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11 Benefits and Side Effects of Arginine (12 Contraindications To Be Noted)

Arginine (L-Arginine) is an essential amino acid, found in a variety of animal foods (meat, poultry and fish), in addition to synthesizing protein, arginine is also involved in many physiological reactions, regulating physiological functions, is the most versatile amino acid

What are the benefits of arginine in empirical medicine? Are there any side effects or contraindications? See text analysis for details.

What is arginine?

Strictly speaking, arginine is a semi-essential amino acid that plays an important role in many metabolic pathways because it acts as a precursor to the synthesis of biologically active substances such as nitric oxide, growth hormone, and creatine, which are essential for cell proliferation, increased antioxidant defenses, and enhanced cellular protective mechanisms.

One of the most famous is arginine’s ability to act as a precursor to nitric oxide synthesis.

Nitric oxide is an important biological signaling molecule in the human body, and unlike laughing gas (nitrous oxide), it is not exciting, but it can determine your health.

Nitric oxide can act on various tissues and act as a neurotransmitter in the brain; It is also an important regulatory substance in the immune system; Even the cardiovascular system is vasodilator and anti-atherosclerotic factor.

In most cases, arginine is synthesized endogenously enough to meet the needs of the human body and does not require additional supplementation.

However, in certain physiological and pathological states, such as growth, pregnancy, and disease, such as infection and cancer, arginine often requires endogenous synthesis in multiple tissues through the arginine-citrulline cycle.

What are the proven benefits of arginine?

1. Arginine improves adverse birth outcomes in newborns

Despite significant global progress in improving maternal, newborn and child health over the past two decades, preterm births and low birth weight etc. Adverse birth outcomes remain an important challenge, especially in low- and middle-income countries.

Poor water, sanitation and hygiene control can also increase the likelihood of contracting diseases, including intestinal helminth infections that can lead to conditions such as anaemia, which can adversely affect fetal survival and growth.

Poor maternal health during pregnancy is associated with preterm birth (<37 weeks’ gestation) and low birth weight (<2500 g), and adverse neonatal events associated with respiratory distress syndrome, neurocognitive impairment, developmental delays etc.

A systematic literature review and meta-analysis (10 RCTs) suggests that arginine supplementation in women with a history of adverse pregnancy outcomes significantly reduces the risk of intrauterine growth retardation, preterm birth, and respiratory distress syndrome in newborns compared with controls, and significantly increases birth weight and gestational age. Note 1

In addition, arginine supplementation significantly improved the Apgar Score in women at high risk of preeclampsia, women with preeclampsia, pregnancy, or mild chronic hypertension compared with controls.

*Conclusion: Oral arginine may help reduce some adverse birth outcomes in women with a history of adverse pregnancy outcomes, but more research is needed to support this due to small sample sizes

2. Arginine enhances athletic performance

Physical activity requires a long period of high metabolic rate and adequate nutrition to maintain performance at the highest level.

Therefore, adequate nutrition is important for tissue growth and repair, and is necessary for athletes to fully recover between training and competition, directly improving performance, indirectly benefiting from providing training support, physical control, reducing musculoskeletal pain, recovering quickly from injury and improving mood.

A systematic literature review and meta-analysis (15 randomized placebo-controlled trials) noted a positive effect of arginine supplementation on anaerobic and aerobic exercise-related fitness test results. Note 1

Regarding the dose, differences between acute and chronic regimens were observed, indicating that the two strategies may have different mechanisms and responses.

In acute protocols, spermine supplementation of 60.90 g/kg body weight (approximately 0 g to 15 g) between 10 and 11 minutes before exercise improves anaerobic and aerobic exercise outcomes.

On the other hand, chronic arginine supplementation (1.5 to 2 g/day) for 4 to 7 weeks and higher doses (10 to 12 g/day for 8 weeks) also favored aerobic and anaerobic performance, respectively.

*Conclusion: Arginine supplementation may have a positive effect on improving exercise performance, but due to insufficient number of studies and heterogeneity, more studies are needed to further validate

3. Arginine is beneficial to blood lipid regulation

Prevention and treatment of dyslipidemia are considered an integral part of cardiovascular disease prevention interventions, as dyslipidemia is a serious risk factor for cardiovascular events such as coronary heart disease, cerebral ischemia, cerebral infarction and peripheral vascular disease.

To date, statins remain the treatment of choice because they have been shown to reduce the risk of developing major vascular events by lowering LDL cholesterol, while treating dyslipidemia can reduce the risk of heart disease by about 5% over 30 years.

A general literature review and meta-analysis (11 randomized controlled trials, 561 participants) noted that arginine supplementation only helped reduce serum triglyceride levels and had no significant help in altering total cholesterol, low or high-density lipoprotein cholesterol. Note 1

*Conclusion: Arginine supplementation can help improve triglyceride levels, but it is not significantly beneficial to other blood lipid indicators, and more studies are needed to confirm the effect on hyperlipidemia

4. Arginine is good for weight loss

The World Health Organization defines obesity as a condition in which the percentage of body fat increases to the level of damage to health and well-being, and declares it a “global pandemic” that affects more than 6 million adults worldwide, and that number continues to grow.

It is the result of a complex interplay of factors such as genetics, lifestyle, eating habits, energy expenditure, nutrition, and metabolism.

A systematic literature review and meta-analysis (8 randomized controlled trials, 461 participants) noted, Note 1

Overall, oral arginine (daily dose ranging from 2 to 9 g, intervention period from 3 weeks to 25 weeks) significantly reduced waist circumference (WMD: -2.97 cm) compared with placebo, but did not have a significant effect on body mass index (BMI) and weight.

However, subgroup analyses found that the effect of arginine in reducing body weight and body mass index was seen in participants with long-term interventions (≥ 8 weeks) and daily doses < 8 g.

The mechanism behind it may be related to arginine promoting lipid utilization, insulin signaling, and glucose transport.

*Conclusion: Oral arginine may be of positive benefit in improving weight-related measures, but more large trials are needed to support this due to the heterogeneity of the studies included

5. Arginine is beneficial for erectile dysfunction

Erectile dysfunction, defined as the inability to achieve or maintain an erection sufficient for sexual performance, increases with age, with prevalence ranging from 2% in men under 40, to 52% in men aged 40 to 70, and more than 85% in men aged 80 and older.

In addition, coronary artery disease, obesity, smoking, depression, hypertension, preoperative pelvic surgery, spinal cord injury and other psychological variables are also one of the factors that contribute to the pathogenesis.

The development of erectile dysfunction often has a significant impact on men’s interpersonal, social, emotional, and especially mental health.

A systematic literature review and meta-analysis (10 randomized controlled trials of 540 patients with mild to moderate erectile dysfunction) suggested that oral arginine-related supplements (daily doses ranging from 1500 mg to 5000 mg) significantly improved erectile dysfunction compared with placebo or no treatment. Note 1

In addition, subgroup analysis showed that arginine-related supplements improved subdomain scores of the International Index of Erectile Function, including overall satisfaction, sexual satisfaction, orgasmic function, and erectile function (but there was no significant difference in libido scores).

*Conclusion: The use of arginine or arginine-containing supplements may be beneficial in improving symptoms in patients with mild to moderate erectile dysfunction, but more high-quality evidence is needed due to the heterogeneity of the studies included

6. Arginine improves immune function

The immune system is a complex and multifaceted network of specialized organs, tissues, cells, proteins, and chemicals that evolved to protect its host from a variety of pathogens, such as bacteria, viruses, fungi, parasites, and cancer cells.

Proper nutrition (glucose, amino acids and fatty acids) is necessary for the various cells of the immune system to function optimally and respond to damaged and invading viruses and bacteria.

Extreme diets, especially protein-energy malnutrition, have far-reaching effects in reducing immune function and increasing the risk of opportunistic infections.

A meta-analyses (11 randomized controlled trials, 321 participants) noted that arginine supplementation increased CD4⁺T cell proliferation and reduced associated infectious morbidity. Note 1

*Conclusion: Oral arginine can help improve immune function, but due to small sample size and possible bias, more large trials are needed to support it

7. Arginine regulates blood pressure

Hypertension is a latent, common, and fatal condition that is often caught incidentally during routine doctor’s exams or workplace health checks.

It is estimated that 10 billion people worldwide have high blood pressure, and in the United States alone, about 8000 million people over the age of 20 have high blood pressure.

According to statistics, 51% of stroke deaths and 45% of coronary heart disease deaths are caused by elevated blood pressure, in addition, high blood pressure also increases the risk of heart disease, heart failure, stroke and kidney disease.

A meta-analysis of 11 randomized, double-blind, placebo-controlled trials with 387 participants noted that oral arginine (median dose of 9 g daily for 4 weeks) significantly reduced systolic blood pressure by 5.39 mm Hg and diastolic blood pressure by 2.66 mm Hg compared with placebo. Note 2

*Conclusion: Oral arginine has the effect of regulating blood pressure, but due to small sample size and possible publication bias, more large trials are needed to further confirm

8. Arginine is beneficial to acute myocardial infarction

Acute myocardial infarction is the disease with the highest morbidity and mortality rate in the world, mainly caused by the rupture of atherosclerotic plaques, leading to coronary artery thrombosis and blockage.

Although about 75% of patients with acute myocardial infarction survive for more than 1 year, their mortality rate is significantly higher than in the general population.

A meta-analysis (2 randomized, double-blind, placebo-controlled trials of 927 patients with acute myocardial infarction) noted that there was no clear difference in total clinical events between oral arginine compared with placebo, including: all-cause mortality, myocardial reinfarction, successful resuscitation, pulmonary edema, recurrent myocardial ischemia, heart failure, adverse events, and loss to follow-up. Note 3

*Conclusion: For patients with acute myocardial infarction who are undergoing treatment, the additional use of arginine has not had a beneficial effect on clinical outcomes

9. Arginine is beneficial for dentin hypersensitivity

Dentine hypersensitivity is characterized by short, sharp pain in the exposed dentin when stimulated, usually associated with heat, evaporation, tactile, penetrating or chemical substances, and cannot be attributed to any other dental defect or pathological factor.

In adults, the prevalence of dentin hypersensitivity ranges from 5% to 85%, especially in 30-40 years, and may be related to dental hygiene and diet.

A systematic literature review and meta-analysis (14 randomised controlled trials of dentin sensitivity) found that arginine-containing toothpaste was associated with better overall symptom improvement than placebo or control (potassium salt and strontium-containing toothpaste). Note 5

*Conclusion: For dentin sensitivity, the use of arginine-containing toothpaste may have a positive effect on symptom improvement

10. Arginine is beneficial for head and neck cancer

Head and neck cancers are cancers that occur in the aero-digestive tract and are the sixth most common cancer in the world, accounting for 6% of solid tumors, with about 650,000 new head and neck cancers diagnosed each year and 350,000 deaths.

More than 90% of head and neck cancers are squamous cell carcinomas, most of which are located in the mouth and larynx (about 60% to 70%), other areas are: nasal cavity, pharynx, middle ear, salivary glands, thyroid, soft tissue, bone, and cartilage, while salivary adenocarcinoma, melanoma, soft tissue tumors, and lymphomas are rare (about 10%).

A systematic literature review and meta-analysis (including 6 randomized controlled trials) suggested that the use of arginine enteral formulas reduced fistulas complications associated with head and neck cancer surgery and reduced hospital length of stay. Note 6

*Conclusion: For patients undergoing head and neck cancer surgery, the use of arginine enteral nutrition formula reduces the risk of some complications and reduces the length of hospital stay

11. Arginine reduces the risk of preepilepsy

Pre-eclampsia refers to a state of hypertension during pregnancy with a prevalence of 2% to 8%, most commonly between 27 and 40 weeks’ gestation, and is defined as systolic blood pressure > 140 mmHg or diastolic blood pressure ≥90 mmHg, and proteinuria ≥ 24.0 g within 3 hours.

Preepilepsy not only increases the risk of underweight in newborns, but may also increase the risk of early-onset cardiovascular diseases such as chronic hypertension, ischaemic heart disease, and stroke in the future of the mother and offspring.

A systematic review (7 randomized controlled studies with 884 pregnant women) noted that arginine had the effect of reducing the incidence of preepilepsy in both those at high risk of hypertension and preepilepsy. Note 7

*Conclusion: For high-risk groups, arginine can reduce the risk of preepileptic disease, but the small sample size is limited, and more studies are needed

Are there any side effects f arginine?

Arginine is a safe health ingredient for most people when taken for a short period of time, but a small number of side effects have been reported, such as gastrointestinal discomfort (bloating, diarrhea, abdominal pain), allergies, nausea, respiratory inflammation and headaches.

A small study found that high doses of arginine (30 g daily) may relax the base esophageal sphincter and increase the risk of gastroesophageal reflux. Note 10


Safety precautions (12 contraindications for use)

1. May increase gastric acid secretion, if you have peptic ulcer or take non-steroidal anti-inflammatory drugs, please use with caution

2. Do not use it in combination with hypoglycemic or blood pressure lowering drugs, which may interfere with the effect of drugs

3. Do not use for patients with abnormal liver and kidney function (arginine may increase blood potassium concentration and may cause danger in some cases)

4. Do not use by herpes patients (may cause disease to worsen)

5. Patients with acute myocardial infarction should not use it, which may increase mortality, but other studies have not found this result. Note 11

6. The safety of pregnant women, lactating women, children or infants is unknown (please avoid use)

7. Do not use Guanidinoacetate methyltransferase deficiency (a rare genetic disorder of transfer enzyme deficiency that cannot metabolize arginine)

8. Do not use for patients with low blood pressure, because arginine may have a blood pressure lowering effect

9. Do not use for two weeks before surgery

10. Do not use it with vasodilator drugs, because arginine has the effect of increasing blood flow, if used together may increase the chance of dizziness, related drug names are: nitroglycerin, isosorbide (isosorbide nitrate)

11. Do not use it together with the treatment of male erectile dysfunction drug Sildenafil (Viersteel), because arginine and Viersteel have the same blood lowering effect, if used together, it may cause blood pressure to be too low

12. A meta-analysis (including 11 randomized controlled trials) mentioned that for the following subjects (cancer patients older than 60 years, C-reactive protein levels greater than 3 mg/dl, and enteral formulations), the use of arginine may increase the value of inflammation indicators: C-reactive protein, so it is important to pay attention to relevant objects. Note 12

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