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Alpha-Linolenic Acid Reduces Risk of Nonfatal MI

Posted: Wednesday, July 23, 2008

The consumption of a diet containing vegetable oils rich in alpha-linolenic acid (ALA) is associated with significant reductions in the risk of nonfatal myocardial infarction (MI), a new study has shown. 

Investigators say the protective effect of ALA is evident among individuals with low intakes, suggesting the greatest benefit might be in developing countries, where fatty-acid consumption is limited.

"The potential for benefit is great when the baseline intake is low," said lead investigator Dr Hannia Campos (Harvard Medical School, Boston, MA). "In countries where people eat very little fish  "and some of these countries have almost no sources of omega-3 fatty acids because they cook with corn or sunflower oils"  the consumption of vegetable oils with ALA could have a major impact on heart disease."

In an editorial accompanying the published study, Dr William Harris (University of South Dakota, Sioux Falls) said that the data are suggestive and would be good news for individuals who will not or cannot eat fish, but more studies are still needed. "If ALA were able to do the same 'heavy lifting' that [eicosapentaenoic acid] EPA and [docosahexaenoic acid] DHA do, this would be welcomed news, because the capacity to produce ALA is essentially limitless, whereas there are only so many fish in the sea," he writes.

ALA is an intermediate-chain n-3 polyunsaturated fatty acid that is often overshadowed by the more famous long-chain members of the n-3 family, namely EPA and DHA acids that are found in fish oils. ALA intake has increased during the past several decades, however, mainly through the consumption of vegetable oils such as soybean, canola, and flaxseed oil. Campos said some studies have shown that low ALA intake was associated with a risk of coronary heart disease and sudden cardiac death, and others, although not all, have suggested an inverse association between ALA consumption and risk of MI.

In this study, 1819 patients who survived an MI provided samples of adipose tissue for analysis of fatty-acid stores and completed a validated food questionnaire, with 1817 matching controls doing the same. ALA in the adipose tissues ranged from 0.36% in the lowest decile to 1.04% in the highest decile. The corresponding median levels for ALA intake were 1.11 g/day to 2.35 g/day.

In a multivariate model that included smoking, physical activity, history of diabetes, hypertension, fat intake, and waist-to-hip ratio, among others, there was an observed inverse relationship between adipose tissue ALA and dietary ALA intake and risk of nonfatal MI.

 
Deciles of adipose tissue, ALA intake, and risk of MI
 
Decile
1
2
3
4
5
6
7
8
9
10
ALA intake, g/day
1.11
1.25
1.38
1.38
1.52
1.62
1.79
1.83
2.08
2.35
Median, % ALA in adipose tissue
0.36
0.45
0.5
0.55
0.6
0.64
0.7
0.77
0.88
1.04
Relative risk of MI (95% CI)
-
0.94 (0.66 - 1.34)
0.85 (0.59 - 1.24)
0.59 (0.40 - 0.87)
0.52 (0.34 - 0.78)
0.51 (0.34 - 0.79)
0.43 (0.30 - 0.67)
0.45 (0.28 - 0.71)
0.37 (0.23 - 0.59)
0.41 (0.25 - 0.67)
 
"The relationship between ALA and myocardial infarction was nonlinear," said Campos. "We see a dose effect, but only up to about 0.7% of adipose tissue, which corresponds to about 1.8 g/day. Increasing intake further was not associated with increased protection. This is why we hypothesized that if we were to conduct a study in a population already within this range, you're not likely to see an effect."
 
Campos said modest intakes of ALA appear to convey benefit, with small amounts of flaxseed oil, even just half a teaspoon, or one to two teaspoons of soybean oil, sufficient to increase ALA intake to 1.8 g/day. More commonly, salad dressings using canola or soybean oil would be enough to increase intakes to cardioprotective levels.
 
In terms of underlying mechanisms, some have speculated that the protective benefit is mediated by converting ALA to EPA, but Campos said the data from this study do not support that hypothesis, as ALA correlated poorly with adipose and erythrocyte EPA. There are data supporting ALA in reducing low-density lipoprotein (LDL)-cholesterol and triglyceride levels, but ALA is thought to reduce the expression of inflammatory markers, although the data at this point are still inconclusive, she said.
 
In an unrelated study published online July 7, 2008 in Hypertension, Japanese investigators, led by Dr Katsuyuki Miura (Shiga University of Medical Science, Otsu, Japan), observed an independent inverse correlation between dietary linoleic acid and systolic and diastolic blood pressure [3]. Among individuals with higher linoleic acid consumption � in this study, as high as 9 g/day � the effect on systolic and diastolic blood pressure was a reduction of approximately 1.4 mm Hg and 0.9 mm Hg, respectively.
 
In his editorial, Harris notes that the findings by Campos and colleagues are at odds with other studies, particularly a recent meta-analysis of six studies showing no significant difference between coronary heart disease patients and controls in adipose linoleic acid. The best bet for discovering the true effect of linoleic acid on coronary heart disease risk is the Alpha-Omega Study, a 4800-patient study in which subjects are randomized to 400 mg of EPA plus DHA, 2 g of linoleic acid, both, or neither. The primary end point is cardiac mortality, and results are expected in 2009.

Source: Diabetes In Control: The results of the study and editorial are published online July 8, 2008 in Circulation. Campos H, Baylin A, Willett WC. Alpha-linolenic acid and risk of nonfatal acute myocardial infarction. Circulation. 2008;DOI:10.1161/CIRCULATIONAHA.107.762419. Available at: http://circ.ahajournals.org. Harris WS. Cardiovascular risk and alpha-linolenic acid. Circulation. 2008;DOI: 10.1161/CIRCULATIONAHA.108.791467. Available at: http://circ.ahajournals.org. Miura K, Stamler J, Nakagawa H, et al. Relationship of dietary linoleic acid to blood pressure. Hypertension. 2008;52:DOI:10.1161/HYPERTENSIONAHA.108.112383. Available at: http://hyper.ahajournals.org.

 
 
 
 
 
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