Glucose Synthesis & Energy Boost

 

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L-Arginine is an amino acid proven in clinical trials to enhance libido, increase sexual stamina, and treat erectile dysfunction. 

Sexual stimulation begins in the brain, where neurotransmitters fire signals down the spinal cord to the genitals.  These signals in turn cause the release of certain chemicals which allow blood to flow to the penis.  The main chemical responsible for this process is called cyclic guanosine monophosphate, or cGMP.  The neurotransmitter responsible for releasing cGMP is nitric oxide, NO. 

(Read what the Mayo Clinic Says about
the Use of L-Arginine.)

 

The number of reported cases of impotence is on the rise in the United States, with more than fifteen million men being affected.  Impotence is often a result of illness, injury, or prescription drug side effects.  Though erectile dysfunction most commonly affects older men, it is not an inevitable result of aging.  Impotence is very often completely curable and preventable.

The well-known male enhancement drug Viagra works by increasing the potency of NO and by maximizing cGMP levels by inhibiting an enzyme which destroys cGMP.  The result is a treatment for impotency and an increase in sexual desire.  Unfortunately, however, as with most prescription drugs, Viagra causes some unwanted side effects, such as migraines, blurry vision, and indigestion. 

L-Arginine on the other hand can provide the same benefits of Viagra without the unwanted side effects.  L-Arginine is the amino acid used to synthesize NO in the body.  Higher L-Arginine levels allow for higher NO levels, and higher NO levels allow for increased sensitivity and ability to form an erection. 

A New York University School of Medicine study found that six out of fifteen subjects using L-Arginine experienced better sexual performance, while none of the fifteen subjects given a placebo reported any benefits.  Numerous studies support the use of L-Arginine as a natural male enhancement remedy, and it does not carry the dangerous and unwanted side effects of prescription drugs like Viagra.

Because L-Arginine has the ability to dilate blood vessels, it can also be used to help treat conditions such as angina, atherosclerosis, coronary artery disease, heart failure, intermittent claudication, and vascular headache.  It stimulates protein synthesis, making it of interest to body builders and beneficial for wound healing and increasing sperm count.

 

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REFERENCES:
Abel T, Knechtle B, Perret C, et al. Influence of chronic supplementation of arginine aspartate in endurance athletes on performance and substrate metabolism - a randomized, double-blind, placebo-controlled study. Int J Sports Med. 2005 Jun;26(5):344-9.

Black P, Max MB, Desjardins P, et al. A randomized, double-blind, placebo-controlled comparison of the analgesic efficacy, onset of action, and tolerability of ibuprofen arginate and ibuprofen in postoperative dental pain. Clin Ther. 2002;24(7):1072-1089.

Carrier, M, Pellerin M, Perrault LP, et al. Cardioplegic arrest with L-arginine improves myocardial protection: results of a prospective randomized clinical trial. Ann.Thorac.Surg. 2002;73(3):837-841.

Cartledge JJ, Davies AM, Eardley I. A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis. BJU.Int 2000;85(4):421-426.

Garhofer G, Resch H, Lung S, et al. Intravenous administration of L-arginine increases retinal and choroidal blood flow.Am J Ophthalmol. 2005 Jul;140(1):69-76.

Gianotti L, Braga M, Nespoli L, et al. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology 2002;122(7):1763-1770.

Hladunewich MA, Derby GC, Lafayette RA, et al. Effect of L-arginine therapy on the glomerular injury of preeclampsia: a randomized controlled trial.Obstet Gynecol. 2006 Apr;107(4):886-95.

Houwing RH, Rozendaal M, Wouters-Wesseling W, et al. A randomised, double-blind assessment of the effect of nutritional supplementation on the prevention of pressure ulcers in hip-fracture patients. Clin Nutr. 2003;22(4):401-405.

Koga Y, Akita Y, Junko N, et al. Endothelial dysfunction in MELAS improved by l-arginine supplementation. Neurology. 2006 Jun 13;66(11):1766-9.

Korting G, Smith S, Wheeler M, et al. A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. J Urol. 1999;161(2):558-565.

Lebret T, Herve JM, Gorny P, et al. Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction. Eur.Urol. 2002;41(6):608-613.

Miller HI, Dascalu A, Rassin TA, et al. Effects of an acute dose of L-arginine during coronary angiography in patients with chronic renal failure: a randomized, parallel, double-blind clinical trial. Am.J.Nephrol. 2003;23(2):91-95.

Mansoor JK, Morrissey BM, Walby WF, et al. L-arginine supplementation enhances exhaled NO, breath condensate VEGF, and headache at 4,342 m. High Alt Med Biol. 2005 Winter;6(4):289-300.

Polan ML, Hochberg RB, Trant AS, et al. Estrogen bioassay of ginseng extract and ArginMax, a nutritional supplement for the enhancement of female sexual function. J.Womens Health (Larchmt.) 2004;13(4):427-430.

Schulman SP, Becker LC, Kass DA, et al. L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA. 2006 Jan 4;295(1):58-64.

MAYO CLINIC ON L-ARGININE:

Background
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. Creatine degrades to creatinine at a constant rate, and is cleared from the body by the kidney.

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

Arginine is a precursor of nitric oxide, which causes blood vessel relaxation (vasodilation). Preliminary evidence 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. Arginine also stimulates protein synthesis and has been studied for wound healing, bodybuilding, enhancement of sperm production (sperma-togenesis), and prevention of wasting in people with critical illness.

Arginine hydrochloride contains high chloride content and has been used for the treatment of metabolic alkalosis. This use should be under the supervision of a qualified healthcare professional.

Most people likely do not need to take arginine supplements because the body usually makes sufficient amounts.

Synonyms
Arg, arginine, arginine hydrochloride (intravenous formulation), ibuprofen-arginate (Spedifen®), L-arg, L-arginine, 2-amino-5-guanidinopentanoic acid.

Note : Arginine vasopressin is different from arginine/L-arginine, with an entirely different mechanism. NG-monomethyl-L-arginine is different from arginine/L-arginine, and functions as an inhibitor of nitric oxide synthesis.

Dietary sources of arginine : Walnuts, filberts, pecans, Brazil nuts, sesame and sunflower seeds, brown rice, raisins, coconut, gelatin, buckwheat, almonds, barley, cashews, cereals, chicken, chocolate, corn, dairy products, meats, oats, peanuts.

Evidence
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidence      Grade*

Growth hormone reserve test / pituitary disorder diagnosis
Intravenously administered arginine can be used to evaluate growth hormone reserve in individuals with suspected growth hormone deficiency. For example, in patients with suspected panhypopituitarism, growth/stature abnormalities, gigantism/acromegaly, or pituitary adenoma. This is an FDA labeled indication for arginine. Grade A

Inborn errors of urea synthesis
In patients with inborn errors of urea synthesis, high blood ammonia levels and metabolic alkalosis may occur, particularly in patients with ornithine carbamoyl transferase (OCT) deficiency or carbomoyl phosphate synthetase (CPS) deficiency. Arginine can be a helpful treatment by shifting the way the body processes nitrogen, but should be avoided in patients with hyperargininemia (high arginine levels). Other drugs may have similar benefits, such as citrulline, sodium benzoate, or sodium phenylbutyrate, although dialysis may be necessary initially. This use of arginine should be supervised by a qualified healthcare professional. Grade     A

Adrenoleukodystrophy (ALD)
Adrenoleukodystrophy (ALD) is a rare inherited metabolic disorder characterized by the loss of fatty coverings (myelin sheaths) on nerve fibers in the brain, and progressive destruction of the adrenal gland. ALD is inherited as an x-linked genetic trait that results in dementia and adrenal failure. Injections of arginine have been proposed to help manage this disorder, although most study results are inconclusive. Further research is needed to evaluate the use of arginine in ALD.            Grade C

Burns
A randomized, controlled clinical trial designed to evaluate immune function of patients given 15 milligrams of arginine orally suggests that arginine may help with the recovery of immune function and protein function in partial-thickness burn patients. Further research is necessary in this area before a conclusion can be drawn.            C

Coronary artery disease / angina
There is initial evidence from several studies that arginine taken by mouth or by injection improves exercise tolerance and blood flow in arteries of the heart. Benefits have been shown in some patients with coronary artery disease and angina. A small randomized, controlled clinical trial studied the effects of a medical food bar enriched with L-arginine and a combin-ation of other nutrients in the management of chronic stable angina. The authors found that this arginine-rich medical food, when used with traditional therapy, improves vascular function, exercise capacity and aspects of quality of life in these patients. However, further research is needed to confirm these findings and to establish doses that may be safe and effective.   C

Critical illness
Some studies suggest that arginine may provide benefits when added to nutritional supplements during critical illnesses (for example, in patients being treated in intensive care units). However, it is unclear what the specific role of arginine may be in improving recovery. A randomized, controlled clinical trial was designed to study the effects of a high-protein formula enriched with arginine, fiber, and antioxidants in early nutrition therapy of critically ill patients. The study measured infections in the hospital intensive care unit (ICU), length of hospital stay, and death rates. Patients fed the high-protein diet enriched with arginine, fiber and antioxidants developed fewer hospital infections than patients fed a standard high-protein diet. There was no difference in length of ICU hospital stay or death rate. Overall the scientific data to date does not show benefit for only L-arginine supplementation, nor does it show harm. At this time there is no rationale for the routine supplementation of arginine alone to enhance recovery from serious illness. Because of the potential for harm, this amino acid should only be administered to critically ill patients in large doses under carefully monitored study conditions.      C

Dental pain (ibuprofen arginate)
A well-designed multicenter, randomized, controlled clinical trial found that ibuprofen-arginate (Spedifen®) reduced pain faster after dental surgery compared to conventional ibuprofen alone. The study included 498 patients who were given ibuprofen-arginate, ibuprofen, or placebo after dental surgery. The degree of pain relief, onset of action, and tolerability of both ibuprofen-arginate and ibuprofen were compared. It was found that ibuprofen arginate relieved pain faster and adverse events with ibuprofen-arginate were similar to those seen with ibuprofen alone. Another similar trial concluded that patients treated with ibuprofen-arginate rated its overall effectiveness higher than those treated with ibuprofen alone. Adverse event profiles were similar across all treatment groups. Further research is merited in this area.   C

MELAS syndrome
One study found that two years of supplementation with oral L-arginine significantly improved endothelial function in patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke). Further research is merited in this area.    C

Gastrointestinal cancer surgery
Supplementation with an oral combination of arginine and omega-3 fatty acids may reduce length of hospital stay and infections after surgery in gastrointestinal cancer patients. There is conflicting evidence as to when to give the combination (either before or after surgery). Both strategies have been reported as superior to conventional treatment (no artificial nutrition) at reducing infections after surgery and reducing hospital stay. In a large, randomized, controlled clinical trial, malnourished cancer patients were given oral enteral nutrition supplemented by arginine, omega-3 fatty acids and RNA before surgery. It was found that supplementation with the combination before surgery reduced complications after surgery and hospital stay. A different randomized, controlled clinical trial in patients with gastrointestinal cancer studied the effects of an enteral diet supplemented with arginine, omega-3 fatty acids and glutamine (administered after surgery) on immune function and inflammatory response. This study reported the supplement to be well-tolerated with positive effects on immune and inflammatory response. Further research is needed to determine the possible effects of arginine alone.C

Heart failure (CHF)
Studies of arginine in patients with chronic heart failure have shown mixed results. Some studies report improved exercise tolerance. Additional studies are needed to confirm these findings before a firm conclusion can be drawn.            C

Heart protection during coronary artery bypass grafting (CABG)
Arginine-supplemented "blood cardioplegic solution" is proposed to have protective properties for the heart. A randomized, controlled clinical trial using this solution in patients undergoing heart surgery (coronary artery bypass grafting) reports improved heart protection. Further research is needed before a firm conclusion can be drawn.            C

High blood pressure
A small study suggests that arginine taken by mouth may dilate the arteries and temporarily reduce blood pressure in hypertensive patients with type 2 diabetes. Larger, high-quality studies are needed before a recommendation can be made.       C

Immunomodulator
Preliminary study results suggest that arginine supplementation may enhance the immune response elicited by the pneumococcal vaccine in older people. More studies are needed to confirm these results.       C

Migraine headache
Preliminary studies suggest that adding arginine to ibuprofen therapy may decrease migraine headache pain.       C

Myocardial infarction
Study results of arginine supplementation after myocardial infarction (heart attack) are mixed. Further research is needed before a recommendation can be made. A cardiologist and pharmacist should be consulted prior to initiation of arginine therapy.           C

Peripheral vascular disease / claudication
Intermittent claudication is a condition characterized by leg pain and fatigue due to buildup of cholesterol plaques or clots in leg arteries. A small number of studies report that arginine therapy may improve walking distance in patients with claudication. Further research is needed before a firm conclusion can be drawn.            C

Pre-eclampsia (high blood pressure in pregnancy)
Early study suggests that prolonged dietary supplementation with L-arginine may decrease blood pressure that is too high in pregnant women. Further research is needed to confirm these results. C

Pressure ulcers
Studies of arginine for pressure ulcers show mixed results. Further research is needed before a conclusion can be drawn.            C

Recovery after surgery
One study suggests that arginine may provide benefits when used as a supplement after surgery. It is not clear what the specific role of arginine may be in improving immune function, or what dose is safe or effective.             C

Transplants
Dietary supplementation with L-arginine and canola oil has been associated with decreased rejection rates after the first month in renal transplant patients. Due to reductions in cardiac events, long-term benefits for patient survival may be particularly important. Further research is needed to confirm these results.            C

Wound healing
Arginine has been suggested to improve the rate of wound healing in elderly individuals. A randomized, controlled clinical trial reported improved wound healing after surgery in head and neck cancer patients, following the use of an enteral diet supplemented with arginine and fiber. Arginine has also been used topically (on the skin) to attempt to improve wound healing. Further research is necessary in this area before a firm conclusion can be drawn.        C

Key to grades
A Strong scientific evidence for this use
B Good scientific evidence for this use
C Unclear scientific evidence for this use
D Fair scientific evidence against this use (it may not work)
F Strong scientific evidence against this use (it likely does not work)

Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

AIDS/HIV, ammonia toxicity, anti-aging, beta-hemoglobinopathies, cancer, cardiac syndrome X, cold prevention, cystic fibrosis, dementia, diabetes, glaucoma, growth hormone stimulation, hemolytic uremic syndrome (HUS), hepatic encephalopathy, high cholesterol, increased muscle mass, infantile necrotizing enterocolitis, infection, inflammatory bowel disease, ischemic stroke, liver disease, lower esophageal sphincter relaxation, low sperm count, metabolic acidosis, obesity, osteoporosis, pain, peritonitis, pre-term labor contractions, pulmonary hypertension (high blood pressure in the lungs), Raynaud's phenomenon, sepsis, sexual function in women, sickle cell anemia, stomach motility disorders, stomach ulcer, stroke, supplementation to a low protein diet, thrombotic thrombocytopenic purpura (TTP), tumors.

Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies
Anaphylaxis (severe allergic reaction) has occurred after arginine injections. People with a known allergy should avoid arginine. Signs of allergy may include rash, itching or shortness of breath.

Side Effects and Warnings
Arginine has been well tolerated by most people in studies lasting for up to six months, although there is a possibility of serious adverse effects in some individuals.

Stomach discomfort, including nausea, stomach cramps or an increased number of stools, may occur. People with asthma may experience a worsening of symptoms if arginine is inhaled, which may be related to allergy. Headache has also been reported.

Other potential side effects include low blood pressure and changes in numerous chemicals and electrolytes in the blood. Examples include high potassium, high chloride, low sodium, low phosphate, high blood urea nitrogen and high creatinine levels. People with liver or kidney disease may be especially sensitive to these complications and should avoid using arginine except under medical supervision. After injections of arginine, low back pain, flushing, headache, numbness, restless legs, venous irritation and death of surrounding tissues have been reported.

In theory, arginine may increase the risk of bleeding. Patients using anticoagulants (blood thinners) or antiplatelet drugs, or with underlying bleeding disorders, should speak with a qualified healthcare provider before using arginine and should be monitored.
Arginine may increase blood sugar levels. Caution is advised in patients taking prescription drugs to control sugar levels.

Pregnancy and Breastfeeding
Arginine cannot be recommended as a supplement during pregnancy and breast-feeding because there is not enough scientific information available.

L-arginine has been used in women with preeclampsia until day 10 postpartum but should not be used without supervision of an OB/GYN and pharmacist.

Methodology
This patient information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

 

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Selected references
1. Abel T, Knechtle B, Perret C, et al. Influence of chronic supplementation of arginine aspartate in endurance athletes on performance and substrate metabolism - a randomized, double-blind, placebo-controlled study. Int J Sports Med. 2005 Jun;26(5):344-9.

2. Black P, Max MB, Desjardins P, et al. A randomized, double-blind, placebo-controlled comparison of the analgesic efficacy, onset of action, and tolerability of ibuprofen arginate and ibuprofen in postoperative dental pain. Clin Ther. 2002;24(7):1072-1089.

3. Carrier, M, Pellerin M, Perrault LP, et al. Cardioplegic arrest with L-arginine improves myocardial protection: results of a prospective randomized clinical trial. Ann.Thorac.Surg. 2002;73(3):837-841.

4. Cartledge JJ, Davies AM, Eardley I. A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis. BJU.Int 2000;85(4):421-426.

5. Garhofer G, Resch H, Lung S, et al. Intravenous administration of L-arginine increases retinal and choroidal blood flow.Am J Ophthalmol. 2005 Jul;140(1):69-76.

6. Gianotti L, Braga M, Nespoli L, et al. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology 2002;122(7):1763-1770.

7. Hladunewich MA, Derby GC, Lafayette RA, et al. Effect of L-arginine therapy on the glomerular injury of preeclampsia: a randomized controlled trial.Obstet Gynecol. 2006 Apr;107(4):886-95.

8. Houwing RH, Rozendaal M, Wouters-Wesseling W, et al. A randomised, double-blind assessment of the effect of nutritional supplementation on the prevention of pressure ulcers in hip-fracture patients. Clin Nutr. 2003;22(4):401-405.

9. Koga Y, Akita Y, Junko N, et al. Endothelial dysfunction in MELAS improved by l-arginine supplementation. Neurology. 2006 Jun 13;66(11):1766-9.

10. Korting G, Smith S, Wheeler M, et al. A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. J Urol. 1999;161(2):558-565.

11. Lebret T, Herve JM, Gorny P, et al. Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction. Eur.Urol. 2002;41(6):608-613.

12. Miller HI, Dascalu A, Rassin TA, et al. Effects of an acute dose of L-arginine during coronary angiography in patients with chronic renal failure: a randomized, parallel, double-blind clinical trial. Am.J.Nephrol. 2003;23(2):91-95.

13. Mansoor JK, Morrissey BM, Walby WF, et al. L-arginine supplementation enhances exhaled NO, breath condensate VEGF, and headache at 4,342 m. High Alt Med Biol. 2005 Winter;6(4):289-300.

14. Polan ML, Hochberg RB, Trant AS, et al. Estrogen bioassay of ginseng extract and ArginMax, a nutritional supplement for the enhancement of female sexual function. J.Womens Health (Larchmt.) 2004;13(4):427-430.

15. Schulman SP, Becker LC, Kass DA, et al. L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA. 2006 Jan 4;295(1):58-64.

RESEARCH & CITATIONS

The role of NO synthases in arginine-dependent small intestinal and colonic carcinogenesis.
Author:           Yerushalmi,-H-F; Besselsen,-D-G; Ignatenko,-N-A; Blohm-Mangone,-K-A; Padilla-Torres,-J-L; Stringer,-D-E; Cui,-H; Holubec,-H; Payne,-C-M; Gerner,-E-W
Citation: Mol-Carcinog. 2006 Feb; 45(2): 93-105
Abstract:  Arginine is catabolized by NOS2 and other nitric oxide synthases to form nitric oxide. We evaluated the roles of dietary arginine and Nos2 in Apc-dependent intestinal tumorigenesis in Min mice with and without a functional Nos2 gene. NOS2 protein was expressed only in intestinal tissues of Apc(Min/+) Nos2+/+ mice. NOS3 expression was higher in intestinal tissues of mice lacking Nos2, mainly in the small intestine. When diet was supplemented with arginine (0.2% and 2% in drinking water), lack of Nos2 results in decreased tumorigenesis in both small intestine and colon. In Nos2 knockout mice, supplemental arginine (up to 2%) caused a decrease in small intestinal tumor number and size. The arginine-dependent decrease was associated with an increase in nitrotyrosine formation and apoptosis in the region of intestinal stem cells.

Mice expressing Nos2 did not show these changes. These mice did, however, show an arginine-dependent increase in colon tumor number and incidence, while no effect on apoptosis was seen. These changes were associated with increased nitrotyrosine formation in epithelial cells. Mice lacking Nos2 did not show changes in tumorigenesis or nitrotyrosine formation, while demonstrating an arginine-dependent increase in apoptosis. These data suggest that Nos2 and dietary arginine have significant effects on intestinal and colonic tumorigenesis in Min mice. In both tissues, loss of Nos2 is associated with decreased tumorigenesis when mice are supplemented with dietary arginine. In the small intestine, Nos2 prevents the arginine-induced decrease in tumor number and size, which is associated with NOS3 expression and increased apoptosis. In the colon, Nos2 is required for the arginine-induced increase in tumor number and incidence. Copyright 2005 Wiley-Liss, Inc.

The effects of sustained-release-L-arginine formulation on blood pressure and vascular compliance in 29 healthy individuals.
Author:           Miller,-A-L
Citation: Altern-Med-Rev. 2006 Mar; 11(1): 23-9
Abstract: Vascular endothelial function is crucial to cardiovascular function and thus to blood perfusion to the heart and throughout the body. A number of substances are produced and secreted by vascular endothelial cells, the most important of which is nitric oxide, a potent regulator of vascular function. Nitric oxide diffuses from endothelial cells into underlying smooth muscle, causing relaxation, which results in vasodilation. When this process is inhibited or inadequate the arteries cannot dilate as necessary, resulting in hypertonicity and reduced blood flow. Such endothelial dysfunction also causes increased platelet and monocyte adhesiveness and smooth muscle proliferation, processes thought to be at the genesis of atherosclerotic plaque formation. Since L-arginine is the body's only substrate for nitric oxide synthesis, adequate L-arginine must be present for proper nitric oxide production. In this open label trial, a group of 29 asymptomatic individuals were given L-arginine (1,050 mg, as Perfusia-SR, a sustained-release preparation) twice daily (total 2.1 g daily) for one week. Systolic blood pressure was reduced in 62 percent of participants compared to baseline, with a non-significant mean decrease in all patients of 4 mm Hg.

Diastolic blood pressure was reduced in 69 percent of participants, with a mean reduction of 3.7 mm Hg (p = 0.005). In the 10 individuals who were borderline or hypertensive (systolic > 130 or diastolic > 85), there was a mean systolic reduction of 11 mm Hg (p = 0.05), while normotensives (n = 19) had a mean systolic decrease of only 0.22 mm Hg. Diastolic blood pressure was decreased a non-significant 4.9 mm Hg in borderline or hypertensives and 4.5 mm Hg in normotensives (p = 0.026). Vascular elasticity relates to endothelial function, and can be measured non-invasively. At baseline and follow-up, vascular compliance was assessed via digital pulse wave analysis (DPA; Meridian Medical). After one week, pulse wave analysis showed a significant increase in large artery compliance (mean 23% improvement; p = 0.02) and a non-significant increase in small artery compliance (mean 23% improvement; p = 0.15). This study demonstrates blood pressure reductions, especially in patients with borderline or frank hypertension, as well as improved vascular compliance - an indicator of improved endothelial function and perfusion - after a one-week trial of sustained-release L-arginine. Poor endothelial function due to inadequate endothelial nitric oxide production is present in hypertension, as well as in numerous other aspects of cardiovascular disease, including angina, erectile dysfunction, cerebrovascular disease, and peripheral vascular disease. This is the first study showing a moderate dose of sustained-release L-arginine can improve endothelial function and blood pressure.

 

 

L-arginine supplementation causes additional effects on exercise-induced angiogenesis and VEGF expression in the heart and hind-leg muscles of middle-aged rats.
Author:           Suzuki,-J
Citation: J-Physiol-Sci. 2006 Feb; 56(1): 39-44
Abstract: The effects of dietary L-arginine supplementation on exercise-induced angiogenesis and VEGF expression were examined in male middle-aged (12 months old) Wistar rats. Exercise training lasted for six weeks at 20 m/min on a 0% gradient for 10-60 min/day. Rats in the L-arginine-treated groups drank water containing 2.5% L-arginine. According to histochemical identification of the capillary profile, in the soleus muscle the capillary-to-fiber (C:F) ratio showed a significantly greater value in the L-arginine-treated training group than in both the sedentary control and training groups. Training with L-arginine significantly increased the C:F ratio in the subendocardium of the left ventricle, whereas training alone did not. In the plantaris muscle, training with or without L-arginine significantly increased the capillary density, but it did not affect the C:F ratio. A Western blot analysis showed that training with L-arginine significantly increased VEGF protein expression by 2.9-fold in the soleus muscle and by 1.7-fold in the left ventricle, but the increase with training alone was insignificant. The tissue endothelial nitric oxide synthase protein levels were significantly increased in both the soleus (by 1.3-fold) and the left ventricle (by 1.4-fold) only after training with L-arginine supplementation. In the plantaris muscle, these protein levels did not change after either training or L-arginine treatment. The present results suggest that in middle-aged rats, L-arginine administration caused additional effects on exercise-induced angiogenesis by presumably promoting VEGF expression in the hind-leg muscle as well as in the left ventricle.

Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats.
Author:           Fu,-W-J; Haynes,-T-E; Kohli,-R; Hu,-J; Shi,-W; Spencer,-T-E; Carroll,-R-J; Meininger,-C-J; Wu,-G
Citation: J-Nutr. 2005 Apr; 135(4): 714-21
Abstract: This study was conducted to test the hypothesis that dietary supplementation of arginine, the physiologic precursor of nitric oxide (NO), reduces fat mass in the Zucker diabetic fatty (ZDF) rat, a genetically obese animal model of type-II diabetes mellitus. Male ZDF rats, 9 wk old, were pair-fed Purina 5008 diet and received drinking water containing arginine-HCl (1.51%) or alanine (2.55%, isonitrogenous control) for 10 wk. Serum concentrations of arginine and NO(x) (oxidation products of NO) were 261 and 70% higher, respectively, in arginine-supplemented rats than in control rats. The body weights of arginine-treated rats were 6, 10, and 16% lower at wk 4, 7, and 10 after the treatment initiation, respectively, compared with control rats. Arginine supplementation reduced the weight of abdominal (retroperitoneal) and epididymal adipose tissues (45 and 25%, respectively) as well as serum concentrations of glucose (25%), triglycerides (23%), FFA (27%), homocysteine (26%), dimethylarginines (18-21%), and leptin (32%). The arginine treatment enhanced NO production (71-85%), lipolysis (22-24%), and the oxidation of glucose (34-36%) and octanoate (40-43%) in abdominal and epididymal adipose tissues. Results of the microarray analysis indicated that arginine supplementation increased adipose tissue expression of key genes responsible for fatty acid and glucose oxidation: NO synthase-1 (145%), heme oxygenase-3 (789%), AMP-activated protein kinase (123%), and peroxisome proliferator-activated receptor gamma coactivator-1alpha (500%). The induction of these genes was verified by real-time RT-PCR analysis. In sum, arginine treatment may provide a potentially novel and useful means to enhance NO synthesis and reduce fat mass in obese subjects with type-II diabetes mellitus.

Arginine supplementation does not enhance serum nitric oxide levels in elderly nursing home residents with pressure ulcers.
Author: Stechmiller,-J-K; Langkamp-Henken,-B; Childress,-B; Herrlinger-Garcia,-K-A; Hudgens,-J; Tian,-L; Percival,-S-S; Steele,-R
Citation: Biol-Res-Nurs. 2005 Apr; 6(4): 289-99
Abstract: The purpose of this study was to determine whether arginine supplementation enhances in vitro (neutrophil burst and mitogen-induced lymphocyte proliferation) and in vivo (delayed-type hypersensitivity [DTH] and serum nitric oxide) measures of immune function in nursing home elders with pressure ulcers. Twenty-six elders, 65 years of age or older, with one or more pressure ulcers, were randomized to receive 8.5 g of arginine or an isonitrogenous supplement for 4 weeks. Immune function studies and serum arginine, ornithine, citrulline, and nitric oxide were measured at baseline, 4 weeks postsupplementation (Week 4) and after a 6-week washout (Week 10). At Week 4, serum ornithine increased (p = .01) and arginine trended to increase (p = .055), but there was no increase in citrulline or nitric oxide with arginine supplementation. There were no differences in neutrophil burst or DTH responses between groups. Whole blood mitogen-induced proliferation decreased significantly at Week 10 in the isonitrogenous but not in the arginine-supplemented group. There is mounting concern that arginine supplementation during an inflammatory state could be detrimental due to overwhelming nitric oxide production. A key finding of this study is that arginine supplementation did not increase serum nitric oxide levels over that observed in elders with pressure ulcers given an isonitrogenous supplement.

Secondhand tobacco smoke impairs neurogenic and endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle: improvement with chronic oral administration of L-arginine.
Author:           Gocmez,-S-S; Utkan,-T; Duman,-C; Yildiz,-F; Ulak,-G; Gacar,-M-N; Erden,-F
Citation: Int-J-Impot-Res. 2005 Sep-Oct; 17(5): 437-44
Abstract: The first goal of this study was to examine the effect of secondhand smoking on neurogenic, endothelium- and cGMP-dependent relaxant responses of rabbit corpus cavernosum smooth muscle. Our second goal was to determine whether such an effect can be prevented by oral administration of L-arginine. Male New Zealand rabbits were divided into control, chronic passive cigarette smoking and L-arginine treatment groups. Relaxant or contractile responses in isolated corpus cavernosum smooth muscle strips were determined by using in vitro muscle technique. There was no significant difference in the relaxant response of the strips to papaverine, sodium nitroprusside and contractile response to KCl among the groups. Relaxant responses to acetylcholine and electrical field stimulation and contractile response to phenylephrine were significantly decreased in the strips of the smoking group than that of the control group.

The impaired relaxations of strips were markedly improved by treatment of L-arginine, but the contractile responses to phenylephrine were not affected. These data indicate that secondhand smoking may impair both neurogenic and endothelium-dependent relaxation of corpus cavernosum smooth muscle, and may contribute to the etiology of impotence. Chronic dietary supplementation with L-arginine offsets the impairment of neurogenic and endothelial relaxation. Therefore, we suggest that secondhand smoking exposure to cigarette produces selective impairment of neurogenic and endothelium-dependent relaxation of corpus cavernosum smooth muscle via a mechanism related to the decreased production and/or availability of nitric oxide.


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