Abstract
This prospective cohort study examined the association between dietary acid load and cardiovascular disease (CVD) incidence, CVD mortality, and all-cause mortality in an Iranian population. A total of 6,482 adults (59.83% female) aged 35-65 years from the Mashhad Stroke and Heart Atherosclerosis Disorder (MASHAD) study were followed for ten years. Dietary acid load was assessed using net endogenous acid production (NEAP), potential renal acid load (PRAL), and dietary acid load (DAL). Multivariable Cox proportional hazards regression and nonlinear restricted cubic spline models were used. Compared to the first quartile, PRAL was associated with higher CVD mortality in the second (OR: 1.974; 95% CI 1.138-3.424) and third quartiles (OR: 2.323; 95% CI 1.397-3.862) while the highest quartile showed no significant association (OR: 1.335; 95% CI 0.724-2.460). DAL showed similar associations in the second (OR: 1.768; 95% CI 1.046-2.991) and third quartiles (OR: 1.709; 95% CI 1.010-2.894), but not the fourth one (OR: 1.673; 95% CI 0.971-2.883). NEAP was associated with CVD mortality only in the second quartile (OR: 1.802; 95% CI 1.083-2.997). No significant associations were found for all-cause mortality or CVD incidence. Cubic models confirmed a nonlinear relationship for PRAL (P = 0.004) and mid-level associations for DAL (P = 0.009). This nonlinear pattern indicates that the risk of CVD mortality peaks at moderate dietary acid load levels, possibly reflecting adverse metabolic effects of both high acid and high alkaline diets. Overall, these findings suggest that moderate dietary acid load may increase CVD mortality risk, requiring further investigation.