Unilever Health & Wellbeing Series
Optimal intakes of alpha-linolenic acid for heart health
There is convincing evidence and scientific consensus that replacing saturated fatty
acids (SAFA) with polyunsaturated fatty acids (PUFA) in the diet decreases the risk of
coronary heart disease (CHD). Although omega-6 (linoleic acid (LA) is the major
dietary PUFA, it is acknowledged that both omega-6 and omega-3 PUFA are important
for heart health. The two types of omega-3 fatty acids in the diet, ‘vegetable’ omega-3
fatty acid (alpha-linolenic acid (ALA) and ‘marine’ omega-3 fatty acids
(eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are both reported to
have beneficial effects on heart health. Although ALA is the most abundant omega-3
fatty acid in the diet, most research has focused on the heart health benefits of
EPA&DHA. Although the evidence is less strong and extensive than for EPA & DHA,
the available evidence supports a beneficial effect of ALA on heart health.
Authors:
Ans Eilander and Peter Zock (Unilever R&D)
Scientific review
ALA is the most abundant omega-3 fatty acid in the diet
Polyunsaturated fatty acids (PUFA) can be classified into two groups: omega-3 and omega-6 fatty
acids. There is convincing evidence and consensus that replacing saturated fatty acids (SAFA) with
PUFA in the diet decreases the risk of CHD, with an estimated 10% reduction in CHD for each
increase of 5% of energy in PUFA at the expense of SAFA (1-4). It has been suggested that this
beneficial effect of PUFA as observed in randomized controlled trials (RCTs) should mainly be
attributed to the omega-3 fatty acids and that increasing omega-6 fatty acid intake alone is not
effective and would be even harmful (5). However, the available evidence is too limited to disentangle
the effect of omega-6 and omega-3 PUFA, The vegetable oils and diets investigated in the RCTs
contained all mainly omega-6 PUFA, which make them a likely candidate for the beneficial effect of
vegetable PUFA. Moreover, several health authorities recognise that both omega-6 and omega-3
fatty acids are important for maintenance of healthy cholesterol levels, thereby decreasing the risk of
CHD (2;6;7). ALA (C18:3n-3), an essential fatty acid, is the predominant omega-3 PUFA in the diet.
As it cannot be synthesised in the body it is considered an essential nutrient and must be obtained
from the diet. ALA is mainly found in a variety of vegetable oils (in particular rapeseed (canola),
flaxseed and soybean), seeds and nuts. The other type of major omega-3 fatty acids in the diet are
called long chain (LC) PUFA or marine omega-3 fatty acids (e.g. mainly present in seafood and fish
oils), which are for the largest part eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid
(DHA, C22:6n-3). However, EPA+DHA can also be obtained by conversion (elongation and
desaturation) from ALA in the human body. These fatty acids are important structural constituents of
membranes and tissues and play a vital role in many physiological and molecular processes. Higher
intakes of EPA+DHA have been linked to many health outcomes, including brain development and
function, cardiovascular health and inflammatory response. The evidence for a protective effect of
intake of fish and its omega-3 fatty acids (EPA+DHA) on cardiovascular disease (CVD) and in
Optimal intakes of alpha-linolenic acid for heart health (2011)
particular (fatal) heart disease is well documented and considered strong for primary prevention in the
general population.
ALA is a precursor for EPA and DHA, but conversion is limited
It is unclear, whether the essentiality of ALA is due to the action of ALA itself or to ALA being a
precursor for EPA+DHA. In a critical review of human studies, the conversion of ALA to EPA was
estimated to be a modest 8%; while the extent of conversion to DHA was much smaller at 0.05% (8).
Furthermore, the conversion of ALA to EPA+DHA varies between people and is likely to be influenced
by gender and the absolute amounts of ALA and LA in the diet (9;10). The consensus is that
conversion of ALA to EPA+DHA in humans is limited with an average overall conversion rate of about
4-5% (11).
For optimal heart health an omega-3 fatty acid intake up to 2% of dietary energy (en%) is
recommended, of which at least 250 mg should come from EPA+DHA. It is important to consider that
ALA intake recommendations are set both in the context of adequate intakes needed to prevent
deficiencies and more recently as optimal intakes needed to prevent chronic diseases, in particular
cardiovascular disease (CVD). To prevent deficiency symptoms, a minimum intake of >0.5 en% ALA
is recommended for adults ((2). This intake level is easily achieved in a balanced diet and in the
general population ALA deficiency is rarely observed. FAO (2) recommends that diets should provide
between 0.5 and 2.0 en% of total omega-3 fatty acids, of which the higher value includes the
recommendation for ALA and that for EPA+DHA of 0.25-2.0 g/d as part of a healthy diet.
ALA intakes are often lower than recommended for optimal heart health
A concern is that average ALA intake levels of adults and children are generally below levels
recommended for optimal heart health. Available intake data from National Dietary Surveys indicate
that average ALA intakes in different populations range from 0.5-1 en%, so ALA intake should be
increased to reach the level recommended for optimal heart health (Harika et al, submitted).
Possible adverse effects are unlikely
Adverse effects of ALA intake have hardly been reported (12). A link between ALA concentrations
and increased prostate cancer risk has been suggested, but a causal relation is not considered likely
(13). A recent meta-analysis of 8 case-control and 8 prospective studies with inconsistent findings
showed a borderline statistically significant higher risk of prostate cancer with high ALA intakes.
However, these associations disappeared after adjustment for heterogeneity and publication bias
(14).
Clinical and prospective studies suggest that ALA intake reduces the incidence of CHD
Most studies on effects of omega-3 on heart health have focused on the long-chain omegas
EPA+DHA. This is evident from a systematic review that identified far more studies examining the
effects of EPA+DHA or fish consumption on CVD outcomes than studies on effects of ALA (12). The
potential of ALA to affect CVD risk, in particular coronary heart disease (CHD), has been studied in
only a few clinical endpoints trials and in about 10 high quality, epidemiologic studies. One early
primary trial did not find and effect on CHD incidence, possibly because duration of the study (1 year)
was too short (15). The results of the Lyon Heart Study, a secondary prevention trial, indicate that a
Mediterranean diet enriched with ALA can significantly lower the risk of cardiovascular death (16;17).
The intake of ALA in the intervention diet was over 0.6 en%, which was about 1.8g/d ALA, compared
with 0.7g ALA in the control diet. However, a major limitation of this trial is that multiple changes were
made in the diet, which makes it impossible to quantify the contribution of ALA to the observed lower
risk of CHD. Two other secondary prevention trials have reported on the effects of ALA supplements
(18) and an ALA-enriched “Indo-Mediterranean diet” (19) on the risk of CHD. However, the reliability
of results reported by this research group have been seriously questioned (20), and can therefore not
be taken as credible evidence for an effect of ALA on CHD. More recently, the Alpha-Omega Trial
showed no statistically significant effect of a low dose of 1.9 g/d ALA provided during 40 months on
major cardiovascular events, including death from CHD in patients who had myocardial infarction.
However, a borderline significant lower rate of cardiovascular events on ALA treatment was observed
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Optimal intakes of alpha-linolenic acid for heart health (2011)
in female patients (21). The authors indicate that the drug therapy used by the patients in their trial
may have obscured possible beneficial effects of ALA.
A meta-analysis (22) of five prospective cohort studies observed an inverse association between the
intake of ALA and risk of CHD in most (23-26) but not all studies (27). The meta-analysis showed that
a high ALA intake compared to a low ALA intake was associated with a lower borderline statistically
significant risk of CHD mortality (RR=0.79, 95% CI 0.60, 1.04). Another prospective study (nested
case-control in the Cardiovascular Heath study) observed significantly lower fatal ischemic heart
disease with higher ALA concentrations (28). Updated analyses from the Health Professional FollowUp study (14 years follow-up) and the Nurses’ Health Study (18 years follow-up) confirmed the
significant reductions in risk of CHD with increased ALA intakes (29;30) that were earlier reported
(24;26). Two case-control studies suggest that ALA intake is associated with a lower risk of CHD
(31;32); while one study observed an increased CHD risk with higher ALA intake (33). A large crosssectional study in men and women observed a significantly lower prevalence of CHD with higher
intakes of ALA (34). A review on ALA and clinical cardiovascular outcomes concluded that, there is
evidence from only one observational study that supports a protective effect against nonfatal
myocardial infarction. However, no significant protective associations were observed between ALA
status and risk of heart failure, atrial fibrillation, and sudden death (35). Moreover, in a large cohort
study, ALA intake was also not associated with risk of CHD events (36).
Although benefits have not been observed consistently and the number of high quality clinical and
prospective cohort studies is small, the available evidence supports that higher ALA intakes may
reduce the risk of CHD.
ALA may affect several cardiovascular risk markers and cardiovascular end points
Specific biological mechanisms by which ALA could reduce CVD risk are still largely unknown and
needs to be addressed in further studies. The conversion of ALA to LCPUFA has been suggested as
a way via which ALA could confer heart health benefits (37;38). However, as discussed above, the
conversion of ALA to LCPUFA is limited and it is well possible that ALA has favorable cardiovascular
effects by itself. Beneficial effects on multiple cardiovascular risk markers including cholesterol, blood
pressure, glucose, inflammation, thrombosis, and arrhythmias have been reported (39-42). A review
concluded that ALA intake did not significantly modify several cardiovascular risk factors (including
total cholesterol, triglycerides, weight, body mass index, LDL, diastolic blood pressure, systolic blood
pressure, VLDL, and apolipoprotein B) (43). A review of studies on ALA intake and CVD published
between 2008 and 2010 showed that the evidence for protective effects of ALA is inconsistent for
CVD risk markers, including blood lipids, low-density lipoprotein oxidation, lipoprotein(a), and
apolipoproteins A-I and B (35). Conflicting results were found for studies of ALA in relation to
inflammatory markers and glucose metabolism in the same review (35). Furthermore, it has been
reported that low ALA intake may increase the risk of incident stroke in western countries (36;44), but
results were not confirmed in a study in Japan (45).
In summary, evidence is currently inconclusive for a beneficial role of ALA on cardiovascular end
points other than CHD and biologic mechanisms of possible beneficial effects are unclear.
The effect of ALA on blood lipids and lipoproteins is about similar to that of LA
The potential beneficial effects of ALA on the risk of CHD can only for a small part be explained by its
effect on blood lipids. While total vegetable PUFA have a favourable effect on the blood lipoprotein
profile (46); the evidence is much more established for LA than ALA, mainly because the majority of
total PUFA in the diet consists of LA. Very few studies have examined the specific effect of ALA on
blood lipids. When ALA is examined by comparing the effects of exchanging oils (e.g. exchanging
linseed oil and sunflower seed oil to compare directly with LA), generally no differences in effect on
cholesterol and triglyceride levels have been observed (47-52). This suggests that ALA has an almost
similar beneficial effect on the blood lipoprotein profile as LA. Because ALA is only a minor part of
total PUFA (ALA+LA) in the diet, the potential impact on blood lipids would be small. Furthermore,
ALA does not share the powerful triglyceride lowering effects of EPA+DHA (48;53;54). Assuming
ALA is as effective as LA (the major unsaturated fatty acid in the diet), the predicted effects on blood
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Optimal intakes of alpha-linolenic acid for heart health (2011)
lipids of ALA in amounts as recommended or studied are too small to explain a relation between
higher ALA intakes and lower risk of CHD.
Conclusions
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For optimal heart health, a total omega-3 fatty acid intake of up to 2 en% is recommended, of
which at least 1 en% should be ALA and at least 250 mg should be EPA+DHA
Available evidence supports a beneficial effect of ALA on heart health, although this evidence is
less strong and extensive than for marine omega-3 fatty acids
Replacing dietary SAFA with PUFA (in practice mainly LA plus some ALA) lowers CHD risk
The omega-3 to omega-6 ratio is not a useful concept
The effect of ALA is small compared to LA because ALA makes up only a minor part of total
vegetable PUFA in the diet
Although ALA contributes to maintenance of LDL cholesterol concentrations, this effect is too
small to explain the inverse relation between ALA intake and CHD
The mechanisms by which ALA can contribute to heart health are not clear
There is not enough evidence to assess if the contribution of dietary ALA to heart health is a direct
effect of ALA or a indirect effect, via (limited) conversion in the body to EPA+DHA
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