Sex, but not the presence of a positive CVD risk factor, mediates the effects of dietary capsaicin on blood lipid levels

Cardiovascular Disease (CVD) is the leading cause of death in the United States. CVD risk can be quantified through several factors, including family history of premature CVD, dyslipidemia, hypertension, diabetes, smoking, and obesity. Eating spicy peppers and their active ingredient, capsaicin, a known agonist of the transient receptor potential vanilloid type 1, is suggested to reduce CVD events, although the direct mechanism of its effect remains unclear. PURPOSE: To identify potential sex-specific changes in measures associated with CVD risk in response to 6 weeks of dietary capsaicin supplementation, as well as differences between individuals with at least one CVD risk factor and individuals with none. METHODS: A randomized double-blind placebo-controlled design was utilized to assess the effectiveness of capsaicin vs. placebo control. Variables collected that relate to Atherosclerotic CVD (ASCVD) risk assessment included total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), systolic blood pressure (SBP), body mass index (BMI), waist-to-hip ratio (W:H), history of diabetes, smoking, and family history of premature CVD. RESULTS: Measures of CVD risk, including LDL, HDL, SBP, BMI, W:H, and aggregate lifetime ASCVD risk score, did not change significantly over time between treatment groups. However, there was a significant three-way interaction between time, condition, and sex on TC levels (F=4.521, p=0.04, ηp2=0.109). We did not observe a significant interaction between time, condition, and risk factor presence on TC levels (F=0.065, p=0.80, ηp2=0.002). HDL cholesterol also tended to exhibit the same trend (F=3.719, p=0.06, ηp2=0.091). Females receiving the capsaicin increased TC over placebo, whereas males exhibited a decline with treatment. The same directional outcomes were observed in HDL CONCLUSIONS: Though the ASCVD risk score did not change, or in accordance to the presence of a positive CVD risk factor in response to chronic dietary capsaicin, including sex, altered the lipid response to dietary capsaicin. The mechanism by which dietary capsaicin may reduce CVD risk may be, in part, through alterations of blood lipid profile, but it appears to exhibit a sexual dimorphism. FUNDING: This work was funded by the AHA awarded to SJI (#24AIREA1247045). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.