Monday, August 19, 2013

When Hype Meets Reality: D-Aspartic Acid Turns Out to Be Another Supplemental Nonstarter in First Human Trial With Any Relevance for Healthy Young Men

Training "on" D-Aspartic Acid is like training on guar gum.
Busted! D-Aspartic acid aka DAA is another "natural anabolic agent" that turns out to be more of a revenue- than a hormone-booster with muscle building prowess. And you know what? It took Darryn S. Willoughby and Brian Leutholtz from the  Exercise and Biochemical Nutrition Lab, Human Performance, and Recreation at Baylor University exactly 28 days and 20 apparently healthy, recreationally active, resistance trained (3x per week or more in the past year) men with an average age of 22.8 ± 4.67 years (BMI 24.65 kg/m²) to prove that d-aspartic acid (DAA) supplements belong to this never-ending list of supplemental non-starters.

Things that work: 28 days, 4x per week heavy resistance training; things that don't work DAA capsules

Willoughby and Leutholtz assigned their participants in a random, double-blinded fashion to one of the two study arms. Subjects in both arms of the study followed a standardized periodized 28-day resistance training program split into 2 upper-extremity (A1, A2) and 2 lower-extremity (B1, B2) exercise sessions each week. With an overall training volume of 16 exercises sessions with 9x upper- and 8x lower-body exercises
  • A1, A2 - upper body: bench press, lat pull, shoulder press, seated rows, shoulder shrugs, chest flies, biceps curl, triceps press down, and abdominal curls
  • B1, B2 - lower body: leg press, or squat, back extension, step ups, leg curls, leg extension,heel raises, and abdominal crunches
the same workout hat shown to elicit significant improvements in body composition in two previous studies on VPX' preworkout products (learn more; cf. Shelmadine. 2009; Spillane. 2011). The participants performed 3 sets of 10 repetitions at 70% - 80% of the previously established 1-RM for all exercises and had 2 minutes of passive rest between the sets. Contrary to the said VPX studies, the participants had to refrain from taking any kitchen-sink pre-/post-workout supplements, as well as the obvious roids, prohormones or other ergogenic substances that would compromise the study results. Instead, they received either...
  • 4 capsules containing 3 g of guar gum (PLA), or
  • 4 capsules containing 3 g of D-ASP (Better Body Sports, Ventura, CA, USA)
The dosing was identical to the manufacturers recommendation and based on the previous study by Topo et al. (2009) that caused the whole DAA hype back ~5 years ago (see figure 2, as well).
Figure 1: Endocrine and body composition changes with placebo or DAA supplementation (Willoughby. 2013)
That fact the whole hoopla was exactly that: All hype! is difficult to refute, if you take a look at the study outcomes in figure 1 or the researchers' conclusion:
"[...] 28 days of D-ASP of supplementation at a daily dose of 3 g is ineffective in upregulating the activity of the HPG axis and has no preferential effects in which to increase skeletal muscle mass and strength in resistance-trained men." (Willoughby. 2013)
In their discussion of what might be the physiological reasons for the non-existent effects on the gonadal production of testosterone the researchers state:
Figure 2: Comparison of the hormonal effect of DAA in sedentary men with low testosterone levels (Topo. 2009) vs. trainees with normal to high levels of testosterone (Willoughby. 2013)
"Based on our data presented herein, this [=the fact that the serum levels of DAA were higher than normal, but nothing happened] may indicate another potential mechanistic reason why the HPG [hypothalamus > pituitary > gonads] axis was not affected by D-ASP supplementation. Although we observed nonsignificant increases in serum D-ASP in the DAA group, we showed significant increases in DDO levels in response to D-ASP supplementation. The degradative role of DDO is to catalyze the oxidative deamination of D-amino acids to generate the corresponding 2-oxo acids, along with hydrogen peroxide and ammonia (or methylamine).

In rodents, the administration of D-ASP was shown to increase DDO activity (Nagasaki. 1994; Yamada.1989), suggesting that DDO activity is induced by increased levels of D-ASP. Based on this information, in the present study, it is possible that because of the higher baseline levels of testosterone, as a means of androgen-regulated feedback of the HPG axis, the level of serum D-ASP induced by supplementation was conceivably being degraded by DDO at a rate that rendered it unable to effectively activate the HPG axis." (Willoughy. 2013)
Or to put is simply: If DAA works at all, it works only in guys like the participants of the 2009 study by Topo et al. who had baseline testosterone levels at the lower end of the normal range (4.5ng/ml) at the beginning of the study and average levels (6.4ng/ml) at the end of the study period. In trained athletes with testosterone levels in the range of 8ng/ml such as the guys in the Willoughby study the negative feedback will prevent any further increase in testosterone.

Does testosterone actually build muscle and are natty test boosters worth your money? (learn more)
Bottom line: Before we have counter-evidence (this is science guys, you can't say something definitive based on one study) there is no good reason for someone with normal testosterone levels to spend money on D-Aspartic acid supplements.

Whether the same would be true for guys on post-cycle therapy or those who want to combat diet- / overtraining induced reductions in testosterone would certainly be worth investigating. Other aspects that could make a difference are the form of delivery (although this did not seem to be a problem; after all the DAA levels rose) and the provision of adjuvants to block the negative feedback on the HPG (see explanation above).

References:
  • Nagasaki H. Gender-related differences of mouse liver-D-aspartate oxidase in the activity and response to administration of D-aspartate and peroxisome proliferators. Int J Biochem 1994;26:415–23.
  • Shelmadine B, Cooke M, Buford T, Hudson G, Redd L, Leutholtz B, et al. Effects of 28 days of resistance exercise and consuming a commercially available pre-workout supplement, NO-shotgun, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers in males. J Int Soc Sports Nutr
    2009;6:16.
  • Spillane M, Schwarz N, Leddy S, Correa T, Minter M, Longoria V, et al. Effects of 28 days of resistance exercise while consuming commercially available pre- and post-workout supplements, NO-shotgun and NO-synthesize on body com position, muscle strength and mass, markers of protein synthesis, and clinical safety markers in males. Nutr Metab (Lond) 2011;8:78
  • Topo E, Soricelli A, D'Aniello A, Ronsini S, D'Aniello G. 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;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.  Nutrition Research, Available online 15 August 2013. 
  • Yamada R, Nagasaki H, Nagata Y, Wakabayashi Y, Iwashima A. Administration ofD-aspartate increasesD-aspartate oxidase activity in mouse liver. Biochim Biophys Acta 1989;990:325–8.