Arginine

Arginine


Arginine (or L-Arginine) is an amino acid involved in numerous areas of human biochemistry, including ammonia detoxification, hormone secretion, and the immune system. Arginine is also well known as a precursor to nitric oxide, a key component of endothelial-derived relaxing factor. The endothelium is the lining inside blood vessels and arginine supplements help make more nitric oxide. Therefore, arginine, by making more nitric oxide helps to relax and dilate blood vessels.
Nitric oxide is a messenger molecule involved in a variety of endothelium-dependent effects in the cardiovascular system. Because of arginine's nitric oxide-stimulating effects, it may potentially be useful in angina pectoris, congestive heart failure, hypertension, coronary heart disease, preeclampsia, intermittent claudication, and erectile dysfunction. In addition, arginine has been studied for its role in HIV/AIDS, athletic performance, burns and trauma, diabetes and syndrome X, male and female infertility, and interstitial cystitis. Source: Appleton J., Altern Med Rev. 2002 Dec;7(6):512-22.
Dr. Sahelian says: Even though arginine has been claimed to be useful for some of the conditions listed above, it would be premature to be overly excited. Much research needs to be done before we can be more confident about arginine's potential. However, so far, arginine appears to have a role to play in conditions involving blood vessel dilation. Whether the dilation is short lived or continues for an adequate period is still being evaluated.


Arginine and Erectile Dysfunction

One of the more popular supplements for sexual dysfunction is L-arginine, also referred to as arginine. Arginine is a versatile amino acids in animal cells, serving as a precursor for the making not only of proteins but also of nitric oxide, urea, glutamate, and creatine. What makes l-arginine interesting is that it can be metabolized to nitric oxide (NO). NO is the most powerful chemical known to dilate and engorge blood vessels in the penis and clitoris. What does the research say about the role of arginine in erectile dysfunction?


A Low dose of l-arginine, at 500 mg three times a day, has not been found to be effective for erectile dysfunction.

A double-blind, placebo-controlled study of 50 men with erectile dysfunction tested arginine at a dose of 5 grams per day for six weeks. About a third of the participants who received arginine showed improvement, and that improvement was greater than the 10% improvement seen in the placebo group.

Arginine has been studied in combination with other nutrients as a treatment for sexual dysfunction in women. A small trial found some improvement with a combination treatment providing a daily dose of 2,500 mg of arginine, as well as ginseng, ginkgo, and damiana. In a four-week, double-blind study, 77 women with decreased libido were given either the combination product or a placebo. Those taking the arginine-blend showed statistically greater improvement, reporting increased sexual desire in 71% of participants given the treatment. In the placebo group, 42% reported an increased libido. Other improvements included relative satisfaction with sex life and heightened clitoral sensation. No significant side effects were seen in either group. However, we don't know if the arginine had anything to do with the results.

A study done at the University of Texas at Austin examined the effects of arginine, combined with yohimbine, on sexual arousal in postmenopausal women. Twenty-four women participated in three sessions in which sexual responses to erotic stimuli were measured following treatment with either arginine glutamate (6 g) plus yohimbine (6 mg), yohimbine alone (6 mg), or a placebo, using a randomized, double-blind design. Sexual responses were measured at one hour after taking the supplements. Compared to placebo, the combined oral administration of arginine and yohimbine substantially increased vaginal pulse amplitude responses to the erotic film. It is well known that yohimbine, alone, has a significant effect on sexuality and whether arginine was a factor is not known.


Mechanism of Action of Arginine

The most likely explanation for the mild effectiveness of arginine is its conversion into nitric oxide. As discussed in Chapter 2 of Natural Sex Boosters book, nitric oxide is converted into cGMP, which becomes the secondary messenger that causes smooth muscle relaxation, resulting in more blood going into the genital organs, which leads to erections. However, nitric oxide is quickly metabolized and any potential effectiveness of arginine could be very short lived.


Potential Arginine Benefits

There is some supporting evidence that arginine may be helpful in reducing angina and lowering blood pressure (see studies bottom of page). Research indicates supplemental arginine reduces pulmonary resistance and blood pressure. Arginine supplementation improves renal function in patients with chronic heart failure. Polish researchers have found that arginine supplementation increases exercise tolerance in stable coronary artery disease patients. Oral L-arginine improves endothelial function in older healthy individuals. However, I am not convinced yet that arginine is a worthwhile supplement for erectile function or sexual enhancement, at least in low dosages.


L Arginine Dosage

L Arginine is available most often as 1,000 mg capsules and in powder form. Dosage of l arginine depends on the condition being treated.


History of Arginine

L arginine was first isolated in 1886. In 1932, L arginine was found to be required for the generation of urea, which is necessary for the removal of toxic ammonia from the body. In 1939, L arginine was also shown to be required for the synthesis of creatine.


Arginine Deficiency

Symptoms of arginine deficiency include poor wound healing, hair loss, skin rash, constipation, and fatty liver. Arginine is considered a semi-essential amino acid, because although it is normally synthesized in sufficient amounts by the body, arginine supplementation is sometimes required (for example, due to inborn errors of urea synthesis, protein malnutrition, excessive lysine intake, burns, peritoneal dialysis, rapid growth).


Arginine and Nitric Oxide

Arginine is a precursor of nitric oxide, which causes blood vessel relaxation. Although there is some evidence that suggests that arginine may be useful in the treatment of medical conditions that are improved by vasodilation, such as angina, atherosclerosis, coronary artery disease, erectile dysfunction, heart failure, intermittent claudication/peripheral vascular disease, and vascular headache, more proof is needed. The appropriate dosage and long term safety is not clear at this time. Arginine also stimulates protein synthesis and has been studied for wound healing, bodybuilding, enhancement of sperm production (spermatogenesis), and prevention of wasting in people with critical illness.


Arginine Research Update

L-Arginine improves vascular function by overcoming deleterious effects of ADMA, a novel cardiovascular risk factor.
Altern Med Rev. 2005 Mar;10(1):14-23.

There is abundant evidence that the endothelium plays a crucial role in the maintenance of vascular tone and structure. One of the major endothelium-derived vasoactive mediators is nitric oxide (NO), an endogenous messenger molecule formed in healthy vascular endothelium from the amino acid precursor L-arginine. Endothelial dysfunction is caused by various cardiovascular risk factors, metabolic diseases, and systemic or local inflammation. One mechanism that explains the occurrence of endothelial dysfunction is the presence of elevated blood levels of asymmetric dimethylarginine (ADMA)--an L-arginine analogue that inhibits NO formation and thereby can impair vascular function. Supplementation with L-arginine has been shown to restore vascular function and to improve the clinical symptoms of various diseases associated with vascular dysfunction


Plasma arginine concentrations are reduced in cancer patients: evidence for arginine deficiency?
American Journal of Clinical Nutrition, Vol. 81, No. 5, 1142-1146, May 2005

The disturbances leading to cancer cachexia remain to be unraveled. Preliminary evidence suggests that arginine availability in cancer is reduced. However, no valid data are available on plasma arginine concentrations in cancer patients. Objective: We aimed to determine whether there is evidence for disturbed arginine metabolism in cancer. Design: We measured plasma arginine concentrations postabsorptively in patients with various types of tumors, hypothesizing that arginine concentrations would be lower than those in age- and sex-matched control subjects. Patients with localized tumors with a range of metabolic implications were studied: breast cancer (no weight loss), colonic cancer (sometimes weight loss), and pancreatic cancer (usually weight loss). Plasma amino acid concentrations were measured by HPLC. Results: Plasma arginine concentrations were lower in patients with cancer (breast cancer: 80 ± 3 compared with 103 ± 9 µmol/L; colonic cancer: 80 ± 3 compared with 96 ± 7 µmol/L; pancreatic cancer: 76 ± 5 compared with 99 ± 7 µmol/L; P < 0.05 versus respective age- and sex-matched control subjects), irrespective of tumor type, weight loss, tumor stage, or body mass index (correlations with P > 0.05). Conclusions: Malignant tumors associated with various degrees of metabolic derangements are all associated with decreased plasma arginine concentrations, even without weight loss. This suggests that decreased arginine availability is a specific feature of the presence of cancer. These disturbances in arginine metabolism could contribute to the cascade of metabolic events leading to cancer cachexia.


Oral L-arginine improves hemodynamic responses to stress and reduces plasma homocysteine in hypercholesterolemic men.
J Nutr. 2005 Feb;135(2):212-7.

When administered intravenously, l-arginine substantially reduces blood pressure (BP) and peripheral vascular resistance in healthy adults and in patients with vascular disease. Oral l-arginine has been shown to improve endothelial function; however, it is not clear whether oral administration has significant effects on systemic hemodynamics. In a randomized, placebo-controlled, crossover study we tested whether oral l-arginine (12 g/d for 3 wk) affected hemodynamics, glucose, insulin, or C-reactive protein in 16 middle-age men with hypercholesterolemia. After each treatment, hemodynamic variables were measured at rest and during 2 standardized stressor tasks (a simulated public-speaking task and the cold pressor).


Regardless of treatment, the stressor tasks increased BP and heart rate (P Effect of oral L-arginine on oxidant stress, endothelial dysfunction, and systemic arterial pressure in young cardiac transplant recipients.
Am J Cardiol. 2004 Sep 15;94(6):828-31. Department of Pediatrics, University of Virginia, Charlottesville, VA

Oral L-arginine therapy reverses endothelial dysfunction and attenuates high blood pressure in hypertensive cardiac transplant recipients. L-arginine corrects derangements in the vascular endothelial nitric oxide (NO)-dependent signaling pathway. Our data support the concept that cardiac transplant recipients use excess endogenous NO from L-arginine supplementation to buffer increased vascular oxidant stress.


Effect of L-arginine on age-related changes in macrophage phagocytic activity.
Immunol Invest. 2004 Aug;33(3):287-93.

Aging is associated with decline in the functioning of immune cells and reductions in serum L-arginine and excretion of nitric oxide metabolites. Studies have shown that L-arginine plays an important role in many physiological, biological and immunological processes. The present study was performed to determine if treatment with L-arginine could prevent age-related changes in phagocytic function of peritoneal macrophages. The effects of L-arginine on phagocytic activity of peritoneal macrophages were compared between young and middle-aged rats. Studies were performed in four groups of rats for 8 weeks: group 1 (3 month-old) received physiological saline; group 2 (3 month-old) received L-arginine; group 3 (12 month-old) received physiological saline; group 4 (12 month-old) received L-arginine.

There were no significant differences in percentage of cells which were phagocytized. However, the phagocytosis of activated charcoal by peritoneal macrophages reduced with age. Thus, the phagocytic index was lower in macrophages of middle-aged rats. L-arginine treatment increased phagocytosis by peritoneal macrophages of both young and middle-aged rats. L-arginine-induced augmentation in phagocytosis by macrophages were much higher in the middle-aged rats compared with young rats. In summary, we found that L-arginine prevented the age-related reduction in phagocytic capability of peritoneal macrophages. l arginine side effects.


Effect of oral L-arginine on blood pressure and symptoms and endothelial function in patients with systemic hypertension, positive exercise tests, and normal coronary arteries. Am J Cardiol. 2004 Apr 1;93(7):933-5.

Thirteen hypertensive patients with microvascular angina were studied before and after receiving oral L-arginine (4 weeks, 2 g, 3 times daily). L-arginine significantly improved angina class, systolic blood pressure at rest, and quality of life. Maximal forearm blood flow, plasma L-arginine, L-arginine : asymmetric dimethyl arginine ratio, and cyclic guanylate monophosphate increased significantly after treatment. In medically treated hypertensive patients with micro-vascular angina, oral L-arginine may represent a useful therapeutic option.


Acute pancreatitis possibly due to arginine use: A case report.
Turk J Gastroenterol. 2004 Mar;15(1):56-8.

Arginine has been used by millions of athletes over the past 20 years to enhance production of human growth hormone. The effects of arginine supplementation include increased fat burning and muscle building, enhanced immunity, and improvement in erectile function in men. Excessive doses of basic amino acids such as ethionine, methionine and lysine are known to damage the rat pancreas. Recent studies have demonstrated that excessive doses of arginine induce necrotizing pancreatitis in rats. In this article, we report a 16-year-old male patient hospitalized in our clinic because of severe pain in upper abdomen, nausea and vomiting who was suspected to have arginine-induced acute pancreatitis.


The influence of two different doses of L arginine oral supplementation on nitric oxide (NO) concentration and total antioxidant status (TAS) in atherosclerotic patients.
Med Sci Monit. 2004 Jan;10(1):CR29-32.

The purpose of this study was to assess the effect of two different doses in 28-day L arginine oral supplementation on nitric oxide (NO) concentration and total antioxidant status (TAS) in patients with atherosclerotic peripheral arterial disease. 32 patients were divided into 2 groups receiving L-arginine at 3i2 g/day (group A) or 3i4 g/day (group B). RESULTS: Group A showed substantially higher NO levels after 14 and 28 days of therapy. In group B, the NO level increase was substantial after 28 days. Noticeably higher total antioxidant statuses were noted in both groups: group A showed this only after 28 days of treatment, while group B exhibited substantial increase in TAS after 7, 14 and 28 days of L-arginine supplementation.

CONCLUSIONS: Oral supplementation of L arginine for 28 days leads to substantial increases in NO and TAS levels (comparable in both groups of patients) in the blood of patients with atherosclerotic peripheral arterial disease at Fontaine's stages II and III. The TAS concentration rise points to an antioxidative effect of L arginine oral supplementation.


Treatment of erectile dysfunction with pycnogenol and L-arginine.
J Sex Marital Ther. 2003 May-Jun;29(3):207-13.

Penile erection requires the relaxation of the cavernous smooth muscle, which is triggered by nitric oxide (NO). We investigated the possibility of overcoming erectile dysfunction by increasing the amounts of endogenous NO. For this purpose, we orally administered Pycnogenol, because it is known to increase production of NO by nitric oxide syntase together with L-arginine as substrate for this enzyme. The study included 40 men, aged 25-45 years, without confirmed organic erectile dysfunction. Throughout the 3-month trial period, patients received 3 ampoules Sargenor a day, a drinkable solution of the dipeptide arginyl aspartate (equivalent to 1.7 g L arginine per day). During the second month, patients were additionally supplemented with 40 mg Pycnogenol two times per day; during the third month, the daily dosage was increased to three 40-mg Pycnogenol tablets. After 1 month of treatment with L-arginine, a statistically nonsignificant number of 2 patients experienced a normal erection. Treatment with a combination of L-arginine and Pycnogenol for the following month increased the number of men with restored sexual ability to 80%. Finally, after the third month of treatment, 92% of the men experienced a normal erection. We conclude that oral administration of L-arginine in combination with Pycnogenol causes a significant improvement in sexual function in men with erectile dysfunction without any side effects. l arginine benefit.


Dietary supplementation with L-arginine or placebo in women with pre-eclampsia.
Staff AC.. Departments of Obstetrics and Gynecology, Ulleval University Hospital, Kirkeveien 166, Oslo, Norway.

To investigate the effect of dietary intake of the NO-donor L-arginine on the diastolic blood pressure in women with pre-eclampsia. A randomized double-blind study was designed to compare the effect of L-arginine and placebo in pre-eclamptic women with gestational length ranging from 28+0 to 36+0 weeks. The women received orally 12 g of L-arginine or placebo daily for up to 5 days. The primary end-point was to identify a difference in diastolic blood pressure alteration between the two groups after 2 days of intervention. There was no statistically significant alteration in diastolic blood pressure in the L-arginine group compared with the placebo group after 2 days of treatment.

CONCLUSIONS: Oral L-arginine supplementation did not reduce mean diastolic blood pressure after 2 days of treatment compared with placebo in pre-eclamptic patients with gestational length varying from 28 to 36 weeks. Whether L-arginine treatment could be clinically beneficial for the mother or the fetus if started earlier in the disease process than for the women in our study remains to be seen.


Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients.
Hum Reprod. 1999 Jul;14(7):1690-7.

The objective of the present study was prospectively and randomly to evaluate the role of L-arginine in improving uterine and follicular Doppler flow and in improving ovarian response to gonadotrophin in poor responder women. A total of 34 patients undergoing assisted reproduction was divided in two groups according to different ovarian stimulation protocols: (i) flare-up gonadotrophin-releasing hormone analogue (GnRHa) plus elevated pure follicle stimulating hormone (pFSH) (n = 17); and (ii) flare-up GnRHa plus elevated pFSH plus oral L-arginine (n = 17). The plasma and follicular fluid concentrations of arginine, citrulline, nitrite/nitrate (NO2-/NO3-), and insulin-like growth factor-1 (IGF-1) were assayed. In the L-arginine treated group a lower cancellation rate, an increased number of oocytes collected, and embryos transferred were observed. In the same group, increased plasma and follicular fluid concentrations of arginine, citrulline, NO2-/NO3-, and IGF-1 was observed. Significant Doppler flow improvement was obtained in the L-arginine supplemented group. Three pregnancies were registered in these patients. No pregnancies were observed in the other group. It was concluded that oral L-arginine supplementation in poor responder patients may improve ovarian response, endometrial receptivity and pregnancy rate. l arginine hcl.


Oral L-arginine improves endothelial function in healthy individuals older than 70 years.
Bode-Boger SM. University Hospital, Otto-von-Guericke University, Magdeburg, Germany.

Ageing is associated with progressive endothelial dysfunction in normal humans. Flow-mediated dilation (FMD) of the brachial artery is impaired in elderly individuals with cardiovascular disease and vascular nitric oxide (NO) bioavailability is reduced. We investigated whether oral L-arginine, the substrate for NO synthesis, can improve impaired FMD in healthy very old people. In a prospective, double-blind, randomized crossover trial, 12 healthy old subjects took L-arginine (8 g p.o. two times daily) or placebo for 14 days each, separated by a wash-out period of 14 days. L-Arginine significantly improved FMD, whereas placebo had no effect. After L-arginine, plasma levels of L-arginine increased significantly, but placebo had no effect. As NO synthesis can be antagonized by its endogenous inhibitor asymmetric dimethyl L-arginine (ADMA), we determined ADMA plasma concentrations, which were elevated at baseline in comparison to healthy middle-aged individuals. ADMA remained unchanged during treatment, but L-arginine supplementation normalized the L-arginine/ADMA ratio. We conclude that in healthy very old age endothelial function is impaired and may be improved by oral L-arginine supplementation, probably due to normalization of the L-arginine/ADMA ratio. arginine pyroglutamate/


Practical recommendations for immune-enhancing diets.
J Nutr. 2004 Oct;134(10 Suppl):2868S-2872S; discussion 2895S.

Immune-enhancing diets contain nutrients that have putative benefits, including arginine, (n-3) fats, glutamine, nucleotides, and structured lipids. Although under most circumstances the systemic inflammatory response is beneficial to the host, improving the eventual outcome of injury, infection, or inflammation, excessive proinflammation (leading to cardiac, hepatic, and mitochondrial dysfunction) or excessive counterinflammation (leading to immune depression) can worsen outcome. In critically ill septic patients, the synthesis of arginine can be exceeded by its catabolism to nitric oxide (NO) and urea, rendering arginine conditionally essential. In patients with sepsis, increased production of NO increases serum nitrite and nitrate levels, whereas levels in patients with trauma and trauma with sepsis are lower than in controls. In septic patients, supplemental arginine might further increase NO levels and be potentially harmful through excessive proinflammation. However, administration of increased amounts of arginine might improve immune function in surgical and trauma patients by increasing NO production in macrophages. Thus, the effects of arginine and (n-3)-fat supplementation might be expected to be complementary- arginine might improve cytokine and NO production in patients with immunodepression, whereas (n-3) fats might be beneficial when there is excessive proinflammation, particularly when supplemental arginine is supplied, by reducing cytokine-induced eicosanoid production.


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