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Omega-3 Fatty Acids: DHA & EPA

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Executive Summary

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Why Omega-3s Are Non-Negotiable

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The Problem with Standard Omega-3 Supplements

Most fish oil supplements use ethyl ester (EE) forms for cost-effective purification. The problem:

1. Requires enzymatic hydrolysis — Pancreatic lipase must cleave the ethyl group before absorption
2. Bile-dependent — Poor absorption without adequate dietary fat
3. Slow absorption — Peak plasma levels delayed 8-12 hours
4. Variable bioavailability — 20-60% absorption depending on meal composition

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The NTRPX Solution: AvailOm® Lysine Complex

NTRPX Systems utilize AvailOm® from Evonik — a revolutionary omega-3 delivery system that complexes free fatty acids with the essential amino acid L-lysine:

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Part I: Docosahexaenoic Acid (DHA) — The Brain’s Structural Lipid

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The Brain’s Fat Dependency

The human brain is a lipid-rich organ:

• 60% fat by dry weight — highest fat percentage of any organ except adipose
• 78% of myelin sheath is lipid — the insulating layer around axons
• Phospholipids comprise 55% of brain lipid content
• DHA is the most abundant omega-3 in the brain and retina

DHA specifically:

• Comprises 40% of all PUFAs in the brain
• Comprises 60% of PUFAs in the retina
• Makes up 50% of neuronal plasma membrane weight
• Is 30%+ of phosphatidylserine (PS) fatty acid content in neurons

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Why DHA Cannot Be Replaced

The brain has an absolute preference for DHA. When DHA is depleted, the body attempts compensation with docosapentaenoic acid (DPA, 22:5n-6) — an omega-6 analog. However:

• DPA has different membrane properties than DHA
• Phospholipids containing DPA are inferior substrates for phosphatidylserine synthesis
• This results in reduced PS levels and impaired neuronal function
• Studies show DHA-depleted animals have impaired learning and memory

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Mechanisms of DHA Action

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1. Membrane Fluidity & Architecture

DHA has six double bonds in a 22-carbon chain — the most unsaturated common fatty acid. This creates:

• Extreme flexibility — the carbon chain rapidly isomerizes between conformations
• Increased membrane fluidity — allows embedded proteins to move and function
• Optimal receptor function — G-protein coupled receptors require fluid membranes
• Enhanced neurotransmitter release — vesicle fusion depends on membrane dynamics

Mechanism Detail: DHA’s six cis double bonds create a kinked, highly flexible structure. When incorporated into membrane phospholipids, DHA molecules create “loose packing” areas that increase membrane fluidity. This fluidity is essential for:

• Neurotransmitter receptor conformational changes
• Ion channel gating
• Synaptic vesicle fusion and recycling
• Signal transduction cascades

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2. Phosphatidylserine (PS) Synthesis & Neuronal Survival

DHA-containing phospholipids (PC and PE) are the preferred substrates for PS biosynthesis in the brain. This matters because:

• PS is the major anionic phospholipid in the inner leaflet of neuronal membranes
• PS concentrations in brain gray matter are exceptionally high (15-20% of phospholipids)
• PS provides negative charge essential for recruiting signaling proteins

The Akt Survival Pathway:

1. DHA supplementation → increased membrane PS content
2. Increased PS → enhanced Akt membrane translocation
3. Akt activation → phosphorylation of pro-survival targets
4. Result: Enhanced neuronal survival under stress

Studies show DHA-supplemented neurons are protected against:

• Serum starvation
• Oxidative stress
• Amyloid-β toxicity
• Glutamate excitotoxicity

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3. Brain-Derived Neurotrophic Factor (BDNF)

DHA increases BDNF through:

• CREB phosphorylation activation
• Epigenetic modulation of BDNF gene expression
• Reduced BDNF methylation (epigenetic silencing)

BDNF is the brain’s “fertilizer” — it:

• Promotes neurogenesis (new neuron formation)
• Supports synaptic plasticity
• Enhances learning and memory consolidation
• Protects against neurodegeneration

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4. Specialized Pro-Resolving Mediators (D-Series)

DHA is the precursor for D-series resolvins, protectins, and maresins — collectively called Specialized Pro-Resolving Mediators (SPMs): Neuroprotectin D1 (NPD1) is of particular importance:

• Synthesized in the brain from DHA via 15-LOX
• Potently neuroprotective — picomolar concentrations effective
• Inhibits amyloid-β-induced apoptosis
• Reduces oxidative stress-induced cell death
• Modulates microglial activation toward protective phenotype

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DHA Deficiency: Consequences

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Part II: Eicosapentaenoic Acid (EPA) — The Resolution Architect

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EPA: The Anti-Inflammatory Omega-3

Unlike DHA, which accumulates extensively in neural membranes, EPA passes through the brain more transiently. Its magic lies in what it becomes:

1. Not highly stored in brain phospholipids at steady state
2. Rapidly metabolized when it enters the brain
3. Converted to SPMs that resolve inflammation
4. Competes with arachidonic acid for enzymatic conversion

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Mechanisms of EPA Action

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1. Competition with Arachidonic Acid (AA)

Arachidonic acid (AA, 20:4n-6) is the precursor to pro-inflammatory eicosanoids:

• Prostaglandins (PGE2, PGD2)
• Thromboxanes (TXA2)
• Leukotrienes (LTB4)

EPA competes with AA at multiple levels: Membrane Competition:

• EPA and AA compete for incorporation into phospholipids
• Higher EPA → lower membrane AA content
• Less AA available for release during inflammation

Enzyme Competition:

• EPA competes for COX-1, COX-2, and lipoxygenases
• EPA-derived products are less inflammatory than AA-derived
• Example: PGE3 (from EPA) is less inflammatory than PGE2 (from AA)

Δ5-Desaturase Inhibition:

• EPA inhibits Δ5-desaturase
• This reduces conversion of DGLA → AA
• Further decreases AA production

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2. E-Series Resolvins

EPA is converted to E-series resolvins via cytochrome P450 and lipoxygenase pathways: These resolvins signal through specific GPCRs:

• ChemR23 (ERV1): RvE1 receptor on monocytes, dendritic cells
• BLT1: RvE1 also binds leukotriene B4 receptor (antagonist)
• CMKLR1: RvE2 receptor

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3. Depression & Mood: EPA’s Domain

Meta-analyses consistently show EPA is the active antidepressant in omega-3 research: Key Findings (Multiple Meta-Analyses):

• EPA-predominant formulations (≥60% EPA) show significant antidepressant effects
• DHA-predominant formulations show minimal to no benefit for depression
• Optimal dose appears to be 1-2g EPA per day
• Effect size: SMD = -0.28 to -0.50 (small to medium effect)

Proposed Mechanisms:

1. Anti-inflammatory: Depression associated with elevated IL-6, TNF-α, CRP — EPA reduces these
2. Neuroplasticity: EPA increases N-acetyl-aspartate (neuronal marker) in brain
3. Phospholipid turnover: EPA increases cerebral phosphomonoester/phosphodiester ratio
4. Serotonin modulation: Indirect effects via inflammation-neurotransmitter crosstalk

Clinical Pearl: EPA appears most effective in patients with elevated inflammatory markers (high CRP). This supports the inflammation-depression hypothesis and suggests EPA works by resolving neuroinflammation.

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4. Cardiovascular Protection

EPA’s cardiovascular benefits include:

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Part III: AvailOm® Technology — Superior Delivery Science

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The Science of Lysine Complexation

Traditional omega-3 delivery faces fundamental chemistry challenges: Ethyl Esters (EE):

• Requires hydrolysis by pancreatic lipase
• Must be emulsified by bile salts
• Absorption is highly fat-dependent
• Poor absorption on empty stomach

Triglycerides (TG):

• Better than EE but still requires lipase and bile
• Moderately fat-dependent

AvailOm® Free Fatty Acid-Lysine Complex:

1. Complexation with L-lysine creates a stable solid powder
2. In the stomach, the complex rapidly dissociates to free fatty acids + lysine
3. Free fatty acids are directly absorbed by enterocytes
4. No enzymatic hydrolysis required
5. No bile salt emulsification needed
6. Absorption occurs even on an empty stomach

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Clinical Evidence for Superior Bioavailability

Wageningen University Study (2020):

• First in-human pharmacokinetic trial
• 8 healthy female volunteers
• Crossover design: AvailOm® vs. standard ethyl ester
• Result: 5× higher bioavailability (AUC) for AvailOm®
• Faster Tmax (peak reached sooner)

BioTeSys Study (2024):

• 21 healthy subjects (10 men, 11 women)
• Three-way crossover: AvailOm® (Lys-FFA) vs. EE vs. TG
• Results:
  • 9.33× higher bioavailability vs. EE (0-12h)
  • 8.09× higher bioavailability vs. EE (0-24h)
  • 1.57× higher bioavailability vs. TG (0-12h)
  • 1.44× higher bioavailability vs. TG (0-24h)
• Higher ΔCmax and faster Tmax vs. both comparators

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Additional AvailOm® Benefits

Bonus L-Lysine: AvailOm® provides ~14% L-lysine by weight — an essential amino acid that:

• Supports collagen synthesis
• Required for calcium absorption
• Precursor for carnitine (fat transport into mitochondria)
• Supports immune function

Unmatched Stability:

• 4 year shelf life without refrigeration

• No oxidation concerns (peroxide/anisidine values remain low)
• No antioxidants required (though Vitamin E can be added)

Formulation Flexibility:

• Powder form allows tablets, capsules, stick packs, functional foods
• No fishy taste or reflux
• Directly compressible into tablets

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Part IV: DHA & EPA in the NTRPX Ecosystem

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Product Placement Strategy

Daily Total: 700mg DHA + 700mg EPA = 1,400mg combined EPA+DHA

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Synergies within NTRPX Systems

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DHA + Phosphatidylserine (PS)

DHA increases membrane PS content → PS is included in ASG Boost™ → amplified effect:

• DHA provides substrate for PS-DHA synthesis
• Exogenous PS provides additional PS
• Result: Maximized Akt activation and neuronal protection

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EPA + Curcumin (ASG Recover™)

Both EPA and curcumin target inflammation through complementary mechanisms:

• EPA → E-series resolvins → resolution of inflammation
• Curcumin → NF-κB inhibition → prevention of inflammatory cascade
• Combined: Synergistic anti-inflammatory effect

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DHA + Vitamin D3 + K2 (ASG Boost™)

The “fat-soluble synergy triad”:

• DHA: Structural lipid requiring adequate vitamin D for metabolism
• Vitamin D3: Regulates serotonin synthesis (TPH2) — DHA enhances receptor function
• Vitamin K2: Prevents vascular calcification; neuroprotective via Gas6
• Combined with AvailOm® oil matrix: Enhanced absorption of D3 and K2

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Omega-3 + B-Vitamins (Homocysteine)

Both omega-3s and B-vitamins (B6, B9, B12) reduce homocysteine and cardiovascular risk:

• B-vitamins: Direct homocysteine metabolism (methionine cycle)
• Omega-3s: Reduce inflammatory consequences of elevated homocysteine
• Combined: Additive cardiovascular and cognitive protection

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Omega-3 + Magnesium

Magnesium is required for proper omega-3 metabolism:

• Mg2+ is a cofactor for enzymes in fatty acid metabolism
• Mg2+ modulates membrane fluidity (synergistic with DHA)
• Both support healthy inflammation response
• Combined: Optimized omega-3 utilization

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Circadian Considerations

Why EPA in the evening?

• Resolution of the day’s inflammatory burden
• Sleep involves tissue repair (anti-inflammatory state)
• EPA-derived resolvins support nocturnal recovery
• Synergy with magnesium glycinate (ASG Recover™) for relaxation

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Part V: Whole Food Sources — The Dietary Context

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Omega-3 Content of Common Foods

*Mackerel includes additional omega-3s beyond EPA+DHA

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Food Equivalents for NTRPX Daily Dose

To match the 1,400mg combined EPA+DHA from one full day of NTRPX Systems (Boost + Sustain + Recover), you would need to consume:

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The Math Problem

The American Heart Association recommends 1-2 servings of fatty fish per week for cardiovascular health. Let’s calculate: Average American fish consumption:

• ~1 serving (3 oz) fatty fish per week
• Provides: ~600-800mg EPA+DHA per week
• Daily average: 85-115mg EPA+DHA

Recommended intake for optimal health:

• General: 250-500mg EPA+DHA daily
• Cardiovascular disease: 1,000mg EPA+DHA daily
• Elevated triglycerides: 2,000-4,000mg EPA+DHA daily

The Gap: Most Americans get ~100mg/day but need 250-1,000mg/day. That’s a 2.5-10× deficit that supplementation addresses.

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Why Supplementation Makes Sense

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Dietary Strategy for NTRPX Users

Aim for synergy: Use NTRPX omega-3s as a reliable base, then add whole food sources when practical:

1. Baseline: ASG Boost™ + Sustain™ + Recover™ = 1,400mg EPA+DHA daily
2. Bonus: 2 servings fatty fish per week = +200-400mg EPA+DHA average daily
3. Total: ~1,600-1,800mg EPA+DHA daily — optimal range

Best whole food additions:

• Canned sardines (convenient, inexpensive, sustainable)
• Wild salmon (1-2x/week)
• Mackerel (high omega-3, moderate mercury)
• Oysters (bonus zinc, B12, and other minerals)

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Part VI: Dosing, Timing & Safety

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NTRPX Recommended Doses

*Pregnant women should ensure at least 200-300mg DHA daily per international guidelines

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Timing Recommendations

With Fat-Containing Meals (Traditional Omega-3s): Standard fish oil requires dietary fat for optimal absorption — take with meals containing at least 10-15g fat. AvailOm® Advantage: Because AvailOm® delivers omega-3s as free fatty acids (not requiring bile or lipase), it can be taken:

• With or without food
• On an empty stomach (still fully absorbed)
• With low-fat meals (no absorption penalty)

NTRPX Protocol:

• ASG Boost™ (morning, with breakfast) — pairs with fat-soluble vitamins (D, K, E)
• ASG Sustain™ (afternoon, with or without food) — flexibility for schedule
• ASG Recover™ (evening, with dinner or before bed) — supports overnight recovery

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Safety Profile

Generally Recognized as Safe (GRAS): EPA and DHA from fish oil have GRAS status and are extremely well-tolerated. Upper Limits:

• FDA: Up to 3g/day EPA+DHA from supplements is safe
• EFSA: Up to 5g/day EPA+DHA is safe for most adults
• NTRPX daily dose (1.4g) is well within safe range

Potential Side Effects (Dose-Dependent): Drug Interactions: Contraindications:

• Fish/shellfish allergy (consider algae-based alternatives)
• Scheduled surgery (may need to stop 1-2 weeks before)
• Active bleeding disorders

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Part VII: Quality & Sourcing

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AvailOm® Quality Standards

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Sustainability

AvailOm® omega-3s are sourced from:

• Certified sustainable fisheries (Friend of the Sea, MSC)
• Small, short-lived fish (anchovy, sardine) — lower in contaminants
• Responsible harvesting practices

Algae-based AvailOm® options are also available for vegetarian/vegan applications (High DHA Algae grade).

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Part VIII: Summary — The NTRPX Omega-3 Protocol

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Key Takeaways

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The Bottom Line

Omega-3 fatty acids aren’t optional — they’re essential building blocks that your body cannot manufacture. DHA literally builds your brain; EPA keeps your body from destroying itself through unresolved inflammation. Most people are woefully deficient. NTRPX Systems solve this problem with AvailOm® technology — delivering highly bioavailable EPA and DHA in precise, circadian-optimized doses across the product suite. The result: structural support for cognition, resolution capacity for inflammation, and cardiovascular protection — all without the fishy burps, variable absorption, or quality concerns of standard fish oil supplements. Your neurons will thank you.

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References

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