L-Arginine

L-Arginine: Usage, Health Benefits & Side Effects

L-arginine is a semi-essential/conditionally essential amino acid.

There are three main categories of amino acids; essential amino acids, non-essential amino acids, and semi-essential amino acids:

  • Essential amino acids are acquired primarily through diet
  • Non-essential amino acids are mainly synthesized by the body
  • Semi-essential amino acids are synthesized in the body but in insufficient amounts, therefore; their production is complemented by dietary sources [1]

L-arginine is popular among various populations for its purported health benefits and performance enhancement capabilities.

It features prominently as a key active ingredient in many dietary supplements.

In this article, we turn to science to determine the efficacy of L-arginine as a therapeutic agent.

In the end, you will establish whether L-arginine can treat and manage all those health conditions purported by popular websites.


 

What is L-arginine?

L-arginine is a semi-essential amino acid. It is synthesized in the body through either of two processes:

  • The recycling of amino acids through normal protein turnover
  • It can also be made afresh through the synthesis of arginine precursor compounds [2]

The main organs where L-arginine synthesis occurs is mainly the kidneys and a smaller percentage in the liver.

However, the quantities of L-arginine produced by these processes do not always suffice its functions in the body.

The homeostasis (equilibrium point) of L-arginine plasma levels is regulated by protein turnover, arginine synthesis, metabolism, and dietary arginine intake [3].

To maintain this equilibrium, dietary intake of L-arginine is deemed necessary from time to time.

Certain foods, particularly proteins are rich in L-arginine. According to research studies, the quantity of L-arginine is various protein foods ranges from 3%-15% [4].

Some of the richest dietary sources of L-arginine are meats, fish, soy, and nuts like peanuts and walnuts.

The occurrence of L-arginine in the mammalian protein was discovered in 1895.

We will look at the specific functions of L-arginine in the body later on the “how it works” segment of this article.


 

Is L-arginine Safe?

Research studies on the adverse effects of L-arginine have proven it to be relatively safe for consumption.

It has no adverse effects on the endocrine, heparin, and renal functions in adults.

However, when taken in large doses L-arginine has been shown to cause gastronomic issues among some users.

The symptoms of gastronomic issues include bloating, abdominal pain, nausea, and diarrhea [5].

The research also revealed that L-arginine may not be safe for people with or at risk of cancer.

On the other side, Long-term use of L-arginine has even been proven to delay the onset of type 2 diabetes and improve the symptoms of cardiovascular disease[6][7].


 

How Does L-arginine Work?

L-arginine has been credited with many health benefits; from treating erectile dysfunction to managing critical illnesses.

For this reason, L-arginine supplementation is popular among different populations and age groups.

To establish the validity of L-arginine’s claimed health benefits, we need to understand its functions in the body.

Let us look at the role of L-arginine in various physiological functions in the body.

L-arginine is a substrate for Nitric Oxide Synthase (NOS) production. Being a substrate means that L-arginine is broken down to produce the enzyme NOS.

NOS is released in the vascular endothelial and immune cells and is a precursor for the production of Nitric Oxide (NO). Nitric oxide is an important signaling molecule.

As a precursor for the production of NO, L-arginine is involved in protein phosphorylation and gene expression.

Phosphorylation affects enzyme activity while gene expression is the process by which instructions in DNA are converted to functional products such as proteins [8][9].

L-arginine’s phosphorylation and gene expression functions make it an important signaling molecule too.

L-arginine is also an essential component of the urea cycle [10]. In the urea cycle, ammonia from protein catabolism is converted into urea and excreted in urine.

L-arginine is broken down to produce urea and ornithine. While urea is excreted as urine, the ornithine is redirected back to the mitochondria to restart the urea cycle [11].

Apart from being a substrate for NOS synthesis, L-arginine is involved in other metabolic pathways that lead to the formation of compounds like creatine, L-ornithine, L-glutamate, and polyamines.


 

Health Benefits of L-arginine

Health Benefits of L-Arginine

Below are some of the health benefits associated with L-arginine supplementation.

Let us look at what scientific research studies have to say about L-arginine’s effects on the following health conditions.

1. Helps with the management of blood pressure and cardiovascular disease. 

What the science says

A series of clinical studies have been conducted to establish the effects of L-arginine on cardiovascular disease.

In the first trial, they infused L-arginine into the coronary arteries of the subjects with coronary disease.

The researchers measured the coronary response flow to acetylcholine (a neurotransmitter) before and after the administration of L-arginine.

The results from the study showed that L-arginine enhanced blood flow response to acetylcholine in subjects with coronary disease [12].

However, there was no change in the control subjects. Subsequent clinical trials on the impact of L-arginine on blood flow yielded mixed results[13].

Some people are predisposed to experience improved blood flow as a result of L-arginine supplementation while others are not.

The underlying factors that may contribute to this mixed phenomenon are, however, unknown.

Human study on the effects of L-arginine on blood pressure was conducted among ethnically diverse salt-sensitive and salt-resistant subjects.

In all the cases, L-arginine was proven to aid in the reduction of the mean arterial pressure [14].

While studies prove that indeed L-arginine helps control blood pressure, the results on its efficacy in managing cardiovascular conditions are mixed.

2. Blood Sugar Regulation

L-arginine supplementation is believed to help improve insulin sensitivity.

What the science says

Research studies have shown that a low dose of L-arginine helps improve insulin sensitivity in both subjects with type 2 diabetes as well as diabetes-free subjects [15].

One study on the effects of L-arginine on insulin resistance was conducted using rats. Three groups of rats each with a dozen rats were the test subjects.

The first group was fed on a standard diet, the second group on a high-fat diet, and the last group on a high-fat diet supplemented with L-arginine. After 42 days, glucose-insulin was measured.

While there was an increase in insulin and cholesterol levels in group 2, there was no increase in these factors in group three despite the consumption of a high-fat diet [16].

From the above research studies, we can conclude that L-arginine not only improves insulin sensitivity, it can also help manage cholesterol levels.

3. Enhanced Athletic Performance.

L-arginine is popular as an active ingredient in many pre-workout supplements.

It is believed to enhance physical performance and endurance. It is also believed to promote muscle regeneration and aid in the modulation of body composition.

What the science says

L-arginine is necessary for the synthesis of creatine. Creatine has been proven to improve muscle function by increasing muscular strength and muscle fiber size.

A study was conducted to establish whether an increase in L-arginine is directly proportional to an increase in creatine.

From the study, it emerged that the ingestion of L-arginine from dietary sources does not affect creatine levels.

Any increase in creatine production results from L-arginine supplementation [17].

L-arginine is also a precursor for the synthesis of Nitric Oxide (NO) which is a signaling molecule.

Nitric oxide regulates various muscle functions including force production, respiration, and glucose homeostasis.

Although L-arginine increases NO production, research into whether elevated NO levels contribute to enhanced muscle performance remains largely inconclusive.

While various studies indicate that L-arginine supplementation promotes muscle strength, endurance, and recovery others yielded conflicting results [18]

4. Treatment of Erectile Dysfunction

Some men use L-arginine as an alternative remedy to correct erectile dysfunction.

What the science says

Nitric oxide as a signaling molecule is essential for penile erection. As men advance in age, so does the production of NO inhibitors which in extreme cases may cause erectile dysfunction [19].

On average, 52% of men over the age of 40 suffer from erectile dysfunction at some point.

For most men, the problem is often unpredictable and does not require the use of regular prescription medication.

A few placebo studies have been conducted to establish the efficacy of L-arginine in tackling erectile dysfunction. Other studies on the same subject tested L-arginine alongside other elements.

Some studies showed that a dose of 3g or less of L-arginine per day is ineffective in tackling erectile dysfunction.

Other studies showed that subjects who used 2.8mg-6mg of L-arginine per day for a period of six weeks reported positive effects on erectile dysfunction.

However, for the second set of studies, the positive results were not vetted using standardized questionnaires. Both sets of studies also used a rather small number of subjects [20].

On the other hand, studies on L-arginine combined with other compounds yielded positive results. L-arginine combined with pycnogenol (pine bark extract) had the following positive effects on subjects:

  • Decreased time to achieve an erection
  • Increased duration of erection
  • Increase in sperm quality and sperm count
  • 50 couples from the study reported getting pregnant after using the combination [21]

Other compounds that yielded positive results alongside L-arginine on mild erectile dysfunction include; L-citrulline, L-carnitine, adenosine monophosphate, and agrimax.

Note, however, that there are no human studies on L-citrulline +L-arginine yet. Only one human study has been conducted on L-citrulline + Adenosine monophosphate.

5. Aids in the Treatment and Prevention of Preeclampsia. 

Some people vouch for the intake of L-arginine during pregnancy to help treat or prevent the occurrence of preeclampsia.

What the science says

Preliminary data suggest that dietary supplementation of L-arginine may lower the risk of preeclampsia. It does so by promoting vasodilation through increased production of nitric oxide [22].

Raised levels of Asymmetric dimethylarginine (ADMA), a competitive inhibitor of NOS, is a potential contributor to preeclampsia.

Impaired maternal endothelial dysfunction is common among women who eventually develop preeclampsia [23].

ADMA is associated with endothelial dysfunction among some women.

Several studies were conducted among 884 pregnant women with the pregnancy-related hypersensitive disease and those considered to be at risk of preeclampsia.

The studies revealed that L-arginine supplementation during pregnancy significantly reduced the risk of preeclampsia [24].

Note, however, that the mechanism through which L-arginine tackles Preeclampsia remains largely unknown. Based on this fact, there is limited data on L-arginine’s impact on infant health.

The sample size used was also rather small hence more research needs to be conducted on larger populations.

6. Aids in Healing of Wounds

Some people believe that L-arginine speeds up the healing process of wounds.

What the science says

For a wound to heal, platelets, inflammatory cells, fibroblasts, and epithelial cells are involved. All the cells above can produce nitric oxide either in a constitutive manner or in response to inflammatory cytokines.

The healing spectrum associated with NO ranges from inflammation, cell proliferation (growth and division), and angiogenesis (development of new blood vessels).

All NOS enzymes play specific roles in the healing process from the inflammatory phase to the scar remodeling phase.

The NO synthesized by NOS modulates cytokine cascades that work on various phases of the healing process.

In a controlled study, sets of mice with 2.5cm dorsal skin incision were on L-arginine supplementation for 14 days.

The post-study examination determined that L-arginine dietary supplementation enhanced wound breaking strength as well as collagen deposition on the mice [25].

While the NO pathway is one way through which L-arginine enhances healing; L-arginine has also been shown to improve wound cell function by decreasing the inflammatory response to the wound site.

7. Improved Immune Response

What the science says

When it comes to immunity, L-arginine can work either way.

Small doses of dietary L-arginine have been proven to promote protein synthesis, improve blood tissue supply, inhibit inflammatory responses, and reduce platelet adhesion. All these factors contribute to the body’s wellness.

On the other hand, in high doses, L-arginine promotes inflammatory responses which might aggravate tissue trauma.

Clinical trials on the impact of L-arginine on immunity is limited due to the small populations used as well as the lack of control subjects [26].


 

Side Effects

L-arginine is relatively safe to use. However, it has been associated with gastronomical issues in some people.

The side effects hinting at the gastronomical issues include:

  • Bloating
  • Abdominal pain
  • Nausea
  • Diarrhea

L-arginine has also been shown to aggravate pregnancy sickness when used in pregnant women. The symptoms include:

  • Headaches
  • Nausea
  • Dizziness

Usage of L-Arginine


 

Usage and Dosing Considerations

L-arginine supplementation can be recommended to tackle various issues from pregnancy to blood sugar regulation.

The recommended daily dose of L-arginine depends largely on the reason for taking it [27].

The dose also varies for adults and children. As with any other supplements read the label carefully and follow the recommended dose on specific brands of L-arginine supplements.

While L-arginine is relatively safe, it is advisable to consult your doctor before taking it as a supplement.

Conduct thorough research and ensure that it is indeed helpful for your condition. 


 

Risks and Precautions

If you are prone to allergies, please consult a physician before using L-arginine supplementation.

L-arginine is also considered rather unsafe for people with cancer and those at a higher risk of getting cancer.


 

FAQs

Who should not take L-arginine?

L-arginine is relatively safe for both children and adults to take. However, it can be detrimental for people with cancer and those at a higher risk of getting cancer.

People who are allergic to the amino acid arginine should also not take L-arginine.

 How fast does L-arginine work?

The speed at which L-arginine will take effect depends largely on the reason for which you are taking it.

For example, L-arginine supplements for improved exercise performance will show results quicker than L-arginine for the treatment of preeclampsia.

Individual physiological factors are other considerations because people react differently to different substances.

Does L-arginine make you last longer in bed?

There is some evidence to support that L-arginine can be used to treat mild to medium cases of erectile dysfunction.

L-arginine used along with Pycnogenol decreased the time taken to achieve an erection and increased the duration of erection.

How much L-arginine is safe for use per day?

The recommended daily dose of L-arginine depends largely on the reason for taking it. There are recommended doses for specific therapies.

Consult your doctor and follow the instructions given on the L-arginine supplement label. 


 

Summary

L-arginine is popular among users for two main reasons; its health benefits and the fact that it is a natural remedy with limited side effects.

It is, however, important to note that while some of L-arginine’s purported benefits have been proven others are yet to be proven.

Consult your doctor before deciding to use L-arginine supplementation as a therapy for tackling any health issue.

If you decide to take L-arginine dietary supplements, adhere to the recommended dose.

Conduct research into the effective clinical dose of L-arginine recommended for specific health conditions.

Related:


References
  1. https://www.researchgate.net/publication/260210809_Amino_acids_A_review_article
  2. https://www.sciencedirect.com/topics/neuroscience/arginine
  3. https://www.sciencedirect.com/science/article/pii/S2090123210000573
  4. https://academic.oup.com/jn/article/137/6/1650S/4664939
  5. https://academic.oup.com/jn/article/146/12/2587S/4589981
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267392/
  7. https://academic.oup.com/jn/article/137/6/1650S/4664939
  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944195/
  9. https://www.nature.com/scitable/topicpage/gene-expression-14121669/
  10. https://www.ncbi.nlm.nih.gov/books/NBK513323/
  11. https://www.annualreviews.org/doi/pdf/10.1146/annurev.nutr.22.110801.140547
  12. https://academic.oup.com/jn/article/137/6/1650S/4664939
  13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793528/#CR14
  14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728371/
  15. https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2362.1997.1730718.x
  16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565209/#
  17. https://jissn.biomedcentral.com/articles/10.1186/1550-2783-1-2-35
  18. https://jissn.biomedcentral.com/articles/10.1186/1550-2783-1-2-35
  19. https://clinicaltrials.gov/ct2/show/NCT00777075
  20. https://www.sciencedirect.com/science/article/pii/S2090123210000573#bib29
  21. https://journals.sagepub.com/doi/full/10.1177/2631831818822018
  22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366568/#CR3
  23. https://pubmed.ncbi.nlm.nih.gov/12737861/
  24. https://www.nature.com/articles/jhh2013100
  25. https://www.researchgate.net/publication/12396995_
  26. http://apjcn.nhri.org.tw/server/APJCN/23/3/351.pdf
  27. https://medlineplus.gov/druginfo/natural/875.html

Add comment