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Home > Anti-aging Research > L-Arginine


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  • L-arginine Enhances Effect of Radiation on Brain Metastases - Medscape, 11/17/21 - "63 patients with brain metastases related to solid tumors — such as non-small cell lung cancer (51%), triple-negative breast cancer (21%), and melanoma (8%) — were randomized to receive oral L-arginine 10 g or placebo prior to each fraction of radiation. The whole-brain radiation therapy protocol consisted of a total dose of 32.0 Gy, administered in 20 fractions, followed by a boost of 22.4 Gy that adhered to the same fractionation schedule. The investigators used the Fisher's exact test or the Cox-Mantel test to compare responses ... The majority of patients had an uncontrolled primary tumor, multiple metastatic sites, and multiple brain metastases. The median follow-up after the end of the treatment was 5 months (range, 1 - 55 months) ... L-arginine was well tolerated and did not produce short- or long-term (more than 6 months) adverse events. The overall response rate was significantly higher in the L-arginine group than in the placebo group (77.4% vs 22.0%; P < .001), as was the symptomatic response rate (93.5% vs 50.0%; P = .002) ... Complete neurologic responses were three times more likely in patients pretreated with L-arginine than in those pretreated with placebo, although the difference was not significant (29.0% vs 9.4%; P = .059). And at 6 months, patients in the L-arginine group were four times more likely to be free from neurologic progression than patients in the placebo group (82.0% vs 20.0%; ... Median overall progression-free survival was longer in the L-arginine group than in the placebo group (5 vs 2 months" - See L-arginine products at Amazon.com.
  • Arginine, an inexpensive oral drug, could enhance radiation therapy for cancer - Science  Daily, 11/6/21 - "Arginine, also called L-arginine, is inexpensive and widely available, generally considered safe, and can get relatively easily from the bloodstream into the brain. The idea of using it to treat cancer arose from observations that tumors often aid their own survival by producing high levels of the related molecule nitric oxide (NO). The latter regulates multiple processes in the body including the flow of blood through blood vessels, and tumors cells often make more NO by upregulating their production of special enzymes called NO synthases, which synthesize NO from arginine ... patients were treated with high-dose arginine or placebo oral suspensions an hour before radiotherapy for their brain metastases -- tumors in the brain that represent the spread from primary tumors elsewhere, such as the lungs ... Six months after their courses of radiotherapy, 82 percent of the arginine group had improvement, or at least no worsening, of their neurological symptoms, compared with 20 percent in the placebo group. Most of the arginine-treated patients who died during the study did so because of their cancers' spread elsewhere in the body ... Moreover, although metastatic cancer usually has a dire prognosis, there were some arginine-treated patients whose tumors in and outside the brain disappeared, suggesting the possibility of cures"
  • Oral Arginine Emerges as Potential Adjuvant for Vaso-Occlusive Crisis Management - Medscape, 12/11/19 - "Oral arginine supplementation significantly increased plasma arginine levels and improved acute pain-related outcomes in Nigerian children with sickle cell disease ... Low plasma arginine levels are associated with acute pain requiring hospitalization in Nigerian children with sickle cell disease, and have also been shown in a prior study in the United States to predict pediatric vaso-occlusion ... Despite similar baseline Numerical Pain Scale (PS) scores (8.7 and 8.4 on a 0–10 scale), day 5 pain scores were 1.2 vs. 2.0, and the mean daily rate of decline was 1.5 vs. 1.1 cm/day ... By day 5, 54% of patients on arginine were already home, as compared with just 24% in the placebo arm"
  • Depression linked to reduced arginine levels - Science Daily, 2/21/18 - "Arginine is an amino acid which the body uses to produce, e.g., nitric oxide. Nitric oxide, in turn, is a nervous system and immune defence mediator, and it also plays a role in vascular regulation ... It is possible that depression-induced inflammatory responses lead to reduced arginine levels. This may result in insufficient production of nitric oxide for the needs of the nervous system and circulation. However, we don't know yet what exactly causes reduced arginine bioavailability in people with depression ... The concentrations of three amino acids, namely arginine, citrulline and ornithine, were analysed from their fasting glucose samples, and this data was used to calculate their GABRs ... Although our study shows that people with depression have reduced arginine bioavailability, this doesn't mean that taking an arginine supplement would protect against depression. That's an area for further research ... Arginine bioavailability was slightly higher in people who had recovered from depression than in people who remained depressed. However, a more extensive set of data and a longer follow-up period are necessary for estimating arginine's role in depression recovery"
  • Naturally occurring amino acid could improve oral health - Science Daily, 5/7/15 - "in the lab L-arginine -- found in red meat, poultry, fish and dairy products, and is already used in dental products for tooth sensitivity--stopped the formation of dental plaque ... nearly 24 percent of adults in the United States have untreated dental caries, and about 39 percent have moderate-to-severe periodontitis, a number that rises to 64 percent for those over age 65 ... It appears arginine can change how cells stick together, and can trigger bacteria within biofilms to alter how they behave so that they no longer stick to surfaces"
  • Chowing down on watermelon could lower blood pressure, study suggests - Science Daily, 4/3/14 - "the group was divided into two. For the first six weeks, one group was given four grams of the amino acid L-citrulline and two grams of L-arginine per day, both from watermelon extract. The other group was given a placebo for 6 weeks ... consuming watermelon had a positive impact on aortic blood pressure and other vascular parameters" - See L-citrulline at Amazon.com and L-arginine products at Amazon.com.
  • Arginine Therapy Shows Promise for Sickle Cell Pain - Science Daily, 9/16/13 - "A deficiency of nitric oxide, a potent vasodilator, has been identified in sickle cell disease and may contribute to episodes of blocked vessels and pain. Since arginine is a building block of nitric oxide, researchers hypothesized that arginine could be a beneficial treatment for pain related to sickle cell disease ... a randomized, double blind placebo control clinical trial of 38 children with sickle cell disease hospitalized for 56 episodes of pain. The research team discovered a 54 percent reduction in the use of opioid pain medication and significantly lower pain scores at hospital discharge in those treated with arginine over those receiving placebo"
  • Amino Acid With Promising Anti-Diabetic Effects - Science Daily, 9/9/13 - "the amino acid is just as effective as several well-established drugs for type 2 diabetics ... researchers subjected lean and obese animal models to a so-called glucose tolerance test, which measures the body's ability to remove glucose from the blood over time ... both lean and fat laboratory mice benefit considerably from arginine supplements. In fact, we improved glucose metabolism by as much as 40% in both groups. We can also see that arginine increases the body's production of glucagon-like peptide-1 (GLP-1), an intestinal hormone which plays an important role in regulating appetite and glucose metabolism, and which is therefore used in numerous drugs for treating type 2 diabetes"
  • Arginine and proline enriched diet may speed wound healing in diabetes - Science Daily, 11/15/12 - "Researchers divided 18 rats into three groups that were either fed a standard diet, a high-protein diet, or a high protein diet supplemented with arginine and proline (ARG+PRO) ... Rats on both high protein diets had better nitrogen balance than those on the standard diet. However, the wounds of the rats on the ARG+PRO diet showed more new blood vessel growth on day 5. New blood vessel growth is an essential part of wound healing as the blood vessels supply nutrition and oxygen to growing tissue ... arginine and proline supplementation could offer new hope for effective treatment in diabetic patients with chronic wounds" - See L-arginine products at Amazon.com and L-proline products at Amazon.com.
  • Effect of Oral L-Arginine Supplementation on Blood Pressure - Medscape, 12/30/11 - "This meta-analysis of randomized, double-blind, placebo-controlled trials brought evidence that oral L-arginine supplementation, compared with placebo, significantly lowered systolic BP by 5.39 mm Hg (95% CI −8.54 to −2.25) and diastolic BP by 2.66 mm Hg (95% CI −3.77 to −1.54)"
  • Dietary Supplement May Help Prevent Preeclampsia - WebMD, 5/19/11 - "women who ate daily food bars containing the amino acid L-arginine and antioxidant vitamins during pregnancy had a much lower incidence of preeclampsia than women who ate bars containing the antioxidant vitamins alone or bars containing neither supplement ... far fewer of the women in the L-arginine plus vitamin group developed preeclampsia (12.7%) than women in the vitamin-alone (22.5%) group and no-supplement (30.2%) group"
  • The Effects of L-Arginine and Yohimbine on Sexual Arousal in Postmenopausal Women with FSAD - University of Texas at Austin Dept. of Psychiatry
  • Research identifies the herbal supplements that are effective in treating anxiety - Science Daily, 10/6/10 - "A systematic review of research into the use of nutritional supplements for the treatment of anxiety disorders has found strong evidence for the use of extracts of passionflower or kava and combinations of L-lysine and L-arginine ... We found mixed results -- while passionflower or kava and L-lysine and L-arginine appeared to be effective, St John's Wort and magnesium supplements were not"
  • Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review - Nutr J. 2010 Oct 7;9(1):42 - "based on this systematic review, strong evidence exists for the use of herbal supplements containing extracts of passionflower or kava and combinations of L-lysine and L-arginine as treatments for anxiety symptoms and disorders. Magnesium-containing supplements and other herbal combinations may hold promise, but more research is needed before these products can be recommended to patients. St. John's wort monotherapy has insufficient evidence for use as an effective anxiolytic treatment"
  • Arginine Discovery Could Help Fight Human Obesity - Science Daily, 2/12/09 - "arginine, an amino acid, reduces fat mass in diet-induced obese rats and could help fight human obesity ... dietary arginine supplementation shifts nutrient partitioning to promote skeletal-muscle gain ... The findings were published recently in the Journal of Nutrition ... arginine supplementation for a 12-week period decreased the body fat gains of low-fat and high-fat fed rats by 65 percent and 63 percent, respectively. The long-term arginine treatment did not have any adverse effects on either group ... funded by the American Heart Association"
  • Pine bark extract boost for blood flow and heart health - Nutra USA, 10/18/07 - "Acetylcholine stimulates the cells of arteries to produce NO from L-arginine faster ... In turn, the NO causes the muscle surrounding arteries to relax, which results in an increase of blood vessel diameters. When subjects had taken Pycnogenol the relaxation of arteries was increased by 42 per cent as compared to the group taking placebo tablets" - See Pycnogenol at Amazon.com and citicholine at Amazon.com.
  • Statins' Effect on Endothelial Function Enhanced by L-arginine in Some Patients - Doctor's Guide, 6/11/07 - "endothelium-dependent dilation (EDD) ... simvastatin had no appreciable effect on EDD (6.2+/-1.2% vs. 6.1+/-0.9%) in subjects with elevated ADMA. However, the addition of L-arginine to simvastatin significantly improved EDD (9.8+/-1.5% vs. 5.3+/-0.8%; P <.01). There were also significant improvements in EDD in response to L-arginine alone"
  • Restoring Sexual Potency? - Dr. Weil, 5/4/06 - "Arginine ... Ginkgo biloba ... Ashwaganda"
  • Don't Take L-Arginine for Heart Attack - WebMD, 1/3/06 - "All six deaths were among the 78 heart attack patients who added L-arginine to their normal medical treatment regimen. There were no deaths among the 75 heart attack patients who did not receive L-arginine"
  • The high five for hypertension - Functional Foods & Nutraceuticals, 12/04 - "Co-enzyme Q10 ... Omega-3 fatty acids ... Garlic ... L-arginine ... Calcium"
  • OTC Cream Improves Blood Flow in Feet - WebMD, 1/8/04 - "arginine does increase blood flow, but it is not yet clear if this translates into fewer foot ulcers or better healing of ulcers"
  • Nitric Oxide Now -- Ask Me How -  WashingtonPost.com, 10/6/03 - "In the arteries, the innermost layer of cells releases nitric oxide to signal smooth muscle cells to dilate (increase the diameter of) the arteries. This allows blood to flow more freely, particularly during exercise ... By the 1990s, many scientists saw nitric oxide as the next great weapon for treating heart disease, impotence and even bacterial infections ... Niteworks has L-arginine and also L-citrulline, which recycles spent L-arginine by resupplying it with atoms it lost producing nitric oxide ... "Ninety dollars a month? That's obscene," Murad said. "You can probably get [vitamin] C and E for pennies a day. You can probably get arginine for about a dollar a day"" - See L-citrulline at Amazon.com.
  • Arginine Supplements May Help Treat Pulmonary Hypertension in Sickle Cell - Medscape, 6/30/03
  • Protecting Blood Vessels From Stress - WebMD, 1/15/03 - "vitamins can improve blood flow and prevent the long-term development of atherosclerosis -- or hardening of the arteries -- when given in combination with an amino acid known as L-arginine ... antioxidants might work together with L-arginine to prevent inflammation in the branch areas of blood vessels ... although antioxidants may not reverse or repair pre-existing damage within blood vessels, they may slow the long-term progression of atherosclerosis"
  • L-Arginine Minimises Stroke Damage in Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes - Doctor's Guide, 10/16/02
  • Natural Remedy for Erectile Dysfunction - New Hope Natural Media, 9/5/02 - "received three separate treatments for two weeks each, in random order: (1) 3.25 grams of arginine plus 6 mg of yohimbine, (2) yohimbine alone and (3) placebo ... Combination treatment was considered successful by 40% of the participants, compared with 28.9% with yohimbine alone and 17.8% with placebo ... Arginine is available in health food stores without a prescription, but yohimbine can be obtained only with a doctor's prescription. Although the herb yohimbe is sold in health food stores, it contains much less yohimbine than the amount used in the new study" - See l-arginine at Amazon.com.
  • Yohimbine Plus L-Arginine Potential Therapy For Mild To Moderate Erectile Dysfunction - Doctor's Guide, 7/31/02 - "randomly assigned 45 men with erectile dysfunction to treatment with 6 mg of L-arginine glutamate combined with 6 mg of yohimbine hydrochloride, to 6 mg of yohimbine hydrochloride alone, or to placebo ... They took the drugs orally one to two hours before intended sexual intercourse ... Changes in this score [Index of Erectile Function (IIEF)] were significantly greater among patients taking yohimbine plus L-arginine compared to those taking placebo" - Note: That "6 mg of L-arginine glutamate" has to be a misprint.  It probably should have been 6 grams as in a U. of Texas study on postmenopausal women.
  • Arginine and Fish Oil May Help Cancer Patients Undergoing Chemotherapy - Life Extension Magazine, 7/02
  • L-Arginine Application Speeds Healing of Anal Fissure - Doctor's Guide, 6/10/02
  • Concepts and Controversies in Nutrition, Immune-Enhancing Formulas - Medscape, 3/21/02 - "Immune-enhancing formulas (IEFs), also known as immune-modulating formulas, include arginine, glutamine, nucleic acids, and omega-3 fatty acids"
  • The Wizard is Oz - Life Extension Magazine, 11/01 - "Best-selling author and nutritional guru to the rich and famous, Oz Garcia is singing the praises of the Life Extension Foundation and its products in his newest book, The Healthy High Tech Body, published in September 2001 ... Supplements at the top of Garcia's list of recommendations ... DHA ... NADH ... Alpah Lipoic Acid ... Acetyl-L-Carnitine ... An expanded list of his recommendations includes lycopene, gamma tocopherol, vinpocetine, SAMe, folic acid, carnosine, glutathione, DMAE, Huperzine A, probiotics, MSM, secretagogues, arginine pyroglutamate, IP-6, bioflavonoid formulas and grape skin/seed extracts"
  • Nutritional Supplement Boosts Immune Function In Surgery Patients - Intelihealth, 9/13/01 - "A new study published in the journal Lancet suggests that people who are at high risk of infection after heart surgery may benefit from taking a nutritional supplement containing L-arginine and omega-3 fatty acids"
  • Quinopril and L-Arginine Improves Endothelial Function In Hypertensive Patients - Doctor's Guide, 6/21/01
  • Study: Supplement Can Help Take the 'Dys' Out of Female Sexual Dysfunction, Researchers Promote Idea of 'Sexual Wellness' - WebMD, 6/5/01 - "ArginMax -- a dietary cocktail consisting of ginseng, ginkgo, B vitamins, calcium, folic acid, and other vitamins and minerals -- is being heralded as one component of a lifestyle that improves sexual performance and helps prevent problems associated with intimacy"
  • Want a love potion? What to know before you try - CNN, 6/15/00 - "a study of 21 men with "mild to moderate" impotence taking a supplement called ArginMax (3,000 milligrams per day) found big improvements in erection and sexual satisfaction."
  • Immune-Enhancing Therapy Shortens Hospital Stays By Three Days - Doctor's Guide, 12/23/99 - "The trials, conducted at medical centers in the U.S. and Europe, compared patients receiving standard enteral nutrition with patients who received commercially available immune-enhancing therapies containing arginine and glutamine (naturally occurring amino acids), nucleotides (found in yeast), and omega-3 fatty acids (found in fish oil) ... Our study shows that immunonutrition can make a significant contribution to reducing the number of infections and length of hospital stay in critically ill patients"
  • Women and Sex Drive -  Life Enhancement Magazine, 12/99 - "Because the amino acid arginine is the precursor to nitric oxide, its ingestion and concomitant elevation in the serum accomplish much the same goal as Viagra, as several studies have borne out"
  • Arginine for Muscles, Memory, Sex and More - Life Enhancement Magazine, 12/99 - "Arginine is the primary source of the nitrogen that results in production of the important biomolecule nitric oxide (NO) ... NO helps defend the body against invading bacteria2 and parasites. In the brain, where it is formed in nerve cells, it diffuses in all directions, activating all cells in the vicinity, thus modulating many functions, including behavior and gastrointestinal transit flow. The release of NO is absolutely essential for motor learning in the cerebellum (coordination), and it also appears to be necessary for long-term potentiation in the brain, which is the mechanism involved in long-term memory. NO is now also thought to be important in our olfactory (smelling) sensations and our capacity to identify different scents ... Free arginine has been shown to help prevent a destructive process known as cross-linking, which is associated with accelerated aging. Excessive cross-linking reactions inevitably damage the kidneys, necessitating dialysis in advanced age"
  • Study finds new therapy for impotence - CNN, 10/27/99 - "Nitric oxide is the messenger, if you will, the signaling molecule, and without that signal you can't get that signal from the brain to the penis for the erectile process ... An amino acid call L-argenine produces nitric oxide in the body"
  • Be All That You Can Be - Life Enhancement Magazine, 7/99 - "the erections were harder and longer-lasting and so forth when they were using L-arginine. The two studies I have in mind used 2,800 mg and 2,500 mg of arginine, respectively"
  • Viagra anniversary sees herbal competitors by the dozens - CNN, 3/26/99 - "Since the main problem in impotence is actually a problem with circulation of the blood vessels in the penis, l-arginine holds great promise for men with physical impotence"
  • Prosexual Enhancement - Life Enhancement Magazine, 3/97 - "According to numerous anecdotal reports from highly satisfied arginine users since the early 1980s, dietary L-arginine can give men erections that are bigger, harder, more frequent, and longer lasting. Some men also report that L-arginine gives them greater endurance. In women, L-arginine has been reported to increase the intensity of sensation during sex. One highly athletic 30-something woman tells about the time she told her doctor about her L-arginine use. "My doctor almost fell off his chair when I told him how many times a night I do it - six-times," she said. "He's definitely taking arginine now, too.""


  • Arginine catabolism metabolites and atrial fibrillation or heart failure risk: two case-control studies within the PREDIMED trial - Am J Clin Nutr 2022 May 16 - "Inverse associations with incident AF were observed for arginine [OR per 1 SD (95% CI): 0.83 (0.73, 0.94)]) and homoarginine [0.87 (0.76, 0.98)], whereas positive associations were found for the asymmetric dimethylarginine/symmetric dimethylarginine ratio (ADMA/SDMA) [1.15 (1.01, 1.31)] and citrulline [1.19 (1.01, 1.39)]. For HF, inverse associations were found for arginine [0.82 (0.69, 0.97)] and homoarginine [0.81 (0.68, 0.96)], and positive associations for the ADMA/SDMA ratio [1.19 (1.02, 1.41)], N1-acetylspermidine [1.34 (1.12, 1.60)], and diacetylspermine [1.20 (1.02, 1.41)]. In the stratified analysis according to the dietary intervention, the lower HF risk associated with arginine was restricted to participants in the MedDiet groups" - See arginine products at Amazon.com.
  • Attenuation of chronic tension headache frequency and severity with daily L-arginine and aged garlic extract dietary supplementation - Eur J Clin Nutr 2021 Jul 23 - "A 74-year-old female subject with suboptimal management of episodic tension headache was treated with a daily dose of 1.5 g L-arginine and 1.2 g aged garlic extract (AGE) ... Within 6 weeks of commencing treatment, her self-reported symptoms improved markedly and were sustained at 2 years following commencement. We propose that the putative beneficial effect of L-arginine and AGE in this patient is because of the well-established systemic vasodilatory effects of L-arginine and aged garlic extract. On the hypothesis that migraine is precipitated by cerebral microvascular constriction, we recommend a double-blind randomised controlled trial to clinically test this hypothesis in migraine patients" - See l-arginine products at Amazon.com and l-arginine at iHerb and garlic supplements at Amazon.com and garlic at iHerb.com.
  • l -Arginine Can Enhance the Beneficial Effect of Losartan in Patients with Chronic Aortic Regurgitation and Isolated Systolic Hypertension - Int J Angiol 2021 Jun;30(2) - "chronic aortic regurgitation (CAR) and isolated systolic hypertension (ISH) ... Both groups had a significant reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP), left ventricular end-diastolic volume index (LVEDVI), LV end-systolic volume index (LVESVI), LV mass index (LVMI), and LV mean wall stress after 6- and 12-month treatment ( p <0.01 in all comparisons). Both groups had a significant increase in LV ejection fraction and exercise duration after 6- and 12-month treatment ( p < 0.01 in all comparisons). Using multivariate linear regression analysis, only losartan + l -arginine therapy achieved a significantly lower LVESVI (38.89 ± 0.23 mL/m 2 ), LVEDVI (102.3 ± 0.3 mL/m 2 ), LVMI (107.6 ± 0.3 g/m 2 ), SBP (123.5 ± 1.0 mm Hg), and greater exercise duration (7.38 ± 0.02 minutes) than those of the losartan-only treated groups ( p <0.01 in all comparisons). These findings suggest that early co-administrative strategy provides a beneficial approach to favorably influence the natural history of CAR"
  • l-Arginine Alleviates Hydrogen Peroxide-Induced Oxidative Damage in Ovine Intestinal Epithelial Cells by Regulating Apoptosis, Mitochondrial Function, and Autophagy - J Nutr 2021 Mar 9 - "Previous studies demonstrated that dietary l-arginine (Arg) alters the equilibrium between reactive oxygen species (ROS) generation and biological defenses to resist oxidant-induced toxicity. Whether supplying Arg can protect ovine intestinal epithelial cells (OIECs) from hydrogen peroxide (H2O2)-induced oxidative damage is unclear ... Supply of Arg protects OIECs against H2O2-induced damage partly by improving mitochondrial function and alleviating cellular apoptosis and autophagy"
  • Long lasting protective effects of early l-arginine treatment on endothelium in an in vitro study - Clin Nutr 2021 Mar 3 - "Excess nutrient supply, such as high fat and high glucose intake, promotes oxidative stress and advanced glycation end products accumulation. Oxidative stress and AGE accumulation cause pathological elevation of arginase activity and pro-inflammatory signaling implicated in endothelial dysfunction. Several studies showed positive effects of l-arginine supplementation in endothelial function but little is currently known about the role of l-arginine as prevention of endothelial dysfunction caused by excessive nutrient supply (overfeeding). Our aim was to evaluate a possible protective effect of l-arginine on endothelial dysfunction caused by excessive nutrient supply (overfeeding), using human endothelial cells line in an in vitro study ... Endothelial EA.hy926 cells were pre-treated with 1.72 mM of l-arginine for 24 h and afterwards subjected to nutritional stress (high lipid, high insulin and high glucose concentrations) for further 24 h ... l-arginine pretreatment reduces AGEs generation ... An early l-arginine treatment is able to prevent oxidative stress and AGEs accumulation caused by overfeeding in human endothelial cell line by regulating STAB1/RAGE gene expression and by reducing excess arginase activity. The positive effects of l-arginine pretreatment continue even after treatment discontinuation in normal conditions"
  • Effects of Arginine Supplementation on Athletic Performance Based on Energy Metabolism: A Systematic Review and Meta-Analysis - Nutrients. 2020 May 2 - "Results revealed that Arg supplementation could improve aerobic (SMD, 0.84; 95% CI, 0.12 to 1.56; magnitude of SMD (MSMD), large; I2, 89%; p = 0.02) and anaerobic (SMD, 0.24; 95% CI, 0.05 to 0.43; MSMD, small; I2, 0%; p = 0.01) performance tests. In conclusion, acute Arg supplementation protocols to improve aerobic and anaerobic performance should be adjusted to 0.15 g/kg of body weight ingested between 60-90 min before. Moreover, chronic Arg supplementation should include 1.5-2 g/day for 4-7 weeks in order to improve aerobic performance, and 10-12 g/day for 8 weeks to enhance anaerobic performance"
  • Arginine therapy in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes - Curr Opin Clin Nutr Metab Care. 2019 Nov 5 - "We would like to inform clinicians that the systematic administration of oral and intravenous L-arginine is therapeutically beneficial and clinically useful for patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), when they maintain plasma arginine concentration at least 168 μmol/l ... L-arginine is known to be an important precursor of NO to normalize the endothelial function in MELAS. In our clinical trial followed by 7 years follow-up study, the systematic administration of L-arginine to patients with MELAS significantly improved the survival curve of patients compared with natural history. Maintaining plasma arginine concentration at least 168 μmol/l may prevent the ictuses through the putative pathophysiologic mechanism and optimal normalization of endothelial dysfunction"
  • l-Citrulline Supplementation: Impact on Cardiometabolic Health - Nutrients. 2018 Jul 19;10(7) - "Diminished bioavailability of nitric oxide (NO), the gaseous signaling molecule involved in the regulation of numerous vital biological functions, contributes to the development and progression of multiple age- and lifestyle-related diseases. While l-arginine is the precursor for the synthesis of NO by endothelial-nitric oxide synthase (eNOS), oral l-arginine supplementation is largely ineffective at increasing NO synthesis and/or bioavailability for a variety of reasons. l-citrulline, found in high concentrations in watermelon, is a neutral alpha-amino acid formed by enzymes in the mitochondria that also serves as a substrate for recycling l-arginine. Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis. Supplementation with l-citrulline has shown promise as a blood pressure lowering intervention (both resting and stress-induced) in adults with pre-/hypertension, with pre-clinical (animal) evidence for atherogenic-endothelial protection. Preliminary evidence is also available for l-citrulline-induced benefits to muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/older populations" - See l-citrulline at Amazon.com.
  • L-Arginine and B vitamins improve endothelial function in subjects with mild to moderate blood pressure elevation - Eur J Nutr. 2016 Nov 5 - "unique combination of L-arginine with the vitamins B6, folic acid and B12 ... Subjects aged 40-65 years with mild to moderate blood pressure (BP) elevation not treated with anti-hypertensive drugs were randomly assigned to either the dietetic product (n = 40) or a matching placebo (n = 41) for 3 months with open follow-up for a further 3 months ... his trial confirmed the effective and safe use of dietary management with L-arginine in combination with B vitamins. The primary efficacy analysis demonstrated a statistically significant superiority of the combination of L-arginine with B vitamins over placebo in improving and restoring impaired endothelial function and lowering BP in patients with mild to moderate blood pressure elevation" - [Nutra USA]
  • Supplemental Citrulline Is More Efficient than Arginine in Increasing Systemic Arginine Availability in Mice - J Nutr. 2017 Feb 8 - "Arginine is considered to be an essential amino acid in various (patho)physiologic conditions of high demand. However, dietary arginine supplementation suffers from various drawbacks, including extensive first-pass extraction. Citrulline supplementation may be a better alternative than arginine, because its only fate in vivo is conversion into arginine ... Citrulline supplementation is more efficient at increasing arginine availability than is arginine supplementation itself in mice" - See BulkSupplements Pure L-Citrulline DL-Malate 2:1 Powder at Amazon.com and BulkSupplements Pure L-Arginine HCL Powder at Amazon.com.
  • The effect of l-arginine supplementation on body composition and performance in male athletes: a double-blinded randomized clinical trial - Eur J Clin Nutr. 2017 Jan 25 - "Athletes received daily either 2 g per day l-arginine supplement or the same amount of placebo (maltodextrin) for 45 days ... Sport performance (VO2 max) significantly increased in l-arginine supplementation group (4.12±6.07) compared with placebo group (1.23±3.36) (P=0.03). This increase remained significant even after adjustment of baseline values, physical activity and usual dietary intake of subjects throughout the study. No significant effect of l-arginine supplementation was found on weight, BMI, BFM and LBM"
  • The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males - Biosci Biotechnol Biochem. 2017 Feb;81(2):372-375 - "Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined" - [Nutra USA] - See BulkSupplements Pure L-Arginine HCL Powder at Amazon.com and BulkSupplements Pure L-Citrulline Powder at Amazon.com.
  • Randomized Prospective Double-Blind Studies to Evaluate the Cognitive Effects of Inositol-Stabilized Arginine Silicate in Healthy Physically Active Adults - Nutrients. 2016 Nov 18;8(11) - "Inositol-stabilized arginine silicate (ASI; Nitrosigine®) has been validated to increase levels of arginine, silicon and nitric oxide production. To evaluate potential enhancement of mental focus and clarity, ASI (1500 mg/day) was tested in two double-blind placebo-controlled crossover (DBPC-X) studies using the Trail Making Test (TMT, Parts A and B) ... These findings show that ASI significantly improved the ability to perform complex cognitive tests requiring mental flexibility, processing speed and executive functioning" - See Nitrosigine® at Amazon.com.
  • Oral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover study - Journal of the International Society of Sports Nutrition 201613:6 - "L-Citrulline supplementation significantly increased plasma L-arginine levels and reduced completion time by 1.5 % (p < 0.05) compared with placebo. Moreover, L-citrulline significantly improved subjective feelings of muscle fatigue and concentration immediately after exercise" - [Nutra USA]
  • L-Arginine promotes gut hormone release and reduces food intake in rodents - Diabetes Obes Metab. 2016 Feb 11 - "L-Arg reduced food intake and stimulated gut hormone release in rodents" - See L-arginine products at Amazon.com.
  • Arginine behaviour after arginine or citrulline administration in older subjects - Br J Nutr. 2015 Dec 1:1-6 - "Arginine (ARG) and its precursor citrulline (CIT) are popular dietary supplements, especially for the elderly. However, age-related reductions in lean body mass and alterations in organ functions could change their bioavailability ... In conclusion, a single CIT administration in the elderly is safe and well tolerated, and CIT proves to be a better in vivo ARG precursor than ARG itself in healthy elderly subjects" - See citrulline at Amazon.com.
  • The Role of CD36 in the Effect of Arginine in Atherosclerotic Rats - Med Sci Monit. 2015 May 24 - "The addition of arginine has a significant effect on reducing rat atherosclerosis development, which may be attributed to both the down-regulation of CD36 expression in rat aortic endothelial and blood mononuclear cells and the NO pathway"
  • l-Citrulline, But Not l-Arginine, Prevents Diabetes Mellitus-Induced Glomerular Hyperfiltration and Proteinuria in Rat - Hypertension. 2014 May 27 - "l-citrulline administered to diabetic rats increases plasma l-arginine concentration, which prevents the diabetes mellitus-induced glomerular hyperfiltration, filtration fraction, and proteinuria, possibly by a vascular effect" - See l-citrulline at Amazon.com.
  • Efficacy of arginine-enriched enteral formulas in the reduction of surgical complications in head and neck cancer: A systematic review and meta-analysis - Clin Nutr. 2014 May 4 - "Arginine improves healing and modulates inflammation and the immune response. A systematic review and meta-analysis were conducted to assess whether arginine-enriched enteral formulas reduce complications (fistulas, wound infections, other infections) and hospital length of stay (LoS) in patients undergoing surgery for head and neck cancer ... The administration of arginine-enriched enteral nutrition led to a significant reduction in fistulas and hospital stay in patients undergoing surgery for head and neck cancer"
  • L-Arginine Supplementation Prevents Increases in Intestinal Permeability and Bacterial Translocation in Male Swiss Mice Subjected to Physical Exercise under Environmental Heat Stress - J Nutr. 2013 Nov 20 - "core body temperature (Tcore) ... Our results indicate that dietary l-arginine supplementation preserves the integrity of the intestinal epithelium during exercise under heat stress, acting through mechanisms that are independent of Tcore regulation"
  • Effects of watermelon supplementation on arterial stiffness and wave reflection amplitude in postmenopausal women - Menopause. 2013 May;20(5):573-7 - "In a randomized cross-over study, 12 postmenopausal women (mean [SE] age, 57 [1] y; mean [SE] body mass index, 38.1 [2.1] kg/m; mean [SE] SBP, 153 [4] mm Hg) were assigned to watermelon supplementation (L-citrulline/L-arginine 6 g/d) or placebo supplementation for 6 weeks ... baPWV (-1.2 [0.3] m/s, P < 0.001), aortic SBP (-10 [3] mm Hg, P < 0.01), and aortic diastolic blood pressure (-7 [1] mm Hg, P < 0.001) decreased after watermelon supplementation compared with placebo ... Watermelon supplementation reduces arterial stiffness and aortic SBP by reducing pressure wave reflection amplitude in obese postmenopausal women with hypertension" - Note:  A -10 on the systolic is about what you'd get with prescription medications. - See Stimulin at Amazon.com (1,875 mg of L-citrulline) and L-arginine products at Amazon.com.
  • Regulation of brown adipose tissue development and white fat reduction by L-arginine - Curr Opin Clin Nutr Metab Care. 2012 Nov;15(6):529-38 - "Brown adipose tissue (BAT), which is present in humans, plays an important role in oxidation of fatty acids and glucose ... L-arginine increases mammalian BAT growth and development via mechanisms involving gene expression, nitric oxide signaling, and protein synthesis. This enhances the oxidation of energy substrates and, thus, reduces white fat accretion in the body. L-arginine holds great promise in preventing and treating obesity in humans"
  • L-Arginine enhances glucose and lipid metabolism in rat L6 myotubes via the NO/ c-GMP pathway - Metabolism. 2012 Aug 10 - "The amino acid Arginine (Arg) is the main biological precursor of nitric oxide (NO) and has been described to improve insulin sensitivity in diabetes and obesity. We investigated the molecular mechanisms involved in the long-term effects of Arg on glucose and lipid metabolism ... We provide evidence that Arg improves glucose and lipid metabolism in skeletal muscle, in parallel with increased phosphorylation of Akt and AMPK-α. These effects were mediated by the NO/c-GMP pathway. Thus, arginine treatment enhances signal transduction and has a beneficial effect of metabolism in skeletal muscle through direct activation of Akt and AMPK pathways"
  • Orally administered L-arginine and glycine are highly effective against acid reflux esophagitis in rats - Med Sci Monit. 2011 Dec 22;18(1):BR9-15 - "L-alanine and L-glutamine exert a deleterious effect on the esophagitis, while L-arginine and glycine are highly protective" - See L-arginine products at Amazon.com and L-glycine at Amazon.com.
  • Effect of oral l-arginine supplementation on blood pressure: A meta-analysis of randomized, double-blind, placebo-controlled trials - Am Heart J. 2011 Dec;162(6):959-65 - "We included 11 randomized, double-blind, placebo-controlled trials involving 387 participants with oral l-arginine intervention ranging from 4 to 24 g/d. Compared with placebo, l-arginine intervention significantly lowered systolic BP by 5.39 mm Hg (95% CI -8.54 to -2.25, P = .001) and diastolic BP by 2.66 mm Hg (95% CI -3.77 to -1.54, P < .001). Sensitivity analyses restricted to trials with a duration of 4 weeks or longer and to trials in which participants did not use antihypertensive medications yielded similar results. Meta-regression analysis suggested an inverse, though insignificant (P = .13), relation between baseline systolic BP and net change in systolic BP"
  • Propionyl-L-carnitine, L-arginine and niacin in sexual medicine: a nutraceutical approach for erectile dysfunction - Andrologia. 2011 Oct 4 - "In a group of 54 unselected men (35-75 years), consecutively presenting to our ED clinic and naive to other ED treatments, we carried out a single-blind, one-arm study to evaluate the effects of a 3-month supplementation with propionyl-L-carnitine, L-arginine and niacin on their sexual performance ... Analyses on GAQs revealed that treatment improved erections in 40% of cases, with a partial response occurring in up to 77% of enrolled subjects. These preliminary findings indicate that the favourable cardiovascular effects of nutraceuticals might also reflect on male sexual function with possible implication in the treatment and prevention of ED. This study documents a considerable patients' interest toward nutritional supplementation - as first-line or adjunctive treatment to PDE5 inhibitors - that goes beyond the measurable increment in penile rigidity" - See propionyl-l-carnitine products at Amazon.com, niacin at Amazon.com and L-arginine products at Amazon.com.
  • Clinical Assessment of a Supplement of Pycnogenol® and l-arginine in Japanese Patients with Mild to Moderate Erectile Dysfunction - Phytother Res. 2011 May 27 - "Subjects were instructed to take a supplement (Pycnogenol® 60 mg/day, l-arginine 690 mg/day and aspartic acid 552 mg/day) or an identical placebo for 8 weeks, and the results were assessed using the five-item erectile domain (IIEF-5) of the International Index of Erectile Function. Additionally, blood biochemistry, urinalysis and salivary testosterone were measured. Eight weeks of supplement intake improved the total score of the IIEF-5. In particular, a marked improvement was observed in 'hardness of erection' and 'satisfaction with sexual intercourse'. A decrease in blood pressure, aspartate transaminase and γ-glutamyl transpeptidase (γ-GTP), and a slight increase in salivary testosterone were observed in the supplement group. No adverse reactions were observed during the study period. In conclusion, Pycnogenol® in combination with l-arginine as a dietary supplement is effective and safe in Japanese patients with mild to moderate erectile dysfunction" - See Pycnogenol at Amazon.com, L-arginine products at Amazon.com and l-aspartic acid at Amazon.com.
  • Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction - Urology. 2011 Jan;77(1):119-22 - "L-arginine supplementation improves nitric oxide-mediated vasodilation and endothelial function; however, oral administration has been hampered by extensive presystemic metabolism. In contrast, L-citrulline escapes presystemic metabolism and is converted to L-arginine, thus setting the rationale for oral L-citrulline supplementation as a donor for the L-arginine/nitric oxide pathway of penile erection ... A total of 24 patients, mean age 56.5 +/- 9.8 years, were entered and concluded the study without adverse events. The improvement in the erection hardness score from 3 (mild ED) to 4 (normal erectile function) occurred in 2 (8.3%) of the 24 men when taking placebo and 12 (50%) of the 24 men when taking L-citrulline (P < .01). The mean number of intercourses per month increased from 1.37 +/- 0.93 at baseline to 1.53 +/- 1.00 at the end of the placebo phase (P = .57) and 2.3 +/- 1.37 at the end of the treatment phase (P < .01). All patients reporting an erection hardness score improvement from 3 to 4 reported being very satisfied" - See citrulline malate at Amazon.com.
  • Perioperative arginine-supplemented nutrition in malnourished patients with head and neck cancer improves long-term survival - Am J Clin Nutr. 2010 Sep 29 - "Plasma arginine concentrations are lower in patients with cancer, which indicates that arginine metabolism may be disturbed in these patients. Arginine supplementation has been associated with positive effects on antitumor mechanisms and has been shown to reduce tumor growth and to prolong survival. Furthermore, the prognosis of patients with head and neck cancer remains disappointing. Insufficient intake frequently leads to malnutrition, which contributes to high morbidity and mortality rates ... The group receiving arginine-enriched nutrition had a significantly better overall survival (P = 0.019) and better disease-specific survival (P = 0.022). Furthermore, the arginine-supplemented group had a significantly better locoregional recurrence-free survival (P = 0.027). No significant difference in the occurrence of distant metastases or occurrence of a second primary tumor was observed between the groups"
  • Effect of Long-Term L-Arginine Supplementation on Arterial Compliance and Metabolic Parameters in Patients with Multiple Cardiovascular risk Factors: Randomized, Placebo-Controlled Study - J Cardiovasc Pharmacol. 2010 Jun 7 - "large artery elasticity index (LAEI) ... Although large artery elasticity index (LAEI) did not differ significantly between the groups at baseline (10.64.3 vs.11.64.5 ml/mm HgX100, p=0.346), at the end of the study LAEI was significantly greater in patients treated with L-arginine than in the placebo group (12.73.4 vs. 8.02.8 ml/mm HgX10, p<0.0001). Systemic vascular resistance was significantly lower in patients treated with L-arginine than in the placebo group after 6 months. Small artery elasticity index (SAEI) did not differ significantly between the groups at baseline or at the end of the study. Serum aldosterone decreased significantly in Group 1 from 10.76.3 to 8.45.0 ng/ml (p=0.008), but did not change in the placebo group. CONCLUSION:: L-arginine supplementation improves LAEI in patients with multiple cardiovascular risk factors. This improvement was associated with a decrease in systolic blood pressure, peripheral vascular resistance as well as a decrease in aldosterone levels. The results suggest that long term L-arginine supplementation has beneficial vascular effects in pathologic disease states associated with endothelial dysfunction"
  • Pro-ulcer effects of resveratrol in mice with indomethacin-induced gastric ulcers are reversed by l-arginine - Br J Pharmacol. 2010 Jan 8 - "Although resveratrol is currently being evaluated in pre-clinical studies as a potential cancer chemopreventive agent and cardiovascular stress-releasing compound, treatment with resveratrol severely delays healing of pre-existing gastric ulcers. Resveratrol treatment can also induce endothelial NOS (eNOS) expression ... Resveratrol significantly aggravated damage from indomethacin-induced gastric ulcers, and delayed healing, as shown by increased DS and MPO activity. The mRNA for cyclooxygenase (COX)-1, but not that for COX-2, was inhibited by resveratrol treatment, with reduced synthesis of PGE(2) by gastric tissue. However, resveratrol treatment induced eNOS gene expression and shifted the eNOS/iNOS balance. l-Arginine given before resveratrol in mice with indomethacin-induced ulcers significantly increased tissue NO synthesis and improved ulcer healing" - See L-arginine products at Amazon.com.
  • Regulation of nitric oxide production in health and disease Curr Opin Clin Nutr Metab Care. 2009 Oct 16 - "The role of the cofactor tetrahydrobiopterin in nitric oxide production and its relation with arginine availability is indicated as an important explanation for the arginine paradox. This offers potential for nitric oxide regulation by dietary factors such as arginine or its precursors and vitamin C. Because diets with a high saturated fat content induce high plasma fatty acid levels, endothelial nitric oxide production is often impaired due to a reduction in nitric oxide synthase 3 phosphorylation. Increasing the arginine availability by arginine therapy or arginase inhibition was, therefore, proposed as a potential therapy to treat hypertension. Recent studies in septic patients and transgenic mice models found that inadequate de-novo arginine production from citrulline reduces nitric oxide production. Citrulline supplementation may, therefore, be a novel therapeutic approach in conditions of arginine deficiency" - See L-arginine products at Amazon.com and l-citrulline at Amazon.com.
  • Dietary Supplementation of L-Arginine and Conjugated Linoleic Acid Reduces Retroperitoneal Fat Mass and Increases Lean Body Mass in Rats - J Nutr. 2009 May 13 - "We conclude that CLA and arginine modulated adipose tissue metabolism by separate, but not additive, effects. Also, CLA and arginine may have depressed muscle protein turnover" - See conjugated linoleic acid at Amazon.com and l-arginine products at Amazon.com.
  • Dietary L-Arginine Supplementation Reduces White Fat Gain and Enhances Skeletal Muscle and Brown Fat Masses in Diet-Induced Obese Rats - J Nutr. 2008 Dec 23 - "l-arginine-HCl ... Despite similar energy intake, absolute weights of white fat pads increased by 98% in control rats over a 12-wk period but only by 35% in arginine-supplemented rats. The arginine treatment reduced the relative weights of white fat pads by 30% and enhanced those of soleus muscle by 13%, extensor digitorum longus muscle by 11%, and brown fat by 34% compared with control rats ... arginine treatment resulted in lower serum concentrations of leptin, glucose, triglycerides, urea, glutamine, and branched-chain amino acids, higher serum concentrations of nitric-oxide metabolites, and improvement in glucose tolerance. Thus, dietary arginine supplementation shifts nutrient partitioning to promote muscle over fat gain and may provide a useful treatment for improving the metabolic profile and reducing body white fat in diet-induced obese rats" - See arginine products at Amazon.com.
  • Addition of 2.5g l-arginine in a fatty meal prevents the lipemia-induced endothelial dysfunction in healthy volunteers - Atherosclerosis. 2008 Nov 6 - "2.5g l-arginine, but not phenyalanine or leucine, is able to prevent the lipemic dysfunction of the endothelium"
  • Kidney damage after renal ablation is worsened in endothelial nitric oxide synthase (-/-) mice and improved by combined administration of L-arginine and antioxidants - Nephrology (Carlton). 2008 Jun;13(3):218-27 - "A combination of L-arginine and antioxidant treatment ameliorated renal damage"
  • Long Term N-Acetylcysteine and L-Arginine Administration Reduces Endothelial Activation and Systolic Blood Pressure in Hypertensive Patients with Type 2 Diabetes Mellitus - Diabetes Care. 2008 Feb 11 - "The NAC+ARG administration seems to be a potential well-tolerated antiatherogenic therapy since it improves the endothelial function in hypertensive patients with type 2 diabetes by improving NO bioavailability via reduction of the oxidative stress and increase of NO production. Our study's results give prominence to its potential use in the primary and secondary cardiovascular prevention in these patients"
  • Pharmacokinetics of arginine and related amino acids - J Nutr. 2007 Jun;137(6):1646S-9S
  • Biomarkers of arginine and lysine excess - J Nutr. 2007 Jun;137(6):1662S-8S - "Arginine supplementation is used in several disease states. In arginine-deficient states, supplementation is a logical choice of therapy. However, the definition of an arginine-deficient state is complex. For example, plasma arginine levels could be within normal range but intracellular arginine levels could be reduced because of membrane transport problems. Lysine competes with arginine for transport into the cell. In these situations, arginine supplementation of higher than required levels is proposed. Arginine has several important functions in metabolism as it is a precursor of metabolically active components such as nitric oxide (NO), ornithine, creatine, and polyamines"
  • Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans - Biomed Res. 2007 Apr;28(2):85-90 - "the treatment with L-lysine and L-arginine decreased the basal levels of salivary cortisol and chromogranin-A (a salivary marker of the sympatho-adrenal system) in male subjects"
  • l-Arginine, the substrate for NO synthesis: An alternative treatment for premature atherosclerosis? - Int J Cardiol. 2006 Jul 20 - "l-arginine administration may be useful in patients with premature atherosclerosis"
  • Treatment with supplementary arginine, vitamin C and zinc in patients with pressure ulcers: A randomised controlled trial - Clin Nutr. 2005 Nov 14;24(6):979-987 - "In this small set of patients, supplementary arginine, vitamin C and zinc significantly improved the rate of pressure ulcer healing"
  • Effects of vitamin C on intracoronary L-arginine dependent coronary vasodilatation in patients with stable angina - Heart. 2005 Oct;91(10):1319-23 - "L-arginine dependent coronary segment vasodilatation was augmented by the antioxidant vitamin C in patients with coronary artery disease. Thus, vitamin C may have beneficial effects on nitric oxide bioavailability induced by L-arginine"