L-arginine supplementation and risk factors of cardiovascular diseases in healthy men: a double-blind randomized clinical trial. Endocrine and lipid effects of oral L-arginine treatment in healthy postmenopausal women. Oral L-Arginine Administration Improves Anthropometric and Biochemical Indices Associated With Cardiovascular Diseases in Obese Patients: A Randomized, Single Blind Placebo Controlled Clinical Trial Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. Supplementation with L-arginine favorably influences plasminogen activator inhibitor type 1 concentration in obese patients. A randomized, double blind trial Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. l-Arginine Supplementation in Peripheral Arterial Disease: No Benefit and Possible Harm Arginine supplementation modulates pig plasma lipids, but not hepatic fatty acids, depending on dietary protein level with or without leucine Oral L-arginine improves endothelial function in healthy individuals older than 70 years Dietary L-arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans. L-arginine supplementation prolongs exercise capacity in congestive heart failure. Oral L-arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men. Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease. Endothelium-dependent vasodilation is independent of the plasma L-arginine/ADMA ratio in men with stable angina: lack of effect of oral L-arginine on endothelial function, oxidative stress and exercise performance. L-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides. Oral L-arginine in patients with coronary artery disease on medical management. Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure.
Context : The effect of L-arginine on risk factors of cardiovascular diseases ( CVD ) has mostly focused on western countries . Since cardiovascular diseases is the second cause of death in Iran and , as far as we are aware , there have been no studies about the effect of L-arginine on CVD risk factors , the aim of this trial was to assess the effects of L-arginine supplementation on CVD risk factors in healthy men . Objective : The purpose of this study was to evaluate the effect of low-dose L-arginine supplementation on CVD risk factors ( lipid profile , blood sugar and blood pressure ) in Iranian healthy men . Design , setting , participants : We conducted a double-blind r and omized controlled trial in 56 patients selected from sport clubs at the Isfahan University of Medical Science between November 2013 and December 2013 . Interventions : Healthy men received L-arginine supplementation ( 2000 mg daily ) in the intervention group or placebo ( 2000 mg maltodextrin daily ) in the control group for 45 days . Main outcome measure : The primary outcome measures were we measured the levels of fasting blood sugar , blood pressure and lipid profile including triglyceride ( TG ) , cholesterol , LDL and HDL in healthy subjects . It was hypothesized that these measures would be significantly improved in those receiving L-arginine supplementation . at the beginning and end of the study . Results : In this trial , we had complete data for 52 healthy participants with mean age of 20.85±4.29 years . At the end of study , fasting blood sugar ( P=0.001 ) and lipid profile ( triglycerideTG ( P<0.001 ) , cholesterol ( P<0.001 ) , LDL ( P=0.04 ) , HDL ( P=0.015 ) ) decreased in the L-arginine group but we found no significant change in the placebo group . In addition , the reduction of fasting blood sugar and lipid profile in L-arginine was significant compared with placebo group . No significant changes were found about systolic ( P=0.81 ) and diastolic blood pressure either in L-arginine or placebo group . ( P=0.532 ) . Conclusion : The use of L-arginine significantly improved outcomes compared to placebo As a substrate for nitric oxide synthesis , L-arginine may give the same protection as estrogen , but its other biologic effects may adversely affect atherogenesis . Therefore , possible endocrine and lipid effects of L-arginine were investigated in a double-blind , placebo-controlled , single crossover study . After r and omization , oral L-arginine ( 9 g ) or placebo was given daily for 1 month , with crossover to the alternate therapy after a 1-month washout period , to 10 postmenopausal women receiving no estrogen .  Compared with placebo , L-arginine increased growth hormone ( 1.5+/-1.8 mg/L vs. 0.6+/-0.6 mg/L , P = .04 ) but had no effect on insulin and catecholamines . Total cholesterol , triglyceride , apolipoprotein E , and low- , very-low- , and high-density lipoprotein cholesterol levels were also unaffected . Lipoprotein(a ) measured by an immunoturbidimetric method was increased by L-arginine in 9 of 10 women relative to placebo ( 0.46+/-0.35 g/L vs. 0.38+/-0.30 g/L , P = .053 ) , and the changes in lipoprotein(a ) levels significantly correlated with the relative increase in growth hormone ( r = 0.85 , P = .03 ) . However , lipoprotein(a ) measured by an enzyme-linked immunosorbent assay failed to demonstrate significant changes . Lack of an increase by  L-arginine in lipoprotein(a ) with a verifiable apolipoprotein(a ) isoform-independent method , despite an increase in growth hormone , questions the validity of previous observations for growth hormone-induced increases in lipoprotein(a ) . The observed lack of effect on major endocrine hormones and lipid profile support the safety of oral L-arginine administration Background : Recently , the potential of L-arginine supplementation as a novel and effective strategy for weight loss and improving biochemical parameters in obese patients has been under consideration . Objectives : To evaluate the influence of 8-week oral L-arginine supplementation on body mass index ( BMI ) , waist circumference ( WC ) , triceps skinfold ( TS ) , subscapular skinfold ( SS ) , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , plasma fasting blood sugar ( FBS ) , glycated hemoglobin ( HbA1c ) , triglyceride ( TG ) , total cholesterol ( TC ) , low-density lipoprotein ( LDL ) , high-density lipoprotein ( HDL ) , and malondialdehyde ( MDA ) in patients with BMI values > 29.9 or visceral obesity ( WC > 102 cm in men or > 88 cm in women ) . Patients and Methods : Ninety obese patients were included in a single-blind r and omized controlled trial . Patients were r and omized to receive either L-arginine ( 3 or 6 g thrice daily ) or placebo for 8 weeks . Anthropometric and biochemical indices , dietary intake , and blood pressure values were measured at the baseline and after the 8-week intervention . Results : Significant decreases in anthropometric parameters , blood pressure ( SBP , DBP ) , FBS , HbA1c , LDL , MDA ( P < 0.001 ) , TG ( P = 0.02 ) , and TC ( P = 0.002 ) and a significant increase in HDL ( P < 0.001 ) were observed in the intervention group , compared to the control group . In the control group , no significant differences were found between the baseline and end-of-intervention measurements . Conclusions : In conclusion , oral L-Arginine supplementation appears to improve anthropometric parameters , blood pressure values , and some blood biochemical indices associated with cardiovascular disease prevention In hypercholesterolemic rabbits , oral L-arginine ( the substrate for endothelium derived nitric oxide ) attenuates endothelial dysfunction and atheroma formation , but the effect in hypercholesterolemic humans is unknown . Using high resolution external ultrasound , we studied arterial physiology in 27 hypercholesterolemic subjects aged 29+/-5 ( 19 - 40 ) years , with known endothelial dysfunction and LDL-cholesterol levels of 238+/-43 mg/dl . Each subject was studied before and after 4 wk of L-arginine ( 7 grams x 3/day ) or placebo powder , with 4 wk washout , in a r and omized double-blind crossover study . Brachial artery diameter was measured at rest , during increased flow ( causing endothelium-dependent dilation , EDD ) and after sublingual glyceryl trinitrate ( causing endothelium-independent dilation ) . After oral L-arginine , plasma L-arginine levels rose from 115+/-103 to 231+/-125 micromol/liter ( P<0.001 ) , and EDD improved from 1.7+/-1.3 to 5.6+/-3.0 % ( P<0.001 ) . In contrast there was no significant change in response to glyceryl trinitrate . After placebo there were no changes in endothelium-dependent or independent vascular responses . Lipid levels were unchanged after L-arginine and placebo . Dietary supplementation with L-arginine significantly improves EDD in hypercholesterolemic young adults , and this may impact favorably on the atherogenic process Background : Elevated plasminogen activator inhibitor type 1 ( PAI 1 ) plays an important role in the pathogenesis of excess blood coagulability in obese patients .  L-arginine supplementation has shown to be associated with enhanced cardiovascular and metabolic health . The aim of the study was to assess the effect of L-arginine supplementation on PAI 1 concentration and to evaluate the relation to changes in nitric oxide ( NO ) plasma level , insulin sensitivity ( M value ) , and total antioxidant status ( TAS ) in obese patients . Material /subjects and methods : A r and omized , double-blind , placebo-controlled study was conducted from March 2010 to June 2011 . Eighty-eight obese patients were r and omly assigned to receive either 9 g of L-arginine or placebo daily for 6 months . At baseline and after 6 months , selected anthropometrical measurements and blood biochemical analyses were performed , and PAI 1 , NO , TAS levels were assessed . Insulin sensitivity was evaluated using the hyperinsulinemic euglycemic clamp technique . Results : We found that 6-month L-arginine supplementation result ed in significant decrease of PAI 1 . Significant increase of NO , TAS , and insulin sensitivity level were noticed . In a group of patients treated with L-arginine , negative correlation between a change of insulin sensitivity value and a change of PAI 1 concentration was found . Conclusions : The present findings demonstrate favorable influence of L-arginine supplementation on PAI 1 concentration in obese patients . Beneficial influence is related to insulin sensitivity improvement . The potential therapeutic role of L-arginine administration in patients with obesity needs further investigation BACKGROUND Coronary endothelial dysfunction is characterized by an imbalance between endothelium-derived vasodilating and vasoconstricting factors and coronary vasoconstriction in response to the endothelium-dependent vasodilator acetylcholine . Thus , the present double-blind , r and omized study was design ed to test the hypothesis that long-term , 6-month supplementation of L-arginine , the precursor of the endothelium-derived vasodilator NO , reverses coronary endothelial dysfunction to acetylcholine in humans with nonobstructive coronary artery disease . METHODS AND RESULTS Twenty-six patients without significant coronary artery disease on coronary angiography and intravascular ultrasound were blindly r and omized to either oral L-arginine or placebo , 3 g TID . Endothelium-dependent coronary blood flow reserve to acetylcholine ( 10(-6 ) to 10(-4 ) mol/L ) was assessed at baseline and after 6 months of therapy . There was no difference between the two study groups in clinical characteristics or in the coronary blood flow in the response to acetylcholine at baseline . After 6 months , the coronary blood flow in response to acetylcholine in the subjects who were taking L-arginine increased compared with the placebo group ( 149 + /- 20 % versus 6 + /- 9 % , P < 0.05 ) . This was associated with a decrease in plasma endothelin concentrations and an improvement in patients ' symptoms scores in the L-arginine treatment group compared with the placebo group . CONCLUSIONS Long-term oral L-arginine supplementation for 6 months in humans improves coronary small-vessel endothelial function in association with a significant improvement in symptoms and a decrease in plasma endothelin concentrations . This study proposes a role for L-arginine as a therapeutic option for patients with coronary endothelial dysfunction and nonobstructive coronary artery disease Background — l-Arginine is the precursor of endothelium-derived nitric oxide , an endogenous vasodilator . l-Arginine supplementation improves vascular reactivity and functional capacity in peripheral arterial disease ( PAD ) in small , short-term studies . We aim ed to determine the effects of long-term administration of l-arginine on vascular reactivity and functional capacity in patients with PAD . Methods and Results — The Nitric Oxide in Peripheral Arterial Insufficiency ( NO-PAIN ) study was a r and omized clinical trial of oral l-arginine ( 3 g/d ) versus placebo for 6 months in 133 subjects with intermittent claudication due to PAD in a single-center setting . The primary end point was the change at 6 months in the absolute claudication distance as assessed by the Skinner-Gardner treadmill protocol . l-Arginine supplementation significantly increased plasma l-arginine levels . However , measures of nitric oxide availability ( including flow-mediated vasodilation , vascular compliance , plasma and urinary nitrogen oxides , and plasma citrulline formation ) were reduced or not improved compared with placebo . Although absolute claudication distance improved in both l-arginine– and placebo-treated patients , the improvement in the l-arginine – treated group was significantly less than that in the placebo group ( 28.3 % versus 11.5 % ; P=0.024 ) . Conclusions — In patients with PAD , long-term administration of l-arginine does not increase nitric oxide synthesis or improve vascular reactivity . Furthermore , the expected placebo effect observed in studies of functional capacity was attenuated in the l-arginine – treated group . As opposed to its short-term administration , long-term administration of l-arginine is not useful in patients with intermittent claudication and PAD Background In the present study , the effect of arginine and leucine supplementation , and dietary protein level , were investigated in commercial crossbred pigs to clarify their individual or combined impact on plasma metabolites , hepatic fatty acid composition and mRNA levels of lipid sensitive factors . The experiment was conducted on fifty-four entire male pigs ( Duroc × Pietrain × Large White × L and race crossbred ) from 59 to 92 kg of live weight . Each pig was r and omly assigned to one of six experimental treatments ( n = 9 ) . The treatments followed a 2 × 3 factorial arrangement , providing two levels of arginine supplementation ( 0 vs. 1 % ) and three levels of basal diet ( normal protein diet , NPD ; reduced protein diet , RPD ; reduced protein diet with 2 % of leucine , RPDL ) . Results Significant interactions between arginine supplementation and protein level were observed across plasma lipids . While dietary arginine  increased total lipids , total cholesterol , HDL-cholesterol , LDL-cholesterol , VLDL-cholesterol and triacylglycerols in NPD , the inverse effect was observed in RPD . Overall , dietary treatments had a minor impact on hepatic fatty acid composition . RPD increased 18:1c9 fatty acid while the combination of leucine and RPD reduced 18:0 fatty acid . Arginine supplementation increased the gene expression of FABP1 , which contributes for triacylglycerols synthesis without affecting hepatic fatty acids content . RPD , with or without leucine addition , upregulated the lipogenic gene CEBPA but downregulated the fat oxidation gene LPIN1 . Conclusions Arginine supplementation was responsible for a modulated effect on plasma lipids , which is dependent on dietary protein level . It consistently increased lipaemia in NPD , while reducing the correspondent metabolites in RPD . In contrast , arginine had no major impact , neither on hepatic fatty acids content nor on fatty acid composition . Likewise , leucine supplementation of RPD , regardless the presence of arginine , promoted no changes on total fatty acids in the liver . Ultimately , arginine , leucine and dietary protein reduction seem to be unrelated with fatty liver development 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 prospect i ve , double-blind , r and omized crossover trial , 12 healthy old subjects ( age 73.8 6 2.7 years ) 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 . FMD was determined by high-resolution ultrasound in the brachial artery during reactive hyperaemia . Baseline artery diameter was 3.88 6 0.18 mm . l-Arginine signifi cantly improved FMD ( to 5.7 6 1.2 % , p , 0.0001 ) , whereas placebo had no effect ( -0.25 6 0.7 % ; n.s . ) . After  L-arginine , plasma levels of L-arginine increased signifi cantly ( 114.9 6 11.6 versus 57.4 6 5.0 mmol/l ) , 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 ( 3.9 6 0.2 versus 1.0 6 0.1 mmol/l ; p , 0.0001 ) . ADMA remained unchanged during treatment , but L-arginine supplementation normalized the L-arginine/ADMA ratio ( p , 0.05 ) . 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 OBJECTIVES The present study was design ed to test the hypothesis that long-term dietary supplementation with the nitric oxide precursor L-arginine would enhance vascular or platelet-derived nitric oxide activity , or both , and thereby inhibit platelet reactivity in hypercholesterolemic humans . BACKGROUND We have shown that reduced vascular activity of nitric oxide in hypercholesterolemic rabbits can be restored by L-arginine supplementation . The improvement in nitric oxide activity is associated with an inhibition of platelet aggregation ex vivo . This effect is most likely due to increased elaboration of endothelium- or platelet-derived nitric oxide , or both , because the inhibition of platelet reactivity was associated with elevation of intraplatelet cyclic guanosine monophosphate and was reversed by the nitric oxide synthase antagonist N-methyl-arginine . METHODS In a double-blinded , r and omized , placebo-controlled trial , hypercholesterolemic patients were assigned to L-arginine hydrochloride , 8.4 g/day orally , or placebo for 2 weeks . Platelet-rich plasma was obtained for aggregometry induced by collagen ( 1 to 10 micrograms/ml ) at four points : baseline , after 2 weeks of treatment , after a 2-week washout and after a long-term washout of 16 weeks on average . Aggregation was quantified by light transmittance and expressed as a percent transmittance observed with platelet-poor plasma . RESULTS Compared with normocholesterolemic control subjects , platelets from hypercholesterolemic subjects stimulated with 5 micrograms/ml of collagen showed increased aggregability ( 68.6 % in hypercholesterolemic patients vs. 54.5 % in normocholesterolemic control subjects , p < or = 0.02 ) . After 2 weeks of treatment with L-arginine ( but not placebo ) , platelet reactivity was modestly reduced ; this effect persisted for 2 weeks after discontinuation of arginine ( 52.6 % in arginine-treated patients vs. 65.1 % in normocholesterolemic control subjects , p = 0.07 ) . After 18 weeks ( i.e. , 16 weeks after discontinuing arginine treatment ) , the platelets of hypercholesterolemic patients once again became hyperaggregable , and the extent of platelet aggregation was significantly increased compared with the 4-week point ( 73.6 % after vs. 52.6 % during arginine treatment , p < 0.01 ) . No significant change in platelet reactivity was seen in placebo-treated hypercholesterolemic patients throughout the study . L-Arginine treatment was well tolerated without side effects . CONCLUSIONS This double-blinded , placebo-controlled study demonstrates that dietary supplementation with L-arginine can modestly attenuate the increased platelet reactivity seen in hypercholesterolemic patients . The data are consistent with our previous studies in hypercholesterolemic animals , demonstrating that L-arginine restores endogenous nitric oxide activity and inhibits platelet aggregation . Enhancement of endogenous nitric oxide activity is a potential novel therapeutic strategy worthy of further study BACKGROUND In congestive heart failure ( CHF ) , endothelial dysfunction may contribute to impairment of exercise induced vasodilatation and decreased exercise capacity . We hypothesised that administration of L-arginine , a precursor of nitric oxide ( NO ) and postulated antioxidant , may improve endothelium-dependent vasodilatation and exercise capacity and also exert antioxidant activity . AIMS To investigate the effect of oral supplementation with L-arginine on exercise capacity and markers of oxidative stress in patients with mild to moderate CHF . METHODS The study had a r and omised double-blind cross-over design . Twenty one patients with stable NYHA II-III CHF underwent three exercise tests : initially , after oral administration of L-arginine ( 9 g/day for 7 days ) or placebo . Blood was sample d prior to each test for plasma lipid peroxides , reduced sulphydryl groups and leukocyte oxygen free radical production . RESULTS We found a higher prolongation of exercise duration time after L-arginine than after placebo ( 99+/-106 vs 70+/-99 s , p<0.05 ) . There were no significant differences in markers of free radical activity . CONCLUSIONS In patients with chronic stable CHF , oral supplementation with L-arginine prolongs exercise duration which may be due to NO-induced peripheral vasodilatation . The antioxidant properties of L-arginine have not been confirmed in this ex vivo study OBJECTIVES Our aim was to assess the effect of oral L-arginine on endothelial or platelet physiology in humans . BACKGROUND L-Arginine is the substrate for nitric oxide synthesis , and in cholesterol-fed rabbits , oral L-arginine improves endothelium-dependent dilation , inhibits platelet aggregation and reduces atheroma . In hypercholesterolemic humans , intravenous L-arginine immediately improves endothelium-dependent dilation ; however , the vascular effects of oral L-arginine in healthy humans have not previously been investigated . METHODS In a prospect i ve , double-blind , r and omized crossover trial , 12 healthy young men 27 to 37 years old took  L-arginine ( 7 g three times daily ) or placebo for 3 days each , separated by a washout period of 7 to 14 days . RESULTS After L-arginine , plasma levels of arginine ( mean + /- SEM 303 + /- 36 vs. 128 + /- 12 mumol/liter , p = 0.01 ) and urea ( 6.7 + /- 0.5 vs. 5.2 + /- 0.2 mmol/liter , p < 0.01 ) were higher than levels measured after placebo , and platelet aggregation in response to adenosine diphosphate was markedly impaired ( 37 + /- 12 % vs. 81 + /- 3 % , p = 0.02 ) . The inhibition of platelet aggregation correlated with the plasma level of L-arginine ( r = 0.74 , p = 0.01 ) , and it could be completely or partially reversed by ex vivo incubation with N-monomethyl-L-arginine , a specific nitric oxide synthase inhibitor . Platelet cyclic guanosine monophosphate levels were higher after oral L-arginine than at baseline ( 1.91 + /- 0.46 vs. 1.38 + /- 0.40 pmol/10(9 ) platelets , p = 0.04 ) . No changes were seen in fasting lipid levels , heart rate , blood pressure , endothelium-dependent dilation of the brachial artery ( measured in response to reactive hyperemia , using external vascular ultrasound ) ( 6.1 + /- 0.7 % vs. 6.5 + /- 0.7 % , p = NS ) or in plasma levels of nitrosylated proteins ( a marker of in vivo nitric oxide production ) ( 3.5 + /- 0.5 vs. 3.3 + /- 0.4 mumol/liter , p = NS ) 1 to 1.5 h after the last dose of L-arginine . CONCLUSIONS In these healthy young adult men , oral L-arginine inhibited platelet aggregation by way of the nitric oxide pathway . However , it had no effect on systemic hemodynamic variables , plasma nitrosylated protein levels or endothelium-dependent dilation . Therefore , at certain doses , oral L-arginine may result in a relatively platelet-specific increase in nitric oxide production L-Arginine is the physiological substrate for nitric oxide synthesis by the vascular endothelium . In hypercholesterolaemic rabbits , oral L-arginine reduces atheroma , improves endothelium-dependent dilatation and reduces monocyte/endothelial cell adhesion . The effect of oral L-arginine on endothelial physiology is unknown , however , in humans with established atherosclerosis . In a prospect i ve , double-blind , r and omised crossover trial , ten men aged 41 + /- 2 years with angiographically proven coronary atherosclerosis took L-arginine ( 7 g three times per day ) or placebo for 3 days each , with a washout period of 10 days . After L-arginine , compared to placebo , plasma levels of arginine were increased ( 318 + /- 18 vs. 124 + /- 9 mumol/l , P < 0.01 ) and endothelium-dependent dilatation of the brachial artery ( measured as the change in diameter in response to reactive hyperaemia , using external vascular ultrasound ) was improved ( 4.7 + /- 1.1 vs. 1.8 + /- 0.7 % , P < 0.04 ) . No changes were seen in endothelium-independent dilatation of the brachial artery ( measured as the change in diameter in response to sublingual nitroglycerine ) , blood pressure , heart rate or fasting lipid levels . Serum from six of the ten subjects after L-arginine and placebo was then added to confluent monolayers of human umbilical vein endothelial cells for 24 h , before human monocytes obtained by countercurrent centrifiguation elutriation were added and cell adhesion assessed by light microscopy . Adhesion was reduced following L-arginine compared to placebo ( 42 + /- 2 vs. 50 + /- 1 % , P < 0.01 ) . In young men with coronary artery disease , oral L-arginine improves endothelium-dependent dilatation and reduces monocyte/endothelial cell adhesion OBJECTIVES This study was design ed to determine the effect of two weeks ' treatment with L-arginine on the ratio of plasma L-arginine to asymmetric dimethylarginine ( ADMA ) , oxidative stress , endothelium-dependent vasodilatation to acetylcholine , exercise performance and heart rate variability in men with stable angina . BACKGROUND The ratio of plasma L-arginine : ADMA has been proposed as a determinant of endothelium-dependent dilation ; dietary supplementation with L-arginine has been shown to improve endothelium-dependent vasodilation and symptoms in some conditions . METHODS Men ( n = 40 ) with stable angina , at least one epicardial coronary artery with a stenosis > 50 % and a positive exercise test were r and omized to receive L-arginine ( 15 g daily ) or placebo for two weeks according to a double-blind parallel-group design . Plasma L-arginine , ADMA , 8-epi-prostagl and in F2alpha ( a marker of oxidative stress ) and forearm vasodilator responses to brachial artery infusion of nitroprusside and acetylcholine  ( + /-L-arginine ) were measured . A st and ard Bruce protocol exercise test was performed before and at the end of the treatment period . RESULTS Plasma L-arginine increased after oral L-arginine , whereas ADMA remained unchanged , leading to an increase in the L-arginine/ADMA ratio of 62 + /- 11 % ( mean + /- SE , p < 0.01 ) . Despite a significant enhancement in acetylcholine response by intra-arterial L-arginine at baseline , this response remained unchanged after oral L-arginine . Measures of oxidative stress and exercise performance after L-arginine/placebo were similar in placebo and active groups . CONCLUSIONS In men with stable angina , an increase in plasma L-arginine/ADMA ratio after two weeks ' oral supplementation with L-arginine is not associated with an improvement in endothelium-dependent vasodilatation , oxidative stress or exercise performance We recently noticed a possible triglyceride-lowering effect during dietary supplementation with L-arginine . The major limitation of prior studies on L-arginine , however , was that triglyceride levels were not the primary end point , and patients were not necessarily hypertriglyceridemic . Therefore , we conducted a 2-arm , r and omized , double-blind study in 33 hypertriglyceridemic patients to investigate the hypothesis that oral L-arginine may lower serum triglyceride levels in hypertriglyceridemic patients on and off statins .  The study consisted of a 6-week run-in phase , 6 weeks of treatment with L-arginine ( n = 22 , 1.5 g bid ) or placebo ( n = 11 ) , and a 6-week extension period where simvastatin ( 20 mg qd ) was added . All patients received dietary advice during each study visit . Routine and lipid laboratory parameters were determined in the local routine clinical laboratory . Treatment with L-arginine alone had no effects on serum lipids compared to placebo . The combination of L-arginine with simvastatin led to a significantly stronger reduction in triglycerides compared to placebo plus simvastatin ( -140.5 + /- 149.2 mg/dL vs -56.1 + /- 85.0 mg/dL ; P = .048 ) . In addition , we found simvastatin-induced  increases in aspartate transaminase and fibrinogen to be attenuated by L-arginine as compared to placebo . We conclude from our data that L-arginine enhances the effects of simvastatin on lipid metabolism , but it has no triglyceride-lowering effects when given alone BACKGROUND Vascular nitric oxide ( NO ) bioavailability is reduced in patients with coronary artery disease ( CAD ) . We investigated whether oral L-arginine , the substrate for NO synthesis , improves homeostatic functions of the vascular endothelium in patients maintained on appropriate medical therapy and thus might be useful as adjunctive therapy . METHODS AND RESULTS Thirty CAD patients ( 29 men ; age , 67+/-8 years ) on appropriate medical management were r and omly assigned to L-arginine ( 9 g ) or placebo daily for 1 month , with crossover to the alternate therapy after 1 month off therapy , in a double-blind study . Nitrogen oxides in serum ( as an index of endothelial NO release ) , flow-mediated brachial artery dilation ( as an index of vascular NO bioactivity ) , and serum cell adhesion molecules ( as an index of NO-regulated markers of inflammation ) were measured at the end of each treatment period . L-Arginine significantly increased arginine levels in plasma ( 130+/-53 versus 70+/-17 micromol/L , P<0.001 ) compared with placebo . However , there was no effect of L-arginine on nitrogen oxides ( 19.3+/-7.9 versus 18 . 6+/-6.7 micromol/L , P=0.546 ) , on flow-mediated dilation of the brachial artery ( 11.9+/-6.3 % versus 11.4+/-7.9 % , P=0.742 ) , or on the cell adhesion molecules E-selectin ( 47.8+/-15.2 versus 47.2+/-14.4 ng/mL , P=0.601 ) , intercellular adhesion molecule-1 ( 250+/-57 versus 249+/-57 ng/mL , P=0.862 ) , and vascular cell adhesion molecule-1 ( 567+/-124 versus 574+/-135 ng/mL , P=0.473 ) . CONCLUSIONS Oral L-arginine therapy does not improve NO bioavailability in CAD patients on appropriate medical management and thus may not benefit this group of patients BACKGROUND Patients with heart failure have reduced peripheral blood flow at rest , during exercise , and in response to endothelium-dependent vasodilators . Nitric oxide formed from L-arginine metabolism in endothelial cells contributes to regulation of blood flow under these conditions . A r and omized , double-blind crossover study design was used to determine whether supplemental oral L-arginine can augment peripheral blood flow and improve functional status in patients with moderate to severe heart failure . METHODS AND RESULTS Fifteen subjects were given 6 weeks of oral L-arginine hydrochloride ( 5.6 to 12.6 g/d ) and 6 weeks of matched placebo capsules in r and om sequence . Compared with placebo , supplemental oral L-arginine significantly increased forearm blood flow during forearm exercise , on average from 5.1 + /- 2.8 to 6.6 + /- 3.4 mL. min-1 . dL-1 ( P < .05 ) . Furthermore , functional status was significantly better on L-arginine compared with placebo , as indicated by increased distances during a 6-minute walk test ( 390 + /- 91 versus 422 + /- 86 m , P < .05 ) and lower scores on the Living With Heart Failure question naire ( 55 + /- 28 versus 42 + /- 26 , P < .05 ) . Oral L-arginine also improved arterial compliance from 1.99 + /- 0.38 to 2.36 + /- 0.30 mL/mm Hg ( P < .001 ) and reduced circulating levels of endothelin from 1.9 + /- 1.1 to 1.5 + /- 1.1 pmol/L ( P < .05 ) . CONCLUSIONS Supplemental oral L-arginine had beneficial effects in patients with heart failure . Further studies are needed to confirm the therapeutic potential of supplemental oral L-arginine and to identify mechanisms of action in patients with heart failure
This meta- analysis concludes that l-arginine supplementation can significantly reduce blood TAG levels ; however , there is insufficient evidence to support its hypocholesterolaemic effects .
A number of clinical trials have examined the effect of l-arginine on lipid profile in recent years ; however , the results remain equivocal .
Therefore , the present study aims to summarise and quantitatively examine the available evidence on the effectiveness l-arginine supplementation on lipid parameters using a systematic review and meta-analytic approach .