Harris, n-3, 2004
Harris, n-3, 2004
Harris, n-3, 2004
-3
, found mainly in
O fish oils,
are said to be beneficial in conMEGA
KEY POINTS
208
VOLUME 71 NUMBER 3
FATTY ACIDS
MARCH 2004
OMEGA-3 FAMILY
Linoleic acid
C18:2 omega-6
First double bond at the 6th position
from the methyl (omega) end
2 double bonds
18 carbons long
C18:3 omega-3
Arachidonic acid
C20:4 omega-6
C20:5 omega-3
C22:6 omega-3
2-Series prostaglandins
Thromboxane A2
Prostacyclin I2
4-Series leukotrienes
3-Series prostaglandins
Thromboxane A3
Prostacyclin I3
5-Series leukotrienes
FIGURE 1. The omega-6 and omega-3 families of polyunsaturated fatty acids. Of the
omega-3 fatty acids, alpha-linolenic acid is found in plant oils, whereas EPA and DHA are
found in fish oils. Both arachidonic acid and EPA are substrates for cyclooxygenases and
lipoxygenases, each producing a different family of compounds with differing
physiological actions. The nomenclature used to describe fatty acids is illustrated using
linoleic acid as an example.
VOLUME 71 NUMBER 3
MARCH 2004
209
FISH OILS
HARRIS
TA B L E 1
GRAMS OF OMEGA-3
OIL PER 3-OZ SERVING
Tuna
Light, canned in water, drained
White, canned in water, drained
Fresh
Sardines
Salmon
Sockeye or pink
Chinook
Coho, farmed
Coho, wild
Atlantic, farmed
Atlantic, wild
Mackerel
Herring
Pacific
Atlantic
Trout, rainbow
Farmed
Wild
Cod
Atlantic
Pacific
Catfish
Farmed
Wild
Flounder/Sole
Oyster
Pacific
Eastern
Lobster
Crab, Alaskan king
Shrimp, mixed species
Clam
Scallop
0.26
0.73
0.24-1.28
0.98-1.70
12
4
2.5-12
2-3
1.05
1.48
1.09
0.91
1.09-1.83
0.9-1.56
0.34-1.57
3
2
3
3
1.5-2.5
2-3.5
2-8.5
1.81
1.71
1.5
2
0.98
0.84
3
3.5
0.13
0.24
23
12.5
0.15
0.2
0.42
20
15
7
1.17
0.47
0.070.41
0.35
0.27
0.24
0.17
2.5
6.5
7.542.5
8.5
11
12.5
17.5
*Omega-3
fatty acid content varies widely with the season, the diet and age of the fish, and the storage and
preparation methods. Values based on US Department of Agriculture Nutrient Data Laboratory, available on the
Internet at www.nalusda.gov/fnic/foodcomp/. Accessed February 2, 2004.
210
VOLUME 71 NUMBER 3
MARCH 2004
FISH OILS
HARRIS
TA B L E 2
0.19
0.30
0.50
0.70.9
5
3
2
1
*Values
Direct proof
of a cardiac
benefit of
alpha-linolenic
acid is lacking
212
acids) such as the 3-series (2-series for arachidonic acid) prostaglandins, prostacyclins, and
thromboxanes, and the 5-series (4-series for
arachidonic acid) leukotrienes.6
The metabolites of EPA are generally less
active than the proinflammatory and prothrombotic metabolites derived from arachidonic acid (FIGURE 1). The omega-3 and the
omega-6 fatty acids compete for conversion
into these important metabolites. Thus, tissue
levels are largely determined by dietary intake
levels.7
ARE OMEGA-3 FATTY ACIDS
CARDIOPROTECTIVE?
What is the evidence that omega-3 fatty acids
prevent heart disease? In a word, the evidence
is strong for EPA and DHA, and spotty for
ALA.
Population studies around the world and
within the United States consistently show a
protective association between EPA, DHA,811
and ALA1214 and heart disease, but a beneficial effect of fish oils is also supported by compelling supplementation studies,1517 which
are lacking for ALA. Studies comparing populations with low vs high blood levels of marine
omega-3 fatty acids found the risk for death
from cardiovascular disease to be as much as
90% lower in those with high blood levels.8,9
But association does not prove causation.
Causation is more clearly demonstrated in
randomized, controlled trials. In one such
study, the Diet and Reinfarction Trial
VOLUME 71 NUMBER 3
TA B L E 3
Food sources
of alpha-linolenic acid *
FOOD
Flaxseed oil
Flaxseeds
Canola oil
Soybean oil
Walnuts, English
Olive oil
8.5
2.2
1.3
0.9
0.7
0.1
EPA/DHA per day found that supplementation appeared to make carotid artery plaques
more stable.24
Nevertheless, there is very little information on the biological effects of low intakes
(less than 1 g/day) used in the major clinical
trials. For example, the benefits for total mortality observed in the GISSI Prevention
study17 were unaccompanied by any change in
lipid profile, and no other possible mechanisms were examined.
Data from epidemiologic and randomized
clinical trials suggest that omega-3 fatty acids
decrease the risk of sudden cardiac death, presumably via reduced susceptibility to malignant arrhythmias.25 The evidence for this
mechanism has been derived primarily from
animal and cell culture studies, and the physiological relevance to humans consuming less
than about 1 g/day of EPA/DHA is not clear.
Nevertheless, according to this theory, as
EPA and DHA are incorporated into cellular
membranes throughout the body, they do two
things. First, they displace the omega-6 fatty
acid arachidonic acid (the substrate for synthesis of thromboxane A2, leukotriene B4, and
all 2-series prostaglandins), which could
reduce proinflammatory and prothrombotic
processes. While theoretically attractive,
there are no clinical trial data showing that
high omega-6 intake has adverse cardiovascular effects,26 and higher tissue levels of arachidonic acid are not associated with increased
risk for coronary heart disease.27,28
VOLUME 71 NUMBER 3
MARCH 2004
215
FISH OILS
HARRIS
TA B L E 4
The AHA
recommends
1 g of EPA/DHA
per day
CAPSULES
TO PROVIDE 1 G
180/120
180/120
460/370
180/120
180/120
180/120
180/120
180/120
180/120
180/120
180/120
180/120
216/144
180/120
180/120
216/144
180/120
173/120
516/344
3
3
1
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
1
COST TO PROVIDE 1 G
$0.07
$0.07
$0.11
$0.13
$0.15
$0.15
$0.17
$0.19
$0.20
$0.20
$0.21
$0.21
$0.22
$0.23
$0.25
$0.27
$0.31
$0.30
$0.44
*This
is not an exhaustive list, and periodic sale prices may be lower than these retail prices. Sales tax is not
included. Many other products are available via the Internet, but shipping and handling charges must be considered in determining overall cost.
This is a liquid; therefore, doses are in teaspoons or tablespoons instead of capsules.
216
EPA/DHA
(MG/CAPSULE)
VOLUME 71 NUMBER 3
no known heart disease, the AHA recommends eating oily fish at least twice a week, or
about 500 mg of EPA/DHA per day. Much
higher intake, ie, from 2 to 4 g per day, is needed to lower triglyceride levels, and this should
be done in consultation with a physician.
The AHAs nutrition committee recommends oily fish as the preferred source of
omega-3 fatty acids (TABLE 1, TABLE 2) but
acknowledges that, for people who cannot or
will not eat enough fish to meet this target, an
EPA/DHA supplement could be considered in
consultation with their physician.
At present, we have no compelling data to
suggest that either EPA or DHA is the primary, active component. They appear to act in
synergy. Thus, products that contain both in
ratios ranging from 2:1 to 1:2 are probably
equally beneficial, although this has not been
rigorously examined.
MARCH 2004
Fish oil
supplements
are permitted
to claim that
they may
reduce the risk
IS WILD FISH BETTER
THAN FARMED FISH?
of coronary
Both wild fish and farmed fish are good heart disease
sources of omega-3, as seen in TABLE 1.
As the public demand for fish such as
high-quality salmon has increased, so has the
popularity of fish farming. These farms operate much like a feed lot for cattle, where uniform feeding and conditions for exercise (or
lack thereof) result in products of uniform
composition. Farmed fish are fed rations that
contain fish protein and fish oil, so farmed fish
also contain omega-3 fatty acids.
The omega-3 content of wild fish is more
unpredictable and depends on the maturity of
the fish and when it is caught. For example,
salmon caught as they are just beginning their
VOLUME 71 NUMBER 3
MARCH 2004
217
FISH OILS
HARRIS
Amounts of
contaminants
in farmed
salmon are
small and do
not outweigh
the benefits
Fish oil supplements are available as a triglyceride-based form or as a methyl or ethyl ester
form. Previous work in our laboratory showed
that serum levels of EPA/DHA were raised
equally well with a triglyceride or a methyl
ester preparation.34 Thus, there is little justification for choosing one formulation over the
other.
Omega-3 products in the methyl ester or
ethyl ester form are usually more concentrated
than triglyceride forms: ie, fewer capsules per
day are required to achieve target intakes.
They are also more expensive. In the GISSIPrevention study, an ethyl ester product was
used (Omacor, Pronova Biocare, Oslo,
Norway), which contains 850 mg of
EPA/DHA ethyl esters per 1-g capsule.
Omacor is not currently available in the
United States.
DHA vs EPA
There is also little evidence that one of the
two long-chain omega-3 fatty acids is more
cardioprotective than the other. While some
studies have pointed to blood pressure benefits
specific to DHA35 or to triglyceride-lowering
specific to EPA,36 these studies utilized about
eight times the dose of DHA and EPA used in
the GISSI-Prevention study. The evidence to
date for clinical benefit has been generated
with a combination of EPA and DHA, and
until compelling evidence from low-dose studies with pure fatty acids is available, there is no
218
VOLUME 71 NUMBER 3
MARCH 2004
FISH OILS
HARRIS
220
VOLUME 71 NUMBER 3
FISH OILS
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
HARRIS
CORRECTION
CME ANSWERS
Answers to the credit test on page 263
of this issue
1A2E3A4C5A6D7E8C9D
10 C 11 E 12 D 13 C 14 A
VOLUME 71 NUMBER 3
MARCH 2004
221