Consumption of dietary alpha-linolenic acid and cardiovascular disease.

Alpha-linolenic acid and total cardiovascular disease (CVD).

Results: Data about alpha-linolenic acid in relation to total cardiovascular disease was provided by 2 cohorts of (very) small size, including 310 cases.
A nonsignificant protective effect was found in one cohort (Dolecek TA [12]). No association was found in the other cohort, though the effect size was similar. The average RR = 0.62.
Effect modification: No data was found.
Subjects with prevalent disease: No data was found.

Conclusion: No significant associations were found. Inconclusive evidence was found for an association between consumption of dietary alpha-linolenic acid and total cardiovascular disease.

**Prospective studies of dietary (alpha-)linolenic acid and total cardiovascular disease:**
Author	Cohort name	Cases	End point	Relative Risk (RR)
32) Laaksonen DE (2005)	The Kuopio Ischaemic Heart Disease Risk Factor Study	78	Mortality	RR = 0.63 (0.33-1.21; P = 0.18).
12) Dolecek TA (1992)	The Multiple Risk Factor Intervention Trial	232	Mortality	RR = 0.61 (P = 0.10).
		Total number of cases: 310		Average RR = 0.62

Alpha-linolenic acid and coronary heart disease (CHD).

Results:
Coronary heart disease risk: Data was provided by 6 cohorts, including 6,517 cases.
A significant protective effect was found against sudden death, but not other CHD in one cohort (Albert CM [13]), and a nonsignificant protective effect against total CHD risk was found in another cohort (Mozaffarian D [13]). RR's were available from 5 cohorts. The average RR = 0.95.
Coronary heart disease mortality: Data was provided by 5 cohorts, including 1,924 cases.
A significant protective effect was found against sudden death, but not other CHD mortality in one cohort (Albert CM [13]), and a nonsignificant protective effect against total CHD mortality was found in another cohort (Pietinen P [19]). The average RR = 0.87.
Effect modification:

A significant protective effect against total CHD risk was found only among subjects with low EPA/DHA in one cohort (Mozaffarian D [13]), but no effect modification by long-chain n-3 fatty acids was found in another cohort (Albert CM [13]).
No significant effect modification was found by smoking status, alcohol intake, linolenic acid intake trans fat intake, or vitamin E supplement use (Hu FB [13]), age (Albert CM [13]), aspirin use (Hu FB [13], Albert CM [13]), or intakt of n6 fatty acids (Albert CM [13], Mozaffarian D [13]).

Subjects with prevalent disease: No significant effect against sudden death was found among women with CVD (Albert CM [13]).

Conclusion: Some protective effects were found, but these were restricted to specific CHD end points, or nonsignificant. Inconclusive evidence was found for an association between consumption of dietary alpha-linolenic acid and coronary heart disease.

**Prospective studies of dietary (alpha-)linolenic acid and coronary heart disease risk:**
Author	Cohort name	Cases	End point	Relative Risk (RR)
19) Pietinen P (1997)	The ATBC Study	1,399	Risk	RR = 0.96 (0.80-1.14; P = 0.91).
13) Albert CM (2005)	The Nurses' Health Study	206 sudden death, 641 other fatal CHD, and 1,604 nonfatal MI	Mortality, and Nonfatal MI	Sudden death: RR = 0.60 (0.37-0.96; P = 0.02). Other CHD death: RR = 1.01 (0.77-1.33). Nonfatal MI: RR = 1.09 (0.92-1.29; P = 0.38).
13) Mozaffarian D (2005)	The Health Professionals Follow-up Study	2,306	Risk	HR = 0.84 (0.71-1.00).
12) Dolecek TA (1992)	The Multiple Risk Factor Intervention Trial	175	Mortality	RR = 0.66 (P = NS).
7) Oomen CM (2001)	The Zutphen Elderly Study	98	Risk	RR = 1.68 (0.86-3.29; P = 0.17).
1) Oglesby P (1963)	The Western Electric Study	88	Risk	No significant association.
		Total number of cases: 6,517		Average RR = 0.95

**Prospective studies of dietary (alpha-)linolenic acid and coronary heart disease mortality:**
Author	Cohort name	Cases	End point	Relative Risk (RR)
19) Pietinen P (1997)	The ATBC Study	635	CHD	RR = 0.71 (0.49-1.02; P = 0.07).
13) Albert CM (2005)	The Nurses' Health Study	206 sudden death, and 641 other fatal CHD	CHD	Sudden death: RR = 0.60 (0.37-0.96; P = 0.02). Other CHD death: RR = 1.01 (0.77-1.33).
13) Mozaffarian D (2005)	The Health Professionals Follow-up Study	218	Sudden death	HR = 1.15 (0.69-1.93).
12) Dolecek TA (1992)	The Multiple Risk Factor Intervention Trial	175	CHD	RR = 0.66 (P = NS).
7) Oomen CM (2001)	The Zutphen Elderly Study	49	CHD	RR = 1.59 (0.62-4.08; P = 0.26).
		Total number of cases: 1,924		Average RR = 0.87

Alpha-linolenic acid and stroke.

One article was found examining the relation between alpha-linonelic acid and ischemic stroke risk (He K [13]). No association was found (no data shown).

Grams

Percentage of total kilocalories

RR = 0.61 (P = < 0.10) for the highest vs lowest quintile of consumption.

Amount specific data (grams):
0.9: RR = 1.
1.3: RR = 0.93
1.6: RR = 0.66
1.9: RR = 0.88
2.8: RR = 0.61

RR = 0.66 (P = < 0.05) for the highest vs lowest quintile of consumption.

Amount specific data (% of calories):
0.4: RR = 1.
0.5: RR = 0.86
0.6: RR = 0.97
0.7: RR = 0.66
1.0: RR = 0.66

Major coronary events
(1,399 cases)

Coronary death
(635 cases)

RR = 0.96 (0.80-1.14; P = 0.911) for the highest vs lowest quintile of consumption.

Amount specific data (intake in g):
0.9: RR = 1.
1.2: RR = 0.94 (0.80-1.11).
1.5: RR = 0.99 (0.84-1.17).
1.9: RR = 1.01 (0.86-1.20).
2.5: RR = 0.96 (0.80-1.14).

RR = 0.75 (0.52-1.10; P = 0.050) for the highest vs lowest quintile of consumption.

Amount specific data (intake in g):
0.9: RR = 1.
1.2: RR = 0.95 (0.74-1.21).
1.5: RR = 0.94 (0.71-1.24).
1.9: RR = 0.87 (0.63-1.20).
2.5: RR = 0.75 (0.52-1.10).

After additional adjustment for vitamin E, vitamin C, and beta carotene, the RR became: 0.71 (0.49-1.02; P = 0.07).

Sudden cardiac death
(occuring within 1 hour of symptom onset)
(206 cases)

Other fatal CHD
(641 cases)

Nonfatal MI
(1,604 cases)

RR = 0.60 (0.37-0.96; P = 0.02) for the highest vs lowest quintile of consumption.

Amount specific data (% of energy):
0.37: RR = 1.
0.45: RR = 0.86 (0.57-1.29).
0.52: RR = 0.76 (0.50-1.16).
0.60: RR = 0.62 (0.39-0.98).
0.74: RR = 0.60 (0.37-0.96).

Absolute intake: 1% of energy = 1,93 g/day.

RR = 1.01 (0.77-1.33; P = 0.74) for the highest vs lowest quintile of consumption.

Amount specific data (% of energy):
0.37: RR = 1.
0.45: RR = 1.13 (0.89-1.43).
0.52: RR = 0.92 (0.71-1.18).
0.60: RR = 0.96 (0.74-1.25).
0.74: RR = 1.01 (0.77-1.33).

RR = 1.09 (0.92-1.29; P = 0.38) for the highest vs lowest quintile of consumption.

Amount specific data (% of energy):
0.37: RR = 1.
0.45: RR = 1.03 (0.88-1.20).
0.52: RR = 1.01 (0.86-1.19).
0.60: RR = 1.02 (0.86-1.20).
0.74: RR = 1.09 (0.92-1.29).

Sudden cardiac death.
Stratified by history of nonfatal CVD before the SCD:

No prior history of CVD
(159 cases)

Prior history of CVD
(57 cases)

RR = 0.59 (0.34-1.02; P = 0.03) for the highest vs lowest quintile of consumption.

Amount specific data (% of energy):
0.37: RR = 1.
0.45: RR = 0.89 (0.56-1.41).
0.52: RR = 0.86 (0.54-1.39).
0.60: RR = 0.60 (0.35-1.03).
0.74: RR = 0.59 (0.34-1.02).

RR = 0.53 (0.19-1.45; P = 0.33) for the highest vs lowest quintile of consumption.

Amount specific data (% of energy):
0.35: RR = 1.
0.43: RR = 0.68 (0.28-1.64).
0.49: RR = 0.38 (0.14-1.06).
0.58: RR = 0.76 (0.30-1.88).
0.72: RR = 0.53 (0.19-1.45).

Sudden cardiac death.
Stratified by long-chain n-3 fatty acids:

High EPA/DHA (> 0.09% of energy)

Low EPA/DHA (≤ 0.09% of energy)

RR = 0.41 (0.21-0.79; P = 0.049; [P = 0.008 for the highest intake of both fatty acics]) for the highest vs lowest quintile of consumption.

Amount specific data (Quintiles not defined):
Q1: RR = 0.75
Q2: RR = 0.70
Q3: RR = 0.74
Q4: RR = 0.46
Q5: RR = 0.41

RR = 0.64 (P = 0.12) for the highest vs lowest quintile of consumption.

Amount specific data (Quintiles not defined):
Q1: RR = 1 (reference group)
Q2: RR = 0.79
Q3: RR = 0.60
Q4: RR = 0.62
Q5: RR = 0.64

Sudden death
(218? cases)

Nonfatal MI
(1,521? cases)

Total CHD
(2,306? cases)

HR = 1.15 (0.69-1.93) for each 1 g/d.

HR = 0.52 (0.14-1.90) for each 1 g/d of ALA intake among men with low EPA + DHA intake (< 100 mg/d). But no association was found among men with a higher EPA + DHA intak (≥ 100 mg/d. No data shown).

HR = 0.82 (0.67-1.02) for each 1 g/d.

HR = 0.42 (0.23-0.75; P = 0.004) for each 1 g/d of ALA intake among men with low EPA + DHA intake (< 100 mg/d). But no association was found among men with a higher EPA + DHA intak (≥ 100 mg/d. No data shown).

HR = 0.84 (0.71-1.00) for each 1 g/d.

HR = 0.53 (0.34-0.83; P = 0.008) for each 1 g/d of ALA intake among men with low EPA + DHA intake (< 100 mg/d). But no association was found among men with a higher EPA + DHA intak (≥ 100 mg/d. No data shown).

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 ALA: RR = 1 (Reference) for < 1080 mg/d.
High ALA: RR = 0.95 (0.64-1.43) for ≥ 1080 mg/d.

Low ALA: RR = 0.88 (0.56-1.36) for < 1080 mg/d.
High ALA: RR = 0.93 (0.64-1.35) for ≥ 1080 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 ALA: RR = 1 (Reference) for < 1080 mg/d.
High ALA: RR = 0.85 (0.72-0.99) for ≥ 1080 mg/d.

Low ALA: RR = 0.98 (0.84-1.15) for < 1080 mg/d.
High ALA: RR = 0.89 (0.77-1.02) for ≥ 1080 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 ALA: RR = 1 (Reference) for < 1080 mg/d.
High ALA: RR = 0.88 (0.78-0.99) for ≥ 1080 mg/d.

Low ALA: RR = 0.93 (0.82-1.07) for < 1080 mg/d.
High ALA: RR = 0.89 (0.79-0.99) for ≥ 1080 mg/d.

Fatal CHD
(232 cases, and an additional 74 cases among women with a prior MI)

Nonfatal MI
(597 cases)

RR = 0.55 (0.32-0.94; P = 0.01) for the highest vs lowest quintile of consumption.

Amount specific data (g/d):
0.71: RR = 1.
0.86: RR = 0.99 (0.66-1.48).
0.98: RR = 0.90 (0.59-1.39).
1.12: RR = 0.67 (0.42-1.09).
1.36: RR = 0.55 (0.32-0.94).

Further adjustment for intakes of fish n-3 fatty acids, oleic acid, trans fatty acids, cholesterol, folate, or fiber did not materially alter the association.

Alpha-linolenic acid from plant sources:
RRs by quintiles: 1.0, 1.17 (0.80-1.74), 0.83 (0.52-1.30), 0.55 (0.33-0.94), and 0.64 (0.36-1.13; P = 0.03).
Excluding women who had diabetes of hypercholesterolemia at baseline:
RRs by quintiles: 1.0, 0.93, 0.80, 0.58, and 0.55 (0.29-1.07; P = 0.04).
Among women with a prior MI:
RRs by quintiles: 1.0, 0.61 (0.28-1.30), 0.90 (0.41-1.97), 0.61 (0.24-1.52), and 0.35 (0.12-1.01; P = 0.07).
Effect modification: The association did not vary appreciably with intakes of linoleic acid, or n-3 fatty acids from fish, and were similar by smoking status (current vs never), and alcohol drinking status (current vs never).

RR = 0.85 (0.61-1.19; P = 0.50) for the highest vs lowest quintile of consumption.

Amount specific data (g/d):
0.71: RR = 1.
0.86: RR = 0.92 (0.71-1.21).
0.98: RR = 0.94 (0.71-1.25).
1.12: RR = 1.02 (0.76-1.19).
1.36: RR = 0.85 (0.61-1.19).

Fatal IHD. Stratified by vitamin E supplement use:

Nonusers

Vitamin E supplement users

RR = 0.57 for the highest vs lowest quintile of consumption.

Amount specific data (g/d):
0.71: RR = 1 (Reference group)
0.86: RR = 1.01
0.98: RR = 0.94
1.12: RR = 0.71
1.36: RR = 0.57

RR = 0.36 for the highest vs lowest quintile of consumption.

Amount specific data (g/d):
0.71: RR = 1.02
0.86: RR = 0.87
0.98: RR = 0.66
1.12: RR = 0.43
1.36: RR = 0.36

Fatal IHD. Stratified by intake of trans fatty acids:

Tertile 1 of trans fatty acids

Tertiles 2 & 3 of trans fatty acids

RR = 0.39 for the highest vs lowest quintile of consumption.

Amount specific data (g/d):
0.71: RR = 1 (Reference group)
0.86: RR = 0.97
0.98: RR = 1
1.12: RR = 0.55
1.36: RR = 0.39

RR = 0.6 for the highest vs lowest quintile of consumption.

Amount specific data (g/d):
0.71: RR = 1.01
0.86: RR = 1.02
0.98: RR = 0.86
1.12: RR = 0.73
1.36: RR = 0.6

Fatal IHD. Stratified by aspirin use:

Aspirin nonusers

Aspirin users

RR = 0.51 (0.24-1.09; P = 0.08) for the highest vs lowest quintile of consumption.

RR = 0.60 (0.28-1.31; P = 0.06) for the highest vs lowest quintile of consumption.

Total MI (including non-fatal MI and fatal cHD):
(734 cases)

Fatal CHD:
(229 cases)

RR = 0.80 (0.63-1.03; P = 0.07) for the highest vs lowest quintile of consumption.

Amount specific data (g/day):
0.8: RR = 1.
0.9: RR = 1.00 (0.79-1.26).
1.1: RR = 0.97 (0.77-1.23).
1.2: RR = 0.98 (0.78-1.24).
1.5: RR = 0.80 (0.63-1.03).

RR for a proportion of energy of 1%:
RR = 0.53 (0.30-0.95; P = < 0.05).
After additional adjustment for total fat: RR = 0.41 (0.21-0.80; P = < 0.01).

RR = 1.03 (0.66-1.59; P = 0.76) for the highest vs lowest quintile of consumption.

Amount specific data (g/day):
0.8: RR = 1.
0.9: RR = 1.12 (0.72-1.72).
1.1: RR = 1.02 (0.66-1.58).
1.2: RR = 1.35 (0.90-2.03).
1.5: RR = 1.03 (0.66-1.59).

RR for a proportion of energy of 1%:
RR = 0.89 (0.34-2.36).
After additional adjustment for total fat: RR = 0.57 (0.18-1.79).

Grams

Percentage of total kilocalories

RR = 0.66 (P = NS) for the highest vs lowest quintile of consumption.

Amount specific data (grams):
0.9: RR = 1.
1.3: RR = 0.96
1.6: RR = 0.56
1.9: RR = 0.96
2.8: RR = 0.66

RR = 0.58 (P = < 0.05) for the highest vs lowest quintile of consumption.

Amount specific data (% of calories):
0.4: RR = 1.
0.5: RR = 0.72
0.6: RR = 0.80
0.7: RR = 0.61
1.0: RR = 0.58

Total CAD:
(98 cases)

Fatal coronary artery disease:
(49 cases)

RR = 1.68 (0.86-3.29; P = 0.17) for the highest vs lowest tertile of consumption.

Amount specific data (% of energy):
< 0.45: RR = 1.
0.45-0.58: RR = 1.49 (0.82-2.70).
≥ 0.58: RR = 1.68 (0.86-3.29).

RR = 1.59 (0.62-4.08; P = 0.26) for the highest vs lowest tertile of consumption.

Amount specific data (% of energy):
< 0.45: RR = 1.
0.45-0.58: RR = 0.99 (0.43-2.28).
≥ 0.58: RR = 1.59 (0.62-4.08).

Total CAD:

Alpha-linolenic acid from sources with trans fatty acids
(e.g., margarine, cooking fat, butter, cookies, pastries, meat, dairy products, and bread)
(98 cases)

Alpha-linolenic acid from sources without trans fatty acids
(e.g., cereals, legumes, vegetables, and fruit)
(98 cases)

RR = 1.51 (0.75-3.04; P = 0.31) for the highest vs lowest tertile of consumption.

Amount specific data (% of energy):
< 0.40: RR = 1.
0.40-0.52: RR = 1.42 (0.78-2.57).
> 0.52: RR = 1.51 (0.75-3.04).

RR = 1.15 (0.63-2.11; P = 0.67) for the highest vs lowest tertile of consumption.

Amount specific data (% of energy):
< 0.04: RR = 1.
0.04-0.06: RR = 1.06 (0.62-1.81).
> 0.06: RR = 1.15 (0.63-2.11).

**Prospective studies of dietary alpha-linolenic acid and stroke:**
Author	Cohort name	Subjects	Years of follow-up	Cases	End point	Consumption of	Relative Risk (RR)	Adjustments
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)	608?	Ischemic stroke incidence (fatal and nonfatal)	Alpha-linolenic acid (not defined)	There was no apparent or statistically significant overall association between alpha-linolenic acid intake and risk of stroke (data not shown).	Not defined for this variable, possibly: 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.

Prospective studies of dietary alpha-linolenic acid and stroke:

Author

Cohort name

Subjects

Years of follow-up

Cases

End point

Consumption of

Relative Risk (RR)

Adjustments

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)

608?

Ischemic stroke incidence (fatal and nonfatal)

Alpha-linolenic acid (not defined)

There was no apparent or statistically significant overall association between alpha-linolenic acid intake and risk of stroke (data not shown).

Not defined for this variable, possibly: 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.

Cardiovascular disease & Diet. A systematic review.

Literature review.

Relating various aspects of our
diet to heart disease and stroke.

Consumption of dietary alpha-linolenic acid and cardiovascular disease.

Alpha-linolenic acid and total cardiovascular disease (CVD).

Alpha-linolenic acid and coronary heart disease (CHD).

Alpha-linolenic acid and stroke.

Cardiovascular disease & Diet. A systematic review.

Literature review.

Relating various aspects of ourdiet to heart disease and stroke.

Consumption of dietary alpha-linolenic acid and cardiovascular disease.

Alpha-linolenic acid and total cardiovascular disease (CVD).

Alpha-linolenic acid and coronary heart disease (CHD).

Alpha-linolenic acid and stroke.

Relating various aspects of our
diet to heart disease and stroke.