Clinical trial NCT06252519: Pharmacokinetic Profile of N-Acetyl Cysteine
Official title: Pharmacokinetic Profile of N-Acetyl Cysteine in Self-reported Healthy Men and Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pharmacokinetics
Keywords: N-Acetyl Cysteine
N-Acetyl Cysteine Ethyl Ester
Lead sponsor: University of Memphis
Sponsor class: OTHER
Collaborators: name: Nature Fusions
First posted: 2024-02-09
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized cross-over single-blinded study
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

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

Primary outcomes:
measure: Area under the concentration curve for glutathione
timeFrame: 24 hour period following supplement ingestion
measure: Terminal Half-life of glutathione
timeFrame: 24 hour period following supplement ingestion
measure: Peak concentration of glutathione
timeFrame: 24 hour period following supplement ingestion
measure: Time to maximum concentration
timeFrame: 24 hour period following supplement ingestion
measure: Lag time
timeFrame: 24 hour period following supplement ingestion
measure: Apparent volume distribution during terminal elimination phase
timeFrame: 24 hour period following supplement ingestion
measure: Oral Clearance of glutathione
timeFrame: 24 hour period following supplement ingestion
Secondary outcomes:
measure: Blood Malondialdehyde
timeFrame: 0 min prior to supplement ingestion (baseline)
measure: Blood Malondialdehyde
timeFrame: 2 hours following supplement ingestion
measure: Blood Malondialdehyde
timeFrame: 4 hours following supplement ingestion
measure: Blood Malondialdehyde
timeFrame: 8 hours following supplement ingestion
measure: Blood Malondialdehyde
timeFrame: 24 hours following supplement ingestion
measure: Blood Advanced Oxidation Protein Products
timeFrame: 0 min prior to supplement ingestion (baseline)
measure: Blood Advanced Oxidation Protein Products
timeFrame: 2 hours following supplement ingestion
measure: Blood Advanced Oxidation Protein Products
timeFrame: 4 hours following supplement ingestion
measure: Blood Advanced Oxidation Protein Products
timeFrame: 8 hours following supplement ingestion
measure: Blood Advanced Oxidation Protein Products
timeFrame: 24 hours following supplement ingestion
measure: Brunel Mood Scale
timeFrame: 0 min prior to supplement ingestion (baseline)
measure: Brunel Mood Scale
timeFrame: 2 hours following supplement ingestion
measure: Brunel Mood Scale
timeFrame: 4 hours following supplement ingestion
measure: Brunel Mood Scale
timeFrame: 8 hours following supplement ingestion
measure: Brunel Mood Scale
timeFrame: 24 hours following supplement ingestion
measure: Subjective Feelings
timeFrame: 0 min prior to supplement ingestion (baseline)
measure: Subjective Feelings
timeFrame: 2 hours following supplement ingestion
measure: Subjective Feelings
timeFrame: 4 hours following supplement ingestion
measure: Subjective Feelings
timeFrame: 8 hours following supplement ingestion
measure: Subjective Feelings
timeFrame: 24 hours following supplement ingestion
Other outcomes:
measure: Heart Rate
timeFrame: 0 min prior to supplement ingestion (baseline)
measure: Heart Rate
timeFrame: 0.25 hours following supplement ingestion
measure: Heart Rate
timeFrame: 0.5 hours following supplement ingestion
measure: Heart Rate
timeFrame: 1 hour following supplement ingestion
measure: Heart Rate
timeFrame: 1.5 hours following supplement ingestion
measure: Heart Rate
timeFrame: 2 hours following supplement ingestion
measure: Heart Rate
timeFrame: 4 hours following supplement ingestion
measure: Heart Rate
timeFrame: 6 hours following supplement ingestion
measure: Heart Rate
timeFrame: 8 hours following supplement ingestion
measure: Heart Rate
timeFrame: 24 hours following supplement ingestion
measure: Diastolic Blood Pressure
timeFrame: 0 min prior to supplement ingestion (baseline)
measure: Diastolic Blood Pressure
timeFrame: 0.25 hours following supplement ingestion
measure: Diastolic Blood Pressure
timeFrame: 0.5 hours following supplement ingestion
measure: Diastolic Blood Pressure
timeFrame: 1 hour following supplement ingestion
measure: Diastolic Blood Pressure
timeFrame: 1.5 hours following supplement ingestion
measure: Diastolic Blood Pressure
timeFrame: 2 hours following supplement ingestion
measure: Diastolic Blood Pressure
timeFrame: 4 hours following supplement ingestion
measure: Diastolic Blood Pressure
timeFrame: 6 hours following supplement ingestion
measure: Diastolic Blood Pressure
timeFrame: 8 hours following supplement ingestion
measure: Diastolic Blood Pressure
timeFrame: 24 hours following supplement ingestion
measure: Systolic Blood Pressure
timeFrame: 0 min prior to supplement ingestion (baseline)
measure: Systolic Blood Pressure
timeFrame: 0.25 hours following supplement ingestion
measure: Systolic Blood Pressure
timeFrame: 0.5 hours following supplement ingestion
measure: Systolic Blood Pressure
timeFrame: 1 hour following supplement ingestion
measure: Systolic Blood Pressure
timeFrame: 1.5 hours following supplement ingestion
measure: Systolic Blood Pressure
timeFrame: 2 hours following supplement ingestion
measure: Systolic Blood Pressure
timeFrame: 4 hours following supplement ingestion
measure: Systolic Blood Pressure
timeFrame: 6 hours following supplement ingestion
measure: Systolic Blood Pressure
timeFrame: 8 hours following supplement ingestion
measure: Systolic Blood Pressure
timeFrame: 24 hours following supplement ingestion
Locations:
city: Memphis
country: United States
facility: Center for Nutraceutical and Dietary Supplement Research
state: Tennessee
Study officials:
affiliation: University of Memphis
name: Richard Bloomer, PhD
role: PRINCIPAL_INVESTIGATOR
References: