You are on page 1of 10

ARTHRITIS & RHEUMATOLOGY

Vol. 67, No. 7, July 2015, pp 1933–1942
DOI 10.1002/art.39115
C 2015, American College of Rheumatology
V

Food Sources of Protein and Risk of Incident Gout in the
Singapore Chinese Health Study
Gim Gee Teng,1 An Pan,2 Jian-Min Yuan,3 and Woon-Puay Koh4
Objective. Prospective studies evaluating diet in
relation to the risk of gout in Asian populations are
lacking. The purpose of this study was to examine the
relationship between the consumption of dietary protein from each of its major sources and the risk of gout
in a Chinese population.
Methods. We used data from the Singapore
Chinese Health Study, a prospective cohort of 63,257
Chinese adults who were 45–74 years old at recruitment
during the years 1993–1998. Habitual diet information
was collected via a validated semiquantitative food frequency questionnaire, and physician-diagnosed gout
was self-reported during 2 followup interviews up to the
year 2010. Cox proportional hazards models were used
to calculate the hazard ratios (HRs) and 95% confidence
intervals (95% CIs), with adjustment for potential confounders, among 51,114 eligible study participants who
were free of gout at baseline and responded to our followup interviews.
Results. A total of 2,167 participants reported
physician-diagnosed gout during the followup period.

The multivariate-adjusted HRs (with 95% CIs) of gout,
comparing the first quartile with the fourth quartile,
were as follows: 1.27 (1.12–1.44; P for trend < 0.001) for
total protein, 1.27 (1.11–1.45; P for trend < 0.001) for
poultry, 1.16 (1.02–1.32; P for trend 5 0.006) for fish
and shellfish, 0.86 (0.75–0.98; P for trend 5 0.018)
for soy food, and 0.83 (0.73–0.95; P for trend 5 0.012) for
nonsoy legumes. No statistically significant associations
were found with protein intake from other sources (red
meat, eggs, dairy products, grains, or nuts and seeds).
Conclusion. In this Chinese population living in
Singapore, higher total dietary protein intake from mainly
poultry and fish/shellfish was associated with an increased risk of gout, while dietary intake of soy and nonsoy legumes was associated with a reduced risk of gout.
Gout is estimated to affect ;5% of the middleaged and elderly population worldwide (1). In recent
decades, the prevalence of gout in Asian countries is
approaching that observed in Western populations
(2–5). The disease burden of gout results from the loss
of physical function and work productivity (6,7), as well
as from death from cardiovascular causes (4,8–10).
Gout is also associated with other chronic diseases, such
as obesity, diabetes mellitus, hypertension, and hyperlipidemia, which are on a rising trend worldwide (11).
Diet plays an important role in the development
and management of gout (12,13). Since high-protein
foods tend to contain large quantities of purines, patients with gout or hyperuricemia are generally advised
to avoid food sources of protein, including meat, seafood, soy, and nonsoy legumes (14–17). However, the
data concerning the association between food sources of
protein and gout remain unclear, and prospective studies have been limited mainly to Caucasian populations.
For example, two large prospective studies in Caucasian
men showed a positive association between gout and
intake of meat and seafood (18,19) and an inverse association with low-fat dairy products (18).

Supported by the NIH (grants R01-CA-144034 and UM1CA-182876).
1
Gim Gee Teng, MBBS, MD: National University Health
System, Singapore, Singapore, and National University of Singapore,
Yong Loo Lin School of Medicine, Singapore; 2An Pan, PhD: National
University of Singapore, Saw Swee Hock School of Public Health, Singapore, and Huazhong University of Science and Technology, School
of Public Health and Tongji Medical College, Wuhan, China; 3JianMin Yuan, MD, PhD: University of Pittsburgh Cancer Institute, and
University of Pittsburgh Graduate School of Public Health, Pittsburgh,
Pennsylvania; 4Woon-Puay Koh, MBBS, PhD: Duke–NUS Graduate
Medical School, Singapore, and National University of Singapore,
Saw Swee Hock School of Public Health, Singapore.
Address correspondence to Gim Gee Teng, MBBS, MD,
University Medicine Cluster, Division of Rheumatology, National
University Health System, NUHS Tower Block, 1E Kent Ridge
Road, Singapore 119228, Singapore (e-mail: gim_gee_teng@nuhs.
edu.sg); or to Woon-Puay Koh, MBBS, PhD, Office of Clinical
Sciences, Duke–NUS Graduate Medical School Singapore, 8 College
Road Level 4, Singapore 169857, Singapore (e-mail: woonpuay.
koh@duke-nus.edu.sg).
Submitted for publication October 15, 2014; accepted in
revised form March 10, 2015.
1933

meats (red meat [pork/beef]. height. scanner-readable questionnaire that ascertained information on demographics.700 kcal/day for men).. telephone interviews were conducted again among 39. The participants were instructed to select from 8 consumption frequency categories (ranging from “never or hardly ever” to “two or more times a day”) and 3 portion sizes (small. SUBJECTS AND METHODS Study population. A major reason for nonparticipation in the followup interview was that the subject had died. poultry.wiley. At recruitment.322 in followup 1 and 39. respectively. condiments. seafood. dairy products. The differences between baseline characteristics by physician-diagnosed gout were examined using the chi-square test for categorical variables and Student’s t-test for continuous variables.” The interviewers confirmed that the participants had gout but not another form of arthritis by verifying with the participants that the diagnosis of gout was based on joint pain and swelling attributed to reported hyperuricemia by their physicians.257 participants in the Singapore Chinese Health Study. grains.e.1934 TENG ET AL The Chinese diet is distinct from that in the West. tobacco use. poultry. nonsoy legumes. medium. Participants with prevalent gout that had been diagnosed before baseline (n 5 1.3. soy foods and nonsoy legumes. and preserved foods. the participants were asked “Have you been told by a doctor that you have gout?” If the response was “yes. or the latest followup interview. . physical activity.322 participants were contacted for telephone interviews to update information on lifestyle factors and medical history (21).1 years versus 55.39115/abstract). fruits. A total of 54. The correlation coefficient for energy intake and selected nutrients from the FFQ versus the 24-hour recalls ranged between 0.000 kcal/day for women and . and fish and shellfish). Dietary advice for gout patients was not a criterion for case definition because of the variation and inconsistency in dietary advice among physicians. vegetables. and all participants gave informed consent. soy foods. we examined the relationship between dietary intake of protein from each of its major sources (i. These foods were covered under the categories of rice and noodles. Habitual diet during the preceding year was captured using a validated 165-item food frequency questionnaire (FFQ). They were also more likely to be male and to have smoked at some point in their lives and to have a lower education level but a higher prevalence of self-reported hypertension and diabetes mellitus at baseline (Supplementary Table 1. the Hokkien and Cantonese. The number of person-years at risk contributed by each participant was calculated from the date of the baseline interview to the date of reported gout diagnosis.087) or those with missing age at gout diagnosis (n 5 9) were also excluded.528 in followup 2). nuts and seeds. death.114 participants (Figure 1). Statistical analysis. and nuts/seeds) and incident gout in a prospective cohort of middle-aged and older Chinese adults living in Singapore. dairy products. The FFQ was validated in two 24-hour recall assessments as well as by re-administration to 810 cohort participants (20). the current analysis included data from 51. We further excluded 1. Between 1999 and 2004. The dietary intake of protein and the food sources of Figure 1.257 Chinese adults ages 45–74 years at baseline (1993–1998) (20). available on the Arthritis & Rheumatology web site at http://onlinelibrary. The participants were recruited from persons living in government housing estates and were restricted to the 2 major dialect groups. face-to-face interviews were conducted in the participants’ homes by trained interviewers using a structured. At both followup interviews. and medical history. which was developed specifically for this cohort study and has been described in detail elsewhere (20). beverages. compared to those who participated in at least 1 followup interview. Hence. aided by the use of photographs). Incident gout cases. The dietary nutrients were derived according to the Singapore Food Composition Database. All interviews were tape-recorded and subjected to quality checks. data from prospective studies on diet and gout in the Chinese population are sparse.1002/art.24 and 0.3.600 or . or large. Between 2006 and 2010.290 participants with cancer at baseline and 841 participants who reported extreme calorie intakes (. meat. The Singapore Chinese Health Study is a population-based cohort of 63. who originated from the contiguous provinces of Fujian and Guangdong. The differences between the mean values of most pairs of assessments for energy and nutrients were within 10% of each other.79 (22).528 participants for updated lifestyle factors and medical history. However.” the participant was then asked to “Please also tell me the age at which you were first diagnosed. whichever occurred first. hence. The FFQ included 165 food items commonly consumed by this population. Assessment of diet and covariates. 52. The study was approved by the institutional review boards of the National University of Singapore and the University of Pittsburgh.916) were older at recruitment (61. as expected. 1993–1998. in southern China.8 years). Flow chart showing inclusion of study participants from the initial cohort of 63. those who did not participate (n 5 8. com/doi/10.341 participants participated in either or both followup interviews (52. weight. In this study.700 or .

.0 6 10.947) P* 55.05.686 (7.50 6 1. gm/1.001 1. nonsoy legumes. mean 6 SD Calories.2 6 2.000 person-years in men and 294 per 100.151 at followup 1 and 1.000 kcal Fish and shellfish. and to have higher education levels and higher BMI than their counterparts.0. or $4.0.167 subjects reported new-onset physician-diagnosed gout (1.470 (21.114 participants (568. and fish and shellfish at baseline than those who remained free of gout (Table 1). All analyses were performed using SAS version 9.17 .0 hours/ week). % kcal Soy protein.000 kcal/day and including total energy as a covariate in the model.001 0.983 (8.0. eggs. .9 kg/m2.1) 23.9 6 11.4 6 2. Tests for trend were performed by using median values of intake in the quartile categories as continuous variables in the Cox regression models. RESULTS After a mean 6 SD followup of 11. categorized according to those who developed gout and those who remained free of gout Characteristic Demographic features Age.0.623 (74.7) 88 (4.167) Subjects without gout (n 5 48.001 . monthly.1) 13. or current).1 6 3. Baseline characteristics of 51. (%) .4 1.114 participants in the Singapore Chinese Health Study 1993–2010.016 at followup 2).0–23.001 .9 kg/m2.000 kcal Poultry.193 (55. mean 6 SD years No. no.001 . soy foods.2 6 3.9 hours/week $4 hours/week Body mass index.976 person-years).6 36. red meat (including pork.571 (3.1) 1.7 6 11. kcal Red meat.553 6 518 18. (%) ever smoked Comorbid conditions.0. education level (none.0. (%) male No.001 0. beef and lamb). and total energy intake (kcal/day).252 (29. mean 6 SD kg/m2 Alcohol intake.4) 3.DIET AND GOUT 1935 the protein were analyzed in quartiles.940 (8.1) 1. weekly or daily alcohol drinkers.151 (77.1 years (range 45–87 years).5–3.0) 55. 0.7 6 7.001 0. We further adjusted for dietary intake of vegetables.001 .7) 14.6 6 17.9) 23.3) 10.0. red meat. no. no. sex. a total of 2. primary school.0 6 7.0–27.1 6 3. This method is an “isocaloric” analysis and controls for confounding by energy intake with an intuitive interpretation as a measure of dietary composition (23). former.47 6 0.0.9 hours/week. dairy products.07 798 (36.0) 651 (30.2) 215 (9. ever smokers.74 .000 kcal Total protein.0.2) 737 (34.5–3.5 1.9) 329 (15.5 37. (%) Cantonese dialect speakers No. 24. (%) secondary school or higher No.1) 1.2 6 17.9) 24.001 3. smoking status (never.3 6 8.0 kg/m2). The selection of potential confounders was based primarily on prior consideration of their associations with either dietary intake or risk of gout in this population. % kcal Subjects with gout (n 5 2.0.10 * P values were determined by chi-square test for categorical variables and by Student’s t-test for continuous variables.99 .0 kg/m2.0.2) . or higher). weekly.2 231 (10.856 (14. A basic model (model 1) included age (years).067 (49. nuts and seeds. and all grain products (all in quartiles) (model 3).2) 1. Table 1. fish and shellfish.0) 3.6 15. or $28. (%) Weekly consumption Daily consumption Daily dietary intake. secondary school. poultry.369 (47. The mean 6 SD age at diagnosis was 61. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for developing gout by using the lowest quartile of dietary intake as the reference group.001 0. and year of baseline interview (1993–1995 or 1996–1998).0. gm/1. Participants with incident gout were more likely to be male.1 14. An additional model (model 2) included dialect (Hokkien/Cantonese). poultry. and statistical significance was based on 2-sided probability of 0. or daily).7 years among 51.5 hours/week 0.7 20.528 (41. Heterogeneity of the diet–gout associations between men and women was tested with an interaction term in the models. body mass index (BMI.7 6 9.2 software (SAS Institute).001 .0 12. Participants who developed gout also had high levels of consumption of total protein. 20.3 38.20. physical activity (.0.5 15.8) 159 (7. self-reported history of hypertension or diabetes mellitus.000 person-years in women. The incidence rates of gout standardized to the age structure of the whole cohort were 504 per 100.5 hours/week. (%) Hypertension Diabetes mellitus Physical activity. The distributions of selected characteristics and dietary exposures are shown in Table 1.620 6 540 19. We used the multivariate nutrient density method in the analyses by computing the intake of protein or its major food sources per 1.0. fruits.01 . Incident gout cases also had a higher prevalence of self-reported hypertension at baseline as compared to noncases.001 .813 (28. gm/1.4 1. alcohol consumption (none.5) .9) 6.

P for trend 5 0. with an HR for comparison of the first and fourth quartiles of 0. and fish/shellfish with gout remained largely unchanged. P for trend 5 0. The consumption of red meat was positively associated with the risk of gout.06).59.33) 1.99 (0.006) for fish and shellfish. The positive relationship of total protein.85–1.83 (95% CI 0.89 (95% CI 0. of cases/person-years Multivariate model 1 Multivariate model 2 Q1 Q2 Q3 Q4 P for trend 480/138.0.789 0.11) 0.15–1. Multivariate model 2 was adjusted for the same variables as for model 1 plus dialect.75–0. of cases/person-years Multivariate model 1 Multivariate model 2 Soy protein.005).70–0.55.06 * Linear trend was tested by assigning to participants the median value for the quartile and assessing this as a continuous variable. and year of interview.027) for fish and shellfish.04–1. When analyzing the individual sources of dietary protein intake (Table 3).35 (95% CI 1. dietary intake of soy protein was associated with a marginally significant inverse association. % kcal/day No.06).767 1.34 (1.com/ doi/10. For the inverse association with soy foods and nonsoy legumes.001) for poultry.32 (95% CI 1. Multivariate model 1 was adjusted for age.317 subjects. P for trend . During followup 1 and followup 2.001) (Table 2).279 gout cases were included in this analysis.001) for poultry.36. There was no statistically significant association between other food groups (i.09 (0. the HR for comparison of the first and fourth quartiles was 1.44. In contrast. alcohol use.11–1. body mass index. but a marginally significant trend toward increasing risk in women (P for interaction 5 0..167 participants in the Singapore Chinese Health Study 1993–2010.30) 515/144. we found that consumption of soy foods and nonsoy legumes was associated with a reduced risk of gout.e. P for trend 5 0.06 (0.18 (1.32. No significant interactions were found for other food groups. red meat.012) for nonsoy legumes.05. % kcal/day No.00 1.001) for total protein. the HR for comparison of the first and fourth quartiles was 1. available on the Arthritis & Rheumatology web site at http://onlinelibrary.02–1. P for trend .01) 0.08) 545/145.02–1.83–1.854 1.10) 0.96 (0.19–1. but this was attenuated after additional adjustment for other dietary variables.018) for soy foods and 0.85–1.0.83 (95% CI 0. nuts and seeds. A total of 48.1002/art.00 553/143.1936 TENG ET AL Table 2.27 (95% CI 1.313 0.98.93 (0.184 1.12–1.57.89 (0. P for trend 5 0.96–1.13–1.27 (95% CI 1. 0.01. In the multivariateadjusted model with dietary variables. P for trend 5 0.55 0.00 1. P for trend 5 0. physical activity.23) 1. although the risk estimates were attenuated to . respectively). the inverse relationship of soy protein and soy foods with gout was attenuated to null (P for trend 5 0. the HR for comparison of the first and fourth quartiles of total protein intake was 1. However. We further performed a 4-year lag sensitivity analysis (Supplementary Table 2.317 subjects responded positively at either or both followup interviews. we observed a positive association with poultry and fish/shellfish.wiley. and the results were similar between men and women. poultry.93–1. but not in men (P for interaction 5 0.96 (0.79–1.20) 608/143.86 (95% CI 0.51) 1. while the association between nonsoy legumes and gout was not materially changed. and fish/shellfish. In the multivariateadjusted model with dietary variables. the participants were also asked if they had been diagnosed as having any other form of arthritis (including but not limited to osteoarthritis and rheumatoid arthritis). In contrast. 0.99–1. education level.98. sex.001 546/134.094 1.88–1. Hazard ratios and 95% confidence intervals for the risk of gout in 2.001 .95.02 and 0. and total energy.16 (95% CI 1. there was a non–statistically significant trend toward decreasing risk between dairy products and gout in men. A total of 9.09) 0. and 1.00 564/142.73–0. with an HR for comparison of the first and fourth quartiles of 1.87–1. smoking status.14–1.12–1.79–1. 1. P for trend 5 0. We further examined the associations in men and women separately (Table 4). baseline presence of diabetes mellitus. High total protein consumption was associated with an increased risk of gout.86 and P for trend 5 0. 0. and 1. The positive association with fish and shellfish.36. P for trend . or grain products) and risk of gout.020 0.805 participants with 1. P for trend 5 0. We did a secondary analysis excluding these 9.16 (95% CI 0.39115/abstract). respectively). and the HR comparing the first and fourth quartiles was 0.44) .45. baseline presence of hypertension. In contrast. with an HR for comparison of the first and fourth quartiles of 0. and the results remained essentially the same for the positive association with intake of total protein.98 (0. poultry. and the inverse association with nonsoy legumes persisted in women.931 1.34 (95% CI 1.04). For example. eggs. by dietary protein intake* Quartile of energy-adjusted protein intake Protein Total protein.27 (1.15 (1. dairy products.05) 523/145.

07) 0.07 (0.29 0. gm/1.92 (95% CI 0.85–1.82–1.004 0.95 (0.94–1.22) 1.244 0.38) 1.07) 0.93 (0.604 1. Multivariate model 1 was adjusted for age.28) 555/144.75–0.78–0.86–1.212 1.81–1.96–1.92–1.92–1. of cases/person-years Multivariate model 1 Multivariate model 2 Multivariate model 3 All grain products. nuts.001 .05–1.00 1.20) 519/144. was associated with an increased risk of gout.000 kcal/day No.91 (0.06 (0. the HR of the higher 3 quartiles combined was 0.97) 0.693 1.08) 0.91 (0.737 0.00 510/142.08) 0.000 kcal/day No. Hazard ratios and 95% confidence intervals for the risk of gout in 2.86–1.88–1.91 (0. baseline presence of diabetes mellitus.89–1. gm/1. of cases/person-years Multivariate model 1 Multivariate model 2 Multivariate model 3 Poultry.305 0.03–1.96 (0.06 (0.33) 1.89 (0.08) 0.09) 0.012 500/138. soy foods.79–1.00) 0.932 1.167 participants in the Singapore Chinese Health Study 1993–2010.16) 561/144.82–1.73–0.191 1.98 (0.04) 508/145.95 (0.96 (0.16 (1.00 539/143.95 (0.72–0.90 0.04 (0.14) 614/143.0.06) 0.00 1.85–1.11) 0.001 498/137.99–1.612 0.004 0.14 (1.00 1.0.00 1.000 kcal/day No.79–1.80–1.87–1.81–1.95) 0.38 (1.32) .14–1.321 1. gm/1.12) 471/135.90–1. Multivariate model 3 was adjusted for the same variables as for model 2 plus dietary intake of vegetables.96 (0.84–1. smoking status.80 0.86–1.92 (0.22 (1.00 560/144.82 (0.365 1. of cases/person-years Multivariate model 1 Multivariate model 2 Multivariate model 3 Fish and shellfish.93 (0.94) 0.94 (0.179 1.95–1.992 0.73–0.86–1.14) 0.368 1.28) 654/145.88–1.94–1.02 (0. and all grain products.83–1.96 0.24) 1.03 (0. of cases/person-years Multivariate model 1 Multivariate model 2 Multivariate model 3 P for trend Q1 Q2 Q3 Q4 473/140.83–1.00 558/143.10) 0.02) 564/146.78–1.09 (0.18) 594/140.95 (0. of cases/person-years Multivariate model 1 Multivariate model 2 Multivariate model 3 Soy foods.07) 590/142.358 0.09–1. baseline presence of hypertension.86–1.80–1.85–1.91–1. body mass index.99 (0.33) 1.04) for nonsoy legumes.94 (0.18 (1.001 .12 (0. gm/1.02) 0.84–1.06) 0.91–1.00 563/143. of cases/person-years Multivariate model 1 Multivariate model 2 Multivariate model 3 Nuts and seeds.79–1.008 0. higher consumption of poultry and fish/shellfish.DIET AND GOUT 1937 Table 3. and total energy.16–1.20) 0.17) 1. and year of interview. by source of dietary protein* Quartiles of energy-adjusted food intake Source of dietary protein Red meat.67 603/144.84 (0.92 (0.338 1.826 1.00 1.76–0.89 (0.98 (0.13) 0.97) 0.08) 0.96–1. gm/1.91 (0.005 0. nuts and seeds.87 (0.35) 1. fish and shellfish.77 * Linear trend was tested by assigning to participants the median value of the quartile and assessing this as a continuous variable.86–1.00 1.03) 0. of cases/person-years Multivariate model 1 Multivariate model 2 Multivariate model 3 Nonsoy legumes.00 1.84–1.97 (0. sex.755 0.24) 1. nonsoy legumes.08 (0.00 555/144.00 1.04–1.17) 1.00 (0.06) 0.03–1. become nonsignificant.000 kcal/day No.17 (1. eggs.804 0.91 (0. red meat.341 0.00 1.89 (95% CI 0.10) 0.96 (0. fruits.30) 1.00 1.85–1.001 0.97 (0.00 1.99) 0.945 0.03) 498/145.28 (1.94–1.77–0.588 0.94 (0. all of the higher quartiles (quartiles 2–4) still exhibited reduced risk as compared to the lowest quartile of intake.83 (0.0.12) 0. alcohol use. but not eggs.000 kcal/day No.85–1. gm/1.83–1.85–1.01 (0.450 1. of cases/person-years Multivariate model 1 Multivariate model 2 Multivariate model 3 Eggs.06) 0.13 (0.0.95 (0.00 536/143.00 1.94) 0.00 1. education level.85–1.24) 0.08) 544/142.019 0.000 kcal/day No.08 (0.48) 1.00 558/142.07) 0.19) 1.09) 540/145.23) 1.09 (0.10 (0.25 422/135.09) 0.92) 539/146.06) 0.81 (0.88 (0.92–1. DISCUSSION The present study demonstrated that among the Chinese population in Singapore.02) 555/142.00 1.523 1.83–1.00 1.96 (0.98–1.27 (1.09) 0.05 (0.83 (0.90) 0.10) 0.88–1.97–1.16 (1.411 0.81–1.796 1.01–1.97 (0.31 (1.531 1.72 562/134.92 (0.39 0.000 kcal/day No.13 (0.0.262 0.86 (0.93) 0.00) 0.001 .199 0. dairy products.95 (0.259 0. or seeds and grain products.474 1.99 (0.02–1.00 1.81–1.31) 1.71–0.96 (0.406 1.80–1.84–1.006 1.28) 1.06 (0.58 555/141.86 (0.99 (0.728 1.018 542/133. of cases/person-years Multivariate model 1 Multivariate model 2 Multivariate model 3 Dairy products.98) 0.006 536/138.18) 1.001 0.00 1. as compared to the lowest quartile of intake.97 (0. gm/1.03 (0.000 kcal/day No.94 (0.11–1.94 (0.96 (0.44) 1.84–1.10) 508/140.94–1.99–1.20) 1.04 (0.03) 0.56) 1. In the multivariate-adjusted model with dietary variables.85–1.80 (0.09) 0.00 538/146.04) 0.08) 0.05) 536/140. poultry.96 (0.85–1.37 0.19 (1. gm/1. gm/1.07) 545/145.45) .74–0.81–1.97 0. This study is the first prospective study to . Multivariate model 2 was adjusted for the same variables as for model 1 plus dialect.22–1. physical activity.86–1.392 1.00 1.97–1.74–0.19 0.637 0.000 kcal/day No.22) 1.01) for soy foods and 0.

20) 0.08 (0.04) 0. of cases HR (95% CI) P for interaction 305 336 283 269 1.75–1.27 346 318 288 241 1.29) 0.72–1.82 (0.13–1.92 (0.07 (0.000 kcal/day‡ Q1 Q2 Q3 Q4 P for trend Nuts and seeds.77–1.59) 0.36 (1.32 (1.00 1.000 kcal/day‡ Q1 Q2 Q3 Q4 P for trend Fish and shellfish.37 (1. gm/1.29 0.01 (0.10) 0. HRs and 95% CIs for the risk of gout in 1.85–1.65) .93 (0. % kcal/day† Q1 Q2 Q3 Q4 P for trend Red meat.97–1.13 (0.77–1.21) 0.22) 0.39 270 244 240 220 1.02 204 244 241 285 1.16 246 253 246 229 218 288 321 366 1.058 200 235 257 282 1.95 (0.45 323 297 296 277 1.76 (0.85 (0.90–1.92–1.16) 0.37) 1.91 (0.00 1.20) 1.79–1.86–1.14) 0.41) 1.81–1.04 (0.29) 1.55 0.77–1.97) 0.00 (0.90 (0.000 kcal/day‡ Q1 Q2 Q3 Q4 P for trend Women No.21) 1.64–0.26) 1.04 (0.17 (0.03 (0. gm/1.78–1.27) 1.21 (1.03–1.69–1.86 (0.31) 0.17) 0.001 0.007 0.06 204 248 234 288 1.00 0.34) 1.87–1.18 228 208 244 294 1.71–1. gm/1.57 175 213 249 337 1.67) 0.07) 0.06) 0.88 (0.14) 0.47 227 286 315 365 1.04 (0.73–1.17) 0.00 0.19 (1.77 (0.02) 0.89 (0.04 0.00 1.34) 1.02 (0.09) 0.12 (0.86–1.23) 0.193 men and women who participated in the Singapore Chinese Health Study 1993–2010.86–1.75–1.91 (0.86–1.19 (0.85 (0.22) 0.98 (0.77–1.00 1.74–1.81–1.79–1.84 327 352 300 214 1.12–1.10 (0.99–1.000 kcal/day‡ Q1 Q2 Q3 Q4 P for trend Dairy products.000 kcal/day‡ Q1 Q2 Q3 Q4 P for trend Nonsoy legumes.01 (0. gm/1. gm/1.08) 0.84–1.87–1.15 (0.03) 0.24) 1.35) 1.99 (0.97 (0.74–1.003 0.77–1. gm/1.79–1.00 0.90 0.93 (0.93 (0.0.00 0.18) 1.00 1.00 1.00 1.91–1.71 .98–1.37) 1.91–1.11 (0.84–1.97–1.81–1.10) 0.46 0.06) 1.79–1.85–1. gm/1.83–1.92–1.07) 0.91–1.08 (0.27) 1.00 1.64–0.86–1.83–1.00 0.08) 0.01 (0.10–1.061 175 228 232 339 1.84–1.14) 1.24) 1.00 (0.95 (0.10 (0.1938 TENG ET AL Table 4.00) 0.78 0.88 (0.05 241 313 292 347 1.00) 0.12 (0.88 (0.00 0.00 1. % kcal/day† Q1 Q2 Q3 Q4 P for trend Soy protein.00) 0.36) 1.00 0.49 272 319 324 278 1.003 0.04 358 314 267 254 1.81–1.43) 0.94 (0.94) 0.43) 0.02 (0.06 (0.000 kcal/day‡ Q1 Q2 Q3 Q4 P for trend Poultry.01–1.71 259 245 227 243 1.31) 1.76 1. of cases HR (95% CI) No. gm/1.000 kcal/day‡ Q1 Q2 Q3 Q4 P for trend Soy foods.39) 1.09) 0.75–1.10) 1.92–1.84–1. by source of dietary protein* Men Source of dietary protein Total protein.83 (0.97 (0.92 (0.92 (0.54 244 253 244 233 1.00 0.95–1.0 1.68–0.89) 0.000 kcal/day‡ Q1 Q2 Q3 Q4 P for trend Eggs.93–1.14 (0.79–1.00 0.43) 0.02 292 302 296 303 1.91 (0.04 (0.25) 0.35) 0.19 (0.07) 0.

and total energy.78 304 238 249 183 1.00 0. and lentils. body mass index. with only a small proportion of beef and lamb (3%). soy foods. To the best of our knowledge. poultry. Hence. including red meat and seafood. while a recent prospective study in mainland China showed that shrimp and shellfish intake. beans.87 (0. HRs 5 hazard ratios. In a cross-sectional study of Taiwanese men. the mean energy-adjusted intake of dairy products in men (35. smoking status.2 gm/1.75–1. Choi et al (18) showed that meat intake. Poultry constituted 21. nuts and seeds.82–1. Furthermore. dialect. physical activity. education level. † The multivariate model was adjusted for age.990 male runners followed up over a period of 8 years. with the majority being chicken (78% versus 22% duck). ‡ The multivariate model was adjusted for age. and total energy. such as soy foods and nonsoy legumes. year of interview. The Health Professionals Followup Study did not report any significant association between the intake of purine-rich vegetables. which are commonly consumed by Western populations. year of interview. body mass index.80–1. other meats.00 (0. In a cross-sectional study of Taiwanese men older than 65 years. In a prospective study of 28.6% of all meat intake.95 (0.11) 0. alcohol use. and all grain products. baseline presence of diabetes mellitus. and we acknowledge that this result may be due to chance. poultry (chicken and duck).73–1.21) 0. which included nonsoy legumes such as peas. was associated with an increased risk of developing gout in adults with hyperuricemia over a 5-year followup (26). fish and pork were the 2 most common types in both dialect groups and sexes. such as beef and lamb or mutton. baseline presence of diabetes mellitus. dairy products. 95% CIs 5 95% confidence intervals. smoking status. and the risk of gout in this cohort was consistent with the findings of previous studies. the red meat intake in this population consisted mainly of pork (97%). Our finding of increased risk of gout with intake of meat.0% and 30. respectively. We are unable to offer any reason for the biologic plausibility of the disparate findings of the association of dairy product with gout risk in men versus women. of cases HR (95% CI) P for interaction All grain products.000 kcal/day) was much lower than that in women (54.81–1. of cases HR (95% CI) No.DIET AND GOUT Table 4. The intake of dairy products in this Asian population is generally lower than that in Western populations (20). alcohol use. eggs. our finding of an inverse association between the intake of plant-based food sources of protein. was associated with an increased risk of gout. Among these. as obtained from 7-day dietary records. such as poultry and fish/ shellfish. fruits.0%. nonsoy legumes. consumption of poultry and shellfish was associated with an increased likelihood of being treated for hyperuricemia or gout (25).92 0. the risk of gout was shown to increase with higher intake of meat (19). pork.7% of all meats consumed. education level.74–1. no study has examined the association between intake of dairy products and risk of gout in women specifically.1% of all meats consumed by our study participants (24). constituted only . 1939 (Cont’d) Men Women Source of dietary protein No. fish and shellfish.14) 0. We previously analyzed data from 24-hour recall interviews with 986 cohort members who represented a randomly selected 3% of the study population recruited between February 1993 and August 1996 (20) and found that fish. Our finding of a positive association between meat intake and risk of gout is consistent with evidence from other epidemiologic studies. high intake of soy products was associated with a low likelihood of receiving treatment for hyperuricemia or .000 kcal/day‡ Q1 Q2 Q3 Q4 P for trend 299 300 306 288 1. show a possible protective association of soy foods and nonsoy legumes on the risk of developing gout. physical activity. are thus consistent with previous studies in both Western and Asian populations. and the risk of gout (18).21) 0. In contrast. gm/1. dialect. constituting 38.94 (0. baseline presence of hypertension.000 kcal/day). In contrast.97 (0. baseline presence of hypertension. and crustaceans (primarily prawns/shrimp and cuttlefish) accounted for 98.150 Caucasian men who were followed up over a period of 12 years.00 0.8 gm/1. From the Health Professionals Followup Study of 47.93 * Linear trend was tested by assigning to participants the median value of the quartile and assessing this as a continuous variable. our finding of a possible interaction between sex and dairy products in association with a risk of gout needs to be validated in future studies. Hence.92 (0.04) 1. as well as for dietary intake of vegetables.16) 0. red meat.

In this study. and we did not TENG ET AL collect information on the treatment of the disease. it would result in an underestimation (as opposed to an overestimation) of the true relative risk. Since such misclassifications are likely to be nondifferential. soy and nonsoy legumes are plausible vegetable-based meat substitutes with possible beneficial effects for patients with gout. even though there were differences between the subjects who were included in the study and those who were excluded. if true. A national health and dietary survey in Taiwan evaluated the dietary trends for hyperuricemia using a 28-item FFQ and showed that higher frequency of intake of soy products was associated with reduced blood urate levels (3). such as cardiovascular diseases (36). China.37). are not associated with an increased risk of gout. our study is the first prospective study to suggest a possibly protective effect of soy foods on the risk of developing gout. to increase the accuracy of self-reported physician-diagnosed gout. To our knowledge. requiring the presence of intraarticular urate crystals or tophus as the gold standard for the diagnosis of gout was not feasible. and the intake of soy products contributed . The validity of classifying patients with gout in the primary care setting using the ACR criteria is further limited (39). One potential limitation is that gout was self-reported. are also perpetuated by non–evidence-based patient education materials (14. Other limitations of this study include the possible misclassification of dietary intake from the use of a FFQ.1940 gout (25). Another strength is the lack of recall bias in exposures. these nonparticipants would be expected to have been older and to have had other baseline characteristics that were different from those who participated. all of our statistical models included these factors as covariates. intervention studies administering tofu or isolated soy protein to gout or healthy individuals have not shown clinically relevant elevation of urate levels (28. To remove possible confounding bias due to these factors. had lower blood urate levels (27). Another study among 55 young Chinese Buddhist vegetarians and 59 Chinese medical students (nonvegetarians) in Taiwan found that vegetarians. whereby gout was defined by an affirmative answer to the question “Have you been told by a doctor that you have gout?” In addition. Hence. low concordance between physician assessments and various gout criteria is common (40). lentils. A comprehensive approach to measuring and controlling for multiple potential risk factors for gout minimized the likelihood of spurious associations. The high specificity of the American College of Rheumatology (ACR) preliminary criteria for a diagnosis of gout is often not met in epidemiologic studies (38). As with population-based studies. Even in English-speaking health professionals. however. and Singapore (30). may be mediated through the promotion of weight loss (31) and an enhanced uricosuric effect (32. In conclusion. Contrary .35). given that information on dietary intake was collected from participants many years before the diagnosis of gout was made. 30% of cases who reported to have gout did not fulfill the ACR criteria (18). and since the main reason for nonparticipation was the death of the study subject. the conclusions of the present study should be valid.5 times that of nonvegetarians. such as beans. this prospective study demonstrated that total protein intake of poultry and fish/shellfish was associated with an increased risk of gout. The myths about restricting plant-based foods that are high in purines.33).5–10% of the overall dietary protein intake in Asian countries such as Japan. Counteracting these popular myths. soy. Although large-scale cohort studies in the US (37) have shown that 94% of self-reported gout can be validated through review of medical records for fulfillment of the ACR criteria. we adopted the same methodology used in other cohort studies (9. The strength of this study is the large number of incident gout cases identified from a population-based prospective cohort with a relatively long followup period. Soy products. and investigators have suggested that self-report of physician-diagnosed gout is appropriate for epidemiologic studies (41). our data provide further evidence that plant sources of protein. Validation using drug prescription data and medical records was not feasible in our study. and certain vegetables. such as soy milk and tofu. it is therefore important to determine the effect of soy on the risk of gout.29). are important plant sources of protein in many Asian countries. Finally. A recent International Life Science Institute survey found that an overwhelming 50–80% of health care professionals believed that soy foods should be avoided and advised their gout patients accordingly (34). we had trained our interviewers to further enquire if the joint pain and swelling from gout had been attributed by their physicians to hyperuricemia. such as soy and nonsoy legumes. Given the protective effect of soy products and nonsoy legumes on the risk of other undesirable health outcomes. As soy foods are also gaining popularity in the Western countries. Finally. The protective association between soy and gout. our study excluded subjects who did not participate in the followup interviews. Two population-based cohorts in the US showed that self-report of physician-diagnosed gout had moderateto-good reliability and sensitivity. Our study has some limitations. whose consumption of soybean products was 3.

Nutr Cancer 2006. J Am Diet Assoc 2007. Schumacher HR Jr. 12. 10. 1990-1999. org/PDFs/goutsociety-allaboutgoutanddiet-0113. et al. Seow A. Nutr Cancer 2001. Circulation 2007. Doherty M. 22. 18. Gout epidemiology: results from the UK General Practice Research Database. et al. et al.com. Kundukulam J. Risk factors for gout developed from hyperuricemia in China: a five-year prospective cohort study. Luo SF.87:1480–7. Estimated Asian adult soy protein and isoflavone intakes. Acquisition of data.17 Suppl 1:324–8. Pan. Grandits G. Strand V. Howe GR. Bardin T. Stram DO. Gout is associated with more comorbidities. Wang Y. Saag KG. Singh JA. J Am Coll Nutr 1992. Our findings from this population-based cohort of Chinese subjects living in Singapore provide evidence for establishing dietary guidelines for the prevention of gout that would be applicable to other Asian populations. Curhan G. NIH. Anderson JW. Neogi T. Beneficial effects of soy protein consumption for renal function. Arakawa K. vigorously active men. MedlinePlus medical encylopedia: soy. Analysis and interpretation of data. Monroe KR. Zhang W. et al. Moriwaki Y. Williams PT. Pike MC. 3. Wu AH. URL: http://www. Willett WC. Choi HK.64:1431–46. 8. Independent impact of gout on mortality and risk for coronary heart disease. Koh WP. Hankin JH. ACKNOWLEDGMENTS We thank Siew-Hong Low (National University of Singapore) for supervising the field work of the Singapore Chinese Health Study and Kazuko Arakawa and Renwei Wang for the development and maintenance of the cohort study database. Willett W. Roddy E. Yuan. 28. Park S. Sarwar G. Changes in serum and urinary uric acid levels in normal human subjects fed purine-rich foods containing different amounts of adenine and hypoxanthine. Curhan G. Am J Clin Nutr 1993. Singh MK. Messina M. Gout: an independent risk factor for all-cause and cardiovascular mortality. AUTHOR CONTRIBUTIONS All authors were involved in drafting the article or revising it critically for important intellectual content. 21.58:354–9. Wang F. Choi HK.33:705–10.65:1312–24. Yamakita J. Teng. Bilker WB. 27. and lifestyle modifications for gout. Risk factors for gout and prevention: a systematic review of the literature.151:358–70. 24. Epidemiology. Krishnan E.nlm.10: R17.ukgoutsociety. See LC. Karlson EW. Wigley R. Calibration of the dietary questionnaire for a multiethnic cohort in Hawaii and Los Angeles. Mikuls TR. Svendsen K.11:353–8. Am J Epidemiol 2000. consumption of soy foods and nonsoy legumes may have beneficial effects on the risk of gout. . Part 1. Conditions and treatment: gout.49:141–6. UK Gout Society. et al. Singh JA. Eur J Clin Nutr 2005. 9. Yang HQ.71: 924–8.14:195–202. Wilkens LR. Yu MC. et al. Am J Clin Nutr 1997. Koh. Gordon BA. Lin YS. Tsutsumi Z. National Library of Medicine. Curr Opin Rheumatol 2011. Atkinson K. FitzGerald JD. Kushi LH. 2.168:1104–10. Lv J.sg/PatientCare/ConditionsAndTreatments/Pages/ Gout. et al.116:894–900. the founding Principal Investigator of the Singapore Chinese Health Study for creating the food and nutrient variables used in this study. Dr. 16. singhealth. Prospective study of dietary patterns and persistent cough with phlegm among Chinese Singaporeans. Yuan JM. Pan. Effects of diet. Ko YS. Effect of tofu (bean curd) ingestion on uric acid metabolism in healthy and gouty subjects. Chang WC. Singapore Chinese Health Study: development. 23. 29. 17.65 Suppl: 1220S–8S. EULAR evidence based recommendations for gout. Ann Rheum Dis 2011. Teng GG.46:1441–4.gov/medlineplus/ency/ article/007204. We acknowledge Mimi C. Mortality due to coronary heart disease and kidney disease among middle-aged and elderly men and women with gout in the Singapore Chinese Health Study. 31. Conaghan P.htm. Rheumatology (Oxford) 2010. Butler LM. Koh WP. poorer health-related quality of life and higher healthcare utilisation in US veterans. Saag KG. J Rheumatol 2001.28:1640–6. Zhao S. Hyperuricemia and gout in Taiwan: results from the Nutritional and Health Survey in Taiwan (1993-96). Preliminary study: soy milk as effective as skim milk in promoting weight loss. Koh 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. Higashino K. Khanna D. Yang HN. et al. Yamamoto T. Darmawan J. Luebbers P. 15. 13. Purine-rich foods. Doherty M. URL: http://www. Sheu CT. Brule D. Chen SB. Arch Intern Med 2008.59:16–23. 30. Dietary intake and the risk of hyperuricemia. and the risk of gout in men. Stram DO. Potential sources of carcinogenic heterocyclic amines in the Chinese diet: results from a 24-hour dietary recall study in Singapore. Singhealth. Koh WP. Reddy SG. Yan S. Chuang SY. Chen R. Neaton JD. risk factors.173:264–70. URL: http://www. Zeng QY.67:1310–6. REFERENCES 1. Lukaszuk JM. Khanna PP. Pan WH. Lee HP. Saag KG. Hwang JS. Arthritis Care Res (Hoboken) 2012.nih. Farrar JT. Lee HP. Takahashi S. 6. Yu. Yeh WT. and calibration of the quantitative food frequency questionnaire. Hemostatic factors and blood lipids in young Buddhist vegetarians and omnivores. Ann Rheum Dis 2006.8 Suppl 1:S2. London SJ. and all authors approved the final version to be published. Teng.55:1–12. Low SH. Is gout associated with reduced quality of life? A case-control study. Yuan. Adv Exp Med Biol 1998. Chin CJ. Part II.DIET AND GOUT 1941 to popular belief. Ann Rheum Dis 2005. Ang LW. Trends in hyperuricemia and gout prevalence: Nutrition and Health Survey in Taiwan from 1993-1996 to 2005-2008. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Kuller LH. 25.20:301–8. Lee SC. Barskova V. Diet factsheet. Long-term cardiovascular mortality among middle-aged men with gout. Lee MH.39:187–95. physical activity and performance. 7. Tsai KS. Koh. N Engl J Med 2004. Ann Rheum Dis 2008. Rheumatol Int 2013. dairy and protein intake. Park S. Hsieh YT. Study conception and design.107:1811–4. Asia Pac J Clin Nutr 2011. 14. Rheumatology (Oxford) 2007. Arthritis Res Ther 2006. Aging Male 2011. 11. Xiao ZY. Savoie L.pdf. Management.350:1093–103. gout and chronic kidney disease in elderly Taiwanese men. 2012 American College of Rheumatology guidelines for management of gout. Kuo CF. Li C. Koh. Nagata C. Pan WH. Fernandes S. 32. Zhang W.431:839–42. and body weight on incident gout in ostensibly healthy. 26. Hankin JH. Rheumatic diseases in China. Am J Respir Crit Care Med 2006. Pascual E. Am J Clin Nutr 2008. Bae S. Adjustment for total energy intake in epidemiologic studies. Arthritis Res Ther 2008. Low SH. Yu MC. Tseng M.23:192–202.64:267–72. 20.aspx. Pan WH. Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Choi H. validation. 5. 19. Asia Pac J Clin Nutr 2008. Chang HY. 4.

Soy consumption. McAdams MA. van Weel C. Validity of gout diagnoses in administrative data. hyperuricemia and gout: a review of the epidemiologic and clinical data. Hamet P. Asia Pac J Clin Nutr 2011. Harrold LR.20:347–58. Janssens HJ. and pro-inflammatory cytokines: a brief review of the literature.20:895–900. Messina MJ. 36. TENG ET AL 38. 39. et al. 37. 41.67:213–21. Preliminary criteria for the classification of the acute arthritis of primary gout. Jonnalagadda SS. Messina M. Decker JL. Masi AT. Arthritis Rheum 2007. Coresh J. Am J Clin Nutr 1991. Verdy M. Soyfoods. PetitClerc C.asp. URL: http://www. 40. Andrade SE. Ann Rheum Dis 2010.38:135–41.sg. Gelber AC. Milk. van Riel PL.1942 33. Arch Intern Med 1997. Beavers KM. Limited validity of the American College of Rheumatology criteria for classifying patients with gout in primary care. Gout and risk for subsequent coronary heart disease: the Meharry-Hopkins Study. J Rheumatol 2011. et al. . Nutrition.com. Fouayzi H. Pearson TA. Chan P. Martin C. Garrel DR. McCarty DJ. Janssen M. Wallace SL.53:665–9.69:1255–6.157: 1436–40. Fransen J. Maynard JW. 34.com. Questions and answers on the topic of gout. Robinson H. Mikuls TR. Brule D. Arthritis Rheum 1977. Nutr Rev 2009.and soy-protein ingestion: acute effect on serum uric acid concentration.sg/atd/atdgout. Klag MJ. Yu TF. Baer AN. et al. van de Lisdonk EH. Kottgen A. Thomas J. adhesion molecules. Saag KG.57:103–8. Mead LA. Clipp S. Yood RA.nutrition. 35. Thomas DJ. Reliability and sensitivity of the self-report of physician-diagnosed gout in the campaign against cancer and heart disease and the atherosclerosis risk in the community cohorts. Messina VL.