Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights.

Summary

In a randomized crossover study of 75 young adults, sucralose acutely increased hypothalamic blood flow and hunger responses compared with sucrose, without raising glucose. Sucrose elevated glucose and reduced medial hypothalamic perfusion, whereas sucralose strengthened hypothalamic connectivity with motivational and somatosensory regions.

Key Findings

• Sucralose vs sucrose increased hypothalamic blood flow (P<0.018) and hunger responses (P<0.001).
• Sucralose vs water increased hypothalamic blood flow (P<0.019) but did not change hunger ratings.
• Sucrose, but not sucralose, raised peripheral glucose, correlating with reduced medial hypothalamic blood flow (P<0.007).
• Sucralose increased functional connectivity between the hypothalamus and motivation/somatosensory brain regions.

Clinical Implications

Counseling on non-caloric sweetener use may consider potential acute increases in hypothalamic appetite signaling, especially in individuals with obesity; further chronic trials are needed before changing guidelines.

Limitations

• Acute, single-exposure study; long-term metabolic and behavioral effects remain unknown
• Young adult sample limits generalizability to older populations or those with comorbidities

Future Directions

Conduct longer-term randomized trials assessing repeated sucralose exposure on appetite, energy intake, body weight, and neuroendocrine responses across BMI strata.