Abstract
Background:
Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association.
Methods:
This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results.
Results:
During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1–2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3–5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6–7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week (Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD (Ptrend = 0.011) and MCEs (Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD (Pinteraction = 0.037).
Conclusions:
Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Keywords: Prospective cohort studies, Spicy food consumption, Vascular disease, Healthy lifestyle, China Kadoorie Biobank, Stroke, Ischemic heart disease, Major coronary events
Introduction
Vascular diseases, including cardiovascular and cerebrovascular diseases, are becoming increasingly prevalent and have become the main cause of morbidity and mortality worldwide.[1–5] Especially in China, vascular disease-specific deaths account for more than 40% of the total deaths each year.[6–8] Therefore, exploring the risk factors related to vascular diseases is needed for early prevention.
As an important part of the human diet worldwide, spicy food has a long history of use.[9–11] Interestingly, cumulative evidence has demonstrated that capsaicin, the main nutrient component of spicy food, is helpful in improving vascular function,[12–14] as well as vascular disease prognosis, which was found in a previous study.[15] Most studies of European populations have reported that spicy food consumption is associated with a decreased risk of multiple diseases, such as hypertension, diabetes, vascular diseases, and obesity.[11,16–18] However, due to ethnic differences in diet and lifestyle, it may be inappropriate to extrapolate the findings in European populations to Chinese population. Hence, the relationship between spicy food consumption and vascular diseases in the Chinese population remains unclear.
Therefore, we aimed to investigate the association between spicy food consumption and the incidence of vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease in the prospective China Kadoorie Biobank (CKB) cohort of 486,335 participants, which may provide additional dietary guidance for the prevention of vascular diseases.
Methods
Ethical approval
This research was conducted using CKB Resource (application ID: DAR-2020-00120). The use of the CKB cohort was approved by the Ethical Review Committee of the Chinese Center for Disease Control and Prevention (Beijing, China) and the Oxford Tropical Research Ethics Committee, University of Oxford (Oxford, UK), and all participants provided written informed consent before taking part in the study. Access to CKB data was granted under Project Number DAR-2020-00120.
Study design and participants
This study was performed using the large-scale CKB prospective cohort of 512,723 participants from 10 different geographical regions in China who were aged 30–79 years at enrollment. Participants have been followed up until December 31, 2018. Further details of the CKB study design have been described elsewhere.[19–21] Additional information on the subjects is presented in the Supplementary Material, http://links.lww.com/CM9/C41.
Participants with a self-reported history of cancer or vascular disease (n = 26,344), those with negative values for the duration of spicy food consumption (n = 42), and those with missing body mass index (BMI) data (n = 2) were excluded from the study, and 486,335 participants were ultimately included in the study [Supplementary Figure 1, http://links.lww.com/CM9/C41].
Assessment of spicy food consumption
The variables regarding spicy food consumption were derived from the following: (1) consumption frequency: never/almost never and only occasionally (i.e., <1 day/week), 1–2 days/week, 3–5 days/week, and 6–7 days/week; (2) strength of spice: weak, moderate, and strong; and (3) the main sources of spice usually used: chili sauce, chili oil, dried chili pepper, fresh chili pepper, and others or unknown. Participants who ate spicy food more than once a week were defined as regular consumers. Additionally, we included 1603 participants who completed the same questionnaire twice within 1.5 years from baseline to the first resurvey. The Spearman’s coefficient of the frequency of spicy food consumption in the two questionnaires completed within 1.5 years was 0.73, indicating good reproducibility of spicy food consumption [Supplementary Table 1, http://links.lww.com/CM9/C41]. Detailed information on the assessment of spicy food consumption is provided in the Supplementary Material, http://links.lww.com/CM9/C41.
Follow-up and outcome measures
Participants were followed up periodically to minimize loss to follow-up. All fatal and non-fatal disease outcomes were obtained by linkage, using the unique national identification number of each participant, with disease registries and national health insurance claim databases. The national health insurance claim databases, which cover 96% of CKB participants, helped to improve the accuracy of diagnosis and further data collection.
The primary outcomes of this study were vascular disease (I00–I99), IHD (I20–I25), MCEs (I20–I25 [fatal], I21–I23), cerebrovascular disease (I60–I69), stroke (subarachnoid stroke [I60], hemorrhagic stroke [I61], ischemic stroke [I63], other or unspecified stroke [I64]), and non-stroke cerebrovascular disease (I62, I65–I69), as defined by the International Classification of Disease, 10th Edition (ICD-10). Additional information is presented in the Supplementary Material, http://links.lww.com/CM9/C41.
Statistical analysis
Consumption frequency was the main exposure variable. A Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between spicy food consumption and the risk of vascular disease. After adjusting for potential risk factors, the following multivariable models were established: (1) model 1: unadjusted; (2) model 2: adjusted for sex, age, and study site; (3) model 3: additionally adjusted for educational level, marital status, alcohol consumption, smoking status, physical activity, household income, BMI, intake frequencies of red meat, fruits, and vegetables, and diagnosis of hypertension at baseline.
Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics, including sex, age, physical activity in metabolic equivalent of task (MET), BMI, urban and rural area, smoking status, and drinking status.
In addition, we calculated healthy lifestyle scores by aggregating eight dietary and lifestyle factors, including smoking status (health level: no current smoking or having stopped smoking ≥15 years), alcohol consumption (health level: <25 g/day and <15 g/day for men and women, respectively), physical activity (health level: ≥20 MET h/day), BMI (health level: 18.5–23.9 kg/m2), waist-to-hip ratio (WHR) (health level: <0.90 and 0.85 for men and women, respectively), red meat consumption (health level: <5 days/week), preserved vegetable consumption (health level: <3 days/week), and fresh fruit/vegetable consumption (health level: >5 days/week). Participants were classified into three groups: a favorable lifestyle (including 6–8 healthy factors), an intermediate lifestyle (including 4–5 healthy factors), and an unfavorable lifestyle (including 0–3 healthy factors) group. We then evaluated the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease.
In addition, several sensitivity analyses were performed to assess the reliability of the association results: (1) an analysis in which participants who developed an event of interest during the first two years of follow-up were excluded; (2) an analysis in which additional seasonal adjustments were made; (3) an analysis in which additional adjustments were made for women’s menarche age, number of pregnancies, and menopause status; and (4) an analysis in which additional adjustment was made for diabetes. Moreover, we also explored the associations of the age at which spicy food began to be eaten regularly, the strength of spicy food eating, and the main sources of spice with vascular diseases risk, respectively.
All statistical analyses were performed using R Statistical Software (v4.2.2, R Foundation, Vienna, Austria). P values (two-sided) <0.05 were considered significant.
Results
Baseline characteristics of participants
A total of 486,335 participants were included in the current analysis, 59.07% of whom were women and 43.13% of whom were from urban areas, with a mean age of 51.53 years at baseline [Table 1]. Overall, 42.84% (208,331/486,335) of the participants were regular spicy food consumers; among these participants, 15.20% (31,657/208,331), 13.66% (28,459/208,331), and 71.14% (148,215/208,331) reported consuming spicy food 1–2 days/week, 3–5 days/week, and 6–7 days/week, respectively. The frequency of spicy food consumption varied greatly across the 10 study areas [Figure 1]. For example, in Hunan and Sichuan, 99.7% (56,738/56,912) and 77.9% (42,716/54,859) of participants consumed spicy food more than one day per week. Compared with participants consuming spicy foods less than once a week, those regular consumers were more likely to be current smokers and alcohol drinkers, to consume red meat and preserved vegetables more frequently, and to have lower levels of systolic blood pressure (SBP). Among regular consumers, those who consumed spicy foods almost every day (6–7 days/week) preferred a stronger spice intensity, consumed spice starting at an early age, and had a high proportion intake of fresh chili pepper and dried chili pepper.
Table 1.
Baseline characteristics of the participants according to weekly spicy food consumption.
| Characteristics | Frequency of spicy food consumption per week | All participants (n = 486,335) | |||
|---|---|---|---|---|---|
| <1 day (n = 278,004) | 1–2 days (n = 31,657) | 3–5 days (n = 28,459) | 6–7 days (n = 148,215) | ||
| Age (years) | 52.75 ± 10.67 | 49.14 ± 10.01 | 49.08 ± 9.81 | 50.24 ± 10.22 | 51.53 ± 10.55 |
| Female | 167,118 (60.11) | 17,458 (55.15) | 15,749 (55.34) | 86,969 (58.68) | 287,294 (59.07) |
| Urban | 148,771 (53.51) | 18,268 (57.71) | 16,537 (58.11) | 26,197 (17.67) | 209,773 (43.13) |
| Education level | |||||
| Primary school or lower | 140,524 (50.55) | 12,973 (40.98) | 11,297 (39.70) | 82,355 (55.56) | 247,149 (50.82) |
| Middle school | 77,014 (27.70) | 9422 (29.76) | 8691 (30.54) | 43,184 (29.14) | 138,311 (28.44) |
| High school or higher | 60,466 (21.75) | 9262 (29.26) | 8471 (29.77) | 22,676 (15.30) | 100,875 (20.74) |
| Household income (CNY/year) | |||||
| <20,000 | 147,011 (52.88) | 16,254 (51.34) | 15,131 (53.17) | 99,753 (67.30) | 278,149 (57.19) |
| 20,000–34,999 | 74,233 (26.70) | 8410 (26.57) | 6892 (24.22) | 30,639 (20.67) | 120,174 (24.71) |
| ≥35,000 | 56,760 (20.42) | 6993 (22.09) | 6436 (22.61) | 17,823 (12.03) | 88,012 (18.10) |
| Smoking status | |||||
| Non-current | 204,401 (73.52) | 20,816 (65.75) | 18,448 (64.82) | 97,274 (65.63) | 340,939 (70.10) |
| Current | 73,603 (26.48) | 10,841 (34.25) | 10,011 (35.18) | 50,941 (34.37) | 145,396 (29.90) |
| Drinking status | |||||
| Non-current | 131,481 (47.29) | 12,003 (37.92) | 10,355 (36.39) | 68,224 (46.03) | 222,063 (45.66) |
| Current | 146,523 (52.71) | 19,654 (62.08) | 18,104 (63.61) | 79,991 (53.97) | 264,272 (54.34) |
| SBP (mmHg) | |||||
| <120 | 86,654 (31.17) | 11,318 (35.75) | 10,332 (36.30) | 49,780 (33.59) | 158,084 (32.51) |
| 120–139 | 109,744 (39.48) | 12,626 (39.88) | 11,378 (39.98) | 62,371 (42.08) | 196,119 (40.33) |
| ≥140 | 81,606 (29.35) | 7713 (24.36) | 6749 (23.71) | 36,064 (24.33) | 132,132 (27.17) |
| BMI (kg/m2) | |||||
| <18.5 | 11,430 (4.11) | 1022 (3.23) | 935 (3.29) | 8027 (5.42) | 21,414 (4.40) |
| 18.5–23.9 | 140,267 (50.46) | 16,156 (51.03) | 14,217 (49.96) | 84,987 (57.34) | 255,627 (52.56) |
| 24.0–27.9 | 95,325 (34.29) | 10,891 (34.40) | 9892 (34.76) | 43,527 (29.37) | 159,635 (32.82) |
| ≥28.0 | 30,982 (11.14) | 3588 (11.33) | 3415 (12.00) | 11,674 (7.88) | 49,659 (10.21) |
| Physical activity (MET h/day) | 21.13 ± 14.47 | 23.70 ± 13.36 | 23.75 ± 13.48 | 21.50 ± 12.89 | 21.56 ± 13.90 |
| Weekly consumption* (days) | |||||
| Red meat | 3.60 ± 2.64 | 3.86 ± 2.74 | 3.94 ± 2.70 | 3.66 ± 2.52 | 3.66 ± 2.62 |
| Fresh vegetables | 6.86 ± 0.70 | 6.46 ± 1.52 | 6.64 ± 1.09 | 6.90 ± 0.60 | 6.84 ± 0.79 |
| Fresh fruits | 2.44 ± 2.69 | 2.91 ± 2.80 | 2.79 ± 2.78 | 2.08 ± 2.39 | 2.38 ± 2.62 |
| Preserved vegetables | 1.88 ± 2.60 | 2.62 ± 2.68 | 2.68 ± 2.67 | 1.98 ± 2.35 | 2.01 ± 2.55 |
| Strength of spicy food eating | |||||
| Weak | – | 21,660 (68.42) | 15,370 (54.01) | 23,413 (15.80) | 60,443 (12.43) |
| Moderate | – | 9043 (28.57) | 10,263 (36.06) | 53,356 (36.00) | 72,662 (14.94) |
| Strong | – | 954 (3.01) | 2826 (9.93) | 71,446 (48.20) | 75,226 (15.47) |
| Age started to eat spicy food regularly (years) | – | 25.39 ± 13.42 | 23.81 ± 13.40 | 11.63 ± 9.38 | 15.39 ± 12.22 |
| Types of spicy food eating commonly† | – | ||||
| Fresh chili pepper | – | 19,596 (61.90) | 19,441 (68.31) | 131,031 (88.41) | 170,068 (34.97) |
| Dried chili pepper | – | 11,894 (37.57) | 13,265 (46.61) | 115,591 (77.99) | 140,750 (28.94) |
| Chili sauce | – | 13,678 (43.21) | 13,165 (46.26) | 62,876 (42.42) | 89,719 (18.45) |
| Chili oil | – | 15,467 (48.86) | 15,383 (54.05) | 63,201 (42.64) | 94,051 (19.34) |
| Others or don’t know | – | 7894 (24.94) | 7106 (24.97) | 33,890 (22.87) | 48,890 (10.05) |
| Diseases | |||||
| Vascular disease | 80,172 (28.84) | 7615 (24.05) | 7166 (25.18) | 41,172 (27.78) | 136,125 (27.99) |
| IHD | 28,369 (10.20) | 2747 (8.68) | 2617 (9.20) | 12,956 (8.74) | 46,689 (9.60) |
| MCEs | 6060 (2.18) | 535 (1.69) | 452 (1.59) | 3050 (2.06) | 10,097 (2.08) |
| Cerebrovascular disease | 46,855 (16.85) | 4328 (13.67) | 4167 (14.64) | 24,764 (16.71) | 80,114 (16.47) |
| Stroke | 35,607 (12.81) | 3172 (10.02) | 3098 (10.89) | 14,849 (10.02) | 56,726 (11.66) |
| Non-stroke cerebrovascular disease | 21,564 (7.76) | 2026 (6.40) | 1880 (6.61) | 14,628 (9.87) | 40,098 (8.24) |
Data are presented as mean ± standard deviation or n (%). *Average weekly consumptions of red meal, fresh fruit, fresh vegetables, and preserved vegetables were calculated by assigning participants to the midpoint of their consumption category. †Each individual may choose multiple types. BMI: Body mass index; IHD: Ischemic heart disease; MCEs: Major coronary events; MET: Metabolic equivalent of task; SBP: Systolic blood pressure. –: Not application.
Figure 1.
Frequency of spicy food consumption.
Association between spicy food consumption and vascular diseases
During a median follow-up time of 12.1 years, 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Compared with participants who consumed spicy food less than once a week, for those who consumed spicy food 1–2 days/week, 3–5 days/week, and 6–7 days/week, the adjusted HRs for vascular disease were 0.95 (0.93, 0.97; P <0.001), 0.96 (0.94, 0.99; P = 0.003), and 0.97 (0.95, 0.99; P = 0.002), respectively (Ptrend <0.001; Table 2, Supplementary Figure 2, http://links.lww.com/CM9/C41). Interestingly, a negative association was also observed in the risk of IHD, with corresponding HRs of 0.95 (0.91, 0.99), 0.98 (0.94, 1.03), and 0.96 (0.93, 0.99), respectively (Ptrend = 0.011) and in the risk of MCEs, with corresponding HRs of 0.96 (0.87, 1.06), 0.87 (0.78, 0.96), and 0.91 (0.84, 0.98), respectively (Ptrend = 0.002; Table 2, Supplementary Figure 2, http://links.lww.com/CM9/C41). However, no significant association was found between cerebrovascular disease, stroke, and non-stroke cerebrovascular disease risk and spicy food consumption (Ptrend >0.05).
Table 2.
The association between spicy food consumption and the risk of vascular disease.
| Items | No. of participants | Frequency of spicy food consumption per week | ||||
|---|---|---|---|---|---|---|
| <1 day | 1–2 days | 3–5 days | 6–7 days | Ptrend | ||
| No. of participants | 486,335 | |||||
| Vascular disease | ||||||
| No. of events* | 136,125 | 80,172 | 7615 | 7166 | 41,172 | |
| Model 1† | 1.00 | 0.80 (0.78, 0.81) | 0.84 (0.82, 0.86) | 0.93 (0.92, 0.94) | <0.001 | |
| Model 2‡ | 1.00 | 0.97 (0.94, 0.99) | 0.98 (0.96, 1.01) | 0.98 (0.96, 1.00) | 0.035 | |
| Model 3§ | 1.00 | 0.95 (0.93, 0.97) | 0.96 (0.94, 0.99) | 0.97 (0.95, 0.99) | <0.001 | |
| IHD | ||||||
| No. of events* | 46,689 | 28,369 | 2747 | 2617 | 12,956 | |
| Model 1† | 1.00 | 0.83 (0.80, 0.86) | 0.88 (0.85, 0.92) | 0.84 (0.82, 0.85) | <0.001 | |
| Model 2‡ | 1.00 | 0.97 (0.93, 1.01) | 1.01 (0.96, 1.05) | 0.97 (0.94, 1.01) | 0.152 | |
| Model 3§ | 1.00 | 0.95 (0.91, 0.99) | 0.98 (0.94, 1.03) | 0.96 (0.93, 0.99) | 0.011 | |
| MCEs | ||||||
| No. of events* | 10,097 | 6060 | 535 | 452 | 3050 | |
| Model 1† | 1.00 | 0.76 (0.70, 0.83) | 0.72 (0.65, 0.79) | 0.93 (0.89, 0.97) | <0.001 | |
| Model 2‡ | 1.00 | 0.98 (0.89, 1.08) | 0.87 (0.78, 0.96) | 0.88 (0.82, 0.95) | <0.001 | |
| Model 3§ | 1.00 | 0.96 (0.87, 1.06) | 0.87 (0.78, 0.96) | 0.91 (0.84, 0.98) | 0.002 | |
| Cerebrovascular disease | ||||||
| No. of events* | 80,114 | 46,855 | 4328 | 4167 | 24,764 | |
| Model 1† | 1.00 | 0.78 (0.76, 0.81) | 0.84 (0.82, 0.87) | 0.97 (0.95, 0.98) | <0.001 | |
| Model 2‡ | 1.00 | 0.96 (0.93, 0.99) | 0.99 (0.95, 1.02) | 1.00 (0.98, 1.03) | 0.873 | |
| Model 3§ | 1.00 | 0.94 (0.91, 0.97) | 0.96 (0.93, 0.99) | 0.99 (0.96, 1.01) | 0.079 | |
| Stroke | ||||||
| No. of events* | 56,726 | 35,607 | 3172 | 3098 | 14,849 | |
| Model 1† | 1.00 | 0.76 (0.73, 0.79) | 0.83 (0.80, 0.86) | 0.76 (0.74, 0.77) | <0.001 | |
| Model 2‡ | 1.00 | 0.96 (0.92, 0.99) | 0.99 (0.95, 1.03) | 1.01 (0.98, 1.04) | 0.599 | |
| Model 3§ | 1.00 | 0.94 (0.90, 0.98) | 0.96 (0.92, 1.00) | 1.00 (0.97, 1.03) | 0.444 | |
| Non-stroke cerebrovascular disease | ||||||
| No. of events* | 40,098 | 21,564 | 2026 | 1880 | 14,628 | |
| Model 1† | 1.00 | 0.80 (0.77, 0.84) | 0.83 (0.80, 0.87) | 1.27 (1.24, 1.29) | <0.001 | |
| Model 2‡ | 1.00 | 0.96 (0.92, 1.01) | 0.98 (0.93, 1.03) | 1.00 (0.96, 1.04) | 0.679 | |
| Model 3§ | 1.00 | 0.94 (0.90, 0.99) | 0.95 (0.91, 1.00) | 0.97 (0.94, 1.01) | 0.064 | |
*During a median follow-up time of 12.1 years. †Model 1: The HRs (95% CIs) were estimated using Cox proportional hazard model without adjustment for any covariate. ‡Model 2: The HRs (95% CIs) were estimated using Cox proportional hazard model adjusted for sex, study site, and age. §Model 3: The HRs (95% CIs) were estimated using Cox proportional hazard model additionally adjusted for educational level (no formal school, primary school, middle school, high school, college, or university or higher); marital status (married, widowed, divorced or separated, or never married); alcohol consumption (never, formerly regular, occasional, or currently regular); smoking status (non-current smoker, occasional, most days, or daily); physical activity (MET, h/day); household income (<20,000 CNY/year, 20,000–34,999 CNY/year, ≥35,000 CNY/year); BMI; intake frequencies of red meat, fruits, and vegetables (rarely/never or monthly, 1–3 days/week, 4–6 days/week, daily); diagnosis of hypertension in the baseline (no or yes). BMI: Body mass index; CIs: Confidence intervals; HRs: Hazard ratios; IHD: Ischemic heart disease; MCEs: Major coronary events; MET: Metabolic equivalent of task.
Subgroup and sensitivity analyses
Furthermore, in the stratification analysis, we evaluated the heterogeneity of associations based on different demographic characteristics. As shown in Figure 2, when stratified by BMI, smoking, and drinking status, there was no significant heterogeneity in the association between spicy food consumption and vascular disease risk (Pheterogeneity >0.05). However, compared with participants who consumed spicy food less than once a week, a stronger association with vascular disease risk was observed in individuals who were female (HR = 0.94, 0.92–0.96, Pheterogeneity = 0.038), younger (<65 years, HR = 0.87, 0.85–0.88, Pheterogeneity <0.001), had less physical activity (<10.76 MET h/day, HR = 0.92, 0.90–0.95, Pheterogeneity <0.001), and lived in rural areas (HR = 0.94, 0.92–0.96, Pheterogeneity <0.001).
Figure 2.
Subgroup analysis of the associations between regular consumption of spicy food and vascular disease risk. The HRs (95% CIs) for the risk of vascular disease were used to compare participants who ate spicy foods ≥1 day a week with those who ate spicy foods less than once a week. Estimates were made using Cox proportional hazard models with stratification for age, sex, region, and adjustment for educational level, marital status, alcohol consumption, smoking status, physical activity, household income, BMI, intake frequencies of red meat, fruits, and vegetables, diagnosis of hypertension in the baseline. BMI: Body mass index; CIs: Confidence intervals; HRs: Hazard ratios; MET: Metabolic equivalent of task.
Interestingly, the heterogeneity among different age groups was also observed in individuals with IHD (Pheterogeneity = 0.006; Supplementary Figure 3, http://links.lww.com/CM9/C41), cerebrovascular disease (Pheterogeneity <0.001; Supplementary Figure 4, http://links.lww.com/CM9/C41), stroke (Pheterogeneity <0.001; Supplementary Figure 5, http://links.lww.com/CM9/C41), and non-stroke cerebrovascular disease (Pheterogeneity <0.001; Supplementary Figure 6, http://links.lww.com/CM9/C41), but not in those with MCEs (Pheterogeneity = 0.100; Supplementary Figure 7, http://links.lww.com/CM9/C41). People living in rural areas also had a lower risk of IHD (Pheterogeneity = 0.002; Supplementary Figure 3, http://links.lww.com/CM9/C41), MCEs (Pheterogeneity = 0.001; Supplementary Figure 7, http://links.lww.com/CM9/C41), and non-stroke cerebrovascular disease (Pheterogeneity = 0.017; Supplementary Figure 6, http://links.lww.com/CM9/C41).
In the sensitivity analysis, the associations of spicy food consumption with the risk of each event did not materially change after further adjusting for diabetes [Supplementary Table 2, http://links.lww.com/CM9/C41]. However, when participants who developed an event of interest during the first two years of follow-up were excluded, spicy food consumption was no longer associated with IHD risk (Ptrend = 0.100), but was significantly associated with a decreased risk of cerebrovascular disease (Ptrend = 0.013) and non-stroke cerebrovascular disease (Ptrend = 0.008). After additional adjustment for season, spicy food consumption was significantly negatively associated with cerebrovascular disease risk (HR = 0.95 [0.92–0.98], 0.95 [0.92–0.99], and 0.96 [0.93–0.98] among individuals who consumed spicy food 1–2 days/week, 3–5 days/week, and 6–7 days/week, respectively; Ptrend <0.001), which may imply that season is one of the factors of cerebrovascular disease. In addition to the frequency of spicy food consumption, the age when one started to eat spicy food, the strength of spicy food eating, and the main source of spice also had a significant inverse association with the risk of vascular disease [Supplementary Table 3, http://links.lww.com/CM9/C41].
Joint effects of spicy food consumption and the healthy lifestyle score
Subsequently, eight lifestyle factors were used to construct a healthy lifestyle score, which was significantly associated with a lower risk of vascular disease (Ptrend <0.001, Supplementary Table 4, http://links.lww.com/CM9/C41). By integrating spicy food consumption and the healthy lifestyle score, we found that among participants eating spicy food 3–5 days/week, those who lived in a favorable lifestyle had stronger inverse associations with the risk of cerebrovascular disease (Pheterogeneity = 0.039) and stroke (Pheterogeneity = 0.045, Figure 3). In addition, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD (Pinteraction = 0.037, Supplementary Table 5, http://links.lww.com/CM9/C41).
Figure 3.
The association between spicy food consumption and vascular disease risk stratified by healthy lifestyle categories. The HRs (95% CIs) were estimated using Cox proportional hazard models with stratification for age, sex, region, and adjustment for household income, marital status, and education level. CIs: Confidence intervals; HRs: Hazard ratios.
Discussion
In this large prospective study of the Chinese population, a significant inverse association between spicy food consumption and the risk of vascular disease was found, especially in young people and individuals living in rural areas. The inverse association remained in the risk of IHD and MCEs. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD.
Previous studies showed the evidence that spicy food intake had beneficial effects on cardiovascular and cerebrovascular diseases.[11,22–25] However, the association between eating spicy food and the risk of vascular diseases has not been well studied in large population-based observational studies. Population studies in other countries have focused on the mortality of diseases.[11,25] In the Chinese population, most researches were limited in specific regions, diseases, or age groups.[22–24] Using a larger sample size with more factors and vascular diseases considered, we obtained favorable evidence of the inverse association between spicy food consumption and the risk of vascular diseases.
The protective effect of spicy food consumption against vascular diseases is attributed to capsaicin, the major pungent bioactive component of chili pepper.[13,26] Previous studies have shown that capsaicin affects vascular function through several pathways.[27–29] First, capsaicin can upregulate the messenger RNA (mRNA) and protein levels of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), which mediates the regulatory mechanism of cholesterol and bile acid homeostasis, and leads to the cholesterol-lowering effects.[27] Second, capsaicin can regulate the vascular tone by activating transient receptor potential vanilloid 1 (TRPV1), and thus increasing endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production.[28] Third, capsaicin can increase the antioxidant capacity of blood vessels by reducing the level of malondialdehyde (MDA, a marker of oxidative stress) and increasing the activity of superoxide dismutase (SOD, an enzyme that mitigates oxidative stress).[29] Consistent with previous evidence, we found a significant inverse association between spicy food consumption and the risk of vascular disease. Similar trends were observed in the risk of IHD (HR ranged from 0.95 to 0.98) and MCEs (HR ranged from 0.87 to 0.96).
The protective effect of spicy food against vascular disease may be affected by several factors, especially lifestyle factors and dietary habits. Previous randomized controlled studies indicated that capsaicin showed effects including anti-atherosclerotic, anti-obesogenic,[30,31] and appetite-reducing effects.[32,33] However, these studies did not account for the differences in lifestyles and changes in eating habits. For these participants, pepper, as an essential seasoning, can improve dietary flavor and increase appetite. Due to the special Chinese food culture, most consumers who eat spicy food daily are smokers and/or drinkers, and their diet mostly includes foods that are high in salt, oil, and high energy.[34] Therefore, we constructed a healthy lifestyle score[35] and classified the study population into three groups (the favorable, intermediate, and unfavorable lifestyle groups). The inverse associations of spicy food with the risk of vascular disease, IHD, and MCEs were almost observed among participants with different healthier lifestyle scores.
In addition, the bioavailability and bioaccessibility of capsaicin may also be involved. The pharmacological effects of capsaicin depend on several factors, the most important being its concentration in the target tissues. Low doses of capsaicin displayed various preventive effects, which were not observed in participants with long-term high-dose capsaicin exposure.[36] This may also partly explain why the apparent protective association between spicy food consumption and vascular disease risk was restricted to participants consuming spice with weak or moderate intensity in the present study.
This is a large-scale study to examine the association between spicy food consumption and the risk of vascular diseases in the Chinese population. It is important to note that our prospective study was performed with a sufficient sample size, with adjustment for several established and potential confounders to obtain reliable estimation, as well as with more analyses (e.g., joint analysis with the healthy lifestyle score). However, several limitations need to be noted. First, the impact of the level of spicy food intake and different peppers (e.g., red pepper) should be further refined. Second, more potential confounding factors (e.g., energy intake, oil and salt intake, triglycerides, cholesterol, and socioeconomic status) need to be considered in the future. Third, several biases (e.g., population selection, recall bias, self-reported dietary intake, and outcome capture) limited the reliability of our study, which needs to be considered in the further research.
In conclusion, this study found a significant inverse association between spicy food consumption and the risk of vascular disease, especially in those who were younger and living in rural areas. The disease-based subgroup analysis indicated that the inverse associations remained in IHD and MCEs risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD. Overall, this large-scale study examined the association between spicy food consumption and the risk of vascular diseases in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases. Nevertheless, further in-depth studies are needed to elucidate the causal roles and mechanisms of spicy food intake in reducing the risk of vascular disease.
Acknowledgments
We thank the Chinese Center for Disease Control and Prevention, Chinese Ministry of Health, National Health and Family Planning Commission of China, and 10 provincial/regional Health Administrative Departments. The most important acknowledgment is to the participants in the study and the members of the survey teams in each of the 10 regional centers, as well as to the project development and management teams based at Beijing, Oxford, and the 10 regional centers.
Funding
This work was supported by the National Natural Science Foundation of China (Project Nos. 82173620 and 82373690 to Y.Z. and 82204156 to D.Y.). This study was also funded by the Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD).
Conflicts of interest
None.
Supplementary Material
Footnotes
Dongfang You, Dianjianyi Sun, and Ziyu Zhao contributed equally to this work.
How to cite this article: You DF, Sun DJY, Zhao ZY, Song MY, Pan LL, Wu YQ, Tang YD, Lu MY, Shao F, Shen SP, Bai JL, Yi HG, Zhang RY, Wei YY, Ma HX, Xu HY, Yu CQ, Lv J, Pei P, Yang L, Chen YP, Chen ZM, Shen HB, Chen F, Zhao Y, Li LM; On behalf of the China Kadoorie Biobank Collaborative Group. Spicy food consumption and risk of vascular disease: Evidence from a large-scale Chinese prospective cohort of 0.5 million people. Chin Med J 2025;138:1696–1704. doi: 10.1097/CM9.0000000000003177
References
- 1.GBD 2019 Diseases and Injuries Collaborators . Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020;396:1204–1222. doi: 10.1016/S0140-6736(20)30925-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.GBD 2017 Causes of Death Collaborators . Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392:1736–1788. doi: 10.1016/S0140-6736(18)32203-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Tsao CW Aday AW Almarzooq ZI Alonso A Beaton AZ Bittencourt MS, et al. Heart disease and stroke statistics – 2022 update: A report from the American Heart Association. Circulation 2022;145:e153–e639. doi: 10.1161/CIR.0000000000001052. [DOI] [PubMed] [Google Scholar]
- 4.Zou Z Cini K Dong B Ma Y Ma J Burgner DP, et al. Time trends in cardiovascular disease mortality across the BRICS: An age-period-cohort analysis of key nations with emerging economies using the Global Burden of Disease Study 2017. Circulation 2020;141:790–799. doi: 10.1161/CIRCULATIONAHA.119.042864. [DOI] [PubMed] [Google Scholar]
- 5.Wang Z, Ma L, Liu M, Fan J, Hu S. Summary of the 2022 Report on Cardiovascular Health and Diseases in China. Chin Med J 2023;136:2899–908. doi: 10.1097/CM9.0000000000002927. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Gao B Wang F Zhu M Wang J Zhou M Zhang L, et al. Cardiovascular health metrics and all-cause mortality and mortality from major non-communicable chronic diseases among Chinese adult population. Int J Cardiol 2020;313:123–128. doi: 10.1016/j.ijcard.2020.04.048. [DOI] [PubMed] [Google Scholar]
- 7.Zhou M Wang H Zeng X Yin P Zhu J Chen W, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 2019;394:1145–1158. doi: 10.1016/S0140-6736(19)30427-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Writing Committee of the Report on Cardiovascular Health, Diseases in China . Report on cardiovascular health and diseases in China 2021: An updated summary. Biomed Environ Sci 2022;35:573–603. doi: .10.3967/bes2022079.35945174 [Google Scholar]
- 9.Kaefer CM, Milner JA. The role of herbs and spices in cancer prevention. J Nutr Biochem 2008;19:347–361. doi: 10.1016/j.jnutbio.2007.11.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Du Y, Lv Y, Zha W, Hong X, Luo Q. Chili consumption and risk of gastric cancer: A meta-analysis. Nutr Cancer 2021;73:45–54. doi: 10.1080/01635581.2020.1733625. [DOI] [PubMed] [Google Scholar]
- 11.Chopan M, Littenberg B. The association of hot red chili pepper consumption and mortality: A large population-based cohort study. PLoS One 2017;12:e0169876. doi: 10.1371/journal.pone.0169876. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Tsui PF, Lin CS, Ho LJ, Lai JH. Spices and atherosclerosis. Nutrients 2018;10:1724. doi: 10.3390/nu10111724. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Sharma SK, Vij AS, Sharma M. Mechanisms and clinical uses of capsaicin. Eur J Pharmacol 2013;720:55–62. doi: 10.1016/j.ejphar.2013.10.053. [DOI] [PubMed] [Google Scholar]
- 14.Sun F, Xiong S, Zhu Z. Dietary capsaicin protects cardiometabolic organs from dysfunction. Nutrients 2016;8:174. doi: 10.3390/nu8050174. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Lv J Qi L Yu C Yang L Guo Y Chen Y, et al. Consumption of spicy foods and total and cause specific mortality: Population based cohort study. BMJ 2015;351:h3942. doi: 10.1136/bmj.h3942. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Taghizadeh M Farzin N Taheri S Mahlouji M Akbari H Karamali F, et al. The effect of dietary supplements containing green tea, capsaicin and ginger extracts on weight loss and metabolic profiles in overweight women: A randomized double-blind placebo-controlled clinical trial. Ann Nutr Metab 2017;70:277–285. doi: 10.1159/000471889. [DOI] [PubMed] [Google Scholar]
- 17.Rigamonti AE Casnici C Marelli O De Col A Tamini S Lucchetti E, et al. Acute administration of capsaicin increases resting energy expenditure in young obese subjects without affecting energy intake, appetite, and circulating levels of orexigenic/anorexigenic peptides. Nutr Res 2018;52:71–79. doi: 10.1016/j.nutres.2018.02.002. [DOI] [PubMed] [Google Scholar]
- 18.Amini MR Sheikhhossein F Bazshahi E Hajiaqaei M Shafie A Shahinfar H, et al. The effects of capsinoids and fermented red pepper paste supplementation on blood pressure: A systematic review and meta-analysis of randomized controlled trials. Clin Nutr 2021;40:1767–1775. doi: 10.1016/j.clnu.2020.10.018. [DOI] [PubMed] [Google Scholar]
- 19.Chen Z Lee L Chen J Collins R Wu F Guo Y, et al. Cohort profile: The Kadoorie Study of Chronic Disease in China (KSCDC). Int J Epidemiol 2005;34:1243–1249. doi: 10.1093/ije/dyi174. [DOI] [PubMed] [Google Scholar]
- 20.Li LM Lv J Guo Y Collins R Chen JS Peto R, et al. The China Kadoorie Biobank: Related methodology and baseline characteristics of the participants (in Chinese). Chin J Epidemiol 2012;33:249–255. [PubMed] [Google Scholar]
- 21.Chen Z Chen J Collins R Guo Y Peto R Wu F, et al. China Kadoorie Biobank of 0.5 million people: Survey methods, baseline characteristics and long-term follow-up. Int J Epidemiol 2011;40:1652–1666. doi: 10.1093/ije/dyr120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Zhang Y, Lu ZL, Zhang WS, Jin YL, Zhu T, Xu L. Association between spicy foods consumption and cardiovascular disease risk factors: Guangzhou Biobank Cohort Study. BMC Public Health 2022;22:1278. doi: 10.1186/s12889-022-13697-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Li Q Chang M Lai R Zhang H Song L Wang X, et al. Potential benefits of spicy food consumption on cardiovascular outcomes in patients with diabetes: A cohort study of the China Kadoorie Biobank. Nutrition 2023;112:112062. doi: 10.1016/j.nut.2023.112062. [DOI] [PubMed] [Google Scholar]
- 24.Chen L Tang W Wu X Zhang R Ding R Liu X, et al. Eating spicy food, dietary approaches to stop hypertension (DASH) score, and their interaction on incident stroke in Southwestern Chinese aged 30–79: A prospective cohort study. Nutrients 2023;15:1222. doi: 10.3390/nu15051222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Bonaccio M Di Castelnuovo A Costanzo S Ruggiero E De Curtis A Persichillo M, et al. Chili pepper consumption and mortality in Italian adults. J Am Coll Cardiol 2019;74:3139–3149. doi: 10.1016/j.jacc.2019.09.068. [DOI] [PubMed] [Google Scholar]
- 26.Nilius B Appendino G, et al. Spices: The savory and beneficial science of pungency. In: Nilius B, Amara SG, Lill R, Offermanns S, Gudermann T, Petersen OH, eds. Reviews of physiology, biochemistry and pharmacology. (Vol. 164), Cham: Springer International Publishing; 2013: 1–76. [DOI] [PubMed] [Google Scholar]
- 27.Zhang L, Zhou M, Fang G, Tang Y, Chen Z, Liu X. Hypocholesterolemic effect of capsaicinoids by increased bile acids excretion in ovariectomized rats. Mol Nutr Food Res 2013;57:1080–1088. doi: 10.1002/mnfr.201200716. [DOI] [PubMed] [Google Scholar]
- 28.Ching LC Kou YR Shyue SK Su KH Wei J Cheng LC, et al. Molecular mechanisms of activation of endothelial nitric oxide synthase mediated by transient receptor potential vanilloid type 1. Cardiovasc Res 2011;91:492–501. doi: 10.1093/cvr/cvr104. [DOI] [PubMed] [Google Scholar]
- 29.Yang S, Liu L, Meng L, Hu X. Capsaicin is beneficial to hyperlipidemia, oxidative stress, endothelial dysfunction, and atherosclerosis in Guinea pigs fed on a high-fat diet. Chem Biol Interact 2019;297:1–7. doi: 10.1016/j.cbi.2018.10.006. [DOI] [PubMed] [Google Scholar]
- 30.Cha YS Kim SR Yang JA Back HI Kim MG Jung SJ, et al. Kochujang, fermented soybean-based red pepper paste, decreases visceral fat and improves blood lipid profiles in overweight adults. Nutr Metab 2013;10:24. doi: 10.1186/1743-7075-10-24. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Yoneshiro T Aita S Matsushita M Kayahara T Kameya T Kawai Y, et al. Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest 2013;123:3404–3408. doi: 10.1172/JCI67803. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Yoshioka M St-Pierre S Drapeau V Dionne I Doucet E Suzuki M, et al. Effects of red pepper on appetite and energy intake. Br J Nutr 1999;82:115–123. doi: 10.1017/S0007114599001269. [PubMed] [Google Scholar]
- 33.Ludy MJ, Mattes RD. The effects of hedonically acceptable red pepper doses on thermogenesis and appetite. Physiol Behav 2011;102:251–258. doi: 10.1016/j.physbeh.2010.11.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Wen Q Wei Y Du H Lv J Guo Y Bian Z, et al. Characteristics of spicy food consumption and its relation to lifestyle behaviours: Results from 0.5 million adults. Int J Food Sci Nutr 2021;72:569–576. doi: 10.1080/09637486.2020.1849038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Lv J Yu C Guo Y Bian Z Yang L Chen Y, et al. Adherence to healthy lifestyle and cardiovascular diseases in the Chinese population. J Am Coll Cardiol 2017;69:1116–1125. doi: 10.1016/j.jacc.2016.11.076. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Rollyson WD Stover CA Brown KC Perry HE Stevenson CD McNees CA, et al. Bioavailability of capsaicin and its implications for drug delivery. J Control Release 2014;196:96–105. doi: 10.1016/j.jconrel.2014.09.027. [DOI] [PMC free article] [PubMed] [Google Scholar]