L-Arginine research and publications

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The following excerpts are from medical journals and studies involving L-arginine. Their findings continue to support the assertion that l-arginine supplementation can have significant benefits on heart disease and cardiovascular health.  The research also show that l-arginine supplements are not all the same and a good formulation is critical in achieving maximum benefits.

L Arginine studies and research

L-Arginine supplement 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 nitric oxide 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 l arginine concentrations are reduced in cancer patients: evidence for arginine deficiency?

American Journal of Clinical Nutrition, Vol. 81, No. 5, 1142-1146, May 2005
Preliminary evidence suggests that arginine availability in cancer is reduced. However, no valid data are available on plasma arginine concentrations in cancer patients. We aimed to determine whether there is evidence for disturbed arginine metabolism in cancer. 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 arginine concentrations were lower in patients with cancer irrespective of tumor type, weight loss, tumor stage, or body mass index. 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 supplement improves hemodynamic responses to stress and reduces plasma homocysteine in hypercholesterolemic men

J Nutr. 2005 Feb;135(2):212-7.
When administered intravenously, the benefit of l arginine supplement is that it 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. We tested whether oral l-arginine (12 grams per d for 3 weeks) affected hemodynamics, glucose, insulin, or C-reactive protein in 16 middle-age men with high cholesterol. 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 </= 0.02). Relative to placebo, l arginine changed cardiac output, diastolic BP (-1.9 mm Hg), pre-ejection period (+3.4 ms), and plasma homocysteine. The change in plasma l-arginine was inversely correlated with the change in plasma homocysteine. Contrary to the results of previous studies of l arginine administered intravenously, oral administration did not affect total peripheral resistance or plasma insulin. Oral l-arginine also did not affect plasma glucose, C-reactive protein, or lipids. This pattern of findings is consistent with the hypothesis that oral l-arginine reduces BP. This study is the first to describe a hemodynamic mechanism for the hypotensive effect of oral l arginine and the first to show substantial reductions in homocysteine with oral administration.

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 nitric oxide from L-arginine supplementation to buffer increased vascular oxidant stress.

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, 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.

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).  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. Oral supplementation of L arginine for 28 days leads to substantial increases in nitric oxide and TAS levels 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.
We investigated the possibility of overcoming erectile dysfunction by increasing the amounts of endogenous itric oxide. For this purpose, we orally administered Pycnogenol, because it is known to increase production of nitric oxide 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.

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 L-arginine on the diastolic blood pressure in women with pre-eclampsia. A study was designed to compare the effect of L-arginine and placebo in pre-eclamptic women. The women received orally 12 grams 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. 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.

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); and (ii) flare-up GnRHa plus elevated pFSH plus oral L-arginine. 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.

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. Twelve healthy old subjects took L arginine (8 grams orally. 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 supplement use, plasma levels of L-arginine increased significantly, but placebo had no effect. We conclude that in healthy very old age endothelial function is impaired and may be improved by oral L-arginine supplementation.

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 and urea, rendering arginine conditionally essential. In patients with sepsis, increased production of nitric oxide increases serum nitrite and nitrate levels, whereas levels in patients with trauma and trauma with sepsis are lower than in controls. In septic patients, arginine supplements might further increase nitric oxide 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 nitric oxide production in macrophages. Thus, the effects of arginine and (n-3)-fat supplementation might be expected to be complementary- arginine might improve cytokine and nitric oxide 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.

Related Information

Source: Ray Sahelian M.D

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