Hemoglobin A1c Levels Modify Associations between Dietary Acid Load and Breast Cancer Recurrence

Background: Metabolic acidosis promotes cancer metastasis. No prospective studies have examined the association between dietary acid load and breast cancer recurrence among breast cancer survivors, who are susceptible to metabolic acidosis. Hyperglycemia promotes cancer progression and acid formation; however, researchers have not examined whether hyperglycemia can modify the association between dietary acid load and breast cancer recurrence. Methods: We studied 3081 early-stage breast cancer survivors enrolled in the Women’s Healthy Eating and Living study who provided dietary information through 24-h recalls at baseline and during follow-up and had measurements of hemoglobin A1c (HbA1c) at baseline. We assessed dietary acid load using two common dietary acid load scores, potential renal acid load (PRAL) score and net endogenous acid production (NEAP) score. Results: After an average of 7.3 years of follow-up, dietary acid load was positively associated with recurrence when baseline HbA1c levels were ≥ 5.6% (median level) and ≥5.7% (pre-diabetic cut-point). In the stratum with HbA1c ≥ 5.6%, comparing the highest to the lowest quartile of dietary acid load, the multivariable-adjusted hazard ratio was 2.15 (95% confidence interval [CI] 1.34-3.48) for PRAL and was 2.31 (95% CI 1.42-3.74) for NEAP. No associations were observed in the stratum with HbA1c levels were <5.6%. P-values for interactions were 0.01 for PRAL and 0.05 for NEAP. Conclusions: Our study demonstrated for the first time that even at or above normal to high HbA1c levels, dietary acid load was associated with increased risk of breast cancer recurrence among breast cancer survivors. Impacts: Our study provides strong evidence for developing specific dietary acid load guidelines based on HbA1c levels.