The global sports nutrition market is projected to reach $44 million by 2021, according to Allied Market Research.1 The current sports nutrition market, which is dominated by North America, consists of products intended to improve energy, performance, recovery, and muscle growth. Historically these products have long targeted disciplined athletes and bodybuilders. In recent years, however, the demand for these products has expanded to include lifestyle and recreational users.
While protein products account for the majority of sports nutrition sales, non-protein products like pre-workout products are a mainstay for the category. These multi-ingredient products are marketed to increase energy, strength, and muscle pumps. Along with creatine, beta-alanine, and caffeine, ingredients touted to increase nitric oxide (NO) are common in preworkout supplements.
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Nitric oxide supplements
Nitric oxide (NO) is a signaling molecule involved in many cell processes, including vasodilation, or widening of the blood vessels.2 Wider blood vessels increase the delivery of nutrients and oxygen to the working muscles during exercise, enhancing muscle growth and recovery. L-Arginine is one of these ingredients commonly included in preworkout products for the purpose of increasing endogenous NO.
With the help of nitric oxide synthase (NOS), arginine directly produces NO. Accordingly, this process is called the l-arginine-NO pathway (Fig. 1). When taken as a supplement, L-arginine is thought to spike levels of arginine in the blood and in turn, increase NO production and blood flow to the working muscles. When arginine is taken orally, however, it’s subject to first pass metabolism by the intestines and liver. This means a large percentage (as much as 38 percent) of L-arginine is broken down before it gets a chance to reach the bloodstream.3
L-citrulline on the other hand, a precursor of L-arginine, does not undergo metabolism by the intestines and liver and inhibits arginase, the enzyme that breaks down L-arginine.4 For this reason, L-citrulline supplementation increases levels of L-arginine in the body more than supplementing with L-arginine itself and why L-citrulline is also a common preworkout ingredient.
Nitrate supplementation
Increasingly popular is the use of nitrates (NO3-) as a means for increasing NO bioavailability. In the body, nitrates are converted to bioactive nitrite (NO2-) and subsequently NO through a series of reactions (Fig. 1). Nitrates are supplied in the diet through the consumption of vegetables and drinking water, with vegetables contributing more than 85 percent of the total dietary intake of nitrate.5
Numerous studies have shown that nitrate supplementation, either in the form of nitrate salts (e.g., sodium nitrate) or food-based ingredients like beetroot, increases plasma nitrite concentrations, a marker for nitric oxide, which have been shown to enhance endurance capacity and performance.6 This leaves supplement manufacturers vacillating between which to use. Both have their inherent benefits and pitfalls.
Nitrate salts
Studies assessing the impact of nitrate salts on exercise performance have utilized both sodium nitrate (NaNO3) and potassium nitrate (KNO3). Nitrate salts, specifically sodium nitrate, are a white crystalline, water-soluble solid. It is an approved food additive (E250) commonly used as a preservative and color fixative in cured meats and poultry.
The use of sodium nitrate as a preservative and curing agent has not been without controversy, though. While nitrate is relatively non-toxic, its metabolites and reaction products e.g., nitrite and nitrosamines, have raised concerns because of implications for adverse health effects such as cancer. However, there is no evidence that nitrate is carcinogenic to humans.7 Still, the negative connotation surrounding nitrate salts may limit its marketability as a dietary ingredient to the “hardcore” bodybuilding demographic. Nonetheless, sodium nitrate is an inexpensive, effective pre-workout ingredient and should be dosed appropriately.
Nitrates comprise approximately 73 percent of the total weight of sodium nitrate.8 This means for every gram of sodium nitrate, 730mg would come from nitrate and 270mg from sodium. To reach the studied clinical dose, which ranges between 400 and 800 mg of nitrate, a 600mg to 1g dose of sodium nitrate per serving is needed.9
Beetroot
Of recently, beetroot as a vessel for nitrates has gained traction in the sports nutrition category largely in response to the proliferation of research suggesting improved exercise performance.10
Beetroot contains 1-3 percent of nitrate per gram of raw material. Assuming a beetroot extract is standardized to contain 3 percent nitrate, a hefty 13g dose would be needed to deliver 400 mg of nitrate. This is impractical from an economic and palatability standpoint. Beetroot powder is also hygroscopic and will absorb moisture which may lead to caking.
These considerations have led to the development of convenient, concentrated beetroot juice shots, sachets, and beetroot-juice bars. Innovation has also led to the creation of standardized beetroot-based gels as an alternative vessel for nitrate.11
These products allow marketers to provide consumers with products that are sold as conventional foods, but have supplement-like positioning with consistent levels of nitrate and therefore predictable physiological benefit.
Considerations
As the research surrounding not only the ergogenic but also the health benefits of nitrate continues to rise, so will the demand for these ingredients and products.
Sodium nitrate, unlike beetroot powder, is inexpensively able to deliver an efficacious dose of nitrate in relatively small quantities, making it a prime ingredient for multi-ingredient pre-workout formulas. In contrast, a fundamental shift towards naturally functional food-based ingredients like beetroot, as well as a demand for presumably safer products are forces set to redefine the sports nutrition market.
In either case, nitrate tends to exert greater physiological benefit when taken for several days compared to acutely (two to three hours before exercise).6 This places the burden on manufacturers to provide delivery systems enticing people to consume their product daily.
Further reading:
- Heavyweight Product Development Match-Up: MRP or Protein Powder?
- Whey Protein: Formulating With Human Life’s Most Effective Protein
- Whey Protein: Formulation Considerations, Part 2
- Diet Pill Dominance: 5 Must-Haves to Win in Today’s Fat Burner Market
References
- Sports Nutrition Market by Type (Protein Powder, Iso Drink Powder, Creatine, BCAA, Supplement Powder, RTD Protein Drinks, Iso and Other Sports Drinks, Carbohydrate Drinks, Protein Bars, Carbohydrate/Energy Bars), Distribution Channel (Large Retail & Mass Merchandisers, Small Retail, Drug & Specialty Stores, Fitness Institutions, Online) – Global Opportunity Analysis and Industry Forecasts, 2014 – 2021. Allied Market Research, 2016.
- Stamler JS, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev. 2001; 81(1): 209-37.
- Castillo L, Chapman TE, Yu YM, Ajami A, Burke JF, Young VR. Dietary arginine uptake by the splanchnic region in adult humans. Am J Physiol. 1993; 265(4 Pt 1): E532-9.
- Romero MJ, Platt DH, Caldwell RB, Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev. 2006; 24(3-4):275-90.
- Gangolli SD, van den Brandt PA, Feron VJ, et al. Nitrate, nitrite and N-nitroso compounds. Eur J Pharmacol. 1994; 292(1):1-38.
- Jones AM. Dietary nitrate supplementation and exercise performance. Sports Med. 2014; 44(Suppl 1):S35-45.
- Nitrate in Vegetables – Scientific Opinion of the Panel on Contaminants in the Food Chain. European Food Safety Authority,
- SODIUM NITRATE. National Center for Biotechnology Information. PubChem Compound Database, S National Library of Medicine, 2005.
- Flueck JL, Bogdanova A, Mettler S, Perret C. Is beetroot juice more effective than sodium nitrate? The effects of equimolar nitrate dosages of nitrate-rich beetroot juice and sodium nitrate on oxygen consumption during exercise. Appl Physiol Nutr Metab. 2016; 41(4):421-9.
- Van De Walle GP, Vukovich MD. The Effect of Nitrate Supplementation on Exercise Tolerance and Performance: A Systematic Review and Meta-Analysis. J Strength Cond Res. 2017; doi:10.1519/JSC.0000000000002046.
- Morgado M, de Oliveira GV, Vasconcellos J et al. Development of a beetroot-based nutritional gel containing high content of bioaccessible dietary nitrate and antioxidants. Int J Food Sci Nutr. 2016; 67(2):153-60.
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Very interesting article. We are currently looking into a formula to include ingredients that would approach boosting NO from the 3 different pathways….this will be interesting to see the results from this.
Hi Andy, there are two pathways of NO production. One is oxidative which uses l-arginine and produces NO and l-citrulline. The second is a reductive pathway where nitrate is the substrate; this pathway is preferred in hypoxic conditions — such as exercise.
Thank you for this great article! I would argue that there are many more pathways for NO production, as reviewed in both of these articles:
Bryan NS. Nitric oxide enhancement strategies. Future Sci OA. 2015;1(1). doi:10.4155/FSO.15.48
Bogdan C. Nitric oxide and the immune response. Nat Immunol. 2001;2(10):907-916. doi:10.1038/ni1001-907
Hi Detrick, thank you for reading. As discussed in the articles that you cited, nitric oxide production does involve different enzyme isoforms and non-enzymatic pathways.
To date the two pathways in this article are the ones discovered. There are several strategies instead to increase NO production. One is arginase inhibition (eg. by lysine and ornithine)