Apple's content activate Nrf2

Apples and apple juice contain chemicals that activate Nrf2. Research shows mixed results.

Apples are a rich source of phytochemicals, in particular of polyphenols, which can act as Nrf2 inducers due to their chemical structure. The oxidative diphenols in apple and apple-derived products are mainly represented by 1,2-diphenols; quercetin and its glycosides are the most abundant flavonols, along with procyanidins and their monomers catechin and epicatechin, and chlorogenic acid (R1)

The aim of this study was to evaluate the effect of phloretamide (PA), an apple constituent, on the activation of the Nrf2 transcription factor and the expression of its target genes.

The treatment of cells with PA resulted in the translocation of Nrf2 from cytosol to nucleus in both cell lines, but increased the level of its transcript and protein only in THLE-2 cells. In this cell line an increased level of GSTA, GSTP, GSTT, NQO1 mRNA was also observed. Increased expression of GSTs was confirmed by enhancement of their protein levels. The increase in p53 protein content observed in THLE-2 may be associated with its stabilization induced by the enhancement of NQO1 level.

These results suggest that PA has rather chemopreventive than chemiotherapeutic potential and acts similarly as apple dihydrochalcones through the induction of detoxification/antioxidative enzymes. (R2)

Fructose-induced rise of Uric acid, not polyphenols, are responsible for increase of antioxidant activity in plasma

The study “Uric acid but not apple polyphenols is responsible for the rise of plasma antioxidant activity after apple juice consumption in healthy subjects” (R5) investigated how quickly drinking a large amount of apple juice (1L) affects blood antioxidant levels and what causes these changes. The researchers specifically looked at whether the benefits came from apple polyphenols or from increased uric acid caused by fructose metabolism. They conducted a controlled experiment with 12 healthy non-smoking adults, testing three different beverages: regular clear apple juice, clear apple juice without polyphenols (placebo), and water (negative control). They measured multiple markers of antioxidant activity (FRAP and DPPH) along with uric acid and phenolic compounds at specific intervals after consumption.

The results showed that all beverages, including the control drinks, led to increased antioxidant activity in the blood, peaking one hour after consumption. Importantly, they found that this increase was strongly correlated with rising uric acid levels, while there were no significant changes in phenolic compounds. There were also no substantial differences between the effects of regular apple juice and the polyphenol-free version, suggesting that the polyphenols weren’t responsible for the antioxidant effects.

Key Highlights:

1. Main Findings:
   • All beverages increased blood antioxidant capacity
   • Peak antioxidant activity occurred at 1 hour post-consumption
   • No significant differences between regular and polyphenol-free juice effects
2. Biochemical Insights:
   • Strong correlation between serum uric acid and antioxidant activity
   • No significant changes in plasma phenolics and quercetin levels
   • Fructose metabolism, not polyphenols, drove the antioxidant increase
3. Experimental Design:
   • 12 healthy subjects (average age 32 years, weight 73 kg)
   • Three test beverages: clear apple juice, polyphenol-free apple juice, and water
   • Measurements taken at 0, 1, 2.5, and 4 hours after consumption
4. Clinical Implications:
   • Short-term apple juice consumption may not be an effective way to increase antioxidant activity
   • The increase in uric acid could be problematic as it’s a risk factor for various diseases
   • Questions the conventional wisdom about fruit juice and antioxidant benefits

Open Questions

1. How does Fructose from apples and apple juice affect metabolism?