Stress-related Changes in Inflammation
Conditions
Keywords
affect, inflammation
Brief summary
This study is designed to examine the effects of fish oil on immune function and mood in medical students.
Detailed description
This study will examine how supplementation with omega-3 polyunsaturated fatty acids (key fish oil components) affects immune and mood responses to examination stress. This study will examine these outcomes in medical students during academic examination periods as well as less stressful non-exam periods. Participants will take fish oil supplements or placebo pills for approximately 3 months during which time relevant mood, endocrine, and immune measures will be assessed. For detailed information about the study, please visit our website at http://www.stressandhealth.org
Interventions
DIETARY_SUPPLEMENTomega-3 supplementation
2.5 g/day omega-3
DIETARY_SUPPLEMENTOral omega-3 fish oil placebo
to match experimental dosage
Sponsors
Office of Dietary Supplements (ODS)
National Center for Complementary and Integrative Health (NCCIH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* OSU preclinical medical or dental student, or graduate nursing student * male or female
Exclusion criteria
* taking certain medications with immune or endocrine effects * chronic health conditions * smoking * excessive use of alcohol or caffeine * significant digestive problems * routine use of fish oil or flaxseed supplements or high fish intake * fish allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum ln(IL-6) | every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points) | log-transformed serum Interleukin-6 (IL-6) Serum cytokine levels provide an assessment of systemic inflammation, the cytokine level circulating throughout the body. Higher levels are typically interrupted as worse unless an individual is acutely ill. Stimulated cytokine production reflects the inflammatory cytokine production capacity of monocytes. |
| Serum ln(TNF-a) | every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points) | log-transformed serum Tumor Necrosis Factor-alpha (TNF-alpha) All cytokine measurements (e.g., IL-6 and TNF-a, serum and stimulated) were analyzed across time; however, no stress effects were found. Therefore, all assessments post-supplementation were averaged (time points 3-6) and analyzed to determine whether fish oil supplementation had an effect. Pooling these 4 assessments provides a better estimate of an individual's cytokine levels because single time point measurements can be affected by changes in exercise, alcohol consumption, or sleep in the preceding 24-48 hours. |
| Stimulated ln(IL-6) | every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points) | log-transformed stimulated IL-6 Serum cytokine levels provide an assessment of systemic inflammation, the cytokine level circulating throughout the body. Higher levels are typically interrupted as worse unless an individual is acutely ill. Stimulated cytokine production reflects the inflammatory cytokine production capacity of monocytes. |
| Stimulated ln(TNF-alpha) | every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points) | log-transformed stimulated TNF-alpha |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ln(Beck Anxiety Score) | every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points) | log-transformed Beck anxiety score, min-max values - 0-4.1: higher means greater anxiety |
| ln(CES-D) | every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points) | log-transformed Center for Epidemiologic Studies Depression Scale (CES-D) score The CES-D is a self-report scale designed to measure current symptoms of depression rated on a four-point likert scale. Scores range from 0-60, with higher scores indicating a higher frequency of depressive symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo oral Omega-3 fish oil supplementation | 34 |
| Omega-3 Fish Oil Supplement oral Omega-3 fish oil supplementation, 2.496 grams of omega-3/day (2085 mg of eicosapentaenoic acid \[EPA\] and 348 mg of docosahexaenoic acid \[DHA\]) | 34 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Omega-3 Fish Oil Supplement | Placebo | 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 | 34 Participants | 34 Participants | 68 Participants |
| Age Continuous | 23.9 years STANDARD_DEVIATION 2 | 23.4 years STANDARD_DEVIATION 1.7 | 23.6 years STANDARD_DEVIATION 1.9 |
| Region of Enrollment United States | 34 participants | 34 participants | 68 participants |
| Sex: Female, Male Female | 16 Participants | 14 Participants | 30 Participants |
| Sex: Female, Male Male | 18 Participants | 20 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 34 | 20 / 34 |
| serious Total, serious adverse events | 0 / 34 | 0 / 34 |
Outcome results
Primary
Serum ln(IL-6)
log-transformed serum Interleukin-6 (IL-6) Serum cytokine levels provide an assessment of systemic inflammation, the cytokine level circulating throughout the body. Higher levels are typically interrupted as worse unless an individual is acutely ill. Stimulated cytokine production reflects the inflammatory cytokine production capacity of monocytes.
Time frame: every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points)
Population: intention to treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Serum ln(IL-6) | 0.054 ln(pg/mL) | Standard Error 0.07 |
| Omega-3 Fish Oil Supplement | Serum ln(IL-6) | 0.051 ln(pg/mL) | Standard Error 0.069 |
p-value: 0.9795% CI: [-0.18, 0.18]Mixed Models Analysis
Primary
Serum ln(TNF-a)
log-transformed serum Tumor Necrosis Factor-alpha (TNF-alpha) All cytokine measurements (e.g., IL-6 and TNF-a, serum and stimulated) were analyzed across time; however, no stress effects were found. Therefore, all assessments post-supplementation were averaged (time points 3-6) and analyzed to determine whether fish oil supplementation had an effect. Pooling these 4 assessments provides a better estimate of an individual's cytokine levels because single time point measurements can be affected by changes in exercise, alcohol consumption, or sleep in the preceding 24-48 hours.
Time frame: every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points)
Population: intention to treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Serum ln(TNF-a) | 0.61 ln(pg/mL) | Standard Error 0.028 |
| Omega-3 Fish Oil Supplement | Serum ln(TNF-a) | 0.54 ln(pg/mL) | Standard Error 0.027 |
p-value: 0.0695% CI: [-0.15, 0.002]Mixed Models Analysis
Primary
Stimulated ln(IL-6)
log-transformed stimulated IL-6 Serum cytokine levels provide an assessment of systemic inflammation, the cytokine level circulating throughout the body. Higher levels are typically interrupted as worse unless an individual is acutely ill. Stimulated cytokine production reflects the inflammatory cytokine production capacity of monocytes.
Time frame: every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points)
Population: intent to treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Stimulated ln(IL-6) | 11.1 ln(pg/mL) | Standard Error 0.051 |
| Omega-3 Fish Oil Supplement | Stimulated ln(IL-6) | 10.9 ln(pg/mL) | Standard Error 0.05 |
p-value: 0.0495% CI: [-0.3, -0.009]Mixed Models Analysis
Primary
Stimulated ln(TNF-alpha)
log-transformed stimulated TNF-alpha
Time frame: every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points)
Population: intention to treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Stimulated ln(TNF-alpha) | 7.4 ln(pg/mL) | Standard Error 0.061 |
| Omega-3 Fish Oil Supplement | Stimulated ln(TNF-alpha) | 7.3 ln(pg/mL) | Standard Error 0.06 |
p-value: 0.0895% CI: [-0.33, 0.018]Mixed Models Analysis
Secondary
ln(Beck Anxiety Score)
log-transformed Beck anxiety score, min-max values - 0-4.1: higher means greater anxiety
Time frame: every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points)
Population: intention to treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | ln(Beck Anxiety Score) | 1.2 units | Standard Error 0.075 |
| Omega-3 Fish Oil Supplement | ln(Beck Anxiety Score) | 0.93 units | Standard Error 0.076 |
p-value: 0.0495% CI: [-0.44, -0.011]Mixed Models Analysis
Secondary
ln(CES-D)
log-transformed Center for Epidemiologic Studies Depression Scale (CES-D) score The CES-D is a self-report scale designed to measure current symptoms of depression rated on a four-point likert scale. Scores range from 0-60, with higher scores indicating a higher frequency of depressive symptoms.
Time frame: every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points)
Population: intention to treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | ln(CES-D) | 1.6 scores on a | Standard Error 0.097 |
| Omega-3 Fish Oil Supplement | ln(CES-D) | 1.6 scores on a | Standard Error 0.098 |
p-value: 0.9395% CI: [-0.26, 0.29]Mixed Models Analysis