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

Abstract

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.

Epidemiologic Evidence for Association between a High Dietary Acid Load and the Breast Cancer Risk

“…The existing epidemiologic evidence related to acid load and cancer risk is limited, restricted to BC [21,23,25], colorectum [34,35], and pancreas [36]. The research works related to BC are not consistent enough [21,[23][24][25]. There were positive associations for acid load with BC risk among American and Puerto Rican women [21,23], but it was not associated among Iranian ones [25].…”

“…There were positive associations for acid load with BC risk among American and Puerto Rican women [21,23], but it was not associated among Iranian ones [25]. Some studies reported results about the influence of the acid load on the metabolic condition (hyperinsulinism and/or diabetes) [34,35] and the association with BC recurrence and survival [23,24]. One of these, identified acid load as a novel dietary factor that may lead to inflammation and hyperglycemia [23].…”

“…We calculated the diet-dependent acid load using previously defined formulas [15,16] and applied in other epidemiologic studies on BC risk [21,25] as well as on recurrence [23,24]: potential renal acid load (PRAL) and net endogenous acid production (NEAP). These measurements were calculated as follows: The PRAL score takes into account the intestinal absorption rates for protein, potassium, calcium, magnesium, and phosphate and has been validated against urine pH in healthy adults [15].…”

“…Conversely, alkaline diets or diets lower in diet-dependent acid load may be protective, especially for Estrogen Receptor-negative BC [21]. Nevertheless, there is limited and inconsistent epidemiologic evidence on the association between diet-dependent acid load and BC risk [22], focused on its incidence and recurrence risk [21,[23][24][25]. Therefore, we decided to explore possible associations of diet-dependent acid load and the risk of BC among Uruguayan women.…”

Association between dietary acid load and cancer risk and prognosis: An updated systematic review and meta-analysis of observational studies

“…In 2016, Fenton and Huang ( 15 ) conducted a systematic review and found only one study focused on the association between DAL and cancer risk, which suggested null results. Interestingly, several epidemiological studies have published their results in recent years, but the findings have been controversial ( 16 – 25 ). For example, a large cohort study with 43,570 participants showed that consumption of high DAL food increased the risk of breast cancer ( 19 ).…”