Pharmacokinetic Profile of N-Acetyl Cysteine

Not Applicable

Completed

• Conditions: Pharmacokinetics
• Interventions: Dietary Supplement: NAC; Dietary Supplement: Neuro-NAC; Dietary Supplement: Neuro-NAC XS

• Registration Number: NCT06252519
• Lead Sponsor: University of Memphis

Brief Summary

The study compares three different formulations containing N-Acetyl Cysteine, with regards to acute absorption over a 24-hour period, following single ingestion. The formulations are traditional N-Acetyl Cysteine, N-Acetyl Cysteine Ethyl Ester, and a product containing a combination of N-Acetyl Cysteine Ethyl Ester, glycine, and two minerals with antioxidant potential (selenium and molybdenum) that might enhance the effect of N-Acetyl Cysteine Ethyl Ester. Subjects will report to the lab on three different occasions to consume the products, using a randomized cross-over design, and blood will be collected periodically (for the initial 8 hours and then again at 24 hours) per standard, routinely used pharmacokinetic /pharmacodynamic study protocols for evaluation of circulating glutathione concentrations. The hypothesis for this study is that the combination of N-Acetyl Cysteine Ethyl Ester + glycine will yield the greatest increase in glutathione, followed by N-Acetyl Cysteine Ethyl Ester, followed by N-Acetyl Cysteine. These findings will provide initial evidence specific to the bioavailability of these treatments following a single acute ingestion and may guide future recommendations regarding routine use.

Detailed Description

One method of enhancing the uptake of N-Acetyl Cysteine following oral ingestion is to use the ethyl ester form, referred to as N-Acetyl Cysteine Ethyl Ester, which exerts remarkable antioxidant potential . N-Acetyl Cysteine Ethyl Ester is also available as a dietary supplement, has been well-investigated and known to be much more effective than traditional N-Acetyl Cysteine, in terms of elevating glutathione levels. In addition, recent work indicates that inclusion of the amino acid glycine along with very high dose N-Acetyl Cysteine results in an increase in glutathione, which may have health enhancing benefits for a variety of conditions. Such an elevation in glutathione may provide for antioxidant benefits which can reduce oxidative stress and possibly aid various aspects of overall health, as oxidative stress is associated with disease and aging.

The study compares three different formulations containing N-Acetyl Cysteine, with regards to acute absorption over a 24-hour period, following single ingestion. The formulations are traditional N-Acetyl Cysteine, N-Acetyl Cysteine Ethyl Ester, and a product containing a combination of N-Acetyl Cysteine Ethyl Ester, glycine, and two minerals with antioxidant potential (selenium and molybdenum) that might enhance the effect of N-Acetyl Cysteine Ethyl Ester. Subjects will report to the lab on three different occasions to consume the products, using a randomized cross-over design, and blood will be collected periodically (for the initial 8 hours and then again at 24 hours) per standard, routinely used pharmacokinetic /pharmacodynamic study protocols for evaluation of circulating glutathione concentrations. The hypothesis for this study is that the combination of N-Acetyl Cysteine Ethyl Ester + glycine will yield the greatest increase in glutathione, followed by N-Acetyl Cysteine Ethyl Ester, followed by N-Acetyl Cysteine. These findings will provide initial evidence specific to the bioavailability of these treatments following a single acute ingestion and may guide future recommendations regarding routine use.

Study Timeline

• Study Start: 2023-09-18
• Primary Completion: 2023-12-13
• Study First Submitted: 2024-02-01
• Study First Submitted QC: 2024-02-01
• Study First Posted: 2024-02-09
• Study Completion: 2024-05-22
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-10
• Last Update Posted: 2024-12-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

• Recreationally active (2 or more days per week of exercise for greater than 30 minutes/day)
• Body mass index between 18-29.9 kilograms per meter squared
• fast overnight (greater than 10 hours)
• willing to adhere to study procedures

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Exclusion Criteria

• tobacco user
• chronic disease, including diagnosed digestive disorders
• allergy or sensitivity to study product
• alcohol consumption within 24 hours of study visit
• caffeine consumption within 24 hours of study visit
• active infection or illness
• lactating, pregnant, planning to become pregnant during study

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
NAC, Neuro-NAC XS, then Neuro-NAC	Neuro-NAC XS	Participants receive single dose of NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC XS while on controlled diet. One week later, participants receive 1 dose Neuro-NAC while on controlled diet.
Neuro-NAC, then NAC, then Neuro-NAC XS	Neuro-NAC	Participants receive single dose of Neuro-NAC while on controlled diet. One week later, participants receive 1 dose NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC XS while on controlled diet.
Neuro-NAC, then Neuro-NAC XS, then NAC	NAC	Participants receive single dose of Neuro-NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC XS while on controlled diet. One week later, participants receive 1 dose NAC while on controlled diet.
NAC, then neuro-NAC, then Neuro-NAC XS	NAC	Participants receive single dose of NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC XS while on controlled diet.
NAC, then neuro-NAC, then Neuro-NAC XS	Neuro-NAC	Participants receive single dose of NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC XS while on controlled diet.
NAC, Neuro-NAC XS, then Neuro-NAC	NAC	Participants receive single dose of NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC XS while on controlled diet. One week later, participants receive 1 dose Neuro-NAC while on controlled diet.
Neuro-NAC, then NAC, then Neuro-NAC XS	NAC	Participants receive single dose of Neuro-NAC while on controlled diet. One week later, participants receive 1 dose NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC XS while on controlled diet.
Neuro-NAC XS, then NAC, then Neuro-NAC	Neuro-NAC XS	Participants receive single dose of Neuro-NAC XS while on controlled diet. One week later, participants receive 1 dose NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC while on controlled diet.
Neuro-NAC XS, then Neuro-NAC, then NAC	Neuro-NAC XS	Participants receive single dose of Neuro-NAC XS while on controlled diet. One week later, participants receive 1 dose Neuro-NAC while on controlled diet. One week later, participants receive 1 dose NAC while on controlled diet.
NAC, then neuro-NAC, then Neuro-NAC XS	Neuro-NAC XS	Participants receive single dose of NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC XS while on controlled diet.
Neuro-NAC, then NAC, then Neuro-NAC XS	Neuro-NAC XS	Participants receive single dose of Neuro-NAC while on controlled diet. One week later, participants receive 1 dose NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC XS while on controlled diet.
NAC, Neuro-NAC XS, then Neuro-NAC	Neuro-NAC	Participants receive single dose of NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC XS while on controlled diet. One week later, participants receive 1 dose Neuro-NAC while on controlled diet.
Neuro-NAC, then Neuro-NAC XS, then NAC	Neuro-NAC XS	Participants receive single dose of Neuro-NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC XS while on controlled diet. One week later, participants receive 1 dose NAC while on controlled diet.
Neuro-NAC XS, then NAC, then Neuro-NAC	NAC	Participants receive single dose of Neuro-NAC XS while on controlled diet. One week later, participants receive 1 dose NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC while on controlled diet.
Neuro-NAC XS, then NAC, then Neuro-NAC	Neuro-NAC	Participants receive single dose of Neuro-NAC XS while on controlled diet. One week later, participants receive 1 dose NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC while on controlled diet.
Neuro-NAC XS, then Neuro-NAC, then NAC	Neuro-NAC	Participants receive single dose of Neuro-NAC XS while on controlled diet. One week later, participants receive 1 dose Neuro-NAC while on controlled diet. One week later, participants receive 1 dose NAC while on controlled diet.
Neuro-NAC, then Neuro-NAC XS, then NAC	Neuro-NAC	Participants receive single dose of Neuro-NAC while on controlled diet. One week later, participants receive 1 dose Neuro-NAC XS while on controlled diet. One week later, participants receive 1 dose NAC while on controlled diet.
Neuro-NAC XS, then Neuro-NAC, then NAC	NAC	Participants receive single dose of Neuro-NAC XS while on controlled diet. One week later, participants receive 1 dose Neuro-NAC while on controlled diet. One week later, participants receive 1 dose NAC while on controlled diet.

Primary Outcome Measures

Name	Time	Method
Time to maximum concentration	24 hour period following supplement ingestion	The time to reaching the maximum concentration of reduced glutathione over oxidized glutathione will be determined for each supplement
Area under the concentration curve for glutathione	24 hour period following supplement ingestion	The area under the concentration curve for reduced glutathione over oxidized glutathione will be calculated for each supplement.
Terminal Half-life of glutathione	24 hour period following supplement ingestion	The terminal half-life of reduced glutathione over oxidized glutathione will be calculated for each supplement
Lag time	24 hour period following supplement ingestion	The lag time of each supplement will be determined.
Peak concentration of glutathione	24 hour period following supplement ingestion	The peak concentration of reduced glutathione over oxidized glutathione will be determined for each supplement
Apparent volume distribution during terminal elimination phase	24 hour period following supplement ingestion	The apparent volume distribution during terminal elimination phase will be determined for reduced glutathione over oxidized glutathione
Oral Clearance of glutathione	24 hour period following supplement ingestion	The oral clearance of each supplement will be determined.

Secondary Outcome Measures

Name	Time	Method
Brunel Mood Scale	24 hours following supplement ingestion	The brunel mood scale is a 24-item scale that consists of basic mood descriptors rated by the subject using a 5-point Likert scale where a score of 0 = not at all, 1 = a little, 2 = moderately, 3 = quite a bit, and 4 = extremely.
Blood Malondialdehyde	24 hours following supplement ingestion	The concentration of malondialdehyde in blood will be measured millimoles per liter
Blood Advanced Oxidation Protein Products	24 hours following supplement ingestion	The concentration of blood advanced oxidation protein products will be measured in units of micromoles Chloramine per liter
Subjective Feelings	24 hours following supplement ingestion	Subjective feelings will be self-assessed by subjects for energy, mood, motivation, focus, attention, irritability, and jitters the subject using a 100 mm visual analog scale from 0 (none) to 10 (extreme)

Trial Locations

Locations (1)

Center for Nutraceutical and Dietary Supplement Research; 🇺🇸 Memphis, Tennessee, United States