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The DAA (D-Aspartic Acid) Paradox

D-Aspartic Acid has the potential to increase or decrease Testosterone and Estrogen.

I have been watching the D-Aspartic Acid (DAA) research for a number of years. I first became interested in this ingredient for aiding fertility in my naturopathic clinic. The initial research showed promise as an inducer of aromatase to aid females to enhance conversion of testosterone to estrogen during the follicular phase which is important in maturing follicles for ovulation.

There was some promising animal studies showing good conversion of testosterone to estrogen via aromatase induction and subsequent reduction in testosterone with increasing estrogen. Similar things were found to occur in male testes with increased aromatization of testosterone to make estrogen. More details about these studies are listed below.

DAA was also shown to improve sperm production and function and it was well known to increase testosterone and LH in animal studies and the world was getting excited over this excitatory compound to influence hormonal production.

The challenge was understanding the compound and knowing how best to use it as it has the potential to increase or decrease estrogen and testosterone so understanding the mechanism of action and dosage strategy is important.

There was some interesting research in the 90’s showing improvements to sperm qualities and potential improvements in fertility.

I used it in my clinic in both male and female clients for the first 2 weeks of the menstrual cycle leading up to ovulation, but I stopped using it as I found it to be unpredictable but have been fascinated by this ingredient as it showed great promise.

Over the last couple of decades further research has been done and I have watched this ingredient become a popular supplement and am constantly being asked for my opinion on it and whether I would prescribe it again and how to use it.

Here is a review of the literature and the DAA story thus far;

What is DAA?

D-Aspartic Acid (DAA) is a naturally occurring non-essential amino acid. It is found in the protein components of foods and good dietary sources include casein, soy and corn. It can also be made in the body from L-aspartate. DAA is also available in supplemental form as a natural component of casein, collagen, soy protein, corn protein and as sodium-d-aspartate, D-aspartic acid and indirectly by supplementing with L-aspartate which can be converted to D-aspartate endogenously as required. DAA supplements are marketed as “testosterone boosters”.

How does DAA work?

DAA accumulates in neuroendocrine tissue such as the pituitary gland, pineal gland and gonads (testes and ovaries) where it works as an excitatory compound to stimulate the release of hormones.  As the levels of DAA build up in these tissues it increases the production and release of hormones; of particular interest are testosterone and LH. LH is released from the pituitary gland and it signals the release of testosterone from the testes and progesterone from the ovaries. Once the testosterone has been released in excess; the body works to maintain homeostasis by balancing the hormonal ratios. Negative feedback mechanisms in the pituitary gland switch off further testosterone release to drop testosterone levels and the body starts converting testosterone to estrogen via the enzyme aromatase; DAA also supports this by increasing the aromatization of testosterone to estrogen and testosterone levels drop while estrogen increases to normalize the ratios and maintain equilibrium.

Which hormone it will increase is proportional to existing endogenous and exogenous hormone levels and is regulated by normal negative feedback mechanisms and these conversion pathways; this is what makes DAA supplementation challenging and unpredictable. There is adequate DAA in the diet to fuel the neuroendocrine system especially if the diet is protein adequate. Supplementing with high doses of DAA to saturate the neuroendocrine system and trigger excessive release of hormones will create a temporary spike followed by increased negative feedback and increased conversion to estrogen to maintain hormonal balance.

This is demonstrated in studies that show increase in testosterone after using approximately 3g/day for 12 days of supplementation but other studies show significant drops after 28 days. The higher the doses; the greater the drops in testosterone levels.

As DAA is available naturally in dietary protein it is hard to cycle off DAA to allow the neuroendocrine tissue to deplete its stores and become sensitive to supplementation again as it would if it was a foreign substance or exogenously administered testosterone as seen with testosterone replacement therapy.

Literature review

There have been numerous animal studies confirming the varying actions of DAA to either increase or decrease testosterone and estrogen depending on reproductive cycles. The studies confirmed that DAA is capable of increasing testosterone release and subsequent estrogen production by increasing aromatase activity. The studies on lizards and frogs can’t really relate to humans so they started testing on mammals and came to the same conclusions.

Assisi L Et al. Enhancement of aromatase activity by D-aspartic acid in the ovary of the lizard Podarcis s. sicula. Reproduction. 2001 May;121(5):803-8.

Di Fiore MM et al. D-aspartic acid is implicated in the control of testosterone production by the vertebrate gonad. Studies on the female green frog, Rana esculenta. J Endocrinol. 1998 May;157(2):199-207

Raucci et al. D-Asp: a new player in reproductive endocrinology of the amphibian Rana esculenta. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Nov 1;879(29):3268-76. doi: 10.1016/j.jchromb.2011.04.007. Epub 2011 Apr 13

Lamanna C et al. Endogenous testicular D-aspartic acid regulates gonadal aromatase activity in boar. J Endocrinol Invest. 2006 Feb;29(2):141-6.

Lamanna C et al. Involvement of D-Asp in P450 aromatase activity and estrogen receptors in boar testis.Amino Acids. 2007 Jan;32(1):45-51. Epub 2006 Jun 1.

Lamanna C et al. D-Aspartic acid and nitric oxide as regulators of androgen production in boar testis. Theriogenology. 2007 Jan 15;67(2):249-54. Epub 2006 Sep 22. 1

Di Fiore MM et al. Opposing effects of D-aspartic acid and nitric oxide on tuning of testosterone production in mallard testis during the reproductive cycle Reprod Biol Endocrinol. 2008 Jul 4;6:28. doi: 10.1186/1477-7827-6-28.

Human studies for testosterone production showed similar trends as seen in the other animal mammal studies. In 2009 Topo et al studied a product which supplied approximately 3g of sodium-d-aspartate combined with an undisclosed amount of vitamins B12, B6 and folate in 23 men for 12 days compared to 20 men using placebo (placebo was sodium chloride, vitamins B6, B12 and folate) and this study showed an increase in LH and testosterone release compared to placebo. In this study they also studied the mechanism of action in rats.

Topo E 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 Oct 27;7:120. doi: 10.1186/1477-7827-7-120.

These findings were replicated using the DADAVIT TM product supplying approximately 2.6g of DAA for 90 days and showed improvement in testosterone levels and sperm production in infertile men with hormonal problems and sperm deficiencies. Unfortunately, this is not applicable to the general population or in healthy trained men. So further studies were designed to try and recreate these effects in the general population.

Gemma D’Aniello et al. D-Aspartate, a Key Element for the Improvement of Sperm Quality. Advances in Sexual Medicine, 2012, 2, 47-53

In 2013, Willoughby et al. studied 3g per day for 28 days and showed no effects on body composition, muscle strength, testosterone or estrogen associated in resistance-trained men.

Willoughby DS et al. 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 Oct;33(10):803-10. doi: 10.1016/j.nutres.2013.07.010. Epub 2013 Aug 15.

In 2015, Melville GW et al tried to reproduce the same study as Willoughby et al but also tested 6g dose as well as the 3g dose to try and establish the effective dose. The 3g dose had a drop in testosterone instead of an increase but this drop was not statistically significant and they also showed the same as previous studies confirming that 3g per day for 28 days has no effect on improving serum hormones, performance or body composition. But the real surprising find in the study was that the 6g dose showed a greater drop in testosterone that was statistically significant compared to the 3g dose and placebo.

Three and six grams supplementation of d-aspartic acid in resist  

Melville GW et al. Three and six grams supplementation of d-aspartic acid in resistance trained men. J Int Soc Sports Nutr. 2015 Apr 1;12:15. doi: 10.1186/s12970-015-0078-7. eCollection 2015.

Other DAA hormonal effects

In mammals DAA in neuroendocrine tissue facilitates the secretion of Prolactin from the pituitary gland and acts as a negative regulator for melatonin synthesis in the pineal gland.

Di Fiore MM et al. Current knowledge of D-aspartate in glandular tissues. Amino Acids. 2014 Aug;46(8):1805-18. doi: 10.1007/s00726-014-1759-2. Epub 2014 May 17.

DAA also enhances prolactin secretion by blocking the feel good hormone Dopamine from being released. Dopamine blocks prolactin secretion. Dopamine is also involved in self worth and the reward centres of the brain.

Pampillo M et al. The effect of D-aspartate on luteinizing hormone-releasing hormone, alpha-melanocyte-stimulating hormone, GABA and dopamine release. Neuroreport. 2002 Dec 3;13(17):2341-4.

Prolactin secretion combined with increased aromatase activity is associated with the formation of gynecomastia (man boobs). Any link with DAA supplementation and gynecomastia is purely speculative at this stage but it is a hypothesis worth investigating further.

2 replies to “The DAA (D-Aspartic Acid) Paradox”

  1. Great article, I am beginning to make sense out of that 12 day period thing. a lot of these studies got going on.

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