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Bacopa Extract: The Definitive NTRPX Evaluation

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Executive Summary

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Detailed Analysis

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1. Synapsa® (CDRI-08) — THE GOLD STANDARD

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Clinical Evidence Portfolio

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Mechanisms of Action (Validated)

┌─────────────────────────────────────────────────────────────────┐
│              SYNAPSA MECHANISM OF ACTION                        │
├─────────────────────────────────────────────────────────────────┤
│                                                                 │
│  ACETYLCHOLINE SYSTEM                                          │
│  ───────────────────                                           │
│  • Inhibits acetylcholinesterase (AChE)                        │
│  • Activates choline acetyltransferase (ChAT)                  │
│  • Increases ACh levels in hippocampus and cortex              │
│                                                                 │
│  SEROTONIN SYSTEM                                              │
│  ────────────────                                              │
│  • Increases 5-HT levels in hippocampus                        │
│  • Modulates TPH2 (tryptophan hydroxylase)                     │
│  • Upregulates SERT (serotonin transporter)                    │
│                                                                 │
│  GABA SYSTEM                                                   │
│  ──────────                                                    │
│  • Enhances GABA-A receptor subunit expression                 │
│  • Upregulates glutamate decarboxylase                         │
│  • Contributes to anxiolytic effect                            │
│                                                                 │
│  NEUROPROTECTION                                               │
│  ───────────────                                               │
│  • Antioxidant (reduces lipid peroxidation)                    │
│  • Anti-inflammatory (reduces TNF-α, IL-6)                     │
│  • Protects against β-amyloid toxicity                         │
│  • Increases BDNF expression                                   │
│                                                                 │
│  SYNAPTIC PLASTICITY                                           │
│  ──────────────────                                            │
│  • Increases dendritic branching (hippocampus)                 │
│  • Enhances long-term potentiation (LTP)                       │
│  • Upregulates GluN2B (NMDA receptor subunit)                  │
│                                                                 │
└─────────────────────────────────────────────────────────────────┘

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Side Effect Profile

• A feature for evening/sleep products (anxiolytic, sleep quality)
• A manageable consideration for daytime use (timing, dose adjustment)

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NTRPX Verdict: Synapsa®

• ✅ Deepest clinical evidence of any Bacopa extract
• ✅ Proven across multiple populations (adults, children, elderly)
• ✅ Both acute AND chronic effects demonstrated
• ✅ Validated mechanisms of action
• ✅ Strong safety profile
• ✅ Regulatory acceptance (GRAS, NDI)

• ⚠️ Takes 4-6 weeks for full cognitive effects
• ⚠️ Mild sedation possible (context-dependent)

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2. Cognance® — THEORETICALLY COMPELLING, CLINICALLY UNPROVEN

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The Ebelin Lactone Theory

1. Bacosides themselves are NOT the active compounds
2. They must be converted to aglycones (like ebelin lactone) in the gut
3. Ebelin lactone has direct CNS receptor activity
4. Ebelin lactone crosses the BBB efficiently

┌─────────────────────────────────────────────────────────────────┐
│              COGNANCE PROPOSED MECHANISM                        │
├─────────────────────────────────────────────────────────────────┤
│                                                                 │
│  5-HT2A RECEPTOR (ALLOSTERIC MODULATION)                       │
│  ──────────────────────────────────────                        │
│  • Positive allosteric modulator (NOT direct agonist)          │
│  • Increases receptor sensitivity to endogenous serotonin      │
│  • Theorized "microdose-like" effects on cognition             │
│  • Enhanced cognitive flexibility, creativity                   │
│                                                                 │
│  M1 MUSCARINIC RECEPTOR (DIRECT AGONISM)                       │
│  ─────────────────────────────────────────                     │
│  • "Holy grail" target for cognition                           │
│  • Selective M1 agonists are rare in nature                    │
│  • Memory and learning enhancement                             │
│                                                                 │
│  CLAIMED ADVANTAGES                                            │
│  ─────────────────                                             │
│  • Faster onset (days vs weeks)                                │
│  • No lethargy (avoids GABA-A activation)                      │
│  • Pre-metabolized = more bioavailable                         │
│                                                                 │
└─────────────────────────────────────────────────────────────────┘

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The Evidence Gap

• In silico docking studies (Ramasamy 2015)
• In vitro receptor binding assays (Ramasamy 2015)
• Anecdotal reports from users
• Manufacturer’s claims

• ❌ Independent human RCTs
• ❌ Peer-reviewed clinical trials on Cognance specifically
• ❌ Head-to-head comparisons vs standard Bacopa
• ❌ Long-term safety data

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NTRPX Verdict: Cognance®

• Ebelin lactone’s receptor profile is genuinely interesting
• The bioavailability argument is scientifically sound
• The mechanism could explain why traditional Bacopa takes weeks to work

• NTRPX standards require clinical proof, not theoretical plausibility
• “Should work” ≠ “proven to work”
• The lack of RCTs means we cannot verify claims of superiority
• Novel extraction process = unknown unknowns

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3. Bacognize® — SOLID BUT NOT DIFFERENTIATED

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Clinical Evidence

• Primary outcome (sleep): NOT significant vs placebo
• Secondary outcomes: Improved emotional wellbeing (+14%), pain reduction, general health
• Biomarkers: Reduced salivary IgA and α-amylase (stress markers)

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NTRPX Verdict: Bacognize®

• Good quality dossier
• Clean label positioning
• Stress/adaptogen evidence

• Fewer RCTs than Synapsa
• Differentiation is quality assurance, not novel mechanism
• Primary endpoint (sleep) failed in main trial

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4. BacoMind® — MARKETING > EVIDENCE

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Clinical Evidence

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NTRPX Verdict: BacoMind®

• “Full-spectrum” and “9 bioactives” are marketing terms
• Limited peer-reviewed evidence of superiority vs other extracts
• No clear mechanistic differentiation
• Cannot verify claims against standard Bacopa

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The Lethargy Question: Context Matters

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The Key Insight: It Depends on the Product

1. Affects only ~5-10% of users
2. Often resolves after 2-4 weeks of use
3. Can be mitigated by timing (evening dosing)
4. Is dose-dependent (lower doses = less sedation)

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NTRPX Optimal Integration

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Product-Specific Recommendations

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SOL (Morning Cognitive Stack)

• Proven cognitive enhancement
• Lower dose mitigates sedation
• Synergy with existing Sol ingredients (creatine, nooLVL)
• Builds chronic cognitive benefits with daily use

• Improved working memory accuracy
• Enhanced information processing speed
• Reduced anxiety/stress
• Neuroprotection

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LUNA (Sleep/Recovery Stack)

• GABA enhancement becomes a feature (anxiolytic, sleep quality)
• Full dose maximizes cognitive building effects overnight
• Synergy with Luna’s relaxation profile
• Clinical data supports sleep routine improvements (Kean 2022)

• Reduced anxiety before sleep
• Improved sleep routine/quality
• Overnight memory consolidation
• Chronic cognitive enhancement (builds over weeks)

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Head-to-Head Comparison Matrix

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Final Recommendation

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Primary: Synapsa® (CDRI-08)

1. Evidence Depth: No other Bacopa extract comes close to Synapsa’s clinical validation
2. Proven Efficacy: Meta-analyses confirm cognitive benefits
3. Population Breadth: Validated in adults, children, and elderly
4. Mechanism Clarity: Well-characterized pharmacology
5. Regulatory Acceptance: GRAS, NDI, global acceptance
6. Context Flexibility: Works for both cognitive (Sol) and sleep (Luna) applications

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Product Integration

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The Cognance Question

NTRPX does not formulate based on “should work.” We formulate based on “proven to work.”

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References

1. Stough C, et al. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology. 2001;156(4):481-484.
2. Roodenrys S, et al. Chronic effects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology. 2002;27(2):279-281.
3. Calabrese C, et al. Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial. J Altern Complement Med. 2008;14(6):707-713. PMC3153866
4. Downey LA, et al. An acute, double-blind, placebo-controlled crossover study of 320 mg and 640 mg doses of a special extract of Bacopa monnieri (CDRI 08) on sustained cognitive performance. Phytother Res. 2013;27(9):1407-1413. PubMed 23281132
5. Kongkeaw C, et al. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. J Ethnopharmacol. 2014;151(1):528-535. PubMed 24252493
6. Ramasamy S, et al. In Silico and In Vitro Analysis of Bacoside A Aglycones and Its Derivatives as the Constituents Responsible for the Cognitive Effects of Bacopa monnieri. PLOS ONE. 2015;10(5):e0126565. PubMed 25965066
7. Kumar N, et al. Efficacy of standardized extract of Bacopa monnieri (Bacognize®) on cognitive functions of medical students: a six-week, randomized placebo-controlled trial. Evid Based Complement Alternat Med. 2016;2016:4103423.
8. Kean JD, et al. Effects of Bacopa monnieri (CDRI 08®) in a population of males exhibiting inattention and hyperactivity aged 6 to 14 years: A randomized, double-blind, placebo-controlled trial. Phytother Res. 2022;36(1):528-541. PubMed 35041248
9. Lopresti AL, et al. Effects of a Bacopa monnieri extract (Bacognize®) on stress, fatigue, quality of life and sleep in adults with self-reported poor sleep: A randomised, double-blind, placebo-controlled study. J Funct Foods. 2021;85:104671.
10. Aguiar S, Borowski T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Res. 2013;16(4):313-326. PMC3746283