D-Aspartic acid (D-AA) is the D-amino acid that is one of the most important regulators of the testicular testosterone production — it is synthesised and stored in the testis, where it activates the Leydig cells to produce the testosterone through the StAR protein, the P450scc enzyme, and the 3beta-HSD pathway. The D-aspartic acid is unique among the amino acids because it is the only D-amino acid that has been shown to have a specific and potent hormonal function in the human body — it acts as a local hormone in the testis, where it stimulates the testosterone synthesis and the testosterone release from the Leydig cells, and it is therefore one of the most important and most specific regulators of the male reproductive function. The D-aspartic acid levels in the testis are approximately 2-5 mM (which is 100-1000 times higher than the D-aspartic acid levels in the blood), and this high concentration of the D-aspartic acid in the testis is maintained by the serine racemase (which converts the L-aspartic acid to the D-aspartic acid) and by the D-aspartic acid oxidase (DAAO), which degrades the D-aspartic acid. Without adequate D-aspartic acid and Leydig cell activation, the testosterone production is reduced, the sperm count falls, and the male hypogonadism develops — the hallmark of the D-aspartic acid deficiency and of the low testosterone states in men. The typical dietary D-aspartic acid intake from the protein-rich foods (meat, fish, poultry, eggs, dairy) is very low (less than 1mg daily), and the endogenous synthesis from the L-aspartic acid in the testis is the primary source of the D-aspartic acid in the body — making it a conditionally essential compound that may become deficient in men with the low testosterone, the reduced Leydig cell function, or the impaired serine racemase activity.
D-Aspartic Acid and the Leydig Cell Function
D-aspartic acid supports the testicular testosterone production by activating the StAR protein (the steroidogenic acute regulatory protein), which is the rate-limiting step in the steroidogenesis pathway — the StAR protein is responsible for the transport of the cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane, where the P450scc enzyme converts the cholesterol to the pregnenolone, the first and rate-limiting step in the steroidogenesis pathway. The D-aspartic acid activates the StAR protein by binding to a specific D-aspartic acid receptor (which has been identified in the Leydig cell membranes), and this activation leads to the increased cholesterol transport, the increased pregnenolone production, and the increased testosterone synthesis and release. The D-aspartic acid also activates the P450scc enzyme and the 3beta-HSD enzyme (the other rate-limiting enzymes in the steroidogenesis pathway), thereby promoting the conversion of the cholesterol to the testosterone through the full steroidogenesis pathway. This multi-target activation of the steroidogenic enzymes by the D-aspartic acid makes it one of the most potent and most specific stimulators of the testicular testosterone production known — and it explains why the D-aspartic acid supplementation has been shown to increase the testosterone levels in men with the low baseline testosterone.
The clinical importance of the D-aspartic acid for the male reproductive health is underscored by the observation that the D-aspartic acid supplementation increases the testosterone levels and improves the sperm count in men with the low testosterone and with the male infertility. A study in 20 men with the low testosterone (total testosterone less than 10 nmol/L) found that the D-aspartic acid supplementation at 3g daily for 12 days significantly increased the total testosterone (by 30-40%) and the free testosterone (by 25-35%) — demonstrating the potent testosterone-boosting effect of the D-aspartic acid in men with the low testosterone. Another study in 30 men with the oligoasthenozoospermia (low sperm count and motility) found that the D-aspartic acid supplementation at 2g daily for 3 months significantly increased the sperm count (by 20-30%) and the sperm motility (by 15-25%) — demonstrating the potent fertility-enhancing effect of the D-aspartic acid in men with the male infertility.
Practical Application
For general D-aspartic acid supplementation for the testosterone and for the male reproductive support, the evidence-based approach is to supplement with 2-3g of D-aspartic acid daily (as the pure D-aspartic acid powder or capsule, taken in divided doses of 1g, 2-3 times per day). The D-aspartic acid should be taken cyclically (for example, 3g daily for 12 days, followed by a 7-day break) to prevent the downregulation of the D-aspartic acid receptors in the Leydig cells and to maximise the testosterone-boosting effect. The D-aspartic acid is generally well-tolerated with no significant adverse effects at doses up to 6g daily, though it may cause the headache or the acne in some individuals at the high doses (due to the increased testosterone levels). For comprehensive testosterone and male reproductive support, D-aspartic acid pairs well with the zinc (which is required for the Leydig cell function and for the testosterone synthesis — the zinc deficiency is one of the most common causes of the low testosterone, and the combined zinc and D-aspartic acid supplementation is more effective than either compound alone for the testosterone support), with the magnesium (which is a cofactor for many of the enzymes of the steroidogenesis pathway and which has complementary effects on the testosterone production and on the muscle strength), with the vitamin D (which is a regulator of the testosterone production and which works synergistically with the D-aspartic acid for the Leydig cell function — the vitamin D deficiency is associated with the low testosterone and with the reduced Leydig cell function, and the combined supplementation of the D-aspartic acid and the vitamin D is more effective than either compound alone for the testosterone support), and with the fenugreek extract (which is a natural testosterone booster that works through a complementary mechanism involving the inhibition of the aromatase and the SHBG, and which works synergistically with the D-aspartic acid for the testosterone enhancement and for the male reproductive support).
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