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
Introduction
In men desiring to increase their muscle mass and strength and enhance their exercise/sport performance, the androgenic hormone testosterone can undoubtedly play a beneficial role. d-Aspartic acid (D-ASP) has recently emerged on the exercise/sports supplement market and is being touted as a means of increasing muscle mass and strength owing to its ability to increase endogenous levels of testosterone. In rats, D-ASP has been shown to activate the hypothalamo-pituitary-gonadal axis (HPG axis) by facilitating the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, luteinizing hormone (LH) from the pituitary gland, and testosterone from the testes [1]. In addition, a more recent study involved D-ASP supplementation in rats and men that resulted in significant increases in LH and testosterone for both species [2]. As a result of these studies, the nutrition/sport supplement industry has attempted to take advantage of this information by manufacturing D-ASP–containing products with the intent of these products increasing endogenous testosterone levels, presumably by activation of the HPG axis. Furthermore, these products are being marketed on the premise that increases in endogenous testosterone will result in increases in muscle mass, especially when ingested in conjunction with a resistance training program.
An endogenous amino acid present in nervous tissues and endocrine glands of humans [3], D-ASP is considered to play an important neuromodulating role in activating the HPG axis. For example, in males, this axis is responsible for synthesizing endogenous testosterone and occurs due to D-ASP converting to N-methyl d-aspartic acid (NMDA) by d-aspartate methyltransferase (NMDA synthetase). In the hypothalamus, NMDA binds to its receptor, a subtype of the l-glutamate receptor, and potentiates glutaminergic neurotransmission [4], which results in the release of GnRH [5]. The release of GnRH from the hypothalamus then triggers the release of both follicle-stimulating hormone and LH from the pituitary gland. The effect of these 2 hormones on the testes is that follicle-stimulating hormone stimulates spermatogenesis and LH stimulates testosterone synthesis [5].
In an attempt to provide a feedback mechanism for the HPG axis, in which to maintain normal, physiological levels of endogenous circulating testosterone, the enzyme d-asparate oxidase (DDO) is capable of degrading D-ASP by way of deaminative oxidation [6]. In addition, D-ASP is also capable of inducing an increase in the activity of aromatase, the enzyme responsible for the conversion of testosterone to 17β-estradiol (estrogen) [7]. Additional data support this and help confirm that D-ASP is involved in the local production of estrogen [8].
Because there are data supporting the role of D-ASP supplementation in increasing endogenous testosterone levels, this amino acid product may prove beneficial as a means in which to increase muscle performance associated with heavy resistance training. However, because there appears to be a paucity of human studies dealing with D-ASP supplementation, and apparently none when D-ASP is ingested in conjunction with resistance training, we hypothesized that D-ASP would not increase endogenous testosterone levels or improve muscular performance associated with resistance training. Therefore, the purpose of this study was to determine the effects of resistance exercise and D-ASP supplementation on body composition, muscle strength, and serum hormones associated with the HPG axis in resistance-trained men.
Section snippets
Experimental approach
In a randomized, double-blind manner, participants engaged in 28 days of heavy resistance training while also ingesting 3 g/d of either placebo (PLC) or D-ASP. Testing and evaluation occurred before (day 0) and after (day 29) and involved assessments of body composition, muscle strength, and serum hormones associated with the HPG axis. This approach was based on the premise that after ingesting the D-ASP supplement, muscle mass and strength may be preferentially affected compared with PLC owing
Participant demographics
Twenty-four participants began the study; however, 4 were withdrawn because of reasons unrelated to the study. One participant became ill, 1 sustained an injury unrelated to the study, and 2 became too busy with their schedule; therefore, none of the 4 were able to remain compliant with the resistance training program. As a result, 20 participants completed the study. The PLC group (n = 10) had an average (±SD) age of 21.25 ± 1.03 years, height of 179.68 ± 6.42 cm, total body mass of 80.99 ±
Discussion
In this study, we sought to determine the effects of 28 days of heavy resistance training and D-ASP supplementation on body composition, muscle strength, and serum hormones associated with the HPG axis in resistance-trained men. Herein we report similar increases in muscle mass and strength in both groups associated with resistance training similar to our previous studies, which used the identical training protocol [9], [10]. We also found that D-ASP supplementation had no effects on serum
Acknowledgment
We would like to thank the individuals who participated in this study. This study was partially supported by a D-ASP donation from Better Body Sports. Funding from this study came from the Exercise and Biochemical Nutrition Laboratory at Baylor University. The authors declare that they have no competing interests.
References (23)
- et al.
d-Aspartate—an important bioactive substance in mammals: a review from an analytical and biological point of view
J Chromatogr B Analyt Technol Biomed Life Sci
(2011) d-Aspartic acid: an endogenous amino acid with an important neuroendocrine role
Brain Res Rev
(2007)- et al.
A physiological mechanism to regulate d-aspartic acid and NMDA levels in mammals revealed by d-aspartate oxidase deficient mice
Gene
(2006) - et al.
High-throughput determination of free d-aspartic acid in mammals by enzyme immunoassay using specific monoclonal antibody
Anal Biochem
(2006) - et al.
Long acting testosterone undecanoate therapy in men with hypogonadism: results of a pharmacokinetic clinical study
J Urol
(2008) - et al.
Biological role of d-amino acid oxidase and d-aspartate oxidase. Effects of d-amino acids
J Biol Chem
(1993) - et al.
Administration of d-aspartate increases d-aspartate oxidase activity in mouse liver
Biochim Biophys Acta
(1989) - 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) - et al.
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) - et al.
Reproductive implication of d-aspartic acid in human pre-ovulatory follicular fluid
Hum Reprod
(2007)
Enhancement of aromatase activity by d-aspartic acid in the ovary of the lizard Podarcis s. sicula
Reproduction
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2022, Clinical TherapeuticsCitation Excerpt :In a systematic review published in 2017, d-Asp supplementation enhanced testosterone levels in male animal studies, but the results were inconsistent with human studies.106 Of importance, only 4 human research studies were included of which 3 studies107–109 were performed on resistance-trained or physically active men and 1 study on male volunteers at in vitro fertilization.105 Regarding the latter, the patients were healthy young adults (n = 23; 27 to 37 year of age) and thus had normal testosterone levels.
New insights on the influence of free D-aspartate metabolism in the mammalian brain during prenatal and postnatal life
2020, Biochimica et Biophysica Acta - Proteins and ProteomicsCitation Excerpt :Given the neurotoxic effects of persistent d-Asp exposure in mouse models, possible disadvantages of d-Asp supplementation should be taken into account to develop appropriate administration schedules, based on short-term/intermittent treatments. However, studies performed so far in humans have shown that d-Asp administration has no toxicological consequences and does not affect parameters related to the skeletal muscle mass or hormonal biomarkers associated with hypothalamic-pituitary-gonadal axis [103–107]. As an alternative to oral d-Asp treatment, new therapeutic strategies focused on compounds with inhibitory activity against DDO are also being evaluated to improve cerebral d-Asp availability and reduce potential side-effects associated with excessive d-Asp stimulation [108].
Exercise, training, and the hypothalamic–pituitary–gonadal axis in men
2019, Current Opinion in Endocrine and Metabolic ResearchCitation Excerpt :More recently, cortisol and testosterone dynamics after exhaustive endurance exercise have been described in endurance-trained males, suggesting that recovery from endurance exercise sessions at the ventilatory threshold might require up to 72 h for free testosterone to return to baseline values [51]. Undoubtedly, the type of sports [52,53] and the kind of exercise [54,55] influence testosterone secretion and profile in a different way, although gonadotropins remain unchanged. Recently, a comparison study between old and young men has shown that long-term resistance training did not impact either on testosterone metabolism or the HPG axis, although this type of training increased muscle mass and strength in both old and young men [56].
Upper-body resistance exercise augments vastus lateralis androgen receptor-DNA binding and canonical Wnt/β-catenin signaling compared to lower-body resistance exercise in resistance-trained men without an acute increase in serum testosterone
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