Are Pre Workout Supplements Harmful or Helpful? : Creatine

We discussed in the last two articles about beta alanine and l-citrulline and their benefit in pre workout supplements. Now lets take a look at one of the most known white powders used by beginners and pros alike; creatine.

If you missed the last two articles you can find them here:

https://pharmacybrute.wordpress.com/2014/08/20/are-pre-workouts-harmful-or-helpful-beta-alanine/

https://pharmacybrute.wordpress.com/2014/08/14/are-pre-workout-supplements-harmful/

Creatine is a chemical that is primarily located in human muscle. It helps the formation of ATP in the body which is our main source of energy. It is this energy that we all need to do anything and everything. Without ATP we die. Period. If we weren’t able to create ATP even for a couple of minutes, we’d fall over and probably die. That’s how crucial it is.

Creatine has been popular for several years and no doubt if anyone has been to a gym in recent memory you might have seen someone sucking down creatine in just about any color of the rainbow. There is a reason that so many people take it. It’s because it works.

One study showed that 1 rep max in arm flexion increased significantly more over placebo with creatine loading and maintenance. Fat free mass also increased in the creatine group but no difference was found in the placebo group. [1]

In another study, total work done during 3 Wingate tests. For those unfamiliar with the Wingate test you can find out more about it here:

http://www.sport-fitness-advisor.com/wingate-test.html

One rep max on the bench press increased significantly by 6% and total lifting volume was increased. [2] These effect took 2 weeks of supplementation to achieve.

In a group of seniors (over 65 years old) creatine increased fat free mass and strength compared to placebo over 14 weeks of training. No significant side effects were noted. [3]

In another study 1 rep max on bench press, leg press and maximal reps on preacher curls was increased in the creatine group over placebo. [4] This study looked at two forms of creatine, the monohydrate and the phosphate forms. There was no significant difference between the two indicating that the form of creatine one takes isn’t important.

Another study found yet a similar increase in strength in knee extensions and time to fatigue, but noted no differences in hand strength, leading the researchers to conclude that creatine helps large muscle groups but not small ones. [5]

In one study of patients with Amyotrophic Lateral Sclerosis (ALS), creatine was loaded as is typically done with weightlifters. Maximal voluntary isometric muscular contraction was increased after 7 days of supplementation in 70% of patients in knee extensors and 53% in elbow flexors. [6] While not a cure creatine may be helpful for some of the symptoms of ALS.

So if you get an Ice Bucket challenge, maybe along with a donation you can give someone with ALS some creatine.

Another trial showed similar results for people with Parkinson’s that were weight training. [7]

Football players were divided into a creatine group and placebo group and given 5g/day creatine with no loading phase. They trained for ten weeks. Bench press increased by about 3kg, squats by about 25kg, and power cleans by about 7kg over placebo. [8] One conclusion from this study is the lack of need for a loading phase if someone is to take this in the long term.

In a meta analysis of 22 studies, researchers found that,

the average increase in muscle strength (1, 3, or 10 repetition maximum [RM]) following creatine supplementation plus resistance training was 8% greater than the average increase in muscle strength following placebo ingestion during resistance training (20 vs. 12%)” [9]

The average increase in weightlifting performance was 14% greater with creatine.

As far as dangers with creatine…well I’m not aware of any. Some claim that it will hurt your kidneys. Well from all the studies I’ve seen that’s just not going to happen. There are anecdotal stories about people having kidney problems and while I’m not one to dismiss anecdotes I think that if it were a kidney killer the FDA would’ve stopped it by now especially since it isn’t regulated.

There are many more studies that looked at creatine. It is probably one of the most studied strength enhancing supplements around. Bottom line is that it works and is effective.

Do you need to take creatine? That’s up to you. I’m not advocating for or against on this one but if you choose to it should be safe and not cause problems.

Some people don’t like creatine because they think it makes a person look “puffy” and that the muscles just are getting inflated because of the water weight. It is true that creatine does pull more water into the muscle cell. This is important for the muscle to get stronger and function properly. This is also a cause of dehydration if you’re not adequately drinking water.

Many people will load creatine when they start taking it, but as seen in the football players this is probably unneccessary if taken for many weeks. Some people do experience nausea during the loading phase. If this is the case reducing to a maintenance phase dose should take care of that.

Because of how it works, it isn’t necessary to supplement with creatine just before workouts like caffeine would be. That means you can take it at night before bed if you want.

Creatine appears to be better utilized in the presence of insulin, meaning that many take it with juice or other high glycemic carbs. Whey protein can spike insulin quite high too. [10-11] So taking some whey right after might be one way to increase utilization.

Some people are of the opinion that creatine should be cycled. I haven’t seen any data one way or the other and seeing as how most studies of this nature don’t last more than 14 or 15 weeks it’s hard to know for sure. Cycling may be wise in the long term using it for 2 months and then off a month.

Review Points

-Creatine is effective at increasing strength and power with weight training

-Likely no loading phase is necessary

-Side effect profile looks safe

-5g/day is the typical given dose

-8% increases are the average in strength augmentation

-Creatine will likely increase fat free mass

-Because of osmotic effects it is important to stay hydrated while supplementing

-Taking whey or high glycemic carbs may increase uptake in the muscles

-Cycling might be a good idea in the long term

 

I’d like to hear from you. Have you noticed a difference with creatine? Have you had any adverse effects from it?

CIAO

Disclaimer: All info on this website is for education purposes only. Any dietary or lifestyle changes that readers want to make should be done with the guidance of a competent medical practitioner. The author assumes no responsibility nor liability for the use or dissemination of this information. Anyone who chooses to apply this information for their own personal use does so at their own risk.

 

1.Becque, M. Daniel, John D. Lochmann, and Donald R. Melrose. “Effects of oral creatine supplementation on muscular strength and body compositioin.” Medicine and Science in Sports and Exercise 32.3 (2000): 654-658.

2.Earnest, Conrad P., et al. “The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition.” Acta Physiologica Scandinavica 153.2 (1995): 207.

3.Brose, Andrea, Gianni Parise, and Mark A. Tarnopolsky. “Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults.” The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 58.1 (2003): B11-B19.

4.PEETERS, BRIAN M., CHRISTOPHER D. LANTZ, and JERRY L. MAYHEW. “Effect of oral creatine monohydrate and creatine phosphate supplementation on maximal strength indices, body composition, and blood pressure.” The Journal of Strength & Conditioning Research 13.1 (1999): 3-9.

5.Urbanski, R. L., W. J. Vincent, and B. B. Yaspelkis 3rd. “Creatine supplementation differentially affects maximal isometric strength and time to fatigue in large and small muscle groups.” International journal of sport nutrition 9.2 (1999): 136-145.

6.Mazzini, L., et al. “Effects of creatine supplementation on exercise performance and muscular strength in amyotrophic lateral sclerosis: preliminary results.” Journal of the neurological sciences 191.1 (2001): 139-144.

7.Hass, Chris J., Mitchell A. Collins, and Jorge L. Juncos. “Resistance training with creatine monohydrate improves upper-body strength in patients with Parkinson disease: a randomized trial.” Neurorehabilitation and neural repair 21.2 (2007): 107-115.

8.PEARSON, DAVID R., DEREK G. HAMBX WADE RUSSEL, and TOM HARRIS. “Long-term effects of creatine monohydrate on strength and power.” The Journal of Strength & Conditioning Research 13.3 (1999): 187-192.

9.Rawson, Eric S., and JEFF S. VOLEK. “Effects of creatine supplementation and resistance training on muscle strength and weightlifting performance.” The Journal of Strength & Conditioning Research 17.4 (2003): 822-831.

10.Claessens, Mandy, et al. “The effect of different protein hydrolysate/carbohydrate mixtures on postprandial glucagon and insulin responses in healthy subjects.” European journal of clinical nutrition 63.1 (2007): 48-56.

11.Morifuji, Masashi, et al. “Comparison of different sources and degrees of hydrolysis of dietary protein: effect on plasma amino acids, dipeptides, and insulin responses in human subjects.” Journal of agricultural and food chemistry 58.15 (2010): 8788-8797.

 

Are Pre Workouts Harmful or Helpful? Beta-Alanine

In part 1 of pre workouts (PW) we discussed that some manufacturers have added chemicals that are banned by the FDA as supplements to increase performance and what to look out for. Then we discussed that L-citrulline may be beneficial for exercise but the jury is still out and more studies need to be done. If you missed it check it out here:

https://pharmacybrute.wordpress.com/2014/08/14/are-pre-workout-supplements-harmful/

In this post lets take a look at beta-alanine (BA) and see if it merits your time or money.

Beta-alanine: Performance enhancer or just another white powder?

BA is a modified form of the amino acid alanine. When it enters the body it is transformed into carnosine which acts as a buffer to drops in pH. This is likely to occur with lactate production during exercise.

As an aside, BA can cause pins and needles or warmth when ingested. This is more likely to occur as the dose increases. While for some this is uncomfortable it is important to know that it isn’t harmful.

But is it useful?

STUDY TIME!

In the first study researchers looked at trained 400 meter sprinters. They separated the 15 young men into two groups, placebo and BA supplementation. It started as 2.4 g/day during the first 4 days, 3.6 g/day during the subsequent 4 days, and from then on 4.8 g/day until the end of the study which was 4-5 weeks.

Carnosine levels increased with supplementation and knee extension torque was increased, but time taken to run the 400 meter sprint was not decreased. [1] The authors noted that even in trained athlete’s carnosine levels can be raised but that 4-5 weeks of supplementation either wasn’t enough time or just wasn’t going to decrease sprint times.

In a rowing study, elite rowers from Belgium were separated into placebo and BA groups. Carnosine was measured in the soleus and gastrocnemius (calves) and performance was measured in 100m, 200m, 2000m and 6000m times. The BA dose was 5g/day as 1g doses every 2 hours for 7 weeks.

Carnosine increased as in the previous study. The increased amount of carnosine did improve performance in the 2000m race, although times were not significantly faster. What this means is that the athletes that had the greater increase in carnosine levels from baseline did in fact perform the tests more quickly. As a whole group there was no difference.[2]

In a cycling high intensity interval training study, 46 college aged men were given 6g/day of BA for 3 weeks then 3g/day for another 3 weeks or placebo. VO2 peaks power was measured (O2 utilization) and body composition as well. Subjects focused on 90-110% of individuals VO2 max during the first 3 weeks, then 115% VO2 max during the 2nd 3 weeks.

Diet was to stay the same during the protocol. Participants also performed total time to exhaustion tests at 110% VO2.

Maximal oxygen consumption and time to exhaustion improved in both groups from baseline to 3 weeks but only improved again from 3-6 weeks in the BA group. Ventillory threshold showed no changes except in the placebo group from 3-6 weeks. [3]

It makes sense that improvements would be seen in both groups as high intensity exercise repeated over time will increase fitness levels. The change from 3-6 weeks is what makes BA seem to outshine over placebo.

Although there was an increase in lean body mass in the BA group during the first 3 weeks I don’t look at these results with much attention. Since the diets weren’t controlled in ward setting there are far too many confounders to really pay attention to any “significant changes”.

The authors did not that the BA group did train at higher workloads and at longer periods of time over placebo, but no significant difference was noted.

In another cycling study 16 highly trained cyclists were separated into BA or placebo at 68mg/kg over 4 weeks and looked at muscle contraction power and average power over 4 minutes of cycling. Average power/repetition was significantly increased. Fatigue index was significantly reduced. Average power output was higher in the BA group but it didn’t reach significance. [4]

In a study of swimmers, BA was given to the test group at 4.8g/day for 4 weeks then 3.2g/day after for 6 weeks. Training set times were improved at 4 weeks with supplementation but not at 10. There was a very small but insignificant improvement in competition performance. [5] What gets me is that the test group didn’t have a very good mask compared to placebo. Because BA can cause paresthesia (pins and needles) it was easy for 12 out of 22 in the test group to tell they were downing BA while 12 out of 19 in the placebo group guess correctly because of absence of paresthesia and 3 could tell because of taste. That could have caused quite a confounding of results.

Think about it. If you knew you were getting a supplement, the real deal, could your psychology increase your performance alone? If you knew you weren’t getting the real deal would you try as hard? I guess we won’t know, at least not in this group.

It’s akin to giving some people a brand new corvette and some others a VW bug and seeing who is going to drive the speed limit more of the time. Need I say more?

Another study looking at rowers came up with mostly negative results. Similar to the above mentioned rowing study, rowers times decreased at the 750m mark and 1000m mark but the decreases were both less than 1 second. [6]

In an endurance test of leg extensors, participants held a leg extension in a machine until exhaustion. The active dose of BA was 6.4g/day as 800mg tabs 8x/day separated by 2 hours each compared to placebo over 4 weeks.

After 4 weeks the active group was able to increase time to exhaustion by over 9 seconds, compared to the placebo group which decreased in time. [7]

A meta-analysis concluded that supplementation was greatest for activities that last between 60-240 seconds and at a dose of 179g total is supplemented. Benefits above 240 seconds overall were significant but not as pronounced. The researchers also commented that it is beneficial in high intensity activities. Most of the studies were conducted on men so no real concrete conclusions could be made about the benefits in women. [8]

A review of the literature has come to similar conclusions about BA. [9] There seems to be enough evidence to support ergogenic effect for high intensity exercise and more research is needed to quantify it. It appears that people with lower starting carnosine levels may benefit more from BA than others whose baseline is higher, but again more research is needed.

Another issue with many of the studies is the small sample size. Small size makes it difficult to detect true benefit from anything. I personally believe there is a benefit to be more readily detected from BA supplementation, but until they can consistently prove it with larger samples I can only speculate.

Review Points

-Beta-alanine raises carnosine levels in cells which can buffer decreases in pH

-Beta-alanine appears to benefit exercise when:

* exercise lasts at least 60-240 seconds in duration

*doses are on a regular basis and probably at least 4-5g/day

-Doses can be multiple times a day and don’t have to be pre workout to be effective

-Beta-alanine appears to have no side effects other than paresthesia

As I stated before I think BA has potential to be useful. I use it myself and have felt both the paresthesia and increased endurance while lifting and sprinting. I would like to see more conclusive studies on it but I’m not holding my breath in the mean time.

Next we’ll discuss creatine.

CIAO

Disclaimer: All info on this website is for education purposes only. Any dietary or lifestyle changes that readers want to make should be done with the guidance of a competent medical practitioner. The author assumes no responsibility nor liability for the use or dissemination of this information. Anyone who chooses to apply this information for their own personal use does so at their own risk.

1.Derave, Wim, et al. “β-Alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters.” Journal of applied physiology 103.5 (2007): 1736-1743.

2.Baguet, Audrey, et al. “Important role of muscle carnosine in rowing performance.” Journal of Applied Physiology 109.4 (2010): 1096-1101.

3.Smith, Abbie E., et al. “Effects of β-alanine supplementation and high-intensity interval training on endurance performance and body composition in men; a double-blind trial.” Journal of the International Society of Sports Nutrition 6.1 (2009): 1-9.

4.Howe, Samuel T., et al. “The effect of Beta-Alanine supplementation on isokinetic force and cycling performance in highly trained cyclists.” International Journal of Sports Nutrition and Exercise Metabolism 23.6 (2013): 562-570.

5.Chung, Weiliang, et al. “Effect of 10 week Beta-alanine supplementation on competition and training performance in elite swimmers.” Nutrients 4.10 (2012): 1441-1453.

6.Ducker, Kagan J., Brian Dawson, and Karen E. Wallman. “Effect of beta-alanine supplementation on 2000m rowing ergometer performance.” International journal of sport nutrition and exercise metabolism 23.4 (2013): 336-343.

7.Sale, Craig, et al. “β-alanine supplementation improves isometric endurance of the knee extensor muscles.” Journal of the International Society of Sports Nutrition 9.1 (2012): 1-7.

8.Hobson, Ruth M., et al. “Effects of β-alanine supplementation on exercise performance: a meta-analysis.” Amino acids 43.1 (2012): 25-37.

9.Culbertson, Julie Y., et al. “Effects of beta-alanine on muscle carnosine and exercise performance: a review of the current literature.” Nutrients 2.1 (2010): 75-98.

Are Pre Workout Supplements Harmful?

**UPDATED**

Many people who workout will, even with proper diet in place, find that some days they are just dragging. It might be the kids keep them up at night, it might be a late night with friends or a late movie or it could be stress at work is sapping their energy. Whatever the case some days it is just hard to pull yourself outta bed to do anything. (Once I let gravity pull me out of bed thinking once I was out I’d get up…..I woke up an hour later on my floor and it was even harder to get up. Lame!)

Others may go to workout in the afternoon when they are feeling the early afternoon nap coming on. It’s a similar situation for many people. It’s a “the spirit is willing but the flesh is weak” type of thing. You WANT to move but your body says “No chance buddy”.

Other people are able to get started but have a hard time staying focused on what they’re doing or just can’t seem to get through a workout. Others are looking to get pumped up even more than what they naturally achieve through weights. Enter the pre workout drink.

Before I dive into pre-workouts I want to comment on nutrition. If you are getting the afternoon nap time grab your teddy bear and snooze feeling around 1 or 2 PM, look at your diet and see if you’re getting enough protein in the morning and some slower digesting carbs both in the morning and around lunch. Protein especially has a stabilizing effect on blood sugar.

Pre Workouts (PW for the rest of the post) are touted as giving you energy and being able to give you incredible pumps. They also claim to give you focus and drive to finish the most intense workouts.

They’ve also been reported to cause dangerous side effects.[1,2]

These news reports discussed a chemical called 1-3 dimethylamylamine or DMAA. This is a form of amphetamine which releases norepinephrine in the central nervous system and may also act as a direct agonist on 5-HT receptors (serotonin) and at higher doses may also release serotonin.

What does this mean? Well it means your brain gets overloaded with a whole bunch of neurostimulants and you feel like talking 1000 words per second, running 3 minute miles and otherwise doing anything and everything in a focused and speedy manner. No bueno.

The good news is that the companies that were making these supplements were ordered by the FDA to stop and destroy them, but just in case here is a list of other names that DMAA goes by:

  • 1,3-DMAA
  • 1,3-Dimethylamylamine
  • 1,3-Dimethylpentylamine
  • 2-Amino-4-methylhexane
  • 2-Hexanamine, 4-methyl- (9CI)
  • 4-Methyl-2-hexanamine
  • 4-Methyl-2-hexylamine
  • Dimethylamylamine
  • Geranamine
  • Methylhexanamine
  • Methylhexanenamine
  • InChIKey=YAHRDLICUYEDAU-UHFFFAOYSA-N
  • Pelargonium graveolens extract
  • Geranium extract

If you happen to have a PW that contains one of these listed ingredients it is a great idea to throw them out. The reason that amphetamines and other drugs in the same class are Schedule II by the DEA is because of strong addiction potential and abuse potential. You need a prescription from your doc that cannot have any refills by law and fill it at a pharmacy to legally have it in your possession. So yeah.

These are powerful stimulants that can cause serious heart problems. Blood pressure can rise and cause stroke and infarctions in susceptible people. These aren’t to be taken lightly.

Besides the products that have been yanked from the market what about the others that are out there?

PWs are filled with many ingredients. Many are clumped together and then listed as “proprietary blend” which means you don’t know how much of each ingredient is actually present in a serving. Some have brand names of supplements such as CarnoSyn which may impress upon a person that since it’s brand it must be good.

Lets take a look at some of these ingredients and see what they are and what they do.

THE PUMP!!

Looking for that insane "pump"?

Looking for that insane “pump”?

Many PW contain l-arginine or l-citrulline. These are amino acids which help to increase the production of NO or nitric oxide. NO is what is responsible for vasodilation which means that it opens up the blood vessels and allows more blood flow into muscles. Drugs such as nitroglycerin, used for angina, use this principle to open up vessels in the cardiac muscle to relieve chest pain.

Because muscles are able to receive more blood they become engorged and feel inflated or pumped. Anyone who has lifted heavy weights knows exactly what I’m talking about. It does feel as if though your muscles are super tight and huge. It is a pretty cool feeling if I do say so myself.

This is one of the main two reasons people buy PWs. They want that insane pump. Does and increased pump do much for strength or performance?

One study looked at men doing leg extensions with or without a tourniquet. Increases in growth hormone were seen as well as norepinephrine and lactate over controls. While this study doesn’t show strength increases because it was just one round it does suggest that the proper hormones are in place to increase strength such as growth hormone and norepinephrine and lactate. For an interesting article on the history of those you can read this [3].

But that doesn’t tell us about performance. Another study looked at performance in older females (average age 58) and found that occlusion did produce increases in strength and hypertrophy. [4]

In another study rugby players had vascular occlusion of their legs and performed leg extensions compared to controls. Low intensity exercise was performed and after 8 weeks the group with occluded legs had increases in torque during the exercise compared to the other groups. [5]

Another study looking at young male athletes showed similar results. [6] It should be noted the results were small but still significant and resulted in better extension but not flexion.

These studies show that occlusion does help in strength, but what about the actual supplement to increase NO? After all it is thought that if you increase pump it is actually like occluding the muscle because less blood is leaving than entering.

In one study done with ornithine and arginine (ingredients to increase NO) subjects either received these or placebo and were subjected to strength training. The active trial group did gain greater strength than placebo. [7]

In another study in men ages 30-50 who had trained previously were given l-arginine alpha-ketoglutarate vs placebo over 8 weeks. Significant improvement in 1 repetition max bench press was noted but there was no difference in aerobic capacity or body composition. [8] It should also be noted this was a 12g dose/day as 4g three times daily.

Looking at 1 rep max, researchers in Spain found that citrulline was able to increase the number of repetitions done in a placebo crossover design in 41 men. The subjects also reported that they had decreased muscle soreness after 1 and 2 days compared to placebo.[9]

Another study found that after ingestion of l-arginine, 3 sets of 10 repetitions of elbow flexion (curls) and blood volume and total work was measured. The researchers found in this study that blood volume in the muscle did increase, but work performed did not. Muscle oxygenation increased with each subsequent set but was not significant. [10]

The researchers in this last study postulated that no difference was seen in strength because of the exercise protocol used. While many of the other studies looked at protocols to exhaustion or more than 30 repetitions, this protocol was simply 3 sets of 10 separated by 2 min breaks. They were also maximal voluntary contractions (ie no weights). Hard to measure how much more work the biceps might do when the subjects are told to flex hard. It’s almost like seeing how much work a crane can do without attaching any weights and having the operator make it lift “heavier”.

It appears that using a NO precursor such as arginine or citrulline may be beneficial at increasing strength in athletes. Of note, citrulline appears to bypass the liver and be converted in the kidneys to arginine. It has become a popular supplement to replace arginine and doesn’t appear to have the need to be cycled.

The spanish dose used in the above study was 8gm of citrilluine malate. That was around 0.1gm/kg body weight.One study looking at cyclist looked at 6gm citrulline malate 2hrs prior to exercise and growth hormone increased more in this group than in the placebo group as well as enhancing amino acid utilization.[11]

The problem is most PW have 3gm or so. You can triple the dose but you’ll be tripling everything else too and as we’ll see in the next post or two tripling caffeine might not be a good thing.

Another thing to consider is diarrhea. Arginine and ornithine can cause GI upset and diarrhea at doses of 10gm. Some people I’ve read have problems at lower doses. Citrulline has seen no GI upset at 15gm doses, at least in one study. [12] Citrulline appears to be better tolerated on the stomach.

Many who have used these before can attest that some of these PWs can cause severe diarrhea.

My recommendation is that citrulline is a benefit to workouts and strength and endurance, but at the right dose.

Summary Points:

-NO producers such as arginine and citrulline are beneficial in increasing strength

-Citrulline is preferred now over arginine

-Citrulline malate dose is at least 6gm before exercise and probably best taken 45-60 min  preworkout.

-Citrulline appears to benefit fatigue and benefits soreness 1 and 2 days after workout

-Citrulline only has two studies showing real exercise benefit. More evidence is needed to officially say that it indeed helps as an ergogenic aid.

-Arginine does increase blood flow but probably doesn’t increase performance.

 

Anecdotally I believe citrulline helps me tremendously, but that is my own N=1 and I can’t speak for the general population. If it helps you comment below.

In the next PW article we will discuss beta-alanine.

CIAO

 

1. http://californiawatch.org/dailyreport/sports-supplement-has-dangerous-ingredient-lawsuit-claims-15057

2. http://baltimore.cbslocal.com/2013/04/12/its-like-crack-doctor-on-pre-workout-supplement-ingredient/

3.http://www.sciencedaily.com/releases/2007/05/070531191121.htm

4. Takarada, Yudai, et al. “Effects of resistance exercise combined with moderate vascular occlusion on muscular function in humans.” Journal of Applied Physiology 88.6 (2000): 2097-2106.

5.Takarada, Yudai, Yoshiaki Sato, and Naokata Ishii. “Effects of resistance exercise combined with vascular occlusion on muscle function in athletes.” European journal of applied physiology 86.4 (2002): 308-314.

6.Takarada, Yudai, Tomomi Tsuruta, and Naokata Ishii. “Cooperative effects of exercise and occlusive stimuli on muscular function in low-intensity resistance exercise with moderate vascular occlusion.” Japanese Journal of Physiology 54.6 (2004): 585-592.

7.Elam, R. P., et al. “Effects of arginine and ornithine on strength, lean body mass and urinary hydroxyproline in adult males.” The Journal of sports medicine and physical fitness 29.1 (1989): 52-56.

8.Campbell, Bill, et al. “Pharmacokinetics, safety, and effects on exercise performance of L-arginine α-ketoglutarate in trained adult men.” Nutrition 22.9 (2006): 872-881.

9.Pérez-Guisado, Joaquín, and Philip M. Jakeman. “Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness.” The Journal of Strength & Conditioning Research 24.5 (2010): 1215-1222.

10.Álvares, Thiago Silveira, et al. “Acute l-arginine supplementation increases muscle blood volume but not strength performance.” Applied Physiology, Nutrition, and Metabolism 37.1 (2012): 115-126.

11.Sureda, Antoni, et al. “L-citrulline-malate influence over branched chain amino acid utilization during exercise.” European journal of applied physiology 110.2 (2010): 341-351.

12.Moinard C, et al. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. (2008)