Air Pollution Toxicity
Conditions
Keywords
air pollution, oxidative stress, intervention
Brief summary
Carnosine is a naturally occurring peptide found in high levels in skeletal muscle and the brain and is also available commercially as a dietary supplement. Since carnosine has anti-oxidant properties and air pollution exposure induces a state of oxidative stress, the purpose of this study is to see if those taking carnosine as a dietary supplement are protected from air pollution-induced oxidative stress and adverse cardiovascular outcomes.
Detailed description
This is a placebo controlled, randomized, double-blind, interventional trial investigating the efficacy of carnosine in reducing the effects of particulate matter air pollution (PM2.5). A total of 240 participants from the Louisville metropolitan and neighboring areas will be randomized into two dietary supplement study groups - carnosine (n=120) versus placebo (n=120). Intervention of study dietary supplements will occur from May through September, when the levels of PM2.5.are highest in the Louisville, KY area. Study participants will be given a daily oral dose of total of 2 grams of carnosine (or placebo) for a total of 12 consecutive weeks (during May through September). Urinary levels of carnosine will be used to screen and identify potential candidates with low carnosine levels. Those with levels less than the median levels of the population, will be invited to participate in the study. The following measurements will be performed - blood and urine sample collection, physical examination, arterial stiffness, physical function, and self-reported surveys on environmental exposure, sleep, diet, and exercise. Supplement intervention (carnosine or placebo) will be initiated at the time of Baseline Assessment and will continue for 12 weeks from that date. Two follow up visits will occur at 6 weeks and 12 weeks respectively after initiating supplementation. This innovative clinical investigation will provide an insight into the pre and post intervention effects of a cheap, safe, and over-the-counter available dietary supplement in countering the effects of air pollution.
Interventions
DIETARY_SUPPLEMENTL-carnosine
a naturally occurring di-peptide
OTHERplacebo
an identically appearing supplement
Sponsors
National Institute of Environmental Health Sciences (NIEHS)
University of Louisville
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
double blind (participant, investigator)
Intervention model description
placebo controlled, randomized, double-blind
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Individuals between 22-65 years of age of either gender and all ethnicities, 2. All genders and all ethnicities 3. Residing in or near the Louisville metropolitan area 4. Consumes some type of meat/fish at least once a month during the past 3 months 5. Carnosine levels below the median level of the population 6. Agrees to complete all study visits and follow study intervention regimen 7. Will be living in the study area throughout the study period, with no more than 1 week away from the study area.
Exclusion criteria
1. Consumed any dietary supplement more than 3 times per week in the past 4 weeks (one month) 2. Current / ongoing treatment for substance abuse 3. Currently undergoing treatment or have conditions which may cause participant to be immunosuppressed 4. Diseases Affecting Peripheral Cell Count (i.e. Autoimmune Diseases - Hashimoto, Rheumatoid Arthritis, SLE, Rheumatoid Arthritis, Sjogren syndrome, Ankylosing Spondylitis, Takayasu arteritis, Kawasaki disease, Polyarteritis nodosa.) 5. Diseases Affecting Bone Marrow capacity 6. Diagnosis of any active cancer 7. Recent organ / kidney transplant or replacement (Active/Long-Term Medications) 8. Type 1 Diabetes Mellitus 9. Untreated thyroid disease 10. Untreated anemia 11. Current acute infections (Influenza, fever, etc.) 12. HIV positive status 13. Active/current Hepatitis HepA, HepB or HepC or in past 6 months 14. Currently or planning to be Pregnant / lactating 15. Prisoners / vulnerable populations 16. Other medical conditions that compromise completion of study 17. Unwilling to provide consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endothelial Progenitor Cells | 3 months | circulating pro-angiogenic cells |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Augmentation Index | 3 months | index of arterial function |
| Endothelial Microparticles | Samples were collected from each participant at baseline, after ~6wk of intervention, and after ~12wk of intervention. Measurement will be performed on archived samples once assay is in place. | index of endothelial damage |
| Platelet Monocyte Aggregates | 3 months | percentage of CD14 events that are co-stained with CD41 (platelet glycoprotein GPIIb); also levels of CD62P (P-selectin) expression |
Countries
United States
Participant flow
Pre-assignment details
Only screened participants with the lowest levels of endogenous carnosine (n=299) were invited to participate in the full study.
Participants by arm
| Arm | Count |
|---|---|
| L-carnosine Group Each participant will be given a daily oral dose of 2 grams of carnosine for 12 weeks
L-carnosine: a naturally occurring di-peptide | 153 |
| Placebo Group Each participant will be given a daily oral dose of 2 grams of placebo for 12 weeks
placebo: an identically appearing supplement | 146 |
| Total | 299 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 13 | 13 |
Baseline characteristics
| Characteristic | L-carnosine Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 153 Participants | 146 Participants | 299 Participants |
| Age, Continuous | 44.4 years STANDARD_DEVIATION 12.4 | 45.1 years STANDARD_DEVIATION 12.4 | 44.8 years STANDARD_DEVIATION 12.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 17 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 130 Participants | 116 Participants | 246 Participants |
| Region of Enrollment United States | 153 participants | 146 participants | 299 participants |
| Sex: Female, Male Female | 89 Participants | 84 Participants | 173 Participants |
| Sex: Female, Male Male | 64 Participants | 62 Participants | 126 Participants |
| urinary carnosine levels | 11.3 nmol/mg creatinine STANDARD_DEVIATION 26.6 | 12.7 nmol/mg creatinine STANDARD_DEVIATION 17.6 | 12.1 nmol/mg creatinine STANDARD_DEVIATION 22.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 153 | 0 / 146 |
| other Total, other adverse events | 24 / 153 | 16 / 146 |
| serious Total, serious adverse events | 3 / 153 | 3 / 146 |
Outcome results
Primary
Endothelial Progenitor Cells
circulating pro-angiogenic cells
Time frame: 3 months
Population: For some participants in both groups, insufficient blood samples were collected or there were errors in processing and data collection. Thus, the n=130 for both groups does not match with number of participants in the study visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| L-carnosine | Endothelial Progenitor Cells | 0.0025 # cells per CD41 minus cells | Standard Error 0.0004 |
| Placebo Group | Endothelial Progenitor Cells | 0.0027 # cells per CD41 minus cells | Standard Error 0.0007 |
Secondary
Augmentation Index
index of arterial function
Time frame: 3 months
Population: For some participants, this data could not be collected, so the n does not equal the total number of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| L-carnosine | Augmentation Index | 122.6 percentage of pulse pressure | Standard Deviation 10.8 |
| Placebo Group | Augmentation Index | 121.4 percentage of pulse pressure | Standard Deviation 10.4 |
Secondary
Endothelial Microparticles
index of endothelial damage
Time frame: Samples were collected from each participant at baseline, after ~6wk of intervention, and after ~12wk of intervention. Measurement will be performed on archived samples once assay is in place.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| L-carnosine | Endothelial Microparticles | 1057 microparticles per microliter | Standard Error 177 |
| Placebo Group | Endothelial Microparticles | 709 microparticles per microliter | Standard Error 69 |
Secondary
Platelet Monocyte Aggregates
percentage of CD14 events that are co-stained with CD41 (platelet glycoprotein GPIIb); also levels of CD62P (P-selectin) expression
Time frame: 3 months
Population: For some participants, blood samples were not collected or there were errors in processing or data collection. Thus n=132 and 128 is less than total number of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| L-carnosine | Platelet Monocyte Aggregates | 12.3 percent of events | Standard Error 0.65 |
| Placebo Group | Platelet Monocyte Aggregates | 10.8 percent of events | Standard Error 0.58 |