- L-Citrulline is well tolerated and no related side-effects have been observed
- L-Citrulline is easily taken up by the gut
- L-Citrulline increases blood levels of citrulline, arginine and ornithine in the systemic circulation
- L-citrulline is a non-essential amino acid as it can be manufactured in the body from intestinal glutamine stores in enterocytes. Supplementing with citrulline has a sparing effect on glutamine stores.
- Very little oral L-Citrulline is lost in urine as citrulline (less than 1%) and the remaining 99% is either reabsorbed into systemic circulation or converted to arginine.
- Very little urea, nitrates or nitrites or citrulline is lost in urine after oral doses of citrulline, this suggests increased utilization of arginine in protein synthesis.
- The increased nitrogen balance that occurs after oral citrulline is an indicator of increased whole body protein synthesis. Therefore, citrulline itself may have a protein anabolic effect by enhancing nitrogen balance and inducing muscle protein synthesis.
- Citrulline converts to Arginine in a biochemical process involving Aspartic Acid
- L-Citrulline increases L-arginine in the systemic circulation twice as effectively as supplementing with arginine itself.
- 83% of circulating citrulline is taken up by the kidneys and converted to arginine. [i]This accounts for 60% of de novo arginine synthesis. The available arginine is then used for conversion to NO for vasodilation, production of urea and incorporation into protein synthesis for muscle regeneration and repair.[ii][iii][iv]
- “L-Citrulline supplementation has been proved to be safe and psychologically well accepted by patients. Its role as an alternative treatment for mild to moderate erectile dysfunction, improves hardness and quality of erection as a vasodilator.”[v]
- L-Citrulline reduces ammonia and lactate[vi]
- L-arginine is converted to nitric oxide by nitric oxide synthase and L-citrulline is regenerated as a by-product and recycled.
- Citrulline malate lead to a 23% enhancement of specific force production, 52.92% more repetitions. A significant decrease of 40% in muscle soreness at 24 hours and 48 hours.
- Citrulline-malate ingestion significantly increases the plasma concentration of citrulline, arginine, and ornithine. Growth hormone also increases after exercise with citrulline-malate supplementation. [vii][viii][ix][x][xi][xii][xiii][xiv][xv][xvi][xvii][xviii][xix][xx][xxi]
- Creatine is not the same thing as creatinine that is on your blood tests.
- Creatinine is waste.
- The kidneys eliminate creatinine
- About 2% of muscle creatine is lost with normal water loss every day.
- More muscle mass = more creatinine production
- Supplementation, exercise, and dietary creatine from meatwill increase creatinine levels
- Kidney disease, drugs, and salicylates / salicylic acid can reduce creatinine clearance
- Creatine monohydrate is the most studied and predictable form of creatine.[xxii]
- Lower levels of creatine in females, children, wasting diseases, starvation, and corticosteroid use
- Creatine supplementation reduces muscle damage[xxiii]
- Interesting paper on creatine loading and maintenance doses[xxiv]
- Not as scientifically proven as testosterone booster as once thought. [xxv]
- D-Aspartic acid (DAA) is an excitatory neurotransmitter / nerve irritant that triggers nerve conduction to activate cells. The function of the cell exposed to DAA will determine its effects. When certain parts of testicles are activated by DAA they make testosterone. But in ovaries DAA makes estrogen, in fat cells DAA makes estrogen as it activates aromatase to convert testosterone to estrogen. Basically how it will work in you is unpredictable. Your body composition and gender will have a massive influence on what hormone or neurotransmitter it will activate. If you are female or male with above 10% body fat than it will most likely increase estrogen more than testosterone. [xxvi][xxvii][xxviii]
- DAA blocks melatonin synthesis in pineal gland and increases prolactin[xxix]
- In 2013; 3 grams of in trained men DAA didn’t show any improvements for body composition, hormones, strength after 28 days[xxx]
- In 2015; 3 and 6 grams was studied and the 6 gram dose was even worse and significantly dropped testosterone levels and free testosterone!
The link to the podcast relating to this post can be found here: (or search for us on itunes – ATP Project)
[i] Marcel CG van de Poll et al. Renal metabolism of amino acids: its role in interorgan amino acidexchange. Am J Clin Nutr 2004;79:185–97.
[ii] Francesco Saverio Dioguardi. “To Give or Not to Give? Lessons from the Arginine Paradox”. J Nutrigenet Nutrigenomics 2011;4:90–98
[iii] Castillo L, et al. Splanchnic metabolism of dietary arginine in relation to nitric oxide synthesis in normal adult man. Proc Natl Acad Sci USA 1993; 90: 193–7.
[iv] Walker HA,McGing E, Fisher I, Böger RH, Bode-Böger SM, Jackson G, Ritter JM, Chowienczyk PJ.
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. J Am Coll Cardiol 2001; 38: 499–505
[v] Cormio L,et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. 2011 Jan;77(1):119-22.
[vi] Wilkinson DJ, Smeeton NJ, Watt PW. Ammonia metabolism, the brain and fatigue; revisiting the link. Prog Neurobiol. 2010 Jul;91(3):200-19. Epub 2010 Feb 4.
[vii] Edzard Schwedhelm, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and
L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol / 65:1 / 51–59 / 51
[viii] Urschel KL, Shoveller AK, Uwiera RR, Pencharz PB, Ball RO. Citrulline is an effective arginine precursor in enterally fed neonatal piglets. J Nutr 2006; 136: 1806–13.
[ix] Kuhn KP, Harris PA, Cunningham GR, Robbins IM, Lawson WE, Summar ML, Christman BW. Oral citrulline effectively elevates plasma arginine levels for 24 hours in normal volunteers. Circulation 2002; 106: II1–766S.
[x] Romero MJ, Platt DH, Caldwell RB, Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev 2006; 24: 275–90
[xi] Thibault R et al. Oral citrulline does not affect whole body protein metabolism in healthy human volunteers: Results of a prospective, randomized, double-blind, cross-over study. ,Clin Nutr. 2011 Jul 4. [Epub ahead of print]
[xii] Sureda A, et al. L-citrulline-malate influence over branched chain amino acid utilization during exercise.
Eur J Appl Physiol. 2010 Sep;110(2):341-51. Epub 2010 May 25.
[xiii] Sureda A,et al. Effects of L-citrulline oral supplementation on polymorphonuclear neutrophils oxidative burst and nitric oxide production after exercise. Free Radic Res. 2009 Sep;43(9):828-35. Epub 2009 Jul 6.
[xiv] Giannesini B, et al. Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle.
Eur J Pharmacol. 2011 Jun 6. [Epub ahead of print]
[xv] Giannesini B, et al. Beneficial effects of citrulline malate on skeletal muscle function in endotoxemic rat.
Eur J Pharmacol. 2009 Jan 5;602(1):143-7. Epub 2008 Nov 17.
[xvi] Romero MJ, et al. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):275-90.
[xvii] Giannesini B, Le Fur Y, Cozzone PJ, Verleye M, Le Guern ME, Bendahan D. Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle. Eur J Pharmacol. 2011 Jun 6. [Epub ahead of print]
[xviii] Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. 2010 May;24(5):1215-22.
[xix] Giannesini B, Le Fur Y, Cozzone PJ, Verleye M, Le Guern ME, Bendahan D. Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle. Eur J Pharmacol. 2011 Sep 30;667(1-3):100-4. Epub 2011 Jun 6.
[xx] Carole Rouge´,1 Clotilde Des Robert,1,2,4 Alexander Robins,1 Olivier Le Bacquer,1 Christelle Volteau,5
Marie-France De La Cochetie`re,3 and Dominique Darmaun1,4 Manipulation of citrulline availability in humans, Am J Physiol Gastrointest Liver Physiol 293: G1061–G1067, 2007.
[xxi] C. Moinard et al. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. British Journal of Nutrition (2008), 99, 855–862
[xxii] Jager R, et al. Analysis of the efficacy, safety, and regulatory status of novel forms of Creatine. Amino Acids (2011) 40:1369-1383
[xxiii] Jooyong K, et al. Role of Creatine supplementation in exercise induced muscle damage. A mini review. Journal of exercise rehabilitation 2015;11(5):244-250
[xxiv] Robinson T, et al. Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic renal function. Br J Sp[orts Med 2000;34;284-288
[xxv] Topo E, Soricelli A, D’Aniello A, Ronsini S, D’Aniello G.
The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats. Reprod Biol Endocrinol. 2009 Oct 27;7:120
[xxvi] Willoughby DS1, Leutholtz B. D-aspartic acid supplementation combined with 28 days of heavy resistance training has no effect on body composition, muscle strength, and serum hormones associated with the hypothalamo-pituitary-gonadal axis in resistance-trained men. Nutr Res. 2013 Oct;33(10):803-10. doi: 10.1016/j.nutres.2013.07.010. Epub 2013 Aug 15.
[xxvii] Burrone L1, Santillo A, Pinelli C, Baccari GC, Di Fiore MM. Induced synthesis of P450 aromatase and 17β-estradiol by D-aspartate in frog brain. J Exp Biol. 2012 Oct 15;215(Pt 20):3559-65. Epub 2012 Jul 5.
[xxviii] Amino Acids. 2007 Jan;32(1):45-51. Epub 2006 Jun 1. Involvement of D-Asp in P450 aromatase activity and estrogen receptors in boar testis. Lamanna C1, Assisi L, Botte V, Di Fiore MM.
[xxix] Di Fiore MM, et al. Current knowledge of D-Aspartate in glandular tissues. Amino Acids 2014 Aug; 46(8):1805-18
[xxx] Willoghby DS, et al. D-Aspartic acid supplementation combined with 28 days of heavy resistance training has no effect on body composition, muscle strength, and serum hormones associated with the hypothalamo-pituitary-gonadal axis in resistance-trained men. Nutr Res. 2013 Oct; 33 (10):803-10