Whole grain metabolite 3,5-dihydroxybenzoic acid is a beneficial nutritional molecule with the feature of a double-edged sword in human health: a critical review and dietary considerations

Nonprocessed foodstuffs of plant origin, especially whole-grain cereals, are considered to be health-promoting components of the human diet. While most of their well-studied effects derive from their high fiber content and low glycemic index, the presence of underrated phenolic phytonutrients has recently been brought to the attention of nutritionists. In this review, we report and discuss findings on the sources and bioactivities of 3,5-dihydroxybenzoic acid (3,5-DHBA), which is both a direct dietary component (found, e.g., in apples) and, more importantly, a crucial metabolite of whole-grain cereal-derived alkylresorcinols (ARs). 3,5-DHBA is a recently described exogenous agonist of the HCAR1/GPR81 receptor. We concentrate on the HCAR1-mediated effects of 3,5-DHBA in the nervous system, on the maintenance of cell stemness, regulation of carcinogenesis, and response to anticancer therapy. Unexpectedly, malignant tumors take advantage of HCAR1 expression to sense 3,5-DHBA to support their growth. Thus, there is an urgent need to fully identify the role of whole-grain-derived 3,5-DHBA during anticancer therapy and its contribution in the regulation of vital organs of the body via its specific HCAR1 receptor. We discuss here in detail the possible consequences of the modulatory capabilities of 3,5-DHBA in physiological and pathological conditions in humans.

Automated summary

Nonprocessed plant-based foods, especially whole-grain cereals, are considered beneficial for human health due to their high fiber content and low glycemic index. In addition, the phenolic phytonutrient 3,5-dihydroxybenzoic acid (3,5-DHBA), derived from whole-grain cereals, has recently been found to have important health effects. This review focuses on the sources and bioactivities of 3,5-DHBA, particularly its role as an agonist of the HCAR1/GPR81 receptor and its effects on the nervous system, cell stemness, carcinogenesis, and response to anticancer therapy. We also discuss the potential implications of 3,5-DHBA modulation in physiological and pathological conditions in humans.