Let’s take a break from the heavy science talk to reflect on standard decision-making practice for purchasing pre-workout supplements. Times are changing as leading companies reformulate their pre-workout products and resonant influence from the arginine debacle is obviously setting in. So, by ingredient, we’re going to take an inclusive approach and examine what should be in an educated consumer’s pre-workout product of choice, not what shouldn’t be.
The Big Three
Caffeine: The acute performance enhancement benefits of caffeine are well-documented and ubiquitously experienced throughout the world of sport and leisure alike. (1, 2, 3) Pick a random pre-workout supplement up off the shelf and chances are it contains caffeine, so when you’re making your decision, it should come down to the dose. If the dose is listed, 200mg should do the trick. If you need more, it’s time to go caffeine-free for a while.
Nitrate: Finally bursting on the scene, nitrate is making its way into many new formulas, and rightfully so. If you have read my previous article on 1,3-dimethylamylamine, you should know how nitrate augments vasodilation. In case you didn’t, the molecular pharmacology isn’t all too important here, but know that the nitrate ion (NO3-) is a nitric oxide donor. There is no obscure endogenous enzymatic cascade, substrate to enzyme ratio, or other weird stipulation. The nitrate ion is essentially reduced to nitric oxide in the body, simple as that. Now, while nitrate-containing extracts are great and all, we really want to be able to figure out how much we’re getting, as there certainly are both upper and lower limits of dose dependency. If it’s in a prop blend, you’re going to need to do some guesswork, but if not, here’s a quick conversion for reference: creatine nitrate (CrN): 32% nitrate by mass; 321mg nitrate per 1g CrN. I’ve found the sweet spot at around 650mg nitrate, or 2g CrN.
An adjunct to nitrate, vitamin C: A few months ago I wrote a pretty extensive, heavy analysis of the relationship between nitrosamine formation (dangerous) and vitamin C (eliminates any suspected danger). The jist of it- add 200mg vitamin C with your nitrate supplement just to be safe. Once you try nitrate, you’re going to want to make it a long term thing, so I suggest you take this route (or purchase a product that already contains vitamin C, which most do).
Citrulline Malate/l-citrulline: Speaking of obscure enzymatic pathways, citrulline certainly encapsulates such. With respect to endogenously formed nitric oxide (i.e. formed from arginine by endothelial nitric oxide synthase), citrulline basically shifts equilibrium in your body favorably for nitric oxide production, something oral arginine does not do. For the first time, in Janurary, 2008, Schwedhelm et al. found that oral l-citrulline increased NO-dependent vasodilatation in healthy adults. (4) Of course there are some issues with their design regarding relevance, especially with mean subject age being 57, but perhaps I will delve into a real analysis another time. For now, we’ll keep it there. As a less questionable function or l-citrulline, it augments bicarbonate reabsorption in the renal system (kidneys), which means it can indirectly attenuate acidity (therein decrease soreness) in skeletal muscle. (6) Note that this has nothing to do with “the lactic acid buildup brah!!!111”. This property, decreasing muscle soreness during exercise, is apparent in the relevant research. (5)
As for extraneous ergogenic properties of malate without citrulline, the focus is on a biological process called an anaplerotic reaction. Speculation respects ATP production with malate as an intermediary, but it goes in the pseudoscience vault until more research shows up.
Now, the main issue here with citrulline is the dose (ranging from 3g l-citrulline to 8g cit-mal, 2:1 cit:mal in the relevant research) and prop blends don’t make the buyer’s job any easier. Unfortunately, it’s really a trial and error thing, and if you’re an experienced pre-workout product user, you’ll know when it’s under-dosed and you’ll know when it’s not.
Is that all?
No, not even close, but for the sake of brevity, these three ingredients (plus vitamin C if you’re using nitrate) alone, but in the right doses, should profoundly accelerate your performance, endurance, and strength in the gym. This conclusion begs the question: will there be a part 2?
1. Stuart, Gene R.; Hopkins, Will G.; Cook, Christian; Cairnes, Simeon P. “Multiple Effects of Caffeine on Simulated High-Intensity Team-Sport Performance” Medicine & Science in Sports & Exercise: November 2005 - Volume 37 - Issue 11 - pp 1998-2005 doi: 10.1249/01.mss.0000177216.21847.8a Applied Sciences: Physical Fitness and Performance.
2. Martin J. Jarvis. Does caffeine intake enhance absolute levels of cognitive performance? Journal of Psychopharmocology Volume 110, Numbers 1-2, 45-52, DOI: 10.1007/BF02246949
3. Bruce, Clinton R.; Anerson, Megan E.; Fraser, Steven F.; Stepto, Nigel K.; Klein, Rudi; Hopkins, William G.; Hawley, John A. “Enhancement of 2000-m rowing performance after caffeine ingestion”. Medicine & Science in Sports & Exercise: November 2000 - Volume 32 - Issue 11 - pp 1958-1963. Applied Sciences: Physical Performance and Fitness.
4. Edzard Schwedhelm, Renke Maas, Ralf Freese2, Donald Jung, Zoltan Lukacs, Alen Jambrecina, William Spickler4, Friedrich Schulze, Rainer H. Böger. “Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism” British Journal of Clinical Pharmacology Volume 65, Issue 1, pages 51–59, January 2008. DOI: 10.1111/j.1365-2125.2007.02990.x
5. Pérez-Guisado J, Jakeman PM. “Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness.” Department of Medicine, University of Córdoba, Córdoba, Spain. Journal of Strength and Conditioning Res. 2010 May; 24 (5):1215-22.
6. Callis, A, Magnan De Bornier, B, Serrano, JJ, Bellet, H, and Saumade, R.
Activity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man. Department of Medical Biophysics, Institut de Biologie, Montpellier, France. Arzneimittelforschung. 1991 Jun;41(6):660-3.
The Big Three
Caffeine: The acute performance enhancement benefits of caffeine are well-documented and ubiquitously experienced throughout the world of sport and leisure alike. (1, 2, 3) Pick a random pre-workout supplement up off the shelf and chances are it contains caffeine, so when you’re making your decision, it should come down to the dose. If the dose is listed, 200mg should do the trick. If you need more, it’s time to go caffeine-free for a while.
Nitrate: Finally bursting on the scene, nitrate is making its way into many new formulas, and rightfully so. If you have read my previous article on 1,3-dimethylamylamine, you should know how nitrate augments vasodilation. In case you didn’t, the molecular pharmacology isn’t all too important here, but know that the nitrate ion (NO3-) is a nitric oxide donor. There is no obscure endogenous enzymatic cascade, substrate to enzyme ratio, or other weird stipulation. The nitrate ion is essentially reduced to nitric oxide in the body, simple as that. Now, while nitrate-containing extracts are great and all, we really want to be able to figure out how much we’re getting, as there certainly are both upper and lower limits of dose dependency. If it’s in a prop blend, you’re going to need to do some guesswork, but if not, here’s a quick conversion for reference: creatine nitrate (CrN): 32% nitrate by mass; 321mg nitrate per 1g CrN. I’ve found the sweet spot at around 650mg nitrate, or 2g CrN.
An adjunct to nitrate, vitamin C: A few months ago I wrote a pretty extensive, heavy analysis of the relationship between nitrosamine formation (dangerous) and vitamin C (eliminates any suspected danger). The jist of it- add 200mg vitamin C with your nitrate supplement just to be safe. Once you try nitrate, you’re going to want to make it a long term thing, so I suggest you take this route (or purchase a product that already contains vitamin C, which most do).
Citrulline Malate/l-citrulline: Speaking of obscure enzymatic pathways, citrulline certainly encapsulates such. With respect to endogenously formed nitric oxide (i.e. formed from arginine by endothelial nitric oxide synthase), citrulline basically shifts equilibrium in your body favorably for nitric oxide production, something oral arginine does not do. For the first time, in Janurary, 2008, Schwedhelm et al. found that oral l-citrulline increased NO-dependent vasodilatation in healthy adults. (4) Of course there are some issues with their design regarding relevance, especially with mean subject age being 57, but perhaps I will delve into a real analysis another time. For now, we’ll keep it there. As a less questionable function or l-citrulline, it augments bicarbonate reabsorption in the renal system (kidneys), which means it can indirectly attenuate acidity (therein decrease soreness) in skeletal muscle. (6) Note that this has nothing to do with “the lactic acid buildup brah!!!111”. This property, decreasing muscle soreness during exercise, is apparent in the relevant research. (5)
As for extraneous ergogenic properties of malate without citrulline, the focus is on a biological process called an anaplerotic reaction. Speculation respects ATP production with malate as an intermediary, but it goes in the pseudoscience vault until more research shows up.
Now, the main issue here with citrulline is the dose (ranging from 3g l-citrulline to 8g cit-mal, 2:1 cit:mal in the relevant research) and prop blends don’t make the buyer’s job any easier. Unfortunately, it’s really a trial and error thing, and if you’re an experienced pre-workout product user, you’ll know when it’s under-dosed and you’ll know when it’s not.
Is that all?
No, not even close, but for the sake of brevity, these three ingredients (plus vitamin C if you’re using nitrate) alone, but in the right doses, should profoundly accelerate your performance, endurance, and strength in the gym. This conclusion begs the question: will there be a part 2?
1. Stuart, Gene R.; Hopkins, Will G.; Cook, Christian; Cairnes, Simeon P. “Multiple Effects of Caffeine on Simulated High-Intensity Team-Sport Performance” Medicine & Science in Sports & Exercise: November 2005 - Volume 37 - Issue 11 - pp 1998-2005 doi: 10.1249/01.mss.0000177216.21847.8a Applied Sciences: Physical Fitness and Performance.
2. Martin J. Jarvis. Does caffeine intake enhance absolute levels of cognitive performance? Journal of Psychopharmocology Volume 110, Numbers 1-2, 45-52, DOI: 10.1007/BF02246949
3. Bruce, Clinton R.; Anerson, Megan E.; Fraser, Steven F.; Stepto, Nigel K.; Klein, Rudi; Hopkins, William G.; Hawley, John A. “Enhancement of 2000-m rowing performance after caffeine ingestion”. Medicine & Science in Sports & Exercise: November 2000 - Volume 32 - Issue 11 - pp 1958-1963. Applied Sciences: Physical Performance and Fitness.
4. Edzard Schwedhelm, Renke Maas, Ralf Freese2, Donald Jung, Zoltan Lukacs, Alen Jambrecina, William Spickler4, Friedrich Schulze, Rainer H. Böger. “Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism” British Journal of Clinical Pharmacology Volume 65, Issue 1, pages 51–59, January 2008. DOI: 10.1111/j.1365-2125.2007.02990.x
5. Pérez-Guisado J, Jakeman PM. “Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness.” Department of Medicine, University of Córdoba, Córdoba, Spain. Journal of Strength and Conditioning Res. 2010 May; 24 (5):1215-22.
6. Callis, A, Magnan De Bornier, B, Serrano, JJ, Bellet, H, and Saumade, R.
Activity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man. Department of Medical Biophysics, Institut de Biologie, Montpellier, France. Arzneimittelforschung. 1991 Jun;41(6):660-3.