Research articlel-Ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism
Introduction
Fatigue is a common symptom both in sickness and in health [1], [2], [3]. Chronic or accumulated fatigue can affect an individual's performance. In addition, long-term accumulated fatigue can lead to karoshi (death as a result of overwork). Recently, there has been a great increase in the use of over-the-counter supplements and naturally occurring nutraceuticals for the attenuation of fatigue. However, there are no established treatment recommendation for fatigue. One reason for this has been the lack of standardized fatigue-inducing tasks or appropriate methods for objective quantification of fatigue.
Fatigue is best defined as difficulty in initiating or sustaining voluntary activities [4]. It can be subdivided into physical and mental fatigue. Recently, we succeeded in establishing physical fatigue-inducing tests and in developing some methods for evaluating physical fatigue [5], [6]. By using those, we sought to evaluate the effects of a candidate antifatigue substance on physical fatigue.
Muscular exercise causes rapid adenosine triphosphate consumption, and energy deficiency is an important factor in fatigue [7]. Thus, exogenous dietary substances that can lead to adenosine triphosphate production are considered to be candidate antiphysical fatigue materials.
In addition, physical exercise inducing fatigue elevates blood ammonia level [8], and cerebral ammonia uptake and accumulation during exercise provoke the subjective feeling of fatigue [9].
l-Ornithine is a free amino acid that is not coded for by DNA or involved in protein synthesis. l-Ornithine promotes growth hormone release by stimulating the pituitary gland [10]. Growth hormone promotes the metabolism of carbohydrates, proteins, and lipids [11]. In addition, l-ornithine is one of the products of the action of the enzyme arginase on l-arginine, creating urea. Therefore, l-ornithine is a central part of the urea cycle, which allows for the disposal of excess nitrogen [12]. Therefore, l-ornithine is considered to inhibit the increase in blood ammonia level caused by physical load. l-Ornithine is expected to improve the efficiency of energy production to promote the ammonia detoxification. For these reasons, we investigated the effects of l-ornithine administration on physical fatigue in healthy volunteers.
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Subjects
Seventeen healthy volunteers (40.9 ± 11.8 years of age; 9 women and 8 men; height, 163.6 ± 8.1 cm; body weight, 58.2 ± 9.8 kg; body mass index, 21.7 ± 3.1 kg/m2 [mean ± SD]) were enrolled in this double-blind, randomized, placebo-controlled, 2-way crossover trial. The participants were recruited using an advertisement. Subjects taking chronic medication, supplemental vitamins, or amino acids; subjects with a body weight less than 40 kg; and subjects who had a blood hemoglobin level less than
Physiological examination
Physiological parameters after l-ornithine administration are summarized in Table 1. Systolic blood pressure and diastolic blood pressure did not differ among the 2 groups at any examination points. Heart rate in the l-ornithine group was higher than in the placebo group.
Visual analog scale
The VAS score for ‘fatigue feeling’ in the l-ornithine group was not changed compared with that in the placebo group at any examination points. In females, however, the increase in fatigue feeling from preload to postrecovery
Discussion
Acute fatigue is a physiological phenomenon that disappears after a certain period of rest. In contrast, however, long-term fatigue sometimes causes irreversible damage, and the compensation mechanisms that function in recovery from acute fatigue are no longer effective. Therefore, the development of clinically proven antifatigue agents is very important.
To assess the effect of substances on physical fatigue, it is important to evaluate energy metabolism under the physical load, the subjects'
Acknowledgment
This work was supported in research funding by Kyowa Hakko Kogyo Co, Ltd. We thank Kathy Meister for editorial help with the manuscript.
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