention has been given to metabolic events in skeletal muscle, there is an increasing amount of interest in changes in brain biochemistry and their link with fatigue.

The central fatigue hypothesis suggests a link between plasma tryptophan, a precumor of the neuro-transmitter 5hydmxytrypta-

mine (serotonin), and a disinclination for spontaneous activity.’ Tryptophan binds to the same sites on plasma albumin as fatty acids, and so when the concentration of plasma fatty acids are low, then the amount of free hyptophan is low. However, during prolonged exercise there is an increase in the concentration of plasma fatty acids, and so tryptophan is displaced and the amount of free tryptophan available for transport across the blood-brain banier increases, leading to a rise in the concentration of semtonin.

Some studies suggest that the delay in the onset of fatigue, when a glucose solution is ingested during exercise, may be a consequence of glucose-induced decreased plasma fatty acids and, therefore, in free tryptophan concentration.‘o The carrier mechanism responsible for the translocation of tryptophan is competitively shared with large neutral amino acids, which includes the branched chain amino acids (BCAA). Increasing the plasma BCAA concentration has been proposed as a method of reducing tryptophan transport into the brain, thus reducing the potential large increase in serotonin concentration.

In this issue of Nutition, ” this potential nutritional method of delaying the onset of fatigue is described in a study on the influence of ingesting a solution of branched-chain amino acids on plasma and muscle concentrations of amino acids during prolonged submaximal exercise. The authors report, however, that there was no difference in the maximum amount of work their subjects could perform during a 20-min period of all out exercise immediately after an hour of submaximal cycling. In the same study, but reported else-

554 EDITORIAL COMMENTS

where, the authors found that the perceived rate of exertion was lower for the subjects during the BCAA trial compared with the placebo trial. In this study, ingesting BCAA resulted in a reduction in the amount of muscle glycogen used during exercise. This sug- gests that the oxidation of the BCAA may have spated the limited glycogen stores. Had the experimental design been such that the subjects were required to exercise to exhaustion, at a constant sub- maximal intensity that presents a clear challenge to their glycogen stores, then an improvement in endurance performance may have been achieved as a result of the more economical use of the limited carbohydrate stores. Adopting this experimental design, van Hall and colleagues ‘* found no improvement in performance when their subjects ingested either a low or a high dose of BCAA. Neither did they find that the ingestion of ttyptophan decreased exercise capacity. Therefore, the hypothesis that increases in the plasma tryptophan concentrations make a significant contribution to fatigue has yet to be substantiated.

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8.

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CLYDE WILLIAMS, BSC, MSC, PHD Department of Physical Exercise,

Sports Science, and Recreation Management Loughborough University

Loughborough, UK

REFERENCES

10.

11.

12. 1. Christensen EH, Hansen 0. Arbeitsfahigkeit und Ehmahrung.

Stand Arch Physiol 1939;81:160

Hultman E. Studies on muscle metabolism of glycogen and active phosphate in man with special reference to exercise and diet. Stand J Clin Invest 1967;19(suppl 94):l Gollmck PD, Ianuzzo CD, Williams C, et al. Effect of prolonged, severe exercise on the ultrastructure of human skeletal muscle. Intern. Z Agew Physiol 1969;27:257 Tsintzas KO, et al. Carbohydrate ingestion and single muscle fibre glycogen metabolism during prolonged running in man. J Appl Physiol (in press) Gaitanos GC, et al. Human muscle metabolism during intermittent maximal exercise. J Appl Physiol 1993;75:712 Coggan A, Coyle E. Carbohydrate ingestion during prolonged exer- cise: effects on metabolism and performance. Exer Sports Sci Rev 1991;l Tsintzas K, et al. The effect of carbohydrate ingestion during exer- cise on a 30 km race. Int J Sport Nutr 1993;3:127 Tsintzas 0, et al. Carbohydrate ingestion and glycogen utilization in different muscle fibre types in man. J Physiol 1995;489:243 Newsholme E, Acworth I, Blomstrand E. Amino acids, brain neuro- transmitters and functional links between muscle and brain that is important in sustained exercise. In: Benzi G, ed. Advances in myochemisiry. London: John Libby, 1987:127 Davis JM, et al. Effects of carbohydrate feedings on plasma free tryptophan and branched-chain amino acids during prolonged cy- cling. Eur J Appl Physiol 1992;65:513 Blomstrand E. Influence of ingesting a solution of branched-chain amino acids on plasma and muscle concentrations of amino acids during prolonged submaximal exercise. Nutrition 1996; 12:485 van Hall .I, et al. Ingestion of branched-chain amino acids and tryptophan during sustained exercise in man: failure to affect per- formance. J Physiol 1995;486:789

More Attention on Oral Nutritional Supplementation

For many years, oral nutritional supplementation has at- tracted little attention in clinical medicine compared with the scientific and practical interest attached to intravenous and en- teral nutrition. It is therefore of practical clinical interest that McWhirter and Pennington’ in this issue of Nutrition demon- strate that the effect of simple nutritional intervention based on a single liquid supplement did not differ from the favorable result obtained by overnight tube feeding. This result, obtained in a broad spectrum of undernourished patients, is in agreement with former controlled studies in more narrowly defined patient populations. Substantial improvements in energy and protein consumption have been seen in elderly patients with hip frac- tures, *J in malnourished patients with severe chronic obstruc- tive pulmonary disease,4-6 tients,7-9

in long-term studies in cancer pa- and after various gastrointestinal operations.” In

many of these studies, and in the study by McWhirter and Pennington, it was demonstrated that sip feeding between main meals did not alter the overall solid food in-take2-4*‘0 and an improvement in main meal intake was reported when supple- ments were given to patients after gastrointestinal surgery.”

Although much is known about the importance of providing sufficient oral nutrition during and after disease and trauma, little is known about the clinical importance of supplying pa- tients with liquid supplements. Randomized controlled studies have demonstrated a more favorable outcome in thin elderly patients with hip fractures,3 there were fewer complications and better hand grip strength in those patients who underwent gastrointestinal surgery, I1 there was a tendency toward a lower mortality in patients with alcoholic liver disease, I2 and a better pulmonary function after 6 weeks of nutritional supplementa- tion in patients with chronic obstructive pulmonary disease.4V5 Some of these studies should be repeated,3V”z’2 and more work should be done before we know for certain that prevention or treatment of mild or moderate undernutrition in the hospital will be of clinical importance for the patients during the hospital stay or during the convalescense at home.

In all the above-mentioned studies, only one type of supple- ment was offered to the patients. A higher nutritional intake may be expected from a selection of supplements, and every