NITRIC OXIDE BOOSTERS: What Does the Science Say?
-THE LAB RAT-
By Tim Ziegenfuss, Ph.D
NITRIC OXIDE BOOSTERS: What Does the Science Say?
Does “NO” mean “yes?” If only it were that simple. In the supplement world, anecdotes are powerful things. They can make or break a product quicker than a Roy Jones Jr. fight. Nitric oxide (NO) boosters are a prime example – they have enjoyed a relatively good reputation for beneficial effects despite little direct, product-specific supportive science. In this short treatise, I will dig into some of the science behind NO boosters in the hopes of determining whether or not they have a place in your stable of bodybuilding supplements. I’ll also share some compelling new data on Gaspari Nutrition’s SuperPump250™ that has other companies selling NO boosters green with envy. And for the record, this article is not meant to endorse or slam any NO boosters, it’s simply my interpretation of ongoing clinical research. (For those who have trouble reading between the lines, that means I don’t receive any type of regular compensation [$ or free supplements] from Gaspari Nutrition.)
Those readers that dig the science like I do and are into the “nuts and bolts” of NO boosters should read this entire piece, head to Medline, and pull down the full references. Those that are late for the gym or are just interested in the “bottom line” can skip ahead to the NITRIC OXIDE RESEARCH section.
NITRIC OXIDE BACKGROUND
NO is a small, highly reactive gas molecule that impacts a host of biological functions in muscle, including: force production, autoregulation of blood flow, myocyte differentiation, respiration, and glucose homeostasis.4 The biosynthesis of NO requires l-arginine, oxygen, nicotinamide adenine dinucleotide phosphate (NADPH), and five cofactors (flavin adenine nucleotide, flavin mononucleotide, tetrahydrobiopterin, heme, and calmodulin). The synthesis of NO in muscle is mediated by a family of enzymes called NO synthases, of which there are three different forms (isoforms). Type 1 NO synthase, also referred to as neuronal (or nNOS), is thought to be the predominate form in skeletal muscle.4 nNOS is found in high concentrations along the muscle cell membranes of fast-twitch muscle fibers, where motor neurons innervate the various muscle fibers (neuromuscular junctions), as well as the myotendinous (muscle-tendon) junctions.2 As we will see shortly, these are physiologically strategic positions since they afford paracrine and autocrine-like functions to NO.
Figure 1. The biosynthesis of NO from arginine produces citrulline.
At first glance, the biological effects of NO seem dichotomous. On the one hand, NO has effects that most body builders would consider beneficial, such as increases in skeletal muscle blood flow, improved glucose transport, protection against reactive oxygen species (antioxidant effects), and the stabilization of proteins that make up the cytoskeleton of muscle cells. On the other hand, NO also has effects that many in the iron game would consider negative, namely the inhibition of acetylcholine release from pre-synaptic terminals, the inhibition of calcium release from the sarcoplasmic reticulum, inhibition of glycolysis, decreases in ATP synthesis from phosphocreatine, and decreases in mitochondrial respiration.2,4,6 Only when viewed collectively does the overall role of NO become clear: energy conservation. Put simply, NO helps match energy consumption with energy demand.
Before deciding whether or not to use a NO booster, it is important to examine all available data (however sparse) on the effects of NO boosters in humans. After all, many of the aforementioned effects have been observed in animals and/or using in vitro models.
NITRIC OXIDE RESEARCH
To the best of my knowledge, despite a dozen or more NO products on the market, only two studies have been performed on NO boosters.1,5 The first was done at Baylor University by Dr. Rick Kreider’s group (regular readers of MD should be familiar with Dr. Kreider and his outstanding work) and presented at the International Society of Sports Nutrition annual meeting. In that study, 35 men took either 12 grams/day of the leading NO booster or a placebo for eight weeks. All subjects were placed on a standardized training program and were asked not to change their dietary habits. Changes in body fat and lean mass (assessed via dual energy x-ray absorptiometry), upper body strength (via 1-repetition maximum bench press), and lower body performance (via sprint cycling and isokinetic endurance testing) were made before and after four and eight weeks of training and supplementation. Comprehensive blood chemistries were also examined for changes in cholesterol levels, liver enzymes, white cell counts, markers of catabolism, etc. The results of this comprehensive study were very interesting. For starters, supplementation with NO did not affect training-induced changes in body weight, body fat, or lean mass. However, the NO group did increase their bench press strength about 13 pounds more than the placebo group, and their peak sprint power by 78 watts (for some reason, the placebo groups’ peak power on the bike went down during the post-test). In contrast, two other indices of lower body sprint performance (time to peak power and rate to fatigue) were negatively affected by the current “quintessential” NO booster. Lower body isokinetic muscle endurance and blood chemistries were unaffected. In summary then, supplementation with the category-leading NO booster for eight weeks had no effect on three variables (body weight, body fat, lean mass), improved two (bench press strength, peak cycle sprint power) and made two others worse (time to peak power, rate of fatigue). On a positive note, NO boosting appears to be completely safe, at least during an eight-week period of supplementation in healthy males.
The second NO booster study I am aware of was performed on Gaspari Nutrition’s SuperPump250™. This study is particularly unique because it attempted to document acute changes in lean mass from a single dose of the product. The researchers reasoned that if SuperPump250™ boosted NO levels in muscle, the resulting vasodilation of arterial blood vessels should cause an expansion in the volume of lean tissue mass, particularly if supplementation was superimposed on a training session. Until the study is presented at a scientific meeting I can not divulge too many quantitative details, but here’s what I can say with certainty: in contrast to the Baylor study that found no change in lean mass over eight weeks of supplementation, subjects that consumed SuperPump250™ thirty minutes prior to training experienced a rapid, significant increase in estimated lean mass after only one dose. Let’s get to some details. In this pilot study, male subjects with at least two years of weight training experience completed a standardized workout (i.e., 5 sets x 10 reps for the biceps alternated with 5 sets x 10 reps for the triceps) under two conditions: 1) SuperPump250™ and 2) placebo. Consistent with good research design, diet and physical activity were tightly controlled (and duplicated) prior to each trial, and all subjects completed the trials in random order. In addition, all weights, reps and rest periods were kept exactly the same from one trial to the next. As in the Baylor study, changes in lean mass were measured with one of the most sensitive body composition devices currently available, dual energy x-ray absorptiometry (DEXA). After the statistical smoke cleared, the workout itself (i.e., the placebo trial) resulted in a respectable 3.5% increase in estimated lean mass of the arms. In contrast, during the SuperPump250™ trial, subjects experienced a 9% increase in estimated lean mass of the arms. Although more data (including a training study) are needed to verify these volume-induced effects, this two-and-a-half-fold increase in estimated lean mass relative to the placebo indicates that SuperPump250™ can markedly enhance the anabolic effects of training, particularly since it is known that increases in fluid volume cause increases in muscle protein synthesis and decreases in muscle protein breakdown.3 Put another way, taking SuperPump250™ prior to training may just make gaining muscle size twice as easy.
1. Campbell, B, J. Baer, M. Roberts et al. Effects of arginine alpha-ketoglutarate supplementation on body composition and training adaptations. Sports Nutrition Reviews 1(1):S14, 2004. Accessed online November 11, 2004.
2. Kaminski, H.J. and F.H. Andrade. Nitric oxide: biologic effects on muscle and role in muscle diseases. Neuromuscular Disorders 11:517-254, 2001.
3. Haussinger, D., F. Lang, and W. Gerok W. Regulation of cell function by the cellular hydration state. American Journal of Physiology 267, E343–E355, 1994.
4. Stamler, J.S., and G. Meissner. Physiology of nitric oxide in skeletal muscle. Physiological Reviews 81(1):209-237, 2001.
5. Vacanti, T., B. Campbell, J. Baer et al. Effects of arginine alpha-ketoglutarate supplementation on markers of catabolism and health status. Sports Nutrition Reviews 1(1):S15, 2004. Accessed online November 11, 2004.
6. Zhang, J.S., W.E. Kraus, and G.A. Truskey. Stretch-induced nitric oxide modulates properties of skeletal muscle cells. American Journal of Physiology Cell Physiology 287:C292-C299, 2004.