Dave Barr has dug deep into the latest studies on arginine-based nitric-oxide (NO2) supplements. What he's found will surely blow the lid off this latest supplement debacle. If you missed Part 1, you can find it here.
There's one last theory that needs to be explored before this whole arginine supplementation myth can be buried: arginine and glycogen storage.
The idea put forth by the supplement companies is that arginine will increase blood flow and therefore carbohydrate delivery to muscle, subsequently increasing its uptake and storage. Of course, the whole impact of insulin is nowhere to be seen in their advertisements, but this physiological fact isn't lost on those conducting the research.
We've already seen one study using exercise with arginine showing that this combination had no effect, but there's another study worth mentioning – and this time they gave conditioned athletes so much arginine that all of the subjects got sick from it!
Yaspelkis and Ivy (1999) found that combined carbohydrate and arginine supplementation (seven grams per hour for three hours for a 200 pound athlete) non-significantly enhanced glycogen replenishment, compared to carbs alone, following cycling exercise in a carb depleted state.
In keeping with our findings, there was a decrease in glucose oxidation in the former group so that more could be used for glycogen storage. This makes sense, because both the amino acid itself, and the extra insulin release it can cause, will reduce the amount of glucose that's "burned off."
You might think that if these illness-inducing dosages of arginine don't work, then nothing will! But hold on, there's a better way to get the results we're after. If you want to do a much better job at storing glycogen and enhancing recovery, use whole proteins with your carbs! The benefits of this practice have been confirmed by the same research group in both earlier and later studies, and each time, the results were statistically significant (30, 22).
To summarize these results, subjects were given enough arginine to make them sick, and this still wasn't as effective as when whole proteins were used! In fact, the authors concluded: "The present investigation indicates that the ingestion of a single amino acid-carbohydrate supplement may not be nearly as effective as a carbohydrate-protein supplement in stimulating insulin secretion and thus enhancing muscle glycogen storage."(29).
Now if you really want to enhance glycogen storage, use something with high GI carbs and a high quality fast protein. This will have a double impact by creating a strong insulin spike and utilizing the anti-catabolic effect of the protein for maximum glycogen resynthesis.
To make matters worse for the industry folks, trained individuals have been shown to have a decreased arginine-induced insulin response (13), which would make these so-called arginine hemodilator products even less effective for us – as though that were possible. Bear in mind that this may be a result of enhanced insulin sensitivity, but it remains yet another question in the already pigeon-holed evidence for the efficacy of these supplements.
On a positive note, the enhanced insulin sensitivity that comes with endurance training (and possibly resistance training) increases the ability of insulin to stimulate blood flow (16). Additionally, the more insulin sensitive we are, the more blood flow becomes limiting to increases in glucose uptake (3). This means that glucose uptake happens so rapidly that blood flow just can't keep up with demand.
So we're less sensitive to arginine-induced insulin secretion, more sensitive to insulin stimulating blood flow, and blood flow can become limiting to nutrient uptake by the muscles. Putting this all together, it's clear that we need to focus on insulin production rather than arginine supplementation for maximizing our nutrient uptake. So now we're faced with the potential problem of really needing to jack up insulin levels for it to maximally enhance nutrient uptake.
Allow me to solve the problem by introducing a powerful, highly effective hemodilator: Surge®!
Yup, the same Surge® that we've always known and loved is a potent stimulator of muscle blood flow, glycogen resynthesis, and protein synthesis. It already does most everything expensive arginine supplements claim to do (but can't), plus a whole lot more.
Allow me to reiterate that the Surge formula has not been changed. It's still the same, near perfect, great tasting supplement most of you have always used. I'm also not claiming that you're suddenly going to have crazy new effects from Surge if you've been using it, or that Biotest has jumped on the bandwagon and started marketing it as a hemodilator. Rather, what I'm saying is that other companies have been hyping up some crazy theory while Biotest has always provided a proven blood flow stimulator that does so much more.
Oh, my skeptical, science savvy friend, you want evidence? Well it's all there in the carbohydrate and protein research literature!
One landmark study showed that even a full hour after training, blood flow remained elevated by 30% compared to rest, when an amino acid and carbohydrate formula was consumed right after the workout (28)! What's even better is that consuming the drink before exercise increased blood flow by over 300% during training, while a 200% increase was observed without drink consumption. In other words, you get an additional 100% increase from resting blood flow when the carbs and protein are taken before your workout! The pre-workout drink also maintained an elevated blood flow by 66% over normal resting values an hour after the workout.
While these data are certainly impressive, they don't mean anything unless they can also demonstrate that this increase in blood flow actually helped stimulate amino acid uptake by the muscle (i.e. protein synthesis). In fact, compared to rest, the pre-workout drink maintained amino acid uptake by ~230% a full 60 minutes after training, and the post-workout drink by 165%.
Now that's scientifically supported blood flow and amino acid uptake – something the so-called hemodilator products don't have.
If you're interested in even more science on Surge, along with methods to maximize its effectiveness, then be sure to check out the >Consumer Report detailing these very points.
And now cutting edge science has just given us yet another reason to get excited about a properly formulated workout drink. A new research study will appear soon in a peer reviewed journal about a Surge-like drink and its effects on muscle protein synthesis. Now, when I say "Surge-like," I mean that this product was nearly identical to Surge without the addition of glutamine, isoleucine, and valine. In fact, when I first saw it, I thought that this study was funded by Biotest! While the results were impressive, Biotest had nothing to do with it – unless you take into account that they inadvertently provided the idea for the formula.
As you'd expect, the pseudo-Surge gave huge increases in muscle protein synthesis following resistance training, even without the addition of extra leucine. The really cool part is that the addition of a single amino acid, leucine (like that in Surge) increased muscle protein synthesis by an additional 16% (20).
Although that finding didn't reach statistical significance, protein synthesis was significantly correlated with the amount of leucine ingested and further demonstrates the value of this essential amino acid. This makes Surge the first and only supplement scientifically shown to stimulate muscle protein synthesis. Not creatine, not glutamine, and certainly not some lame arginine-based NO2 supplement!
While it may be sad to see the dogma destroyed on arginine the way it was for glutamine, at least we can keep focus on leucine as the anabolic amino acid. Even still, leucine supplementation alone will have little effect on muscle protein synthesis without the addition of the other essential amino acids. This is because we need those other building blocks from which to build and repair muscle tissue.
Putting it another way: we can have all the anabolic signals in the world trying to make protein, but if there's no raw material, the job just ain't getting done! This is why a leucine-enriched protein carbohydrate supplement like Surge fills all the needs we have.
The Final Theory:
Fast Protein (Added Leucine) + High GI Carbohydrates → Insulin → Nitric Oxide → Vasodilation → Nutrient Delivery → Muscle Growth and Strength
- As we become more trained we become less sensitive to the effects of arginine, but more sensitive to the effects of insulin.
- Blood flow becomes more limiting to nutrient uptake as our training status improves, making it important to focus on insulin induced hemodilation.
- Protein and carbohydrate combinations have been shown to enhance glycogen resynthesis better than an arginine/carbohydrate mixture.
- Blood flow is enhanced by the consumption of pre- and post-workout drinks.
- Protein and carbohydrate drinks have been shown to stimulate muscle protein synthesis.
- Quantity of leucine was positively correlated with muscle protein synthesis in a post-workout drink.
- Surge combines all of the aforementioned ingredients and is the first supplement ever shown to enhance muscle protein synthesis.
If you've been reading with an open mind, then you've likely come to the conclusion that arginine-based nitric-oxide supplements have absolutely no value for anyone looking to put on muscle or become stronger. This isn't only because of the studies showing that they lack an effect, but more importantly because the direct effects of insulin have benefits that have been proven time and time again.
Finally, we've always known that pre- and post-workout nutrition are staples for meeting our goals. Now we have another reason to use a high quality training drink: leucine.
With the pro-hormone ban now in full effect, you'll be inundated with even more ads for arginine containing supplements, but armed with this knowledge you can just shrug them off and help others save their money. After all, the rabbit hole runneth deep indeed.
Consider the dogma destroyed!
Special thanks to Nathan Devey, David Lounsbury, and those who assisted in the editing of this document.
- Adams MR, et al. Oral -arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men. J. Am. Coll. Cardiol. 1995;26:1054–1061.
- Baron AD. Hemodynamic actions of insulin. Am J Physiol. 1994 Aug;267(2):E187-202.
- Baron AD, et al. Interaction between insulin sensitivity and muscle perfusion on glucose uptake in human skeletal muscle: evidence for capillary recruitment. Diabetes. 2000 May;49(5):768-74.
- Beaumier L, et al. Urea cycle intermediate kinetics and nitrate excretion at normal and "therapeutic" intakes of arginine in humans. Am J Physiol. 1995 Nov;269(5):E884-96.
- Besset A, et al. Increase in sleep related GH and Prl secretion after chronic arginine aspartate administration in man. Acta Endocrinol (Copenh). 1982 Jan;99(1):18-23.
- Bode-Boger SM, et al. L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. Br J Clin Pharmacol. 1998 Nov;46(5):489-97.
- Buvat J, et al. Endocrine screening in 1,022 men with erectile dysfunction: clinical significance and cost-effective strategy. J Urol. 1997 Nov;158(5):1764-7.
- Campbell B, et al. Effects of arginine alpha-ketoglutarate supplementation on body composition and training adaptations. Sports Nutrition Review Journal 1 (1): S10, 2004.
- Castillo L, et al. Plasma arginine, citrulline, and ornithine kinetics in adults, with observations on nitric oxide synthesis. Am J Physiol. 1995 Feb;268(2):E360-7.
- Chaput de Saintonge DM, et al. Harnessing placebo effects in health care Lancet. 1994 Oct 8;344(8928):995-8.
- Chin-Dusting JP, et al. Effects of in vivo and in vitro -arginine supplementation on healthy human vessels. J. Cardiovasc. Pharmacol. 1996;28:158–166.
- Chin-Dusting JP, et al. Dietary supplementation with -arginine fails to restore endothelial function in forearm resistance arteries in patients with severe heart failure. J. Am. Coll. Cardiol. 1996;27:1207–1213.
- Dela F, et al. Diminished arginine-stimulated insulin secretion in trained men. J Appl Physiol. 1990 Jul;69(1):261-7.
- Gater DR, et al. Effects of arginine/lysine supplementation and resistance training on glucose tolerance. J Appl Physiol. 1992 Apr;72(4):1279-84.
- Giugliano D, et al. The vascular effects of L-Arginine in humans. The role of endogenous insulin. J Clin Invest. 1997 Feb 1;99(3):433-8.
- Hardin DS, et al. Mechanisms of enhanced insulin sensitivity in endurance-trained athletes: effects on blood flow and differential expression of GLUT 4 in skeletal muscles. J Clin Endocrinol Metab. 1995 Aug;80(8):2437-46.
- Hishikawa K, et al. Effect of systemic L-arginine administration on hemodynamics and nitric oxide release in man. Jpn Heart J. 1992 Jan;33(1):41-8.
- Kerksick C, et al. Pharmacokinetic profile of time released and non-time released Arginine. Sports Nutrition Review Journal 1. (1): S9, 2004.
- Kirsch I, and Sapirstein G. Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication. Prevention & Treatment. Volume 1, Article 0002a, posted June 26, 1998.
- Koopman R, et al. The combined ingestion of protein and free leucine with carbohydrate increases post-exercise muscle protein synthesis in vivo in male subjects. Am J Physiol Endocrinol Metab. In Press 2005.
- Kurz S, et al. Insulin and the arginine paradox. J Clin Invest. 1997 Feb 1;99(3):369-70.
- Ivy JL, et al. Early postexercise muscle glycogen recovery is enhanced with a carbohydrate-protein supplement. J Appl Physiol. 2002 Oct;93(4):1337-44.
- Macdonald MJ, et al. Perspective: emerging evidence for signaling roles of mitochondrial anaplerotic products in insulin secretion. Am J Physiol Endocrinol Metab. 288: E1-E15, 2005.
- Marcell TJ, et al. Oral arginine does not stimulate basal or augment exercise-induced GH secretion in either young or old adults. J Gerontol A Biol Sci Med Sci. 1999 Aug;54(8):M395-9.
- Richmonds CR, et al. Nitric oxide synthase expression and effects of nitric oxide modulation on contractility of rat extraocular muscle. FASEB J. 2001 Aug;15(10):1764-70.
- Robinson TM, et al. L-arginine ingestion after rest and exercise: effects on glucose disposal. Med Sci Sports Exerc. 2003 Aug;35(8):1309-15.
- Steinberg HO, et al. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. Clin Invest. 1994 Sep;94(3):1172-9.
- Tipton KD, et al. Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exercise. Am J Physiol Endocrinol Metab. 2001 Aug;281(2):E197-206.
- Yaspelkis, BB, III, et al. The effect of a carbohydrate-arginine supplement on post-exercise carbohydrate metabolism. Int J Sport Nutr. 9: 241-250, 1999.
- Zawadzki KM, et al. Carbohydrate-protein complex increases the rate of muscle glycogen storage after exercise. J Appl Physiol. 1992 May;72(5):1854-9.