L-arginine, nitric oxide production and muscle hypertrophy

L-arginine, nitric oxide production and muscle hypertrophy

Arginine is a non-essential amino acid. In other words, our body can synthesize it from the protein that we eat on a daily basis. In order to understand its important, let’s see how it becomes nitric oxide and what is its role in muscle hypertrophy

Why do Athletes take the amino acid L-Arginine?

Every professional or amateur athlete wants more muscle efficiency and a better vascularization in order to:

  1. Ensure the nutrient and oxygen supply to the muscles.
  2. Improve the elimination of lactic acid, the main trigger of muscle fatigue.

These are the goals of athletes whose objective is muscle hypertrophy, speed or strength.

Woman running under the rain

That is why scientists have studied the mechanisms through which these features improve. The result is nitric oxide, a molecule that is obtained from the amino acid L-arginine. Even though it is the smallest one produced by our organism, it is one of the main vasodilators produced by the human body.

How does L-Arginine become Nitric Oxide?

  • Once absorbed by the digestive tract, this amino acid travels through the bloodstream to the tissues or target organs that need it at that moment.
  • After entering the cell, L-arginine transforms into nitric oxide and another molecule, L-citrulline. This is due to the effect of a cytoplasmic enzyme called nitric oxide synthase (NO synthase).

Nitric oxide production from L-arginine

What is Nitric Oxide?

Nitric oxide is a free radical that protects the cells instead of damaging them. However, our body does not store it, rather, it produces it whenever we need it. That is why we should take L-arginine supplementation daily at least.

Its production requires strong and stressful stimuli at a metabolic level (cold, intense physical exercise, etc). Therefore, if we want to increase its levels safely, we need to perform high intensity exercise (HIIT). In fact, there is not enough evidence to prove that moderate exercise also increases its blood levels.

Man weightlifting and muscle tissue

Strong muscle stimuli activate many metabolic pathways that stimulate the muscle hypertrophy. Consequently, our own muscles will trigger the necessary mechanisms to adapt to the stimuli. For instance, it can do so if it needs more (hyperplasia) and thicker (hypertrophy) muscle fibers.

Properties of Nitric Oxide

First of all, let’s assess the positive properties of nitric oxide for the body:

  • Antibacterial effect, since it helps to fight against infectious organisms, specially bacteria.
  • Anti-inflammatory effect, since it inhibits part of the pro-inflammatory molecules.
  • Helping to deal with cancer cells.

For the bloodstream

  • Regulating the vasodilation, this is a significantly beneficial property for those who suffer hypertension and/or heart problems. Moreover, it can work as an anti-coagulant, avoiding the thrombi that cause heart attacks. In addition, its presence in the bloodstream relaxes the blood vessels and makes them wider. Heart puzzle
  • Increasing the blood flow to the nervous system and working as a neurotransmitter in the brain. Consequently, it improves the long-term memory.
  • Stimulating the angiogenesis or the creation of new blood vessels that will provide more nutrients and oxygen to the muscles. Therefore, it will speed up the elimination of lactate, improving the performance.
  • Helping to regenerate the muscle by shortening the post-workout recovery. This is due to the fact that it enhances the cell division, stimulating the muscle hypertrophy. Moreover, nitric oxide stimulates the muscle satellite cells, that is, those in charge of splitting themselves up to create more muscle cells.

Study and other properties

  • Protecting the integrity of the muscle fibers during the workout. Specially in those movements that involve the eccentric contraction of the muscle. This can be clearly seen in a study conducted on rats where they made 4 groups: a Control group (C) which rested and three groups that had to run in a treadmill to simulate eccentric exercise. From these three groups, one of them did not take anything (R), another took L-arginine (RA) and the last took L-arginine mixed with another supplement (RN). After the tests, they measured the degree of muscle fibril deterioration from all the groups. Therefore, the group that had the highest rate was the one that took nothing. On the contrary, the one that had less was the one that only took L-arginine, almost reaching the levels of the control group.

Number of fibers in the study

  • Stimulating the same metabolic pathway as viagra, causing a similar effect. Therefore, it could be useful for those who suffer mild erectile dysfunction.
  • Increasing the amount of mitochondria (mitochondrial biogenesis) improving the use of fatty acids by the skeletal muscle. Moreover, it increases the amount of mitochondrial enzymes. These elements will increase the ATP production, the molecule in charge of providing energy for the whole body.

Cell and nitric oxide

More specifically, this image shows the metabolic pathway triggered both by physical exercise and nitric oxide inside the cell. Strong muscle stimuli affect the gen PGC-1α. In turn, it stimulates the transcription of different genes involved in the creation of new muscle; the creation of new mitochondria that will perform the respiratory chain; as well as more ATP production; and genes involved in the utilization of fatty acids as a source of energy (β-oxidation).

Cons of Nitric Oxide

In order to assess a substance properly, we also need to take into account its disadvantages. Above all, we need to be aware of the consequences of a bad supplementation. The cons of nitric oxide that we currently know are:

  • An excess of nitric oxide throughout the years has been related to neurodegenerative diseases like Parkinson or Alzheimer. Although this has only occurred in cases where the levels have increased endogenously. Nevertheless, do not push your luck with excessive levels of this substance.
  • Moreover, it can damage the DNA and trigger gene alterations since it is an oxidant substance.

L-arginine supplementation for more nitric oxide

As we have already explained, our body does not store nitric oxide. Therefore, it is better to distribute the dose of this supplement in several servings. After all, this can increase the amount of nitric oxide in the body up to a 46% according to several studies.

However, we should make our body produce its own nitric oxide, otherwise, its endogenous production could drop.

It is important to emphasize the fact that our body is a machine that only synthesizes what it needs.

Therefore, if we always have enough nitric oxide, it would not need to produce it. That is why it is advisable to use this supplementation every two or three months, for instance and stop for two or three months. Actually, we can use a different supplement for that period of time.

Do not combine this supplement with complex B vitamins, since they inhibit the production of nitric oxide.

Sources of Arginine

There are foods that also have more L-arginine, like the ones that contain omega 3 fatty acids (walnuts and oily fish), dairy products, red meat, and polyphenols (like grapes, pure cocoa and red berries). There are other that specially stand out such as beet and watermelon. In fact, they also hydrate our body with water, apart from providing minerals, vitamins and L-arginine during the summer.

Beet juice


In this article, we have tried to explain the functioning of nitric oxide and its role during the workout. Moreover, we have tried to talk about all the advantages and disadvantages of L-arginine supplementation. This is a good supplement for those athletes who are stuck in their progression towards their goals. However, we always need to be cautious and well-informed about supplements and their effects.


  1. Bentley R, Gray SR, Schwarzbauer C, Dawson D, Frenneaux M, He J. Dietary nitrate reduces skeletal muscle oxygenation response to physical exercise: a quantitative muscle functional MRI study. Physiol Rep. 2014;2(7).
  2. Lomonosova YN, Shenkman BS, Kalamkarov GR, Kostrominova TY, Nemirovskaya TL. L-arginine supplementation protects exercise performance and structural integrity of muscle fibers after a single bout of eccentric exercise in rats. PLoS One. 2014;9(4):e94448.
  3. Morales RC, Bahnson ES, Havelka GE, Cantu-Medellin N, Kelley EE, Kibbe MR. Sex-based differential regulation of oxidative stress in the vasculature by nitric oxide. Redox Biol. 2015;4:226-33.
  4. Pearson SJ, Hussain SR. A review on the mechanisms of blood-flow restriction resistance training-induced muscle hypertrophy. Sports Med. 2015;45(2):187-200.
  5. Rybalkin SD, Yan C, Bornfeldt KE, Beavo JA. Cyclic GMP phosphodiesterases and regulation of smooth muscle function. Circ Res. 2003;93(4):280-91.
  6. Scarpulla RC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev. 2008;88(2):611-38.

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About Carlos Sánchez
Carlos Sánchez
Carlos Sánchez has a degree in Human Nutrition and Dietetics, and therefore all his actions are rigorously backed by science.
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