Diet for stroke prevention

Abstract

Lifestyle is far more important than most physicians suppose. Dietary changes in China that have resulted from increased prosperity are probably responsible for a marked rise in coronary risk in the past several decades, accelerating in recent years. Intake of meat and eggs has increased, while intake of fruits, vegetables and whole grains has decreased. Between 2003 and 2013, coronary mortality in China increased 213%, while stroke mortality increased by 26.6%. Besides a high content of cholesterol, meat (particularly red meat) contains carnitine, while egg yolks contain phosphatidylcholine. Both are converted by the intestinal microbiome to trimethylamine, in turn oxidised in the liver to trimethylamine n-oxide (TMAO). TMAO causes atherosclerosis in animal models, and in patients referred for coronary angiography high levels after a test dose of two hard-boiled eggs predicted increased cardiovascular risk. The strongest evidence for dietary prevention of stroke and myocardial infarction is with the Mediterranean diet from Crete, a nearly vegetarian diet that is high in beneficial oils, whole grains, fruits, vegetables and legumes. Persons at risk of stroke should avoid egg yolk, limit intake of red meat and consume a diet similar to the Mediterranean diet. A crucial issue for stroke prevention in China is reduction of sodium intake. Dietary changes, although difficult to implement, represent an important opportunity to prevent stroke and have the potential to reverse the trend of increased cardiovascular risk in China.

Full text

44 SpenceJD. Stroke and Vascular Neurology 2018;3:e000130. doi:10.1136/svn-2017-000130
Open access
Diet for stroke prevention
J David Spence1,2
1Stroke Prevention &
Atherosclerosis Research
Centre, Robarts Research
Institute, London, Ontario,
Canada
2Neurology and Clinical
Pharmacology, University of
Western Ontario, London,
Ontario, Canada
Correspondence to
ProfessorJ DavidSpence;
dspence@ robarts. ca
To cite: SpenceJD. Diet for
stroke prevention. Stroke and
Vascular Neurology 2018;3:
e000130. doi:10.1136/svn-
2017-000130
Received 8 December 2017
Revised 29 December 2017
Accepted 29 December 2017
Published Online First
13January2018
►http:// dx. doi. org/ 10. 1136/
svn- 2018- 000171
Review
ABSTRACT
Lifestyle is far more important than most physicians
suppose. Dietary changes in China that have resulted
from increased prosperity are probably responsible for a
marked rise in coronary risk in the past several decades,
accelerating in recent years. Intake of meat and eggs has
increased, while intake of fruits, vegetables and whole
grains has decreased. Between 2003 and 2013, coronary
mortality in China increased 213%, while stroke mortality
increased by 26.6%. Besides a high content of cholesterol,
meat (particularly red meat) contains carnitine, while egg
yolks contain phosphatidylcholine. Both are converted
by the intestinal microbiome to trimethylamine, in turn
oxidised in the liver to trimethylamine n-oxide (TMAO).
TMAO causes atherosclerosis in animal models, and in
patients referred for coronary angiography high levels after
a test dose of two hard-boiled eggs predicted increased
cardiovascular risk. The strongest evidence for dietary
prevention of stroke and myocardial infarction is with
the Mediterranean diet from Crete, a nearly vegetarian
diet that is high in beneficial oils, whole grains, fruits,
vegetables and legumes. Persons at risk of stroke should
avoid egg yolk, limit intake of red meat and consume a
diet similar to the Mediterranean diet. A crucial issue for
stroke prevention in China is reduction of sodium intake.
Dietary changes, although difficult to implement, represent
an important opportunity to prevent stroke and have the
potential to reverse the trend of increased cardiovascular
risk in China.
When ranked in order of importance, among
the interventions available to prevent stroke,
the three most important are probably
diet, smoking cessation and blood pressure
control.1 Hypertension and smoking cessa-
tion are discussed in other papers in this issue
of the journal. In this paper I discuss diet and
stroke prevention.
IMPORTANCE OF LIFESTYLE
Lifestyle is much more important than
most physicians suppose. In the US Health
Professionals study and the Nurses’ Health
Study, poor lifestyle choices accounted for
more than half of stroke.2 Participants who
achieved all five healthy lifestyle choices—not
smoking, moderate intake of alcohol, a body
mass index <25, daily exercise for 30 min and
a healthy diet score in the top 40%—had
an 80% reduction of stroke compared with
participants who achieved none. In a study
in Swedish women, all five choices reduced
the risk of stroke by 60%.3 Among Swedish
men with hypertension and dyslipidaemia,
all five healthy behaviours reduced coronary
events by more than 80%.4
HARMFUL DIETARY TRENDS
In the USA, the worst of the lifestyle choices
is diet. The American Heart Association statis-
tical report of 2015 indicated that only 0.1% of
Americans consumed a healthy diet and only
8.3% consumed a moderately healthy diet.5
In China, the consumption of meat and eggs
has increased markedly in recent years, while
consumption of whole grains, vegetables and
fruit has declined.6 This probably accounts
for much of the increase in fasting cholesterol
levels7 and in coronary disease6 8 in China at
the same time. Stroke is much more common
than myocardial infarction in China, and in
the past most strokes were due to hyperten-
sion. What has happened in China is that
myocardial infarctions have increased mark-
edly, with a much smaller increase in stroke.
Between 2003 and 2013, stroke mortality per
100 000 in urban people increased from 102.44
to 125.56 (a 26.6% increase), while coronary
mortality increased from 16.46/100 000 urban
people to 51.46/100 000 (a 213% increase)6
(figure 1). Undoubtedly strokes due to large
artery disease in China will have increased
in proportion during that time, the opposite
of what was seen in a Canadian stroke clinic
population between 2002 and 2012.9
TRENDS IN DIETARY GUIDELINES
In the past, a low-fat diet was recommended
to reduce cardiovascular risk; however, as
pointed out by Willett and Stampfer,10 the
low-fat diet was essentially ‘pulled from thin
air’ by a committee trying to imagine a diet
that would lower fasting levels of low-density
lipoprotein (LDL) cholesterol. Recent dietary
guidelines tend to recommend a dietary
pattern, rather than specifying limits to intake
of particular foods or nutrients. Increasingly,
guidelines are recommending reduction
of intake of animal fat and increased intake
of fruits and vegetables—a more plant-
based diet. The Dietary Approaches to Stop
Hypertension (DASH) diet11 emphasised
fruits, vegetables and low-fat dairy foods with
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reduced intake of saturated fat, total fat and cholesterol;
it included whole grains, poultry, fish and nuts, and was
reduced in red meat, sweets and sugar-containing bever-
ages. This appears to be similar to the Mediterranean diet,
but there are important differences: the Mediterranean
diet also emphasises whole grains, fruits and vegetables,
but it is high in beneficial oils (olive and canola), low in
dairy products and contains much less animal flesh. In a
retrospective article,12 Ancel Keys, the leader of the Seven
Countries Study, described it as follows: ‘The heart of this
diet is mainly vegetarian, and differs from American and
northern European diets in that it is much lower in meat
and dairy products and uses fruit for dessert’.
EVIDENCE FOR THE MEDITERRANEAN DIET
The diet with the best evidence for stroke prevention is
the Mediterranean diet from Crete. In the Seven Coun-
tries Study, it was discovered that coronary risk in Crete
was 1/15th that in Finland and only 40% of that in
Japan.10 In a retrospective article, Ancel Keys described
it as ‘a mainly vegetarian diet…favoring fruit for dessert’.
The diet is not a low-fat diet; it is a low glycaemic/high-fat
diet with 40% of calories from beneficial fats such as olive
and canola oil, and high in whole grains, fruits, vegeta-
bles and legumes (peas, lentils, beans, nuts and so on)
(figure 2).
n secondary prevention, in the Lyon Diet Heart Study,13
the Mediterranean diet was approximately twice as effi-
cacious as was simvastatin in the contemporaneous Scan-
dinavian Simvastatin Survival Study (4S).14 Both studies
enrolled patients who had survived a myocardial infarc-
tion; in the Lyon Diet Heart Study, the Mediterranean
diet reduced coronary events and stroke by more than
70% in 4 years; in the 4S trial, simvastatin reduced recur-
rent coronary events by 40% in 6 years. In primary preven-
tion, in the Spanish Primary Prevention of Cardiovascular
Disease with a Mediterranean Diet (PREDIMED) study,15
a low-fat diet was compared with two Mediterranean diet
arms: one fortified with olive oil, while the other fortified
with mixed nuts. Both versions of the Mediterranean diet
significantly reduced cardiovascular events; the nut-forti-
fied version reduced stroke by 47% in 5 years.
PROBLEMS WITH LOW-FAT DIETS
In recent years there has been much said about how the
dietary villain is not cholesterol and egg yolk but sugar,
and some have mistakenly blamed the Mediterranean diet
for the low-fat diet that has resulted in a marked increase
in carbohydrate intake, with increases in diabetes and
obesity.16 However, the low-fat diet did not result from
Figure 1 Trends in cardiovascular mortality in China, 2003–
2013. (A) Increase in mortality from myocardial infarction and
(B) increase in mortality from stroke. Myocardial infarction
increased much more steeply than stroke, probably in
large part because of changes in diet in China over time
with increased prosperity. Strokes in China are largely due
to hypertension, whereas myocardial infarctions are more
closely related to intake of meat and egg yolk. (Reproduced
with permission from the European Heart Journal, Weiwei et
al.6)
Figure 2 The Mediterranean diet. The Mediterranean diet
is a high-fat/lowglycaemic diet with 40% of calories from
fat; however, the fat is mainly benecial oils such as olive
and canola. Among men in the Seven Countries Study, the
coronary risk in Crete was only 1/15th of that in Finland,
where most of the fat was saturated fat (accompanied by
cholesterol), and 40% of that in Japan, where the diet is
a low-fat diet favouring sh.(Reproduced from Willet and
Stampfer.10)
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46 SpenceJD. Stroke and Vascular Neurology 2018;3:e000130. doi:10.1136/svn-2017-000130
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the discovery of the Mediterranean diet. With its high fat
content (40% of calories from fat, mainly olive oil)10 and
emphasis on whole grains, the Mediterranean diet is actu-
ally a low glycaemic diet.
The result of this discussion has been a widespread and
popular, but entirely mistaken, move to increased use of
low-carbohydrate (low-carb) diets, with a high intake of
cholesterol and animal fat. This is disastrous, and to a
great extent due to propaganda of the food industry.17
Like the sugar industry18 the meat and egg industries
spend hundreds of millions of dollars on propaganda,
unfortunately with great success.19–21 Box 1 provides links
to information about this issue.
An Israeli diet study22 provided perhaps the best
evidence that the Cretan Mediterranean diet is actu-
ally better than a low-carb diet for diabetes and insulin
resistance. Overweight residents in an institution, who
obtained their meals from the cafeteria, were randomised
to a low-fat diet, a low-carb diet or the Mediterranean
diet. Adherence was 95% at 1 year and 86% at 2 years,
unusually good for dietary studies. Weight loss was iden-
tical on the low-carb and Mediterranean diet, and both
were significantly better than the low-fat diet. Among
participants with diabetes, fasting glucose, fasting insulin
levels and insulin resistance were clearly the best on the
Mediterranean diet.22
Propaganda of the egg industry and the red meat industry
Following an exposé of the propaganda of the sugar
industry in which the ‘smoking gun’ was unearthed in
archives,18 Nestle17 commented on the attempts of the
food industry in general to influence public beliefs. I
commented on the egg industry and the meat industry.19
The two pillars of the egg industry propaganda are
a red herring and a half-truth. The red herring is a
misplaced focus on the effects of diet on fasting lipids.
Diet is not about the fasting state; it is about the postpran-
dial state.23 24 For ~4 hours after a high-fat/high-choles-
terol meal, there is marked oxidative stress, endothelial
dysfunction and arterial inflammation.25
The half-truth is the slogan ‘eggs can be part of a healthy
diet for healthy people’. This is based on two US studies
that did not find harm from egg consumption except
among participants who became diabetic, in whom an
egg a day ‘only’ doubled coronary risk.26 27 However, as
discussed above, the US diet is so bad that it is difficult to
show harm from any component (figure 3). In Greece,
however, where the Mediterranean diet is the norm, an
egg a day increased coronary risk fivefold among persons
with diabetes, and even 10 g per day of egg (a sixth of
a large egg) increased coronary risk by 54%.28 Egg
consumption also increases the risk of diabetes.29
The 2016 US guideline
In 2016, when the new US dietary guideline was released,
there were headlines trumpeting ‘It’s OK to eat choles-
terol again; the new guideline says so’. But it was not
true. In the first paragraph, the press release said that
there were insufficient data to recommend a specific
limit to cholesterol intake, as in the past (300 mg/day
for healthy people or 200 mg/day for those at risk of
vascular disease).30 However, the second paragraph said:
‘However, cholesterol intake should be as low as possible
within the recommended eating pattern’ (which resem-
bles a Mediterranean diet). The paragraphs should have
been reversed. There are still good reasons to recom-
mend a cholesterol intake below 200 mg/day (less than
one large egg yolk), and other guidelines do so.31
It is little understood that ‘people at risk of vascular
disease’ essentially means everyone who aspires to achieve
a healthy old age.32 A 20-year-old man might think he can
eat eggs and smoke with impunity, because his stroke or
myocardial infarction are 45 years in the future. But why
would he want to bring it on sooner?33
Effects of the intestinal microbiome
Although dietary cholesterol does not increase fasting
lipid levels by much, it clearly does increase coronary
mortality.34 35 However, there is increasing recognition
of the importance of the intestinal microbiome.36 While
cholesterol content is essentially the same for any kind of
animal flesh, red meat has more saturated fat, and has ~4
times as much carnitine as chicken or fish. Carnitine from
red meat37 and phosphatidylcholine from egg yolk37 are
converted by the intestinal bacteria to trimethylamine,
in turn oxidised in the liver to trimethylamine n-oxide
(TMAO) (figure 4). TMAO causes atherosclerosis in
animal models,37 and in patients undergoing coronary
angiograms plasma levels in the top quartile of TMAO
levels after a test dose of two hard-boiled eggs predicted
a 2.5-fold increase in the 3-year risk of stroke, myocar-
dial infarction or vascular death.38 A 12-ounce Hardee’s
Monster Thickburger39 contains 265 mg of cholesterol
and 320 mg of carnitine. The yolk of a 65 g egg contains
237 mg of cholesterol and 250 mg of carnitine, so two egg
yolks are worse than the 12-ounce burger. Patients at risk
of stroke should avoid red meat and egg yolk.
Besides TMAO, there are other toxic metabolites
produced by the intestinal bacteria from amino acids,
including P-cresyl sulfate, hippuric acid, indoxyl sulfate,
P-cresyl glucuronide, phenyl acetyl glutamine and phenyl
sulfate. These toxic metabolites of the intestinal micro-
biome are renally excreted, so they may be termed
‘Gut-derived Uremic Toxins’ (GDUT). Their blood levels
are very high in patients with renal failure. Other uraemic
Box 1 Links to videos about egg industry propaganda
►http://nutritionfacts.org/video/
eggs-and-cholesterol-patently-false-and-misleading-claims/.
►http://nutritionfacts.org/video/
eggs-vs-cigarettes-in-atherosclerosis/.
►http://nutritionfacts.org/video/egg-cholesterol-in-the-diet/.
►http://nutritionfacts.org/video/
how-the-egg-board-designs-misleading-studies/.
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toxins that have high plasma levels in renal failure are
thiocyanate, asymmetric dimethylarginine and homocys-
teine. Homocysteine accounts for only ~20% of the effect
of renal impairment on carotid plaque burden40; we
hypothesised40 that GDUT may account for much of the
very high risk associated with renal failure.41 Renal func-
tion declines linearly with age, and by age 80 the average
estimated glomerular filtration rate in patients attending
Figure 3 Diet is the worst of the risk issues in the USA. Prevalence (unadjusted) estimates for poor, intermediate and ideal
cardiovascular health for each of the sevenmetrics of cardiovascular health in the American Heart Association 2020 goals, US
children aged 12–19 years, National Health and Nutrition Examination Survey (NHANES) 2011–2012. *Healthy diet score data
reect 2009–2010 NHANES data.(Reproduced with permission from Wolters Kluwer, Mozaffarian etal.5)
Figure 4 Trimethylamine n-oxide(TMAO) is produced by the intestinal bacteria from phosphatidylcholine. Carnitine (largely
from red meat) and phosphatidylcholine (largely from egg yolk) are converted by the intestinal bacteria to trimethylamine, which
in turn is oxidised by the liver to TMAO. TMAO causes atherosclerosis in animal models and markedly increases the risk of
stroke, myocardial infarction and cardiovascular mortality, particularly in persons with renal impairment. It also accelerates
decline of renal function. (Permission requested to reproduce from Wangetal.58) FMO, avin-containing monooxygenase.
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a stroke prevention clinic is below 60 mL/min/1.73 m2.40
We have evidence that even moderate renal impair-
ment significantly increases plasma levels of the GDUT
(submitted for publication). This means that persons
with renal impairment, including most elderly patients,
should avoid red meat and egg yolk.
COFFEE AND TEA
The role of regular consumption of tea or coffee on
cardiovascular risk has not been tested in randomised
controlled trials. There is moderately good evidence that
consumption of coffee and tea reduces risk of myocar-
dial infarction, but little mention of stroke in that body
of literature. It seems likely that reduction of myocardial
infarction would be associated with reduction of stroke
risk.
Coffee consumption has been controversial for many
years. An early report from the Framingham Study indi-
cated that tea, but not coffee, reduced the risk of myocar-
dial infarction.42 For both tea and coffee there are two
issues to be considered: the effects of caffeine and the
effects of antioxidants. Some evidence that caffeine in
coffee may be harmful came from a study in which slow
metabolisers of caffeine (because of a variant of the
CYP1A2 genotype) appeared to have increased the risk of
myocardial infarction.43 A recent meta-analysis indicates
that consuming 3–5 cups per day of coffee reduces cardio-
vascular risk.44 As both decaffeinated and regular coffee
appear to have equal benefit with regard to reduction of
cardiovascular disase and diabetes,45 46 it seems likely that
benefits of coffee are from bioflavonoids.
Both green tea and other forms of tea reduce cardio-
vascular risk. Green tea lowers blood pressure and LDL
cholesterol,47 and improves endothelial function.48
However, there are differences between green tea and
black tea. A report from the Rotterdam study49 indicated
that consumption of the bioflavonoids quercetin, kaemp-
ferol and myricetin may account for the reduction of
myocardial infarction observed with black tea consump-
tion. The cardiovascular benefit of green tea, on the
other hand, has been associated with catechins.50
Consumption of both tea and coffee appears to be
beneficial. It is not known if consuming both tea and
coffee would be more beneficial. Since consumption of
these beverages is a personal preference with cultural
differences across countries, it seems unlikely that physi-
cians would prescribe one or the other.
CONSUMPTION OF ALCOHOL
Consumption of alcohol is a two-edged sword. Moderate
consumption of alcohol (<9 standard drinks per week for
women or 14 for men)51 appears to reduce cardiovas-
cular risk compared with drinking no alcohol,52 whereas
heavy consumption increases risk, particularly for stroke,
and particularly for intracerebral haemorrhage. In a
recent large population-based study (n=114 859, followed
for 6 years)52: ‘Heavy drinking (exceeding guidelines)
conferred an increased risk of presenting with unheralded
coronary death (1.21, 95% CI 1.08 to 1.35), heart failure
(1.22, 1.08 to 1.37), cardiac arrest (1.50, 1.26 to 1.77),
transient ischaemic attack (1.11, 1.02 to 1.37), ischaemic
stroke (1.33, 1.09 to 1.63), intracerebral haemorrhage
(1.37, 1.16 to 1.62), and peripheral arterial disease (1.35;
1.23 to 1.48), but a lower risk of myocardial infarction
(0.88, 0.79 to 1.00) or stable angina (0.93, 0.86 to 1.00)’.
Two likely mechanisms are that heavy alcohol consump-
tion may increase the risk of atrial fibrillation and also
increase blood pressure,51 in some individuals more than
others. Moderate alcohol consumption does not appear
to increase the risk of atrial fibrillation.53
DIETARY SODIUM
A major dietary issue in China is sodium intake. The
relationship of sodium intake to hypertension in China
was reviewed in 2014.54 Most of the sodium (~75%) in
the diet comes from soy sauce and added condiments.
The major cause of stroke in China is hypertension, and
hypertension is poorly controlled,55 in part because of the
cost of medication.56 Restriction of sodium intake has the
potential to improve blood pressure control, particularly
in patients with higher blood pressures,11 at no finan-
cial cost. Patients should be encouraged to use light soy
sauce in limited quantities and increase other approaches
to flavouring food, such as lemon juice, vinegar, ginger,
spices, herbs and hot peppers. Again, such changes would
represent a cultural change that would be a challenge to
implement.
So what diet would be recommended for patientsat risk of
stroke?
Patients at risk of stroke should limit their intake of
animal flesh, avoiding red meat and egg yolk. They
should have a high intake of beneficial oils such as olive
and canola, whole grains, vegetables, fruits and legumes.
Egg white is a good source of protein, so omelettes, frit-
tatas and egg salad sandwiches made with egg whites or
with egg white-based substitutes are a good substitute for
a meat-based meal. Box 2 summarises my recommenda-
tions for helping patients learn to make a healthy diet
enjoyable. The recipe booklet that I give to my patients
Box 2 Dietary recommendations for patients at risk of
stroke
►No egg yolks: use egg whites, egg beaters, egg creations or similar
substitutes.
►Flesh of any animal: a serving the size of the palm of the hand or
less,~every other day (or half that daily).
►Seldom red meat, mainly fish and chicken.
►High intake of olive oil andcanola oil.
►Only whole grains.
►High intake of vegetables, fruit andlegumes.
►Avoid deep-fried foods andhydrogenated oils (trans fats).
►Avoid sugar and refined grains, and limit potatoes.
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can be downloaded from http://www. imaging. robarts.
ca/ SPARC/.
To accomplish this, patients need to think of their
meatless day not as a punishment day, but as a gourmet
cooking class day: ‘Having fun learning how to make
healthy eating tasty’.57
A measure that should be considered in China would
be converting the population to whole grain rice instead
of polished rice. This would no doubt be extremely diffi-
cult, but it would reduce the risk of diabetes, stroke and
myocardial infarction.
CONCLUSION
Diet is an important part of stroke prevention. Reducing
sodium intake, avoiding egg yolks, limiting the intake of
animal flesh (particularly red meat), and increasing the
intake of whole grains, fruits, vegetables and lentils would
contribute importantly to reversing the trend to increased
cardiovascular risk in China.
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.
Data sharing statement No additional data are available.
Guest chief editor J David Spence
Open access This is an open access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-commercially,
and license their derivative works on different terms, provided the original work is
properly cited and the use is non-commercial. See: http://creativecommons.org/
licenses/by-nc/4.0/
© Article author(s) (or their employer(s) unless otherwise stated in the text of the
article) 2018. All rights reserved. No commercial use is permitted unless otherwise
expressly granted.
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