American Journal of Cardiology
Volume 99, Issue 9 , Pages 1230-1233, 1 May 2007

Relation of Omega-3 Fatty Acid Intake to Other Dietary Factors Known to Reduce Coronary Heart Disease Risk

  • David Keith Cundiff, MD

      Affiliations

    • Department of Internal Medicine, Los Angeles County and USC Medical Center, Los Angeles, California
    • Corresponding Author InformationCorresponding author: Tel: 562-438-8805; fax: 562-433-4809.
    • ,
  • Amy Joy Lanou, PhD

      Affiliations

    • Department of Health and Wellness, University of North Carolina, Asheville, North Carolina
    • ,
  • Claudio Renato Nigg, PhD

      Affiliations

    • Department of Public Health Sciences & Epidemiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii.

Received 7 July 2006; received in revised form 13 December 2006; accepted 13 December 2006.

Article Outline

Data supporting the inverse correlation of fish or long-chain ω-3 fatty acid (FA) (eicosapentaenoic acid plus docosahexaenoic acid) supplement consumption and coronary heart disease are inconclusive and may be confounded by other dietary and lifestyle factors. Using the Diabetic Control and Complications Trial (DCCT) database (n = 1,441), correlations between consumption of ω-3 FAs and saturated FAs to dietary variables (kilocalories, macronutrients, sodium, and cholesterol) and to age, gender, exercise level, and tobacco use were tested using Pearson correlation coefficients. Long-chain ω-3 FA intake inversely correlated with consumption of calories (r = −0.16, p <0.0001), percent calories from total fat (r = −0.14, p <0.0001), and percent calories from saturated FAs (r = −0.21, p <0.0001) and directly with dietary fiber intake (grams per 1,000 kcal, r = 0.20, p <0.0001). In the DCCT database, long-chain ω-3 FAs (i.e., fish consumption) inversely correlated with an overall low risk nutritional profile for coronary heart disease. In conclusion, these findings provide evidence that associations observed in studies suggesting a benefit of fish or long-chain ω-3 FAs may be due to a convergence of greater fish intakes with an overall healthier dietary pattern rather than with a specific effect of long-chain ω-3 FAs.

 

In October 2006, the food and nutrition committee of the Institute of Medicine declared that eating fish and shellfish is associated with overall lower risk for developing heart disease. However, it called this finding “preliminary” because: “It is not certain whether this is because substituting the lean protein of seafood for fatty cuts of meat reduces consumers’ intake of saturated fat and cholesterol or because of the protective effects of omega-3 fatty acids, which are found in relatively high amounts in many fish species.”1 Given the inconclusive nature of the potential relation between long-chain ω-3 fatty acids (FAs) and risk of coronary heart disease (CHD)2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 and the mercury and other toxins prevalent in fish,21 more clarity regarding possible confounding dietary factors in fish consumers is important to promote an understanding of this relation and to frame public policy statements. In this study, the relation of long-chain ω-3 FA intake to intake of other nutrients and other potential confounders was analyzed using the Diabetic Control and Complications Trial (DCCT) nutritional database. This publicly available dataset contains nutritional data on 1,441 North American subjects collected over 9 years.

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Methods 

The DCCT computerized datasets in Statistical Analysis System (SAS) format with documentation purchased from the National Technical Information Service were used for this study. Because this dataset is in the public domain, this post hoc analysis did not need to be authorized by the DCCT study group.

The DCCT eligibility criteria and screening methods have been previously reported in detail.22 At baseline, all subjects had to be 13 to 39 years of age, deficient in C-peptide, and without hypertension, hypercholesterolemia, severe diabetic complications, or other medical conditions. Investigators recruited 1,441 study participants (761 men and 680 women; 96.5% Caucasian, 2.0% African-American, and 1.5% other races) between 1983 and 1989, comprising 726 subjects in the primary prevention study and 715 in the secondary intervention study. At the end of the trial in 1993, the mean time on study was 6.5 years (range 3.8 to 9.7).23 Institutional review boards in the 29 diabetes specialty centers approved the trial, so further approval by a human subjects research committee was not required.

Trained dietitians interviewed participants and conducted a modified Burke-type diet history24 that took ∼1.5 to 2 hours to complete. This diet evaluation instrument had a high reproducibility on repeated administrations of diet history.25 Dietitians collected quantitative and qualitative information representing a usual week of dietary intake over the previous year. Subsequently, dietitians obtained follow-up diet histories at years 2 and 5 and at the end of the study.22 Diet histories were evaluated with nutritional analysis software.

For this analysis, nutrient intake predictive of a heart healthy dietary pattern—energy, dietary fiber, total FAs, saturated FAs, linoleic acid, α-linolenic acid (ALA), long-chain ω-3 FAs (eicosapentaenoic acid plus docosahexaenoic acid), sodium, and cholesterol—was evaluated. In addition, relations of nutrient intake to age, gender, average exercise level (measured on a 4-point scale), and smoking (overall packs per year smoked while in the study) were analyzed.

In addition, because the American Heart Association recommends consuming 1 g/day of long-chain ω-3 FAs from oily fish, the nutrient profile of oily fish (i.e., salmon, mackerel, herring, sardines, halibut, trout, and oyster) containing 1 g/day of long-chain ω-3 FAs was compared with unselected fish, beef, and ALA-containing foods (e.g., soybeans, walnut, and flaxseeds) using an equal weight of these foods determined using the US Department of Agriculture Nutrient Database.26

In the DCCT database, men consumed 51.1% more kilocalories than women (women, 1,818 kcal/day, 95% confidence interval ±47; men, 2,748 kcal/day, 95% confidence interval ±47) and mean intakes ± SE of women and men decreased significantly per year (women, −7.2 ± 2.08 kcal/day/year; men, −29.5 ± 3.41 kcal/day/year). Hence, gender and age confound the correlations between intake of macronutrients in grams and sodium and cholesterol in milligrams. Therefore, standardized measurements such as percent caloric intake for fats, grams per 1,000 kcal/day of dietary fiber, and milligrams per 1,000 kcal/day for sodium and cholesterol were analyzed.

Pearson correlation functions were used to relate fish oil ω-3 FA intake with other nutrient intakes, exercise levels, and tobacco consumption. The data met assumptions for Pearson correlation because data on lifestyle and nutrient variables are normally distributed in a large population and differ independently of each other.27

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Results 

Long-chain ω-3 FA intake and ALA consumption averaged 0.04% (0.09 g/day) and 0.62% (1.61 g/day) of kilocalories, respectively (Table 1). Long-chain ω-3-FA intake inversely correlated with intake of calories, total FAs, saturated FAs, and sodium, and positively correlated with dietary fiber consumption (Table 2). Saturated FA consumption correlated directly with intake of calories, total FAs, and sodium and inversely with dietary fiber. ALA had similar but weaker associations as did saturated FAs. Older subjects tended to have more long-chain ω-3 FAs in their diets (age vs long-chain ω-3 FA intake in percent kilocalories, r = 0.17, p <0.0001). Adjusting for age only slightly attenuated the strength of the correlations.

Table 1. Average intake of long-chain ω-3 fatty acids and other nutrients in the DCCT database (n = 1,441)
NutrientIntake/day, Mean ± SD
Kilocalories2,310±725
ω-3 FAs from fish
g0.09±0.10
%kcal0.04±0.04
ALA
g1.61±0.62
%kcal0.68±0.16
Total FA
g94.9±37.0
%kcal36.4±5.46
Saturated FA
g32.8±14.1
%kcal12.6±2.42
Dietary fiber
g24.2±8.0
g/1,000 kcal10.8±3.0
Cholesterol
mg340±161
mg/1,000 kcal146±48.1
Sodium
mg4,300±1,382
mg/1,000 kcal1,877±281
Table 2. Fish oil ω-3 and saturated fatty acid intake correlated with other variables in the DCCT database (n = 1,441)
NutrientsFish ω-3 FAs (%kcal)Saturated Fatty FAs (%kcal)ALA (%kcal)
rp Valuerp Valuerp Value
Kilocalories−0.16<0.00010.31<0.00010.050.06
Total FAs (%kcal)−0.14<0.00010.82<0.00010.59<0.0001
Saturated FAs (%kcal)−0.21<0.0001——0.36<0.0001
ALA (%kcal)0.12<0.00010.36<0.0001——
Dietary fiber (mg/1,000 kcal)0.20<0.0001−0.65<0.0001−0.20<0.0001
Cholesterol (g/1,000 kcal)0.10<0.00010.43<0.00010.25<0.0001
Sodium (mg/1,000 kcal)−0.060.020.030.210.15<0.0001
Age (yrs)0.17<0.0001−0.060.030.040.12
Exercise (1–4 scale)0.020.41−0.070.01−0.050.07
Tobacco use (pack/yr)−0.020.400.17<0.00010.050.05
Sex (F = −; M = +)0.030.220.16<0.00010.020.42

As presented in Table 2, the higher saturated FA intake associated with not eating fish is itself associated with less exercise and more tobacco use. Further, when ω-3 FAs are regressed with all 10 variables listed in Table 2, only saturated FAs, cholesterol, sodium, calories, and age remain significant at the 0.05 level. Total fat and dietary fiber are no longer significantly related because of their relations to the dominant factors of saturated fat and cholesterol. Saturated fat and cholesterol strongly directly correlate with total fat (r = 0.82, p <0.0001 and r = 0.43, p <0.0001, respectively) and strongly inversely correlate with dietary fiber (r = −0.65, p <0.0001 and r = −0.31, p <0.0001, respectively). In this multiple regression model, saturated fat and cholesterol account for 8.9% of the variance in ω-3 FA (percent kilocalories) consumption, whereas calories and sodium account for only 1.0% of the variance.

As presented in Table 3, consuming 1.0 g/day of long-chain ω-3 FAs requires an intake of 87 g/day of oily fish. Substituting 87 g/day of red meat with oily fish decreases saturated FA consumption by 4 g/day. The ALA-rich foods are higher in calories and total fat but have abundant fiber and no cholesterol.

Table 3. Nutrient content of oily fish containing 1.0 gram ω-3 fatty acids compared with an equal weight of unselected fish, red meat, and α-linolenic acid–rich foods⁎
Mean Nutrients/100 (g)Oily Fish† (n = 68)Unselected Fish (n = 195)Red Meat‡ (n = 620)ALA-Rich Foods§ (n = 3)
Weight (g)87.087.087.087.0
Kilocalories12895.7197319
Long-chain ω-3 FAs (g)1.000.550.120.00
ALA (g)0.010.050.005.94
Total FAs (g)6.613.8314.428.8
Saturated FAs (g)1.460.845.472.11
Dietary fiber (g)0.000.000.0011.3
Cholesterol (mg)50.357.286.80.00
Sodium (mg)20317728482.9

⁎From US Department of Agriculture Nutrient Database for Standard Reference, release 17.26

†Salmon, herring, mackerel, sardines, tuna, trout, oysters, and halibut.

‡Beef, lamb, veal, game, and pork.

§Nuts, seeds, and soybeans.

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Discussion 

The dietary data from DCCT showed a strong positive correlation between fish intake (considering long-chain ω-3 FAs a marker for fish) and a nutrient intake profile associated with a lower CHD risk. A difference of 0.19 g/day of long-chain ω-3 FAs corresponds to a difference of 8.3 g/day in intake of saturated FAs (data not shown). Only 1 other study in the medical literature has examined the relation of fish intake to overall dietary consumption. The Cardio 2000 Study from Greece used a case-control method to investigate the association between fish consumption and development of nonfatal acute coronary syndromes. Using types of foods as categorical variables rather than quantitating nutrient intakes, this study found that fish intake was associated with consumption of the following other foods: red meat was inversely related in patient and control groups (p <0.001 for the 2 comparisons), and vegetables, fruit, and legumes were directly associated (p <0.001 for all patient and control groups).28

Results of prospective cohort studies addressing the question of whether higher levels of long-chain ω-3 FAs and/or fish consumption might decrease the risk of CHD are mixed and inconclusive.2, 3, 4, 5, 6, 7, 8, 9, 10, 11 Many of the prospective cohort studies did not measure or adjust for possible dietary confounders (saturated FA and cholesterol intake, and so forth) or lifestyle factors such as exercise or smoking habit.2, 3, 4, 5, 6, 7, 8, 9, 10 Hence, results of these studies may be confounded by associated significant differences in intake of important nutrients for CHD risk such as saturated FAs and cholesterol.

Data from randomized controlled trials12, 13, 14, 15, 16, 17, 18, 19, 20 are also inconclusive. The 21% decrease in sudden cardiovascular death in the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI) trial12 suggests an antiarrhythmic effect of fish oil supplements. However, the trend toward a proarrhythmic effect of long-chain ω-3 FA supplements in the study by Raitt et al17 (p = 0.19) throws any antiarrhythmic or other benefit into question. Even if long-chain ω-3 FA supplements do decrease CHD morbidity and mortality in high-risk patients, the Indian Experiment of Infarct Survival—416 suggests that ALA supplements from mustard oil may be as good as fish oil supplements in decreasing CHD risks.

Nilsen et al15 randomized 300 patients after myocardial infarction to receive supplements of fish oil 4 g/day versus corn oil 4 g/day. Forty-two patients (28%) in the ω-3 group and 36 (24%) in the corn oil group (p = NS) developed ≥1 cardiac event (cardiac death, resuscitation, recurrent myocardial infarction, or unstable angina). In each group, 5.3% had cardiac deaths.15

In a trial from Italy that examined the incidence of postoperative atrial fibrillation after coronary artery bypass grafting, 27 patients (33.3%) in the control group and 12 patients (15.2%) in the long-chain ω-3 FA group (p = 0.013) developed atrial fibrillation. The patients treated with ω-3 FAs had shorter hospital stays, but overall clinical benefits were questionable.19 Two more relatively small randomized controlled trials involving long-chain ω-3 FA supplements with CHD risk factor (surrogate) end points provided no clinical evidence for or against fish oil supplements.18, 20

Another question is whether any possible benefit of ω-3 FAs implies the need for fish rather than ω-3 FAs from plant sources. The Lyon Diet Heart Study randomized 605 subjects after myocardial infarction to a Mediterranean-type diet rich in ALA or to a “prudent diet” similar to the former American Heart Association Step 1 diet. After a mean follow-up of 27 months, overall mortalities were 20 with the prudent diet, and 8 with the ALA-rich diet (adjusted relative risk 0.30, 95% confidence interval 0.11 to 0.82, p = 0.02).13 The protective effect extended to 4 years. In this trial, FA intake differed significantly between groups: patients on the prudent diet averaged 0.29% of kilocalories (0.67 g/day) as ALA and 11.7% (27.1 g/day) as saturated fat, whereas those on the Mediterranean diet averaged 0.84% of kilocalories (1.82 g/day) as ALA and 8.0% (17.3 g/day) as saturated FAs. Long-chain ω-3 FA intakes were not reported.14 In the Lyon Heart Trial, the 9.8-g/day lower saturated fat intake with the Mediterranean diet versus the prudent diet (<30% dietary fat similar to that of the American Heart Association) may account for most or all of the 70% decrease in overall mortality rather than the 1.15-g/day higher intake of ALA.

Because lack of fish consumption is associated with eating more saturated FAs and high saturated FA intake relates to more smoking and less exercise (Table 2), lifestyle factors and dietary factors may confound the relation of fish consumption with CHD. For many years, the American Diabetes Association has encouraged people with diabetes to eat more fruits and vegetables and to substitute fish and poultry for red meat. Hence, ω-3 FA consumption may be a marker for compliance with dietary recommendations by the American Diabetes Association and even possibly lifestyle recommendations (e.g., exercise and avoid smoking).

If fish consumption worldwide has these strong associations with intake of an overall low CHD risk diet and other healthy behaviors generally as the data suggest that it does in subjects in Greece and the DCCT, then all cohort studies showing an inverse association of fish consumption with CHD events are potentially confounded by a fish-related overall low CHD risk diet. In other words, fish intake would be a marker of a low CHD risk diet and may not itself be causally related to fewer CHD events or lower mortality. To further clarify this finding, the relation of fish and/or long-chain ω-3 FA intake with overall saturated fat and cholesterol consumption should be analyzed in other databases.

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PII: S0002-9149(07)00143-9

doi:10.1016/j.amjcard.2006.12.032

American Journal of Cardiology
Volume 99, Issue 9 , Pages 1230-1233, 1 May 2007

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