Since the inception of the Thermolife lineup a few years ago, nitrates have been a popular ingredient sold in dietary supplements. They are claimed to increase nitric oxide (NO) and provide all-day pumps. But do they live up to the hype? Let's take a look.
Do Nitrates Increase NO?
The answer is a resounding yes. Most NO products seek to exploit the classic pathway:
Citrulline -> Arginine -> eNOS -> NO
Nitrates, conversely are free from the rate-limiting steps and enzymatic barriers that "slow down" the classic pathway (this is partly why arginine does not work for increasing NO). As such, nitrates serve as an "exogenous" source of nitric oxide:
NO3 (nitrate) -> NO2 (nitrite) -> NO
So nitrates will indeed increase NO, and they will do so in a manner more effective than arginine/citrulline in healthy populations .
This leads to the next question: will nitrates provide "all-day" pumps? Well, NO will induce venous pooling and pumps/vascularity, and the half-life of nitrate salts is up to 8 hours, so nitrates will provide "long-lasting pumps," not so much all-day.
Will nitrates enhance performance?
Mechanism #1 - Improved efficiency of oxygen consumption
Absolutely, and the data here is remarkable. The data from one trial shows that time to exhaustion is increased without any accompanying changes in metabolic biomarkers indicative of energetic stress (i.e. lactate), meaning that nitrates effectively enhance muscular efficiency . This performance-enhancing effect is observed during low-intensity exercise (i.e. LISS cardio, high rep work) , moderate intensity exercise , and high intensity exercise (traditional weight training, HIIT, etc) [3, 4]. Of particular note, numerous studies have found that nitrates increase performance during intermittent, high intensity exercise bouts [4, 6]. Sound familiar? That's exactly what weight training is (HIIT too).
While we're briefly mentioning cardio, nitrates improve cardio performance as well, both for LISS (walking) and full-on running (MISS, HIIT) [7,8].
This makes nitrates the ideal performance-enhancing supplement for all conditions: cardio and lifting, of any intensity. You're missing out by not using this.
Mechanism #2 - Increasing calcium release from the sarcoplasmic reticulum
If you recall from our previous discussion of amentoflavone (http://anabolicminds.com/forum/supplements/255669-coops-corner-7-a.html), increasing calcium release in the muscle cell results in improved contractile force:
"The final trigger in muscle contraction is an increase in calcium in the muscle cell. This calcium is stored in an organelle known as the sarcoplasmic reticulum and is released in response to a neural stimulus. The calcium binds to key muscle proteins that result in contraction, and it has been shown that the more calcium released into the muscle cell, the more force is produced."
Amentoflavone acts on the ryanodine receptor, a receptor that lies downstream of another receptor in the muscle contraction cascade known as the dihydropyridine receptor (DHPR). Nitrates act on the DHPR to augment calcium release and increase muscle contractility, resulting in improved strength , an effect that has been documented in humans as well as the murine model [15, 16].
Of note, this may mean that combining nitrates and amentoflavone, which act on two separate portions of the calcium-release pathway, can create additive or possibly synergistic effects, depending on which step is limiting.
Bottom line: combine nitrates and amentoflavone. Both increase strength via complementary mechanisms.
Can nitrates directly increase muscle mass?
So we already established that nitrates increase NO/pumps/vascularity as well as performance via multiple mechanisms. These effects will indirectly result in muscle growth by pushing yourself harder and longer during training sessions. But can nitrates directly induce muscle growth?
Recent research has looked into NO as a possible method to induce myogenesis, and so far, the data is promising: nitrates may indeed be directly myogenic and aid in the muscle building process. Vasodilation via NO may increase MPS and mTOR activity in muscle cells [10, 11], and NO appears to play a direct role in the formation of new muscle cells [12-14]. This is fairly novel, because muscle typically grows via hypertrophy and myonuclear accretion from nearby satellite cells, and nitrates act directly on this pool of precursor satellite cells.
Which type of nitrate is best?
You want a nitrate salt, no beetroot extracts (which provide a fraction of the effective dose). Speaking in approximations regarding amino acid nitrates, 1 gram of amino acid nitrates should provide an ergogenic effect as per the data, with 2 grams probably being the optimal MAX dose. Taking more than this will probably be ergolytic due to the drop in BP.
As for the amino acid that is used, I'm partial to creatine or arginine nitrate.
I'd use creatine nitrate if I didn't have another source of creatine. By creating a salt, the creatine gains improved solubility and can be used even at < 3 grams to saturate creatine stores, in theory. So this can double up as a creatine and nitrate product if used at a high enough dose.
Arginine nitrate is my personal favorite because data shows arginine reduces nitrate tolerance . It's unclear how big of an issue nitrate tolerance (or the phenomenon wherein nitrates' effects "wear off" with time) is for supplemental nitrates, but if you want to err on the side of caution and avoid tolerance formation, arginine nitrate is your best bet.
Of note, I also recommend vitamin C with nitrates for preventing gastric nitrosamine formation, and NAC can be used as well to potentiate the effects of nitrates.
Hope you enjoyed this week's spotlight. Stay tuned for episode #4
1. Lundberg JO, et al. (2008). The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov.
2. Larsen, F. J., E. Weitzberg, J. O. Lundberg, and B. Ekblom. "Effects of Dietary Nitrate on Oxygen Cost during Exercise." Acta Physiologica 191.1 (2007): 59-66. Web.
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11. Timmerman KL, et al. (2010). Insulin stimulates human skeletal muscle protein synthesis via an indirect mechanism involving endothelial-dependent vasodilation and mammalian target of rapamycin complex 1 signaling. J Clin Endocrinol Metab.
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13. Buono, Roberta, Chiara Vantaggiato, Viviana Pisa, Emanuele Azzoni, Maria Teresa Bassi, Silvia Brunelli, Clara Sciorati, and Emilio Clementi. "Nitric Oxide Sustains Long-Term Skeletal Muscle Regeneration by Regulating Fate of Satellite Cells Via Signaling Pathways Requiring Vangl2 and Cyclic GMP." Stem Cells 30.2 (2012): 197-209. Web.
14. Palma, Clara, and Emilio Clementi. "Nitric Oxide in Myogenesis and Therapeutic Muscle Repair." Molecular Neurobiology 46.3 (2012): 682-92. Web.
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16. Hernandez, A., T. A. Schiffer, N. Ivarsson, A. J. Cheng, J. D. Bruton, J. O. Lundberg, E. Weitzberg, and H. Westerblad. "Dietary Nitrate Increases Tetanic [Ca2 ]i and Contractile Force in Mouse Fast-twitch Muscle." The Journal of Physiology 590.15 (2012): 3575-583. Web.