The past decade has seen a boom in the supplement industry, with new products cropping up on a regular basis. The majority of these products eventually fade, making way for “the next big thing.” In this article we will cover what just might be that next thing and one of the most exciting supplements to come along in quite a while. We will also explore a few of the more popular supplements currently on the market and weigh the potential benefits against the potential risks of these products. Additionally, I’ll provide an Anabolic Index rating for each supplement, which quantifies exactly how much each product will help you achieve your goals.
Covered in this Article:
- The newest rock solid performance enhancing supplement
- Potentially harmful supplement ingredients
- Arginine (aka Nitric Oxide stimulators)
Beta alanine (BA) is a naturally occurring amino acid in our bodies, and is fairly unexciting. The interesting part happens when BA combines with another amino acid called histidine forming a dipeptide known as Carnosine. Carnosine normally exists in our muscles, acting primarily as a buffer to resist changes in pH. Over the past few years, research has shown additional benefits of Carnosine, which makes it so intriguing for us. Much like creatine, we can “load” our muscles with Carnosine by supplementing with BA, thus reaping even greater benefits (12, 13).
The buffering of lactic acid by Carnosine doesn’t seem like a big deal at first glance. In fact, some may dismiss the true benefits by assuming that this simply means less of a burning sensation will occur when training. But, increasing buffering capacity cannot only improve performance; it has the potential to increase muscle growth and strength gains.
As far as training, the ability to push harder means a greater stimulus for adaptation for strength and muscle growth. This is especially true for the high threshold fast fibers, because these are the fibers that have the greatest capacity for Carnosine storage. Intra-muscular Carnosine levels are largely fiber type dependent, in that; the faster the muscle, the more Carnosine it has (24). Taking this one step further, Carnosine itself contributes some of the contractile properties responsible for fiber typing. In other words, fast muscles may have specific contractile properties because they have a lot of Carnosine; and it is Carnosine that helps make them fast. This is supported by several studies showing that Carnosine enhances maximum contraction speed of fibers, meaning that our muscles can contract more quickly (2, 26). From this, it stands to reason that fast athletes like sprinters are known to have more muscle Carnosine than endurance athletes (20).
BA and Fast Twitch Fibres:
The proper application of this concept is of critical importance, so let’s look at it in another way. It is often cited that humans have three main fiber types, which are (slowest to fastest): “Type I”, “Type IIA”, and “Type IIB” (21). Unfortunately, this is a bit of a misrepresentation, because humans do not actually have the lightning fast and powerful IIB fibers. Instead, our fastest type is a slower version called “IIX” (21).
Due to its ability to enhance contraction speed, increasing muscle Carnosine levels could conceivably move us closer to that IIB ideal! You can imagine the implications of this in everything from football to Olympic Weightlifting.
If Carnosine levels are elevated, they may protect against damage to our nerves, allowing them to fire at a faster rate than if damaged. Practically speaking, instead of performing at 90% the day after exercise, Carnosine may help you perform closer to optimum level. This is particularly useful for athletes who are repeatedly using the same muscles, without the ability to simply rest and recover for a few days.
By protecting nerve cells against oxidative damage, Carnosine may lead to synchronous muscle and nervous system recovery, and ultimately facilitate training while each tissue is optimized. This could not only provide a more powerful training stimulus (12, 23), but the advantages of being able to train more frequently are clear.
In terms of direct practical application, strength athletes and powerlifters are most concerned with neural recovery. This makes BA supplementation perfect for these athletes who want to keep the nervous system running quickly and efficiently. One of the greatest benefits of BA is that its use as a supplement is widely applicable, by both athletes and those interested in changing their physique. The people who benefit most from BA supplementation are the same as those who benefit from creatine. These athletes play sports including: football, hockey, wrestling/MMA, track etc. The ability of BA supplementation to enhance contraction speed even makes it useful for sports like table tennis, where quickness and agility are paramount.
Of course, BA is perfect for people looking to gain muscle and strength – just like creatine. Finally, due to the potential of enhancing neural recovery, beta alanine supplementation works well for strength athletes and powerlifters.
In summary, the following effects are noted due to Beta Alanine supplementation:
- Faster muscle contraction
- Resistance to anaerobic fatigue
- Increased stimulus for strength/muscle growth
- Enhanced neural protection and recovery
There are few supplements around these days that we can actually trust, so it’s pretty exciting when something like Beta Alanine comes around. With the numerous benefits to the human body, coupled with the observed increase in athletic performance, Beta Alanine is sure to be around for years to come!
Although BA is not directly anabolic, its ability to enhance gym performance yields the following score.
- Anabolic Index rating: 1
A number of supplements currently on the market contain a completely unnecessary and potentially dangerous substance called Glycocyamine.
Glycocyamine is a substance known to increase our blood levels of homocysteine, which is believed to be a risk factor for cardiovascular disease. This means that we’re potentially more likely to have heart disease/atherosclerosis when our homocysteine levels are high. Lest we forget, cardiovascular disease is still the #1 killer in the Western world.
Some have attempted to justify their consumption of glycocyamine based upon recent research suggesting that the correlation between cardiovascular disease and homocysteine levels isn’t as strong as once thought. In other words, a weaker correlation means that you have a slightly lesser chance of dying as once thought, should you consume this substance. Awesome!
Glycocyamine = Nervous System Damage?
As potentially dangerous as the correlation to cardiovascular disease is, it gets worse. Glycocyamine has also been described as “neurotoxic action” (17).
Glycocyamine has an inhibitory effect on a brain enzyme called the sodium pump (27, 28). This isn’t just any enzyme; the sodium pump is responsible for all nerve signals that happen in our body. So important is this enzyme, it exists not only in nerve cells, but also in every single cell in the body. This means that although only the brain has been studied (so far), glycocyamine has the potential to disrupt the proper functioning of every cell.
This is BAD.
For those concerned with performance (and if you’re reading this, you very likely are), our muscles have a high concentration of the sodium pump. After studying it in the lab for 7 years, I can tell you that this enzyme is critical for proper muscle contraction and optimal performance. Based on this, it’s no surprise to learn that high glycocyamine levels have been implicated in reducing muscle strength (15).
Generally, I would be the first to call for studies that are more specific to strength athletes, but in this case we’re talking about health. When it comes to a supplement having potentially harmful effects, even in vitro and animal studies should give us cause for concern.
What’s the Point?
Realistically speaking, the idea of consuming glycocyamine is simply absurd, but there has to be a reason why it’s in there. The primary theory behind its use is that it is converted to creatine by our bodies, so taking in more glycocyamine results in higher creatine and homocysteine levels.
Glycocyamine is intended as a creatine substitute, however, the absurdity lies in the fact that it does not elevate creatine levels to any greater extent than simply supplementing with creatine. And until glycocyamine is converted, the “neurotoxic action” is still a problem. Perhaps when creatine was close to a dollar per serving, glycocyamine’s use as a creatine booster might have had relevance. However, creatine monohydrate is now one of the least expensive (and most effective) supplements available rendering substitutes completely unnecessary, especially a substitute far more expensive with the potential for harmful side effects.
Due to its potential ability to impair the nervous system, and subsequently muscle contraction (irrespective of health issues), glycocyamine earns the following.
- Anabolic Index Rating: -1 (with a potential for harming health)
A certain creatine like supplement on the market (as well as several copycat products), contain a potentially dangerous compound that is ergolytic; i.e. something that decreases athletic performance.
This chemical is Guanidinopropionic Acid (GPA). GPA binds the creatine transporter thus preventing creatine transport into various tissues. The problem lies in the fact that most of our tissues can’t generate creatine so it has to be transported in. And obstructed transporters means cellular creatine levels are reduced.
It bears repeating that creatine isn’t just a supplement, but a naturally occurring substance in our bodies that we need to survive! You are familiar with the positive impact of a 20% creatine increase – imagine an 80% reduction! Just seven days of GPA induced creatine depletion can not only reduce muscle strength (11), but has also been shown to convert fast-twitch muscle to slow-twitch! So this substance could make you weaker and slower!
Your Brain on GPA:
These effects alone should be plenty to make you avoid supplements containing GPA, but wait! There’s more! There’s also a potentially dangerous side to consider as both our hearts and brains have creatine transporters!!! Messing around with your two most vital organs is never a great idea. While the brain seems to compensate for decreases in energy supply caused by GPA (19), your body must still adapt to reduced energy levels and who wants that! Additionally, three separate studies have shown that creatine levels in the heart dropped by 80-87% with GPA consumption in rats (6, 18,14). Now you can see why it’s nearly impossible to perform human studies using this substance. One has to wonder what manufacturers were thinking when they approved production of GPA containing supplements.
One particular supplement (“NO-Xplode”) combines GPA with our old friend Glycocyamine. Sadly, glycocyamine (also known as guanidinoacetate) has been picked up by a number of different supplement companies. Unfortunately, these substances aren’t just isolated to a single product — they’re popping up in all kinds of different supplements (including some protein powders)!
It’s my opinion that products containing either of these substances should be pulled off the market and the formulas changed, but the FDA is powerless until harm has already been done. So, before you supplement with something, do your research and KNOW WHAT YOU’RE CONSUMING!
Because of the powerful effect of blocking creatine uptake into all cells (irrespective of potential health problems), including muscle, GPA has the resulting score.
- Anabolic Index rating: -3 (with a potential for harming health)
Arginine AKG (Nitric Oxide Stimulators):
Arginine supplements (aka NO stimulators, aka Nitric Oxide supplements) have arguably become the most the most hyped up products of the past couple of years. The theory behind the supplement is that taking high amounts of the amino acid arginine will result in its conversion to the molecule called nitric oxide (NO). Because NO is largely responsible for increasing the size of blood vessels, the idea is that greater levels of NO will stimulate blood flow. Finally, if we can stimulate more blood flow to working muscles we can have:
- Greater removal of metabolic by products that can shut down muscle contraction. This could result in greater muscular endurance and overall performance.
- Increased nutrient delivery. If our muscles require energy to work or amino acids to grow, an elevated blood flow could increase the supply. This could result increased performance and muscle growth.
Show Me the Money:
Now that we know the theory behind the supplements, let’s take a look at the supporting evidence. Fortunately for us, there is quite a bit of data on the subject.
- Study 1(25) -Dose: 21 grams. Measured Result: No effect on glycogen storage following exercise
- Study 2 (5) -Dose: 6g either IV or orally. Measured Result: No effect on blood flow
- Study 3 (1) -Dose: 7g for 3 days. Measured Result: No effect on blood flow
- Study 4 (9) -Dose: 20g a day for 20 days Measured Result: No effect on blood flow
- Study 5 (10) -Dose: 20g a day for 20 days Measured Result: No effect on blood flow
- Study 6 (22) -Dose: 10g +70g carbohydrates Measured Result: No effect on blood flow or nutrient uptake
Collectively it appears as though the theory behind arginine and NO is bunk, but there may be an explanation. NO is a very powerful molecule that can not only induce oxidaftive damage and regulate blood flow, but also acts as a signal between communicating nerve cells. As a result, NO levels are tightly regulated. In fact, our body’s natural arginine levels are already far higher than should be required to stimulate NO production.
Taking this one step further, even an arginine-free diet for nearly a week had no effect on NO synthesis (8). Once again, this shows how important control of NO is to our normal body functioning, and how little the impact of arginine consumption can be.
Some people will scoff at the above findings because they used regular arginine, while the current arginine supplements have an AKG molecule attached to them. Will the AKG suddenly override the body’s desperate need to regulate NO levels? Even the question itself seems a little at this point.
Fortunately, one group decided to specifically look at arginine AKG (AAKG) taken at 12g a day for 8 weeks (Campbell). This study is of particular interest not only due to the specificity of the supplement used, but also because the subjects were people who regularly resistance trained. Unfortunately, blood flow was no examined.
At the end of the 8 week supplementation and training routine, there was no effect of AAKG on muscle mass or fat loss (7). Considering the lack of impact of other arginine supplements, this should not be surprising. What is surprising however is the incredible amount of strength the AAKG group added to their bench press 19lbs compared to a 6lb increase in the placebo group!
With unbelievable results like this, why haven’t you already ordered your arginine supplements? Well, for some it may be because the results are a little too good to be true. Looking at it critically, adding nearly 20lbs to a max bench in 8 weeks borders on “steroidlike” effects. What makes this even more interesting is that no changes in muscle were seen, which means that this strength gain was strictly a result of improvements in the nervous system. This is strange, particularly because these neural adaptations come far more slowly to trained subjects (which these were).
Although I find the data hard to believe as they stand, there is one more place to look for evidence: the web. Although I’m reluctant to point to this subjective and largely unreliable source, it can be very helpful in situations like this.
It seems as though some people perceive an effect from these supplements, but the strange thing is that no one can agree on exactly how the results manifest themselves. Most importantly, no one is claiming to feel steroid like effects from these supplements. Now you’d have to think that a group that really wants to believe the advertising would have the perception of the greatest results. So when even this group doesn’t agree, you have to wonder what’s going on.
As a final point on the study in question, it is important to note that an increase in cycling power was achieved through AAKG supplementation. This is often represented simply as “power” in advertisements, which although clinically correct, is meant to conjure up images of POWERful men, POWERlifting, and explosive POWER (as in Olympic weightlifting). Of course the reality is that this measure relates to none of these things. Sadly, it is theorized that the only reason for this increase in cycling power is due to an increase in muscle creatine content any benefit from which would pale in comparison to direct creatine supplementation.
So far it looks as though arginine and AAKG supplements don’t do a whole lot for blood flow, nutrient uptake, or muscle growth, but there may be a bright spot to all this. It is well know that arginine is a powerful stimulator of insulin secretion and in turn (4), insulin stimulates blood flow (3)! So although arginine can’t directly increase NO levels, it at least has the possibility to do so through insulin. Now looking at the collective data, it appears as though any such effect in negligible, and the resulting changes in muscle growth are nil, but it’s nice to know that the theory has at least some connection to reality – no matter how small.
In direct contrast the theory, all data to date indicate that arginine ingestion cannot stimulate either NO production or blood flow. Muscle mass is not affected by AAKG supplementation, although the question of effects on muscle strength remain open. Whatever the case, we need to stop calling them “nitric oxide supplements”. Perhaps “insulin supplements” would be more appropriate. For its complete lack of ability to affect muscle mass, arginine AKG receives the following…
- Anabolic Index Rating: 0
Clearly the popularity of supplements has more to do with marketing hype than actual efficacy. By understanding what we’re putting in our body, we’ll not only be able to optimize our results, but do it safely as well. The Anabolic Index was designed to show people exactly what the effects of supplementation are, such that the best overall combinations can be used.
Written by David Barr
Discuss, comment or ask a question
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1. Adams MR, Forsyth CJ, Jessup W, Robinson J, Celermajer DS. Oral arginine inhibits platelet aggregation but does not enhance endothelium – dependent dilation in healthy young men. J. Am. Coll. Cardiol. 26 (1995), pp. 1054—1061
2. Avena RM, Bowen WJ. Effects of carnosine and anserine on muscle adenosine triphosphatases. J Biol Chem. 1969 Mar 25;244(6):1600-4. 66% increase in activity
3. Baron AD. Hemodynamic actions of insulin. Am J Physiol. 1994 Aug;267(2 Pt 1):E187-202
4. Beaumier L, Castillo L, Ajami AM, Young VR. Urea cycle intermediate kinetics and nitrate excretion at normal and “therapeutic” intakes of arginine in humans. Am J Physiol. 1995 Nov;269(5 Pt 1):E884-96
5. Bode-Boger SM, Boger RH, Galland A, Tsikas D, Frolich JC. L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. Br J Clin Pharmacol. 1998 Nov;46(5):489-97
6. Boehm E, Chan S, Monfared M, Wallimann T, Clarke K, Neubauer S. Creatine transporter activity and content in the rat heart supplemented by and depleted of creatine. Am J Physiol Endocrinol Metab. 2003 Feb;284(2):E399-406.
7. Campbell B, Roberts M, Kerksick C, Wilborn C, Marcello B, Taylor L, Nassar E, Leutholtz B, Bowden R, Rasmussen C, Greenwood M, Kreider R.Pharmacokinetics, safety, and effects on exercise performance of l-arginine alpha-ketoglutarate in trained adult men. Nutrition. 2006 Sep;22(9):872-81.
8. Castillo L, Sanchez M, Vogt J, Chapman TE, DeRojas-Walker TC, Tannenbaum SR, Ajami AM, Young VR. Plasma arginine, citrulline, and ornithine kinetics in adults, with observations on nitric oxide synthesis. Am J Physiol. 1995 Feb;268(2 Pt 1):E360-7
9. Chin-Dusting JP, Alexander CT, Arnold PJ, Hodgson WC, Lux AS, Jennings GL. Effects of in vivo and in vitro -arginine supplementation on healthy human vessels. J. Cardiovasc. Pharma-col. 28 (1996), pp. 158—166
10. Chin-Dusting JP, Kaye DM, Lefkovits J, Wong J, Bergin P, Jennings GL. Dietary supple-mentation with -arginine fails to restore endothelial function in forearm resistance arteries in pa-tients with severe heart failure. J. Am. Coll. Cardiol. 27 (1996), pp. 1207—1213
11. Gagnon M, Maguire M, MacDermott M, Bradford A. Effects of creatine loading and deple-tion on rat skeletal muscle contraction. Clin Exp Pharmacol Physiol. 2002 Oct;29(10):885-90.
12. Harris RC, Hill C, Wise JA. Effect of Combined ß-alanine and creatine monohydrate sup-plementation on exercise performance. Medicine & Science in Sports & Exercise. 35(5) Sup-plement 1:S218, May 2003.
13. Harris RC, CA Hill, HJ Kim, L Boobis, C Sale, DB Harris, JA Wise,. Beta alanine supple-mentation for 10 weeks significantly increased muscle carnosine levels. FASEB J. 19(5) II 566.8 2005
14. Horn M, Remkes H, Stromer H, Dienesch C, Neubauer S. Chronic phosphocreatine deple-tion by the creatine analogue beta-guanidinopropionate is associated with increased mortality and loss of ATP in rats after myocardial infarction. Circulation. 2001 Oct 9;104(15):1844-9.
15. Kan HE, Buse-Pot TE, Peco R, Isbrandt D, Heerschap A, de Haan A. Lower force and im-paired performance during high-intensity electrical stimulation in skeletal muscle of GAMT-deficient knockout mice. Am J Physiol Cell Physiol. 2005 Jul;289(1):C113-9.
16. Kurz S, Harrison DG. Insulin and the arginine paradox. J Clin Invest. 1997 Feb 1;99(3):369-70
17. Neu A, Neuhoff H, Trube G, Fehr S, Ullrich K, Roeper J, Isbrandt D. Activation of GABA(A) receptors by guanidinoacetate: a novel pathophysiological mechanism. Neurobiol Dis. 2002 Nov;11(2):298-307.
18. Neubauer S, Hu K, Horn M, Remkes H, Hoffmann KD, Schmidt C, Schmidt TJ, Schnackerz K, Ertl G. Functional and energetic consequences of chronic myocardial creatine depletion by beta-guanidinopropionate in perfused hearts and in intact rats. J Mol Cell Cardiol. 1999 Oct;31(10):1845-55.
19. O’Gorman E, Beutner G, Wallimann T, Brdiczka D. Biochim Biophys Acta. Differential ef-fects of creatine depletion on the regulation of enzyme activities and on creatine-stimulated mi-tochondrial respiration in skeletal muscle, heart, and brain. 1996 Sep 12;1276(2):161-70
20. Parkhouse WS, McKenzie DC, Hochachka PW, Ovalle WK. Buffering capacity of depro-teinized human vastus lateralis muscle. J Appl Physiol. 1985 Jan;58(1):14-7.
21. Pette D, Staron RS.Transitions of muscle fiber phenotypic profiles. Histochem Cell Biol. 2001 May;115(5):359-72.
22. Robinson TM, Sewell DA, Greenhaff PL. L-arginine ingestion after rest and exercise: effects on glucose disposal. Med Sci Sports Exerc. 2003 Aug;35(8):1309-15
23. Suzuki Y, Ito O, Mukai N, Takahashi H, Takamatsu K. High level of skeletal muscle car-nosine contributes to the latter half of exercise performance during 30-s maximal cycle ergome-ter sprinting. Jpn J Physiol. 2002 Apr;52(2):199-205.
24. Turinsky J, Long CL Free amino acids in muscle: effect of muscle fiber population and den-ervation. Am J Physiol. 1990 Mar;258(3 Pt 1):E485-91.
25. Yaspelkis, BB, III, and Ivy JL. The effect of a carbohydrate-arginine supplement on post-exercise carbohydrate metabolism. Int J Sport Nutr 9: 241-250, 1999
26. Yun J, Parker CJ Jr. Biochim Biophys Acta. 1965 Oct 25;110(1):212-4. The effect of car-nosine on myofibrillar ATPase activity. 60% increase in activity
27. Zugno AI, Stefanello FM, Streck EL, Calcagnotto T, Wannmacher CM, Wajner M, Wyse AT. Inhibition of Na+, K+-ATPase activity in rat striatum by guanidinoacetate. Int J Dev Neurosci. 2003 Jun;21(4):183-9.
28. Zugno AI, Franzon R, Chiarani F, Bavaresco CS, Wannmacher CM, Wajner M, Wyse AT. Evaluation of the mechanism underlying the inhibitory effect of guanidinoacetate on brain Na+, K+-ATPase activity. Int J Dev Neurosci. 2004 Jun;22(4):191-6.
29. Zugno AI, Scherer EB, Schuck PF, Oliveira DL, Wofchuk S, Wannmacher CM, Wajner M, Wyse AT. Intrastriatal administration of guanidinoacetate inhibits Na+, K+-ATPase and creatine kinase activities in rat striatum. Metab Brain Dis. 2006 Mar;21(1):41-50.”Oxidative damage”