Bottom Line: Arginine has not been shown to treat cancer in humans.
Arginine is an amino acid that is produced by the body. It has been used for various conditions such as high blood pressure, heart conditions, migraine headaches and erectile dysfunction. Arginine has also been shown in clinical studies to enhance wound healing, immune function and athletic performance.
Angina There is scientific evidence that supports the benefit of arginine for angina. These effects are due to its vasodilatory properties.
Atherosclerosis (Hardening of blood vessel walls) A few studies have shown that arginine may be effective for atherosclerosis
Wound healing This use is supported by evidence from clinical trials
Immune stimulation Arginine given in high doses may increase immune function in breast cancer patients
Erectile dysfunction Arginine has been shown in clinical trials to help improve sexual function in men
Migraine headache When taken with ibuprofen, arginine increased pain relief in patients with migraine headaches
Type 2 Diabetes Along with a low calorie diet and exercise, arginine may increase weight loss and improve insulin response in type 2 diabetic patients.
High Blood Pressure In this study, 13 patients with hypertension and angina were given 2 grams of oral Arginine for 4 weeks. This was in addition to medication for hypertension and angina. Researchers observed a decrease in hypertension and angina attacks. Patients also reported improved quality of life.
Immune suppression Thirty-six patients with colorectal cancer scheduled for surgery were divided into two groups. Each group received 750ml/day of arginine, omega-3 fatty acids and ribonucleic acid orally for 5 days. Blood test results showed that patients who received the oral supplements maintained the immune system cell count compared to those in the control group.
If you are taking medicine for high blood pressure, heart conditions, or erectile dysfunction (arginine may have additive blood pressure lowering effects.)
Arginine is an amino acid that is synthesized in the body. Oral arginine has been used for various conditions such as hypertension, angina, atherosclerosis, migraine headache, and erectile dysfunction. Its vasodilatory properties are thought to be responsible for the beneficial effects. Arginine has also been used to enhance wound healing, immune function, and athletic performance. Arginine supplementation has been studied in cancer patients. Postoperative enteral formulas enhanced with arginine may improve wound healing in gastric cancer patients undergoing gastrectomy (1). In head and neck cancer patients, arginine-enhanced formulas may improve fistula rates and immunity, thus reducing infection and length of stay postoperatively (2)(3). In addition, arginine supplementation by enteral feeding may decrease shock in severely burned patients (4), and high-dose arginine supplementation may increase natural killer (NK) cell activity and lymphokine-activated killer (LAK) cell activity in patients with breast cancer (5)(6). Arginine may also help to reduce nephrotoxicity caused by cyclosporine (7)(8). However, one study demonstrated that arginine may stimulate breast tumor growth in vivo (9).
Some studies support potential uses of arginine in coronary artery and peripheral artery diseases (PADs) (10)(11)(12)(13); however, long term supplementation of arginine may actually worsen PAD (14). Furthermore, arginine supplementation does not benefit the blood pressure and kidney function in women with preeclampsia (15). Large doses of oral arginine improved subjective assessment of sexual function in men with organic erectile dysfunction (16). Arginine added to ibuprofen may increase pain relief in patients with migraine headaches (17). In addition, oral arginine has been studied for its effect on modifying or preventing the development of nitrate tolerance during continuous transdermal nitroglycerin therapy (18). Arginine has been shown to enhance growth hormone release by inhibition of endogenous somatostatin (19). No significant adverse effects have been reported in clinical studies lasting up to 3 months (5)(20)(21).
Arginine is unique among amino acids for its vasodilatory properties (11). Arginine acts as a precursor for the synthesis of endogenous nitric oxide (NO) via the action of nitric oxide synthase (NOS). Nitric oxide's functions as a paracrine-signaling molecule mediating vasodilation and inhibition of platelet activation, monocyte and leucocyte adhesion, and smooth muscle cell proliferation. Nitric oxide also helps to control vascular oxidative stress and redox-regulated gene expression (22). Arginine is also needed for the synthesis of creatine which is important in muscle contraction (22). In colorectal adenoma cells, arginine reduces the expression of survivin, an inhibitor of apoptosis, and induces iNOS expression (23).
Absorption Dietary arginine amounts to approximately 2-6g/day depending on protein intake levels (21). The kidney is the main organ for endogenous arginine synthesis from L-ornithine and L-citrulline precursors. The liver also synthesizes arginine, but it is reutilized in the urea cycle and therefore contributes little to plasma arginine fluctuations (22). After ingestion, a small amount of arginine is metabolized by the liver and the enterocytes (24). The enzyme arginase converts arginine to ornithine, with 50% of orally ingested arginine undergoing this route. Distribution Data on the pharmacokinetics of oral arginine in humans is limited. Animal studies found the highest tissue concentrations in the heart, skin, liver, small intestine and stomach (22). Metabolism/Excretion Half of orally ingested arginine are converted to ornithine by the enzyme arginase. Normally, most Arginine is reabsorbed in the kidneys.
Large doses of arginine can increase urinary excretion of lysine (21).
Due to arginines vasodilatory properties, theoretically it may have additive hypotensive effects with drugs such as antihypertensives, sildenafil and nitrates (11)(20).
Wilson AM, et al. L-arginine supplementation in peripheral arterial disease: no benefit and possible harm. Circulation. Jul 10 2007;116(2):188-195. Because arginine supplementation provides short-term benefits to patients with peripheral artery disease (PAD), the objective of the Nitric Oxide in Peripheral Arterial Insufficiency (NO-PAIN) study, a prospective, randomized, double-blind, placebo-controlled trial, was to assess its long-term benefits. After 6 months of arginine (3 g/day) or placebo, 133 participants with PAD were examined for claudication distance and NO availability. Reduced improvements in NO, flow-mediated vasodilation, and walking distance were detected in participants receiving arginine as compared to the placebo group. The discordance between previously reported short-term studies and this long-term study may be due to unknown counterregulatory mechanisms such as arginase induction.
Palloshi A, Fragasso G, Piatti P, et al. Effect of oral L-arginine on blood pressure and symptoms and endothelial function in patients with systemic hypertension, positive exercise tests, and normal coronary arteries. Am J Cardiol. 2004;93(7):933-935. Thirteen patients with grade 2 to 3 hypertension, microvascular angina and positive exercise tests received 2 grams of oral Arginine for 4 weeks. The patients were on full antihypertensive and antianginal therapy aimed at optimal control of blood pressure. Compared with baseline measurements, Arginine supplementation significantly decreased mean systolic blood pressure at rest (166 +/- 27 to 146 +/- 12 mm Hg; p<0.005). The frequency of angina attacks decreased from 12 +/- 3 to 4 +/- 1 per week, and nitroglycerin use decreased from 9 +/ 2 to 3 +/- 1 per week. The patients self-rated overall quality of life increased. (p values < 0.001) The authors suggest that Arginine may represent a useful therapeutic option for hypertension and microvascular angina, However, this study is based on a small sample size. Large well-designed clinical trials are needed to confirm this effect.
Huynh NT, Tayek JA. Oral arginine reduces systemic blood pressure in type 2 diabetes: its potential role in nitric oxide generation. J Am Coll Nutr. 2002;21(5):422-427. Six patients with stable weight, 5 year histories of diabetes, and mild hypertension were admitted to a clinical research center for three days and put on a low-sodium diet. Hypertension and diabetic medications were stopped on the evening prior to admission. Patient were randomized to receive oral arginine the second or third day of the study. No placebo was used on the non-treatment day. Each patient received 3 grams of arginine every hour for 10 hours. Systolic blood pressure was reduced from 135 +/- 7 to 123 +/- 8mmHg; p < 0.05. Diastolic blood pressure was reduced from 86.9 +/- 1.7 to 80.7 +/- 2.4 mmHg; p < 0.05. Blood pressure reductions occurred 2 hours after oral arginine administration and returned to normal within one hour of stopping administration, which may be due to the effect of acute hyperglycemia on reduced nitric oxide generation and impaired coronary artery dilation in type 2 diabetes. Limitations of this study are the small sample size and lack of placebo.
Matsuda A, Takasaki H, Suzuki H, et al. Preoperative Oral Immune-Enhancing Nutritional Supplementation Corrects Th1/Th2 Imbalance in Patients Undergoing Elective Surgery for Colorectal Cancer. Dis Colon Rectum 2006 ;49(4):507-16. Thirty-six patients with colorectal cancer scheduled for surgery were randomly divided into two groups; 19 patients received preoperative 750ml/day oral supplementation containing arginine, omega-3 fatty acids and ribonucleic acid for five days. The control group did not receive oral supplementation pre or post-operatively. Peripheral blood samples were drawn on the morning of surgery and 3, 7 and 14 days postoperatively. Flow cytometry determined the proportions of CD4+ T cells producing intracellular cytokines. Th1/Th2 balance shifted to Th2 dominance in the control group. Th2 dominance is associated with immune suppression in the cancer bearing state preoperatively, and surgical stress postoperatively. The supplemented group maintained the preoperative levels of Th1/Th2 until day 14. Preoperative immunonutrition may correct the altered Th1/Th2 balance in the preoperative cancer-bearing state and postoperatively.
de Luis DA, Izaola O, Cuellar L, Terroba MC, Aller R. Randomized clinical trial with an enteral arginine-enhanced formula in early postsurgical head and neck cancer patients. Eur J Clin Nutr. Nov 2004;58(11):1505-1508. At surgery, 90 patients with oral and laryngeal cancer were randomly assigned to one of two groups. In the first group 45 patients received an enteral formula enriched with arginine and fiber. In the second group 45 patients received an isonitrogenous, isocaloric formula also containing fiber. Perioperatively and on day 14 post operatively various parameters were evaluated. There were no significant intergroup differences in respect to albumin, prealbumin, transferrin and lymphocytes. Gastrointestinal tolerance (diarrhea) was higher in the arginine enhanced group (40% Group I, 13% Group II: P<0.05) Postoperative infections were similar in both groups (4% Group I, 9% Group II: ns) Fistula occurred less in the arginine-enhanced group (5% Group I, 11% Group II: P<0.05) Wound infection was similar in both groups and not statistically significant. The postoperative length of stay was better in the arginine-enhanced group (25.8+/-15 days Group I, 35+/-24.6 Group II: P<0.05) Arginine enriched formulas may improve fistula rates and length of stay in head and neck cancer patients postoperatively.
