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The topic of today's discussion is pre workout supplements. Let's talk about some fluorescent drinks.





Can they really give the performance benefits supplement companies claim? Are they safe? What exactly is in this stuff? Why do I need a master's in molecular chemistry to read the labels? Are they a total waste of money? Who comes up with the ridiculous names? Will they really give you the Xtreme Bionic Gorilla Nightmare Zone Skin Rupturing Muscles you've always wanted?



Let's take a close look at exactly what goes into these products, how they can benefit your performance, and what claims they fail to live up to.



Note: this article examines pre workout supplements in the context of resistance training. No discussion will be made on endurance or aerobic exercise. Similarly, the purpose and effect of these ingredients will be looked at only in the scope of performance enhancement. Many of the following have additional applications, side effects, drug interactions, additional medical considerations, and so on. This article is not intended to thoroughly discuss the entire cadre of potential effects from any of the following substances. Lastly, this article will only examine the effects of supplementation past normal baseline, with the assumption that no deficiency is present unless otherwise noted. This is, as you will see later, critical in understand/disproving certain claims made by supplement companies.





What Are Pre Workout Supplements?

There's lots of different supplements that could be labeled as "pre workout". This article specifically focuses on products that market themselves as pre workout supplement cocktails which contain a mixture of a whole bunch of stuff thrown into one jar.





They come in many different varieties. Some of the more popular choices include Jack3d, N.O. Xplode, Superpump Max, Craze, Cellucor C4, Black Powder, Animal Rage, The Curse, White Flood, Nano Vapor, N.O. Monster, XPand, and many more.





An important factor is that these products contain many or all of the same ingredients in varying amounts, with the remainder being some kind of proprietary or "special" ingredient. Each one is a bit different from its peers. Some are fairly standard, and some throw in very potent chemicals (that tend to be banned before too long, as in the case of ephedrine/DMAA and so on)





Therefore, we will examine the most common ingredients and a few of the less common ones. This article will NOT examine every ingredient ever put in any pre workout supplement. I would advise you to track down a specific ingredient list before making a purchase and see for yourself if there's anything questionable therein.



What's In This Stuff?

Let's take a look at a few common choices:

A quick look will reveal that there's some common ingredients, some that only a few share, and some that are unique to certain brands. The remainder of the article will look at exactly what these ingredients do for sure, what they may do, and what they absolutely do not do.



Ingredients (Alphabetical)



Adenosine-5'-Triphosphate Disodium

This is just plain old ATP in oral supplement form.



Let's nip this one right in the bud: oral ATP is not bioavailable. A study by Coolen et al, 2011 and other similar studies conclude that oral supplementation of ATP fail to increase ATP levels. It's simply broken down in the small intestine. Even at very high doses, far above what you'd find in a pre workout supplement, it still does nothing.



Oral ATP just doesn't work.





Arginine, Nitric Oxide Discussion of arginine must be prefaced with a brief primer on nitric oxide.



Nitric oxide is a gas which serves a host of functions in the body. As far as performance enhancement goes, we're concerned with it's vasodilative properties. Similar to how nitroglycerin or Viagra work, nitric oxide causes the relaxation and opening of blood vessels. The idea is that increasing nitric oxide levels will aid in inducing hyperemia (increased blood flow, the "pump") in muscle tissue.



Unfortunately, it isn't that simple. Blood pressure, smooth muscle (blood vessel) tone, and cardiac output are tightly regulated processes. Even if nitric oxide production was upregulated, your body has plenty of ways to return blood flow to whatever it thinks it should be at, which is generally commensurate with your activity level at the time. In other words, you aren't likely to fool your body into diverting 25% more blood than it needs to your biceps.



A fairly comprehensive symposium/review by Tschakovsky and Joyner, 2008 on multiple iterations of research all based on this topic indicates that the body is just too damned good at compensation. Increased levels of nitric oxide are generally counteracted by changes elsewhere to keep blood flow on point. Even in studies where direct infusions were used, it was concluded that nitric oxide does not increase vasodilation during exercise or hyperemia in muscle tissue.

All of that being said, the premise of arginine supplementation is that it is a precursor to nitric oxide production, and that supplementation will upregulate nitric oxide. A study by Alvarez et al, 2012, showed that arginine supplementation does not increase nitric oxide production. There's a healthy body of research on nitric oxide's effects and arginine's inability to upregulate production. In short, there's no evidence that nitric oxide causes hyperemia, and even if it did, there's no evidence that arginine supplementation increases nitric oxide.



On a related note, there's quite a few compelling studies which indicate that repeat dose dietary nitrates do in fact offer performance benefits. A review by Ferreria and Behnke, 2010, examine quite a few studies which all show that daily supplementation of dietary nitrates, most commonly in the form of beetroot juice, does in fact lower blood pressure, reduce the O2 and ATP cost of exercise, and may give the benefits people were looking for all along from nitric oxide based pre workout supplements.



The mechanisms through which this happens appear to be unclear; acute/single dose supplementation seems to do nothing, but daily use for 5-7 days does appear to offer marked performance benefits. Though none of the studies have been done on high intensity resistance exercise per se, the results remain promising.





...dietary NO 3 −, administered in the form of beetroot juice (500 ml/day for 6 days), decreases resting systolic blood pressure (SBP) and O 2 consumption during walking and running. ...authors selectively remove NO 3 − from beetroot juice to produce a NO 3 −-free juice as placebo. There was no placebo effect in any of the variables measured. Thus the decrease in O 2 uptake and SBP in their investigations can be assigned to dietary NO 3 −, rather than other compounds present in beetroot juice (e.g., polyphenols and/or quercetin). Moreover, the responses occurred in the absence of changes in phosphocreatine (PCr) recovery kinetics (estimate of mitochondrial oxidative capacity). Lastly, the effects of dietary NO 3 − occurred within 2.5 h and promoted an increase in exercise tolerance (11). Whether dietary inorganic NO 3 − is given as beetroot juice (1, 2, 11) or pharmacologically (12), the responses are seemingly consistent across different exercise modalities, although the precise mechanisms remain unclear.

This is an interesting topic, and one I may do more writing on later. Note that a few pre workout supplements do contain beetroot extract/quercetin, but I have no idea if that would emulate the effects of daily beetroot juice, especially in such small quantities. I doubt it, since the effective dosage of beetroot juice in clinical studies seems to be rather high (high enough to cause red stools and tooth staining).





B3

B3 will come in the form of niacin, nicotinamide, or niacinamide, or inositol hexanicotinate.





B3 is purported as a mood elevator, depression fighter, and fatigue reducer. The entire theory behind B3 supplementation is that it improves the availability of NAD/NADH, which are co-factors in ATP production. They also play a role in neurotransmitter production, including dopamine and adrenaline.





A study by Forsyth, et al, 1999, indicated that oral NADH could be an effective in treating chronic fatigue syndrome. Perhaps the most significant for our purposes are studies by Kay et al, 2000 and Moline et al, 2001, which showed some promise for NADH as counteracting the effects of sleep deprivation and jet lag.

It must be understood that these are pilot studies. They're simply a peek into whether or not there's a possibility or response to supplementation. None of them were conclusive enough to make any statements, and to my knowledge there's not a single quality study done on the subject of NADH/NAD as a performance enhancer. Furthermore, most of the studies that do exist used a sublingual (under the tongue) delivery method as opposed to the oral supplementation found in pre workouts, and also used NADH directly, instead of the niacin or nicotinamide found in pre workout supplements.





Does B3 supplementation offer any benefit to athletic performance, mental focus, or energy production? No one really knows. The cursory studies might indicate that B3 is an energy booster under the conditions of significant fatigue/sleep deprivation, but no one really knows at this point. The science is simply not there in any capacity.





B6

This will usually show up as pyridoxine hydrochloride or pyrodoxal-5'-phosphate.



Like B3, B6 is a co-factor in energy production, specifically in regards to the conversion of glycogen to glucose. It also plays a role in the production of dopamine, serotonin, and adrenaline.





The supposed benefit of supplementation is more efficient usage of carbohydrates/glycogen, as well as an upregulation of neurotransmitter production (mood enhancement, motivation, focus).

A scientific review of multiple studies by Malouf and Evans, 2003, revealed that there was no statistical difference in cognitive function between placebo and B6 groups. A similar review by Balk et al, 2006, showed the same findings.





To my knowledge, there is a complete absence of research on the subject of B6 as an improver of glycogenolysis, carbohydrate utilization, or anything of that nature.





There is literally not a single quality study on B6 as a performance enhancer of any kind. What the supplement companies seem to be calling this is a mood enhancer/motivator and glucose liberator; what science they're basing that on is completely absent. There's no evidence whatsoever that glycogenolysis is somehow improved, or that neurotransmitter production is upregulated.





The research would suggest that B6 as a performance enhancer is completely bunk.





B12

B12 will usually be in the forms of cyanocobalamin and methylcobalamin.



B12 is involved in the production of red blood cells, and appears to play a role in the maintenance of the myelin sheath that covers nerve cells. B12 supplementation is primarily used to treat b12 deficiency, pernicious anemia, and cyanide poisoning. I haven't seen evidence that it does much of anything when supplemented above normal values and below dangerous levels.



The same reviews by Malouf and Evans, 2003 and Balik et al, 2006, indicates that supplementation offers no cognitive improvement in normal populations. Studies by Lukaski, 2004, Hvas et al, 2004 and quite a few others show no cognitive function improvement compared to placebo.



This one is a head scratcher. I don't even understand what this is supposed to do, let alone if it lives up to claims. Are supplement companies claiming this will enhance mood or neurological function? There is absolutely no research to suggest that it does.



It has been said elsewhere, but it bears repeating that supplementation to cure deficiency and supplementation above normal values are two very separate things.







Beta Alanine/Carnosine

Beta alanine is an amino acid which serves as a precursor to carnosine production. Carnosine is a dipeptide which has a prominent role in buffering H+ ions/pH during intense activity.



The idea is that oral supplementation increases substrate availability for caronosine production, which in turn elevates muscle carnosine concentrations. This would allow increase work output at a high intensity From a meta-analysis by Hobson et al, 2012 :

...further support for the buffering role of carnosine in skeletal muscle comes from the higher concentrations found in fast-twitch muscle fibres (Harris et al. 1998), which experience the greatest levels of H+ accumulation during extreme physical work. In isolated muscle, the absence of carnosine as a buffering agent leads to fatigue due to acidification, which does not occur when carnosine is present in the surrounding medium (Severin et al.1953).

The meta-analysis, a comprehensive review of current literature by Culbertseon et al, 2012, a study by Caruso, 2010, and plenty of others all conclude that beta alanine supplementation does improve intramuscular carnosine availability and help buffer muscle acidity, granting considerable anaerobic/resistance exercise performance benefits.



That being said, the exact mechanisms at play, the measurable effect, proper dosing, and what activities it most aids are all in need of more research.



Somewhat similar to creatine, beta alanine supplementation allows for a bit more work output during all out activity, potentially letting you get that extra rep or that couple more seconds of hard sprinting. Whereas creatine allows for a prolonged stay in the ATP-PC energy pathway, carnosine staves off muscle acidity from all out activity.



Since fatigue from muscle acidity tends to set in a bit after the switch from the ATP-PC energy system to the glycolytic energy system, you can expect beta alanine supplementation to come into play just after creatine. In terms of resistance training, you might have creatine supplementation exerting its effects on the 1-3 rep range, and carnosine doing so on a higher rep range.

Caffeine

Every pre workout supplement not marked caffeine free will contain caffeine. I won't spend much time on this one as the performance benefits of caffeine are extremely well documented and you probably already know exactly how you respond to it.





What merits discussion is the variance of caffeine dosage between supplements, as it can be significant. The average dose per serving is around ~130mg; the highest of the lot is SCREAM, with 300mg. For reference, the average 7 oz cup of coffee contains between 100-130 mg depending on brew method, and some serving suggestions recommend up to 3 scoops at a time. Be aware that if you switch from coffee or one pre workout to another, the caffeine dosage can vary considerably.





Many companies won't disclose the amount of caffeine in their product, or label it as a proprietary blend. There's really no reason for this and I have no idea why it happens. A good rule of thumb would be to expect between 100mg-300mg per serving.





Carnitine/Tartate

Carnitine is an acid required for the transport of fatty acids to mitochondria for oxidation, and is often paired with tartate to boost absorption.



A study by Volek et al, 2001, indicates that carnitine+tartate supplementation offers benefits in mitigating tissue damage, perceived muscle soreness, and other exercise induced catabolic biomarkers following a 5 set, 15-20 rep squat protocol.



A review by Sahlin, 2011, indicates that supplementation standalone carnitine supplementation reduces lactic acid build up, which increases work capacity and delays fatigue. The kicker is that it took six months of consistent supplementation to do anything. Note that this was without the addition of tartate.



Most research more or less denounces oral carnitine supplementation as ineffective under normal circumstances, because who's going to supplement something for six months for minor improvements? Tartate seems to greatly improve carnitine uptake by muscle tissue, and necessitates the need for new research. It seems that carnitine may in fact offer quite a few performance and recovery benefits when paired up with tartate, but more research is needed.



Understand that carnitine supplementation alone is not particularly bioavailable. Be wary of pre workout supplements that don't also include tartate.





Creatine

Creatine is a proven enhancer of short term, maximal intensity performance. Like caffeine, its effects are extremely well documented. Supplementation increases the intramuscular availability of phosphocreatine, which acts as a phosphate reservoir for ATP synthesis. This allows the body to churn out more ATP as needed to power the ATP-PC energy system just a little bit longer to get out that extra bit of intense effort. If you'd like to know more about creatine as a standalone supplement, there's an extensive article in the nutrition section.





It has very few known side effects, especially at the dosages seen in pre workout supplements, and can largely be considered quite safe. The only concerns may be minor gastrointestinal irritation, bloating, and water retention. As with many other ingredients, creatine behooves adequate hydration to minimize the occurrence of side effects.





The amount of creatine per serving ranges from 1g to 3g. Depending on the amount of servings ingested, this is a relatively modest amount. If you use creatine as a standalone supplement in conjunction with pre workout supplements, care should be taken to avoid excess. Though excess creatine will be excreted, too much can increase the risk of dehydration and gastrointestinal problems. Establish how much creatine is in your pre workout supplement and either make up the difference or avoid standalone supplementation altogether.





Citrulline/Malate

Similar to premise of nitric oxide/arginine, citrulline is proposed to be a vasodilator/stimulator of hyperemia. It must be pretty powerful stuff considering bodybuilding.com labels it as an "Insane Pump and Vascularity Initiator" in their SCREAM product.



Citrulline is prone to the same logic as arginine; even if it did increase arginine availability/upregulate nitric oxide (possible), would the downstream effect ultimately increase vasodilation/cause muscle hyperemia? (no).



There isn't enough research to make a statement on the former. The only research available on citrulline as a nitric oxide upregulator involves rats and not humans, and even then, the rats had various deficiencies or metabolic conditions. There's no quality research directly measuring the effects of citrulline supplementation on nitric oxide regulation or vasodilation/hyperemia during exercise.



Personally, I wouldn't get my hopes up on this stuff giving you Xtreme Skin Ripping Pumps and Garden Hose Vascularity.



Glucoronalactone

Glucoronalactone is a molecule that plays a structural role in connective tissue.



Some have claimed that it has detoxifying, liver protecting properties, as well as some energy/cognition benefits.



There's practically no real information or study on glucoronalactone anywhere. What research there is has been done on animals, and what little information there is on its effects is entirely anecdotal.



Could it possibly be an ergogenic aid? Perhaps a better question is; why are companies throwing in a practically unstudied compound into a product?



Glutamine

Glutamine is a non-essential, naturally occurring amino acid.



The proposed benefit of glutamine supplementation is that it helps counteract proteolysis/gluconeogenesis of muscle tissue (muscle breakdown), particularly during intense activity, and helps provide aminos for protein synthesis (new muscle construction). Glutamine is also utilized by the organs responsible for immune system health. It's been postulated that supplementation supports immune function indirectly since hard training increases the demand on glutamine by the muscles, and by extension, reduces the availability for the organs responsible for immune function.



A study by Gleeson, 2008, showed that there were no significant improvements in immune health, anabolic growth, or protein sparing, even when paired with heavy resistance exercise.



In regards to immune function, the study indicates that though glutamine plasma concentrations are increased with supplementation, glutamine concentrations are practically never low enough to depress immune function in the first place, even under the conditions of severe burns or wounds. Even so, it was shown that glutamine plasma concentrations fall only under very long bouts of prolonged exercise (3+ hours), and actually increased in response to acute, high intensity exercise.



As stated in the study, protein synthesis requires sufficient levels of essential amino acids, not the presence of non-essential forms. In other words, if there's plenty of the 9 essentials, throwing some glutamine on top isn't going to do a whole lot.



As with many pre workout ingredients, there's a huge void of credible science backing any claims. What little there is suggests that glutamine supplementation is ineffective as a performance enhancer, anabolic agent, immune system booster, or protein sparer.



Lastly, there's been claims that glutamine "increases growth hormones by 400%". This is a great example of an absurd statistic looked at in a vacuum. While a large dose of glutamine may in fact do just that, a bout of resistance exercise will increase growth hormones by up to 20,000%.



Leucine/Isoleucine/Valine (Branched Chain Amino Acids)

Branched chain amino acids are a subset of essential amino acids. It's practically common knowledge at this point that ensuring adequate essential BCAA's both before and after a workout goes a long way in promoting protein synthesis, signaling mTOR, and combating muscle catabolism.



One example study by Gran and Cameron-Smith, 2011, delineates the benefits of BCAA's and there's plenty of other research to back it up. The overall benefits of adequate BCAA's are well established at this point, but is there any reason supplement with them pre workout?



First, it's important to realize that BCAA's come packaged along with many protein sources, being as they're essential. Whey protein is about 22% BCAA's, egg whites are about 70% BCAA's. Most hard trainers are getting plenty of BCAA's through maintaining adequate dietary protein either way. If you're eating in the ballpark of 1-1.5g protein per pound of body weight, there's pretty much no possible way you aren't getting plenty of BCAA's through your diet.



In that light, are BCAA's useful pre workout? By now, most know that training in a completely fasted, protein absent state is not a smart choice. You could supplement with 5-10g BCAA's pre or post workout, or just eat a couple egg whites/have a protein shake.



I see BCAA supplementation as having a very specific application for those who enjoy training on an empty stomach, but understand that they really shouldn't be training on an empty stomach. As mentioned on his site, this is a method Martin Berkhan recommends for those using Intermittent Fasting and training in the fasted window.





Magnesium, Phosphorus, Calcium, Vitamin C, Sodium, Potassium

I lump all of these into the same category, though they of course serve different functions in the body. These are all essentially vitamins and minerals that have been shown to often be somewhat deficient in a hard training population.



You can get them here, through diet, from a multivitamin/mineral, or direct supplementation. What should be recognized is that bioavailability varies greatly between forms of vitamins/minerals. For instance, the magnesium in these supplements is usually either undisclosed, or magnesium citrate. This form is far less bioavailable than magnesium oxide or hydroxide.



If you're looking for something that implicitly adresses vitamin/mineral deficiency, I wouldn't rely on a pre workout supplement to do it.



Stimulants (Non-Caffeine)

These come and go as legal climates change. The supplement business has a laundry list of quite powerful and potentially quite dangerous stimulants that have ended up on the banned substance list, including ephedrine and other -phedrines, amphetamines, 1,3-dimethylamylamine (DMAA), and many, many others.



Many pre workout supplements contain only caffeine and a few other ingredients that are supposed to be cognitive/focus/energy enhancers, such as the ones that have already been discussed. Less frequently, they may contain more powerful stimulants that are not (yet) banned.



This varies company to company and changes all the time. I would advise always looking under the stimulant section (or whatever ridiculous descriptor the company uses) for unrecognized substances and looking into them before use.





Taurine

Taurine is a prevalent organic acid found naturally in the body, and has been a very common food additive in recent years, most notably in energy drinks. It's involved in a great deal of biological processes, most notably osmoregulation and bile salt production.





It's been suggested by a few pilot studies that taurine paired with caffeine improve cognitive function, and that taurine alone may improve athletic performance. However, the research and evidence on the effects of taurine, if any, are practically non-existent.





Almost every study involving taurine has been done on energy drinks as a whole, or treatment to specific disease such as congestive heart failure, which renders them useless in discussing standalone taurine as a sports supplement. Despite its widespread use, there's not a whole lot known about taurine supplementation. Though research has discovered no side effects from supplementation, there's no studies on any long term effects either.





A study by Galloway et al, 2008, showed that oral taurine supplementation does elevate plasma taurine levels significantly (13 fold), but fails to elevate intramuscular taurine concentrations or effect carbohydrate or fat oxidation, PCr content, VO2 max, blood glucose and free fatty acid concentrations, or any other relative performance biomarkers. However, the study did show that post exercise concentration of threonine, an essential amino acid, was elevated, and that there may be some effect on BCAA interaction. On the whole, nothing too dramatic.





Lack of evidence prohibits a definitive statement, but cursory studies makes me very doubtful that taurine offers much of anything performance-wise.. The bottom line is that you get a lot of taurine in your diet, and it's shown to simply be excreted when taken in excess. I very seriously doubt that supplementation does much of anything at all.



Tyrosine Tyrosine is a common nonessential amino acid which plays a role in protein synthesis and neurotransmitter production.

Similar to the B vitamins, tyrosine supplemention is propsed as a cognitive function and energy booster. It's usually labelled under some kind of Xtreme Mental Lasor HyperFocus Initiation Protocol Formula, which really just means it's grouped with the stimulants.

The only two studies which test tyrosine as an ergogenic aid to exercise, performed by Struder et al, 1998, and Chinevere et al, 2001, showed no benefits or difference from placebo.

Similar to many other ingredients in pre workouts, what we're seeing here is that research suggested tyrosine supplementation could improve healthy neurotransmitter production under times of great or chronic stress, in which those neurotransmitter can run low or be depressed. There is no evidence to suggest that it offers any benefit to a healthy, non-clinically depressed, non-sleep deprived individual.

If you're serious enough to get gym time, then you're almost certainly serious enough to not absoluely neglect recovery, in which case tyrosine will likely offer no benefit.



Notable Issues With Pre Workout Supplements The efficacy of each ingredient notwithstanding, we've got some shady practices that all of these supplement companies are guilty of, to varying degrees.

The most concerning is the inclusion of practically unstudied compounds. You can bet that every substance in a pre workout is safe enough for acute use, that there would likely never be a dosage of anything high enough to cause real problems, and that there will be 50 different warnings on not overdosing. In an industry where word of mouth is (unfortunately) everything, the last thing a supplement company wants is a bad reputation. That being said, there's ingredients in most pre workout supplements which have absolutely no research on long term effects or chronic use, if any relevant research at all.

Secondly, much of the labeling is just flat out false advertising. You probably don't need me to tell you that supplement companies sometimes exaggerate claims, but a thorough examination shows that it's perhaps more serious. How is it even remotely ethical or honest to label something as "Insane Pump and Vascularity Igniter" when there is no evidence whatsoever to even suggest such a thing? Companies have access to the exact same studies that we all do, and probably a lot more. Much of the advertisements and claims are no more than blatant lies.



It's a double-edged sword that supplement companies aren't strictly regulated by the FDA. On one hand, they have the legal latitude to market all sorts of potentially (but probably not at all) beneficial ingredients without legal scrutiny or prescription use. They're free to call something a "blood flow amplifier" or, "cell voluminizing and growth complex" and base it off of, at best, conjecture. Bottom line, don't trust the companies, know your ingredients and their specific dosages and interactions, do research on proprietary blends or fishy substances.

Another consideration is the balancing act between different ingredients. For instance, does your pre workout supplement have higher or lower levels of creatine or beta alanine relative to caffieine or other stimulants? What if you're looking for 4-6g of creatine, but that entails ingesting another half a gram of caffeine to get it? This should absolutely influence your decision making process, as it's quite easy to be forced into taking a large dose of stimulants in order to get enough of the other ingredients you want.

Lastly, a somewhat unscrupulous practice that practically all of these companies use is renaming an innocuous or mundane sounding compound as something sexy and exotic. For instant, Gaspari labels their Peak ATP as containing adenosine 5'-triphosphate disodium and WOW, that sure sounds fancy! Except Adenosine 5'-triphosphate disodium is really just plain old ATP, the same stuff you make 100+ lbs of every day in your own liver and kidneys. Another example is N.O. Xplode listing 20 different subtypes of creatine, when it's all just creatine. It isn't "wrong", just a somewhat disingenuous marketing strategy.



Safety

Safety is a very difficult thing to quantify. It is of course possible to experience uncommon reactions to any substance, and there's a whole lot of different ingredients in pre workouts. In that regard, any such cocktail probably increases the risk of adverse reactions and makes it nearly impossible to determine exactly what could be causing problems. I haven't seen any particular ingredients that have acute side effects substantial enough to be labeled "unsanfe". Apart from that, if I were forced to comment I would say that pre workout supplements are generally safe for most users, provided they have some common sense on dosing and know how to read a label.



The words "pre workout supplement" and "addiction" often go hand in hand. I think addiction is a pretty strong word, but I could certainly see them being habit-forming. This isn't unique to pre workout supplements per se, but more specifically attributable to their relatively high stimulant concentration. If you enjoy a pleasant buzz from caffeine, then sure, anything you can get upwards of 7 cups of coffee's worth of caffeine from at a whack is likely to hook you.



Apart from that, there's probably a marginal risk of psychological addiction in that if you buy into them doing everything they're advertised to do, then you'll probably have a hard time going without that "extra edge". This is probably the most common complaint of chronic users; when they don't have their precious miracle juice, they just "feel weaker".



Note: these statements implicitly exclude any companies that sneak in potent stimulants or banned substances.



Summary

What you'll find in pre workout supplements is a mixture of ingredients that are more or less proven, possibly beneficial, flat out bunk, and even some that are just big question marks.



Are pre workout supplements worth using? That depends entirely on you. Are you the type who only wants to drop money on something proven effective/doesn't like the idea of putting unknowns into their body? If so, you're probably better off cherry picking bulk ingredients yourselfl. If you're a "can't hurt, might help" kind of person or you don't mind spending a bit extra for the convenience/good taste, then pre workout supplements are probably what you're after.



Understand that the majority of the claimed benefits are based off of corollary or unfounded conclusions often drawn from research that's been manipulated, taken out of context, or based off of practically nothing. It's often times a "One isolated study done on rats showed that XYZ could possibly elevate mood in those with depression/other conditions/a serious deficiency, so we threw in 5000% of your RDA cuz energy" approach.





Also, be aware that companies can list ingredients in various ways. For instance, some label B3, B6, and B12 with RDA's; others just throw them under an energy blend in undisclosed amounts and use more exotic terminology. I don't understand why companies do this, but they do. It's probably for the same reasons that Ultra Anabolic Sodium Chloride Hydration Absorptive Bulking Complex sounds sexier than table salt.



Lastly, know that often times, a less bioavailable/effective form of a substance will be used, probably because they're the cheaper. For instance, magnesium will often be of the citrate form and not oxide; yohimbe will usually be bark extract and not HCl, etc. If this concerns you, obtain the preferred form separately.



References

Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome Linda M Forsyth, Harry G Preuss, Ana L MacDowell, Leonard Chiazze, George D Birkmayer, Joseph A Bellanti. ANNALS OF ALLERGY, ASTHMA, AND IMMUNOLOGY, February, 1999, Volume 82, Number 2



Reinikainen KJ, et al. Neurotransmitter changes in Alzheimer's disease: implications to diagnostics and therapy. Neurosci Res. 1990;27:576-86.



Birkmayer JG. Coenzyme nicotinamide adenine dinucleotide: New therapeutic approach for improving dementia of the Alzheimerâ€™s type. Ann Clin Lab Sci. 1996;26(1):1-9



Kay GG, Viirre E, Clark J. Stabilized NADH as a countermeasure for jet lag. Presented at: 48th International Congress of Aviation and Space Medicine; September 17-21, 2000; Rio de Janeiro, Brazil.



Moline ML, Rebeta JL, Flye BL, et al. Effectiveness of NADH in alleviating effects of sleep deprivation in healthy middle-aged adults. Abstract presented at: The First International Conference on Mechanisms of Action of Nutraceuticals; October 2001.



Malouf R, Grimley Evans J. The effect of vitamin B6 on cognition. Cochrane Database Syst Rev 2003:CD004393.



Balk EM, Raman G, Tatsioni A, Chung M, Lau J, Rosenberg IH. Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials. Arch Intern Med 2007;167:21-30.



Lukaski HC. Vitamin and mineral status: effects on physical performance. Nutrition 2004;20:632-44.



Hvas AM, Juul S, Lauritzen L, Nexø E, Ellegaard J. No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. J Affect Disord 2004;81:269-73



Thiago S Alvares, Carlos A Conte-Junior, Joab T Silva, and Vânia Margaret F Paschoalin. Acute L-Arginine supplementation does not increase nitric oxide production in healthy subjects, 2012. doi:10.1186/1743-7075-9-54



Michael E Tschakovsky and Michael J Joyner. Nitric oxide and muscle blood flow in exercise. Applied physiology of nutrition and metabolism, vol 33, pp 151-161, 2008.

Michael Gleeson. Dosing and Efficacy of Glutamine Supplementation in Human Exercise and Sport Training. J. Nutr. October 2008 vol. 138 no. 10 2045S-2049S



Erik J. C. M. Coolen, Ilja C. W. Arts, Otto Bekers, Chris Vervaet, Aalt Bast, and Pieter C. Dagnelie. Oral Bioavailability of ATP after prolonged supplementation. British Journal of Nutrition (2011), 105, 357–366.



Leonardo F. Ferreria, Bradley J. Behnke. A toast to health and performance! Beetroot juice lowers blood pressure and the O2 cost of exercise. December 23, 2010, doi: 10.​1152/​japplphysiol.​01457.​2010



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