Table 4.
Studies included in the systematic review of the effect of N-Acetylcysteine supplementation on health biomarkers.
| First Author, Year of Publication, and Country |
Study Design | Participants (Baseline Sample Size, Age, Sex, Withdrawals, and Final Group Sample Size) | Intervention | Outcomes | Results IG vs. CG |
|---|---|---|---|---|---|
| Christensen et al., 2019, Denmark [21] | Randomized, double-blind crossover, placebo-controlled trial | 11 ♂ Well-trained cyclists Age (mean ± SD) 28 ± 7 years Height (mean ± SD) 183 ± 7 cm Body mass (mean ± SD) 73 ± 10 kg Peak VO2max (mean ± SD) 69 ± 7 mL/min/kg Study withdrawals: 1 (to illness) n = 10 |
1500 mg (20 mg/kg) capsules NAC (Fagron BV, Rotterdam, The Netherlands) 60 min before the test 1 day Washout period: 6 days |
Peak Power Blood Lactate Cycling Economy VO2max TAC Adverse reactions |
↔ Peak Power ↔ Blood Lactate ↔ Cycling Economy ↔ VO2max ↔TAC ↔ Side Effects |
| Corn et al., 2011 USA [22] |
Randomized, double-blind crossover, placebo-controlled trial | 7 ♂ Healthy Age (Range) 20–24 years Body mass (mean ± SD) 89.1 ± 11 kg Height (mean ± SD) 183 ± 5 cm Study withdrawals: 0 |
72.3 ± 1.3 mg/kg Capsules NAC (Physiologics, Northglenn, CO, USA) 60 min before the test 1 day Washout period: 3 days |
Peak Power Time to exhaustion (80, 90, 100, 110%) VO2max GSH |
↑* Peak Power ↑* Time to exhaustion 80% ↔ VO2max ↑* GSH |
| Ferreira et al., 2011 USA [29] |
Randomized, double-blind crossover, placebo-controlled trial | 17 ♂ Healthy Age (mean ± SD) 30 ± 2 years Body Weight (mean ± SD) 86 ± 5 kg |
9 or 18 mg/kg capsules NAC (Physiologics, Northglenn, CO, USA), morning and evening before the test day 35.70 or 140 mg/kg liquid solution NAC (American Regent Laboratories Inc. Shirley, NY, USA), 60 min before the test 1 day Washout period: 7 days |
GSH GSSG CySH CySS CySSG TGSH TCyS |
↑* GSH (140 mg/kg) ↓* GSSG (70, 140 mg/kg) ↑* CySH ↑* CySS ↓* CySSG (70, 140 mg/kg) ↔ TGSH ↑* TCyS ↔ CySH:TCyS ratio (capsules) ↑* CySH:TCyS ratio (líquid) |
| Leelarungrayub et al., 2011 Thailand [30] | Randomized controlled trial | 36 ♂ Healthy Age (range) 20–24 years Body mass index (range) 18.5–24.9 kg/m2 Study withdrawals: 7 16 participants IG 13 participants CG |
1200 mg/day Two doses (600 mg) NAC effervescent powder (FLUIMUCIL A 600, ZAMBON Switzerland, Ltd., Cadempino, Switzerland) 7 days |
Blood Lactate VO2máx % FI TAC TNF-α. CK |
↓* Blood Lactate ↔ VO2máx ↑* % FI ↑* TAC ↔ TNF- α. ↔ CK |
| McKenna et al., 2006, Australia [31] | Randomized, double-blind crossover, placebo-controlled trial | 7 ♂ High endurance trained (running or cycling) 4–5 times per week 1–2 h per day experience ≥ 2 years Age (mean ± SD) 27.1 ± 5.6 years, Weight (mean ± SD) 76.7 ± 10.9 kg Height (mean ± SD) 180 ± 5.4 cm Study withdrawals: 0 |
Intravenous infusion NAC 125 mg/kg/h for 15 min before test plus 25 mg/kg/h until the end of the test. Washout period: 7 days |
Time to exhaustion VO2máx Hb Hct Na+/K+ pump activity Plasma K+ Plasma Electrolyte (Na+, Cl−, Ca2+) Acid–Base Status (HCO3−, PCO2, H+) |
↑* Time to exhaustion ↑* VO2máx ↔ Hb ↔ Hct ↓* Na+/K+ pump activity ↓* Plasma K+ ↔ Plasma Electrolyte ↔ Acid–Base Status |
| Medved et al., 2003, Australia [32] |
Randomized, double-blind crossover, placebo-controlled trial counterbalanced | 8 ♂ Healthy Age (mean ± SD) 22.5 ± 2.4 years Body mass (mean ± SD) 77.81 ± 10.3 kg Height (mean ± SD) 177.6 ± 1.6 cm Study withdrawals: 0 |
Intravenous infusion NAC 125 mg/kg/h for 15 min before test plus 25 mg/kg/h until the end of the test. Washout period: 5–7 days |
Time to exhaustion Total work (kJ) GSH GSSG CySH, CySS TGSH GSH:TGSH ratio Hb Hct Plasma Electrolyte (Na+, Cl−, Ca2+) K+ Acid–Base Status (HCO3-, PCO2−) Adverse reactions |
↔ Time to exhaustion ↔ Total work (kJ) ↑* GSH ↓* GSSG ↑* CySH, ↑* CySS ↔ TGSH ↔ GSH:TGSH ratio ↔ Hb ↔ Hct ↔ Plasma Electrolyte (Na+, Cl−, Ca2+) ↑* K+ ↔ Acid–Base Status (HCO3−, PCO2−) ↑ Side Effects |
| Medved et al., 2004, Australia [33] |
Randomized, double-blind crossover, placebo-controlled trial | 8 ♂ Endurance trained (running or cycling) 4–5 times per week 1–2 h per day experience ≥ 2 years Age (mean ± SD) 27.1 ± 5.6 years Body mass (mean ± SD) 76.7 ± 10.9 kg Height (mean ± SD) 180.3 ± 5.4 cm Study withdrawals: 0 |
Intravenous infusion NAC 125 mg/kg/h for 15 min before test plus 25 mg/kg/h until the end of the test. Washout period: 5–7 days |
Time to exhaustion Total work (kJ) GSH GSSG CySH, CySS TGSH GSH:TGSH ratio Adverse reactions |
↑* Time to exhaustion ↑* Total work (kJ) ↑* GSH ↔ GSSG ↑* TGSH ↑* CySH (muscle; plasma) ↑* CySS (muscle; plasma) ↔ GSSG:TGSH ratio ↔ TSGH:GSH ratio ↑ Side Effects |
| Merry et al. 2010, Australia [34] |
Randomized, double-blind crossover, placebo-controlled trial counterbalanced | 9 ♂ Healthy physically active Age (mean ± SD) 23 ± 2 years Weight (mean ± SD) 79.7 ± 3.4 kg Height (mean ± SD) 179 ± 3 cm Study withdrawals: 0 |
Intravenous infusion NAC (Parvolex, Faulding Pharmaceuticals) 125 mg/kg/h for 15 min before test plus 25 mg/kg/h until the end of the test. Washout period: 14 days |
Blood Lactate O2 Consumption HR RER RPE GSH GSSG GSH:GSSG ratio CySH (muscle; plasma) CySS S-glutathionylation Tyrosine nitration PCr, Cr ATP, ADP, AMP AMP:ATP ratio muscle glycogen Insulin NEFA Adverse reactions |
↔ Blood Lactate ↔ O2 Uptake ↔ HR ↔ RER ↔ RPE ↔ GSH ↔ GSSG ↔ GSH:GSSG ratio ↑* CySH (muscle; plasma) ↑* CySS ↓* S-glutathionylation ↔ Tyrosine nitration ↔ PCr, Cr ↔ ATP, ADP, AMP ↔ AMP:ATP ratio ↔ muscle glycogen ↔ Insulin ↔ NEFA ↔ Side Effects |
| Nielsen et al., 1998, Denmark [35] | Randomized, double-blind crossover, placebo-controlled | 14 ♂ Healthy oarsmen trained Age (mean ± SE) 27 ± 1 years Weight (mean ± SE) 80 ± 2 kg Height (mean ± SE) 189 ± 2 cm VO2max (mean ± SE) 5.1 ± 0.2 L/min |
6000 mg/day 2 daily capsules NAC (ASTRA, Copenhagen, Denmark), 3000 mg Morning and evening meals for 3 days before the experiment, and 2 h before the exercise protocol Washout period: 21 days |
Lymphocytes CD3+ CD4+ CD8+ CD14+ CD16+ CD19+ CD56+ NK activity |
↔ Lymphocytes ↔ CD3+ ↔ CD4+ ↔ CD8+ ↔ CD14+ ↔ CD16+ ↔ CD19+ ↔ CD56+ ↔ NK activity |
| Petersen et al., 2012, Australia [36] |
Randomized, double-blind crossover, placebo-controlled | 8 ♂ Endurance trained (running or cycling) 4–5 times per week 1–2 h per day experience ≥ 2 years Age (mean ± SD) 27.1 ± 5.6 years Body mass (mean ± SD) 76.7 ± 10.9 kg Height (mean ± SD) 180.3 ± 5.4 cm VO2peak 65.6 ± 2.2 mL/kg Study withdrawals: 0 |
Intravenous infusion NAC 125 mg/kg/h for 15 min before test plus 25 mg/kg/h until the end of the test. Washout period: 7 days |
MnSOD JNK ERK1/2 p38 MAPK NF-kB/p65 IkBα IL-6 MCP-1 HSP70 PGC-1α |
↓* MnSOD ↓* JNK ↔ ERK1/2 ↔ p38 MAPK ↓*NF-kB/p65 ↔ IkBα ↔ IL-6 ↔ MCP-1 ↔ HSP70 ↔ PGC-1α |
| Rhodes et al, 2019, Australia [16] | Double-blind, pre-post, placebo-controlled | 17 ♂ Semi-professional/Semi-elite rugby players Age (mean ± SD) 20.4 ± 0.9 years Weight (mean ± SD) 103.0 ± 12.0 kg Height (mean ± SD) 182.3 ± 7.4 cm Yo-Yo Intermittent Recovery Test Level 1 (mean ± SD) 17.4 ± 1.73 Level Study withdrawals: 4 6 participants IG 7 participants CG |
IG: 1 g/day (2 × 50 mg capsules) NAC (Nutrabio Labs Inc., Middlesex, NJ, USA) CG: 1 g (2 × 50 mg capsules) of placebo (sucrose and salt mixture) For 6 days. |
Muscle soreness Broken bronco shuttle test Fastest shuttle time (High-intensity exercise) Side effects |
↑ Muscle Soreness ↔ Broken bronco shuttle test ↑ Fastest shuttle time ↔ Side Effects |
| Silva et al. 2008, Brazil [23] |
Randomized, controlled, single-blind trial | 29 ♂ Healthy physically active Age (mean ± SD) 21.3 ± 4 years Weight (mean ± SD) 74.5 ± 7.7 kg Height (mean ± SD) 177.2 ± 6.9 cm Study withdrawals: 4 8 participants IG 9 participants CG 8 participants IG + CG |
1 capsule/day 10 mg/kg NAC 14 days before the eccentric exercise protocol and 7 days after exercise CG (21 days; placebo) IG (21 days; NAC) IG + CG (14 days NAC + 7 days placebo) |
MDA Carbonylation levels TNF-α IL-10 Muscle pain |
↔ MDA ↔ Carbonylation levels ↑* TNF- α ↑*IL-10 ↓ Muscle Pain |
| Slattery et al., 2014, Australia [24] | Randomized, double-blind crossover, placebo-controlled | 10 ♂ Well-trained triathletes Age (mean ± SD) 23.6 ± 3.2 years Weight (mean ± SD) 70.5 ± 7.2 kg Height (mean ± SD) 179.8 ± 4.4 cm VO2max (mean ± SD) 663.3 ± 4.8 mL/kg/min Study withdrawals: 2 (injury and illness) |
1200 mg NAC (Batch: 254709, The Melbourne Food Ingredient Depot, Victoria, Melburne, Australia), 2 * 600 mg capsules 9 days and 2 h before the test Washout period: 21 days |
Average Power 5, 10, 15 s Total work Blood lactate RPE TAC GSH GSSG GSH: GSSG ratio XO TRABS FRAP IL-6, MPC-1 NF-kB Adverse reactions |
↑* Average Power 5, 10, 15 s ↔ Total work ↔ Blood lactate ↔ RPE ↑* TAC ↔ GSH ↔ GSSG ↔ GSH: GSSG ratio ↔ XO ↓* TRABS ↔ FRAP ↓* IL-6 ↓* MPC-1 ↑* NF-kB ↔ Adverse reactions |
| Smith et al., 2016, USA [25] | Randomized, double-blind crossover, placebo-controlled | 10 ♂ Non-endurance trained Age (mean ± SD) 21.8 ± 1.2 years Weight (mean ± SD) 77.1 ± 17.5 kg Height (mean ± SD) 174.9 ± 9.3 cm Peak Power (mean ± SD) 6.0 ± 1.3 W Study withdrawals: 0 |
70 mg/kg NAC 600 mg/capsule 60 min before the test Washout period: 7 days |
Time to Exhaustion GSH GSSG GSH: GSSG CySH CySS BABF DAB |
↔ Time to Exhaustion ↑* GSH ↑* GSSG ↓* GSH: GSSG ↑* CySH ↑* CySS ↔ BABF ↔ DAB |
| Zembron-Lancy et al., 2007, Poland [27] | Randomized placebo-controlled | 30 ♂ Healthy young trained (Canoeists and Rowers) Age (mean ± SD) CG 21.5 ± 1.4 years IG 21.9 ± 1.7 years Body Mass (mean ± SD) CG 87.2 ± 10.6 kg IG 87.1 ± 12.8 kg Height (mean ± SD) CG 181.7 ± 8.3 cm IG 180.7 ± 7.4 cm Body Fat (mean ± SD) CG 14.4 ± 4.6 % IG 14.5 ± 5.6 % Study withdrawals: 0 15 participants IG 15 participants CG |
IG: 1800 mg/day NAC (Hexal AG, Holzkirchen, Germany) as powder dissolved in 50 mL water CG: 3 × 350 mg/day Saccharum Lactis as powder dissolved in 50 mL water |
Protein Thiols SOD GPx CAT TBARS Pro-Antioxidant ratio |
↑* Protein Thiols ↔ SOD ↑* GPx ↔ GR ↔ CAT ↓* TBARS ↑* Pro-Antioxidant ratio |
| Zembron-Lancy et al., 2010, Poland [26] | 15 ♂ Healthy students Age (mean ± SD) 20.3 ± 2.3 years Body Mass (mean ± SD) 83.4 ± 14.4 kg Height (mean ± SD) 180.0 ± 1.0 cm Study withdrawals: 0 8 participants IG 7 participants CG |
IG: 1200 mg/day NAC 2 daily doses (1st dose in the morning in a fasted state and the second dose 2 h before an evening meal) for 8 days prior to and 1 dose 600 mg on the day of exercise trial Each dose as powder dissolved in 50 mL of water CG: Lactose as powder dissolved in 50 mL of water |
Time to exhaustion Peak Power GSH GPx GR PC TBARS EPO Hb Hct MVC MHC RCB |
↔ Time to exhaustion ↔ Peak Power ↑* GSH ↑* GPx ↑* GR ↓* PC ↓* TBARS ↑* EPO ↑* Hb ↑* Hct ↑* MVC ↑* MHC ↓* RCB |
Abbreviations: ↑ = no significant increase; ↓ = no significant decrease; ↔ = no significant change. ↑* = significant increase; ↓* = significant decrease; *: Indicates significant values (p < 0.05); CG: control Group; IG: Intervention Group; NAC = N-acetylcysteine; SD = Standard deviation; VO2max = Maximum Oxygen Volume; O2 = Oxygen; FI = Fatigue Index; HR = Hear Rate; RPE = Rating of Perceived Exertion; RER = Respiratory Exchange Ratio; TAC = Capacity Antioxidant Total; GSH = Reduced Glutathione; GSSG = Oxidated Glutathione; TGSH = total glutathione; CySH = Cysteine; TCyS = Total Cysteine; CySSG = cysteine glutathione disulphide; CySS = Cystine; SOD = Superoxide Dismutase; MnSOD = Manganese Superoxide Dismutase; MDA = Malonyl Dialdehyde; XO = Xanthine Oxidase; TRABS = Thiobarbituric Acid Reactive Substances; FRAP = iron reducing capacity; CAT = Catalase; GR = Glutathione Reductase; GPx = Glutathione Peroxidase; CK = Creatine Kinase; TNF-α = Tumour Necrosis Factor Alpha; Hb = Haemoglobin; Hct = Haematocrit; PCr = Phosphocreatine; Cr = Creatine; ATP = Adenosine triphosphate; ADP = Adenosine Diphosphate; AMP = Adenosine Monophosphate; NEFA = Non-Esterified Fatty Acids; NK = Natural Killer; JNK = C-Jun-terminal Kinase; MCP-1 = monocyte chemoattractant protein 1; MAPK = mitogenic activation protein kinase; NF-kB = nuclear factor kappa B; IκBα = nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha; IL = Interleukin; PGC-1a = peroxisome proliferator-activated receptor coactivator 1α; HSP-70 = Heat Shock Proteins 70; PC = Carbonyl Proteins.