| 23) Nagata C (2002) | The Takayama Study | 13,355 men and 15,724 women aged 35 or older.
(Japan) | 7
(1992-1999) | 308 men, and
327 women | Cardiovascular disease mortality | Fish oil |
Stratified by gender:
| Men | Women |
HR = 0.76 (0.54-1.07; P = 0.27) for the highest vs lowest quintile of consumption.
Amount specific data (median intake in mg/day):
410: HR = 1.
602: HR = 0.74 (0.51-1.08).
788: HR = 0.71 (0.49-1.03).
1,051: HR = 0.82 (0.58-1.15).
1,582: HR = 0.76 (0.54-1.07). |
HR = 0.77 (0.55-1.00; P = 0.16) for the highest vs lowest quintile of consumption.
Amount specific data (median intake in mg/day):
332: HR = 1.
486: HR = 0.82 (0.59-1.15).
635: HR = 0.79 (0.58-1.11).
832: HR = 0.86 (0.62-1.20).
1,253: HR = 0.70 (0.55-1.00). |
Age, total energy, marital status, BMI, smoking status, exercise, and history of hypertension.
Additionally for men: alcohol intake, coffee intake, and history of diabetes mellitus.
Additionally for women: age at menarche, and history of hysterectomy. |
| 22) Folsom AR (2004) | The Iowa Women's Health Study | 41,836 women aged 55-69, and free of heart disease or cancer. | 1986-2000 | 1,589? | Cardiovascular disease mortality | Omega-3 fatty acids from fish (excluding fish oil supplements) | No association was found (results not shown). | Age, energy intake, education level, physical activity level, alcohol consumption, smoking status, pack-years of cigarette smoking, age at first livebirth, estrogen use, vitamin use, BMI, waist/hip ratio, diabetes, hypertension, intake of whole grains, fruits and vegetables, red meat, cholesterol, and saturated fat. |
| 17) Morris MC (1995) | The Physician's Health Study | 21,185 men aged 40-84, and without a history of MI, stroke, transient ischemic attacks, cancer, liver/renal disease, peptic ulcer, gout, current use of aspirin, other platelet-active drugs, or NSAID's.
(USA) | 4
(1983-1988) | See variables | Cardiovascular events (fatal/nonfatal myocardial infarction; fatal/nonfatal stroke; sudden death; and other CVD) | Long-chain omega 3 fatty acids from seafood (EPA & DHA from canned tuna fish; dark meat fish [e.g., mackerel, salmon, sardines, bluefish, swordfish]; other fish; and shrimp, lobster, or scallops as a main dish.
Excluding alpha-linolenic acid, and fish oil supplements) |
Total cardiovascular events
(525 cases) | Cardiovascular death
(acute MI, other IHD, sudden death, stroke, and other CVD)
(121 cases) |
RR = 1.1 (0.8-1.5; P = 0.63) for the highest vs lowest quintile of consumption.
Amount specific data (g/week):
< 0.5: RR = 1.
0.5-< 1.0: RR = 1.3 (1.0-1.8).
1.0-< 1.7: RR = 1.3 (1.0-1.7).
1.7-< 2.3: RR = 0.9 (0.7-1.3).
≥ 2.3: RR = 1.1 (0.8-1.5).
|
RR = 1.5 (0.8-2.9; P = 0.80) for the highest vs lowest quintile of consumption.
Amount specific data (g/week):
< 0.5: RR = 1.
0.5-< 1.0: RR = 1.6 (0.8-3.0).
1.0-< 1.7: RR = 1.6 (0.9-3.0).
1.7-< 2.3: RR = 0.9 (0.5-1.9).
≥ 2.3: RR = 1.5 (0.8-2.9).
|
Age, aspirin and beta-carotene assignment, smoking, alcohol consumption, obesity, diabetes mellitus, vigorous exercise, parental history of MI, history of hypertension, history of hypercholesterolemia, vitamin supplement use, and saturated fat intake. |
| 13) Virtanen JK (2008) | The Health Professionals Follow-up Study | 40,230 men aged 40-75 and free of major chronic disease.
(USA) | 18
(1986-2004) | 3,639 | Primary CVD incidence (fatal or nonfatal MI and fatal or nonfatal stroke) | EPA + DHA (from the consumption of all seafood) |
RR = 1.12 (0.92-1.36; P = 0.16) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
< 0.05: RR = 1.
0.05-< 0.2: RR = 0.98 (0.83-1.15).
0.2-< 0.4: RR = 0.93 (0.78-1.10).
0.4-< 0.6: RR = 0.91 (0.76-1.10).
≥ 0.6: RR = 1.12 (0.92-1.36). | Age, BMI, smoking, physical activity, history of diabetes, hypertension or hypercholesterolemia, first-degree family history of MI before age 60, first degree family history of colon cancer, aspirin use, multivitamin use, glycemic load, and intakes of protein, fiber, trans fat, saturated fat, n-6 fatty acids, alpha-linolenic acid, red meat, total calories, and alcohol. |
| 12) Dolecek TA (1992) | The Multiple Risk Factor Intervention Trial (MRFIT) | 6,250 men aged 35-57, and at a high risk of CHD.
(USA) | 10.5
(?-1985) | 232? | Cardiovascular disease mortality | Dietary n-3 fish fatty acids | This was a randomized trial, but only data from the "usual care" group was analyzed.
| Grams | Percentage of total kilocalories |
RR = 0.60 (P = < 0.01) for the highest vs lowest quintile of consumption.
Amount specific data (grams):
0.000: RR = 1.
0.009: RR = 1.06
0.046: RR = 0.93
0.153: RR = 0.93
0.664: RR = 0.60
|
RR = 0.55 (P = < 0.01) for the highest vs lowest quintile of consumption.
Amount specific data (% of calories):
0.000: RR = 1.
0.004: RR = 1.08
0.019: RR = 0.81
0.063: RR = 1.08
0.284: RR = 0.55
|
Age, race, smoking, baseline diastolic blood pressure, HDL, LDL, and alcohol. |
| 12) Dolecek TA (1991) | The Multiple Risk Factor Intervention Trial (MRFIT) | 6,258 men aged 35-57, and at a high risk of developing CHD based upon smoking status, diastolic blood pressure, and serum cholesterol levels.
(USA) | ?-1985 | 232 | CVD mortality | Dietary long-chain omega 3 fatty acids from fish [EPA (20:5), DPA (22:5), and DHA (22:6)] | This was a randomized trial, but only data from the "usual care" group was analyzed.
RR = 0.59 (No 95% CI; P = 0.004) for the highest vs lowest quintile of consumption.
Amount specific data (g):
0.000: RR = 1
0.009: RR = 1.06
0.046: RR = 0.92
0.153: RR = 0.92
0.664: RR = 0.59 | Age, race, baseline smoking, diastolic blood pressure, HDL and LDL levels. |
Prospective studies of dietary long-chain omega-3 fatty acids from fish and coronary heart disease:
| Author | Cohort name | Subjects | Years of follow-up | Cases | End point | Consumption of | Relative Risk (RR) | Adjustments |
| 46) Manger MS (2010) | The Western Norway B Vitamin Intervention Trial (WENBIT) | 2,412 men and women aged > 18, and undergoing coronary angiography for suspected CAD and/or aortic valve stenosis. Nearly 90% of the participants used statins. | 1999-2004 to 2006 | 292? | Coronary events (coronary death, nonfatal AMI, and unstable angina pectoris) | Cod liver oil (cod liver oil, or cod liver oil capsules) | No difference in risk was found between users and nonusers (data not shown). | Age, sex, left venticular ejection fraction, diabetes mellitus, hypertension, current smoker, acute coronary syndrome, and current use of statins.
The association did not change after additional adjustment for BMI, serum triglycerides, previous AMI, previous PCI, previous CABG, previous cerebrovascular disease or carotid artery stenosis, previous peripheral arterial disease, extend of CAD, current us of beta-blockers, current use of angiotensin-converting enzyme inhibitors, and dietary intakes of saturated fatty acids, n-6 fatty acids, fiber, alpha-linolenic acid, thiamine, riboflavin, and tocopherol. |
| 44) Joensen AM (2010) | The Danish Diet, Cancer and Health Cohort | 55,434 men and women aged 50-64, and without unstable angina pectoris, MI, or cancer. | 7.6
(1993-97 to 2004) | 1,124? | Acute coronary syndrome (62 unstable angina pectoris, 885 non-fatal MI and 177 fatal MI) | Marine n-3 PUFA (not defined, but excluding fish oil capsules) |
| Men | Women |
HR = 0.81 (0.64-1.04) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
0.00-0.39: HR = 1.
0.39-0.58: HR = 0.83 (0.67-1.03).
0.58-0.79: HR = 0.81 (0.65-1.01).
0.79-1.08: HR = 0.90 (0.71-1.13).
> 1.08: HR = 0.81 (0.64-1.04).
|
HR = 0.97 (0.62-1.52) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
0.00-0.38: HR = 1.
0.38-0.57: HR = 0.85 (0.57-1.26).
0.57-0.76: HR = 1.09 (0.73-1.63).
0.76-1.02: HR = 1.31 (0.86-1.98).
> 1.03: HR = 0.97 (0.62-1.52).
|
Smoking, BMI, time of moderate to vigorous physical activity, history of diabetes mellitus, systolic blood pressure, total cholesterol, alcohol consumption, total intake of fruit, vegetables, saturated fat, monounsaturated fat and n-6 PUFA, and for women HRT. |
| 44) Joensen AM (2010) | The Danish Diet, Cancer and Health Cohort | 55,434 men and women aged 50-64, and without unstable angina pectoris, MI, or cancer. | 7.6
(1993-97 to 2004) | 1,124? | Acute coronary syndrome (62 unstable angina pectoris, 885 non-fatal MI and 177 fatal MI) | Marine EPA (not defined, but excluding fish oil capsules) |
| Men | Women |
HR = 0.84 (0.66-1.06) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
0.00-0.09: HR = 1.
0.09-0.14: HR = 0.87 (0.70-1.08).
0.14-0.20: HR = 0.86 (0.69-1.08).
0.20-0.28: HR = 0.86 (0.69-1.08).
> 0.28: HR = 0.84 (0.66-1.06).
|
HR = 0.93 (0.60-1.42) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
0.00-0.08: HR = 1.
0.08-0.13: HR = 0.92 (0.62-1.36).
0.13-0.19: HR = 1.11 (0.75-1.66).
0.19-0.24: HR = 1.57 (1.04-2.38).
> 0.24: HR = 0.93 (0.60-1.42).
|
Smoking, BMI, time of moderate to vigorous physical activity, history of diabetes mellitus, systolic blood pressure, total cholesterol, alcohol consumption, total intake of fruit, vegetables, saturated fat, monounsaturated fat and n-6 PUFA, and for women HRT. |
| 44) Joensen AM (2010) | The Danish Diet, Cancer and Health Cohort | 55,434 men and women aged 50-64, and without unstable angina pectoris, MI, or cancer. | 7.6
(1993-97 to 2004) | 1,124? | Acute coronary syndrome (62 unstable angina pectoris, 885 non-fatal MI and 177 fatal MI) | Marine DPA (not defined, but excluding fish oil capsules) |
| Men | Women |
HR = 0.89 (0.68-1.16) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
0.00-0.05: HR = 1.
0.05-0.07: HR = 0.98 (0.78-1.22).
0.07-0.09: HR = 0.94 (0.74-1.18).
0.09-0.11: HR = 0.90 (0.71-1.15).
> 0.11: HR = 0.89 (0.68-1.16).
|
HR = 0.98 (0.60-1.60) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
0.00-0.04: HR = 1.
0.04-0.06: HR = 0.73 (0.49-1.10).
0.06-0.07: HR = 1.12 (0.74-1.71).
0.07-0.09: HR = 0.93 (0.60-1.45).
> 0.09: HR = 0.98 (0.60-1.60).
|
Smoking, BMI, time of moderate to vigorous physical activity, history of diabetes mellitus, systolic blood pressure, total cholesterol, alcohol consumption, total intake of fruit, vegetables, saturated fat, monounsaturated fat and n-6 PUFA, and for women HRT. |
| 44) Joensen AM (2010) | The Danish Diet, Cancer and Health Cohort | 55,434 men and women aged 50-64, and without unstable angina pectoris, MI, or cancer. | 7.6
(1993-97 to 2004) | 1,124? | Acute coronary syndrome (62 unstable angina pectoris, 885 non-fatal MI and 177 fatal MI) | Marine DHA (not defined, but excluding fish oil capsules) |
| Men | Women |
HR = 0.81 (0.63-1.03) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
0.00-0.23: HR = 1.
0.23-0.35: HR = 0.84 (0.68-1.04).
0.35-0.48: HR = 0.84 (0.68-1.05).
0.48-0.65: HR = 0.88 (0.70-1.11).
> 0.65: HR = 0.81 (0.63-1.03).
|
HR = 1.00 (0.64-1.57) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
0.00-0.20: HR = 1.
0.20-0.32: HR = 0.83 (0.56-1.23).
0.32-0.43: HR = 1.10 (0.74-1.65).
0.43-0.59: HR = 1.05 (0.70-1.60).
> 0.59: HR = 1.00 (0.64-1.57).
|
Smoking, BMI, time of moderate to vigorous physical activity, history of diabetes mellitus, systolic blood pressure, total cholesterol, alcohol consumption, total intake of fruit, vegetables, saturated fat, monounsaturated fat and n-6 PUFA, and for women HRT. |
| 42) Levitan EB (2010) | The Swedish Mammography Cohort | 36,234 women without HF, MI, or diabetes. | 1998-2006 | 651 | Heart failure events (hospitalization for or death from hf) | Marine omega-3 (the sum of EPA, and DHA from food sources) |
All women:
(651 cases) | Women without hypertension:
(401 cases) |
RR = 0.81 (0.63-1.05) for the highest vs lowest quintile of consumption.
Amount specific data (g/day):
0.14: RR = 1.
0.23: RR = 0.87 (0.69-1.11).
0.30: RR = 0.83 (0.64-1.07).
0.38: RR = 0.88 (0.69-1.12).
0.57: RR = 0.81 (0.63-1.05).
|
RR = 0.83 (0.60-1.15) for the highest vs lowest quintile of consumption.
Amount specific data (g/day):
0.14: RR = 1.
0.23: RR = 1.04 (0.77-1.40).
0.30: RR = 0.94 (0.68-1.29).
0.38: RR = 1.00 (0.73-1.37).
0.57: RR = 0.83 (0.60-1.15).
These associations were not adjusted for macronutrients.
|
Results did not differ materially when fatty acids from fish oil supplements were included in the calculation.
Age, education, BMI, physical activity, cigarette smoking, living alone, postmenopausal hormone use, total energy intake, alcohol intake, fiber intake, sodium intake, intake of red or processed meat, family history of MI, history of hypertension, history of high cholesterol, and protein, saturated fat, monounsaturated fat, non-marine omega 3 fatty acids, and omega 6 fatty acids. |
| 42) Levitan EB (2009) | The Cohort of Swedish Men | 39,367 men aged 45-79, without a history of cancer, heart failure, MI, or diabetes. | 1998-2004 | 597 | Heart failure incidence (hospitalization for or death from HF) | Marine omega-3 fatty acids (the sum of EPA and DHA from food sources) |
Men without a history of major chronic disease:
| Marine omega-3 fatty acids | Marine omega-3 fatty acids & fish oil from capsules |
HR = 1.00 (0.77-1.29) for the highest vs lowest quintile of consumption.
Amount specific data (g/day):
0.01-0.22: HR = 1.
0.24-0.31: HR = 0.94 (0.74-1.20).
0.32-0.40: HR = 0.67 (0.50-0.90).
0.41-0.54: HR = 0.89 (0.68-1.16).
0.55-8.54: HR = 1.00 (0.77-1.29).
|
HR = 1.05 (0.82-1.36) for the highest vs lowest quintile of consumption.
Amount specific data (Quintiles not defined):
Q1: HR = 1.
Q2: HR = 0.99 (0.77-1.27).
Q3: HR = 0.73 (0.54-0.97).
Q4: HR = 0.97 (0.75-1.27).
Q5: HR = 1.05 (0.82-1.36).
|
Men with a history of MI or diabetes
(? cases)
| Marine omega-3 fatty acids |
HR = 1.30 (0.92-1.83) for the highest vs lowest quintile of consumption.
Amount specific data (Quintiles not defined):
Q1: HR = 1.
Q2: HR = 1.04 (0.72-1.48).
Q3: HR = 0.87 (0.58-1.28).
Q4: HR = 1.12 (0.77-1.62).
Q5: HR = 1.30 (0.92-1.83).
|
Age, BMI, physical activity, energy, alcohol, fibre, sodium, and red or processed meat consumption, education, family history of MI, cigarette smoking, marital status, history of hypertension, and high cholesterol.
Further adjustment for macronutrients did not materially change the results. |
| 27) Mozaffarian D (2005) | The Cardiovascular Health Study | 4,738 men and women aged ≥ 65, and free of congestive heart failure.
(US) | 12
(1989-90 to ) | 955? | Congestive heart failure incidence | Dietary EPA + DHA from fish meals, including shellfish | HR = 0.63 (0.57-0.94; P = 0.009) for the highest vs lowest quintile of consumption (> 487 vs < 92 mg/day, respectively). | Age, gender, race, enrollment site, education, diabetes, BMI, prevalent heart disease/stroke, total caloric intake, smoking, leisure-time physical activity, intakes of saturated fat, fruits, vegetables, and alcohol. |
| 27) Mozaffarian D (2003) | The Cardiovascular Health Study | 3,910 men and women aged ≥ 65 and free of known CVD. | 9.3 | See variables | Heart disease | Dietary n-3 PUFAs from fish meals |
Total IHD death (combined fatal MI + CHD death)
(247? cases) | Arrhytmic IHD death (from primary and secondary arrhytmia)
(148? cases) | Nonfatal MI
(363? cases) |
| HR = 0.58 (0.38-0.90) for each 1 g/d EPA + DHA.
|
HR = 0.45 (0.25-0.81) for each 1 g/d EPA + DHA.
|
HR = 0.89 (0.64-1.22) for each 1 g/d EPA + DHA.
|
Age, gender, education, diabetes, current smoking, pack-years of smoking, tuna/other fish and fried fish/fish sandwich consumption, BMI, systolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, C-reactive protein, and intake of saturated fat, alcohol, beef/pork, fruits, and vegetables. |
| 23) Nagata C (2002) | The Takayama Study | 13,355 men and 15,724 women aged 35 or older.
(Japan) | 7
(1992-1999) | 63 men, and
52 women | Ischemic heart disease mortality | Fish oil |
Stratified by gender:
| Men | women |
| HR = 1.05 (0.56-1.97; P = 0.91) for the highest vs lowest tertile of consumption (not defined). |
HR = 0.73 (0.37-1.45; P = 0.37) for the highest vs lowest tertile of consumption (not defined). |
Age, total energy, marital status, BMI, smoking status, exercise, and history of hypertension. |
| 22) Folsom AR (2004) | The Iowa Women's Health Study | 41,836 women aged 55-69, and free of heart disease or cancer. | 1986-2000 | 922? | Coronary heart disease mortality | Omega-3 fatty acids from fish (excluding fish oil supplements) | No association was found (results not shown). | Age, energy intake, education level, physical activity level, alcohol consumption, smoking status, pack-years of cigarette smoking, age at first livebirth, estrogen use, vitamin use, BMI, waist/hip ratio, diabetes, hypertension, intake of whole grains, fruits and vegetables, red meat, cholesterol, and saturated fat. |
| 20 Yuan JM (2001) | The Shanghai Cohort Study | 18,244 men aged 45-64 from Shanghai (China), and without a history of cancer. | 12
(1986-89 to 1998) | See variables | Ischemic heart disease death | N-3 fatty acids from seafood |
Acute myocardial infarction
(including sudden death and nonsudden cardiac death within 28 days)
(113 cases) | Other ischemic heart disease
(74 cases) |
RR = 0.43 (0.23-0.81; P = 0.02) for the highest vs lowest quintile of consumption.
Amount specific data (g/week):
< 0.27: RR = 1.
0.27-0.43: RR = 0.39 (0.20-0.75).
0.44-0.72: RR = 0.67 (0.42-1.08).
0.73-1.09: RR = 0.53 (0.29-0.97).
≥ 1.10: RR = 0.43 (0.23-0.81).
|
RR = 0.71 (0.32-1.57; P = 0.68) for the highest vs lowest quintile of consumption.
Amount specific data (g/week):
< 0.27: RR = 1.
0.27-0.43: RR = 0.82 (0.38-1.75).
0.44-0.72: RR = 0.83 (0.42-1.61).
0.73-1.09: RR = 1.11 (0.54-2.30).
≥ 1.10: RR = 0.71 (0.32-1.57).
|
Age, total energy intake, level of education, BMI, current smoking, cigarettes smoked, alcohol, history of diabetes, and history of hypertension.
Separate inclusion of intake levels of red meats; poultry; vegetables; fruit; soybeans and soy products; legumes; carbohydrate; protein; total fat; saturated, monounsaturated, and polyunsaturated fats other than n-3 fatty acids; and cholesterol did not materially alter the association with fatal MI. |
| 19) Pietinen P (1997) | The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study | 21,930 male smokers (≥ 5 cigarettes/day) aged 50-69, and free of CVD, diabetes or cancer.
(Finland) | 6.1
(1985-88 to 1993) | See variables | Major coronary events (first nonfatal myocardial infarction, or coronary heart disease death) | Omega-3 fish fatty acids (not defined) |
Major coronary events
(1,399 cases) | Coronary death
(635 cases) |
RR = 1.15 (0.97-1.35; P = 0.119) for the highest vs lowest quintile of consumption.
Amount specific data (intake in g):
0.2: RR = 1.
0.3: RR = 0.94 (0.80-1.12).
0.4: RR = 1.03 (0.87-1.21).
0.5: RR = 1.02 (0.86-1.20).
0.8: RR = 1.15 (0.97-1.35).
|
RR = 1.30 (1.01-1.67; P = 0.056) for the highest vs lowest quintile of consumption.
Amount specific data (intake in g):
0.2: RR = 1.
0.3: RR = 0.94 (0.73-1.22).
0.4: RR = 1.01 (0.78-1.30).
0.5: RR = 1.10 (0.86-1.42).
0.8: RR = 1.30 (1.01-1.67).
After additional adjustment for vitamin E, vitamin C, and beta carotene, the RR became: 1.29 (1.01-1.65; P = 0.07).
|
Age, treatment group, smoking, BMI, blood pressure, intakes of energy, alcohol, and fiber, education, and physical activity.
The model for coronary death is also adjusted for trans-saturated and cis-monounsaturated fatty acids. |
| 17) Albert CM (1998) | The Physician's Health Study | 20,551 men aged 40-84, and without a history of MI, stroke, transient ischemic attack, or cancer.
(USA) | 11
(1983-1995) | 133 | Sudden death | Dietary marine N-3 fatty acids (from fish or shellfish: canned tuna fish; dark meat fish [eg, mackerel, salmon, sardines, bluefish, or swordfish]; other fish; and shrimp, lobster, or scallops as a main dish) |
RR = 0.43 (0.20-0.93; P = 0.21) for the highest vs lowest quintile of consumption.
Amount specific data (g/mo):
< 0.3: RR = 1.
0.3-< 2.7: RR = 0.58 (0.28-1.21).
2.7-< 4.9: RR = 0.34 (0.15-0.74).
4.9-< 7.4: RR = 0.60 (0.29-1.27).
≥ 7.4: RR = 0.43 (0.20-0.93). | Age, aspirin and beta carotene treatment assignment, evidence of CVD, BMI, smoking status, history of diabetes, history of hypertension, history of hypercholesterolemia, alcohol, vigorous exercise, vitamine E, vitamin C, and multivitamin use. |
| 17) Morris MC (1995) | The Physician's Health Study | 21,185 men aged 40-84, and without a history of MI, stroke, transient ischemic attacks, cancer, liver/renal disease, peptic ulcer, gout, current use of aspirin, other platelet-active drugs, or NSAID's.
(USA) | 4
(1983-1988) | See variables | Myocardial infarction (excluding silent infarctions) | Long-chain omega 3 fatty acids from seafood (EPA & DHA from canned tuna fish; dark meat fish [e.g., mackerel, salmon, sardines, bluefish, swordfish]; other fish; and shrimp, lobster, or scallops as a main dish.
Excluding alpha-linolenic acid, and fish oil supplements) |
Total myocardial infarction
(281 cases) | Nonfatal myocardial infarction
(259 cases) |
RR = 1.2 (0.8-1.8; P = 0.98) for the highest vs lowest quintile of consumption.
Amount specific data (g/week):
< 0.5: RR = 1.
0.5-< 1.0: RR = 1.6 (1.1-2.4).
1.0-< 1.7: RR = 1.4 (1.0-2.2).
1.7-< 2.3: RR = 1.2 (0.8-1.8).
≥ 2.3: RR = 1.2 (0.8-1.8).
|
RR = 1.1 (0.7-1.8; P = 0.99) for the highest vs lowest quintile of consumption.
Amount specific data (g/week):
< 0.5: RR = 1.
0.5-< 1.0: RR = 1.5 (1.0-2.3).
1.0-< 1.7: RR = 1.3 (0.9-2.0).
1.7-< 2.3: RR = 1.2 (0.8-1.9).
≥ 2.3: RR = 1.1 (0.7-1.8).
|
Age, aspirin and beta-carotene assignment, smoking, alcohol consumption, obesity, diabetes mellitus, vigorous exercise, parental history of MI, history of hypertension, history of hypercholesterolemia, vitamin supplement use, and saturated fat intake. |
| 15) Järvinen R (2006) | The Finnish Mobile Clinic Health Survey | 2,775 men, and 2,445 women aged 30-79, and free of CHD. | 21.5
(1967-72 to 1992) | See variables | CHD death | Long-chain n-3 fatty acids (fish specific EPA and DHA) |
Men:
(335 cases) | Women:
(163 cases) |
RR = 0.96 (0.68-1.38; P = 1.00) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
≤ 0.17: RR = 1.
0.18-0.27: RR = 1.00 (0.70-1.44).
0.28-0.39: RR = 1.11 (0.78-1.57).
0.40-0.59: RR = 1.10 (0.77-1.56).
≥ 0.60: RR = 0.96 (0.68-1.38).
|
RR = 0.73 (0.44-1.19; P = 0.31) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
≤ 0.11: RR = 1.
0.12-0.17: RR = 0.67 (0.40-1.13).
0.18-0.24: RR = 1.14 (0.72-1.79).
0.25-0.36: RR = 0.75 (0.46-1.23).
≥ 0.37: RR = 0.73 (0.44-1.19).
|
Age, energy intake, area, BMI, serum cholesterol, blood pressure, smoking, occupation and diabetes. |
| 13) Mozaffarian D (2005) | The Health Professionals Follow-up Study | 45,722 men aged 40-75, and free of CVD.
(USA) | 14
(1986-2000) | See variables | CHD incidence (sudden death, other CHD death, and nonfatal MI) | Dietary EPA + DHA from seafood (not defined, but excluding supplements) |
Sudden death (218? cases):
HR = 0.65 (0.47-0.88) for ≥ 250 vs < 250 mg/day.
Sudden death.
Stratified by n-6 polyunsaturated fat intake:
Low n-6 (< 11.2 g/d)
(108 cases) | High n-6 (≥ 11.2 g/d)
(110 cases) |
Low EPA/DHA: RR = 1 (Reference) for < 250 mg/d.
High EPA/DHA: RR = 0.52 (0.34-0.79) for ≥ 250 mg/d.
|
Low EPA/DHA: RR = 0.76 (0.52-1.11) for < 250 mg/d.
High EPA/DHA: RR = 0.60 (039-0.93) for ≥ 250 mg/d.
|
Nonfatal MI.
Stratified by n-6 polyunsaturated fat intake:
Low n-6 (< 11.2 g/d)
(757 cases) | High n-6 (≥ 11.2 g/d)
(764 cases) |
Low EPA/DHA: RR = 1 (Reference) for < 250 mg/d.
High EPA/DHA: RR = 1.16 (0.99-1.36) for ≥ 250 mg/d.
|
Low EPA/DHA: RR = 1.09 (0.93-1.28) for < 250 mg/d.
High EPA/DHA: RR = 1.09 (0.91-1.29) for ≥ 250 mg/d.
|
Total CHD.
Stratified by n-6 polyunsaturated fat intake:
Low n-6 (< 11.2 g/d)
(1,166 cases) | High n-6 (≥ 11.2 g/d)
(1,140 cases) |
Low EPA/DHA: RR = 1 (Reference) for < 250 mg/d.
High EPA/DHA: RR = 1.05 (0.92-1.19) for ≥ 250 mg/d.
|
Low EPA/DHA: RR = 0.97 (0.85-1.10) for < 250 mg/d.
High EPA/DHA: RR = 1.02 (0.89-1.16) for ≥ 250 mg/d.
|
Age, BMI, smoking, physical activity, history of diabetes, hypertension, or hypercholesterolemia, aspirin use, alcohol use, intake of protein, saturated fat, dietary fiber, monounsaturated fat, trans fatty acids, total calories, and ALA. |
| 13) Stampfer MJ (2000) | The Nurses' Health Study | 84,129 women who were free of CVD, cancer, and diabetes.
(USA) | 14
(1980-1994) | 1,128? | Major coronary events (nonfatal myocardial infarction or coronary heart disease death) | Marine n-3 fatty acids (not defined) | A significant protective effect was found for the highest vs lowest quintile of consumption (> 0.1% of energy from marine n-3 fatty acids; no data shown). | Age, time periods, parental history of MI before age 60, menopausal status, use of postmenopausal hormones, history of hypertension, and history of high cholesterol levels. |
| 13) Ascherio A (1995) | The Health Professionals Follow-up Study | 44,895 male health professionals aged 40-75, and free of CVD. | 6
(1986-1992) | 1,543 | CHD (fatal coronary disease, nonfatal myocardial infarction, and coronary-artery bypass grafting or angioplasty) | N-3 fatty acids from fish (dark meat fish [1.37 g/portion]; canned tuna [0.69 g]; other fish [0.17 g]; and shrimp, lobster, or scallops [0.46 g]) |
RR = 1.12 (0.96-1.31; P = 0.09) for the highest vs lowest quintile of consumption.
Amount specific data (g/day):
0.01-0.11: RR = 1.
0.12-0.19: RR = 0.98 (0.83-1.15).
0.20-0.28: RR = 0.97 (0.83-1.15).
0.29-0.41: RR = 0.99 (0.84-1.17).
0.42-6.52: RR = 1.12 (0.96-1.31).
Additional adjustment for physical activity and intake of vitamin E and carotene strengthened the association: RR = 1.22 (1.03-1.44).
No association was found among men with low linolenic acid.
Coronary-artery bypass grafting
(735 cases) | Nonfatal myocardial infarction
(554 cases) | Any myocardial infarction
(811 cases) |
RR = 1.16 (0.92-1.47; P = 0.09) for the highest vs lowest quintile of consumption.
Amount specific data (g/day):
0.01-0.11: RR = 1.
0.12-0.19: RR = 0.97 (0.76-1.24).
0.20-0.28: RR = 1.05 (0.82-1.33).
0.29-0.41: RR = 1.15 (0.91-1.45).
0.42-6.52: RR = 1.16 (0.92-1.47).
|
RR = 1.09 (0.85-1.41; P = 0.44) for the highest vs lowest quintile of consumption.
Amount specific data (g/day):
0.01-0.11: RR = 1.
0.12-0.19: RR = 0.93 (0.72-1.21).
0.20-0.28: RR = 0.89 (0.68-1.16).
0.29-0.41: RR = 0.78 (0.59-1.03).
0.42-6.52: RR = 1.09 (0.85-1.41).
|
RR = 1.09 (0.88-1.35; P = 0.48) for the highest vs lowest quintile of consumption.
Amount specific data (g/day):
0.01-0.11: RR = 1.
0.12-0.19: RR = 1.00 (0.81-1.25).
0.20-0.28: RR = 0.92 (0.74-1.15).
0.29-0.41: RR = 0.86 (0.69-1.08).
0.42-6.52: RR = 1.09 (0.88-1.35).
Stratified analysis:
No significant inverse association was seen in any of the subgroups defined according to risk factors for coronary disease.
|
Age, energy, BMI, smoking habits, alcohol consumption, history of hypertension, history of diabetes, history of hypercholesterolemia, family history of MI, and profession. |
| 13) Ascherio A (1995) | The Health Professionals Follow-up Study | 44,895 male health professionals aged 40-75, and free of CVD. | 6
(1986-1992) | 264 | Fatal CHD (including sudden death) | N-3 fatty acids from fish (dark meat fish [1.37 g/portion]; canned tuna [0.69 g]; other fish [0.17 g]; and shrimp, lobster, or scallops [0.46 g]) |
RR = 1.03 (0.70-1.52; P = 0.94) for the highest vs lowest quintile of consumption.
Amount specific data (g/day):
0.01-0.11: RR = 1.
0.12-0.19: RR = 1.14 (0.78-1.66).
0.20-0.28: RR = 0.95 (0.64-1.41).
0.29-0.41: RR = 1.03 (0.70-1.52).
0.42-6.52: RR = 1.03 (0.70-1.52).
Sudden death (death within one hour of the onset of symptoms. 89 cases):
Age-adjusted RR = 1.10 (0.56-2.13). | Age, energy, BMI, smoking habits, alcohol consumption, history of hypertension, history of diabetes, history of hypercholesterolemia, family history of MI, and profession. |
| 12) Dolecek TA (1992) | The Multiple Risk Factor Intervention Trial (MRFIT) | 6,250 men aged 35-57, and at a high risk of CHD.
(USA) | 10.5
(?-1985) | 175? | Coronary heart disease mortality | Dietary n-3 fish fatty acids | This was a randomized trial, but only data from the "usual care" group was analyzed.
| Grams | Percentage of total kilocalories |
RR = 0.61 (P = < 0.05) for the highest vs lowest quintile of consumption.
Amount specific data (grams):
0.000: RR = 1.
0.009: RR = 1.08
0.046: RR = 0.92
0.153: RR = 0.89
0.664: RR = 0.61
|
RR = 0.50 (P = < 0.05) for the highest vs lowest quintile of consumption.
Amount specific data (% of calories):
0.000: RR = 1.
0.004: RR = 1.07
0.019: RR = 0.82
0.063: RR = 1.12
0.284: RR = 0.50
|
Age, race, smoking, baseline diastolic blood pressure, HDL, LDL, and alcohol. |
| 12) Dolecek TA (1991) | The Multiple Risk Factor Intervention Trial (MRFIT) | 6,258 men aged 35-57, and at a high risk of developing CHD based upon smoking status, diastolic blood pressure, and serum cholesterol levels.
(USA) | ?-1985 | 175 | CHD mortality | Dietary long-chain omega 3 fatty acids from fish [EPA (20:5), DPA (22:5), and DHA (22:6)] | This was a randomized trial, but only data from the "usual care" group was analyzed.
RR = 0.60 (No 95% CI; P = 0.02) for the highest vs lowest quintile of consumption.
Amount specific data (g):
0.000: RR = 1
0.009: RR = 1.08
0.046: RR = 0.91
0.153: RR = 0.88
0.664: RR = 0.60 | Age, race, baseline smoking, diastolic blood pressure, HDL and LDL levels. |
Prospective studies of .dietary long-chain omega-3 fatty acids from fish and stroke:
| Author | Cohort name | Subjects | Years of follow-up | Cases | End point | Consumption of | Relative Risk (RR) | Adjustments |
| 23) Nagata C (2002) | The Takayama Study | 13,355 men and 15,724 women aged 35 or older.
(Japan) | 7
(1992-1999) | 137 men, and
132 women | Cerebrovascular disease mortality | Fish oil |
Stratified by gender:
| Men | women |
| HR = 1.19 (0.78-1.81; P = 0.37) for the highest vs lowest tertile of consumption (not defined). |
HR = 0.87 (0.58-1.30; P = 0.49) for the highest vs lowest tertile of consumption (not defined). |
Age, total energy, marital status, BMI, smoking status, exercise, and history of hypertension. |
| 22) Folsom AR (2004) | The Iowa Women's Health Study | 41,836 women aged 55-69, and free of heart disease or cancer. | 1986-2000 | 313? | Stroke mortality | Omega-3 fatty acids from fish (excluding fish oil supplements) | No association was found (results not shown). | Age, energy intake, education level, physical activity level, alcohol consumption, smoking status, pack-years of cigarette smoking, age at first livebirth, estrogen use, vitamin use, BMI, waist/hip ratio, diabetes, hypertension, intake of whole grains, fruits and vegetables, red meat, cholesterol, and saturated fat. |
| 20) Yuan JM (2001) | The Shanghai Cohort Study | 18,244 men aged 45-64 from Shanghai (China), and without a history of cancer. | 12
(1986-89 to 1998) | 480 | Stroke mortality | N-3 fatty acids from seafood |
RR = 1.00 (0.75-1.33; P = 0.36) for the highest vs lowest quintile of consumption.
Amount specific data (g/week):
< 0.27: RR = 1.
0.27-0.43: RR = 0.76 (0.57-1.03).
0.44-0.72: RR = 0.76 (0.58-0.98).
0.73-1.09: RR = 0.93 (0.69-1.24).
≥ 1.10: RR = 1.00 (0.75-1.33). | Age, total energy intake, level of education, BMI, current smoking, cigarettes smoked, alcohol, history of diabetes, and history of hypertension. |
| 17) Morris MC (1995) | The Physician's Health Study | 21,185 men aged 40-84, and without a history of MI, stroke, transient ischemic attacks, cancer, liver/renal disease, peptic ulcer, gout, current use of aspirin, other platelet-active drugs, or NSAID's.
(USA) | 4
(1983-1988) | 173 | Fatal and nonfatal stroke (infarcts caused by thrombotic or embolic occlusion of cerebral arteries [ischemic stroke], and intracerebal hemorrhage due to rupture of a vessel) | Long-chain omega 3 fatty acids from seafood (EPA & DHA from canned tuna fish; dark meat fish [e.g., mackerel, salmon, sardines, bluefish, swordfish]; other fish; and shrimp, lobster, or scallops as a main dish.
Excluding alpha-linolenic acid, and fish oil supplements) |
RR = 1.0 (0.6-1.6; P = 0.49) for the highest vs lowest quintile of consumption.
Amount specific data (g/week):
< 0.5: RR = 1.
0.5-< 1.0: RR = 0.9 (0.6-1.6).
1.0-< 1.7: RR = 1.1 (0.7-1.8).
1.7-< 2.3: RR = 0.7 (0.4-1.2).
≥ 2.3: RR = 1.0 (0.6-1.6). | Age, aspirin and beta-carotene assignment, smoking, alcohol consumption, obesity, diabetes mellitus, vigorous exercise, parental history of MI, history of hypertension, history of hypercholesterolemia, vitamin supplement use, and saturated fat intake. |
| 15) Montonen J (2009) | The Finnish Mobile Clinic Health Examination Survey | 3,958 men and women aged 40-79 and free of heart disease. | 28
(1967-1994) | See variables | CVA incidence | Marine long-chain n-3 fatty acids (not defined) |
Total cerebrovascular disease
(659 cases) | Intracerebral haemorrhage
(80 cases) | Thrombosis or embolia
(364 cases) |
RR = 1.01 (0.80-1.28; P = 0.90) for the highest vs lowest quartile of consumption.
Amount specific data (mg/d):
102: RR = 1.
202: RR = 0.97 (0.78-1.21).
332: RR = 0.91 (0.73-1.14).
655: RR = 1.01 (0.80-1.28).
|
RR = 1.56 (0.77-3.15; P = 0.22) for the highest vs lowest quartile of consumption.
Amount specific data (mg/d):
102: RR = 1.
202: RR = 1.20 (0.61-2.34).
332: RR = 1.28 (0.65-2.53).
655: RR = 1.56 (0.77-3.15).
|
RR = 0.91 (0.66-1.26; P = 0.66) for the highest vs lowest quartile of consumption.
Amount specific data (mg/d):
102: RR = 1.
202: RR = 0.95 (0.71-1.28).
332: RR = 0.99 (0.74-1.33).
655: RR = 0.91 (0.66-1.26).
|
Age, sex, energy intake, smoking, BMI, physical activity, geographic area, occupation, diabetes, use of postmenopausal hormones, hypertension, serum cholesterol, and consumptions of butter, vegetables, fruits, and berries. |
| 13) He K (2002) | The Health Professional's Follow-up Study | 43,671 men aged 40-75, and free of diabetes mellitues and CVD. | 12
(1986-1998) | See variables | Stroke incidence (fatal and nonfatal) | Omega-3 polyunsaturated fatty acids (EPA and DHA from fish and seafood) |
Total stroke
(608 cases) | Ischemic stroke
(embolism or thrombosis)
(377 cases) | Hemorrhagic stroke
(subarachnoid and intracerebral)
(106 cases) |
RR = 0.87 (0.56-1.37; P = 0.71) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
< 0.05: RR = 1.
0.05-< 0.2: RR = 0.77 (0.52-1.14).
0.2-< 0.4: RR = 0.77 (0.52-1.14).
0.4-< 0.6: RR = 0.71 (0.46-1.10).
≥ 0.6: RR = 0.87 (0.56-1.37).
|
RR = 0.73 (0.43-1.25; P = 0.73) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
< 0.05: RR = 1.
0.05-< 0.2: RR = 0.56 (0.35-0.88).
0.2-< 0.4: RR = 0.63 (0.40-0.98).
0.4-< 0.6: RR = 0.54 (0.32-0.91).
≥ 0.6: RR = 0.73 (0.43-1.25).
|
RR = 1.14 (0.34-3.84; P = 0.87) for the highest vs lowest quintile of consumption.
Amount specific data (g/d):
< 0.05: RR = 1.
0.05-< 0.2: RR = 1.29 (0.45-3.75).
0.2-< 0.4: RR = 1.02 (0.35-3.00).
0.4-< 0.6: RR = 0.89 (0.27-2.87).
≥ 0.6: RR = 1.14 (0.34-3.84).
|
Ischemic stroke. Stratified by alpha-linolenic acid intake:
| 0.23-0.91 g/d | 0.91-1.14 g/d | 1.14-5.82 g/d |
0.03 g/d: RR = 1.
0.16: RR = 0.61 (0.29-1.30).
0.40: RR = 0.70 (0.32-1.54).
|
0.03 g/d: RR = 1.
0.16: RR = 0.38 (0.18-0.83).
0.40: RR = 0.29 (0.13-0.64).
|
0.03 g/d: RR = 1.
0.16: RR = 0.82 (0.30-2.29).
0.40: RR = 0.89 (0.32-2.50).
|
Ischemic stroke. Joint classification with alpha-linolenic acid intake:
| 0.23-0.91 g/d | 0.91-1.14 g/d | 1.14-5.82 g/d |
0.03 g/d: RR = 1. Reference group
0.16: RR = 0.63 (0.31-1.29).
0.40: RR = 0.68 (0.33-1.40).
|
0.03 g/d: RR = 1.69 (0.67-4.25).
0.16: RR = 0.67 (0.33-1.39).
0.40: RR = 0.53 (0.25-1.10).
|
0.03 g/d: RR = 0.68 (0.22-2.07).
0.16: RR = 0.62 (0.30-1.29).
0.40: RR = 0.69 (0.33-1.45).
|
Age, smoking, BMI, physical activity, history of hypertension, use of aspirin, fish oil, multivitamins, intake of total calories, total fat, saturated fat, trans-unsaturated fat, alcohol, potassium, magnesium, total servings of fruits and vegetables, and hypercholesterolemia. |
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