Serenity — Advanced Stress Resilience and Relaxation Support

Stress is a neuroendocrine event. Serenity was formulated to address it at that level.*

When the brain perceives a stressor — physical, psychological, or environmental — it activates the HPA axis (hypothalamic-pituitary-adrenal), triggering a cortisol and adrenaline cascade that prepares the body for action. In acute situations, this response is adaptive and healthy. When the stress response becomes chronic — activated repeatedly without adequate recovery — the cascade disrupts sleep architecture, suppresses immune function, imbalances mood neurotransmitters, and accelerates the neuroendocrine aging process.*

Serenity was designed to support the HPA axis and the GABAergic calming pathways that counterbalance the stress response — with five clinically studied ingredients targeting cortisol rhythm balance, GABA-mediated calming, serotonergic mood support, and gut-brain axis resilience. Fast-acting and non-sedating — formulated for the practitioner whose patients need stress support that works alongside their daily lives, not in spite of them.*

KEY SUPPORTED BENEFITS

Serenity is formulated to support:*

• Healthy HPA-axis regulation and cortisol rhythm balance*
• Healthy stress response — adaptive, not suppressed*
• Emotional resilience, mood stability, and calm focus*
• GABAergic tone — relaxation without sedation or dependency*
• Serotonergic and dopaminergic neurotransmitter balance*
• Restorative sleep onset and sleep quality without grogginess*
• Gut-brain axis balance and GABA production via the enteric nervous system*
• Antioxidant neuroprotection and healthy neuronal function*

THE FIVE-PATHWAY STRESS RESILIENCE SYSTEM

• HPA-Axis & Cortisol Balance → Holixer™ Holy Basil (−66% hair cortisol · 2 human RCTs · 170 subjects)
• GABAergic Calming → DHH-B (GABA-A/C receptor modulation · fast-acting · non-habit forming)
• Mood & Serotonergic Support → affron® (8 human trials · −33% anxiety · −32% depression scores)
• Gut-Brain GABA Production → LP815™ L. plantarum (next-generation GABA-producing probiotic)
• Alpha-Wave Calm Focus → L-TeaActive® L-Theanine (calm alertness · alpha brainwave activity)

THE FORMULA

Holixer™ (Ocimum tenuiflorum / Holy Basil Extract, standardized to ≥5% Ocimum Bioactive Complex)

Role: HPA-Axis Regulation, Cortisol Balance & Restorative Sleep Support

Holixer™ is a patented, clinically studied extract of Ocimum tenuiflorum — known as Holy Basil or Tulsi — standardized to a proprietary Ocimum Bioactive Complex (OBC) containing five specific bioactives: Rabdosin, Rosmarinic acid, Luteolin-7-O-β-glucuronide, Ociglycoside I, and Apigenin-7-O-β-glucuronide. It is among the most clinically validated adaptogenic ingredients in the current practitioner supplement market.*

Holixer™ is the highest-priority clinical differentiator in the Serenity formula — with two completed human RCTs demonstrating objective cortisol reduction, improved sleep quality, and buffered HPA-axis stress response.*

Clinical Evidence — Holixer™:*

Study 1 — Primary RCT (8-week double-blind, randomized, placebo-controlled trial, n=100, Frontiers in Nutrition, 2022):*

• Significantly lower salivary cortisol (p=0.001) following acute stress exposure (Maastricht Acute Stress Test) versus placebo
• Significantly lower salivary amylase (p=0.001) — a sympathetic nervous system activation marker — following acute stress versus placebo
• Significantly lower systolic (p=0.010) and diastolic (p=0.025) blood pressure response to acute stress
• Significantly lower subjective stress ratings under acute stress challenge (p<0.001)
• Significantly lower hair cortisol at 8 weeks (p=0.025) — a chronic, objective measure of cumulative cortisol output*
• Significantly improved Athens Insomnia Scale scores (p=0.025)*
• Significantly improved Perceived Stress Scale scores (p=0.003)*
• Well-tolerated — no major adverse effects reported

Study 2 — Expanded clinical program (n=170 subjects, 2025):*

• 37% reduction in stress scores
• 66% reduction in hair cortisol levels within 4 weeks
• Significant improvement in insomnia symptoms versus placebo within two weeks
• Improved sleep efficiency, fewer nighttime awakenings, more restorative non-REM sleep
• Better next-day cognitive performance
• Award-winning ingredient at NutraIngredients 2025

The mechanism behind Holixer™'s cortisol-balancing effects is multi-layered:*

• HPA-axis regulation through adaptogenic modulation of the hypothalamic-pituitary adrenal cascade*
• Buffering of the sympatho-adrenal medullary (SAM) system response*
• Reduction in stress-induced alterations in serotonin and dopamine*
• Antioxidant defense against oxidative stress generated during HPA-axis activation*
• Anti-inflammatory support — rosmarinic acid and luteolin both modulate inflammatory pathways activated by chronic stress*

DHH-B (Dihydrohonokiol-B from Magnolia officinalis Bark Extract)

Role: GABA-A/C Receptor Modulation, Fast-Acting GABAergic Calming & Neuroprotection

DHH-B is a partially reduced derivative of honokiol — one of the primary bioactive compounds in Magnolia bark extract — formed as the pharmacologically active metabolite of honokiol's biotransformation. Where parent honokiol requires repeated administration to accumulate the metabolite responsible for its calming effects, DHH-B provides those effects directly and rapidly.*

Mechanism — GABAergic Calming: DHH-B acts on the GABA-A and GABA-C receptor-gated chloride channel complex in the brain. A key published study demonstrated DHH-B modulates GABA-C receptor-mediated chloride channel activity in hippocampal neurons — an action not reproduced by magnolol, an inactive honokiol isomer, confirming mechanism specificity.*

affron® (Crocus sativus Stigma Extract, standardized to >3.5% Lepticrosalides®)

Dose: 28 mg Role: Serotonergic & Dopaminergic Mood Support, Anxiety Resilience & HPA-Axis Balance

affron® is the most extensively clinically studied standardized saffron extract available — with eight published human clinical trials supporting its role in mood, emotional wellbeing, stress resilience, and sleep quality. It is also featured in HERgevity™ Balance for its perimenopause-specific mood and anxiety support.

In Serenity, affron® addresses the neurochemical dimension of stress response that DHH-B and Holixer™ do not directly target: the serotonergic and dopaminergic signaling that determines emotional tone, anxiety resilience, and mood stability under chronic stress.*

Crocin and crocetin support serotonergic and dopaminergic neurotransmitter signaling. Safranal supports GABA-ergic tone and has been shown to support endogenous melatonin production — connecting mood, stress, and sleep quality through a single ingredient.*

Clinical Evidence — affron® (stress and anxiety context):*

• Meta-analysis across 23 independent trials: saffron at 28–30 mg daily demonstrated large positive treatment effects on anxiety and depressive symptoms*
• Stress resilience trial (n=128, 8 weeks): significantly improved emotional wellbeing, stress scores, and mood stability versus placebo*
• 12-week large-scale trial (Journal of Nutrition, 2025, n=202): 72% of affron® participants showed significant improvement in emotional wellbeing versus 54% in placebo*
• Athletes/high-demand populations: affron® supported mood stability, reduced stress perception, and improved sleep quality in active adults under performance pressure*
• Consistent at 28 mg daily — the exact dose used in Serenity*

LP815™ (Lactiplantibacillus plantarum / GABA-Producing Probiotic)

Role: Gut-Brain Axis GABA Production, Microbiome-Mediated Calming & Emotional Resilience

LP815™ is a next-generation GABA-producing probiotic strain of Lactiplantibacillus plantarum — identified through computational modeling and high-throughput screening for its superior capacity for consistent endogenous GABA production in the gut environment.*

GABA (gamma-aminobutyric acid) is the primary inhibitory neurotransmitter in the central nervous system — the key molecular signal for calming, relaxation, and balanced stress response. The gut produces and communicates GABA to the brain through the vagal nerve and enteric nervous system — a bidirectional pathway now widely recognized as central to mood regulation and stress resilience.*

Most conventional probiotics produce small, variable amounts of GABA. LP815™ was specifically selected for its demonstrated capacity to produce meaningful, consistent GABA levels in the gut environment — supporting a steady, natural sense of calm throughout the day and night through the gut-brain axis.*

In Serenity, LP815™ addresses the gut-brain dimension of stress resilience — complementing DHH-B's direct GABAergic receptor modulation in the CNS with upstream gut-mediated GABA production through the enteric nervous system.*

LP815™ also:*

• Supports microbiome balance and gut barrier integrity under stress conditions*
• Contributes to healthy vagal tone — the autonomic nervous system pathway that regulates heart rate variability and stress recovery*
• Works without sedation — supporting calm throughout the day, not just at bedtime*

L-TeaActive® L-Theanine

Dose: Clinically validated dose Role: Alpha-Wave Calming, GABA/Serotonin Balance & Synergistic Stress Modulation

L-TeaActive® L-Theanine is a high-purity, standardized L-Theanine — a naturally occurring amino acid concentrated in green and black tea that supports a state of relaxed alertness through alpha brain-wave activity modulation.*

L-Theanine's calming mechanism is non-sedating: rather than inducing drowsiness, it promotes alpha brain-wave activity — the brain state associated with calm focus, creative thinking, and effortless attention. This alpha-wave effect is measurable within 30–45 minutes of ingestion.*

Neurotransmitter mechanisms:*

• Supports GABA activity — adding to LP815™'s gut-derived GABA production and DHH-B's GABAergic receptor modulation*
• Supports healthy serotonin and dopamine balance — complementing affron®'s serotonergic activity through a different molecular pathway*
• Crosses the blood-brain barrier rapidly and efficiently*

In Serenity's multi-pathway architecture, L-Theanine is the synergistic amplifier — working simultaneously with every other ingredient in the formula to smooth onset, extend duration, and create a coherent, calming neurochemical environment.*

Clinical Evidence — L-Theanine:*

• Multiple human RCTs demonstrate improved relaxation without drowsiness, reduced stress perception, and improved accuracy during demanding cognitive tasks*
• Improvement in subjective stress and anxiety under demanding conditions within 2 hours of ingestion*
• EEG studies confirm alpha brain-wave induction at 50–200 mg doses in humans*
• Well-tolerated with an established long-term safety profile from tea consumption*

FAST-ACTING AND LONG-TERM SUPPORT

Serenity is designed to work across two distinct timeframes:

Acute support (within 30–90 minutes): DHH-B and L-Theanine provide fast-acting GABAergic and alpha-wave calming — making Serenity effective as needed for acute stress situations in addition to daily use.*

Sustained support (2–8 weeks): Holixer™'s cortisol-balancing and HPA-axis regulation effects are cumulative — with the strongest evidence at 4–8 weeks of consistent daily use. LP815™'s gut-brain axis GABA production also builds with consistent use. affron®'s mood and emotional wellbeing support is measurable from 2 weeks and strengthens through 8–12 weeks.*

Recommended as both a daily foundational formula and an acute support option.*

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† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.