Despite the extensive profiling of fruit-waste-derived bioactives and their associated therapeutic potentials (e.g., antioxidant, anti-inflammatory, antidiabetic), the review makes repeated inferences about biological efficacy without addressing one of the most fundamental pharmacokinetic constraints, namely, the bioavailability and metabolic stability of these compounds in vivo.
How do the authors reconcile the strong therapeutic claims made for compounds like phloridzin, catechins, anthocyanins, and chlorogenic acid, which are known to undergo rapid metabolism, low absorption, and microbial degradation in the gut, with the absence of discussion on their pharmacologically active forms or actual systemic bioactivity in humans?
This issue becomes particularly problematic in sections where IC₅₀ values from in vitro assays are presented as indicators of therapeutic efficacy without acknowledging that:
Polyphenols like quercetin and chlorogenic acid often exhibit less than 1% oral bioavailability,
Flavonoid glycosides are extensively transformed into inactive metabolites before reaching systemic circulation,
Antioxidant assays (e.g., DPPH, FRAP) conducted in vitro do not reflect redox behavior under physiological conditions.
Thus, by emphasizing the high content of these compounds in fruit waste and associating them with disease-modulating potential, the review risks overstating the translational relevance of compositional data without integrating the crucial dimension of bioaccessibility, metabolism, or bioefficacy.
This raises a core question:
Can compositional profiling alone justify therapeutic conclusions without accounting for post-digestive biotransformation and systemic bioactivity? Shouldn’t this be a mandatory consideration in any review making health-related claims about dietary bioactives?