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D-Aspartic Acid as a supplement

Recently D-Aspartic Acid has been suggested as a supplement to boost testosterone levels in infertile men as well as in athletes. However, given the limited published literature, further research is needed to clearly assess and study the role of D-aspartic acid in a humans body. Below is a short review of the recent literature as it pertains to D-aspartic acid and other D-amino acids in mammals and humans.



Figure 1: Structural models of L- and D-Aspartic Acid.

D-amino acids have been shown to occur in higher organisms. In particular, recent research indicates that D-amino acids are present in neuroendocrine tissues. For example, D-serine occurs in glial cells and is abundant in brain regions enriched in N-methyl-D-aspartate (NMDA) receptors. The ion channel protein NMDA receptor is a glutamate receptor found in nerve cells. The receptor is activated when glutamate and glycine or D-serine bind to it. Glutamate (Glu, E) is the major excitatory neurotransmitter and plays a central role in the functioning of the central nervous system (CNS). D-Aspartic acid (D-Asp, D-D) is found in some neuronal pathways. In epinephrine-containing glandular tissue, for example in the adrenal medulla, it appears to regulate hormone synthesis and release.

According to Topo et al. (2009), sodium D-aspartate induces an enhancement of LH and testosterone release in humans and rats. In the pituitary gland and the testes, D-Asp is synthesized by a D-aspartase racemase. The enzyme converts L-Asp into D-Asp. Taken together, Topo et al. conclude that D-Asp is a physiological amino acid occurring in the pituitary gland and testes and that its role is in regulation and synthesis of luteinizing hormone (LH) and testosterone in humans and rats. According to finding by Topo et al., D-Asp appears to play a crucial role in reproduction. It's possible suggested role is that of a neuromodulator or its involvement in biosynthesis and release of sexual hormones. Also, in recent studies in men, a lower D-Asp content was found in oligoasthenoteratospermic seminal fluid and spermatozoon. Oligoasthenoteratospermia refers to a reduction in the motilty and number of spermatozoa or mature motile sex cells, and a change in their morphology. It is one of the most causes of infertility in men. Also, a relationship between the amount and motility of semen and the content of D-Asp was observed. In women, D-Asp occurs in the follicular fluid as a physiological component, and it was found that the concentration of D-Asp in the fluid is reduced in older women. Also, the concentration of D-Asp in the follicular fluid was found to be lower as well as the quality of the oocytes and the level of fertilization was also found to be lower.

The study by Togo et al. evaluated the effects of D-aspartate administration on luteinizing hormone (LH) and testosterone production in humans and rats. Furthermore, the research group aimed to understand the biochemical mechanisms by which D-Asp induces the synthesis and release of LH and testosterone. Togo et al. reported  effects of an oral dose of sodium D-aspartate (DADAVIT®) on humans: After 12 days of D-Asp treatment, 20 out of 23 (87%) participants had significantly increased concentrations of LH in their blood as compared to basal values. Also, the levels of testosterone in the serum of the participants were significantly increased compared with basal levels, as well.

 

However, in a more recent study performed by Melville et al. in 2015 in which 24 males in their twenties with a minimum of two year’s experience in resistance training participated,  the researchers found a reduction in serum testosterone levels. A daily dose of six grams of D-aspartic acid decreased levels of total testosterone and free testosterone (D6). Also, taking three grams of D-aspartic acid had no significant effect on either testosterone markers. It is currently unknown what effect this reduction in testosterone will have on strength and hypertrophy gains.

So far two studies on D-Asp supplementation have been conducted on humans. According to Topo et al., 12 days of supplementation (3.12 g.d−1), significantly increased testosterone levels by 42% (4.5–6.4 ng.ml−1). However, a cohort of healthy sedentary male IVF patients (27–37 years), with low initial testosterone levels (~4.55 ng.ml−1), were studied. In comparison, Willoughby and Leutholtz reported that after 29 days of supplementation (3 g.d−1) and resistance training the levels of total testosterone and free testosterone were not significantly altered. This study observed resistance trained men (age: 22.8 ± 4.67 years old; training age: > 1 year) which had higher initial testosterone levels (~7.96 ng.ml−1). Melville et al. argue that the difference in outcome between these two studies can in part be explained by differences in training status and basal testosterone levels. The reported basal testosterone levels of resistant trained men range from approximately 5.8 to 8.6 ng.ml−1 (20 to 30 nmol.l−1). Whereas that of untrained men range from about 4.9 to 6.6 ng.ml−1 (17 to 23 nmol.l−1).

Apparently, supplementation with D-Asp appears to increase testosterone levels in untrained men but not in trained men unless the optimal dose for this supplement has presently not been determined for trained men.

Furthermore, there is evidence that D-Asp may play a role as a neuromodulator since lower levels of D-Asp are reported to occur in the postmortem prefrontal cortex (PFC) of patients with schizophrenia.

Taken together, recent findings suggest that D-amino acids are a new type of neuromodulators, but caution may need to be taken when using D-aspartic acid as a supplement.


Reference

Colone M, Marelli G, Unfer V, Bozzuto G, Molinari A, Stringaro A.; Inositol activity in oligoasthenoteratospermia--an in vitro study. Eur Rev Med Pharmacol Sci. 2010 Oct;14(10):891-6.

D'Aniello G, Ronsini S, Guida F, Spinelli P, D'Aniello A: Occurrence of D-aspartic acid in human spermatozoa: Possible role in reproduction. Fertil Steril. 2005, 84: 1444-1449. 10.1016/j.fertnstert.2005.05.019.

D'Aniello G, Grieco N, Di Filippo MA, Cappiello F, Topo E, D'Aniello E, Ronsini S: Reproductive implication of D-aspartic acid in human pre-ovulatory follicular fluid. Human Reprod. 2007, 22: 3178-3183. 10.1093/humrep/dem328.

Errico, F., Nisticò, R., Di Giorgio, A., Squillace, M., Vitucci, D., Galbusera, A., … Usiello, A. (2014). Free D-aspartate regulates neuronal dendritic morphology, synaptic plasticity, gray matter volume and brain activity in mammals. Translational Psychiatry, 4(7), e417–. http://doi.org/10.1038/tp.2014.59

Errico F, Nistico R, Napolitano F, Mazzola C, Astone D, Pisapia T, et al. Increased D-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice. Neurobiol Aging. 2011;32:2229–2243. [PubMed]

Takemitsu Furuchi and Hiroshi Homma; Free D-Aspaptate in Mammals. Biol Pharm. Bull. 28(9) 1566-1570 (2005).

Geoffrey W Melville, Jason C Siegler and Paul WM Marshall; Three and six grams supplementation of d-aspartic acid in resistance trained men. Journal of the International Society of Sports Nutrition201512:15. DOI: 10.1186/s12970-015-0078-7.

Enza Topo, Andrea Soricelli, Antimo D'Aniello, Salvatore Ronsini and Gemma D'Aniello.; The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats. Reproductive Biology and Endocrinology20097:120. DOI: 10.1186/1477-7827-7-120.

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(10):803–10.