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Nitrosigine

What is Nitrosigine?

Nitrosigine is a source of inositol stabilized arginine silicate developed and patented by Nutrition 21, which was launched in 2013. This compound was developed specifically for the bodybuilding and sports nutrition market to support an increase in nitric oxide production, pump and blood flow during exercise. To date, there are 19+ studies (including human studies) showing that Nitrosigne is a safe and effective ingredient that can enhance exercise performance. Nitrosigne's performance-enhancing properties appear to be based on its ability to increase blood flow and influence silicate absorption.

How is Nitrosigne produced?

Nitrosigine is produced by combining arginine and silicate and stabilizing it with inositol - a vitamin-like compound found in plant and animal sources. This prevents premature breakdown of nitrosigne and prolongs its effect in the body for up to 6 hours). Preclinical studies have shown that Nitrosigne is superior to regular arginine in terms of blood flow markers and that it has a positive effect on silicate absorption. Both can improve athletic performance and general health. Let's first look at the effects of the two primary components of Nitrosigne before going into more detail about the overall effects and benefits of Nitrosigne.

What is arginine and what effects does it have?

Arginine is a conditionally essential amino acid that plays various roles in the body, including the following:

  • Increasing nitric oxide levels
  • Dilating the arteries and increasing blood flow
  • Removing toxic ammonia from the body
  • Improving immune function
  • Wound healing

For the purpose of this article, we are most interested in arginine's vasodilator and blood flow enhancing properties. Unfortunately, research shows that arginine on its own is less effective than expected, primarily due to the poor absorption of pure arginine in supplement form.

What is silicate and what effects does it have?

Silicate is a colorless compound found in foods such as oats, cucumber, rice, wheat and avocados. Silicate can have the following effects when taken orally:

  • Strengthen the connective tissue of the brain
  • Promote relaxation of the endothelium (the walls of the blood vessels)
  • Promote bone health
  • Improve memory performance
  • Stabilize insulin secretion by the pancreas

In terms of exercise performance, we are most interested in silicate's ability to promote relaxation of the endothelium, which can increase circulation and blood flow to working muscles.

How does Nitrosigine work?

Nitrosigine works in two ways:

  1. It increases blood flow before and after exercise by dilating the veins due to an increase in nitric oxide levels. In this context, two studies have shown that Nitrosigne can almost double the maximum blood flow compared to arginine HCl.
  2. It significantly increases the silicate levels in the blood, which further promotes relaxation of the blood vessels.

Benefits of Nitrosigine for the pump

Arginine is required for the synthesis of nitric oxide. However, arginine in its free form is not stable enough to unfold its full benefits in the body. Nitrosigine has been studied in clinical trials on human volunteers for its effects in increasing nitric oxide synthesis. Healthy male volunteers were given four servings of Nitrosigine for two weeks. The subjects' arginine levels rose significantly within 30 minutes of ingestion and remained elevated for 5 hours. At the end of the two-week study phase, the subjects' baseline arginine levels were higher than on the first day of the study. An increase in nitric oxide levels was also observed in a number of subjects, particularly towards the end of the study (1). A randomized double-blind study in a cross-over design from 2016 came to the conclusion that subjects who took 500 mg Nitrosigne per day for 14 days had 70% higher arginine plasma levels compared to the placebo group (3). The arginine plasma levels also remained elevated for longer than in the placebo group. A clinical study also showed that Nitrosigne can not only significantly increase arginine levels, but also nitric oxide levels (4). Nitric oxide has been shown to play a key role in increasing blood flow to working muscles. Preclinical studies have also shown that nitrosigne is almost five times more effective than arginine HCl in widening arteries and increasing blood flow (2). In direct comparison with arginine HCl, nitrosigine thus appeared to have a far superior effect in terms of its ability to relax the blood vessels (2). This suggests that nitrosigine may be a superior form of arginine. Nitrosigine also improves blood protein levels, which represent a wide range of important physiological functions and play critical roles in a number of cellular processes. In one study, for example, Nitrosigne was able to increase the levels of the blood protein kallistatin, which can increase blood flow, by 32% (5). Nitrosigne can also increase silicate levels in the blood after a single dose (6). Silicate strengthens the walls of the arteries and improves their flexibility, which helps to increase blood flow. Blood flow is important during both endurance and resistance training as it allows better delivery of oxygen and nutrients to the working muscles. Increased blood flow is important both during and after training, as it can promote muscle growth and recovery in addition to training performance. For training with weights, this means that Nitrosigine can improve the quality and strength of the muscle pump. Nitrosigine can increase pre-exercise energy levels and muscle pump, as well as reduce markers of exercise-induced muscle damage after exercise.

In a placebo-controlled, double-blind, crossover study, the following was observed in subjects who consumed 1500 mg of Nitrosigne per day for four days (3).

  • Higher levels of perceived energy compared to a placebo
  • Higher levels of hyperemia (muscle pump) compared to a placebo (1.8 vs. 0.8 cm)
  • Increased blood flow (measured by ultrasound) compared to placebo (59.9 vs. 49.9 cm)
  • Reduced creatine kinase levels (a marker of exercise-induced muscle damage) by 56% compared to a placebo, indicating 44% less muscle damage

Nitrosigne can improve focus, mental flexibility and mental processing speed.

In one study, Nitrosigne was shown to increase mental sharpness and focus by 33% within 15 minutes. The influence of Nitrosigne on mental acuity increases with increasing duration of intake (3). Another study showed that Nitrosigne can increase levels of the blood protein afamin, which improves cognitive function, by 46% (5).

How quickly does the effect set in and how long does it last?

The effects of Nitrosigne start just 15 minutes after ingestion (3) and scientific studies show that it increases arginine blood levels for up to 6 hours (2). In comparison, arginine HCl was only able to increase arginine blood levels for one hour in studies (7).

Nitrosigine disadvantages and side effects

No undesirable side effects of nitrosigine have been observed in human studies (14). The manufacturer also states that the US Food and Drug Administration has evaluated nitrosigines and declared them to be generally safe and harmless, and has approved them for use in supplements.

Taken on its own, arginine can cause digestive discomfort in some people due to the poor absorbability of this compound. Due to the increased bioavailability (through a combination of arginine with silicate) this is not a problem with Nitrosigne.

People with low blood pressure and people taking blood pressure medication should consult their doctor before consuming Nitrosigne, as the vasodilating effects of Nitrosigne can result in a natural reduction in blood pressure.

Nitrosigine intake recommendation and timing of intake

As Nitrosigine increases arginine levels in the body just 15 minutes after ingestion, it is recommended to take this ingredient around 15 to 30 minutes before training. Nitrosigine can be taken daily and even on non-training days to increase baseline arginine levels.

The optimal dosage of Nitrosigine to increase athletic performance appears to be 1500 mg per serving according to studies.

Combinations of Nitrosigine with other supplements

Nitrosigine can be combined with a number of other ingredients to increase nitric oxide levels such as citrulline and agmatine. It can also be used in combination with a range of pre-workout ingredients including caffeine and beta alanine.

Conclusion

Nitrosigne is an interesting compound for enhancing athletic performance that can have the following benefits:

  1. Boosting key factors to increase blood flow. More specifically, Nitrosigne increases nitric oxide levels and promotes relaxation of blood vessels.
  2. Time-optimized effect that starts as soon as 15 minutes after ingestion and increases arginine blood levels for up to 6 hours.
  3. Boosts training energy quickly and safely.
  4. Improved mental sharpness and focus by 33%.
  5. Generates an increased pump by delivering more oxygen and nutrients to working muscles while removing waste products faster.
  6. Combats exercise-induced muscle damage by reducing creatine kinase levels by 56%.

References

  1. Kalman et al (2014), A clinical evaluation to determine the safety, pharmacokinetics and pharmacodynamics of an inositol-stabilized arginine silicate dietary supplement in healthy adult males. FASEB, 28: Supplement LB418
  2. Proctor et al (2005), A novel complex of arginine-silicate improves micro- and macrovascular function and inhibits glomerular sclerosis in insulin-resistant JCR:LA-cp rats. Diabetologia, 48: 1925-32
  3. Rood-Ojalvo S, Sandler D, Veledar E, Komorowski J. The benefits of inositol-stabilized arginine silicate as a workout ingredient. Journal of the International Society of Sports Nutrition. 2015; 12(Suppl 1):P14.
  4. Kalman DS, Feldman S, Samson A, Krieger DR. A clinical evaluation to determine the safety, pharmacokinetics, and pharmacodynamics of an inositol-stabilized arginine silicate dietary supplement in healthy adult males. Clinical Pharm: Adv and Applica. 2015; 7:103-109.
  5. Komorowski J, Rood-Ojalvo S, El-Sohemy A. Arginine silicate supplementation decreases markers of cardiovascular, renal and metabolic dysfunction and increases markers of vasodilation and cardiovascular health in healthy adult males. FASEB Journal. 2015; 29:748.2.
  6. Proctor SD, Vine DF, Russell JC. Metabolic effects of a novel silicate inositol complex of the nitric oxide precursor arginine in the obese insulin-resistant JCR: LA-cp rat. Metabolism Clinical and Experimental. 2007; (56):1318-1325.
  7. Komorowski J, Perez Ojalvo S. A pharmacokinetic evaluation of the duration of effect of inositol-stabilized arginine silicate and arginine hydrochloride in healthy adult males. The FASEB Journal. 2016; 30(1) Supplement 690.17.