Pharmacokinetic Profile of N-Acetyl Cysteine

Pharmacokinetic Profile of N-Acetyl Cysteine in Self-reported Healthy Men and Women

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 Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Dietary supplement: NAC; Dietary supplement: Neuro-NAC; Dietary supplement: Neuro-NAC XS

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 Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38152
      • Center for Nutraceutical and Dietary Supplement Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAC, then neuro-NAC, then 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.	Dietary supplement: NAC; 1 375 mg capsule containing N-acetyl cysteine; Dietary supplement: Neuro-NAC; 3 capsules containing a total of 375 mg N-Acetyl L-Cysteine Ethyl Ester; Dietary supplement: Neuro-NAC XS; 3 capsules containing a total of 75 mcg Selenium, 150 mcg Molybdenum, 1800 mg Glycine, and 375 mg N-Acetyl L-Cysteine Ethyl Ester
Experimental: NAC, Neuro-NAC XS, then 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.	Dietary supplement: NAC; 1 375 mg capsule containing N-acetyl cysteine; Dietary supplement: Neuro-NAC; 3 capsules containing a total of 375 mg N-Acetyl L-Cysteine Ethyl Ester; Dietary supplement: Neuro-NAC XS; 3 capsules containing a total of 75 mcg Selenium, 150 mcg Molybdenum, 1800 mg Glycine, and 375 mg N-Acetyl L-Cysteine Ethyl Ester
Experimental: Neuro-NAC, then NAC, then 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.	Dietary supplement: NAC; 1 375 mg capsule containing N-acetyl cysteine; Dietary supplement: Neuro-NAC; 3 capsules containing a total of 375 mg N-Acetyl L-Cysteine Ethyl Ester; Dietary supplement: Neuro-NAC XS; 3 capsules containing a total of 75 mcg Selenium, 150 mcg Molybdenum, 1800 mg Glycine, and 375 mg N-Acetyl L-Cysteine Ethyl Ester
Experimental: Neuro-NAC, then Neuro-NAC XS, then 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.	Dietary supplement: NAC; 1 375 mg capsule containing N-acetyl cysteine; Dietary supplement: Neuro-NAC; 3 capsules containing a total of 375 mg N-Acetyl L-Cysteine Ethyl Ester; Dietary supplement: Neuro-NAC XS; 3 capsules containing a total of 75 mcg Selenium, 150 mcg Molybdenum, 1800 mg Glycine, and 375 mg N-Acetyl L-Cysteine Ethyl Ester
Experimental: Neuro-NAC XS, then NAC, then 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.	Dietary supplement: NAC; 1 375 mg capsule containing N-acetyl cysteine; Dietary supplement: Neuro-NAC; 3 capsules containing a total of 375 mg N-Acetyl L-Cysteine Ethyl Ester; Dietary supplement: Neuro-NAC XS; 3 capsules containing a total of 75 mcg Selenium, 150 mcg Molybdenum, 1800 mg Glycine, and 375 mg N-Acetyl L-Cysteine Ethyl Ester
Experimental: Neuro-NAC XS, then Neuro-NAC, then 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.	Dietary supplement: NAC; 1 375 mg capsule containing N-acetyl cysteine; Dietary supplement: Neuro-NAC; 3 capsules containing a total of 375 mg N-Acetyl L-Cysteine Ethyl Ester; Dietary supplement: Neuro-NAC XS; 3 capsules containing a total of 75 mcg Selenium, 150 mcg Molybdenum, 1800 mg Glycine, and 375 mg N-Acetyl L-Cysteine Ethyl Ester

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Malondialdehyde	The concentration of malondialdehyde in blood will be measured in millimoles per liter	0 min prior to supplement ingestion (baseline)
Blood Malondialdehyde	The concentration of malondialdehyde in blood will be measured millimoles per liter	2 hours following supplement ingestion
Blood Malondialdehyde	The concentration of malondialdehyde in blood will be measured millimoles per liter	4 hours following supplement ingestion
Blood Malondialdehyde	The concentration of malondialdehyde in blood will be measured millimoles per liter	8 hours following supplement ingestion
Blood Malondialdehyde	The concentration of malondialdehyde in blood will be measured millimoles per liter	24 hours following supplement ingestion
Blood Advanced Oxidation Protein Products	The concentration of blood advanced oxidation protein products will be measured in units of micromoles Chloramine per liter	0 min prior to supplement ingestion (baseline)
Blood Advanced Oxidation Protein Products	The concentration of blood advanced oxidation protein products will be measured in units of micromoles Chloramine per liter	2 hours following supplement ingestion
Blood Advanced Oxidation Protein Products	The concentration of blood advanced oxidation protein products will be measured in units of micromoles Chloramine per liter	4 hours following supplement ingestion
Blood Advanced Oxidation Protein Products	The concentration of blood advanced oxidation protein products will be measured in units of micromoles Chloramine per liter	8 hours following supplement ingestion
Blood Advanced Oxidation Protein Products	The concentration of blood advanced oxidation protein products will be measured in units of micromoles Chloramine per liter	24 hours following supplement ingestion
Brunel Mood Scale	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.	0 min prior to supplement ingestion (baseline)
Brunel Mood Scale	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.	2 hours following supplement ingestion
Brunel Mood Scale	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.	4 hours following supplement ingestion
Brunel Mood Scale	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.	8 hours following supplement ingestion
Brunel Mood Scale	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.	24 hours following supplement ingestion
Subjective Feelings	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)	0 min prior to supplement ingestion (baseline)
Subjective Feelings	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)	2 hours following supplement ingestion
Subjective Feelings	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)	4 hours following supplement ingestion
Subjective Feelings	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)	8 hours following supplement ingestion
Subjective Feelings	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)	24 hours following supplement ingestion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	0 min prior to supplement ingestion (baseline)
Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	0.25 hours following supplement ingestion
Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	0.5 hours following supplement ingestion
Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	1 hour following supplement ingestion
Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	1.5 hours following supplement ingestion
Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	2 hours following supplement ingestion
Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	4 hours following supplement ingestion
Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	6 hours following supplement ingestion
Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	8 hours following supplement ingestion
Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	24 hours following supplement ingestion
Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	0 min prior to supplement ingestion (baseline)
Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	0.25 hours following supplement ingestion
Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	0.5 hours following supplement ingestion
Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	1 hour following supplement ingestion
Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	1.5 hours following supplement ingestion
Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	2 hours following supplement ingestion
Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	4 hours following supplement ingestion
Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	6 hours following supplement ingestion
Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	8 hours following supplement ingestion
Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	24 hours following supplement ingestion
Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	0 min prior to supplement ingestion (baseline)
Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	0.25 hours following supplement ingestion
Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	0.5 hours following supplement ingestion
Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	1 hour following supplement ingestion
Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	1.5 hours following supplement ingestion
Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	2 hours following supplement ingestion
Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	4 hours following supplement ingestion
Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	6 hours following supplement ingestion
Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	8 hours following supplement ingestion
Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	24 hours following supplement ingestion

Collaborators and Investigators

• Sponsor: University of Memphis
• Collaborators: Nature Fusions
• Investigators: Principal Investigator: Richard Bloomer, PhD, University of Memphis

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2023
• Primary Completion (Actual): December 13, 2023
• Study Completion (Actual): May 22, 2024

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: February 1, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: N-Acetyl Cysteine; N-Acetyl Cysteine Ethyl Ester
• Other Study ID Numbers: PRO-FY2023-417

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No