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Klinisk Biokemi i Norden · 3 2015
diabetic controls. In conclusion, plasma phospholipid
relative concentrations of EPA were negatively asso-
ciated, while those of DHA were positively associated
with total mortality in diabetics. This difference in
associations suggests a differential effect of EPA and
DHA in patients with type 2 diabetes.
In
paper III
[3], the relation between long-chain
n 3 fatty acids and overall mortality in acutely
sick elderly patients was investigated. Frail, elderly
patients (n=254) acutely admitted to St Olavs Hos-
pital in central Norway were examined. The plasma
phospholipid concentration of EPA was used as a
surrogate marker for dietary intake of marine fatty
acids. Mortality rates were evaluated after 3 years of
follow-up. Cox proportional hazard analysis was used
to calculate hazard ratios adjusted for important bio-
chemical and clinical covariates. The hazard ratio of
overall mortality was significantly higher in patients
with EPA concentrations in the lowest quartile than
in patients in the upper 3 quartiles (adjusted hazard
ratio: 0.52; 95% CI: 0.35, 0.77). The upper 3 quartiles
were not significantly different from one another (P=
0.94). We conclude that in this population, mortality
was inversely and nonlinearly associated with EPA
concentrations. Approximately 25% of the popula-
tion had EPA concentrations below the indicated
threshold for maximal protection, suggesting that
only this part of the population might have benefited
from additional EPA intake.
Further studies
In this thesis, we have documented the association
between biomarkers of long-chain n-3 fatty acid
dietary intake and mortality in two different patient
populations. However, these are merely associations.
To demonstrate causal effects, it is necessary to
perform randomized clinical trials. Two important
observations from the present work could improve
future studies. First, information on background
diet should be taken into account when allocating
patients and analyzing the results. Second, our results
suggest that EPA and DHA have different effects.
These are fatty acids previously considered equiva-
lent in relation to most clinical endpoints, including
mortality. Verification of this observation requires a
study design and statistical analysis that allows for
this possibility.
The present recommendation to the general popu-
lation is to increase the dietary intake of long-chain
n-3 fatty acids. There is a large industry involved
in responding to this demand, and concern has
rightfully been expressed because of limited natural
resources. In spite of increasing fishing activities,
global catches are in decline due to exploited wild
fish stock. At present rate of fishing, the world fish
population may eventually collapse by 2050. Aqua-
culture with present procedures and technology is
not able to compensate. As fish farms often raise
carnivorous fish fed on diets made of meal and oils
from smaller fish, the burden on wild stock increases
with aquaculture. There are also negative socio-eco-
nomic consequences in developing countries where
an important source of protein is deprived for the
sake of the developed world, whose major problems
are overnutrition and physical inactivity. As EPA
and DHA are produced by plants, algae, yeast and
other unicellular organisms, alternatives to fish oils
exist and are being developed. Further research is
required to obtain sustainable sources of long-chain
n-3 fatty acids if current recommendations are to be
implemented in large populations.
References
1. Lindberg M, Midthjell K, Bjerve KS. Long-
term tracking of plasma phospholipid fatty
acid concentrations and their correlation with
the dietary intake of marine foods in newly
diagnosed diabetic patients: results from a
follow-up of the HUNT Study, Norway. Brit J
Nutr 2013;109:1123-34.
2. Lindberg M,
Åsberg
A, Midthjell K, Bjerve
KS. Plasma phospholipid EPA and DHA are
divergently associated with overall morta-
lity in newly diagnosed diabetic patients:
results from a follow-up of the Nord-Trøndelag
Health (HUNT) Study, Norway. J Nutr Sci
2013;2:1-8.
3. Lindberg M, Saltvedt I, Sletvold O, Bjerve KS.
Long-chain n-3 fatty acids and mortality in
elderly patients. Am J Clin Nutr 2008;88:722-
9.
