Nutrition and Metabolism of Lipids 117cholesterol-raising effects of dietary cholesterol, and
a phenomenon of increased susceptibility to dietary
cholesterol in some individuals for some, as yet,
unknown reason.
To place these dietary infl uences on blood choles-
terol in perspective with other cholesterol-lowering
strategies, a metaanalysis of dietary intervention trials
undertaken by the World Health Organization
(WHO) revealed that dietary modifi cation could
achieve reductions in serum cholesterol of between
only 4% and 5%. This fi nding is in sharp contrast to
the potent effects of cholesterol-lowering drugs, which
can reduce serum cholesterol by 30–40% and have
been shown, unequivocally, to reduce the incidence of
death from CHD. It also highlights the need to address
other risk factors which are more responsive to dietary
change.
Fat quantity versus quality: importance
of the ratio of n-6:n-3 polyunsaturated
fatty acids
The underlying principle for a reduction in total fat
intake is to reduce energy intake from the consump-
tion of the most energy-dense macronutrient in order
to prevent weight gain and ultimately obesity. The
current recommendation for the UK is to reduce
energy derived from fat to 35% or less. Since weight
gain is associated with raised plasma TAGs and abnor-
malities in circulating lipoproteins, reducing total fat
intake should, in theory, reduce blood lipids. However,
in practice there is little evidence to support such an
effect within populations. Metaanalyses have revealed
that little benefi t is to be gained, at least in terms of
changes in blood lipids, by reducing total fat without
altering the composition of dietary fatty acids.
Metaanalyses have also helped to resolve the issue of
what represents the most appropriate replacement
nutrient for SFAs. Since PUFAs, and specifi cally lin-
oleic acid, were shown to counter the actions of SFAs
and were abundant in natural sources such as sun-
fl ower and corn oils, they were an obvious fi rst choice.
The alternative was to substitute fat with dietary car-
bohydrate. There have been problems associated with
both of these approaches. First, increasing dietary lin-
oleic acid excludes the lesser abundant, but more met-
abolically active, n-3 PUFA, and especially the longer
chain (C20–C22) members of this series derived from
marine oils [C20:5 (eicosapentaenoic acid) and C22:6
(docosahexaenoic acid)]. Overemphasis on linoleic
acid in the food industry, together with a widespread
resistance to the consumption of fi sh, has increased
the ratio of n-6 to n-3 PUFAs in northern Europe and
the USA since the 1970s. This situation has major
implications for the development of abnormalities in
circulating lipoproteins, since defi ciency in eicosapen-
taenoic acid and docosahexaenoic acid could help to
promote an increase in plasma TAG. This could occur
through an overproduction of endogenous TAG
(VLDL) in the liver and intolerance to dietary (exoge-
nous) fat, and lead to the development of dyslipidemia
known as an ALP (see Section 6.5). The frequency of
this dyslipidemia is believed to be very rare in
Mediterranean countries that have a high intake of
dietary n-3 PUFA and an n-6:n-3 ratio closer to 1.
High-carbohydrate diets have been shown to increase
plasma TAG. Carbohydrate-induced hypertriacylglyc-
erolemia is not, as was originally thought, a short-
term adaptive response in the liver, as it changes its
pattern of oxidation from fat to carbohydrate, but a
real phenomenon associated with the overconsump-
tion of the non-milk extrinsic sugars, sucrose and
fructose, most notably in individuals with insulin-
resistant dyslipidemia. There is evidence to suggest
that this effect can be avoided by limiting the intake of
sucrose and increasing the intake of slowly absorbed
carbohydrate with a low impact on blood glucose.
The results of several metaanalyses of dietary inter-
vention trials support dietary MUFAs as the most
favored substitute for dietary saturated fatty acids,
and even linoleic acid in areas of high intake.Effects of n-3 polyunsaturated fatty acids
from plants and fi sh
The current dietary recommendation for the intake
of long-chain n-3 PUFAs (eicosapentaenoic acid/doc-
osahexaenoic acid) in the UK is 450 mg/day (SACN,
2004). This was to increase intake by consuming two
portions of fi sh per week, one of which should be oily
(e.g., mackerel, sardines). This recommendation was
based on evidence from a host of epidemiological and
intervention studies, which showed that regular fi sh
consumption could reduce the risk of sudden cardiac
death. Since this an acute end-point of CHD, the ben-
efi ts of fi sh oil have been ascribed to the prevention
of fatal cardiac arrhythmia, and, to a lesser extent,
coronary thrombosis, but not to any favorable effects
on blood lipids. However, there is also convincing
evidence to show that fi sh oil supplementation (1 g/