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Nutrition and the risk of stroke

Nutrition and the risk of stroke
Lancet Neurol 2012; 11: 66–81
Poor nutrition in the fi rst year of a mother's life and undernutrition in utero, infancy, childhood, and adulthood
This online publication
predispose individuals to stroke in later life, but the mechanism of increased stroke risk is unclear. Overnutrition also
has been corrected.
increases the risk of stroke, probably by accelerating the development of obesity, hypertension, hyperlipidaemia, and
The corrected version
diabetes. Reliable evidence suggests that dietary supplementation with antioxidant vitamins, B vitamins, and calcium
fi rst appeared at
does not reduce the risk of stroke. Less reliable evidence suggests that stroke can be prevented by diets that are prudent,
on December 22, 2011
aligned to the Mediterranean or DASH (Dietary Approaches to Stop Hypertension) diets, low in salt and added sugars,
Department of Neurology,
high in potassium, and meet, but do not exceed, energy requirements. Trials in progress are examining the eff ects of
Royal Perth Hospital,
vitamin D and marine omega-3 fatty acid supplementation on incidence of stroke. Future challenges include the need
Western Australia
to improve the quality of evidence linking many nutrients, foods, and dietary patterns to the risk of stroke.
Body fat content is estimated by body mass index Between 1970 and 2008, the incidence of stroke in high- (BMI), which is a measure of weight in kilograms divided income countries fell by 42%, from 163 (95% CI 98–227) to by the square of height in metres.15 Adults with a BMI of 94 (72–116) per 100 000 person years.1 This decline coincided 18·5–24·9 kg/m² are categorised as being of normal with increased public awareness of the dangers to health weight, individuals with a BMI of 25·0 to 29·9 kg/m² as gjhankey@cyllene.uwa.edu.au
posed by high blood pressure, high blood cholesterol, and overweight, and those with a BMI of 30 kg/m² or more as cigarette smoking, and reduced pre valence of these risk obese.15 A drawback of this measure is that diff erent factors in the population.2 By contrast, between 1970 and ethnic groups have diff erent proportions of fat to lean 2008, the incidence of stroke in low-income and middle- income countries increased by more than 100%, from 52 Other measures of nutritional status include indicators (95% CI 33–71) to 117 (79–156) per 100 000 person years.1 of visceral adiposity, such as the waist-to-hip ratio, waist- This increase coincided with food and lifestyle changes to-height ratio, and waist circumference,17 and indicators arising from industrialisation and urbanisation.3,4 of protein status, such as serum albumin and prealbumin Modernisation, over consumption of calories, and increased prevalence of obesity, metabolic syndrome, and type 2
diabetes mellitus threaten to stem the decline of stroke How common is malnutrition?
incidence in high-income countries and to accelerate the Undernutrition is common, under-recognised, and
increase in stroke incidence in low-income and middle-
undertreated. In the UK, about 5% of the population income countries.5–7 Accurately assess have a BMI of below 18·5 kg/m².13 In UK hospitals, the standing the role of nutrition in the causes and prevalence of malnutrition is reported to range from consequences of stroke will be crucial in developing and 13% to 40%.18,21 The prevalence of undernutrition in-implementing strategies to minimise the global burden of creases at least two times in the elderly and in those stroke.8–12 The aim of this Review is to examine the evidence with chronic disease, and three times in people living linking nutrition and diet to the risk of stroke.
in institutional care, such as survivors of stroke.13,14 The elderly are especially prone to defi ciencies of specifi c Nutritional status
micronutrients such as folate.13 Malnutrition is also What is malnutrition?
common in situations of poverty, social isolation, and Malnutrition has no universally accepted defi nition but substance misuse.
describes a defi ciency, excess, or imbalance in a wide range An estimated 1·46 billion adults and 170 million of nutrients, resulting in a measurable adverse eff ect on children worldwide are now classifi ed as overweight, body composition, function, and clinical outcome.13 including 502 million adults who are obese.5 In the Undernutrition describes a long-standing defi ciency of USA, two-thirds of adults are overweight and one-third essential nutrients, most commonly energy (kJ or calories) obese,6,22 and the incidence and prevalence of being and protein,14 whereas overnutrition describes an excess overweight or obese in children and adults are intake of nutrients (most commonly saturated fats and increasing.5–7,22–24carbohydrates) for metabolic and health requirements.
Is malnutrition a risk factor for stroke?
How is nutritional status assessed?
The methods used to investigate the eff ects of nutritional Nutritional assessment is not standardised. The simplest factors on the risk of stroke have limitations (panel 1),27 measure of nutritional status is bodyweight, but it can and the results of such studies should be interpreted with be confounded by height and ethnic origin, and, in caution, bearing in mind the criteria that need to be severe protein malnutrition, by fl uid retention due to fulfi lled to establish a causal association between a risk hypoalbuminaemia.
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Mother and fetus
Panel 1: Methods used to establish a causal association between a risk factor and disease
Observational studies suggest that poor nutrition in the The quality of the evidence used to establish a causal association between a nutritional fi rst year of a woman’s life leads to deformity of the bony factor and the risk of stroke is determined by the study design, study quality, consistency, pelvis.30,31 During subsequent pregnancy in adulthood, a and directness (ie, the extent to which the study participants, interventions, and outcome fl at pelvis impairs the mother’s ability to sustain growth of measures are similar to those of interest).25,26 The optimal study design is determined by the placenta and fetus, as manifest by lower placental the research question, but each design has its limitations: weight, smaller head circumference, and lower birth weight of the baby.30,31 In turn, these factors seem to be associated Observational cohort or case-control studies
with an increased risk of stroke in the mother’s off spring.30,31 Studies of this type frequently report associations between nutritional factors and stroke The mechanism by which poor maternal nutrition and risk that are strong, dose-related, independent of other vascular risk factors, and poor growth in utero might increase the risk of stroke biologically plausible. However, epidemiological studies cannot eliminate bias and could be linked to hypertension and raised plasma confounding in any association between a risk factor and stroke.27 The association could fi brinogen concentrations in adulthood, and a permanent be due to reverse causality bias (eg, stroke could lead to a change in diet) or residual adverse eff ect on vascular structure and function.32,33 confounding by other factors, known and unknown, that increase both the risk factor and the risk of stroke (eg, renal impairment). Any association could also be indicative of measurement error in the assessment of nutritional exposures, often at only one or a few Observational evidence suggests that poor growth in points in time, and bias if loss to follow-up occurs.
childhood due to poor nutrition is associated with an Meta-analysis of epidemiological studies
increased risk of stroke in later life.31 Table 1 shows that for Although meta-analyses of multiple epidemiological studies reduce random error every one SD decrease in the diff erence between bodyweight (chance) and increase the generalisability (external validity) of the results, they cannot at 2 years and that predicted from birthweight, the hazard eliminate bias and confounding and have their own limitations. For example, ratio for stroke in adulthood increased by about 18% (hazard heterogeneity could be introduced by methodological diff erences between studies, and ratio 1·18, 95% CI 1·03–1·28).31 Continued failure to gain publication bias could arise if small studies with null results are not published.
weight during childhood is also associated with an increased risk of stroke in later life; for every one unit SD decrease in Randomised trials
weight at diff erent ages during childhood, the hazard ratio Randomisation is the best method to minimise bias and confounding, and establish for stroke increased by 4–20% (table 2).31 These data suggest causality. However, randomised trials are not always feasible. When they are, the results that biological vulnerability to stroke begins during early are also prone to random error if the sample size is inadequate, and are not generalisable life and develops throughout the lifespan to increase risk of beyond the type of participant recruited.
stroke later in life. This hypothesis is supported by Systematic review and meta-analysis of randomised trials
observational data showing a 25% higher incidence of This method produces the most reliable form of evidence of causality between a stroke among US adults who had lived as children in the nutritional risk factor and the occurrence of stroke. This approach minimises random southeastern states, or so-called stroke belt, of the USA, error and maximises generalisability. However, systematic reviews of randomised trials where stroke mortality rates are highest.34 also have their limitations, including potential for publication bias, study-quality bias, and outcome-recording bias.
Adults Few data correlate undernutrition in adulthood with risk of stroke. A collaborative analysis of 57 prospective studies Number of patients
Hazard ratio (95% CI)
in which 894 576 adults were followed up for a mean of Weight at 2 years minus predicted weight (kg) 13 years (deaths during the fi rst 5 years were excluded to limit reverse causality) showed that, in the lower range (15–25 kg/m²), each 5 kg/m² lower BMI was associated with a non-signifi cant trend towards an increase in stroke mortality by 9% (hazard ratio 1·09, 95% CI 0·97–1·22).35 The association was stronger for haemorrhagic stroke (1·32, 1·00–1·72) than for ischaemic stroke (1·15, 0·91–1·47) but was not signifi cant.35 Among 8920 individuals with renal impairment who started renal dialysis, undernourishment, low bodyweight, Modifi ed from Osmond and colleagues,31 by permission of Wolters Kluwer Health.
and low serum albumin at baseline were independent, Table 1: Association of poor growth in the fi rst 2 years of life with an increased risk of stroke in adulthood
signifi cant predictors of incident stroke after a median follow-up of 3·1 years.19 height ratio, or waist circumference.6,17,36–45 Individuals Overnutrition
with a BMI of 30 kg/m² or more have double the Obesity is associated with an increased risk of stroke, incidence of ischaemic and haemorrhagic stroke whether measured by BMI, waist-to-hip ratio, waist-to- compared with individuals with a BMI of less than www.thelancet.com/neurology Vol 11 January 2012
Which nutrients aff ect the risk of stroke?
Hazard ratio (95% CI) for stroke per one unit
Antioxidant vitamins
SD decrease in weight at diff erent ages
Many nutrients can aff ect the risk of stroke (panel 2). The oxidation hypothesis of atherosclerosis—that oxidation of low-density lipoprotein (LDL) cholesterol (lipid peroxidation) allows it to accumulate in artery walls and promote atherosclerosis81—prompted several studies of antioxidant vitamins in the prevention of A meta-analysis of 68 randomised trials of antioxidant Table 2: Association of low bodyweight at birth, during infancy, and in
childhood (poor growth) with an increased risk of stroke in later life
showed that overall, antioxidants had no eff ect on mortality (relative risk 1·02, 95% CI 0·98–1·06).47 Prevalence
Odds ratio
Population attributable
However, multivariate meta-regression analyses showed risk (99% CI)
that low-bias risk trials (as defi ned by adequate generation of treatment allocation sequence, allocation concealment, masking, and follow-up) were signifi cantly associated with mortality.47 In 47 low-bias trials with Waist-to-hip ratio (tertile 3 vs tertile 1) 180 938 participants, the antioxidant supplements signi- Apolipoprotein B to A1 ratio (tertile 3 vs tertile 1) fi cantly increased mortality (relative risk 1·04, 95% CI 1·02–1·08), especially exposure to vitamin A (1·16, Unhealthy diet risk score (tertile 3 vs tertile 1) 1·10–1·24), β-carotene (1·07, 1·02–1·11), and vitamin E (1·04, 1·01–1·07); vitamin C (1·06, 0·94–1·20) and selenium (0·90, 0·80–1·02) had no signifi cant eff ect on mortality.47 β-carotene, the biologically active metabolite of vitamin A, Multivariable model adjusted for age, sex, and region. Risk factors for all stroke in 3000 patients with acute fi rst stroke did not aff ect stroke rates in 82 483 participants enrolled in (within 5 days of symptom onset) compared with 3000 controls with no history of stroke who were matched with cases three randomised trials (odds ratio 1·0, 95% CI 0·91–1·09),48 for age and sex, and who were assessed in 22 countries between 2007 and 2010 in the INTERSTROKE study.45 Modifi ed from O’Donnell and colleagues,45 by permission of Elsevier. *Cardiac causes include atrial fi brillation or fl utter, previous but did increase all-cause mortality in 138 113 participants myocardial infarction, rheumatic valve disease, or prosthetic valve disease.
in eight randomised trials (1·07, 1·02–1·11) and cardiovascular mortality among 131 551 participants in six Table 3: Risk factors for stroke
randomised trials (1·10, 1·03–1·17).48 23 kg/m².37 Each unit increase in BMI is associated with an increase in the adjusted risk of stroke by about 6% Vitamin C is a water-soluble antioxidant in plasma that (relative risk 6%, 95% CI 4–8).37 Among adults who are helps regenerate oxidised vitamin E. Although obser va-overweight or obese (BMI 25–50 kg/m²), each 5 kg/m² tional studies suggest that increased dietary intake and increase in BMI is associated with about 40% higher plasma concentrations of vitamin C are associated mortality from stroke (hazard ratio 1·39, 95% CI independently with reduced rates of stroke,82,83 large 1·31–1·48).35 Individuals with a waist-to-hip ratio in the highest supplementation in preventing stroke and other clinical tertile (>0·96 in men and >0·93 in women) have a 65% outcomes.49–51increased risk of stroke (odds ratio 1·65, 99% CI 1·36–1·99) compared with individuals in the lowest Vitamin Etertile (<0·91 in men and <0·86 in women).45 The Vitamin E is a lipid-soluble antioxidant that increases the population attributable risk of stroke associated with an resistance of LDL cholesterol to oxidation, reduces increased waist-to-hip ratio is 26·5% (99% CI 18·8–36·0; proliferation of smooth muscle cells, and reduces adhesiveness of platelets to collagen. This vitamin Although BMI, waist-to-hip ratio, and waist circum- inhibits lipid peroxidation by scavenging reactive oxygen ference do not meaningfully improve prediction of stroke risk when added to causal risk factors such as systolic In 2010, a meta-analysis of seven randomised trials blood pressure and history of diabetes, excess adiposity with 116 567 individuals revealed that vitamin E had no remains a major modifi able determinate of these causal eff ect on risk of incident total stroke (relative risk 0·98, risk factors.46 Hence, controlling adiposity is likely to help 95% CI 0·91–1·05) but increased the risk of incident haemorrhagic stroke (1·22, 1·00–1·48) and reduced the www.thelancet.com/neurology Vol 11 January 2012
Panel 2: Eff ects of nutrients on the risk of stroke
Antioxidant vitamins
Supplementation by more than 0·5 g per day does not prevent Supplementation increases all-cause mortality.47 stroke, might increase the risk of stroke,69,70 and can increase the risk of myocardial infarction by 31% (95% CI 2–67).69 Supplementation increases cardiovascular and all-cause mortality47,48 and does not prevent stroke.48 High intake is not associated with increased risk of stroke.71 Supplementation does not prevent stroke.49–51 Reduced intake does not reduce risk of stroke.72 Supplementation increases all-cause mortality47 and does not High intake is not associated with increased risk of stroke.71 B vitamins (folic acid)
High intake is not associated with increased risk of stroke.71,73 Supplementation does not prevent stroke in populations with high folate intake;53 defi ciency could be a causal and treatable Supplementation reduces cardiovascular events and death by risk factor for stroke in regions of low folate intake.54 8% (95% CI 1–15),74 but in one randomised trial it did not reduce Vitamin D
stroke risk (hazard ratio 1·04, 95% CI 0·62–1·75).75 Defi ciency is associated with hypertension, cardiovascular disease, and stroke.55 Supplementation is not proven to prevent High intake is associated with reduced risk of stroke.76 cardiovascular events.56 Randomised trials investigating vitamin D supplementation are in progress.57 Carbohydrates
High glycaemic index and glycaemic load
High intake of food with these nutritional qualities is associated Supplementation by 5 g per day is associated with a 23% with increased blood glucose and bodyweight.77 High intake is (95% CI 6–43) increased risk of stroke.58 Reduction in salt intake associated with increased stroke mortality.78 is not proven to reduce stroke. Reduction by 2 g per day reduces cardiovascular events by 20% (95% CI 1–36);59,60 reduction also High intake is associated with reduced blood pressure, blood Potassium
Supplementation by 1 g per day is associated with an 11% High intake is not associated with risk of stroke.80 (95% CI 3–17) reduction in the risk of stroke; 66 supplementation is not proven to prevent stroke. Supplementation by 0·8 g per day reduces blood pressure by 5/3 mm Hg.67,68 risk of incident ischaemic stroke (0·90, 0·82–0·99).85 risk of all types of stroke combined, and ischaemic stroke Heterogeneity among the studies was not evident due to large artery disease, small artery disease, and (I²=12·8%; p for heterogeneity=0·33). However, in 2011, embolism from the heart in observational studies.86–89 an updated meta-analysis of 13 randomised trials of Although homocysteine can be lowered by up to 25% vitamin E in 166 282 participants showed no signifi cant (95% CI 22–28) with folic acid and by a further 7% (4–9) benefi t in the prevention of stroke of any type (relative with vitamin B12 (median dose 0·4 mg [range 0·4–1·0] risk 1·01, 95% CI 0·96–1·07), ischaemic stroke (1·01, per day),90 randomised trials of folic acid versus control 0·94–1·09), or haemorrhagic stroke (1·12, 0·94–1·33).52 showed no eff ect of supplementation with folic acid on Signifi cant heterogeneity among the studies was not all stroke (relative risk 0·96, 95% CI 0·87–1·06).53 The evident (p for heterogeneity=0·37).
results of genetic epidemiological studies are concordant The reasons for the discrepancy in fi ndings for the eff ect with those from randomised trials in populations with of vitamin E on the pathological subtypes of stroke in the established or increasing folate intake but, in populations two meta-analyses52,85 might be the inclusion of six with low folate intake (eg, Asia), the genetic studies additional trials, longer follow-up data from one shared suggest that lowering total homocysteine by 3·8 μmol/L trial, and perhaps (although not stated) recurrent as well could reduce stroke by 22% (95% CI 10–32).54 Because no as incident strokes in the updated meta-analysis.52 large, reliable randomised trials of total homocysteine reduction in regions of low folate intake have been done, B vitamins
whether supplementing the diet or fortifying food with Increased serum concentrations of total homocysteine folic acid in these regions could reduce stroke incidence have been associated independently with an increased is not known.
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In individuals who are folate-replete, vitamin B12 is an independently increased the odds of all stroke (odds ratio important determinant of total homocysteine, and 1·5, 95% CI 1·0–2·3), but that most of the eff ect was subclinical vitamin B12 defi ciency is not uncommon.91 driven by an increase in odds of haemorrhagic stroke Subgroup analyses from randomised trials raise the (3·5, 95% CI 1·6–7·6).98 Indeed, about 20% (95% CI hypothesis that use of high doses of vitamin B12 in 1–38) of all primary intracerebral haemorrhages were people who are folate-replete but vitamin B12 defi cient attributable to adding salt to food.98could substantially lower total homocysteine and risk of A meta-analysis of six randomised trials showed that a stroke.91–94 This hypothesis requires confi rmation a priori reduction in dietary salt intake by 2·0–2·3 g (half a in clinical trials.
teaspoon) per day was associated with a reduction in cardiovascular events by 20% (relative risk 0·80, 95% CI Vitamin D
0·64–0·99).59,60 However, no randomised trials of the Observational studies report an association between eff ect of salt reduction on risk of stroke or its pathological defi ciency of 25-hydroxyvitamin D and an increased and aetiological subtypes have been done.
incidence of hypertension, carotid artery atherosclerosis, Excess salt intake might increase cardiovascular and and cardiovascular disease, including stroke.55,95 Although stroke risk by increasing blood pressure and causing randomised trials show that vitamin D supplementation fi brosis in the heart, kidneys, and arteries.99 Reducing lowers blood pressure55 and improves endothelial dietary salt intake by 6 g a day reduces systolic and function in the short term,96 two trials showed no signi- diastolic blood pressure by 4 and 2 mm Hg, respectively, fi cant eff ect on cardiovascular events of vitamin D in people without hypertension, 7 and 4 mm Hg, supplementation at moderate to high doses (relative risk respectively, in those with hypertension,100,101 and 23 and 0·90, 95% CI 0·77–1·05) or of vitamin D plus calcium 9 mm Hg, respectively, in people with resistant hyper-supplementation (1·04, 0·92–1·18).56 tension.61 Sodium reduction by 6 g per day also blunts the For more on the VITAL study see
The VITamin D and OmegA-3 triaL (VITAL) is currently age-related rise in blood pressure by about 0·5 mm Hg randomly assigning 20 000 people to receive 2000 IU of per year.62,63 The response of blood pressure to sodium vitamin D3 (cholecalciferol) per day or placebo, as well as reduction is direct and progressive, but non-linear; 1 g of marine omega-3 fatty acids per day or placebo, for decreasing sodium intake by about 0·9 g per day causes a 5 years.57 The primary outcome of the study is total cancer greater reduction in blood pressure when the starting and major cardiovascular events (a composite of sodium intake is about 2·3 g per day than when it is myocardial infarction, stroke, and death due to about 3·5 g per day.64,65cardiovascular events).57 Minerals
A higher potassium intake of 42 mmol/L (1·64 g) per An observational study of 38 772 older women (mean day was associated with a 21% reduced risk of stroke age 61·6 years in 1986) reported that subsequent after 5–19 years of follow-up of 247 cantly in users of 11 observational studies (relative risk 0·79, 95% CI multivitamins (hazard ratio 1·06, 95% CI 1·02–1·10; 0·60–0·90).102 For every increase in potassium intake by absolute risk increase 2·4%), folic acid (1·15, 1·00–1·32; 1·0 g per day, the risk of stroke decreased by 11% 5·9%), vitamin B6 (1·10, 1·01–1·21; 4·1%), iron (1·10, (relative risk 0·89, 95% CI 0·83–0·97).66 If causal, the 1·03–1·17; 3·9%), magnesium (1·08, 1·01–1·15; 3·6%), association might be mediated by lowered blood zinc (1·08, 1·01–1·15; 3·0%), and copper (1·45, pressure; increasing potassium intake by 20 mmol 1·20–1·75; 18·0%), and decreased in users of calcium (0·78 g) or more per day lowers blood pressure by an (0·91, 0·88–0·94; 3·8%).97 These results and the eff ects average of 4·9 mm Hg systolic blood pressure and on risk of stroke and its subtypes require confi rmation 2·7 mm Hg diastolic blood pressure in patients with by randomised trials.
hypertension.67,68 Randomised trials are needed to establish the independent eff ects of long-term increases in dietary potassium intake on stroke risk, but are Most adult populations around the world have average unlikely to be undertaken because of technical daily salt intakes of higher than 6 g, and many in eastern culties and possible ethical constraints.
Europe and Asia of more than 12 g, mostly from processed foods.58 Observational studies show that sustained high Calcium daily salt intake of 5 g on average (86 mmol [one Many guidelines recommend adequate calcium intake as teaspoon]) is associated with a 23% greater risk of stroke part of the prevention or treatment of osteoporosis,103 (pooled relative risk 1·23, 95% CI 1·06–1·43) and a 17% despite the fact that calcium supplements only marginally greater rate of total cardiovascular disease (relative risk reduce the risk of fracture.104 Interventional studies show 1·17, 1·02–1·34).58 No data on stroke subtypes were that calcium supplements improve some risk factors for available but a large prospective, community-based, case- stroke such as blood pressure,105,106 bodyweight,106 and control study reported that adding salt to food not only serum-lipid concentrations,107 and observational studies www.thelancet.com/neurology Vol 11 January 2012
suggest that high calcium intake might protect against reduce the risk of stroke (hazard ratio 1·02, 95% CI stroke.108,109 However, a recent observational study of 0·90–1·15) in 48 835 postmenopausal women.72 However, 34 670 women reported that increasing calcium intake was trends towards greater reductions in risk of coronary not associated with altered risk of any stroke or ischaemic heart disease were seen with low intakes of trans fat and stroke, but was associated with an increased risk of saturated fat,72 suggesting that the type of fats consumed haemorrhagic stroke (for highest vs lowest tertile; adjusted might be more relevant for cardiometabolic health than relative risk 2·04, 95% CI 1·24–3·35).110 Randomised trials the proportion of calories consumed from total fat.113,114 have shown that, after a median of 3·6 years (IQR 2·7–4·3), calcium supplementation (≥500 mg per day), without co- administered vitamin D, is associated with a signifi cant Consumption of industrially produced trans fatty acids increase in myocardial infarction (hazard ratio 1·31, from partially hydrogenated vegetable oils are the most 1·02–1·67) and a trend towards an increase in stroke (1·20, potent fat-related risk factor for coronary heart disease.115,116 Although observational studies suggest no signifi cant Co-administration of calcium plus vitamin D relation between trans fat consumption and risk of supplements for an average of 6·2 years was associated stroke,71 no reliable observational data or data from with an increased risk of stroke (relative risk 1·20, 95% CI randomised trials on the association of trans fatty acids 1·00–1·43), myocardial infarction (1·21, 1·01–1·44), and with stroke subtypes are available.
the composite of myocardial infarction or stroke (1·16, 1·02–1·32) among 20 090 individuals in three placebo- A meta-analysis of eight observational studies showed that Some studies do not distinguish between calcium intake of saturated fat in the highest quintile was not taken alone and calcium co-administered with vitamin D. associated with an increased risk of stroke compared with An analysis of such studies showed that calcium alone or intake in the lowest quintile (relative risk 0·81, 95% CI calcium plus vitamin D increased the risk of stroke 0·62–1·05).73 Suffi cient statistical power in these studies (hazard ratio 1·19, 95% CI 1·02–1·39), myocardial was not available to assess whether the observed infarction (1·26, 1·07–1·47), and the composite of stroke associations between saturated fat intake and stroke risk or myocardial infarction (1·17, 1·05–1·31) over a mean were modifi ed or confounded by the cardiometabolic follow-up of 5·9 years in 24 869 people in six randomised eff ects of nutrients, such as refi ned carbohydrates, starches, trials.70 These data suggest that treating 1000 people with and sugars, which might be exchanged for saturated fatty calcium or calcium and vitamin D for 5 years would acids.113,117 Data on the relation between saturated fat intake cause an additional six myocardial infarctions or strokes and risk of subtypes of stroke were also restricted.
and prevent three fractures. However, methodological caveats exist that limit the conclusiveness of this evidence. Furthermore, when calcium and vitamin D supplements No reliable studies of the association between increased are used as an adjunct to bisphosphonates in the intake of polyunsaturated fatty acids and stroke risk have treatment of osteo porosis, no adverse eff ect on been done, but observational studies and randomised trials cardiovascular safety and survival occurs.111,112 Randomised suggest that consumption of these fatty acids in place of trials of the eff ects of calcium, with or without vitamin D, saturated fatty acids reduces incidence of coronary heart on the risk of stroke, its pathological and aetiological disease.113,118 For each 5% of energy obtained from subtypes, and other vascular and non-vascular outcomes polyunsaturated fatty acids, instead of saturated fatty acids, are warranted.
the risk of coronary heart disease is reduced by 10% (relative risk 0·90, 95% CI 0·83–0·97).118 Fats
An observational study of 43 732 men in the USA showed
Marine-derived omega-3 (or n-3) polyunsaturated fatty acids that, compared with the lowest quintile, the risk of Human beings rely on direct dietary consumption of ischaemic stroke over 14 years of follow-up was not omega-3 polyunsaturated fatty acids, which include increased in those in the highest quintile for intake of eicosapentaenoic acid (20:5 omega-3) and decosahexaenoic total fat (adjusted relative risk 0·91, 95% CI 0·65–1·28; p acid (22:6 omega-3) from oily fi sh such as salmon, for trend 0·77), animal fat (1·20, 0·84–1·70; p for trend herring, trout, and sardines.1130·47), saturated fat (1·16, 0·81–1·65; p for trend 0·59), A meta-analysis of 11 randomised trials including vegetable fat (1·07, 0·77–1·47; p for trend 0·66), dietary 39 044 patients showed that random allocation to the cholesterol (1·02, 0·75–1·39; p for trend 0·99), omega-3 fatty acids eicosapentaenoic acid or monosaturated fat (0·88, 0·64–1·21; p for trend 0·25), or decosahexaenoic acid for 2·2 years (mean) signifi cantly transunsaturated fat (0·87, 0·62–1·22; p for trend 0·42).71 reduced cardiovascular deaths (odds ratio 0·87, 95% CI These fi ndings are supported by a large randomised trial 0·79–0·95), sudden cardiac death (0·87, 0·76–0·99), all-in which a reduction of mean total fat intake by 8·2% of cause mortality (0·92, 0·85–0·99), and non-fatal energy intake over 8·1 years (mean) did not signifi cantly cardiovascular events (0·92, 0·85–0·99) compared with www.thelancet.com/neurology Vol 11 January 2012
placebo.74 The eff ect could be mediated by an anti- Increased dietary fi bre reduces blood pressure, blood arrhythmic eff ect or other benefi cial eff ects on blood glucose, serum triglycerides, and LDL cholesterol79 but pressure, concentration of plasma triglycerides, and no reliable data on its eff ect on risk of stroke and stroke markers of thrombosis and infl ammation.119 However, a subsequent randomised trial showed that in 2501 patients with a history of myocardial infarction, Protein
unstable angina, or ischaemic stroke, random assignment
Observational studies in Japan have shown that increased to a daily dietary supplement containing omega-3 fatty protein intake is associated with reduced risk of stroke.123 acids (600 mg of eicosapentaenoic acid and decosa- hexaenoic acid at a ratio of 2:1) for a median of 4·7 years animal, or vegetable protein and risk of stroke was
had no signifi cant eff ect on stroke (hazard ratio 1·04, reported in a cohort study of 43 960 men in the USA.80
95 CI% 0·62–1·75) or major vascular events (1·08,
0·79–1·47).75 The eff ect of treatment on stroke subtypes Which foods and beverages aff ect the risk
was not reported.
of stroke?
Many foods and beverages aff ect the risk of stroke
Plant-derived omega-3 (n-3) polyunsaturated fatty acids (panel 3). The INTERSTROKE study45 reported that, The plant-derived n-3 polyunsaturated fatty acid within food groupings (adjusted for age, sex, and region; α-linolenic acid is an essential fatty acid found mainly in tertile 3 vs tertile 1), increased consumption of fi sh (odds vegetable oils such as soybean, canola, and fl axseed, and ratio 0·78, 99% CI 0·66–0·91) and fruit (0·61, 0·50–0·73)
in walnuts. An observational study of 20 069 Dutch were associated with reduced risk of stroke.45
adults showed that, compared with the bottom quintile
(Q1) of α-linolenic acid intake (less than 1·0 g per day), Fish
participants in high quintiles (Q2–Q5) had a 35–50% Fish can be an excellent source of protein and the
lower risk of incident stroke; hazard ratios were 0·65 essential omega-3 fatty acids eicosapentaenoic acid and
(0·43–0·97; Q2), 0·49 (0·31–0·76; Q3), 0·53 (0·34–0·83;
decosahexaenoic acid. A meta-analysis of 15 observational Q4), and 0·65 (0·41–1·04; Q5) after 8–13 years of follow- studies reported that an increase in consumption of three up.76 These results need confi rmation in randomised servings per week of fi sh was associated with a 6% trials.
(95% CI 1–11) lower risk of stroke.124 No signifi cant heterogeneity among the studies was reported Carbohydrates
(I²=25·7%).124 Some studies suggest that consumption of Like fat intake, carbohydrate intake in quantities that oily fi sh drives the inverse association between fi sh intake exceed energy requirements (positive energy imbalance) and stroke risk139,140 and others suggest that the con-is a major determinant of weight gain and adiposity,113 sumption of lean fi sh (cod, saithe, and fi sh fi ngers), but and the quality of carbohydrate intake also aff ects not other fi sh types (eg, salmon, white fi sh, and char, metabolic health. Consumption of refi ned sugars in herring, or mackerel), is associated with a lower risk of liquid form promotes weight gain.113 The glycaemic index stroke.141 The eff ect of the consumption of lean fi sh could is a measure of how much a standard quantity of food be confounded by the fact that herring and salmon are raises blood glucose levels compared with a standard commonly eaten salted in Sweden, thus aff ecting blood quantity of glucose or white bread. The glycaemic load is a measure of the product of the glycaemic index of a food Studies that have examined pathological subtypes of item and the available carbohydrate content of that item. stroke suggest that fi sh consumption is associated with a Foods with a high glycaemic index, such as sugar- lower risk of ischaemic stroke but not haemorrhagic sweetened beverages and refi ned carbohydrates and stroke.142 However, no reliable data from randomised
starches, increase fasting blood glucose. Glycated trials of the eff ect of fi sh consumption on the risk of
proteins, and beverages and foods with high glycaemic stroke or its subtypes are available.143–145
load, including added sugars, increase bodyweight.77
High carbohydrate intake from foods with a high Fruit and vegetables
glycaemic index, added sugars, and high dietary glycaemic
Increased fruit and vegetable intake (more than fi ve load also leads to reduced intake of essential nutrients servings per day) was associated with a lower risk of stroke and has been associated with an increased risk of stroke than was intake of fewer than three servings per day mortality and coronary heart disease in women in (relative risk 0·74, 95% CI 0·69–0·79) and three to fi ve observational studies.78,120,121 Replacement of saturated fats servings per day (0·89, 0·83–0·97) in 257 551 individuals with carbohydrates that have a high glycaemic index is followed up for 13 years.125 However, vegetable intake alone associated with an increased risk of myocardial infarction was not associated with a reduced risk of stroke (odds ratio (hazard ratio for myocardial infarction per 5% increment 0·91, 99% CI 0·75–1·10) in the INTERSTROKE study.45 If of energy intake of carbohydrates 1·33, 95% CI the association between fruit and vegetable intake is 1·08–1·64).122 validated, the mechanism might be that consumption of www.thelancet.com/neurology Vol 11 January 2012
fi ve or more daily portions of fruit and vegetables reduces blood pressure by about 4·0 mm Hg (95% CI 2·0–6·0) Panel 3: Eff ects of foods and beverages on the risk of
systolic and 1·5 mm Hg (0·2–2·7) diastolic.126 Increased consumption by three servings per day is associated A meta-analysis of observational studies including with a 6% (95% CI 1–11) lower risk of stroke.124 152 630 individuals showed that total meat consumption was associated with a 24% higher risk of ischaemic stroke Fruit and vegetables
per daily serving (relative risk 1·24, 95% CI 1·08–1·43).127 Consumption of more than fi ve servings of fruit and Among subtypes of meat, consumption of unprocessed vegetables per day is associated with a 26% (95% CI 21–31) red meats (which contain saturated fatty acids, cholesterol, lower risk of stroke.125 Consumption of more than fi ve and haem iron113) was not associated with a signifi cant servings per day lowers blood pressure by 4·0/1·5 mm Hg.126 increase in risk of ischaemic stroke or total stroke mortality (relative risk per 100 g serving per day 1·17, 95% CI, 0·40–3·43) and nor was intake of processed meats (which Each daily serving is associated with a 24% (95% CI 8–43) contain high levels of salt and other preservatives;113 relative risk 1·14, 95% CI, 0·94–1·39).127 However, a recent large cohort study of 40 291 men reported that processed meat Consumption is not a proven risk factor for stroke.127 consumption was positively associated with an increased risk of stroke (multivariate relative risk for highest vs lowest quintiles 1·23, 95% CI 1·07 to 1·40) after a mean Consumption was associated with an increased risk of stroke follow-up of 10·1 years.128 Further studies of meat in one observational study128 but not in another.127 consumption by subtype and risk of stroke by pathological and aetiological subtypes are needed.
MilkConsumption is not associated with risk of stroke.129 Dairy
The dairy products milk, cheese, and butter have a high
Reduced-fat milk (vs full-strength milk) saturated fat and calcium content that could increase the Consumption is associated with lower risk of stroke.98 risk of stroke. However, a meta-analysis of six cohort Chocolate
studies showed that milk intake was not associated with High consumption is associated with a 29% (95% CI 2–48) risk of stroke (relative risk 0·87, 95% CI 0·72–1·05).129 A subsequent large cohort study reported that dairy fat intake was associated with slightly increased all-cause mortality in women (per 10 g per day; rate ratio 1·04, 95% CI Moderate consumption (3–4 cups per day) is associated with 1·01–1·06) and fermented milk was associated with a a 17% (95% CI 8–26) lower risk of stroke.131,132 possible protective eff ect against stroke mortality.146 Case- control studies suggest that consumption of reduced-fat or Moderate consumption (≥3 cups per day) is associated with a skimmed milk, compared with full-strength milk, is 21% (95% CI 15–27) lower risk of stroke.133 associated with reduced odds of all stroke (odds ratio 0·49, 95% CI 0·31–0·76) and ischaemic stroke (0·43, Sugar-sweetened beverages
High intake is associated with increased obesity, diabetes, metabolic syndrome, and coronary heart disease.134–136 Chocolate
Whole grains
Observational studies suggest that individuals with the High intake is associated with a 21% (95% CI 15–27) lower highest levels of chocolate consumption have a 29% (95% CI 2–48) lower rate of stroke and 37% (10–56) lower rate of cardiovascular disease than those with the lowest levels of chocolate consumption.130 If valid, the mechanism Intake is not associated with risk of stroke.138 of this association might include antihypertensive, anti-infl ammatory, antiatherogenic, and antithrombotic coff ee consumption might have a weak non-linear inverse association with risk of stroke (p for non-linearity=0·005).131 Compared with no coff ee consumption, the relative risks of stroke were 0·86 (95% CI 0·78–0·94) for two cups of A meta-analysis of 11 prospective studies of coff ee per day, 0·83 (0·74–0·92) for three to four cups per 479 689 parti cipants in which three or more categories of day, 0·87 (0·77–0·97) for six cups per day, and 0·93 coff ee consumption were correlated with the subsequent (0·79–1·08) for eight cups per day. Marginal between-occurrence of 10 003 cases of stroke reported that moderate www.thelancet.com/neurology Vol 11 January 2012
The association between coff ee consumption and Increased whole grain intake (pooled average pathological subtype of stroke was examined in a single 2·5 servings a day vs 0·2 servings a day) was associated cohort study of 34 670 women, which reported that, after with a trend towards a lower risk of incident stroke events a mean follow-up of 10·4 years, consumption of at least (odds ratio 0·83, 95% CI 0·68–1·02) and a signifi cantly one cup of coff ee a day was associated with a lower risk of lower risk of cardiovascular disease events (0·79, ischaemic stroke and subarachnoid haemorrhage but not 0·73–0·85) in seven observational studies whereas haemorrhagic stroke compared with consumption of less refi ned grain intake was not associated with incident cardiovascular disease events (1·07, 0·94–1·22).137 This association, if causal, is unlikely to be mediated by blood pressure because caff eine intake is not associated Rice
with a long-term increase in blood pressure compared Rice intake was not associated with risk of stroke
with a caff eine-free diet or with decaff einated coff ee, (adjusted hazard ratio per one SD increment of energy-
despite the fact that caff eine intake of 200–300 mg adjusted risk intake 0·97, 95% CI 0·90–1·04) in a study
produces an acute mean increase in blood pressure of that followed 83 752 Japanese adults for a median of
8·1 mm Hg (95% CI 5·7–10·6) systolic and 5·7 mm Hg 14·1 years.138
(95% CI 4·1–7·4) diastolic for 3 h or more.147 The eff ect
could be due to the action of the phenolic compounds in
coff ee, which might increase resistance of LDL cholesterol Legumes include beans, peas, chickpeas, and lentils; their independent eff ects on risk of stroke are unknown. Although chronic coff ee consumption is associated However, randomised trials have shown that soy- with a lower risk of stroke,131,132 some preliminary evidence containing foods produce a non-signifi cant reduction in suggests an acutely increased risk of ischaemic stroke in blood pressure by about 5·8 mm Hg systolic and the hour after coff ee intake (relative risk 2·0, 95% CI 4·0 mm Hg diastolic,152 and isolated soy protein or 1·4 to 2·8), especially in infrequent coff ee drinkers (one isofl avones (phytoestrogens) lower diastolic blood cup or less a day).148 Because these results could mirror pressure by 2 mm Hg and LDL cholesterol by 3%.153recall bias, they require confi rmation.
Which dietary patterns aff ect the risk of stroke?
Dietary patterns can have various eff ects on risk of stroke A meta-analysis of nine observational studies of (panel 4). Several studies have developed and assessed 194 965 individuals reported that consumption of three or diet scores as a risk factor for stroke, often in conjunction more cups of tea (green or black) a day was associated with other lifestyle factors.45,154–156with a 21% (95% CI 15–27%) lower risk of stroke than in those who consumed less than one cup a day (I²=23·8%).133 Healthy versus unhealthy diets
Population-based studies do not suggest that tea lowers In the Women’s Health Study of 37 636 women aged blood pressure,149 but it might have a favourable eff ect on 45 years or older, a healthy diet was defi ned as one high endothelial function and reduce the oxidation of LDL in cereal fi bre, folate, and omega-3 fatty acids, with a cholesterol.150,151 high ratio of polyunsaturated to saturated fat, and low in trans fats and glycaemic load, but was unexpectedly Sugar-sweetened beverages
associated with an increased risk of stroke over 10 years High intake of sugar-sweetened beverages leads to lower of follow-up.154intake of more healthy beverages and is associated with In the Nurses’ Health Study of 71 243 women and the adiposity, and an increased incidence of diabetes mellitus, Health Professionals Follow-Up Study of 43 685 men, a metabolic syndrome, and coronary heart disease.134–136 score within the top 40% of a healthy diet score (as However, no reliable data exist that relate intake of sugar- defi ned by high intakes of fruits, vegetables, soy, nuts, sweetened beverages to incidence of stroke.
and cereal fi bre; a high ratio of polyunsaturated to saturated fat and chicken plus fi sh to red meat; low intake Whole grains
of trans fats; and use of multivitamins for ≥5 years) was Whole grains comprise bran, germ, and endosperm associated with a trend towards a lower risk of stroke in from natural cereal.113 Bran contains soluble and men (relative risk 0·90, 95% CI 0·80–1·00) but not in insoluble dietary fi bre, B vitamins, minerals, fl avonoids, women (1·10, 0·89–1·16).155and tocopherols; germ contains many fatty acids, The INTERSTROKE study45 identifi ed an unhealthy antioxidants, and phytochemicals; and endosperm diet as a signifi cant risk factor for stroke (table 3). An provides largely starch (carbohydrate polysaccharides) unhealthy diet risk score was derived from a simple and storage proteins.113 Consumption of whole grains 19-item qualitative food-group-frequency questionnaire improves glucose-insulin homoeostasis and endothelial about consumption of meat, salty snacks, fried foods, function, and possibly reduces infl ammation and fruits, green leafy vegetables, cooked vegetables, and improves weight loss.137 other raw vegetables (a high score indicating a poorer www.thelancet.com/neurology Vol 11 January 2012
[increasingly unhealthy cardiovascular] diet). Compared were at lower risk of stroke than those in the bottom with the lowest (fi rst) quartile, the odds ratio of stroke in quintile (relative risk 0·87, 95% CI 0·73–1·02; p for the highest (third) tertile was 1·35 (99% CI 1·11–1·64). trend 0·03).158 The protective eff ect of the Mediterranean The adjusted population-attributable risk of stroke for diet on stroke risk has also been reported in case-control the top two tertiles compared with the bottom quartile of the dietary risk score was 18·8% (99% CI 11·2–29·7).45 The Mediterranean diet is more eff ective than a low-fat diet in reducing oxidised LDL concentrations and blood Prudent versus western diets
pressure162,163 and, in obese individuals, improving weight A prudent diet, characterised by high intakes of fruits, loss and lowering the ratio of total to high-density vegetables, legumes, fi sh, and whole grains, was lipoprotein cholesterol.164 associated with a lower risk of stroke after 14 years of
follow-up of 71 768 women (relative risk 0·78, 95% CI Vegetarian diets
0·61–1·01; comparing extreme quintiles) whereas a Compared with typical western diets, vegetarian diets
western diet, characterised by high intakes of red and can reduce blood pressure165 but lactovegetarian (milk
processed meats, refi ned grains, and sweets and desserts,
consumed) and vegan (no animal products consumed) was associated with an increased risk of stroke (relative diets have not been shown to reduce blood pressure, risk 1·58, 95% CI 1·15–2·15; comparing the highest with bodyweight, concentrations of blood lipids, or insulin lowest quintiles of the western diet).156 Vegetarians might have improved survival compared DASH-style diets
with non-vegetarians167 but, if so, whether it is because The Dietary Approaches to Stop Hypertension (DASH) the components of the diet (plant-based foods) replace diet contains a high intake of plant foods, fruits and unhealthy processed meats and other processed and fast vegetables, fi sh, poultry, whole grains, low-fat dairy foods or whether the diet is a marker of individuals products, and nuts, while minimising intake of red meat, (vegetarians) who might be more health conscious in sodium, sweets, and sugar-sweetened beverages. other aspects of their lifestyle behaviours is unclear.
Adherence to the DASH-style diet was associated with a lower risk of stroke during 24 years of follow-up of 88 517 middle-aged women (aged 34–59 years; multivariate Panel 4: Eff ects of dietary patterns on the risk of stroke
relative risk across quintiles of the DASH score were 1·0 Healthy diet
[reference; Q1], 0·92 [95% CI 0·81–1·05; Q2], 0·91 High intake of a healthy diet was associated with an increased risk of stroke in one [0·80–1·03; Q3], 0·89 [0·78–1·02; Q4], and 0·82 observational study154 and a reduced risk of stroke in another observational study155 [0·71–0·94; Q5]; p=0·002 for trend).157 The DASH diet lowers blood pressure and improves blood lipids Unhealthy diet
compared with typical western diets,161 which might High intake of an unhealthy diet is associated with an increased risk of stroke45 and a population-attributable risk of stroke of 19% (99% CI 11–30)45 Prudent diet
Mediterranean diets
In women, high intake of a prudent diet is associated with a lower risk of stroke than is The Mediterranean diet is a collection of eating habits traditionally followed by people in the diff erent countries bordering the Mediterranean Sea. This diet is charac- Western diet
terised by a high consumption of fruit, vegetables, In women, high intake of a western diet is associated with a higher risk of stroke than is legumes, and complex carbohydrates (whole grains); a moderate consumption of fi sh; consumption of olive oil DASH-style diet
as the main source of fats (monounsaturated); a low-to- In women, high intake of a DASH-style diet is associated with a lower risk of stroke than is moderate amount of red wine during meals; and low consumption of red meat, refi ned grains, and sweets. A meta-analysis of 18 observational studies involving Mediterranean diet
2 190 627 people showed that a two-point increase in In women, high intake of a Mediterranean diet is associated with a lower risk of adherence to the Mediterranean diet was associated stroke,158,159 cardiovascular disease, cardiovascular mortality, and all-cause mortality160 with a signifi cant reduction of overall mortality (relative risk 0·92, 95% CI 0·90–0·94) and cardiovascular Vegetarian diet
incidence or mortality (0·90, 0·87–0·93) over 4–20 years of follow-up.160 One study examined the eff ect of the Mediterranean diet on stroke in 74 886 women over the Japanese diet
following 20 years and reported that those with the greatest adherence to the Mediterranean diet—in the DASH=Dietary Approaches to Stop Hypertension.
top quintile of the alternate Mediterranean diet score— www.thelancet.com/neurology Vol 11 January 2012
hypertensive small vessel disease from its many other Search strategy and selection criteria
causes. Consequently, important potential eff ects of nutrients, foods, beverages, and dietary patterns on specifi c I searched PubMed articles published from 1970 to October, 2011, using the search terms pathophysiological mechanisms of one stroke subtype “stroke”, “nutrition”, “undernutrition”, “overnutrition”, “nutrients”, “foods”, “diet”, could have been diluted and missed by assessing a single “dietary patterns”, “overweight”, “obesity”, “mortality”, “prospective cohort studies”, outcome of stroke. The same applies to nutritional factors; “randomized controlled trial(s)”, “systematic review”, and “meta-analysis”. Articles were overall negative associations between total fat or total also identifi ed through searches of reference lists and my own fi les. Studies were selected carbohydrate intake and stroke risk could mask important for inclusion on the basis of a judgment about the quality of the evidence according to associations between specifi c subtypes of fat and subtypes four key elements: study design, study quality, consistency, and directness (ie, the extent of carbohydrate intake that infl uence health and stroke to which the study participants, interventions, and outcome measures are similar to those risk. These limitations have led one commentator to of interest), as proposed by the Grading of Recommendations Assessment, Development lament: “almost every nutritional ‘fact’ is in reality an and Evaluating (GRADE) working group. For each nutrient, food, or dietary pattern, only opinion, often based on poor quality evidence.”174 the studies with the highest level of evidence were included. If randomised trials had not However, the few randomised trials that have been been undertaken and only observational data were available, studies were included if they undertaken provide more reliable conclusions than do were prospective, population-based, and large, with standardised diagnostic criteria for previous epidemiological studies—that dietary sup- stroke outcome events (and, ideally, also pathological and aetiological stroke subtypes), plementation with antioxidant vitamins, B vitamins, and prolonged follow-up, and statistical adjustment for the eff ect of other potential calcium do not reduce the risk of stroke. Indeed, calcium prognostic variables by means of multiple regression analysis. Studies were excluded if might increase myocardial infarction, and β-carotene, serious limitations to study quality and major uncertainty about directness existed. Only vitamin A, and vitamin E might increase mortality. Less articles published in English were included.
reliable observational data suggest that a lower risk of stroke could be associated with diets that are low in salt For more on the GRADE
Japanese diets
and added sugars, high in potassium, and contain the working group see http://www.
Traditional Japanese diets, characterised by increased ingredients of a Mediterranean diet. The overall quality intake of fi sh, plant foods (soybean products, seaweeds, of an individual’s diet (ie, dietary pattern) and balance vegetables, fruits), and sodium (soy sauce and added between energy intake and expenditure seem to be more salt), decreased intake of refi ned carbohydrates and important determinants of stroke risk than individual animal fat (meats), and appropriate energy balance have nutrients and foods.
been associated in ecological studies with some of the Further research is needed to improve the quality of lowest rates of coronary heart disease in the world.123,168–171 evidence relating to the association of many nutrients, In observational cohort studies, the Japanese dietary foods, and dietary patterns with stroke risk. To establish a pattern has also been associated with a reduced risk of causative role for specifi c nutrients, foods, and dietary cardiovascular mortality (hazard ratio for the highest vs patterns in the pathogenesis of stroke, adequately lowest quartile 0·73, 95% CI 0·59–0·90).172 powered, large randomised trials are needed in which However, the rates of stroke in Japan remain high, the patient population and intervention are carefully perhaps because of the greater relevance of hypertension described and the outcomes not only include all stroke to stroke than coronary heart disease, and the eff ect of the but also distinguish fi rst-ever and recurrent stroke, and high sodium diet and, for men, high alcohol consumption pathological and aetiological subtypes of stroke. A large in the Japanese population. By contrast, low saturated fat randomised trial is currently examining the eff ect of (meat) and high n3-polyunsaturated fat (fi sh) in the vitamin D and marine omega-3 fatty acid supplementation Japanese diet could contribute to the low prevalence of on incidence of stroke.57 To examine the eff ects of hypercholesterolaemia, which is more relevant to risk of interactions between diff erent genetic and environmental coronary heart disease than to stroke.173 factors, large genetic epidemiological studies that minimise bias, confounding, measurement error, and Conclusions and future directions
Many studies have assessed the associations between At a population level, the two main nutritional threats to dietary exposures and stroke risk. The fi ndings are diverse, global health and risk of stroke are over-consumption of mainly because most studies are epidemiological and calories and salt. These behaviours are a normal response prone to substantial methodological challenges of bias, by people to an abnormal environment.5 Our living confounding, and measurement error. Furthermore, most environments have become more conducive to studies have classed stroke as a composite outcome, consumption of energy and less conducive to expenditure without distinguishing fi rst-ever stroke from recurrent of energy in developed and increasingly in developing stroke, ischaemic stroke from haemorrhagic stroke regions. Most of the salt in our diet is added to food before (pathological stroke subtypes), ischaemic stroke due to it is sold. If the environment is not changed to increase large artery disease from that due to small artery disease energy expenditure and to supply healthy food in and embolism from the heart (aetiological subtypes of appropriate, aff ordable, and accessible quantities, the ischaemic stroke), and haemorrhagic stroke due to obesity epidemic will not be reversed and, by 2050, 60% of www.thelancet.com/neurology Vol 11 January 2012
men and 50% of women in the UK could be clinically 5 Swinburn BA, Sacks G, Hall KD, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet 2011; obese.175 Unlike the tobacco and cardiovascular disease 378: 804–14.
epidemic, the obesity and salt epidemics have not been 6 Wang YC, McPherson K, Marsh T, Gortmaker SL, Brown M. Health reversed by public health interventions and policies aimed and economic burden of the projected obesity trends in the USA
and the UK. Lancet 2011; 378: 815–25.
at individuals to change personal choice and behaviour.5,175,176 Finucane MM, Stevens GA, Cowan MJ, et al, and the Global Burden A whole-system approach, involving many sectors, is of Metabolic Risk Factors of Chronic Diseases Collaborating Group crucial to tackling the obesity and salt epidemics.5–7,175–180 (Body Mass Index). National, regional, and global trends in body-mass index since 1980: systematic analysis of health Integrated action is required by national and local examination surveys and epidemiological studies with 960 country- governments, industry and communities, and families years and 9·1 million participants. Lancet 2011; 377: 557–67.
and the societies in which they live. Potential policies 8 Strong K, Mathers C, Bonita R. Preventing stroke: saving lives around the world. Lancet Neurol 2007; 6: 182–87.
include the following initiatives: to assess and understand Cecchini M, Sassi F, Lauer JA, Lee YY, Guajardo-Barron V, the size and nature of the problem; to establish Chisholm D. Tackling of unhealthy diets, physical inactivity, and communication strategies to improve public knowledge obesity: health eff ects and cost-eff ectiveness. Lancet 2010; about food and behaviours relating to food; to engage with 376: 1775–84.
10 Franklin BA, Cushman M. Recent advances in preventive cardiology the food industry to set fair and progressive standards and and lifestyle medicine: a themed series. Circulation 2011; 123: 2274–83.
targets for nutrient contents in processed foods, food 11 Sacco RL. Achieving ideal cardiovascular and brain health: labelling, and market advertising; to implement multiple opportunity amid crisis: Presidential Address at the American Heart
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progressive inter ventions to change behaviours at all levels 12 Goldstein LB, Bushnell CD, Adams RJ, et al, and the American (individual, local, national, and global); and to serially Heart Association Stroke Council, and the Council on monitor the eff ects of the above inter ventions.176–180 Cardiovascular Nursing, and the Council on Epidemiology and Prevention, and the Council for High Blood Pressure Research, and Population-wide salt-reduction programmes that are the Council on Peripheral Vascular Disease, and Interdisciplinary led by governments and engage with industry to remove Council on Quality of Care and Outcomes Research. Guidelines for salt at its source could be highly cost eff ective. In the the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American USA, modest, population-wide reductions in dietary salt Stroke Association. Stroke 2011; 42: 517–84.
of up to 3 g per day (1·2 g of sodium per day) are projected 13 Saunders J, Smith T. Malnutrition: causes and consequences. to reduce the annual number of new cases of stroke by Clin Med 2010; 10: 624–27.
32 000 to 66 000, similar to the benefi ts of population- 14 Foley NC, Salter KL, Robertson J, Teasell RW, Woodbury MG. Which reported estimate of the prevalence of malnutrition after wide reductions in tobacco use, obesity, and cholesterol stroke is valid? Stroke 2009; 40: e66–74.
levels.181–183 The UK Government has accepted the 15 Clinical guidelines on the identifi cation, evaluation, and treatment challenge to set and enforce salt targets for foods.63,176 The of overweight and obesity in adults: executive summary. Expert Panel on the Identifi cation, Evaluation, and Treatment of potential eff ect of adopting a healthy diet policy on Overweight in Adults. Am J Clin Nutr 1998; 68: 899–917.
population health, agricultural production, trade, the 16 Deurenberg P, Yap M, van Staveren WA. Body mass index and global economy, and livelihoods is likely to be substantial percent body fat: a meta analysis among diff erent ethnic groups.
Int J Obes Relat Metab Disord 1998; 22: 1164–1171.
in some countries,184 and the eff ects could be realised 17 Bodenant M, Kuulasmaa K, Wagner A, et al, and the MORGAM Project. Measures of abdominal adiposity and the risk of stroke: the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Confl icts of interest
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committees of the AMADEUS trial (Sanofi -Aventis), ROCKET-AF trial 19 Seliger SL, Gillen DL, Tirschwell D, Wasse H, Kestenbaum BR, (Johnson & Johnson), and BOREALIS trial (Sanofi -Aventis), the steering Stehman-Breen CO. Risk factors for incident stroke among patients committee of the TRA 2°P–TIMI 50 trial, the stroke outcome with end-stage renal disease. J Am Soc Nephrol 2003; 14: 2623–31.
adjudication committee of the ACTIVE-W, ACTIVE-A, RE-LY, and 20 Gao C, Zhang B, Zhang W, Pu S, Yin J, Gao Q. Serum prealbumin AVERROES trials, and for speaking at sponsored scientifi c symposia and (transthyretin) predict good outcome in young patients with consulting on advisory boards for Bristol-Myers Squibb, cerebral infarction. Clin Exp Med 2011; 11: 49–54.
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