What human studies have evaluated the cognitive and mood effects of hesperidin in otherwise healthy adults?

Human Studies on Hesperidin for Neurological and Psychological Benefits

One pilot randomized controlled trial in older adults demonstrated that hesperidin-containing supplementation significantly improved cognitive functions—particularly attention, learning, and memory—and reduced fall risk, though the study combined hesperidin with diosmin and proanthocyanidins rather than testing hesperidin alone. 1

Primary Human Evidence

Cognitive and Motor Function Study (2026)

The most robust human evidence comes from a randomized crossover-controlled pilot study of 36 elderly patients who received Altermor® (containing hesperidin, diosmin, and proanthocyanidins) for 8-week periods. 1

Key findings include:

• Statistically significant improvements in cognitive function compared to controls, with particular benefits in attention, learning, and memory domains 1
• Significant reduction in fall risk in both experimental groups versus controls 1
• Dose-independent effects: No significant differences emerged between 1 stick/day versus 2 sticks/day dosing, suggesting a threshold effect rather than dose-response relationship 1
• Attention improvements were measurable as early as 1 week after initiation 1

Critical limitation: This study used a combination product, making it impossible to isolate hesperidin's specific contribution from the other active compounds. 1

Cerebral Blood Flow and Cognition

Clinical trials referenced in systematic reviews indicate that dietary supplements rich in hesperidin can improve cerebral blood flow, cognition, and memory performance, though these studies are not detailed in the provided evidence and require further clinical confirmation. 2

Preclinical Evidence Supporting Human Potential

While not human studies, extensive preclinical research provides mechanistic rationale for the observed clinical effects:

Neuroprotective Mechanisms

Hesperidin exerts neuroprotection through multiple pathways: 3, 2

• Inhibition of β-amyloid aggregation and enhancement of endogenous antioxidant defenses 2
• Reduction of neuroinflammation and apoptosis via modulation of NF-κB, iNOS, COX-2, and GFAP-positive astrocytes 4
• Improvement of mitochondrial dysfunction and regulation of autophagy 2
• Promotion of neurogenesis through AMPK/BDNF/CREB pathway activation 2

Cognitive Impairment Models

In animal models of Alzheimer's-type dementia, hesperidin (100-200 mg/kg) prevented cognitive impairment by:

• Modulating acetylcholinesterase activity, improving memory consolidation as measured by Morris water maze performance 4
• Attenuating oxidative stress markers: restoring depleted glutathione and reducing lipid peroxidation (TBARS) 4
• Inhibiting neuronal cell death through suppression of inflammatory markers 4

Evidence Gaps and Clinical Implications

The current human evidence base is extremely limited. 3, 2

What We Know:

• One small pilot study (n=36) shows cognitive benefits in older adults, but used a combination product 1
• Clinical trials suggest improvements in cerebral blood flow and memory, but details are sparse 2

What We Don't Know:

• Hesperidin's isolated effects independent of other flavonoids 1
• Optimal dosing in humans for neurological benefits 1, 2
• Long-term safety profile in human populations 3, 2
• Efficacy in specific conditions like mild cognitive impairment, depression, or diagnosed dementia 1, 2

Clinical Considerations:

For otherwise healthy adults seeking cognitive enhancement:

• The pilot study suggests potential benefit for attention, learning, and memory in older adults, though the evidence is preliminary 1
• Hesperidin appears safe based on its natural occurrence in citrus fruits and preclinical safety data 5
• The compound demonstrates anti-inflammatory, antioxidant, and insulin-sensitizing properties that may support brain health 5

Common pitfalls to avoid:

• Do not extrapolate animal study results directly to human efficacy—the mechanistic data is promising but requires clinical validation 3, 2
• Do not assume combination products prove hesperidin's individual efficacy 1
• Do not recommend hesperidin as a substitute for evidence-based treatments in diagnosed neurological or psychiatric conditions 2

Future research priorities:

• Isolated hesperidin trials in humans with standardized cognitive assessments 2
• Studies in populations with mild cognitive impairment or early dementia 1
• Dose-finding studies to establish optimal therapeutic ranges 2
• Long-term safety monitoring in clinical populations 3