Elsevier

Nutrition

Volume 24, Issue 3, March 2008, Pages 233-238
Nutrition

Applied nutritional investigation
Effects of oral administration of caffeine and D-ribose on mental fatigue

https://doi.org/10.1016/j.nut.2007.12.002Get rights and content

Abstract

Objective

We examined the effects of administering two different candidate antifatigue substances, caffeine and D-ribose, on mental fatigue.

Methods

In a double-blinded, placebo-controlled, three-way crossover design, 17 healthy volunteers were randomized to oral caffeine (200 mg/d), D-ribose (2000 mg/d), or placebo for 8 d. As fatigue-inducing mental tasks, subjects performed a 30-min Uchida-Kraepelin psychodiagnostic test and a 30-min advanced trail-making test on four occasions.

Results

During the tasks, the task performance of the caffeine group was better than that of the placebo group. However, after the fatigue-inducing tasks, although subjective perception of fatigue, motivation, or sleepiness was not significantly different, plasma branched-chain amino acid levels in the caffeine group were lower than those of the placebo group. Administration of D-ribose had no effect.

Conclusion

Because plasma branched-chain amino acid levels are decreased by mental fatigue, these results suggest that administration of caffeine improved task performance through the enhancement of central nervous system activity without increasing the sensation of fatigue. However, further decreases in branched-chain amino acid levels indicate that caffeine might promote deeper fatigue than placebo. Unfortunately, research subsequent to our study design has shown that D-ribose dosing higher than we used is needed to see a clinical effect and therefore no conclusions can be made from this study as to the efficacy of D-ribose.

Introduction

Fatigue is a common symptom 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, interest has increased in the use of over-the-counter supplements and naturally occurring nutrients for the attenuation of fatigue. However, there are no established pharmacologic, supplementary, or complementary treatment recommendations for fatigue. One reason it is difficult to establish these treatment recommendations for fatigue is that few standardized fatigue-inducing tasks with relatively short duration, accompanying appropriate evaluation methods for fatigue, have been developed.

Fatigue is best defined as difficulty in initiating or sustaining voluntary activities [4]; it can be classified into physical and mental fatigue. Recently, we succeeded in establishing 4-h physical and mental fatigue-inducing tests and in developing evaluation methods for physical and mental fatigue (task performance and some laboratory findings; Nozaki et al., unpublished observations) accompanying the fatigue-inducing tests. In this study, we determined the effects of two different candidate antifatigue substances on mental fatigue.

Caffeine is widely used as an arousal-inducing substance. Almost all caffeine comes from dietary sources (beverages and food), most of it from coffee and tea. Oral caffeine supplementation has been reported to improve cognitive task performance [5], [6], [7] and to inhibit delayed reaction time of a task during sleep deprivation [8]. Accordingly, caffeine can be a candidate antifatigue substance affecting mental fatigue.

D-ribose is the sugar moiety of adenosine triphosphate and has received interest as a metabolic supplement [9]. Oral D-ribose supplementation has been reported to increase adenine nucleotide synthesis in muscles and exercise capacity in certain clinical populations [10], and it was thought that increasing adenine nucleotide availability might enhance high-intensity exercise capacity. We found reduced energy utilization in the brain in an animal model of fatigue [11]. Thus, D-ribose can also be a candidate antifatigue substance affecting mental fatigue, although it is not clear whether the role of D-ribose on the energy state of the brain is similar to that in the muscle.

The aim of our study was to test the effects of two candidate antifatigue substances, caffeine and D-ribose, on mental fatigue using recently established mental fatigue-inducing tests and evaluation methods.

Section snippets

Subjects

Seventeen healthy volunteers (36.5 ± 5.2 y of age [mean ± SD], nine women and eight men) were enrolled in double-blinded, randomized, placebo-controlled, three-way crossover trials. The participants were recruited by advertisement. People who currently smoked, had a history of medical illness, were taking long-term medication or supplemental vitamins, had a body weight <40 kg, had donated blood within 1 mo before the study, or had blood hemoglobin levels <12.0 g/dL were excluded from the

Results

Baseline characteristics of the study group are summarized in Table 1. Subjective scores, advanced trail-making test performance (number of errors and reaction time to push the “R” circle 70 times), serum cortisol, plasma adrenocorticotropic hormone, and plasma BCAA levels of the caffeine and D-ribose groups were not significantly different from those of the placebo group.

The performance of the study group during mental tasks is summarized in Table 2. In section 3 of the advanced trail-making

Discussion

We found that oral administration of caffeine (200 mg) for 1 wk improved task performance during fatigue-inducing mental tasks. However, after the fatigue-inducing tasks, although the subjective sensation of fatigue, motivation, or sleepiness was not significantly different, plasma BCAA levels of the caffeine group were lower than those of the placebo group.

Consistent with our results, oral caffeine supplementation has been reported to improve cognitive task performance [5], [6], [7] and to

Conclusion

We demonstrated that oral administration of caffeine improved task performance with decreased plasma BCAA levels and without an increased sensation of fatigue, motivation, or sleepiness. Acute fatigue is a physiologic phenomenon that disappears after a period of rest. In contrast, long-term fatigue is sometimes irreversible, and the compensation mechanisms that are useful in reducing acute fatigue are no longer effective [23]. In this view, administration of caffeine might introduce unfavorable

Acknowledgments

The authors thank Dr. Kathy Meister for editorial help with the manuscript.

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    This work was supported in part by Special Coordination Funds for Promoting Science and Technology and the 21st Century COE Program “Base to Overcome Fatigue” from the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government.

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