Sulforaphane triggers fasting-like responses in human cells, enhancing mitochondrial function, autophagy, and nutrient-sensing pathways, while suppressing glucose uptake and mTOR signalling – mimicking the benefits of caloric restriction.
January 2025 – Frontiers in Nutrition
Key takeaways
- Mimics fasting at the cellular level: Sulforaphane acutely engages multiple starvation-response pathways, suppressing insulin signalling and mTOR activity while increasing autophagy and stress-related gene expression. These effects mimic a cellular fasted state, even in nutrient-rich conditions, suggesting that sulforaphane could replicate some of the health-promoting benefits of caloric restriction without requiring dietary changes
- Boosts mitochondrial resilience: Sulforaphane preserves mitochondrial membrane potential, increases mitochondrial mass, and maintains a reduced redox environment within the mitochondrial matrix. These changes enhance mitochondrial resistance to oxidative stress and promote mitophagy, indicating improved mitochondrial quality control and energy efficiency, key features of long-term cellular health and protection against age-related decline
- Enhances autophagy and lysosomal biogenesis: The compound significantly increases autophagic flux, even more than established inducers like rapamycin, and amplifies autophagy when combined with other stressors. It also upregulates lysosomal biogenesis via the CLEAR gene network, reinforcing cellular renewal and debris clearance mechanisms that are crucial for longevity and maintaining metabolic homeostasis with age
- Alters glucose metabolism via TXNIP suppression: Sulforaphane initially reduces glucose uptake and lactate production, mimicking metabolic slowdown seen in fasting. This effect reverses after 24 hours due to suppressed TXNIP expression, a key regulator of glucose transport, achieved by inhibiting an enzyme in the hexosamine biosynthetic pathway, highlighting sulforaphane’s potential to fine-tune energy metabolism in response to cellular stress
Read the article at: Plafker, Kendra S., et al. “Sulforaphane acutely activates multiple starvation response pathways.” Frontiers in Nutrition, vol. 11, 2025, doi:10.3389/fnut.2024.1485466.
