Dietary Intervention Study to Determine the
Effects of Cold Water Prawns on Blood Lipids
and Lipoproteins
by Dr Bruce Griffin
Faculty of Health & Medical Sciences
University of Surrey, United Kingdom
I am presenting today the results of a small intervention study with
prawns, the first such set of results in the UK. Before I do that, I would
like to touch on the issues of dietary cholesterol and cholesterol in
relation to coronary heart disease (CHD).
Looking at a cross section of a coronary artery, we can see the lumen and
here a plaque. We have known for many years that these plaques contain
cholesterol.
Coronary Heart Disease and Thrombosis
Thrombus
Lumen
Cholesterol
Coronary atherosclerosis
Coronary thrombosis
People can live with these plaques throughout their lives without
suffering any effects. It is only when they become unstable and the
fibrous cap ruptures that a coronary thrombosis, or heart attack, occurs. It
is worth mentioning that deaths from CHD have actually gone down
considerably over the last 30 years, but we are still seeing about 300,000
a year and these still cost the NHS a great deal of money.
We have heard a great deal about blood cholesterol this morning, and
while I appreciate the analogy from Bill Lands’ that LDL is only smoke
and we should be treating the fire, which is inflammation, we must not
forget that it is the smoke that kills most people in a fire, and that raised
LDL cholesterol is an indisputable risk factor for coronary disease. There
is incontrovertible evidence from large prospective cohort studies and
randomly controlled intervention studies to link raised plasma
LDLcholesterol to an increased risk of heart disease. A blood cholesterol
level of between 5 to 6 mmols per litre is associated with an absolute risk
of CHD of about 20% , which is unremarkable. There are other sources of
CHD risk under consideration within the context of the meeting today,
the most important of which is cardio-metabolic risk arising from obesity
and diabetes, and these are treatable with omega 3 fatty acids, but we
must not lose sight of the fact that blood cholesterol level is indeed a risk
factor.
The mission today is to inform you about dietary cholesterol and to try to
dispel some of the mythology surrounding the links between dietary
cholesterol, blood cholesterol and LDL (which transports cholesterol
around the body) and the links with CHD.
So I will take a few moments to tell you that there is no convincing
evidence to link dietary cholesterol with increased CHD. The real culprit
in our diet is saturated fat, which many of us over consume in gramquantities relative to only milligrams of dietary cholesterol, from such
foods as seafood and eggs.
The egg industry has led the way in trying to dispel this myth by
undertaking a scientific evaluation of existing evidence. This has revealed
that there is no convincing evidence to link dietary cholesterol with
increased CHD risk.. For the majority of people, eating an egg a day is
not going to raise LDL cholesterol to a level that is clinically significant.
The implications of this finding are that other sources of dietary
cholesterol should not be restricted on the grounds that they might have
an adverse effect in raising LDL cholesterol and coronary risk; this is
scientifically unfounded.
We have heard about metabolic syndrome this morning and how people
with this are an important target population for treatment with long-chain
omega-3 fatty acids. I think that this is absolutely correct. Obesity is
increasing at an unprecedented rate. Obesity and insulin resistance are
associated with a wide range of risk factors; intolerance to glucose,
dyslipidaemia and hypertension. This is a very common presentation of
risk in the general population, probably 25-30% of the middle-aged
population show at least some features of this syndrome. The omega 3s
do not lower LDL cholesterol per se but they can change the quality of
circulating LDL by making it larger and less dense, and less likely to
cause plaque formation and CHD. One way by which they might do this
is by making LDL less susceptible to oxidation that occurs with
inflammation, an event that can initiate CHD
Here we have pro-inflammatory and pro-coagulable states which impact
on vascular function, leading to some of these end-points, and
manifesting themselves in CHD
Manifestations of Cardiovascular Disease
Atherosclerosis
Thrombosis
Arrhythmias
1-2g/d
2–3g/d
0.5–1g/d
Anti-atherogenic
Anti-thrombogenic
Anti-arrhythmic
Anti-inflammatory
Long chain n-3 PUFA
This slide illustrates that long-chain omega-3 fatty acids impact on all
manifestations of cardiovascular disease in a quantitative fashion; they
slow atherogenesis, prevent thrombosis and stabilise plaques at the same
time. It is very important to identify the target population. We heard
earlier about the difficulty of trying to increase consumption of long
chain omega-3 fatty acids. I think one of the ways forward is to lift the
restrictions on sources of these fatty acids such as shellfish.
One reason for performing a dietary intervention with prawns was to
provide evidence to either support or refute dietary recommendations to
restrict shellfish on the basis that the dietary cholesterol content would
increase blood cholesterol. Prawns are one of the most commonly
consumed shellfish in the UK and they are a rich source of long-chain
omega-3 fatty acids.
Study Rationale
Prawns represent the greatest percentage of all shellfish
consumed in the UK diet but patterns of consumption are
negatively influenced by the scientifically unfounded belief
that shellfish raise blood cholesterol
They also represent a major dietary source of long chain
n-3 PUFA (eicosapentaenoic & docosahexaenoic acids)
Study Aim
To determine the effect of cold water prawns on total serum
and LDL cholesterol and other biomarkers of CHD risk,
relative to an appropriate control, in normal, healthy men
The study aimed to determine the effect of these prawns on total serum
and LDL cholesterol and other lipid based markers of CHD, as compared
with an appropriate control. The subjects were healthy male volunteers
aged 20-70, university staff and students. The inclusion criteria were
normo-lipidaemic non-smokers with normal cholesterol and triglyceride
levels. We also had to ask whether any had shellfish allergy. For the
control we chose crab-sticks (ocean fish-sticks). The rationale for using
225g portions was based on the cholesterol content of the prawns, since
300-400 mg of dietary cholesterol is equivalent in cholesterol content to
about 2 eggs. This is also a level of intake at which the gut reduces its
absorption of dietary cholesterol. The rationale for choosing crab sticks as
a control was that they have a similar composition in terms of macronutrients, including energy and fat. The control was low in cholesterol
and long-chain omega-3 fatty acids. It was also easy to introduce into the
diet in a similar way to the prawns. The study was designed as a random
controlled cross-over.We randomised subjects to either the crabstick
control or the prawns for 4 weeks. Then after a 4 week ‘wash-out’ period,
they were placed on the other treatment, so all subjects receive both the
prawns and the control.
Composition (/100g) of Prawns and Crabsticks
Energy
Protein
Fat
Cholesterol
EPA+DHA
(Kcals)
(g)
(g)
(mg)
(mg)
100
21.2
1.73
165
547
Shelled,
& cooked
62
13.9
0.74
131
267
Crab sticks
115
7.80
1.60
trace
trace
Cold water prawn
(in shell)
225g prawns deliver
between 295-371mg
cholesterol & 0.6-1.2g
EPA+DHA per day
The subjects were randomised to receive 225g of either prawns or
crabsticks initially. There were no constraints or instructions given on the
methods they used to prepare and consume either the test or the control
during the cross-over study. The subjects were asked not to consume
other fish or shellfish, but otherwise to stick to their normal diet. The
intervention delivered between 300 to 400 mg cholesterol per day and 0.6
and 1.2 g of long-chain omega-3 fatty acids.
Our outcome measures included total plasma cholesterol and LDL
cholesterol; small dense LDL, a feature of the metabolic syndrome. Also,
plasma triglycerides, HDL cholesterol, blood pressure, body weight and
dietary intakes.
Outcome Measures
 Total plasma cholesterol and LDL cholesterol
 Small, dense LDL
 Plasma triacylglycerol (TAG)
 HDL cholesterol
 Plasma apoproteins B and A-I
 Blood pressure
 Body weight
 Dietary intakes (WINDIET)
The baseline characteristics of the subjects were as follows.
Characteristics of Subjects at Baseline
(pre-prawn & pre-control)
Subjects: 21 normal, healthy non-smoking males; mean age 41 years
(range 19-67) 18 Caucasians, 3 Asians.
Pre-Prawn
Pre-Control
UK (35-44yr)
Body weight (kg)
82.1 (12.2)
81.9 (12.6)
-
Blood pressure (mmHg)
125 / 73
124 / 72
130 / 76
68% >5.0
Plasma cholesterol (mM)
5.1 (1.1)
5.1 (0.9)
Plasma triacylglycerol (mM)
1.3 (0.5)
1.2 (0.6)
LDL-cholesterol (mM)
3.0 (0.9)
3.0 (0.7)
HDL-cholesterol (mM)
1.6 (0.4)
1.6 (0.4)
8% <1.0
Values are means (SD)
All 21 participants completed the study. Blood pressure was slightly
lower than the national average for this age-group. Their cholesterol level
was close to the national average (68% of people have cholesterol above
5.0).
Dietary intakes were compared with average UK intakes obtained from
the National Dietary Survey data of 2003. Their protein intake was
slightly higher and fat intake slightly lower than the national average, as
was their intake of saturated fat.
The most important point to emphasise is the difference in the intake of
dietary cholesterol, nearly 800mg in the prawn group and only 275 mg in
the control group, which is below the national average.
Dietary intakes versus UK intake (NDNS 03)
Energy (Kj)
(Kcals)
Prawn
Control
8,162 (1,648)
(1,940)
8,840 (2,664)
(2,099)
UK
9,880-8,610
Carbohydrate (%E)
(g)
43 (7)
(208)
49 (10)
(259)
48%E
275g
Protein (%E)
(g)
24 (4)
(114)
19 (5)
(101)
16.5%E
(88g)
Total fat (%E)
(g)
30 (5)
(64)
29 (8)
(66)
36%E
(87g)
SFA (g)
19 (5)
21 (10)
33g (13%E)
PUFA (g)
14 (8)
11 (7)
MUFA (g)
22 (6)
22 (10)
794 (186)**
275 (92)
Cholesterol (mg)
Alcohol (%E)
7 (8)
304mg/d
7 (6)
Values are means (SD) ** p<0.001
The results are presented as ‘Box and Whisker’ plots, which show the
median and the distribution of values as quartiles. The bar across the box
is the median, and I also include the arithmetic means.
So what do we see for the total cholesterol value? Statistically we are
comparing the post-prawn and post-control values. You can see
immediately that the distributions are almost identical. There was
variation in the median, but this was not statistically significant.
It is apparent from the equivalent distributions of plasma cholesterol that
eating 225g prawns a day had no effect on the concentration of total
plasma cholesterol.
cum
Chol
Total plasma
cholesterol
(mmol/l)
Total Plasma Cholesterol
5.1 ± 0.8
7
5.1 ± 0.8
6
5
4
3
1
Pre-prawn
2
3
Post-prawn
Pre-control
code
4
Post-control
Turning to LDL cholesterol, it’s the same story.; the distributions are
equal, so no change in either total or LDL cholesterol post prawn or post
control.
LDL cholesterol & Small, Dense LDL
4.5
Total LDL cholesterol
4.0
C94
cumLDL
Plasma
cholesterol (mmol/l)
3.5
3.0
2.5
2.0
3.02 ± 0.6
1.5
2.98 ± 0.6
1.0
1
2
3
4
Small, Densecode
LDL cholesterol
0.6 ± 0.4*
1.0
*p=0.035
0.4 ± 0.2
0.5
0.0
Pre-prawn
1
Post-prawn
2
Pre-control
Post-control
3
4
code
When you look at the small dense LDL, there was a suggestion it was
slightly higher in the control group, but not statistically different.
Fortriacylglycerol there was again no difference in the distribution of
values.
Plasma Triacylglycerol
cum TG
Plasma triacylglycerol (mmol/l)
2.5
1.23 ± 0.42
1.15 ± 0.43
1.5
0.5
Pre-prawn
1
Post-prawn
2
Pre-control
3
Post-control
4
code
There was no effect on the LDL/HDL ratio, which is commonly viewed
as a risk factor for coronary disease. There was also no effect on body
weight, which remained stable throughout the interventions, as did
systolic and diastolic blood pressures.
The most important finding was that the prawns had no effect on the total
or LDL cholesterol.
So what do we conclude? Adding 400mg of dietary cholesterol to the
habitual diet of this group of normo-lipidaemic men was not associated
with an increase in total or LDL plasma cholesterol. Prawn consumption
should therefore not be restricted on a basis that it may have an effect on
total or LDL cholesterol.
There were no other effects, including those typically produced by longchain omega-3 fatty acid, such as a decrease in plasma triacylglycerol and
an increase in HDL. However, when you look at the baseline of the
subjects, they showed no evidence of increased cardio-metabolic risk as
would be found in an obese and diabetic groups
I think this is one of the most convincing confirmations of a nullhypothesis; that dietary cholesterol does not increase blood cholesterol. I
wish to acknowledge Mrs Cheryl Isherwoodwho was responsible for the
organisation and management of this study.