Can Polyphenols Improve Sleep? Emerging Insights Says YES!

Polyphenols, like the ones in ACEND, help with Sseep

June 2, 2025
Contributing Authors: Team TRILITY / ACEND

Poor sleep is no longer just an inconvenience—it’s a global health crisis. Insufficient or poor-quality sleep is linked to an increased risk of obesity, cardiovascular disease, diabetes, depression, neurodegeneration, and even premature death. While pharmaceuticals remain the standard treatment for insomnia, they often come with side effects and the risk of dependency. But what if a class of naturally occurring compounds—polyphenols—could help regulate sleep, improve sleep quality, and restore circadian rhythms by nourishing the gut-brain axis?

Recent advances in neuroscience and nutritional biochemistry suggest that flavonoids, a subgroup of polyphenols found in fruits, vegetables, and botanicals, may play a surprising role in sleep regulation. In this article, we explore how polyphenols—especially those found in medical foods like ACEND—support sleep by reducing neuroinflammation, modulating neurotransmitters, and enhancing microbiota-gut-brain communication.

Sleep, Brain Health, and the Inflammatory Burden

Sleep is a dynamic biological process regulated by a web of systems: the circadian rhythm, hypothalamic-pituitary-adrenal (HPA) axis, gut microbiome, and neurotransmitter balance. When these systems become dysregulated—due to chronic inflammation, stress, poor diet, or age—sleep suffers. Elevated inflammatory markers like IL-6, TNF-α, and CRP are repeatedly associated with insomnia and disrupted REM cycles .

Chronic inflammation doesn’t just disturb sleep; it also impairs sleep architecture—the structure of different sleep stages. As sleep becomes fragmented, the brain’s glymphatic system, responsible for clearing waste (including amyloid-beta), becomes compromised, setting the stage for neurodegeneration.

The Gut-Brain-Sleep Axis: Why Your Microbiome Matters

Emerging science confirms that gut microbes help regulate sleep by producing and metabolizing compounds such as serotonin, gamma-aminobutyric acid (GABA), and short-chain fatty acids (SCFAs). These metabolites travel via the vagus nerve and bloodstream, directly influencing brain function and circadian rhythms.

Polyphenols, especially flavonoids, act as prebiotics—feeding beneficial microbes like Bifidobacteria and Lactobacillus—which are linked to improvements in sleep duration and quality . Furthermore, these microbes metabolize polyphenols into bioactive compounds that can cross the blood-brain barrier and interact with neurotransmitter receptors, influencing everything from melatonin production to stress resilience.

Key Mechanisms: How Polyphenols Influence Sleep

1. Anti-Inflammatory Action in the Brain

Flavonoids such as quercetin, luteolin, and epicatechin inhibit pro-inflammatory cytokines like IL-6 and TNF-α in brain regions associated with sleep regulation, such as the hypothalamus and brainstem . This helps restore healthy neuronal signaling required for deep, restorative sleep.

2. GABA Modulation

Polyphenols can modulate GABAergic signaling, which is crucial for sleep initiation. Studies show that flavonoids like apigenin and dihydromyricetin enhance GABA-A receptor activity, mimicking the action of sedative-hypnotics without the side effects .

3. Melatonin Pathway Support

Some polyphenols—especially resveratrol and curcumin—enhance melatonin synthesis by upregulating arylalkylamine N-acetyltransferase (AANAT), a key enzyme in melatonin production. Additionally, they protect the pineal gland from oxidative stress, supporting circadian regulation .

4. Crossing the Blood-Brain Barrier

Flavonoids like dihydroquercetin (taxifolin) and luteolin are small molecules, allowing them to efficiently cross the blood-brain barrier. This enables them to act directly on neural tissue, unlike many larger compounds that remain in peripheral circulation.

Metabolites that Matter: From Gut to Brain

Polyphenols are not absorbed in their native form. Instead, they’re transformed by gut microbes into bioavailable phenolic acids and urea-cycle derivatives that retain or even enhance their biological activity. For example:

Quercetin → 3,4-dihydroxyphenylacetic acid
Epicatechin → valerolactones, which interact with brain GABA receptors
Resveratrol → dihydroresveratrol, shown to improve sleep latency

These metabolites impact neurotransmission, neuroplasticity, and sleep-wake cycles, highlighting the importance of both polyphenol intake and gut microbiota diversity for sleep health.

Polyphenols in ACEND That Support Sleep

ACEND, a medical food formulated to reduce chronic inflammation and support whole-system recovery, includes multiple polyphenols and flavonoids clinically shown to influence sleep biology:

Luteolin (98%) – inhibits mast cell activity in the brain and reduces IL-6
Dihydromyricetin – mimics benzodiazepine-like GABA-A activity without addiction potential
Green Tea Extract (90% epicatechins) – supports both stress reduction and microbiota health
Curcurouge® (curcumin) – boosts melatonin synthesis and circadian gene expression
Quercetin Dihydrate – modulates histamine and supports blood-brain barrier stability

These compounds work synergistically, not only calming inflammation but also repairing neural circuitry and supporting the gut-brain-sleep feedback loop.

Flavonoids help you sleep

Sleep as a Biomarker of Recovery

From athletes to patients recovering from chronic illness, improved sleep is a sign of healing. Polyphenols don’t sedate—they restore. By calming systemic inflammation, enhancing neurotransmission, and repairing gut-brain communication, medical foods like ACEND provide non-pharmacological support for sleep health that evolves with the body’s needs.

And unlike synthetic sleep aids, which often lead to morning grogginess and tolerance, polyphenols promote long-term neuroregulation without impairing natural rhythms.

So…

The future of sleep health may lie not just in melatonin pills or sleep hygiene protocols, but in nourishing the microbiota and calming the brain—from the inside out. Polyphenols, through their multidimensional impact on inflammation, neurotransmitters, and circadian biology, offer a promising avenue for sustainable, natural sleep restoration.

For individuals navigating chronic inflammation, aging, or sleep disorders, incorporating a medical food like ACENDinto a daily routine may not only improve sleep—it may unlock a cascade of healing throughout the body.

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Note: Always consult with a healthcare professional before considering any treatment options or significant dietary changes.