Acute supplementation with a curcuminoid-based formulation fails to enhance resting or exercise-induced NRF2 activity in males and females

Josh Thorley; Abrar Alhebshi; Ana Rodriguez-Mateos; Zicheng Zhang; Stephen J Bailey; Neil R W Martin; Nicolette C Bishop; Tom Clifford

doi:10.1039/d4fo02681k

Acute supplementation with a curcuminoid-based formulation fails to enhance resting or exercise-induced NRF2 activity in males and females

Josh Thorley, Abrar Alhebshi, Ana Rodriguez-Mateos, Zicheng Zhang, Stephen J Bailey, Neil R W Martin, Nicolette C Bishop, Tom Clifford

Nutritional Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Purpose: Exercise and (poly)phenols may activate nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that coordinates antioxidant synthesis. The purpose of this study was to determine whether curcuminoid supplementation augments resting and exercise-induced NRF2 activity. Methods: In a double-blinded, randomised, between-subjects design, 14 males and 12 females performed plyometric exercise (100 drop jumps, 50 squat jumps) following 4 d supplementation with a curcuminoid-based formulation (CUR + EX; n = 13; ∼200 mg d ⁻¹ curcuminoids) or a placebo (PLA + EX; n = 13). NRF2/DNA binding in peripheral blood mononuclear cells, plasma glutathione peroxidase (GPX), and plasma cytokines (interleukin-6 [IL-6], tumour necrosis factor-alpha [TNF-α]) were measured pre-, post-, 1, 2 h post-exercise. Curcuminoid metabolites were measured 0, 1, 2 h post-administration of a single bolus. Results: Total area under the curve for total curcuminoid metabolites was greater in CUR + EX (p < 0.01), with bioavailability peaking at 2 h post administration (CUR + EX: [0 h] 80.9 ± 117 nM [1 h] 76.6 ± 178.5 nM [2 h] 301.1 ± 584.7 nM; PLA + EX: [0 h] 10.4 ± 1.6 [1 h] 8.5 ± 2.6 [2 h] 10.6 ± 2.1). NRF2 activity did not increase in PLA + EX (p = 0.78) or CUR + EX (p = 0.76); however, curcuminoid metabolite concentrations did positively predict NRF2/DNA binding (R ² = 0.39; p = 0.02). Exercise increased IL-6 (p = 0.03) but TNF-α was unresponsive (p = 0.97) and lower across PLA + EX (p = 0.03). GPX activity was higher in CUR + EX (p < 0.01) but not in PLA + EX (p = 0.94). Conclusion: Supplementation with a curcuminoid-based formulation failed to augment resting or exercise-induced NRF2/DNA binding; however, higher concentrations of curcuminoid metabolites predicted NRF2/DNA binding response, suggesting effects may be dependent on bioavailability.

Original language	English
Pages (from-to)	10782-10794
Number of pages	13
Journal	Food & Function
Volume	15
Issue number	21
DOIs	https://doi.org/10.1039/d4fo02681k
Publication status	E-pub ahead of print - 11 Oct 2024

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10.1039/d4fo02681k

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Thorley, J., Alhebshi, A., Rodriguez-Mateos, A., Zhang, Z., Bailey, S. J., Martin, N. R. W., Bishop, N. C., & Clifford, T. (2024). Acute supplementation with a curcuminoid-based formulation fails to enhance resting or exercise-induced NRF2 activity in males and females. Food & Function, 15(21), 10782-10794. Advance online publication. https://doi.org/10.1039/d4fo02681k

@article{b12a1f0579a3449eb70d9f69098cbb19,

title = "Acute supplementation with a curcuminoid-based formulation fails to enhance resting or exercise-induced NRF2 activity in males and females",

abstract = "Purpose: Exercise and (poly)phenols may activate nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that coordinates antioxidant synthesis. The purpose of this study was to determine whether curcuminoid supplementation augments resting and exercise-induced NRF2 activity. Methods: In a double-blinded, randomised, between-subjects design, 14 males and 12 females performed plyometric exercise (100 drop jumps, 50 squat jumps) following 4 d supplementation with a curcuminoid-based formulation (CUR + EX; n = 13; ∼200 mg d −1 curcuminoids) or a placebo (PLA + EX; n = 13). NRF2/DNA binding in peripheral blood mononuclear cells, plasma glutathione peroxidase (GPX), and plasma cytokines (interleukin-6 [IL-6], tumour necrosis factor-alpha [TNF-α]) were measured pre-, post-, 1, 2 h post-exercise. Curcuminoid metabolites were measured 0, 1, 2 h post-administration of a single bolus. Results: Total area under the curve for total curcuminoid metabolites was greater in CUR + EX (p < 0.01), with bioavailability peaking at 2 h post administration (CUR + EX: [0 h] 80.9 ± 117 nM [1 h] 76.6 ± 178.5 nM [2 h] 301.1 ± 584.7 nM; PLA + EX: [0 h] 10.4 ± 1.6 [1 h] 8.5 ± 2.6 [2 h] 10.6 ± 2.1). NRF2 activity did not increase in PLA + EX (p = 0.78) or CUR + EX (p = 0.76); however, curcuminoid metabolite concentrations did positively predict NRF2/DNA binding (R 2 = 0.39; p = 0.02). Exercise increased IL-6 (p = 0.03) but TNF-α was unresponsive (p = 0.97) and lower across PLA + EX (p = 0.03). GPX activity was higher in CUR + EX (p < 0.01) but not in PLA + EX (p = 0.94). Conclusion: Supplementation with a curcuminoid-based formulation failed to augment resting or exercise-induced NRF2/DNA binding; however, higher concentrations of curcuminoid metabolites predicted NRF2/DNA binding response, suggesting effects may be dependent on bioavailability.",

author = "Josh Thorley and Abrar Alhebshi and Ana Rodriguez-Mateos and Zicheng Zhang and Bailey, {Stephen J} and Martin, {Neil R W} and Bishop, {Nicolette C} and Tom Clifford",

note = "Publisher Copyright: {\textcopyright} 2024 The Royal Society of Chemistry.",

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day = "11",

doi = "10.1039/d4fo02681k",

language = "English",

volume = "15",

pages = "10782--10794",

journal = "Food & Function",

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TY - JOUR

T1 - Acute supplementation with a curcuminoid-based formulation fails to enhance resting or exercise-induced NRF2 activity in males and females

AU - Thorley, Josh

AU - Alhebshi, Abrar

AU - Rodriguez-Mateos, Ana

AU - Zhang, Zicheng

AU - Bailey, Stephen J

AU - Martin, Neil R W

AU - Bishop, Nicolette C

AU - Clifford, Tom

PY - 2024/10/11

Y1 - 2024/10/11

N2 - Purpose: Exercise and (poly)phenols may activate nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that coordinates antioxidant synthesis. The purpose of this study was to determine whether curcuminoid supplementation augments resting and exercise-induced NRF2 activity. Methods: In a double-blinded, randomised, between-subjects design, 14 males and 12 females performed plyometric exercise (100 drop jumps, 50 squat jumps) following 4 d supplementation with a curcuminoid-based formulation (CUR + EX; n = 13; ∼200 mg d −1 curcuminoids) or a placebo (PLA + EX; n = 13). NRF2/DNA binding in peripheral blood mononuclear cells, plasma glutathione peroxidase (GPX), and plasma cytokines (interleukin-6 [IL-6], tumour necrosis factor-alpha [TNF-α]) were measured pre-, post-, 1, 2 h post-exercise. Curcuminoid metabolites were measured 0, 1, 2 h post-administration of a single bolus. Results: Total area under the curve for total curcuminoid metabolites was greater in CUR + EX (p < 0.01), with bioavailability peaking at 2 h post administration (CUR + EX: [0 h] 80.9 ± 117 nM [1 h] 76.6 ± 178.5 nM [2 h] 301.1 ± 584.7 nM; PLA + EX: [0 h] 10.4 ± 1.6 [1 h] 8.5 ± 2.6 [2 h] 10.6 ± 2.1). NRF2 activity did not increase in PLA + EX (p = 0.78) or CUR + EX (p = 0.76); however, curcuminoid metabolite concentrations did positively predict NRF2/DNA binding (R 2 = 0.39; p = 0.02). Exercise increased IL-6 (p = 0.03) but TNF-α was unresponsive (p = 0.97) and lower across PLA + EX (p = 0.03). GPX activity was higher in CUR + EX (p < 0.01) but not in PLA + EX (p = 0.94). Conclusion: Supplementation with a curcuminoid-based formulation failed to augment resting or exercise-induced NRF2/DNA binding; however, higher concentrations of curcuminoid metabolites predicted NRF2/DNA binding response, suggesting effects may be dependent on bioavailability.

AB - Purpose: Exercise and (poly)phenols may activate nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that coordinates antioxidant synthesis. The purpose of this study was to determine whether curcuminoid supplementation augments resting and exercise-induced NRF2 activity. Methods: In a double-blinded, randomised, between-subjects design, 14 males and 12 females performed plyometric exercise (100 drop jumps, 50 squat jumps) following 4 d supplementation with a curcuminoid-based formulation (CUR + EX; n = 13; ∼200 mg d −1 curcuminoids) or a placebo (PLA + EX; n = 13). NRF2/DNA binding in peripheral blood mononuclear cells, plasma glutathione peroxidase (GPX), and plasma cytokines (interleukin-6 [IL-6], tumour necrosis factor-alpha [TNF-α]) were measured pre-, post-, 1, 2 h post-exercise. Curcuminoid metabolites were measured 0, 1, 2 h post-administration of a single bolus. Results: Total area under the curve for total curcuminoid metabolites was greater in CUR + EX (p < 0.01), with bioavailability peaking at 2 h post administration (CUR + EX: [0 h] 80.9 ± 117 nM [1 h] 76.6 ± 178.5 nM [2 h] 301.1 ± 584.7 nM; PLA + EX: [0 h] 10.4 ± 1.6 [1 h] 8.5 ± 2.6 [2 h] 10.6 ± 2.1). NRF2 activity did not increase in PLA + EX (p = 0.78) or CUR + EX (p = 0.76); however, curcuminoid metabolite concentrations did positively predict NRF2/DNA binding (R 2 = 0.39; p = 0.02). Exercise increased IL-6 (p = 0.03) but TNF-α was unresponsive (p = 0.97) and lower across PLA + EX (p = 0.03). GPX activity was higher in CUR + EX (p < 0.01) but not in PLA + EX (p = 0.94). Conclusion: Supplementation with a curcuminoid-based formulation failed to augment resting or exercise-induced NRF2/DNA binding; however, higher concentrations of curcuminoid metabolites predicted NRF2/DNA binding response, suggesting effects may be dependent on bioavailability.

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U2 - 10.1039/d4fo02681k

DO - 10.1039/d4fo02681k

M3 - Article

C2 - 39392053

SN - 2042-6496

VL - 15

SP - 10782

EP - 10794

JO - Food & Function

JF - Food & Function

IS - 21

ER -

Acute supplementation with a curcuminoid-based formulation fails to enhance resting or exercise-induced NRF2 activity in males and females

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