Characteristics of Study Participants
The median age of 38,027 subjects was 55.53 ± 12.21 years in the total population. Table 1 presents the general characteristics of the participants according to the spicy food flavor and the spicy food intake frequency. Participants with preference to heavier spicy flavor tended to be younger in age; be male with married or cohabiting; have more total energy intake; less drinking and smoking status; more physical activity; higher BMI and serum urate level; less T2DM and hypertension status. (all P trend < 0.001). Similar difference of distribution in these selected variables also were found among four spicy food intake frequency groups (all P trend < 0.001).
Table 1. Demographic and clinical characteristics of study participants according to spicy food flavor and intake frequency
Variable
|
Spicy food flavor
|
Ptrend
|
Spicy food intake frequency
|
Ptrend
|
No
|
Mild
|
Middle
|
Heavy
|
Never
|
1-2d/week
|
3-5d/week
|
6-7 d/week
|
Mean
|
SD
|
Mean
|
SD
|
Mean
|
SD
|
Mean
|
SD
|
Mean
|
SD
|
Mean
|
SD
|
Mean
|
SD
|
Mean
|
SD
|
No. participants
|
16282
|
14889
|
5326
|
1530
|
12361
|
3268
|
3264
|
10026
|
Age (years)
|
58.3
|
11.4
|
53.9
|
12.3
|
52.3
|
12.4
|
52.1
|
11.5
|
<0.001
|
58.2
|
11.7
|
51.6
|
13.2
|
51.4
|
13.5
|
54.4
|
11.6
|
<0.001
|
Male (%)
|
37.8
|
38.4
|
44.1
|
46.4
|
<0.001
|
39.1
|
38.1
|
44.6
|
42.1
|
<0.001
|
Educational level (%)
|
<0.001
|
<0.001
|
Illiterate and Elementary
|
49.0
|
41.5
|
41.0
|
42.8
|
48.4
|
33.6
|
34.7
|
45.6
|
Middle school
|
37.1
|
41.8
|
41.9
|
43.5
|
36.1
|
41.4
|
41.4
|
40.8
|
High school and above
|
13.9
|
16.7
|
17.2
|
13.7
|
15.5
|
25.0
|
23.9
|
13.7
|
Marital status (%)
|
<0.001
|
<0.001
|
Married/cohabiting
|
87.9
|
90.7
|
91.9
|
92.0
|
88.2
|
91.4
|
90.8
|
91.7
|
Widowed/single/divorced/separation
|
12.1
|
9.3
|
8.1
|
8.0
|
11.8
|
8.6
|
9.2
|
8.3
|
Smoking status(%)
|
<0.001
|
<0.001
|
Nonsmoker
|
76.6
|
72.4
|
66.5
|
61.1
|
75.6
|
74.6
|
67.0
|
68.3
|
Ex-smoker
|
8.6
|
7.7
|
7.1
|
6.8
|
8.4
|
6.5
|
7.9
|
7.4
|
smoker
|
14.9
|
19.9
|
26.4
|
32.1
|
16.0
|
18.8
|
25.2
|
24.3
|
Drinking status(%)
|
<0.001
|
<0.001
|
Nondrinker
|
82.7
|
75.6
|
68.1
|
68.9
|
83.2
|
77.2
|
72.1
|
72.6
|
Ex-drinker
|
5.3
|
4.0
|
4.1
|
4.4
|
5.3
|
3.7
|
4.4
|
4.8
|
Drinker
|
12.1
|
20.4
|
27.7
|
26.7
|
11.5
|
19.0
|
23.5
|
22.6
|
Physical activity (%)
|
<0.001
|
<0.001
|
Low
|
34.8
|
30.8
|
28.7
|
31.4
|
35.8
|
34.4
|
31.8
|
26.1
|
Middle
|
37.2
|
38.9
|
37.2
|
35.9
|
35.4
|
32.3
|
37.5
|
39.7
|
High
|
28.0
|
30.3
|
34.0
|
32.7
|
28.8
|
33.3
|
30.8
|
34.2
|
Dietary pattern
|
<0.001
|
<0.001
|
Pattern I
|
18.6
|
20.9
|
23.2
|
27.5
|
18.7
|
20.9
|
22.6
|
21.8
|
Pattern II
|
30.7
|
35.3
|
33.9
|
38.8
|
28.6
|
29.1
|
30.2
|
41.3
|
Pattern III
|
22.4
|
19.2
|
20.1
|
16.4
|
23.0
|
22.3
|
20.8
|
16.9
|
Pattern Ⅳ
|
28.4
|
24.6
|
22.9
|
17.3
|
29.7
|
27.6
|
26.4
|
20.0
|
Total energy intake (kcal/d)
|
2387
|
661.1
|
2467
|
663.9
|
2531
|
691.2
|
2700
|
695.3
|
<0.001
|
2368
|
662.8
|
2367
|
652.6
|
2443
|
662.1
|
2604
|
693.1
|
<0.001
|
BMI ( kg/m 2)
|
24.63
|
3.52
|
24.94
|
3.51
|
25.20
|
3.75
|
25.13
|
3.68
|
<0.001
|
24.57
|
3.51
|
25.01
|
3.62
|
24.83
|
3.66
|
24.85
|
3.57
|
<0.001
|
Serum creatinine (umol /L)
|
62.58
|
14.9
|
61.58
|
13.72
|
61.45
|
13.37
|
62.68
|
12.94
|
<0.001
|
63.23
|
15.27
|
62.52
|
14.74
|
63.78
|
14.41
|
62.36
|
13.07
|
<0.001
|
Serum urate level (umol /L)
|
282.43
|
77.0
|
287.7
|
80.5
|
290.7
|
82.8
|
301.6
|
84.1
|
<0.001
|
288.5
|
77.6
|
296.9
|
83.9
|
301.4
|
86.7
|
297.2
|
81.2
|
<0.001
|
T2DM (%)
|
10.6
|
8.5
|
8.88
|
8.6
|
<0.001
|
10.0
|
8.1
|
7.4
|
8.0
|
<0.001
|
Hypertension (%)
|
36.5
|
30.88
|
29.5
|
22.7
|
<0.001
|
36.2
|
31.7
|
30.2
|
27.7
|
<0.001
|
Dyslipidemia (%)
|
37.8
|
37.0
|
38.4
|
39.5
|
0.084
|
38.7
|
38.8
|
38.4
|
38.7
|
0.984
|
SD, standard deviation.
*Statistical analyses: Spearman correlation for continuous variables and Cochran-Mantel-Haenszel tests for categorical variable
Prevalence of hyperuricemia
The prevalence of hyperuricemia according to the categories of spicy food flavor and intake frequency are depicted in Figure 1. In the total population, the crude and age-standardized prevalence of hyperuricemia according to the spicy food flavor were 9.03%, 10.02%, 10.21% and 11.90% (crude) and 10.30%, 12.47%, 13.76% and 15.67% (standardized), respectively (Fig. 1A). Similarly, the crude and age-standardized prevalence of hyperuricemia were 9.94%, 12.61%, 13.15%, and 11.65% (crude) and 11.66%, 14.50%, 15.44%, and 15.91% (standardized) across the groups of spicy food intake frequency, respectively (Fig. 1B). In addition, increasing trends in the prevalence of hyperuricemia were observed with the level of spicy flavor or intake frequency ( all P trend < 0.001).
Table 2. OR (95%CI) of hyperuricemia according to spicy food flavor and spicy food intake frequency
Events/N
|
Model 1
|
Model 2
|
Model 3
|
Model 4
|
Spicy food flavor
|
OR (95%CI)
|
OR (95%CI)
|
OR (95%CI)
|
OR (95%CI)
|
No
|
1366/16282
|
1.00 (Reference)
|
1.00 (Reference)
|
1.00 (Reference)
|
1.00 (Reference)
|
Mild
|
1750/14889
|
1.12 (1.04, 1.21)
|
1.10 (1.00, 1.20)
|
1.09 (1.00, 1.19)
|
1.05 (0.96, 1.15)
|
Middle
|
611/5326
|
1.15 (1.03, 1.27)
|
1.11 (0.99, 1.26)
|
1.10 (0.97, 1.24)
|
1.02 (0.91, 1.16)
|
Heavy
|
181/1530
|
1.42 (1.21, 1.67)
|
1.21 (1.01, 1.45)
|
1.21(1.10, 1.46)
|
1.13 (0.93, 1.36)
|
Each level increment
|
1.10 (1.06, 1.14)
|
1.06 (1.01, 1.11)
|
1.06 (1.01, 1.10)
|
1.03 (0.98, 1.08)
|
P trend
|
<0.001
|
0.011
|
0.017
|
0.276
|
Spicy food
intake frequency
|
Never
|
762/12361
|
1.00 (Reference)
|
1.00 (Reference)
|
1.00 (Reference)
|
1.00 (Reference)
|
1-2d/week
|
265/3268
|
1.31 (1.16, 1.47)
|
1.18 (1.04, 1.34)
|
1.15 (1.01, 1.31)
|
1.10 (0.97, 1.25)
|
3-5d/week
|
511/3246
|
1.37 (1.22, 1.54)
|
1.16 (1.03, 1.32)
|
1.14 (1.01, 1.30)
|
1.10 (0.97, 1.26)
|
6-7d/week
|
1180/10026
|
1.19 (1.10, 1.30)
|
1.15 (1.05, 1.26)
|
1.15 (1.05, 1.26)
|
1.10 (0.99, 1.21)
|
Each level increment
|
1.02 (1.01, 1.04)
|
1.02 (1.01, 1.03)
|
1.02 (1.01, 1.03)
|
1.01 (0.99, 1.02)
|
P trend
|
<0.001
|
0.007
|
0.007
|
0.078
|
Model 1: unadjusted.
Model 2: adjusted for age, gender, education level, marital status, smoking and drinking status, physical activity, dietary pattern, serum creatinine, total energy intake.
Model 3: adjusted for model 2 plus T2DM, hypertension and dyslipidemia status.
Model 4: adjusted for model 2 plus BMI
Association of spicy food intake with hyperuricemia
As shown in Table 2, the findings revealed a positive relationship between spicy food intake and hyperuricemia. After adjusting multiple variables in model 3, , the ORs (95% CIs) of Mild, Middle, and Heavy compared with no preference for spicy food flavor were 1.09 (1.00-1.19), 1.10 (0.97-1.24) and 1.21 (1.10-1.46), respectively (P trend =0.017). The OR (95% CI) for hyperuricemia of each level increased was 1.06 (1.01-1.10). Compared with never spicy food intake, the adjusted OR (95% CI) for 1-2 days/week, 3-5 days/week, and 6-7 days/week were 1.15 (1.01-1.31), 1.14 (1.01-1.30) and 1.15 (1.05-1.26), respectively (P trend =0.007), the adjusted OR for each level increment in spicy food intake frequency was 1.02 (1.01-1.03). But the association between spicy food flavor or intake frequency and hyperuricemia was significantly attenuated after further adjustment for BMI in model 4 ( all P trend > 0.05).
Association of spicy food intake with BMI and serum urate level
The associations of spicy food flavor, intake frequency with BMI and serum urate level are summarized in Table 3. After adjusting multiple variables in model 2, compared with no preference for spicy food flavor, the β Coefficients and 95% CI of Mild, Middle, and Heavy with BMI were 0.29 (0.20, 0.38), 0.50 (0.37, 0.63) and 0.49 (0.28, 0.70), respectively (P trend < 0.001). Compared with never spicy food intake, the adjusted OR (95% CI) for 1 or 2 days/week, 3 or 5 days/week, and 6 or 7 days/week was 0.39 (0.26, 0.53), 0.26 (0.12, 0.40) and 0.27 (0.17, 0.36), respectively. Similarly, in model, the Mild, Middle, and Heavy flavor were associated with a 5.27 μmol/L (95% CI : 3.47, 7.08), 4.62 μmol/L (2.08, 7.17) and 10.78 μmol/L (6.70, 14.86) higher serum urate levels; the 1-2 days/week, 3-5 days/week, and 6-7 days/week intake frequency were associated with 5.29 μmol/L (95% CI : 2.59, 7.12), 4.40 (1.69, 7.12) and 5.80μmol/L (3.91, 7.68).
Table 3 The association (β Coefficients and 95% CI) of spicy food flavor or intake frequency with BMI and serum urate level.
|
Spicy food flavor
|
Spicy food intake frequency
|
No (n=16282)
|
Mild
(n=14889)
|
Middle
(n=5326)
|
Heavy
(n=1530)
|
Never
(n=12361)
|
1-2d/week
(n=3268)
|
3-5d/week
(n=3246)
|
6-7d/week
(n=10026)
|
BMI (kg/m 2 )
|
Model 1
|
Reference
|
0.30 (0.22, 0.38)
|
0.56 (0.45, 0.67)
|
0.51 (0.33, 0.70)
|
Reference
|
0.44 (0.30, 0.57)
|
0.26 (0.13, 0.40)
|
0.28 (0.19, 0.38)
|
Model 2
|
Reference
|
0.29 (0.20, 0.38)
|
0.50 (0.37, 0.63)
|
0.49 (0.28, 0.70)
|
Reference
|
0.39 (0.26, 0.53)
|
0.26 (0.12, 0.40)
|
0.27 (0.17 0.36)
|
Serum urate level (μmol/L)
|
Model 1
|
Reference
|
5.32 (3.55, 7.08)
|
8.24 (5.78, 10.70)
|
19.13 (14.96, 23.30)
|
Reference
|
8.35 (5.24, 11.46)
|
12.79 (9.67, 15.91)
|
8.67 (6.54, 10.79)
|
Model 3
|
Reference
|
5.27 (3.47, 7.08)
|
4.62 (2.08, 7.17)
|
10.78 (6.70, 14.86)
|
Reference
|
5.29 (2.59, 7.99)
|
4.40 (1.69, 7.12)
|
5.80 (3.91, 7.68)
|
Model 1: unadjusted.
Model 2: adjusted for age, gender, education level, marital status, smoking and drinking status, physical activity, dietary pattern, total energy intake.
Model 3: adjusted for age, gender, education level, marital status, smoking and drinking status, physical activity, dietary pattern, total energy intake, serum creatinine.
Table 4. Mediation analysis of the relationship between spicy food flavor or intake frequency and hyperuricemia by BMI.
Spicy food flavor
|
Spicy food intake frequency
|
Mediation analysis
|
Parameter estimate (95% CI)
|
OR (95% CI)
|
Parameter estimate (95% CI)
|
OR (95% CI)
|
Total effect
|
0.0598 (0.0136, 0.1060)
|
1.062 (1.014, 1.112)
|
0.0175 (0.0048, 0.0301)
|
1.018 (1.005, 1.030)
|
Direct effect path c’
|
0.0255 (-0.0222, 0.0731)
|
1.026 (0.978, 1.076)
|
0.0120 (-0.0010, 0.0250)
|
1.012 (0.998, 1.025)
|
Path a
|
0.2191 (0.1685, 0.2696)
|
1.245 (1.184, 1.309)
|
0.0356 (0.0221, 0.0491)
|
1.036 (1.022, 1.050)
|
Path b
|
0.1560 (0.1454, 0.1667)
|
1.169 (1.156, 1.181)
|
0.1560 (0.1454, 0.1667)
|
1.169 (1.156, 1.181)
|
Indirect effect path ab
|
0.0342 (0.0266, 0.0426 )
|
1.035 (1.027, 1.044)
|
0.0055 (0.0035, 0.0079)
|
1.006 (1.004, 1.008)
|
Adjusted for age, gender, education level, marital status, smoking and drinking status, physical activity, dietary pattern, total energy intake, serum creatinine, T2DM, hypertension and dyslipidemia status.
BMI, body mass index; CI, confidence interval.
Path c’ indicates the path from spicy food flavor or intake frequency to hyperuricemia (Outcome) when controlled for BMI (Mediator). Path a indicates the path from spicy food flavor or intake frequency to BMI (Mediator), Path b indicates the path from BMI (mediator) to hyperuricemia (Outcome). Path ab coefficients represent 5,000 bootstrapped samples and bias-corrected 95% CIs.
Mediating role of BMI
Table 4 provides results of regressions conducted to test for mediation effects and Figure 2 illustrates the output model for the mediation effect of BMI. The total effect spicy food flavor on hyperuricemia was significant (total effect, OR=1.062; 95% CI=1.014-1.112; P=0.011). The estimated ORs (95%CIs and P value) of a significant indirect effect mediated by BMI and a nonsignificant direct effect were 1.035 (95% CI=1.027-1.044 and P=0.0042) and 1.026 (95% CI=0.978-1.076 and P=0.2948), respectively (Fig. 2A). Similarly, the total effect spicy food flavor on hyperuricemia also was significant (total effect, OR=1.018; 95% CI=1.005-1.030; P=0.007). A significant indirect effect mediated by BMI (OR=1.006; 95% CI=1.004-1.008; P=0.0011) and a nonsignificant direct effect (OR=1.012; 95% CI=0.998-1.025; P=0.0711) were also included in the mediating process (Fig. 2B). The finding confirmed our hypothesis that the relationship between spicy food intake and hyperuricemia was mediated by BMI.