An analysis of Cellucor C4 Extreme Pre-workout dietary supplement w/ NO3 technology

A few days ago I stopped by the local GNC to buy some whey protein. In retrospect I partially wish I had just bought it online, as I would have probably saved a few dollars and avoided a sequence of awkward exchanges with the store owner.

In one of these exchanges, I pointed at some small containers on the shelf and asked what they were. It turns out they were ‘pre workout drinks’ which, according to the store owner “you see people drinking before their workout”. He offered $4 off, but even with this savings, each container was $30 (1 container = 30 servings).  I told him I prefer to research things before buying them, hoping to cut CLL-30105-5off his advances. However, he continued on an extended argument about how practical and economical the product is. I hate stonewalling people, but I felt I had little choice in this case.

The store owner was nice enough to give me a free sample, though, which made the awkward exchanges worthwhile (in so much as they have resulted in this interesting blog post).

These ‘pre-workout drinks’ are quite something, and in this article I will go through and analyze their ingredients. A while ago I wrote an article which analyzes many of the ingredients found in many energy drinks. The idea that there might be compounds which are ‘mental stimulants’, yet are non habit forming and have no harmful side effects, is a popular concept within certain intellectual circles, where they are known as ‘nootropics’. In my previous article, the overall conclusion is that the key ingredients found in most energy drinks are caffeine and sugar.  It remains my opinion that caffeine and sugar are the only two really effective nootropics on the market today. [Unless one broadens their definition of ‘nootropics’ to include long-term supplements] Caffeine and sugar are very well proven scientifically to be effective stimulants (although they differ greatly on what they do, how they work and what their healthy dose ranges are). For most of the other ingredients, I found little or no evidence showing they do anything to enhance mental performance but also no evidence showing they are harmful either.

CELLUCOR_C4_LABELI will go through the ingredients in the order they are listed, which should correspond to their weight fraction in the mix. Note that these are the amounts in 1 scoop (5.7 grams) , corresponding to half of one of the sample bags.

Beta alanine (1500 mg) This is a modified amino acid. According to Wikipedia, “β-Alanine is not used in the biosynthesis of any major proteins or enzymes“. There appears to be one study which shows a small effect on athletic performance, but I’m skeptical of it because it wasn’t posted in a peer reviewed journal. However, a review article in a peer review journal provides some biophysical basis for its action, suggesting that it can delay the onset of muscle fatigue. They also say that studies have shown it’s efficacy. In their abstract they also mention ” Symptoms of paresthesia may be observed if a single dose higher than 800 mg is ingested.” If you’re like I was and don’t know what paresthesia is, it is “a sensation of tickling, tingling, burning, pricking, or numbness of a person’s skin with no apparent long-term physical effects.”

Creatine Nitrate (1000 mg)  no doubt many of you have heard of this ingredient. Creatine Nitrate (C4H9N3O2.HNO) is a salt which dissolves in your stomach into 77 % creatine and 23 % nitrate by weight.[link] Wikipedia mentions three scientific studies looking for cognitive improvement due to creatine enhancement, two found some a slight enhancement over many weeks, another found no effect. I’d rather not go into all the details about creatine here, partly because the 777 mg of creatine here is not very much. Most bodybuilding professionals recommend 20 – 25g a day during the ‘loading phase’ which lasts 5-6 days. Thereafter, according to the American College of Sports Medicine,  2 g a day are necessary to maintain a slight surplus, due to natural degradation.[link] So in other words, the 777 mg in this product will only remain in your system for a few days at most, and probably won’t do much. Consider that creatine breaks down into a combination of three amino acids:  glycine, arginine, and methionine. (For a low level description of creatine chemistry, see here). All three of these can be found in GNC whey protein, at about twice the mg amounts per serving. Even though creatine is very popular, because of this fact I’m skeptical whether it is any more effective than whey protein, which, supplies more mgs of those amino acids per each dollar of cost. Almost all of the websites providing information about creatine are linked to suppliers trying to sell it, even websites that appear to be reviews by health professionals. The boom in creatine sales has been self perpetuating, with many people citing the boom in sales as strong evidence for its efficacy , thus leading to more sales. The placebo effect is probably very important here as well – if people are optimistic about their athletic results, they will achieve more in the weight room, and also feel more excited about whatever results they get, which they will happily attribute to the creatine. If one really wants to find out if creatine has a special biological mechanism of action besides just supplying three important amino acids, one should consult the scientific literature, something which I haven’t done.

Main ‘active’ ingredients

Nitrate This brings us to the 233mg of nitrate that was just referenced, which is advertised on the package as “NO3 technology”. This component annoys me. They seem to be playing off the public’s ignorance here, probably hoping people will confuse it with NOS (nitrous oxide, N2O, or laughing gas)  [NOS is found in some energy drinks, as a dissolved gas]  Creatine nitrate is formed by mixing creatine and nitric acid (HNO3). When it dissolves in the stomach, it seems pretty clear that the result should be nitrate ions (NO3-). In theory I suppose it’s possible that nitric oxide (NO) (which is a free radical) could form instead, but according to Wikipedia NO is converted by the body into nitrate for subsequent processing by the kidneys and disposal in the urine.  The troubling thing is that nitrate is a toxin (ever heard of nitrate contamination, or acid rain?). According to Wikipedia : “Nitrites oxidize the iron atoms in hemoglobin from ferrous iron (2+) to ferric iron (3+), rendering it unable to carry oxygen.”  This seems counterproductive to a workout.

Arginine AKG  (1000 mg) Arginine is one of the 20 ‘essential’ amino acids. It can be produced by our bodies, although not when we are infants. You might wonder then, if this compound is being produced and used all the time by our bodies for routine cell maintenance, what possible effects could be from consuming an extra gram? Well, first of all we need to understand that this is Arginine alpha-ketoglutarate (AAKG) is a salt of the amino acid arginine and alpha-ketoglutaric acid.  According to Wikipedia, “α-Ketoglutaric acids is sold as a dietary supplement and to body builders as AKG or a-KG with the claim that it improves peak athletic performance. This claim is based on studies that show excess ammonia in the body can combine with alpha-ketoglutarate, reducing problems associated with ammonia toxicity.[link] However, the only studies that show alpha-ketoglutarate can reduce ammonia toxicity have been performed in hemodialysis patients”

Vitamin C (250mg). There are two reasons this was included –  flavor and health appeal. People like vitamin C because it’s good for the immune system. Too much (several grams) might prevent proper absoption of other vitamins, but at the 250mg level there’s nothing to worry about. I have also heard anecdotal that Vitamin C ‘gives one energy’ but I don’t think there is any good reason to believe that. I don’t have any problem with this ingredient – gyms have a fair share of germs.

N-Acetyl-L-Tyrosine – there’s a good chance this was included solely because it has a fancy name! N-Acetyl L-Tyrosine is advertised as a “more rapidly absorbed and bioavailable form of the amino acid L-tyrosine, and is less prone to urinary excretion L-Tyrosine is converted in the body to key biological compounds, including epinephrine, dopamine, L-dopa, CoQ10, thyroid hormones, and melanin. The B vitamins pyridoxine (B-6), and folic acid are provided to assist in the conversion process.”.link Based on a quick glance on Wikepdia, it seems true that Tyrosine plays an essential role in many biological processes. For instance, ‘In dopaminergic cells in the brain, tyrosine is converted to levodopa by the enzyme tyrosine hydroxylase (TH) TH is the rate-limiting enzyme involved in the synthesis of the neurotransmitter dopamine‘ .  However, the fact it is essential in many processes doesn’t mean  mean it will boost athletic or mental performance beyond by just providing a nutrient the body uses for routine maintenance.  Wikipedia cites three scientific articles concluding “tyrosine does not seem to have any significant effect on mood, cognitive or physical performance in normal circumstances”

Caffeine Anhydrous (135mg) – this is, in my opinion, by far the most important ingredient. Numerous studies have shown caffeine enhances athletic performance, by reducing inflammation and opening airways, among other things. It also promotes focus, especially on repetitive tasks, such as lifting weights. The ‘anhydrous’ term just means there is no water, and the only reason this term was included is probably to make it sound fancy.

Mucuna pruriens (standardized for L-Dopa) This is one of the ingredients that caught my eye. L-DOPA is aprecursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine.  According to Wikipedia, L-Dopa can cause a lot of different side effects. This alone discourages me from taking it or researching it further. Also from Wikipedia: “Mucuna pruriens is a tropical legume known as velvet bean or cowitch”

Bitter Orange (Citrus aurantium)(fruit)(30% Synephrine)(Advantra Z(R)) : Synephrine is marketed as a ‘weight loss compound’. I found this quite annoying, because no where on the packaging does it mention weight loss. I am trying to achieve the opposite – weight gain – and many other people who go to the gym are doing the same. They don’t say how many mg of Synephrine are actually included, but according to Wikipedia 2-20 mg of synephrine are usually included in dietary supplements. As you can find on Wikipedia, there are several peer reviewed journal articles linking synephrine consumption with severe cardiovascular reactions.For instance, “ The Mayo Clinic published a report that suggested a link between Stacker 2 pills and increased risk of ischemic stroke, increased blood pressure, and myocardial infarction”. In one case, an otherwise healthy 24 year old male with no significant risk factors incurred heart problems and a heart attack. [luckily, because he was being treated at the time, he survived]. [link]  The bottom line here is I would stay away from this!

Niacinamide – from Wikipedia: “Nicotinic acid, also known as niacin, is converted to nicotinamide in vivo, and, though the two are identical in their vitamin functions, nicotinamide does not have the same pharmacological and toxic effects of niacin, which occur incidental to niacin’s conversion. Thus nicotinamide does not reduce cholesterol or cause flushing,[1] although nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults”_

Folate (as Folic Acid) – I guess this is here because it tyrosine sellers claim it helps with the conversion of tyrosine into other compounds (I didn’t bother to see if there is actually any evidence for this). It’s also possible they just wanted to add something that sounds healthy and which doesn’t cost much or take up much mass (it’s only 250mcg, which is 62% of one’s daily value).

Pyridoxal 5-Phosphate from Wikipedia: “It is the active form of vitamin B6, which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine.”

Vitamin B12 (35mcg, 588 % DV)- this is another B vitamin. I’m not sure what the obscession with B vitamins is nowadays. From what I can tell there is no reason to believe they ‘give you energy’ or ‘increase your endurance’. On the other hand, from what I read while I was researching energy drinks, large quantities of B vitamins can be consumed with little health risk. For instance, one shot of ‘5 hour energy’ contains a whopping 500mcg or 8333% DV.

Calcium (25mg, 3%) – as with vitamin B12, this was included just to make the product seem more healthy and because people know calcium is necessary for the bone hardening which accompanies muscle growth. However, the amount here is negligible and of no consequence.

Other minor ingredients

Natural and artificial flavors – they don’t say what these are but I doubt they are healthy for you.

Citric acid – this is likely in there to improve the flavor

Malic acid – this is a common souring agent. Apparently it is more sour and less sweet than citric acid.

Silicon dioxide – mmmm sand! SO2 is found in many processed foods as an anti-caking agent.

Calcium silicate – this is another anti-caking agent. Whey they need two is beyond me. According to one website, “Excess intake of Calcium Silicate has been known to trigger bronchitis and diminish lung function. Short-term exposure to the chemical can cause eye irritations and mild respiratory tract disorders. People with ADD should abstain from consuming foods containing Calcium Silicate as it can exacerbate the disorder.” [link]

Sucralose – This is an artificial sweetener. From what I’ve read in the past, it’s considered pretty safe.

FD&C Yellow # 5 – I didn’t really research this much at all, but a quick glance on Wikipedia shows that it is banned in Norway and Austria, which is cause for concern. I try to stay away from artificial coloring agents in general.

Acesulfame Potassium (Ace-K) – this is another artificial sweetener. Why they need this, especially when this is much more controversial and has a worse reputation than Sucralose, is hard to say. Perhaps having two artificial sweeteners helps make the sweetness taste more genuine.


Stay away from this product! The only useful ingredients for improving workout performance here are caffeine, creatine, and Beta alanine. Caffeine can easily be obtained by other means. In my opinion creatine & beta alanine are not worth the cost of buying separately, but one could if one wanted I suppose. The rest of the ingredients are a hodgepodge mix of amino acids and vitamins, along with some chemicals which are likely to do more harm than good. It’s definitely not worth spending money on this crap , let alone putting in your body.