Cardiovascular Diseases, Inflammation, Mood Disorders
Conditions
Keywords
Fish Oil, Omega-3 fatty acids, Affect, Depression, Anger, Nutrition, Impulsivity, Aggression, Cognition, Behavior
Brief summary
Omega-3 fatty acids are a certain kind of fish fat that has recently been shown to have health benefits. This study will examine the effectiveness of fish oil supplementation for reducing the early signs of heart disease risk and for improving mood, impulsivity, and anger levels.
Detailed description
Cardiovascular disease (CVD) is a broad term that includes diseases that affect the heart and blood vessels, including coronary heart disease, heart failure, high blood pressure, stroke and vascular dementia. CVD is the leading cause of death in the United States, resulting in 700,000 deaths each year. Preliminary research has shown that increased consumption of fish, specifically the omega-3 fatty acids found in fish oil, has beneficial effects in people with CVD. Fish oil may also have positive effects on the psychological health and well-being of people with psychiatric disorders. However, more research is needed to confirm the positive physical and psychological effects of fish oil in healthy adults. The purpose of this study is to explore potentail effects of fish oil supplementation on CVD mechanisms and risk markers, and on depressive symptoms, antagonistic disposition, and levels of impulsivity and aggression. This study will enroll healthy adults who habitually consume low quantities of long-chain omega-3 fatty acids. Participants will be randomly assigned to receive either fish oil supplements or placebo on a daily basis for 4 months. Study visits will occur at baseline and Months 2 and 4. At the baseline and Month 4 visits, participants will undergo the following measures as primary study aims: blood collection for inflammatory markers; heart rate and variability measurements; and interviews, psychological tests, and questionnaires to assess mood, disposition, impulsivity, and aggression. As secondary aims, we will test for any effects of fish oil on cognitive performance and, if a main effect on inflammatory markers is found, we will test for moderation by select genetic polymorphisms. As an exploratory aim, we will test for any effects of fish oil on structural or functional brain imaging. (This exploratory aim was mistakenly listed as a secondary aim at the time of trial registration.)
Interventions
DIETARY_SUPPLEMENTFish Oil
Participants will take 2 grams (1400 mg EPA and DHA) of fish oil supplements on a daily basis.
DIETARY_SUPPLEMENTSoybean Oil (Placebo)
Participants will take 2 grams of soybean oil supplements on a daily basis.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
National Center for Complementary and Integrative Health (NCCIH)
Office of Dietary Supplements (ODS)
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Currently employed at least 25 hours a week, but does not regularly work the third shift (i.e., night shift) * English is primary language * Consumes less than 300 mg/day of long-chain omega-3 fatty acids.
Exclusion criteria
* Serious allergy to fish (e.g., anaphylaxis, bronchospasm, serious skin reaction) * History of atherosclerotic disease (e.g., myocardial infarction) or treatment of angina or claudication (e.g., angioplasty) * Reported history of schizophrenia or bipolar disorder * Long-term hepatitis * Kidney failure * Stroke or other neurological disorder * Lung disease requiring drug treatment * Stage 2 high blood pressure, defined as systolic blood pressure of 160 mm Hg or greater and diastolic blood pressure of 100 mm Hg or greater * Alcohol consumption of more than five drinks per day each week (i.e., more than 35 alcoholic drinks each week) * Pregnant or breastfeeding * Currently taking any cardiovascular, psychotropic, glucocorticoid, lipid-lowering, insulin, or weight loss medications * Currently taking fish oil supplements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration | baseline and month 4 | High frequency (.12 to .40 Hz) heart rate variability natural log transformed paced respiration in Hertz units (Hz) |
| Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration | baseline and month 4 | Total power (0 to .40 Hz) heart rate variability natural log transformed paced respiration in Hertz (Hz) units. |
| Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Unpaced Respiration | baseline and month 4 | Mean successive difference in inter-beat intervals natural log transformed unpaced respiration in milliseconds (msec) |
| High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration | baseline and month 4 | High frequency (.12 to .40 Hz) heart rate variability natural log transformed unpaced respiration in Hertz (Hz) units |
| Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration | baseline and month 4 | Total power (0 to .40 Hz) heart rate variability natural log transformed unpaced respiration in Hertz (Hz) units |
| Circulating Serum Interleukin-6 (IL-6) | Baseline and Month 4 | Systemic inflammation: fasting serum Interleukin-6 (IL-6) |
| C-reactive Protein (CRP) | baseline and month 4 | fasting serum C-reactive protein (CRP) in milligrams per liter (mg/L) |
| Negative Affect | baseline and month 4 | Negative affect questions adapted from the Positive and Negative Affect Schedule - Expanded Form administered via ecological momentary assessment. The minimum value is 1, and the maximum value is 6. A higher score are worse (more negative affect). |
| Impulsivity | baseline and month 4 | Barratt Impulsiveness Scale. The minimum value is 34, and the maximum value is 120. A higher score suggests a worse outcome. |
| Aggression | baseline and month 4 | Bus-Perry Aggression Questionnaire. The minimum value is 14, and the maximum value is 53. A higher score suggests a worse outcome. |
| Hostility, Barefoot Score | baseline and month 4 | The 27-item Barefoot Hostility Scale. The minimum value is 1, and the maximum value is 30. A higher score suggests a worse outcome. |
| Trait Anger | baseline and month 4 | State-Trait Anger Expression Inventory. The minimum value is 10, and the maximum value is 40. A higher score suggests a worse outcome. |
| Anger Expression | baseline and month 4 | State-Trait Anger Expression Inventory. The minimum value is 0, and the maximum value is 72. A higher score suggests a worse outcome. |
| Type A, Total Score | baseline and month 4 | Structured Interview - Type A Behavior Pattern using the Interpersonal Hostility Assessment Technique (IHAT). The minimum value is 0, and the maximum value is 12. A higher score suggests a worse outcome. |
| Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Paced Respiration | baseline and month 4 | Mean successive difference in inter-beat intervals natural log transformed paced respiration in milliseconds |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Executive Function | Baseline and Month 4 | Executive function was comprised of trail making B - A time, digit span forward and digit span backward completions. Performance scores on each task were converted into Z-scores, and then averaged across tasks. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate higher function (better outcome). The analysis compared changes in Z-scores between the two treatment groups. |
| Learning / Episodic Memory | Baseline and Month 4 | Learning/episodic memory was comprised of d' from the four word memory task and the average performance across all trials of the Rey auditory verbal learning test. Performance scores on each task were converted into Z-scores, and then averaged across tasks. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate higher function (better outcome). The analysis compared changes in Z-scores between the two treatment groups. |
| Psychomotor Speed | Baseline and Month 4 | Psychomotor speed was comprised of trail making A time, Stroop word-only time and color-only time. Performance scores on each task were converted into Z-scores, and then averaged across tasks. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate higher function (better outcome). The analysis compared changes in Z-scores between the two treatment groups. |
| Fluid Intelligence | Baseline and Month 4 | This outcome was based upon matrix reasoning task raw score, block design task raw score and spatial span forward raw score. Performance scores on each task were converted into Z-scores, and then averaged across tasks. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate higher function (better outcome). The analysis compared changes in Z-scores between the two treatment groups. |
| Moderation of Effects of Fish Oil on Inflammatory Markers by Select Genetic Polymorphisms | Measured at Month 4 | Circulating serum concentrations of IL6 and CRP before and after supplementation with fish oil or placebo. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Structural & Functional MRI | Baseline and month 4 | Measures of brain structure and function from magnetic resonance imaging |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fish Oil Participants will take fish oil supplements daily for 4 months.
Fish Oil: Participants will take 2 grams (1400 mg EPA and DHA) of fish oil supplements on a daily basis. | 134 |
| Placebo Participants will take soybean oil (placebo) supplements daily for 4 months.
Soybean Oil (Placebo): Participants will take 2 grams of soybean oil supplements on a daily basis. | 138 |
| Total | 272 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 5 |
| Overall Study | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | Fish Oil | 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 | 134 Participants | 138 Participants | 272 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 132 Participants | 136 Participants | 268 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 22 Participants | 43 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 109 Participants | 116 Participants | 225 Participants |
| Region of Enrollment United States | 134 participants | 138 participants | 272 participants |
| Sex: Female, Male Female | 76 Participants | 78 Participants | 154 Participants |
| Sex: Female, Male Male | 58 Participants | 60 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 61 / 134 | 17 / 138 |
| serious Total, serious adverse events | 0 / 134 | 0 / 138 |
Outcome results
Primary
Aggression
Bus-Perry Aggression Questionnaire. The minimum value is 14, and the maximum value is 53. A higher score suggests a worse outcome.
Time frame: baseline and month 4
Population: All randomized participants were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Aggression | Baseline | 28.14 units on a scale | Standard Deviation 8.32 |
| Fish Oil | Aggression | Month 4 | 27.75 units on a scale | Standard Deviation 8.9 |
| Placebo | Aggression | Baseline | 27.55 units on a scale | Standard Deviation 7.51 |
| Placebo | Aggression | Month 4 | 27.46 units on a scale | Standard Deviation 7.72 |
p-value: 0.6395% CI: [-1.57, 0.94]Mixed Models Analysis
Primary
Anger Expression
State-Trait Anger Expression Inventory. The minimum value is 0, and the maximum value is 72. A higher score suggests a worse outcome.
Time frame: baseline and month 4
Population: All randomized participants were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Anger Expression | Baseline | 24.73 units on a scale | Standard Deviation 8.86 |
| Fish Oil | Anger Expression | Month 4 | 22.83 units on a scale | Standard Deviation 8.63 |
| Placebo | Anger Expression | Baseline | 24.50 units on a scale | Standard Deviation 8.38 |
| Placebo | Anger Expression | Month 4 | 23.25 units on a scale | Standard Deviation 7.77 |
p-value: 0.5295% CI: [-1.83, 0.92]Mixed Models Analysis
Primary
Circulating Serum Interleukin-6 (IL-6)
Systemic inflammation: fasting serum Interleukin-6 (IL-6)
Time frame: Baseline and Month 4
Population: 11 participants had chronic inflammatory conditions at baseline and were excluded, leaving 129 in fish oil and 132 in placebo groups.~The 17 subjects who did not finish the study were retained through use of single-imputation analysis. Any subject missing both baseline and 4-month data could not be retained. TThis applied to 2 fish oil and 1 placebo participants for IL-6, leaving 127 and 131, respectively in the analysis population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fish Oil | Circulating Serum Interleukin-6 (IL-6) | baseline | 1.13 pg/mL |
| Fish Oil | Circulating Serum Interleukin-6 (IL-6) | Month 4 | 0.88 pg/mL |
| Placebo | Circulating Serum Interleukin-6 (IL-6) | baseline | 1.01 pg/mL |
| Placebo | Circulating Serum Interleukin-6 (IL-6) | Month 4 | 0.81 pg/mL |
p-value: 0.5995% CI: [-0.27, 0.19]ANOVA
Primary
C-reactive Protein (CRP)
fasting serum C-reactive protein (CRP) in milligrams per liter (mg/L)
Time frame: baseline and month 4
Population: 11 participants had chronic inflammatory conditions at baseline and were excluded, leaving 129 in fish oil and 132 in placebo groups.~The 17 subjects who did not finish the study were retained through use of single-imputation analysis. Any subject missing both baseline and 4-month data could not be retained. This applied to 4 fish oil and 3 placebo participants for CRP, leaving 125 and 129, respectively, in the analysis population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fish Oil | C-reactive Protein (CRP) | baseline | 1.00 mg/L |
| Fish Oil | C-reactive Protein (CRP) | month 4 | 0.94 mg/L |
| Placebo | C-reactive Protein (CRP) | baseline | 0.67 mg/L |
| Placebo | C-reactive Protein (CRP) | month 4 | 0.64 mg/L |
p-value: 0.2195% CI: [-0.24, 0.19]ANOVA
Primary
High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration
High frequency (.12 to .40 Hz) heart rate variability natural log transformed paced respiration in Hertz units (Hz)
Time frame: baseline and month 4
Population: One participant was excluded from the analysis due to missing both at baseline and 4-month data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration | Baseline | 5.93 ln(hertz) | Standard Deviation 1.52 |
| Fish Oil | High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration | Month 4 | 5.74 ln(hertz) | Standard Deviation 1.66 |
| Placebo | High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration | Baseline | 6.15 ln(hertz) | Standard Deviation 1.38 |
| Placebo | High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration | Month 4 | 6.13 ln(hertz) | Standard Deviation 1.28 |
p-value: 0.1695% CI: [-0.41, 0.07]Mixed Models Analysis
Primary
High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration
High frequency (.12 to .40 Hz) heart rate variability natural log transformed unpaced respiration in Hertz (Hz) units
Time frame: baseline and month 4
Population: One participant was excluded from the analysis due to missing both at baseline and 4-month data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration | Baseline | 5.37 ln(hertz) | Standard Deviation 1.4 |
| Fish Oil | High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration | Month 4 | 5.29 ln(hertz) | Standard Deviation 1.41 |
| Placebo | High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration | Baseline | 5.61 ln(hertz) | Standard Deviation 1.28 |
| Placebo | High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration | Month 4 | 5.51 ln(hertz) | Standard Deviation 1.21 |
p-value: 0.7495% CI: [-0.18, 0.25]Mixed Models Analysis
Primary
Hostility, Barefoot Score
The 27-item Barefoot Hostility Scale. The minimum value is 1, and the maximum value is 30. A higher score suggests a worse outcome.
Time frame: baseline and month 4
Population: All randomized participants were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Hostility, Barefoot Score | Month 4 | 13.30 units on a scale | Standard Deviation 6.53 |
| Fish Oil | Hostility, Barefoot Score | Baseline | 13.58 units on a scale | Standard Deviation 6.52 |
| Placebo | Hostility, Barefoot Score | Baseline | 12.54 units on a scale | Standard Deviation 6.21 |
| Placebo | Hostility, Barefoot Score | Month 4 | 12.58 units on a scale | Standard Deviation 6.13 |
p-value: 0.595% CI: [-1.25, 0.61]Mixed Models Analysis
Primary
Impulsivity
Barratt Impulsiveness Scale. The minimum value is 34, and the maximum value is 120. A higher score suggests a worse outcome.
Time frame: baseline and month 4
Population: All randomized participants were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Impulsivity | Baseline | 60.44 units on a scale | Standard Deviation 8.53 |
| Fish Oil | Impulsivity | Month 4 | 60.41 units on a scale | Standard Deviation 9.27 |
| Placebo | Impulsivity | Baseline | 59.57 units on a scale | Standard Deviation 8.44 |
| Placebo | Impulsivity | Month 4 | 59.38 units on a scale | Standard Deviation 8.97 |
p-value: 0.8695% CI: [-1.21, 1.44]Mixed Models Analysis
Primary
Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Paced Respiration
Mean successive difference in inter-beat intervals natural log transformed paced respiration in milliseconds
Time frame: baseline and month 4
Population: One participant was excluded from the analysis due to missing both at baseline and 4-month data..
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Paced Respiration | Baseline | 2.99 ln(milliseconds) | Standard Deviation 0.77 |
| Fish Oil | Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Paced Respiration | Month 4 | 2.92 ln(milliseconds) | Standard Deviation 0.83 |
| Placebo | Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Paced Respiration | Baseline | 3.13 ln(milliseconds) | Standard Deviation 0.69 |
| Placebo | Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Paced Respiration | Month 4 | 3.08 ln(milliseconds) | Standard Deviation 0.63 |
p-value: 0.6895% CI: [-0.16, 0.1]Mixed Models Analysis
Primary
Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Unpaced Respiration
Mean successive difference in inter-beat intervals natural log transformed unpaced respiration in milliseconds (msec)
Time frame: baseline and month 4
Population: One participant was excluded from the analysis due to missing both at baseline and 4-month data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Unpaced Respiration | Baseline | 2.97 ln(milliseconds) | Standard Deviation 0.71 |
| Fish Oil | Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Unpaced Respiration | Month 4 | 2.95 ln(milliseconds) | Standard Deviation 0.71 |
| Placebo | Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Unpaced Respiration | Baseline | 3.11 ln(milliseconds) | Standard Deviation 0.67 |
| Placebo | Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Unpaced Respiration | Month 4 | 3.03 ln(milliseconds) | Standard Deviation 0.59 |
p-value: 0.3595% CI: [-0.06, 0.18]Mixed Models Analysis
Primary
Negative Affect
Negative affect questions adapted from the Positive and Negative Affect Schedule - Expanded Form administered via ecological momentary assessment. The minimum value is 1, and the maximum value is 6. A higher score are worse (more negative affect).
Time frame: baseline and month 4
Population: All randomized participants were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fish Oil | Negative Affect | Baseline | 1.76 units on a scale |
| Fish Oil | Negative Affect | Month 4 | 1.73 units on a scale |
| Placebo | Negative Affect | Baseline | 1.69 units on a scale |
| Placebo | Negative Affect | Month 4 | 1.59 units on a scale |
p-value: 0.9295% CI: [0.69, 1.5]Mixed Models Analysis
Primary
Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration
Total power (0 to .40 Hz) heart rate variability natural log transformed paced respiration in Hertz (Hz) units.
Time frame: baseline and month 4
Population: One participant was excluded from the analysis due to missing both at baseline and 4-month data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration | Baseline | 7.02 ln(hertz) | Standard Deviation 1.1 |
| Fish Oil | Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration | Month 4 | 6.94 ln(hertz) | Standard Deviation 1.1 |
| Placebo | Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration | Baseline | 7.21 ln(hertz) | Standard Deviation 0.97 |
| Placebo | Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration | Month 4 | 7.18 ln(hertz) | Standard Deviation 0.92 |
p-value: 0.5995% CI: [-0.24, 0.14]Mixed Models Analysis
Primary
Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration
Total power (0 to .40 Hz) heart rate variability natural log transformed unpaced respiration in Hertz (Hz) units
Time frame: baseline and month 4
Population: One participant in placebo group was excluded from the analysis due to missing both at baseline and 4-month data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration | Month 4 | 6.98 ln(hertz) | Standard Deviation 0.97 |
| Fish Oil | Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration | Baseline | 7.05 ln(hertz) | Standard Deviation 0.98 |
| Placebo | Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration | Month 4 | 7.15 ln(hertz) | Standard Deviation 0.87 |
| Placebo | Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration | Baseline | 7.13 ln(hertz) | Standard Deviation 0.97 |
p-value: 0.2895% CI: [-0.27, 0.08]Mixed Models Analysis
Primary
Trait Anger
State-Trait Anger Expression Inventory. The minimum value is 10, and the maximum value is 40. A higher score suggests a worse outcome.
Time frame: baseline and month 4
Population: All randomized participants were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Trait Anger | Baseline | 16.07 units on a scale | Standard Deviation 3.69 |
| Fish Oil | Trait Anger | Month 4 | 15.39 units on a scale | Standard Deviation 3.32 |
| Placebo | Trait Anger | Baseline | 16.01 units on a scale | Standard Deviation 3.33 |
| Placebo | Trait Anger | Month 4 | 15.03 units on a scale | Standard Deviation 3.21 |
p-value: 0.2595% CI: [-0.23, 0.88]Mixed Models Analysis
Primary
Type A, Total Score
Structured Interview - Type A Behavior Pattern using the Interpersonal Hostility Assessment Technique (IHAT). The minimum value is 0, and the maximum value is 12. A higher score suggests a worse outcome.
Time frame: baseline and month 4
Population: All randomized participants were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fish Oil | Type A, Total Score | Baseline | 1.0 units on a scale |
| Fish Oil | Type A, Total Score | Month 4 | 1.0 units on a scale |
| Placebo | Type A, Total Score | Baseline | 1.0 units on a scale |
| Placebo | Type A, Total Score | Month 4 | 1.0 units on a scale |
p-value: 0.5295% CI: [0.67, 2.24]Mixed Models Analysis
Secondary
Executive Function
Executive function was comprised of trail making B - A time, digit span forward and digit span backward completions. Performance scores on each task were converted into Z-scores, and then averaged across tasks. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate higher function (better outcome). The analysis compared changes in Z-scores between the two treatment groups.
Time frame: Baseline and Month 4
Population: One participant in placebo group was excluded from the analysis due to missing both at baseline and 4-month data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Executive Function | baseline | -0.02 Z-score | Standard Deviation 0.57 |
| Fish Oil | Executive Function | Month 4 | 0.07 Z-score | Standard Deviation 0.62 |
| Placebo | Executive Function | baseline | 0.02 Z-score | Standard Deviation 0.61 |
| Placebo | Executive Function | Month 4 | 0.03 Z-score | Standard Deviation 0.63 |
p-value: 0.7695% CI: [-0.09, 0.39]Repeated Measures MANOVA
Secondary
Fluid Intelligence
This outcome was based upon matrix reasoning task raw score, block design task raw score and spatial span forward raw score. Performance scores on each task were converted into Z-scores, and then averaged across tasks. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate higher function (better outcome). The analysis compared changes in Z-scores between the two treatment groups.
Time frame: Baseline and Month 4
Population: One participant in placebo group was excluded from the analysis due to missing both at baseline and 4-month data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Fluid Intelligence | baseline | -0.02 Z-score | Standard Deviation 0.85 |
| Fish Oil | Fluid Intelligence | Month 4 | -0.005 Z-score | Standard Deviation 0.82 |
| Placebo | Fluid Intelligence | baseline | 0.02 Z-score | Standard Deviation 0.9 |
| Placebo | Fluid Intelligence | Month 4 | 0.05 Z-score | Standard Deviation 0.83 |
p-value: 0.5495% CI: [-0.3, 0.18]Repeated Measures MANOVA
Secondary
Learning / Episodic Memory
Learning/episodic memory was comprised of d' from the four word memory task and the average performance across all trials of the Rey auditory verbal learning test. Performance scores on each task were converted into Z-scores, and then averaged across tasks. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate higher function (better outcome). The analysis compared changes in Z-scores between the two treatment groups.
Time frame: Baseline and Month 4
Population: One participant in placebo group was excluded from the analysis due to missing both at baseline and 4-month data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Learning / Episodic Memory | baseline | 0.01 Z-score | Standard Deviation 0.87 |
| Fish Oil | Learning / Episodic Memory | Month 4 | 0.18 Z-score | Standard Deviation 0.85 |
| Placebo | Learning / Episodic Memory | baseline | -0.01 Z-score | Standard Deviation 0.86 |
| Placebo | Learning / Episodic Memory | Month 4 | 0.12 Z-score | Standard Deviation 0.87 |
p-value: 0.6295% CI: [-0.18, 0.3]Repeated Measures MANOVA
Secondary
Moderation of Effects of Fish Oil on Inflammatory Markers by Select Genetic Polymorphisms
Circulating serum concentrations of IL6 and CRP before and after supplementation with fish oil or placebo.
Time frame: Measured at Month 4
Population: This aim was conditional and was not completed per the protocol.
Secondary
Psychomotor Speed
Psychomotor speed was comprised of trail making A time, Stroop word-only time and color-only time. Performance scores on each task were converted into Z-scores, and then averaged across tasks. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate higher function (better outcome). The analysis compared changes in Z-scores between the two treatment groups.
Time frame: Baseline and Month 4
Population: One participant in placebo group was excluded from the analysis due to missing both at baseline and 4-month data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fish Oil | Psychomotor Speed | baseline | 0.04 Z-score | Standard Deviation 0.63 |
| Fish Oil | Psychomotor Speed | Month 4 | 0.13 Z-score | Standard Deviation 0.54 |
| Placebo | Psychomotor Speed | baseline | -0.04 Z-score | Standard Deviation 0.6 |
| Placebo | Psychomotor Speed | Month 4 | 0.007 Z-score | Standard Deviation 0.57 |
p-value: 0.4295% CI: [-0.21, 0.26]Repeated Measures MANOVA
Other Pre-specified
Structural & Functional MRI
Measures of brain structure and function from magnetic resonance imaging
Time frame: Baseline and month 4