General characteristics
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 by categories of the spicy food flavor and the spicy food intake frequency. Participants with heavier spicy flavor were more likely to be younger in age, be male with married or cohabiting, have more total energy intake, less likely to be drinker and smoker, more physical activity, higher BMI and serum urate level, and less T2DM and hypertension status (all P trend < 0.001). Similar differences of distribution in these selected variables were also found among four groups of intake frequency (all P trend < 0.001).
Table 1. Sociodemographic characteristics of participants grouped by 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. T2DM, type 2 diabetes mellitus
Prevalence of hyperuricemia
The prevalence of hyperuricemia across different categories of spicy food flavor and intake frequency is displayed in Figure 1. In all participants, the crude prevalence of hyperuricemia with No, Mild, Middle, and Heavy spicy flavors were 9.03%, 10.02%, 10.21% and 11.90%, respectively; and the corresponding age-standardized hyperuricemia prevalence were 10.30%, 12.47%, 13.76% and 15.67%, respectively (Fig. 1A). Similarly, the crude prevalence of hyperuricemia with intake frequency of Never, 1-2 d/week, 3-5 d/ week and 6-7 d/week were 9.94%, 12.61%, 13.15%, and 11.65%, respectively; and the corresponding age-standardized hyperuricemia prevalence were 11.66%, 14.50%, 15.44%, and 15.91%, respectively (Fig. 1B). In addition, increased trends in the prevalence of hyperuricemia were observed with the increasing level of spicy flavor and intake frequency (all P trend < 0.001).
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 controlling for multiple variables in model 3, the ORs (95% CIs) of Mild, Middle, and Heavy flavors compared with no 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 adjusted OR (95% CI) for each level increment in spicy flavor strength was 1.06 (1.01-1.10). Compared with those without intake in spicy food, participants in intake frequency of 1-2 days/week, 3-5 days/week, and 6-7 days/week were 1.15, 1.14 and 1.15 times more likely to have hyperuricemia (P trend =0.007). The adjusted OR (95% CI) for each level increment in spicy food intake frequency was 1.02 (1.01-1.03). But the association of spicy food flavor or intake frequency with hyperuricemia was significantly attenuated after additional adjustment for BMI in model 4 (all P trend > 0.05).
Table 2. OR (95%CI) of hyperuricemia grouped by spicy food flavor and 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 BMI and serum urate level
The associations of spicy food flavor, intake frequency with BMI and serum urate level are presented in Table 3. After adjusting for potential confounders in model 2, compared with no 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 those without intake in spicy food, the adjusted ORs (95% CIs) for 1-2 days/week, 3-5 days/week, and 6-7 days/week were 0.39 (0.26, 0.53), 0.26 (0.12, 0.40) and 0.27 (0.17, 0.36), respectively. Similarly, in model 3, the Mild, Middle, and Heavy flavor were associated with a 5.27μmol/L (95% CI : 3.47, 7.08), 4.62μmol/L (2.08, 7.17) and 10.78μmol/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 5.29μmol/L (95% CI : 2.59, 7.12), 4.40μmol/L (1.69, 7.12) and 5.80μmol/L (3.91, 7.68) higher serum urate levels.
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.
Mediating role of BMI
Table 4 provides results of mediation analyses and Figure 2 demonstrates the model process of BMI mediated the relationship of spicy food intake with hyperuricemia. 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 was also 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 results verified our hypothesis that the association of spicy food intake with hyperuricemia was mediated by BMI.
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; OR, odd ratio; CI, confidence interval; T2DM, type 2 diabetes mellitus.
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.