Citrulline Does Not Increase Blood Flow or Protein Synthes

Royd The Noyd

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New paper from Stu Phillips lab.


Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise
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Abstract

Ageing is associated with anabolic resistance; a reduced sensitivity of myofibrillar protein synthesis (MPS) to postprandial hyperaminoacidemia, particularly with low protein doses. Impairments in postprandial skeletal muscle blood flow and/or microvascular perfusion with hyperaminoacidemia and hyperinsulinemia may contribute to anabolic resistance. We examined whether providing citrulline, a precursor for arginine and nitric oxide synthesis, would increase arterial blood flow, skeletal muscle microvascular perfusion, MPS, and signalling through mTORC1. Twenty one elderly males (65-80 y) completed acute unilateral resistance exercise prior to being assigned to ingest a: high dose (45g) of whey protein (WHEY), or a low dose (15g) of whey protein with 10g of citrulline (WHEY+CIT), or with 10g of non-essential amino acids (WHEY+NEAA). A primed continuous infusion of L-[ring-13C6] phenylalanine with serial muscle biopsies was used to measure MPS and protein phosphorylation, while ultrasound was used to measure microvascular circulation under basal and postprandial conditions in both a rested (FED) and exercised (EX-FED) leg. Argininemia was greater in WHEY+CIT vs. WHEY and WHEY+NEAA from 30-300 min post-exercise (P<0.001), but there were no treatment differences in blood flow, or microvascular perfusion (all P>0.05). Phosphorylation of p70S6kThr389 was greater in WHEY vs. WHEY+NEAA (P=0.02). Postprandial MPS was greater in WHEY vs. WHEY+CIT and WHEY+NEAA under both FED (WHEY: ~128%; WHEY+CIT: ~56%; WHEY+NEAA: ~38%) and EX-FED (WHEY: ~251%; WHEY+CIT: ~124%; WHEY+NEAA: ~108%) conditions (P=0.003). Citrulline co-ingestion with a low quantity of protein was ineffective in augmenting the anabolic properties of protein compared to non-essential amino acids.
 

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Nice find. The MPS data is no surprise given the magnitude of the whey alone bolus, but I'm surprised NO was not increased despite the increase in arginine. Prior data does indeed show an NO increase. Perhaps,

1. The elderly population lacks sufficient NOS activity to compensate for the increase in arginine. Although more likely is the finding that arginase levels increase with age.

2. Exercise (following ingestion, not prior to) is a pre-requisite for activation of eNOS to the magnitude that would significantly increase NO.
 
Royd The Noyd

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Nice find. The MPS data is no surprise given the magnitude of the whey alone bolus, but I'm surprised NO was not increased despite the increase in arginine. Prior data does indeed show an NO increase. Perhaps,

1. The elderly population lacks sufficient NOS activity to compensate for the increase in arginine. Although more likely is the finding that arginase levels increase with age.

2. Exercise (following ingestion, not prior to) is a pre-requisite for activation of eNOS to the magnitude that would significantly increase NO.
I'm surprised they used old vs. Young subjects. That's unlike McMasters. I think your #1 is supported with animal research.
 
Quadzilla99

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I bought my 65 year old father a gym membership and take him to work out. I give him some citrulline and nitrates before we go the gym. Guess the citrulline is a waste of time then?
 
Quadzilla99

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Like I give him 1 gram potassium nitrate, 500 mg agmatine, 500 mg NAC, 200 mg caffeine, and 200 mg vitamin C one hour before I take him and then I give him a BCAA drink with 4 grams citrulline when we get there so like 15-20 minutes before he starts working out. He drinks it in the car and then he stretches/warms up for 20 minutes before he lifts
 
Afi140

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Thanks for posting.
 
RecompMan

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Nice find. The MPS data is no surprise given the magnitude of the whey alone bolus, but I'm surprised NO was not increased despite the increase in arginine. Prior data does indeed show an NO increase. Perhaps, 1. The elderly population lacks sufficient NOS activity to compensate for the increase in arginine. Although more likely is the finding that arginase levels increase with age. 2. Exercise (following ingestion, not prior to) is a pre-requisite for activation of eNOS to the magnitude that would significantly increase NO.
This due to formation of AGE?
 

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So citrulline is a waste? Was going to get High volume, it as 5g l-citrulline, but if it does not have any pump or endurance effect I skip it.
 

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So citrulline is a waste? Was going to get High volume, it as 5g l-citrulline, but if it does not have any pump or endurance effect I skip it.
It could have muscle protective properties IIRC which turns the odds in your favour for better recovery.
 
nattydisaster

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So citrulline is a waste? Was going to get High volume, it as 5g l-citrulline, but if it does not have any pump or endurance effect I skip it.
lol...don't over extrapolate. It is a waste if you are an elderly person looking to enhance bloodflow

It will be pretty impossible to try to tell someone a 5g dose of L-citrulline didnt give them a sick pump compared to when they don't take it.

If you are a middle aged man, you will be better off: http://www.ncbi.nlm.nih.gov/pubmed/21067832

There is also a number of studies on L-citrulline-malate (not the same citrulline malate that is sold today) for its performance benefits and other benefits that fit the fitness industry:

http://www.ncbi.nlm.nih.gov/pubmed/20499249

http://www.ncbi.nlm.nih.gov/pubmed/20386132

http://www.ncbi.nlm.nih.gov/pubmed/21908948 (animal)

http://www.ncbi.nlm.nih.gov/pubmed/21195829 (non-elderly)

There are more...but...that should suffice
 

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So citrulline is a waste? Was going to get High volume, it as 5g l-citrulline, but if it does not have any pump or endurance effect I skip it.
I'd advise re-reading this post:
Nice find. The MPS data is no surprise given the magnitude of the whey alone bolus, but I'm surprised NO was not increased despite the increase in arginine. Prior data does indeed show an NO increase. Perhaps,1. The elderly population lacks sufficient NOS activity to compensate for the increase in arginine. Although more likely is the finding that arginase levels increase with age.2. Exercise (following ingestion, not prior to) is a pre-requisite for activation of eNOS to the magnitude that would significantly increase NO.
Since pretty much every other citrulline study shows benefits, the reason for this study's conclusion is clearly due to something in the methodology. As I stated, they consumed the citrulline postworkout. High volume is a preworkout, and all the preworkout studies demonstrated benefit...which should be the obvious way to take it anyway.
 

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lol...don't over extrapolate. It is a waste if you are an elderly person looking to enhance bloodflowIt will be pretty impossible to try to tell someone a 5g dose of L-citrulline didnt give them a sick pump compared to when they don't take it. If you are a middle aged man, you will be better off: http://www.ncbi.nlm.nih.gov/pubmed/21067832There is also a number of studies on L-citrulline-malate (not the same citrulline malate that is sold today) for its performance benefits and other benefits that fit the fitness industry:http://www.ncbi.nlm.nih.gov/pubmed/20499249http://www.ncbi.nlm.nih.gov/pubmed/20386132http://www.ncbi.nlm.nih.gov/pubmed/21908948 (animal)http://www.ncbi.nlm.nih.gov/pubmed/21195829 (non-elderly)There are more...but...that should suffice
Great, I have always felt an increase in pump when dosing 10g citrulline malate. Will get some high volume then. :)
I'd advise re-reading this post:Since pretty much every other citrulline study shows benefits, the reason for this study's conclusion is clearly due to something in the methodology. As I stated, they consumed the citrulline postworkout. High volume is a preworkout, and all the preworkout studies demonstrated benefit...which should be the obvious way to take it anyway.
Missed your post. thank you.
 
Royd The Noyd

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Egh


Citrulline stimulates muscle protein synthesis in the post-absorptive state in healthy people fed a low-protein diet - A pilot study.

Clin Nutr. 2014 May 4;

Authors: Jourdan M, Nair KS, Carter RE, Schimke J, Ford GC, Marc J, Aussel C, Cynober L

Abstract
BACKGROUND & AIMS: Amino acid (AA) availability is critical to maintain protein homeostasis and reduced protein intake causes a decline in protein synthesis. Citrulline, an amino acid metabolite, has been reported to stimulate muscle protein synthesis in malnourished rats.
METHODS: To determine whether citrulline stimulates muscle protein synthesis in healthy adults while on a low-protein diet, we studied 8 healthy participants twice in a cross-over study design. Following a 3-days of low-protein intake, either citrulline or a non-essential AA mixture (NEAA) was given orally as small boluses over the course of 8 h. [ring-(13)C6] phenylalanine and [(15)N] tyrosine were administered as tracers to assess protein metabolism. Fractional synthesis rates (FSR) of muscle proteins were measured using phenylalanine enrichment in muscle tissue fluid as the precursor pool.
RESULTS: FSR of mixed muscle protein was higher during the administration of citrulline than during NEAA (NEAA: 0.049 ± 0.005; citrulline: 0.060 ± 0.006; P = 0.03), while muscle mitochondrial protein FSR and whole-body protein turnover were not different between the studies. Citrulline administration increased arginine and ornithine plasma concentrations without any effect on glucose, insulin, C-peptide, and IGF-1 levels. Citrulline administration did not promote mitochondria protein synthesis, transcripts, or citrate synthesis.
CONCLUSIONS: Citrulline ingestion enhances mixed muscle protein synthesis in healthy participants on 3-day low-protein intake. This anabolic action of citrulline appears to be independent of insulin action and may offer potential clinical application in conditions involving low amino acid intake.
 
Driven2lift

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Is that enhancement likely specific to the scenario of otherwise low protein intake, or should/could it also be of benefit in times if adequate/high intake?
 

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That diet wasn't that low protein, it was roughly 50g which is the RDA. I would have thought a regular group of researchers would consider that a normal protein intake.

But it looks like citrulline was probably acting through mTOR. Which is in line with the rat studies on citrulline, showing an effect similar to leucine. Regardless, I don't think I'd change how I dose citrulline to try to manipulate this effect. Preworkout is still the way to go
 

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That diet wasn't that low protein, it was roughly 50g which is the RDA. I would have thought a regular group of researchers would consider that a normal protein intake.
interesting viewpoint
honest question for you, I am curious: do you really consider RDA values to be a semblance of any reality? and do researchers embrace this stance as well, as you infer? srs question..this would help me understand a bit further how you view things and assess some of these studies..
I mean, the " standard" RDA you call normal here, is simply the barest minimum amount in order to prevent sickness & illness from malnutrition, things like avoiding rickets and scurvy...if that is not considered low, I do not know what is
 
Royd The Noyd

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interesting viewpoint
honest question for you, I am curious: do you really consider RDA values to be a semblance of any reality? and do researchers embrace this stance as well, as you infer? srs question..this would help me understand a bit further how you view things and assess some of these studies..
I mean, the " standard" RDA you call normal here, is simply the barest minimum amount in order to prevent sickness & illness from malnutrition, things like avoiding rickets and scurvy...if that is not considered low, I do not know what is
He's just clarifying the abstract (which doesn't define "low protein"). Calm down bro.
 

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Calm down bro.
whoa....do I seem upset to you? I actually went out of my way to be clear that I was asking for simple clarification on his view point
if that post there makes you think I have angst or am upset, then gawd forbid you see some of my other posts....
lol
 
Royd The Noyd

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whoa....do I seem upset to you? I actually went out of my way to be clear that I was asking for simple clarification on his view point
if that post there makes you think I have angst or am upset, then gawd forbid you see some of my other posts....
lol
U mad
 

mr.cooper69

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interesting viewpoint
honest question for you, I am curious: do you really consider RDA values to be a semblance of any reality? and do researchers embrace this stance as well, as you infer? srs question..this would help me understand a bit further how you view things and assess some of these studies..
I mean, the " standard" RDA you call normal here, is simply the barest minimum amount in order to prevent sickness & illness from malnutrition, things like avoiding rickets and scurvy...if that is not considered low, I do not know what is
No, I obviously don't think this lol. But the mainstream does
 

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The powers that be make the most money from fat and out of shape people!
 
paula

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Is 6grams of L citruline is the correct clinicaly dose?
 
Quadzilla99

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Is 6grams of L citruline is the correct clinicaly dose?
Study used 8 grams cit mal so 4-5.5 grams citrulline depending on their percentage used. Cit mal is usually 1:1 or 2:1 citrulline to malate I think
 

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As little as 3g pure citrulline has been used to positive effect
 
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Original flavors are good. New flavors, just aren't fair ;)
Lol find yourself sneaking extra scoops just for the taste factor?
Be careful not to over-pump those muscles :p
 
MuscleReview

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But L-Citrulline and L-Arginine can be an effective combination for sexual potency.
 
Royd The Noyd

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New paper...good news for you watermelon lovers.

Effects of Supplemental Citrulline Malate Ingestion During Repeated Bouts of Lower-body Exercise in Advanced Weight Lifters.

J Strength Cond Res. 2014 Sep 15;

Authors: Wax B, Kavazis AN, Weldon K, Sperlak J

Abstract
The purpose of this investigation was to test the efficacy of citrulline malate supplementation on exercise performance, blood lactate, heart rate and blood pressure during lower-body dynamic resistance exercise. We hypothesized that citrulline malate ingestion prior to performing submaximal repeated bouts of multiple lower body resistance exercises would improve performance. Twelve advanced resistance trained male subjects participated in a randomized, counterbalanced, double blind study. Subjects were randomly assigned to placebo or citrulline malate (8 g) groups and then performed repeated bouts of multiple lower body resistance exercise. Specifically, subjects performed five sequential sets (60% one-repetition maximum) to failure on the leg press, hack squat, and leg extension machines. Blood lactate, heart rate, systolic blood pressure, and diastolic blood pressure were determined pre and post exercise. The exercise protocol resulted in sequential significant (p < 0.05) decrease in the number of repetitions in all three exercises. However, subjects in the citrulline malate group performed significantly (p < 0.05) higher number of repetitions during all three exercises compared to placebo group. Blood lactate and heart rate were significantly increased (p < 0.05) post-exercise compared to pre-exercise, but were not significantly different between citrulline malate and placebo (p > 0.05). No significant (p > 0.05) differences were detected for blood pressure measurements. In conclusion, our results suggest that citrulline malate supplementation may be beneficial in improving exercise performance during lower-body multiple-bout resistance exercise in advanced resistance trained men.
 
Afi140

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New paper...good news for you watermelon lovers. Effects of Supplemental Citrulline Malate Ingestion During Repeated Bouts of Lower-body Exercise in Advanced Weight Lifters. J Strength Cond Res. 2014 Sep 15; Authors: Wax B, Kavazis AN, Weldon K, Sperlak J Abstract The purpose of this investigation was to test the efficacy of citrulline malate supplementation on exercise performance, blood lactate, heart rate and blood pressure during lower-body dynamic resistance exercise. We hypothesized that citrulline malate ingestion prior to performing submaximal repeated bouts of multiple lower body resistance exercises would improve performance. Twelve advanced resistance trained male subjects participated in a randomized, counterbalanced, double blind study. Subjects were randomly assigned to placebo or citrulline malate (8 g) groups and then performed repeated bouts of multiple lower body resistance exercise. Specifically, subjects performed five sequential sets (60% one-repetition maximum) to failure on the leg press, hack squat, and leg extension machines. Blood lactate, heart rate, systolic blood pressure, and diastolic blood pressure were determined pre and post exercise. The exercise protocol resulted in sequential significant (p < 0.05) decrease in the number of repetitions in all three exercises. However, subjects in the citrulline malate group performed significantly (p < 0.05) higher number of repetitions during all three exercises compared to placebo group. Blood lactate and heart rate were significantly increased (p < 0.05) post-exercise compared to pre-exercise, but were not significantly different between citrulline malate and placebo (p > 0.05). No significant (p > 0.05) differences were detected for blood pressure measurements. In conclusion, our results suggest that citrulline malate supplementation may be beneficial in improving exercise performance during lower-body multiple-bout resistance exercise in advanced resistance trained men.
nice. Watermelon is my favorite fruit :)
 
Driven2lift

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Thanks for the update on this!

Citrulline is a must-have for me

I can tell the difference without it immediately, ever since adding bulk to my pre I will never look back

Glad newer pres are dosing it properly now, High Volume and Conqu3r being some
 
Royd The Noyd

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I'm not sure if this new one is posted here yet (I feel like maybe it was but google search isnt finding it):

Effects of Supplemental Citrulline-Malate Ingestion on Blood Lactate, Cardiovascular Dynamics, and Resistance Exercise Performance in Trained Males.

J Diet Suppl. 2015 Feb 12. [Epub ahead of print]
Effects of Supplemental Citrulline-Malate Ingestion on Blood Lactate, Cardiovascular Dynamics, and Resistance Exercise Performance in Trained Males.
Wax B1, Kavazis AN, Luckett W.
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Abstract
ABSTRACT Citrulline-malate (CM) has been proposed to provide an ergogenic effect during resistance exercise; however, there is a paucity of research investigating these claims. Therefore, we investigated the impact that CM supplementation would have on repeated bouts of resistance exercise. Fourteen resistance-trained males participated in a randomized, counterbalanced, double-blind study. Subjects were randomly assigned to placebo (PL) or CM (8 g) and performed three sets each of chin-ups, reverse chin-ups, and push-ups to failure. One week later, subjects ingested the other supplement and performed the same protocol. Blood lactate (BLa), heart rate (HR), and blood pressure (BP) were measured preexercise, with BLa measured a second time immediately following the last set, while HR and BP were measured 5 and 10 min postexercise. Citrulline-malate ingestion significantly increased the amount of repetitions performed for each exercise (chin-ups: PL = 28.4 ± 7.1, CM = 32.2 ± 5.6, p = .003; reverse chin-ups: PL = 26.6 ± 5.6, CM = 32.1 ± 7.1, p = .017; push-ups: PL = 89.1 ± 37.4, CM = 97.7 ± 36.1, p < .001). Blood lactate data indicated a time effect (p < .001), but no treatment differences (p = .935). Systolic BP data did not show differences for time (p = .078) or treatment (p = .119). Diastolic BP data did not show differences for time (p = .069), but indicated treatment differences (p = .014) for subjects ingesting CM. Collectively, these findings suggests that CM increased upper-body resistance performance in trained college-age males.
 
Royd The Noyd

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^I havent read that paper, but based on those average number of reps those dudes were strong relative to body weight.
 
Quadzilla99

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WHat were the rep ranges?
 
Quadzilla99

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I guess if I am reading it right its like sets or one set of around 30 reps?
 
Royd The Noyd

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Effects of Supplemental Citrulline-Malate Ingestion on Blood Lactate, Cardiovascular Dynamics, and Resistance Exercise Performance in Trained Males.

Randomized controlled trial
Wax B, et al. J Diet Suppl. 2016.
Show full citation
Abstract
Citrulline-malate (CM) has been proposed to provide an ergogenic effect during resistance exercise; however, there is a paucity of research investigating these claims. Therefore, we investigated the impact that CM supplementation would have on repeated bouts of resistance exercise. Fourteen resistance-trained males participated in a randomized, counterbalanced, double-blind study. Subjects were randomly assigned to placebo (PL) or CM (8 g) and performed three sets each of chin-ups, reverse chin-ups, and push-ups to failure. One week later, subjects ingested the other supplement and performed the same protocol. Blood lactate (BLa), heart rate (HR), and blood pressure (BP) were measured preexercise, with BLa measured a second time immediately following the last set, while HR and BP were measured 5 and 10 min postexercise. Citrulline-malate ingestion significantly increased the amount of repetitions performed for each exercise (chin-ups: PL = 28.4 ± 7.1, CM = 32.2 ± 5.6, p = .003; reverse chin-ups: PL = 26.6 ± 5.6, CM = 32.1 ± 7.1, p = .017; push-ups: PL = 89.1 ± 37.4, CM = 97.7 ± 36.1, p < .001). Blood lactate data indicated a time effect (p < .001), but no treatment differences (p = .935). Systolic BP data did not show differences for time (p = .078) or treatment (p = .119). Diastolic BP data did not show differences for time (p = .069), but indicated treatment differences (p = .014) for subjects ingesting CM. Collectively, these findings suggests that CM increased upper-body resistance performance in trained college-age males.
 
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Effects of Supplemental Citrulline-Malate Ingestion on Blood Lactate, Cardiovascular Dynamics, and Resistance Exercise Performance in Trained Males.

Randomized controlled trial
Wax B, et al. J Diet Suppl. 2016.
Show full citation
Abstract
Citrulline-malate (CM) has been proposed to provide an ergogenic effect during resistance exercise; however, there is a paucity of research investigating these claims. Therefore, we investigated the impact that CM supplementation would have on repeated bouts of resistance exercise. Fourteen resistance-trained males participated in a randomized, counterbalanced, double-blind study. Subjects were randomly assigned to placebo (PL) or CM (8 g) and performed three sets each of chin-ups, reverse chin-ups, and push-ups to failure. One week later, subjects ingested the other supplement and performed the same protocol. Blood lactate (BLa), heart rate (HR), and blood pressure (BP) were measured preexercise, with BLa measured a second time immediately following the last set, while HR and BP were measured 5 and 10 min postexercise. Citrulline-malate ingestion significantly increased the amount of repetitions performed for each exercise (chin-ups: PL = 28.4 ± 7.1, CM = 32.2 ± 5.6, p = .003; reverse chin-ups: PL = 26.6 ± 5.6, CM = 32.1 ± 7.1, p = .017; push-ups: PL = 89.1 ± 37.4, CM = 97.7 ± 36.1, p < .001). Blood lactate data indicated a time effect (p < .001), but no treatment differences (p = .935). Systolic BP data did not show differences for time (p = .078) or treatment (p = .119). Diastolic BP data did not show differences for time (p = .069), but indicated treatment differences (p = .014) for subjects ingesting CM. Collectively, these findings suggests that CM increased upper-body resistance performance in trained college-age males.
Interesting. Good find RH
 
cheftepesh1

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Found this very interesting
 

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Effects of Supplemental Citrulline-Malate Ingestion on Blood Lactate, Cardiovascular Dynamics, and Resistance Exercise Performance in Trained Males.

Randomized controlled trial
Wax B, et al. J Diet Suppl. 2016.
Show full citation
Abstract
Citrulline-malate (CM) has been proposed to provide an ergogenic effect during resistance exercise; however, there is a paucity of research investigating these claims. Therefore, we investigated the impact that CM supplementation would have on repeated bouts of resistance exercise. Fourteen resistance-trained males participated in a randomized, counterbalanced, double-blind study. Subjects were randomly assigned to placebo (PL) or CM (8 g) and performed three sets each of chin-ups, reverse chin-ups, and push-ups to failure. One week later, subjects ingested the other supplement and performed the same protocol. Blood lactate (BLa), heart rate (HR), and blood pressure (BP) were measured preexercise, with BLa measured a second time immediately following the last set, while HR and BP were measured 5 and 10 min postexercise. Citrulline-malate ingestion significantly increased the amount of repetitions performed for each exercise (chin-ups: PL = 28.4 ± 7.1, CM = 32.2 ± 5.6, p = .003; reverse chin-ups: PL = 26.6 ± 5.6, CM = 32.1 ± 7.1, p = .017; push-ups: PL = 89.1 ± 37.4, CM = 97.7 ± 36.1, p < .001). Blood lactate data indicated a time effect (p < .001), but no treatment differences (p = .935). Systolic BP data did not show differences for time (p = .078) or treatment (p = .119). Diastolic BP data did not show differences for time (p = .069), but indicated treatment differences (p = .014) for subjects ingesting CM. Collectively, these findings suggests that CM increased upper-body resistance performance in trained college-age males.
and this study has been replicated in lower body and chest at 8grams CM. MaxReps, anyone?
 

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