Volume 15, Issue 1 (1-2017)                   IJRM 2017, 15(1): 1-10 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Roshanzamir F, Safavi S M. The putative effects of D-Aspartic acid on blood testosterone levels: A systematic review. IJRM. 2017; 15 (1) :1-10
URL: http://journals.ssu.ac.ir/ijrmnew/article-1-794-en.html
1- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
2- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran , safavimorteza@yahoo.com
Abstract:   (2216 Views)
Background: D-Aspartic acid (D-Asp) is in invertebrate and vertebrate neuroendocrine tissues, where it carries out important physiological functions. Recently, it has been reported that D-Asp is involved in the synthesis and release of testosterone and is assumed can be used as a testosterone booster for infertile men, and by athletes to increase muscle mass and strength.
Objective: The aim of this review is to summarize available evidence related to the effects of D-Asp on serum testosterone levels.
Materials and Methods: We conducted a systematic review of all type studies, which evaluated the effect of the D-Asp on blood testosterone including published papers until October 2015, using PubMed, ISI Web of Science, ProQuest and Scopus database.
Results: With 396 retrieved records, 23 animal studies and 4 human studies were included. In vivo and in vitro animal studies revealed the effect of D-Asp depending on species, sex and organ-specific. Our results showed that exogenous D-Asp enhances testosterone levels in male animal’s studies, whereas studies in human yielded inconsistent results. The evidence for this association in man is still sparse, mostly because of limited number and poor quality studies.
Conclusion: There is an urgent need for more and well-designed human clinical trials with larger sample sizes and longer duration to investigate putative effects of D-Asp on testosterone concentrations.
Full-Text [PDF 198 kb]   (301 Downloads) |   |   Full-Text (HTML)  (253 Views)  
Type of Study: Original Article |

1. D'Aniello A. D-Aspartic acid: an endogenous amino acid with an important neuroendocrine role. Brain Res Rev 2007; 53: 215-234. [DOI:10.1016/j.brainresrev.2006.08.005]
2. D'Aniello A, Giuditta A. Identification of D‐aspartic acid in the brain of Octopus vulgaris lam. J Neurochem 1977; 29: 1053-1057. [DOI:10.1111/j.1471-4159.1977.tb06508.x]
3. Okuma E, Fujita E, Amano H, Noda H, Abe H. Distribution of Free D-Amino Acids in the Tissues of Crustaceans. Fisher Sci 1995; 61: 157-160. [DOI:10.2331/fishsci.61.157]
4. Di Fiore M, Assisi L, Botte V, D'Aniello A. D-Aspartic acid is implicated in the control of testosterone production by the vertebrate gonad. Studies on the female green frog, Rana esculenta. J Endocrinol 1998; 157: 199-207. [DOI:10.1677/joe.0.1570199]
5. Raucci F, Assisi L, D'Aniello S, Spinelli P, Botte V, Di Fiore M. Testicular endocrine activity is upregulated by D-aspartic acid in the green frog, Rana esculenta. J Endocrinol 2004; 182: 365-376. [DOI:10.1677/joe.0.1820365]
6. Assisi L, Botte V, D'Aniello A, Di Fiore M. Enhancement of aromatase activity by D-aspartic acid in the ovary of the lizard Podarcis s. sicula. Reproduction 2001; 121: 803-808. [DOI:10.1530/rep.0.1210803]
7. Raucci F, D'Aniello S, Di Fiore M. Endocrine roles of D-aspartic acid in the testis of lizard Podarcis s. sicula. J Endocrinol 2005; 187: 347-359. [DOI:10.1677/joe.1.06115]
8. D'Aniello A, Di Fiore M, Fisher G. Occurrence of D-aspartic acid in animal tissues and its role in the nervous and endocrine systems. Trends Comp Biochem Physiol 1998; 4: 1-24.
9. Neidle A, Dunlop DS. Developmental changes in free D-aspartic acid in the chicken embryo and in the neonatal rat. Life Sci 1990; 46: 1517-1522. [DOI:10.1016/0024-3205(90)90424-P]
10. Dunlop DS, Neidle A, McHale D, Dunlop DM, Lajtha A. The presence of free D-aspartic acid in rodents and man. Biochem Biophys Res Com 1986; 141: 27-32. [DOI:10.1016/S0006-291X(86)80329-1]
11. Hashimoto A, Nishikawa T, Oka T, Hayashi T, Takahashi K. Widespread distribution of free D-aspartate in rat periphery. FEBS Lett 1993; 331: 4-8. [DOI:10.1016/0014-5793(93)80286-4]
12. Hashimoto A, Kumashiro S, Nishikawa T, Oka T, Takahashi K, Mito T, et al. Embryonic development and postnatal changes in free D‐aspartate and D‐serine in the human prefrontal cortex. J Neurochem 1993; 61: 348-351. [DOI:10.1111/j.1471-4159.1993.tb03575.x]
13. Fisher GH, D'Aniello A, Vetere A, Padula L, Cusano GP, Man EH. Free D-aspartate and D-alanine in normal and Alzheimer brain. Brain Res Bulletin 1991; 26: 983-985. [DOI:10.1016/0361-9230(91)90266-M]
14. D'Aniello A, Di Fiore MM, Fisher GH, Milone A, Seleni A, D'Aniello S, et al. Occurrence of D-aspartic acid and N-methyl-D-aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release. FASEB J 2000; 14: 699-714. [DOI:10.1096/fasebj.14.5.699]
15. Wang H, Wolosker H, Morris J, Pevsner J, Snyder S, Selkoe D. Naturally occurring free D-aspartate is a nuclear component of cells in the mammalian hypothalamo-neurohypophyseal system. Neuroscience 2002; 109: 1-4. [DOI:10.1016/S0306-4522(01)00545-0]
16. Topo E, Soricelli A, Di Maio A, D'Aniello E, Di Fiore MM, D'Aniello A. Evidence for the involvement of D-aspartic acid in learning and memory of rat. Amino Acids 2010; 38: 1561-1569. [DOI:10.1007/s00726-009-0369-x]
17. Spinelli P, Brown ER, Ferrandino G, Branno M, Montarolo PG, D'Aniello E, et al. D‐aspartic acid in the nervous system of Aplysia limacina: Possible role in neurotransmission. J Cell Physiol 2006; 206: 672-681. [DOI:10.1002/jcp.20513]
18. Sakai K, Homma H, Lee J-A, Fukushima T, Santa T, Tashiro K, et al. Emergence of D-aspartic acid in the differentiating neurons of the rat central nervous system. Brain Res 1998; 808: 65-71. [DOI:10.1016/S0006-8993(98)00599-X]
19. Hashimoto A, Oka T, Nishikawa T. Anatomical Distribution and Postnatal Changes in Endogenous Free D‐Aspartate and D‐Serine in Rat Brain and Periphery. Eur J Neurosci 1995; 7: 1657-1663. [DOI:10.1111/j.1460-9568.1995.tb00687.x]
20. Lee J-A, Homma H, Sakai K, Fukushima T, Santa T, Tashiro K, et al. Immunohistochemical localization of D-aspartate in the rat pineal gland. Biochem Biophys Res Com 1997; 231: 505-508. [DOI:10.1006/bbrc.1996.5902]
21. Lee J-A, Homma H, Tashiro K, Iwatsubo T, Imai K. D-Aspartate localization in the rat pituitary gland and retina. Brain Res 1999; 838: 193-199. [DOI:10.1016/S0006-8993(99)01718-7]
22. Sakai K, Homma H, Lee J-A, Fukushima T, Santa T, Tashiro K, et al. Localization ofd-Aspartic Acid in Elongate Spermatids in Rat Testis. Arch Biochem Biophys 1998; 351: 96-105. [DOI:10.1006/abbi.1997.0539]
23. D'Aniello G, Tolino A, D'aniello A, Errico F, Fisher GH, Di Fiore MM. The Role of d-Aspartic Acid and N-Methyl-d-Aspartic Acid in the Regulation of Prolactin Release 1. Endocrinology 2000; 141: 3862-3870. [DOI:10.1210/endo.141.10.7706]
24. Wang H, Wolosker H, Pevsner J, Snyder S, Selkoe D. Regulation of rat magnocellular neurosecretory system by D-aspartate: evidence for biological role (s) of a naturally occurring free D-amino acid in mammals. J Endocrinol 2000; 167: 247-252. [DOI:10.1677/joe.0.1670247]
25. D'Aniello A, Di Cosmo A, Di Cristo C, Annunziato L, Petrucelli L, Fisher G. Involvement of D-aspartic acid in the synthesis of testosterone in rat testes. Life Sci 1996; 59: 97-104. [DOI:10.1016/0024-3205(96)00266-4]
26. Ota N, Shi T, Sweedler JV. D-Aspartate acts as a signaling molecule in nervous and neuroendocrine systems. Amino Acids 2012; 43: 1873-1886. [DOI:10.1007/s00726-012-1364-1]
27. Matsuda S, Katane M, Maeda K, Kaneko Y, Saitoh Y, Miyamoto T, et al. Biosynthesis of d-aspartate in mammals: the rat and human homologs of mouse aspartate racemase are not responsible for the biosynthesis of d-aspartate. Amino Acids 2015; 47: 975-985. [DOI:10.1007/s00726-015-1926-0]
28. D'Aniello G, Ronsini S, Notari T, Grieco N, Infante V, D'Angel N, et al. d-Aspartate, a key element for the improvement of sperm quality. Adv Sex Med 2012; 2: 47-53. [DOI:10.4236/asm.2012.24008]
29. Furuchi T, Homma H. Free D-aspartate in mammals. Biol Pharma Bullet 2005; 28: 1566- 1570. [DOI:10.1248/bpb.28.1566]
30. Di Fiore MM, Santillo A, Baccari GC. Current knowledge of d-aspartate in glandular tissues. Amino Acids 2014; 46: 1805-1818. [DOI:10.1007/s00726-014-1759-2]
31. Burrone L, Raucci F, Di Fiore MM. Steroidogenic gene expression following D-aspartate treatment in frog testis. Gen Comp Endocrinol 2012; 175: 109-117. [DOI:10.1016/j.ygcen.2011.10.006]
32. Nazouri A-S, Khosravifar M, Akhlaghi A-A, Shiva M, Afsharian P. No relationship between most polymorphisms of steroidogenic acute regulatory (StAR) gene with polycystic ovarian syndrome. Int J Reprod BioMed 2015; 13: 771.
33. Nagata Y, Homma H, Lee J-A, Imai K. D-Aspartate stimulation of testosterone synthesis in rat Leydig cells. FEBS Lett 1999; 444: 160-164. [DOI:10.1016/S0014-5793(99)00045-9]
34. Nagata Y, Homma H, Matsumoto M, Imai K. Stimulation of steroidogenic acute regulatory protein (StAR) gene expression by D-aspartate in rat Leydig cells. FEBS Lett 1999; 454: 317-320. [DOI:10.1016/S0014-5793(99)00840-6]
35. Huang AS, Beigneux A, Weil ZM, Kim PM, Molliver ME, Blackshaw S, et al. D-Aspartate regulates melanocortin formation and function: behavioral alterations in D-aspartate oxidase-deficient mice. J Neurosci 2006; 26: 2814-2819. [DOI:10.1523/JNEUROSCI.5060-05.2006]
36. Lamanna C, Assisi L, Botte V, Di Fiore M. Involvement of D-Asp in P450 aromatase activity and estrogen receptors in boar testis. Amino Acids 2007; 32: 45-51. [DOI:10.1007/s00726-006-0351-9]
37. Lamanna C, Assisi L, Vittoria A, Botte V, Di Fiore MM. d-Aspartic acid and nitric oxide as regulators of androgen production in boar testis. Theriogenology 2007; 67: 249-254. [DOI:10.1016/j.theriogenology.2006.07.016]
38. Di Fiore MM, Lamanna C, Assisi L, Botte V. Opposing effects of D-aspartic acid and nitric oxide on tuning of testosterone production in mallard testis during the reproductive cycle. Reprod Biol Endocrinol 2008; 6: 1. [DOI:10.1186/1477-7827-6-28]
39. Raucci F, Di Fiore MM. The reproductive activity in the testis of Podarcis s. sicula involves D-aspartic acid: a study on c-kit receptor protein, tyrosine kinase activity and PCNA protein during annual sexual cycle. Gen Comp Endocrinol 2009; 161: 373-383. [DOI:10.1016/j.ygcen.2009.02.002]
40. 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; 7: 1482-1488. [DOI:10.1186/1477-7827-7-120]
41. Raucci F, Di Fiore MM. d-Asp: A new player in reproductive endocrinology of the amphibian Rana esculenta. J Chromatograph B 2011; 879: 3268-3276. [DOI:10.1016/j.jchromb.2011.04.007]
42. Burrone L, 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; 215: 3559-3565. [DOI:10.1242/jeb.073296]
43. Santillo A, Pinelli C, Burrone L, Baccari GC, Di Fiore MM. D-Aspartic acid implication in the modulation of frog brain sex steroid levels. Gen Comp Endocrinol 2013; 181: 72-76. [DOI:10.1016/j.ygcen.2012.11.003]
44. Santillo A, Falvo S, Chieffi P, Burrone L, Baccari GC, Longobardi S, et al. d-aspartate affects NMDA receptor-extracellular signal-regulated kinase pathway and upregulates androgen receptor expression in the rat testis. Theriogenology 2014; 81: 744-751. [DOI:10.1016/j.theriogenology.2013.12.009]
45. Raucci F, D'Aniello A, Di Fiore MM. Stimulation of androgen production by D-aspartate through the enhancement of StAR, P450scc and 3β-HSD mRNA levels in vivo rat testis and in culture of immature rat Leydig cells. Steroids 2014; 84: 103-110. [DOI:10.1016/j.steroids.2014.03.016]
46. Di Nisio A, De Toni L, Ferigo M, Rocca M, Speltra E, Ferlin A, et al. d-Aspartic acid stimulates steroidogenesis through the delay of LH receptor internalization in a mammalian Leydig cell line. J Endocrinol Invest 2015; 39: 207-213. [DOI:10.1007/s40618-015-0333-4]
47. Falvo S, Di Fiore MM, Burrone L, Baccari GC, Longobardi S, Santillo A. Androgen and Estrogen modulation by D-Aspartate in Rat Epididymis. Reprod Fertil Dev 2015; 28: 1865-1872. [DOI:10.1071/RD15092]
48. 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; 7: 1. [DOI:10.1186/1477-7827-7-120]
49. Willoughby DS, 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; 33: 803-810. [DOI:10.1016/j.nutres.2013.07.010]
50. Bloomer RJ, Gunnels TA, Moran RG, Schriefer JM. Influence of a D-aspartic Acid/Sodium Nitrate/Vitamin D3 Dietary Supplement on Physiological Parameters in Middle-aged Men: A Pilot Study. Open Nutraceut J 2015; 8: 43-48. [DOI:10.2174/1876396001508010043]
51. Melville GW, Siegler JC, Marshall PW. Three and six grams supplementation of d-aspartic acid in resistance trained men. J Int Soc Sports Nutr 2015; 12: 15. [DOI:10.1186/s12970-015-0078-7]
52. Morgentaler A, Dobs AS, Kaufman JM, Miner MM, Shabsigh R, Swerdloff RS, et al. Long acting testosterone undecanoate therapy in men with hypogonadism: results of a pharmacokinetic clinical study. J Urol 2008; 180: 2307-2313. [DOI:10.1016/j.juro.2008.08.126]
53. Burrone L, Di Giovanni M, Di Fiore MM, Chieffi Baccari G, Santillo A. Effects of D‐Aspartate Treatment on D‐Aspartate Oxidase, Superoxide Dismutase, and Caspase 3 Activities in Frog (Rana esculenta) Tissues. Chem Biodivers 2010; 7: 1459-1466. [DOI:10.1002/cbdv.200900331]

Send email to the article author

© 2020 All Rights Reserved | International Journal of Reproductive BioMedicine

Designed & Developed by : Yektaweb