Meta-analysis evaluating the impact of chili-pepper intake on all-cause and cardiovascular mortality: A systematic review

Background Dietetics today occupy a significant place in the field of research, helping to discover cardiovascular benefits of healthy diets and consumption of organic foods such as fruits, vegetables, legumes, nuts, and whole grains. One of the components of vegetable-based diet is chili pepper (CP) which has been found to affect all-cause mortality. Methods MEDLINE, EMBASE, Scopus, EBSCO, and Cochrane (Wiley) Central Register of Controlled Trials were searched from inception till January 9, 2020, identifying all relevant studies using keywords and truncations. Studies were included if (1) they were observational or randomized in nature (2) included patients consuming CP and (3) evaluated direct comparison between regular and rarely/never CP consumption. Results Our preliminary search yielded 6976 articles. Post exclusion and after full-text screening, four potential observational studies with a population of 570,762. Pooled analysis found reduced all-cause mortality in CP consumers compared to nonconsumers with a risk ratio (RR) of 0.75 [95% CI: 0.64–0.88; p = 0.0004; I 2 = 97%]. The RR for CVD, cancer related and CVA deaths were 0.74 [95% CI: 0.62–0.88; p = 0.0006, I 2 = 66%], 0.77 [95% CI: 0.71–0.84; p = 0.0001; I 2 = 49%] and 0.76 [95% CI: 0.36–1.60; p = 0.47; I2 = 93%], respectively. Conclusion Statistically significant results of our analysis put forward a rationale indicating an association between lower risk of all-cause, cardiovascular and cancer related deaths and CP consumption.


Introduction
Dietetics today occupy a significant place in the field of research, helping to discover cardiovascular benefits of healthy diets and consumption of organic foods such as fruits, vegetables, legumes, nuts, and whole grains. One of the components of vegetable-based diet is chili pepper (CP) which has been found to affect all-cause mortality [1]. The chemical constituent of CP, capsaicin, has been shown to reduce all-cause mortality and deaths caused by CVD (cardiovascular disease), cancer and CVA (cerebrovascular accidents). However, absence of randomization and insufficient evidence [2] in previous studies has hindered demonstrating an association between CP consumption and mortality. This warrants a meta-analysis to study CP effects and benefits.

MEDLINE, EMBASE, Scopus, EBSCO, and Cochrane (Wiley) Central
Register of Controlled Trials were searched from inception till January 9, 2020, identifying all relevant studies using keywords and truncations. Studies were included if (1) they were observational or randomized in nature (2) included patients consuming CP and (3) evaluated direct comparison between regular and rarely/never CP consumption. Primary outcome of interest was all-cause mortality and secondary outcomes included deaths by CVD, CVA and cancer. Pooled risk ratios and 95% confidence intervals were calculated using random-effect and generic inverse variance methods. A p-value <0.05 was considered significant. Reporting quality was evaluated using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [3] and methodological quality using the Assessment of Multiple Systematic Reviews (AMSTAR-2) tool [4].

Results
Our preliminary search yielded 6976 articles. Post exclusion and after full-text screening, four potential observational studies with a population of 570,762 (259,184 consumed CP; 311,578 rarely/never consumed CP) met the inclusion criteria and thus included in the metaanalysis [1,[5][6][7]. The studies used Food Frequency Questionnaire (FFQ), National Health and Nutrition Examination Survey (NHANES) to study the effects of CP consumption. Study characteristics are summarized in Table 1. Pooled analysis found reduced all-cause mortality in CP consumers compared to non-consumers with a risk ratio (

Discussion
This is the first meta-analysis carried out to assess the impact of CP consumption on all-cause, CVD and cancer related mortality. Our results show significant benefit from CP consumption in preventing such deaths as opposed to rare or no CP consumption. The lack of data on mode, quantity and frequency of CP consumption leads to non-standardization, along with variable populations in control and intervention groups leading to high heterogeneity level. The significant reduction of relative risk is supported by two potential processes. First, capsaicin promotes the activation of the TRPV1 (Transient receptor potential cation channel sub-family V member 1) receptor which through a cascade effect leads to thermogenesis, fat metabolism and other energy dissipation processes [8]. This way energy equilibrium shifts help in weight-reduction, consequently lowering the risk of CVD incidence [9]. Likewise, weight-reduction was observed in 30 participants in the study by Yoshioka et al. [10] where a diet rich in fat was supplemented with capsaicin. Second, theTRPV1, receptor found in epicardium, has been proposed to prevent myocardial infarction, through the release of substance P [11]. The TRPV1 dependent release of serotonin helps thrombin in platelet activation. This mechanism accounts for the pro-coagulating property of capsaicin and justifies the negative impact of CP on CVD and CVA deaths [12].

Conclusion
To our knowledge, this is the first systematic review and metaanalysis that attempt to identify association between CP consumption and mortality. Statistically significant results of our analysis put forward a rationale indicating an association between lower risk of all-cause, cardiovascular and cancer related deaths and CP consumption (Fig. 1).

Declaration of competing interest
None to declare.