Elsevier

Nutrition Research

Volume 28, Issue 11, November 2008, Pages 738-743
Nutrition Research

Research article
l-Ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism

https://doi.org/10.1016/j.nutres.2008.08.008Get rights and content

Abstract

We examined the effects of l-ornithine administration on physical fatigue. In a double-blind, placebo-controlled, 2-way crossover study, 17 healthy volunteers were randomized to l-ornithine (2000 mg/d for 7 days and 6000 mg/d for 1 day as l-ornithine hydrochloride) or placebo for 8 days. The fatigue-inducing physical task consisted of workload trials on a cycle ergometer at fixed workloads for 2 hours on 2 occasions. We found that oral l-ornithine administration promoted lipid metabolism and activated the urea cycle from serum triacylglycerol, ketone bodies, free fatty acids, and blood ammonia level changing. l-ornithine significantly attenuated the subjective feeling of fatigue (measured by visual analog scale at postrecovery) compared with postload (P < .01). Moreover, in female subjects, the subjective feeling of fatigue was significantly lower compared with the placebo group (P < .05). In the physical performance test in female subjects, the decrease in mean speed for 10 seconds maximum pedaling from 0.5- to 3.5-hour trials in the group receiving l-ornithine was smaller than that in the group receiving placebo (P < .05). These results suggest that l-ornithine has an antifatigue effect by increasing the efficiency of energy consumption and promoting the excretion of ammonia. l-ornithine is a free amino acid and is not rich in meats or fish, so it is difficult to obtain amounts of l-ornithine from ordinary meals that would be sufficient to promote the antifatigue effect. We recommend l-ornithine intake as a nutritional supplement in cases of physical fatigue.

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.

Section snippets

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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