Facts about arginine

Proargi-9 plus l-arginine nitric oxide nutrition

Amino acids constitute an extremely interesting issue in the world of clinical and sports dietetics. In addition to its standard nutritional functions and supporting the construction of enzymes, hormones and antibodies, we can distinguish many other effects on the body’s physiology, including blood flow control and many other aspects. Arginine is such an amino acid, classified as one of the so-called stimulators of nitric oxide secretion. Therefore, it’s interesting to explore the application of this amazing remedy. You will learn how this agent, classified so far for use by bodybuilders, can support regeneration and we can successfully use it to fight metabolic diseases.

Nitric oxide (NO) is a relatively new subject of pharmacological research. The first study to start further exploring how this compound works was published just 33 years ago. Nevertheless, its role has had such a huge impact on the research community that nearly 40,000 studies with the name of this molecule in the title have been published so far and more than 70,000 studies refer to the role of this molecule in a greater or lesser sense. The impact of this compound on the body is very wide, that can be read in the headlines of the above-mentioned studies: from the effects related to muscle mass hypertrophy, through increasing glycogen saturation and ending with supporting the treatment of erectile dysfunction and reducing arterial hypertension. So, before we refer to the issue of arginine and the role of its supplementation,

A Brief History of Nitric Oxide

“Only a few know what a muscle pump is. To understand this, you have to experience it. It’s the most wonderful feeling I know. I want to pump, because then my muscles will grow. The pump means my muscles are filling with blood and they are getting really hard, the skin is so tight as if it is about to burst. I have a feeling that someone has inflated my muscles with air. It’s a fantastic feeling. “
Arnold Schwarzenegger

Nitric oxide was discovered in 1977 by Ferid Murad. The scientist showed that nitroglycerin – and similar heart medications – causes the production of nitric oxide, that in turn leads to an enlarged diameter of the blood vessels and more blood flow. A few years later, in 1980, Furchgott and Zawadzki found that intact endothelium of blood vessels releases endothelium-derived relaxing factor (EDRF) under the influence of acetylcholine. It wasn’t until 1987 that Louise Ignarro identified EDRF as nitric oxide. Nitric oxide was the molecule of 1992 and its discovery was considered one of the greatest biological discoveries of the 20th century. Robert Furchgott was awarded the Nobel Prize in 1988 with Ignarro and Murad for explaining the role of nitric oxide as an agent acting on the nervous system that controls smooth muscles. The research of three scientists contributed to the invention of the drug for erectile dysfunction – sildenafil (Viagra).

Biochemical basis of the mechanism of NO formation

In the body, nitric oxide is formed from the guanidine group of the amino acid L-arginine in a reaction catalyzed by several isoforms of the enzyme nitric oxide synthase (eNOS). The reaction requires the presence of molecular oxygen and co-factors: NADPH, FAD as well as tetrahydrobiopterin (BH4). An interesting fact is that it is due to the guanidine group contained in the arginine molecule that it affects the production of nitric oxide. This group contains few compounds, that include, among others: arginine, creatine, glycocyamine and guanidinopropionate. This scientific fact explains why only some amino acids can increase NO production while others don’t. However, taking into account the fact that the above molecules are very closely related to creatine – they are either substrates for its creation or are its intermediates – this explains, why some athletes also experience a strong pumping effect during supplementation with this agent. Of course, it depends on a very high receptor sensitivity and not everyone will feel this effect.

Why arginine conquered supplementation

When our nutritional system is depleted of arginine, instead of nitric oxide, a superoxide radical is formed, that reacts with nitric oxide to form a compound that belongs to the group of free radicals. It can cause a significant impairment in the area of blood vessels, that is a very unfavorable phenomenon – the lumen of the blood vessels cannot expand and the action of free radicals leads to damage to the endothelium of blood vessels that promotes for example, the aggregation of platelets and cholesterol, leading to blockages and hypertension. People who avoid a diet rich in proteins are particularly vulnerable to arginine deficiencies in the body. In most people who include meat, fish, eggs and dairy products in their diet, as well as nutrients for sportsmen, no deficiency of this amino acid is observed. Arginine supplementation thus restores the proper course of nitric oxide synthesis and thus – prevents the increased incidence of cardiovascular diseases (including atherosclerosis and hypertension). L-arginine increases the level of certain hormones that regulate metabolism (e.g. growth hormone, insulin, adrenaline) that increases the amount of nitric oxide and improves blood flow control. Healthy nitric oxide production is critical to any process in the body requiring blood circulation. Nitric oxide accelerates the healing of wounds after cuts, abrasions, injuries of muscles, tendons and ligaments. It also prevents atherosclerosis (hardening of the arteries), erectile dysfunction and diabetes. What about the athletes? Research results also show that arginine, taken with carbohydrates, can help start the recovery process in all athletes, not just bodybuilders. Although the main advertising slogans of nitric oxide boosters mainly say about the amazing feeling of the muscle pump described by Arnold, the effects of these supplements go beyond this aspect. During one of the tests performed, the participants were given a carbohydrate product or a carbohydrate-arginine product 1, 2 and 3 hours after the end of training. These supplements contained 1 g of carbohydrate for every kg of exercising body weight or a mixture of 1 g of carbohydrates and 0.08 g of arginine for every kg of exercising body weight. The observed increase in muscle glycogen during the four-hour regeneration process after training was much faster in those sporangians who were given a carbohydrate-arginine mixture. Researchers attributed these results to the ability of arginine to increase the bioavailability of glucose, thanks to that larger amounts are converted into glycogen and stored in the muscles, so it’s better to use NO boosters with carbohydrates both before training, to strengthen the muscle pump and also immediately after it – for example, to increase the bioavailability of glucose. Arginine can also help fight obesity. It prevents the growth of fat cells and stimulates the growth of highly thermogenic brown adipose tissue that accelerates the body’s caloric and fat burning reactions. Additionally, arginine acts as a chemical signal to speed up the metabolism, so larger amounts are transformed into glycogen and stored in the muscles.

Let us return, however, to the phenomenon of the muscle pump described by Arnold. The muscle pump was once considered a temporary physical condition in that the muscles become filled with blood. Many leading physiologists believed that the pump played no role in muscle growth. A few years ago, this view was beginning to change.

Nitric oxide enzyme synthase is responsible for the conversion of L-arginine into nitric oxide. It is the source of the pump we want so much. Current research suggests that NO is more than just a vasodilator – it actually triggers the process of muscle hypertrophy. Previous experiments have shown that a spike in NO production leads to the release of hepatocyte growth factor (HGF) into the extracellular matrix and then to the activation of satellite cells responsible for muscle growth. This means that a sudden increase in NO levels can enhance the anabolic response to exercise. Its administration after training also has a positive effect on the IGF-1 burst and the associated long-term anabolic effects and stimulation of testosterone secretion.

Various forms of arginine

Arginine alpha-ketoglutarate is a salt made of the amino acid arginine and alpha-ketoglutaric acid. AAKG products are effective in increasing the level of anabolic hormones and amino acid metabolites, including insulin-like growth factor (IGF-1). AAKG also works anti-catabolic, supporting protein synthesis and thus causes muscle growth. Research on arginine alpha-ketoglutarate has shown that it improves both the metabolism of amino acids (especially arginine) and the electrolyte profile in hemodialysis patients – both of that can help bodybuilders who are highly stressful. Thanks to its participation in the metabolism of proteins, arginine alpha-ketoglutarate is considered to be a product that increases both anabolic and anti-catabolic processes.

Although standard arginine is a more practical stimulant of growth hormone production, its derivative AAKG has a better effect on vasodilation. If we want to maximize the transport of an ingredient to the muscles by increasing blood flow, it will be better to use arginine alpha-ketoglurate as a form more stable after digestion and therefore more effective.

Arginine HCl (arginine hydrochloride) is a form that is perfectly soluble in water, but gives a bitter taste and is less digestible than the form of arginine conjugated with ketoglutaric acid.

Arginine malate is very bioavailable, easily digestible and works quickly, unfortunately for a short time.

Of course, it would be wise to combine an ester that works very quickly with an ester that works slower but more steadily. The most sensible solution will be to combine citrulline malate with arginine alpha-ketoglutarate. It’s no wonder that most products sold as supplements have several forms of arginine in their composition.

What about citrulline?

Citrulline participates in the synthesis of the mediator in the form of nitric oxide and facilitates its production under exercise conditions. At the same time, together with adenosine triphosphate (ATP), it takes part in the act of contraction of muscle fibers. Citrulline is also the basic precursor of creatine, converted into arginine and glycocyamine. It influences the increase in the rate of phosphocreatine synthesis. It also belongs to the so-called a pool of non-protein nitrogen that is created as a result of the catabolism of muscle proteins. As a result, this substance exhibits strong anti-catabolic activity.

Research proves that citrulline malate can reduce fatigue during exhausting training. According to scientific data, supplementation with citrulline malate increased the production of ATP by 34% as a result of the oxidation reaction and the rate of phosphocreatine regeneration by 20%. The authors of this study concluded that the changes in muscle metabolism caused by the administration of citrulline malate indicate that it may promote energy production through oxidative reactions. This supplement increases endurance through a number of separate mechanisms. First, it improves the excretion of hydronium ions – the product of the breakdown of ATP during intense exercise and ammonia from the blood during training. In addition, citrulline malate in combination with arginine can cause vasodilation, that also improves endurance and reduces fatigue. The only significant disadvantage of this supplement is the dose you need to consume to see positive results. If citrulline malate is administered alone, you often need to take at least 6 g per serving. We can take citrulline malate by dividing the doses into morning (3 g) and evening or pre-training doses. This amount is enough to start with to see any effects. If our body tolerates this dosage, in later stages we will be able to increase the daily dose to 10 g. We should notice the effects after two or three workouts, when our body’s blood level increases. Citrulline malate is fantastic if we want to improve recovery between workouts and even better if we want to reduce fatigue during cardio sessions, because it improves our condition and endurance. what you need to consume to see positive results.

Threats to the NO production process

It has been already mentioned that one of the threats to the production of nitric oxide is too little arginine in the diet, that disrupts NO production by competing with the superoxide anion for nitric oxide synthase (eNOS). Oxidative stress is considered to be one of the key threats to this reaction, that is why we observe the positive effects of combining arginine and citrulline with substances that eliminate free radicals. Clayton Camic from the University of Nebraska-Lincoln in the USA has proven that using a supplement containing arginine (1.5 or 3 g of arginine and grape seed extract containing polyphenols that are strong antioxidants) for 4 weeks increases endurance by about 20%. This compound may work by increasing blood flow that controls releasing growth hormone or improving the function of the cells lining the blood vessels. Promising effects of eNOS support were also shown by a preparation called Vinitrox, consisting of a combination of grape extract and apples with strict proportions. In the conducted research it turned out that of all the mixtures it supported the action of nitric oxide synthase the most, mainly by blocking reactive oxygen species negatively affecting the concentration of eNOS and the production of nitric oxide.

Another threat is the stimulation of enzymes called iNOS and cNOS, that in some cases reduce the body’s response to the administered arginine after just a few doses. As a result, the production of endogenous nitric oxide is largely blocked and the blood vessels are no longer subject to this dilation effect. The action of iNOS reduces the synthesis of nitric oxide by increasing the production of ADMA (asymmetric dimethylarginine). The comforting information is that this process can be controlled, for example, by binding arginine to the alpha-ketoglutarate ester, adding antioxidants or agmatine. By inhibiting this process, the degradation of arginine and the production of nitric oxide is not reduced, even during long-term use, that is very good news for people,

One of the biggest enemies of eNOS activity is the frequent coexistence of the following factors: oxidative stress, high levels of uric acid and problems with sugar metabolism. So insulin-resistant people or those who suffer from pre-diabetes, may also have problems with high blood pressure, muscle pump during training, but also may be plagued by erectile dysfunction. Exactly the same symptoms can manifest in gout or too little antioxidant use compared to ongoing free radical damage.

A significant problem is also the shortage of the aforementioned cofactors: NADPH, FAD and also tetrahydrobiopterin (BH4). An interesting issue is also the supply of the neurotransmitter agmatine. It is a neuromodulatory metabolite of arginine, that is characterized by the ability to antagonize NMDA receptors of the glutamatergic system.

Help from antioxidants

The athlete’s diet should contain as many products of animal origin as possible, characterized by the highest digestibility, the power inherent in plants must not be forgotten. Many beneficial compounds cannot be synthesized in an animal organism. However, we have the opportunity to absorb them from plant products. Much is said today about the influence of antioxidants and nutraceuticals on the athlete’s diet. It is also important to address the role of polyphenols. In the light of the latest research, the patented polyphenol extract obtained from apples and grapes – ViNitrox, can not only increase the efficiency of the muscle pump, but also support your health by reducing blood pressure, delaying fatigue and reducing inflammation.

For intensely training athletes in a speed and strength character, a vegan diet would not be the best idea. However, we must not forget that many of the substances contained in them contribute to the proper growth of cells, protect against cancer and have a tonic effect on the heart and nervous system. The active ingredients accumulated in plants include folic acid, antioxidant vitamins – A, E and C.

The largest group of antioxidants is polyphenols. These are very promising compounds, valued not only for their strong antioxidant properties. This very broad group includes derivatives of dihydroxybenzoic acid and dihydroxycinnamic acid, flavone derivatives, flavonoids and isoflavonoids, as well as derivatives of stilbene, catechins, coumarins, anthocyanins, lignans, lignins and many other substances. Polyphenols are very widely distributed in the plant world. No wonder, since the group of compounds is so huge. They are found in fruits, vegetables, plant-based beverages, as well as in spices and herbal medicines. A rich source of polyphenols are such fruits as: chokeberry, cherries, black currant, apples, citrus, blueberries, grapes and kiwi. Among vegetables, lettuce, cabbage, onion, spinach, broccoli, pepper and garlic. Cereal seeds, nuts and legumes contain a lot of polyphenols. Among the drinks, green tea, red wine, coffee and cocoa stand out with a significant content.

Polyphenols act mainly as an antioxidant and disrupt the chain reactions of free radical formation; prevent the formation of reactive oxygen species by inhibiting the enzymes that generate them. The antioxidant effect of polyphenols also involves the removal (scavenging) of already produced active oxygen species. Phenolic compounds owe the above extraordinary properties to their chemical structure. It consists of a benzene ring, characterized by an electron deficiency. It acts on the oxygen atom of the hydroxyl group, that in turn contributes to lowering the electron density on the oxygen atom. Such a system leads to a weaker bond of hydrogen with oxygen in the hydroxyl group. Due to such weakening of bonds, oxygen more readily gives up hydrogen, so that polyphenols can fulfill antioxidant functions. This has been documented in the case of atherosclerosis, cancer and inflammation. The antiatherosclerotic effect of polyphenols results from their indirect vasodilating and anti-aggregating action. Providing the body with polyphenols in the diet or herbal medicines can prevent the consequences of atherosclerotic changes such as: myocardial infarction, stroke, ischemic heart disease, senile macular degeneration, cataracts, Alzheimer’s disease and the aging process. The anticancer activity of polyphenols overlaps with the antioxidant effect on free radicals, that are considered to initiate the neoplastic process. The mechanism of the anti-tumor action is also associated with the inhibition of DNA damage by free oxygen radicals. The anti-inflammatory effect is complex and is associated with the inhibition of prostaglandin biosynthesis. The removal of reactive oxygen species also plays a role in this process, as free radicals are pro-inflammatory. Polyphenols are also antihistamines, reducing allergic reactions, inhibiting the reproduction of viruses, protecting the circulatory system and preventing diseases of old age.

As you can see, the broad action of polyphenols is based mainly on antioxidant properties, that have a multifaceted effect on the human body – from improving well-being, through inhibiting DNA damage and reducing inflammation, to improving the function of eNOS (nitric oxide synthase), acting anti-sclerotic, lowering blood pressure and support the phenomenon of the muscle pump.

Polyphenol that has made a career not only in supplementation

Resveratrol belongs to phenolic compounds and is probably the most frequently mentioned compound in terms of cardiovascular protection. The level of resveratrol in grapes is 50-400 μg / g fresh weight, in red wines produced from them 0.92-1.37 mg / ml, in white wines 0.04 mg / ml and in grape juice 0.05 mg / ml.

Resveratrol has a positive effect primarily on the cardiovascular system. It inhibits the aggregation of platelets, thanks to that it prevents the formation of dangerous blood clots and also reduces the absorption of LDL cholesterol in the walls of blood vessels, thanks to that it reduces the risk of atherosclerosis, as well as other cardiovascular diseases, including heart attack and coronary disease. It has been proven that the effect of resveratrol on the protection of the cardiovascular system is mainly due to the inhibition of lipid oxidation and their deposition in the cells of the arterial walls. It limits the release of VLDL from the liver, so that a smaller amount of the LDL fraction is found in the plasma. In addition, resveratrol has been proven to lower blood pressure. The study was conducted on thirty people with coronary artery disease. They were given 600 mg of red grape extract containing 0,9 mg of trans-resveratrol. Already 60 minutes after consumption, an increase in blood flow through the blood vessels was observed, that again indicates the excellent pumping properties of polyphenols.

According to scientists, resveratrol influences the regulation of energy balance, that may prevent diet-related diseases – obesity (resveratrol stimulates the breakdown of fat cells by activating adiponectin) and related metabolic disorders, such as insulin resistance and diabetes. In the case of existing cancers, it may even inhibit their spread and metastasis. Researchers also argue that this antioxidant reduces the risk of neurodegenerative diseases, including Alzheimer’s disease and can also prevent osteoporosis. Another study on resveratrol found that it can activate the SIRT1 gene, that is also activated when you eat a low-calorie diet. Recent reports indicate that the combination of two synergistic sirtuin activators in the form of leucin,

The current meta-analysis of the data indicates the potential effect of resveratrol on blood sugar levels, but suggests that only in people with impaired sugar tolerance (insulin resistance or diabetes), but also in physically active people. The meta-analysis included 11 randomized trials showing that resveratrol significantly reduced fasting glucose and insulin levels in diabetics. It has also shown that resveratrol can lower levels of glycosylated hemoglobin (HbA1c), a marker of excess blood glucose and insulin resistance in diabetics. No significant effect was observed in nondiabetic, physically inactive subjects. However, scientists noted that this polyphenol increases the expression of the insulin-dependent glucose transporter GLUT4, that improves glucose uptake by muscle tissue within the anabolic window. To sum up, ingestion of resveratrol significantly improved glucose levels and insulin sensitivity in patients with type 2 diabetes, but not in those with normal blood sugar levels. The beneficial effect was also noted in physically active people with no health problems with normal glucose tolerance.

Other studies only on resveratrol have shown anti-cancer, anti-inflammatory properties, beneficial effects on the cardiovascular system, blood sugar levels, protection against Alzheimer’s disease and other degenerating diseases of the nervous system and increasing the body’s endurance.

Arginine and other NO boosters in various sports

Before considering the use of nitric oxide boosters, we need to summarize their effects:

By relaxing the endothelium of the blood vessels, it increases the blood flow to the muscles, that results in a pumping effect. As a result of the increased tension of muscle cells, it is easier to demonstrate their microtrauma, that becomes the essence of muscle hypertrophy.

• Taken after training, it strengthens the secretion of IGF-1, stimulates satellite cells and improves the saturation of muscles with glycogen, that significantly accelerates regenerative processes
• By expanding the lumen of blood vessels, it increases the supply of oxygen and nutrients to the muscles and accelerates the outflow of acidifying metabolites that impair regeneration.
• It increases the rate of ATP production and the regeneration of phosphocreatine, thanks to that it increases training efficiency
• It makes muscle cells more sensitive to glucose
• It promotes the metabolism of adipose tissue
• Ensures the flexibility of blood vessels, that allows you to tolerate high heart rate and protect against cardiovascular diseases, including atherosclerosis

Taking into account the above aspects, we can conclude that supplementation with nitric oxide boosters will bring a positive effect in any sport discipline and endurance athletes and martial arts fighters are unjustly afraid of this supplement. You just need to consider the correct dosage and the time to take it. For bodybuilders, it will be reasonable to use more than 0.2 g of arginine per kilogram of proper body weight daily, breaking it down into about 0.1-0.15 g / kg before training and the same amount afterwards. As part of improving oxygen transport, fat burning and increasing the rate of regeneration of energy substrates in endurance sports and martial arts, it is suggested to take 0.08 g / kg in two portions separated from the training in order to avoid the feeling of a muscle pump, that can be a big obstacle in these sports. .

Louise Ignarro suggested supplementing with arginine from 5 g per day upwards. According to many researchers, arginine and other products that affect the production of nitric oxide is a substance that can be called a panacea – a drug that is good for everything.