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Man VS. Food
The effect of red meat on health is an issue often debated in
the media, whether that is its links to cancer or to obesity
and cardiovascular health. However, is it red meat, or
specifically processed red meat that is harmful? And how
does red meat increase cardiovascular disease risk?
Ischaemic heart disease and stroke are the top two causes of
death in the world, accounting for 25.1%, and there is a lack
of consensus in scientific papers on the subject. Therefore
we feel this was a current and relevant topic to investigate.
Aims and Objectives
• To investigate the potential detrimental effects of
consuming both processed and unprocessed red meat
on cardiovascular health .
• To look into the mechanisms of red meat (processed and
unprocessed) on cardiovascular health.
• To examine red meat consumption and cardiovascular health
in different cultures and the impact of westernisation
• To think about the future – should we stay away from
processed red meat altogether? Or is there a safe limit?
This site was made by a group of University of Edinburgh
medical students who studied this subject over 10 weeks as part
of the SSC. This website has not been peer reviewed. We certify
that this website is our own work and that we have
authorisation to use all the content (e.g. figures / images) used
in this website.
We would like to thank our tutor Zsanett Bahor for her guidance
and support throughout the project.
Total Website Word count: 8850
Word count minus Contributions page, References page, Critical
Appraisal Appendix, Information Search Report, Word Version
appendix and other sections clearly marked as Appendices: 5930
BACKGROUND KNOWLEDGE
Epidemiology
Cardiovascular disease (CVD) is an umbrella term
encompassing diseases of the heart and blood vessels. The 4
main types of CVD are 1:
• Coronary heart disease
• Stroke
• Peripheral Vascular disease
• Aortic disease
CVD is the largest cause of death in the world, with Ischaemic
Heart disease and stroke alone accounting for 25.1% of all
deaths 2. Every year in England and Wales, 124,000 deaths are
caused by CVD and 1/3 of men and 1/4 of women will die from
this disease 3, 4. However, this is compounded by the morbidity
related to the disease, as for every death, there are two cases of
complications, due to the effects of non-fatal strokes and heart
attacks 3.
Globally, deaths from CVD are expected to rise to 23.3 million
deaths by 2030 2.
CVD has a variety of risk factors, many of which are derived
from lifestyle and are consequently modifiable. The main ones
are 4:
• Age
• Sex – The cardio-protective effects of oestrogen mean that
women are less likely to develop CVD than men 5.
• Family history – due to a combination of shared genetic and
environmental factors
• Smoking
• Hypertension
• Hypercholestraemia – High total serum or high Low Density
Lipoprotein (LDL) concentration increases risk. This is
related to both genetics and diet.
• Obesity
• Hypertension
Process of atherosclerosis
A key factor in the precipitation of many cardiovascular events
is the process of atherosclerosis 6. This is the build up of plaques
in the arteries, with stable plaques leading to angina and
claudication, and unstable ones to MI and stroke.
1.
Endothelial injury
The process begins with damage to the endothelium. This
damage can be caused by hypertension, exposure to chemicals
in smoking, or high blood lipid content.
2.
Endothelial Dysfunction
The damaged endothelium leads to an increased movement of
LDLs to the sub-endothelium and increased monocyte adhesion
and activation.
3.
Macrophage activation
Activated macrophages generate Radical Oxygen Species (ROS)
leading to the oxidation of LDLs. They also produce cytokines,
attracting further inflammatory cells to the area. Usually
macrophages take up LDLs through receptor-mediated
endocytosis with a negative feedback system, but oxidised LDL
is not recognised. Instead, the modified LDL is absorbed by a
scavenger receptor with no negative feedback, leading to a
macrophage full of lipid. It is these Foam Cells that form the
fatty streaks.
4.
Smooth muscle recruitment
Growth factors released by the damaged endothelium and
activated macrophages cause the migration of smooth muscle
cells from the tunica media to tunica intima, and their
proliferation in the intima.
5.
Fibrous Cap Formation
The muscle cells secrete collagen in response to the cytokines
released, leading to the formation of a fibrous cap over the foam
cell accumulation. The cap is fragile, but its calcification makes
it prone to rupture. At this stage, Angina or Claudication may
occur.
6.
Rupture
A rupture of the plaque exposes the blood to collagen, starting
the intrinsic coagulation cascade, leading to a thrombus and
ischaemia. Alternatively, part of the plaque may break off and
become an embolus 3, 7.
The process of atherosclerosis.
(From Grahams Child, Wikimedia Commons)
Diet and CVD
As both hypercholestraemia and obesity are risk factors for
CVD, it is clear that diet can have a large influence on the
likelihood of someone developing the disease.
Consuming excess saturated fats has a large effect on
developing CVD. As well as raising net blood cholesterol levels,
saturated fat also increases blood LDL levels, which are a key
component in atherosclerosis 8 . This is the most recognised
method by which red meat can contribute to CVD.
LDLs are atherogenic as they transport cholesterol to the tissues
of the body, where they can be incorporated into blood
vessels.
High Density Lipoproteins (HDLs) carry cholesterol
from the tissues to the liver to be metabolised, and so can be
seen as “good cholesterol” 9 . Therefore, as well as net
cholesterol levels in the blood, it is also important to have the
correct balance of HDL and LDL.
Red meat contains relatively high amounts of saturated fat
compared to white meats, and so over-consumption will
increase the risk of atherosclerosis 3, 10.
Although saturated fats and atherosclerosis are a definite cause
of CVD, there is controversy as additional factors and
mechanisms may be involved. In a meta-analysis that involved
1,218,380 individuals, Micha et al. found that it was the salt and
preservatives in processed red meat that caused damage, and
that unprocessed meat had no effect of cardiovascular health 11.
Furthermore, evidence from studies such as the cohort study by
Sinha et al. involving 555,653 participants has shown that
although processed meat is worse, increasing unprocessed red
meat also increases CVD risk 12 . As such, it is difficult to come
to a conclusion, as there are many studies that despite being well
designed and with large participation rates, give different
results. This controversy is particularly relevant in a public
health context, as dietary guidelines should not place restrictions
on foods that do not cause harm.
MAIN BODY
MECHANISMS OF DAMAGE
There are many proposed mechanisms as to why the
consumption of red meat could be having a detrimental effect on
our cardiovascular health and here, we will focus on a few of
these in detail. The first mechanism that we will mention is the
theory that the microbes in our gut play a role.
In a study performed by A. Koeth et al. 13, it is suggested that
the metabolism of a chemical known as L- carnitine, a
trimethylamine very similar in chemical structure to choline and
often found in red meat, contributes to the promotion of
atherosclerosis. This was based on a previous study produced by
the same research group, that linked microbial breakdown of
choline in the gut to CVD pathogenesis, due to it producing a
chemical known as trimethylamine N-oxidase (TMAO)14. To
investigate if this was also the case for L- carnitine, they
performed various experiments on both humans and mice.
Firstly, they demonstrated that TMAO was produced when Lcarnitine was broken down by microbiota. They did this by
measuring TMAO plasma levels in 5 human subjects before and
after treatment with antibiotics, and again once the flora in the
gut were allowed to recover to normal levels. TMAO was barely
detected during the treatment period, but was detected during
the 2 periods of non-treatment, indicating that gut flora is
required for the production of TMAO from L-carnitine.
However, we appreciate that this is an extremely small sample
size and the results that the study witnessed here could purely be
down to chance.
The most notable part of the investigation is that they looked at
the fasting L-carnitine concentration in a cohort of 2, 595 stable
subjects undergoing elective cardiac evaluation, and it’s relation
to CVD risk. They saw a significant dose-dependant relationship
between the level of fasting plasma L-carnitine concentration
and prevalent CVD, which remained true when the results were
adjusted for traditional CVD risk factors. However, when they
looked at the relationship between the fasting plasma L-carnitine
concentrations and incident CVD, there was no significant
association, except for in the Cox regression model (which is a
statistical analysis method that allows you to look at the survival
rates of patients in relation to a given variable) 15 and only in
those subjects with currently high levels of plasma TMAO. This
suggests that the problem lies with the TMAO, and not the Lcarnitine itself.
A systematic review by Dinicolantonio et al. 16 agrees with this
finding that it is not the L-carnitine itself that is the problem.
This review analysed 13 trials were supplementation of Lcarnitine was compared with control in patients with an acute
myocardial infarction. They found that the L-carnitine
supplementation caused a 27% reduction in all cause mortality
and a 65% reduction in the development of ventricular
arrhythmias when compared with placebo , therefore
demonstrating that L-carnitine actually has a beneficial effect on
the
cardiovascular
system
following
an
acute
coronary syndrome. The proposed mechanism behind this
beneficial effect was seen to be multifactorial, but probably is
related to L-carnitine’s ability to facilitate the transport of long
chain fatty acids from the cytosol of myocardial cells to the
mitochondrial matrix, where they undergo β oxidation and the
toxic intermediates, that often induce ischaemia, are removed. It
is also proposed to reduce left ventricular dilation (LVD) after
an acute myocardial infarction, which is significant as LVD is
often a strong indicator that the patient may progress to heart
failure. This review suffered from the common limitations of
such reviews, such as all but one of the trials reviewed having a
small sample size, and not all of them being double-blinded.
However, this review does propose an interesting new treatment
avenue for acute coronary syndromes and highlights a
mechanism by which the consumption of red meat may actually
be beneficial to patients who have suffered a cardiovascular
incident. This should be explored further with the production of
a large cohort study.
Looking once again at the study by Koeth et al. 13 interestingly,
this study found that vegetarians and vegans have less of an
ability to produce TMAO from L-carnitine than omnivores do.
They compared 23 vegans and vegetarians with 51 omnivores,
and found that the non-meat eaters had significantly lower
fasting TMAO levels than the omnivores. They also examined a
subset of the 23 vegans and vegetarians (although the paper does
not put an exact number on the subset) and found that after
supplementation with L-carnitine, that they had a markedly
reduced ability to synthesise TMAO from L-carnitine. This
suggests that your long-term diet has an effect on the microbiota
in your gut and, hence, your ability to metabolise certain
products.
Having deduced that plasma TMAO levels seem to have an
effect on the promotion of atherosclerosis, the authors set about
determining why this was. Through their investigations, they
found various reasons. Firstly, TMAO alters cholesterol and
sterol metabolism, by increasing forward cholesterol transport
and decreasing reverse cholesterol transport. TMAO also
promotes the macrophage cholesterol accumulation and the
surface expression of SRC and CD36 on the macrophages,
which is important in the formation of foam cells. Finally,
TMAO appears to lower the expression of Cxp7a1 enzyme,
which is involved in the rate-limiting step of the catabolism of
cholesterol. Although this study had flaws such as a small
sample size, it highlights a potentially viable reason for the
detrimental cardiovascular effects associated with red meat and
could highlight a new way to tackle treating CVD.
Another proposed mechanism underlying red meat consumption
being detrimental to our health is the theory that the iron in red
meat can have an influence on our blood pressure, and, as we
know, hypertension is a well known risk factor for CVD. Iron is
hypothesised to play a detrimental part in atherosclerotic disease
because it can enhance oxidative stress due to the Fenton and
Haber- Weiss reactions 17. A cross sectional study performed by
Tzoulaki et al. 18, looked at 4680 men and woman of a similar
age from the UK, USA, China and Japan, and compared an
average of 8 blood pressure readings with the amount of meat
reportedly consumed by the subjects in the past 24 hours. They
measured their results in relation to the total amount of iron, the
amount of haem iron (found in meat) and the amount of nonhaem iron (found in vegetables, cereals, beans etc.) consumed
by the participants.
The results showed that the consumption of red meat was
positively associated with blood pressure, with the highest
quartile of meat eaters having a 1.25mmHg increase in systolic
blood pressure and a 0.73mmHg increase in diastolic blood
pressure on average.
However, the results also showed that both total iron
consumption and non-haem iron intake had an inverse relation
to blood pressure. They also found that haem iron intake was
positively associated with blood pressure, but the association
wasn’t high enough to be statistically relevant.
Another paper looking at the effects of red meat consumption on
the mortality rate of cardiovascular diseases and cancer 19,
found that their results were still moderately attenuated after
adjusting for haem iron. This suggests that although haem iron
may not have a strong association with increasing blood
pressure, it may be having some affect on the survival rates of
certain diseases, including CVD.
From these studies, it appears that the theory of iron in red meat
being involved in the pathogenesis of CVD may be justified, but
more research would be needed to clarify these results.
However, there is discussion as to whether it is the red meat
itself, or the processing of the meat that causes the problem.
PROCESSED VS
UNPROCESSED RED
MEATS
Another area in which there is debate is whether there is a
significant difference between the effects of unprocessed red
meat and processed meat and the incidence of CVD.
There have been several claims that consumption of processed
meat has a 20-40% higher risk of CVD than unprocessed red
meat, which has been claimed to have no association with
coronary heart disease11. It has been suggested that the
reasoning behind this difference on health is due to the
preservatives, such as sodium and nitrous compounds, added to
the meat when it is heated and processed. The addition of
sodium is claimed to be responsible for up to two thirds of the
detrimental cardiovascular health difference between processed
and unprocessed meat11. Processed meats, particularly bacon
and hot dogs, have been found to contain up to 400% more
sodium than unprocessed meats. This inevitably attributes
towards a higher blood pressure, affecting cardiovascular health
by causing hypertension20. There are many proposed theories as
to why high salt intake is linked to hypertension and the precise
mechanism still remains unclear. One study suggests that there
may be blood volume expansion due to water retention21.
Additionally, regular high sodium consumption weakens arterial
compliance and causes endothelial damage20, thus contributing
towards the process of atherosclerosis and increasing the
chances of developing coronary heart disease. This claim has
been supported by further evidence that has demonstrated that a
low-sodium diet appears to significantly reduce the risk of heart
failure and other coronary diseases22. However, it is important
to consider that sodium intake is not the sole cause of
hypertension and therefore we must acknowledge other factors
that may cause an increase in blood pressure and eventually,
CVD.
Furthermore, the addition of nitrates and related compounds in
processed meats have been hypothesized to influence
cardiovascular health. It has been suggested that they have
atherosclerotic promoting properties and cause vascular
dysfunction11. However another study suggested that dietary
nitrates and nitrites may have protective properties on the
cardiovascular system22. Therefore, it is evident that we must
consider the other mechanisms underlying the destructive
effects of processed meat on cardiovascular health. When
nitrites enter the human gastric system with certain food
additives, it produces a compound called N-Nitrosamines which
has been found to have destructive effects on the cardiovascular
system23. Upon treating rats with N-Nitrosamines, they found
that LDL levels increased whilst HDL levels markedly
decreased. High levels of LDL contributes to atherosclerosis by
inducing inflammatory cells to the arterial wall whereas low
HDL means that these cells and excess cholesterol are not
removed from the arterial lumen23. Together, it is evident that
N-Nitrosamines are likely to increase the risk of CVD simply by
promoting the atherosclerotic process. The potential factors in
processed meat that cause a detrimental effect on the
cardiovascular system in comparison to unprocessed red meat
opens up many areas of potential research.
Another way in which processed red meat has been said to
contribute to CVD is through the consumption of high amounts
of advanced glycation end products, as discussed in many
papers24,25,26. Advanced glycation end products (AGEs) are
modifications of proteins or lipids that have become
nonenzymatically glycated and oxidised after exposure to
sugars. The presence and build-up of AGEs in both intracellular
and extracellular structures has been shown to contribute to the
development of atherosclerosis25,26,27. Elevated levels of AGEs
have been reported in those particularly suffering from type-2
diabetes with coronary heart disease, confirming that AGEs
induce vascular injury by a variety of mechanisms28.
AGEs are most commonly endogenously formed. This process
is regularly linked with diabetes, as sufferers have
accumulations of AGEs as a result of hyperglycaemia and
increased oxidative stress29. CVD is a long-term complication
of diabetes, and therefore someone with high AGE levels and
diabetes is much more likely to go on to suffer from CVD.
On the other hand, AGEs have been shown to originate from
exogenous sources, such as diet29. AGEs are naturally present in
animal products, but the process of cooking, in particular
broiling, roasting, searing, grilling and frying, accelerates new
formation24,25. Prolonged heating and high temperatures when
processing food can also have this effect29. Foods particularly
high in protein and lipids e.g. meat, egg yolks and cheese are
seen to have high levels of AGEs26, but one prominent study, by
Uribarri et al., found that it was meats in particular that
contained the highest levels. Moreover, a more recent article for
‘Today’s Dietician’ confirmed that it is in fact red meats rather
than white where AGEs are most prevalent24. Uribarri et al.
concluded that the build-up of AGEs due to the processing of
meats and other animal products offers a valid explanation for
the detrimental health effects seen within the Western diet25.
This study was interesting and robust, as it carried out research
into a less publicised risk factor for CVD; its main strength
being that it was carried out on a multi-ethnic population, so it
took into account differences in cultural eating habits. However,
participants were only sampled from the same area, Manhattan,
and therefore the study may not be representative of the wider
population.
Several receptors have been identified for AGEs; however, the
most important in vascular injury is named RAGE27. The
interaction of AGEs with RAGE has been shown to increase
oxidative stress and induce a state of endothelial cell
activation27. In the vasculature, the main pathological outcome
of AGE interaction with endothelial surface RAGE is the
induction of intracellular ROS28. Through a variety of signalling
pathways, ROS induction leads to the activation of many genes,
including tumour necrosis factors, interferon-γ, cell adhesion
molecules and interleukins 1, 6 and 8. These genes are very
important in the process of inflammation and atherosclerosis28.
Another mechanism, by which AGEs cause vascular injury, is
the trapping of LDL in the subendothelium. There is increased
retention of LDL in the wall of the aorta and increased detection
by macrophages at this site. Therefore, there is increased
localisation of AGE-LDL in blood vessels leading to increased
production of foam cells, which, as discussed previously, go on
to form fatty streaks, the precursors of atheromatous plaques29.
In addition, AGEs have been shown to quench nitrous oxide
(NO) availability and activity within the wall of blood vessels 28.
Nitrous oxide is essential in the maintenance of the vasculature,
as it inhibits leukocyte adhesion to vessel walls, vascular
smooth muscle growth and platelet adhesion and aggregation.
All of these processes may lead to the progression of
atherosclerosis if not effectively regulated27.
Furthermore, the structure and function of many important
matrix molecules can be severely altered by AGEs28. Collagen
is one of these molecules, found in the vessel wall with a
particularly long-half life, and is a major target for AGE
modification29. AGEs accumulate on these proteins and can
cause formation of cross-links27, which trap other molecules
such as immunoglobulins, LDL and soluble plasma proteins
inside28. The cross-linking leads to an increased extracellular
matrix area, which leads to an increase in the stiffness of the
blood vessels27. Arterial stiffness puts a greater pressure on the
heart, as it has to increase its contractility to ensure the same
volume of blood is being ejected as if the arteries were healthy.
This can lead to hypertrophy of the heart, increasing the
likelihood of a cardiac event.
There is a considerable amount of research into the ways of
pharmacologically preventing the accumulation of AGEs within
the body, particularly looking at blocking the interaction
between AGE ligands and their receptor, RAGE27. However,
more immediately, institutions such as the American Heart
Association have come up with some solutions to avoiding AGE
overconsumption25. A greatly reduced intake of AGEs can be
accomplished by an increased consumption of legumes, fish,
low-fat milk products, fruits, vegetables and wholegrain, and by
reducing the consumption of fatty meats, solid fats and highly
processed food, especially processed red meat25. The method of
preparing and cooking food can also prevent AGE intake.
Preparing meat by marinating it in lemon juice or vinegar for up
to an hour before cooking has been shown to form less than half
the amount of AGEs than in untreated meat25. Finally, cooking
methods such as stewing, steaming, poaching and boiling could
be better publicised in order to educate the general public about
low AGE-producing cooking methods25.
As discussed, AGEs have a variety of mechanisms by which
they can accelerate the process of atherosclerosis, increasing the
likelihood of cardiac events in those who have high levels in
their body, particularly as a result of consuming large quantities
of processed red meat. In order to avoid an increased risk of
CVD, processed red meat should be avoided.
Having explored the detrimental health effects of processed red
meats, we have acknowledged that it’s increasing consumption
may be due to the westernisation of our diets.
WESTERNISATION
In the last fifty years or so, the westernisation of diets has had
detrimental health effects in both thriving cities and isolated
communities all over the world, particularly concerning those in
developing countries where the sudden influx of fatty and
sugary foods has caused the incidence of non-communicable
diseases to sky rocket30. This aptly named “meat-sweet” diet is
characterised by an increased consumption of saturated fats, red
and processed meats, and a low intake of fruits, vegetables and
fibre31. The dramatic change in lifestyle in recent years, where it
is now far more convenient to buy a pre-prepared, fat-laden
burger than to cook a healthy family meal, is a huge risk factor
of developing diabetes and coronary heart disease32.
Genetically speaking, humans existing today are not completely
dissimilar to the Stone Age hunter-gatherers in the late
palaeolithic era33. Although varying greatly both seasonally and
location-wise, the diets of Palaeolithic humans consisted mainly
of animal protein from game; the meat from which was leaner,
containing far less fat, than twenty first century factory farmed
beef33. With this high intake of red meat, one would expect our
Palaeolithic ancestors to have had atherosclerotic arteries and
high blood pressure; however, due to the meat containing a
higher degree of polyunsaturated fats and the people having a
more active lifestyle, this is not the case33. Conversely, a
sedentary lifestyle and high intake of saturated fats has
contributed to the modern man being at risk of “diseases of
civilisation”, such as hypertension, diabetes and cancer33.
A study in Japan found positive correlations between mortality
from coronary heart disease in men (ages 55 to 59 years old) and
an increase in western foods, such as those containing animal
protein and cholesterol34. This study considered dietary changes
throughout the whole country, in both traditional rural areas and
modern urban areas, making it more applicable worldwide. In
Alaskan natives, where the traditional diet is hugely reliant on
fat, it is interesting to see that replacing this with a similarly
fatty western diet still increases the risk of CVD. This is thought
to be due to specific fatty acids rather than the total fat intake;
the fatty acid make-up of the traditional marine based Alaskan
diet promotes better cardiovascular health compared to that of a
typical western diet35.
Nowadays, with 35% of Scottish men suffering from
hypertension and CVD being the UK’s biggest killer36, it is
suggestive that it is not the meat itself, but what we are doing to
it and how it is being eaten which is contributing to the
premature deaths of thousands of individuals. The meat we eat
nowadays is completely different to the wild game that our
ancestors once ate; factory-farmed meats differ hugely in their
lipid profile and chemical pollutant content37. Long-chain
unsaturated omega-3 fatty acids are abundant in plant materials,
and are also present in the meat of game animals. The
consumption of this n-3 fatty acid by humans was far greater in
Palaeolithic times, and it has been shown to increase the
concentration of HDLs, lower blood pressure and have a
beneficial effect on cardiac muscle rhythmic stability37. Modern
meat contains more saturated fatty acids38, which are linked to
an increased risk of coronary heart disease39. Cattle that have
been fed solely on grass have much higher concentrations of
conjugated linoleic acid (CLA) in their meat tissue; this is an
isomer of octadecadienoic acid and the principle dietary source
of it is from ruminant meat and milk 40. CLA has been found to
comprise of anti-carcinogenic and anti-atherogenic properties in
animal studies40, reiterating that what we feed domesticated
livestock has huge implications on the quality of the meat. There
are also major health implications involved in this high-demand
production of meat; feeding cows ruminant waste material in an
effort to relieve the tension between food supply and demand is
what brought about bovine spongiform encephalopathy, or mad
cow disease41.
So, looking at what we have found in our research, how much, if
any read meat is safe?
SO HOW MUCH, IF ANY,
RED MEAT IS SAFE?
Whilst we have gone into depth on the pathophysiology of how
red/ processed meat affects CVD risk, there is also a wealth of
epidemiological evidence – and disagreement – on the subject.
The Seven Countries Study42 sparked current interest, as it was
the first to find a significant correlation between red meat and
CVD. Since, many studies have agreed, linking red meat with
stroke and ischaemic heart disease43, atherosclerosis44, and
acute coronary syndrome45.
However more recently, scrutiny has changed to the processing
procedures of meats. Micha et al.‘s large meta-study found the
increased salt and preservatives in processed meat to be the
disease causing mechanism rather than the fat content found in
all red meat, only finding a link between CVD and processed
meats11. However, there are conflicting studies which claim that
while processed red meat is indeed more detrimental to
cardiovascular health, unprocessed red meat is still associated
with a 13% increased risk of death from cardiovascular causes
for every additional daily portion46.
Whilst associations aren’t always consistent, there is enough
significant evidence to link processed red meat consumption
with CVD. Whether unprocessed red meat consumption is also a
risk factor is more controversial, and difficult to assess as diet is
very complex, as are the mechanisms and risk factors for CVD.
These inconsistencies limit the reliability of current
recommended intakes for red meat. The government’s current
guidelines, issued by the Department of Health, recommend that
anyone eating more than 90g of red/processed meat per day
should aim to cut down to 70g a day, which is the UK daily
average47. This recommendation is based on links between
eating these foods and bowel cancer, but does not evaluate or
provide information on red/processed meat intake as a risk
factor for CVD. Considering that coronary heart disease is the
leading cause of death in the UK and worldwide1, this is not
something to be overlooked.
For example, Pan A et al.19 estimated from analysis of two large
cohort studies that by reducing the amount of red/processed
meat eaten a day by half, to around 42g, 9.3% of deaths in men
and 7.6% of deaths in women could be prevented. This same
research found a dose-response relationship between red meat
intake and all-cause mortality, which is a good basis to
recommend cutting down consumption.
Graph to show dose-response relationship between red meat intake and mortality.
Reproduced with permission from Pan A[19]
The EPIC study48 looked at meat consumption and mortality
across 10 European countries, considering a very heterogeneous
diet across a large sample size. It found no statistically
significant associations between red meat intake and CVD, but
concluded that Europeans consuming high amounts of processed
meat are at an increased risk of an early death, especially due to
CVD. Furthermore, it was estimated that 3.3% of deaths could
be prevented if these men and women ate less than 20g of
processed meat a day. Current government guidelines47 don’t
reflect this advice, as they don’t highlight that processed meat is
considered to have a greater negative impact on health11,19,48,49
than unprocessed red meat in their dietary recommendations.
However, it is important to take into consideration other
confounding factors when looking at complex disease processes
such as those involved with CVD. Men and women with a
higher intake of red meat are more likely to be current smokers,
to drink alcohol and to have a higher BMI. They are less likely
to consume fruits and vegetables and to be physically active
19,48.
All of the above are key determinants in the risk of
developing cardiovascular disease50,51,52. This could imply that
in fact red/processed meat consumption is not a significant risk
factor in the development of CVD, but rather a confounding
factor of another variable. Researchers adjusted data to
eliminate the aforementioned confounding variables11,19, 48,51
but these statistical adjustments may not be significant enough.
For example, a low socioeconomic status is associated with
eating more processed foods and fattier, cheaper cuts of meat 53.
It is also strongly associated with increased prevalence of
smoking54, obesity55 and lower consumption of fruits and
vegetables54. Therefore it could be the case that the trends
between red/processed meat consumption and CVD are actually
due to the overarching factor of socioeconomic status.
Table to show cardiometabolic risk factor hazard ratio between vegetarian and nonvegetarian adventists. Reproduced with permission from Le LT[57]
To work around this, we can look at studies of populations with
very similar health behaviours, with meat intake being one of
the only significant variables. Epidemiological study of
Adventists, a Christian denomination, allows one such
opportunity, as the Church doctrine places a strong emphasis on
healthy living, including abstinence from tobacco and alcohol 56.
Vegetarianism is also encouraged by the Church, with around
50% of Adventist members following a vegetarian diet and the
rest following a diet similar to the rest of the western
population57. One review of three large Adventist Cohorts found
that vegetarians had greatly reduced risks of developing
hypertension, type-2 diabetes, metabolic syndrome and obesity
which can explain why in all three cohorts analysed, vegetarians
had 26% to 68% lower risks of mortality from ischaemic heart
disease, CVD, and cerebrovascular disease57. These figures
were significant even having been adjusted for age, sex,
smoking status, race, educational level, alcohol and other factors
related to CVD. These results back up the epidemiological and
pathophysiological evidence we have previously reviewed – that
reduction in consumption of meat is cardio-protective. Another
study analysing mortality between vegetarians and nonvegetarians found that vegetarians had an ischemic heart disease
death rate ratio of 0.78 compared to non-vegetarians, and that
even ‘semi-vegetarians’ (those who ate fish only or meat less
than once a week) had a death rate reduction of 0.66 implying
that a reduction in meat consumption is still beneficial, if not as
good as abstinence.
Benefits
When considering how much red meat to consume you must not
only look at the detrimental effects but also the benefits. Red
meat is nutritional and a source of vitamins and minerals that are
essential to health. A 100g portion of raw ground beef contains
36%, 29% and 84% of your Vitamin B3, B6, and B12
recommended daily nutrient intakes (RNIs) respectively. It also
provides 20% of your Iron, 66% of your Zinc and 28% of your
Selenium RNIs.58 Red meat is a better source of haem iron than
either poultry or fish, and also more bioavailable than non-haem
iron from plant sources. Iron-deficiency anaemia is a major
nutritional problem affecting high and low socioeconomic
populations worldwide.59 Red meat is also the largest source of
Vitamin B12 in the diet with just 100g supplying nearly your
entire daily-recommended intake. The methylation cycle occurs
in all cells in the body and it requires adequate levels of B12 as
well as B6 and folate. Without these nutrients the enzymes
cannot function properly leading to increased levels of
homocysteine – a risk factor for cardiovascular disease and
stroke. So in moderation red meat can have protective effects.59
CONCLUSION
Upon reviewing the evidence, we believe that unprocessed lean
red meat consumption, in moderation, is not a risk factor for
cardiovascular disease and is an important dietary source of
protein and nutrients. We came to this conclusion as there is not
enough evidence associating unprocessed red meat with
cardiovascular disease, particularly when consumed in moderate
quantities as part of a balanced diet.
However, the same cannot be said of processed red meat, which
has much evidence linking it to CVD. Whether there are safe
limits to processed red meat intake is controversial, but from the
studies we have reviewed we can conclude that there are great
benefits to reducing consumption to low levels, although
complete abstinence from processed red meats appears to be
more cardio-protective still. What is obvious is that the health
properties of processed and unprocessed meats are vastly
different, and that it is an important public health issue that
government guidelines should be updated to advise people more
accurately on healthy food choices.
We found multiple limitations and inconsistencies across the
literature, which could have an impact on the validity of their
results and be the cause of current conflicting information.
Studies regularly didn’t monitor cooking methods, fat content of
different cuts of meat or degree of fat trimming and, as
discussed, dietary fat has a large impact on CVD risk. There
were inconsistencies in how studies classified processed and
unprocessed meat and data collection was usually by selfreported questionnaire – a method notorious for the introduction
of bias. There is also a lack of studies focusing solely on lean
unprocessed red meat. Furthermore, confounding variables are
numerous and important when considering both CVD and diet,
as we have previously discussed, and studies may not have
taken accounted for these accordingly. Further research in this
area is needed in order to clarify how cardio-protective reducing
red and processed meats may be, ideally in the form of large
clinical trials where a prescribed diet is monitored and followed
up over a long period of time.
PROJECT DIARY
Week 1
This was the first time the group met with Ms Bahor and so the
purpose of the meeting was to brain storm ideas of where we
wanted to take the project. Ms Bahor had deliberately left the
project description vague so that we could control it from the
start. We narrowed the ideas down to “diet’s of the world” or
the “effect of red meat in the diet”. With little prior knowledge
in the group we opted to go away and research these topics over
the following week to make an informed decision about what
topic to take on.
Week 2
In our second meeting, we discussed that although that many of
the topics we spoke about last week were interesting, such as the
health benefits of the Mediterranean diet, or Vegan vs
Vegetarian Vs Omnivorous diet, we needed to focus on
something more specific for our project. Many of us had looked
specifically at the possible harmful effects of red meat so we
decided to follow this route. We thought this would be a good
topic as it was specific, with plenty of primary research in many
areas relating to red meat, may be linked to heart disease, or
how supposedly animal proteins from food can ‘switch on’
cancer promoters such as IGF-1. Because of this we decided not
to narrow our research to one disease, but rather for now look at
the many harmful effects that eating red meat ma cause.
Week 3
A lot of the studies looked at the difference between consuming
processed and unprocessed red meat and so we thought it was
important to explore the difference between the two. Potential
health effects include looking at CVD, hypertension, stroke,
cancer, diabetes. We also should also look at the mechanism of
consuming red meat on ONE of these diseases. Probably focus
on cardiovascular and cancer then include a small section about
additional diseases that have been seen to be linked with red
meat consumption.
Everyone gave a short summary of their article and everything is
going on the right track: diabetes, hypertension, CHD,
pancreatic cancer, bowel cancer, stomach and liver cancer,
stroke and type 2 diabetes were explored in these articles.
Week 4
In this meeting, we decided to consolidate the objectives of our
project. We also decided to focus on the effects of red meat
consumption on cardiovascular health and not cancer. Our
finalised aim is: To investigate the potential detrimental effects
of eating both processed and unprocessed red meat on
cardiovascular health.
We came up with several ideas for objectives:
• To look into the mechanism of red meat (processed and
unprocessed) on CV health.
• To look at the substances that differentiate processed and
unprocessed red meats and their differing effects on CV
health.
• Red meat consumption and CV health in different cultures and
westernisation
• Cooking method and redness of the meat
• To look at other diseases that red meat has been demonstrated
to have a negative effect on
• To think about the future – should we stay away from
processed red meat altogether? Compare normal diet to
vegetarianism
• To see if we there should be a daily limit to red meat
consumption.
• To look at other risk factors of CV health and red meat
consumption e.g. socioeconomic group, age, smokers,
alcohol (processed meat is cheaper)
Conor would also write the critical appraisal for the group, but
we would all make contributions after the presentations next
week.
Week 5
We continued with members presenting their critical appraisals.
Then went onto discuss these themes:
Physiological
mechanisms, processed vs unprocessed, westernisation of diets
and should we avoid meat altogether.
Week 6
Lucy and Kerr presented their informal critical appraisal.
We
discussed how everybody was feeling in regards to the
delegation of parts of the essay. We spoke about what we had
written over the past week and explained certain bits of it and
what our plans were to achieve in the coming week. Izzy
explained advanced glycation end products.
Amy explained the
mechanisms of process meats leading to cardiovascular
problems. For next week we are to continue our parts of the
essay, to feedback to the group in the next session.
Week 7
Amy and Jacqueline presented their critical appraisals
Planned to all read Connor’s paper this week so we can point
out anything we think he has missed or things we want to query
about his critical appraisal when he presents it next week
James read out his section on epidemiology, risk factors and
mechanisms of cardiovascular disease.
Jobs still to do:
• Conclusion
• Critical appraisal
• Collate references
• Search history and search methods report
• Put all together onto website
• Contributions page
• Order on website
Essay outline
– James – Background
– Jacqueline – General mechanisms
– Amy and Izzy – processed vs unprocessed mechanisms
– Kerr – westernisations
– Alice and Lucy – What is healthiest
– Conclusion
2.
3.
4.
Worked out we’re roughly on track for word count
Complete sections and reference properly
Everyone to put up their sections on to Facebook so we
can all read and find out what overlaps/ what is missing
Week 8
This week:
Alice presented her critical appraisal on a paper about meat and
fat intake as risk factors for pancreatic cancer. Conor also
presented his critical appraisal, but as his paper will be the
group’s critical appraisal, we asked him the relevant questions
and gave him feedback, rather than our tutor. James has nearly
finished the introduction and no one had any improvements that
they thought should be made to the conclusion.
For next week:
3.
We will collate our references and Alice will check that it
is all done properly.
4.
We will all read and comment on each others sections.
5.
We will email the relevant organisations and people about
being able to use their diagrams in our project.
We aim to be finished by the next meeting on Monday.
CONTRIBUTIONS
• James Hazelwood’s role was to do most of the research of
background knowledge for this project. He wrote the
‘background knowledge’ page on the epidemiology of
CHD, pathophysiology of CHD and UK recommendations
of meat consumption.
• Amy Walter researched the differences in processed and
unprocessed red meat and their different health effects on
the cardiovascular system. She looked at the addition of
preservatives during processing, which mainly included
sodium and nitrate compounds. Also, along with Izzy
Utting, Amy wrote the search report.
• Alice McKinnes researched government guidelines on
red/processed meat intake, vegetarian vs none vegetarian
diets, and epidemiological evidence on what, if any,
amounts of red meat are safe to consume. Also collated the
•
•
•
•
•
references and, along with Lucy Dobbs, wrote the
conclusion.
Lucy Dobbs researched the long term effects of eating red
meat and wrote part of the how much red meat, if any, is
safe? She also wrote the conclusion in conjunction with
Alice McKinnes.
Izzy Utting researched processed red meat and the
mechanisms by which it causes detrimental cardiovascular
health effects. Looked further into advanced glycation end
products and wrote this part of the website. She also
cowrote the search report with Amy Walter. Izzy was the
creative genius behind the drawing designs.
Kerr Hartop researched the evolution of the western diet and
comparisons of our diet effects on health to other cultures
around the world.
Jacqueline Quinn helped to research effects of meat on the
cardiovascular system and wrote the section on the
mechanisms of eating red meat resulting in poor health.
Conor Rankin edited the website, putting together the pages
from the other members. He also wrote the critical
appraisal appendix, organised the project diary and wrote
the contributions page.
CRITICAL APPRAISAL
Mediterranean diet and CHD: the Greek European
Prospective Investigation into Cancer and Nutrition Cohort
Aims:
• To investigate the association of adherence to the
Mediterranean diet (MD) with cardiovascular disease
(CVD) incidence,
• Assess the morality in the ‘Greek European Prospective
Investigation into Cancer and Nutrition cohort’ (GEPIC).
Population: The study used a cohort of volunteers aged 20-86
recruited between 1994-1999 from all over Greece, with data
being collected until 2009.
Study Design: Cohort-study
Study Size: 23929 adult men and women without CVD or
cancer at enrollment.
Statistical Tests: This study used a cox regression to evaluate
the effect of several variables on the time it takes for CHD to
develop and the results showed adherence to MD leads to a
statistically significant (p=0.003) reduction in morality.
Outcome Measure: The study measured the number of
participants developing coronary heart disease (CHD) and
morality of CHD in relation to MD. This was an appropriate
measurement as the cohort study allowed a inverse causal
association to be formed between a MD and CHD.
Main Results: 636 participants (426 male and 210 female)
developed CHD, among them 240 died. There was a dose
response pattern with higher adherence to MD inversely
associated with a reduction in CHD morality – a two point
increase in MD score leads to a CHD morality reduction by 19%
in males and 25% in females. There was also an association of
traditional risk factors (obesity, smoking and old age) with CHD
and death.
Sources of Bias: There are several potential biases that could
have adversely affected this study: (i) Recall bias as patients had
to fill in the food frequency questionnaire (FFQ) retrospectively
with their dietary habits and this could tend to the null, people
are more likely to underreport their health damaging behaviours.
This is confirmed by the study as women have a stronger
inverse association of MD and CHD, possibly due to women
having a better recollection and more accurate reporting; (ii)
Follow up data was collected by interview which gives rise to
observation bias, any participants who develop CHD could be
probed for answers to match the expected hypothesis.
Strengths:
• The study design allowed a causal link to be established
between the MD and CHD as CHD was measured using
incidence (diagnosis during the study) over prevalence.
The study excluded subjects with prevalent cardiac disease
or cancer and any participate without follow up data to
reduce bias.
• With 23,929 participants, the GEPIC is a large study making
the results more reliable. Furthermore there are slightly
more females than males in the study which is
representative of the population.
Weaknesses:
5.
The authors of this study found a correlation between
males eating meat and CHD however they do not
distinguish between different types of meat, particularly
processed and non-processed meat, which could have
different effects on health.
6.
Data was collected by follow up interview, which isn’t
completely reliable as variation between interviewers
could have resulted in bias.
7.
The study did take into consideration and adjust for some
confounding factors such as education level but didn’t take
into account others such as cooking methods, e.g. frying
food in butter, which increase the risk of CHD.
Conclusion: We as a group, feel that the study design and the
results identified make it a valid study. The authors addressed
the aims confirming that adhering to the MD has an inverse
association with CHD and that other health damaging
behaviours also contribute. Although there were some sources
of bias they did not affect the reliability of the results as the
sample size was so large.
MD and CHD Paper
INFORMATION SEARCH
REPORT
An unhealthy diet is considered a major risk factor for many
diseases. There has been recent interest in the news and several
hypotheses suggest that red meat consumption has a particular
detrimental effect on health. In order to get an overview of this
topic, we watched the documentary “World’s Best Diet”, which
allowed us to enhance our understanding of the different global
diets and their correlation with the general health of the nation.
We decided to examine this relationship further and looked at
several studies that showed a significant relationship between
red meat intake and cancer, diabetes and CVD. We used a wide
range of online databases, including Google Scholar, PubMed,
and particularly Ovid MEDLINE, on which we carried out a
MeSH search.
In order to narrow our research, we focused specifically on the
effects and mechanisms of red meat on cardiovascular health.
We looked at a combination of meta-analyses and primary
research articles, which focused on certain aspects of CVD such
as hypertension, stroke and coronary heart disease. Vegetarian
and Seventh-day Adventist diets were also of particular interest
to us, especially in connection to the incidence of CVD. The
meta-analyses were useful for comparing large and diverse
populations.
The key words we used in these searches included “red meat” or
“processed meat”. We exploded “heart disease” in the MeSH
search so that it would encompass all types of coronary heart
diseases. We made the results more specific by combining “red
meat” AND “heart disease” with the Boolean operator.
When trying to access articles, it was often difficult to obtain the
full text. The abstract was rarely sufficient for our depth of
research and therefore this proved a problem in some cases. We
overcame this by signing up to websites or using the university
access login.
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