DOI 10.1212/WNL.0000000000000551 published online June 11, 2014Neurology 

Zhizhong Zhang, Gelin Xu, Fang Yang, et al. Quantitative analysis of dietary protein intake and stroke risk

This information is current as of June 11, 2014

http://www.neurology.org/content/early/2014/06/11/WNL.0000000000000551.full.htmllocated on the World Wide Web at:

The online version of this article, along with updated information and services, is

Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of

® is the official journal of the American Academy of Neurology. Published continuouslyNeurology 

ARTICLES

Zhizhong Zhang, MD,PhD*

Gelin Xu, MD, PhD*Fang Yang, MD, PhDWusheng Zhu, MD, PhDXinfeng Liu, MD, PhD

Correspondence toDr. Liu:xfliu2@vip.163.com

Editorial, page 13

Supplemental dataat Neurology.org

Quantitative analysis of dietary proteinintake and stroke risk

ABSTRACT

Objective: To perform ameta-analysis of prospective studies to evaluate the relation between die-tary protein intake and stroke risk.

Methods: Relevant studies were identified by searching PubMed and Embase through November2013, and by reviewing the reference lists of retrieved articles. We included prospective cohortstudies that reported relative risks (RRs) with 95% confidence intervals (CIs) for the associationbetween dietary protein intake and stroke risk.

Results: The meta-analysis included 7 prospective studies involving 254,489 participants. Thepooled RR of stroke for the highest compared with the lowest dietary protein intake was 0.80(95%CI 0.66–0.99). Dose-response analysis indicated that a 20-g/d increment in dietary proteinintake was associated with a 26% reduction in stroke risk. Stratifying by protein type, the RR ofstroke for animal protein was 0.71 (95%CI 0.50–0.99). Sensitivity analysis restricted to studieswith control for common risk factors yielded similar results, and omission of any single study didnot change the overall result.

Conclusion: These findings suggest that moderate dietary protein intake may lower the risk ofstroke. Neurology® 2014;83:1–7

GLOSSARYCI 5 confidence interval; RR 5 relative risk.

Stroke is a major cause of death and permanent disability worldwide.1 Primary prevention ofstroke is therefore of utmost importance. Lifestyle factors have important roles in the preventionof stroke, among which dietary protein intake has received great interest. Studies have shownthat dietary protein may reduce stroke risk via its favorable effects on blood pressure.2,3 More-over, an animal study on stroke-prone spontaneously hypertensive rats indicated that rats with ahigh-protein diet had a delayed onset of stroke.4

Since the 1980s, many studies have investigated the association between dietary protein intakeand risk of stroke. However, the results of these studies remain conflicting rather than conclusive.Therefore, we performed a meta-analysis of prospective cohort studies with the following objec-tives: (1) to summarize the epidemiologic evidence on the association between dietary proteinintake and stroke risk; (2) to examine the dietary protein intake in relation to the risk of strokeaccording to stroke subtype, protein type, and characteristics of study population; and (3) to eval-uate the potential dose-response pattern between dietary protein intake and risk of stroke.

METHODS Literature search and selection. We conducted the literature search on PubMed and Embase through November

2013 using the key words “protein intake” combined with “stroke,” “cerebrovascular disease,” “cerebrovascular disorder,” and “cer-

ebrovascular accident.” Moreover, we reviewed the reference lists of retrieved articles to identify additional relevant studies.

We included studies if they met the following criteria: (1) prospective design; (2) the exposure of interest was intake of dietary pro-

tein, including total protein, animal protein, and vegetable protein; (3) the outcome of interest was fatal/nonfatal stroke and stroke

subtypes; and (4) reported the relative risk (RR) and the corresponding 95% confidence interval (CI). Three authors (Z.Z., G.X.,

and X.L.) independently evaluated the retrieved studies according to the selection criteria. Discrepancies among the 3 reviewers were

resolved by consensus.

*These authors contributed equally to this work.

From the Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province, China.

Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

© 2014 American Academy of Neurology 1

ª 2014 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Published Ahead of Print on June 11, 2014 as 10.1212/WNL.0000000000000551

Data extraction and quality assessment. We extracted the

following data for each study: the first author’s last name, publi-

cation year, study location, age, sex, sample size, length of follow-

up, protein intake assessment and comparison method, RR from

the most fully adjusted model for the highest compared with the

lowest dietary protein intake and the corresponding 95% CI, and

covariates adjusted for in the multivariate analysis.

We used a 9-star system based on the Newcastle-Ottawa

Scale5 to assess the study quality in this meta-analysis. The full

score was 9 stars, and the high-quality study was defined as a

study with .8 awarded stars.

Statistical analysis. We extracted the RRs or hazard ratios from

the selected studies and computed their standard errors from the

respective CIs. We evaluated the heterogeneity among studies

with the Q and I2 statistic.6 We calculated the pooled risk esti-

mates using either fixed-effects models or, in the presence of

heterogeneity, random-effects models.7 In addition, we

examined the variables of geographic area, sample size, length

of follow-up, publication year, and quality score in a meta-

regression model to explore the possible heterogeneity among

studies. We also used the between-study variance (t2) to

quantify the degree of heterogeneity and the percentage of t2 to

depict the level of explained heterogeneity of the variables.8

Moreover, we conducted subgroup analyses according to stroke

subtype, protein type, geographic region, history of hypertension,

sex, and quality score to evaluate the potential effect modification

of these variables on the results.

Because characteristics of cohorts, assessment methods of pro-

tein intake and endpoint, and adjustments for confounding factors

were not consistent among studies, we further performed sensitivity

analysis to explore possible explanations for heterogeneity and to

examine how the various exclusion criteria affect the overall results.

We also evaluated the influence of a single study on the overall risk

estimate by deleting each study in turn.

In the dose-response meta-analysis, we adopted the method

proposed by Greenland and Longnecker9 and Orsini et al.10 to

compute the trend from the correlated log RR estimates across

categories of protein intake. For every study, the median or

mean protein intake for each category was assigned to each

corresponding RR. When the study did not provide the median

or mean intake per category, we assigned the midpoint of the

upper and lower boundaries in every category as the average

intake. If the study did not report the upper or lower boundary

for the highest and lowest category, we assumed that the bound-

ary had the same amplitude as the nearest category. We exam-

ined a potential nonlinear relationship between protein intake

and stroke risk by modeling protein intake using restricted

cubic splines with 3 knots at percentiles 25%, 50%, and 75%

of the distribution.11 We calculated the p value for nonlinearityby testing the null hypothesis that the coefficient of the second

spline is equal to 0. Moreover, we assessed publication bias

using the Egger test.12

We used STATA version 12.0 (StataCorp, College Station,

TX) for the statistical analyses and considered p , 0.05 as statis-

tically significant.

RESULTS Literature search and study characteristics.

The search strategy yielded 236 entries. Afterexclusion of studies that did not fulfill the inclusioncriteria, 10 remaining articles seemed to be relevantfor this meta-analysis (figure 1). We furtherexcluded 4 of these 10 articles for the followingreasons: review (n 5 2), and no RR or 95% CIreported (n 5 2). We included one additionalarticle from the reference review. Finally, ourpresent meta-analysis included 7 prospectivestudies13–19 involving 254,489 participants.

Table 1 shows the characteristics of the 7 studies.Four studies were conducted in the United States, 2in Japan, and one in Sweden. The length of follow-upranged from 10.4 to 18 years, with a median of 14years. The cohort sizes ranged from 859 to 85,764(total 254,489). Four studies assessed the dietary pro-tein intake by food frequency questionnaire and3 studies by 24-hour dietary recall. The quality scoresof each of the included studies are shown in table e-1on the Neurology® Web site at Neurology.org. Thequality scores ranged from 7 to 9, and the medianscore was 8.

Protein intake and stroke risk. Figure 2 shows themultivariable-adjusted RRs for each study and thecombined RR for the highest vs the lowest categoriesof dietary protein intake. For the 7 studies, 6 showedthat protein intake was associated with decreased riskof stroke, 3 of which16,18,19 were statistically significant.Only one study showed an opposite trend.17 Overall,compared with subjects in the lowest dietary proteinintake, those in the highest had a 20% (95% CI 1%–

34%) lower risk of stroke after adjustment for otherrisk factors.

Figure 1 Flowchart of study selection

CI 5 confidence interval; OR 5 odds ratio; RR 5 relative risk.

2 Neurology 83 July 1, 2014

ª 2014 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Stratifying analysis. In the subgroup analyses by strokesubtype, dietary protein intake showed a protective effectfor intracerebral hemorrhage (table 2). Stratifying by pro-tein type, animal protein and vegetable protein intakecould lower risk of stroke by 29% and 12%, respectively(figure 2 and table 2). Stratifying by sex, the associationsbetween dietary protein intake and risk of stroke werestronger in females than in males (table 2). We alsoobserved the protective effect of dietary protein intakein high-quality studies (.8 stars).

Dose-response meta-analysis. We next assessed thedose-response relationship between protein intakeand risk of stroke. The dose-response analysisincluded 5 studies.13–16,19 We observed no evidenceof a nonlinear relationship between dietary proteinintake and stroke risk (p for nonlinearity 5 0.93).The dose-response analysis indicated that the risk ofstroke decreased by 26% (RR 0.74, 95% CI 0.65–0.84; figure 3) for every 20-g/d increment in totalprotein intake.

Sensitivity analyses. We conducted sensitivity analysesto explore potential sources of heterogeneity in theassociation between dietary protein intake and stroke

risk and to examine the influence of various exclusioncriteria on the overall risk estimate. We found that thestudy by Preis et al.17 accounted for the observed het-erogeneity.When we omitted this study, the combinedRR was 0.75 (95% CI 0.61–0.91) with marginal het-erogeneity (p 5 0.125, I2 5 42.0%). Hypertensionand diabetes were potential confounders of the associ-ation between dietary protein intake and stroke risk.The results persisted when we excluded the study13

that did not adjust for hypertension or diabetes (RR0.79, 95% CI 0.63–0.99), with substantial evidence ofheterogeneity (p 5 0.01, I2 5 67.6%). Further omis-sion of any single study did not materially alter theoverall combined RR, with a range from 0.73 to 0.85.

Meta-regression. We used meta-regression analysis toexplore the potential sources of heterogeneity. Wefound that length of follow-up (#14 vs .14 years)alone could explain 45.46% of the t2 in the meta-regression analyses, whereas year of publication(before and after 2010) could explain 8.01% of the t2.

Publication bias. Visual inspection of the funnel plotdid not identify remarkable asymmetry. Egger test alsoshowed no evidence of publication bias (p 5 0.24).

Table 1 Characteristics of the included studies

Ref. CountrySex andage, y

No. incohort

Follow-up, y

Protein intakeassessment Outcome

Intakecomparison Adjustment for covariates

13 US M/F 50–79 859 12 24-h dietary recall Fatal stroke Continuousvariable

Age, sex, potassium, and calories

14 US F 34–59 85,764 14 FFQ Fatal/nonfatalstroke

Quintile (V vs I) Age, smoking, time interval, BMI, alcohol,menopausal status and postmenopausalhormone use, exercise, aspirin, multivitamin use,vitamin E use, n-3 fatty acid, calcium, historiesof hypertension, diabetes, high cholesterollevels, total energy intake, cholesterol, fat, andprotein

15 Japan M/F 40–69 4,775 14 24-h dietary recall Fatal/nonfatalstroke

Quartile (IV vs I) Age, sex, quartiles of total energy intake andBMI, hypertension, diabetes, serum totalcholesterol, smoking, ethanol, and menopausalstatus

16 Japan M/F 35–89 3,731 14 24-h diary Fatal stroke Tertile (III vs I) Age, sex, radiation dose, city, BMI, smokingstatus, alcohol habits, and medical history ofhypertension and diabetes

17 US M 40–75 43,960 18 FFQ Fatal/nonfatalstroke

Quintile (V vs I) Age, quintiles of percentage of energy fromsaturated fat, monounsaturated fat,polyunsaturated fat, trans fat, quintiles ofcalories, fiber, folate, vitamin B6, vitamin B12,potassium, vitamin C, magnesium, total omega-3fatty acids, glycemic index, physical activity,family history of MI, BMI, smoking, alcohol,multivitamin use, hypertension,hypercholesterolemia, and diabetes

18 US F 50–79 80,730 12 FFQ Fatal/nonfatalstroke

Continuousvariable

Ethnicity, education, history of cardiovasculardisease, family history of prematurecardiovascular disease, smoking status,hypertension, treated diabetes, statin use,aspirin use, prior hormone use, and recreationalphysical activity

19 Sweden F 49–83 34,670 10.4 FFQ Fatal/nonfatalstroke

Quintile (V vs I) Age, combination of smoking status and pack-years of smoking, education, BMI, total physicalactivity, history of hypertension and diabetes,aspirin use, family history of MI, intakes of totalenergy, alcohol, calcium, cholesterol, total fat,fruits, and vegetables

Abbreviations: BMI 5 body mass index; FFQ 5 food frequency questionnaire; MI 5 myocardial infarction; US 5 United States.

Neurology 83 July 1, 2014 3

ª 2014 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

DISCUSSION In the past 2 decades, the role of die-tary protein in the development of stroke hasbeen increasingly recognized. Our meta-analysiscontaining 254,489 participants provides evidencethat protein intake is independently associated witha decreased risk of stroke. The protective effect ofdietary protein against risk of stroke may in part beattributable to its blood pressure–lowering effect. Astudy has indicated that a higher intake of the aminoacid arginine could enhance levels of the endogenousvasodilator nitric oxide and reduce blood pressure.20

A randomized trial has also shown that substitution ofdietary carbohydrates with protein reduced bloodpressure.21 Because hypertension is a crucial riskfactor for stroke, it is plausible that a higher intakeof dietary protein may reduce stroke risk.

In addition to lowering blood pressure, the proteindiet also significantly lowered triglycerides, total cho-lesterol, and non–high-density lipoprotein cholesterol,compared with the carbohydrate diet.21 An animalstudy indicated that a moderate increase in dietarycrude protein content could reduce fat deposition.22

Also, a study has shown that doenjang, a fermentedsoybean paste that is a rich source of protein, resultedin a 25.4% reduction in adipocyte size compared withno supplementation.23 Moreover, dietary protein mayalso decrease stroke risk via a substitution effect, replac-ing intake of other potentially harmful foods.

In our study, the reduced risk of stroke was more evi-dent for animal protein than vegetable protein. A possi-ble interpretation is that the range of protein intakebetween the highest and lowest categories was narrowerfor vegetable protein (15.6 g/d) than for animal protein(34.7 g/d) in our meta-analysis, which made it more dif-ficult to observe a statistically significant association.Among different protein sources, fish consumptionhas been associated with decreased risk of stroke,24

whereas red meat consumption has been associatedwith increased stroke risk.25,26 In addition, comparedwith Westerners, Asians tend to eat more fish and lessred meat. In our meta-analysis, decreased stroke riskwas observed in 2 Japanese studies15,16 and one study17

in which fish was the primary source of animal protein.These results indicated that stroke risk may be reducedby replacing red meat with other protein sources suchas fish.

Meta-analysis is an important method to revealtrends that might not be evident in a single study.With the accumulative evidence, we were able toenhance the precision of the risk estimates and con-duct subgroup analyses to explore sources of hetero-geneity, hence increasing the clinical relevance ofour findings. In addition, all included studies adopteda prospective cohort design, which minimized thepossibility of recall and selection biases. Moreover,the presence of a dose-response relationship further

Figure 2 Forest plot of cohort studies examining dietary protein intake and stroke risk

CI 5 confidence interval; RR 5 relative risk.

4 Neurology 83 July 1, 2014

ª 2014 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

strengthened the association of dietary protein intakewith risk of stroke.

This meta-analysis also had several limitations.First, as a meta-analysis of observational studies, thepossibility that other factors may account for theobserved association cannot be excluded. Thus, cau-tion with interpretation of data is necessary. Dietaryprotein intake tends to be associated with other

nutrients that may prevent stroke, such as potassi-um,27,28 magnesium,29 and dietary fiber.30 However,the association between protein intake and risk ofstroke persisted when we confined the analysis tostudies that adjusted for these risk factors. Second,there was substantial heterogeneity among includedstudies, which was not surprising given the differencesin population characteristics, sample sizes, and adjust-ments for potential confounders. Our subgroup andsensitivity analyses showed that studies conducted infemales, and with a higher quality score, providedhomogeneous results. Third, misclassification of die-tary exposures and the long interval between exposureand outcome may affect our meta-analysis results,particularly in some observational studies in whichdiet was assessed at enrollment (at one time point)and was self-reported through a food frequency ques-tionnaire. This will inevitably lead to some misclassi-fication of dietary exposures. Only 2 studies in thismeta-analysis updated the information about dietduring follow-up.14,17 Misclassification of dietary pro-tein intake may have been present in the remainingstudies that assessed diet at baseline only, which couldlead to an underestimation of the true associationbetween dietary protein intake and stroke risk.

Figure 3 Dose-response relationship between dietary protein intake and strokerisk

Table 2 Stratification analyses of dietary protein intake and stroke risk

Group No. of studies RR (95% CI)

Heterogeneity test

x2 p I2, %

Total stroke 7 0.80 (0.66–0.99) 15.44 0.017 61.1

Ischemic stroke 4 0.82 (0.65–1.04) 9.47 0.024 68.3

Intracerebral hemorrhage 3 0.57 (0.39–0.85) 0.29 0.866 0.0

Subarachnoid hemorrhage 2 0.79 (0.47–1.33) 0.11 0.738 0.0

Protein type

Animal protein 5 0.71 (0.50–0.99) 13.07 0.011 69.4

Vegetable protein 5 0.88 (0.76–1.02) 1.17 0.884 0.0

Geographic region

United States 4 0.91 (0.82–1.00) 7.44 0.059 59.7

Japan 2 0.49 (0.28–0.83) 0.35 0.557 0.0

Sweden 1 0.74 (0.61–0.90) — — —

History of hypertension

Yes 2 0.57 (0.40–0.80) 0.05 0.827 0.0

No 2 0.76 (0.58–0.99) 3.81 0.051 73.8

Sex

Male 1 1.14 (0.90–1.44) — — —

Female 3 0.83 (0.75–0.92) 4.55 0.103 56.1

Quality score

£8 stars 4 0.88 (0.68–1.15) 8.64 0.035 65.3

>8 stars 3 0.71 (0.59–0.86) 2.25 0.325 11.1

Abbreviations: CI 5 confidence interval; RR 5 relative risk.

Neurology 83 July 1, 2014 5

ª 2014 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Therefore, in addition to assessing the dietary expo-sure at enrollment, further studies should update theassessment of dietary exposure periodically during thefollow-up (e.g., every 2–4 years).

Stroke is a leading cause of death and disabilityworldwide. The association between dietary proteinintake and stroke risk remains inconsistent. Findingsfrom our study aimed at addressing this issue andresolving the inconsistency are both timely and crucial.According to the result of our meta-analysis, a 20-g/dincrement in protein intake was associated with areduction in the risk of stroke of 26%. This risk reduc-tion would be translated into a reduction of 1,482,000stroke deaths every year worldwide and is expected toproduce overall health benefits by decreasing the levelof disability.31 Protein intake may be increased by well-described dietary changes, as recommended by guide-lines for stroke prevention and treatment. To date,large-scale, randomized, controlled trials, which pro-vide the strongest evidence for establishing a causation,have not been implemented to directly assess the effectof protein intake on stroke risk. Considering the com-pelling evidence from our study, such trials are antic-ipated to draw definitive conclusions.

In summary, this meta-analysis of prospectivestudies suggests that moderate dietary protein intakemay lower the risk of stroke. Further experimentalstudies are needed to confirm the beneficial effectsof protein intake.

AUTHOR CONTRIBUTIONSStudy concept and design: Z.Z. and X.L. Data collection: Z.Z., G.X.,

and X.L. Statistical analyses: Z.Z. and G.X. Manuscript writing: Z.Z.

Interpretation of results: Z.Z., G.X., F.Y., W.Z., and X.L. Critical revi-

sion of the manuscript: Z.Z., G.X., and X.L. X.L. had full access to all of

the data in the study and takes responsibility for the integrity of the data

and the accuracy of the data analysis.

STUDY FUNDINGSupported by the National Natural Science Foundation of China

(31200938, 81220108008), and the Natural Science Foundation of Jin-

ling Hospital (2012009). The funders had no role in study design, data

collection and analysis, decision to publish, or preparation of the

manuscript.

DISCLOSUREThe authors report no disclosures relevant to the manuscript. Go to

Neurology.org for full disclosures.

Received November 20, 2013. Accepted in final form February 6, 2014.

REFERENCES1. Bonita R, Mendis S, Truelsen T, Bogousslavsky J, Toole J,

Yatsu F. The Global Stroke Initiative. Lancet Neurol

2004;3:391–393.

2. Elliott P, Stamler J, Dyer AR, et al. Association between

protein intake and blood pressure: the INTERMAP Study.

Arch Intern Med 2006;166:79–87.

3. Altorf-van der Kuil W, Engberink MF, Brink EJ, et al.

Dietary protein and blood pressure: a systematic review.

PloS One 2010;5:e12102.

4. Chiba T, Itoh T, Tabuchi M, Satou T, Ezaki O. Dietary

protein, but not carbohydrate, is a primary determinant of

the onset of stroke in stroke-prone spontaneously hyper-

tensive rats. Stroke 2009;40:2828–2835.

5. Stang A. Critical evaluation of the Newcastle-Ottawa scale

for the assessment of the quality of nonrandomized studies

in meta-analyses. Eur J Epidemiol 2010;25:603–605.

6. Higgins JP, Thompson SG. Quantifying heterogeneity in

a meta-analysis. Stat Med 2002;21:1539–1558.

7. DerSimonian R, Laird N. Meta-analysis in clinical trials.

Control Clin Trials 1986;7:177–188.

8. Whitehead A, Whitehead J. A general parametric approach

to the meta-analysis of randomized clinical trials. Stat Med

1991;10:1665–1677.

9. Greenland S, Longnecker MP. Methods for trend estima-

tion from summarized dose-response data, with applications

to meta-analysis. Am J Epidemiol 1992;135:1301–1309.

10. Orsini N, Bellocco R, Greenland S. Generalized least

squares for trend estimation of summarized dose-

response data. Stata J 2006;6:40–57.

11. Orsini N, Li R, Wolk A, Khudyakov P, Spiegelman D.

Meta-analysis for linear and nonlinear dose-response rela-

tions: examples, an evaluation of approximations, and soft-

ware. Am J Epidemiol 2012;175:66–73.

12. Egger M, Davey Smith G, Schneider M, Minder C. Bias

in meta-analysis detected by a simple, graphical test. BMJ

1997;315:629–634.

13. Khaw KT, Barrett-Connor E. Dietary potassium and

stroke-associated mortality: a 12-year prospective popula-

tion study. N Engl J Med 1987;316:235–240.

14. Iso H, Stampfer MJ, Manson JE, et al. Prospective study

of fat and protein intake and risk of intraparenchymal

hemorrhage in women. Circulation 2001;103:856–863.

15. Iso H, Sato S, Kitamura A, Naito Y, Shimamoto T,

Komachi Y. Fat and protein intakes and risk of intrapar-

enchymal hemorrhage among middle-aged Japanese. Am J

Epidemiol 2003;157:32–39.

16. Sauvaget C, Nagano J, Hayashi M, Yamada M. Animal

protein, animal fat, and cholesterol intakes and risk of

cerebral infarction mortality in the Adult Health Study.

Stroke 2004;35:1531–1537.

17. Preis SR, Stampfer MJ, Spiegelman D, Willett WC,

Rimm EB. Lack of association between dietary protein

intake and risk of stroke among middle-aged men. Am J

Clin Nutr 2010;91:39–45.

18. Prentice RL, Huang Y, Kuller LH, et al. Biomarker-calibrated

energy and protein consumption and cardiovascular disease

risk among postmenopausal women. Epidemiology 2011;22:

170–179.

19. Larsson SC, Virtamo J, Wolk A. Dietary protein intake

and risk of stroke in women. Atherosclerosis 2012;224:

247–251.

20. Appel LJ. The effects of protein intake on blood pressure and

cardiovascular disease. Curr Opin Lipidol 2003;14:55–59.

21. Appel LJ, Sacks FM, Carey VJ, et al. Effects of protein,

monounsaturated fat, and carbohydrate intake on blood

pressure and serum lipids: results of the OmniHeart Ran-

domized Trial. JAMA 2005;294:2455–2464.

22. Mohiti-Asli M, Shivazad M, Zaghari M, Aminzadeh S,

Rezaian M, Mateos GG. Dietary fibers and crude protein

content alleviate hepatic fat deposition and obesity in

broiler breeder hens. Poult Sci 2012;91:3107–3114.

23. Kwak CS, Park SC, Song KY. Doenjang, a fermented

soybean paste, decreased visceral fat accumulation and

6 Neurology 83 July 1, 2014

ª 2014 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

adipocyte size in rats fed with high fat diet more effectively

than nonfermented soybeans. J Med Food 2012;15:1–9.

24. Larsson SC, Orsini N. Fish consumption and the risk of

stroke: a dose-response meta-analysis. Stroke 2011;42:

3621–3623.

25. Kaluza J, Wolk A, Larsson SC. Red meat consumption

and risk of stroke: a meta-analysis of prospective studies.

Stroke 2012;43:2556–2560.

26. Bernstein AM, Pan A, Rexrode KM, et al. Dietary protein

sources and the risk of stroke in men and women. Stroke

2012;43:637–644.

27. D’Elia L, Barba G, Cappuccio FP, Strazzullo P. Potassium

intake, stroke, and cardiovascular disease: a meta-analysis

of prospective studies. J Am Coll Cardiol 2011;57:

1210–1219.

28. Larsson SC, Orsini N, Wolk A. Dietary potassium intake

and risk of stroke: a dose-response meta-analysis of pro-

spective studies. Stroke 2011;42:2746–2750.

29. Larsson SC, Orsini N, Wolk A. Dietary magnesium intake

and risk of stroke: a meta-analysis of prospective studies.

Am J Clin Nutr 2012;95:362–366.

30. Zhang Z, Xu G, Liu D, Zhu W, Fan X, Liu X. Dietary

fiber consumption and risk of stroke. Eur J Epidemiol

2013;28:119–130.

31. Strong K, Mathers C, Bonita R. Preventing stroke: saving

lives around the world. Lancet Neurol 2007;6:182–187.

Neurology 83 July 1, 2014 7

ª 2014 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

DOI 10.1212/WNL.0000000000000551 published online June 11, 2014Neurology 

Zhizhong Zhang, Gelin Xu, Fang Yang, et al. Quantitative analysis of dietary protein intake and stroke risk

This information is current as of June 11, 2014

ServicesUpdated Information &

00000000551.full.htmlhttp://www.neurology.org/content/early/2014/06/11/WNL.00000including high resolution figures, can be found at:

Supplementary Material

00000000551.DC2.htmlhttp://www.neurology.org/content/suppl/2014/06/11/WNL.00000

00000000551.DC1.htmlhttp://www.neurology.org/content/suppl/2014/06/11/WNL.00000Supplementary material can be found at:

Subspecialty Collections

http://www.neurology.org//cgi/collection/stroke_preventionStroke prevention

iologyhttp://www.neurology.org//cgi/collection/risk_factors_in_epidemRisk factors in epidemiology

http://www.neurology.org//cgi/collection/cohort_studiesCohort studiesfollowing collection(s): This article, along with others on similar topics, appears in the

  Permissions & Licensing

http://www.neurology.org/misc/about.xhtml#permissionsor in its entirety can be found online at:Information about reproducing this article in parts (figures,tables)

  Reprints

http://www.neurology.org/misc/addir.xhtml#reprintsusInformation about ordering reprints can be found online: