Nitric oxide (NO∙), initially known as endothelium derived relaxing factor (EDRF), is biosynthesized within the body from L-arginine and oxygen by a variety of nitric oxide synthase enzymes (Col lier and Vallance, 1991). Nitric oxide is a gaseous chemical compound that acts as an important signaling molecule within the human body. Nitric oxide has been shown to decrease platelet and leukocyte adhesion, as well as to decrease the proliferation of smooth muscle cells. These effects are important in reference to decreasing clot and lesion formation within blood vessels, which may be associated with non-fatal and fatal outcomes (e.g., heart attack, stroke). Recent evidence also indicates that NO∙ may be involved in both glucose and fatty acid oxidation (Jobgen et al., 2006). Although, perhaps the most well studied effect of NO∙ is in facilitating vasodilation (opening of blood vessels).
The endothelium (inner layer) of blood vessels is involved in NO∙ production, which acts on vascular smooth muscle cells to promote vasodilation. For this reason alone, nitric oxide has received considerable attention over the past 20+ years from scientists. In fact, NO was recognized as “molecule of the year” by Science in 1992. Additionally, the Nobel Prize in Physiology or Medicine was awarded in 1998 to Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries related to NO∙. Over the past 5 years in particular, NO has received a great deal of attention from health and fitness enthusiasts, as well as from sports supplement companies who widely market products cl aiming to increase NO production. In this regard, the primary desired effect is the potential increase in blood flow.
It is evident that the majority of such products contain various forms of L-arginine as the chief ingredient. Unfortunately, as discussed below, this may not be appropriate when considering all variables know to affect the response to L-arginine treatment (e.g., dosage, route of administration, species studied). Equally important, although L-arginine is the precursor to NO∙ biosynthesis, it has been suggested that this amino acid is not the rate limiting component (Kurz and Harrison, 1997) and that nitric oxide synthase enzymes may be most important to NO∙ biosynthesis. Therefore, adding excess L-arginine may do little to promote increased NO∙ production, as most individuals already have adequate L-arginine available for NO∙ biosynthesis. What they may need is an increase in certain enzymes that appear to ultimately control NO∙ production. The supposed “effect” that individuals may experience when using many of the marketed products may be more dependent on the sugar contained within the product, as opposed to the L-arginine. This is because sugar intake results in an insulin spike, and insulin itself has been shown to yield a vasodilating effect (Giugliano et al., 1997; Steinberg et al., 1994).
Despite this, it is evident that dietary supplements marketed to increase NO∙ production are rampant within the supplement industry. In fact, a quick scan of many of the popular bodybuilding magazines indicates that in any given month there can be more than 30 pages of advertisements that focus solely on this particular class of supplements! As with many dietary supplements, the scientific evidence for effect for these products is virtually nonexistent. Of course, some of the chief ingredients found within some of these products may have been shown to result in a measurable increase in NO∙ or an increase in blood flow. But a careful review of the original investigations indicates that the dosing suggested by the manufacturer of the product is often FAR less than that used in the original investigation. More importantly, the route of administration is often different. That is, many original investigations using a given ingredient have used intravenous injection and not oral intake, as is being marketed by supplement companies. This is of particular importance, as L-arginine at an oral dosage of only 10 grams per day has been noted to have an unpleasant taste and in some cases result in gastric distress (Robinson et al., 2003). It has also been reported that oral intake of L-arginine of 20+ grams per day results in arginine absorption that is highly variable across subjects, and does not result in any significant increase in vasodilation (Adams et al., 1995; Chin-Dusting e t al., 1996), unlike findings from many studies involving intravenous injection. Other work involving direct comparisons between intravenous and oral intake of L-arginine agrees with these findings (Bode-Boger et al., 1998), indicating no effect of oral L-arginine intake on vasodilation, partly due the fact that oral L-arginine bioavailability is only ~68%. Hence, based on the available evidence, it seems unlikely that oral L-arginine intake will result in any improvement in blood flow. Lastly, some of the original investigations have used animals (typically rodents) as test subjects and not humans, or have involved experiments in vitro (i.e., outside of a living organism). Generalizations to humans cannot always be made from such studies. Collectively, the fact remains that no nutritional supplements marketed to increase NO∙ have been shown in a controlled laboratory study involving human subjects to increase blood levels of NO
Go to any message board or any supplement store and you’ll find people “raving” about various NO products saying what a great pump it gave them.
Here are some things I pulled off the message boards about people talking about taking a certain NO product and their reviews. Get ready to laugh! ( I thought it was funny at least)
This is the best pre-workout supplement available. I have tried several different brands to improve my workouts and this has fit the bill. In my opinion the Orange is by far the best tasting flavor available. Lemon Lime is the worst.
Great product, provides great pumps high concentration lots of energy while I haven't experienced any side effects I definitely would recommend this product to anyone. Anytime I am feeling like not working out - this stuff gets you pumped and ready to go. My workouts are truly more aggressive and it's hard for me to stop once I'm at the gym. You will most likely develop a tolerance to this stuff: The first day I took one scoop and once bouncing off the walls - 6 weeks later I have to take 2 scoops to get that same feeling. Other than that it is definitely a great product!
This product does what it claims. Fantastic pumps and engery to boot.
One of the best Nitric Oxide products out there.It beat NO2 Grey as far as strength and pump in the Gym. Pump was good for 24+ hours, very good for every other day supplement. Price is half of what NO2 Grey cost($46 compared to $85-$100).The only thing i can find wrong with this product is it can cause some stomach discomfort and a little hot flashing. Try taking half the packet-wait 15-30 minutes before taking other half!!!
(Side note for this last comment, the stomach discomfort is caused by all the krappy Chinese ingredients in this product. I categorize these supplements as 9 Ckitchen sink supplements” Supplements that contain 100 different ingredients to make it look really fancy on the back of the label. But in reality the product should say on the back “Made in China)
So if you got 1000’s if not tens of thousands of supplement users saying they took a particular NO product and it worked for them what gives? How come all of these thousands of people that are using NO products say they work? How it gave them great pumps, how it increased their squat or bench press? How come every single online supplement website and brick and mortar vitamin store sells NO products. They wouldn’t sell me something that didn’t work, would they?…
Here’s some tricks the supplement company’s use to make an L-arginine supplement supposedly work. To make that guy in the gym say, “Man I take Red Blood NO Pump Vasodialtor Extreme with a high tech version of arginine and man it really gives me energy and pumps me up!!!” Well wake up stupid and quit buying supplements that you see advertised in the muscle magazines.
#1 The “But I did get a pump, must’ve been for this NO supplement trick”.
“Our NO supplement gives you “skin-tearing pump”, advertises a big juiced up bodybuilder in some muscle magazine. You take the supplement and you do actually get a pump. Therefore you come to the conclusion the supplement actually did “work”. Here’s a fact, during exercise muscles need an increase of blood flow. Your body will automatically direct more blood to the veins. When you are NOT exercising approximately 15 to 20% of the blood pump from the heart goes the muscle. When you ARE exercises, at peak, up to 80% of the blood goes to the muscle. No supplement is needed for this, no special L-arginine, nothing, your body increases 4-fold the amount of blood going to the muscle, thereby giving you the “pump”. Here’s a typical NO product with just straight up arginine. This product will have zero effect on your body, but since you take it and then train and get pumped you think it’s the product that actually caused the pump.
-Arginine Alpha Keto-Glutarate (AAKG) (Triple Action Super Duper Knock Your Balls Off Nitric Oxide Matrix) L-Arginine AKG, L-Arginine Ethyl Ester, L-Citrulline
Wow with this one you get “triple action arginine action, “more like triple nothing action!
#2 The “Man this product gets me really wired and pumped trick”
A Supplement company will make a NO product that has a formula of some crazy form of L-Arginine, usually called the proprietary “mind blowing, garden hose vein matrix” and then they list ingredients, something like this
(Nitric Oxide Super Duper full of bull**** and the kitchen sink Matrix) D-glucose monosaccharide, l-arginine, l-aspartic acid, disodium phosphate, dipotassium phosphate, dicalcium phosphate, xanthinol nicotinate, l-arginine ketoisocaproic acid, l-arginine ethyl ester HCL, l-norvaline, l-norvaline ethyl ester HCL, l-citrulline, citrulline malate, l-citrulline ethyl ester, l-histidine alpha ketogluterate, gynostemma pentaphyllium extract (root) standardized to 85% gypenosides, acetyl-l-carnitine l-arginine dihydrochloride, salvia miltiorrhiza bunge extract (root) standardized to 10% cryptotansinone, artichoke flavonoids (as cynara scolymus L.) (root) standardized to 5% chlorogenic acid, crataegus pinnauficia bunge extract (fruit).
Secondly, they will add amphetamies but call them focus or energy proprietary blends and they usually look something like this.
(Energy Hopped up Blend to make you feel like you drank 5 cups of coffe) (Caffeine anhydrous supplying 200mg of caffeine, wasaba japonica powder [root], yohimbine HCL [as pausinystalia yohimbe] [bark], schisandra chinensis extract [fruit] standardized for 2% schisanrinsides, alpha lipoic acid, theobroma c acao extract [seed] standardized for 6% theobromine)
Therefore you take this supplement, get wired, because caffeine gets you wired, that is common sense, and you get pumped, because that is what happens automatically when you work out. Bingo the supplement worked!! (yea and for the same thing you could have spent $3.99 for a thing of Red Bull)
#3 The adding high GI carbs to give you an increased insulin level trick
A lot of NO supplements will contain high GI carbs like maltodextrin and dextrose. Maltodextrin increase insulin levels in the body which in turn has a direct effect on vasodilation. Of course the product will contain varies forms of L-arginine but of course we now know arginine is worthless when it comes to NO production.
Take a look at what this supplement company calls dextrose (a cheap corn processed ingredients).
Nansomal Rapid Transport Matrix Esodex (molecularly charged beta-D-glucose)
#4 The toss in some creatine monohydrate and call it a NO product trick
I would say about 70% of NO products contain creatine. Wonder Why? Take a look at something I found. This product tried to use every form of creatine and then every form of arginine. Really it doesn’t make any sense, but since every supplement company is a follower of the next….WTF why not?
Tricreatine Malate, Dicreatine Malate, Creatine Monohydrate, Magnesium Creatine Chelate. L-Taurine, Betaine Anhydrous, Citrulline Malate, Arginine AKG, Beta-Alanine, Alpha Lipoic Acid, 4-Hydroxyisoleucine (20%).
Here’s another
Kre-Alkalyn 1.5 g Creatine Ethyl Ester 1.1 g Tri-Creatine Malate 1.5 g Betaine Hydrochloride 2 g Taurine (micronized) 2 g N-Acetyl-L-Glutamine 1.1 g (Arginine alpha ketogluterate, arginine ethyl ester dihydrochloride) (Beta-alanine, glycerol monostearate, medium chain triglycerides, citrulline ethyl ester malate, l-norvaline, guanidinopropionic acid, gynostemma pentaphyllum, ornithine alpha ketogluterate, arginine ketoisocaproate, r-alpha lipoic acid, rutaecarpine, glycocyamine)
Once again we see a company taking various forms of creatine and various forms of arginine. Most of these products are worthless (I think all forms of creatine are ****, except for CREAPURE, and Conjugated Creatine, see my previous email for that article) Taking this product will result in consuming large amounts of creatinine, not creatine.
So what now? What could one do to achieve a better pump? Here are a few things that are NOT based on bull****, lies, bogus ingredients, and deception. They are based on the truth
#1 Use creatine monohydrate or Conjugated Creatine. I only recommend Creapure or Con-Cret. Any other form is from China and could possible contain large amounts of creatinine. (see my email for more info on the quality of creatine)
#2 Take high GI carbs pre workout 1.5 hours before. This is an easy one but does have its drawbacks.
#3 Testosterone. Probably the most effective! Increase your testosterone levels one way or another and I guarantee you will get the best pumps of your life.
#4. Find a supplement that is actually PROVEN to increase Nitric Oxide. What???? Yes that is right, find an ingredient that actually DOES increase Nitric Oxide. Wait a second, I just wrote an article about how arginine is worthless junk. Well I’m not talking about arginine. There is an ingredient that has been proven in studies to raise NO levels. The ingredient is called Glycine Propion yl-L-Carnitine (GPLC). Glycine Propionyl-L-Carnitine (GPLC) is a USP grade dietary ingredient which consists of a molecular bonded form of propionyl-L-carnitine and one of the carnitine precursor amino acids, glycine. Two recent studies have demonstrated an increase in blood levels of NOx with oral GPLC intake, at a daily dosage of 4.5 grams (Bloomer et al., 2007; in press). These findings agree with other recent work using PLC exclusively (Lofreddo et al., 2007) which demonstrated an increase in blood NOx in response to 6 grams per day of PLC given via intravenous infusion.
The first study to use GPLC involved previously sedentary men and women who were assigned to supervised aerobic exercise with or without treatment for eight weeks (Bloomer et al., in press). A significant increase in resting levels of blood NOx was noted for subjects receiving GPLC compared to placebo (in a double blind design). Subjects who received GPLC were also noted as having lower levels of lipid peroxidation, a measure of free radical mediated oxidation of lipids. This is important, as increased free radical production is associated with impaired NO bioavailability.
The second study to use GPLC involved resistance trained men who were assigned to GPLC and a placebo for four weeks each, with a two week washout period between each four week ph ase—also using a double blind design (Bloomer et al., 2007). At the end of each four week phase, resting blood samples were obtained, in addition to blood samples following static forearm exercise (used to induce a further increase in NO). Blood NOx was noted to be higher in response to the forearm exercise with GPLC compared to placebo, a finding that may have implications related to enhanced blood flow during acute bouts of exercise.
Need for Further Research
If a given oral dietary supplement is in fact capable of stimulating an increase in circulating NO(to date, GPLC is the only such ingredient reported in the scientific literature to do so), to observe a desired effect it must be assumed that 1) the increase in circulating NO will cause an increase in blood flow to working skeletal muscle, 2) the increase in blood flow will be associated with an increase in oxygen and nutrient delivery, and 3) the increase in oxygen and nutrient delivery will promote a) an increase in work capacity during exercise and b) enhanced recovery post exercise. Study pertaining to these variables in human subjects using this class of nutritional supplement is indeed in its infancy. Continued work over the next couple of years will hopefully provide new insight into addressing these interesting and important issues.
Practical Applications
It is well documented that NO acts in blood vessel dilation and improved blood flow. For athletes and fitness enthusiasts, this is essential because greater blood flow is associated with increased oxygen and nutrient delivery to skeletal muscle. This may be important both during the exercise bout (to aid in performance and to improve the muscle “pump”), as well as during the recovery period (to aid in nutrient delivery to help facilitate exercise recovery). In this way, products aimed at increasing NO may prove helpful. To date, GPLC is the only dietary ingredient reported to promote such an effect, which may be enhanced if consumed with carbohydrate rich meals, as insulin has been shown to promote vasodilation (Giugliano et al., 1997; Steinberg et al., 1994) and to enhance carnitine retention (Stephens et al., 2006; 2007), which may apply to GPLC (a novel form of carnitine). Continued research on this ingredient will provide additional information pertaining to the potential for enhanced blood flow, and subsequent enhanced performance and recovery associated with exercise.
