Pharmacokinetic Profile of N-Acetyl Cysteine

Pharmacokinetics Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06252519
• Other study ID #: PRO-FY2023-417
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 18, 2023
• Est. completion date: February 28, 2024

Study information

• Verified date: February 2024
• Source: University of Memphis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 8
• Est. completion date: February 28, 2024
• Est. primary completion date: December 13, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Pharmacokinetics

Intervention

Dietary Supplement:
• NAC
1 375 mg capsule containing N-acetyl cysteine
• Neuro-NAC
3 capsules containing a total of 375 mg N-Acetyl L-Cysteine Ethyl Ester
• 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

Locations

Country	Name	City	State
United States	Center for Nutraceutical and Dietary Supplement Research	Memphis	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
University of Memphis	Nature Fusions

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	0 min prior to supplement ingestion (baseline)
Other	Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	0.25 hours following supplement ingestion
Other	Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	0.5 hours following supplement ingestion
Other	Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	1 hour following supplement ingestion
Other	Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	1.5 hours following supplement ingestion
Other	Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	2 hours following supplement ingestion
Other	Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	4 hours following supplement ingestion
Other	Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	6 hours following supplement ingestion
Other	Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	8 hours following supplement ingestion
Other	Heart Rate	Heart Rate will be assessed in beats per minute using an automated blood pressure cuff.	24 hours following supplement ingestion
Other	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)
Other	Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	0.25 hours following supplement ingestion
Other	Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	0.5 hours following supplement ingestion
Other	Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	1 hour following supplement ingestion
Other	Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	1.5 hours following supplement ingestion
Other	Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	2 hours following supplement ingestion
Other	Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	4 hours following supplement ingestion
Other	Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	6 hours following supplement ingestion
Other	Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	8 hours following supplement ingestion
Other	Diastolic Blood Pressure	Diastolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	24 hours following supplement ingestion
Other	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)
Other	Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	0.25 hours following supplement ingestion
Other	Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	0.5 hours following supplement ingestion
Other	Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	1 hour following supplement ingestion
Other	Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	1.5 hours following supplement ingestion
Other	Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	2 hours following supplement ingestion
Other	Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	4 hours following supplement ingestion
Other	Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	6 hours following supplement ingestion
Other	Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	8 hours following supplement ingestion
Other	Systolic Blood Pressure	Systolic blood pressure will be assessed in millimeters mercury using an automated blood pressure cuff.	24 hours following supplement ingestion
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Lag time	The lag time of each supplement will be determined.	24 hour period following supplement ingestion
Primary	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
Primary	Oral Clearance of glutathione	The oral clearance of each supplement will be determined.	24 hour period following supplement ingestion
Secondary	Blood Malondialdehyde	The concentration of malondialdehyde in blood will be measured in millimoles per liter	0 min prior to supplement ingestion (baseline)
Secondary	Blood Malondialdehyde	The concentration of malondialdehyde in blood will be measured millimoles per liter	2 hours following supplement ingestion
Secondary	Blood Malondialdehyde	The concentration of malondialdehyde in blood will be measured millimoles per liter	4 hours following supplement ingestion
Secondary	Blood Malondialdehyde	The concentration of malondialdehyde in blood will be measured millimoles per liter	8 hours following supplement ingestion
Secondary	Blood Malondialdehyde	The concentration of malondialdehyde in blood will be measured millimoles per liter	24 hours following supplement ingestion
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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