The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats
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Background: D-aspartic acid is an amino acid present in neuroendocrine tissues of invertebrates and vertebrates, including rats and humans. Here we investigated the effect of this amino acid on the release of LH and testosterone in the serum of humans and rats. Furthermore, we investigated the role of D-aspartate in the synthesis of LH and testosterone in the pituitary and testes of rats, and the molecular mechanisms by which this amino acid triggers its action. Methods: For humans: A group of 23 men were given a daily dose of D-aspartate (DADAVIT®) for 12 days, whereas another group of 20 men were given a placebo. For rats: A group of 10 rats drank a solution of either 20 mM D-aspartate or a placebo for 12 days. Then LH and testosterone accumulation was determined in the serum and D-aspartate accumulation in tissues. The effects of D-aspartate on the synthesis of LH and testosterone were gauged on isolated rat pituitary and Leydig cells. Tissues were incubated with D-aspartate, and then the concentration (synthesis) of LH and cGMP in the pituitary and of testosterone and cAMP in the Leydig cells was determined. Results: In humans and rats, sodium D-aspartate induces an enhancement of LH and testosterone release. In the rat pituitary, sodium D-aspartate increases the release and synthesis of LH through the involvement of cGMP as a second messenger, whereas in rat testis Leydig cells, it increases the synthesis and release of testosterone and cAMP is implicated as second messenger. In the pituitary and in testes D-Asp is synthesized by a D-aspartate racemase which convert L-Asp into D-Asp. The pituitary and testes possesses a high capacity to trapping circulating D-Asp from hexogen or endogen sources. Conclusion: D-aspartic acid is a physiological amino acid occurring principally in the pituitary gland and testes and has a role in the regulation of the release and synthesis of LH and testosterone in humans and rats.
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From included studies on D-Aspartic acid and creatine, no clear benefit towards elevating testosterone was established.
“Overall, from our included studies on D-Aspartic acid and creatine, no clear benefit towards elevating testosterone was established.[77][78][79][80]”
From A systematic appraisal of emerging alternative therapies in men’s health and wellness (2025) · cites this paper as [77]
The Results section reports that 12 days of D-aspartate treatment significantly increased serum testosterone in the human participants, from 4.5 to 6.4 ng/ml (Table 1). That is contrary to attributing a finding of no clear testosterone benefit from D-aspartate to this paper. The paper does not test creatine or assess the citing authors’ overall synthesis of their included studies. (LLM, conf=0.88)
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- Authors
- Topo, E., Soricelli, A., D'Aniello, A., Ronsini, S., & D'Aniello, G.
- Affiliations
- Stazione Zoologica Anton Dohrn (IT)
- Parthenope University of Naples (IT)
- ORCID
- Soricelli, Andrea
- Venue
- Reproductive Biology and Endocrinology
- Published
- 2009-10-27
- Volume
- 7
- Issue
- 1
- Pages
- 120-120
- ISSN
- 1477-7827 (ISSN-L)
- PMC
- PMC2774316
- OpenAlex
- W2135320785
- Cited by
- 125
- References
- 30
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 7 · 2023: 11 · 2022: 10 · 2021: 5 · 2020: 11 · 2019: 10 · 2018: 6 · 2017: 12 · 2016: 10 · 2015: 8 · 2014: 11 · 2013: 3 · 2012: 3
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Reproductive Biology and Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- CINECA IRIS Institutial research information system (Parthenope University of Naples) (submittedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- D-aspartic acid, luteinizing hormone, testosterone, pituitary gland, Leydig cells, cyclic GMP, cyclic AMP, second messengers, male fertility
- MeSH terms
- Adult, Animals, Blood Chemical Analysis, Chromatography, High Pressure Liquid, Humans, Luteinizing Hormone, Male, Pituitary Gland, Placebos, Testis, Testosterone, Signal Transduction, Rats, Wistar, D-Aspartic Acid, Rats
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