MUSCLE EFFLUX OF GLUTAMINE
IN ORAL CREATINE OVERSUPPLIED SPORTSMEN
CAN MIMIC STRESS CONDITIONS
WITH INCREASED RISKS OF ATHLETIC TRAUMAS

By Renato COCCHI MD, neurologist and medical psychologist.

 

Key words: sport, glutamine, creatine, stress, glutamate, acethylcholine, athletic traumas.

(Italian translation)

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During the 2nd World Congress on Stress (Melbourne, 1998) Dr G. Tassani and I asserted that stress, even the first phase of overtraining syndrome, induces an increased supply of peripheral Acetylcholine (ACh) for increased availability of its precursor, the choline. This happens because brain reduced turnover of ACh reduces the blood-barrier transport into the brain of choline, but also by an increased efflux of choline from the brain. As for the vagal district, an increasing of ACh during stress had experimental evidence (Hata et al. 1986; Kita et al., 1986).

The vagal stimulation grows because the direct link between hypothalamic glutamate hyperfunction, and stimulation of some vagal brain nuclei like Nucleus Dorsalis Vagi and Nucleus Tracti Solitarii. (Kunos et al., 1995; Pluzhnichenko, 1997; Yoneda and Tache', 1995). As for heart, if the sympathetic system is unable to compensate the increased vagal stimulation, one person could have vagal syncope or an irreversible fatal collapse.

Since many physicians have a poor understanding of the dynamic of that mechanism, often we erroneously heard about heart infarcts in such cases. Luckily these are rare events as spontaneous ones. Out of the body districts under the vagal control we maintain that it happens the same increasing of the peripheral ACh (ours are only clinical data, now).

That drives to postures unbalance and to a power magnification of the athletic gesture. This is the result of a magnified but wrong setting of postures, when they usually set according to their brain kinetic memory mirroring normal conditions.

So postures can play at their excursion's limits, with reduced margins for recovery. In that state a provoked athletic trauma could be heavier, because the postures do not easily allow the balance to reset, being at work with poor compensating margins. In the same time the voluntary athletic gesture becomes magnified and powerful because of muscular fibres increased stimulation due to a larger amount of ACh into the end-plate.

The loose of synchronism between postures working at their limits and magnified athletic gesture can end to a spontaneous athletic trauma. In other terms, in a stress situation like that, one can reach an increased easiness to spontaneous athletic traumas and more severity in provoked athletic traumas.

 

Which role could play a creatine excess diet in this mechanism?

Creatine's function is to favour the resynthesis of phospho-creatine, and so the muscular ATP production. The increasing of the body muscular mass could be due to the extra work the larger amount of ATP lets doing, since physical fatigue appears later. Red muscles are the greater producers of glutamine and it comes out by means of ATP (Meister, 1956 and 1969; Graham and MacLean, 1998; Yoo, Field and McBurney, 1997).

There is a key point. There is an efflux of l-glutamine from muscles during extended muscular exercise (Graham and McLean, 1998). This fact deals to suggest that the induced fatigue, due to ATP decreasing, be a defense mechanism to avoid muscular fibres' damages like sprains, when muscular work extends. Athletes with overtraining stress have low levels of glutamine for months or years (Rowbottom, Keast and Morton, 1996).

Glutamine is the main precursor of the brain glutamate (Baxter, 1975; Ward, Thanki and Bradford, 1983; Laake et al., 1995; Shuplakow et al., 1977). In all stress conditions at all origin they have, there is growing of the brain glutamate, the more spread excitatory neurotransmitter that produces cascade negative reactions when in excess. (See: Friedman MJ, Charney DS and Deutch AY. Neurobiologcal and clinical consequences of stress, Philadelphia, Lippicott-Raven 1995).

Sometimes athletes tried to increase their own athletic performances with high doses' creatine diet (up to 20-30 g daily = 5.0-7.5 kg of red meat). If so they set off also an up efflux of muscular glutamine into blood, according to the increased muscular synthesis of glutamine.

Blood glutamine easily crosses the blood-brain barrier and so makes the brain glutamate increasing. In absence of stress this fact could be not neurochemically relevant although some symptoms of the increased brain glutamate could arise, like in stress.

When in a stressed condition, the oversupply of creatine diet in athletes could increase the harmful followings of the stress itself. By analogy it is about the same of giving sugar to a diabetic person. I use creatine in the form of creatine-phosphate as an anti-fatigue drug since more than 20 years and glutamine since at least 22 years (Cocchi, 1976).

Daily doses do not reach more than 2g for creatine-phosphate and 500mg for glutamine. In athletes excess creatine diet without considering stress conditions or even to fight stress conditions at muscular level is surely a hazardous practice. 

References. Baxter FC. Some recent advances in studies of GABA metabolism and compartmentation. In: Roberts E, Chase TN, Tower DB (eds). GABA in nervous system function. New York, Raven 1976: 61-87.

Cocchi R. Antidepressive properties of l-glutamine. Preliminary report. Acta psychiat belg 1976, 76: 658-666.

Cocchi R, Tassani G. Spontaneous athletic trauma as the result of overtraining stress. Paper presented during the 2nd World Congress on Stress, Melbourne 25-29 Oct. 1998.

Graham TE, MacLean DA: Ammonia and aminoacid metabolism in skeletal muscle: human, rodent and canine models. Med Sci. Sport Exerc 1998, 30: 34-46.

Hata T, Kita T, Higashiguchi T, Ichida S. Total Ach content, and activities of choline acetyltransferase and acetylcholinesterase in brain and duodenum of SART-stressed (repeated cold-stressed) rat. Japan. J Pharmacol 1986, 41: 475-485.

Horger BA, Roth RH. Stress and central amino acid system. In: Friedman MJ, Charney DS, Deutch AJ. (eds). Neurobiological and clinical consequences of stress: From normal adaptation to PTSD. Philadelphia, Lippincott-Raven 1995: 61-81.

Kita T, Hata T, Higashiguchi T, Itoh E., Kavabata A. Changes of total acetylcholine and the activity of related enzymes in SART-(repeated cold)-stressed rat brain and duodenum. Japan. J Pharmacol 1986, 40: 174-177.

Kunos G, Varga K. The tachycardia associated with the defense reaction involves activation of both GABA A and GABA B receptors in the nucleus tracti solitarii. Clin Exper Hhypertens 1995, 17: 91-100.

Laake J.H. et al.: Glutamine from glial cells is essential for the maintenance of the nerve terminal pool of glutamate: Immunogold evidence from hippocampal slice cultures. J. Neurochem. 1995, 65: 871-881.

Meister A. Metabolism of l-glutamine. Physiol Rev 1956, 36: 103-126.

Meister A. On the synthesis and utilisation of l-glutamine. Harvey Lect. 1969, 63: 139-168.

Pluzhnichenko EB. Spatial organization of hypothalamic neurons projecting to the "gastric region" of the vagosolitary complex. Neurosci Behav Physiol 1997, 27: 688-691.

Rowbottom DG, Keast D, Morton AR. The emerging role of glutamine as an indicator of exercise stress and overtraining. Sports Med 1996, 21: 80-97.

Shuplakow O. et al.: Glial and neuronal glutamine pools at glutamergic synapses with distinct properties. Neuroscience 1977, 77: 1201-1212.

Ward HK, Thanki CM, Bradford HF. Glutamine and glucose as precursors of transmitter amino acids: Ex vivo studies. J Neurochem 1983, 40: 855-860.

Yoneda M, Tache' Y. SMS 201-995-induced stimulation of gastric acid via the dorsal vagal complex and inhibition via the hypothalamus in anaesthetized rats. Br J Pharmacol 1995, 116: 2303-2309.

Yoo S.S., Field C.J., McBurney M.I.: Glutamine supplementation maintains intramuscular glutamine concentrations and normalizes lymphocyte function in infected early weaned pigs. J. Nutr. 1997, 127: 2253-2259.

 

Presented at the 6th International Congress on Amino Acid, Bonn August 3-7, 1999 

 

Author's address: dr Renato COCCHI, via Rabbeno, 3
42100 Reggio Emilia (Italy)

renatococchi@libero.it

 

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