NAC Lowers DOMS, Initially, but on Day 5-6 it Makes Things Worse | Plus: Putative Performance Benefit is Negligible

In the long run, choking the exercise-induced fire too much is going to negate all the cherishable benefits of working out.

As a SuppVersity reader, you know what hormesis is and are aware that the proinflammatory assault of exercise, is an essential stimulant to musculoskeletal adaptation - a number of human and dozens of animal experiments show: if you quell the production of pro-inflammatory reactive oxygen species with high doses of vitamin C and E the growth and health response to exercise will be impaired. And vitamin C + E are not the only radical scavengers with this side effect.

In 2013, I wrote about a study that clearly demonstrated how N-acetyl-l-cysteine aka NAC "Reduces Inflammation, Muscle Injury & Cytokine Expression, but Impairs Anabolic Signaling, Satellite Cell Activity and Recovery" (re-read it) - keep that in mind before getting overly excited.
Hence, NAC supplements shouldn't be used chronically. To control the inflammatory response to a workout and be able to return to the grind earlier, however, many people still rely on its noticeable ability to reduce early onset of DOMS (deep onset muscle soreness - learn more).

Is taking NAC ever a good idea for athletes?

Well, the good news for NAC lovers is: When used during a short competition, sportsmen and -women can actually benefit from the anti-DOMS effects, a recent study from the University of Auckland (Rhodes 2018) confirmed when it investigated...

"whether NAC supplementation decreases muscle soreness and enhances performance in a semi-elite sport setting [as well as] adverse effects and the tolerability of oral NAC supplementation" (Rhodes 2018).

The bad news is that using NAC for that very purpose won't just impair long-term gains, it would also backfire in terms of the what one could call a delayed DOMS response (if DOMS wasn't already delayed onset muscle soreness, obviously) on day 5-6 of the recovery period.

Figure 1: Schematic overview of the experimental design. Preliminary YYIRT-L1 performance measures were taken during preseason training, and post-supplementation performance measures were performed on days 5 and 6 of supplementation (NAC or placebo). Side effects and subjective muscle soreness were monitored through a daily TXT message during the supplementation period. NAC = N-acetylcysteine (Rhodes 2018).

That's at least what Rhodes' et al's observation that the initial "likely protective effect" (−19% ± 27%) on subjective muscle soreness of the 28 semi-professional, semi-elite male rugby players (age = 20.4 ± 0.9 yrs, height = 182.3 ± 7.4 cm, weight = 103 ± 12 kg, Yo-Yo Intermittent Recovery Test Level 1 [YIRT-L1] = 17.14 ± 1.73 level) who participated in the study, turned out to be reversed after 5-6 days of supplementation with 1g of NAC to when the authors observed a "very likely harmful effect" (71% ± 59%).

Figure 2: Running times (lower = better) and subjectively measured muscle soreness before during and at the end of the 6-day intervention with 1g of NAC in 28 semi-professional, semi-elite male rugby players (Rhodes 2018).

The effects on the actual exercise performance during the shuttle-run, on the other hand, were negligible - yes, this means you can safely ignore them. Everbody can tell that by looking at the running times in Figure 2, ... and yes, I don't care that the results of the “sportsci” parallel group trial spreadsheet (Hopkins 2015) suggest a "likely beneficial performance effect on maximum shuttle sprint time (2.4%; 90% confidence limit ± 4.8%)".
To be fair, I should point out that the authors refrain from claiming to have a found a practically relevant performance benefit, when they write that..."this study was unable to demonstrate a clear effect of 1 g NAC on total time to complete a broken bronco exercise protocol" - that this was due to the low dosage of NAC, which is what they claim right after the cited passage, though, sounds a bit biased; and that despite the quoted results from a 2011 study by Cobley et al. (Cobley 2011), who gave their participants a higher dose of 50 mg/kg/day and observed an increase in YYIRT-L1 performance over time, with the greatest performance enhancement seen on the last testing session (three sessions in total).

When it comes to choosing whether and at which dose to use NAC (or vitamin C and vitamin E) you must consider hormetic dose-response relationship between stress exposure (X-axis) and adaptational response (Y-axis). Stimulatory effects occur in the low-dose region at the left of the no-observed-effects-level (NOAEL), whereas adverse effects occur in the high-dose region at the right of the NOAEL - The higher your baseline stress the more likely you'll benefit from antioxidants by reducing the background noise and enhancing the signal:noise ratio (Agathokleous 2018)

Overall, we need more research before we can - with some confidence - advice athletes to consume (high dose) NAC supplements during phases of intense competition; and that is particularly true for the purported recovery- and performance-enhancing effects semi-elite athletes are supposed to experience during exercise sessions with a high turnaround rate.
References:

• Agathokleous, Evgenios, Mitsutoshi Kitao, and Edward J. Calabrese. "Environmental hormesis and its fundamental biological basis: Rewriting the history of toxicology." Environmental research 165 (2018): 274-278.
• Cobley, James N., et al. "N-Acetylcysteine’s attenuation of fatigue after repeated bouts of intermittent exercise: practical implications for tournament situations." International journal of sport nutrition and exercise metabolism 21.6 (2011): 451-461.
• Rhodes, etal. "Acute Effect of Oral N-Acetylcysteine on Muscle Soreness and Exercise Performance in Semi-Elite Rugby Players". Journal of Dietary Supplements (2018).