The history of nitrogen oxide boosters

To understand the complexity and effectiveness of supplements in the pre-workout category, you need to know what started it all: nitric oxide boosters. Nitric oxide is a gas that has made a name for itself in the supplement industry. Just over a decade ago, nitric oxide was anything but a household name in gyms or supplement stores. However, this was soon to change.

The first nitric oxide booster supplements consisted of just a single amino acid: L-arginine. Today, such supplements consist of a combination of a variety of advanced ingredients and technical delivery systems. Virtually overnight, this supplement category has gone from an unknown nobody to a muscle-building superstar. Hardly any other supplement has ever undergone such an evolution in such a short period of time. How did this happen? Here is the story of the efforts that have transformed nitric oxide boosters into the most innovative supplements you can find on the market today.

What is nitric oxide?

Nitric oxide is a gaseous molecule that relaxes the smooth muscle cells of blood vessels, causing the blood vessels to dilate, allowing more blood to flow to the muscles. This increased blood flow also means the supply of more nutrients such as amino acids and glucose, which increase energy production during exercise and delay fatigue. In addition, toxic metabolic products are removed more quickly and muscle regeneration is accelerated during and after training.

What does science say?

Numerous studies support the effectiveness of nitric oxide booster supplements. The first study was conducted with arginine alpha ketoglutarate (arginine AKG) and concluded that subjects who took this compound over an eight-week period before training were able to significantly increase their bench press strength. Other studies conducted with arginine confirm that arginine increases muscle strength, reduces muscle fatigue and allows subjects to train longer and at a higher intensity than members of the control group.

Born in the lab

As with most supplements, nitric oxide started in the lab. Unlike most other supplement ingredients, the nitric oxide molecule helped the scientists who decoded its function in 1986 to win a Nobel Prize. After this discovery, word quickly spread about nitric oxide's ability to relax blood vessels and thereby increase blood flow. This not only led to a huge amount of medical research into the exact effects of nitric oxide, but also attracted the attention of scientists in the supplement industry. One company stood out: MRI (Medical Reseach Industry) immediately understood the effects nitric oxide could have on muscle growth. Increasing blood flow to the muscles during exercise generates a stronger muscle pump and allows more nutrients and oxygen to be delivered to the muscles, resulting in more energy during muscle contractions.

In 1997, MRI developed the very first nitric oxide booster, which was launched under the name NO2. Back then, NO2 was basically nothing more than a dose of the amino acid arginine. However, as simple as this may sound, it was very effective as arginine can easily be converted into nitric oxide in the body. Since regular L-arginine is not particularly well absorbed by the body, MRI used a form of arginine called L-arginine alpha-ketoglutarate (arginine AKG for short), which is basically arginine with an alpha-ketoglutarate molecule attached to it. The alpha-ketoglutarate increases the absorption rate of arginine so that the body can absorb more arginine per dose. And the more arginine the body absorbs, the more nitric oxide it can produce - at least up to a point.

The humble beginnings

Arginine AKG became a big hit. Users of this active ingredient loved the stronger pump they experienced in the gym and the ability to train at a higher intensity. The increase in nitric oxide production went viral and this led every major sports supplement manufacturer and even a majority of the smaller companies to focus their scientists, development team and marketing team on creating a better nitric oxide supplement. Many supplement manufacturers simply followed in MRI's footsteps and launched their own versions of NO2 that also contained arginine alpha ketoglutarate or other forms of arginine.

Other supplement manufacturers quickly realized that even though arginine is quite effective at increasing nitric oxide levels in the body, there is a limit to the amount of arginine the body can convert to nitric oxide. The limiting factor in this conversion is an enzyme called nitric oxide synthase (NOS for short). Nitric oxide synthase is the enzyme needed to catalyze the conversion of arginine to nitric oxide. Increasing the activity of this enzyme increases the amount of arginine that is converted into nitric oxide and, of course, the amount of nitric oxide that is produced. There are several ingredients that have been shown to increase the activity of nitric oxide synthase. These compounds include:

• Pycnogenol: This antioxidant flavonoid, extracted from the bark of French maritime pine trees, provides other antioxidant health benefits in addition to increasing nitric oxide production by increasing nitric oxide synthase activity.
• American Ginseng: This form of ginseng, also known as Panax Quinquefolius, contains active ingredients called ginsenosides, which have been shown to increase nitric oxide synthase activity.
• Gynostemma Pentaphyllum: This plant, also known as Jiaogulan, is often referred to as southern ginseng as it grows mainly in southern and central China and has a chemical composition and function similar to Asian ginseng. The active compounds contained in Jiaogulan are called gypenosides and act in a similar way to the ginsenosides contained in ginseng by increasing the activity of the enzyme nitric oxide synthase.
• Histidine: Together with beta-alanine, this amino acid forms the active substance carnosine, which is of crucial importance for muscle strength and endurance. Histidine is also a precursor of histamine, which is involved in the body's immune response. In addition to this, histamine also increases the activity of the enzyme nitric oxide synthase. With the discovery of these excipients, supplement manufacturers began to combine them with other ingredients in nitric oxide booster supplements to bring even more effective nitric oxide boosters to the market. This helped this supplement category to become even more effective and popular and sales of nitric oxide booster supplements continued to rise.

Combined benefits

In the early days of nitric oxide boosters, most products focused solely on increasing nitric oxide levels. However, the beginning of the 21st century marked the start of a new era of nitric oxide supplements. The continuous pressure to improve existing products eventually led to the development of N.O.-Xplode by BSN, which marked the beginning of combined pre-workout products. N.O.-Xplode was the first nitric oxide booster supplement to combine stimulants and other performance-enhancing compounds with ingredients to increase nitric oxide production.

Before the introduction of complete pre-workout formulas, consumers had to rely solely on stimulants to get them through a tough training session, using combination products containing ingredients such as caffeine and ephedrine. With this in mind, BSN launched N.O.-Xplode. Although the supplement category of nitric oxide booster supplements had been on the market for some time and was enjoying increasing popularity, it was not yet synonymous with pre-workout supplements. Additionally, there were no "all-in-one" pre-workout formulas that provided nitric oxide boosters for pumps, creatine for strength gains, caffeine for increased energy and electrolytes for better hydration. N.O.-Xplode was born out of the need to satisfy all the needs for a muscle growth stimulating workout: Energy, mental focus, workout intensity (endurance, strength and hydration) and pump.

Nitric oxide booster supplements today

One way this supplement category continues to evolve is by moving away from arginine and using other ingredients to increase nitric oxide levels. One of the companies that has continued to drive this development is MPH, which launched the NO Bomb product in 2010. Until then, arginine and arginine AKG were the ingredients of choice used in most nitric oxide boosters. With Glyco Carn (Glycine Proponyl-L-Carnitine-GPLC), one of the active ingredients in NO Bomb, a new nitric oxide booster ingredient appeared on the scene.

In addition to this, NO-Bomb took advantage of another new discovery in the field of nitric oxide production: the nitrate-nitrite pathway. This newly discovered pathway acts independently of the arginine pathway and studies conducted with nitrate-rich beet juice have shown this pathway to be highly effective in increasing nitric oxide levels. NO-Bomb contained a standardized beet extract that activates the nitrate-nitrite pathway and increases nitric oxide levels. Perhaps the biggest breakthrough in nitric oxide production to date, however, is the ability to deliver a direct source of nitric oxide to the body. The supplement company Muscle Meds has launched eNoxide, the first supplement to deliver a true nitric oxide molecule. eNoxide is not a nitric oxide precursor, but a true nitric oxide molecule bound to an amino acid transport molecule. After absorption into the body, this compound dissolves and releases real nitric oxide.

The future of nitric oxide boosters

Just as nitric oxide boosters have continued to evolve over the last 15 years, they will continue to evolve in the future and become even more effective than they are today. Although it is not possible to predict exactly what discoveries will be made in the world of nitric oxide boosters, some experts suspect that future products are likely to contain compounds that reduce muscle protein breakdown. A nitric oxide booster with added anti-catabolic protection is likely to be the next natural advancement. So far, the goal has been to increase performance by eliminating all limitations and maximizing the stimulants used. However, the real goal is to build more muscle while reducing body fat, and this cannot be achieved simply by maximizing performance. In the future, a supplement that allows users to maintain every gram of muscle they've built through the use of an effective nitric oxide booster/pre-workout supplement will make this supplement category even more important for strength and power athletes.

The history of nitric oxide and nitric oxide booster supplements at a glance:

• 1772: Nitric oxide is discovered by Joseph Priestly. For the next 200 years, nitric oxide is thought to be a toxic gas
• 1986: Scientists discover that nitric oxide is naturally produced in the body of humans and other mammals and relaxes blood vessels
• 1997: The company Medical Research Institute (MRI) launches the supplement NO2, which contains arginine alpha ketoglutarate (AKG) as an active ingredient.
• 1998: The discovery of nitric oxide and its role in the dilation of blood vessels is awarded the Nobel Prize for Medicine.
• 1999: The company Maximum Human Performance (MPH) launches the supplement TRIAC, which combines arginine and creatine.
• 2004: BSN launches the product NO-Xplode, which combines nitric oxide boosters with stimulants, creatine and electrolytes.
• 2005: Muscle Tech launches naNOx0, a nitric oxide booster in the form of caplets with rapid delivery for an almost immediate onset of action.
• 2008: BSN expands the NO-Xplode formula to include beta-alanine and several other forms of creatine
• 2009: Muscle Meds launches eNOXIDE, in which nitric oxide is bound to an amino acid and which releases nitric oxide in the body when this bond is broken.
• 2010: MPH launches NO-Bomb, the first supplement to contain a clinical dose of GPLC and deliver nitrates as nitric oxide precursors.
• 2011: UGENX launches PUMP'D Nitric Gel, a gel for application to the skin that enables a local increase in nitric oxide-mediated blood flow.

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