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Is D-Aspartic Acid the Next Coming of Creatine?It’s far from a secret. Ask just about anyone what the most powerful muscle-building substance in thehuman body is and you’ll likely get a response like “Well, I’d have to say testosterone, for sure…” andwith good reason. We’re talking about what separates the men from the boys here, the parent compoundfor nearly every anabolic steroid[1], and the basis for over-the-counter “designer steroids.” Even oldschool pro-hormones like androstenedione were used just to elevate blood testosterone back in the day[2].On the other hand, ask certain “gurus” of current-day bodybuilding chemical warfare and you might get adifferent answer: “It’s growth hormone that turns good physiques into great ones.”If you’re a health conscious bodybuilder and/or a natural competitor reading this, you might be thinking atthis point: “Geez, OK, another article on drugs…” If you’re tempted click a new link, don’t. This article isfor you. On the other hand, if you’re a “hormonally enhanced” athlete, you might be thinking, “OK, I gotthis one covered – testosterone and growth hormone together. Got it.” You, too, might be tempted to stopreading. Don’t. Indeed, this article is for you, too, my mighty friend.There’s a product on the shelves right now that, much like creatine, has the potential to be a staple in thesupplement regimen for both natural and “enhanced” bodybuilders. (Believe it or not, in the early nineties,there was tremendous doubt that something as simple and “natural” as creatine could elicit “drug-like”effects on gym performance and anabolism. Today we know better[3].) What I’m talking about is anamino acid, simpler structurally than even creatine, called D-Aspartic acid (DAA), and it’s producednaturally by your body from run-of-the-mill, dietary L-Aspartic acid. DAA, however, is special because itcontrols hormonal output and more importantly, like creatine, supplementing with it loads DAA into yourendocrine (hormone producing) tissues. This means that you, in turn, can control the production ofhormones like testosterone and most likely even growth hormone[4].That’s the good news. Unfortunately, the jury’s still out on the particulars of DAA (cycling it, side effects,etc.), much like it was for creatine decades ago. While it’s clear is that DAA stimulates hormonalsecretion, less certain are it’s potency (e.g., dose-response relation) and all the hormones it affects whenhumans supplement with it.DAA: Hormonal QuarterbackFigure 1 is a nearly embarrassing, but useful oversimplification of testosterone and growth hormone controlthat illustrates how DAA is essentially a hormonal quarterback for the hypothalamus and pituitary gland (inthe brain), and the gonads (we’ll focus on the testes), collectively known as the Hypothalamic-PituitaryGonadalor –Testicular axis (HPTA):• The Hypothalamus: The “master gland” in the brain, involved in appetite, thermoregulation andoutput of a multitude of hormones. In particular, it releases gonadotrophin releasing hormone(GnHR) and growth hormone releasing hormone (GHRH) that control the pituitary release ofgonadotrophins (so-called because they affect the gonads) and growth hormone, respectively.• Pituitary Gland: The workhorse of the hypothalamus. It releases the gonadotrophins [luteinizinghormone (LH) and follicle stimulating hormone (FSH)] as well as our fat-burning friend, growthhormone (GH), and several over hormones.• Gonads: The testes and ovaries. They release testosterone (and progesterone) in men, andestrogen and progesterone in women. In men, testosterone and estrogen (produced fromtestosterone via enzymatic aromatization) feed back to inhibit GnRH, LH and FSH release. Inwomen, estrogen, progesterone, LH and FSH delicately and reciprocally coordinate ovulation(ovarian cycle) and prepare the uterus for pregnancy or menstruation (menstrual cycle)[5].
The GoodFigure 1 shows how, for each of the glands of the HPTA, DAA is basically a hormonal “on switch.” Earlyin life, DAA helps coordinate nervous system development, but by adulthood, its primary job is inendocrine control[4]. (Nonetheless, research in adult animals suggests supplemental DAA enhancesmemory and learning[6].) Via L-aspartic acid conversion or direct supplemention, DAA triggers release ofGnRH, LH, FSH, testosterone and growth hormone, with increases of ~2-4 fold seen in male rats after injection with DAA[7]. In these male animals (and hopefully in men, too), DAA does not affect estradiol(an estrogen) or cortisol[4]. As with the HPTA itself, DAA also mediates hormonal homeostasis. Forexample, while triggering testosterone release, DAA also increases testicular aromatase (in animalresearch), thus also lowering testosterone via conversion to estrogen[8, 9]. Not surprisingly, healthy levelsof gonadal DAA are associated with normal sperm[10] and oocyte[11]development in humans.In 2009, the rubber finally hit the road research-wise for this nifty amino acid’s chance to become abodybuilding supplement. A group of Italian scientists led by Gemma D’Aniello fed both rats and humansDAA and watched the hormonal fireworks (importantly demonstrating that DAA is orally bioavailable inboth species)[12]. Drinking DAA-supplemented water increased DAA in rat testes ~7 fold, triggering 2ndmessenger signaling (cAMP and cGMP) and elevating blood LH and testosterone by ~50% and >100%,respectively. (L-Aspartic acid was worthless in this regard.)DAA did the trick in men, too. After 12 days of a single ~3 gram dose in the morning (equivalent to thedaily dose given to the rats[13]), DAA boosted LH by 33% and testosterone by 42%. Apparently, it takessome time to “load” the DAA into the endocrine tissues, as no effect was noted after the first 6 days ofsupplementation. Much like our good friend creatine, it seems that there is some percentage of “nonresponders”(about 10% in this study) whose hormonal levels may not be affected by the DAA.D’Aniello’s group cleverly followed up 3 days after discontinuing the DAA supplement and found thattestosterone (but not LH) was still elevated, possibly due to residual DAA in the testes[12].The Bad?Unfortunately, DAA may not be all fun and games when it comes to hormone boosting. D’Aniello’sstudy[12] did not track hormones beyond the 3 day follow-up and failed to report estrogen levels at all,leaving us to wonder what happens post-supplementation. As noted before, male rats injected with DAAshow dramatic increases in growth hormone and testosterone, but progesterone[7] and prolactin[14, 15] arealso increased 2.5 – 3 fold. This may not bode well for men using DAA. Combining a progestagen (likeprogesterone) and elevating testosterone is quite a potent method of male contraception[16].Supraphysiological levels of prolactin devastate sexual performance and libido in men and women[17] andmay increase cancerous tumor risk, as well[18].The Ugly?As they say, “This could get ugly.” DAA’s actions are mediated partially via conversion to N-Methyl DAsparticAcid (NMDA; Figure 1)[4], a well-known excitotoxin (i.e., a compound that literally can exciteneurons to death). Hopefully, because the body controls this conversion process, DAA supplementationdoes not risk nerve cell death[19]. Little is known about female endocrine responses to DAA, or how itmight affect the developing nervous system of a pre-pubescent or adolescent athlete, so let’s also hope thatwarning labels are heeded in this regard.D-Aspartic Acid on TrialIs DAA “hormonal creatine,” on its way to supplement greatness? For the natural bodybuilder, deep intocontest preparation, might DAA be the salvation for depressed testosterone levels[20]? For the “enhanced”athlete attempting to restore endogenous hormonal output, will DAA become a staple of “post-cycletherapy?” Is DAA a godsend for packing on lean muscle mass, a natural alternative for hormonereplacement therapy, and the next big thing in anti-aging, or does it cause unwanted hormone elevation, andthus more hormonal havoc than it’s worth?...Just like creatine 20 years ago, DAA is now on trial. My suspicion is that the “verdict” on D-Ascorbic acidwill be preceded by many colorful, controversial, and even unexpected testimonies from bodybuilders inthe trenches, the scientific community, and the supplement companies selling this powerful amino acid.
The GoodFigure 1 shows how, for each of the glands of the HPTA, DAA is basically a hormonal “on switch.” Earlyin life, DAA helps coordinate nervous system development, but by adulthood, its primary job is inendocrine control[4]. (Nonetheless, research in adult animals suggests supplemental DAA enhancesmemory and learning[6].) Via L-aspartic acid conversion or direct supplemention, DAA triggers release ofGnRH, LH, FSH, testosterone and growth hormone, with increases of ~2-4 fold seen in male rats after injection with DAA[7]. In these male animals (and hopefully in men, too), DAA does not affect estradiol(an estrogen) or cortisol[4]. As with the HPTA itself, DAA also mediates hormonal homeostasis. Forexample, while triggering testosterone release, DAA also increases testicular aromatase (in animalresearch), thus also lowering testosterone via conversion to estrogen[8, 9]. Not surprisingly, healthy levelsof gonadal DAA are associated with normal sperm[10] and oocyte[11]development in humans.In 2009, the rubber finally hit the road research-wise for this nifty amino acid’s chance to become abodybuilding supplement. A group of Italian scientists led by Gemma D’Aniello fed both rats and humansDAA and watched the hormonal fireworks (importantly demonstrating that DAA is orally bioavailable inboth species)[12]. Drinking DAA-supplemented water increased DAA in rat testes ~7 fold, triggering 2ndmessenger signaling (cAMP and cGMP) and elevating blood LH and testosterone by ~50% and >100%,respectively. (L-Aspartic acid was worthless in this regard.)DAA did the trick in men, too. After 12 days of a single ~3 gram dose in the morning (equivalent to thedaily dose given to the rats[13]), DAA boosted LH by 33% and testosterone by 42%. Apparently, it takessome time to “load” the DAA into the endocrine tissues, as no effect was noted after the first 6 days ofsupplementation. Much like our good friend creatine, it seems that there is some percentage of “nonresponders”(about 10% in this study) whose hormonal levels may not be affected by the DAA.D’Aniello’s group cleverly followed up 3 days after discontinuing the DAA supplement and found thattestosterone (but not LH) was still elevated, possibly due to residual DAA in the testes[12].The Bad?Unfortunately, DAA may not be all fun and games when it comes to hormone boosting. D’Aniello’sstudy[12] did not track hormones beyond the 3 day follow-up and failed to report estrogen levels at all,leaving us to wonder what happens post-supplementation. As noted before, male rats injected with DAAshow dramatic increases in growth hormone and testosterone, but progesterone[7] and prolactin[14, 15] arealso increased 2.5 – 3 fold. This may not bode well for men using DAA. Combining a progestagen (likeprogesterone) and elevating testosterone is quite a potent method of male contraception[16].Supraphysiological levels of prolactin devastate sexual performance and libido in men and women[17] andmay increase cancerous tumor risk, as well[18].The Ugly?As they say, “This could get ugly.” DAA’s actions are mediated partially via conversion to N-Methyl DAsparticAcid (NMDA; Figure 1)[4], a well-known excitotoxin (i.e., a compound that literally can exciteneurons to death). Hopefully, because the body controls this conversion process, DAA supplementationdoes not risk nerve cell death[19]. Little is known about female endocrine responses to DAA, or how itmight affect the developing nervous system of a pre-pubescent or adolescent athlete, so let’s also hope thatwarning labels are heeded in this regard.D-Aspartic Acid on TrialIs DAA “hormonal creatine,” on its way to supplement greatness? For the natural bodybuilder, deep intocontest preparation, might DAA be the salvation for depressed testosterone levels[20]? For the “enhanced”athlete attempting to restore endogenous hormonal output, will DAA become a staple of “post-cycletherapy?” Is DAA a godsend for packing on lean muscle mass, a natural alternative for hormonereplacement therapy, and the next big thing in anti-aging, or does it cause unwanted hormone elevation, andthus more hormonal havoc than it’s worth?...Just like creatine 20 years ago, DAA is now on trial. My suspicion is that the “verdict” on D-Ascorbic acidwill be preceded by many colorful, controversial, and even unexpected testimonies from bodybuilders inthe trenches, the scientific community, and the supplement companies selling this powerful amino acid.
