Inositol-Stabilized Arginine Silicate Reduces Exercise Induced Muscle Damage and Increases Perceived Energy Original Research

Main Article Content

Danielle Greenberg
Katie Emerson
Sarah Ojalvo Perez
Sarah Sylla
James Komorowski


Nitric Oxide, hyperemia, myoglobin, salivary nitrite


Introduction: Inositol-stabilized arginine silicate (ASI; Nitrosigine®) significantly increases circulating arginine and nitric oxide (NO).  We examined ASI effects on objective and subjective indicators of muscle recovery, blood flow and energy. 

Methods:  In a double-blind, placebo-controlled crossover-design, subjects (n=16) were given ASI (1,500 mg/day) or placebo for 4 days, with a 7-day washout period. Measurements occurred at baseline, 24, 48, and 72 h. On test days, subjects performed stress inducing leg extension exercises associated with muscle soreness. Following exercise, recovery markers creatine kinase (CK), myoglobin and lactate dehydrogenase (LDH), doppler ultrasound blood flow, leg circumference, salivary nitrite tests were measured. The Profile Mood States (POMS), VAS scales, vigor-activity cognitive tests were administered.    

Results: Serum CK but not LDH was significantly reduced in the ASI group on day 1 and 24, 48, and 72 h post-exercise (p<0.05); myoglobin was reduced on d1 and at 24 h post-exercise. No negative heart rate or blood pressure effects were observed. Reactive hyperemia indicated by leg circumference showed greater increases in the ASI group at 72 h (p<0.05).  No differences were found in salivary nitrite levels (p=0.265).  Perceived energy POMS responses increased in the ASI group compared to placebo (p=0.039) but no differences were found in subjective muscle recovery as determined by VASs.

Conclusions: ASI may be beneficial for fitness goals by increasing blood flow, and reducing muscle damage and perceived energy.

Abstract 65 | PDF Downloads 45


1. Kalman DS, Feldman S, Samson A, Krieger DR. A clinical evaluation to determine the safety, pharmacokinetics, and pharmacodynamics of an inositol-stabilized arginine silicate dietary supplement in healthy adult males. Clin Pharmacol. 2015;7:103-109.
2. Komorowski JR, Hewlings S. Chapter 59 - Inositol-Stabilized Arginine Silicate: A Novel Nitric Oxide-Boosting Ingredient for Sports Nutrition and Improved Cognition. In: Bagchi D, Nair S, Sen CK, eds. Nutrition and Enhanced Sports Performance (Second Edition). Academic Press; 2019:683-689.
3. Moncada S, Higgs A. The L-arginine-nitric oxide pathway. New England Journal of Medicine. 1993;329(27):2002-2012.
4. Proctor SD, Kelly SE, Vine DF, Russell JC. Metabolic effects of a novel silicate inositol complex of the nitric oxide precursor arginine in the obese insulin-resistant JCR:LA-cp rat. Metabolism: clinical and experimental. 2007;56(10):1318-1325.
5. Levine AB, Punihaole D, Levine TB. Characterization of the Role of Nitric Oxide and Its Clinical Applications. Cardiology. 2012;122(1):55-68.
6. Buffoli B, Foglio E, Borsani E, Exley C, Rezzani R, Rodella LF. Silicic acid in drinking water prevents age-related alterations in the endothelium-dependent vascular relaxation modulating eNOS and AQP1 expression in experimental mice: An immunohistochemical study. Acta Histochemica. 2013;115(5):418-424.
7. Jurkić LM, Cepanec I, Pavelić SK, Pavelić K. Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy. Nutrition & metabolism. 2013;10(1):2.
8. Martin KR. Silicon: The Health Benefits of a Metalloid. In: Sigel A, Sigel H, Sigel RKO, eds. Interrelations between Essential Metal Ions and Human Diseases. Dordrecht: Springer Netherlands; 2013:451-473.
9. Komorowski J, Perez Ojalvo S. A Pharmacokinetic Evaluation of the Duration of Effect of Inositol‐Stabilized Arginine Silicate and Arginine Hydrochloride in Healthy Adult Males. The FASEB journal. 2016;30:690.617.
10. Kalman DS, Feldman S, Samson A, Krieger DR. A clinical evaluation to determine the safety, pharmacokinetics, and pharmacodynamics of an inositol-stabilized arginine silicate dietary supplement in healthy adult males. Clinical pharmacology: advances and applications. 2015;7:103.
11. Babateen AM, Shannon OM, Mathers JC, Siervo M. Validity and reliability of test strips for the measurement of salivary nitrite concentration with and without the use of mouthwash in healthy adults. Nitric Oxide. 2019;91:15-22.
12. Kalman D. Comparison of cellular nitric oxide production from various sports nutrition ingredients: PG.16 p33. Journal of the International Society of Sports Nutrition. 2016;13(1):33.
13. Boucher JL, Moali C, Tenu JP. Nitric oxide biosynthesis, nitric oxide synthase inhibitors and arginase competition for L-arginine utilization. Cellular and Molecular Life Sciences. 1999;55(9):1015.
14. Böger RH, Bode-Böger SM. The clinical pharmacology of L-arginine. Annual review of pharmacology and toxicology. 2001;41(1):79-99.
15. Komorowski J, Perez Ojalvo S, Sylla S, Veledar E. Arginase inhibition by inositol-stabilized arginine silicate (ASI.; Nitrosigine®); a novel mechanism by which ASI enhances arginine bioavailability. Dietary Bioactive Components Curr Dev Nutr. 2018;2:49.
16. Proctor SD, Kelly SE, Russell JC. A novel complex of arginine–silicate improves micro- and macrovascular function and inhibits glomerular sclerosis in insulin-resistant JCR:LA-cp rats. Diabetologia. 2005;48(9):1925-1932.
17. Rogers JM, Gills J, Gray M. Acute effects of Nitrosigine® and citrulline malate on vasodilation in young adults. Journal of the International Society of Sports Nutrition. 2020;17(1).
18. Morris Jr SM. Arginine: beyond protein. The American journal of clinical nutrition. 2006;83(2):508S-512S.
19. Flynn NE, Meininger CJ, Haynes TE, Wu G. The metabolic basis of arginine nutrition and pharmacotherapy. Biomedicine & Pharmacotherapy. 2002;56(9):427-438.
20. Campbell BI, La Bounty PM, Roberts M. The ergogenic potential of arginine. Journal of the International Society of Sports Nutrition. 2004;1(2):1-4.
21. Napoli C, de Nigris F, Williams-Ignarro S, Pignalosa O, Sica V, Ignarro LJ. Nitric oxide and atherosclerosis: an update. Nitric oxide. 2006;15(4):265-279.
22. Dong J-Y, Qin L-Q, Zhang Z, et al. Effect of oral l-arginine supplementation on blood pressure: A meta-analysis of randomized, double-blind, placebo-controlled trials. American Heart Journal. 2011;162(6):959-965.
23. Wu G, Meininger CJ, Knabe DA, Baze FW, Rhoads MJ. Arginine nutrition in development, health and disease. Current Opinion in Clinical Nutrition & Metabolic Care. 2000;3(1):59-66.
24. Alvares TS, Meirelles CM, Bhambhani YN, Paschoalin VM, Gomes PS. L-Arginine as a potential ergogenic aid in healthy subjects. Sports Medicine. 2011;41(3):233-248.
25. Yavuz HU, Turnagol H, Demirel AH. Pre-exercise arginine supplementation increases time to exhaustion in elite male wrestlers. Biology of sport. 2014;31(3):187.
26. Bailey SJ, Winyard PG, Vanhatalo A, et al. Acute L-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise tolerance. Journal of applied physiology. 2010;109(5):1394-1403.
27. Buford. Glycine-arginine-ketoisocaproic acid improves performance of repeated cycling sprints. Medicine and science in sports and exercise. 2004;36.
28. Liu T-H, Wu C-L, Chiang C-W, Lo Y-W, Tseng H-F, Chang C-K. No effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletes. The Journal of nutritional biochemistry. 2009;20(6):462-468.
29. Yamada M, Huang Z, Dalkara T, et al. Endothelial Nitric Oxide Synthase-Dependent Cerebral Blood Flow Augmentation by L-Arginine After Chronic Statin Treatment. Journal of Cerebral Blood Flow & Metabolism. 2000;20(4):709-717.
30. Evans M, Zakaria N, Marzuk M, Perez Ojalvo S, Sylla S, Komorowski J. An evaluation of the effects of inositol-stabilized arginine silicate (ASI; Nitrosigine®) in preventing the decline in cognitive function caused by strenuous exercise. Journal of the International Society of Sports Nutrition. 2018;15:3.
31. Kalman D, Harvey PD, Perez Ojalvo S, Komorowski J. Randomized Prospective Double-Blind Studies to Evaluate the Cognitive Effects of Inositol-Stabilized Arginine Silicate in Healthy Physically Active Adults. Nutrients. 2016;8(11).
32. Lau WY, Muthalib M, Nosaka K. Visual Analog Scale and Pressure Pain Threshold for Delayed Onset Muscle Soreness Assessment. Journal of Musculoskeletal Pain. 2013;21(4):320-326.
33. Curran SL, Andrykowski MA, Studts JL. Short Form of the Profile of Mood States (POMS-SF): Psychometric information. Psychological Assessment. 1995;7(1):80-83.
34. Hoskins PR. Measurement of arterial blood flow by Doppler ultrasound. Clinical Physics and Physiological Measurement. 1990;11(1):1.
35. Hoeper MM, Oudiz RJ, Peacock A, et al. End points and clinical trial designs in pulmonary arterial hypertension: clinical and regulatory perspectives. Journal of the American College of Cardiology. 2004;43(12S):S48-S55.
36. Jobgen WS, Fried SK, Fu WJ, Meininger CJ, Wu G. Regulatory role for the arginine–nitric oxide pathway in metabolism of energy substrates. The Journal of nutritional biochemistry. 2006;17(9):571-588.
37. Centeno A, Fernández-Sanjurjo M, Revuelta C, Royuela L, Jimenez-Saiz S. L-Arginine as a Nutritional Supplement in Physical Exercise. Nutrition & Food Science International Journal. 2017;2(4).
38. Campbell B, Roberts M, Kerksick C, et al. Pharmacokinetics, safety, and effects on exercise performance of l-arginine α-ketoglutarate in trained adult men. Nutrition. 2006;22(9):872-881.
39. Wax B, Kavazis AN, Webb HE, Brown SP. Acute L-arginine alpha ketoglutarate supplementation fails to improve muscular performance in resistance trained and untrained men. Journal of the International Society of Sports Nutrition. 2012;9(1):1-6.
40. Greer BK, Jones BT. Acute arginine supplementation fails to improve muscle endurance or affect blood pressure responses to resistance training. The Journal of Strength & Conditioning Research. 2011;25(7):1789-1794.
41. Durante W, Johnson FK, Johnson RA. Arginase: a critical regulator of nitric oxide synthesis and vascular function. Clinical and experimental pharmacology & physiology. 2007;34(9):906.
42. Caldwell RB, Toque HA, Narayanan SP, Caldwell RW. Arginase: an old enzyme with new tricks. Trends in pharmacological sciences. 2015;36(6):395-405.
43. Sahin K, Orhan C, Tuzcu M, Hayirli A, Komorowski JR, Sahin N. Effects of dietary supplementation of arginine-silicate-inositol complex on absorption and metabolism of calcium of laying hens. PloS one. 2018;13(1):e0189329.
44. Evans RW, Fernstrom JD, Thompson J, Morris SM, Kuller LH. Biochemical responses of healthy subjects during dietary supplementation with L-arginine. The Journal of nutritional biochemistry. 2004;15(9):534-539.
45. Downes CP. Inositol phospholipids and neurotransmitter-receptor signalling mechanisms. Trends in Neurosciences. 1983;6:313-316.