L-arginine in cardiac arrhythmias: protection or cause?

Cardiovascular diseases are the leading cause of death worldwide. Although not every cardiac arrhythmia is directly life-threatening, prolonged cardiac arrhythmias in particular can trigger cardiac insufficiency and even heart attacks. So a healthy heart is very important.

There are many ways to prevent and treat cardiac arrhythmia. The natural amino acid arginine is said to have such an effect. But does arginine really help with cardiac arrhythmia and how does it work in the body? In this article we clarify.

the essentials in brief

• Arginine is a natural amino acid that is produced by the body itself. However, since it is not produced in sufficient quantities in all situations, intake through food, for example, is necessary.
• Arginine is the precursor to nitric oxide, which causes blood vessels to dilate. Thus, arginine can lower high blood pressure.
• The exact mechanism of action of arginine is still unknown. Although no increase in endogenous nitric oxide production is to be expected from an increased plasma arginine concentration, this has been observed in studies.

L-arginine for cardiac arrhythmias: what you should know

Cardiac arrhythmias are divided into three categories. Bradycardia is the heart beating too slowly, tachycardia is the heart beating too fast, and arrhythmia is the irregular heartbeat. These categories can have different causes.

The blood pressure-lowering property of arginine has been well studied and proven, but there is no evidence of an influence on the electrical impulses that trigger the heartbeat.

What is L-arginine?

L-arginine is an α-amino acid. The L indicates the spatial arrangement of the molecules, in this case on the left. The right "D-form" cannot be recognized by the body's own enzymes. If arginine is spoken of, L-arginine is usually meant.

Although arginine is produced by the body itself, in some situations, such as the growth phase, this is not sufficient and it must be supplemented through food or supplementation. These are called semi-essential amino acids.

What functions does arginine have?

Arginine plays an important role in human metabolism. It is the precursor to protein synthesis and other important molecules such as nitric oxide, ornithine, polyamines, agmatine, proline, glutamate, creatine and urea.

molecule	Task
nitric oxide	A messenger substance with many tasks. Promotes blood circulation and the formation of new blood vessels. Play an important role in the immune system.
ornithine	Carrier responsible for the removal of metabolic waste products.
polyamines	Present in all living cells. Plays a central role in the regulation of molecular signaling pathways.
agmatine	Probably a neurotransmitter, but is still part of more detailed investigations.
proline	Important for the formation and health of connective tissue and bones.
glutamate	Plays a crucial role as a signal transmitter or neurotransmitter. Necessary for memory, sensory perception and movement.
creatine	A carbon-nitrogen compound responsible for energy metabolism in skeletal muscles.
urea	End product of the urea cycle. Used to detoxify ammonia.

Especially in the growth phase, a sufficient supply of arginine is necessary for optimal development. For adults, arginine is particularly important in conditions such as trauma, burn injuries, small bowel resections, and kidney failure.(1)

How does arginine work in the body?

Depending on a role , arginine works differently in the body. In the context of cardiac arrhythmias, its functioning is relevant to the synthesis of nitric oxide (NO). Arginine is a substrate for the endothelium-specific isoform of nitric oxide synthase (eNOS), thereby promoting increased nitric oxide synthesis by vascular endothelium. NO diffuses from the endothelial cells into the smooth muscles, where it causes relaxation, which leads to a widening of the blood vessels (vasodilation).

The exact mechanism of action of arginine is not fully known.

However, when there is a deficiency of tetrahydrobiopterin, eNOS production becomes a source of oxygen radicals. Arginine supplementation also increases homocysteine ​​production. This can lead to deterioration of endothelial function and atherosclerosis.(2)

Asymmetric dimethylarginine (ADMA) can compete with arginine for NOS binding and thus inhibit NO production. With high levels of ADMA, arginine appears to normalize endothelial function.(3)

Is arginine good for the heart?

The positive effect of arginine on blood pressure has been proven several times.(4,5) Lowering blood pressure can relieve the heart and thus have a positive effect. However, no improvement was seen in patients with heart failure compared to the placebo group.(6)

Arginine can relax smooth muscles via nitric oxide and thus dilate blood vessels, which leads to a reduction in blood pressure. This can relieve the heart. (Image source: Myriams photos/ Pixabay)

It is believed that different results about the effects of arginine are due to a different ratio of arginine and ADMA in the body. At high levels of ADMA, arginine appears to increase NO availability, leading to improvements in hemodynamic and cardiac function.(7)

What role does arginine play in cardiac arrhythmias?

Does arginine protect against cardiac arrhythmias or can it even be a trigger? Studies provide very different results on the connection between arginine and cardiac arrhythmias. When can the additional intake help and when does it become dangerous? In the next part we will clarify.

Can arginine cause cardiac arrhythmia?

In 2014, German scientists discovered a new gene that can lead to life-threatening cardiac arrhythmias. In one patient, multiple mutated genes worked together to change the rhythm of the electrical signals that make the heart beat. The mutated potassium channel "TASK-4" incorrectly has arginine at position 88, which increases its conductivity for ions three-fold.(8)

However, this is an isolated case. A connection with an increased intake of arginine has not been proven. How this mutation can occur and whether it occurs more frequently must be shown in future studies.

Can Arginine Prevent Cardiac Arrhythmias?

The scientific evidence on the effects of arginine on the heart is inconclusive. While arginine's blood pressure-lowering property can provide relief to the heart, which can reduce the risk of cardiac arrhythmia, in patients with atherosclerosis, arginine's production of peroxynitrite and consumption of nitric oxide can make atherosclerosis worse.

Whether arginine protects against cardiac arrhythmia cannot yet be said with certainty.

In a randomized, double-blind, placebo-controlled study in which patients with ST-segment elevation myocardial infarction were treated with L-arginine, six of the patients treated with L-arginine died over the 6 months while none in the placebo group died.(9)

Patients with previous cardiovascular diseases should therefore consult a doctor before taking arginine supplements. In healthy patients, arginine supplementation may have beneficial effects on blood pressure and help the body repair damaged vessels in the heart.(8)

Where else is arginine used?

Oral arginine supplements are probably the most common among athletes. The same mechanisms that can have a positive effect on the heart should also be used here. Athletes expect improved blood circulation through higher NO values, increased performance and even indirect support for muscle building. Arginine is therefore particularly popular with bodybuilders.

Arginine is popular with athletes and especially bodybuilders, as they hope to increase performance through improved blood circulation. (Image source: Victor Freitas/ Pexels)

The improved blood circulation should also help in bed. Some men therefore use arginine as a natural sexual enhancer. Although a study on 40 infertile men was able to show that arginine significantly improves sperm mortality (10), there are different results on the "sporting" increase in performance.(11,12)

How many mg of arginine per day?

It is not generally possible to say how much arginine a person needs per day. In the growth phase and in the case of certain diseases, additional arginine must be taken in at least through food. With a healthy diet, this shouldn't be a problem. Healthy people and above all athletes can, under certain circumstances, perceive a positive effect through additional supplementation.

In connection with cardiac arrhythmia, things get a little more difficult. With high ADMA values, an additional intake of arginine can relieve the heart due to the increased NO production. However, studies have found a negative effect of arginine supplementation in patients with atherosclerosis and acute ST-segment elevation myocardial infarction. In these cases, the daily dose should be kept low.

What side effects does arginine have?

Caution should be exercised in people with acute heart problems. Individual studies observed a positive influence of arginine in people with acute heart problems. However, there are also studies that show an increased risk in this case. If you have heart problems, you should consult a doctor before supplementing with arginine.

So far, no serious side effects have been found in healthy people, even when taking high doses. Ingesting large amounts of arginine can result in symptoms similar to those of a hangover . These include nausea, diarrhea and headaches.(13)

Conclusion

Arginine is said to have many positive properties. It plays an important role in the human cardiovascular system and fulfills several functions. However, its exact mechanisms of action are still not fully understood. This is probably the reason for the different results on the benefit of arginine supplementation. Serious side effects only seem to occur in the case of previous illnesses.

In healthy people, there is nothing to be said against an additional intake of arginine, specifically through food or dietary supplements. In some life situations this may even be necessary. Arginine can be taken as a supplement if you have a heart problem, but this should be done after consultation and not at your own discretion.

References

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2. Aronson, Jeffrey K., ed. Meyler's side effects of drugs: the international encyclopedia of adverse drug reactions and interactions. Elsevier, 2015, Pages 674-675 Source
3. Rainer H. Böger, The Pharmacodynamics of L-Arginine, The Journal of Nutrition, Volume 137, Issue 6, June 2007, Pages 1650S - 1655S Source
4. Miller AL. The effects of sustained-release L-arginine formulation on blood pressure and vascular compliance in 29 healthy individuals. Altern Med Rev. 2006 Mar;11(1):23-9. PMID: 16597191. Source
5. Dong JY, Qin LQ, Zhang Z, Zhao Y, Wang J, Arigoni F, Zhang W. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011 Dec;162(6):959-65. doi: 10.1016/j.ahj.2011.09.012. Epub 2011 Nov 8. PMID: 22137067. Source
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7. Visser, Marlieke, et al. "The role of asymmetric dimethylarginine and arginine in the failing heart and its vasculature." European journal of heart failure 12.12 (2010): 1274-1281. Source
8. Friedrich, Corinna, et al. "Gain‐of‐function mutation in TASK‐4 channels and severe cardiac conduction disorder." EMBO molecular medicine 6.7 (2014): 937-951. Source
9. Schulman, Steven P., et al. "TRAITEMENT PAR L-ARGININE DE L'INFARCTUS AIGU DU MYOCARDE: L'ESSAI CLINIQUE RANDOMISE VINTAGE MI (VASCULAR INTERACTION WITH AGE IN MYOCARDIAL INFARCTION)." JAMA-français 295.2 (2006): a11. Source
10. Scibona M, Meschini P, Capparelli S et al. [L-arginine and male infertility]. Minerva Urologica e Nefrologica = The Italian Journal of Urology and Nephrology. 1994 Dec; 46(4):251-251 253.Source
11. Gil, Sam. "The effects of acute arginine supplementation on 10 mile cycling time trial performance in young adult males." (2012). Source
12. Bailey, Stephen J., et al. "Acute L-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise tolerance." Journal of Applied Physiology 109.5 (2010): 1394-1403. Source
13. Evans, Rhobert W., et al. "Biochemical responses of healthy subjects during dietary supplementation with L-arginine." The Journal of nutritional biochemistry 15.9 (2004): 534-539. Source