Citrulline Malate

H2N NH

O O

NH2

OH

L-citrullineO

HO

O OHOH

Malate (Malic acid)

Introduction L-citrulline is a non essential amino acid

Malate is an intermediate of the tricarboxylic acid cycle (TCA)

Originally developed:

1. Improve muscle performance for asthenia sufferers

2. Improve recovery time from physical activity for individuals with acute diseases

Recent research for athletic population:

3. Enhances aerobic energy production

4. Augment muscle force output

5. Mitigate muscle fatigue

(Wax et al., 2015)

How it works3 proposed mechanisms of action:1. Excess availability of citrulline allows the

acceleration of the urea cycle therefore facilitating the clearance of ammonium.

2. Malate acts as an metabolic shuttle between cytoplasm and mitochondria.

3. Nitric Oxide (NO) regulates glucose uptake and oxidation, mitochondriogenesis, contractile functions, blood flow, fatty acid oxidation and muscle repair in skeletal muscle.

(Pérez-Guisado and Jakeman, 2010)

Citrulline Malate on Aerobic Energy Production

(Bendahan et al., 2002)

Citrulline Malate on Aerobic Energy Production

Before

During

After

Rate of oxidative ATP production (%EC)

54 (12)

74 (4)

45 (6)

Before

During

After

Virec 16.9 (2.9)

24.2 (3.2)

16.4 (1.9)

(Bendahan et al., 2002)

Bendahan et al. (2002) Conclusions

Rate of muscle oxidative ATP production during exercise increase with CM supplementation

Rate of PCr recovery after exercise increased with CM supplementation

(Bendahan et al., 2002)

(Nissim et al., 2003)

How it works

Citrulline Malate on Recovery & Fatigue

(López-Cabral et al., 2012)

Citrulline Malate on Recovery

(López-Cabral et al., 2012)

Citrulline Malate on Fatigue

(López-Cabral et al., 2012)

López-Cabral et al. (2012) Conclusions

Expected results in recovery and fatigue are achieved quicker with 6g/day vs 3g/day dose although both have similar efficacy after 2weeks

CM enhances lactate clearance and fatigue recovery of high performance athletes.

(López-Cabral et al., 2012)

Citrulline Malate on Recovery

(Sureda et al., 2010)

Citrulline Malate on Recovery

CM raises plasma L-arginine concentrationCM augments nitrite, creatine, ornithine and

urea and hormones (GH)CM augments nitrogen availability allowing

increases in protein synthesis and protein content in muscle during exercise

(Sureda et al., 2010)

Sureda et al. (2010) Conclusions

CM reduced and delayed the onset of the immunosuppressive mechanisms associated with intense exercise

CM improves the recovery process from intense training therefore avoiding symptoms associated with overtraining.

(Sureda et al., 2010)

Citrulline Malate on Performance & Muscle

Soreness

(Pérez-Guisado and Jakeman, 2010)

Citrulline Malate on Performance

Reps (PL) Reps (CM) %Increase

Responders

Set 1

12.27 ± 0.45

12.39 ± 0.49

0.97 8 (19.51%)

Set 4

6.00 ± 1.61 7.05 ± 1.73 17.50 25 (60.97%)

Set 1

9.24 ± 2.08 10.32 ± 1.75

11.69 31 (75.60%)

Set 4

3.59 ± 1.40 5.49 ± 1.53 52.92 41 (100%)

(Pérez-Guisado and Jakeman, 2010)

Citrulline Malate on Muscle Soreness

Muscle Soreness

PL CM %Decrement

24hr post workout

3.12 ± 0.60

1.88 ± 0.64

39.74

48hr post workout

3.90 ± 0.70

2.27 ± 0.67

41.79Muscle Soreness

Responders

Non-responders

Worse

24hr post workout

40 (97.56%)

1 (2.44%) 0 (0)

48hr post workout

37 (90.24%)

4 (9.76%) 0 (0)

(Pérez-Guisado and Jakeman, 2010)

Pérez-Guisado and Jakeman (2010)

Conclusions CM reduces fatigue by increasing rate of oxidative ATP

production during exercise and the rate of PCr recovery after exercise

Single dose of CM 1hr prior to exercise is an effective ergogenic aid

CM increases athletic performance in high intensity anaerobic exercise with short rest periods

CM attenuates post exercise muscle soreness

(Pérez-Guisado and Jakeman, 2010)

Citrulline Malate on Fatigue

(Wax et al., 2015)

Citrulline Malate on Fatigue

(Wax et al., 2015)

Citrulline Malate on Fatigue

(Wax et al., 2015)

Wax et al. (2015) Conclusions

•CM improved fatigue thus allowing an increase in work capacity of 19%•CM improved overall performance by 9%•No influence on blood lactate from either CM or PL•However 3 minute recovery between all sets and exercises could have allowed metabolic recovery whilst mitigating acidosis, lactate and ammonium accumulation in the working muscle

(Wax et al., 2015)

Safety

(López-Cabral et al., 2012; Pérez-Guisado and Jakeman, 2010; Sureda et al., 2010)

Dosage & Timing8g 1hr prior

(Wax et al., 2015; Pérez-Guisado and Jakeman, 2010)

Availability

(AllMax Nutrition Citrulline Malate 2:1 at Bodybuilding.com, 2015; LiveLong Nutrition Citrulline Malate at Bodybuilding.com, 2015; Myprotein, 2015; PrimaForce Citrulline Malate at Bodybuilding.com, 2015)

Cost

Brand Cost No Servings

Serving Size

Cost per Serving

Prima Force

£16.86 100 2g 17p

Allmax Nutrition

£12.82 40 2g 32p

LiveLong Nutrition

£16.21 33 3g 49p

MyProtein £12.99 250 2g 5p

(AllMax Nutrition Citrulline Malate 2:1 at Bodybuilding.com, 2015; LiveLong Nutrition Citrulline Malate at Bodybuilding.com, 2015; Myprotein, 2015; PrimaForce Citrulline Malate at Bodybuilding.com, 2015)

WADA & Informed Sport

(Informed-sport.com, 2015; World Anti-Doping Agency, 2014)

WADA & Informed Sport

(AllMax Nutrition Citrulline Malate 2:1 at Bodybuilding.com, 2015; Informed-sport.com, 2015; LiveLong Nutrition Citrulline Malate at Bodybuilding.com, 2015; Myprotein, 2015; PrimaForce Citrulline Malate at Bodybuilding.com, 2015; World Anti-Doping Agency, 2014)

ConclusionsCM increases athletic performance in high intensity

anaerobic exercise with short rest periodsCM attenuates post exercise muscle sorenessCM enhances lactate clearance and fatigue recovery

of high performance athletes therefore avoiding symptoms associated with overtraining.

Rate of muscle oxidative ATP production during exercise increase with CM supplementation

Rate of PCr recovery after exercise increased with CM supplementation

(Wax et al., 2015; López-Cabral et al., 2012; Pérez-Guisado and Jakeman, 2010; Sureda et al., 2010; Nissim et al., 2003; Bendahan et al., 2002)

Type of Athlete that would benefit

Athletes looking to relieve post exercise muscle soreness

Intensive training or preparation engaging anaerobic metabolism resulting in increased lactate, ammonia and acidosis

High intensity anaerobic exercise with short rest periods such as;

1. Strength training2. Sprint sessions

(Wax et al., 2015; López-Cabral et al., 2012; Pérez-Guisado and Jakeman, 2010; Sureda et al., 2010; Nissim et al., 2003; Bendahan et al., 2002)

References AllMax Nutrition Citrulline Malate 2:1 at Bodybuilding.com, (2015). AllMax Nutrition Citrulline

Malate 2:1 at Bodybuilding.com. [online] Bodybuilding.com. Available at: http://uk.bodybuilding.com/store/allmax-nutrition/citrulline-malate-2-1.html?&_requestid=159765 [Accessed 25 Apr. 2015].

Bendahan, D., Mattei, J., Confort-Gouny, S., Le Guern, M. and Cozzone, P. (2002). Citrulline/malate promotes aerobic energy production in human exercising muscle. British Journal of Sports Medicine, 36(4), pp.282-289.

Informed-sport.com, (2015). Home | Informed-Sport. [online] Available at: http://informed-sport.com [Accessed 25 Apr. 2015].

LiveLong Nutrition Citrulline Malate at Bodybuilding.com, (2015). LiveLong Nutrition Citrulline Malate at Bodybuilding.com. [online] Bodybuilding.com. Available at: http://uk.bodybuilding.com/store/live/citrulline-malate.html?&_requestid=160020 [Accessed 25 Apr. 2015].

López-Cabral, J., Rivera-Cisneros, A., Rodríguez-Camacho, H., Sánchez-González, J., Serna-Sánchez, I. and Trejo-Trejo, M. (2012). Modification of fatigue indicators using citrulline malate for high performance endurance athletes. Rev Latinoamer Patol Clin, 59(4), pp.194-201.

Myprotein, (2015). Citrulline Malate. [online] Available at: http://www.myprotein.com/sports-nutrition/citrulline-malate/10529326.html?autocomplete=productsuggestion [Accessed 25 Apr. 2015].

References Nissim, I., Horyn, O., Luhovyy, B., Lazarow, A., Daikhin, Y., Nissim, I. and Yudkoff, M.

(2003). Role of the glutamate dehydrogenase reaction in furnishing aspartate nitrogen for urea synthesis: studies in perfused rat liver with 15N. Biochem. J., 376(1), p.179.

Pérez-Guisado, J. and Jakeman, P. (2010). Citrulline Malate Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness. Journal of Strength and Conditioning Research, 24(5), pp.1215-1222.

PrimaForce Citrulline Malate at Bodybuilding.com, (2015). PrimaForce Citrulline Malate at Bodybuilding.com. [online] Bodybuilding.com. Available at: http://uk.bodybuilding.com/store/prima/citrullinemalate.html?&_requestid=159677 [Accessed 25 Apr. 2015].

Sureda, A., Córdova, A., Ferrer, M., Pérez, G., Tur, J. and Pons, A. (2010). l-Citrulline-malate influence over branched chain amino acid utilization during exercise. Eur J Appl Physiol, 110(2), pp.341-351.

Wax, B., Kavazis, A., Weldon, K. and Sperlak, J. (2015). Effects of Supplemental Citrulline Malate Ingestion During Repeated Bouts of Lower-Body Exercise in Advanced Weightlifters. Journal of Strength and Conditioning Research, 29(3), pp.786-792.

World Anti-Doping Agency, (2014). Prohibited List. [online] Available at: https://www.wada-ama.org/en/resources/science-medicine/prohibited-list [Accessed 25 Apr. 2015].