Biochem Genet (2017) 55:387–394

DOI 10.1007/s10528-017-9807-8

ORIGINAL ARTICLE

The Effect of Citrulline/Malate on Blood Lactate Levels

in Intensive Exercise

Fatih Kiyici1 • Hüseyin Eroğlu2 •

N. Fazil Kishali1 • Guleda Burmaoglu1

Received: 21 November 2016 / Accepted: 14 June 2017 / Published online: 29 June 2017
Ó Springer Science+Business Media, LLC 2017

Abstract The purpose of this study was to examine the effects of Citrulline/Malate
supplementation with intensive training on blood lactate level in active handball
players. The athletes were subjected to intense training for 4 weeks, 4 days a week,
mainly pre-season strength and technique training. In this training period, stimol
group (n = 11) athletes were given stimol 3 times a day as 1 g for breakfast, 1 g for
lunch, and 1 g for dinner while the placebo group (n = 11) athletes were given only
placebo in the same dosage and the same color at the same time. Blood lactate levels
in athletes were measured 4 times, prior to and after a 1-month program as follows:
rest (R), end effort (EE), recuperation 5 min (R5 m), and recuperation 20 min
(R20 m). Blood lactate levels were compared both as intra-group and between the
groups. In intra-group comparison, no change was observed in blood lactate levels
in placebo group while a significant difference was found in the levels of stimol
group as p \ 0.05 with a 49.8% decrease in blood lactate level. In the measurements
between groups, in the post-test measurements made after the training period,
significant differences as p \ 0.05 were found with a 60.7% decrease in blood
lactate level EE. Considerable decline was seen especially immediately after
exercise in blood lactate levels of the athletes being given stimol supplement. In this
case, we can say that Citrulline/Malate supplementation may contribute positively
to the performance of athletes and may help postpone fatigue at excessive or pro-
longed activity.

This study was presented at XXXII World Congress of Sports Medicine, Rome-ITALY/2012 as poster
presentation.

& Fatih Kiyici

[email protected]
1
Faculty of Sport Sciences, Ataturk University, 25240 Erzurum, Turkey
2
Department of Physical Education and Sport, Kahramanmaraş Sütcü Imam University,
Kahramanmaraş, Turkey

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Keywords Exercise
Citrulline malate
Blood lactate

Introduction

Deformation is the reality that a sportsman can suddenly encounter. It is impossible

that the sportsmen and trainers know when they will become invalid. In such a case,
the risk of deformation should be eliminated or minimized. While the sportsman
who races strained during the competition gets weak, he/she can disable by
enforcing his/her body during the performance that should be done. The science of
sport upholds sport with the scientific works by keeping in step with the developing
technology. Ergogenic supplements can assist in that the sportsmen can tire late and
rally earlier as a result of research.
Stimol consists of the malic acid-linked amino acid citrulline. When arginine and
nitric oxide levels rise due to citrulline, it leads to more blood flow to muscles. More
blood flow leads to high oxygen and nutrient transfer, so more muscle energy is
produced. Citrulline is also critical for the removal of ammonia from the body
(Perine and Stoppani 2010). Citrulline malate (CM) is used as a performance-
enhancing athletic dietary supplement and it reduce muscle fatigue in a preliminary
clinical trial (Crenn et al. 2000).
Citrulline malate is a nonessential amino acid that increases exercise perfor-
mance in males. However, based on physiological differences between genders,
these results cannot be extrapolated to females. Therefore, the purpose of this
investigation was to evaluate effects of acute CM supplementation on upper- and
lower-body weightlifting performance in resistance-trained females (Glenn et al.
2015).
The beneficial effects of CM may be related to both the malate and the citrulline
interfering with the muscle energy metabolism level. Malate is an intermediate of
tricarboxylic acid cycle (TCA) and its addition could increase energy production
(Bendahan et al. 2002; Wagenmakers 1998). Also citrulline has been shown to
expedite the clearance of plasma ammonium and lactate, and might be involved in
the destruction of muscle metabolism by-products thereby paying to the enhance-
ment of muscle function (Briand et al. 1992; Verleye et al. 1995).
Nitric oxide (NO) produces citrulline malate (CM) in the NO synthase (NOS)
pathway and increases exercise performance in young. With age, NO production
decreases and augmented NO production may provide beneficial effects on sports
performance among masters’ athletes (Glenn et al. 2016).
A single dose of L-citrulline or watermelon juice as a pre-exercise addition
appears to be unproductive in improving exercise performance; however, greater
doses of L-citrulline have been shown to be innocent and are currently left
unexamined (Cutrufello et al. 2015).
Citrulline malate is known to limit the harmful effect of asthenic state on muscle
function, but the effect on healthy condition is poorly documented (Giannesini et al.
2011). Citrulline malate (CM) suggested an ergogenic effect during resistance
exercise; however, there are a small number of studies investigating these claims
(Wax et al. 2016). Although previous studies are not yet clear on the effect of CM

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metabolism, the effects on the metabolism of lactate are observed (Fornaris et al.
1984).
The main aim of this study was to examine the effects of Citrulline/Malate
supplementation on blood lactate level in active handball players.

Subjects and Methods

Ethical Statement

An institutional review board for human experimentation approved the protocol

(Ataturk University Faculty of Medicine Ethics Committee, authorization number
B.30.2.ATA.0.01.00/9). Informed consent was obtained from each participant, and
the processes followed were in agreement with the ethical standards of the
responsible committee on human experimentation and with the Helsinki Declaration
of 1975, as revised in 2008.

Athletes

Twenty-two athletes who were active players in the First Handball League of
Turkey participated voluntarily in the study. Athletes were divided into two separate
groups as Placebo (P, n = 11) group and Stimol group (S, n = 11). Antropo-
morphometric and physiological variables of the athletes are shown in Table 1.

Methods

The athletes were subjected to intense training for 4 weeks, 4 days a week, mainly
pre-season strength and technique training. In this training period, stimol group
athletes were given stimol 3 times a day as 1 g for breakfast, 1 g for lunch, and 1 g
for dinner while the placebo group athletes were given only placebo in the same
dosage and the same color at the same time. Blood lactate levels in athletes were
measured 4 times, prior to and after a 1-month program as follows: rest (R), end

Table 1 Antropo-
Parameters Citrulline malate group Placebo group
morphometric and physiological
Mean ± Std Mean ± Std
variables of the athletes
Age (year) 21.57 ± 4.58 18.00 ± 2.00
Height (cm) 179.86 ± 5.73 179.27 ± 10.55
Weight (kg) 70.59 ± 7.08 79.35 ± 7.08
BMI (kg/m2) 21.84 ± 1.88 24.34 ± 3.49
BMR 1816.43 ± 131.94 1987.64 ± 307.00
FAT (%) 6.91 ± 3.16 9.28 ± 4.12
FATMASS 5.00 ± 2.47 7.95 ± 5.46
FFM 65.67 ± 8.85 71.40 ± 15.51
TBW (%) 48.05 ± 4.30 52.26 ± 11.36

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effort (EE), recuperation 5 min (R5 m), and recuperation 20 min (R20 m).
Physiological characteristics of the athletes were determined at the beginning and
at the end of the program by Tanita TBF-300 body analyzer.

Statistics

Statistical significance in changes of response variables was attained using within

group Wilcoxson and between groups Mann–Whitney U. Differences were
considered significant at p \ 0.01 and p \ 0.05 (SPSS, Ver. 17.0, Chicago, IL,
USA).

Discussion

The study showed that supplement of stimol efficiently decreases in blood lactate
level especially immediately after exercise in sportsmen (Table 2). Plasma lactate
levels were compared both as intra-group and between the groups. In intra-group
comparison, no change was observed in lactate levels in placebo group while a
significant difference was found in the levels of stimol group as p \ 0.05 with a
49.8% decrease in blood level. In the measurements between groups, in the post-test
measurements made after the training period, significant differences as p \ 0.05
were found with a 60.7% decrease in plasma lactate level immediately after exercise
(Table 2).
Citrulline malate is used in Europe for years to help with aging and muscle
fatigue and produces more energy (Jackson 2004). Under healthy conditions, it has
an ergogenic effect associated with an improvement in muscle contraction
efficiency (Giannesini et al. 2011). The changes in muscle metabolism produced
by CM treatment indicate that CM may promote aerobic energy production
(Bendahan et al. 2002).
Significantly decrease of 40% in muscle soreness at 1 and 2 days after the
pectoral trainings and a higher percentage response than 90% was achieved with
CM supplementation. The only side effect reported was that 14.63% of the subjects
felt stomach ailments. Perez-Guisado and Jakeman (2010) have come to the
conclusion that using CM might be beneficial increase athletic performance in high-
intensity anaerobic exercises with short resting period and to relieve post-exercise
muscle fatigue. Thus, athletes who are in intensive preparatory stages with high
level of training or competitive events have stated that they will be able to earn
profits from CM.
Today, reducing fatigue during exercise is extremely important in terms of
making the ongoing workouts healthier. Some studies have suggested that CM
actually enhances energy in human and animal muscles. In the study, researchers
found that using CM 6 g daily for 15 days had a 20% increase in creatine phosphate
recovery after exercise, a feeling of fatigue during exercise and a 34% increase in
ATP production (Jackson 2004).
On the other hand, single dose of L-citrulline or watermelon juice as a pre-
exercise supplement is said to be ineffective without improving exercise

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 Table 2 The effects of Citrulline/Malate (stimol) supplementation on blood lactate level in active male athletes
Blood lactate Time Citrulline malate group Placebo group Between groups
Biochem Genet (2017) 55:387–394

Measurement Mean ± SE z p\ % change Mean ± SE z p\ % change z p\

Rest Pre 1.83 ± 0.18 0.542 – 5.5 1.80 ± 0.22 1.402 – 31.9 0.000 –
Post 1.93 ± 0.30 2.64 ± 1.39 0.743
End effort Pre 13.44 ± 8.18 2.366 0.05 -50.2 11.62 ± 3.36 0.770 – -5.3 0.136 0.05
Post 6.69 ± 3.88 11.03 ± 3.03 2.225
Recuperation 5 min Pre 10.04 ± 5.35 0.000 – -8.7 7.88 ± 2.31 1.719 – 12.7 0.589 –
Post 9.17 ± 5.42 9.03 ± 4.11 0.583
Recuperation 20 min Pre 2.19 ± 0.35 1.367 – -4.1 2.74 ± 0.76 0.105 – 1.4 1.1772 –
Post 2.10 ± 0.43 2.78 ± 0.95 1.570
391

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performance; however, more doses of L-citrulline have been shown to be safe

(Cutrufello et al. 2015).
Short-term oral administration of L-CM in some patients, not only in sports,
decreased pulmonary arterial hypertension (PAH) slightly and improved exercise
capacity and quality of life in patients with PAH without serious side effects
(Kashani et al. 2014). The faster recovery of the physical capacity after acute
illnesses was confirmed by double-blind, placebo-controlled studies (Creff 1982;
Dauverchain 1982; Commandré 1978).
Bendahan et al. (2002) found out in their study that there were a significant
reduction in the feeling of fatigue, a 34% increase in the rate of oxidative ATP
production during exercise, and a 20% increase in the rate of phosphocreatine
recovery after exercise. In conclusion, they declared that changes in muscle
metabolism produced by CM treatment indicate that CM may promote aerobic
energy production.
Athletes or sportsmen can raise their performances by CM during the high-
intensity anaerobic exercises. CM is also effective by increasing the resistance to
fatigue in infected rats (Perez-Guisado and Jakeman 2010).
According to the data obtained in the study conducted, it is revealed that CM
reinforcement under healthy conditions has an ergogenic effect related to
improvement of muscle contraction efficiency (Giannesini et al. 2011). In a similar
conclusion, Wax et al. (2016) found that CM increased performance of upper body
resistance in males in the age of educated college. Consuming the pre-competitive
CM has the potential to improve the performance of tennis players in tennis athletes
(Glenn et al. 2016). Previous oral L-citrulline administration during a cycling
improves NO synthesis for oxidative burst without oxidative damage and the use of
plasma arginine (polymorph nuclear neutrophils) for PMNs (Sureda et al. 2009).
During the upper body exercises, acute CM supplementation in the teeth reduced
upper- and lower-body resistance exercise performance. This demonstrates that
athletes competing with sports-strength-based needs can potentially increase
performance by acutely reinforcing CM (Glenn et al. 2015).
CM may be useful to increase athletic performance in high-intensity anaerobic
exercises with short rest periods and to alleviate muscle pain after exercise. For this
reason, athletes at an intensive preparatory stage with a high level of training or
competitive activities are said to be able to make profits from the CM (Perez-
Guisado and Jakeman 2010). It is also in the research that citrulline malate intake
significantly increases the amount of repetition for each exercise (Wax et al. 2016).
Although decrease in stimol group and increase in placebo group were
determined in lactate levels at Recuperation 5 min and Recuperation 20 min after
exercise, this was not statistically significant (Table 2). Our findings are in line with
previous studies conducted in activity of CM on the metabolism of lactic acid
(Fornaris et al. 1984). The reason for this might be associated with the person’s
fitness level of recovery time. On the other hand, Vanuxem et al. (1990) showed that
CM enhances elimination of NH3 during the recovery period therefore; serum
lactate levels did not differ between placebo and CM groups.
Jackson said that CM may help you get more reps in the gym or go longer on the
training. Additionally, anecdotal evidence from athletes using CM products reveals

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strong fatigue-diminishing and performance-enhancing effects (Jackson 2004).

Besides of this, Wax et al. (2016) said that CM supplementation may be beneficial
in improving exercise performance during lower-body multiple-bout resistance
exercise in advanced resistance-trained men.

Results

As a result of our research, there was no difference at the time of resting; there was a
noticeable decrease end of effort and no difference at the time of recuperation 5 min
and 20 min in plasma lactate levels of athletes given stimol supplement. In this case,
we can say that Citrulline/Malate supplement can make a positive contribution to
the performance of the athletes with fatigue-retarding effect.

Acknowledgements This work was supported by Scientific Research Projects Unit of the Ataturk
University.

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